1) The document discusses candidate molecules that may act as tumor suppressors for human uterine mesenchymal tumors. It focuses on LMP2/β1i, which is expressed in normal myometrium but defective or absent in human uterine leiomyosarcoma (Ut-LMS).
2) Mice deficient in LMP2/β1i spontaneously develop Ut-LMS, with similarities to the human disease. This suggests LMP2/β1i may function as a tumor suppressor for Ut-LMS.
3) While tumor suppressor pathways like p53 and Rb are often disrupted in cancers, their roles in Ut-LMS tumorigenesis are unclear
The group at UCSF Benioff Children's Hospital is researching epigenetic mechanisms involved in gene expression reprogramming. They have two main projects: 1) studying AID, an enzyme that can demethylate DNA and may play a role in the epithelial-mesenchymal transition (EMT) process linked to cancer metastasis, and 2) characterizing super-enhancers (SEs), clusters of enhancers that regulate genes key to cell identity and cancer, to identify new therapeutic targets. They are also developing a CRISPR-based gene therapy for hemoglobinopathies like sickle cell disease.
Odontogenic ameloblast-associated protein (ODAM) inhibits growth and migratio...Enrique Moreno Gonzalez
The Odontogenic Ameloblast-associated Protein (ODAM) is expressed in a wide range of
normal epithelial, and neoplastic tissues, and we have posited that ODAM serves as a novel
prognostic biomarker for breast cancer and melanoma. Transfection of ODAM into breast
cancer cells yields suppression of cellular growth, motility, and in vivo tumorigenicity.
Herein we have extended these studies to the effects of ODAM on cultured melanoma cell
lines.
1. The document presents a computational model that analyzes gene expression profiles of breast cancer patients to identify intermediate epithelial-mesenchymal transition (EMT) states.
2. The model evaluates patient data and finds some quasi-epithelial and quasi-mesenchymal gene expression patterns with high stability scores, indicating possible intermediate EMT stages.
3. The results confirm previous studies showing that induction of EMT in mammary epithelial cells leads to expression of stem cell markers and properties through acquisition of mesenchymal traits.
Analysis of primary breast tumour stromal cells and their potential role in d...Marion Hartmann
Although malignant epithelial cells are the origin of breast cancer and the main focus of research, evidence is increasing that the tumour microenvironment plays an important role in disease progression. Cellular interactions within the breast cancer microenvironment promote tumour growth, invasion, metastasis and resistance to therapy. Breast tumour stroma consists of various cell types including immunocytes, pericytes, endothelial cells and carcinoma associated fibroblasts. Stromal cells are the predominant cell type in the tumour microenvironment. Tumour stromal cells actively secrete growth factors, chemokines and cytokines that support tumourigenesis. Although the tumour promoting effect of stromal-epithelial interactions is recognized, the precise mechanisms involved are poorly understood. Further characterisation of tumour stromal cells will facilitate elucidation of these interactions.
This document discusses a study to create tissue engineering models of breast cancer metastasis. The researchers will develop 3D scaffolds mimicking adipose and bone tissue with varying stiffness. They will seed metastatic breast cancer cells onto the scaffolds to study changes in gene expression, histology, and markers as the cells metastasize from softer adipose-like scaffolds to stiffer bone-like scaffolds. The goal is to better understand the mechanisms driving breast cancer metastasis in order to develop new prevention and treatment strategies.
Breast cancer stem cells have been identified as tumor-initiating cells that have high expression of CD44 and low/no expression of CD24. They undergo epithelial-mesenchymal transition processes controlled by co-expression of Oct-4 and Nanog. Disruption of pathways like p53 and Ras along with telomerase activation can cause normal cells to become cancer stem cells. Curcumin may inhibit breast cancer stem cells by preventing epithelial-mesenchymal transition and migration through up-regulation of E-cadherin and β-catenin. Targeting breast cancer stem cells could lead to more effective cancer treatments.
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...Mădălin Margan
This document summarizes research on the molecular profiles of normal human breast tissue and how it may influence breast carcinogenesis. It finds that normal breast tissue is heterogeneous, containing epithelial and non-epithelial cells at different stages of maturation. Stem cells in normal tissue can be classified into subgroups based on cytokeratin expression and regenerative ability. Some studies show molecular abnormalities in histologically normal breast tissue from cancer patients compared to controls, suggesting field cancerization. While the origins of breast cancers are still debated, their development involves genetic mutations in epithelial cells, though the complete mechanisms remain unclear. The molecular mapping of normal breast tissue could help further elucidate the mechanisms of breast carcinogenesis.
Mammary-Type Myofibroblastoma of the Elbow: A Case of a Rare Upper Extremity ...CrimsonPublishersOPROJ
Mammary-Type Myofibroblastoma of the Elbow: A Case of a Rare Upper Extremity Tumor by Randle Ramsey* in Crimson Publishers: Orthopaedic research journals impact factor
The group at UCSF Benioff Children's Hospital is researching epigenetic mechanisms involved in gene expression reprogramming. They have two main projects: 1) studying AID, an enzyme that can demethylate DNA and may play a role in the epithelial-mesenchymal transition (EMT) process linked to cancer metastasis, and 2) characterizing super-enhancers (SEs), clusters of enhancers that regulate genes key to cell identity and cancer, to identify new therapeutic targets. They are also developing a CRISPR-based gene therapy for hemoglobinopathies like sickle cell disease.
Odontogenic ameloblast-associated protein (ODAM) inhibits growth and migratio...Enrique Moreno Gonzalez
The Odontogenic Ameloblast-associated Protein (ODAM) is expressed in a wide range of
normal epithelial, and neoplastic tissues, and we have posited that ODAM serves as a novel
prognostic biomarker for breast cancer and melanoma. Transfection of ODAM into breast
cancer cells yields suppression of cellular growth, motility, and in vivo tumorigenicity.
Herein we have extended these studies to the effects of ODAM on cultured melanoma cell
lines.
1. The document presents a computational model that analyzes gene expression profiles of breast cancer patients to identify intermediate epithelial-mesenchymal transition (EMT) states.
2. The model evaluates patient data and finds some quasi-epithelial and quasi-mesenchymal gene expression patterns with high stability scores, indicating possible intermediate EMT stages.
3. The results confirm previous studies showing that induction of EMT in mammary epithelial cells leads to expression of stem cell markers and properties through acquisition of mesenchymal traits.
Analysis of primary breast tumour stromal cells and their potential role in d...Marion Hartmann
Although malignant epithelial cells are the origin of breast cancer and the main focus of research, evidence is increasing that the tumour microenvironment plays an important role in disease progression. Cellular interactions within the breast cancer microenvironment promote tumour growth, invasion, metastasis and resistance to therapy. Breast tumour stroma consists of various cell types including immunocytes, pericytes, endothelial cells and carcinoma associated fibroblasts. Stromal cells are the predominant cell type in the tumour microenvironment. Tumour stromal cells actively secrete growth factors, chemokines and cytokines that support tumourigenesis. Although the tumour promoting effect of stromal-epithelial interactions is recognized, the precise mechanisms involved are poorly understood. Further characterisation of tumour stromal cells will facilitate elucidation of these interactions.
This document discusses a study to create tissue engineering models of breast cancer metastasis. The researchers will develop 3D scaffolds mimicking adipose and bone tissue with varying stiffness. They will seed metastatic breast cancer cells onto the scaffolds to study changes in gene expression, histology, and markers as the cells metastasize from softer adipose-like scaffolds to stiffer bone-like scaffolds. The goal is to better understand the mechanisms driving breast cancer metastasis in order to develop new prevention and treatment strategies.
Breast cancer stem cells have been identified as tumor-initiating cells that have high expression of CD44 and low/no expression of CD24. They undergo epithelial-mesenchymal transition processes controlled by co-expression of Oct-4 and Nanog. Disruption of pathways like p53 and Ras along with telomerase activation can cause normal cells to become cancer stem cells. Curcumin may inhibit breast cancer stem cells by preventing epithelial-mesenchymal transition and migration through up-regulation of E-cadherin and β-catenin. Targeting breast cancer stem cells could lead to more effective cancer treatments.
Molecular Portrait of the Normal Human Breast Tissue and Its Influence on Bre...Mădălin Margan
This document summarizes research on the molecular profiles of normal human breast tissue and how it may influence breast carcinogenesis. It finds that normal breast tissue is heterogeneous, containing epithelial and non-epithelial cells at different stages of maturation. Stem cells in normal tissue can be classified into subgroups based on cytokeratin expression and regenerative ability. Some studies show molecular abnormalities in histologically normal breast tissue from cancer patients compared to controls, suggesting field cancerization. While the origins of breast cancers are still debated, their development involves genetic mutations in epithelial cells, though the complete mechanisms remain unclear. The molecular mapping of normal breast tissue could help further elucidate the mechanisms of breast carcinogenesis.
Mammary-Type Myofibroblastoma of the Elbow: A Case of a Rare Upper Extremity ...CrimsonPublishersOPROJ
Mammary-Type Myofibroblastoma of the Elbow: A Case of a Rare Upper Extremity Tumor by Randle Ramsey* in Crimson Publishers: Orthopaedic research journals impact factor
This document discusses epithelial-mesenchymal transition (EMT) and its role in cancer metastasis. It summarizes findings from a study using a triple-transgenic mouse model of breast cancer metastasis that found: 1) Primary tumor cells disseminated and formed metastases while maintaining their epithelial phenotype, not undergoing EMT. 2) Inhibiting EMT with miR-200 had no effect on metastasis. 3) Non-EMT tumor cells were sensitive to chemotherapy, whereas mesenchymal cells were resistant. The study provides evidence that EMT may not be required for cancer metastasis in this model.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
MSC CM suppresses epithelial ovarian cancer cells in vitro in a concentration-dependent manner. When ovarian cancer cells were treated with MSC CM at concentrations of 100%, 75%, 50%, and 25% for 72 hours, cell morphology changes were observed including cell shrinkage, debris and reduced cell numbers compared to control. MTT assays showed reduced proliferation and Annexin V testing demonstrated increased early and late apoptosis. Cell cycle analysis found an increased sub-G1 phase, indicating apoptosis. Expression of embryonic stemness genes was also progressively suppressed in cancer cells treated with MSC CM compared to control. Therefore, MSC CM has potential as an ovarian cancer inhibitor by creating new treatment modalities.
