Pub Date : 2016-03-09eCollection Date: 2016-01-01DOI: 10.4137/BIC.S36679
Bratati Ganguly, Sonia C Dolfi, Lorna Rodriguez-Rodriguez, Shridar Ganesan, Kim M Hirshfield
Defects in DNA repair lead to genomic instability and play a critical role in cancer development. Understanding the process by which DNA damage repair is altered or bypassed in cancer may identify novel therapeutic targets and lead to improved patient outcomes. Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) has an important role in DNA repair, and novel therapeutics targeting PARP1 have been developed to treat cancers with defective DNA repair pathways. Despite treatment successes with PARP inhibitors (PARPi), intrinsic and acquired resistances have been observed. Preclinical studies and clinical trials in cancer suggest that combination therapy using PARPi and platinating agents is more effective than monotherapy in circumventing drug resistance mechanisms. Additionally, identification of biomarkers in response to PARPi will lead to improved patient selection for targeted cancer treatment. Recent technological advances have provided the necessary tools to examine many potential avenues to develop such biomarkers. This review examines the mechanistic rationale of PARP inhibition and potential biomarkers in their development for personalized therapy.
{"title":"Role of Biomarkers in the Development of PARP Inhibitors.","authors":"Bratati Ganguly, Sonia C Dolfi, Lorna Rodriguez-Rodriguez, Shridar Ganesan, Kim M Hirshfield","doi":"10.4137/BIC.S36679","DOIUrl":"10.4137/BIC.S36679","url":null,"abstract":"<p><p>Defects in DNA repair lead to genomic instability and play a critical role in cancer development. Understanding the process by which DNA damage repair is altered or bypassed in cancer may identify novel therapeutic targets and lead to improved patient outcomes. Poly(adenosine diphosphate-ribose) polymerase 1 (PARP1) has an important role in DNA repair, and novel therapeutics targeting PARP1 have been developed to treat cancers with defective DNA repair pathways. Despite treatment successes with PARP inhibitors (PARPi), intrinsic and acquired resistances have been observed. Preclinical studies and clinical trials in cancer suggest that combination therapy using PARPi and platinating agents is more effective than monotherapy in circumventing drug resistance mechanisms. Additionally, identification of biomarkers in response to PARPi will lead to improved patient selection for targeted cancer treatment. Recent technological advances have provided the necessary tools to examine many potential avenues to develop such biomarkers. This review examines the mechanistic rationale of PARP inhibition and potential biomarkers in their development for personalized therapy. </p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-02-11eCollection Date: 2016-01-01DOI: 10.4137/BIC.S34417
Bhavna S Paratala, Sonia C Dolfi, Hossein Khiabanian, Lorna Rodriguez-Rodriguez, Shridar Ganesan, Kim M Hirshfield
Significant advances in our knowledge of cancer genomes are rapidly changing the way we think about tumor biology and the heterogeneity of cancer. Recent successes in genomically-guided treatment approaches accompanied by more sophisticated sequencing techniques have paved the way for deeper investigation into the landscape of genomic rearrangements in cancer. While considerable research on solid tumors has focused on point mutations that directly alter the coding sequence of key genes, far less is known about the role of somatic rearrangements. With many recurring alterations observed across tumor types, there is an obvious need for functional characterization of these genomic biomarkers in order to understand their relevance to tumor biology, therapy, and prognosis. As personalized therapy approaches are turning toward genomic alterations for answers, these biomarkers will become increasingly relevant to the practice of precision medicine. This review discusses the emerging role of genomic rearrangements in breast cancer, with a particular focus on fusion genes. In addition, it raises several key questions on the therapeutic value of such rearrangements and provides a framework to evaluate their significance as predictive and prognostic biomarkers.
