1) The human JC virus (JCV) infects over 80% of humans and is associated with the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML).
2) JCV has the ability to transform cells in culture and induce tumors in animal models. Its major oncoprotein, T-antigen, interacts with tumor suppressors like p53 and Rb to deregulate pathways controlling cell proliferation.
3) Studies suggest T-antigen promotes tumorigenesis by interacting with cellular proteins involved in proliferation signaling like IRS-1, disrupting tumor suppressor functions and activating pathways like IGF-1 signaling.
This document discusses the role of Merkel cell polyomavirus (MCPyV) in the skin cancer Merkel cell carcinoma (MCC). It outlines three aims: 1) to determine if MCPyV can transform human cells and cause tumors in animals, 2) to identify wild-type MCPyV and test its infectivity and lytic potential, and 3) to investigate the mechanism of MCPyV-induced transformation through viral protein expression and interactions with cellular proteins. The identification of MCPyV in the majority of MCC tumors suggests it may be the first known human polyomavirus to cause cancer, which could lead to new treatment strategies if the virus's role is fully characterized.
My first proposal, Everyone knows a person that have or had Cancer. We know that Cancer dosen't have a cure an yet the therapies for it, sometimes, do more harm to the person because the therapy do not choose what kind of cell is going to destroy. But if we can develop a new kind of treatment, a less agresive and more effective one, we will increase the survival chances and minimizes the secondary efects.
Oncogenic viruses can cause cancer by inserting their DNA into host cells. DNA tumor viruses encode viral proteins necessary for replication that alter host cell genes and promote uncontrolled growth. RNA tumor viruses carry altered host cell genes not needed for viral replication. Key tumor suppressor genes like p53 and Rb are inactivated by viral oncoproteins from viruses such as human papillomavirus, Epstein-Barr virus, hepatitis B virus, and Merkel cell polyomavirus, leading to cellular transformation and cancer development.
1. The document provides information about the educational and professional background of an individual, including degrees obtained from various institutions between 1973-2013 related to prenatal diagnosis, genetics, and rare syndromes.
2. It discusses various levels of genetics from DNA to populations and highlights key concepts like meiosis, mitosis, chromosomes, and mitochondrial DNA.
3. Genetics and genomics provides information at the cellular level about structure, expression, regulation and pathways/networks, but understanding the whole organism is still incomplete and requires integration of concepts from other fields like physics, chemistry and mathematics.
This document discusses oncogenic viruses and their role in cancer development. It begins with an introduction to viruses and cancer. Key points include that viruses can integrate into host cell DNA and express viral oncoproteins that alter cell growth pathways, leading to cellular transformation over multiple steps. Major oncogenic viruses discussed are human papillomavirus (HPV), hepatitis B and C viruses, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, and human T-cell leukemia virus. The mechanisms of oncogenesis include introducing new oncogenes, altering expression of cellular genes, and affecting DNA repair and genetic stability.
This document summarizes oncogenesis, the process by which normal cells are transformed into cancer cells. It discusses how proto-oncogenes can become activated oncogenes through mutations, increased expression, or chromosomal rearrangements. Oncogenes code for proteins involved in cell growth and division. The document also describes various causes of oncogenesis like genetic/epigenetic changes, DNA damage from endogenous or exogenous sources, field defects, and oncogenic viruses that activate proto-oncogenes or inactivate tumor suppressor genes. The mechanisms of viral oncogenesis and classification of viral oncogenes into growth factors, receptors, signal transducers and transcription factors are summarized as well.
Viral oncogenesis can be caused by retroviruses, DNA viruses, or RNA viruses. Retroviruses may contain cellular oncogenes called v-onc genes. Some retroviruses induce cancer by inserting near cellular proto-oncogenes (c-onc genes), deregulating their expression. c-onc genes encode proteins involved in growth control and differentiation. Their mutation or overexpression can lead to cancer. Both DNA and RNA tumor viruses can integrate into host genomes and induce transformation by expressing early genes. Human viruses linked to cancer include EBV, HBV, HCV, HPV, and HIV. HIV causes AIDS by depleting CD4+ T cells, leaving the immune system vulnerable to opportunistic infections.
Cancer is caused by unusual cell growth due to genetic mutations and can form benign or malignant tumors. Oncolytic viral therapy uses viruses that specifically infect and destroy cancer cells by exploiting differences between normal and cancer cells. Various strategies are used for tumor targeting including pro-apoptotic targeting using viral genes, transcriptional targeting by placing viral genes under tumor-specific promoters, and transductional targeting based on overexpression of receptors on cancer cells. Adenoviruses and reoviruses have been studied extensively as oncolytic viruses due to their ability to selectively replicate in and lyse cancer cells.
This document discusses the role of Merkel cell polyomavirus (MCPyV) in the skin cancer Merkel cell carcinoma (MCC). It outlines three aims: 1) to determine if MCPyV can transform human cells and cause tumors in animals, 2) to identify wild-type MCPyV and test its infectivity and lytic potential, and 3) to investigate the mechanism of MCPyV-induced transformation through viral protein expression and interactions with cellular proteins. The identification of MCPyV in the majority of MCC tumors suggests it may be the first known human polyomavirus to cause cancer, which could lead to new treatment strategies if the virus's role is fully characterized.
My first proposal, Everyone knows a person that have or had Cancer. We know that Cancer dosen't have a cure an yet the therapies for it, sometimes, do more harm to the person because the therapy do not choose what kind of cell is going to destroy. But if we can develop a new kind of treatment, a less agresive and more effective one, we will increase the survival chances and minimizes the secondary efects.
Oncogenic viruses can cause cancer by inserting their DNA into host cells. DNA tumor viruses encode viral proteins necessary for replication that alter host cell genes and promote uncontrolled growth. RNA tumor viruses carry altered host cell genes not needed for viral replication. Key tumor suppressor genes like p53 and Rb are inactivated by viral oncoproteins from viruses such as human papillomavirus, Epstein-Barr virus, hepatitis B virus, and Merkel cell polyomavirus, leading to cellular transformation and cancer development.
1. The document provides information about the educational and professional background of an individual, including degrees obtained from various institutions between 1973-2013 related to prenatal diagnosis, genetics, and rare syndromes.
2. It discusses various levels of genetics from DNA to populations and highlights key concepts like meiosis, mitosis, chromosomes, and mitochondrial DNA.
3. Genetics and genomics provides information at the cellular level about structure, expression, regulation and pathways/networks, but understanding the whole organism is still incomplete and requires integration of concepts from other fields like physics, chemistry and mathematics.
This document discusses oncogenic viruses and their role in cancer development. It begins with an introduction to viruses and cancer. Key points include that viruses can integrate into host cell DNA and express viral oncoproteins that alter cell growth pathways, leading to cellular transformation over multiple steps. Major oncogenic viruses discussed are human papillomavirus (HPV), hepatitis B and C viruses, Epstein-Barr virus, Kaposi's sarcoma-associated herpesvirus, and human T-cell leukemia virus. The mechanisms of oncogenesis include introducing new oncogenes, altering expression of cellular genes, and affecting DNA repair and genetic stability.
This document summarizes oncogenesis, the process by which normal cells are transformed into cancer cells. It discusses how proto-oncogenes can become activated oncogenes through mutations, increased expression, or chromosomal rearrangements. Oncogenes code for proteins involved in cell growth and division. The document also describes various causes of oncogenesis like genetic/epigenetic changes, DNA damage from endogenous or exogenous sources, field defects, and oncogenic viruses that activate proto-oncogenes or inactivate tumor suppressor genes. The mechanisms of viral oncogenesis and classification of viral oncogenes into growth factors, receptors, signal transducers and transcription factors are summarized as well.
Viral oncogenesis can be caused by retroviruses, DNA viruses, or RNA viruses. Retroviruses may contain cellular oncogenes called v-onc genes. Some retroviruses induce cancer by inserting near cellular proto-oncogenes (c-onc genes), deregulating their expression. c-onc genes encode proteins involved in growth control and differentiation. Their mutation or overexpression can lead to cancer. Both DNA and RNA tumor viruses can integrate into host genomes and induce transformation by expressing early genes. Human viruses linked to cancer include EBV, HBV, HCV, HPV, and HIV. HIV causes AIDS by depleting CD4+ T cells, leaving the immune system vulnerable to opportunistic infections.
Cancer is caused by unusual cell growth due to genetic mutations and can form benign or malignant tumors. Oncolytic viral therapy uses viruses that specifically infect and destroy cancer cells by exploiting differences between normal and cancer cells. Various strategies are used for tumor targeting including pro-apoptotic targeting using viral genes, transcriptional targeting by placing viral genes under tumor-specific promoters, and transductional targeting based on overexpression of receptors on cancer cells. Adenoviruses and reoviruses have been studied extensively as oncolytic viruses due to their ability to selectively replicate in and lyse cancer cells.
This document outlines oncolytic viruses as anticancer agents. It begins with an introduction discussing the rising rates of cancer deaths worldwide and in Nigeria. It then provides historical background on early human trials of viruses for cancer treatment in the 1940s-1970s. The document discusses the characteristics and mechanisms of action of ideal oncolytic viruses, including their ability to selectively infect and lyse cancer cells. It also examines the genomic organization of several oncolytic viruses like adenovirus, maraba virus, herpes simplex virus, vaccinia virus, and poliovirus. Finally, it reviews current genetic manipulations of oncolytic viruses in clinical trials and their targeting of tumors.
Basis of viral oncogenesis and the most common viruses causing cancer and their mechanism of causing cancer. Helpful for undergraduate and postgraduate teaching.
This document discusses the mechanisms by which DNA and RNA viruses can transform cells and cause cancer. It explains that viruses can integrate their genetic material into host cell DNA, activating oncogenes and inactivating tumor suppressor genes. This disrupts the normal cell growth and division processes. Oncogenic viruses are classified based on their genetic material as either DNA tumor viruses or RNA tumor viruses, which are retroviruses. The document provides examples of specific human oncogenic viruses and discusses how viral oncogenes activate and the multi-step process of oncogenesis. Both acute and chronic transforming retroviruses are described.
Cancer stem cells have implications in clinical settings. Only a small portion (<1%) of tumor cells can form new tumors, known as tumor initiating cells or cancer stem cells. These cells express specific cell surface markers that can be identified using flow cytometry and fluorescence-activated cell sorting. Targeting cancer stem cells is important for therapy because they are resistant to chemotherapy and radiation. Combination therapies that target cancer stem cell pathways such as Hedgehog and Wnt signaling or aldehyde dehydrogenase activity may be more effective treatments.
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus".