Monocytes are part of the myeloid family and play active roles in cancer development and progression. In tumors, monocytes differentiate into tumor-associated macrophages (TAMs) which promote tumor growth, angiogenesis, invasion and metastasis through secretion of various enzymes and cytokines. TAMs represent up to 50% of the tumor mass and are a dominant cell type in the tumor microenvironment. TAMs can be classified into M1 and M2 subtypes, with M2 TAMs contributing to cancer-related inflammation and being key players in the tumor microenvironment. Targeting monocytes and TAMs is a promising approach for cancer immunotherapy.
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.
The document discusses the relationship between obesity, adipokines like leptin, and colorectal cancer risk. In vitro studies show that leptin can induce several hallmarks of cancer in colon epithelial cells, including proliferation, angiogenesis, and evasion of apoptosis. A clinical study found that higher BMI, waist circumference, and leptin levels were associated with increased risk of tubular adenomas in men aged 50-65, suggesting obesity-related factors may promote early colorectal tumorigenesis. The authors conclude that for obese individuals with elevated adipokines, the recommended age for first colonoscopy may need to be lowered.
Changes in Melatonin Biorhythms and Immune-Neuroendocrine Interactions in Onc...CrimsonPublishersGGS
Changes in Melatonin Biorhythms and Immune-Neuroendocrine Interactions in Oncological Patients of Different Age by Labunets Irina F in Gerontology Journal
This study analyzed the mitochondrial morphology of three breast cell lines - HTB-125 (non-tumorigenic), HTB-126 (invasive ductal carcinoma), and HTB-22 (adenocarcinoma). The results showed HTB-22 exhibited the shortest mitochondrial length, indicating a pro-fission phenotype, while HTB-126 did not differ significantly from HTB-125. This suggests alterations in mitochondrial dynamics may influence the tumorigenesis of HTB-22 cells but not HTB-126 cells. Future studies will examine apoptotic signaling pathways controlled by the fission protein Drp1 in HTB-22 cells.
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.
Cancer is one of the leading causes of death in developed countries. The glioblastoma is the most aggressive type of brain tumor. Serglycin (SG) is an intracellular proteoglycan that regulates the storage and activity of inflammatory mediators and bioactive molecules in secretory vesicles. Studies have shown SG is overexpressed in several cancer cell lines and promotes an aggressive phenotype. The thesis studied the effect of suppressing the SG gene in highly metastatic brain cancer cells LN-18. The results revealed that suppressing SG reduced cell proliferation, mobility, and expression of bioactive molecules in the extracellular matrix.
Overweight and obesity can influence different stages of cancer development from initiation to progression. Adipose tissue surrounding tumors, known as tumour-associated adipocytes, can promote cancer progression through secretion of inflammatory molecules like IL-6. This pro-inflammatory environment in adipose tissue is amplified in obesity. Cancer-associated adipocytes undergo changes including delipidation and acquisition of an inflammatory phenotype. They stimulate tumor cell invasion and metastasis through paracrine signaling involving IL-6 and other factors. This cross-talk between tumor cells and adipocytes contributes to poor prognosis in cancers like breast and prostate cancer.
Macrophage polarization by HRG and its effects on TumorAshish Bihani
Macrophages in tumors normally exhibit an M2 phenotype that promotes angiogenesis and tumor growth. Histidine-rich glycoprotein (HRG) can repolarize these tumor-associated macrophages (TAMs) to an M1 phenotype by blocking Fcγ receptors and downregulating placental growth factor (PIGF). This skews TAMs away from M2-like and induces them to secrete factors that normalize tumor vasculature, reduce hypoxia, and increase anti-tumor immunity. As a result, HRG treatment decreases tumor growth and metastasis by reeducating TAMs and improving delivery of chemotherapy through normalized vessels.
This document discusses several topics related to gene regulation and transcription factors. It summarizes research that found mutations accumulating in gene regulatory elements in colorectal cancer samples. While transcription factors like CTCF and cohesins were generally protected from mutations, tumors with more CTCF site mutations tended to have more mutations throughout their genomes. Another study identified a new structural role for the ATF5 protein in cell division within the centrosome, in addition to its role regulating gene expression. Failure of centrosome duplication can lead to issues with cell division and conditions like cancer. Understanding these transcription factors and their roles is important for learning about disease mechanisms and developing treatments.
This document summarizes a presentation on weight loss and cancer risk reduction. It discusses how weight gain increases cancer risk, and how modest weight loss through dietary interventions can reduce cancer risk. Clinical trials show intermittent energy restriction may be more effective for weight loss and insulin reduction than daily energy restriction. Weight loss interventions are also discussed after a cancer diagnosis, though randomized trials are still needed. The presentation concludes by discussing targeting overweight individuals for weight loss interventions to reduce cancer risk.
Diagnostic Biomarker Candidates Including NT5DC2 for Human Uterine Mesenchyma...YogeshIJTSRD
Unfortunately, uterine leiomyosarcoma still has a poor prognosis. The National Cancer Institute reported that the median overall survival mOS at stage I to stage IV of leiomyosarcoma was 31 months. Takuma Hayashi | Kenji Sano | Tomoyuki Ichimura | Susumu Tonegawa | Nobuo Yaegashi | Ikuo Konishi "Diagnostic Biomarker Candidates Including NT5DC2 for Human Uterine Mesenchymal Tumors" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-3 , April 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38686.pdf Paper URL: https://www.ijtsrd.com/medicine/other/38686/diagnostic-biomarker-candidates-including-nt5dc2-for-human-uterine-mesenchymal-tumors/takuma-hayashi
This proposal outlines a thesis project to investigate the role of chemokines CCL19b and CCL25b in recruiting T cells into melanoma tumors. The student hypothesizes that inducing expression of these chemokines in melanoma cell lines transplanted into an animal model will increase T cell recruitment and reduce tumor burden. The proposal provides background on melanoma, the immune system response to tumors, and current immunotherapy strategies including adoptive T cell transfer and immune checkpoint inhibitors. If successful, the research could provide a new treatment option or complement existing therapies to improve patient survival rates.
Overweight and obesity are associated with worse cancer outcomes and prognosis. Adipose tissue surrounding tumors, called cancer-associated adipocytes, secrete inflammatory molecules like IL-6 that can promote tumor growth, invasion, and metastasis. In obese conditions, adipose tissue develops a pro-inflammatory state characterized by immune cell infiltration and cytokine expression. This inflamed environment may further enhance cancer-associated adipocytes' effects on tumor progression. Targeting inflammation in adipose tissue, such as with IL-6 blocking antibodies, could potentially improve cancer treatment outcomes, especially in obese patients where adipose tissue inflammation is increased.
Cancer results from a series of molecular events that fundamentally alter the normal properties of cells. In cancer cells the normal control systems that prevent cell overgrowth and the invasion of other tissues are disabled.
Histopathological Patterns of Germ Cell Tumours of Ovary in a Tertiary Level ...inventionjournals
This document summarizes research on histopathological patterns of germ cell tumors of the ovary. The study found that benign cystic teratomas (dermoid cysts) made up the highest percentage at 26.47%, followed by dysgerminoma at 1.96%, immature teratoma at 0.98%, and yolk sac tumor at 0.98%. Germ cell tumors are more common in younger patients and can be benign or malignant. The histopathological patterns and characteristics of various germ cell tumors are described, including dysgerminoma, yolk sac tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, and teratomas. Tumor markers such
Macrophage polarization refers to the process by which macrophages diversify and take on different phenotypes in response to signals from the tumor microenvironment. The two main polarization states are M1 and M2 macrophages. M1 macrophages have anti-tumor properties while M2 macrophages, also known as tumor-associated macrophages (TAMs), promote tumor progression. TAMs influence processes like angiogenesis, immune suppression, tumor growth, metastasis, and chemotherapy resistance. Targeting TAMs is a promising strategy for cancer treatment, and several drugs aim to reprogram TAMs from the M2 phenotype to the M1 phenotype or directly kill M2 macrophages.
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
The document describes a case study of an 18-year-old female patient who developed toxic epidermal necrolysis as a severe adverse reaction to the drug sulfasalazine, which she had been taking for ankylosing spondylitis. She was admitted to the intensive care unit and treated with high dose corticosteroids, fluid replacement, and supportive care. She improved with treatment and was discharged with only post-inflammatory hypopigmentation.
The Comprehensive Review on Fat Soluble Vitaminsiosrphr_editor
This review article deals with brief description of fat soluble vitamins with figures and tables
showing statistical analytical data duly quoting the references wherever necessary. The word “soluble” actually
means “able to be dissolved.” Whether a vitamin is classified as 'fat-soluble' or 'water-soluble' has to do with
how the vitamin is absorbed, stored and removed from the body. Vitamins are tiny organic compounds with a
huge impact on the health and well-being of the body. The body needs a small amount of fat soluble vitamins in
order to stay in optimal health. Fat soluble vitamins play an important role in keeping the body healthy and
functioning from immune system and muscle and heart function, easy flow and clotting of blood as well as eye
health. They are critical to health and wellness–particularly reproductive health and wellness. Low-fat, no-fat
and vegan diets are woefully lacking in fat soluble vitamins. However a diet based on traditional foods can
naturally provide these vitamins. Science is still learning about many of the functions of vitamins. "Too much
vitamin A, D, or K can lead to increased levels that are unhealthy and can cause serious health consequences.
Diseased conditions leading to decreased fat absorption leads to decreased absorption of vitamins. The fatsoluble
vitamins work most safely and effectively when obtained them from natural foods within the context of a
diet rich in all their synergistic partners. If fat soluble vitamins are stored for lengthy time they generate threat
for toxicity than water soluble vitamins and such situation even aggravated, provided they are consumed in
excess. Vitamin products, above the legal limits are not considered food supplements and must be registered as
prescription or non-prescription (over-the-counter drugs) due to their potential side effects. Vitamin A and E
supplements do not provide health benefits for healthy individuals, instead they may enhance mortality, and it is
held proved that beta-carotene supplements can be harmful to smokers
This document discusses epithelial-mesenchymal transition (EMT) and its role in cancer metastasis. It summarizes findings from a study using a triple-transgenic mouse model of breast cancer metastasis that found: 1) Primary tumor cells disseminated and formed metastases while maintaining their epithelial phenotype, not undergoing EMT. 2) Inhibiting EMT with miR-200 had no effect on metastasis. 3) Non-EMT tumor cells were sensitive to chemotherapy, whereas mesenchymal cells were resistant. The study provides evidence that EMT may not be required for cancer metastasis in this model.
