The document summarizes a study on CD24 expression and its role in male urothelial tumorigenesis and metastasis. The study found that:
1) Loss of CD24 was associated with reduced bladder tumor incidence and protected the bladder urothelium from tumorigenesis in mice exposed to a carcinogen.
2) Bladder tumors had higher levels of CD24 mRNA and protein expression than non-cancerous tissue.
3) Loss of CD24 decreased metastasis in male mice and appeared protective against tumorigenesis and metastasis specifically in males.
4) CD24 expression was found to be androgen-regulated, with androgens increasing CD24 expression at the mRNA and
Molecular localization of epstein barr virus and rb tumor suppressor gene exp...Alexander Decker
This document summarizes a study analyzing the expression of Epstein-Barr virus (EBV) and the Rb tumor suppressor gene in prostate tissues. Seventy-two tissue samples, including 40 from prostate cancer and 20 from benign prostatic hyperplasia, were tested for EBV and Rb expression. EBV was detected in 47.5% of cancer samples but only 10% of benign samples, and not in healthy controls. Rb expression was also detected in 47.5% of cancer samples and 10% of benign samples. The high rate of co-expression of EBV and Rb in cancer tissues suggests these factors may play an important role in prostate carcinogenesis.
Tumour markers can play a crucial role in detecting cancer and assessing response to therapy. They are substances produced either by tumour cells or by the body in response to cancer. Oncoproteins are proteins encoded by oncogenes which normally maintain a fine balance between cell proliferation and differentiation but become permanently activated in cancer, stimulating cell growth. Elevated levels of various oncoproteins and other tumour markers can be detected in blood and other body fluids, serving as biomarkers for early cancer detection and prediction of prognosis. Common tumour markers discussed include AFP, CEA, CA19-9, CA15-3, CA125, and proteins associated with growth factors, receptors, and cellular signalling pathways.
Gastric cancer is one of the leading causes of cancer death worldwide. It is a heterogeneous cancer that has been useful for studying carcinogenesis and tumorigenesis. One idea discussed is how the bacterial pathogen H. pylori and the inflammatory cytokine IL-1α cooperate to promote α-catenin translocation, which is associated with epithelial-to-mesenchymal transition (EMT). Another idea is that the inflammatory microenvironment contributes to EMT in gastric cancer by altering cancer cells, potentially through specific immune cells. A third idea is that infection with H. pylori induces EMT markers and the emergence of cancer stem cell-like properties in gastric cells, and eradicating H. pylori reduces these
This document discusses newer tumor markers that can be used for cancer diagnosis, prognosis, and monitoring treatment. It describes various types of biochemical entities that serve as tumor markers, including nucleic acids, proteins, sugars, lipids, and whole tumor cells. Specific examples of tumor markers are discussed, such as enzymes, hormones, oncofetal antigens, tumor-associated proteins, carbohydrate antigens, and genetic markers. The ideal properties of tumor markers and their clinical applications are also summarized.
Dr. Carlos García Echeverría - Simposio Internacional 'Terapias oncológicas a...Fundación Ramón Areces
This document discusses the importance of personalized medicine in drug discovery and development. It describes how understanding a disease's pathogenesis and targeting specific genetic dependencies can lead to more rational drug design compared to empirical approaches. Successful examples are given of targeting drivers of cancer like BCR-Abl in CML and HDM2 amplification in liposarcoma. Combination strategies and imaging companions are discussed to address intratumoral heterogeneity and safely identify patients most likely to benefit from targeted therapies.
Tumor markers are biological substances that are produced by cancer cells or the body's response to cancer. Ideal tumor markers should be highly specific, sensitive, correlate with tumor stage/mass, and predict prognosis. Recent advances include new genetic and viral biomarkers. Tumor markers can be classified as hormones, oncofetal antigens, enzymes, tumor-associated proteins, receptors, and genetic markers. Oncogenes like RAS and C-myc can also serve as markers when mutated or translocated. Establishing biomarkers requires understanding how small molecular changes disrupt cellular functions and cancer initiation.
Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric CancersLAB IDEA
This chapter discusses tumor markers for liver cancer. Liver cancer, or hepatocellular carcinoma, is a major cause of cancer death worldwide. Early detection is important for effective treatment but many cases are asymptomatic and detected late. The guidelines evaluate tumor markers like alpha-fetoprotein for surveillance of high-risk patients and diagnosis of liver cancer, noting their limitations. Recommendations are provided on the appropriate use of tumor markers in conjunction with imaging for managing liver cancer.
This document discusses immunohistochemistry (IHC), which is used to identify tissue antigens through antigen-antibody interactions. It provides details on the IHC process, common antibodies and their targets, and tumor markers. IHC is useful for tumor diagnosis, narrowing differential diagnoses, and detecting unexpected diagnoses. The antibody panels discussed can help determine the primary site of cancers and differentiate between tumor types.
Molecular localization of epstein barr virus and rb tumor suppressor gene exp...Alexander Decker
This document summarizes a study analyzing the expression of Epstein-Barr virus (EBV) and the Rb tumor suppressor gene in prostate tissues. Seventy-two tissue samples, including 40 from prostate cancer and 20 from benign prostatic hyperplasia, were tested for EBV and Rb expression. EBV was detected in 47.5% of cancer samples but only 10% of benign samples, and not in healthy controls. Rb expression was also detected in 47.5% of cancer samples and 10% of benign samples. The high rate of co-expression of EBV and Rb in cancer tissues suggests these factors may play an important role in prostate carcinogenesis.
Tumour markers can play a crucial role in detecting cancer and assessing response to therapy. They are substances produced either by tumour cells or by the body in response to cancer. Oncoproteins are proteins encoded by oncogenes which normally maintain a fine balance between cell proliferation and differentiation but become permanently activated in cancer, stimulating cell growth. Elevated levels of various oncoproteins and other tumour markers can be detected in blood and other body fluids, serving as biomarkers for early cancer detection and prediction of prognosis. Common tumour markers discussed include AFP, CEA, CA19-9, CA15-3, CA125, and proteins associated with growth factors, receptors, and cellular signalling pathways.
Gastric cancer is one of the leading causes of cancer death worldwide. It is a heterogeneous cancer that has been useful for studying carcinogenesis and tumorigenesis. One idea discussed is how the bacterial pathogen H. pylori and the inflammatory cytokine IL-1α cooperate to promote α-catenin translocation, which is associated with epithelial-to-mesenchymal transition (EMT). Another idea is that the inflammatory microenvironment contributes to EMT in gastric cancer by altering cancer cells, potentially through specific immune cells. A third idea is that infection with H. pylori induces EMT markers and the emergence of cancer stem cell-like properties in gastric cells, and eradicating H. pylori reduces these
This document discusses newer tumor markers that can be used for cancer diagnosis, prognosis, and monitoring treatment. It describes various types of biochemical entities that serve as tumor markers, including nucleic acids, proteins, sugars, lipids, and whole tumor cells. Specific examples of tumor markers are discussed, such as enzymes, hormones, oncofetal antigens, tumor-associated proteins, carbohydrate antigens, and genetic markers. The ideal properties of tumor markers and their clinical applications are also summarized.
Dr. Carlos García Echeverría - Simposio Internacional 'Terapias oncológicas a...Fundación Ramón Areces
This document discusses the importance of personalized medicine in drug discovery and development. It describes how understanding a disease's pathogenesis and targeting specific genetic dependencies can lead to more rational drug design compared to empirical approaches. Successful examples are given of targeting drivers of cancer like BCR-Abl in CML and HDM2 amplification in liposarcoma. Combination strategies and imaging companions are discussed to address intratumoral heterogeneity and safely identify patients most likely to benefit from targeted therapies.
