In this seminar presentation we unveiled the role of Androgen and androgen receptors in the progression of prostate cancer into metastatic phenotype and current therapies targeting AR signalling.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...daranisaha
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...eshaasini
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...semualkaira
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...semualkaira
: Prolyl 4-hydroxylase, beta polypeptide (P4HB)
and Glucose‑regulated protein 78 (GRP78) represent for poor
prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer
This study examined the effects of combined inhibition of the Src family kinases (SFK) and insulin-like growth factor 1 receptor (IGF-1R) pathways in prostate cancer (PCa) cells and in mouse models. Dual inhibition of these pathways more potently inhibited PCa tumor growth in vitro and in vivo compared to inhibiting either pathway alone. The combination treatment more completely inhibited Akt phosphorylation and downstream survival pathways in the cancer cells. This suggests that targeting both the SFK and IGF-1R pathways may be a promising therapeutic strategy for PCa by blocking independent and cooperative processes important for tumor growth and survival.
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...JohnJulie1
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...AnonIshanvi
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...daranisaha
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...daranisaha
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...eshaasini
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...semualkaira
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...semualkaira
: Prolyl 4-hydroxylase, beta polypeptide (P4HB)
and Glucose‑regulated protein 78 (GRP78) represent for poor
prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer
This study examined the effects of combined inhibition of the Src family kinases (SFK) and insulin-like growth factor 1 receptor (IGF-1R) pathways in prostate cancer (PCa) cells and in mouse models. Dual inhibition of these pathways more potently inhibited PCa tumor growth in vitro and in vivo compared to inhibiting either pathway alone. The combination treatment more completely inhibited Akt phosphorylation and downstream survival pathways in the cancer cells. This suggests that targeting both the SFK and IGF-1R pathways may be a promising therapeutic strategy for PCa by blocking independent and cooperative processes important for tumor growth and survival.
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...JohnJulie1
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...AnonIshanvi
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...daranisaha
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...EditorSara
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability..
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...semualkaira
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability..
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...semualkaira
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...NainaAnon
This study examined the expression levels of deadenylases in small cell lung cancer (SCLC) clinical samples and their correlation to patient clinical characteristics and survival. Real-time PCR analysis found that the deadenylases PARN, CNOT6, CNOT7, and NOC were differentially expressed between malignant and normal lung tissue samples. Higher expression levels of PARN, CNOT6, and CNOT7 correlated with older patient age and decreased overall survival of 180 days or less. The results suggest these deadenylases may serve as prognostic biomarkers for SCLC patient outcomes.
Epidemiological study protocol on 5 ARI and prostate cancer mortalitymjavan2001
This document outlines a protocol for a retrospective cohort study assessing the association between 5-alpha reductase inhibitor (5ARI) use and prostate cancer mortality. The study will use electronic health record data from four sites from 1992-2010. The primary objective is to compare the risk of prostate cancer mortality between men treated with 5ARIs with or without alpha-blockers versus alpha-blockers alone for benign prostatic hyperplasia. Secondary objectives include assessing risks of metastatic prostate cancer mortality and all-cause mortality. The study will match 5ARI users to alpha-blocker users based on age, year of treatment initiation, race, and prior alpha-blocker use. Outcomes will be identified using electronic algorithms validated
British J Pharmacology - 2021 - Healy - The importance of Ras in drug resista...RajeshKumarRapolu
This document discusses drug resistance in cancer that is mediated by oncogenic Ras mutations. It covers several key points:
1) Ras mutations can cause intrinsic and acquired resistance to chemotherapy and targeted therapies by constitutively activating proliferative and survival pathways. This resistance occurs across many cancer types.
2) Ras mutations contribute to the survival of cancer stem cells through pathways like Wnt/β-catenin and MAPK that promote stem cell self-renewal. Cancer stem cells are intrinsically resistant to chemotherapy.
3) Examples of drug resistance caused by downstream Ras mutations include resistance to EGFR inhibitors in cancers where Ras operates downstream of EGFR. Combination therapies may help prevent resistance arising from minor tumor subclones
This study examines a novel protein called DP103 and its role in regulating the PI3K/AKT/mTOR pathway in gastric cancer. Analysis of patient tissue samples showed increased DP103 expression in gastric cancer tissues compared to normal tissues, and a positive correlation between DP103 and PIK3CA expression. Knocking down DP103 in gastric cancer cells inhibited the PI3K/AKT/mTOR pathway and its downstream targets, and decreased resistance to dual Akt/mTOR inhibitors. The findings suggest DP103 interacts with the PI3K/AKT/mTOR pathway and may mediate drug resistance in gastric cancers with high DP103 expression.