Cord Blood Mesenchymal Stem Cells Conditioned Media Suppress Epithelial Ovari...ijtsrd
MSC CM suppresses epithelial ovarian cancer cells in vitro in a concentration-dependent manner. When ovarian cancer cells were treated with MSC CM at concentrations of 100%, 75%, 50%, and 25% for 72 hours, cell morphology changes were observed including cell shrinkage, debris and reduced cell numbers compared to control. MTT assays showed reduced proliferation and Annexin V testing demonstrated increased early and late apoptosis. Cell cycle analysis found an increased sub-G1 phase, indicating apoptosis. Expression of embryonic stemness genes was also progressively suppressed in cancer cells treated with MSC CM compared to control. Therefore, MSC CM has potential as an ovarian cancer inhibitor by creating new treatment modalities.
Monocytes are part of the myeloid family and play active roles in cancer development and progression. In tumors, monocytes differentiate into tumor-associated macrophages (TAMs) which promote tumor growth, angiogenesis, invasion and metastasis through secretion of various enzymes and cytokines. TAMs represent up to 50% of the tumor mass and are a dominant cell type in the tumor microenvironment. TAMs can be classified into M1 and M2 subtypes, with M2 TAMs contributing to cancer-related inflammation and being key players in the tumor microenvironment. Targeting monocytes and TAMs is a promising approach for cancer immunotherapy.
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.
The document discusses the relationship between obesity, adipokines like leptin, and colorectal cancer risk. In vitro studies show that leptin can induce several hallmarks of cancer in colon epithelial cells, including proliferation, angiogenesis, and evasion of apoptosis. A clinical study found that higher BMI, waist circumference, and leptin levels were associated with increased risk of tubular adenomas in men aged 50-65, suggesting obesity-related factors may promote early colorectal tumorigenesis. The authors conclude that for obese individuals with elevated adipokines, the recommended age for first colonoscopy may need to be lowered.
Changes in Melatonin Biorhythms and Immune-Neuroendocrine Interactions in Onc...CrimsonPublishersGGS
Changes in Melatonin Biorhythms and Immune-Neuroendocrine Interactions in Oncological Patients of Different Age by Labunets Irina F in Gerontology Journal
This study analyzed the mitochondrial morphology of three breast cell lines - HTB-125 (non-tumorigenic), HTB-126 (invasive ductal carcinoma), and HTB-22 (adenocarcinoma). The results showed HTB-22 exhibited the shortest mitochondrial length, indicating a pro-fission phenotype, while HTB-126 did not differ significantly from HTB-125. This suggests alterations in mitochondrial dynamics may influence the tumorigenesis of HTB-22 cells but not HTB-126 cells. Future studies will examine apoptotic signaling pathways controlled by the fission protein Drp1 in HTB-22 cells.
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.
Cancer is one of the leading causes of death in developed countries. The glioblastoma is the most aggressive type of brain tumor. Serglycin (SG) is an intracellular proteoglycan that regulates the storage and activity of inflammatory mediators and bioactive molecules in secretory vesicles. Studies have shown SG is overexpressed in several cancer cell lines and promotes an aggressive phenotype. The thesis studied the effect of suppressing the SG gene in highly metastatic brain cancer cells LN-18. The results revealed that suppressing SG reduced cell proliferation, mobility, and expression of bioactive molecules in the extracellular matrix.
Overweight and obesity can influence different stages of cancer development from initiation to progression. Adipose tissue surrounding tumors, known as tumour-associated adipocytes, can promote cancer progression through secretion of inflammatory molecules like IL-6. This pro-inflammatory environment in adipose tissue is amplified in obesity. Cancer-associated adipocytes undergo changes including delipidation and acquisition of an inflammatory phenotype. They stimulate tumor cell invasion and metastasis through paracrine signaling involving IL-6 and other factors. This cross-talk between tumor cells and adipocytes contributes to poor prognosis in cancers like breast and prostate cancer.
Macrophage polarization by HRG and its effects on TumorAshish Bihani
Macrophages in tumors normally exhibit an M2 phenotype that promotes angiogenesis and tumor growth. Histidine-rich glycoprotein (HRG) can repolarize these tumor-associated macrophages (TAMs) to an M1 phenotype by blocking Fcγ receptors and downregulating placental growth factor (PIGF). This skews TAMs away from M2-like and induces them to secrete factors that normalize tumor vasculature, reduce hypoxia, and increase anti-tumor immunity. As a result, HRG treatment decreases tumor growth and metastasis by reeducating TAMs and improving delivery of chemotherapy through normalized vessels.
This document discusses several topics related to gene regulation and transcription factors. It summarizes research that found mutations accumulating in gene regulatory elements in colorectal cancer samples. While transcription factors like CTCF and cohesins were generally protected from mutations, tumors with more CTCF site mutations tended to have more mutations throughout their genomes. Another study identified a new structural role for the ATF5 protein in cell division within the centrosome, in addition to its role regulating gene expression. Failure of centrosome duplication can lead to issues with cell division and conditions like cancer. Understanding these transcription factors and their roles is important for learning about disease mechanisms and developing treatments.
This document summarizes a presentation on weight loss and cancer risk reduction. It discusses how weight gain increases cancer risk, and how modest weight loss through dietary interventions can reduce cancer risk. Clinical trials show intermittent energy restriction may be more effective for weight loss and insulin reduction than daily energy restriction. Weight loss interventions are also discussed after a cancer diagnosis, though randomized trials are still needed. The presentation concludes by discussing targeting overweight individuals for weight loss interventions to reduce cancer risk.
Diagnostic Biomarker Candidates Including NT5DC2 for Human Uterine Mesenchyma...YogeshIJTSRD
Unfortunately, uterine leiomyosarcoma still has a poor prognosis. The National Cancer Institute reported that the median overall survival mOS at stage I to stage IV of leiomyosarcoma was 31 months. Takuma Hayashi | Kenji Sano | Tomoyuki Ichimura | Susumu Tonegawa | Nobuo Yaegashi | Ikuo Konishi "Diagnostic Biomarker Candidates Including NT5DC2 for Human Uterine Mesenchymal Tumors" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-3 , April 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38686.pdf Paper URL: https://www.ijtsrd.com/medicine/other/38686/diagnostic-biomarker-candidates-including-nt5dc2-for-human-uterine-mesenchymal-tumors/takuma-hayashi
This proposal outlines a thesis project to investigate the role of chemokines CCL19b and CCL25b in recruiting T cells into melanoma tumors. The student hypothesizes that inducing expression of these chemokines in melanoma cell lines transplanted into an animal model will increase T cell recruitment and reduce tumor burden. The proposal provides background on melanoma, the immune system response to tumors, and current immunotherapy strategies including adoptive T cell transfer and immune checkpoint inhibitors. If successful, the research could provide a new treatment option or complement existing therapies to improve patient survival rates.
Overweight and obesity are associated with worse cancer outcomes and prognosis. Adipose tissue surrounding tumors, called cancer-associated adipocytes, secrete inflammatory molecules like IL-6 that can promote tumor growth, invasion, and metastasis. In obese conditions, adipose tissue develops a pro-inflammatory state characterized by immune cell infiltration and cytokine expression. This inflamed environment may further enhance cancer-associated adipocytes' effects on tumor progression. Targeting inflammation in adipose tissue, such as with IL-6 blocking antibodies, could potentially improve cancer treatment outcomes, especially in obese patients where adipose tissue inflammation is increased.
Cancer results from a series of molecular events that fundamentally alter the normal properties of cells. In cancer cells the normal control systems that prevent cell overgrowth and the invasion of other tissues are disabled.
Histopathological Patterns of Germ Cell Tumours of Ovary in a Tertiary Level ...inventionjournals
This document summarizes research on histopathological patterns of germ cell tumors of the ovary. The study found that benign cystic teratomas (dermoid cysts) made up the highest percentage at 26.47%, followed by dysgerminoma at 1.96%, immature teratoma at 0.98%, and yolk sac tumor at 0.98%. Germ cell tumors are more common in younger patients and can be benign or malignant. The histopathological patterns and characteristics of various germ cell tumors are described, including dysgerminoma, yolk sac tumor, embryonal carcinoma, polyembryoma, choriocarcinoma, and teratomas. Tumor markers such
Macrophage polarization refers to the process by which macrophages diversify and take on different phenotypes in response to signals from the tumor microenvironment. The two main polarization states are M1 and M2 macrophages. M1 macrophages have anti-tumor properties while M2 macrophages, also known as tumor-associated macrophages (TAMs), promote tumor progression. TAMs influence processes like angiogenesis, immune suppression, tumor growth, metastasis, and chemotherapy resistance. Targeting TAMs is a promising strategy for cancer treatment, and several drugs aim to reprogram TAMs from the M2 phenotype to the M1 phenotype or directly kill M2 macrophages.
Sulphasalazine Induced Toxic Epidermal Necrolysis A Case Reportiosrphr_editor
The document describes a case study of an 18-year-old female patient who developed toxic epidermal necrolysis as a severe adverse reaction to the drug sulfasalazine, which she had been taking for ankylosing spondylitis. She was admitted to the intensive care unit and treated with high dose corticosteroids, fluid replacement, and supportive care. She improved with treatment and was discharged with only post-inflammatory hypopigmentation.
