Classical Hodgkin Lymphoma (cHL), consists of rare neoplastic Hodgkin and Reed-Sternberg cells (HRS) residing in a prominent inflammatory background. HRS show deregulated activation of multiple signaling pathways and transcription factors. The activation of these pathways and factors is partly mediated through interactions of HRS with various other types of cells in the microenvironment, but also through genetic lesions...
Hepatocellular carcinoma (HCC) arises from mutations in genes that regulate cell growth. While over 40% of HCCs originate from cancer stem cells, the mechanisms of cancer stem cell formation are not fully understood. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in suppressing tumor formation in the liver and intestinal stem cell niches. Loss of TGF-β signaling results in a phenotype similar to Beckwith-Wiedemann syndrome, which is associated with increased cancer risk. Understanding the TGF-β pathway and other key pathways involved in HCC formation could lead to new therapeutic strategies for preventing and treating this lethal cancer.
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.
2012-PLoS One-Viral cross class serpin inhibits T cell fatricidekasinath viswanathan
1) The study examines the ability of two viral serpins, Serp-2 and CrmA, to inhibit vascular inflammation and T lymphocyte apoptosis.
2) In rodent models, purified Serp-2 given systemically after arterial injury markedly reduced plaque growth locally and systemically, while CrmA had no effect.
3) In human cell lines in vitro, Serp-2 selectively inhibited T cell caspase activity and cytotoxic T cell killing of other T cells, reducing fratricide. Both Serp-2 and CrmA inhibited monocyte apoptosis.
4) Serp-2's inhibitory activity depended on granzyme B, as it was reduced in granzyme B-
Gastric Cancer and the Role of Hedgehog- Interacting Protein One as a Prognos...CrimsonpublishersCancer
Hedgehog (Hh) signaling has been linked to foregut development since its initial discovery in Drosophila. The mammalian genome expresses three (3) Hh ligands, with sonic hedgehog (Shh) level of expression is highest in the mucosa of the embryonic and adult foregut. Hedgehog signaling aberrant activation is associated with pathological consequences in a range of human cancer. Hedgehog signaling is of pivotal role in homeostasis, neoplastic transformation, and gastrointestinal cancer development. The ability to track these cell types in tumor micro-environment broadens options for the more efficient screening of subjects predisposed to eventually developing gastric cancer as well as to expand opportunities for prophylactic therapy once atrophic gastritis develops. The Hedgehog-interacting protein (HHIP) gene is an essential homolog for multiple developmental processes. However, the expression and clinical correlation of HHIP in gastric cancer (GC) has not thoroughly been investigated. There is need to explore the expression of HHIP in gastric cancer (GC) and evaluate its clinicopathological and functional correlation.
Epidemiology, Etiopathogenesis, Pathology, Staging of Plasma Cell Dyscrasias....adityasingla007
Plasma cell dyscrasias are a spectrum of monoclonal gammopathies involving overproduction of myeloma proteins by plasma cells. Key points include:
- Plasma cells normally secrete antibodies but in plasma cell dyscrasias a clone overproduces a single antibody type.
- Risk factors include radiation exposure and genetic predispositions. Cytogenetic abnormalities involving immunoglobulin loci and cell cycle genes contribute to pathogenesis.
- Presentations include bone pain, fatigue, infections due to anemia or renal impairment. Investigations show monoclonal protein and clonal bone marrow plasma cells.
- Multiple myeloma, monoclonal gammopathy of unknown significance (MGUS), and smoldering
The role of natural products in regulating pyroptosisLucyPi1
This document reviews the role of natural products in regulating pyroptosis. It begins with background on pyroptosis, describing it as a form of inflammatory programmed cell death. It then discusses how pyroptosis is involved in various diseases and its molecular pathways. The document categorizes 14 natural products that have been shown to affect pyroptosis, including flavonoids like dihydromyricetin and terpenoids like andrographolide. These natural products were found to negatively or positively impact pyroptosis pathways by regulating factors like caspase-1, gasdermin D, and cytokines. The review concludes that natural products have potential as sources of new drugs for diseases related to uncontrolled pyroptosis.
Tuberculosis is a lung disease caused by the bacterium Mycobacterium tuberculosis. It remains a major global health problem. In 2020, there were an estimated 10 million new TB cases and 1.5 million TB deaths worldwide, making it one of the top 10 causes of death globally. The disease disproportionately affects low and middle income countries. Key risk factors include poverty, HIV infection and indoor air pollution. Early diagnosis and complete treatment are important for controlling the spread of the disease.
Flavin-Containing Dimethylaniline Monooxygenase 5 Drives Malignancies in Hepa...semualkaira
Hepatic microsomes play an important role in drug metabolism, but the potential biological functions of hepatic microsome-con- taining proteins in Hepatocellular Carcinoma (HCC) remain un- clear. Here, we used HCC and corresponding adjacent Non-Tumor (NT) tissues to isolate hepatic microsomes and then performed RNA high-throughput sequencing. After screening, flavin-con- taining dimethylaniline monooxygenase (FMO5) showed a significantly high expression level and was associated with poor prognosis in patients with HCC.
Hepatocellular carcinoma (HCC) arises from mutations in genes that regulate cell growth. While over 40% of HCCs originate from cancer stem cells, the mechanisms of cancer stem cell formation are not fully understood. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in suppressing tumor formation in the liver and intestinal stem cell niches. Loss of TGF-β signaling results in a phenotype similar to Beckwith-Wiedemann syndrome, which is associated with increased cancer risk. Understanding the TGF-β pathway and other key pathways involved in HCC formation could lead to new therapeutic strategies for preventing and treating this lethal cancer.
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.
2012-PLoS One-Viral cross class serpin inhibits T cell fatricidekasinath viswanathan
1) The study examines the ability of two viral serpins, Serp-2 and CrmA, to inhibit vascular inflammation and T lymphocyte apoptosis.
2) In rodent models, purified Serp-2 given systemically after arterial injury markedly reduced plaque growth locally and systemically, while CrmA had no effect.
3) In human cell lines in vitro, Serp-2 selectively inhibited T cell caspase activity and cytotoxic T cell killing of other T cells, reducing fratricide. Both Serp-2 and CrmA inhibited monocyte apoptosis.