This document summarizes recent proteomic studies that have enhanced our understanding of discoidin domain receptors (DDRs). Proteomic profiling has identified phosphorylation of DDR1 and DDR2 in lung, cholangiocarcinoma, and sarcoma tumors, demonstrating their activation in vivo. Studies also suggest crosstalk between DDRs and other receptor tyrosine kinases like EGFR in cancer. Chemical proteomics has identified DDRs as off-target binding partners of kinase inhibitors originally developed for other targets like BCR-ABL, highlighting their potential as therapeutic targets. Together, these proteomic approaches are providing new insights into DDR signaling networks and roles in health and disease.
This document summarizes recent research on the role of noncoding RNAs, such as microRNAs and long noncoding RNAs, in prostate cancer progression and castration-resistant prostate cancer. It discusses how some noncoding RNAs are regulated by the androgen receptor and promote tumor growth by influencing processes like apoptosis, cell cycle, and cell invasion. The expression levels of certain microRNAs have been associated with prostate cancer diagnosis, aggressiveness, and treatment resistance. Integrative analyses of androgen receptor binding sites and regulated transcripts have provided new insights into the complex molecular mechanisms driven by noncoding RNAs in prostate cancer.
This document summarizes recent research on the role of noncoding RNAs, such as microRNAs and long noncoding RNAs, in prostate cancer progression and castration-resistant prostate cancer. It discusses how some noncoding RNAs are regulated by the androgen receptor and promote tumor growth by influencing processes like apoptosis, cell cycle, and epigenetic regulation. The expression levels of certain microRNAs have been associated with prostate cancer diagnosis, aggressiveness, and treatment resistance. Integrative analyses of androgen receptor binding sites and regulated transcripts have provided new insights into prostate cancer's molecular mechanisms.
This document discusses new strategies for combating cancer through molecular biology approaches. It describes prevention strategies that focus on pre-invasive lesions by inhibiting carcinogen initiation events, cell proliferation associated with promotion, or the development of the invasive phenotype in precancerous lesions. Targets for prevention strategies include biochemical species produced by carcinogens and aberrantly expressed proteins from genetic/environmental risk factors. Gene expression profiling using cDNA microarrays can help understand carcinogenesis at the molecular level and identify new therapeutic targets. The document also discusses inhibiting metastasis through strategies like modifying cell adhesion with MMP inhibitors or anticoagulants, and inhibiting angiogenesis. Gene therapy approaches for cancer treatment aim to correct genetic mutations or deliver therapeutic genes to stimulate anti-tumor immune
This study analyzed 264 gastric cancers for mutations in exons 9 and 20 of the PIK3CA gene. PIK3CA mutations were found in 42 cases (16%), all heterozygous missense mutations. The most common mutation was H1047R in exon 20 (62% of mutations) and the second most common was Q546K in exon 9 (9.5% of mutations). A meta-analysis of 27 publications found that the ratio of exon 20 to exon 9 mutations varied by cancer type, being highest in gastric cancer. The exon mutation selectivity is a signature of the cancer type.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...JohnJulie1
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
This study aimed to investigate the correlation between the expression of P4HB and GRP78 proteins and their prognostic value in gastric cancer. The study found that P4HB protein expression was positively correlated with GRP78 protein expression in gastric cancer tissue samples. High expression of either P4HB or GRP78 alone, or co-expression of both, was associated with poorer overall survival in patients. When considering postoperative adjuvant chemotherapy, high co-expression of P4HB and GRP78 only represented an unfavorable prognosis in patients who received chemotherapy. A prognostic nomogram incorporating P4HB and GRP78 expression and other factors was developed and found to have better predictive performance than the TNM staging system.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...NainaAnon
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Instructions Respond to your colleague in one of the following TatianaMajor22
Instructions:
Respond to your colleague in one of the following ways:
· If your colleagues’ posts influenced your understanding of these concepts, be sure to share how and why. Include additional insights you gained.
· If you think your colleagues might have misunderstood these concepts, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective.
**minimum of three (3) scholarly references are required for each reply cited within the body of the reply & at the end**
Reply # 1
Sheila Shafer
Initial Post
Top of Form
Constitutive receptor activity/inverse agonism and functional selectivity/biased agonism are two concepts in contemporary pharmacology possessing significant indications for drug use in medicine and research and new drug development processes since a drug can be simultaneously an agonist, an antagonist, and an inverse agonist acting at the same receptor (Berg & Clarke, 2018). Agonists are drugs with affinity (bind to the target receptor) and intrinsic efficacy (change receptor activity to produce a response). Antagonists have affinity but zero intrinsic efficacy; therefore, they bind to the target receptor but do not produce a response. Occupying a fraction of the receptor population (defined by the affinity of the antagonist), an antagonist reduces the probability of occupancy by an agonist. Thus, the presence of an antagonist will reduce receptor occupancy by an agonist with a corresponding reduction in response. Dopamine receptor antagonism is a compelling molecular target for treating various psychiatric disorders, including substance use disorders (Wager et al., 2017).
