Estrogen
Estrogen receptor and signaling pathway
Introduction of cancer and gene involvement
Causes of breast cancer
Type of breast cancer
Different approaches to treat breast cancer
Estrogen receptor antagonism
estrogen signaling pathway, breast cancer
Estrogen
Estrogen receptor and signaling pathway
Introduction of cancer and gene involvement
Causes of breast cancer
Type of breast cancer
Different approaches to treat breast cancer
Estrogen receptor antagonism
This document discusses factors that influence diseases and conditions. It identifies four main components of factors: predisposing factors which increase susceptibility; enabling factors which facilitate manifestation; precipitating factors associated with disease onset; and reinforcing factors which aggravate disease presence. It also discusses important host factors like sex, age, nutritional status, and genetic makeup that influence exposure, susceptibility, or response to agents. Age is linked to increased risk of various diseases, and children under 5 are most vulnerable to infectious diseases due to immature immune systems. Sex also influences disease susceptibility. Nutritional status and genetic makeup further determine disease risk.
The document summarizes key topics discussed at a journal club meeting for medical oncology residents. It includes questions about prognostic factors in breast cancer, genomic analysis technologies for determining breast cancer risk and chemotherapy regimens, and hormonal therapies for ER-positive breast cancers. It also summarizes several research studies and guidelines on intrinsic breast cancer subtypes, prognostic and predictive factors for determining adjuvant systemic therapies, and the Oncotype DX recurrence score assay.
Breast cancer develops from cells in the breast, usually in the lobules or ducts, and can invade nearby healthy tissue and lymph nodes over time. The most common types are ductal carcinoma, which starts in the ducts, and lobular carcinoma, which starts in the lobes. Breast cancer is staged based on tumor size and spread, from Stage 0 (non-invasive) to Stage IV (metastasized to other parts of the body). Risk factors include family history, genetic factors like BRCA1/2 mutations, reproductive factors, and lifestyle factors. Treatment depends on the cancer type and stage, and may involve surgery, radiation, chemotherapy, hormone therapy, and targeted biotherapies.
Newlife India has done research on Genetics of ovarian failure. Maire Peter has done the research on the same. By virtue of the extenssive reasearch we are able to give best results on IVF treatments.
The document discusses the molecular pathology of breast carcinoma. It describes the cellular types in the mammary gland, identification of mammary stem cells, and the epithelial cell hierarchy model. It also covers molecular classification of breast cancer, luminal and basal-like phenotypes, mechanisms of E-cadherin inactivation in lobular carcinoma, breast cancer in hereditary diffuse gastric cancer patients, and morphological and immunohistochemical features of BRCA1 and BRCA2 breast carcinomas.
The study aimed to identify genetic factors associated with pre-eclampsia by genotyping over 650 women affected by pre-eclampsia and their families at 28 SNPs in 7 candidate genes. Using transmission disequilibrium testing to distinguish maternal and fetal effects, they found that none of the genetic variants tested conferred a statistically significant risk of pre-eclampsia based on their criteria. The results emphasize the need for large, well-designed studies to reliably identify genetic risks and avoid false positives.
estrogen signaling pathway, breast cancer
Estrogen
Estrogen receptor and signaling pathway
Introduction of cancer and gene involvement
Causes of breast cancer
Type of breast cancer
Different approaches to treat breast cancer
Estrogen receptor antagonism
This document discusses factors that influence diseases and conditions. It identifies four main components of factors: predisposing factors which increase susceptibility; enabling factors which facilitate manifestation; precipitating factors associated with disease onset; and reinforcing factors which aggravate disease presence. It also discusses important host factors like sex, age, nutritional status, and genetic makeup that influence exposure, susceptibility, or response to agents. Age is linked to increased risk of various diseases, and children under 5 are most vulnerable to infectious diseases due to immature immune systems. Sex also influences disease susceptibility. Nutritional status and genetic makeup further determine disease risk.
The document summarizes key topics discussed at a journal club meeting for medical oncology residents. It includes questions about prognostic factors in breast cancer, genomic analysis technologies for determining breast cancer risk and chemotherapy regimens, and hormonal therapies for ER-positive breast cancers. It also summarizes several research studies and guidelines on intrinsic breast cancer subtypes, prognostic and predictive factors for determining adjuvant systemic therapies, and the Oncotype DX recurrence score assay.
Breast cancer develops from cells in the breast, usually in the lobules or ducts, and can invade nearby healthy tissue and lymph nodes over time. The most common types are ductal carcinoma, which starts in the ducts, and lobular carcinoma, which starts in the lobes. Breast cancer is staged based on tumor size and spread, from Stage 0 (non-invasive) to Stage IV (metastasized to other parts of the body). Risk factors include family history, genetic factors like BRCA1/2 mutations, reproductive factors, and lifestyle factors. Treatment depends on the cancer type and stage, and may involve surgery, radiation, chemotherapy, hormone therapy, and targeted biotherapies.
Newlife India has done research on Genetics of ovarian failure. Maire Peter has done the research on the same. By virtue of the extenssive reasearch we are able to give best results on IVF treatments.
The document discusses the molecular pathology of breast carcinoma. It describes the cellular types in the mammary gland, identification of mammary stem cells, and the epithelial cell hierarchy model. It also covers molecular classification of breast cancer, luminal and basal-like phenotypes, mechanisms of E-cadherin inactivation in lobular carcinoma, breast cancer in hereditary diffuse gastric cancer patients, and morphological and immunohistochemical features of BRCA1 and BRCA2 breast carcinomas.