The Comprehensive Review on Fat Soluble Vitaminsiosrphr_editor
This review article deals with brief description of fat soluble vitamins with figures and tables
showing statistical analytical data duly quoting the references wherever necessary. The word “soluble” actually
means “able to be dissolved.” Whether a vitamin is classified as 'fat-soluble' or 'water-soluble' has to do with
how the vitamin is absorbed, stored and removed from the body. Vitamins are tiny organic compounds with a
huge impact on the health and well-being of the body. The body needs a small amount of fat soluble vitamins in
order to stay in optimal health. Fat soluble vitamins play an important role in keeping the body healthy and
functioning from immune system and muscle and heart function, easy flow and clotting of blood as well as eye
health. They are critical to health and wellness–particularly reproductive health and wellness. Low-fat, no-fat
and vegan diets are woefully lacking in fat soluble vitamins. However a diet based on traditional foods can
naturally provide these vitamins. Science is still learning about many of the functions of vitamins. "Too much
vitamin A, D, or K can lead to increased levels that are unhealthy and can cause serious health consequences.
Diseased conditions leading to decreased fat absorption leads to decreased absorption of vitamins. The fatsoluble
vitamins work most safely and effectively when obtained them from natural foods within the context of a
diet rich in all their synergistic partners. If fat soluble vitamins are stored for lengthy time they generate threat
for toxicity than water soluble vitamins and such situation even aggravated, provided they are consumed in
excess. Vitamin products, above the legal limits are not considered food supplements and must be registered as
prescription or non-prescription (over-the-counter drugs) due to their potential side effects. Vitamin A and E
supplements do not provide health benefits for healthy individuals, instead they may enhance mortality, and it is
held proved that beta-carotene supplements can be harmful to smokers
Chest sonography images in neonatal r.d.s. And proposed gradingiosrphr_editor
BACKGROUND : Lung sonography has been used to monitor the patients of R.D.S. in
N.I.C.U. in recent times.
AIMS : To Describe and Grade the changes of R.D.S. by lung sonography.
SETTING & DESIGN : Tertiary care institutional set up in a rural medical college.
STUDY DURATION : September 2014 to May 2015. Follow-up variable, upto 2 weeks.
PROSPECTIVE, ANALYTICAL STUDY.
MATERIALS AND METHODS -This was a single institute study approved by the institutional ethics
committee. Prior informed consent was obtained from the parents. 100 consecutive patients admitted in
N.I.C.U. WITH gestational age < 36 weeks with respiratory complaints were enrolled. Chest x-ray was
obtained within few hours of admission and lung sonography was performed within 24 hours. Follow – up
sonography was performed as and when necessary. Sonography image was graded and correlated with chest
xray and clinical picture
Correlation of Estrogen and Progesterone Receptor expression in Breast Canceriosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Analytical Study of Urine Samples for Epidemiology of Urinary Tract Infection...iosrphr_editor
The current study was carried out in District Abbottabad aimed to determine the common urinary
tract infections in local community to determine the epidemiology of significant diseases in asymptomatic patients
of renal disorder. In this study a total of 1000 urine samples were examined during 3rd February to 1st April 2015
from patients attending Ayub Teaching Hospital Abbottabad by using dipstick and microscopic analysis of urine.
There were 638 females and 362 males patients examined during this period. The range of age groups is between
1.5 years to 80 years. Results of this study was reported as Pyuria 11%, Proteinuria 21.1%, Hematuria 10.4%,
Epithelial Cells 8.2%, pH 7.8 %, Granular casts 7.3%, Triple phosphate 6.6%, Calcium oxalate 6.4%, Glycosuria
6.3%, Bacteria 6.2% and mucous 4.1%. This study concludes that routing urinalysis should be performed for all
individuals to diagnose the asymptomatic diseases that will help in simple therapeutic measurements as urinalysis
is a simple step to determine the root of Urinary tract disorders.
“Hemodynamic and recovery profile with Dexmedetomidine and Fentanyl in intrac...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Potential Diagnostic Biomarkers for Human Uterine Mesenchymal Tumours Especia...ijtsrd
Aims Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone however, the development of human uterine leiomyosarcoma is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign tumor leiomyoma is yet to be established. It is necessary to analyze risk factors associated with human uterine leiomyosarcoma, in order to establish a diagnostic biomarker and a clinical treatment method. Methodology Histology and Immunofluorescence Staining tissue sections 5 µm were prepared and stained with HandE for routine histological examination or were processed further for immunofluorescence staining with appropriate antibodies. Furthermore, a total of 57 patients between 32 and 83 years of age and diagnosed as having smooth muscle tumors of the uterus were selected from pathological files. Immunohistochemistry staining for LMP2 1i and cyclin E1 was performed on serial human uterine leiomyosarcoma, leiomyoma and myometrium sections. Results Homozygous deficient mice for a proteasome subunit LMP2 1i spontaneously develop uterine leiomyosarcoma, with a disease prevalence of ~40 by 14 months of age. Defective LMP2 1i and cyclin E1 positive expressions in human uterine leiomyosarcoma were demonstrated, but the reverse result was obtained in human leiomyoma and myometrium. Conclusions LMP2 1i and cyclin E1 differential expressions may be one of the risk factors for human uterine leiomyosarcoma. LMP2 1i and cyclin E1 may be potential diagnostic biomarker and targeted molecule for a new therapeutic approach. Takuma Hayashi | Hiroyuki Aburatani | Ikuo Konishi "Potential Diagnostic Biomarkers for Human Uterine Mesenchymal Tumours: Especially LMP2/1i and Cyclin E1-Differential Expressions" 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/ijtsrd62380.pdf Paper Url: https://www.ijtsrd.com/medicine/other/62380/potential-diagnostic-biomarkers-for-human-uterine-mesenchymal-tumours-especially-lmp21i-and-cyclin-e1differential-expressions/takuma-hayashi
Physiological Functions of LMP2 B1i in the Female Reproductive Systemijtsrd
This document summarizes research on the physiological functions of LMP2/β1i in the female reproductive system. It discusses how LMP2/β1i is involved in embryo implantation by regulating trophoblast cell invasion and extracellular matrix degradation through modulation of MMP expression. It also reports that LMP2/β1i deficient mice exhibit uterine neoplasms, and overexpression of LMP2/β1i in trophoblast cells of hydatidiform moles contributes to their highly invasive phenotype. The document further examines the role of LMP2/β1i in preventing spontaneous transformation of uterine mesenchymal cells into tumors.
This document summarizes a research article that discusses genetic polymorphisms of matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in potentially malignant and malignant head and neck lesions. It describes how MMPs degrade the extracellular matrix, a key event in tumor progression and metastasis. It reviews the classification of MMPs and their substrates. It also discusses how MMPs and TIMPs are regulated and expresses polymorphisms that may be associated with cancer susceptibility and prognosis.
TUMOR MICROENVIORNMENT IN HEAD AND NECK CANCER.pptxRhythmKarir
The document summarizes research on the effect of the tumor microenvironment on head and neck cancer. It finds that the microenvironment, composed of cells like cancer-associated fibroblasts and tumor-associated macrophages, plays a key role in tumor progression by modifying the environment to support cancer cell growth, invasion, and metastasis. While past research focused on genetic changes in cancer cells, current evidence indicates the microenvironment contributes substantially to head and neck cancer development and differences in the microenvironment may help explain variations in therapeutic responses.
Overview of Pediatrics Malignancies Essay.docx4934bk
1) The document provides an overview of pediatric malignancies, discussing topics like leukemia, lymphomas, brain tumors, Wilms' tumor, soft tissue sarcomas, and germ cell tumors.
2) It describes the different types of leukemia seen in children, including acute lymphoblastic leukemia (ALL), which accounts for 80-90% of childhood leukemias.
3) The document also discusses lymphomas, brain tumors, Wilms' tumor, rhabdomyosarcoma, retinoblastoma, and germ cell tumors in children, and provides survival rates for some pediatric cancers.
This research article characterizes cancer stem cells derived from MYCN-dependent medulloblastoma (MB), a type of pediatric brain tumor. The researchers established tumor-derived neurosphere cell lines from a genetically engineered mouse model of MB driven by MYCN overexpression. They found that a fraction of these neurospheres were growth factor independent, expressed the stem cell marker CD133, failed to differentiate when MYCN was withdrawn, and were highly tumorigenic when implanted in mouse brains. Treatment with an aurora kinase inhibitor that degrades MYCN extended survival in mice with MB allografts, suggesting it may convert the cancer stem cells to a less aggressive state. The study demonstrates MYCN plays a critical role in expansion and
The pathogenesis of NF1 is complex and involves interrelationships between various elements that manifest at different ages. Café-au-lait spots typically appear in the first year of life, while NF2 vestibular schwannomas usually develop later in the third decade. Symptoms of Schwannomatosis also appear later in life and are non-specific, like pain. Understanding how clinical signs relate to a person's age can help with healthcare and provide insights into pathogenesis. In some cases, genetic analysis may help with diagnosis when clinical symptoms are unclear. Somatic mosaicism can also contribute to limited signs and symptoms.
This document summarizes research on macrophages and immune responses in uterine fibroids. It discusses how uterine fibroids are a typical fibrotic disorder involving excessive extracellular matrix proteins. A proposed model is that fibroid formation results from excessive wound healing driven by dysregulated inflammation. Macrophages play a role in the inflammatory response and tissue repair process, and their dysregulation can lead to uncontrolled tissue repair and pathological fibrosis. Molecules like MCP-1, GM-CSF, TGF-β, activin A and TNF-α are demonstrated to be important for macrophage action and the uncontrolled tissue repair that contributes to fibrosis in uterine fibroids.