Tumor markers are biological substances that are produced by cancer cells or the body's response to cancer. Ideal tumor markers should be highly specific, sensitive, correlate with tumor stage/mass, and predict prognosis. Recent advances include new genetic and viral biomarkers. Tumor markers can be classified as hormones, oncofetal antigens, enzymes, tumor-associated proteins, receptors, and genetic markers. Oncogenes like RAS and C-myc can also serve as markers when mutated or translocated. Establishing biomarkers requires understanding how small molecular changes disrupt cellular functions and cancer initiation.
Use of Tumor Markers in Liver, Bladder, Cervical, and Gastric CancersLAB IDEA
This chapter discusses tumor markers for liver cancer. Liver cancer, or hepatocellular carcinoma, is a major cause of cancer death worldwide. Early detection is important for effective treatment but many cases are asymptomatic and detected late. The guidelines evaluate tumor markers like alpha-fetoprotein for surveillance of high-risk patients and diagnosis of liver cancer, noting their limitations. Recommendations are provided on the appropriate use of tumor markers in conjunction with imaging for managing liver cancer.
This document discusses immunohistochemistry (IHC), which is used to identify tissue antigens through antigen-antibody interactions. It provides details on the IHC process, common antibodies and their targets, and tumor markers. IHC is useful for tumor diagnosis, narrowing differential diagnoses, and detecting unexpected diagnoses. The antibody panels discussed can help determine the primary site of cancers and differentiate between tumor types.
Tumor markers are proteins or mutated proteins that can indicate the presence of cancer. They are useful for screening, diagnosis, monitoring treatment and detecting recurrence, though none are sufficiently sensitive and specific for screening alone. Tumor markers associated with cell proliferation, differentiation, metastasis and other tumor events can provide information about cancer. While not diagnostic, they are helpful for treatment monitoring given their limitations. Proper use requires understanding their sensitivity, specificity and potential causes of false positives.
Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected and measured in bodily fluids or tissues. They can help diagnose certain cancers, distinguish between benign and malignant tumors, monitor treatment response and detect recurrence. However, no single tumor marker is perfect as tumor marker levels can also be elevated in some non-cancerous conditions.
Human cancer development, or oncogenesis, results from genetic changes in oncogenes and tumor suppressor genes. Oncogenes like Ras, Myc, and EGFR promote cancer when overexpressed, while tumor suppressors like p53 and Rb inhibit cancer when functioning normally. Genetic changes from carcinogens, radiation, viruses, or other sources can delete or mutate these genes, altering the control of mitosis and apoptosis and leading to uncontrolled cell growth and the multi-step development of tumors over time. Tumor markers in the blood can indicate the presence, severity, or progression of cancers and help guide treatment responses.
This document summarizes research on mantle cell lymphoma (MCL), a rare type of non-Hodgkin's lymphoma. Key points include:
1) MCL was established as a distinct subtype of lymphoma in 1992 and is characterized by the t(11;14) chromosomal translocation and overexpression of cyclin D1.
2) Current treatments can achieve high response rates but MCL often relapses and no treatment is considered curative for advanced disease.
3) A study found that the combination of lenalidomide and rituximab showed promising efficacy against MCL with an overall response rate of 57% and 33% complete response rate in relapsed/refractory patients.
Tumor markers are substances produced by tumors or the host body in response to tumors. They can be used to detect cancers, determine cancer prognosis, and monitor cancer treatment effectiveness. Some key tumor markers discussed in the document include:
- AFP which is used to detect hepatocellular carcinoma and testicular cancer.
- CEA which is used to detect colorectal cancer recurrence. Rising CEA levels may indicate cancer recurrence while stable levels indicate remission.
- CA125 which is used to detect ovarian and endometrial cancers.
- PSA which is used to screen, stage, and monitor prostate cancer recurrence and treatment.
- HCG which is used to detect germ
Tumor markers are proteins detected in blood that can indicate certain cancers. They are most useful for monitoring response to treatment and detecting early recurrence of cancer. With the exception of PSA, tumor markers lack sufficient accuracy for cancer screening. Some common tumor markers include CA 27.29 for breast cancer, CEA for colorectal cancer, and AFP and beta-hCG for germ cell tumors and liver cancer. While tumor markers can help manage cancer patients, no marker alone guarantees cure or determines treatment; clinical evaluation is also needed.
This document summarizes a research study that investigated the role of long non-coding RNA H19, microRNA miR-29b, and the gene FOXO4 in the apoptosis of retinal Müller cells in diabetic retinopathy. The study found that H19 and FOXO4 expression were increased, while miR-29b expression was decreased, in retinal tissue from diabetic rats and in retinal Müller cells treated with high glucose. Overexpression of H19 promoted retinal Müller cell apoptosis. Knockdown of H19 reversed the effects of high glucose by decreasing cell apoptosis and FOXO4 upregulation. Further experiments indicated that H19 is a target of miR-29b and inhibition of miR-29b
1. Immuno histochemistry is used to detect antigens of interest in tissue sections using antibodies and helps in subtyping cancers of unknown primary, determining prognosis, and guiding personalized treatment.
2. Key markers used in gynecologic cancers include cytokeratins and vimentin to identify epithelial and mesenchymal differentiation, ER and PR to subtype endometrial cancers, and P53 and P16 patterns to distinguish endometrial cancer subtypes.
3. Negative expression of markers like PTEN can also be informative in distinguishing lesions and predicting progression in cancers like endometrial cancer.
Dr. maryalice stetler stevenson lymphoma mrdHitham Esam
Flow cytometry can be used to detect minimal residual disease (MRD) in plasma cell neoplasms such as multiple myeloma. It provides both prognostic information and a way to measure response to drug therapies. Several factors are important for obtaining high quality flow cytometry results, including using bone marrow aspirates within 24 hours of collection, lysing red blood cells, acquiring sufficient events, and using standardized staining and gating strategies. Detection of MRD by flow post-treatment is predictive of patient outcomes and can guide clinical decision making.
This document discusses epithelial tumor markers. It begins by introducing the topic and defining tumor markers as substances produced by or in response to tumors that can be used to detect or characterize tumors. It then describes the ideal properties of tumor markers and various ways to classify them, including as cell surface markers, intracellular markers, types associated with tumor growth, suppression, angiogenesis, and invasion. Specific epithelial and other markers are outlined. Finally, uses of tumor markers are summarized, including for screening, diagnosis, staging, prognosis, evaluating treatment response, and detecting recurrence. Cytokeratins are highlighted as important epithelial markers.
Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected and measured in blood, urine, or body tissues. They can be used to screen for cancers, help diagnose cancer, determine prognosis, stage cancer, detect recurrence, and monitor treatment effectiveness. Common tumor markers include enzymes, hormones, oncofetal antigens, carbohydrates, blood group antigens, proteins, and receptors. Examples are PSA for prostate cancer, CEA for colorectal cancer, CA125 for ovarian cancer, and AFP for liver and germ cell cancers. Tumor marker levels can indicate the presence, location, and spread of cancer as well as how well cancer treatment is working.
Sipuleucel_T Immunotherapy for Metastatic Prostate Cancer after Failing Hormo...mjavan2001
This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.
Tumor markers are biological substances that can be detected in cancer patients that are produced either by the tumor itself or by the body in response to cancer. While ideal tumor markers would be highly specific to cancer, many tumor markers can also be elevated in benign conditions. This can lead to false positives and incorrect interpretation of tumor marker test results. Some conditions that may cause transient or non-transient rises in common tumor markers include cirrhosis, inflammatory bowel disease, pregnancy, and smoking. The lack of specificity of some tumor markers limits their use for screening asymptomatic populations but they can be useful for monitoring known cancer patients. Improved specificity of tumor markers through new technologies may help address this limitation.