The study aimed to identify genetic factors associated with pre-eclampsia by genotyping over 650 women affected by pre-eclampsia and their families at 28 SNPs in 7 candidate genes. Using transmission disequilibrium testing to distinguish maternal and fetal effects, they found that none of the genetic variants tested conferred a statistically significant risk of pre-eclampsia based on their criteria. The results emphasize the need for large, well-designed studies to reliably identify genetic risks and avoid false positives.
This document discusses the relationship between the plasminogen activator inhibitor type-1 (PAI-1) gene polymorphism and recurrent spontaneous abortion. PAI-1 inhibits fibrinolysis, which can increase the risk of thrombosis during pregnancy. Several meta-analyses found an association between the 4G/5G PAI-1 polymorphism and increased risk of recurrent miscarriage in Caucasian, African, and Asian populations, but not in Latino populations. Therapeutic options like anticoagulation therapy or metformin may help reduce the risk of recurrent abortion in women with certain PAI-1 polymorphisms and thrombophilia. More large, prospective studies are still needed to validate these findings.
This document defines premature ovarian failure as the loss of normal ovarian function before age 40, affecting 1% of women. It can be caused by genetic disorders, autoimmune diseases, chemotherapy/radiation, or unknown factors. Symptoms include irregular periods, hot flashes, and fertility issues. The condition is diagnosed through blood tests of follicle-stimulating hormone and estradiol levels. Treatment focuses on hormone replacement therapy and calcium/vitamin D supplements to prevent osteoporosis and relieve symptoms.
This document discusses a proposed experiment to test the hypothesis that increased estrogen levels can activate mutated BRCA1 and BRCA2 genes, leading to breast cancer development. The experiment would involve genetically engineering mice to have these mutated genes. The mice would then be given periodic doses of estrogen over their lifetime to observe if and when their normal cell growth turns cancerous. If cancer develops, repeating the experiment multiple times could help determine if estrogen is sufficient to trigger tumor growth by activating the mutated genes. Positive results may inform future research developing anti-estrogen treatments to prevent cancer formation in high-risk individuals.
This document discusses cancer and provides information about its causes, global burden, history, development process, genetics, types like breast cancer, research areas, and molecular targets for treatment. It notes that cancer is caused by both environmental and genetic factors. While over 80% of cancers are due to nature like radiation and viruses, under 10% are due to nurture or genes. The global cancer burden is outlined and breast cancer is used as a paradigm to discuss heterogeneous subtypes including luminal A, luminal B, basal-like, and ERBB2+ based on molecular profiles and markers. Future work is needed to better integrate molecular and clinical classification of cancers like breast cancer to improve diagnosis, treatment and prognosis.
Breast cancer is caused by heterogeneous tumor cells whose behavior depends on biological features. Molecular subtyping through gene expression profiling can classify tumor types, recognize hereditary implications, identify appropriate therapies, determine prognosis, and avoid unnecessary treatment. The major subtypes are luminal A/B, HER2-enriched, and basal-like, which differ in gene expression, sensitivity to therapies, and clinical outcomes. Understanding the molecular biology of breast cancer is crucial for precision medicine approaches to management.
Brca2 mutation and their influence to cancergalinayakubova
BRCA2 is a gene that helps repair damaged DNA. Certain mutations or variants in the BRCA2 gene increase cancer risk. The document discusses how BRCA2 mutations are inherited and their increased risks for breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer. It provides information on BRCA2 testing, who should consider testing, screening recommendations based on BRCA2 status, and management options like increased screening, risk-reducing surgery, medications, and PARP inhibitors for those with BRCA2 mutations.
1) BRCA status is important for treatment planning in breast cancer patients. Those with BRCA1/2 mutations have increased risk of contralateral breast cancer and benefit more from risk-reducing bilateral mastectomies.
2) Patients with BRCA mutations, especially BRCA1, have better responses to platinum-based chemotherapy compared to non-carriers. Platinum drugs may be a better option for these patients.
3) Testing for a wide panel of hereditary cancer genes is now possible using new sequencing technologies, which may help guide more personalized treatment decisions.
1. Several molecular pathways are involved in breast cancer pathogenesis, including steroid hormone receptors, HER2/neu, cell cycle proteins, and growth factors.
2. Risk factors for breast cancer include increasing age, female gender, family history, genetic mutations, personal history of breast cancer or other breast diseases, reproductive factors, and hormone use.
3. High risk patients are identified using tools like the Gail model and managed through increased screening including breast self-exams, clinical exams, mammograms, and MRI. Preventive options include tamoxifen, raloxifen, and prophylactic surgeries.
Anti-Mullerian Hormone (AMH) -Novel Biomarker & its ApplicationsDr. Rajesh Bendre
Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show ovarian reserve decline.
This study characterized differences between parental breast cancer cells and their exemestane-resistant counterparts. The resistant cells exhibited altered morphology, increased cancer stem cells, and expressed different proteins associated with more abnormal and aggressive subtypes. They also had an altered miRNA profile and increased dependence on growth factor pathways. Inhibition of mTOR decreased cell viability in resistant cells but not cancer stem cell formation. Certain miRNAs, such as 181a, may play a role in resistance by regulating these cellular and molecular changes, and could be potential therapeutic targets for exemestane resistance.
Gene expression profiling in breast carcinomaghoshparthanrs
This document discusses gene expression profiling in breast cancer and its use in classifying tumor subtypes. It describes how gene expression profiling analyzes thousands of genes simultaneously to more accurately classify tumors. Breast cancer is classified into clinical subtypes based on receptor expression, including luminal, HER2-enriched, and basal subtypes. Gene signatures can provide prognostic information to help guide treatment decisions for early-stage breast cancer patients. Tests like Oncotype DX and Mammaprint analyze gene expression from tumor samples to predict the risk of recurrence.