Advances and Problems in Preclinical Models for Childhood Cancerijtsrd
Microblogging today has gotten an acclaimed specific instrument among Neuroblastoma is a sympathetic nervous system disease in children and is the most prevalent solid tumor in childhood, accounting for 15 of all pediatric oncology deaths. Nearly 80 of patients with this clinically active condition do not react to current treatments in the long run. The precise portrayal of tumor biology and diversity is the key obstacle in the discovery and evaluation of novel agents for pediatric drug growth. In addition to this restriction, the low prevalence of neuroblastoma renders it difficult to enroll qualifying patients for early phase clinical trials, emphasizing the importance of thorough preclinical studies to ensure that the right drugs are chosen. To address these issues, researchers need new preclinical models, technologies, and principles. Tissue engineering provides appealing methods for developing three dimensional 3D cell models utilizing different biomaterials and manufacturing techniques that replicate the geometry, dynamics, heterogeneity, metabolic gradients, and cell connectivity of the native tumor microenvironment. We address existing laboratory models and evaluate their ability to reflect the systemic organization and physiological conditions of the human body, as well as current and emerging strategies to recapitulate the tumor niche utilizing tissue engineered platforms in this study. Finally, well talk about how innovative 3Din vitroculture systems might be used to answer unanswered questions in neuroblastoma biology. V. Sah "Advances and Problems in Preclinical Models for Childhood Cancer" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-4 , June 2021, URL: https://www.ijtsrd.compapers/ijtsrd42379.pdf Paper URL: https://www.ijtsrd.combiological-science/neurobiology/42379/advances-and-problems-in-preclinical-models-for-childhood-cancer/v-sah
describe the tumor suppressor genes and examples for downloading the presentation, more presentations , infographics and blogs visit :
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Molecular studies of cells are leading to discover the more complex structure and function of tissues, and how this intervenes in the pathophysiology of diseases. During years scientists have made a laborious job to understand the origin of diseases that in our society are being more prevalent than some decades ago, such as cancer and congenital malformations
Kirchhoff & Zollner_EOTT_Mast cells & endometriosisThomas M. Zollner
1. Mast cells (MCs) may play a key role in the chronic inflammation associated with endometriosis (EMS), an estrogen-dependent inflammatory disease. High numbers of activated MCs have been found near endometriotic lesions.
2. MCs can release various pro-inflammatory cytokines, chemokines, and growth factors that may contribute to EMS pathogenesis by recruiting and activating other immune cells involved in EMS. They may also sensitize nerve fibers, contributing to pelvic pain in EMS patients.
3. Recent evidence suggests MCs in EMS lesions may be activated through Toll-like receptors by damage-associated molecular patterns from retrograde menstruation, or stimulated by local estrogen production
Cancer is uncontrolled cell growth that can lead to tumor formation and be either benign or malignant. It will affect 1 in 3 people during their lifetime. Increased life expectancy and modern lifestyles contribute to higher cancer rates, which are expected to increase by 50% to 15 million new cases annually by 2020 according to a global report. Prevention through healthy lifestyle choices and public health action could reduce cancer incidence by a third worldwide.
Cytokine Immunotherapy: A Forthcoming Visible Feature in Cancer TherapeuticsSachin K. S. Chauhan
The document discusses cytokine immunotherapy as a promising approach for cancer treatment. It notes that cytokines can stimulate the immune system to fight tumors, but that mono-cytokine therapy has limitations. Combined cytokine therapy or cytokine therapy combined with other treatments may be more effective by creating a specific immune response. The document advocates focusing research on combination therapies to help overcome drawbacks of traditional cancer treatments.
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
Similar to IOSR Journal of Pharmacy (IOSRPHR) (16)
Congenital Agenesis Of The Corpus Callosum With Intracerebral Lipoma And Fron...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Evaluation the efficacy of IVIgG in treatment of Hemolytic Disease of Newborniosrphr_editor
Hemolytic disease of newborn (HDN) is an important cause of hyperbilirubinemia in the
neonatal period,and delayed diagnosis and treatment may lead to permanent brain damage. Traditional
neonatal treatment of HDN is intensive phototherapy and exchange transfusion.Intravenous
immunoglobulin(IVIgG) has been introduced as an alternative therapy to exchange transfusion. This study was
conducted to assess the effect of IVIG in HDN .
FIBROLIPOMATOUS HAMARTOMA OF ULNAR NERVE: A RARE CASE REPORT.iosrphr_editor
Nervous fibrolipomatous hamartoma is said to be a rare tumor-like condition involving the peripheral
nerves,in which the epineurium and perineurium are enlarged and distorted by excess of fatty and fibrous tissue
s that infiltrate between and around nerve boundaries. The median nerve is more likely to develop a hamartoma
than other nerves with a predilection for the carpal tunnel.
A fibrolipomatous hamartoma – is a rare, benign, congenital lesion most commonly found in the median nerve,
usually at the level of the wrist or hand.
We report a case of this rare condition in ulnar nerve.
SELF MEDICATION PRACTICES FOR ORAL HEALTH PROBLEMS AMONG DENTAL PATIENTS IN B...iosrphr_editor
This study examined self-medication practices for oral health problems among dental patients in Bangalore, India. The study found that 100% of the 175 dental patients surveyed practiced self-medication. Toothache was the most common triggering factor reported. Analgesics and herbal remedies were commonly used for self-treatment. Most participants consulted pharmacists for advice on self-medication and would see a dentist only if problems persisted after self-medicating. The high prevalence of self-medication indicates a need for education programs to increase awareness of risks.
Clinico-haematological Profile of Falciparum Malaria in a Rural Hospital of T...iosrphr_editor
Aim: To study the clinico-haematological profile malaria in a rural hospital of Tripura.
Material and methods: A cross-sectional hospital-based study was done from at Kulai District
Hospital,Tripura. This hospital based cross sectional study was done on 60 confirmed cases of falciparum
malaria (either by peripheral smear or rapid diagnostic test) admitted in Kulai District Hospital. A case sheet
proforma was prepared and data (demographic profile,clinical feature, investigation, treatment, and
complication) from all indoor patients was collected and analyzed.
Result: Out of 60 patients, 40(66.6%) were males and 20 (33.4%) were females. Most of the patients were
between the age group 21-40 years with the highest prevalence between the age group of 21-30. Fever was the
most common symptom. Anemia was present in 42(70%) patients, out of which 6(10%) patients had severe
anemia. Thrombocytopenia was present in 36(60%) patients.Abnormal liver function tests were observed in
26(43.3%) subjects while abnormal kidney function tests were observed in16(26.6%) patients. All the 60
patients received Artemisinin based antimalarial drugs.
Conclusion: Early detection, prompt management, and adequate supportive therapy may reduce mortality due
to falciparum cerebral malaria.
Indonesian Wild Ginger (Zingiber sp) Extract: Antibacterial Activity against ...iosrphr_editor
The document summarizes a study that tested the antibacterial activity of extracts from three species of wild ginger plants from Indonesia (Zingiber zerumbet, Zingiber amaricans, and Zingiber aromaticum) against Mycoplasma gallisepticum, a pathogen that causes respiratory disease in chickens. Phytochemical analysis revealed the presence of alkaloids, flavonoids, tannins, and terpenoids in the plant extracts. Disc diffusion and minimum inhibitory concentration assays showed that ethanol extracts of dried rhizomes had the strongest inhibitory effects against the pathogen, with minimum inhibitory concentrations ranging from 7.8 to 31.2 mg/ml. The results suggest that extracts from these wild ginger plants
A case of allergy and food sensitivity: the nasunin, natural color of eggplantiosrphr_editor
Abstract: Allergies and food sensitivities can both be considered as "adverse reactions individualistic" to food.
Are pathological and individual forms because they affect a few individuals in way rather serious; immediate
or delayed reactions occur instead with simple effects histamine, or, in severe cases with respiratory and
anaphylactic shock
The eggplant (Solanum melongena L.) is known to cause food allergies in some Asian countries, but detailed
studies on allergies caused by eggplant are lacking, however, it was highlighted the presence of allergens in
edible parts of eggplant with preponderance in the peel .
The purpose of this study was to propose an extraction method rapid, efficient and cost of natural dye from
waste products from the food industry, such as the peels of eggplant, from which it was extracted, isolated and
purified the nasunin,a colored molecule in red-fuchsia.
Nasusin was tested on 58 patients to evaluate the potential sensitizing effect on the skin. The results demonstrate
that allergenic effects are negligible and therefore the nasunin can be used as a colorant in various industrial
sectors with a certain safety margin
Complete NMR Assignment of MogrosidesII A2, II E andIII A1Isolated from Luo H...iosrphr_editor
NMR analysis allowed complete assignments of three known mogrol glycosides, Mogroside IIA2 (1),
II E (2)and IIIA1 (3), isolated from the extracts of Luo Han Guo. Herein, complete 1H and 13C NMR
assignmentsof all threemogrosidesare described based on NMR experiments (1H NMR, 13C NMR, COSY,
HSQC-DEPT, HMBC, NOESY and 1DTOCSY) and mass spectral data.
Nanoemulsion and Nanoemulgel as a Topical Formulationiosrphr_editor
: Nanoemulsion is referred type of emulsion with uniform and extremely small droplet size in the range
of 20-200 nm. Nanoemulsion provides numerous advantages over other carrier such as polymeric nanoparticle
and liposomes, including low cost preparation procedure, high hydrophilic and lipophilic drug loading system
to enhance the longer shelf live upon preserving the therapeutic agents. Incorporating the preparation of
nanoemulsion with hydrogel matrix to produce nanoemulgel exhibited by the two separate systems that forming
it. Nanoemulgel possesses the properties of thixotropic, non-greasy, effortlessly spreadable, easily be removed,
emollient, not staining, soluble in water, longer shelf life, bio-friendly, translucent and agreeable appearance.
Pharmacokinetics of High-Dose Methotrexate in Egyptian Children with Acute Ly...iosrphr_editor
Aim:Since several factors have been shown to influence the clearance of methotrexate, the purpose of this study
was to identify potential relationships between patient covariates and the methotrexate clearance estimates and
deduce a pharmacokinetic model for the estimation of methotrexate clearance in Egyptian pediatric ALL
patients that may help dosage adjustment and achieve target steady-state plasma concentrations in a similar
sittings.
Patients and methods: A total of 94 pediatric patients with B-cell ALL, of whom 70 were the studied population
and 24 were the test population, were treated with four courses of HDMTX doses 2.5 gm/m2
(low-risk arm) or 5
gm/m2
(standard-/high-risk arm) given every other week by intermittent intravenous infusions over 24 hours as
a part of their treatment protocol. Patients were monitored for the 24 hour MTX concentration and the systemic
methotrexate clearance was calculated for each methotrexate dose
Epidemiology of Tuberculosis (TB) in Albania 1998-2009iosrphr_editor
Abstract : In Albania, many people erroneously think that tuberculosis (TB) is a disease of the past-an illness
that no longer constitutes a public health threat. Surveillance is an integral part of tuberculosis (TB) control.