4) Serp-2's inhibitory activity depended on granzyme B, as it was reduced in granzyme B-
Gastric Cancer and the Role of Hedgehog- Interacting Protein One as a Prognos...CrimsonpublishersCancer
Hedgehog (Hh) signaling has been linked to foregut development since its initial discovery in Drosophila. The mammalian genome expresses three (3) Hh ligands, with sonic hedgehog (Shh) level of expression is highest in the mucosa of the embryonic and adult foregut. Hedgehog signaling aberrant activation is associated with pathological consequences in a range of human cancer. Hedgehog signaling is of pivotal role in homeostasis, neoplastic transformation, and gastrointestinal cancer development. The ability to track these cell types in tumor micro-environment broadens options for the more efficient screening of subjects predisposed to eventually developing gastric cancer as well as to expand opportunities for prophylactic therapy once atrophic gastritis develops. The Hedgehog-interacting protein (HHIP) gene is an essential homolog for multiple developmental processes. However, the expression and clinical correlation of HHIP in gastric cancer (GC) has not thoroughly been investigated. There is need to explore the expression of HHIP in gastric cancer (GC) and evaluate its clinicopathological and functional correlation.
Epidemiology, Etiopathogenesis, Pathology, Staging of Plasma Cell Dyscrasias....adityasingla007
Plasma cell dyscrasias are a spectrum of monoclonal gammopathies involving overproduction of myeloma proteins by plasma cells. Key points include:
- Plasma cells normally secrete antibodies but in plasma cell dyscrasias a clone overproduces a single antibody type.
- Risk factors include radiation exposure and genetic predispositions. Cytogenetic abnormalities involving immunoglobulin loci and cell cycle genes contribute to pathogenesis.
- Presentations include bone pain, fatigue, infections due to anemia or renal impairment. Investigations show monoclonal protein and clonal bone marrow plasma cells.
- Multiple myeloma, monoclonal gammopathy of unknown significance (MGUS), and smoldering
The role of natural products in regulating pyroptosisLucyPi1
This document reviews the role of natural products in regulating pyroptosis. It begins with background on pyroptosis, describing it as a form of inflammatory programmed cell death. It then discusses how pyroptosis is involved in various diseases and its molecular pathways. The document categorizes 14 natural products that have been shown to affect pyroptosis, including flavonoids like dihydromyricetin and terpenoids like andrographolide. These natural products were found to negatively or positively impact pyroptosis pathways by regulating factors like caspase-1, gasdermin D, and cytokines. The review concludes that natural products have potential as sources of new drugs for diseases related to uncontrolled pyroptosis.
Tuberculosis is a lung disease caused by the bacterium Mycobacterium tuberculosis. It remains a major global health problem. In 2020, there were an estimated 10 million new TB cases and 1.5 million TB deaths worldwide, making it one of the top 10 causes of death globally. The disease disproportionately affects low and middle income countries. Key risk factors include poverty, HIV infection and indoor air pollution. Early diagnosis and complete treatment are important for controlling the spread of the disease.
Flavin-Containing Dimethylaniline Monooxygenase 5 Drives Malignancies in Hepa...semualkaira
Hepatic microsomes play an important role in drug metabolism, but the potential biological functions of hepatic microsome-con- taining proteins in Hepatocellular Carcinoma (HCC) remain un- clear. Here, we used HCC and corresponding adjacent Non-Tumor (NT) tissues to isolate hepatic microsomes and then performed RNA high-throughput sequencing. After screening, flavin-con- taining dimethylaniline monooxygenase (FMO5) showed a significantly high expression level and was associated with poor prognosis in patients with HCC.
Flavin-Containing Dimethylaniline Monooxygenase 5 Drives Malignancies in Hepa...semualkaira
Hepatic microsomes play an important role in drug metabolism,
but the potential biological functions of hepatic microsome-containing proteins in Hepatocellular Carcinoma (HCC) remain unclear. Here, we used HCC and corresponding adjacent Non-Tumor
(NT) tissues to isolate hepatic microsomes and then performed
RNA high-throughput sequencing
Proteomics Exploration of Chronic Lymphocytic Leukemia_Crimson PublishersCrimsonpublishersCancer
Chronic Lymphocytic Leukemia (CLL) is an adult heme malignancy characterized by the presence of mature-appearing CD5+ B cells in the blood, bone marrow, and secondary lymphoid organs [1]. In the United States, there will be an estimate of 20,720 new cases and 3,930 deaths according to the American Cancer Society statistics. Symptoms include swollen lymph nodes, frequent infections, and fatigue which negatively impacts the quality of life of people affected [1]. CLL is heterogeneous in its progression and clinical outcomes. Factors that contribute to the heterogeneity include the immunoglobulin heavy chain (IGHV) status and chromosomal aberrations [2,3]. There are two subtypes of CLL: Unmutated(U-CLL) and Mutated CLL(M-CLL). 40% and 60% of patients are diagnosed with unmutated and mutated CLL. U-CLL is characterized by the presence of CLL cells that have less than two percent of their IGHV mutated, whereas M-CLL cells have more than two percent mutated [4]. U-CLL is the more aggressive phenotype [2]. These cells have increased responsiveness to antigens that bind the B cell receptor (BCR) versus M-CLL cells [5]. M-CLL is the more indolent phenotype. Increased BCR signaling results in increased cell survival and proliferation [5].
This document summarizes a study examining the role of tropomyosin-related kinase B (TrkB) in metastatic pancreatic cancer. The study found that TrkB was overexpressed in highly metastatic pancreatic cancer cells compared to parental cells. TrkB overexpression correlated with perineural invasion, positive retroperitoneal margins, and shorter time to liver metastasis in patient samples. The metastatic cells also showed increased activation of ERK1/2 and increased expression of IL-8 and VEGF, which are involved in invasion and metastasis. This suggests TrkB overexpression may promote the aggressive growth and metastasis of pancreatic cancer by activating signaling pathways and increasing expression of genes involved in these processes. TrkB may therefore be a novel therapeutic target for pancreatic cancer.
Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeu...Enrique Moreno Gonzalez
Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by
lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently
underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete.