Immunology and recurrent pregnancy lossdr_indiradevi
Dr. Indira Devi Ponugoti is an obstetrician and gynecologist with extensive experience and qualifications. She has held leadership roles in several professional organizations and has contributed to the field through presenting papers and chairing conferences. Recurrent pregnancy loss is defined as three or more consecutive pregnancy losses and has a complex etiology involving anatomical, chromosomal, endocrine, autoimmune, infectious, and unknown factors. The immune system plays an important role in pregnancy through protective mechanisms that allow the semi-allogeneic fetus to implant. Dysregulation of these immune responses may contribute to recurrent pregnancy loss.
Prognostic & predictive factors of breast cancerMohammed Fathy
1) Prognostic factors provide information about a patient's outcome without treatment, while predictive factors provide information about how a patient may respond to a specific treatment.
2) Many clinical factors, pathological features, tissue markers, and genomic expression profiles can provide prognostic and predictive information for breast cancer patients.
3) Key prognostic factors include age, tumor stage, tumor size, nodal involvement, histological grade, hormone receptor status, and intrinsic subtypes. Predictive factors include hormone receptor and HER2 status.
Premature ovarian failure (POF) is characterized by the premature depletion of ovarian follicles before age 40, causing infertility. It is defined as elevated follicle-stimulating hormone levels above 20-40 mIU/mL before age 40 along with irregular or no menstrual periods. POF affects 1-3% of women and has various potential causes including genetic factors, autoimmune disorders, environmental exposures, infections, or idiopathic origins. Diagnosis involves hormone testing and treatment focuses on hormone replacement therapy to manage symptoms while fertility options may include oocyte donation or surrogacy.
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...Adonis Guancia
This document summarizes a presentation on rational options in breast cancer treatment informed by molecular understanding. It discusses the complexity of breast cancer at the molecular level, with every cancer being genetically unique and composed of multiple evolving clones. Standard adjuvant therapies do not fully address all the hallmarks of cancer. For HER2-positive breast cancer, the BCIRG 006 trial showed the TCH regimen of docetaxel, carboplatin and trastuzumab resulted in superior disease-free survival and fewer adverse effects compared to the AC→TH and AC→T regimens, suggesting TCH provides the best risk-benefit ratio.
The document discusses molecular subtyping of breast cancer through gene expression profiling which has identified major subtypes including luminal A, luminal B, HER2-enriched, and basal-like. It describes the characteristic gene expressions and clinical features of each subtype. Molecular subtyping is shown to have prognostic and predictive relevance for breast cancer outcomes and treatment responses.
The Role of Aromatase Inhibitors in Assisted Reproductive TechnologiesUlun Uluğ
This document discusses the role of aromatase inhibitors (AIs) in assisted reproductive technologies. It addresses several key questions:
1. Whether the addition of AIs increases pregnancy rates, which needs further evidence.
2. That the addition of AIs does reduce costs by decreasing the amount of gonadotropins needed.
3. Whether the addition of AIs augments ovarian response, which also needs more evidence.
The document provides background on AIs and their pharmacology. It reviews studies on the use of letrozole in ovarian stimulation protocols and outcomes like pregnancy rates, cost savings, and safety.
1. Recurrent pregnancy loss is defined as two or more clinical pregnancy losses. It can be caused by various uterine, endocrine, inherited thrombophilias, immunological, genetic, and environmental factors.
2. Evaluation involves investigating uterine factors like adhesions and polyps, endocrine disorders like diabetes and thyroid abnormalities, inherited thrombophilias, and immunological issues like antiphospholipid antibody syndrome.
3. Treatment depends on the underlying cause but may include progesterone supplementation, aspirin, heparin, intravenous immunoglobulin, intralipid infusions, and immunomodulation with corticosteroids, granulocyte colony-stimulating factor or tumour necrosis factor alfa
Breast cancer originates from breast tissue, most commonly from the inner lining of milk ducts or lobules. The breast is made up of a network of mammary ducts that lead to lobes containing lobules, which secrete milk stimulated by hormones. There are several types of breast cancer classified based on the location of origin within the breast tissue and whether they have spread. Factors like family history and genetic mutations can increase breast cancer risk, while lifestyle factors like obesity, alcohol use, and lack of physical activity can also impact risk. Treatment may involve surgery, chemotherapy, radiation therapy, and hormonal therapy depending on the cancer type, stage, and receptor status.
Breast cancer originates from breast tissue, most commonly from the inner lining of milk ducts or lobules. The breast is made up of a network of mammary ducts that lead to lobes containing lobules, which secrete milk stimulated by hormones. Breast cancer is classified based on histology and the presence of receptors for estrogen, progesterone and HER2. Factors like genetics, lifestyle, and environment contribute to breast cancer risk. Treatment may involve surgery, chemotherapy, radiation therapy and hormonal therapy depending on cancer stage and receptor status.
This document discusses the relationship between the plasminogen activator inhibitor type-1 (PAI-1) gene polymorphism and recurrent spontaneous abortion. PAI-1 inhibits fibrinolysis, which can increase the risk of thrombosis during pregnancy. Several meta-analyses found an association between the 4G/5G PAI-1 polymorphism and increased risk of recurrent miscarriage in Caucasian, African, and Asian populations, but not in Latino populations. Therapeutic options like anticoagulation therapy or metformin may help reduce the risk of recurrent abortion in women with certain PAI-1 polymorphisms and thrombophilia. More large, prospective studies are still needed to validate these findings.