Cancer arises from normal cells whose nature is permanently changed, causing them to multiply rapidly and not be subject to normal control. Oncogenes are genes capable of transforming normal cells into cancerous cells and result from mutations of normal proto-oncogenes. Both DNA and RNA tumor viruses can transform cells through integration into the host cell DNA, which results in loss of growth control and tumor formation. Retroviruses contain oncogenes (v-onc) that are homologous to cellular proto-oncogenes (c-onc) and can induce transformation after mutation or other changes to the cell's genome.
Como afrontar células madre de cáncer con alimentos Nutriline SRL
III Congreso mundial de medicina y nutrición moluecular e integrativa.
Alejandro Sacha Barrio Healey
"Como Afrontar Células Madre de Cáncer con Alimentos y Plantas"
This document summarizes a study examining infections caused by Enterococcus faecium, a common bacterium in the gastrointestinal tract. The study analyzed 58 patients with hematologic malignancies who developed E. faecium bloodstream infections (BSIs). It found that 23 patients were infected with the vancomycin-resistant strain (VREf) while 35 had the vancomycin-sensitive strain (VSEf). Patients with VREf experienced longer periods of neutropenia compared to controls. The study used pulsed-field gel electrophoresis (PFGE) to analyze the genetic relatedness of E. faecium strains and found they did not share genetic proximity, indicating resistance developed through different mechanisms. The
Slideshow is from the University of Michigan Medical
School's M1 Infectious Disease / Microbiology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1IDM
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.
The document discusses viral oncogenesis and viruses associated with human tumors. It provides a brief history and discoveries related to oncogenic viruses over the years. Some key points include that approximately 10-20% of human tumors are caused by viruses. Viruses can cause cancer through direct introduction of viral oncogenes or indirect modulation of cellular genes. Some major viruses associated with human cancers include human papillomavirus, Epstein-Barr virus, hepatitis B and C viruses, and human T-cell leukemia virus.
This document discusses oncolytic virus therapies, including their mechanisms of action, preclinical studies, experiences with patients, and future outlook. It provides an overview of deletion mutant oncolytic adenoviruses that selectively replicate in cancer cells. Clinical trials have shown safety and some efficacy of these viruses as monotherapies and in combination with other treatments like radiation or chemotherapy. Oncolytic viruses show promise as a novel cancer treatment approach.
here i discussed some human oncogenic viruses , their epidemeology, life cycle, treatment, prevention and control. . oncogenic viruses are cancer causing viruses.
This document discusses the genetic and epigenetic changes that cause cancer. It explains that cancer arises due to alterations that disrupt normal cell proliferation, senescence, and death. Key changes include mutations in oncogenes that increase cell growth and tumor suppressor genes that normally inhibit growth. Cancer development involves multiple genetic hits over time that transform cells and allow unchecked growth. Epigenetic alterations like DNA methylation and histone modifications also contribute to carcinogenesis. The complex interplay between a person's genetic factors and environmental exposures ultimately leads to the development of cancer.
Oncogenic viruses are viruses that can cause cancer. They do so by inserting their DNA into host cells and altering gene expression in ways that promote uncontrolled cell growth and division. Some key points:
- Viruses like HPV, EBV, HBV can lay dormant in the body for years before causing tumors by disrupting tumor suppressor genes or activating oncogenes.
- Oncogenic viruses establish persistent infections to evade the immune system and immunosuppression increases cancer risk.
- Viral oncogenes are incorporated into host cell DNA and cause overexpression of cellular genes involved in growth regulation.
- Cancers linked to oncogenic viruses include cervical cancer from HPV, lymphomas
Stem cells are being explored as a potential therapeutic delivery method for cancer treatment. They can be genetically modified to secrete anticancer proteins or induce cancer cell death. Stem cells may also be used as nanoparticle carriers to deliver chemotherapeutics directly to tumors. Several approaches aim to enhance stem cell efficacy, such as genetic manipulation to improve migration or immune evasion, or using stem cells to deliver oncolytic viruses. While preclinical research is promising, translating stem cell therapies into effective clinical trials faces challenges including regulating safety and demonstrating clear benefits over existing cancer treatments.
Identification of Rare and Novel Alleles in FFPE Tumor Samples | ESHG 2015 Po...Thermo Fisher Scientific
Tumors are becoming recognized as genetically heterogeneous masses of cells with different clonal histories. Identifying the mutations present in these heterogeneous masses can lead to important insights into the future behavior of the tumor and possible intervention mechanisms. However, the rarity of pathogenic mutations in small subsets of cells can make identification of such alleles difficult. In this study, we demonstrate a complete workflow that facilitates the identification of rare and novel alleles from FFPE tumor sections. We collected small regions with different cellular morphologies from lung tumor samples using laser capture microdissection, extracted both DNA and RNA from these regions, and characterized mutations present and transcript abundances by using Ion AmpliSeq™ targeted sequencing. We show that LCM facilitates the detection of alleles that are not detectable in macrodissected tissue scrapes. We also show that different regions of a tumor have very different patterns of alleles detectable and have a great deal of genetic diversity. Finally, we show that RNA expression patterns are also clearly different in the different regions. Interestingly, dissected regions with similar gross tissue morphologies display differences in alleles present and RNA expression patterns. These results suggest how we may in the future use this method to analyze mutations present in a tumor is to microdissect different subregions of the tumor, and using Ion AmpliSeq™ panels to identify the alleles present in those subregions.
Cell within a tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor”.
“CSC can thus only be defined experimentally by their ability to recapitulate the generation of a continuously growing tumor”.
This document outlines the schedule and topics for the Biology 120 Microbiology lecture in the first semester of 2011-2012, including dates for class orientation, topics such as diversity of microorganisms and microbial genetics, dates for exams and journal reports which contribute different percentages to the class grade.
This calendar outlines the schedule of lectures and laboratory exercises for a virology course taught by Prof. Marilen M. Parungao-Balolong. The course covers topics such as viral structure, nomenclature, transmission, replication, viruses and cancer, emerging viruses, and vaccines. Students will take three exams throughout the semester and participate in educational trips and laboratory demonstrations. The course concludes with student presentations on reporting viral outbreaks.
This document outlines oncolytic viruses as anticancer agents. It begins with an introduction discussing the rising rates of cancer deaths worldwide and in Nigeria. It then provides historical background on early human trials of viruses for cancer treatment in the 1940s-1970s. The document discusses the characteristics and mechanisms of action of ideal oncolytic viruses, including their ability to selectively infect and lyse cancer cells. It also examines the genomic organization of several oncolytic viruses like adenovirus, maraba virus, herpes simplex virus, vaccinia virus, and poliovirus. Finally, it reviews current genetic manipulations of oncolytic viruses in clinical trials and their targeting of tumors.
Basis of viral oncogenesis and the most common viruses causing cancer and their mechanism of causing cancer. Helpful for undergraduate and postgraduate teaching.
This document discusses the mechanisms by which DNA and RNA viruses can transform cells and cause cancer. It explains that viruses can integrate their genetic material into host cell DNA, activating oncogenes and inactivating tumor suppressor genes. This disrupts the normal cell growth and division processes. Oncogenic viruses are classified based on their genetic material as either DNA tumor viruses or RNA tumor viruses, which are retroviruses. The document provides examples of specific human oncogenic viruses and discusses how viral oncogenes activate and the multi-step process of oncogenesis. Both acute and chronic transforming retroviruses are described.
Cancer stem cells have implications in clinical settings. Only a small portion (<1%) of tumor cells can form new tumors, known as tumor initiating cells or cancer stem cells. These cells express specific cell surface markers that can be identified using flow cytometry and fluorescence-activated cell sorting. Targeting cancer stem cells is important for therapy because they are resistant to chemotherapy and radiation. Combination therapies that target cancer stem cell pathways such as Hedgehog and Wnt signaling or aldehyde dehydrogenase activity may be more effective treatments.
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor virus" or "cancer virus".
Cancer arises from normal cells whose nature is permanently changed, causing them to multiply rapidly and not be subject to normal control. Oncogenes are genes capable of transforming normal cells into cancerous cells and result from mutations of normal proto-oncogenes. Both DNA and RNA tumor viruses can transform cells through integration into the host cell DNA, which results in loss of growth control and tumor formation. Retroviruses contain oncogenes (v-onc) that are homologous to cellular proto-oncogenes (c-onc) and can induce transformation after mutation or other changes to the cell's genome.
Como afrontar células madre de cáncer con alimentos Nutriline SRL
III Congreso mundial de medicina y nutrición moluecular e integrativa.
Alejandro Sacha Barrio Healey
"Como Afrontar Células Madre de Cáncer con Alimentos y Plantas"
This document summarizes a study examining infections caused by Enterococcus faecium, a common bacterium in the gastrointestinal tract. The study analyzed 58 patients with hematologic malignancies who developed E. faecium bloodstream infections (BSIs). It found that 23 patients were infected with the vancomycin-resistant strain (VREf) while 35 had the vancomycin-sensitive strain (VSEf). Patients with VREf experienced longer periods of neutropenia compared to controls. The study used pulsed-field gel electrophoresis (PFGE) to analyze the genetic relatedness of E. faecium strains and found they did not share genetic proximity, indicating resistance developed through different mechanisms. The
Slideshow is from the University of Michigan Medical
School's M1 Infectious Disease / Microbiology sequence
View additional course materials on Open.Michigan:
openmi.ch/med-M1IDM
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.
The document discusses viral oncogenesis and viruses associated with human tumors. It provides a brief history and discoveries related to oncogenic viruses over the years. Some key points include that approximately 10-20% of human tumors are caused by viruses. Viruses can cause cancer through direct introduction of viral oncogenes or indirect modulation of cellular genes. Some major viruses associated with human cancers include human papillomavirus, Epstein-Barr virus, hepatitis B and C viruses, and human T-cell leukemia virus.
This document discusses oncolytic virus therapies, including their mechanisms of action, preclinical studies, experiences with patients, and future outlook. It provides an overview of deletion mutant oncolytic adenoviruses that selectively replicate in cancer cells. Clinical trials have shown safety and some efficacy of these viruses as monotherapies and in combination with other treatments like radiation or chemotherapy. Oncolytic viruses show promise as a novel cancer treatment approach.
here i discussed some human oncogenic viruses , their epidemeology, life cycle, treatment, prevention and control. . oncogenic viruses are cancer causing viruses.
This document discusses the genetic and epigenetic changes that cause cancer. It explains that cancer arises due to alterations that disrupt normal cell proliferation, senescence, and death. Key changes include mutations in oncogenes that increase cell growth and tumor suppressor genes that normally inhibit growth. Cancer development involves multiple genetic hits over time that transform cells and allow unchecked growth. Epigenetic alterations like DNA methylation and histone modifications also contribute to carcinogenesis. The complex interplay between a person's genetic factors and environmental exposures ultimately leads to the development of cancer.
