Thalidomide a N phthalimido glutarimide, C13 H10 N2 O4 , is a glutamic acid derivative initially introduced as a sedative hypnotic nearly forty years ago. It was withdrawn following numerous reports linking it to a characteristic pattern of congenital abnormalities in babies born to mothers who used the drug for morning sickness. It has gradually been re introduced into clinical practice over the past two decades, albeit under strict regulation, since it was found to be broad spectrum of anti cancer activity. Anti tumor activity of thalidomide may be related to a number of known properties, including anti tumor necrosis factor TNF a and T cell co stimulatory and anti angiogenic activities. Nanoemulsions of thalidomide were prepared in the form of intravenous injection for the treatment of cancer. The therapeutic potential of thalidomide provided motivation to develop more effective derivatives with considerably reduced toxicity. There are two types of thalidomide's immunomodulatory IMiDs analogs are lenalidomide and pomalidomide represent a novel class of compounds with numerous effects on the immune system. These analogs are thought to mediate the anticancer and anti inflammatory effects observed in humans. Thalidomide is currently approved for the treatment of dermal reaction to leprosy and is currently in phase III trials for multiple myeloma MM . IMiDs inhibit the cytokine's tumor necrosis factor a TNF a , interleukins IL 1 a, 6, 12, and granulocyte macrophage colony stimulating factor GM CSF . The repression of the tumor necrosis factor a TNF a expression is the crucial factor of many of the anti inflammatory properties of thalidomide. Rahul Singh Kushwaha | Pankaj Chasta | Aziz Ahmed | Dr. Kaushal K. Chandrol ""A Novel Approach on Thalidomide and their Analogues with their Therapeutic uses and Clinical Application"" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-4 , June 2019, URL: https://www.ijtsrd.com/papers/ijtsrd23233.pdf
Paper URL: https://www.ijtsrd.com/pharmacy/other/23233/a-novel-approach-on-thalidomide-and-their-analogues-with-their-therapeutic-uses-and-clinical-application/rahul-singh-kushwaha
Autism & Related Disabilities is a developmental disorder that affects the brain's normal development of social and communication skills. It is also known as a complex developmental disability. Austin Journal of Autism & Related Disabilities is an open access, peer reviewed scholarly journal committed to publication of unique contributions concerned with Autism & Related Disabilities.
Austin Journal of Autism & Related Disabilities accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of Autism & Related Disabilities.
Formaldehyde increases the sensitivity of breast and ovarian cancer cells to chemotherapeutic drugs like doxorubicin, cisplatin, and 5-fluorouracil in a BRCA1/2-dependent manner. Experiments showed a synergistic growth inhibition effect when formaldehyde was combined with these drugs at low doses in BRCA1/2 deficient cell lines, but not in BRCA1/2 proficient cell lines. Further experiments indicated this synergistic response was due to increased DNA double-strand breaks and cell death, rather than just growth inhibition, when formaldehyde was combined with doxorubicin. The synergistic, cytotoxic response to formaldehyde combinations was also observed in BRCA1/2 deficient ovarian cancer cell
Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecu...Joshua Mangerel
This document summarizes the results of a study that integrated genomic data to identify molecular subgroups in diffuse intrinsic pontine glioma (DIPG), a deadly childhood brain cancer. The study found that DIPG comprises three distinct subgroups - MYCN, silent, and H3-K27M - with differences in mutations, gene expression, methylation, and clinical features. A novel recurrent mutation was discovered in the ACVR1 gene in 20% of DIPGs. The identification of distinct molecular subgroups highlights the heterogeneity of DIPG and could help guide more targeted treatment approaches for this incurable cancer.
Clarithromycin impurities at pharmaffiliatesJazzCrystal
Clarithromycin (Impurities at Pharmaffiliates) is a semi-synthetic antibiotic belongs to the group of macrolide antibiotics. It is used to treat infections caused by bacteria. It also acts as a novel chiral selector for the enantiomeric separation of basic drugs in capillary electrophoresis.
The document summarizes a study investigating the expression and role of apoptosis-related molecules like TRAIL, FasL, and their receptors in pancreatic adenocarcinoma cell lines. The key findings were:
1) The pancreatic cancer cell lines expressed high levels of apoptosis-inducing ligands and receptors but showed variable susceptibility to TRAIL-induced cell death.
2) Treatment with chemotherapy drugs did not increase their susceptibility to apoptosis, likely due to their differential expression of decoy receptors and inhibitor molecules.
3) This suggests pancreatic cancers develop resistance to immune-mediated apoptosis, allowing immune evasion and tumor progression.
The Hedgehog (Hh) signal transduction pathway is involved in diverse physiological processes such as cell survival, proliferation, differentiation, embryonic development, and fetal determination. Perturbations in this pathway leading to its aberrant activation have been implicated in various cancers including acute myeloid leukemia (AML). AML is a highly complex hematological malignancy resulting due to accumulation of abnormal myeloblasts in the bone marrow leading to bone marrow failure and ultimately death. Recently, the role of hedgehog signaling in AML pathogenesis has been uncovered and thus pharmacological targeting of the hedgehog pathway in AML has become a prime therapeutic option. In this mini-review, we highlight the role of the hedgehog pathway in AML and review the latest drugs as well as possible Hh targets in treating AML.
This document discusses doxorubicin (Dox), a commonly used chemotherapeutic agent, and its ability to induce autophagy in tumor cells and cardiomyocytes. Recent research has identified several major biomarkers, such as AMPK, p53, and Bcl-2, that are important for Dox-induced apoptosis. In particular, it is Bcl-2's interaction with Beclin-1 that has refocused attention on Dox's ability to induce autophagy. The document suggests that further research into Dox's molecular signaling in neoplastic and normal cells may help redefine how Dox is clinically used and lead to improved cancer management by potentially exploiting autophagy.
Clarithromycin Impurities at PharmaffiliatesJazzCrystal
Clarithromycin (Impurities at Pharmaffiliates) is a semi-synthetic antibiotic belongs to the group of macrolide antibiotics. It is used to treat infections caused by bacteria. It also acts as a novel chiral selector for the enantiomeric separation of basic drugs in capillary electrophoresis. For more details visit https://www.pharmaffiliates.com/en/parentapi/clarithromycin-impurities.
Autism & Related Disabilities is a developmental disorder that affects the brain's normal development of social and communication skills. It is also known as a complex developmental disability. Austin Journal of Autism & Related Disabilities is an open access, peer reviewed scholarly journal committed to publication of unique contributions concerned with Autism & Related Disabilities.
Austin Journal of Autism & Related Disabilities accepts original research articles, review articles, case reports, clinical images and rapid communication on all the aspects of Autism & Related Disabilities.
Formaldehyde increases the sensitivity of breast and ovarian cancer cells to chemotherapeutic drugs like doxorubicin, cisplatin, and 5-fluorouracil in a BRCA1/2-dependent manner. Experiments showed a synergistic growth inhibition effect when formaldehyde was combined with these drugs at low doses in BRCA1/2 deficient cell lines, but not in BRCA1/2 proficient cell lines. Further experiments indicated this synergistic response was due to increased DNA double-strand breaks and cell death, rather than just growth inhibition, when formaldehyde was combined with doxorubicin. The synergistic, cytotoxic response to formaldehyde combinations was also observed in BRCA1/2 deficient ovarian cancer cell
Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecu...Joshua Mangerel
This document summarizes the results of a study that integrated genomic data to identify molecular subgroups in diffuse intrinsic pontine glioma (DIPG), a deadly childhood brain cancer. The study found that DIPG comprises three distinct subgroups - MYCN, silent, and H3-K27M - with differences in mutations, gene expression, methylation, and clinical features. A novel recurrent mutation was discovered in the ACVR1 gene in 20% of DIPGs. The identification of distinct molecular subgroups highlights the heterogeneity of DIPG and could help guide more targeted treatment approaches for this incurable cancer.
Clarithromycin impurities at pharmaffiliatesJazzCrystal
Clarithromycin (Impurities at Pharmaffiliates) is a semi-synthetic antibiotic belongs to the group of macrolide antibiotics. It is used to treat infections caused by bacteria. It also acts as a novel chiral selector for the enantiomeric separation of basic drugs in capillary electrophoresis.
The document summarizes a study investigating the expression and role of apoptosis-related molecules like TRAIL, FasL, and their receptors in pancreatic adenocarcinoma cell lines. The key findings were:
1) The pancreatic cancer cell lines expressed high levels of apoptosis-inducing ligands and receptors but showed variable susceptibility to TRAIL-induced cell death.
2) Treatment with chemotherapy drugs did not increase their susceptibility to apoptosis, likely due to their differential expression of decoy receptors and inhibitor molecules.
3) This suggests pancreatic cancers develop resistance to immune-mediated apoptosis, allowing immune evasion and tumor progression.
The Hedgehog (Hh) signal transduction pathway is involved in diverse physiological processes such as cell survival, proliferation, differentiation, embryonic development, and fetal determination. Perturbations in this pathway leading to its aberrant activation have been implicated in various cancers including acute myeloid leukemia (AML). AML is a highly complex hematological malignancy resulting due to accumulation of abnormal myeloblasts in the bone marrow leading to bone marrow failure and ultimately death. Recently, the role of hedgehog signaling in AML pathogenesis has been uncovered and thus pharmacological targeting of the hedgehog pathway in AML has become a prime therapeutic option. In this mini-review, we highlight the role of the hedgehog pathway in AML and review the latest drugs as well as possible Hh targets in treating AML.
This document discusses doxorubicin (Dox), a commonly used chemotherapeutic agent, and its ability to induce autophagy in tumor cells and cardiomyocytes. Recent research has identified several major biomarkers, such as AMPK, p53, and Bcl-2, that are important for Dox-induced apoptosis. In particular, it is Bcl-2's interaction with Beclin-1 that has refocused attention on Dox's ability to induce autophagy. The document suggests that further research into Dox's molecular signaling in neoplastic and normal cells may help redefine how Dox is clinically used and lead to improved cancer management by potentially exploiting autophagy.
Clarithromycin Impurities at PharmaffiliatesJazzCrystal
Clarithromycin (Impurities at Pharmaffiliates) is a semi-synthetic antibiotic belongs to the group of macrolide antibiotics. It is used to treat infections caused by bacteria. It also acts as a novel chiral selector for the enantiomeric separation of basic drugs in capillary electrophoresis. For more details visit https://www.pharmaffiliates.com/en/parentapi/clarithromycin-impurities.
Peptidomimetics are being researched as potential anti-cancer drugs with increased selectivity for cancer cells and reduced toxicity compared to existing drugs like cisplatin. Peptidomimetics are thought to induce apoptosis in cancer cells by crosslinking with DNA in the major groove, altering DNA structure and increasing the population of cells in the G1 stage of mitosis. One peptidomimetic drug candidate, AuD8, inhibits tumor growth in mice by binding to proteasomes and inhibiting protein degradation, leading to accumulation of ubiquitin proteins and apoptosis. Triplex metallohelices show potential as well through selective cytotoxicity against various cancer cell lines. However, more research is needed to improve production methods and translate
Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Mult...asclepiuspdfs
During the past four decades, autologous stem cell transplantation (ASCT) has been the first choice and the standard option for the treatment of newly diagnosed patients with multiple myeloma. The introduction of new agents such as thalidomide, lenalidomide, and bortezomib has led to a clear improvement in basic approach and those agents became the standard of care in the induction phase; however, they were not able to play the role of ASCT in term of progression-free survival and overall survival. Debate continues about the best induction, consolidation, and maintenance taking into account the toxicities of these new agents. The new monoclonal antibody (anti CD38) starts to take its place in the induction setting and it seems to be a promising agent in the high-risk group. Until recently, ASCT is the standard treatment for newly diagnosed patients.
This document summarizes a presentation on chiral separation from a pharmaceutical industry perspective. It begins by discussing the tragic lessons from Thalidomide, where one enantiomer was teratogenic while the other had desired effects. It emphasizes the importance of separating single enantiomers due to differences in biological activity and toxicity. It then covers topics like chiral stationary phases used for separation, potential advantages of racemic switches and developing single isomers, and considerations for preclinical and clinical development like enantioselective assays and pharmacokinetics. In concluding, it stresses that isomeric purity must be thoroughly studied and chiral switches should improve safety/efficacy.
Novel 1,3,4-Thiadiazole Linked Amide Derivatives of Pteridone: Synthesis and ...Ratnakaram Venkata Nadh
Cancer is a second leading cause of death after heart attack, in developing as well as undeveloped
countries. It is caused by unregulated growth and metastasis of the abnormal cancer cells.
Cancer can be cured by radiation, immunotherapy and chemotherapy, among them; chemotherapy is a
good treatment for cancer, in which chemotherapeutic drug is used. The anticancer activity of newly
synthesized compounds (13a-j) was carried out on four different types of human cancer cell lines like
MCF-7 (breast), A549 (lung), Colo-205 (colon) and A2780 (ovarian) by the MTT method, and compared
to etoposide used as a positive control. Among them, compound 13g with electron-withdrawing
(3,5-dinitro) group, exhibited more promising activity in all cell lines (MCF-7 = 0.10±0.076 μM, A549
= 0.17±0.039 μM, Colo-205= 0.13±0.022 μM and A2780 = 0.87±0.027μM). This compound may act
as lead drug in cancer chemotherapy. In future, this compound can be examined for clinical studies.
1. This document discusses molecular diagnosis methods for autoimmune bullous diseases, which are characterized by loss of cell-cell or cell-matrix adhesion in the epidermis due to autoantibodies against various adhesion proteins.
2. Key diagnostic methods discussed are direct and indirect immunofluorescence, ELISA and immunoblotting to detect autoantibodies against desmogleins, desmocollins, and other adhesion proteins.
3. The distribution of desmogleins in skin versus mucosa helps explain why some autoimmune bullous diseases predominantly affect skin or mucosa.