This document defines premature ovarian failure as the loss of normal ovarian function before age 40, affecting 1% of women. It can be caused by genetic disorders, autoimmune diseases, chemotherapy/radiation, or unknown factors. Symptoms include irregular periods, hot flashes, and fertility issues. The condition is diagnosed through blood tests of follicle-stimulating hormone and estradiol levels. Treatment focuses on hormone replacement therapy and calcium/vitamin D supplements to prevent osteoporosis and relieve symptoms.
This document discusses a proposed experiment to test the hypothesis that increased estrogen levels can activate mutated BRCA1 and BRCA2 genes, leading to breast cancer development. The experiment would involve genetically engineering mice to have these mutated genes. The mice would then be given periodic doses of estrogen over their lifetime to observe if and when their normal cell growth turns cancerous. If cancer develops, repeating the experiment multiple times could help determine if estrogen is sufficient to trigger tumor growth by activating the mutated genes. Positive results may inform future research developing anti-estrogen treatments to prevent cancer formation in high-risk individuals.
This document discusses cancer and provides information about its causes, global burden, history, development process, genetics, types like breast cancer, research areas, and molecular targets for treatment. It notes that cancer is caused by both environmental and genetic factors. While over 80% of cancers are due to nature like radiation and viruses, under 10% are due to nurture or genes. The global cancer burden is outlined and breast cancer is used as a paradigm to discuss heterogeneous subtypes including luminal A, luminal B, basal-like, and ERBB2+ based on molecular profiles and markers. Future work is needed to better integrate molecular and clinical classification of cancers like breast cancer to improve diagnosis, treatment and prognosis.
Breast cancer is caused by heterogeneous tumor cells whose behavior depends on biological features. Molecular subtyping through gene expression profiling can classify tumor types, recognize hereditary implications, identify appropriate therapies, determine prognosis, and avoid unnecessary treatment. The major subtypes are luminal A/B, HER2-enriched, and basal-like, which differ in gene expression, sensitivity to therapies, and clinical outcomes. Understanding the molecular biology of breast cancer is crucial for precision medicine approaches to management.
Brca2 mutation and their influence to cancergalinayakubova
BRCA2 is a gene that helps repair damaged DNA. Certain mutations or variants in the BRCA2 gene increase cancer risk. The document discusses how BRCA2 mutations are inherited and their increased risks for breast cancer, ovarian cancer, prostate cancer, and pancreatic cancer. It provides information on BRCA2 testing, who should consider testing, screening recommendations based on BRCA2 status, and management options like increased screening, risk-reducing surgery, medications, and PARP inhibitors for those with BRCA2 mutations.
1) BRCA status is important for treatment planning in breast cancer patients. Those with BRCA1/2 mutations have increased risk of contralateral breast cancer and benefit more from risk-reducing bilateral mastectomies.
2) Patients with BRCA mutations, especially BRCA1, have better responses to platinum-based chemotherapy compared to non-carriers. Platinum drugs may be a better option for these patients.
3) Testing for a wide panel of hereditary cancer genes is now possible using new sequencing technologies, which may help guide more personalized treatment decisions.
1. Several molecular pathways are involved in breast cancer pathogenesis, including steroid hormone receptors, HER2/neu, cell cycle proteins, and growth factors.
2. Risk factors for breast cancer include increasing age, female gender, family history, genetic mutations, personal history of breast cancer or other breast diseases, reproductive factors, and hormone use.
3. High risk patients are identified using tools like the Gail model and managed through increased screening including breast self-exams, clinical exams, mammograms, and MRI. Preventive options include tamoxifen, raloxifen, and prophylactic surgeries.
Anti-Mullerian Hormone (AMH) -Novel Biomarker & its ApplicationsDr. Rajesh Bendre
Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show ovarian reserve decline.
This study characterized differences between parental breast cancer cells and their exemestane-resistant counterparts. The resistant cells exhibited altered morphology, increased cancer stem cells, and expressed different proteins associated with more abnormal and aggressive subtypes. They also had an altered miRNA profile and increased dependence on growth factor pathways. Inhibition of mTOR decreased cell viability in resistant cells but not cancer stem cell formation. Certain miRNAs, such as 181a, may play a role in resistance by regulating these cellular and molecular changes, and could be potential therapeutic targets for exemestane resistance.
Gene expression profiling in breast carcinomaghoshparthanrs
This document discusses gene expression profiling in breast cancer and its use in classifying tumor subtypes. It describes how gene expression profiling analyzes thousands of genes simultaneously to more accurately classify tumors. Breast cancer is classified into clinical subtypes based on receptor expression, including luminal, HER2-enriched, and basal subtypes. Gene signatures can provide prognostic information to help guide treatment decisions for early-stage breast cancer patients. Tests like Oncotype DX and Mammaprint analyze gene expression from tumor samples to predict the risk of recurrence.
Immunology and recurrent pregnancy lossdr_indiradevi
Dr. Indira Devi Ponugoti is an obstetrician and gynecologist with extensive experience and qualifications. She has held leadership roles in several professional organizations and has contributed to the field through presenting papers and chairing conferences. Recurrent pregnancy loss is defined as three or more consecutive pregnancy losses and has a complex etiology involving anatomical, chromosomal, endocrine, autoimmune, infectious, and unknown factors. The immune system plays an important role in pregnancy through protective mechanisms that allow the semi-allogeneic fetus to implant. Dysregulation of these immune responses may contribute to recurrent pregnancy loss.
Prognostic & predictive factors of breast cancerMohammed Fathy
1) Prognostic factors provide information about a patient's outcome without treatment, while predictive factors provide information about how a patient may respond to a specific treatment.