Oncogenic viruses are viruses that can cause cancer. They do so by inserting their DNA into host cells and altering gene expression in ways that promote uncontrolled cell growth and division. Some key points:
- Viruses like HPV, EBV, HBV can lay dormant in the body for years before causing tumors by disrupting tumor suppressor genes or activating oncogenes.
- Oncogenic viruses establish persistent infections to evade the immune system and immunosuppression increases cancer risk.
- Viral oncogenes are incorporated into host cell DNA and cause overexpression of cellular genes involved in growth regulation.
- Cancers linked to oncogenic viruses include cervical cancer from HPV, lymphomas
Stem cells are being explored as a potential therapeutic delivery method for cancer treatment. They can be genetically modified to secrete anticancer proteins or induce cancer cell death. Stem cells may also be used as nanoparticle carriers to deliver chemotherapeutics directly to tumors. Several approaches aim to enhance stem cell efficacy, such as genetic manipulation to improve migration or immune evasion, or using stem cells to deliver oncolytic viruses. While preclinical research is promising, translating stem cell therapies into effective clinical trials faces challenges including regulating safety and demonstrating clear benefits over existing cancer treatments.
Identification of Rare and Novel Alleles in FFPE Tumor Samples | ESHG 2015 Po...Thermo Fisher Scientific
Tumors are becoming recognized as genetically heterogeneous masses of cells with different clonal histories. Identifying the mutations present in these heterogeneous masses can lead to important insights into the future behavior of the tumor and possible intervention mechanisms. However, the rarity of pathogenic mutations in small subsets of cells can make identification of such alleles difficult. In this study, we demonstrate a complete workflow that facilitates the identification of rare and novel alleles from FFPE tumor sections. We collected small regions with different cellular morphologies from lung tumor samples using laser capture microdissection, extracted both DNA and RNA from these regions, and characterized mutations present and transcript abundances by using Ion AmpliSeq™ targeted sequencing. We show that LCM facilitates the detection of alleles that are not detectable in macrodissected tissue scrapes. We also show that different regions of a tumor have very different patterns of alleles detectable and have a great deal of genetic diversity. Finally, we show that RNA expression patterns are also clearly different in the different regions. Interestingly, dissected regions with similar gross tissue morphologies display differences in alleles present and RNA expression patterns. These results suggest how we may in the future use this method to analyze mutations present in a tumor is to microdissect different subregions of the tumor, and using Ion AmpliSeq™ panels to identify the alleles present in those subregions.
Cell within a tumor that possess the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor”.
“CSC can thus only be defined experimentally by their ability to recapitulate the generation of a continuously growing tumor”.
This document outlines the schedule and topics for the Biology 120 Microbiology lecture in the first semester of 2011-2012, including dates for class orientation, topics such as diversity of microorganisms and microbial genetics, dates for exams and journal reports which contribute different percentages to the class grade.
This calendar outlines the schedule of lectures and laboratory exercises for a virology course taught by Prof. Marilen M. Parungao-Balolong. The course covers topics such as viral structure, nomenclature, transmission, replication, viruses and cancer, emerging viruses, and vaccines. Students will take three exams throughout the semester and participate in educational trips and laboratory demonstrations. The course concludes with student presentations on reporting viral outbreaks.
This document outlines the calendar of activities for a virology course taught by Prof. Marilen M. Parungao-Balolong. It includes the schedule of lectures and laboratory exercises for each of the 17 weeks of the course. The lectures cover topics like viral structure, nomenclature, transmission, replication, viruses and cancer/vaccines. The corresponding laboratory exercises allow students to learn about viral structure, naming viruses, transmission, bacteriophages, replication, diagnostics and immunology. There are three examinations scheduled throughout the course as well as final presentations on assigned topics relating to vaccines or outbreaks.
This document discusses the historical context and ethical considerations of Edward Jenner's experimental smallpox vaccination in the 1790s. It outlines Jenner's proposal to collect fluid from a cowpox lesion and inject it into a child to test his theory that cowpox protects against smallpox. While some raised concerns about risks of the experimental treatment, Jenner argued that the devastating impacts of smallpox and risks of existing variolation methods justified his study, which was based on observations and aimed to benefit public health. The document imagines a hypothetical ethics review of Jenner's proposal, with various stakeholders questioning aspects like risks, informed consent procedures, and use of a child subject.
The document discusses different perceptions of and approaches to nature and the environment. It outlines major perceptions like everything being connected or nature having a delicate balance. It then discusses environmental ethics and different world views like biocentrism, ecocentrism, and anthropocentrism. Biocentrism and ecocentrism view humans as part of the environment, while anthropocentrism views nature as existing for human use. The document argues that anthropocentric views can lead to problems like overpopulation. It suggests adopting more ecocentric values to better care for the environment. Finally, it defines environmental justice as the fair treatment of all people regarding environmental laws and policies.
Transcription must occur before translation because a ribosome needs an mRNA blueprint to construct a protein. The operator is activated when lactose binds to the lac repressor and inactivated when the lac repressor binds to the operator. The last line shows a sequence of mRNA codons.
This document provides an overview of biodiversity in the Philippines. It begins by defining key terms like endemism. It then discusses the high plant diversity in the Philippines, noting there are an estimated 12,000 plant species, with many ferns, orchids, and mosses being endemic. The document highlights some examples of endemic species within these groups. It also addresses the country's status as one of 17 megadiverse countries and notes the large numbers of endemic animal species like birds, mammals, and reptiles found in the Philippines. Threats to the country's biodiversity like habitat loss are also examined.
Traditional versus Modern Biotechnology (Exam 2 coverage)Marilen Parungao
Traditional (classical) biotechnology includes fermentation, breeding, and the production of antibiotics and vaccines. Fermentation involves using microbes like yeast and bacteria to produce foods and beverages through anaerobic respiration, including beer, wine, cheese, bread and yogurt. Breeding techniques like inbreeding and crossbreeding were used to selectively develop plant and animal varieties with desirable traits. Early methods discovered antibiotics produced by microorganisms and used vaccines containing weakened or killed pathogens to trigger immune responses without causing illness.
This document discusses environmental laws and principles. It covers several international treaties and conventions related to hazardous waste, biological diversity, trade in endangered species, migratory species, and climate change. It also outlines several key Philippine laws concerning chain saws, solid waste management, air quality, animal welfare, mining, and the responsibilities of government and communities in environmental protection.
This document provides an overview of Hepatitis C. It begins with an introduction stating that over 71 million people worldwide are chronically infected with HCV. It then covers the virology of HCV including its structure, genome, replication cycle, genotypes/quasispecies. The epidemiology section discusses the global prevalence and incidence. Pathogenesis outlines how HCV evades the immune system to cause chronic infection. Clinical features are separated into acute hepatitis C and chronic hepatitis C. Extrahepatic manifestations associated with HCV are also summarized.
in this ppt slide you study about oncogene and related viruses. they are very fatal because it responsible for tumor/cancer disease. so, all you read this
Merkel cells are specialized mechanoreceptor cells found in the basal layer of the epidermis that respond to light touch. They are innervated by sensory nerves. Merkel cells help transmit information about pressure and touch sensations to the central nervous system. Merkel cell carcinoma is a rare but aggressive form of skin cancer that is associated with Merkel cell polyomavirus (MCV). MCV infects most children asymptomatically but can later reactivate and integrate into the host cell genome if immune surveillance is compromised. This can lead to mutations that inactivate tumor suppressors and allow cells to proliferate uncontrollably, resulting in Merkel cell carcinoma.
The document discusses tumor viruses, oncogenes, and tumor suppressor genes. It summarizes key findings such as:
1. Peyton Rous discovered viruses can cause cancer in chickens in 1910. Retroviruses like Rous sarcoma virus carry oncogenes that can transform infected cells.
2. Oncogenes were first discovered in viruses and called viral oncogenes. Their normal cellular counterparts are called proto-oncogenes, which regulate cell growth. Activation of proto-oncogenes into oncogenes, such as via mutation, can accelerate cell growth and division leading to cancer.
3. Tumor suppressor genes are normal genes that protect the cell. Their absence can allow
This document discusses viruses that can cause cancer in humans. It describes how certain DNA viruses, like HPV and HBV, integrate into the host cell's genome and influence cell cycle progression by encoding proteins that alter normal cell cycle control genes. This leads to cellular transformation and the potential for tumor development. It provides details on specific human cancer-causing viruses, their viral oncoproteins that subvert the cell cycle, and the cellular targets and cancers they are associated with, such as HPV's role in cervical cancer through the actions of the E6 and E7 proteins.
Epidemiology, Etiopathogenesis, Pathology, Staging of Plasma Cell Dyscrasias....adityasingla007
Plasma cell dyscrasias are a spectrum of monoclonal gammopathies involving overproduction of myeloma proteins by plasma cells. Key points include:
- Plasma cells normally secrete antibodies but in plasma cell dyscrasias a clone overproduces a single antibody type.
- Risk factors include radiation exposure and genetic predispositions. Cytogenetic abnormalities involving immunoglobulin loci and cell cycle genes contribute to pathogenesis.
- Presentations include bone pain, fatigue, infections due to anemia or renal impairment. Investigations show monoclonal protein and clonal bone marrow plasma cells.
- Multiple myeloma, monoclonal gammopathy of unknown significance (MGUS), and smoldering
Cell, Vol. 100, 57–70, January 7, 2000, Copyright 2000 by Cel.docxzebadiahsummers
Cell, Vol. 100, 57–70, January 7, 2000, Copyright 2000 by Cell Press
The Hallmarks of Cancer Review
evolve progressively from normalcy via a series of pre-Douglas Hanahan* and Robert A. Weinberg†
*Department of Biochemistry and Biophysics and malignant states into invasive cancers (Foulds, 1954).