G-protein-coupled receptors (GPCRs) or seven transmembrane receptors (7-TM receptors) are the most prominent family of human cell surface receptors, a large protein group positioned on the cell membrane which binds to extracellular elements (Rehman & Dimri, 2021). GPCRs then transmit signals from extracellular substances to the G protein in the intracellular space. Ion gated channels control access in and out of neurons. The voltage-gated ion channels (VGIC) permit only one type of ion to permeate; ligand-gated ion channels (LGIC) are less selective, enabling two or more types of ions to pass through the channel pore (Clar & Maani, 2021). The agonist spectrum is a comparison that relates to both ion channels and G-protein-linked receptors. Both g couple proteins and ion gated channels are protein receptors embedded in cell membranes that bind to a molecule.
Epigenetics refers to the genetic information directed at defining the role of the entire genome. It studies heritable and stable changes in gene expression occurring through modifications in the chromosome rather than in the DNA sequence. Epigenetic mechanisms regulate gene expression through chemical changes of DNA bases and alterations to the chromosomal superstructure (Al Aboud et al., 2021). Phar ...
Methods, Challenges and Future Directions of Radiogenomics-Crimson PublishersCrimsonpublishersCancer
Tissue response to the radiation is a complex pathophysiological process and is an inherited polygenic trait. Aim of the Radiogenomics studies is to discover related genetic variants that confer tumor or nontumor tissue radio sensitivity as the target of radio-sensitizing and/or radio-protective agents and to identify specific genetic markers for prognosis or risk prediction. The methods for radiogenomics studies include candidate gene approaches, genome-wide association studies, Next-Generation Sequencing (NGS), epigenetic study, and other methods. The future direction of radiogenomics should be the development of the polygenic risk scores that are incorporated into end point-specific clinical models/nomograms.
This document discusses recent advances and ongoing challenges in treating metastatic prostate cancer. Key points include:
1) Androgen deprivation therapy combined with docetaxel or abiraterone plus prednisone is now standard of care for patients initially diagnosed with metastatic disease based on improved survival seen in clinical trials.
2) New, more sensitive imaging techniques are enabling earlier detection of metastases but implications for treatment are still unclear.
3) Longer survival with metastatic disease has prompted questions about optimal treatment of the primary tumor site.
4) Understanding mechanisms of castration resistance, such as altered androgen receptor signaling, may help address ongoing challenges in treating advanced disease.
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...EditorSara
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability..
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...semualkaira
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability..
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...semualkaira
Lung cancer is the second common malignancy and the most aggressive cancer worldwide with late diagnosis and poor prognosis. The search for biomarkers that promote early diagnosis and improve therapeutic strategies focuses to the understanding of the mechanisms underlying cancer development and progression. The deregulation of gene expression is one of the cancer hallmarks reflected to the stability...
Deadenylase Expression in Small Cell Lung Cancer Related To Clinical Characte...NainaAnon
This study examined the expression levels of deadenylases in small cell lung cancer (SCLC) clinical samples and their correlation to patient clinical characteristics and survival. Real-time PCR analysis found that the deadenylases PARN, CNOT6, CNOT7, and NOC were differentially expressed between malignant and normal lung tissue samples. Higher expression levels of PARN, CNOT6, and CNOT7 correlated with older patient age and decreased overall survival of 180 days or less. The results suggest these deadenylases may serve as prognostic biomarkers for SCLC patient outcomes.
Epidemiological study protocol on 5 ARI and prostate cancer mortalitymjavan2001
This document outlines a protocol for a retrospective cohort study assessing the association between 5-alpha reductase inhibitor (5ARI) use and prostate cancer mortality. The study will use electronic health record data from four sites from 1992-2010. The primary objective is to compare the risk of prostate cancer mortality between men treated with 5ARIs with or without alpha-blockers versus alpha-blockers alone for benign prostatic hyperplasia. Secondary objectives include assessing risks of metastatic prostate cancer mortality and all-cause mortality. The study will match 5ARI users to alpha-blocker users based on age, year of treatment initiation, race, and prior alpha-blocker use. Outcomes will be identified using electronic algorithms validated
British J Pharmacology - 2021 - Healy - The importance of Ras in drug resista...RajeshKumarRapolu
This document discusses drug resistance in cancer that is mediated by oncogenic Ras mutations. It covers several key points:
1) Ras mutations can cause intrinsic and acquired resistance to chemotherapy and targeted therapies by constitutively activating proliferative and survival pathways. This resistance occurs across many cancer types.