Annals of Mutagenesis is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Mutagenesis.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Mutagenesis. Annals of Mutagenesis accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of mutagenesis.
Annals of Mutagenesis strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Advances Perspectives in Syncytin-1 From Biology to Clinical Practicessuppubs1pubs1
Syncytin-1 serves as an enveloped membrane glycoprotein encoded from env gene and expressed in placenta specifically as HERV-W member product of human genome playing an essential role in cell fusion process of from trophoblast to syncytiotrophoblast during each individual pregnancy. It is widely maintained that unusual expressive levels of syncytin-1 have close relationships to obstetrical syndromes such as pre-eclampsia as a typical gestational hypertension symptom. In this review, correlations between syncytin-1 and related diseases are in detailed discussions.
This document summarizes a study investigating the role of microRNA-302 in regulating retinal epithelial cell fate by targeting the TGF-β type II receptor. The study demonstrates that microRNA-302 promotes pluripotency in ARPE cells in vitro by regulating TGF-β signaling and epigenetic changes. It also shows that small molecules DZNEP and SB431542 can induce pluripotency by attenuating pathways involved in cell differentiation, supporting the potential for microRNAs and small molecules in regenerative medicine and therapeutics for diseases like diabetic retinopathy.
This research article examines the role of sphingosine-1-phosphate (S1P) in regulating the proliferative and stem-like properties of glioblastoma stem cells (GSCs). The results showed that GSCs rapidly consume ceramide and export S1P into the extracellular environment. Extracellular S1P levels reached nanomolar concentrations in response to increased sphingosine. S1P was also found to act as an autocrine factor that promotes GSC proliferation and maintains their stem-like phenotype. This suggests that microenvironmental S1P critically modulates the GSC population by acting as an autocrine signal to support stemness and favor proliferation, survival, and therapeutic resistance of GSCs.
This review discusses the relationship between the protein arginine methyltransferase (PRMT) family and tumor metastasis. PRMT expression is often elevated in cancers and associated with poorer prognosis. PRMTs regulate metastasis through various mechanisms, including modifying the tumor microenvironment, promoting epithelial-mesenchymal transition, and altering cellular metabolism. Several PRMTs, such as PRMT1 and PRMT5, enhance lung metastasis of breast cancer and other cancers by methylating proteins involved in these pathways. Inhibiting arginine methylation through PRMT inhibitors shows promise in reducing tumor metastasis across cancer types based on preclinical studies.
A 43-Year-Old Male with PCM1-JAK2 Gene Fusion Experienced T-Lymphoblastic Lym...AnonIshanvi
Myeloid/lymphoid neoplasms associated with eosinophilia and PCM1-JAK2 is a provisional entity in WHO 2016. Prior case reports have shown quite a few clinical presentations in different patients with this chromosome translocation,characterized by eosinophilia in combination with myelodysplastic/ myeloproliferative neoplasms, acute myeloid leukemia(AML) and rarely, T-lymphoblastic lymphoma(T-LBL) or B-acute
A 43-Year-Old Male with PCM1-JAK2 Gene Fusion Experienced T-Lymphoblastic Lym...NainaAnon
Myeloid/lymphoid neoplasms associated with eosinophilia and PCM1-JAK2 is a provisional entity in WHO 2016. Prior case reports have shown quite a few clinical presentations in different patients with this chromosome translocation,characterized by eosinophilia in combination with myelodysplastic/ myeloproliferative neoplasms, acute myeloid leukemia(AML) and rarely, T-lymphoblastic lymphoma(T-LBL) or B-acute...
Anemia is a common condition of cancer patients. This is because cancers cause inflammation that decrease red blood cell production. In addition, many chemotherapies are myelosuppressive, meaning they slow down the production of new blood cells by the bone marrow.
Drug Repurposing: Recent Advancements, Challenges, and Future Therapeutics fo...JohnJulie1
Cancer is a prime public health burden that accounts for approximately 9.9 million deaths worldwide. Despite recent advances in treatment regimen and huge capital investment in the pharmaceutical sector, there has been little success in improving the chances of survival of cancer patients.
Abnormal Sodium and Chlorine Level Is Associated With Prognosis of Lung Cance...JohnJulie1
The imbalance of sodium and chloride ions occurs frequently in patients with lung cancer. However, the correlation between ion concentration change and patients prognosis have not been studied thoroughly. Our research will fill the gap, especially for high ion concentration.
Diagnostic Accuracy of Raised Platelet to Lymphocyte Ratio in Predicting Heli...JohnJulie1
Helicobacter Pylori (HP) infection is prevalent among patients with dyspepsia in developing countries with low socioeconomic status. The gold standard investigation is invasive method gastric biopsy through upper GI endoscopy, however non-invasive methods (stool for HP antigen) are not reliable up to the mark also need to wait for two weeks without symptomatic treatment. It is important to have a reliable, cost effective and easily accessible non-invasive marker to diagnose patients with H. pylori infection. Several non-invasive laboratory have been predicted in having the role in diagnosis of H.pylori infection. Therefore, the aim of our study was to determine the diagnostic accuracy of platelet to lymphocyte ratio in predicting H.Pylori infection in patients with dyspepsia.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...JohnJulie1
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells.
•
Fibrous
•
Fibro glandular
•
Adipose (Fatty)
What is Tomosynthesis?
•
Is a 3 dimensional projection
•
Reduces overlapping tissue seen with 2D only
•
15 projections are taken with each combo exposure (7.5) (-7.5)
•
With an average breast (18*24) 3D dose is 1.34, combo is 2.56 Milligrey. (3 Milligrey FDA) (2D is 1.2
Alterations of Gut Microbiota From Colorectal Adenoma to CarcinomaJohnJulie1
Gut microbiota has been implicated as a critical role in the development of colorectal cancer (CRC) and colorectal adenoma (CRA). However, few basic research has revealed the association between gut microbiota and the development of CRA and CRC. We aim to compare the diversity and composition of intestinal flora in CRA and CRC patients, to reveal the changes of intestinal microorganism in the evolution of normal intestinal mucosa-CRA-CRC axis, and to explore potential biomarkers.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...JohnJulie1
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Uretero-Enteric Anastomosis Stricture after Urinary Diversion; Detailed Analy...JohnJulie1
To report the lessons we have learned in the management of uretero-enteric anastomosis stricture (UEAS) in a tertiary urology center over a decade of experience.