This document describes the development of new small molecule inhibitors of the lysine-specific demethylase 1 (LSD1) enzyme. Through virtual screening, the authors identified three compounds (5-7) that showed potential to inhibit LSD1. They synthesized analogs of these compounds and another hit (12). In vitro testing showed that some of the amidoxime analogs are moderate inhibitors of recombinant LSD1 but dramatically change methylation levels of histone 3 lysine 4 (H3K4), a target of LSD1, in lung cancer cells. These changes correlate with increased expression of tumor suppressor genes. The amidoximes represent a new series of epigenetic modulators with potential use as cancer
This document lists 50 publications by Dr. Gilbert Lefèvre from 1987 to 2008. The publications cover a range of topics including:
- Anti-Müllerian hormone and related monoclonal antibodies (publications 1-3)
- Pharmacokinetic studies of drugs like hirudin, artemether, and rivastigmine (publications 4-10, 23-25, 45-50)
- Drug interaction and safety studies of antimalarial and Alzheimer's drugs (publications 26-28, 30-33, 36, 38, 40, 41, 44)
- Pharmacokinetic studies of antimalarial drugs in specific populations like children and Africans (publications 29, 42, 43)
With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/platform.htm
The document summarizes the synthesis of new triazenoazaindole compounds with potential antitumor activity. It introduces that new chemotherapeutic agents are still needed to treat cancer. It describes that a new class of compounds bearing a triazenoazaindole scaffold were synthesized with the aim of identifying new antiproliferative agents. The antiproliferative activity of the compounds was evaluated in five human tumor cell lines and results were expressed as GI50 values, with dacarbazine as a reference, showing the compounds have cytotoxic potential and warrant further investigation.
This chapter discusses thalidomide and its analogs as potential treatments for liver diseases and cirrhosis. Thalidomide was originally developed as a sedative but caused birth defects. It was later found to have anti-inflammatory properties by inhibiting TNF-α. Several analogs have since been synthesized with improved stability, potency, and safety. Experimental studies show that thalidomide and some analogs have anti-cholestatic, anti-necrotic, and anti-fibrotic effects in models of liver injury and cirrhosis. The anti-inflammatory and anti-fibrotic effects are mediated by inhibition of TNF-α and NF-κB pathways. Thalidomide and its analogs may
Combining Old and New: Sensitising Drugs and Other Vaccines To Augment Effica...NeuroAcademy
1) The document discusses combining existing drugs and vaccines like levamisole, BCG, imiquimod, mifamurtide, and dendritic cell vaccines to augment the efficacy of dendritic cell immunotherapy.
2) It provides details on the mechanisms and effects of these drugs, including how they stimulate immune responses and dendritic cell activation.
3) Experimental results are presented showing improved survival rates in cancer patients receiving combined immunotherapy and chemotherapy compared to immunotherapy alone.
Summary of Treatments for Multiple Myeloma.pdfDoriaFang
Currently, there are a variety of drugs available for multiple myeloma, including traditional cytotoxic drugs, immunomodulatory analogs, proteasome inhibitors, antibody-based drugs and CAR T-cell therapy.
This document summarizes a literature review on intra-tumoral lymphocytes (TIL) in breast cancer. The review found that assessing TIL is unnecessary in high-grade tumors but may be useful in intermediate-grade tumors. In neoadjuvant and adjuvant settings, CD3+ lymphocytes correlate with better response to chemotherapy. After chemotherapy, quantifying regulatory T cells (Treg; CD4+FOXP3+) is helpful as decreased levels correlate with better prognosis. While the role of TIL in breast cancer is established, the optimal methods for microscopic assessment and immunohistochemical subtyping of TIL remain unclear.
The document discusses the history and development of thalidomide and its analogues. Thalidomide was originally introduced in the late 1950s as a sedative but was found to cause birth defects in thousands of children after being prescribed to pregnant women for morning sickness. This led to it being withdrawn in 1961. Researchers later discovered that thalidomide and its analogues have immunomodulatory and anti-inflammatory properties, leading to FDA approval to treat cancers and inflammatory diseases. New analogues like lenalidomide and pomalidomide were developed that are more potent with fewer side effects.
The document discusses targeted therapy and its role in treating cancer. It defines targeted therapy as using drugs or substances to recognize and kill cancer cells without harming normal cells. It provides examples of targeted therapy drugs, including Gleevec/Imatinib which treats chronic myeloid leukemia, Velcade/Bortezomib which treats multiple myelomas, and Sutent which treats kidney cancer. The document also discusses how these drugs work, such as by inhibiting tyrosine kinases or blocking protein breakdown in cancer cells.
This document provides an overview of targeted chemotherapy and reviews recent developments. It discusses how targeted therapies like monoclonal antibodies and small molecule inhibitors precisely target molecular changes in cancer cells, potentially causing fewer side effects than traditional chemotherapy. The document outlines several FDA-approved targeted drugs and their indications. It also discusses considerations for targeted therapy like evaluating effectiveness through biomarkers, increased costs compared to chemotherapy, and challenges in determining optimal dosing. Future areas of research discussed include personalized treatment based on a patient's molecular profile and defining dose-response relationships through randomized trials.
The Efficacy of Biological Therapies for Psoriasis - Review Articlepaperpublications3
Abstract: Background: it is indicated that Biological Therapies has great effect in dealing with Psoriasis. Differences in response rates of biologics for the treatment of moderate-to-severe plaque psoriasis have been reported in many published articles.
Objective: this paper aims to declare the effectiveness of biological therapies for psoriasis.
Methods: using the search engine PubMed to prepare comprehensive literature about the specified topic.
Main results: it is indicated that psoriasis is a chronic inflammatory skin disease condition that involves altered expression of a broad spectrum of proinflammatory cytokines which are associated with activation of T cells and proliferation of keratinocytes.
Conclusion: The introduction of targeted biologic therapies has greatly improved the treatment options for psoriasis although the pathogenesis of the autoimmune skin disease has not been fully elucidated. The potential for psoriasis disease is implicit because altered expressions of cutaneous and systemic cytokines are well demonstrated in psoriasis patients.
1) The document discusses various mechanisms of cancer drug resistance, including decreased drug accumulation, alterations in drug targets, drug efflux, compartmentalization, altered apoptosis and autophagy pathways, and the role of the tumor microenvironment in providing protection.
2) It also reviews ways to potentially overcome resistance, such as through multidrug resistance modulators, targeted therapies, immunotherapy and combination therapies.
3) However, it notes that cancer progression, metastasis, inherited or acquired drug resistance, and incomplete understanding of resistance mechanisms still pose challenges to effective cancer treatment.
Vorinostat combined with DNMTi epigenetically controls the proliferation of l...MustafaFathy6
This study evaluated the effects of combining the histone deacetylase inhibitor (HDACi) vorinostat with other chemotherapeutic drugs on lung cancer cells. Vorinostat alone and in combination with carboplatin was most effective at reducing cell viability of A549 lung cancer cells. Global DNA methylation patterns varied depending on the drug combinations, with vorinostat and carboplatin causing hypomethylation and vorinostat and cyclophosphamide resulting in hypermethylation. The results suggest that combining epigenetic and chemotherapeutic drugs may be more effective at controlling lung cancer proliferation than single agents alone. However, more experiments are needed to confirm these findings.
This document discusses chemotherapy options for treating metastatic melanoma. It summarizes a study that compared the effectiveness of Temozolomide alone or in combination with interferon or thalidomide for metastatic melanoma. The study found that all three regimens were well-tolerated and had comparable efficacy, with combination therapies showing potential for better tumor response and survival. Specifically, the combination of Temozolomide and thalidomide seemed the most promising. However, chemotherapy overall has limited effectiveness for melanoma, responding in only about 14% of patients. Alternative treatment options like radiosurgery are also discussed.
This document discusses using nanocomposites for cancer immunotherapy. It describes how tumors evade the immune system through inhibitory cytokines and loss of antigen processing. Current cancer treatments like chemotherapy and radiation have toxicity issues and limited effectiveness. The document proposes using dendritic cell-based immunotherapy as a safer alternative that utilizes the patient's immune system to fight cancer. It reviews literature on using pH-responsive nanoparticles, liposomes, and nanoparticles co-encapsulated with TLR agonists to target dendritic cells and enhance antigen presentation and immune responses, showing potential for effective cancer treatment.
Peptidomimetics are being researched as potential anti-cancer drugs with increased selectivity for cancer cells and reduced toxicity compared to existing drugs like cisplatin. Peptidomimetics are thought to induce apoptosis in cancer cells by crosslinking with DNA in the major groove, altering DNA structure and increasing the population of cells in the G1 stage of mitosis. One peptidomimetic drug candidate, AuD8, inhibits tumor growth in mice by binding to proteasomes and inhibiting protein degradation, leading to accumulation of ubiquitin proteins and apoptosis. Triplex metallohelices show potential as well through selective cytotoxicity against various cancer cell lines. However, more research is needed to improve production methods and translate
Decreasing or Increasing Role of Autologous Stem Cell Transplantation in Mult...asclepiuspdfs
During the past four decades, autologous stem cell transplantation (ASCT) has been the first choice and the standard option for the treatment of newly diagnosed patients with multiple myeloma. The introduction of new agents such as thalidomide, lenalidomide, and bortezomib has led to a clear improvement in basic approach and those agents became the standard of care in the induction phase; however, they were not able to play the role of ASCT in term of progression-free survival and overall survival. Debate continues about the best induction, consolidation, and maintenance taking into account the toxicities of these new agents. The new monoclonal antibody (anti CD38) starts to take its place in the induction setting and it seems to be a promising agent in the high-risk group. Until recently, ASCT is the standard treatment for newly diagnosed patients.
This document summarizes a presentation on chiral separation from a pharmaceutical industry perspective. It begins by discussing the tragic lessons from Thalidomide, where one enantiomer was teratogenic while the other had desired effects. It emphasizes the importance of separating single enantiomers due to differences in biological activity and toxicity. It then covers topics like chiral stationary phases used for separation, potential advantages of racemic switches and developing single isomers, and considerations for preclinical and clinical development like enantioselective assays and pharmacokinetics. In concluding, it stresses that isomeric purity must be thoroughly studied and chiral switches should improve safety/efficacy.
Novel 1,3,4-Thiadiazole Linked Amide Derivatives of Pteridone: Synthesis and ...Ratnakaram Venkata Nadh
Cancer is a second leading cause of death after heart attack, in developing as well as undeveloped
countries. It is caused by unregulated growth and metastasis of the abnormal cancer cells.
Cancer can be cured by radiation, immunotherapy and chemotherapy, among them; chemotherapy is a
good treatment for cancer, in which chemotherapeutic drug is used. The anticancer activity of newly
synthesized compounds (13a-j) was carried out on four different types of human cancer cell lines like
MCF-7 (breast), A549 (lung), Colo-205 (colon) and A2780 (ovarian) by the MTT method, and compared
to etoposide used as a positive control. Among them, compound 13g with electron-withdrawing
(3,5-dinitro) group, exhibited more promising activity in all cell lines (MCF-7 = 0.10±0.076 μM, A549
= 0.17±0.039 μM, Colo-205= 0.13±0.022 μM and A2780 = 0.87±0.027μM). This compound may act
as lead drug in cancer chemotherapy. In future, this compound can be examined for clinical studies.
1. This document discusses molecular diagnosis methods for autoimmune bullous diseases, which are characterized by loss of cell-cell or cell-matrix adhesion in the epidermis due to autoantibodies against various adhesion proteins.
2. Key diagnostic methods discussed are direct and indirect immunofluorescence, ELISA and immunoblotting to detect autoantibodies against desmogleins, desmocollins, and other adhesion proteins.
3. The distribution of desmogleins in skin versus mucosa helps explain why some autoimmune bullous diseases predominantly affect skin or mucosa.
This document describes the development of new small molecule inhibitors of the lysine-specific demethylase 1 (LSD1) enzyme. Through virtual screening, the authors identified three compounds (5-7) that showed potential to inhibit LSD1. They synthesized analogs of these compounds and another hit (12). In vitro testing showed that some of the amidoxime analogs are moderate inhibitors of recombinant LSD1 but dramatically change methylation levels of histone 3 lysine 4 (H3K4), a target of LSD1, in lung cancer cells. These changes correlate with increased expression of tumor suppressor genes. The amidoximes represent a new series of epigenetic modulators with potential use as cancer
This document lists 50 publications by Dr. Gilbert Lefèvre from 1987 to 2008. The publications cover a range of topics including:
- Anti-Müllerian hormone and related monoclonal antibodies (publications 1-3)
- Pharmacokinetic studies of drugs like hirudin, artemether, and rivastigmine (publications 4-10, 23-25, 45-50)
- Drug interaction and safety studies of antimalarial and Alzheimer's drugs (publications 26-28, 30-33, 36, 38, 40, 41, 44)
- Pharmacokinetic studies of antimalarial drugs in specific populations like children and Africans (publications 29, 42, 43)
With the combination of a monoclonal antibody and extremely toxic chemical payloads, these biomacromolecule “warheads” are by far one of the most powerful weapons in the immunotherapy arsenal, bearing the hope as “the beginning of the end” to the battle against cancer. https://www.creative-biolabs.com/adc/platform.htm
The document summarizes the synthesis of new triazenoazaindole compounds with potential antitumor activity. It introduces that new chemotherapeutic agents are still needed to treat cancer. It describes that a new class of compounds bearing a triazenoazaindole scaffold were synthesized with the aim of identifying new antiproliferative agents. The antiproliferative activity of the compounds was evaluated in five human tumor cell lines and results were expressed as GI50 values, with dacarbazine as a reference, showing the compounds have cytotoxic potential and warrant further investigation.
This chapter discusses thalidomide and its analogs as potential treatments for liver diseases and cirrhosis. Thalidomide was originally developed as a sedative but caused birth defects. It was later found to have anti-inflammatory properties by inhibiting TNF-α. Several analogs have since been synthesized with improved stability, potency, and safety. Experimental studies show that thalidomide and some analogs have anti-cholestatic, anti-necrotic, and anti-fibrotic effects in models of liver injury and cirrhosis. The anti-inflammatory and anti-fibrotic effects are mediated by inhibition of TNF-α and NF-κB pathways. Thalidomide and its analogs may
Combining Old and New: Sensitising Drugs and Other Vaccines To Augment Effica...NeuroAcademy
1) The document discusses combining existing drugs and vaccines like levamisole, BCG, imiquimod, mifamurtide, and dendritic cell vaccines to augment the efficacy of dendritic cell immunotherapy.