2) Ras mutations contribute to the survival of cancer stem cells through pathways like Wnt/β-catenin and MAPK that promote stem cell self-renewal. Cancer stem cells are intrinsically resistant to chemotherapy.
3) Examples of drug resistance caused by downstream Ras mutations include resistance to EGFR inhibitors in cancers where Ras operates downstream of EGFR. Combination therapies may help prevent resistance arising from minor tumor subclones
This study examines a novel protein called DP103 and its role in regulating the PI3K/AKT/mTOR pathway in gastric cancer. Analysis of patient tissue samples showed increased DP103 expression in gastric cancer tissues compared to normal tissues, and a positive correlation between DP103 and PIK3CA expression. Knocking down DP103 in gastric cancer cells inhibited the PI3K/AKT/mTOR pathway and its downstream targets, and decreased resistance to dual Akt/mTOR inhibitors. The findings suggest DP103 interacts with the PI3K/AKT/mTOR pathway and may mediate drug resistance in gastric cancers with high DP103 expression.
This document summarizes recent proteomic studies that have enhanced our understanding of discoidin domain receptors (DDRs). Proteomic profiling has identified phosphorylation of DDR1 and DDR2 in lung, cholangiocarcinoma, and sarcoma tumors, demonstrating their activation in vivo. Studies also suggest crosstalk between DDRs and other receptor tyrosine kinases like EGFR in cancer. Chemical proteomics has identified DDRs as off-target binding partners of kinase inhibitors originally developed for other targets like BCR-ABL, highlighting their potential as therapeutic targets. Together, these proteomic approaches are providing new insights into DDR signaling networks and roles in health and disease.
This document summarizes recent research on the role of noncoding RNAs, such as microRNAs and long noncoding RNAs, in prostate cancer progression and castration-resistant prostate cancer. It discusses how some noncoding RNAs are regulated by the androgen receptor and promote tumor growth by influencing processes like apoptosis, cell cycle, and cell invasion. The expression levels of certain microRNAs have been associated with prostate cancer diagnosis, aggressiveness, and treatment resistance. Integrative analyses of androgen receptor binding sites and regulated transcripts have provided new insights into the complex molecular mechanisms driven by noncoding RNAs in prostate cancer.
This document summarizes recent research on the role of noncoding RNAs, such as microRNAs and long noncoding RNAs, in prostate cancer progression and castration-resistant prostate cancer. It discusses how some noncoding RNAs are regulated by the androgen receptor and promote tumor growth by influencing processes like apoptosis, cell cycle, and epigenetic regulation. The expression levels of certain microRNAs have been associated with prostate cancer diagnosis, aggressiveness, and treatment resistance. Integrative analyses of androgen receptor binding sites and regulated transcripts have provided new insights into prostate cancer's molecular mechanisms.
This document discusses new strategies for combating cancer through molecular biology approaches. It describes prevention strategies that focus on pre-invasive lesions by inhibiting carcinogen initiation events, cell proliferation associated with promotion, or the development of the invasive phenotype in precancerous lesions. Targets for prevention strategies include biochemical species produced by carcinogens and aberrantly expressed proteins from genetic/environmental risk factors. Gene expression profiling using cDNA microarrays can help understand carcinogenesis at the molecular level and identify new therapeutic targets. The document also discusses inhibiting metastasis through strategies like modifying cell adhesion with MMP inhibitors or anticoagulants, and inhibiting angiogenesis. Gene therapy approaches for cancer treatment aim to correct genetic mutations or deliver therapeutic genes to stimulate anti-tumor immune
This study analyzed 264 gastric cancers for mutations in exons 9 and 20 of the PIK3CA gene. PIK3CA mutations were found in 42 cases (16%), all heterozygous missense mutations. The most common mutation was H1047R in exon 20 (62% of mutations) and the second most common was Q546K in exon 9 (9.5% of mutations). A meta-analysis of 27 publications found that the ratio of exon 20 to exon 9 mutations varied by cancer type, being highest in gastric cancer. The exon mutation selectivity is a signature of the cancer type.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...JohnJulie1
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...EditorSara
This study aimed to investigate the correlation between the expression of P4HB and GRP78 proteins and their prognostic value in gastric cancer. The study found that P4HB protein expression was positively correlated with GRP78 protein expression in gastric cancer tissue samples. High expression of either P4HB or GRP78 alone, or co-expression of both, was associated with poorer overall survival in patients. When considering postoperative adjuvant chemotherapy, high co-expression of P4HB and GRP78 only represented an unfavorable prognosis in patients who received chemotherapy. A prognostic nomogram incorporating P4HB and GRP78 expression and other factors was developed and found to have better predictive performance than the TNM staging system.