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Flavin-Containing Dimethylaniline Monooxygenase 5 Drives Malignancies in Hepa...semualkaira
Hepatic microsomes play an important role in drug metabolism,
but the potential biological functions of hepatic microsome-containing proteins in Hepatocellular Carcinoma (HCC) remain unclear. Here, we used HCC and corresponding adjacent Non-Tumor
(NT) tissues to isolate hepatic microsomes and then performed
RNA high-throughput sequencing
Proteomics Exploration of Chronic Lymphocytic Leukemia_Crimson PublishersCrimsonpublishersCancer
Chronic Lymphocytic Leukemia (CLL) is an adult heme malignancy characterized by the presence of mature-appearing CD5+ B cells in the blood, bone marrow, and secondary lymphoid organs [1]. In the United States, there will be an estimate of 20,720 new cases and 3,930 deaths according to the American Cancer Society statistics. Symptoms include swollen lymph nodes, frequent infections, and fatigue which negatively impacts the quality of life of people affected [1]. CLL is heterogeneous in its progression and clinical outcomes. Factors that contribute to the heterogeneity include the immunoglobulin heavy chain (IGHV) status and chromosomal aberrations [2,3]. There are two subtypes of CLL: Unmutated(U-CLL) and Mutated CLL(M-CLL). 40% and 60% of patients are diagnosed with unmutated and mutated CLL. U-CLL is characterized by the presence of CLL cells that have less than two percent of their IGHV mutated, whereas M-CLL cells have more than two percent mutated [4]. U-CLL is the more aggressive phenotype [2]. These cells have increased responsiveness to antigens that bind the B cell receptor (BCR) versus M-CLL cells [5]. M-CLL is the more indolent phenotype. Increased BCR signaling results in increased cell survival and proliferation [5].
This document summarizes a study examining the role of tropomyosin-related kinase B (TrkB) in metastatic pancreatic cancer. The study found that TrkB was overexpressed in highly metastatic pancreatic cancer cells compared to parental cells. TrkB overexpression correlated with perineural invasion, positive retroperitoneal margins, and shorter time to liver metastasis in patient samples. The metastatic cells also showed increased activation of ERK1/2 and increased expression of IL-8 and VEGF, which are involved in invasion and metastasis. This suggests TrkB overexpression may promote the aggressive growth and metastasis of pancreatic cancer by activating signaling pathways and increasing expression of genes involved in these processes. TrkB may therefore be a novel therapeutic target for pancreatic cancer.
Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeu...Enrique Moreno Gonzalez
Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by
lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently
underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete.
Annals of Mutagenesis is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Mutagenesis.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all areas of Mutagenesis. Annals of Mutagenesis accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of mutagenesis.
Annals of Mutagenesis strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
Advances Perspectives in Syncytin-1 From Biology to Clinical Practicessuppubs1pubs1
Syncytin-1 serves as an enveloped membrane glycoprotein encoded from env gene and expressed in placenta specifically as HERV-W member product of human genome playing an essential role in cell fusion process of from trophoblast to syncytiotrophoblast during each individual pregnancy. It is widely maintained that unusual expressive levels of syncytin-1 have close relationships to obstetrical syndromes such as pre-eclampsia as a typical gestational hypertension symptom. In this review, correlations between syncytin-1 and related diseases are in detailed discussions.
This document summarizes a study investigating the role of microRNA-302 in regulating retinal epithelial cell fate by targeting the TGF-β type II receptor. The study demonstrates that microRNA-302 promotes pluripotency in ARPE cells in vitro by regulating TGF-β signaling and epigenetic changes. It also shows that small molecules DZNEP and SB431542 can induce pluripotency by attenuating pathways involved in cell differentiation, supporting the potential for microRNAs and small molecules in regenerative medicine and therapeutics for diseases like diabetic retinopathy.
This research article examines the role of sphingosine-1-phosphate (S1P) in regulating the proliferative and stem-like properties of glioblastoma stem cells (GSCs). The results showed that GSCs rapidly consume ceramide and export S1P into the extracellular environment. Extracellular S1P levels reached nanomolar concentrations in response to increased sphingosine. S1P was also found to act as an autocrine factor that promotes GSC proliferation and maintains their stem-like phenotype. This suggests that microenvironmental S1P critically modulates the GSC population by acting as an autocrine signal to support stemness and favor proliferation, survival, and therapeutic resistance of GSCs.
This review discusses the relationship between the protein arginine methyltransferase (PRMT) family and tumor metastasis. PRMT expression is often elevated in cancers and associated with poorer prognosis. PRMTs regulate metastasis through various mechanisms, including modifying the tumor microenvironment, promoting epithelial-mesenchymal transition, and altering cellular metabolism. Several PRMTs, such as PRMT1 and PRMT5, enhance lung metastasis of breast cancer and other cancers by methylating proteins involved in these pathways. Inhibiting arginine methylation through PRMT inhibitors shows promise in reducing tumor metastasis across cancer types based on preclinical studies.
A 43-Year-Old Male with PCM1-JAK2 Gene Fusion Experienced T-Lymphoblastic Lym...AnonIshanvi
Myeloid/lymphoid neoplasms associated with eosinophilia and PCM1-JAK2 is a provisional entity in WHO 2016. Prior case reports have shown quite a few clinical presentations in different patients with this chromosome translocation,characterized by eosinophilia in combination with myelodysplastic/ myeloproliferative neoplasms, acute myeloid leukemia(AML) and rarely, T-lymphoblastic lymphoma(T-LBL) or B-acute
A 43-Year-Old Male with PCM1-JAK2 Gene Fusion Experienced T-Lymphoblastic Lym...NainaAnon
Myeloid/lymphoid neoplasms associated with eosinophilia and PCM1-JAK2 is a provisional entity in WHO 2016. Prior case reports have shown quite a few clinical presentations in different patients with this chromosome translocation,characterized by eosinophilia in combination with myelodysplastic/ myeloproliferative neoplasms, acute myeloid leukemia(AML) and rarely, T-lymphoblastic lymphoma(T-LBL) or B-acute...
