Pub Date : 2010-09-23DOI: 10.2174/1874079001003010049
Fu Li, J. Wallace, Michael C. Ostrowski
ETS factors are involved in cancer progression through transcriptional regulation of factors mediating cell cycle, cell growth, apoptosis, cell adhesion and migration. The biological processes regulated by ETS factors are important not only in tumor cells, but also in the surrounding cells comprising the tumor microenvironment. Additionally, ETS factors can serve as transcriptional activators and repressors to regulate gene expression in a cell context-specific fashion. Here we discuss recent advances in which the regulatory roles of ETS factors in stromal cells are critical during both development and cancer. These new findings uncover the importance of ETS signaling in the stromal compartment of tumors and shed light on new potential mechanisms of ETS factors.
{"title":"ETS Transcription Factors in the Tumor Microenvironment","authors":"Fu Li, J. Wallace, Michael C. Ostrowski","doi":"10.2174/1874079001003010049","DOIUrl":"https://doi.org/10.2174/1874079001003010049","url":null,"abstract":"ETS factors are involved in cancer progression through transcriptional regulation of factors mediating cell cycle, cell growth, apoptosis, cell adhesion and migration. The biological processes regulated by ETS factors are important not only in tumor cells, but also in the surrounding cells comprising the tumor microenvironment. Additionally, ETS factors can serve as transcriptional activators and repressors to regulate gene expression in a cell context-specific fashion. Here we discuss recent advances in which the regulatory roles of ETS factors in stromal cells are critical during both development and cancer. These new findings uncover the importance of ETS signaling in the stromal compartment of tumors and shed light on new potential mechanisms of ETS factors.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"15 1","pages":"49-54"},"PeriodicalIF":0.0,"publicationDate":"2010-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-09-23DOI: 10.2174/1874079001003010040
David P Turner
Most advanced prostate tumors are dependent upon hormonal regulation of the transcriptional activity of the androgen receptor (AR). Current ASCO recommendations for initial treatment of advanced disease target the hormonal mediated regulation of AR activation through androgen deprivation therapy. Despite early treatment efficacy, most prostate tumors progress and re-activate AR transcriptional regulation through alternative biological mechanisms that allow them to circumvent the requirement for androgen. It is the temporal and spatial recruitment of specific AR transcriptional complexes to the promoters of cancer associated target genes that promotes the tumorigenic phenotype in prostate cancer. Increasing published data associates the E Twenty Six (ETS) family of transcription factors with prostate cancer progression and with the transcriptional activity of the AR. Evidence suggests that ETS factors act in concert to both positively and negatively regulate the pathways that control progression to metastatic cancer in prostate tissues. Given the critical roles both ETS factors and the AR play in the development of prostate cancer, mechanistic insight into their transcriptional co-regulation during the hormone sensitive and hormone refractory phases of progression will be provided by determining the contribution of ETS, AR and ETS-AR mediated regulatory control. This review examines the current depth of understanding of the role of the ETS family of transcription factors as transcriptional elements that confer the carcinogenic response to aberrant hormonal activity during prostate cancer progression.