Clinic Correlation and Prognostic Value of P4HB and GRP78 Expression in Gastr...NainaAnon
Prolyl 4-hydroxylase, beta polypeptide (P4HB) and Glucose‑regulated protein 78 (GRP78) represent for poor prognosis of various cancers, while rare research investigate correlation of them. This study aimed to explore correlation and prognostic value of them in gastric cancer (GC).
Instructions Respond to your colleague in one of the following TatianaMajor22
Instructions:
Respond to your colleague in one of the following ways:
· If your colleagues’ posts influenced your understanding of these concepts, be sure to share how and why. Include additional insights you gained.
· If you think your colleagues might have misunderstood these concepts, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective.
**minimum of three (3) scholarly references are required for each reply cited within the body of the reply & at the end**
Reply # 1
Sheila Shafer
Initial Post
Top of Form
Constitutive receptor activity/inverse agonism and functional selectivity/biased agonism are two concepts in contemporary pharmacology possessing significant indications for drug use in medicine and research and new drug development processes since a drug can be simultaneously an agonist, an antagonist, and an inverse agonist acting at the same receptor (Berg & Clarke, 2018). Agonists are drugs with affinity (bind to the target receptor) and intrinsic efficacy (change receptor activity to produce a response). Antagonists have affinity but zero intrinsic efficacy; therefore, they bind to the target receptor but do not produce a response. Occupying a fraction of the receptor population (defined by the affinity of the antagonist), an antagonist reduces the probability of occupancy by an agonist. Thus, the presence of an antagonist will reduce receptor occupancy by an agonist with a corresponding reduction in response. Dopamine receptor antagonism is a compelling molecular target for treating various psychiatric disorders, including substance use disorders (Wager et al., 2017).
G-protein-coupled receptors (GPCRs) or seven transmembrane receptors (7-TM receptors) are the most prominent family of human cell surface receptors, a large protein group positioned on the cell membrane which binds to extracellular elements (Rehman & Dimri, 2021). GPCRs then transmit signals from extracellular substances to the G protein in the intracellular space. Ion gated channels control access in and out of neurons. The voltage-gated ion channels (VGIC) permit only one type of ion to permeate; ligand-gated ion channels (LGIC) are less selective, enabling two or more types of ions to pass through the channel pore (Clar & Maani, 2021). The agonist spectrum is a comparison that relates to both ion channels and G-protein-linked receptors. Both g couple proteins and ion gated channels are protein receptors embedded in cell membranes that bind to a molecule.
Epigenetics refers to the genetic information directed at defining the role of the entire genome. It studies heritable and stable changes in gene expression occurring through modifications in the chromosome rather than in the DNA sequence. Epigenetic mechanisms regulate gene expression through chemical changes of DNA bases and alterations to the chromosomal superstructure (Al Aboud et al., 2021). Phar ...
Methods, Challenges and Future Directions of Radiogenomics-Crimson PublishersCrimsonpublishersCancer
Tissue response to the radiation is a complex pathophysiological process and is an inherited polygenic trait. Aim of the Radiogenomics studies is to discover related genetic variants that confer tumor or nontumor tissue radio sensitivity as the target of radio-sensitizing and/or radio-protective agents and to identify specific genetic markers for prognosis or risk prediction. The methods for radiogenomics studies include candidate gene approaches, genome-wide association studies, Next-Generation Sequencing (NGS), epigenetic study, and other methods. The future direction of radiogenomics should be the development of the polygenic risk scores that are incorporated into end point-specific clinical models/nomograms.
This document discusses recent advances and ongoing challenges in treating metastatic prostate cancer. Key points include:
1) Androgen deprivation therapy combined with docetaxel or abiraterone plus prednisone is now standard of care for patients initially diagnosed with metastatic disease based on improved survival seen in clinical trials.
2) New, more sensitive imaging techniques are enabling earlier detection of metastases but implications for treatment are still unclear.
3) Longer survival with metastatic disease has prompted questions about optimal treatment of the primary tumor site.
4) Understanding mechanisms of castration resistance, such as altered androgen receptor signaling, may help address ongoing challenges in treating advanced disease.