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Anemia is a common condition of cancer patients. This is because cancers cause inflammation that decrease red blood cell production. In addition, many chemotherapies are myelosuppressive, meaning they slow down the production of new blood cells by the bone marrow.
Drug Repurposing: Recent Advancements, Challenges, and Future Therapeutics fo...JohnJulie1
Cancer is a prime public health burden that accounts for approximately 9.9 million deaths worldwide. Despite recent advances in treatment regimen and huge capital investment in the pharmaceutical sector, there has been little success in improving the chances of survival of cancer patients.
Abnormal Sodium and Chlorine Level Is Associated With Prognosis of Lung Cance...JohnJulie1
The imbalance of sodium and chloride ions occurs frequently in patients with lung cancer. However, the correlation between ion concentration change and patients prognosis have not been studied thoroughly. Our research will fill the gap, especially for high ion concentration.
Diagnostic Accuracy of Raised Platelet to Lymphocyte Ratio in Predicting Heli...JohnJulie1
Helicobacter Pylori (HP) infection is prevalent among patients with dyspepsia in developing countries with low socioeconomic status. The gold standard investigation is invasive method gastric biopsy through upper GI endoscopy, however non-invasive methods (stool for HP antigen) are not reliable up to the mark also need to wait for two weeks without symptomatic treatment. It is important to have a reliable, cost effective and easily accessible non-invasive marker to diagnose patients with H. pylori infection. Several non-invasive laboratory have been predicted in having the role in diagnosis of H.pylori infection. Therefore, the aim of our study was to determine the diagnostic accuracy of platelet to lymphocyte ratio in predicting H.Pylori infection in patients with dyspepsia.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...JohnJulie1
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells.
•
Fibrous
•
Fibro glandular
•
Adipose (Fatty)
What is Tomosynthesis?
•
Is a 3 dimensional projection
•
Reduces overlapping tissue seen with 2D only
•
15 projections are taken with each combo exposure (7.5) (-7.5)
•
With an average breast (18*24) 3D dose is 1.34, combo is 2.56 Milligrey. (3 Milligrey FDA) (2D is 1.2
Alterations of Gut Microbiota From Colorectal Adenoma to CarcinomaJohnJulie1
Gut microbiota has been implicated as a critical role in the development of colorectal cancer (CRC) and colorectal adenoma (CRA). However, few basic research has revealed the association between gut microbiota and the development of CRA and CRC. We aim to compare the diversity and composition of intestinal flora in CRA and CRC patients, to reveal the changes of intestinal microorganism in the evolution of normal intestinal mucosa-CRA-CRC axis, and to explore potential biomarkers.
Prognosis of Invasive Micropapillary Carcinoma of the Breast Analyzed by Usin...JohnJulie1
Invasive micropapillary carcinoma (IMPC) is a rare type of breast cancer with high frequency of regional lymph node metastasis. However, the prognosis of IMPC has remained controversial for decades. We aimed to compare the differences of prognosis between IMPC and Invasive ductal carcinoma(IDC) of the breast by utilizing Surveillance, Epidemiology, and End Results (SEER) database.
Uretero-Enteric Anastomosis Stricture after Urinary Diversion; Detailed Analy...JohnJulie1
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Skeletal muscle channelopathy are rare heterogeneous episodic disorders with marked genotypic and phenotypic variability resulting in periodic paralysis, and falls in young people which often misdiagnosed or undiagnosed due to its rarity, often the symptoms are miscommunicated to the treating phycision due to its episodic nature and not uncommonly physical examination by the time patient attend the clinic or hospital will be unremarkable apart from periodic muscle paralysis where patient will presented to ED with flaccid weakness,
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The document summarizes experimental and clinical research on using infrared laser therapy between 890-910 nm to treat breast cancer. Experimental studies showed that lower doses of laser therapy (0.46 J/cm2) inhibited tumor growth more than higher doses. Laser therapy combined with chemotherapy was also effective, particularly with vincristin. Clinical studies on 136 breast cancer patients found that laser therapy before or after surgery, or alone, reduced complications, improved immune function and quality of life, and increased survival time. Histological analysis found over 50% tumor tissue disappeared after effective laser treatment.
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Upper Rectal Cancer: Benefit After Preoperative Chemoradiation Versus Upfront...JohnJulie1
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GASTROINTESTINAL INFECTIONS AND GASTRITIS
Osvaldo Bernardo Muchanga
Gastrointestinal Infections
GASTROINTESTINAL INFECTIONS result from the ingestion of pathogens that cause infections at the level of this tract, generally being transmitted by food, water and hands contaminated by microorganisms such as E. coli, Salmonella, Shigella, Vibrio cholerae, Campylobacter, Staphylococcus, Rotavirus among others that are generally contained in feces, thus configuring a FECAL-ORAL type of transmission.
Among the factors that lead to the occurrence of gastrointestinal infections are the hygienic and sanitary deficiencies that characterize our markets and other places where raw or cooked food is sold, poor environmental sanitation in communities, deficiencies in water treatment (or in the process of its plumbing), risky hygienic-sanitary habits (not washing hands after major and/or minor needs), among others.
These are generally consequences (signs and symptoms) resulting from gastrointestinal infections: diarrhea, vomiting, fever and malaise, among others.
The treatment consists of replacing lost liquids and electrolytes (drinking drinking water and other recommended liquids, including consumption of juicy fruits such as papayas, apples, pears, among others that contain water in their composition).
To prevent this, it is necessary to promote health education, improve the hygienic-sanitary conditions of markets and communities in general as a way of promoting, preserving and prolonging PUBLIC HEALTH.
Gastritis and Gastric Health
Gastric Health is one of the most relevant concerns in human health, with gastrointestinal infections being among the main illnesses that affect humans.
Among gastric problems, we have GASTRITIS AND GASTRIC ULCERS as the main public health problems. Gastritis and gastric ulcers normally result from inflammation and corrosion of the walls of the stomach (gastric mucosa) and are generally associated (caused) by the bacterium Helicobacter pylor, which, according to the literature, this bacterium settles on these walls (of the stomach) and starts to release urease that ends up altering the normal pH of the stomach (acid), which leads to inflammation and corrosion of the mucous membranes and consequent gastritis or ulcers, respectively.