2) It provides details on the mechanisms and effects of these drugs, including how they stimulate immune responses and dendritic cell activation.
3) Experimental results are presented showing improved survival rates in cancer patients receiving combined immunotherapy and chemotherapy compared to immunotherapy alone.
Summary of Treatments for Multiple Myeloma.pdfDoriaFang
Currently, there are a variety of drugs available for multiple myeloma, including traditional cytotoxic drugs, immunomodulatory analogs, proteasome inhibitors, antibody-based drugs and CAR T-cell therapy.
This document summarizes a literature review on intra-tumoral lymphocytes (TIL) in breast cancer. The review found that assessing TIL is unnecessary in high-grade tumors but may be useful in intermediate-grade tumors. In neoadjuvant and adjuvant settings, CD3+ lymphocytes correlate with better response to chemotherapy. After chemotherapy, quantifying regulatory T cells (Treg; CD4+FOXP3+) is helpful as decreased levels correlate with better prognosis. While the role of TIL in breast cancer is established, the optimal methods for microscopic assessment and immunohistochemical subtyping of TIL remain unclear.
The document discusses the history and development of thalidomide and its analogues. Thalidomide was originally introduced in the late 1950s as a sedative but was found to cause birth defects in thousands of children after being prescribed to pregnant women for morning sickness. This led to it being withdrawn in 1961. Researchers later discovered that thalidomide and its analogues have immunomodulatory and anti-inflammatory properties, leading to FDA approval to treat cancers and inflammatory diseases. New analogues like lenalidomide and pomalidomide were developed that are more potent with fewer side effects.
The document discusses targeted therapy and its role in treating cancer. It defines targeted therapy as using drugs or substances to recognize and kill cancer cells without harming normal cells. It provides examples of targeted therapy drugs, including Gleevec/Imatinib which treats chronic myeloid leukemia, Velcade/Bortezomib which treats multiple myelomas, and Sutent which treats kidney cancer. The document also discusses how these drugs work, such as by inhibiting tyrosine kinases or blocking protein breakdown in cancer cells.
This document provides an overview of targeted chemotherapy and reviews recent developments. It discusses how targeted therapies like monoclonal antibodies and small molecule inhibitors precisely target molecular changes in cancer cells, potentially causing fewer side effects than traditional chemotherapy. The document outlines several FDA-approved targeted drugs and their indications. It also discusses considerations for targeted therapy like evaluating effectiveness through biomarkers, increased costs compared to chemotherapy, and challenges in determining optimal dosing. Future areas of research discussed include personalized treatment based on a patient's molecular profile and defining dose-response relationships through randomized trials.
The Efficacy of Biological Therapies for Psoriasis - Review Articlepaperpublications3
Abstract: Background: it is indicated that Biological Therapies has great effect in dealing with Psoriasis. Differences in response rates of biologics for the treatment of moderate-to-severe plaque psoriasis have been reported in many published articles.
Objective: this paper aims to declare the effectiveness of biological therapies for psoriasis.
Methods: using the search engine PubMed to prepare comprehensive literature about the specified topic.
Main results: it is indicated that psoriasis is a chronic inflammatory skin disease condition that involves altered expression of a broad spectrum of proinflammatory cytokines which are associated with activation of T cells and proliferation of keratinocytes.
Conclusion: The introduction of targeted biologic therapies has greatly improved the treatment options for psoriasis although the pathogenesis of the autoimmune skin disease has not been fully elucidated. The potential for psoriasis disease is implicit because altered expressions of cutaneous and systemic cytokines are well demonstrated in psoriasis patients.
1) The document discusses various mechanisms of cancer drug resistance, including decreased drug accumulation, alterations in drug targets, drug efflux, compartmentalization, altered apoptosis and autophagy pathways, and the role of the tumor microenvironment in providing protection.
2) It also reviews ways to potentially overcome resistance, such as through multidrug resistance modulators, targeted therapies, immunotherapy and combination therapies.
3) However, it notes that cancer progression, metastasis, inherited or acquired drug resistance, and incomplete understanding of resistance mechanisms still pose challenges to effective cancer treatment.
Vorinostat combined with DNMTi epigenetically controls the proliferation of l...MustafaFathy6
This study evaluated the effects of combining the histone deacetylase inhibitor (HDACi) vorinostat with other chemotherapeutic drugs on lung cancer cells. Vorinostat alone and in combination with carboplatin was most effective at reducing cell viability of A549 lung cancer cells. Global DNA methylation patterns varied depending on the drug combinations, with vorinostat and carboplatin causing hypomethylation and vorinostat and cyclophosphamide resulting in hypermethylation. The results suggest that combining epigenetic and chemotherapeutic drugs may be more effective at controlling lung cancer proliferation than single agents alone. However, more experiments are needed to confirm these findings.
This document discusses chemotherapy options for treating metastatic melanoma. It summarizes a study that compared the effectiveness of Temozolomide alone or in combination with interferon or thalidomide for metastatic melanoma. The study found that all three regimens were well-tolerated and had comparable efficacy, with combination therapies showing potential for better tumor response and survival. Specifically, the combination of Temozolomide and thalidomide seemed the most promising. However, chemotherapy overall has limited effectiveness for melanoma, responding in only about 14% of patients. Alternative treatment options like radiosurgery are also discussed.
This document discusses using nanocomposites for cancer immunotherapy. It describes how tumors evade the immune system through inhibitory cytokines and loss of antigen processing. Current cancer treatments like chemotherapy and radiation have toxicity issues and limited effectiveness. The document proposes using dendritic cell-based immunotherapy as a safer alternative that utilizes the patient's immune system to fight cancer. It reviews literature on using pH-responsive nanoparticles, liposomes, and nanoparticles co-encapsulated with TLR agonists to target dendritic cells and enhance antigen presentation and immune responses, showing potential for effective cancer treatment.
This study examined the effects of loading different innate immune activators onto microparticles (MP) and introducing them into the tumor microenvironment (TME), with the goal of re-educating tumor-associated innate immune cells (IIC) to mount an anti-tumor response. Lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand, loaded onto MP induced inflammatory cytokines and chemokines in the TME but was insufficient to delay tumor growth on its own. However, LPS combined with a complement C5a receptor (C5aR) ligand on the same MP significantly delayed tumor growth while also modulating cytokine levels. Combining the different ligands on separate MPs did not achieve
This document discusses using nanocomposites for immunotherapy. It describes how tumors escape immune detection through inhibitory cytokines and dysfunctional dendritic cells. Current cancer treatments like chemotherapy and radiation have limitations like toxicity and inability to completely remove tumors or prevent recurrence. The document proposes immunotherapy using dendritic cell-based approaches as a safer alternative that could eliminate tumors via natural immune responses with less toxicity and risk of recurrence. It reviews literature on pH-responsive nanoparticles that effectively deliver antigens to induce immune responses. Different studies demonstrated dendritic cell targeting nanoparticles improved cancer immunotherapy outcomes in animal models.
This document summarizes recent advances in immunotherapy for solid tumors. It discusses how immunotherapy has established itself as an effective treatment strategy, building on William Coley's pioneering work in the late 1800s using bacteria to elicit anti-tumor immune responses. The document outlines several key immunotherapy approaches, including immune checkpoint inhibitors, adoptive cellular therapy, strategies to enhance tumor immunogenicity like radiotherapy and oncolytic viruses, and cancer vaccines. It also discusses how tumor-infiltrating lymphocytes and immunoscore can help predict cancer prognosis and how the immune system interacts with tumors.
Limitations of Immunotherapeutic Approaches for Cancer Treatment_Crimson Publ...CrimsonpublishersCancer
Of the multiple approaches to cancer therapy, few are as complex as those regimens that encompass immune-based agents. Immunotherapeutic approaches have been the central focus of medical investigators for the past several years. This advance in oncologic care is highlighted by the recognition of the Nobel commission in awarding the 2018 Nobel prize to Allison and Honjo [1]. Their seminal work concentrated on an immunotherapeutic approach to combatting cancers via immune checkpoint receptors’ enhancement of the adaptive immune system. A previous review emphasized the potential role of checkpoint inhibitors in the treatment and cure of HIV also through enhancement of adaptive immune function to counter this virus [2].
Antiangiogenesis Tumor Therapy: A Review of Literaturemeducationdotnet
The document provides a literature review on antiangiogenesis tumour therapy. It summarizes four studies that evaluated different antiangiogenesis treatment strategies:
1) A pravastatin study that directly targeted tumour vasculature showed efficacy after 72 hours, with pravastatin traces found in tissues. However, it only used four mice per group.
2) A bevacizumab plus fotemustine study for metastatic melanoma patients showed median survival of 8.3 and 20.5 months but high toxicity, with 5 patients removed. It successfully decreased VEGF-A.
3) A vernolide-A study on mice and endothelial cells showed effects on VEGF and endothelial migration after short periods but no comparisons to
Background and objectives: the 5’nucleotidase (5’NT) is one of
hydrolytic enzymes present in different organs which catalyze
hydrolysis of 5’ nucleotides to ribonucleosides and phosphate.
Malondialdehyde (MDA) is the end product of lipid peroxidation
by oxidative stress (free radicals).
The aim of present study was to measure the serum activity of
5’NT, and MDA concentration in breast tumors.
Material and method: A prospective study was carried out from
May to December 2013 by clinical biochemistry department in
College of Medicine-Hawler Medical University on (30) healthy
female individuals, (group 1) and (30) females with breast tumor
(group 2).
Results: The mean value of serum MDA was significantly higher
in females with breast tumors (group 2), than that of healthy
female individuals, (group 1) (p<0.01),><0.01).
Conclusion: Based on findings of the present study it can be
concluded that breast tumors can cause release of the enzyme
5’NT from tumor cells, and lipid peroxidation by reactive oxygen
species (ROS), which cause elevation of MDA.
1) T-cell receptor (TCR) gene therapy redirects T lymphocytes for cancer immunotherapy by introducing rearranged TCR genes, allowing the T cells to target tumors.
2) Successful TCR gene therapy requires consideration of TCR specificity and affinity, optimal gene constructs, the types of T cells used, and the survival and activity of the modified T cells.
3) The review highlights the rationale and experience with TCR gene therapy and new approaches to enhance its effectiveness.