This study found that colon cancer cells express the chemokine receptor CCR4, which mediates migration of the cells in response to its ligand CCL17 (TARC) through the RhoA/Rho kinase signaling pathway. Quantitative RT-PCR and flow cytometry showed that the colon cancer cell lines HT-29 and AZ-97 expressed CCR4 at both the mRNA and protein levels. Stimulation with CCL17 induced dose-dependent migration of the colon cancer cells, which was inhibited by blocking CCR4 with an antibody or antagonist. CCL17 also increased mRNA levels of RhoA proteins and RhoA activation in the cells. Inhibition of Rho kinase or isoprenylation blocked CCL17-induced cell migration
Lo que un reumatólogo debe saber de inmunoterapia contra el cáncer, abreviadoMauricio Lema
1. The document discusses various mechanisms of cancer immunotherapy including immune checkpoint inhibitors that target CTLA-4 and PD-1/PD-L1 pathways.
2. Key immunotherapy drugs discussed are ipilimumab, nivolumab, pembrolizumab, avelumab, and durvalumab which target CTLA-4 and PD-1/PD-L1 and have shown efficacy in treating cancers like melanoma, lung cancer, head and neck cancer, and kidney cancer.
3. Several clinical trials are summarized that demonstrate improved survival outcomes for immunotherapy compared to chemotherapy or standard treatments in various cancer types and treatment settings.
Update on treatment for lymphoma, Lymphoma Support Ireland meeting - feb 2011...Lymphoma Support Ireland
This document summarizes key information from a presentation on the treatment of lymphoma. It discusses:
1) The classification, incidence, and etiology of both Hodgkin's and non-Hodgkin's lymphomas.
2) Updates on treatment approaches for different lymphoma subtypes including chemotherapy regimens, monoclonal antibodies, and stem cell transplantation.
3) Results from clinical trials evaluating new agents and regimens for indolent non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, T-cell lymphomas, and relapsed Hodgkin's lymphoma.
The document discusses tumor markers, which are substances produced by cancer cells that can be used to identify cancers. It provides objectives for lectures on tumor markers, including defining tumor markers, identifying their clinical value in cancer management, and summarizing major tumor types and their associated markers. Characteristics of ideal tumor markers and examples like AFP, CA-125, CEA, beta-hCG, and PSA are also examined.
The document discusses comprehensive genomic profiling (CGP) of solid tumors. It provides examples of genomic alterations that can be detected by CGP in various cancer types, including NSCLC, gliomas, and others. It describes how CGP interrogates many genes through next-generation sequencing to detect mutations, fusions, and other alterations that may be targeted with specific therapies or provide prognostic information.
Tumour Markers are substances present in the tumour, produced by the tumour or by the host as a response to the presence of the tumour, providing information about biological characteristics of the tumour. these tumour markers may specific for the tissue but often get elevated in neoplastic as well non-neoplastic lesions, further Various analytical platforms available for serum tumour markers lack standardisation. These factors add to interpretative challenges in serum tumour markers
Microabscess in Liver Transplant Recipientshewittwr
This study examines mini-microabscess (MMA) syndrome in liver transplant recipients. The researchers analyzed 57 cases of MMA syndrome in 52 patients and compared them to 19 biopsy-proven cases of cytomegalovirus (CMV) infection. MMA syndrome predominantly affected female transplant recipients and occurred later after transplantation than CMV infection. Histologically, MMAs were smaller and more numerous than CMV-associated microabscesses and lacked viral inclusions. PCR testing did not detect CMV DNA in biopsies with MMAs. MMA syndrome was not found to affect graft or patient survival. The etiology of MMA syndrome remains unclear but it does not appear to be caused by CMV infection.
The document summarizes a study that investigated the effects of arsenic exposure on the expression of tumor suppressor genes ATR, WWOX, and FHIT in human and rat urothelial cells. The study found that arsenic exposure decreased expression of these genes in both human and rat cells. It also found lower expression of these genes in patients with bladder cancer from areas with higher arsenic levels in drinking water compared to lower arsenic areas. Inhibitors of MEK and DNA methyltransferase prevented arsenic suppression of WWOX and FHIT expression.
Tumor markers are proteins or mutated proteins that can indicate the presence of cancer. They are useful for screening, diagnosis, monitoring treatment and detecting recurrence, though none are sufficiently sensitive and specific for screening alone. Tumor markers associated with cell proliferation, differentiation, metastasis and other tumor events can provide information about cancer. While not diagnostic, they are helpful for treatment monitoring given their limitations. Proper use requires understanding their sensitivity, specificity and potential causes of false positives.
Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected and measured in bodily fluids or tissues. They can help diagnose certain cancers, distinguish between benign and malignant tumors, monitor treatment response and detect recurrence. However, no single tumor marker is perfect as tumor marker levels can also be elevated in some non-cancerous conditions.
Human cancer development, or oncogenesis, results from genetic changes in oncogenes and tumor suppressor genes. Oncogenes like Ras, Myc, and EGFR promote cancer when overexpressed, while tumor suppressors like p53 and Rb inhibit cancer when functioning normally. Genetic changes from carcinogens, radiation, viruses, or other sources can delete or mutate these genes, altering the control of mitosis and apoptosis and leading to uncontrolled cell growth and the multi-step development of tumors over time. Tumor markers in the blood can indicate the presence, severity, or progression of cancers and help guide treatment responses.
This document summarizes research on mantle cell lymphoma (MCL), a rare type of non-Hodgkin's lymphoma. Key points include:
1) MCL was established as a distinct subtype of lymphoma in 1992 and is characterized by the t(11;14) chromosomal translocation and overexpression of cyclin D1.
2) Current treatments can achieve high response rates but MCL often relapses and no treatment is considered curative for advanced disease.
3) A study found that the combination of lenalidomide and rituximab showed promising efficacy against MCL with an overall response rate of 57% and 33% complete response rate in relapsed/refractory patients.
Tumor markers are substances produced by tumors or the host body in response to tumors. They can be used to detect cancers, determine cancer prognosis, and monitor cancer treatment effectiveness. Some key tumor markers discussed in the document include:
- AFP which is used to detect hepatocellular carcinoma and testicular cancer.
- CEA which is used to detect colorectal cancer recurrence. Rising CEA levels may indicate cancer recurrence while stable levels indicate remission.
- CA125 which is used to detect ovarian and endometrial cancers.
- PSA which is used to screen, stage, and monitor prostate cancer recurrence and treatment.
- HCG which is used to detect germ
Tumor markers are proteins detected in blood that can indicate certain cancers. They are most useful for monitoring response to treatment and detecting early recurrence of cancer. With the exception of PSA, tumor markers lack sufficient accuracy for cancer screening. Some common tumor markers include CA 27.29 for breast cancer, CEA for colorectal cancer, and AFP and beta-hCG for germ cell tumors and liver cancer. While tumor markers can help manage cancer patients, no marker alone guarantees cure or determines treatment; clinical evaluation is also needed.
This document summarizes a research study that investigated the role of long non-coding RNA H19, microRNA miR-29b, and the gene FOXO4 in the apoptosis of retinal Müller cells in diabetic retinopathy. The study found that H19 and FOXO4 expression were increased, while miR-29b expression was decreased, in retinal tissue from diabetic rats and in retinal Müller cells treated with high glucose. Overexpression of H19 promoted retinal Müller cell apoptosis. Knockdown of H19 reversed the effects of high glucose by decreasing cell apoptosis and FOXO4 upregulation. Further experiments indicated that H19 is a target of miR-29b and inhibition of miR-29b
1. Immuno histochemistry is used to detect antigens of interest in tissue sections using antibodies and helps in subtyping cancers of unknown primary, determining prognosis, and guiding personalized treatment.