In addition to bacterial infections, gastritis and gastric ulcers are associated with several factors, with emphasis on prolonged fasting, chemical substances including drugs, alcohol, foods with strong seasonings including chilli, which ends up causing inflammation of the stomach walls and/or corrosion. of the same, resulting in the appearance of wounds and consequent gastritis or ulcers, respectively.
Among patients with gastritis and/or ulcers, one of the dilemmas is associated with the foods to consume in order to minimize the sensation of pain and discomfort.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
Computer in pharmaceutical research and development-Mpharm(Pharmaceutics)MuskanShingari
Statistics- Statistics is the science of collecting, organizing, presenting, analyzing and interpreting numerical data to assist in making more effective decisions.
A statistics is a measure which is used to estimate the population parameter
Parameters-It is used to describe the properties of an entire population.
Examples-Measures of central tendency Dispersion, Variance, Standard Deviation (SD), Absolute Error, Mean Absolute Error (MAE), Eigen Value
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Pictorial and detailed description of patellar instability with sign and symptoms and how to diagnose , what investigations you should go with and how to approach with treatment options . I have presented this slide in my 2nd year junior residency in orthopedics at LLRM medical college Meerut and got good reviews for it
After getting it read you will definitely understand the topic.
Know the difference between Endodontics and Orthodontics.Gokuldas Hospital
Your smile is beautiful.
Let’s be honest. Maintaining that beautiful smile is not an easy task. It is more than brushing and flossing. Sometimes, you might encounter dental issues that need special dental care. These issues can range anywhere from misalignment of the jaw to pain in the root of teeth.
STUDIES IN SUPPORT OF SPECIAL POPULATIONS: GERIATRICS E7shruti jagirdar
Unit 4: MRA 103T Regulatory affairs
This guideline is directed principally toward new Molecular Entities that are
likely to have significant use in the elderly, either because the disease intended
to be treated is characteristically a disease of aging ( e.g., Alzheimer's disease) or
because the population to be treated is known to include substantial numbers of
geriatric patients (e.g., hypertension).
STAT-6 In Hodgkin Lymphoma Pathobiology and Treatment-Review of the Literature
1. STAT-6 In Hodgkin Lymphoma Pathobiology and Treatment-
Review of The Literature
M Ioannou*
, K Baxevanidou, GK Koukoulis
Department of Pathology, University of Thessaly, Greece
Volume 1 Issue 5- 2018
Received Date: 01 Aug 2018
Accepted Date: 20 Aug 2018
Published Date: 27 Aug 2018
1. Abstract
Classical Hodgkin Lymphoma (cHL), consists of rare neoplastic Hodgkin and Reed-Sternberg
cells (HRS) residing in a prominent inflammatory background. HRS show deregulated activa-
tion of multiple signaling pathways and transcription factors. The activation of these pathways
and factors is partly mediated through interactions of HRS with various other types of cells in
the microenvironment, but also through genetic lesions. Signal transducers and activators of
transcription (STAT) are a family of transcription factors that regulate a broad range of cellu-
lar processes, such as proliferation, differentiation, and survival, in a large variety of cell types.
STAT6 pathway is activated as a response to the binding of cytokines IL-4 and IL-13 to their
receptors on the cell membrane. The ability of activated STAT6 to promote lymphoproliferation
and the requirement for STAT6 in normal cytokine-induced cell proliferation provides a strong
rationale for further study of STAT6 in cHL.
This review outlines the current evidence on the role of STAT6 in cHL. We report on the findings
concerning the involvement of STAT6 in the pathogenesis, as well as in the cross-talk between
tumor cells and their microenvironment. The dependency of HRS on micro environmental
interactions and on deregulated STAT6 signaling pathway may offer novel strategies for targeted
therapies.
Clinics of Oncology
Citation: M Ioannou, K Baxevanidou, GK Koukoulis, STAT-6 In Hodgkin Lymphoma Pathobiology and
Treatment-Review of The Literature. Clinics of Oncology. 2018; 1(5): 1-8.
United Prime Publications: http://unitedprimepub.com
*Corresponding Author (s): M Ioannou, University of Thessaly, School of Health Sci-
ences, Deprtment of Pathology, Panepistimion 3st Biopolis, 41110, Larissa, Greece, E-
mail: mioan@uth.gr
Review Type
3. Introduction
Hodgkin lymphoma (HL) was recognized in the first half of
the 19th
century by Thomas Hodgkin and Samuel Wilks [1,2].
It is one of the most common lymphomas in Western World.
Its annual incidence is 3 cases per 100.000 persons. Neoplastic
tissues usually contain a small number of scattered large mono-
nucleated and multinucleated tumor cells (designated Hodgkin
and Reed-Sternberg cells or HRS cells) residing in an abundant
heterogeneous admixture of non-neoplastic inflammatory and
accessory cells. The latter includes lymphocytes, especially Th2
cells, monocytes, granulocytes, eosinophils, mast cells and his-
tiocytes [1,3,4]. Biological and clinical studies in the last de-
cades have shown that Hodgkin lymphomas are comprised of
two disease entities: nodular lymphocyte predominant Hodgkin
lymphoma (NLPHL) and classical Hodgkin lymphoma (cHL).
Based on the consistence of the microenvironment, the lat-
ter one is divided into four subtypes: nodular sclerosis (80%),
mixed cellularity (15%), lymphocyte rich (5%) and lymphocyte
depleted (<1%) (1, 5, 6). The immunophenotypic and genetic
2. Keywords
Hodgkin lymphoma; STAT6;
Pathobiology; Therapy; Re-
view
features of the mononuclear and multinucleated cells are identi-
cal in these histological subtypes, whereas their clinical features
and association with EBV show differences.
In Ebstein-Barr virus (EBV) positive cases evidence suggest its
role in the pathogenesis of HRS cells [5,7-11]. The prevalence of
EBV in HRS cells varies according to the histological subtype and
epidemiologic factors. The highest frequency is found in mixed
cellularity classical HL and the lower incidence in nodular scle-
rosis classical HL (WHO 2008). EBV is found in 40% of cases in
Western world, however may be seen in up to 90% of cases in
Central and South Africa [5].