Similar to A Novel Approach on Thalidomide and their Analogues with their Therapeutic uses and Clinical Application (20)
‘Six Sigma Technique’ A Journey Through its Implementationijtsrd
The manufacturing industries all over the world are facing tough challenges for growth, development and sustainability in today’s competitive environment. They have to achieve apex position by adapting with the global competitive environment by delivering goods and services at low cost, prime quality and better price to increase wealth and consumer satisfaction. Cost Management ensures profit, growth and sustainability of the business with implementation of Continuous Improvement Technique like Six Sigma. This leads to optimize Business performance. The method drives for customer satisfaction, low variation, reduction in waste and cycle time resulting into a competitive advantage over other industries which did not implement it. The main objective of this paper ‘Six Sigma Technique A Journey Through Its Implementation’ is to conceptualize the effectiveness of Six Sigma Technique through the journey of its implementation. Aditi Sunilkumar Ghosalkar "‘Six Sigma Technique’: A Journey Through its Implementation" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64546.pdf Paper Url: https://www.ijtsrd.com/other-scientific-research-area/other/64546/‘six-sigma-technique’-a-journey-through-its-implementation/aditi-sunilkumar-ghosalkar
Edge Computing in Space Enhancing Data Processing and Communication for Space...ijtsrd
Edge computing, a paradigm that involves processing data closer to its source, has gained significant attention for its potential to revolutionize data processing and communication in space missions. With the increasing complexity and data volume generated by modern space missions, traditional centralized computing approaches face challenges related to latency, bandwidth, and security. Edge computing in space, involving on board processing and analysis of data, offers promising solutions to these challenges. This paper explores the concept of edge computing in space, its benefits, applications, and future prospects in enhancing space missions. Manish Verma "Edge Computing in Space: Enhancing Data Processing and Communication for Space Missions" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64541.pdf Paper Url: https://www.ijtsrd.com/computer-science/artificial-intelligence/64541/edge-computing-in-space-enhancing-data-processing-and-communication-for-space-missions/manish-verma
Dynamics of Communal Politics in 21st Century India Challenges and Prospectsijtsrd
Communal politics in India has evolved through centuries, weaving a complex tapestry shaped by historical legacies, colonial influences, and contemporary socio political transformations. This research comprehensively examines the dynamics of communal politics in 21st century India, emphasizing its historical roots, socio political dynamics, economic implications, challenges, and prospects for mitigation. The historical perspective unravels the intricate interplay of religious identities and power dynamics from ancient civilizations to the impact of colonial rule, providing insights into the evolution of communalism. The socio political dynamics section delves into the contemporary manifestations, exploring the roles of identity politics, socio economic disparities, and globalization. The economic implications section highlights how communal politics intersects with economic issues, perpetuating disparities and influencing resource allocation. Challenges posed by communal politics are scrutinized, revealing multifaceted issues ranging from social fragmentation to threats against democratic values. The prospects for mitigation present a multifaceted approach, incorporating policy interventions, community engagement, and educational initiatives. The paper conducts a comparative analysis with international examples, identifying common patterns such as identity politics and economic disparities. It also examines unique challenges, emphasizing Indias diverse religious landscape, historical legacy, and secular framework. Lessons for effective strategies are drawn from international experiences, offering insights into inclusive policies, interfaith dialogue, media regulation, and global cooperation. By scrutinizing historical epochs, contemporary dynamics, economic implications, and international comparisons, this research provides a comprehensive understanding of communal politics in India. The proposed strategies for mitigation underscore the importance of a holistic approach to foster social harmony, inclusivity, and democratic values. Rose Hossain "Dynamics of Communal Politics in 21st Century India: Challenges and Prospects" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64528.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/history/64528/dynamics-of-communal-politics-in-21st-century-india-challenges-and-prospects/rose-hossain
Assess Perspective and Knowledge of Healthcare Providers Towards Elehealth in...ijtsrd
Background and Objective Telehealth has become a well known tool for the delivery of health care in Saudi Arabia, and the perspective and knowledge of healthcare providers are influential in the implementation, adoption and advancement of the method. This systematic review was conducted to examine the current literature base regarding telehealth and the related healthcare professional perspective and knowledge in the Kingdom of Saudi Arabia. Materials and Methods This systematic review was conducted by searching 7 databases including, MEDLINE, CINHAL, Web of Science, Scopus, PubMed, PsycINFO, and ProQuest Central. Studies on healthcare practitioners telehealth knowledge and perspectives published in English in Saudi Arabia from 2000 to 2023 were included. Boland directed this comprehensive review. The researchers examined each connected study using the AXIS tool, which evaluates cross sectional systematic reviews. Narrative synthesis was used to summarise and convey the data. Results Out of 1840 search results, 10 studies were included. Positive outlook and limited knowledge among providers were seen across trials. Healthcare professionals like telehealth for its ability to improve quality, access, and delivery, save time and money, and be successful. Age, gender, occupation, and work experience also affect health workers knowledge. In Saudi Arabia, healthcare professionals face inadequate expert assistance, patient privacy, internet connection concerns, lack of training courses, lack of telehealth understanding, and high costs while performing telemedicine. Conclusions Healthcare practitioners telehealth perceptions and knowledge were examined in this systematic study. Its collection of concerned experts different personal attitudes and expertise would help enhance telehealths implementation in Saudi Arabia, develop its healthcare delivery alternative, and eliminate frequent problems. Badriah Mousa I Mulayhi | Dr. Jomin George | Judy Jenkins "Assess Perspective and Knowledge of Healthcare Providers Towards Elehealth in Saudi Arabia: A Systematic Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64535.pdf Paper Url: https://www.ijtsrd.com/medicine/other/64535/assess-perspective-and-knowledge-of-healthcare-providers-towards-elehealth-in-saudi-arabia-a-systematic-review/badriah-mousa-i-mulayhi
The Impact of Digital Media on the Decentralization of Power and the Erosion ...ijtsrd
The impact of digital media on the distribution of power and the weakening of traditional gatekeepers has gained considerable attention in recent years. The adoption of digital technologies and the internet has resulted in declining influence and power for traditional gatekeepers such as publishing houses and news organizations. Simultaneously, digital media has facilitated the emergence of new voices and players in the media industry. Digital medias impact on power decentralization and gatekeeper erosion is visible in several ways. One significant aspect is the democratization of information, which enables anyone with an internet connection to publish and share content globally, leading to citizen journalism and bypassing traditional gatekeepers. Another aspect is the disruption of conventional media industry business models, as traditional organizations struggle to adjust to the decrease in advertising revenue and the rise of digital platforms. Alternative business models, such as subscription models and crowdfunding, have become more prevalent, leading to the emergence of new players. Overall, the impact of digital media on the distribution of power and the weakening of traditional gatekeepers has brought about significant changes in the media landscape and the way information is shared. Further research is required to fully comprehend the implications of these changes and their impact on society. Dr. Kusum Lata "The Impact of Digital Media on the Decentralization of Power and the Erosion of Traditional Gatekeepers" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64544.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/political-science/64544/the-impact-of-digital-media-on-the-decentralization-of-power-and-the-erosion-of-traditional-gatekeepers/dr-kusum-lata
Online Voices, Offline Impact Ambedkars Ideals and Socio Political Inclusion ...ijtsrd
This research investigates the nexus between online discussions on Dr. B.R. Ambedkars ideals and their impact on social inclusion among college students in Gurugram, Haryana. Surveying 240 students from 12 government colleges, findings indicate that 65 actively engage in online discussions, with 80 demonstrating moderate to high awareness of Ambedkars ideals. Statistically significant correlations reveal that higher online engagement correlates with increased awareness p 0.05 and perceived social inclusion. Variations across colleges and a notable effect of college type on perceived social inclusion highlight the influence of contextual factors. Furthermore, the intersectional analysis underscores nuanced differences based on gender, caste, and socio economic status. Dr. Kusum Lata "Online Voices, Offline Impact: Ambedkar's Ideals and Socio-Political Inclusion - A Study of Gurugram District" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64543.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/political-science/64543/online-voices-offline-impact-ambedkars-ideals-and-sociopolitical-inclusion--a-study-of-gurugram-district/dr-kusum-lata
Problems and Challenges of Agro Entreprenurship A Studyijtsrd
Noting calls for contextualizing Agro entrepreneurs problems and challenges of the agro entrepreneurs and for greater attention to the Role of entrepreneurs in agro entrepreneurship research, we conduct a systematic literature review of extent research in agriculture entrepreneurship to overcome the study objectives of complications of agro entrepreneurs through various factors, Development of agriculture products is a key factor for the overall economic growth of agro entrepreneurs Agro Entrepreneurs produces firsthand large scale employment, utilizes the labor and natural resources, This research outlines the problems of Weather and Soil Erosions, Market price fluctuation, stimulates labor cost problems, reduces concentration of Price volatility, Dependency on Intermediaries, induces Limited Bargaining Power, and Storage and Transportation Costs. This paper mainly devoted to highlight Problems and challenges faced for the sustainable of Agro Entrepreneurs in India. Vinay Prasad B "Problems and Challenges of Agro Entreprenurship - A Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64540.pdf Paper Url: https://www.ijtsrd.com/other-scientific-research-area/other/64540/problems-and-challenges-of-agro-entreprenurship--a-study/vinay-prasad-b
Comparative Analysis of Total Corporate Disclosure of Selected IT Companies o...ijtsrd
Disclosure is a process through which a business enterprise communicates with external parties. A corporate disclosure is communication of financial and non financial information of the activities of a business enterprise to the interested entities. Corporate disclosure is done through publishing annual reports. So corporate disclosure through annual reports plays a vital role in the life of all the companies and provides valuable information to investors. The basic objectives of corporate disclosure is to give a true and fair view of companies to the parties related either directly or indirectly like owner, government, creditors, shareholders etc. in the companies act, provisions have been made about mandatory and voluntary disclosure. The IT sector in India is rapidly growing, the trend to invest in the IT sector is rising and employment opportunities in IT sectors are also increasing. Therefore the IT sector is expected to have fair, full and adequate disclosure of all information. Unfair and incomplete disclosure may adversely affect the entire economy. A research study on disclosure practices of IT companies could play an important role in this regard. Hence, the present research study has been done to study and review comparative analysis of total corporate disclosure of selected IT companies of India and to put forward overall findings and suggestions with a view to increase disclosure score of these companies. The researcher hopes that the present research study will be helpful to all selected Companies for improving level of corporate disclosure through annual reports as well as the government, creditors, investors, all business organizations and upcoming researcher for comparative analyses of level of corporate disclosure with special reference to selected IT companies. Dr. Vaibhavi D. Thaker "Comparative Analysis of Total Corporate Disclosure of Selected IT Companies of India" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64539.pdf Paper Url: https://www.ijtsrd.com/other-scientific-research-area/other/64539/comparative-analysis-of-total-corporate-disclosure-of-selected-it-companies-of-india/dr-vaibhavi-d-thaker
The Impact of Educational Background and Professional Training on Human Right...ijtsrd
This study investigated the impact of educational background and professional training on human rights awareness among secondary school teachers in the Marathwada region of Maharashtra, India. The key findings reveal that higher levels of education, particularly a master’s degree, and fields of study related to education, humanities, or social sciences are associated with greater human rights awareness among teachers. Additionally, both pre service teacher training and in service professional development programs focused on human rights education significantly enhance teacher’s knowledge, skills, and competencies in promoting human rights principles in their classrooms. Baig Ameer Bee Mirza Abdul Aziz | Dr. Syed Azaz Ali Amjad Ali "The Impact of Educational Background and Professional Training on Human Rights Awareness among Secondary School Teachers" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64529.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/education/64529/the-impact-of-educational-background-and-professional-training-on-human-rights-awareness-among-secondary-school-teachers/baig-ameer-bee-mirza-abdul-aziz
A Study on the Effective Teaching Learning Process in English Curriculum at t...ijtsrd
“One Language sets you in a corridor for life. Two languages open every door along the way” Frank Smith English as a foreign language or as a second language has been ruling in India since the period of Lord Macaulay. But the question is how much we teach or learn English properly in our culture. Is there any scope to use English as a language rather than a subject How much we learn or teach English without any interference of mother language specially in the classroom teaching learning scenario in West Bengal By considering all these issues the researcher has attempted in this article to focus on the effective teaching learning process comparing to other traditional strategies in the field of English curriculum at the secondary level to investigate whether they fulfill the present teaching learning requirements or not by examining the validity of the present curriculum of English. The purpose of this study is to focus on the effectiveness of the systematic, scientific, sequential and logical transaction of the course between the teachers and the learners in the perspective of the 5Es programme that is engage, explore, explain, extend and evaluate. Sanchali Mondal | Santinath Sarkar "A Study on the Effective Teaching Learning Process in English Curriculum at the Secondary Level of West Bengal" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd62412.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/education/62412/a-study-on-the-effective-teaching-learning-process-in-english-curriculum-at-the-secondary-level-of-west-bengal/sanchali-mondal
The Role of Mentoring and Its Influence on the Effectiveness of the Teaching ...ijtsrd
This paper reports on a study which was conducted to investigate the role of mentoring and its influence on the effectiveness of the teaching of Physics in secondary schools in the South West Region of Cameroon. The study adopted the convergent parallel mixed methods design, focusing on respondents in secondary schools in the South West Region of Cameroon. Both quantitative and qualitative data were collected, analysed separately, and the results were compared to see if the findings confirm or disconfirm each other. The quantitative analysis found that majority of the respondents 72 of Physics teachers affirmed that they had more experienced colleagues as mentors to help build their confidence, improve their teaching, and help them improve their effectiveness and efficiency in guiding learners’ achievements. Only 28 of the respondents disagreed with these statements. With majority respondents 72 agreeing with the statements, it implies that in most secondary schools, experienced Physics teachers act as mentors to build teachers’ confidence in teaching and improving students’ learning. The interview qualitative data analysis summarized how secondary school Principals use meetings with mentors and mentees to promote mentorship in the school milieu. This has helped strengthen teachers’ classroom practices in secondary schools in the South West Region of Cameroon. With the results confirming each other, the study recommends that mentoring should focus on helping teachers employ social interactions and instructional practices feedback and clarity in teaching that have direct measurable impact on students’ learning achievements. Andrew Ngeim Sumba | Frederick Ebot Ashu | Peter Agborbechem Tambi "The Role of Mentoring and Its Influence on the Effectiveness of the Teaching of Physics in Secondary Schools in the South West Region of Cameroon" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64524.pdf Paper Url: https://www.ijtsrd.com/management/management-development/64524/the-role-of-mentoring-and-its-influence-on-the-effectiveness-of-the-teaching-of-physics-in-secondary-schools-in-the-south-west-region-of-cameroon/andrew-ngeim-sumba
Design Simulation and Hardware Construction of an Arduino Microcontroller Bas...ijtsrd
This study primarily focuses on the design of a high side buck converter using an Arduino microcontroller. The converter is specifically intended for use in DC DC applications, particularly in standalone solar PV systems where the PV output voltage exceeds the load or battery voltage. To evaluate the performance of the converter, simulation experiments are conducted using Proteus Software. These simulations provide insights into the input and output voltages, currents, powers, and efficiency under different state of charge SoC conditions of a 12V,70Ah rechargeable lead acid battery. Additionally, the hardware design of the converter is implemented, and practical data is collected through operation, monitoring, and recording. By comparing the simulation results with the practical results, the efficiency and performance of the designed converter are assessed. The findings indicate that while the buck converter is suitable for practical use in standalone PV systems, its efficiency is compromised due to a lower output current. Chan Myae Aung | Dr. Ei Mon "Design Simulation and Hardware Construction of an Arduino-Microcontroller Based DC-DC High-Side Buck Converter for Standalone PV System" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64518.pdf Paper Url: https://www.ijtsrd.com/engineering/mechanical-engineering/64518/design-simulation-and-hardware-construction-of-an-arduinomicrocontroller-based-dcdc-highside-buck-converter-for-standalone-pv-system/chan-myae-aung