2. Key markers used in gynecologic cancers include cytokeratins and vimentin to identify epithelial and mesenchymal differentiation, ER and PR to subtype endometrial cancers, and P53 and P16 patterns to distinguish endometrial cancer subtypes.
3. Negative expression of markers like PTEN can also be informative in distinguishing lesions and predicting progression in cancers like endometrial cancer.
Dr. maryalice stetler stevenson lymphoma mrdHitham Esam
Flow cytometry can be used to detect minimal residual disease (MRD) in plasma cell neoplasms such as multiple myeloma. It provides both prognostic information and a way to measure response to drug therapies. Several factors are important for obtaining high quality flow cytometry results, including using bone marrow aspirates within 24 hours of collection, lysing red blood cells, acquiring sufficient events, and using standardized staining and gating strategies. Detection of MRD by flow post-treatment is predictive of patient outcomes and can guide clinical decision making.
This document discusses epithelial tumor markers. It begins by introducing the topic and defining tumor markers as substances produced by or in response to tumors that can be used to detect or characterize tumors. It then describes the ideal properties of tumor markers and various ways to classify them, including as cell surface markers, intracellular markers, types associated with tumor growth, suppression, angiogenesis, and invasion. Specific epithelial and other markers are outlined. Finally, uses of tumor markers are summarized, including for screening, diagnosis, staging, prognosis, evaluating treatment response, and detecting recurrence. Cytokeratins are highlighted as important epithelial markers.
Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected and measured in blood, urine, or body tissues. They can be used to screen for cancers, help diagnose cancer, determine prognosis, stage cancer, detect recurrence, and monitor treatment effectiveness. Common tumor markers include enzymes, hormones, oncofetal antigens, carbohydrates, blood group antigens, proteins, and receptors. Examples are PSA for prostate cancer, CEA for colorectal cancer, CA125 for ovarian cancer, and AFP for liver and germ cell cancers. Tumor marker levels can indicate the presence, location, and spread of cancer as well as how well cancer treatment is working.
Sipuleucel_T Immunotherapy for Metastatic Prostate Cancer after Failing Hormo...mjavan2001
This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.
Tumor markers are biological substances that can be detected in cancer patients that are produced either by the tumor itself or by the body in response to cancer. While ideal tumor markers would be highly specific to cancer, many tumor markers can also be elevated in benign conditions. This can lead to false positives and incorrect interpretation of tumor marker test results. Some conditions that may cause transient or non-transient rises in common tumor markers include cirrhosis, inflammatory bowel disease, pregnancy, and smoking. The lack of specificity of some tumor markers limits their use for screening asymptomatic populations but they can be useful for monitoring known cancer patients. Improved specificity of tumor markers through new technologies may help address this limitation.
This study found that colon cancer cells express the chemokine receptor CCR4, which mediates migration of the cells in response to its ligand CCL17 (TARC) through the RhoA/Rho kinase signaling pathway. Quantitative RT-PCR and flow cytometry showed that the colon cancer cell lines HT-29 and AZ-97 expressed CCR4 at both the mRNA and protein levels. Stimulation with CCL17 induced dose-dependent migration of the colon cancer cells, which was inhibited by blocking CCR4 with an antibody or antagonist. CCL17 also increased mRNA levels of RhoA proteins and RhoA activation in the cells. Inhibition of Rho kinase or isoprenylation blocked CCL17-induced cell migration
Lo que un reumatólogo debe saber de inmunoterapia contra el cáncer, abreviadoMauricio Lema
1. The document discusses various mechanisms of cancer immunotherapy including immune checkpoint inhibitors that target CTLA-4 and PD-1/PD-L1 pathways.
2. Key immunotherapy drugs discussed are ipilimumab, nivolumab, pembrolizumab, avelumab, and durvalumab which target CTLA-4 and PD-1/PD-L1 and have shown efficacy in treating cancers like melanoma, lung cancer, head and neck cancer, and kidney cancer.
3. Several clinical trials are summarized that demonstrate improved survival outcomes for immunotherapy compared to chemotherapy or standard treatments in various cancer types and treatment settings.
Update on treatment for lymphoma, Lymphoma Support Ireland meeting - feb 2011...Lymphoma Support Ireland
This document summarizes key information from a presentation on the treatment of lymphoma. It discusses:
1) The classification, incidence, and etiology of both Hodgkin's and non-Hodgkin's lymphomas.
2) Updates on treatment approaches for different lymphoma subtypes including chemotherapy regimens, monoclonal antibodies, and stem cell transplantation.
3) Results from clinical trials evaluating new agents and regimens for indolent non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, T-cell lymphomas, and relapsed Hodgkin's lymphoma.
The document discusses tumor markers, which are substances produced by cancer cells that can be used to identify cancers. It provides objectives for lectures on tumor markers, including defining tumor markers, identifying their clinical value in cancer management, and summarizing major tumor types and their associated markers. Characteristics of ideal tumor markers and examples like AFP, CA-125, CEA, beta-hCG, and PSA are also examined.
The document discusses comprehensive genomic profiling (CGP) of solid tumors. It provides examples of genomic alterations that can be detected by CGP in various cancer types, including NSCLC, gliomas, and others. It describes how CGP interrogates many genes through next-generation sequencing to detect mutations, fusions, and other alterations that may be targeted with specific therapies or provide prognostic information.
Tumour Markers are substances present in the tumour, produced by the tumour or by the host as a response to the presence of the tumour, providing information about biological characteristics of the tumour. these tumour markers may specific for the tissue but often get elevated in neoplastic as well non-neoplastic lesions, further Various analytical platforms available for serum tumour markers lack standardisation. These factors add to interpretative challenges in serum tumour markers
Microabscess in Liver Transplant Recipientshewittwr
This study examines mini-microabscess (MMA) syndrome in liver transplant recipients. The researchers analyzed 57 cases of MMA syndrome in 52 patients and compared them to 19 biopsy-proven cases of cytomegalovirus (CMV) infection. MMA syndrome predominantly affected female transplant recipients and occurred later after transplantation than CMV infection. Histologically, MMAs were smaller and more numerous than CMV-associated microabscesses and lacked viral inclusions. PCR testing did not detect CMV DNA in biopsies with MMAs. MMA syndrome was not found to affect graft or patient survival. The etiology of MMA syndrome remains unclear but it does not appear to be caused by CMV infection.
The document summarizes a study that investigated the effects of arsenic exposure on the expression of tumor suppressor genes ATR, WWOX, and FHIT in human and rat urothelial cells. The study found that arsenic exposure decreased expression of these genes in both human and rat cells. It also found lower expression of these genes in patients with bladder cancer from areas with higher arsenic levels in drinking water compared to lower arsenic areas. Inhibitors of MEK and DNA methyltransferase prevented arsenic suppression of WWOX and FHIT expression.
This study investigated the effects of arsenic exposure on inflammatory cytokine expression and secretion in human urothelial cells and individuals occupationally exposed to arsenic. The concentrations of arsenic metabolites and inflammatory cytokines IL-8, TNF-α, and TGF-α were significantly higher in the urine of individuals with high arsenic exposure compared to low exposure. Expression of these cytokines was also significantly increased in human urothelial cells exposed to arsenic in vitro. There were significant correlations between urinary cytokine levels and arsenic metabolite concentrations, suggesting arsenic exposure induces cytokine expression and secretion.