These observations have been rendered more con-Hormone Research Institute
University of California at San Francisco crete by a large body of work indicating that the ge-
nomes of tumor cells are invariably altered at multipleSan Francisco, California 94143
†Whitehead Institute for Biomedical Research and sites, having suffered disruption through lesions as sub-
tle as point mutations and as obvious as changes inDepartment of Biology
Massachusetts Institute of Technology chromosome complement (e.g., Kinzler and Vogelstein,
1996). Transformation of cultured cells is itself aCambridge, Massachusetts 02142
multistep process: rodent cells require at least two intro-
duced genetic changes before they acquire tumorigenic
competence, while their human counterparts are moreAfter a quarter century of rapid advances, cancer re-
difficult to transform (Hahn et al., 1999). Transgenicsearch has generated a rich and complex body of knowl-
models of tumorigenesis have repeatedly supported theedge, revealing cancer to be a disease involving dy-
conclusion that tumorigenesis in mice involves multiplenamic changes in the genome. The foundation has been
rate-limiting steps (Bergers et al., 1998; see Oncogene,set in the discovery of mutations that produce onco-
1999, R. DePinho and T. E. Jacks, volume 18[38], pp.genes with dominant gain of function and tumor sup-
5248–5362). Taken together, observations of humanpressor genes with recessive loss of function; both
cancers and animal models argue that tumor develop-classes of cancer genes have been identified through
ment proceeds via a process formally analogous to Dar-their alteration in human and animal cancer cells and
winian evolution, in which a succession of geneticby their elicitation of cancer phenotypes in experimental
changes, each conferring one or another type of growthmodels (Bishop and Weinberg, 1996).
advantage, leads to the progressive conversion of nor-Some would argue that the search for the origin and
mal human cells into cancer cells (Foulds, 1954; Nowell,treatment of this disease will continue over the next
1976).quarter century in much the same manner as it has in
the recent past, by adding further layers of complexity
to a scientific literature that is already complex almost An Enumeration of the Traits
beyond measure. But we anticipate otherwise: those The barriers to development of cancer are embodied
researching the cancer problem will be practicing a dra- in a teleology: cancer cells have defects in regulatory
matically different type of science than we have experi- circuits that govern normal cell proliferation and homeo-
enced over the past 25 years. Surely much of this change stasis. T.
Cell, Vol. 100, 57–70, January 7, 2000, Copyright 2000 by Cel.docxketurahhazelhurst
Cell, Vol. 100, 57–70, January 7, 2000, Copyright 2000 by Cell Press
The Hallmarks of Cancer Review
evolve progressively from normalcy via a series of pre-Douglas Hanahan* and Robert A. Weinberg†
*Department of Biochemistry and Biophysics and malignant states into invasive cancers (Foulds, 1954).
These observations have been rendered more con-Hormone Research Institute
University of California at San Francisco crete by a large body of work indicating that the ge-
nomes of tumor cells are invariably altered at multipleSan Francisco, California 94143
†Whitehead Institute for Biomedical Research and sites, having suffered disruption through lesions as sub-
tle as point mutations and as obvious as changes inDepartment of Biology
Massachusetts Institute of Technology chromosome complement (e.g., Kinzler and Vogelstein,
1996). Transformation of cultured cells is itself aCambridge, Massachusetts 02142
multistep process: rodent cells require at least two intro-
duced genetic changes before they acquire tumorigenic
competence, while their human counterparts are moreAfter a quarter century of rapid advances, cancer re-
difficult to transform (Hahn et al., 1999). Transgenicsearch has generated a rich and complex body of knowl-
models of tumorigenesis have repeatedly supported theedge, revealing cancer to be a disease involving dy-
conclusion that tumorigenesis in mice involves multiplenamic changes in the genome. The foundation has been
rate-limiting steps (Bergers et al., 1998; see Oncogene,set in the discovery of mutations that produce onco-
1999, R. DePinho and T. E. Jacks, volume 18[38], pp.genes with dominant gain of function and tumor sup-
5248–5362). Taken together, observations of humanpressor genes with recessive loss of function; both
cancers and animal models argue that tumor develop-classes of cancer genes have been identified through
ment proceeds via a process formally analogous to Dar-their alteration in human and animal cancer cells and
winian evolution, in which a succession of geneticby their elicitation of cancer phenotypes in experimental
changes, each conferring one or another type of growthmodels (Bishop and Weinberg, 1996).
advantage, leads to the progressive conversion of nor-Some would argue that the search for the origin and
mal human cells into cancer cells (Foulds, 1954; Nowell,treatment of this disease will continue over the next
1976).quarter century in much the same manner as it has in
the recent past, by adding further layers of complexity
to a scientific literature that is already complex almost An Enumeration of the Traits
beyond measure. But we anticipate otherwise: those The barriers to development of cancer are embodied
researching the cancer problem will be practicing a dra- in a teleology: cancer cells have defects in regulatory
matically different type of science than we have experi- circuits that govern normal cell proliferation and homeo-
enced over the past 25 years. Surely much of this change stasis. T ...
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
This document discusses cancer and its genetic basis. It begins by introducing cancer and how it is caused by the accumulation of genetic damage over time through mutations in genes that control cell growth. Key points include: cancers originate from mutations in somatic cells, not germ cells; carcinomas make up over 90% of cancers and originate from endodermal or ectodermal tissues; the ability of cancer cells to invade and metastasize distinguishes malignant from benign tumors. The document then covers specific genetic mutations and cellular processes involved in cancer development.
The document provides an overview of the biology of cancer and pathophysiology of cancer. It discusses that cancer arises due to genetic damage that transforms normal cells into immortal cells that grow uncontrollably. Tumor development is a multistep process involving alterations in oncogenes and tumor suppressor genes, as well as changes like angiogenesis, immortalization, and metastasis. Cancer management is multidisciplinary and aims for prevention, early detection and improving quality of life.
This document provides an overview of cancer, including:
1) Cancer is caused by the accumulation of genetic damage over time that leads to uncontrolled cell growth and proliferation. This "multi-hit" model involves mutations in oncogenes and tumor suppressor genes.
2) Cancer cells exhibit altered growth signaling, immortality, invasion/metastasis, and evasion of apoptosis. Tumor progression involves additional mutations that increase aggressiveness.
3) Diagnosis involves examining tissue morphology and karyotyping to identify abnormal cancer cell characteristics. Advanced tumors develop blood vessels to grow larger than 2mm.
This document provides an overview of cancer biology. It discusses how cancer is caused by the accumulation of genetic mutations over time that disrupt normal cell growth regulation. Key points covered include: the genetic and molecular basis of cancer; common properties of cancer cells like uncontrolled growth; the role of oncogenes and tumor suppressor genes; how mutations in growth factors, receptors, and cell cycle regulators can cause cancer; and the multi-hit model of carcinogenesis. The document also examines specific cancer-causing mutations and molecular mechanisms.
This document provides an overview of cancer biology. It discusses how cancer is caused by the accumulation of genetic damage over time, leading to gain-of-function mutations in oncogenes and loss of function in tumor suppressor genes. This disrupts normal cell growth pathways. Cancer cells exhibit uncontrolled growth, loss of differentiation, ability to invade and metastasize. The "multi-hit" model explains how cancers develop through multiple mutations. Specific cancer-causing mutations in growth factors, receptors, cell cycle proteins and other genes are also summarized.
This document provides an overview of cancer biology. It discusses how cancer is caused by the accumulation of genetic mutations over time that disrupt normal cell growth regulation. Key points covered include: the genetic and molecular basis of cancer; common properties of cancer cells like uncontrolled growth; the role of oncogenes and tumor suppressor genes; how mutations in growth factors, receptors, and cell cycle regulators can cause cancer; and the multi-hit model of carcinogenesis. The document also examines specific cancer-causing mutations and molecular mechanisms.
This document provides an overview of cancer biology. It discusses how cancer is caused by the accumulation of genetic mutations over time that disrupt normal cell growth regulation. Key points covered include: the genetic and molecular basis of cancer; common properties of cancer cells like uncontrolled growth; the role of oncogenes and tumor suppressor genes; how mutations in growth factors, receptors, and cell cycle regulators can cause cancer; and the multi-hit model of carcinogenesis. The document also examines specific cancer-causing mutations and molecular mechanisms.
An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated or expressed at high levels. Most normal cells will undergo a programmed form of rapid cell death (apoptosis) when critical functions are altered and malfunctioning
2000 weinberg. hallsmarcks of cancer new generationNatalia Muñoz Roa
This document summarizes the key hallmarks of cancer that were identified after decades of cancer research. The six essential alterations in cell physiology that were found to collectively dictate malignant growth are: 1) self-sufficiency in growth signals, 2) insensitivity to growth-inhibitory signals, 3) evasion of programmed cell death, 4) limitless replicative potential, 5) sustained angiogenesis, and 6) tissue invasion and metastasis. These six capabilities are thought to be shared by most or all human tumors and represent the successful breaching of anticancer defense mechanisms in cells and tissues. The document provides examples to illustrate each capability and strategies by which cancers acquire them.
Virus-infected monocytes can initiate coagulation and promote inflammation. An in vitro study found that monocytes infected with cytomegalovirus, influenza A virus, or Chlamydia pneumoniae expressed tissue factor and reduced clotting time, indicating initiation of coagulation. The viruses also stimulated monocytes to produce inflammatory cytokines like IL-6 and IL-8. While all three viruses infected monocytes, influenza A most strongly induced cytokine production. This suggests virus-infected monocytes may contribute to both acute coronary events by promoting plaque instability and the chronic atherosclerosis process through sustained inflammation and coagulation.
Virus-infected monocytes can initiate coagulation and promote inflammation. An in vitro study found that monocytes infected with cytomegalovirus, influenza A virus, or Chlamydia pneumoniae expressed tissue factor and reduced clotting time, indicating initiation of coagulation. The viruses also stimulated monocytes to produce inflammatory cytokines like IL-6 and IL-8. While all three viruses infected monocytes, influenza A most strongly induced cytokine production. This suggests virus-infected monocytes may contribute to both acute coronary events by promoting plaque instability and the chronic atherosclerosis process through sustained inflammation and coagulation.
This document discusses biodiversity, including its definition, levels, importance, threats, and status in the Philippines. It defines biodiversity as the variety of life on Earth, including diversity at the genetic, species, and ecosystem levels. The lecture notes cover the three main levels of biodiversity and provides examples. It emphasizes that biodiversity is important to preserve for economic, aesthetic, and scientific reasons. Major threats to biodiversity include habitat loss, overexploitation, climate change, pollution, and invasive species. The document concludes that the Philippines is one of the most biodiverse countries in the world, with over half of its plant and animal species being endemic.
Traditional (classical) biotechnology refers to techniques that have been used for thousands of years, such as fermentation processes. Key applications of fermentation included producing foods like beer, wine, cheese, bread and yogurt. These processes harness microbes like yeast and bacteria to convert sugars into products like ethanol, lactic acid, carbon dioxide and other compounds, allowing foods to be preserved and enhancing flavors. Traditional biotechnology built upon ancient techniques and helped enable major advances in food production and medicine.
Lecture on DNA to Proteins (The Central Dogma of Molecular Biology)Marilen Parungao
- Transcription must occur before translation. Transcription involves copying DNA into mRNA, which is then used as a template for translation.
- The LAC operon is activated under conditions where glucose is low/lactose is high. It is inactivated when glucose is high/lactose is low.
- The DNA sequence provided would be transcribed into an RNA sequence where all Ts would be replaced with Us: 3'-UAC GGC AUU GCA CAU UUU AGG GGC AAU AUU-5'
This document discusses nucleic acids and proteins, including their structures and functions. It provides information on DNA and RNA, such as their components, properties, and roles in coding for proteins. Key experiments that helped identify DNA as the genetic material are summarized, including Griffith's transformation experiment, Avery-MacLeod-McCarty experiment, and Hershey-Chase experiment. Questions are also included about nucleic acid and protein structures and these classic experiments.