Albania has a highTB notification rate and there are doubts about underreporting. The evolution of the
incidence of tuberculosis is presented, together with more detailed figures over the period 1998-2009. These
figures were obtained by the monthly forms (called 14/Sh) compared with the individual notification data.
Objective: To examine the distribution and sources of increased tuberculosis (TB) morbidity and reporting
system deficiencies in the Albania from 1998 through 2009. Metodology: The study is descriptive one conductet
during the period 1998-2009. The statistical analysis is based on data reported from regional level (regional
epidemiological departments) to the central level (Public Health Institute). Results: The main findings were:
discordance between the collected data (individual form) and reported data (monthly form); tuberculosis
incidence rate shows little oscillations which ranges from 6.67 to 9.2 cases/100.000 population; 50% of the
regions show a lack of information on the confirmation of diagnosis and laboratory examination type used for
confirmation. Conclusion: TB disease in high-risk populations where it is difficult to detect, diagnose, and treat;
limitations of current control measures and the need for new tests and treatments, including an effective
vaccine; improving information system, regulation of individual form and personnel training.
Total Phenol and Antioxidant from Seed and Peel of Ripe and Unripe of Indones...iosrphr_editor
Study on total phenol and antioxidantactivity ofsugar apple fruits of various solvent, part of fruits, and level of ripening. Solvent extraction used were 80% (v/v) methanol, 50% (v/v) acetone, boiling water, and 50% (v/v) ethanol. Part of fruits thatbeen used for samples were seed and peel which are normally by products of sugar apple processing, level of ripening were unripe, and ripe sugar apple fruits. Total phenol was determined by Folin-ciocalteau method. Total antioxidant was quantified by 1,1-diphenyl-2-picrylhydrazyl(DPPH) method.Therewas a difference in type of solvent, part of fruits, and level of ripeningon total phenol and antioxidant concentration of sugar apple fruits. Seeds have higher total phenol concentration than peels of this fruits. Unripe sugar apple fruits have higher total phenol and antioxidant than ripe fruit. The best solvent for phenol extraction was ethanol 50%butthe best solvent for antioxidant extraction was acetone 50%.
A Review on Step-by-Step Analytical Method Validationiosrphr_editor
When analytical method is utilized to generate results about the characteristics of drug related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods are fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy which documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of drug, production and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.
A Cross Sectional Study of Ethnic Differences in Occurrence and Severity of A...iosrphr_editor
Non-steroidal anti-inflammatory drugs are the most widely used "over the counter" medication all over the world despite their complications in different major organs. Present studies envisaged for knowing the occurrence and severity of adverse drug reactions from NSAIDs in different ethnic communities of Sikkim. A cross sectional study was undertaken in the medicine outpatients department of a secondary and tertiary care hospital. The patients belonging to Nepalese, Bhutias, Lepchas ethnic communities and others community (settlers from other parts of India) were included to analyzed the data based on the age and gender, ethnicity and ADRs, drugs and ADRs. Severity assessment was done using Hartwing and Siegel scale and causality assessment by Naranjo scale. Total 109 cases of ADRs, predominating in female were detected. Nepalese were the most affected and Gastrointestinal tract (GIT) being the most affected organ in them. Diclofenac showed maximum number of ADRs in all the communities. Maximum number of cases occurred on single day use (40.36%) of drugs. All the cases were belonging to the "possible category" and the maximum being the mild (72.48%) in nature. It is advisable to consider the ethnic/racial differences equally with other factors, to improve the safety and efficacy of a drug.
Hematological and biochemical alterations in malaria and their correlation wi...iosrphr_editor
Malaria is a major health problem in India with 1.04 million cases reported in 2012 leading to 504 deaths. The clinical spectrum depends on the infecting species, level of parasitemia and the immune status of the host. Malaria pathogenesis is based on extensive changes in hematological and biochemical parameters. The objective of this study was to study the clinical features, hematological and biochemical parameters in malaria patients and correlate them with the parasitic index (PI). Material and methods: We conducted a study on 300 malaria patients. The frequency of various symptoms and signs of malaria caused by various plasmodium species were determined. The degree of anemia, WBC count, platelet count serum bilirubin, liver enzymes and serum creatinine levels were studied and their variation depending on the parasitic index was documented. Results: 197 patients had vivax malaria, 76 patients had falciparum malaria and 27 patients had mixed infection. 171 patients had a PI of less than 2%, 100 patients had PI between 2 to 5%, 23 patients had PI between 5 to 10% and only 6 patients had PI of more than 10%. 72.3% of patients had thrombocytopenia, 46.66% had anaemia, 25% had increased bilirubin 29.66% showed increased liver enzymes and 7.66% had increased creatinine levels. Conclusion: There was a correlation between degree of parasitemia and severity of malaria in majority of cases. Derangements in hematological and biochemical parameters were more frequently seen in patients with higher PI. Hence PI can be used as an indicator by the clinician to know the severity of infection and plan appropriate treatment.
Treatment of Uthiravatha Suronitham (Rheumatoid Arthritis) with a Siddha Comp...iosrphr_editor
Uthiravathasuronitham, a vatha disease described by Sage Yugi can be correlated to Rheumatoid arthritis. A 53 year old lady diagnosed as Uthiravathasuronitham was treated with Siddha medicines Karpoora Chindhamani Mathirai and MannennaiKalavaiThylam. A single case study of Uthiravathasuronitham is detailed in this article.The patient presented with pain and swelling in minor joints of hand, wrist, ankle, shoulder joints and morning stiffness. The RA factor, CRP was positive at the time of enrollment. She was admitted in the IPD of Sirappu Maruthuvam Department of National Institute of Siddha for 45 days. The treatment outcome was encouraging. Hence further clinical studies can be carried out.
An analysis of the incidence and causes of road traffic accident in Kisii, Ce...iosrphr_editor
Background: Road traffic accidents (RTAs) are an emerging public health problem. It is estimated that more than 5 million people between 17-40 years of age die annually as a result of RTAs worldwide. Currently, RTA is the tenth leading cause of disease burden in the developing countries, especially in the Sub-Saharan African countries. The objective of the study was to analyze the proportion of accidents by vehicle, as well as investigate group of people vulnerable to RTA.
D-002 treatment attenuates esophagitis in a model of chronic gastro-esophagea...iosrphr_editor
To investigate the effects of D-002 (beeswax alcohols) on esophagitis induced by chronic gastroesophageal reflux (c-GER) in rats. Rats were randomized into a sham and five groups subjected to c-GER: a positive vehicle control, three D-002 (50, 100 and 200 mg/kg), and one omeprazole (20 mg/kg) group, all treated orally for seven days. cGER was induced by ligation of the junction between the forestomach and the duodenal side of the pylorus. Esophageal lesions index (ELI), esophageal malondialdehyde (MDA) and sulfhydril groups (SHG) concentrations were assessed. The positive control group exhibited macroscopically signs of esophageal injury assessed in term of ELI, which was significantly higher than in the negative control. D-002 (50, 100 and 200 mg/kg) reduced the ELI, showing 30.5, 72.9 and 76.4% protection, respectively; and also significantly attenuated the increased MDA (37.4, 63.6 and 94.2%, respectively) and SHG (16.6, 41.6 and 72.9%, respectively) esophageal concentrations versus the positive control. Omeprazole decreased the ELI (80.2%), MDA (99.3%) and SH (85.4%) esophageal concentrations. As conclusions, this study suggest that repeated oral administration with D-002 protects against reflux esophagitis and decreases esophageal lipid peroxidation and protein oxidation markers in rats with c-GER.
Reducing Uveitic Glaucoma: therapeutic judgement is the keyiosrphr_editor
Abstract: Background: Uveitic glaucoma (UG) due to disease and /or therapeutics is an important reason for reduced vision. Different therapeutic regimen employed in uveitis can alter the course of UG. Purpose: Evaluation of prevalence of UG with different commonly used therapy. Study design: Randomised prospective hospital based study Study Period: 2007-2012 Methods: Baseline IOP; Field and optic nerve head photographs were recorded. Three groups were randomised: 1.topical steroid 2.Systemic steroid +gr 1, 3.Topical synthetic steroids, cycloplegic and periorbital triamcinolone injection. Outcome measure: IOP more than 22 mm/4 mm increase from baseline is marker.
Studying the Analgesic, Anti-inflammatory and Antipyretic Properties of The A...iosrphr_editor
The document describes a study that investigated the analgesic, anti-inflammatory, and antipyretic properties of the aqueous extract of parsley (Petroselinum crispum) in experimental animal models. The extract showed significant anti-inflammatory effects in carrageenan, dextran, and histamine-induced paw edema models, as well as in a cotton pellet-induced granuloma model. It also exhibited analgesic effects in acetic acid-induced writhing and hot plate tests. Additionally, the extract reduced yeast-induced hyperpyrexia in rats. The study demonstrates that the aqueous extract of parsley possesses anti-inflammatory, analgesic, and antipyretic activities.
TrustArc Webinar - 2024 Global Privacy SurveyTrustArc
How does your privacy program stack up against your peers? What challenges are privacy teams tackling and prioritizing in 2024?
In the fifth annual Global Privacy Benchmarks Survey, we asked over 1,800 global privacy professionals and business executives to share their perspectives on the current state of privacy inside and outside of their organizations. This year’s report focused on emerging areas of importance for privacy and compliance professionals, including considerations and implications of Artificial Intelligence (AI) technologies, building brand trust, and different approaches for achieving higher privacy competence scores.
See how organizational priorities and strategic approaches to data security and privacy are evolving around the globe.
This webinar will review:
- The top 10 privacy insights from the fifth annual Global Privacy Benchmarks Survey
- The top challenges for privacy leaders, practitioners, and organizations in 2024
- Key themes to consider in developing and maintaining your privacy program
Essentials of Automations: The Art of Triggers and Actions in FMESafe Software
In this second installment of our Essentials of Automations webinar series, we’ll explore the landscape of triggers and actions, guiding you through the nuances of authoring and adapting workspaces for seamless automations. Gain an understanding of the full spectrum of triggers and actions available in FME, empowering you to enhance your workspaces for efficient automation.