The document examines how long-term low-dose exposure of human urothelial cells to sodium arsenite activates the lipocalin-2 (LCN2) gene via promoter hypomethylation. It finds that the LCN2 promoter in arsenic-exposed cells is hypomethylated compared to unexposed cells, leading to increased LCN2 expression. This overexpression of LCN2 enhances cellular transformation, anti-apoptotic activity, and inflammatory responses in the arsenic-exposed cells through mechanisms involving NF-κB and increased iron and reactive oxygen species levels.
This study investigated the role of integrin-linked kinase (ILK) in bladder cancer invasion and progression. The researchers found that invasive bladder cancer cells have high ILK expression, which plays a role in epithelial-to-mesenchymal transition by regulating E-cadherin expression. Knocking down ILK in invasive bladder cancer cells suppressed cell invasion by regulating E-cadherin and MMP-9. Analysis of human bladder cancer samples also showed that high ILK expression correlates with increased invasiveness. Therefore, this study suggests that ILK is important for EMT in bladder cancer and could be a new therapeutic target to suppress tumor progression.
The document discusses a study on CD24 expression in bladder tumorigenesis and metastasis in mice. The study found that loss of Cd24a is associated with reduced tumor incidence in OH-BBN-induced bladder tumors in mice. Cd24a expression was higher in bladder tumors than normal tissue. Loss of Cd24a protected bladder tissue from tumorigenesis and decreased metastasis in male mice. The study also found that CD24 expression is androgen-regulated, and promotes tumor growth and is a prognostic factor for disease-free survival in male patients with bladder cancer.
The document discusses arsenic and its link to bladder cancer. It notes that arsenic is a metalloid that occurs naturally and is used industrially and agriculturally, and can be toxic to humans. Long-term exposure to arsenic through drinking water has been linked to bladder cancer due to its classification as a Class 1 carcinogen. Symptoms of arsenic-induced bladder cancer can include blood in the urine, pain during urination, and back pain. The prognosis depends on cancer stage and grade, with early-stage cancer often curable. Treatment involves removing arsenic from the body and managing the cancer.
This document discusses the etiopathogenesis of prostate carcinoma. It covers epidemiology, risk factors, genetics, and the molecular and pathological characteristics of prostate cancer. Some key points include:
- Prostate cancer is the most common non-skin cancer in American men and the second leading cause of cancer death.
- Risk increases with age and is highest in African Americans and Jamaicans.
- Family history, genetics, inflammation, infections, hormones and lifestyle factors like smoking can increase risk.
- Precancerous conditions like proliferative inflammatory atrophy and high-grade prostatic intraepithelial neoplasia are associated with increased risk of prostate cancer.
Identification Of Pancreatic Cancer Stem Cellsbegelfer
The study identified cancer stem cells in pancreatic tumors that have the ability to self-renew and generate differentiated tumor cells. Highly tumorigenic cancer cells were found that expressed the cell surface markers CD44, CD24, and ESA. These cells showed properties of stem cells by forming tumors in mice after injection, undergoing self-renewal, and generating differentiated progeny. Targeting these cancer stem cells may be needed to effectively treat pancreatic cancer as traditional therapies often miss these cells.
This document discusses tumor markers and their use in monitoring tumor response to therapy. It provides information on different types of tumor markers including proteins, enzymes, hormones, genetic markers and circulating tumor cells. Ideal tumor markers are highly sensitive and specific, correlate with tumor stage and prognosis, and can be used for screening, diagnosis, prognosis, monitoring treatment and detecting recurrence. Examples discussed include CEA, AFP, PSA, CA125 and circulating tumor cells. The Oncotype DX 21-gene recurrence score test and tissue polypeptide specific antigen are also summarized.
Field cancerization refers to genetic and molecular alterations that occur in histologically normal tissue surrounding tumors. These alterations predispose the tissue to developing additional new cancers. The document discusses two cases presenting with multiple primary tumors in the oral cavity and larynx as examples of field cancerization. It then reviews the original description of field cancerization from 1953 and various theories for how it occurs. The concept of an "etiologic field effect" is introduced, which broadens the understanding of cancer susceptibility at the molecular, cellular and environmental levels. Several examples of field cancerization are described for different cancer types. Clinical tools for detecting field cancerization like iodine staining and toluidine blue staining are also mentioned.
- The study examined malondialdehyde (MDA) levels and hematological parameters in 31 newly diagnosed cervical cancer patients at a hospital in India.
- MDA levels, which indicate oxidative stress, were found to be significantly higher in cervical cancer patients compared to healthy volunteers. MDA levels also differed between cancer grades.
- Hematological analysis found reduced red blood cell count and hemoglobin levels and increased white blood cell count in cervical cancer patients relative to normal levels.
- The results suggest that oxidative stress and hematological abnormalities are present at the initial clinical presentation of cervical cancer patients and that MDA may be a predictive marker for disease progression. Controlling oxidative stress and improving nutrition could help cervical cancer treatment
Urothelial carcinoma biomarkers can be detected in urine samples to aid in the diagnosis and monitoring of bladder cancer. Nuclear matrix protein 22 (NMP22) and bladder tumor antigen (BTA) tests detect proteins released by dying tumor cells with reasonable sensitivity and specificity. Urine cytology examines cells for morphological changes, having high sensitivity for high-grade tumors but low sensitivity for low-grade tumors. Newer tests like CxBladder, CertNDx, and microsatellite analysis analyze genetic markers and show promise in improving detection rates, especially for low-grade tumors. No single test is perfect and cystoscopy remains the gold standard, but urine biomarkers provide a non-invasive method to supplement standard evaluation and monitoring of patients
This document discusses various biomarkers used to diagnose and monitor cancer progression. It describes several common cancer antigen biomarkers like PSA, AFP, CA125, CA15-3, and CEA that are detected in serum to identify prostate, liver, ovarian, breast, and colorectal cancers respectively. Other biomarkers mentioned include hCG for germ cell tumors, thyroglobulin for thyroid cancer, heat shock proteins, glucose metabolism measured via FDG-PET scans, circulating tumor cells, and cancer stem cells. The document provides details on each biomarker's applications, typical values, and utility for cancer diagnosis and prognosis.
This document discusses gene therapy as a promising treatment for breast cancer. It begins by providing background on breast cancer prevalence and current treatment options. It then describes how gene therapy could target mutated genes, cancer cell markers, block metastasis, and induce apoptosis. The document focuses on gene therapy approaches for breast cancer, including using antisense technology to inhibit pathogenic genes, RNA interference to downregulate genes like c-myc, and suicide genes to make cancer cells more sensitive to chemotherapy.
Dr. Michael Morse from Duke University and Fight CRC’s Andi Dwyer discuss the state of the science and clinical care of Immunotherapy (IO); giving a glimpse of the contributions of the Fight CRC IO Workgroup.
IMMUNOHISTOCHEMICAL ALTERATIONS IN HEPATOCELLULAR CARCINOMA PATIENTS TREATED ...Jing Zang
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Doxorubicin (Dox) is an anthracycline antibiotic used as a single chemotherapeutic agent for HCC. The present work was conducted to study the immunohistochemical alterations in HCC patients treated with Dox. Thirty cases (24 males and 6 female) with a confirmed diagnosis of hepatocellular carcinoma (HCC) were used. They were divided into 3 groups, group 1. Ten specimens of HCC were taken before Dox treatments, group 2.Ten specimens HCC patients were taken one week after Dox treatment and group 3.Ten specimens of HCC patients were taken two weeks after Dox treatment. Hepatic biopsies were obtained from the three groups and prepared for histological, immunohistochemical (p53, Bcl-2 and CD34) and molecular studies. Histological examination of the specimen of HCC patients, before and after Dox treatment, showed trabecular appeareance, cytoplasmic vacuolation of the hepatocytes, fatty degeneration and necrosis. Cirrhosis appeared in 40% of the patients before treatment and 40% and 30% after one week and 2 weeks of treatment, respectively. Imunohistochemical results revealed an increase in expression of p53, CD34 and Bcl-2 in HCC patients. Overexpression of p53, decrease of Bcl-2 and mild degree of expression of CD34 was recorded in patients treated with Dox. Significant increase in DNA fragmentation was recorded in HCC patients treated by Dox in comparison with untreated HCC.