Similar to UNLOCKING THE SECRETS OF ANDROGEN RECEPTORS IN PROSTATE CANCER SUSCEPTIBILITY, PROGRESSION, DIAGNOSIS AND TREATMENT (20)
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
Gender and Mental Health - Counselling and Family Therapy Applications and In...PsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Chapter wise All Notes of First year Basic Civil Engineering.pptxDenish Jangid
Chapter wise All Notes of First year Basic Civil Engineering
Syllabus
Chapter-1
Introduction to objective, scope and outcome the subject
Chapter 2
Introduction: Scope and Specialization of Civil Engineering, Role of civil Engineer in Society, Impact of infrastructural development on economy of country.
Chapter 3
Surveying: Object Principles & Types of Surveying; Site Plans, Plans & Maps; Scales & Unit of different Measurements.
Linear Measurements: Instruments used. Linear Measurement by Tape, Ranging out Survey Lines and overcoming Obstructions; Measurements on sloping ground; Tape corrections, conventional symbols. Angular Measurements: Instruments used; Introduction to Compass Surveying, Bearings and Longitude & Latitude of a Line, Introduction to total station.
Levelling: Instrument used Object of levelling, Methods of levelling in brief, and Contour maps.
Chapter 4
Buildings: Selection of site for Buildings, Layout of Building Plan, Types of buildings, Plinth area, carpet area, floor space index, Introduction to building byelaws, concept of sun light & ventilation. Components of Buildings & their functions, Basic concept of R.C.C., Introduction to types of foundation
Chapter 5
Transportation: Introduction to Transportation Engineering; Traffic and Road Safety: Types and Characteristics of Various Modes of Transportation; Various Road Traffic Signs, Causes of Accidents and Road Safety Measures.
Chapter 6
Environmental Engineering: Environmental Pollution, Environmental Acts and Regulations, Functional Concepts of Ecology, Basics of Species, Biodiversity, Ecosystem, Hydrological Cycle; Chemical Cycles: Carbon, Nitrogen & Phosphorus; Energy Flow in Ecosystems.
Water Pollution: Water Quality standards, Introduction to Treatment & Disposal of Waste Water. Reuse and Saving of Water, Rain Water Harvesting. Solid Waste Management: Classification of Solid Waste, Collection, Transportation and Disposal of Solid. Recycling of Solid Waste: Energy Recovery, Sanitary Landfill, On-Site Sanitation. Air & Noise Pollution: Primary and Secondary air pollutants, Harmful effects of Air Pollution, Control of Air Pollution. . Noise Pollution Harmful Effects of noise pollution, control of noise pollution, Global warming & Climate Change, Ozone depletion, Greenhouse effect
Text Books:
1. Palancharmy, Basic Civil Engineering, McGraw Hill publishers.
2. Satheesh Gopi, Basic Civil Engineering, Pearson Publishers.
3. Ketki Rangwala Dalal, Essentials of Civil Engineering, Charotar Publishing House.
4. BCP, Surveying volume 1
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
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centuries, evolving its structure over time and space. In the present era, these changes have
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𝐃𝐢𝐬𝐜𝐮𝐬𝐬 𝐭𝐡𝐞 𝐄𝐏𝐏 𝐂𝐮𝐫𝐫𝐢𝐜𝐮𝐥𝐮𝐦 𝐢𝐧 𝐭𝐡𝐞 𝐏𝐡𝐢𝐥𝐢𝐩𝐩𝐢𝐧𝐞𝐬:
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𝐄𝐱𝐩𝐥𝐚𝐢𝐧 𝐭𝐡𝐞 𝐍𝐚𝐭𝐮𝐫𝐞 𝐚𝐧𝐝 𝐒𝐜𝐨𝐩𝐞 𝐨𝐟 𝐚𝐧 𝐄𝐧𝐭𝐫𝐞𝐩𝐫𝐞𝐧𝐞𝐮𝐫:
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Pengantar Penggunaan Flutter - Dart programming language1.pptx
UNLOCKING THE SECRETS OF ANDROGEN RECEPTORS IN PROSTATE CANCER SUSCEPTIBILITY, PROGRESSION, DIAGNOSIS AND TREATMENT
1. A Seminar Presentation
on
UNLOCKING THE SECRETS OF ANDROGEN RECEPTORS IN
PROSTATE CANCER SUSCEPTIBILITY, PROGRESSION,
DIAGNOSIS AND TREATMENT
Presented by:
ZAKARI, Suleiman
22PCP02390
Supervised by:
PROF. O.O. OGUNLANA
1
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2. Outline
Introduction
Androgens and their Receptors
Prostate Cancer (PCa) Susceptibility
Role of Androgen Receptors (AR) in PCa
Targeting AR in PCa
Androgen Deprivation Therapy
Emerging Therapies Targeting AR
Conclusion
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3. Introduction
Prostate Cancer: the cancer that occurs in the
prostate.