The document discusses nutrient cycling and biogeochemical cycles. It explains that nutrients are transported through organisms, atmosphere, water, and land in a series of cycles. The main cycles discussed are the water, oxygen, carbon, nitrogen, phosphorus, and sulfur cycles. It describes the reservoirs, chemical forms, and processes involved in each cycle. It also addresses how human activities like pollution, use of fertilizers, and deforestation can disrupt nutrient cycling and cause issues like eutrophication, ozone depletion, and acid rain. Potential solutions to remediate disrupted cycles, like bioremediation using bacteria, fungi, plants and algae, are also mentioned.
This document provides an overview of Gregor Mendel's experiments with pea plants and the principles of heredity and genetics that he discovered. It discusses Mendel's work crossing pea plants with different traits, such as flower color, and recording the results in subsequent generations. His experiments showed that traits are inherited in discrete units (now known as genes) and follow predictable patterns, such as the 3:1 ratio he observed for dominant and recessive traits in the F2 generation of a monohybrid cross. The document also covers Mendel's principle of independent assortment observed in dihybrid crosses.
The document contains a calendar of activities for Marilen M. Parungao-Balolong covering topics such as calendar of activities, energy concepts and energy flow, ecology, ecosystem concepts, and energy flow, with each topic containing multiple entries attributed to Marilen M. Parungao-Balolong.
The document contains the calendar of activities and lecture notes from a biology class taught by Marilen M. Parungao-Balolong. The lecture covers the fundamentals of chemistry of life, including atoms, chemical bonds, important biological molecules like carbohydrates, lipids, proteins and nucleic acids. It also discusses the domains of life including viruses, prokaryotes and eukaryotes. The functional anatomy of different cell types like plant, animal, bacterial and yeast cells are presented. The lecture concludes with topics on metabolism, catabolism, anabolism, cellular respiration and fermentation.
This document provides an introduction and overview of biotechnology, including definitions of key terms and an historical timeline of important developments in the field. It begins with definitions of biotechnology and genetic engineering. It then outlines the timeline of biotechnology from early domestication and farming in Mesopotamia through modern developments like recombinant vaccines, cloning, and the human genome project. The document concludes with a note about an upcoming meeting to level off on the material.
This document outlines the activities and requirements for a course on biotechnology. It includes lectures, presentations, exams, lab activities and field trips. There will be three exams covering introduction to techniques, applications of biotechnology, and international laws and guidelines. Students will work in groups to present on developing a GMO and create an exhibit for BioWeek. The course will also include virtual laboratory activities covering DNA extraction, PCR, gel electrophoresis, and microarrays. The last meeting will discuss isolating genes from plants and animals as well as human cloning and stem cell research.
The document outlines the content of a lecture on modern biotechnology. It discusses DNA as the genetic material and how genes are passed from parents to offspring in prokaryotic and eukaryotic systems. It also describes how modern biotechnology uses techniques like gene cloning and genetic engineering to develop genetically modified organisms (GMOs) by inserting foreign genes. Specific examples covered include the development of Golden Rice to address vitamin A deficiency and the use of GMOs in health, industry, food, and the environment.
The document discusses the history and development of vaccines from Edward Jenner's pioneering smallpox vaccine in the 18th century to modern vaccines. It covers key topics such as passive and active immunity, commonly used vaccine types including live attenuated, killed/inactivated, subunit/component, toxoid, and DNA vaccines. Safety considerations, efficacy, target groups, and monitoring of vaccine effects are also addressed.
This document provides an overview of controlling microbial growth through various physical and chemical methods. It defines key terms like sterilization, disinfection, sanitization, and antisepsis. Physical methods discussed include heat, radiation, filtration, and desiccation. Chemical methods include sterilants, disinfectants, sanitizers, antiseptics, and preservatives. The document also discusses factors that influence the effectiveness of antimicrobial agents and how their modes of action include damaging membranes, proteins, and nucleic acids. Assessment methods for disinfectants and chemotherapeutic agents like the phenol coefficient test, agar diffusion method, and minimum inhibitory concentration are also summarized.
Microbial growth refers to an increase in the number of microbial cells rather than an increase in cell size. Microbes require certain physical, chemical and nutritional conditions to grow, including a source of carbon, nitrogen, phosphorus and other trace elements. Temperature, pH, oxygen levels and osmotic pressure also influence microbial growth. Pure cultures can be obtained through streak plating and maintained through subculturing or freezing methods like glycerol stocks.
This document contains calendars of activities for Biology 196 for two sections, TBYZ and FBYZ, listing dates from August to October, with speakers, facilitators, and reactors assigned for each date. Students are scheduled to fulfill each role on different dates. The same activity of submitting a review paper to the teacher and reactor is listed for August 14 for both sections.
The document discusses whether microbe extinction should be cared about. It notes that while over 99% of species that have ever lived are extinct, microbes are ubiquitous and diverse. However, their roles in biogeochemical cycles and symbiotic relationships mean local extinctions could have large impacts. Evidence suggests microbes can face extinction through habitat loss, pollution, and climate change. Their potential losses through these human-caused threats to ecosystems should be a concern.
The document discusses the definition and requirements for microbial growth. Microbial growth is defined as an increase in the number of cells rather than cell size. The key requirements for microbial growth include physical factors like temperature, pH, and osmotic pressure as well as chemical nutrients like carbon, nitrogen, sulfur, phosphorus, trace elements, oxygen, and organic growth factors. Different microbes have different temperature, pH, and osmotic pressure preferences and obtain nutrients from various sources.
Humoral immunity is mediated by antibodies and functions to neutralize extracellular microbes and toxins. B-cells respond to and produce antibodies specific for many molecule types. When a B-cell encounters an antigen, it becomes activated and differentiates into a plasma cell that secretes antibodies of that specificity. T-cell help is required for effective antibody responses against protein antigens and drives affinity maturation and isotype switching.
Cell-mediated immunity involves T lymphocytes that combat intracellular microbes. There are two phases: activation of naive T cells by antigen-presenting cells in lymphoid tissues, followed by migration of effector T cells to sites of infection. Effector T cells differentiate into subsets like TH1 and TH2 cells that secrete cytokines activating other immune cells. CD8+ T cells become cytotoxic T lymphocytes that directly kill infected cells. Memory T cells remain after infection clearance to provide rapid protection upon reexposure.
This document contains calendars of activities for Biology 196 for two sections, TBYZ and FBYZ, listing dates from August to October, with speakers, facilitators, and reactors assigned for each date. Students are scheduled to fulfill each role on different dates. The same activity of submitting a review paper to the teacher and reactor is listed for August 14 for both sections.
Ocean lotus Threat actors project by John Sitima 2024 (1).pptxSitimaJohn
Ocean Lotus cyber threat actors represent a sophisticated, persistent, and politically motivated group that poses a significant risk to organizations and individuals in the Southeast Asian region. Their continuous evolution and adaptability underscore the need for robust cybersecurity measures and international cooperation to identify and mitigate the threats posed by such advanced persistent threat groups.
Skybuffer SAM4U tool for SAP license adoptionTatiana Kojar
Manage and optimize your license adoption and consumption with SAM4U, an SAP free customer software asset management tool.
SAM4U, an SAP complimentary software asset management tool for customers, delivers a detailed and well-structured overview of license inventory and usage with a user-friendly interface. We offer a hosted, cost-effective, and performance-optimized SAM4U setup in the Skybuffer Cloud environment. You retain ownership of the system and data, while we manage the ABAP 7.58 infrastructure, ensuring fixed Total Cost of Ownership (TCO) and exceptional services through the SAP Fiori interface.
AI 101: An Introduction to the Basics and Impact of Artificial IntelligenceIndexBug
Imagine a world where machines not only perform tasks but also learn, adapt, and make decisions. This is the promise of Artificial Intelligence (AI), a technology that's not just enhancing our lives but revolutionizing entire industries.
Taking AI to the Next Level in Manufacturing.pdfssuserfac0301
Read Taking AI to the Next Level in Manufacturing to gain insights on AI adoption in the manufacturing industry, such as:
1. How quickly AI is being implemented in manufacturing.
2. Which barriers stand in the way of AI adoption.
3. How data quality and governance form the backbone of AI.
4. Organizational processes and structures that may inhibit effective AI adoption.
6. Ideas and approaches to help build your organization's AI strategy.
GraphRAG for Life Science to increase LLM accuracyTomaz Bratanic
GraphRAG for life science domain, where you retriever information from biomedical knowledge graphs using LLMs to increase the accuracy and performance of generated answers
UiPath Test Automation using UiPath Test Suite series, part 6DianaGray10
Welcome to UiPath Test Automation using UiPath Test Suite series part 6. In this session, we will cover Test Automation with generative AI and Open AI.
UiPath Test Automation with generative AI and Open AI webinar offers an in-depth exploration of leveraging cutting-edge technologies for test automation within the UiPath platform. Attendees will delve into the integration of generative AI, a test automation solution, with Open AI advanced natural language processing capabilities.
Throughout the session, participants will discover how this synergy empowers testers to automate repetitive tasks, enhance testing accuracy, and expedite the software testing life cycle. Topics covered include the seamless integration process, practical use cases, and the benefits of harnessing AI-driven automation for UiPath testing initiatives. By attending this webinar, testers, and automation professionals can gain valuable insights into harnessing the power of AI to optimize their test automation workflows within the UiPath ecosystem, ultimately driving efficiency and quality in software development processes.
What will you get from this session?
1. Insights into integrating generative AI.
2. Understanding how this integration enhances test automation within the UiPath platform
3. Practical demonstrations
4. Exploration of real-world use cases illustrating the benefits of AI-driven test automation for UiPath
Topics covered:
What is generative AI
Test Automation with generative AI and Open AI.
UiPath integration with generative AI
Speaker:
Deepak Rai, Automation Practice Lead, Boundaryless Group and UiPath MVP
Programming Foundation Models with DSPy - Meetup SlidesZilliz
Prompting language models is hard, while programming language models is easy. In this talk, I will discuss the state-of-the-art framework DSPy for programming foundation models with its powerful optimizers and runtime constraint system.
Salesforce Integration for Bonterra Impact Management (fka Social Solutions A...Jeffrey Haguewood
Sidekick Solutions uses Bonterra Impact Management (fka Social Solutions Apricot) and automation solutions to integrate data for business workflows.
We believe integration and automation are essential to user experience and the promise of efficient work through technology. Automation is the critical ingredient to realizing that full vision. We develop integration products and services for Bonterra Case Management software to support the deployment of automations for a variety of use cases.
This video focuses on integration of Salesforce with Bonterra Impact Management.