Sustainable Energy by Paul A. Adekunte | Matthew N. O. Sadiku | Janet O. Sadikuijtsrd
Energy becomes sustainable if it meets the needs of the present without compromising the ability of future generations to meet their own needs. Some of the definitions of sustainable energy include the considerations of environmental aspects such as greenhouse gas emissions, social, and economic aspects such as energy poverty. Generally far more sustainable than fossil fuel are renewable energy sources such as wind, hydroelectric power, solar, and geothermal energy sources. Worthy of note is that some renewable energy projects, like the clearing of forests to produce biofuels, can cause severe environmental damage. The sustainability of nuclear power which is a low carbon source is highly debated because of concerns about radioactive waste, nuclear proliferation, and accidents. The switching from coal to natural gas has environmental benefits, including a lower climate impact, but could lead to delay in switching to more sustainable options. “Carbon capture and storage” can be built into power plants to remove the carbon dioxide CO2 emissions, but this technology is expensive and has rarely been implemented. Leading non renewable energy sources around the world is fossil fuels, coal, petroleum, and natural gas. Nuclear energy is usually considered another non renewable energy source, although nuclear energy itself is a renewable energy source, but the material used in nuclear power plants is not. The paper addresses the issue of sustainable energy, its attendant benefits to the future generation, and humanity in general. Paul A. Adekunte | Matthew N. O. Sadiku | Janet O. Sadiku "Sustainable Energy" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64534.pdf Paper Url: https://www.ijtsrd.com/engineering/electrical-engineering/64534/sustainable-energy/paul-a-adekunte
Concepts for Sudan Survey Act Implementations Executive Regulations and Stand...ijtsrd
This paper aims to outline the executive regulations, survey standards, and specifications required for the implementation of the Sudan Survey Act, and for regulating and organizing all surveying work activities in Sudan. The act has been discussed for more than 5 years. The Land Survey Act was initiated by the Sudan Survey Authority and all official legislations were headed by the Sudan Ministry of Justice till it was issued in 2022. The paper presents conceptual guidelines to be used for the Survey Act implementation and to regulate the survey work practice, standardizing the field surveys, processing, quality control, procedures, and the processes related to survey work carried out by the stakeholders and relevant authorities in Sudan. The conceptual guidelines are meant to improve the quality and harmonization of geospatial data and to aid decision making processes as well as geospatial information systems. The established comprehensive executive regulations will govern and regulate the implementation of the Sudan Survey Geomatics Act in all surveying and mapping practices undertaken by the Sudan Survey Authority SSA and state local survey departments for public or private sector organizations. The targeted standards and specifications include the reference frame, projection, coordinate systems, and the guidelines and specifications that must be followed in the field of survey work, processes, and mapping products. In the last few decades, there has been a growing awareness of the importance of geomatics activities and measurements on the Earths surface in space and time, together with observing and mapping the changes. In such cases, data must be captured promptly, standardized, and obtained with more accuracy and specified in much detail. The paper will also highlight the current situation in Sudan, the degree to which survey standards are used, the problems encountered, and the errors that arise from not using the standards and survey specifications. Kamal A. A. Sami "Concepts for Sudan Survey Act Implementations - Executive Regulations and Standards" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63484.pdf Paper Url: https://www.ijtsrd.com/engineering/civil-engineering/63484/concepts-for-sudan-survey-act-implementations--executive-regulations-and-standards/kamal-a-a-sami
Towards the Implementation of the Sudan Interpolated Geoid Model Khartoum Sta...ijtsrd
The discussions between ellipsoid and geoid have invoked many researchers during the recent decades, especially during the GNSS technology era, which had witnessed a great deal of development but still geoid undulation requires more investigations. To figure out a solution for Sudans local geoid, this research has tried to intake the possibility of determining the geoid model by following two approaches, gravimetric and geometrical geoid model determination, by making use of GNSS leveling benchmarks at Khartoum state. The Benchmarks are well distributed in the study area, in which, the horizontal coordinates and the height above the ellipsoid have been observed by GNSS while orthometric heights were carried out using precise leveling. The Global Geopotential Model GGM represented in EGM2008 has been exploited to figure out the geoid undulation at the benchmarks in the study area. This is followed by a fitting process, that has been done to suit the geoid undulation data which has been computed using GNSS leveling data and geoid undulation inspired by the EGM2008. Two geoid surfaces were created after the fitting process to ensure that they are identical and both of them could be counted for getting the same geoid undulation with an acceptable accuracy. In this respect, statistical operation played an important role in ensuring the consistency and integrity of the model by applying cross validation techniques splitting the data into training and testing datasets for building the geoid model and testing its eligibility. The geometrical solution for geoid undulation computation has been utilized by applying straightforward equations that facilitate the calculation of the geoid undulation directly through applying statistical techniques for the GNSS leveling data of the study area to get the common equation parameters values that could be utilized to calculate geoid undulation of any position in the study area within the claimed accuracy. Both systems were checked and proved eligible to be used within the study area with acceptable accuracy which may contribute to solving the geoid undulation problem in the Khartoum area, and be further generalized to determine the geoid model over the entire country, and this could be considered in the future, for regional and continental geoid model. Ahmed M. A. Mohammed. | Kamal A. A. Sami "Towards the Implementation of the Sudan Interpolated Geoid Model (Khartoum State Case Study)" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63483.pdf Paper Url: https://www.ijtsrd.com/engineering/civil-engineering/63483/towards-the-implementation-of-the-sudan-interpolated-geoid-model-khartoum-state-case-study/ahmed-m-a-mohammed
Activating Geospatial Information for Sudans Sustainable Investment Mapijtsrd
Sudan is witnessing an acceleration in the processes of development and transformation in the performance of government institutions to raise the productivity and investment efficiency of the government sector. The development plans and investment opportunities have focused on achieving national goals in various sectors. This paper aims to illuminate the path to the future and provide geospatial data and information to develop the investment climate and environment for all sized businesses, and to bridge the development gap between the Sudan states. The Sudan Survey Authority SSA is the main advisor to the Sudan Government in conducting surveying, mappings, designing, and developing systems related to geospatial data and information. In recent years, SSA made a strategic partnership with the Ministry of Investment to activate Geospatial Information for Sudans Sustainable Investment and in particular, for the preparation and implementation of the Sudan investment map, based on the directives and objectives of the Ministry of Investment MI in Sudan. This paper comes within the framework of activating the efforts of the Ministry of Investment to develop technical investment services by applying techniques adopted by the Ministry and its strategic partners for advancing investment processes in the country. Kamal A. A. Sami "Activating Geospatial Information for Sudan's Sustainable Investment Map" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63482.pdf Paper Url: https://www.ijtsrd.com/engineering/information-technology/63482/activating-geospatial-information-for-sudans-sustainable-investment-map/kamal-a-a-sami
Educational Unity Embracing Diversity for a Stronger Societyijtsrd
In a rapidly changing global landscape, the importance of education as a unifying force cannot be overstated. This paper explores the crucial role of educational unity in fostering a stronger and more inclusive society through the embrace of diversity. By examining the benefits of diverse learning environments, the paper aims to highlight the positive impact on societal strength. The discussion encompasses various dimensions, from curriculum design to classroom dynamics, and emphasizes the need for educational institutions to become catalysts for unity in diversity. It highlights the need for a paradigm shift in educational policies, curricula, and pedagogical approaches to ensure that they are reflective of the diverse fabric of society. This paper also addresses the challenges associated with implementing inclusive educational practices and offers practical strategies for overcoming barriers. It advocates for collaborative efforts between educational institutions, policymakers, and communities to create a supportive ecosystem that promotes diversity and unity. Mr. Amit Adhikari | Madhumita Teli | Gopal Adhikari "Educational Unity: Embracing Diversity for a Stronger Society" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64525.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/education/64525/educational-unity-embracing-diversity-for-a-stronger-society/mr-amit-adhikari
Integration of Indian Indigenous Knowledge System in Management Prospects and...ijtsrd
The diversity of indigenous knowledge systems in India is vast and can vary significantly between different communities and regions. Preserving and respecting these knowledge systems is crucial for maintaining cultural heritage, promoting sustainable practices, and fostering cross cultural understanding. In this paper, an overview of the prospects and challenges associated with incorporating Indian indigenous knowledge into management is explored. It is found that IIKS helps in management in many areas like sustainable development, tourism, food security, natural resource management, cultural preservation and innovation, etc. However, IIKS integration with management faces some challenges in the form of a lack of documentation, cultural sensitivity, language barriers legal framework, etc. Savita Lathwal "Integration of Indian Indigenous Knowledge System in Management: Prospects and Challenges" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63500.pdf Paper Url: https://www.ijtsrd.com/management/accounting-and-finance/63500/integration-of-indian-indigenous-knowledge-system-in-management-prospects-and-challenges/savita-lathwal
DeepMask Transforming Face Mask Identification for Better Pandemic Control in...ijtsrd
The COVID 19 pandemic has highlighted the crucial need of preventive measures, with widespread use of face masks being a key method for slowing the viruss spread. This research investigates face mask identification using deep learning as a technological solution to be reducing the risk of coronavirus transmission. The proposed method uses state of the art convolutional neural networks CNNs and transfer learning to automatically recognize persons who are not wearing masks in a variety of circumstances. We discuss how this strategy improves public health and safety by providing an efficient manner of enforcing mask wearing standards. The report also discusses the obstacles, ethical concerns, and prospective applications of face mask detection systems in the ongoing fight against the pandemic. Dilip Kumar Sharma | Aaditya Yadav "DeepMask: Transforming Face Mask Identification for Better Pandemic Control in the COVID-19 Era" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64522.pdf Paper Url: https://www.ijtsrd.com/engineering/electronics-and-communication-engineering/64522/deepmask-transforming-face-mask-identification-for-better-pandemic-control-in-the-covid19-era/dilip-kumar-sharma
Streamlining Data Collection eCRF Design and Machine Learningijtsrd
Efficient and accurate data collection is paramount in clinical trials, and the design of Electronic Case Report Forms eCRFs plays a pivotal role in streamlining this process. This paper explores the integration of machine learning techniques in the design and implementation of eCRFs to enhance data collection efficiency. We delve into the synergies between eCRF design principles and machine learning algorithms, aiming to optimize data quality, reduce errors, and expedite the overall data collection process. The application of machine learning in eCRF design brings forth innovative approaches to data validation, anomaly detection, and real time adaptability. This paper discusses the benefits, challenges, and future prospects of leveraging machine learning in eCRF design for streamlined and advanced data collection in clinical trials. Dhanalakshmi D | Vijaya Lakshmi Kannareddy "Streamlining Data Collection: eCRF Design and Machine Learning" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63515.pdf Paper Url: https://www.ijtsrd.com/biological-science/biotechnology/63515/streamlining-data-collection-ecrf-design-and-machine-learning/dhanalakshmi-d
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
"Learn about all the ways Walmart supports nonprofit organizations.
You will hear from Liz Willett, the Head of Nonprofits, and hear about what Walmart is doing to help nonprofits, including Walmart Business and Spark Good. Walmart Business+ is a new offer for nonprofits that offers discounts and also streamlines nonprofits order and expense tracking, saving time and money.
The webinar may also give some examples on how nonprofits can best leverage Walmart Business+.
The event will cover the following::
Walmart Business + (https://business.walmart.com/plus) is a new shopping experience for nonprofits, schools, and local business customers that connects an exclusive online shopping experience to stores. Benefits include free delivery and shipping, a 'Spend Analytics” feature, special discounts, deals and tax-exempt shopping.
Special TechSoup offer for a free 180 days membership, and up to $150 in discounts on eligible orders.
Spark Good (walmart.com/sparkgood) is a charitable platform that enables nonprofits to receive donations directly from customers and associates.
Answers about how you can do more with Walmart!"
A review of the growth of the Israel Genealogy Research Association Database Collection for the last 12 months. Our collection is now passed the 3 million mark and still growing. See which archives have contributed the most. See the different types of records we have, and which years have had records added. You can also see what we have for the future.
Main Java[All of the Base Concepts}.docxadhitya5119
This is part 1 of my Java Learning Journey. This Contains Custom methods, classes, constructors, packages, multithreading , try- catch block, finally block and more.
How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
In this slide, we'll explore how to set up warehouses and locations in Odoo 17 Inventory. This will help us manage our stock effectively, track inventory levels, and streamline warehouse operations.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
help of Advanced technologies like Remote Sensing and Geographic Information Systems is
crucial for coordinated efforts across different administrative levels. Advanced technologies like
Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
structure of plant communities across different temporal and spatial scales. These changes can
occur natural.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
Leveraging Generative AI to Drive Nonprofit InnovationTechSoup
In this webinar, participants learned how to utilize Generative AI to streamline operations and elevate member engagement. Amazon Web Service experts provided a customer specific use cases and dived into low/no-code tools that are quick and easy to deploy through Amazon Web Service (AWS.)
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
How to Manage Your Lost Opportunities in Odoo 17 CRMCeline George
Odoo 17 CRM allows us to track why we lose sales opportunities with "Lost Reasons." This helps analyze our sales process and identify areas for improvement. Here's how to configure lost reasons in Odoo 17 CRM
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
Chapter wise All Notes of First year Basic Civil Engineering.pptxDenish Jangid
Chapter wise All Notes of First year Basic Civil Engineering
Syllabus
Chapter-1
Introduction to objective, scope and outcome the subject
Chapter 2
Introduction: Scope and Specialization of Civil Engineering, Role of civil Engineer in Society, Impact of infrastructural development on economy of country.
Chapter 3
Surveying: Object Principles & Types of Surveying; Site Plans, Plans & Maps; Scales & Unit of different Measurements.
Linear Measurements: Instruments used. Linear Measurement by Tape, Ranging out Survey Lines and overcoming Obstructions; Measurements on sloping ground; Tape corrections, conventional symbols. Angular Measurements: Instruments used; Introduction to Compass Surveying, Bearings and Longitude & Latitude of a Line, Introduction to total station.
Levelling: Instrument used Object of levelling, Methods of levelling in brief, and Contour maps.
Chapter 4
Buildings: Selection of site for Buildings, Layout of Building Plan, Types of buildings, Plinth area, carpet area, floor space index, Introduction to building byelaws, concept of sun light & ventilation. Components of Buildings & their functions, Basic concept of R.C.C., Introduction to types of foundation
Chapter 5
Transportation: Introduction to Transportation Engineering; Traffic and Road Safety: Types and Characteristics of Various Modes of Transportation; Various Road Traffic Signs, Causes of Accidents and Road Safety Measures.
Chapter 6
Environmental Engineering: Environmental Pollution, Environmental Acts and Regulations, Functional Concepts of Ecology, Basics of Species, Biodiversity, Ecosystem, Hydrological Cycle; Chemical Cycles: Carbon, Nitrogen & Phosphorus; Energy Flow in Ecosystems.
Water Pollution: Water Quality standards, Introduction to Treatment & Disposal of Waste Water. Reuse and Saving of Water, Rain Water Harvesting. Solid Waste Management: Classification of Solid Waste, Collection, Transportation and Disposal of Solid. Recycling of Solid Waste: Energy Recovery, Sanitary Landfill, On-Site Sanitation. Air & Noise Pollution: Primary and Secondary air pollutants, Harmful effects of Air Pollution, Control of Air Pollution. . Noise Pollution Harmful Effects of noise pollution, control of noise pollution, Global warming & Climate Change, Ozone depletion, Greenhouse effect
Text Books:
1. Palancharmy, Basic Civil Engineering, McGraw Hill publishers.
2. Satheesh Gopi, Basic Civil Engineering, Pearson Publishers.
3. Ketki Rangwala Dalal, Essentials of Civil Engineering, Charotar Publishing House.
4. BCP, Surveying volume 1
2. International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
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Figure: -1 Showing atomic hybridization of the phthalimide ring
2. PHARMACOLOGY OF THALIDOMIDE AND ITS ANALOGS
Thalidomide was initially utilised as non-sedative and in this way for the management of morning ailment within the 1950s.
but was pulled back within the early 1960s since of visit teratogenicity (phocomelia)[9]. Themedicatecouldbesubordinateof
glutamic corrosive the that comprises of a chiral centre and two amide ring, and it is categorised as an immunomodulatory
specialist that moveover has antiangiogenic properties[10,11]. Thalidomide continue as a blend of both R and S isomers at
physiologic pH. While the S compound appears responsible for teratogenicity, the R compoundresults in sedation. Atanatomy
pH these isomers interconvert, making endevors at separation of the R isomer in an exertion to dispose of teratogenicity
unsuccessful[11].