Epidemiology: The frequency of PCa has risen with an
estimate of one in nine men developing the disease in
their lifetime (Nevedomskaya & Baumgart, 2018). More
than 1.4 million new cases of prostate cancer were
found globally in 2020 (Wang et al., 2022).
Risk factors: Age, race, life style and eating habit,
hereditary and family history.
Androgens and Androgen Receptors: Recent
discoveries by several researchers suggest that AR is
essential for the growth of Pca and the AR gene is
consistently up-regulated during tumor progression
(Student et al., 2020). 3
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4. Androgens and Their Receptors
Androgens are steroid hormones that exert their
effects through the Androgen receptor (AR).
They include testosterone and dihydrotestosterone
(DHT), dehydroepiandrosterone (DHEA), and
androstenedione, among others.
Testosterone is responsible for the growth,
differentiation, and maintenance of prostatic
tissues and the development of male sexual organs
and secondary sex characteristics.
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5. Structure of Androgen Receptor Gene and
Protein
The AR gene is situated on chromosome Xq11-12, The
AR gene consists of eight exons, with exon 1 encoding
the NTD, exons 2-3 encoding the DBD, exon 4 encoding
the HR, and exons 5-8 encoding the LBD as shown in
(see figure 1). AR weighs 110 kDa and has 920 amino
acids (Messner et al., 2020).
Functional domains:
I. NH2-terminal domain (NTD) that contains the
transcriptional activation function 1 (AF-1)
II. A central DNA-binding domain (DBD) linked to hinge
region, and
III. A COOH-terminal ligand-binding domain (LBD), which
is linked to the DBD by a hinge region and contains
the transcriptional activation function 2 (AF-2)
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6. Figure 1: Androgen receptor gene and protein
(Crona & Whang, 2017)
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7. Prostate Cancer Susceptibility
Genetic mutations or alterations that occur in several genes
play the most vital a role in PCa development (Badal et al.,
2020). Mutation of mismatch repair genes (MMR, MLH1, MSH2,
MSH6, and PMS2) and homologous recombination genes
(BRCA1/2, ATM, PALB2, and CHEK2) are currently the most
consistently associated genes with PCa susceptibility (Badal et
al., 2020).
Studies of polymorphisms in androgen-related genes have
shown that the variation in the androgen receptor impacts
the risk of prostate cancer (Song et al., 2023).
A polymorphism sequence of CAG repeats encoding
polyglutamine can be found in the first exon of AR, which
codes for the N-terminal domain. Longer CAG repeats are
linked to androgen insensitivity syndrome, while shorter CAG
repeats are correlated with enhanced AR transcriptional
activity (Allemailem et al., 2021). 7
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8. Role of Androgen Receptor in PCa
AR is a critical player in the development and
progression of PCa (Shaffer et al., 2004). In healthy
prostate tissue, AR signalling is tightly regulated,
and androgens stimulate the growth and
differentiation of prostate epithelial cells.
However, in PCa, AR signalling becomes
dysregulated, and the cancer cells become more
dependent on androgen signalling for their growth
and survival.
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10. Mechanism of Deregulated AR Signalling
Ligand-dependent activation:
I. AR amplification: The AR gene can be duplicated or
amplified, leading to an increase in the number of
AR receptors on the cell surface.
II. AR promiscuity: binds alternative ligands such as
glucocorticoids, adrenal androgens and their
metabolites.
III. AR mutations: Mutations in the AR gene can cause
the receptor to become hypersensitive to
androgens or to activate in response to other
hormones or signaling pathways e.g splice variant.
10
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11. Fig 3: Dysregulated AR in PCa as target (Chandrasekar, et
al., 2015) 11
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12. Ligand-independent activation: In some cases, the
AR can become activated even in the absence of
androgens, through interactions with other
proteins or signaling pathways.
I. Aberrant activation: RTK activation of Akt and
MAPK signalling
II. Modification of co-regulators: co-regulators
inhibits P53 allowing continuous proliferation
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13. Crosstalk between AR signalling and PI3K/Akt
pathway
Research has demonstrated that AR interacts with
other signaling pathways, such as the PI3K/Akt
pathway (Pungsrinont et al., 2021).
PI3K and AR signalling are two crucial pathways
that control cellular growth, survival, and
metabolism in PCa. Crosstalk between these two
pathways has been connected to the
development and progression of numerous
cancers, including PCa (Fig 5).
13
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14. Fig 5: Crosstalk between AR and PI3K signaling
pathway as target (Tortorella et al., 2023)
14
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15. Targeting AR in PCa care
AR signaling is still essential for tumor growth..