{"title":"The Role of ETS Transcriptional Regulation in Hormone Sensitive and Refractory Prostate Cancer","authors":"David P Turner","doi":"10.2174/1874079001003010040","DOIUrl":"https://doi.org/10.2174/1874079001003010040","url":null,"abstract":"Most advanced prostate tumors are dependent upon hormonal regulation of the transcriptional activity of the androgen receptor (AR). Current ASCO recommendations for initial treatment of advanced disease target the hormonal mediated regulation of AR activation through androgen deprivation therapy. Despite early treatment efficacy, most prostate tumors progress and re-activate AR transcriptional regulation through alternative biological mechanisms that allow them to circumvent the requirement for androgen. It is the temporal and spatial recruitment of specific AR transcriptional complexes to the promoters of cancer associated target genes that promotes the tumorigenic phenotype in prostate cancer. Increasing published data associates the E Twenty Six (ETS) family of transcription factors with prostate cancer progression and with the transcriptional activity of the AR. Evidence suggests that ETS factors act in concert to both positively and negatively regulate the pathways that control progression to metastatic cancer in prostate tissues. Given the critical roles both ETS factors and the AR play in the development of prostate cancer, mechanistic insight into their transcriptional co-regulation during the hormone sensitive and hormone refractory phases of progression will be provided by determining the contribution of ETS, AR and ETS-AR mediated regulatory control. This review examines the current depth of understanding of the role of the ETS family of transcription factors as transcriptional elements that confer the carcinogenic response to aberrant hormonal activity during prostate cancer progression.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"3 1","pages":"40-48"},"PeriodicalIF":0.0,"publicationDate":"2010-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-09-23DOI: 10.2174/1874079001003010024
D. Watson, David P Turner, Melissa N. Scheiber, V. Findlay, P. Watson
ETS factors are known to act as positive or negative regulators of the expression of genes including those that control response to various signaling cascades, cellular proliferation, differentiation, hematopoiesis, apoptosis, adhesion, migration, invasion and metastasis, tissue remodeling, ECM composition and angiogenesis. During cancer progression, altered ETS gene expression disrupts the regulated control of many of these biological processes. Although it was originally observed that specific ETS factors function either as positive or negative regulators of transcription, it is now evident that the same ETS factor may function in reciprocal fashions, reflecting promoter and cell context specificities. This report will present a discussion of ETS factor expression during prostate and breast cancer progression and its functional roles in epithelial cell phenotypes. The ETS genes encode transcription factors that have independent activities but are likely to be part of an integrated network. While previous studies have focused on single ETS factors in the context of specific promoters, future studies should consider the functional impact of multiple ETS present within a specific cell type. The pattern of ETS expression within a single tissue is, not surprisingly, quite complex. Multiple ETS factors may be able to regulate the same genes, albeit at different magnitude or in different directions. Furthermore, the precise balance between cancer promotion and inhibition by ETS factors, which may differentially regulate specific target genes, can thus control its progression. These concepts form the basis of the hypothesis that "Ets conversion" plays a critical role during tumor progression. Examples supporting this hypothesis will be described.
{"title":"ETS Transcription Factor Expression and Conversion During Prostate and Breast Cancer Progression","authors":"D. Watson, David P Turner, Melissa N. Scheiber, V. Findlay, P. Watson","doi":"10.2174/1874079001003010024","DOIUrl":"https://doi.org/10.2174/1874079001003010024","url":null,"abstract":"ETS factors are known to act as positive or negative regulators of the expression of genes including those that control response to various signaling cascades, cellular proliferation, differentiation, hematopoiesis, apoptosis, adhesion, migration, invasion and metastasis, tissue remodeling, ECM composition and angiogenesis. During cancer progression, altered ETS gene expression disrupts the regulated control of many of these biological processes. Although it was originally observed that specific ETS factors function either as positive or negative regulators of transcription, it is now evident that the same ETS factor may function in reciprocal fashions, reflecting promoter and cell context specificities. This report will present a discussion of ETS factor expression during prostate and breast cancer progression and its functional roles in epithelial cell phenotypes. The ETS genes encode transcription factors that have independent activities but are likely to be part of an integrated network. While previous studies have focused on single ETS factors in the context of specific promoters, future studies should consider the functional impact of multiple ETS present within a specific cell type. The pattern of ETS expression within a single tissue is, not surprisingly, quite complex. Multiple ETS factors may be able to regulate the same genes, albeit at different magnitude or in different directions. Furthermore, the precise balance between cancer promotion and inhibition by ETS factors, which may differentially regulate specific target genes, can thus control its progression. These concepts form the basis of the hypothesis that \"Ets conversion\" plays a critical role during tumor progression. Examples supporting this hypothesis will be described.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"3 1","pages":"24-39"},"PeriodicalIF":0.0,"publicationDate":"2010-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-09-23DOI: 10.2174/1874079001003010022
D. Watson
The special issue provides a compilation of five review articles and five research articles on ETS transcriptional control, microRNA regulation of mRNA degradation and translation, post-transcriptional control of pre-RNA processing, protein stability and degradation. Thus, this issue highlights the areas that represent the main control mechanisms of gene expression from primary transcription to protein expression.