The mechanism of thalidomide’s activity has been broadly examined about morethan50alongtime amid inthatmorethan 30
speculations had been proposed [12, 13]. Stephens and Fill more classified six theories of thalidomide,centeringonvariations
or dysfunctions in: 1) DNA replication and translation, 2) amalgamation and/or work of development variables, 3)
amalgamation and/or work of integrins, 4) angiogenesis, 5) chondrogenesis, and6) cellpassingordamage[13].Amongthesix
speculations displayed on thalidomide, most bolster has been given to its hostile to angiogenesis exercises.
Thalidomide is ineffectively dissolvable in water, and hence no intravenousarrangementisaccessible.In vitrothalidomidehas
illustrated apoptoic IMiDs and anti-angiogenic impacts. It has been hypothesized that the antiangiogenic impacts of
thalidomide are due to metabolites that hinder forms of angiogenesis intervened by bFGF and/orVEGF[4,14,15].In expansion
thalidomide represses TNF- alpha gene actuation by diminishing NF- alpha B binding[16]. Despite a previouslydemonstrated
interaction between levels of marrow angiogenesis factors and disease activity in myeloma, and an increment within the
angiogenic cytokines bFGF and VEGF in poor prognosis disease, no correlation between expanded microvascular density or
subsequent post treatment decrease in neovascularization was noted in patients with disease responding to thalidomide[5-
7,15,17,18]. It appears unlikely that expanded of angiogenesis alone accounts for the success of thalidomide in controlling
multiple myeloma.
It has been conformed in vitro such thalidomide and its acquaintance can directly inhibit growth of plasma cells, perhaps
through caspase-8 dynamization and subsequent apoptosis[11,19]. Additionally,TNF-alpha not only stimulates pluripotent
adult stem cell secretion of IL-6, but also induces look of adhesion molecules on myeloma and pluripotent grown-up stem
cells[20,21].Since thalidomide may be a strong blocker of TNF-α, the expression of these molecules on pluripotent grown-up
stem cells may well be diminished by treatment, coming about in hindrance of myelomacell attachment anddiminised of TNF-
α stimulated IL-6 emission[22]. Thalidomide may too advance increment of fortified anti-CD3 T cells, which may increment
inhibitory cytokines for myeloma cell development (intergalatic-alpha or IL-12)[23]. While the structure of growth inhibition
by thalidomide remains unclear, there is an established apoptotic effectinvitrothatis enhancedbydexamethasone. Thiseffect
may be partly conquered by IL-6, confirming the potential role of IL-6 suppression as a contributing antimyeloma effect of
thalidomide[24].
2.1. Lenalidomide (CC-5013)
Lenalidomide (3-(7-amino-3-oxo-1H-isoindol-2-yl) piperidine-2,6-dione; Revlimid®)isanimmunomodulatoryanaloguethat
has demonstrated higher potency than thalidomidein the HUVECmultiplicaion andtubecreationassays.In vitro,thedrugisup
to 50K times more strong than thalidomide inhibiting the management of TNF-a by fortified peripheral blood mononuclear
cells[25]. Other in vitro studies marked that factors such asanti-angiogenicworth, modulation of hostimmunity, andapoptosis
are likely to play a part in the clinical activity of lenalidomide, but the exact component of activity of the drug remains
unclear[26] (Figure: -2). Lenalidomide also has a direct cytotoxic effect on myeloma cell lines. G0/G1 development capture
shows up to be related in portion to refreshing of caspase 8 and down direction of hostile to apoptotic proteins such as the
cIAP2 and FLIP[27,28]. Hindrance of lipopolysaccharide-mediated acceptance of COX-2 as well as PGE-2union may moreover
play a part within the drug’s movement[29]. NF-kB is an essential regulator of cytokine management, myeloma cell adhesion
and anti-apoptosis[30]. Lenalidomide, and other immunomodulatory drugs, inhibit and down-regulate NF-kB, which may
interfere with cytokine-stimulated increase of MPCand subsequentadhesiontoBMSCs[27].A keymanagerofleukemiagrowth
and continuity is IL-6[31]. Compared with BMSCs from patients without myeloma, BMSCs of victim with multiple myeloma
release increased levels of IL-6, as well as bFGF and VEGF, which are integral to angiogenesis[31]. Lenalidomide decreases
release of these factors in vitro, resulting in growth inhibition of myeloma cell channel and decreased micro vessel density in
animal models.
3. International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
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Figure: -2 Schematic representation of IMiDs-mediated CRBN balance. Within the non appearance of any IMiDs, CRBN
debases unique substrates and have a certain part of physiological responses(e.g. glutamine system). Inner ligands of
CRBN are conceivably included in this handle. On the other hand, within the nearness of an IMids, the substract specificity
of CRBN is changed and neo-substrates are recognised and experience consequent protein degradation.
IMiDs(Lenalidomide) actuates the breakdown of Ikaros and Aiolos. Instep, unique substractes are collected. Lenalidomide
particularly actuates the debasement Ck1α by authoritative to CRBN.
2.2. Pomalidomide (CC-4047)
Pomalidomide is commercially known asActimid®withIUPAC name;4-amino-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
having clear immunomodulatory properties, represses numerous myeloma with obscure impacts on the human osteoclast
heredity [32]. Early osteoclast forebears are of hematopoietic root and separate into develop bone resorbing multinucleated
osteoclasts. Impacts of CC-4047 and thalidomide on human osteoclastogenesis were examined utilizing in vitro receptor
actuate of NFα-B ligand/MCS figure. The bone marrow societies were treated with CC-4047 for 3 weeks, displaying the
diminished osteoclast arrangement went with by a total hindrance of bone resorption. A move of heredity commitment to
granulocyte colony forming units was a calculate which intervened restraintof osteoclastogenesisbyCC-4047. Treatmentwith
thalidomide displayed a essentially less strong hindrance of osteoclast arrangement and bone resorption. The above-cited
comes about appear that CC-4047 pieces osteoclast separation amid earlystages of osteoclastogenesis.Subsequently,CC-4047
may be a profitable sedate for focusing on both tumors and osteoclastic action in patients with different myeloma and other
illnesses related with osteolytic injuries.
3. PHARMACOLOGICAL ACTIVITY OF THALIDOMIDE AND THEIR ANALOGUE
3.1. Anti-Cancer
The most driving force for utilizing thalidomide to treat patients with cancer came with the revelation of its anti-angiogenic
potential. This too happened to coincide with the emerging conceptthattreatmentcanbeaimed attheframeworkthatbolsters
the development of the tumor, instead of focusingontumorcells straightforwardly.Similitudesbetweenthe angiogenichandle
within the advancement of tumor development and in inveterate irritation moreover loaned advancebolsterfora conceivable
part for thalidomide as an anti-inflammatory operator within the management of cancers. In specific the hostiletotnf impacts
of thalidomide were thought to be pertinent as tnf appears to have a part in angiogenesis by upregulating the expression
ofendothelial integrin, which is deciding for this process[33]. At long final, it is well builtupthat theincrementof TNF-α within
the serum of victim with cancer is frequently related with progressed illness, so utilizing thalidomide to decrease these levels
might demonstrate to be useful within the medication of patients.
3.2. Anti-Myeloma
Thalidomide was serendipitously found to haveagainst myelomaactionwhen itwasconcludeitsagainstangiogenicmovement
might passive the disease by repressing the formation of current blood vessels in this highly vascularized cancer. There's
presently adequate prove to appear that the against cancer action of thalidomide and its analogs in numerous myeloma is
through diverse components and locales in the marrowbone[34] (Figure: -3). It shows the marrowbone microenvironmentin
MM, which contains aberrations in various cellular processes, immunology, and cell interactions. Thalidomide and the IMiDs’
immunomodulatory activities consist of inhibiting the interpretation of IL-6 and TNF-α by BMSCs that in turn inhibit the
growth of multiple myeloma cells. The compoundsalso improve t cell activate and multiplication with the enacted cells at that
point discharging IL-2 and IFN-γ. These cytokines activate NK cells causing lysis of the multiple myeloma cells[34,35]. The
combination of immunomodulatory and non-immunomodulatory anticancer exercises within the bone marrow is thought to
deliver the significant anti-tumor reactions watched in a few numerous myeloma patients. This combination activity has
significant implications for other blood and solid tumor cancers and is currently be inginvestigated in numerous clinicaltests.
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Thalidomides are against incendiary and resistant modulatory drugs. They have been used in the management of multiple
myeloma, pancreatic, prostate and lung cancers and also in autoimmune conditions such as unite versus have illness,
Waldenstrom’s macroglobulinaemia, and EAE, an mammalia model of MS.
Figure: -3. Destinations of action of thalidomide and IMiDs within the bone marrow of different myeloma patients
3.3. Anti-Angiogenesis
The method of reasoning that recommends the potential of thalidomides in cancer treatment is that it can hinder cell
multiplication, advance apoptosis and thus may control tumordevelopment.Byideals of itscapacitytorestrain angiogenesis,it
seem work as an anti-metastasis operator (Table: 1, Figure: -4). Numerous chemokines created by tumors can advancetumor
development, actuate angiogenesis conjointly help with the avoidance of resistant observation. In this manner, it is of
significant intrigued that thalidomides stiflethese chemokinesand combattheimmunologicalbrokennessrelated withtumors.
The capacity to reestablish endogenous safe work has without a doubt been credited to thethalidomides. Afewwhereasprior,
thalidomide was appeared to hinder VEGF and bFGF initiated angiogenesis in corneal angiogenesis [36,37]. Lenalidomide
repressed VEGF induced P13K/Akt flagging and stifled the proangiogenic HIF-1. In vitro, it repressed tubule arrangement by
endothelial cells. In vivo, there was much diminishmentinlungcolonisation of B16-10 murinemelanoma[38].Thalidomideand
the analogs lenalidomide and pomalidomide repressed the in vitro transitory conduct of colorectal carcinoma cells. These
drugs moreover smothered the arrangement of metastaticknobsinvivomurinehas [39].Angiogenesisis an necessarilyhandle
within the pathogenesis and movement of incendiary and autoimmune diseases. MS could be a demyelinating infection ofthe
central apprehensive framework. Angiogenesis may be a steady highlight of demyelinating plaquesofMS.Numerousinducers
of angiogenesis are communicated in these plaques and have been closely partnered in MS as well as within the creature
demonstrate of MS viz. EAE. This has driven to the proposal that restraint of angiogenesis by smothering these effectors or
restraining the components of angiogenic signaling pathways might give a reasonable way to target treatment to oversee MS
[40].
Table: 1 Salient Biological Features Impacted by Thalidomides
Biological Feature Effector Targets
Immune suppression; evasion of immune surveillance Chemokines, ILs, TGF-β, VEGF
Immunomodulation CD41/CD81 T cells
Immune resistance of tumours Immune checkpoint proteins
Tumour growth
Apoptosis Bcl-2
Cell proliferation Cell cycle regulators
Invasion and metastasis Cell adhesion signalling
Angiogenesis VEGF, bFGF
bFGF, basic fibroblast growth factor; IL, interleukin; TGF-β, transforming growth factor-β;
VEGF, vascular endothelial growth factor.
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Figure: -4 Schematic representation of the IGF-I, FGF-2=Angiogenesis pathway within a model cell.
3.4. Thalidomide inhibit cell proliferation and promote apoptosis
The thalidomides suppress cell expansion by interferometer with cell cycle administrative components. Lenalidomide
supressed CLL cells in vitro by focusing on cereblon[41]. Lenalidomide interceded inactivation of cereblon diminishes the
acceptance of p21[42]. Cereblon could be a part of the ubiquitin_e3 ligase cul4_rbx1_ddb1 well-k nownand known to be
particularly focused on by thalidomides [43]. Typically said to lead to the enrollment of zinc finger translation components to
the ubiquitin_E3 complex, their ubiquitination and debasement smothering cell expansion and cell reasonability. NF-κB is
another pathway ensnared in thalidomide activity. Keifer illustrated this over a decade back[44]. Thalidomide repressed IKK
and the NF-κB target qualities IL-8, TRAF1 and c-IAP2. Without a doubt, both thalidomide and lenalidomide square NF-κB
enactment. The hindrance of NF-κB beside checked increment in Bax/Bcl-2 proportion which the impacts on the apoptosis
family qualities were more checked than NF-κB restraint[45]. The mTOR flagging pathway is related with a few cellular forms
such as cell expansion, development, apoptosis, angiogenesis, cell motility and intrusion (Figure: -5 and Table : -1). It seem
encourage crosstalk between VEGF, PI3K/Akt and NF-κB in angiogenesis as implied to prior. The integration of these flagging
systems by mTOR has driven to the recommendation that mTOR inhibitors may well be advantageously united with the
thalidomide. This has been indicated by the cooperative energy seen within the impacts of everolimus and lenalidomide in a
stage I clinical trial including hard-headed numerous myeloma patients. The combined treatment connected with the
downregulation of mTOR signaling [46]. Temsirolimus has too been tried in combination with lenalidomide in another stageI
trial in including patients with progressed shapes of cancerwhereafewreactionwaswatched withnumeroustumor sorts[47].