Calcarea carbonica induces apoptosis in cancer cells in p53-dependent manner ...home
These observations delineate the significance of immuno-modulatory circuit during calcarea carbonicamediated
tumor apoptosis. The molecular mechanism identified may serve as a platform for involving calcarea
carbonica into immunotherapeutic strategies for effective tumor regression
This document summarizes a study exploring the effects of baicalein (BAI) on bladder cancer cells. The study found that BAI inhibits proliferation and promotes apoptosis in bladder cancer cells. It also inhibits bladder cancer cell migration by down-regulating microRNA (miR)-106 expression. Specifically, BAI affects bladder cancer cells by inhibiting the JNK and MEK/ERK pathways through reducing miR-106 levels. P21 was also identified as a target of miR-106. The study utilized techniques like transfection, PCR, western blot analysis, and cell migration assays to analyze these regulatory mechanisms and effects of BAI on bladder cancer cells.
1. Pancreatic neuroendocrine tumors (PNETs) are rare, slow-growing neoplasms that originate from cells that produce and secrete hormones.
2. The most common functional PNETs are insulinomas, gastrinomas, glucagonomas, and VIPomas. Non-functional PNETs make up about 75% of cases.
3. Diagnosis involves biochemical testing for hormone levels, imaging such as CT, MRI, and nuclear imaging to locate the primary tumor and metastases, and pathology to determine grade and stage. Endoscopic ultrasound can help locate small tumors.
TEGENE ALEMU CANCER BIOLOGY SURGERY DEPARTMENTTegeneAlemu
Cancer Biology by Tegene Alemu Jimma Ethiopia
Surgery Role on Oncology
On this seminar
Hallmark of cancer
Cell cycles
Apoptosis of cell
Diagnosis
Therapy
Austin Biochemistry is an open access, peer reviewed, scholarly journal dedicated to publish articles covering all areas of Biochemistry.
The journal aims to promote research communications and provide a forum for doctors, researchers, physicians and healthcare professionals to find most recent advances in all the areas of Biochemistry. Austin Biochemistry accepts original research articles, reviews, mini reviews, case reports and rapid communication covering all aspects of biochemistry.
Austin Biochemistry strongly supports the scientific up gradation and fortification in related scientific research community by enhancing access to peer reviewed scientific literary works. Austin Publishing Group also brings universally peer reviewed journals under one roof thereby promoting knowledge sharing, mutual promotion of multidisciplinary science.
JTM-Functional characterization of human Cd33+ And Cd11b+ myeloid-derived sup...Karolina Megiel
This study examined the ability of human tumor cell lines to induce myeloid-derived suppressor cells (MDSC) from healthy donor peripheral blood mononuclear cells (PBMC) using in vitro co-cultures. Two distinct MDSC subsets were identified and characterized: CD33+ HLA-DRlow HIF1a+/STAT3+ MDSC and CD11b+ HLA-DRlow C/EBPb+ MDSC. The induction of CD33+ MDSC depended on overexpression of IL-1b, IL-6, TNFa, VEGF, and GM-CSF by tumor cells, while CD11b+ MDSC induction correlated with FLT3L and TGF
This presentation was provided by Steph Pollock of The American Psychological Association’s Journals Program, and Damita Snow, of The American Society of Civil Engineers (ASCE), for the initial session of NISO's 2024 Training Series "DEIA in the Scholarly Landscape." Session One: 'Setting Expectations: a DEIA Primer,' was held June 6, 2024.
How to Build a Module in Odoo 17 Using the Scaffold MethodCeline George
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How to Setup Warehouse & Location in Odoo 17 InventoryCeline George
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Strategies for Effective Upskilling is a presentation by Chinwendu Peace in a Your Skill Boost Masterclass organisation by the Excellence Foundation for South Sudan on 08th and 09th June 2024 from 1 PM to 3 PM on each day.
LAND USE LAND COVER AND NDVI OF MIRZAPUR DISTRICT, UPRAHUL
This Dissertation explores the particular circumstances of Mirzapur, a region located in the
core of India. Mirzapur, with its varied terrains and abundant biodiversity, offers an optimal
environment for investigating the changes in vegetation cover dynamics. Our study utilizes
advanced technologies such as GIS (Geographic Information Systems) and Remote sensing to
analyze the transformations that have taken place over the course of a decade.
The complex relationship between human activities and the environment has been the focus
of extensive research and worry. As the global community grapples with swift urbanization,
population expansion, and economic progress, the effects on natural ecosystems are becoming
more evident. A crucial element of this impact is the alteration of vegetation cover, which plays a
significant role in maintaining the ecological equilibrium of our planet.Land serves as the foundation for all human activities and provides the necessary materials for
these activities. As the most crucial natural resource, its utilization by humans results in different
'Land uses,' which are determined by both human activities and the physical characteristics of the
land.
The utilization of land is impacted by human needs and environmental factors. In countries
like India, rapid population growth and the emphasis on extensive resource exploitation can lead
to significant land degradation, adversely affecting the region's land cover.
Therefore, human intervention has significantly influenced land use patterns over many
centuries, evolving its structure over time and space. In the present era, these changes have
accelerated due to factors such as agriculture and urbanization. Information regarding land use and
cover is essential for various planning and management tasks related to the Earth's surface,
providing crucial environmental data for scientific, resource management, policy purposes, and
diverse human activities.
Accurate understanding of land use and cover is imperative for the development planning
of any area. Consequently, a wide range of professionals, including earth system scientists, land
and water managers, and urban planners, are interested in obtaining data on land use and cover
changes, conversion trends, and other related patterns. The spatial dimensions of land use and
cover support policymakers and scientists in making well-informed decisions, as alterations in
these patterns indicate shifts in economic and social conditions. Monitoring such changes with the
help of Advanced technologies like Remote Sensing and Geographic Information Systems is
crucial for coordinated efforts across different administrative levels. Advanced technologies like
Remote Sensing and Geographic Information Systems
9
Changes in vegetation cover refer to variations in the distribution, composition, and overall
structure of plant communities across different temporal and spatial scales. These changes can
occur natural.
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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.
Walmart Business+ and Spark Good for Nonprofits.pdfTechSoup
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CD24 expression
1. NATIONAL CHIAYI UNIVERSITY
Department of Microbiology, Immunology & Biopharmaceuticals
CD24 expression is important in male urothelial tumorigenesis
and metastasis in mice and is androgen regulated
Proc Natl Acad Sci USA. 2012 Dec 18; 109 (51) : E3588-96
MULTIDISCIPLINARY SCIENCES : 4/56
Impact factor: 9.737
Advisor:
Yi-Wen Liu
Professor
Speaker:
Mezbahul Haque
Master’s Student
Date: 10.01.14
3. The majority of bladder cancers are transitional cell carcinomas -
this is by far the most common type of bladder cancer. About 95%
of bladder cancers are this type.