We’ll kick things off by showcasing the most commonly used event-based triggers, introducing you to various automation workflows like manual triggers, schedules, directory watchers, and more. Plus, see how these elements play out in real scenarios.
Whether you’re tweaking your current setup or building from the ground up, this session will arm you with the tools and insights needed to transform your FME usage into a powerhouse of productivity. Join us to discover effective strategies that simplify complex processes, enhancing your productivity and transforming your data management practices with FME. Let’s turn complexity into clarity and make your workspaces work wonders!
A tale of scale & speed: How the US Navy is enabling software delivery from l...sonjaschweigert1
Rapid and secure feature delivery is a goal across every application team and every branch of the DoD. The Navy’s DevSecOps platform, Party Barge, has achieved:
- Reduction in onboarding time from 5 weeks to 1 day
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IOSR Journal of Pharmacy (IOSRPHR)
1. IOSR Journal Of Pharmacy
(e)-ISSN: 2250-3013, (p)-ISSN: 2319-4219
Www.Iosrphr.Org Volume 3, Issue 8 (September 2013), Pp 31-37
31
Candidate Molecules as Tumor Suppressor for Human Uterine
Mesenchymal Tumor
Takuma Hayashi 1,5,6
, Akiko Horiuchi 2
, Susumu Tonegawa 3
, Ikuo Konishi 4
1
Dept. of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine,
Nagano 390-8621, Japan
2
Horiuchi Ladies Clinic, Nagano 390-0821 Japan,
3
Picower Institution, Massachusetts Institute of Technology, MA 02139-4307 USA,
4
Dept. of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Kyoto 606-8507,
Japan,
5
Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Tokyo
102-8666, Japan, 6
SIGMA-Aldrich Collaboration Laboratory.
ABSTRACT : Uterine leiomyosarcoma (Ut-LMS) develops more often in myometrium of the uterine body
than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone
secretion; however, the development of Ut-LMS is not substantially correlated with hormonal conditions, and
the risk factor(s) are not yet known. Importantly, a diagnostic-biomarker, which distinguishes malignant tumor
Ut-LMS from benign tumor leiomyoma (LMA), is yet to be established. Accordingly, it is necessary to examine
risk factor(s) associated with Ut-LMS, to establish a diagnosis and a clinical treatment method. The mice with a
homozygous deficiency for proteasome -ring subunit, low-molecular mass polypeptide (LMP)2/1i
spontaneously develop Ut-LMS, with a disease prevalence of ~37% by 12 months of age. In the recent study, we
found LMP2/1i expression to be absent in human Ut-LMS, but clearly present in other human uterine
mesenchymal tumors including uterine LMA. Further analyses with clinical materials and the gene-modified
mice have not clarified the biological significance of the TP53 and retinoblastoma (Rb) pathway in malignant
myometrium transformation, thus implicating LMP2/1i as an anti-tumorigenic candidate. This role of
LMP2/1i as a tumor suppressor may lead to new therapeutic targets in human Ut-LMS. (191 words)
KEYWORDS: LMP2/1i, p53, Rb, tumor suppressor, leiomyosarcoma, mesenchymal tumor,
I. INTRODUCTION
The uterus is made up of three special layered linings of tissue and muscle. The middle layer of the
uterus is called the myometrium, and it is also known as the muscular uterine layer. It comprises of smooth
muscles which is vital during childbirth to move the baby out of the womb. Uterine mesenchymal tumors, which
develop in the myometrium, have been traditionally divided into benign leiomyoma (LMA) and malignant
uterine leiomyosarcoma (Ut-LMS) based on cytological atypia, mitotic activity and other criteria. Ut-LMS is
relatively rare mesenchymal tumor, having an estimated annual incidence of 0.64 per 100,000 women [1]. Ut-
LMS accounts for 2%~5% of tumors of the uterine body and develops more often in the muscle layer of the
uterine body than in the uterine cervix. As human Ut-LMS is resistant to chemotherapy and radiotherapy,
surgical intervention is virtually the only means of treatment [2-4]. Ut-LMS is an aggressive malignancy, with a
5-year survival of only 35% for tumors confined to the uterus [5]. However, developing an efficient adjuvant
therapy is expected to improve the prognosis for human Ut-LMS. Uterine LMA may occur in as many as
70%~80% of women by the age of 50 years [6]. Distinguishing human uterine LMA from Ut-LMS is very
difficult, and a diagnosis generally requires surgery and cytoscopy [7]. Diagnostic categories for uterine
mesenchymal tumors and morphological criteria are used to assign cases [8,9]. The non standard subtypes of
uterine mesenchymal tumors such as the epithelioid and myxoid types are classified in a different way using
these features, so the establishment of a diagnostic method for the identification of non-standard smooth muscle
differentiation is important [8,9].
High estrogen levels are considered to significantly influence the development of tumors in the uterine
body [10-12]. The molecular mechanisms by which uterine LMA and human Ut-LMS transform are not yet
known, though tumors that have initiated and grown in the myometrium for some reason gradually become
larger due to the influence of the female hormone, estrogen, and generate tumors.
However, no correlation between the development of human Ut-LMS and hormonal conditions, and no
2. Candidate Molecules As Tumor Suppressor…
32
obvious risk factors, have been found. Although cases accompanied by hypocalcaemia or eosinophilia have been
reported, neither clinical abnormality is an initial risk factor for human Ut-LMS. The TP53 tumor suppressor
pathway is one of the most well characterized pathways in various malignant tumors. The retinoblastoma (Rb)
pathway furthermore represents a second major tumor suppressor pathway deregulated in many malignant
tumors. However, correlation between these pathways and human Ut-LMS tumorigenesis is unclearly
understood unlike epithelial malignant tumors i.e. cancer.The ubiqutin-proteasomal degradation pathway is
essential for many cellular processes, including the cell cycle and the regulation of gene expression. In structure,
the proteasome is a cylindrical complex containing a core of four stacked rings around a central pore, each ring
composed of seven individual proteins. The inner two rings are made of seven β ring subunits that contain three
to seven protease active sites. Alternative β-ring forms denoted LMP2/β1i can be expressed in the myometrium
in response to exposure to pro-inflammatory signals such as cytokines, in particular, interferon (IFN)-. Ut-LMS
reportedly occurred in female LMP2/β1i-deficient mice at age 6 months or older, and the incidence at 12 months
of age was about 37%. The determination of the malignant potential of mesenchymal tumors also represents a
significant diagnostic conundrum with important therapeutic ramifications. However, the genetic changes
underlying the neoplastic transformation of uterine smooth muscle cells have not been fully characterized. The
identification of a risk factor and/or biological candidate(s) associated with the development of human Ut-LMS,
i.e. LMP2/β1i, would significantly contribute to the development of preventive and therapeutic treatments.
II. DEVELOPMENT OF UT-LMS IN LMP2/1I-DEFFICIENT MICE.
Cytoplasmic proteins are mostly degraded by a protease complex, which has many substrates
consisting of twenty-eight 20 to 30-kDa subunits, referred to as the 20S proteasome, and it is located in the
nucleus and the cytoplasm [13,14]. The ubiqutin-proteasome degradation pathway is essential for many cellular
processes, including the cell cycle, the regulation of gene expression and immunological function [15]. IFN-
induces the expression of large numbers of responsive genes, proteasome subunits, i.e., LMP2/1i, LMP7/5i
and LMP10/2i [16]. The individual expression of LMP2/1i, LMP7/5i and LMP10/2i subunits in various
cell types or tissues is believed to contribute to the initiation and development of disorders. A recent study
revealed a unique role for LMP7/5i in controlling pathogenic immune responses and provided a therapeutic
rationale for targeting LMP7/5i in autoimmune disorders, especially rheumatoid arthritis [17].
Recent reports demonstrate LMP2/1i as obligatory for tumor surveillance and a tissue- specific role
for LMP2/1i in protection from spontaneous uterus neoplasms [18,19]. Homozygous mice deficient in
LMP2/1i show tissue- and substrate- dependent abnormalities in the biological functions of the proteasome
[18,20]. Ut-LMS reportedly occurred in female LMP2/1i-deficient mice at age 6 months or older, and the
incidence at 14 months of age was about 40% [19,20] (Figure 1). The disease prevalence in mice is similar to
that of human Ut-LMS, which occurs after menopause [19]. Pathological studies of LMP2/1i-deficient uterine
tumors have revealed characteristic abnormalities of human Ut-LMS [19]. The tumors lacked lymphoid
infiltrates, a sign of immune recognition, and consisted of uniform elongated myometrium cells arranged into
bundles (Figure 1). The nuclei of the tumor cells varied in size and shape, furthermore, mitosis was frequent.
The tumor consisted of uniform elongated myometrium cells arranged into bundles. In contrast, the
myometrium cells of its parental mice, C57BL/6 mice were normal in appearance [19,20]. Whereas relatively
few MIB1/ki-67-positive cells, the proliferating cells, were observed in the basal cell layer of the normal
myometrium, most of the basal cells in LMP2/1i-deficient mice vividly expressed MIB1/ki-67 [19] (Figure 1).
This immunohistochemistry (IHC) study indicates abnormal proliferation of the LMP2/1i-lacking cells in the
basal layer. LMP2/1i-deficient mice that have developed Ut-LMS undergo considerable body-weight loss, and
then die by 14 months of age. They also potentially exhibit skeletal muscle metastasis from the Ut-LMS [21].
Therefore these research findings suggest that LMP2/1i-deficient mice with Ut-LMS die as a result of tumor
growth and metastasis. In general, it is not easy to distinguish uterine mesenchymal tumors from human Ut-
LMS, however, in mice, because of such characteristic pathological findings, significant body-weight loss, and
skeletal muscle metastasis, a tumor that develops in the uterus of an LMP2/1i-deficient mouse can be
considered malignant, i.e., an Ut-LMS [19-21].
III. DEFECTIVE LMP2/Β1I EXPRESSION IN HUMAN UT-LMS
The non-standard subtypes of uterine mesenchymal tumors such as the epithelioid and myxoid types
are classified in a different way using these features, so the establishment of a diagnostic method for the
identification of non-standard smooth muscle differentiation is important [7-9]. IHC studies were performed to
demonstrate the validity and reliability of LMP2/1i as a diagnostic biomarker under the combination of other
candidate molecules, for instance cyclin E and calponin h1 [22,23].