2) Many clinical factors, pathological features, tissue markers, and genomic expression profiles can provide prognostic and predictive information for breast cancer patients.
3) Key prognostic factors include age, tumor stage, tumor size, nodal involvement, histological grade, hormone receptor status, and intrinsic subtypes. Predictive factors include hormone receptor and HER2 status.
Premature ovarian failure (POF) is characterized by the premature depletion of ovarian follicles before age 40, causing infertility. It is defined as elevated follicle-stimulating hormone levels above 20-40 mIU/mL before age 40 along with irregular or no menstrual periods. POF affects 1-3% of women and has various potential causes including genetic factors, autoimmune disorders, environmental exposures, infections, or idiopathic origins. Diagnosis involves hormone testing and treatment focuses on hormone replacement therapy to manage symptoms while fertility options may include oocyte donation or surrogacy.
CCO Rational Options in Breast Cancer : How Molecular Understanding Informs T...Adonis Guancia
This document summarizes a presentation on rational options in breast cancer treatment informed by molecular understanding. It discusses the complexity of breast cancer at the molecular level, with every cancer being genetically unique and composed of multiple evolving clones. Standard adjuvant therapies do not fully address all the hallmarks of cancer. For HER2-positive breast cancer, the BCIRG 006 trial showed the TCH regimen of docetaxel, carboplatin and trastuzumab resulted in superior disease-free survival and fewer adverse effects compared to the AC→TH and AC→T regimens, suggesting TCH provides the best risk-benefit ratio.
The document discusses molecular subtyping of breast cancer through gene expression profiling which has identified major subtypes including luminal A, luminal B, HER2-enriched, and basal-like. It describes the characteristic gene expressions and clinical features of each subtype. Molecular subtyping is shown to have prognostic and predictive relevance for breast cancer outcomes and treatment responses.
The Role of Aromatase Inhibitors in Assisted Reproductive TechnologiesUlun Uluğ
This document discusses the role of aromatase inhibitors (AIs) in assisted reproductive technologies. It addresses several key questions:
1. Whether the addition of AIs increases pregnancy rates, which needs further evidence.
2. That the addition of AIs does reduce costs by decreasing the amount of gonadotropins needed.
3. Whether the addition of AIs augments ovarian response, which also needs more evidence.
The document provides background on AIs and their pharmacology. It reviews studies on the use of letrozole in ovarian stimulation protocols and outcomes like pregnancy rates, cost savings, and safety.
1. Recurrent pregnancy loss is defined as two or more clinical pregnancy losses. It can be caused by various uterine, endocrine, inherited thrombophilias, immunological, genetic, and environmental factors.
2. Evaluation involves investigating uterine factors like adhesions and polyps, endocrine disorders like diabetes and thyroid abnormalities, inherited thrombophilias, and immunological issues like antiphospholipid antibody syndrome.
3. Treatment depends on the underlying cause but may include progesterone supplementation, aspirin, heparin, intravenous immunoglobulin, intralipid infusions, and immunomodulation with corticosteroids, granulocyte colony-stimulating factor or tumour necrosis factor alfa
Breast cancer originates from breast tissue, most commonly from the inner lining of milk ducts or lobules. The breast is made up of a network of mammary ducts that lead to lobes containing lobules, which secrete milk stimulated by hormones. There are several types of breast cancer classified based on the location of origin within the breast tissue and whether they have spread. Factors like family history and genetic mutations can increase breast cancer risk, while lifestyle factors like obesity, alcohol use, and lack of physical activity can also impact risk. Treatment may involve surgery, chemotherapy, radiation therapy, and hormonal therapy depending on the cancer type, stage, and receptor status.
Breast cancer originates from breast tissue, most commonly from the inner lining of milk ducts or lobules. The breast is made up of a network of mammary ducts that lead to lobes containing lobules, which secrete milk stimulated by hormones. Breast cancer is classified based on histology and the presence of receptors for estrogen, progesterone and HER2. Factors like genetics, lifestyle, and environment contribute to breast cancer risk. Treatment may involve surgery, chemotherapy, radiation therapy and hormonal therapy depending on cancer stage and receptor status.
Progesterone receptor (PR) plays an important role in breast cancer progression and response to hormone therapy. PR exists as two isoforms, PR-A and PR-B, which act as transcription factors. PR signaling can occur through both nuclear and non-nuclear pathways. While PR expression correlates with better outcomes from hormone therapy, loss of PR is a mechanism of resistance. Targeting the PR pathway through drugs like anti-RANKL agents may be a preventative strategy, while newer endocrine therapies aim to overcome resistance.
Breast cancer is the most common cancer and leading cause of cancer death among women worldwide. Approximately 75% of breast cancers are hormone receptor positive. While endocrine therapies such as tamoxifen and aromatase inhibitors are effective treatments for hormone receptor positive breast cancer, resistance often develops. New targeted therapies are being developed to treat resistant disease, including everolimus which has shown promise in combination with exemestane for advanced breast cancer in a phase III clinical trial. Advances in molecular subtyping and understanding of resistance mechanisms continue to improve personalized treatment of breast cancer.
Adjuvant endocrine therapy in breast cancer Mamdouh Sabry
Adjuvant endocrine therapy is an important treatment for breast cancer patients. Tamoxifen and aromatase inhibitors are commonly used to block the effects of estrogen and progesterone, which can fuel breast cancer growth. Determining menopausal status is crucial for selecting the appropriate endocrine treatment. While adjuvant endocrine therapy improves outcomes for hormone receptor-positive breast cancer, doctors must also monitor for side effects and address issues like future fertility with patients.