Classical HL is a monoclonal lymphoid neoplasm derived (in
most instances from B cells). Despite their derivation from ger-
minal center B cells, HRS have lost much of the B-cell specific
expression program and have acquired B-cell inappropriate gene
products. In addition, deregulated transcription factors in classi-
cal HL promote proliferation and abrogate apoptosis in the neo
plastic cells. Multiple signaling pathways, mainly including nu-
3. deregulation of lineage-specific transcription factors such as E2A
[5], and the Interferon regulating factor (IRF)5 that, together with
NF-κB activation, determine the inflammatory phenotype of HRS
cells [57]. HRS cells express CD30 and CD40, two members of the
tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor
family, and in the majority of cases CD15 (75–85%) and IRF4 [5].
The JAK/STAT signaling pathway represents another key pathway
in pathogenesis of HL. STAT3, STAT5 and STAT6 are activated
and expressed at high level in HL [21, 58]. Given that the activa-
tion of docking domains for STAT monomers is due the activation
of JAK/STAT pathway, the expression of STATs and especially of
STAT6 in HRS cells might represent a possible biomarker of JAK/
STAT activation in tissue specimens. Clinicopathological studies
correlating clinical data and molecular results with immunohisto-
chemical expression of STAT6 protein, could further investigate
this possibility.
Epstein–Barr virus (EBV) is causally associated with approxi-
mately one third of HL cases in socioeconomically developed
countries, while in pediatric HL in Central and South America,
the association can be up to 90% [59]. In patients with AIDS,
EBV-infected HRS cells are present in nearly all cases [60]. Differ-
ent studies have shown that Epstein-BarrVirus contributes to the
transformation of its precursors, as well as the survival and pro-
liferation of the malignant HRS cells [4,5,7]. The EBV+ HRS cells
typically show an EBV latency II gene expression profile, meaning
expression of the viral proteins EBV nuclear antigen 1 (EBNA1)
and latent membrane proteins 1 and 2a (LMP1 and LMP2a) [61].
The EBV-encoded LMP-1 is a viral mimic of the CD40 recep-
tor, and by constitutive signaling it activates potently the nuclear
factorκB, c-Jun N-terminal kinase, and phosphatidylinositol 3-ki-
nase pathways.LMP-1 has been reported as a viral oncoprotein
promoting tumor growth but also apoptotic resistance and im-
mune modulation [9,62,63]. Recently, demonstrated that the in-
duction of LMP-1 by IL-4 and IL-13 is mediated by STAT6 and a
newly defined high-affinity STAT6-binding site in the LMP-1 pro-
moter in HL-derived, EBV-converted KMH2-EBV cell lines [10].
This evidence strongly supports the role of STAT6 in the patho-
genesis of EBV-positive cHL. Furthermore, it indicates that inhi-
bition of the interactions between the cytokines and its specific
receptor or inhibition of the STAT6 signaling pathway might have
beneficial effects in the EBV-positive cases by down-regulating the
expression of LMP-1.
In respect to tumor growth, it has been proved that survival and
proliferation of HRS cells is dependent on STAT3 and STAT6 acti-
vation, since rescission of their activation by neutralizing antibod-
ies, JAK/STAT blockers or siRNAs against STAT3 and STAT6 re-
duced proliferation and induced cell death in vitro [14, 25, 64]. In
addition. pointed out the association between antibody-mediated
neutralization of IL-13, reduced STAT6 phosphorylation and de-
creased HL cell proliferation [19].
Interestingly, Baus et al. [55] demonstrated that knockdown of
STAT6, by using constantly expressed shRNAs against STAT6 by
lentiviral transduction, induced apoptotic cell death in the cHL
cell lines L428 and L1236cHL. In the latter study, the values of
the G1 and G2 cell populations were not affected, suggesting that
STAT6 has a strong effect on cell survival and does not provoke
cell-cycle arrest.
The above data suggest that STAT6 promotes the neoplastic pro-
liferation and consequently it might represent a possible thera-
peutic target.
5.2 Stat6 and Hl Microenvironment
Unlike any other neoplasm, the tumor in cHL is made predomi-
nantly of the non-neoplastic HRS cells rather than the neoplastic
HRS cells, which often constitute no more than 1-3% of the entire
mass [12]. CD4+ T cell lymphocytes are the most abundant cell
type in cHL, clustering around the RS cells [48], and the overpro-
duction of helper T cell type 2 (Th2) cytokines and chemokines
such as interleukin (IL)-13, IL5 and eotaxin [14] is reported in
most cases. The great number of cytokines produced in cHL by
HRS cells promote neoplastic cell growth and survival. At the
same time, the secreted molecules are implicated in the reactions
between the cells of microenvironment and trigger an abnormal
immune response to the HRS cells while support them to over-
come the antitumor activity of cytotoxic T and NK cells [8]. This
is highlighted by expression or secretion of PD-1 ligand, galec-
tin-1 and IL-13 which directly interfere with the functional activ-
ity of T cells, primarily polarize specific T cell subsets towards a
regulatory phenotype, or prevent an effective Th1-response [65-
68].
Early studies reported that IL-13 and IL-13R (alpha)1, the IL-
13-specific receptor chain, are frequently expressed by HL-de-
rived cell lines as well as by HRS cells from biopsy material of
tissues involved by HL. Furthermore, antibody-mediated neu-
tralization of IL-13 in cultures of HL-derived cell lines resulted in
a dose-dependent inhibition of proliferation, and it was associ-
ated with increased apoptosis and with significant decreases in
both cellular proliferation and levels of phosphorylated STAT6 of
HL cell lines [13, 14, 69].
These data support the hypothesis that STAT6 is involved in
cellular interactions that modify the tumor microenvironment
which, on the other hand, regulate the immune response against
tumor cells. Since HRS survival seems to be mostly due the acti-
vated proliferating and proinflammatory cytokine secreting cells
[8, 70], the IL-13/STAT6 signaling, involved in micoenvironmen-
Volume 1 Issue 5 -2018 Review Type
United Prime Publications: http://unitedprimepub.com 3
4. tal interactions, may be an additional target for new therapeutic
approaches.