{"title":"Editorial-Transcriptional and Post-Transcriptional Regulation in Hormone-Dependent Cancer","authors":"D. Watson","doi":"10.2174/1874079001003010022","DOIUrl":"https://doi.org/10.2174/1874079001003010022","url":null,"abstract":"The special issue provides a compilation of five review articles and five research articles on ETS transcriptional control, microRNA regulation of mRNA degradation and translation, post-transcriptional control of pre-RNA processing, protein stability and degradation. Thus, this issue highlights the areas that represent the main control mechanisms of gene expression from primary transcription to protein expression.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"21 1","pages":"22-23"},"PeriodicalIF":0.0,"publicationDate":"2010-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-08-27DOI: 10.2174/1874079001003010016
Zarrag Isa Al-Fify, M. Aly
Cancer is a major cause of death in the world; thus, the prevention of this disease would have a significant impact on public health. Chemoprevention is defined as natural and synthetic pharmacological (chemical) agent to disrupt the process of carcinogenesis. Green tea is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. It is one of the most frequently consumed beverages in the world. Green tea polyphenolics have demonstrated antimutagenic, anticarcinogenic, antioxidant and antipromotional effects. The aim of this work is to study the protective effect of green tea extract against genotoxic damage of dimethylnitros- amine (DMN) in mice bone marrow cells. Our results demonstrated that the administration of green tea extract 24 hr before the DMN injection significantly suppressed DMN-induced chromosomal aberrations and sister chromatid exchanges. The suppression was observed 18 hr, 24 hr and 48 hr after the DMN treatment but no suppressive effect was observed at the early period (6 hr and 12 hr) after the DMN treatment. Furthermore, the suppression was observed in all doses of DMN (4, 5 and 6 mg/kg) investigated. Mice were given green tea 2 hr before the DMN injection displayed no suppressive effect. Mice were given 2% green tea extract as the sole source of drinking water for four days before sacrifice displayed significantly suppressed DMN-induced chromosomal aberrations and sister chromatid exchanges. We conclude that green tea presents significant antigenotoxic concern under the anticipated conditions of use. These results are consistent with other antigenotoxicity studies of green tea.
{"title":"Protective Effect of Green Tea Against Dimethylnitrosamine Induced Genotoxicity in Mice Bone Marrow Cells","authors":"Zarrag Isa Al-Fify, M. Aly","doi":"10.2174/1874079001003010016","DOIUrl":"https://doi.org/10.2174/1874079001003010016","url":null,"abstract":"Cancer is a major cause of death in the world; thus, the prevention of this disease would have a significant impact on public health. Chemoprevention is defined as natural and synthetic pharmacological (chemical) agent to disrupt the process of carcinogenesis. Green tea is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis. It is one of the most frequently consumed beverages in the world. Green tea polyphenolics have demonstrated antimutagenic, anticarcinogenic, antioxidant and antipromotional effects. The aim of this work is to study the protective effect of green tea extract against genotoxic damage of dimethylnitros- amine (DMN) in mice bone marrow cells. Our results demonstrated that the administration of green tea extract 24 hr before the DMN injection significantly suppressed DMN-induced chromosomal aberrations and sister chromatid exchanges. The suppression was observed 18 hr, 24 hr and 48 hr after the DMN treatment but no suppressive effect was observed at the early period (6 hr and 12 hr) after the DMN treatment. Furthermore, the suppression was observed in all doses of DMN (4, 5 and 6 mg/kg) investigated. Mice were given green tea 2 hr before the DMN injection displayed no suppressive effect. Mice were given 2% green tea extract as the sole source of drinking water for four days before sacrifice displayed significantly suppressed DMN-induced chromosomal aberrations and sister chromatid exchanges. We conclude that green tea presents significant antigenotoxic concern under the anticipated conditions of use. These results are consistent with other antigenotoxicity studies of green tea.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2010-05-05DOI: 10.2174/1874079001003010001
J. Shukla, V. S. Thakur, T. Poduval
The electrostatic attraction between the negatively charged components of cancer cells and the positively charged anticancer peptides (ACPs) is believed to play a role in selective disruption of cancer cell membrane. Since arginine (Arg), a cationic amino acid is the most prevalent in these ACPs; we hypothesized that Arg when delivered in saline environment at the pharmacological concentration could become an anticancer molecule. The effects of L-Arg and D-Arg on tumor cell lines were studied. The therapeutic ability of pharmacological doses of Arg in saving the mice from experimental tumors was also evaluated. Both the enantiomers of Arg and not the cationic amino acid L-lysine (L-Lys) or agmatine-sulphate, at 10 mM concentration caused tumor cell clumping when treated in PBS. Arg delivered in PBS (Arg- P) and not in medium (Arg-M) up to 50 mM caused extensive tumor cell membrane damage leading to its death. Arg at 150 mM and above irrespective of chirality and incubation vehicle became an effective antitumor molecule against all the four cell lines tested. L-Arg was not toxic to normal cells like erythrocytes, lymphocytes, NIH 3T3 cells when presented in PBS. Arg cured mice bearing solid tumor fibrosarcoma (FS) when delivered into the tumor either in PBS or medium and lymphosarcoma-ascitic (LSA) tumor when delivered intraperitoneally in PBS. Our studies indicate that Arg can be used for loco-regional tumor therapy with minimal damage to normal cells and the mechanism of anticancer action of Arg is not metabolically driven but through its chemical structure, dose and delivery environment.