Be that as it may, the last mentioned consider included as it were a little number of patients with each tumor sort. Ganesan
displayed the middle generally survival and movement complimentary durability(PFS)of allevaluablepatients.[47] Theysaw
no reaction in HNSCC, NSCLC and endometrial carcinoma. This think about is as well preparatory in nature andthere's agotto
see at bigger number of patientsvwith particular tumor sorts where clinical reaction had been famous. It would be
commendable of note here that plumbagin, a quinoid extricated from the origin of the Ceylon leadwort, has checked anti-
tumour properties, which have been ascribed to its capacity to stifle the NF-κB/AKT/ mTOR/STAT3 flagging hub. Plumbagin
allegedly complemented the acceptance of apoptosis by thalidomide, clearly by STAT3 concealment and enactmentof theJNK
apoptosis course [48]. So there's much defense for utilizing STAT3 inhibitors to diminish the successful measurement of
thalidomide organization. Appropriation of a combination approach might assist decrease the potential disagreeable side
impacts of thalidomide.
Figure: -5 Pathways of thalidomide signalling to control cell proliferation and induce apoptosis and inhibition of
angiogenesis in myelomas and other tumours types.
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3.5. Immunomodulation by Thalidomide
Cancer improvement and movement happen as a result of the misfortune of reconnaissance inferable to a dynamic
concealment of the safe framework. Tumors deliver safe suppressants such as ILs, TGF-β and VEGF. Safe resilience of tumors
more over comes about from the impedance of the separation and development of antigen-declare dendritic cells and the
resulting impedances with the useful interaction with T- and B- lymphoblast and NK cells [49-51]. Techniques planned to
invigorate the safe framework have been advancing over the past a few a long time.The improvementandarrangementof safe
modulators aimed at safe checkpoints to re-activate endogenous resistant reactions have gotten much consideration. Safe
resistance by tumors Immunomodulation by thalidomides appears to stream from tumors being able to embrace and disturb
the resistant inhibitory checkpoint pathways, particularly pointed againstTcellsthatareparticularfortumor antigens(Figure:
-6). Resistant checkpoint proteins adversely or emphatically controlT-cellreaction. Thecooperationbetweenthereceptorand
ligand edge to the hindrance of T-cell enactment and cytokine generation. Balance of T-cell actuation pathways has taken the
shape of utilizing antibodies against T-cell receptors or ligands. CTLA4 could be a checkpoint protein that smothers resistant
reaction. PD-1 and its ligands are fundamental for the avoidance of resistant observation. These checkpoint proteins
downregulate T-cell resistant reactions. Consequently, anti-CTLA4 and PD1 and its substance PDL1 are being assessed. As of
late, Gorgun have appeared that lenalidomidecomplementstheresistantimpactsofPD1/PDL1barricadeindifferentmyeloma.
The heightened effects are interceded by cereblon, which could be a component of one of the hypothesized flagging
frameworks locked in by resistant checkpoint inhibitors talked aboutina afterward area[52].Thethalidomidescan conflictthe
immune resistance of cancers, both hematological malignancies and strong tumors. The reaction of CD41 and CD81cellsfrom
different myeloma patients to thalidomide analogs. Both drugs expanded expansion of and cytokine generation by cluster of
differentiation 41 and cluster of differentiation 81 T cells, improved thelyticcapacityof cytotoxicTlymphocytesanddecreased
the suppressive impacts of Treg (CD41 administrative T cells)onCD81 reactions[53]. Lenalidomide advanced the expansionof
CD81 cells, but at that point it moreover improved a populace of myeloid cells, which were CD11/CD151. These cells were
competent of stifling the multiplication of both CD81 and CD41. This had driven to the hypothesize that lenalidomidecouldbe
advancing both actuating and inhibitory components as a implies of controlling the safe framework [54]. One ought to review
that target particular cd8 cells can be created to restrain angiogenesis. DNA immunizations focusing on VEGFR2 of the tumor
vasculature have been appeared to repress tumor angiogenesis and both modern and built upmetastaticstores[55].Jellbauer
may initiate CD81 cells by immunising creatures with a recombinant Salmonella strain carrying a CD8 epitope from
VEGFR2[56]. Within the B16-F10 melanoma tumor show, the vaccinated creatures appeared acceptance of VEGFR2-specific
CD81 populace, which would have focused on the VEGFR2 communicating tumor vascular endothelium and diminished
metastatic spread into the lungs and decreased tumor development. One can cite numerous occurrences of particular
expression of development variables or their receptors in tumors, which can be targeted in this mold.
Figure: -6 Comparison between the classic demonstrate and the current demonstrate of the target of IMiDs. Within the
ancient demonstrate, IMiDs have different coordinate targets resulting in pleiotropic impacts. Within the current
demonstrate, IMiDs essentially ties CRBN, a essential targets, and initiate pleiotropic impacts by breakdown of different
neo-substrates by CRBN E3 ubiquitin ligase.
3.6. Anti-Leprosy
ENL is an intense vasculitis seen in victim with lepromatous disease after antilepromatous management. It is distinguish by a
excruciating, ulcerative, nodular rash and systemic indication such as hyperpyrexia, arthralgic, polyneuritis, and glomerular
nephritis. Immunologically, it involves components of both a cell mediated immune feedback with raisedIFN-γ, TNF-α, andIL-
12, and an immune complex mediated disease. Consequent to Sheskin’s unique revelation a few controlled and uncontrolled
considers, counting a World Wellbeing Association facilitated random shot composed trial, havebeen distributed affirmingits
viability[57]. More as of late a writing audit by Sheskin in 1980 dissected information from 4552 cases and found the reaction
rate to treatment to be 99%[58]. Its effectiveness is thought to be due to its anticytokine impacts with responders appearinga
checked diminishment in serum TNF-α levels in conjunction with down-regulation of intracellular attachmentmolecule-1and
MHC course II antigen expression on epidermal keratinocytes[59]. Treatmentcan slowlybedecreased after clinical reactionin
spite of the fact that in numerous cases support moo measurements treatment is required for a number of years.
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3.7. Anti-HIV infection
Thalidomide has been observed to improve the wasting associated with AIDS and induce a better appetite [60-63]. The term
‘‘wasting syndrome’’ describes a clinical condition inwhich there is a greater than 10% weight loss without clear identifiable
causes but believed to be related to a multifactorial process[64]. It is characterized by chronic diarrhea, weakness, and fever.
These symptoms in an HIV sero positive individual set up the conclusion of AIDS and are an AIDS-related clinical disease [65].
Elevated levels of TNF-a are ensnared as a causal figure reticence of the synthesis of TNF-a in vitro and in vivo is the rationale
for thalidomide’s use in HIV positive individuals with wasting syndrome[66,67]. In a stray clinical studies of 28 adults with
leading HIV disease, thalidomide (100 mg four times a day) was shown to impede the wasting syndrome and also improvethe
Karnofsky Scale of Performance Status[68]. There was no effect on theCD41Torviral load.Thereisalsoevidencethatinvictim
with both HIV-1 and tuberculosis infections, there is a reduction of both the plasma TNF—a and HIV levels and a weight
gain[69,70]. These observations propose that thalidomide may enhance weight gain by devaluation TNF—a and HIV-1 in
patients who also have tuberculosis. Moreira have appeared that thalidomide and some analogs diminish HIV sort1 duplicate
in anthropoid macrophages[71]. AIDS-related Kaposi sarcoma has been reported to relapse when treated with thalidomide
[72,73]. Thalidomide has too demonstrated exceptionally compelling within the treatment of weakening oropharynx,
esophageal, rectal, and genital ulcers related with HIV disease [74-77]. Typically a valuable aide treatment, particularly when
steroids are contraindicated or demonstrated incapable [78,79].
3.8. Acute Myeloid Leukemia
A as of late detailed trial of thalidomide in 16 patients with hard-headed or backslid AML appearedonetotal reactionenduring
36 months and a temporal diminishment in marrow impacts in two extra patients. There was no relationship between
lessening in levels of angiogenesis and reaction. Hence, organization of thalidomidein AMLisn'tprescribedexteriorthesetting
of clinical trials [80].
4. ADVERSE DRUG REACTIONS OF THALIDOMIDE
Thalidomide is well known for causing adverse reactions (ADRs) to the developing embryo. Sincethedischargeof thesedateit
has been known that Thalidomide will cause fringe neuropathyingrown-upson longtermutilize[81]. Thisisespeciallyseenin
victim using Thalidomide for leprosy or multiple myeloma. It can also causes constipation, dizziness, skin rashes in some
victim, and drowsiness. [82]. Caro reported about the ADRs caused by Thalidomide inmultiplemyelomapatients. Inthisstudy
the frequency of ADR was 83.3%. According to this study most common ADR was neurotoxicity (64.71%), followed by blood
disorders (17.64%), edema (11.76%) and digestive disorders (5.88%). About half of the victims had extreme ADR and in
almost 17.65% of cases were not settled [83]. It was detailed that ADRs of Thalidomide creates inside the primary month of
treatment generally at a quantity of 400 mg/day. Fringe neuropathy has been related with long term utilize of the medicate
(>10 months). The seriousness of the malady changed from gentle to direct. Common side impacts were dosage –dependent
clogging, sedation, lower leg edema, dose-dependent dryness of mouth and skin, event of diseases, queasiness, spewing and
fringe neuropathy [84,85].
5. NEW DEVELOPMENT AND THERAPEUTIC USES
5.1. Scope of nanomedicine as thalidomide pharmacotherapeutics
Intravenous organization may well be an alternative way to form THD accessible to patients with impeded gastrointestinal
work like ulcerations within the upper tract (HIV patients), destitute intestinal assimilation (GVHD) and coma. In any case, its
moo watery dissolvability and moo steadiness impede the improvement of a parenteral detailing, which would be of clinical
intrigued forthese patients[86-90] (Figure: -7). A few pharmaceutical procedures have been depicted to enhance steadiness
and solvency of THD, such as its complexation with hydroxypropyl, cyclodextrin [91], the attempt to utilize the unadulterated
enantiomeric shapes[92] with its affiliation to polymeric carriers[93]. Submicron emulsions, known as nanoemulsions, have
been apply for a long time for parenteral sustenance and medicate conveyance due to their biocompatibility, relative
soundness, capacity to solubilize tall amounts of hydrophobic compounds, capacity to decrease the poisonous quality of
cytotoxic drugs and capacity to ensure drugs from hydrolysis and enzymatic degradation in physiologic conditions[94-97].
Figure: -7 Different stages of Thalidomide
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5.2. THD nanoemulsions preparation
The nanoemulsions were arranged by unconstrained emulsification[98,99]. Briefly, the natural stage comprising of outright
ethanol, oil (castor oil, 10.0%w/w), lipophilic emulsifier (soybean phosphatidylcholine, 3.0%w/w) and THD (polymorphic
frame) already homogenized, were infused into the watery stage comprisingofwater,osmoticspecialist(glycerol, 2.25%w/w)
and a hydrophilic emulsifier (polysorbate 80), beneath attractive blending.The attractiveblendingwaskeptupamid 30 min to
permit the framework to reach balance. The dissolvable extent was 1/2, ethanol/water. Ethanol and abundance water were
evacuated by evaporation beneath decreased weight until a volume of 10mL was come to.ThepHwasbalanced to5.0–5.5 with
HCl 0.01 M. A to begin with set of details was arranged withdiverseconcentrationsofthalidomide(0.01, 0.015,0.02 and 0.05%,
w/w) and no hydrophilic emulsifier and named THD 0.01; THD 0.015; THD 0.02, and THD0.05, accordingly. A while later,
another set of details was optimized withregard tothepolysorbate80substanceandnamedTHD0.01P0.5;THD0.01P1.0;THD
0.01P2.0,and THD 0.01P4.0.
5.3. Thalidomide research and cancer
Dr. Jayesh Mehta (University of Arkansas) discussed preliminary results of research on the effects of thalidomide in treating
multiple myeloma[100]. A study of 84 patients demonstrated that thalidomide showed antitumor activity in advanced and
high-risk multiple myeloma, justifying its incorporation into combination chemotherapy trials. Dr. Jon Glass (New York
University Hospital) presented an overview of research related to the use of thalidomide for brain tumors. Thalidomide has
been appeared to alienate development figure initiated angiogenesis; it also reduces TNF-a production [101]. Potential
effectiveness in the management of a number of neoplasticandinflammatorydisordershasbeensuggested.Preparatory comes
about of a study involving 71 victim with elementary brain tumors treated with thalidomide in sequence with carboplatin
revealed a statistically Critical diminish within the microvascular thickness of these tumors compared with chemotherapy
alone.
5.4. REFRACTORY DISEASE
5.4.1. Single-Agent Thalidomide:
Initially, Singhal reported a stage II trial of thalidomide in victim with advanced refractory MM[102]. Of the 84 patients
studied,76 had previous myeloablativetherapywith stem cellsupport, althoughsomewere relapsingoff therapy. Patientswere
treated with an starting dose of 200 mg/day with dose escalation in 200 mgincrements every2 weeks, in theabsenceof severe
side effects, to a maximum of 800 mg/day. The middle term of treatment was 80 days. Twenty-one patients (25%) achieved
par378 tial remission by criteria of 50% reduction in monoclonal protein. In a as of late distributed upgrade of that initial
report, 169 patients were enrolled and 30% had at least a 50% reduction in paraprotein[103]. Two year occasion free and in
general survival datas were 20% and 48%, respectively, in thisgroupofpatientswithadvanced myeloma. Respondingpatients
had a superior 2-year survival datas (69%) compared with non responding patients (47%). As expected,patientswithnormal
cytogenetics, low plasma cell define list, and Beta-2 microglobulin <3 mg/L had a longer event-free survival.We confirmed a
25% response rate and projected middle reduction length of 15 months in a stage II study of 44 evaluable patientsresistantto
at least a pulse dexamethasone-containing regimen using criteriaof≥50% and≥75%reductionofserumand urine monoclonal
paraprotein, respectively[104,105].Manyothertrialshaveconfirmedthis approximately25% responserateof particular-agent
thalidomide in refractory myeloma (Table: -2) [103-107,108-121].Itisessentialtonotethat manythalidomidetrialshaveused
less stringent criteria (only 25% reduction or stable disease) for determining myeloma response compared to historical data
where approx 50% decrease in monoclonal paraprotein has been required for partial remission.