5.3. Stat6 and Therapy of Hl
The majority of patients with HL are treated with a combination
of multi-drug chemotherapy and radiotherapy. Despite relative
success of therapy, approximately 20% of patients will not be
cured with the current available therapy and the disease will re-
lapse [26]. Moreover, 30-35% of patients with high-risk prognos-
tic features will not be treated [71]. Additionally, patients recur-
ring after autologous and/or allogenic stem cell transplantation
are regarded incurable and are considered to have a median sur-
vival <3 years [72]. Hence, the development of novel therapeutic
agents are needed for patients with refractory or relapsed disease.
Novel therapeutic strategies focus on the special and unique
pathology and microenvironment, the deregulated signaling
pathways, as well as the induction of anti-HRS cell immunity by
modulating the microenvironment. Among the latter, the im-
mune checkpoint inhibitors (e.g. programmed cell death 1/PD-1,
PD1-Ligand/PDL-1) have been proved a breakthrough therapy
for advanced HL [66, 73, 74].
The JAK/STAT pathway is activated in HL as a result of genomic
amplification of JAK2 and/or inactivating mutations in an in-
hibitor of JAK activity, SOCS1 (75). A proof of the therapeutic
potential of JAK inhibitors has been proved by a phase I study
of the JAK inhibitor SB1518, a selective inhibitor of JAK2 and
FLT3. In this study, 14 out of the 34 patients had cHL. Of these
14 patients, 6 patients had a steady disease with the treatment
[31]. Have also supported the positive effects of SB1518, a novel
macrocyclic pyrimidine-based JAK2 inhibitor for the treatment
of HL. More specifically, SB1518 aims the JAK/STAT pathway by
inhibiting tyrosine phosphorylation on JAK2 (Y221) and down-
stream STATs. Hence, SB1518 has probably an anti-proliferative
effect on lymphoid cell lines, driven by mutant or wild type JAK-
2 or FLT3. The latter results from cell cycle arrest and induction
of apoptosis [31].
Furthermore, JAK inhibitors can lead on propitious immuno-
modulary effects. Derenzini et al. [76] showed that AZD1480,
JAK 1/2 inhibitor exhibited immunomodulary effects at low con-
centrations by down regulating the expression of Th2 cytokines
and chemokines (Il-13 and TRAC), as well as STAT3-mediated
reduced expression of PD-L1 and PD-L2, which take part in im-
mune escape mechanisms in HL. In addition. Demonstrated that
JAK2 inhibition by the selective inhibitor, fedratinibdecreased
phosphorylation of JAK2, STAT1, STAT3, and STAT6 and re-
duced the expression of additional downstream targets, includ-
ing PD-L1, Interestingly, the phosphorylation of STAT 1, 3 and 6
was inhibited by chemical JAK2 blockade in a 9p24.1 copy num-
ber-dependent manner in cHL cell lines [20].
Recently presented a JAK 1 /2 inhibitor, ruxolintinib, which re-
duced the phosphorylation of STAT3 and STAT6, as well as the
expression of c-Myc in the HL cell line HDLM-2. These results
were amplified when ruxolintinib was combined with the Bcl-2/
Bcl-xL inhibitor, Navitoclax, or with anti-CD30 toxin conjugate,
brentuximab vedotin (BV). The combination of ruxolitinib with
Navitoclax or BV alone prolonged survival period but did not
cure HDML-2 tumor-bearing mice. On the other, BV combined
with ruxolitinib and/or with Navitoclax led to sustained com-
plete remission in this model of HL. The studies above propose
future use of the combination of BV with ruxolitinib in patients
with HL [77].
The significance of STAT6 inhibition in HL therapy has been
reported. The authors demonstrated a direct antiproliferative ef-
fect of histone deacetylase (HDAC) inhibitor vorinostat on HRS
which was associated with cell cycle arrest and apoptosis and an
immune mediated effect by altering cytokine and chemokines
secretion in the microenvironment due to inhibition of STAT6
phosphorylation [78]. Furthermore demonstrated that the pan-
deacetylase inhibitor panobinostat has potent antiproliferative
activity against Hodgkin lymphoma-derived cell lines. At the
molecular level, panobinostat activated the caspase pathway, in-
hibited STAT5 and STAT6 phosphorylation, and down-regulated
hypoxia-inducible factor 1 α and its downstream targets, glucose
transporter 1 (GLUT1) and vascular endothelial growth factor.
In respect to STAT6 signaling, have shown that specific block-
ing of the IL-4 and IL-13-mediated STAT-6 activation by an IL-4
binding fusion protein APG598 or an IL-4R antagonist APG201
(R121D/Y124D) make HL cells more prone to apoptotic effect
by chemotherapeutic drugs such as Mitomycin C, 5-Fluoracil,
Etoposide, Doxorubicin and Plaxicatel. This outcome is based
on the inhibition of STAT-6 mediated elevation of expression of
the anti-apoptotic Bcl-2 family protein Bcl-xL. Thus, the IL-4/
Il-13-STAT6-Bcl-xL pathway may be a crucial target for HL
treatment [25]. In addition, Demonstrated that treatment of two
IL-13-responsive HL-derived cell lines, with Soluble interleukin-
13Ralpha2 decoy receptor, resulted in the inhibition of cell prolif-
eration, and down-regulated the phosphorylation of STAT6 [24].
All the data investigating the correlation of STAT6 with cHL and
its prognosis are summarized in Table 1.
Volume 1 Issue 5 -2018 Review Type
United Prime Publications: http://unitedprimepub.com 4
5. 6. Conclusion
In conclusion, although the complexity of interactions between
HRS cells and their microenvironment and their functional role
during malignant transformation is not completely understood,
however, emerging data indicate that STAT6 is involved in cHL
pathogenesis and growth, through interplay with cellular signal
transduction pathways. Experimental results following disrup-
tion of microenviromental interactions by STAT6 inhibition gen-
erate optimism for novel therapeutic strategies for HL, possibly
including drugs that block specifically the STAT6 signaling path-
way and particularly the STAT6 protein.
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Reference STAT-6 relatedremarks Association withprognosis
Skinnideretal. 2002
STAT-6 activation in cHL is
mediated by IL-13
Negativeassociationwithprog-
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Skinnideret al. 2002,
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Positiveassociationwithprog-
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Positiveassociationwithprog-
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