{"title":"Arginine: Appropriate Dose and Delivery Environment Makes It an Anticancer Molecule","authors":"J. Shukla, V. S. Thakur, T. Poduval","doi":"10.2174/1874079001003010001","DOIUrl":"https://doi.org/10.2174/1874079001003010001","url":null,"abstract":"The electrostatic attraction between the negatively charged components of cancer cells and the positively charged anticancer peptides (ACPs) is believed to play a role in selective disruption of cancer cell membrane. Since arginine (Arg), a cationic amino acid is the most prevalent in these ACPs; we hypothesized that Arg when delivered in saline environment at the pharmacological concentration could become an anticancer molecule. The effects of L-Arg and D-Arg on tumor cell lines were studied. The therapeutic ability of pharmacological doses of Arg in saving the mice from experimental tumors was also evaluated. Both the enantiomers of Arg and not the cationic amino acid L-lysine (L-Lys) or agmatine-sulphate, at 10 mM concentration caused tumor cell clumping when treated in PBS. Arg delivered in PBS (Arg- P) and not in medium (Arg-M) up to 50 mM caused extensive tumor cell membrane damage leading to its death. Arg at 150 mM and above irrespective of chirality and incubation vehicle became an effective antitumor molecule against all the four cell lines tested. L-Arg was not toxic to normal cells like erythrocytes, lymphocytes, NIH 3T3 cells when presented in PBS. Arg cured mice bearing solid tumor fibrosarcoma (FS) when delivered into the tumor either in PBS or medium and lymphosarcoma-ascitic (LSA) tumor when delivered intraperitoneally in PBS. Our studies indicate that Arg can be used for loco-regional tumor therapy with minimal damage to normal cells and the mechanism of anticancer action of Arg is not metabolically driven but through its chemical structure, dose and delivery environment.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2010-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-12-19DOI: 10.2174/1874079000802010053
B. Tavares-Murta, E. Murta
Leukocyte migration is a key event in the inflammatory response to tumors. The tumor releases specific chemokines that control migration of leukocytes and functions of these cells after their arrival at the tumor site. In addition to these local changes in the tumor microenvironment, the host response to malignant solid tumors also gives rise to systemic effects, the most frequent of which are leukocytosis, neutrophilia and lymphopenia. These hematological findings are significantly correlated with advanced tumor stage and, therefore, poor disease prognosis. The ratio of neutrophil and lymphocyte counts has been suggested as a simple parameter of systemic inflammation in cancer patients. An elevated neutrophil to lymphocyte ratio has been shown to be an independent prognostic factor for cancers at various different sites, suggesting that this parameter is a clinically accessible and useful biomarker for patient survival. The effect of tumor development on circulating leukocyte number has not been clarified. One proposed mechanism is that tumor cells produce soluble factors such as granulocyte colony stimulating factor, which mobilize precursor cells in the bone marrow, or other mediators that alter cell differentiation. Leukocyte counts may be readily obtained at the time of diagnosis, and these data could be useful as stratification factors in clinical trials and in identifying patients with poor prognosis, leading to better treatment strategies.