Low-grade papillary tumours rarely become muscle-invasive and
they frequently harbour gene mutations that constitutively activate
the receptor tyrosine kinase–Ras pathway.
By contrast, most high-grade invasive tumours progress to life-
threatening metastases and have defects in the p53 and FGFR
pathways.
UROTHELIAL
TUMORIGENESIS
Nat Rev Cancer. 2005 Sep;5(9):713-25.
3
4. UROTHELIAL
TUMORIGENESIS
Most urothelial carcinomas (UCs) of the bladder (75%) are present as
superficial tumors at the time of diagnosis.
Tumor staging and grading are considered the best prognostic markers, but
the development of molecular markers may provide useful information for
more effective diagnoses and treatments of bladder cancer. 4
5. CD24 is a cell-surface glycosyl phosphatidylinositol membrane
anchor protein on the surfaces of most human B cells. It can inhibit B
cell differentiation into antibody-forming cells.
Because CD24 as a ligand to P-selectin that is important for
metastatic tumor progression and lung colonization.
Using a doxycycline-inducible system for the expression of
CD24 in breast cancer cells, CD24 has been proved to play a
critical role in proliferation, invasion, and motility in cancer cells.
CD24
Cancer Res (2005) 65:: 10783–10793
5
J Immunol ( 1991) 147:1412–1416
Cancer Res (2000) 60: 6714–6722
6. CD24 is known to be overexpressed in various human
malignancies, both solid and hematological and is usually tied
with a more aggressive course of the disease.
Several studies have reported that the protein is broadly over
expressed in numerous types of cancer cell from the lung, breast,
prostate, liver, kidney, pancreas and ovary, as well as in
lymphomas.
Previous study also revealed that the frequency of CD24 over-
expression was significantly increased in invasive carcinomas
compared with noninvasive carcinomas.
CD24
J. Biol. Chem. 2011, 286:40548-40555.
6
Arch Pathol Lab Med2007, Vol 131, Feb
7. Butyl-(4-hydroxybutyl) nitrosamine (BBN) has been shown
to be a highly potent and specific bladder carcinogen.
Bladder carcinomas were found in all mice, other toxic
effects were absent.
Males developed bladder tumors significantly earlier than
did females.
Early changes in the bladder epithelium were also
delayed in the female.
BBN and bladder cancer
7
Eur J Cancer (1972)8:587–594.
8. A potential mediator of sex-specific differences is the
androgen receptor (AR).
The AR, a member of the nuclear receptor superfamily, is a
ligand-dependent transcriptional factor that mediates the
biologic effects of androgens.
Expression of the AR has been detected in normal bladder
epithelium and in bladder carcinomas from both male and
female patients.
8
Androgen and bladder cancer
J Natl Cancer Inst (2007)99:558–568.
9. OBJECTIVES
9
The authors wanted to evaluate the contribution of CD24
in bladder cancer incidence and progression within a
defined genetic model by exposing Cd24a-deficient mice
to a carcinogen.
And authors also want to find out the answer of a
question, is there any relation between CD24 and
androgen regulation to induce bladder tumorigenesis and
metastasis in male?
10. Experimental Animals and Cell Lines:
C57BL/6 mice deficient for Cd24a and wild type C57BL/6
mice used as controls.
Cell lines: UM-UC-3, TCCSUP and HTB9 human urothelial
carcinoma cell lines.
METHODS:
RT-PCR
CD24 Promoter Reporter Assays.
Computational Binding-Site Predictions.
Chromatin Immunoprecipitation (ChIP).
Histological Analysis of Murine and Human Tissues.
MATERIALS & METHODS
10
14. Ratio of the incidence of malignancy. No differences in histology between
grade-matched WT and Cd24a
deficient mice.
Bladder Tumor Incidence ratio between WT and
Cd24a-Deficient Mice
14
15. Cancerous urothelium exposed to OH-BBN had significantly more
Cd24a than normal urothelium, regardless of the sex of the mice.
Cd24a mRNA Expression Are Increased in OH-BBN–
Induced Bladder Cancer
15
16. After exposure to OH-BBN, bladders from WT mice with cancer were
found to express higher levels of Cd24a protein than dysplastic counterparts.
Cd24a Protein Expression Are Increased in OH-BBN–Induced
Bladder Cancer
16
17. Loss of CD24 is protective
against OH-BBN–induced
bladder cancer in male mice
but not in female mice.
Cd24a Deficiency in Male Mice Delays Bladder
Malignancy
17
18. Schematic of the experimental design for assessing metastatic incidence.
Harboring Primary Tumors to metastasis
18
19. Lung metastatic tissues showed
similar histological architecture.
Comparisons of WT and Cd24a-
deficient females showed no
statistically significant difference in
metastasis.
Cd24a Deficiency Reduces Metastasis in Male Mice
19
20. SUMMARY
Loss of Cd24a is associated with reduced tumor incidence
OH-BBN–induced bladder tumors have high levels of Cd24a
mRNA and protein expression than displasia.
Loss of Cd24a appears to protect bladder urothelium from OH-
BBN–induced tumorigenesis
OH-BBN– induced bladder tumor rates are higher in male WT
mice than in female WT mice.
Loss of Cd24a decreases metastasis in male mice.
20
21. FLOW CHART
Mice model CD24 Deficiency
Effect of Androgen on CD24 Expression
Human Bladder Cancer Cell Study
21
22. Disease-free survival data for male
Tumor CD24 Expression is correlated to disease-free
surviving in male Patients of bladder cancer.
22
Disease-free survival data for female
23. Treatment with R1881 increases
growth compared with DMSO.
Androgen-Induced Growth Is Dependent on CD24
Expression in UM-UC3 cells in vitro and in vivo
Tumors isolated from normal male mice
expressed higher levels of CD24 than
tumors resected from castrated male mice.
R1881 is a synthetic
androgen
23
24. Lysates were collected and analyzed for CD24 and AR protein expression.
Casodex: Casodex is an anti-androgen agent.
CD24 Protein Expression Are Androgen Dependent in
Bladder Cancer Cells.
24
25. Treatment with R1881 increases CD24 expression, an effect that is
abrogated when cells are transfected first with AR siRNA.
CD24 mRNA Expression of UM-UC 3 and TCCSUP cells
25
26. SUMMARY
CD24 is a negative and prognostic factor to the disease-free
surviving in male patients.
Tumor growth promoted by androgen signaling is dependent on
CD24 in vitro and in vivo.
CD24 mRNA and protein expression is regulated by androgen.
26
27. FLOW CHART
Mice model CD24 Deficiency
Effect of Androgen on CD24 Expression
Analysis of CD24 gene promoter affected by
androgen
27
28. R1881 treatment induced a 2.8-fold increase
in the activity of a 1,896-bp CD24 promoter
This mutation blocks R1881-induced
activity of the CD24 promoter.
Synthetic Androgen treatment enhances
the specific CD24 promoter
28
Genomatix MatInspector software
29. The 1,896-bp reporter no longer responds to
R1881 when cells are treated with AR siRNA.
However, AR was not associated with a region
of the CD24 promoter that did not contain a
computationally predicted ARE.
Androgen activates CD24 gene expression through its specific
ARE binding site in the promoter
29
31. Accordingly, the results from this study suggest that CD24
plays a significant role in bladder tumorigenesis and metastasis,
especially in males.
These data also implicate CD24 as an important androgen-
regulated effector in male human bladder cancer and thus
provide a rationale for novel therapeutic approaches targeting
the androgen receptor (AR) in male bladder cancer.