Table: -2 Thalidomide in Resistant Myeloma: Selected Single-Agent and Combination Trials*
Daily Thalidomide Dose (mg) No. of Patients Response Rate* (%) Reference
Single-Agent Trials:
Barlogie 200-800 169 30 [103]
Alexanian 100-400 44 25 [105]
Juliusson 200-800 20 43 [108]
Yakoub-Agha 50-800 83 47 [109]
Raza 200-800 83 47 [110]
Durie 50-400 36 25 [106]
Rajkumar 200-800 36 31 [111]
Tosi 100-800 32 31 [112]
Grosbois 200-800 120 17 [113]
Hus 200-400 53 36 [114]
Trials of Combinations:
Weber 200-800 + D 20 mg/m2×5 d [104]
Dimopoulos 200-800 + D 40 mg×4 d [115]
Palumbo 100 + D 40 mg×4 d [116]
Tosi 100 + D 40 mg×4 d [117]
Coleman 50-200 + B 250-500 mg b.i.d. [107]
Kropff 100-400 + D 20 mg/m2×4 d
+C 1.8 g/m2
[118]
Moehler 400 + C 400 mg/m2×4 d,
+ E 40 mg/m2×4 d, CI
+ D 40 mg ×4 d
[119]
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Barlogie 400 + D 40 mg×4 d
+ P 10 mg/m2×4
+ A 10 mg/m2×4 d
+ C 400 mg/m2×4 d
+ E 40 mg/m2×4 d
[120]
* Studies with >50% M protein
reduction.
D = dexamethasone
B = clarithromycin (Biaxin)
C = cyclophosphamide
E = etoposide
P = cisplatin
A = doxorubicin
CI = continuous infusion
Table: -3 IMiD-3 (CC-5013) for Relapsed/Refractory Multiple Myeloma (Response ≥50% Reduction in M Protein)
Daily Dose
(mg)
Richardson [121] Zangari [122] Total
No. of
Patients
No. of Responsive
Patients
No. of
Patients
No. of Responsive
Patients
No. of
Patients
No. of Responsive
Patients
5 6 1 3 0 9 1
10 8 1 3 0 11 1
25 6 6 3 1 9 1
30 14 3 6 2 20 5
Total 34* 5 (26%) 15 3 (20%) 49 ** 8 (23%)
*Number of
evaluable
patients: 19
**Number of
evaluable
patients: 34
5.4.2. Thalidomide in Combination With Other Agents:
In 1999, we reported results of a trial of thalidomide (doses as previously described for single-agent thalidomide) in combo
with intermittent pulse dexamethasone (dexamethasone 20 mg/m2 per day p.o. on days 1 to 5 and 15 to 19 repeated on
approximately day 30, for a total of two courses, followed by maintenance on days 1 to 5 only, repeated every 4
weeks)[104,122]. In 47 patients with resistant myeloma, 22 patients (46%) were resistant to both thalidomide and pulse
dexamethasone given separately as single agents. The possibility of synergy betweenTHDand dexamethasone was supported
by the surprising response rate of 46% in patients safe to pair drugs given previously as single agents. This result was similar
to the in general reaction rate of 52%. A similar response rate of55% in 44 patientswith refractorymyelomawasalsoreported
by Dimopoulos[115]. Investigators at the collage of Arkansas are evaluating a program of DCEP in combination with
thalidomide, compared with DCEP alone in patients with relapsing high-tumor-mass disease or with poor prognostic
cytogenetics[120]. At a middle take after up of 17 months the reaction rate of 18%, after3 cyclesofDCEP,doubledto36% with
the addition of thalidomide. The same group is investigatingtheDT-PACEprocedureinpatientswithpriortherapyvsintensive
therapy with comparable stem cell transplantation. Among the first 179 patients treated with DT-PACE, only45% were
randomized, largely due to low frequency of response[120]. Eighty victims have been randomized and treated and are
currently evaluable. Complete responses were noted in 26 of 39 patients who received tandem transplants and in only eleven
of forty-one patients continuing on DT-PACE (P=.0005). Two- year occasion free survival was similar at73%inboth arms,but
33 patients who failed DT-PACE went on to receive tandem transplant, making this result difficult to interpret. Because of the
inferior results with continued DT-PACE, the study has been amended to include melphalan 100 mg/m2 withPBSC supportin
the DT-PACE arm. A study of VAD combined with thalidomide in refractory patients was terminated prematurely becauseof a
high rate of thrombotic complications that were attributed to the combination of doxorubicin and
dexamethasone[124,127](Table: -3).
5.5. PREVIOUSLY UNTREATED DISEASE
5.5.1. Single-Agent Thalidomide:
Because of the significant action of thalidomide in refractory myeloma, we and others conducted trials in already untreated
patients. Since the efficacy of thalidomide as asingleagentwaspreviouslyunknown,wefigureoutthalidomide100-200 mgper
day escalating to 400 mg everyday in patients with asymptomatic myeloma[123]. Twenty eight patients considered at tall
hazard for early progression of disease (median 18 months), as determined by criteria we previously established, were
included in this small trial. Partial remission, characterized by a ≥75% reduction in serum in protein synthesis and ≥95%
reduction in urine Bence-Jones protein,was noted in 10 (36%) of the 28 patients. Rajkumar conducted a comaprable trial
noting a response datas of 38% among 16 comparable patients[126,127]. Given the long period of illness stability for
asymptomatic disease, any impact on time to progression or survival will take many years to determine. Since early
management of asymptomatic victims with other agents has not previously improved survival, use of thalidomide in
asymptomatic disease should be restricted to clinical trials until the benefits and long-term side impacts are established.
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5.5.2. Thalidomide in Combination With Other Agents:
The activity of THD and dexamethasone in refractory disease prompted severalinvestigatorstopursuethisregimen in already
untreated patients with symptomatic disease. Rajkumar reported 50 patients treated with 200 mg/day of thalidomide with a
dose escalation each 2 weeks up to 800 mg/day along with 40 mg/day of dexamethasoneonodd cyclesand days1-4 on indeed
cycles[128]. Because 2 of the first 7 patients capable grade 3-4 skin toxicity, subsequent patients were treated with a fixed
thalidomide dose of 200 mg/day. 32 patients (64%) had a ≥50% diminishment in serum m protein. Stem cell collect was
completed without difficulty in 31 patients, and 26 patients proceeded to myeloablative treatment with stemcellsupport.In a
similar trial at our center, 40 patients with untreated myeloma were given thalidomide 100-200 mg per day at bed time with
acceleration up to 400 mg[129]. Dexamethasone 20 mg/m2 everyday was given for 2 courses followed by dexamethasone on
days 1 to 4 only for maintenance. Twenty nine patients (72%) had a ≥75% diminishment in serum protein synthesis or ≥95%
reduction in Bence-Jones proteinuria or both. Complete remission was noted in 7 patients (18%). There was no difficulty in
subsequent stem cell harvest for patients in whom this was attempted. Thalidomide is also currently being evaluated at theat
the college of arkansas as part of induction for myeloablative therapy (total therapy III) [120] (Table: -4).
Table: -4 Selected Studies of Thalidomide in Patients With Untreated Myeloma
Disease Status Thalidomide
Dose (mg)
No. of
Patients
Response
Rate* (%)
Reference
Asymptomatic:
Weber 100-400 28 36 [123]
Rajkumar 200-800 15 38 [127]
Symptomatic:
Rajkumar 200-400
200** + D 40 mg
4 d
50 64 [128]
Weber 100-400 + D 20
mg/m2 4 d
40 72 [129]
* Studies with >50% M protein reduction.
** Dose in the first 7 patients escalated up to 400 mg.
Because of Stevens-Johnson syndrome in 2 patients, dose
was fixed at 200 mg in the next 43 patients.
D = dexamethasone
6. AUTHORIZED USES OF THALIDOMIDE
In spite of the catastrophe related with the sedate,
thalidomide and its subordinates are back on the show case
for the treatment of particular conditions, counting certain
leprosis complications and cancers, for which it speaksto an
elective to calm patients. In most Westernnations where itis
authorized, get to to the sedate is entirely controlled and its
utilize is confined to particular cases. Be that as it may, in
numerous creating nations, sedate controlis insufficientand
babies proceed to be born with birth abandons, whereas it
may well be maintained a strategic gap from.
6.1. In Canada
Since Admirable 4, 2010, the utilize of thalidomide
(THALOMID®) is authorized in Canada for the management
of patients matured 65 or more seasoned who endure from
different myeloma, a sort of bone marrow cancer. Two
thalidomide subordinates are moreover authorized:
REVLIMID® and POMALYST®. Under the hone of
medication a doctor can endorse this medicate for a
condition other than different myeloma.Thalidomide is as it
were accessible through acontrolled dissemination program
called RevAid®. The sedate is entirely contraindicated for
pregnant ladies and ladies at hazard of getting to be
pregnant. As it were program-certified doctors and drug
stores are authorized to endorse thalidomide and patients
that are utilizing it must be enrolled within the
program.Before 2010, canadian doctors may have get to to
thalidomide for the treatment of their patients, but only
through Wellbeing Canada’s Extraordinary Get to Program.
6.2. In United States
Since July 16, 1998, the Nourishment and Sedate
Organization (FDA) of the Joined together States authorizes
the utilize of thalidomide (THALOMID®) within the
treatment of certain shapes of disease complications. Since
Octobre 26, 2006, its utilize is additionally authorized in
cases of numerous myeloma. Thalidomide is open on
medicine as it were through a Chance Assessment and
Moderation Methodology know as THALOMIDREMS®. The
sedate is entirely contraindicated for pregnant ladies. For
ladies of age to conceive, thalidomide can beendorsed,given
that their doctor checks for pregnancy amid the treatment
and illuminates the persistent satisfactorily. As it were
doctors and drug specialists certified by the program are
permitted to endorse and convey THALOMID®.
7. CURRENT & FUTURE DEVELOPMENTS
The recovery of thalidomide which has however to be
endorsed for different myeloma has expanded its
exploratory utilize in various oncological and provocative
conditions. The future of the more potent thalidomide
analogs, particularly lenalidomide and pomalidomide, their
immunomodulatory and anti-angiogenic potency and
apparent lack of thalidomide’ssideeffects, categorizingthem
as potentially important therapeutics in cancer, is very
promising. The IMiDs represent 2G small molecules
compounds with novel components of anti-cancer activity.
Lenalidomide proceeds to be assessed within the treatment
of a few unremitting immune system and auto inflammatory
illnesses based on clinical advantage in different myeloma,
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due to anti-cytokine and against angiogenic properties. The
continuous endeavors to move onward the harmfulness
profile with understanding advance atomic targets will
moreover offer assistance depict the neoplasms for which it
may demonstrate clinical potency. Amalgamation of novel
THD analogs like N-substituted and tetrafluorinated classes
of THD analogs, has been done with the proper
understanding of IMiDs’ metabolism. A few of these analogs
have too appeared note worthy antitumor movement in
preclinical prostate cancer xenotransplants models, which
require further clinical investigation. The therapeutic
impacts of CC-4047 have been assessed in various
experimental models. The promising comes about seen in
clinical studies of imids analogs of THD warrant proceeded
clinical improvement of of the analogs and increased
research efforts in distinguishingproofofpotentialtargetsin
different neoplasms.
8. CONCLUSION
THD is an successful agent within the administration of MM.
Although thalidomide is active, side effects that include
constipation, fatigue, neuropathy, and thrombotic/ embolic
complications may limit its use in some patients. Newer
nonteratogenic derivatives, such as the IMiDs, are also
effective but with a different spectrum of side effects, and
experience remains limited. In the future, combinations of
these specialists with novel components of activity
(thalidomide,IMiDs,proteosomeinhibitors,dexamethasone)
followed by intensive therapy with stem cellsupportearlyin
the disease should result in improved response rates, longer
remissions, and improved survival for more patients.
9. ACKNOWLEDGMENTS
We thank Mr. Aziz Ahmed for his mentorship and Ms.
Deepika Thakur for editing and typing the manuscript.
10. CONFLICT OF INTEREST
The author(s) declare that they have no comflict of interest
with respect to, authorship and publication of this article.
ABBREVIATIONS
MM = Multiple Myeloma
GvHD = Graft versus Host Disease
PBMCs = Peripheral Blood Mononuclear Cells
IMiDs = Immunomodulatory Drugs
NF-κ B = Nuclear Factor kappa-Beta
TNF-α = Tumour Necrosis Factor alpha
IL-1β = Interleukin-1 beta
CMV = Cytomegalovirus
GM-CSF = Granulocyte Macrophage-Colony Stimulating
Factor
VAD = Vincristine-Doxorubicin Dexamethasone
BFGF = Basic Fibroblast Growth Factor
VEGF = Vascular Endothelial Growth Factor
HUVEC = Human Umbilical Vein Endothelial Cells
CTLA4 = Cytotoxic T-Lymphocyte-Associated Antigen 4
PBSC = Peripheral Blood Stem Cell
cIAP2 = Cellular Inhibitor of Apoptosis Protein 2
ENL = Erythema Nodosum Leprosum
COX-2 = Cyclooxygenase 2
FLIP = FLICE Inhibitory Protein
PGE-2 = Prostaglandin E2
IL-6 = Interleukin 6
BMSCs = Bone-Marrow Stromal Cells
MPC = Malignant Plasma Cells
MS = Multiple Sclerosis
DCEC = Dexamethasone, Cyclophosphamide,Etoposide,
and Cisplatin
EAE = Experimental Autoimmune Encephalomyelitis
MHC = Major Histocompatibility Complex
MCS = Macrophage Colony-Stimulating
STAT = Signal Transducers and Activators of
Transcription
CLL = Chronic Lymphocytic Leukemia
JNK = Jun N-Terminal Kinase
mTOR = Mammalian Target of Rapamycin
PD-1 = Programmed cell Death protein 1
AIDS = Acquired Immune Deficiency Syndrome
HIV = Human Immunodeficiency Virus
AML = Acute Myeloid Leukemia
ADRs = Adverse Reactions
THD = Thalidomide
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