Breast cancer is the most commonly diagnosed cancer and leading cause of cancer death in women worldwide. Approximately 30% of patients are premenopausal and 10% are aged 35-45 years old. Around 75% of cases are hormone receptor-positive. Treatment options include surgery, chemotherapy, radiotherapy, endocrine therapy, and monoclonal antibody therapy. Estrogens and progesterone are implicated in breast carcinogenesis, so endocrine therapies that block these hormones' effects can treat hormone receptor-positive breast cancer. Tamoxifen, aromatase inhibitors, ovarian suppression, and selective progesterone modulators are some endocrine agents used. Menopause diagnosis is important for determining appropriate endocrine therapy.
Tamoxifen and its anti-cancerous propertiesSadia Alvi
Tamoxifen is a selective estrogen receptor modulator originally developed as an antifertility drug. It is now commonly used to treat and prevent breast cancer. Tamoxifen undergoes extensive metabolism and is primarily excreted through the bile. It acts as an estrogen receptor antagonist in breast tissue to inhibit cell growth. A special population study found tamoxifen may also be effective for treating brain cancers due to its ability to inhibit protein kinase C and cross the blood-brain barrier.
This document summarizes the molecular biology of esophageal and gastric cancers. It discusses common genetic alterations in these cancers, including oncogenes and tumor suppressor genes. For esophageal cancer, it describes alterations in EGFR, cyclin D1, p53, E-cadherin and other genes. For gastric cancer, it discusses differences between intestinal and diffuse subtypes and common mutations in genes like p53, CDH1 and mismatch repair genes. The document also summarizes proposed molecular classifications of gastric cancer from TCGA and ACRG and their prognostic implications, along with targeted therapies in development or approved for treatment.
1) The study investigated the role of the long non-coding RNA NNT-AS1 in progesterone resistance in endometrial cancer.
2) The researchers found that NNT-AS1 and survivin expression were increased, while miR-542-3p expression was decreased, in progesterone-resistant endometrial cancer cells.
3) Experiments showed that NNT-AS1 regulates progesterone resistance in endometrial cancer by functioning as a competing endogenous RNA for miR-542-3p, thereby regulating survivin expression.
Molecular subtyping of breast cancer through gene expression profiling can identify distinct tumor subtypes with different biological behaviors and responses to therapy. The major subtypes include luminal A/B (ER-positive), HER2-enriched, basal-like (triple-negative), and normal-like. Molecular testing helps determine prognosis, hereditary risk, and appropriate targeted therapies. Hormonal and HER2-targeted therapies are effective treatments for luminal and HER2-positive breast cancers, respectively, while basal-like cancers are more aggressive and difficult to treat.
Preterm labor is a multifactorial problem that current treatment options address only symptomatically rather than causally. Preventative treatment with progesterone can lower preterm birth rates in high-risk groups by over 30%. Tocolysis using beta-adrenergic agonists like terbutaline and fenoterol can be used to prevent premature labor by relaxing the uterus. However, these drugs often cause side effects from activating the sympathetic nervous system.
Breast cancer is the most common female malignancy and is
responsible for about 14% of cancer-related deaths in women
[1]. Triple-negative breast cancer (TNBC), characterized by the
absence of expression of Estrogen Receptor (ER), Progesterone
Receptor (PR), and human epidermal growth factor receptor 2
(HER2), is the most aggressive and deadly subtype of breast cancer
Propolis with its active component CAPE (Caffeic Acid Phenethyl Ester) stops breast cancer cell growth. These results of CAPE are present in the naturopathic formulation
of propolis, a widely available natural substance with an extended safety record, making it a naturally-occurring and readily available epigenetic agent with great potential in breast cancer and oncology in general. The ability to link the biological effects of a naturopathic remedy to the pharmacologic effects seen with an exciting class of drugs in the treatment of cancer opens the door to a host of new therapeutic opportunities for patients.
This document describes a study investigating the role of the protein Morgana in breast cancer metastasis. The study found that knocking down Morgana impaired migration, invasion, and metastasis of breast cancer cells in vitro and in vivo. Mechanistically, Morgana was found to increase the transcriptional activity of NF-κB, leading to increased expression of metastasis-promoting genes like MMP-9. Overexpressing Morgana had the opposite effect of increasing NF-κB target gene expression. Therefore, Morgana appears to promote breast cancer metastasis by activating the NF-κB pathway and increasing expression of pro-metastatic genes.
This document reviews current understanding of cellular receptor signaling pathways that interact with estrogen receptors and their role in resistance to endocrine therapy for breast cancer. It discusses how growth factor pathways like HER2, IGF1R, and FGFR interact with and modify estrogen receptor activity through various mechanisms. This crosstalk can lead to downregulation of estrogen receptors, decreased response to estrogen, and development of resistance. The document also reviews clinical trials examining combination therapies that target these pathways in addition to endocrine therapy, with the aim of reducing or reversing resistance.
This document discusses targeted therapy for breast cancer. It begins by providing background on declining mortality rates for breast cancer over time. It then discusses how cancers develop multiple alterations that allow uncontrolled growth and outlines six essential alterations in cell physiology that contribute to malignancy. The document discusses molecular alterations that occur in breast cancer progression. It defines targeted therapy as drugs that target uniquely disrupted pathways in cancer cells. The document outlines several targeted therapies for breast cancer including hormonal therapies like tamoxifen, aromatase inhibitors, and fulvestrant. It discusses clinical trials demonstrating the benefits of these therapies. It also discusses therapies that target the HER2 receptor like trastuzumab and lapatinib. In summary, the document provides an overview of targeted
1) Aspirin inhibited constitutive NF-κB activity and Cox-2 expression in human pancreatic carcinoma cell lines in a dose-dependent manner.