{"title":"Systemic Leukocyte Alterations in Cancer and their Relation to Prognosis","authors":"B. Tavares-Murta, E. Murta","doi":"10.2174/1874079000802010053","DOIUrl":"https://doi.org/10.2174/1874079000802010053","url":null,"abstract":"Leukocyte migration is a key event in the inflammatory response to tumors. The tumor releases specific chemokines that control migration of leukocytes and functions of these cells after their arrival at the tumor site. In addition to these local changes in the tumor microenvironment, the host response to malignant solid tumors also gives rise to systemic effects, the most frequent of which are leukocytosis, neutrophilia and lymphopenia. These hematological findings are significantly correlated with advanced tumor stage and, therefore, poor disease prognosis. The ratio of neutrophil and lymphocyte counts has been suggested as a simple parameter of systemic inflammation in cancer patients. An elevated neutrophil to lymphocyte ratio has been shown to be an independent prognostic factor for cancers at various different sites, suggesting that this parameter is a clinically accessible and useful biomarker for patient survival. The effect of tumor development on circulating leukocyte number has not been clarified. One proposed mechanism is that tumor cells produce soluble factors such as granulocyte colony stimulating factor, which mobilize precursor cells in the bone marrow, or other mediators that alter cell differentiation. Leukocyte counts may be readily obtained at the time of diagnosis, and these data could be useful as stratification factors in clinical trials and in identifying patients with poor prognosis, leading to better treatment strategies.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"2 1","pages":"53-58"},"PeriodicalIF":0.0,"publicationDate":"2008-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-11-03DOI: 10.2174/1874079000802010042
R. Mirzayans, D. Murray
Our genetic material is constantly damaged by internal sources such as reactive oxygen species and external sources such as ionizing radiation and sunlight. However, we seldom notice these injuries because our cells possess elegant DNA surveillance networks that serve to maintain cellular homeostasis. These networks are complex signal transduction pathways that coordinate cell cycle checkpoints and DNA repair processes to eliminate DNA damage, as well as invoking pathways such as sustained growth arrest (i.e., accelerated senescence) and apoptotic cell death to eliminate injured cells from the proliferating population. The p53 tumor suppressor protein and its downstream effector p21 are key regulators of these various responses. Failure of cells to properly activate p53/p21-mediated events following genotoxic stress may lead to the development of genomic instability and the emergence of malignant cells which exhibit stem cell-like properties. It is therefore not surprising that defects in major players of the DNA surveillance networks are the underlying cause for numerous debilitating human genetic disorders that are characterized by genomic instability, premature aging, and cancer proneness. In this article, we first provide an update on the role of the p53 signaling pathway in determining the fate of human cells following exposure to DNA-damaging agents. We next review the clinical and laboratory features of the most extensively studied human genome instability disorders including xeroderma pigmentosum, Cockayne syndrome, ataxia telangiectasia, and Li-Fraumeni syndrome, and discuss the current knowledge on the biological consequences of deregulated p53 signaling in cells derived from patients with such disorders.
{"title":"Human Genetic Disorders Associated with Genome Instability, Premature Aging and Cancer Predisposition","authors":"R. Mirzayans, D. Murray","doi":"10.2174/1874079000802010042","DOIUrl":"https://doi.org/10.2174/1874079000802010042","url":null,"abstract":"Our genetic material is constantly damaged by internal sources such as reactive oxygen species and external sources such as ionizing radiation and sunlight. However, we seldom notice these injuries because our cells possess elegant DNA surveillance networks that serve to maintain cellular homeostasis. These networks are complex signal transduction pathways that coordinate cell cycle checkpoints and DNA repair processes to eliminate DNA damage, as well as invoking pathways such as sustained growth arrest (i.e., accelerated senescence) and apoptotic cell death to eliminate injured cells from the proliferating population. The p53 tumor suppressor protein and its downstream effector p21 are key regulators of these various responses. Failure of cells to properly activate p53/p21-mediated events following genotoxic stress may lead to the development of genomic instability and the emergence of malignant cells which exhibit stem cell-like properties. It is therefore not surprising that defects in major players of the DNA surveillance networks are the underlying cause for numerous debilitating human genetic disorders that are characterized by genomic instability, premature aging, and cancer proneness. In this article, we first provide an update on the role of the p53 signaling pathway in determining the fate of human cells following exposure to DNA-damaging agents. We next review the clinical and laboratory features of the most extensively studied human genome instability disorders including xeroderma pigmentosum, Cockayne syndrome, ataxia telangiectasia, and Li-Fraumeni syndrome, and discuss the current knowledge on the biological consequences of deregulated p53 signaling in cells derived from patients with such disorders.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"2 1","pages":"42-52"},"PeriodicalIF":0.0,"publicationDate":"2008-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-09-05DOI: 10.2174/1874079000802010025
S. Ingvarsson
Like other cancer types, breast cancer is considered to be a genetic disease. While the majority of genetic changes are somatic, a minority are in germline. About 10-20% of breast cancer is thought to be due to a germline mutation in high-penetrance genes, where the major focus has been on BRCA1 and BRCA2. Some of these mutations are defined as founder mutations. Studies on founder mutations yield important information, mainly due to a large number of available carriers with the same mutation, regarding penetrance, expression, genetic modifiers or low-penetrant genes and influence from the environment. Population studies are also valuable due the possibilities for evaluating clinicopathological data in a group of patients who have the same mutation. In Iceland a rare founder mutation has been detected in BRCA1, and a frequent founder mutation has been detected in BRCA2. In addition to population-based studies on genetics and clinicopathology, an extensive analysis of somatic changes in tumours of BRCA2 founder mutation carriers has been made.