Interested in deploying an integration with Salesforce for Bonterra Impact Management? Contact us at sales@sidekicksolutionsllc.com to discuss next steps.
In the rapidly evolving landscape of technologies, XML continues to play a vital role in structuring, storing, and transporting data across diverse systems. The recent advancements in artificial intelligence (AI) present new methodologies for enhancing XML development workflows, introducing efficiency, automation, and intelligent capabilities. This presentation will outline the scope and perspective of utilizing AI in XML development. The potential benefits and the possible pitfalls will be highlighted, providing a balanced view of the subject.
We will explore the capabilities of AI in understanding XML markup languages and autonomously creating structured XML content. Additionally, we will examine the capacity of AI to enrich plain text with appropriate XML markup. Practical examples and methodological guidelines will be provided to elucidate how AI can be effectively prompted to interpret and generate accurate XML markup.
Further emphasis will be placed on the role of AI in developing XSLT, or schemas such as XSD and Schematron. We will address the techniques and strategies adopted to create prompts for generating code, explaining code, or refactoring the code, and the results achieved.
The discussion will extend to how AI can be used to transform XML content. In particular, the focus will be on the use of AI XPath extension functions in XSLT, Schematron, Schematron Quick Fixes, or for XML content refactoring.
The presentation aims to deliver a comprehensive overview of AI usage in XML development, providing attendees with the necessary knowledge to make informed decisions. Whether you’re at the early stages of adopting AI or considering integrating it in advanced XML development, this presentation will cover all levels of expertise.
By highlighting the potential advantages and challenges of integrating AI with XML development tools and languages, the presentation seeks to inspire thoughtful conversation around the future of XML development. We’ll not only delve into the technical aspects of AI-powered XML development but also discuss practical implications and possible future directions.
Let's Integrate MuleSoft RPA, COMPOSER, APM with AWS IDP along with Slackshyamraj55
Discover the seamless integration of RPA (Robotic Process Automation), COMPOSER, and APM with AWS IDP enhanced with Slack notifications. Explore how these technologies converge to streamline workflows, optimize performance, and ensure secure access, all while leveraging the power of AWS IDP and real-time communication via Slack notifications.
Generating privacy-protected synthetic data using Secludy and MilvusZilliz
During this demo, the founders of Secludy will demonstrate how their system utilizes Milvus to store and manipulate embeddings for generating privacy-protected synthetic data. Their approach not only maintains the confidentiality of the original data but also enhances the utility and scalability of LLMs under privacy constraints. Attendees, including machine learning engineers, data scientists, and data managers, will witness first-hand how Secludy's integration with Milvus empowers organizations to harness the power of LLMs securely and efficiently.
Monitoring and Managing Anomaly Detection on OpenShift.pdfTosin Akinosho
Monitoring and Managing Anomaly Detection on OpenShift
Overview
Dive into the world of anomaly detection on edge devices with our comprehensive hands-on tutorial. This SlideShare presentation will guide you through the entire process, from data collection and model training to edge deployment and real-time monitoring. Perfect for those looking to implement robust anomaly detection systems on resource-constrained IoT/edge devices.
Key Topics Covered
1. Introduction to Anomaly Detection
- Understand the fundamentals of anomaly detection and its importance in identifying unusual behavior or failures in systems.
2. Understanding Edge (IoT)
- Learn about edge computing and IoT, and how they enable real-time data processing and decision-making at the source.
3. What is ArgoCD?
- Discover ArgoCD, a declarative, GitOps continuous delivery tool for Kubernetes, and its role in deploying applications on edge devices.
4. Deployment Using ArgoCD for Edge Devices
- Step-by-step guide on deploying anomaly detection models on edge devices using ArgoCD.
5. Introduction to Apache Kafka and S3
- Explore Apache Kafka for real-time data streaming and Amazon S3 for scalable storage solutions.
6. Viewing Kafka Messages in the Data Lake
- Learn how to view and analyze Kafka messages stored in a data lake for better insights.
7. What is Prometheus?
- Get to know Prometheus, an open-source monitoring and alerting toolkit, and its application in monitoring edge devices.
8. Monitoring Application Metrics with Prometheus
- Detailed instructions on setting up Prometheus to monitor the performance and health of your anomaly detection system.
9. What is Camel K?
- Introduction to Camel K, a lightweight integration framework built on Apache Camel, designed for Kubernetes.
10. Configuring Camel K Integrations for Data Pipelines
- Learn how to configure Camel K for seamless data pipeline integrations in your anomaly detection workflow.
11. What is a Jupyter Notebook?
- Overview of Jupyter Notebooks, an open-source web application for creating and sharing documents with live code, equations, visualizations, and narrative text.
12. Jupyter Notebooks with Code Examples
- Hands-on examples and code snippets in Jupyter Notebooks to help you implement and test anomaly detection models.
HCL Notes und Domino Lizenzkostenreduzierung in der Welt von DLAUpanagenda
Webinar Recording: https://www.panagenda.com/webinars/hcl-notes-und-domino-lizenzkostenreduzierung-in-der-welt-von-dlau/
DLAU und die Lizenzen nach dem CCB- und CCX-Modell sind für viele in der HCL-Community seit letztem Jahr ein heißes Thema. Als Notes- oder Domino-Kunde haben Sie vielleicht mit unerwartet hohen Benutzerzahlen und Lizenzgebühren zu kämpfen. Sie fragen sich vielleicht, wie diese neue Art der Lizenzierung funktioniert und welchen Nutzen sie Ihnen bringt. Vor allem wollen Sie sicherlich Ihr Budget einhalten und Kosten sparen, wo immer möglich. Das verstehen wir und wir möchten Ihnen dabei helfen!
Wir erklären Ihnen, wie Sie häufige Konfigurationsprobleme lösen können, die dazu führen können, dass mehr Benutzer gezählt werden als nötig, und wie Sie überflüssige oder ungenutzte Konten identifizieren und entfernen können, um Geld zu sparen. Es gibt auch einige Ansätze, die zu unnötigen Ausgaben führen können, z. B. wenn ein Personendokument anstelle eines Mail-Ins für geteilte Mailboxen verwendet wird. Wir zeigen Ihnen solche Fälle und deren Lösungen. Und natürlich erklären wir Ihnen das neue Lizenzmodell.
Nehmen Sie an diesem Webinar teil, bei dem HCL-Ambassador Marc Thomas und Gastredner Franz Walder Ihnen diese neue Welt näherbringen. Es vermittelt Ihnen die Tools und das Know-how, um den Überblick zu bewahren. Sie werden in der Lage sein, Ihre Kosten durch eine optimierte Domino-Konfiguration zu reduzieren und auch in Zukunft gering zu halten.
Diese Themen werden behandelt
- Reduzierung der Lizenzkosten durch Auffinden und Beheben von Fehlkonfigurationen und überflüssigen Konten
- Wie funktionieren CCB- und CCX-Lizenzen wirklich?
- Verstehen des DLAU-Tools und wie man es am besten nutzt
- Tipps für häufige Problembereiche, wie z. B. Team-Postfächer, Funktions-/Testbenutzer usw.
- Praxisbeispiele und Best Practices zum sofortigen Umsetzen
Deep Dive: AI-Powered Marketing to Get More Leads and Customers with HyperGro...
Reading assignment s144
1. Oncogene (2003) 22, 6517–6523
& 2003 Nature Publishing Group All rights reserved 0950-9232/03 $25.00
www.nature.com/onc
Viruses and cancer: lessons from the human polyomavirus, JCV
Krzysztof Reiss1 and Kamel Khalili*,1
1
Center for Neurovirology and Cancer Biology, Temple University, Philadelphia, PA 19122, USA
The possible role of eucaryotic viruses in the development vated and causes PML when the immune system is
of cancer has been the subject of intense investigation impaired.
during the past 50 years. Thus far, a strong link between Prior to the AIDS epidemic, PML was considered an
some RNA and DNA viruses and various cancers in extremely rare disorder associated with immunocom-
humans has been established and the transforming activity promising diseases such as lymphomas, or was seen in
of several of the viruses in cell culture and their renal transplant and chemotherapy patients as a
oncogenecity in experimental animals has been well complication of immunosuppressive therapies. How-
documented. Perhaps, one of the most common themes ever, recent reports indicate that 70% of all HIV-1-
among the oncogenic viruses rests in the ability of one or infected patients will exhibit neurological disorders and
more of the viral proteins to deregulate pathways involved between 5 and 8% of all HIV-1-infected patients will
in the control of cell proliferation. For example, inactiva- develop PML (Berger and Concha, 1995). PML is
tion of tumor suppressors through their association with characterized by demyelination due to the cytolytic
viral transforming proteins, and/or impairment of signal destruction of oligodendrocytes, the subset of glial cells
transduction pathways upon viral infection and expression in brain that are responsible for myelin production.
of viral proteins are among the key biological events that Other hallmarks of PML include giant bizarre
can either trigger and/or contribute to the process of astrocytes, hyperchromatic oligodendrocyte nuclei, and
cancer. In recent years, more attention has been paid to multiple foci of demyelination (Major et al., 1992).
human polyomaviruses, particularly JC virus (JCV), The viral genome is comprised of a closed, circular,
which infects greater than 80% of the human population, double-stranded DNA that can be divided into early
due to the ability of this virus to induce a fatal and late coding sequences, and the viral regulatory
demyelinating disease in the brain, its presence in various region. The regulatory region of JCV encompasses the
tumors of central nervous system (CNS) and non-CNS viral origin of DNA replication and a bidirectional
origin, and the oncogenic potential of this virus in several promoter composed of two 98 base pair repeats. The
laboratory animal models. Here, we will focus our viral early sequence that is transcribed before DNA
attention on JCV and describe several pathways employed replication is responsible for the production of T-
by the virus to contribute to and/or accelerate cancer antigen, whereas the viral late genes that are transcribed
development. after DNA replication, produce capsid proteins
Oncogene (2003) 22, 6517–6523. doi:10.1038/sj.onc.1206959 VP1, VP2, and VP3 and the accessory Agnoprotein
(Frisque and White, 1992). The lytic cycle of JCV
Keywords: tumorigenesis; T-antigen; oncogene; JC explains some of the pathological features of PML,
virus; PML hallmarks of which are the destruction of myelin sheaths
and oligodendrocytes, the myelin-producing cells;
and the appearance of astrocytes that exhibit trans-
Introduction formed cell morphology. Evidently, lytic infection
with JCV results in cytolytic destruction of oligoden-
The human neurotropic JC virus (JCV) is the etiologic drocytes, while its abortive replication in astrocytes
agent of progressive multifocal leukoencephalopathy causes morphological changes leaving astrocytes
(PML), a fatal demyelinating disease of the central that resemble transformed cells. In cell culture systems,
nervous system (CNS) (Berger et al., 1998). JCV is a JCV exhibits a narrow tissue specificity in that the
member of the polyomaviruses whose other members virus can replicate most efficiently in primary human
include BK virus and the well-known simian virus 40 fetal glial cells. Studies have also reported weak
(SV40). JCV coexists within the human population, as replication of the virus in B cells (Monaco et al.,
greater than 80% of adults worldwide exhibit JCV- 1996). Owing to the species specificity of the DNA
specific antibodies (Major et al., 1992). Subclinical polymerase, JCV can only replicate in primates, and
infection with the virus occurs in early childhood and humans are thought to represent the natural viral host
the virus remains in a latent stage throughout life, (Frisque and White, 1992).