2) Aspirin did not significantly inhibit the in vitro growth of pancreatic carcinoma cell lines.
3) In an orthotopic mouse model, none of the mice injected with NF-κB inhibited pancreatic carcinoma cells developed tumors, whereas all mice injected with non-inhibited cells developed tumors. Mice receiving prophylactic aspirin treatment showed a significantly lower tumor incidence than mice receiving later aspirin treatment or no treatment.
Fertility, Pregnancy, Contraception, Lactation And Endocrine Therapy In Breas...Mamdouh Sabry
Discussing every detail concerning gynaecologist and obstetrician in breast cancer. As fertility, pregnancy outcome, contraception, lactation, adjuvant hormone therapy and prevention.
Hormone therapy is an important treatment for hormone receptor positive breast cancers. Tamoxifen for 5 years and aromatase inhibitors are effective adjuvant therapies. Trials have shown that aromatase inhibitors are superior to tamoxifen alone for postmenopausal women. Sequential therapy with tamoxifen followed by an aromatase inhibitor also improves outcomes compared to tamoxifen alone. Ongoing research continues to refine the optimal duration and sequencing of hormone therapies.
This document summarizes management strategies for metastatic hormone receptor positive breast cancer. It discusses that hormone receptor positive disease has better survival rates than other subtypes. Roughly 30% of early breast cancer patients will develop advanced or metastatic disease, with 6-10% presenting with metastases initially. Treatment modalities discussed include reducing estrogen production, selective estrogen receptor modulators like tamoxifen, aromatase inhibitors, fulvestrant, progestins, targeted therapies, CDK4/6 inhibitors, PI3K/AKT/mTOR pathway inhibitors, and mTOR inhibitors. Combination treatment strategies are also summarized.
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Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Hiranandani Hospital in Powai, Mumbai, is a premier healthcare institution that has been serving the community with exceptional medical care since its establishment. As a part of the renowned Hiranandani Group, the hospital is committed to delivering world-class healthcare services across a wide range of specialties, including kidney transplantation. With its state-of-the-art facilities, advanced medical technology, and a team of highly skilled healthcare professionals, Hiranandani Hospital has earned a reputation as a trusted name in the healthcare industry. The hospital's patient-centric approach, coupled with its focus on innovation and excellence, ensures that patients receive the highest standard of care in a compassionate and supportive environment.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
These lecture slides, by Dr Sidra Arshad, offer a simplified look into the mechanisms involved in the regulation of respiration:
Learning objectives:
1. Describe the organisation of respiratory center
2. Describe the nervous control of inspiration and respiratory rhythm
3. Describe the functions of the dorsal and respiratory groups of neurons
4. Describe the influences of the Pneumotaxic and Apneustic centers
5. Explain the role of Hering-Breur inflation reflex in regulation of inspiration
6. Explain the role of central chemoreceptors in regulation of respiration
7. Explain the role of peripheral chemoreceptors in regulation of respiration
8. Explain the regulation of respiration during exercise
9. Integrate the respiratory regulatory mechanisms
10. Describe the Cheyne-Stokes breathing
Study Resources:
1. Chapter 42, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 36, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 13, Human Physiology by Lauralee Sherwood, 9th edition
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
2. CONTENTS
1. Estrogen
2. Estrogen receptor and signaling pathway
3. Introduction of cancer and gene involvement
4. Causes of breast cancer
5. Type of breast cancer
6. Different approaches to treat breast cancer
7. Estrogen receptor antagonism
3. ESTROGEN
The primary female sex hormones, estrogens, are responsible for the
control of functions of the female reproductive system, as well as the
development of secondary sexual characteristics that appear during
puberty and sexual maturity.
Estrogens are primarily synthesized in the ovaries, but also in the
adrenal glands and adipose tissue.
Estradiol, the predominant circulating estrogen in humans, it is
mainly secreted by the granulosa cells of the ovarian follicles, and the
corpora lutea.
These include estrone, estradiol, estriol, and estretrol
They consist of one benzene ring, a phenolic hydroxyl group, and a
ketone group (estrone), or one (17β-estradiol), two (estriol), or three
(estretrol) hydroxyl groups.
5. ESTROGEN RECEPTOR
Two type of estrogen receptor are there ERα Erβ
ER-α is expressed in the mammary gland, uterus, ovary, bone, male
reproductive organs (testis, prostate), liver and adipose tissue while ER-β is
mainly expressed in the prostate gland, bladder, ovary, colon, adipose tissue
and immune system
ER-α is also responsible for the maintenance of the female phenotype of the
somatic cells of the ovary by inhibiting the development of male phenotype
interstitial cells (sex steroid-producing) and hence protecting the integrity of
female sex differentiation
ER-β generally counteracts the ER-α promoted cell hyper proliferation in
tissues such as breast and uterus . Therefore, the estrogen signaling is a
balance between the mechanism and effect of these two distinct receptors
which leads to the activation of numerous genes that are responsible for a
wide variety of developmental and organizational changes in females.
6. SIGNALING PATHWAY OF ESTROGEN RECEPTOR
GPER1 signaling pathway occurs
through various second messengers.