{"title":"Population Approach in Breast Cancer Research Based on Integration of Genetic, Clinicopathological and Genealogical Clues","authors":"S. Ingvarsson","doi":"10.2174/1874079000802010025","DOIUrl":"https://doi.org/10.2174/1874079000802010025","url":null,"abstract":"Like other cancer types, breast cancer is considered to be a genetic disease. While the majority of genetic changes are somatic, a minority are in germline. About 10-20% of breast cancer is thought to be due to a germline mutation in high-penetrance genes, where the major focus has been on BRCA1 and BRCA2. Some of these mutations are defined as founder mutations. Studies on founder mutations yield important information, mainly due to a large number of available carriers with the same mutation, regarding penetrance, expression, genetic modifiers or low-penetrant genes and influence from the environment. Population studies are also valuable due the possibilities for evaluating clinicopathological data in a group of patients who have the same mutation. In Iceland a rare founder mutation has been detected in BRCA1, and a frequent founder mutation has been detected in BRCA2. In addition to population-based studies on genetics and clinicopathology, an extensive analysis of somatic changes in tumours of BRCA2 founder mutation carriers has been made.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"2 1","pages":"25-30"},"PeriodicalIF":0.0,"publicationDate":"2008-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68051081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2008-09-05DOI: 10.2174/1874079000802010031
Chao Ma, Jiangbing Zhou, Xiaolu Yin, C. Jie, Dongming Xing, L. Du, Ying Zhang
Human lung cancer remains one of the deadliest diseases worldwide. New approaches are needed for improved lung cancer treatment. In this study, we found that M. tuberculosis culture supernatant (TB-SN) could inhibit human lung cancer cell proliferation through a caspase-dependent apoptosis pathway and induce cell cycle arrest in G1 phase. The active components responsible for the growth inhibitory activities were attributed to some proteins or protein complex with molecular weight more than 100 kD. These findings are significant and may provide new insight into a possible antagonism between M. tuberculosis and lung cancer and also have implications for development of an alternative approach for lung cancer treatment.
{"title":"Mycobacterium tuberculosis Culture Supernatant Induces Cancer Cell Apoptosis and Cell Cycle Arrest","authors":"Chao Ma, Jiangbing Zhou, Xiaolu Yin, C. Jie, Dongming Xing, L. Du, Ying Zhang","doi":"10.2174/1874079000802010031","DOIUrl":"https://doi.org/10.2174/1874079000802010031","url":null,"abstract":"Human lung cancer remains one of the deadliest diseases worldwide. New approaches are needed for improved lung cancer treatment. In this study, we found that M. tuberculosis culture supernatant (TB-SN) could inhibit human lung cancer cell proliferation through a caspase-dependent apoptosis pathway and induce cell cycle arrest in G1 phase. The active components responsible for the growth inhibitory activities were attributed to some proteins or protein complex with molecular weight more than 100 kD. These findings are significant and may provide new insight into a possible antagonism between M. tuberculosis and lung cancer and also have implications for development of an alternative approach for lung cancer treatment.","PeriodicalId":89032,"journal":{"name":"The open cancer journal","volume":"2 1","pages":"31-41"},"PeriodicalIF":0.0,"publicationDate":"2008-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68050588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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