although on rare occasions the virus becomes reacti- In addition to its primary role in the development of
PML, JCV has been shown to be associated with several
*Correspondence: K Khalili; E-mail: kamel.khalili@temple.edu human tumors (Del Valle et al., 2001a). While the
2. Viruses and cancer
K Reiss and K Khalili
6518
etiologic role for JCV in the development of cancer in cells by JCV. Expression of the JCV early protein from
humans remains to be established, there have been the Mad-4 strain of JCV in transgenic animals contain-
several experimental animal models that verify the ing only the early DNA sequences of JCV results in
oncogenic potential of JCV in vivo. Furthermore, the the development of two distinct phenotypes. One line
ability of the JCV early protein to transform human exhibited dysmyelination of the central nervous system
fetal cells has led to the development of several cell lines due to reduced production of myelin proteins, while the
that possess tumorigenic activity in vivo. In this review, other set developed adrenal neuroblastoma (Small et al.,
we have summarized the most recent observations on 1986a, b; Franks et al., 1996). Expression of the JCV
JCV-transformed tumor cells in which the viral protein, early protein from the archetype strain of JCV in FVB/
T-antigen deregulates several cellular pathways that N mice leads to the development of primitive neuroec-
control proliferation. These observations can provide an todermal tumors resembling medulloblastoma (Krynska
alternative working platform for studying oncogenic et al., 1999b). Of note, no evidence for abnormal
pathways utilized by various viruses to induce cancer in myelination of the brain was observed in transgenic
humans. mice harboring tumors. In a different series of studies,
transgenic animals were created using the C57BL/6
JCV and cancer: in vitro and in vivo observations mouse strain expressing the JCV Mad-4 early genome.
After 6–8 months, the mice exhibited pituitary adeno-
Similar to the well-studied SV40, JCV possesses the mas (Gordon et al., 2000). Curiously, some of the
ability to infect and transform primary cultures, animals that had not developed pituitary adenomas
including primary human fetal glial cells and human instead developed malignant peripheral nerve sheath
vascular endothelial cells, albeit to a lesser degree than tumors (MPNST) (Shollar and Gordon, unpublished
SV40 (Fareed et al., 1978; Walker and Padgett, 1978). observations). Histological examination of the various
Almost all JCV-infected transformed cells express the JCV-induced tumors in transgenic mice revealed that
viral early protein and they exhibit altered morphology, while all cells contain the transgene, as expected, only a
enhanced growth rate in low serum medium, the ability subset of cells express T-antigen. Interestingly, results
to form foci in culture, and in some but not all cases, from studies on cell cultures derived from PNETs
induce tumors in Nude mice (Gallia et al., 1998a; Del showed that after several passages, T-antigen-positive
Valle et al., 2001a). Also, transformation of primary cells lose their expression of T-antigen, yet retain their
hamster brain cells by various strains of JCV, including transforming phenotype. While the mechanism involved
Mad-1 and Mad-4, have generated rapidly growing cells in the extinction of T-antigen remains unknown, its has
with several characteristics of a transformed phenotype, been suggested that a ‘hit-and-run’ mechanism may be
including growth in low serum, enhanced production of involved in JCV-induced cancer cells. Results from
plasminogen activator, and anchorage-independent in vitro studies have indicated that T-antigen-positive
growth (Frisque et al., 1980; Kang and Folk, 1992). In and T-antigen-negative medulloblastoma cells derived
addition to the cells of neural origin that seem to be from transgenic mice exhibit similar growth patterns in
readily transformed by the virus, a low incidence of monolayer cultures (Wang et al., 2001). Under ancho-
JCV-mediated transformation in baby hamster kidney rage-independent growth conditions, however, the
cells and in rat fibroblasts has been reported (Bollag T-antigen-positive cells manage to survive in the absence
et al., 1989; Haggerty et al., 1989). In laboratory animals of serum and proliferate upon treatment of cells with
JCV infection often results in the development of insulin-like growth factor 1 (IGF-1). Under similar
tumors. Newborn Syrian hamsters develop a broad conditions, T-antigen-negative cells demonstrate an
range of tumors, including medulloblastomas, primitive attenuated response when stimulated with IGF-1 (Wang
neuroectodermal tumors, astrocytomas, glioblastoma et al., 2001). Similarly, T-antigen-positive cells form
multiforme, and peripheral neuroblastomas after brain tumors when injected subcutaneously in Nude mice,
inoculation with JCV (Walker et al., 1973; Varakis, while the T-antigen-negative cells show limited, if any,
1978; Zu Rhein and Varakis, 1979). While no evidence growth (Krynska et al., 2000).
for productive infection of the tumor cells by JCV has
been observed, expression of the viral early, but not late, Molecular basis of JCV T-antigen-mediated
promoter in the tumor cells leads to the accumulation of
transformation
large amounts of T-antigen (Raj et al., 1995). Similarly,
injection of JCV into the brains of newborn rats induces While the precise mechanism responsible for cellular
undifferentiated neuroectodermal tumors in the cere- transformation by JCV is not fully understood, it is
brum of 75% of the animals (Ohsumi et al., 1986). In believed that the early proteins of the virus, particularly
owl and squirrel monkeys, intracerebral, subcutaneous, T-antigen, by associating with several cellular proteins,
or intravenous inoculation of JCV causes the develop- plays a critical role in this event (Sullivan et al., 2000).
ment of astrocytomas, glioblastomas, and neuroblasto- Like SV40 T-antigen, JCV T-antigen has a modular
mas by 16–24 months of age (London et al., 1983). In structure with multifunctional activities including
accord with the observations in the JCV hamster model, ATPase, helicase, DNA binding, and a-polymerase; all
expression of the JCV early genome was observed in the of which are essential for the process of DNA
absence of the viral late proteins and viral DNA replication (Pipas, 1992; Sullivan et al., 2000). Further-
replication ruling out productive infection of the tumor more, results from protein–protein interaction studies
Oncogene
3. Viruses and cancer
K Reiss and K Khalili
6519
tumor cells (Darbinian et al., 2001). Thus, one may
p53, pRb Tumor Suppressor Pathway
envision a role for T-antigen in the inactivation of Pura
by association in cells in which Pura contributes to the
control of cell proliferation. The cellular chaperone
hsp70 and the insulin receptor substrate 1 (IRS-1), a key
component of the type 1 insulin-like growth factor
p53 JCV-T receptor (IGF-1R), have also been shown to associate
with T-antigen (Baserga, 1999; Sullivan et al., 2000;
p53 JCV-T Lassak et al., 2002).
The association of T-antigen and IRS-1 is of
p21WAF1
X
particular interest as recent studies have suggested that
cyclin-cdk *cyclin-cdk the IGF-1 signaling pathway contributes to prolifera-
tion and survival of medulloblastoma cell lines (Patti
P et al., 2000; Wang et al., 2001; Del Valle et al., 2002a, b).
cdk Rb:E2F Rb + E2F An abundance of IGF-1R, overexpression of IRS-1, and
cyclin
phosphorylation of IGF-1R and IRS-1 have all been
E2F
detected in JCV T-antigen murine cell lines, suggesting
that IGF-1R and T-antigen may cooperate in cellular
transformation (Wang et al., 2001). The use of an
JCV-T Rb JCV-T G1 S
antisense strategy against IGF-1R mRNA and domi-
nant-negative mutants for IGF-1R in in vivo and in vitro
assays established the importance of IGF-1R in growth
Tumor of JCV T-antigen tumor cells (Wang et al., 2001; Reiss
2002). A Of interest, IRS-1 has been found in the
Figure 1 The p53, pRb tumor suppressor pathways. The nucleus of T-antigen-positive cell lines and human
association of T-antigen with p53 leads to inactivation of p53
and downregulation of p21WAF-1 that eventually affects the status
tumor samples, suggesting that T-antigen expression
of pRb phosphorylation by cyclin cdk and the release of E2F. may lead to nuclear localization of IRS-1 (Del Valle
Further, E2F is liberated from pRb:E2F by the interaction of et al., 2002a; Lassak et al., 2002, Tu et al., 2002).
T-antigen with pRb Mapping studies have determined that the N-terminal
portion of IRS-1 interacts with JCV T-antigen and that
this binding is independent from IRS-1 tyrosine
revealed that JCV T-antigen has the capacity to interact phosphorylation and can be strongly inhibited by IRS-
with several critical tumor suppressor proteins including 1 serine phosphorylation. Importantly, competition for
p53 and members of the pRb family (Bollag et al., 1989; IRS-1–T-antigen binding by a dominant-negative mu-
Haggerty et al., 1989; Del Valle et al., 2001a). It is tant of IRS-1 inhibited anchorage-independent prolif-
believed that the association of T-antigen with p53 and eration of JCV T-antigen-transformed medulloblastoma
the pRb family can lead to the inactivation of these cells (Lassak et al., 2002). All of these observations have
tumor suppressors in cells expressing T-antigen and led us to propose a model in which the interaction of
thus, promote uncontrolled proliferation. According to T-antigen and IRS-1 may lead to the uncoupling of
one model, the association of JCV T-antigen with p53 IRS-1 from the IGF-1R and the translocation of IRS-1
abrogates the ability of p53 to augment transcription of to the nucleus (Figure 2). Further studies are needed to
p21/WAF-1, an inhibitor of cyclin kinases, including determine the nuclear function of IRS-1 in the presence
cyclins A and E, and their associated kinases. Under and absence of JCV T-antigen.
normal conditions, a decrease in kinase activity of G1/S In light of recent studies demonstrating the involve-
cyclins:cdks maintains pRb in a hypophosphorylated ment of Wnt signaling in various cancers, including
and active state that in turn sequesters the S phase- medulloblastomas (Morin, 1999; Eberhart et al., 2000)
specific transcription factor, E2F. Not mutually exclu- and the association of JCV with these tumors, it was
sive, T-antigen’s association with pRb can liberate E2F hypothesized that JCV exerts its oncogenic activity, at
from the pRb:E2F complex and permit E2F to exert its least in part, through deregulation of the Wnt signaling
affect on cell proliferation by promoting unscheduled pathway. In normal cells, b-catenin, a key modulator of
transcription of S phase genes (Figure 1). Support for the Wnt pathway, is modified on its N-terminal serine
pRb regulation of T-antigen-induced tumors comes and threonine by phosphorylation and then ubiquiti-
from studies illustrating that overexpression of pRb2/ nated and rapidly degraded by the proteosome pathway
p130 can overcome JCV–T-antigen-mediated tumori- (for review see Polakis 2000; Gao et al., 2002).
genecity in experimental animals (Howard et al., 1998). Degradation of b-catenin occurs by a multiprotein
JCV T-antigen has also been associated with other cytoplasmic complex containing GSK3b, Axin 1, and
cellular proteins such as YB-1 and Pura (Gallia et al., APC. When cells are stimulated by Wnt proteins, the
1998b; Safak et al., 1999). The association of T-antigen function of the GSK3b/Axin1/APC complex is inhibited
with Pura is relevant to the transforming ability of by a lesser known pathway leading to the accumulation
T-antigen, as earlier results have demonstrated that of unphosphorylated and stable b-catenin in the
Pura overexpression suppresses the growth of several cytoplasm.