Of the 54 cases we examined with human Ut-LMS, 46 cases were negative for LMP2/1i expression, 4
3. Candidate Molecules As Tumor Suppressor…
33
cases were focally positive, and 2 cases were partially positive [23]. Two human Ut-LMS cases were stained for
LMP2/1i. The expression levels of LMP2/1i were also evaluated in skeletal muscle and rectum metastases
from individual human Ut-LMS patients [23]. Histological findings were consistent with metastatic LMS for the
skeletal muscle and rectum lesions. In western blotting and RT-PCR experiments, LMP2/1i was expressed in
normal myometrium, but not in human Ut-LMS, both strongly supportive of the IHC findings [22-24] (Figure 2).
IV. TUMOR SUPPRESSOR AND ONCOGENIC PATHWAY IN UT-LMS
The TP53 pathway: Molecular analyses have shown that many of the canonical tumor suppressor pathways,
such as the TP53 and retinoblastoma (Rb) pathways are ablated in these tumors [25]. Furthermore, some
sarcomas also harbor activating oncogenic mutations; such as expression of oncogenic K-ras. Together,
disruption of these genes and pathways are thought to be a driving force in sarcomagenesis. The TP53 tumor
suppressor pathway is one of the most well characterized pathways in cancers [26]. The TP53 gene encodes a
transcription factor required for the activation of numerous DNA damage-dependent checkpoint response and
apoptotic genes [27,28], and thus its activities are often ablated in many cancers. In addition to loss of TP53
functions via inherited germline somatic mutations, the TP53 pathway is commonly disrupted by point
mutations in the TP53 gene during sporadic sarcomagenesis [29]. However, even though TP53 gene alterations
are widely regarded as having a significant impact on sarcomagenesis, many sarcomas retain wild type TP53,
yet phenotypically display a loss of TP53 function. These findings suggest that changes in other components of
the TP53 pathway; such as amplification of Mdm2, a negative regulator of the TP53 pathway, may result in
TP53 inactivation [30,31]. Furthermore, both mice and humans with elevated levels of Mdm2 due to a high
frequency single nucleotide polymorphism in the Mdm2 promoter (Mdm2SNP309) are more susceptible to
sarcoma formation [32-34]. Additionally, deletion or silencing of p19Arf
(p14Arf in human), an inhibitor of the
MDM2-TP53 axis, often results in development of sarcomas. Together, these data indicate that while
inactivation of the TP53 pathway is observed in the vast majority of human sarcomas, the mechanisms leading
to disruption of the pathway can vary greatly.
People who inherit only one functional copy of the TP53 gene will most likely develop tumors in early
adulthood, a disease known as Li-Fraumeni syndrome. More than 50 percent of human tumors contain a
mutation or deletion of the TP53 gene [35]. To increase tumor incidence and better assess the role of systemic
expression of p53 in responses to initiation of Ut-LMS tumorigenesis, LMP2/1i-deficient mice were bred with
Tp53-deficient mice to create Lmp2-/-
Tp53-/-
double knockout mice. Ut-LMS incidence and death rates were
similar in Lmp2-/-
Tp53-/-
mice and closely matched those for control Lmp2-/-
Tp53+/+
mice. The correlation
between defective p53 function and Ut-LMS tumorigenesis is unclear. Although we previously demonstrated
that the abnormal expression of ovarian steroid receptors, p53 and MIB1/ki-67 and mutations of p53 were
frequently associated with human Ut-LMS, defective LMP2/1i expression appears to be more characteristic of
Ut-LMS than any of these factors [22-24].
The retinoblastoma (Rb) pathway: The Rb pathway represents a second major tumor suppressor pathway
deregulated in many sarcomas. Individuals inheriting a germline Rb mutation typically develop cancers of the
eye early in life [36-38]. However, in addition to retinal cancers, these children have a significantly higher
propensity to develop sarcomas than the general population [39]. While inheritance of a germline Rb alterations
increases sarcoma risk, there are also numerous examples of sporadic sarcomas harboring spontaneous Rb
somatic mutations and deletions, particularly osteosarcomas and rhabdomyosarcomas [40]. Furthermore,
p16Ikn4a
, a negative regulator of the CDK-cyclin complexes that phosphorylate and activate Rb, is often deleted
in sarcomas [41,42].
Long term survivors of hereditary retinoblastoma are at risk of developing a variety of non-ocular
second primary malignancies, the most common histological subtype of which is osteosarcoma. The reported
risk varies widely, but a cumulative incidence of 1% for each year of life has been suggested as an approximate
estimate. Earlier reports indicated that many of these malignancies are radiation or chemotherapy induced [43-
46]. However, more recent studies [46-49] suggest that the development of second primary neoplasms in
patients with hereditary retinoblastoma results partly from a genetic predisposition and partly from the
potentiating effect of radiotherapy on tumorigenesis through mutation of the second Rb gene (RB1) allele, the
first RB1 allele being mutated in all patients with hereditary retinoblastoma [50]. A recent analysis of second
primary neoplasms in retinoblastoma survivors revealed that 76% of the second tumors occurred in the head and
neck region and that soft tissue sarcomas
were the single largest category, comprising 24% of the total [49]. The median age at diagnosis of a
second tumor for the entire series was 16.4 years. The youngest patient to develop a soft tissue tumor was 4
4. Candidate Molecules As Tumor Suppressor…
34
years old and the oldest was 41. In previously reported cases of leiomyosarcoma occurring outside the head and
neck region, the patients have been in the 4th to 6th decades. Importantly, in female patients, uterine
leiomyosarcoma has not been reported after hereditary Rb, although simultaneously occurring benign Ut-LMS
have been described [51].
Recent reports describe three patients who developed leiomyosarcomas, one involving the
subcutaneous tissue of the thigh and the pelvic soft tissues and the other the urinary bladder, following
hereditary retinoblastoma 36, 38 and 49 years earlier, respectively [51,52]. We also have reported a case of
primary bladder LMS in a 45-year-old woman with a history of hereditary Rb. The cases we report, together
with others described, suggest that with increasing duration of survival after hereditary retinoblastoma there is
an increased risk of developing leiomyosarcoma in areas remote from the site of irradiation. Such patients thus
require appropriate follow up. Over all research experiments including with gene-deficient mouse models and
clinical research suggest that defective Rb expression does not take part in Ut-LMS onset.
V. CONCLUSION
In the case of gynecological cancers, such as breast cancer, a female hormonal imbalance is often a risk
factor for developing tumors [10-12]. As in the case of uterine LMA, however, a correlation between the
development of human Ut-LMS, the female hormone, and hormone receptors has been unclear. A recent report
showed the expression of LMP2/1i mRNA and protein in luminal and glandular epitheliua, placenta villi,
trophoblastic shells, and arterial endothelial cells [53-55]. These results implicate LMP2/1i in the invasion of
placental villi, degradation of the extracellular matrix, immune tolerance, glandular secretion, and angiogenesis
[53-55]. However, these findings do not help to elucidate the regulatory role of LMP2/1i in human Ut-LMS
tumorigenesis. The LMP2/1i-deficient mouse was the first animal model of spontaneous Ut-LMS to be
established [19,22,23]. In the recent studies, LMP2/1i is reported to negatively regulate human Ut-LMS
independently of its role in the proteasome [56-59]. Moreover, several lines of evidence indicate that calcium
binding protein, calponin h1 clearly affects LMP2/1i-induced cellular morphological chances [58,59]. Further
experiments are also required to elucidate the molecular mechanism of human Ut-LMS tumorigenesis involved
biological significance of LMP2/1i. Histologic and IHC characteristics of uterine mesenchymal tumors
including mitotically active leiomyoma, bizarre leiomyoma, lipoleiomyoma, uterine smooth muscle tumors of
uncertain malignant potential (STUMP), leiomyomatoid angiomatous neuroendocrin tumor (LANT) are
summarized [60-65]. Clarification of the correlation between these factors and the development of human Ut-
LMS and the identification of specific risk factors may lead to the development of new clinical treatments for
the disease.
VI. FINAL CONSIDERATIONS
Human Ut-LMS is refractory to chemotherapy and has a poor prognosis. Defective LMP2/1i
expression is likely to be one of the risk factors in the development of human Ut-LMS as it is in the LMP2/1i-
deficient mouse. While mouse model can not completely predict the outcome of Ut-LMS, the molecular
biological and cytological information obtained from LMP2/1i-deficient mice and human clinical materials
will contribute remarkably to the development of preventive methods, a potential diagnostic-biomarker, and new
therapeutic approaches against human mesenchymal tumors, especially human Ut-LMS.
VII. ACKNOWLEDGEMENTS:
We sincerely thank Professor Luc Van Kaer (Vanderbilt University Medical Centre) for research
support. This study was supported in part by grants from the Ministry of Education, Culture, Science and
Technology, and The Foundation of Osaka Cancer Research, The Ichiro Kanehara Foundation for the Promotion
of Medical Science and Medical Care, The foundation for the Promotion of Cancer Research, The Kanzawa
Medical Research Foundation, The Shinshu Medical Foundation, and The Takeda Foundation for Medical
Science.
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Figure 1. Homozygous mice deficient in LMP2/1i, an interferon (IFN)--inducible factor, show tissue-
7. Candidate Molecules As Tumor Suppressor…
37
and substrate-dependent abnormalities in the biological functions of the proteasome 19,20
. Ut-LMS
reportedly occurred in female LMP2/1i-deficient mice at age 6 months or older, and the incidence at 14
months of age was about 40% 19,20
Figure 2. Defective LMP2/1i expression in human uterine leiomyosarcoma. H.E. staining tissue sections
of uterine leomyosarcoma of LMP2/1i-deficient mouse and patient. Immunohistochmical staining tissue
section of human uterine leiomyosarcoma with anti-human LMP2/1i monoclonal antibody. Extracts of
50 g were resolved by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The
levels of LMP2 and -actin were examined by western blot (W.B.) analysis with appropriate antibodies.
Myo.; human myometrium, LMA; human leiomyoma, LMS; human leiomyosarcoma, HeLa+IFN-;
HeLa cells treated by IFN-.