Phospholipase C Beta (PLCβ), inositol
triphosphate (IP3), nuclear factor of
activated T-cells (NFAT),
calcium/calmodulin-dependent protein
kinase (CamK), cAMP response
element-binding protein (CREB),
adenylate cyclase (AC), protein kinase A
(PKA), phosphoinositide 3-kinase
(PI3K), protein kinase B (Akt), IκB kinase
(IKK), nuclear factor kappa-light-chain-
enhancer of activated B cells (NF-κB),
endothelial nitric oxide synthase
(eNOS), non-receptor tyrosine kinase
(SRC), matrix metallopeptidases (MMPs),
heparin-binding EGF-like growth factor
(HB-EGF), son of sevenless (SOS), Src
homology 2 domain-containing
transforming protein (SHC), growth
factor receptor-bound protein 2 (GRB2),
RAS protein (RAS), RAF kinase (RAF),
mitogen-activated protein kinase kinase
(MEK), extracellular signal-regulated
kinases 1/2 (ERK 1/2), Elk-1
transcription factor (Elk1), p38
7. INTRODUCTION OF CANCER AND THEIR GENE INVOLVEMENT
A normal cell undergoes
regulated division ,
differentiation and apoptosis.
When normal cell have lost
the usual control over their
division ,differentiation and
apoptosis, they become
tumor cell.
8. CANCER RELATED GENES
PROTO-ONCOGENES GENES TUMOR SUPPRESOR GENES
SIS – synthesis of platelet derived
growth factor
BRCA1 and BRCA2 – transcription
factor,
DNA repair
ERBB- synthesis of epidermal
growth factor receptor
NF1 – GTPase
SRC- synthesis of tyrosine kinase TP53- transcription factor
FOS – synthesis of transcription
fator
RB1- cell cycle checkpoint
BRCA1 BRCA2 breast cancer
susceptibility gene are tumor
suppressor gene encoding
proteins involved in the
maintenance of genome
stability through repair of DNA,
cell growth regulation and
control of regulation.
Individual carrying germline
pathogenic mutation in BRCA1
and BRCA2 are at highly
elevated risk of developing
breast and/or ovarian cancer.
9.
10.
11. BREAST CANCER TYPE
Hormone Receptor-Positive Breast
Cancer
About 80% of all breast cancers are “ER-
positive.” That means the cancer cells grow
in response to the hormone estrogen. About
65% of these are also “PR-positive.” They
grow in response to another hormone,
progesterone.
The medication
tamoxifen helps stop cancer from coming
back by blocking hormone receptors,
preventing hormones from binding to them
aromatase inhibitors actually stops
estrogen production. These
include anastrozole (Arimidex), exemestan
e (Aromasin), and letrozole (Femara).
They’re only used in women who’ve
already gone through menopause.
CDK 4/6
inhibitors abemaciclib (Verzenio), palbocic
lib (Ibrance) and ribociclib (Kisqali) are
sometimes used with aromatase inhibitors
or the hormone
therapy fulvestrant (Faslodex).
HER2-Positive Breast Cancer
In about 20% of breast cancers, the cells
make too much of a protein known as
HER2. These cancers tend to be
aggressive and fast-growing.
There are several other targeted therapies
sometimes used in the treatment of
HER2-positive breast cancer. These
include:
Abemaciclib (Verzenio)
Lapatinib (Tykerb)
Margetuximab (Margenza)
Neratinib (Nerlynx)
Pertuzumab (Perjeta)
Tucatinib (Tukysa)
Triple-Negative Breast Cancer
Some breast cancers -- between
10% and 20% -- are known as
“triple negative” because they
don’t have estrogen and
progesterone receptors and don’t
overexpress the HER2 protein.
Many breast cancers associated
with the gene BRCA1 are triple
negative. They are often treated
with surgery, chemotherapy, and
radiation.
talazoparib (Talzenna)
Atezolizumab (Tecentriq) is an
immunotherapy drug used in
combination with the
chemotherapy nab-
paclitaxel (Abraxane) to block a
protein called PD-L1 in certain
breast cancers that are triple
negative.
12. DIFFERENT APPROACHES TO
TREAT BREAST CANCER
(MOLECULAR TARGETS)
cyclin-dependent kinase CDK4 and CDK6 INHIBITION
Antagonise directly estrogen receptor
Prevention of dimerization
Deficiency of coregulatory like SRC1 (proto onco gene)
Increased apoptosis
Inhibition of tyrosine kinase pathway etc.
13. REFERENCES
Kumar N, Gulati H K, Sharma A, “Most recent strategies targeting estrogen receptor
alpha for the treatment of breast cancer” 2020, Molecular Diversity
https://doi.org/10.1007/s11030-020-10133-y
Christy W. S. Tong , Mingxia Wu , William C. S. Cho and Kenneth K. W. To, “Recent
Advances in the Treatment of Breast Cancer” 2018, Front. Oncol.
https://doi.org/10.3389/fonc.2018.00227
Christian J. Gruber, Doris M. Gruber, Isabel M.L. Gruber, Fritz Wieser and Johannes
C. Huber, “Anatomy of the estrogen response element” 2004, TRENDS in
Endocrinology and Metabolism Vol.15 No.2 Elsevier, 73-8.
doi: 10.1016/j.tem.2004.01.008
Chelsea DeLeon , David Q.-H. Wang and Christopher K. Arnatt, “G Protein-Coupled
Estrogen Receptor, GPER1, Offers a Novel Target for the Treatment of Digestive
Diseases” 2020, Front. Endocrinol. https://doi.org/10.3389/fendo.2020.578536
Rainer G , Günter E and Carsten G, “ Estrogen Signaling in ERα-Negative Breast
Cancer: ERβ and GPER” 2019, Front. Endocrinol
https://doi.org/10.3389/fendo.2018.00781
https://www.webmd.com/breast-cancer/breast-cancer-types-er-positive-her2-
positive