Oncogene
4. Viruses and cancer
K Reiss and K Khalili
6520
Wnt Signaling Pathway
IGF-1 Signaling Pathway
JCV-T
β-catenin
(GSK3β. Axin1, APC)
wt
β-catenin β-catenin P
JCV-T wt
JCV-T
mut
β-catenin
wt
LEF
IRS-1 β-catenin β-catenin
IRS-1 JCV-T mut
LEF
degradation
MAPK PI3K Nucleus
PDKs Activation of
c-myc, cycln D1
Others
Akt/PKB cell cycle
Nucleus
Apoptosis Tumor
Cell Others? Figure 3 The Wnt signaling pathway. The Wnt signaling pathway
Cycle? DNA and its well-studied cytoplasmic protein, b-catenin, is regulated by
Repair? Tumor a series of proteins with kinase activity such as GSK3b, Axin, and
APC. A mutation in b-catenin immunizes this protein against
phosphorylation in which the stable proteins associate with LEF-1
Figure 2 The IGF-1 signaling pathway. The IGF-1 signaling
and translocate to the nucleus where they stimulate c-myc, cyclin
pathway via its key component, IRS-1, alters phosphorylation and
D1, and several other cell proliferation genes. JCV T-antigen, by
activity of MAPK and PI3 K that eventually led to tumor
associating with wild-type b-catenin, increases the stability of b-
development. The interaction of T-antigen with IRS-1 translocates
catenin and accelerates its nuclear import
IRS-1 to the nucleus where it can affect cell cycle parameters as well
as other critical events such as DNA repair
small t-antigens, one may ascribe similar functions as
Cytoplasmic b-catenin translocates into the nucleus those established for SV40 small t-antigen for the JCV
where it forms a heterocomplex with DNA binding protein. For example, the cysteines and the central
transcription factors such as TCF/LEF, which have the proline of SV40 small t-antigen appear to be important
potential to stimulate transcription of genes related to for its interaction with and the inhibition of cellular
cell cycle regulation such as c-myc and cyclin D1 (He phosphatase PP2A. As a consequence of PP2A inhibi-
et al., 1998; Shtutman et al., 1999). In several cancer tion by small t-antigen, several cellular kinases are
cells, including PNETs, it was shown that mutations at hyperphosphorylated and their activity is elevated. This
the site of phosphorylation of b-catenin results in was first described for MAPK and its kinase, ERK, then
stabilization of b-catenin, its nuclear import, and extended to JNK and a key ion transporter, the Na/H
enhanced expression of cell cycle regulators (Figure 3). antiporter (Sontag et al., 1993). Activation of the
Examination of the Wnt signaling pathway in JCV T- MAPK family kinases by small t-antigen also leads to
antigen-positive cells compared to T-antigen-negative increased transcription from AP-1-driven promoters,
cells revealed enhanced levels of b-catenin, LEF-1, and consistent with activation of the Elk-1 family of
their downstream target, c-myc, suggesting a role for T- transcription factors (Wheat et al., 1994). Also, JCV
antigen in deregulating the Wnt pathway (Gan et al., small t-antigen may influence protein phosphorylation
2001). Further studies have revealed the ability of T- cascades involved in CREB-related transcriptional
antigen to associate physically with b-catenin and activities (Wheat et al., 1994). In general, the effects of
stabilize wild-type b-catenin. This event was concurrent small t-antigen on intracellular kinases promote cell
with increased levels of b-catenin in the nucleus and growth presumably by accelerating cell entry into the
enhancement of c-myc gene expression (Figure 3). S phase by a complex mechanism that involves proteo-
Through alternative splicing, the early region of JCV some degradation of p27 (Sheaff et al., 1997). Of note,
can also encode several smaller isoforms of large efficient degradation of p27 is required for the accumu-
T-antigen including small t-antigen and T0 135, T0 136, lation of cyclin A and S phase progression (Zerfass-
and T0 165 (Bollag et al., 2000; Prins and Frisque, 2001). Thome et al., 1997). Thus, by favoring the elimination of
Initial studies with the T0 proteins have suggested that p27, small t-antigen may allow cyclin A/cdk2 to
these proteins may contribute to replication of viral orchestrate cell cycle progression.
DNA and suspected to possess some oncogenic poten- In addition to multiple viral early proteins, the JCV
tial (Prins and Frisque, 2001). Little is known about the late region encodes a small protein, named Agnoprotein,
function of JCV small t-antigen, and its potential role in whose open reading frame resides in the leader of the
cellular transformation. However, based on sequence late transcripts. In SV40, Agnoprotein plays a role in the
homology between specific regions of SV40 and JCV lytic cycle of the virus by facilitating nuclear import of
Oncogene
5. Viruses and cancer
K Reiss and K Khalili
6521
the capsid protein (Carswell and Alwine, 1986; Resnick in 28 (32.9%) of 85 tested samples. In a separate series
and Shenk, 1986; Khalili et al., 1988). Similarly, of studies, the presence of JCV in medulloblastomas has
Agnoprotein plays a critical role in productive replica- been established. Parallel reports demonstrate immuno-
tion of JCV, as mutations in the Agnoprotein hamper histochemical detection of JCV T-antigen in 17.3 and
replication of JCV in primary astrocytes (Safak et al., 45% of samples obtained from two separate groups of
2001, unpublished observations). With respect to its medulloblastoma patients (Krynska et al., 1999a; Del
effect on host cells, results from in vitro studies have Valle et al., 2002c). In addition to T-antigen, analysis of
demonstrated that the expression of Agnoprotein in cells medulloblastoma samples has revealed the presence of
leads to upregulation of cyclin A and p21/WAF-1. Agno DNA sequences in 11 (69%) out of 16 samples,
Interestingly, results from protein binding studies have and immunohistochemical analysis showed the presence
revealed the ability of Agnoprotein to interact, although of Agnoprotein in cytoplasm of 11 (55%) out of 20
weakly, with p53, and that the region between residues samples. Importantly, the JCV early gene product, large
1–36 of Agnoprotein that contain a helix–loop–helix T-antigen, was detected in nine (45%) out of 20
motif is essential for this interaction. Thus, it is evident medulloblastoma cases examined.
that in addition to well-studied large T-antigen, other In addition to tumors of the nervous system, more
JCV proteins including small t-antigen, Agnoprotein, recent studies have detected JCV DNA sequences and
and perhaps T0 may play a role in the oncogenic expression of the viral proteins in colorectal carcinoma,
potential of this human polyomavirus. rather than tumors arising from within the nervous
system (Ricciardiello et al., 2001; Enam et al., 2002).
Association of JCV with human cancer Greater than 50% of the tumor samples were found to
express the viral proteins T-antigen and Agnoprotein,
As mentioned earlier, prior to the discovery of JCV, while a number of T-antigen-positive samples also
several reports indicated an association between PML contained b-catenin protein localized to the nucleus
and brain tumors. The first observations were made by (Enam et al., 2002). While VP-1 DNA sequences can be
Richardson in which the post-mortem examination of a amplified from significant numbers of these tumors, VP1
58-year-old man with chronic lymphocytic leukemia and expression by immunohistochemistry has not been
PML revealed the presence of an oligodendroglioma observed in any tumor type, suggesting that the tumors
(Richardson, 1961). In other studies of PML cases cells are not productively infected with JCV, but rather
associated JCV with multiple astrocytomas (Sima et al., transformed by the virus.
1983) and numerous foci of anaplastic astrocytes Interestingly, recent evidence has shown the presence
(Castaigne et al., 1974) were reported. In these cases, of JCV in untreated urban sewage, suggesting transmis-
viral particles were observed in both oligodendrocytes sion of the virus via the fecal–oral route (Bofil-Mas et al.,
and astrocytes, but not in the neoplastic astrocytes. 2001). In addition, JCV DNA has also been found in the
Recently, Shintaku et al. (2000) reported a case of normal human gastrointestinal tract, which further
dysplastic ganglion-like cells in association with PML. supports the possibility that JCV, and other polyoma-
Detailed immunohistochemical studies revealed that viruses, may colonize the gut (Ricciardiello et al., 2000).
the neurons were infected with JCV and expressed These data, taken together with several reports of SV40
JCV T-antigen in the absence of capsid protein, VP1. detection in human mesothelioma, osteosarcoma, and
In addition to cases of simultaneous PML and B-cell lymphoma, suggest that JCV may be observed
cerebral neoplasm, JCV has been found in human brain within other tumor types throughout the body. The
tumors in the absence of any PML lesions. In our recent observations from such clinical samples along with the
work (Del Valle et al., 2001b), 85 clinical specimens data from cell culture and experimental animals add
from the United Kingdom, Greece, and the United further evidence of the involvement of JCV in the
States have been examined for their possible association process of cellular transformation, and strongly suggest
with JCV. These multiple samples represented various a possibility that this human neurotropic polyomavirus
human brain tumors, including oligodendroglioma, may play a role in the development of human brain
astrocytoma, pilocytic astrocytoma, oligoastrocytoma, tumors.
anaplastic astrocytoma, anaplastic oligodendroglioma,
glioblastoma multiforme, gliomatosis cerebri, gliosarco-
ma, ependymoma, and subependymoma. Gene amplifi-
cation using primers that recognize the JCV DNA Acknowledgements
We express our appreciation to past and present members of
sequences followed by Southern blot hybridization have
the Center for Neurovirology and Cancer Biology for their
demonstrated the presence of the viral early sequences in contribution, and to Cynthia Schriver for editorial assistance.
49 (69%) of 71 samples. More importantly, results of This work was made possible by grants awarded by NIH to
immunohistochemical analysis have demonstrated the KR and KK.
expression of JCV T-antigen in the nuclei of tumor cells
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