Conclusion
31
33. 33
Androgen-Induced Growth Is Dependent on CD24
Expression in UM-UC3 cells in vitro and in vivo
(C) Normal and castratedmale nude mice (n = 10) were injected s.c.with 5 × 105
UM-UC-3 cells that had been vector transfected or CD24 transfected as described
previously (5). Graph represents tumor size over time. Data show that castration
can reduce growth of UM-UC-3 tumors and that stable exogenous expression of
CD24 inUM-UC-3 cells can rescue this growth reduction. Error bars indicate SEM.
36. Male and female 7-wk-old Cd24a-deficient mice and WT C57BL/6 control
mice were supplied ad libitum with tap water containing 0.1% OH-BBN;
bottles were refreshed twice a week.
Mice were inspected weekly and observed for signs of distress associated
with bladder lesions, including hematuria and firm bladders. Cohorts of
treated Cd24a-deficient and WT mice were killed at 16-, 24-, and 28-wk
time points.
We harvested bladder, periaortic lymph nodes, liver, lung, and kidney
tissues. A portion of each tissue was preserved in phosphate-buffered 10%
formalin and paraffin embedding for eventual sectioning and staining with
H&E. The remaining tissues were snap frozen in liquid nitrogen and stored
at −80 °C for RNA and protein analyses.
36
37. In this study we used the promoter from UM-UC-3 cells called “CD24-
1896,” Use of Genomatix software on CD24-1896 suggested that an
ARE is located at −1501 to −1475. Mutation of this site was executed
according to instructions from the site-directed mutagenesis protocol.
DNA transfections ofUM-UC-3 cells were carried out using
Lipofectamine (Invitrogen) and 1 μg of plasmid. For specific
experiments, siRNA (20pmol) against luciferase was cotransfected
withDNA. After 24 h cell medium was replaced with medium
containing charcoal-stripped serum.
Cells then were treated with vehicle (ethanol). After 24 h cells were
lysed and assayed for luciferase activity according to the
manufacturer’s instructions (Promega). Luciferase values were
normalized to cell number generated from Cyquant analysis (Life
Technologies).
37
38. UM-UC-3 and TCCSUP cells were grown to 70% confluence in two 15-cm
dishes per treatment. Medium was removed, & fresh medium containing
charcoal-stripped serum and EtOH was added for 2 h.
Then , according to instructions in the Simple ChIP Enzymatic Chromatin
IP Kit (Cell Signaling), paraformaldehyde was added directly to cell
medium (1% final concentration) and quenched with 1 M glycine at room
temperature, and cells (4 × 107) were collected.
Overnight ChIP was set up using 10 μg of chromatin and antibody . After
purification of the immunoprecipitated DNA, three-step qRT-PCR was
used to quantify the DNA levels.
38
39. + CD24 is a glycoprotein expressed at the surface of most B
lymphocytes and differentiating neuroblasts.
+ This gene encodes a sialoglycoprotein that is expressed on mature
granulocytes and in many B cells.
+ The encoded protein is anchored via a glycosyl phosphatidylinositol
(GPI) link to the cell surface.
+ An alignment of this gene's sequence finds genomic locations with
similarity on chromosomes 3p26, 15q21, 15q22, 20q11.2 and Yq11.1.
+ Whether transcription, and corresponding translation, occurs at
each of these other genomic locations needs to be experimentally
determined (source: NCBI).
39
40. + The alcoholic group of administered BBN
is rapidly oxidized to a carboxyl group by
the liver enzymatic system
alcohol/aldehyde dehydrogenase; the
metabolite formed by N-butyl-N-(3-
carboxybutyl) nitrosamine (BCPN) is also
a bladder carcinogen and comes in contact
with the urothelium via the urine.
40
41. + Cancer Res. 1977 Feb;37(2):399-407.
+ Mutagenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine, a bladder carcinogen,
and related compounds.
+ Nagao M, Suzuki E, Yasuo K, Yahagi T, Seino Y.
+ Abstract
+ N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN), which specifically induces bladder tumors,
was shown to be mutagenic to Salmonella typhimurium strains TA 1535 and TA100 in the
presence of an S-9 mix prepared from the liver of rats treated with polychlorinated biphenyl.
Reduced nicotinamide adenine dinucleotide was a more effective cofactor than reduced
nicotinamide adenine dinucleotide phosphate in the activation of BBN by the rat liver S-9
fraction, N-Butyl-N-(3-carboxypropyl)nitrosamine, reported to be the main urinary
metabolite of BBN as well as of N,N-dibutylnitrosamine and to induce urinary bladder
tumors specifically, was found to be mutagenic without metabolic activation by the S-9 mix.
The mutagenicities of 31 compounds related structurally or metabolically to BBN and N,N-
dibutylnitrosamine were tested. Of these compounds, 13 have previously been
demonstrated to be carcinogenic, and nine have been shown to be noncarcinogenic. All the
carcinogenic compounds were found to be mutagenic to strain TA1535 with or without the
S-9 mix. Four of the nine noncarcinogenic compounds were also mutagenic. These "false-
positive" compounds were predicted, in fact, to be carcinogenic.
41
42. + American Heritage
+ Medical Dictionary
+ surrogate sur·ro·gate (sûr'ə-gĭt, -gāt', sŭr'-)
n.
+ One that takes the place of another; a substitute.
+ A person or an animal that functions as a substitute for another, as in a
social or family role.
+ A figure of authority who takes the place of the father or mother in a
person's unconscious or emotional life.
+ A surrogate mother.
42
43. + Mucins are a family of high molecular weight, heavily glycosylated proteins
(glycoconjugates) produced by epithelial tissues in most metazoans.[1] Mucins' key
characteristic is their ability to form gels; therefore they are a key component in
most gel-like secretions, serving functions from lubrication to cell signaling to
forming chemical barriers.[1] They often take an inhibitory role.
+ Glycosylation mainly refers in particular to the enzymatic process that
attaches glycans to proteins, lipids, or other organic molecules. This
enzymatic process produces one of the fundamental biopolymers found in
cells (along with DNA, RNA, and proteins). Glycosylation is a form of co-
translational and post-translational modification.
Proceedings of the National Academy of Sciences
44. 44
Surrogates of death: "a biomarker intended to substitute for a
clinical endpoint".
A surrogate endpoint (or marker) is a measure of effect of a certain
treatment that may correlate with a real clinical endpoint but doesn't
necessarily have a guaranteed relationship. The National Institutes of
Health (USA) define surrogate endpoint as "a biomarker intended to
substitute for a clinical endpoint"
Medical Dictionary
surrogate sur·ro·gate (sûr'ə-gĭt, -gāt', sŭr'-)
n.
One that takes the place of another; a substitute.
A person or an animal that functions as a substitute for
another, as in a social or family role.
A figure of authority who takes the place of the father or
mother in a person's unconscious or emotional life.
45. 45
CD24
Figure 1. (A) A model of CD24. The antigen is composed of a small protein core of 27
amino acids which is attached to the membrane via a GPI-anchor. The protein core has
many potential glycosylation sites for O-linked carbohydrates, rendering the molecule
structurally similar to mucins. To indicate the high degree of glycosylation, carbohydrate
side chains are tentatively depicted in the model. Note, that the number of side chains
and the extent of modification is variable.
47. Assessment of human tumor samples, revealed a similar
relationship between CD24 expression and metastatic recurrence
after radical primary therapy: High CD24 expression in tumors
from males was associated with a reduction in disease-free survival.
Finally, because therapeutic targeting of CD24 has proven
beneficial in multiple xenograft models of human bladder , colon,
and pancreatic cancer, this work provides a rational for the use of
androgen deprivation as a therapeutic modality to reduce CD24
expression in males with CD24-dependent cancers.
Conclusion
47