Some popular therapies used are:
I. Androgen Deprivation Therapy (ADT): ADT can
substantially lower the amount of available
androgens in men with PCa, which in turn lowers
AR's transcriptional activity (Ban et al., 2021).
Abiraterone, enzalutamide, darolutamide, and
apalutamide are a few examples (Negri et al.,
2023).
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16. Emerging Therapies Targeting AR
Despite the fact that ADT can be helpful in symptom
improvement and slowing the spread of PCa, all
patients eventually develop deadly metastatic CRPC
(Tortorella et al., 2023). As a result, novel AR-
targeted therapies, such as second-generation anti-
androgens and androgen receptor signaling
inhibitors (ARSIs).
16
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17. II. Androgen receptor signaling inhibitors
(ARSIs)
Because AR signaling promotes tumor growth,
medicines known as AR signaling inhibitors (ARSIs),
which work to block AR signaling, have long been
used in clinical settings (Jamroze et al., 2021).
These drugs can be used alone or in combination
with other treatments, such as chemotherapy or
radiation therapy, to treat prostate cancer. They
can also be used to manage the symptoms of
advanced prostate cancer. There are several types
of androgen receptor signaling inhibitors,
including:
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18. Anti-androgens: These drugs impair androgen from
forming complex to its receptors, preventing the
cancer cells from receiving the signal to grow and
divide. Examples include bicalutamide, flutamide,
and nilutamide.
GnRH agonists: These drugs reduce the production
of androgens by the testes by inhibiting the release
of gonadotropin-releasing hormone (GnRH) from the
hypothalamus. This causes reduction in
testosterone levels in the body, which can slow the
growth of prostate cancer. Examples include
leuprolide and goserelin.
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19. CYP17 inhibitors: These drugs block an enzyme
called CYP17, which is involved in the production of
androgens in the adrenal gland and in the prostate
cancer cells themselves. Examples include
abiraterone acetate.
Androgen receptor antagonists: These drugs block
the activity of androgen receptors directly,
preventing them from stimulating the growth of
prostate cancer cells. Examples include
enzalutamide and apalutamide.
19
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20. Mechanism of Action of Abiraterone
The de novo synthesis of androgens is activated by
CYP17A1 increased expression and mutation, which
also raises the level of DHEA in the tumor.
Abiraterone is a CYP17A1 enzyme-selective,
irrevocable blocker that has received FDA approval
that efficiently prevents androgen synthesis in the
testis, adrenal gland, and PCa.
20
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21. Mechanism of Action of Abiraterone
According to medical findings, those with metastatic
CRPC who take abiraterone and prednisone together
have longer overall survival times and disease-free
survival times.
21
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22. Conclusion
In conclusion, AR is important in the development and
progression of PCa, and targeting it has proven to be
an effective strategy for treating the disease.
Combining multiple diagnostic strategies, such as
measuring AR and PSA levels, may improve prostate
cancer detection accuracy. More research is needed to
fully understand the complex mechanisms of AR in PCa
and to develop new early detection diagnostic
strategies. Resistance to androgen deprivation therapy
is also a major challenge, and new strategies such as
combinational therapies are required to target AR in
advanced stages of PCa.
22
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23. References
Jamroze, A., Chatta, G. & Tang, D.G. (2021) Androgen receptor (AR)
heterogeneity in prostate cancer and therapy resistance. Cancer Letters.
518, 1–9. doi:10.1016/j.canlet.2021.06.006.
Messner, E.A., Steele, T.M., Tsamouri, M.M., Hejazi, N., Gao, A.C.,
Mudryj, M. & Ghosh, P.M. (2020) The Androgen Receptor in Prostate
Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy.
Biomedicines. 8 (10), 422. doi:10.3390/biomedicines8100422.
Nevedomskaya, E., Baumgart, S.J. & Haendler, B. (2018) Recent
Advances in Prostate Cancer Treatment and Drug Discovery. International
Journal of Molecular Sciences. 19 (5), 1359. doi:10.3390/ijms19051359.
Student, S., Hejmo, T., Poterała-Hejmo, A., Leśniak, A. & Bułdak, R.
(2020) Anti-androgen hormonal therapy for cancer and other diseases.
European Journal of Pharmacology. 866, 172783.
doi:10.1016/j.ejphar.2019.172783.
Tortorella, E., Giantulli, S., Sciarra, A. & Silvestri, I. (2023) AR and
PI3K/AKT in Prostate Cancer: A Tale of Two Interconnected Pathways.
International Journal of Molecular Sciences. 24 (3), 2046.
doi:10.3390/ijms24032046.
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