{"title":"Emerging Role of Genomic Rearrangements in Breast Cancer: Applying Knowledge from Other Cancers.","authors":"Bhavna S Paratala, Sonia C Dolfi, Hossein Khiabanian, Lorna Rodriguez-Rodriguez, Shridar Ganesan, Kim M Hirshfield","doi":"10.4137/BIC.S34417","DOIUrl":"10.4137/BIC.S34417","url":null,"abstract":"<p><p>Significant advances in our knowledge of cancer genomes are rapidly changing the way we think about tumor biology and the heterogeneity of cancer. Recent successes in genomically-guided treatment approaches accompanied by more sophisticated sequencing techniques have paved the way for deeper investigation into the landscape of genomic rearrangements in cancer. While considerable research on solid tumors has focused on point mutations that directly alter the coding sequence of key genes, far less is known about the role of somatic rearrangements. With many recurring alterations observed across tumor types, there is an obvious need for functional characterization of these genomic biomarkers in order to understand their relevance to tumor biology, therapy, and prognosis. As personalized therapy approaches are turning toward genomic alterations for answers, these biomarkers will become increasingly relevant to the practice of precision medicine. This review discusses the emerging role of genomic rearrangements in breast cancer, with a particular focus on fusion genes. In addition, it raises several key questions on the therapeutic value of such rearrangements and provides a framework to evaluate their significance as predictive and prognostic biomarkers. </p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70687061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Fiore, M. Brophy, Sara Turek, V. Kudesia, N. Ramnath, Colleen Shannon, Ryan E Ferguson, S. Pyarajan, Melissa Fiore, J. Hornberger, P. Lavori
The Department of Veterans Affairs (VA) recognized the need to balance patient-centered care with responsible creation of generalizable knowledge on the effectiveness of molecular medicine tools. Embracing the principles of the rapid learning healthcare system, a new clinical program called the Precision Oncology Program (POP) was created in New England. The POP integrates generalized knowledge about molecular medicine in cancer with a database of observations from previously treated veterans. The program assures access to modern genomic oncology practice in the veterans affairs (VA), removes disparities of access across the VA network of clinical centers, disseminates the products of learning that are generalizable to non-VA settings, and systematically presents opportunities for patients to participate in clinical trials of targeted therapeutics.
{"title":"The VA Point-of-Care Precision Oncology Program: Balancing Access with Rapid Learning in Molecular Cancer Medicine","authors":"L. Fiore, M. Brophy, Sara Turek, V. Kudesia, N. Ramnath, Colleen Shannon, Ryan E Ferguson, S. Pyarajan, Melissa Fiore, J. Hornberger, P. Lavori","doi":"10.4137/BIC.S37548","DOIUrl":"https://doi.org/10.4137/BIC.S37548","url":null,"abstract":"The Department of Veterans Affairs (VA) recognized the need to balance patient-centered care with responsible creation of generalizable knowledge on the effectiveness of molecular medicine tools. Embracing the principles of the rapid learning healthcare system, a new clinical program called the Precision Oncology Program (POP) was created in New England. The POP integrates generalized knowledge about molecular medicine in cancer with a database of observations from previously treated veterans. The program assures access to modern genomic oncology practice in the veterans affairs (VA), removes disparities of access across the VA network of clinical centers, disseminates the products of learning that are generalizable to non-VA settings, and systematically presents opportunities for patients to participate in clinical trials of targeted therapeutics.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S37548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686844","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}
M. C. Boonstra, S. D. de Geus, H. A. Prevoo, L. Hawinkels, C. J. van de Velde, P. Kuppen, A. Vahrmeijer, C. Sier
Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than $78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications.
{"title":"Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins","authors":"M. C. Boonstra, S. D. de Geus, H. A. Prevoo, L. Hawinkels, C. J. van de Velde, P. Kuppen, A. Vahrmeijer, C. Sier","doi":"10.4137/BIC.S38542","DOIUrl":"https://doi.org/10.4137/BIC.S38542","url":null,"abstract":"Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than $78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S38542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686698","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}
R. Juergens, K. Zukotynski, A. Singnurkar, D. Snider, J. Valliant, K. Gulenchyn
Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer.
{"title":"Imaging Biomarkers in Immunotherapy","authors":"R. Juergens, K. Zukotynski, A. Singnurkar, D. Snider, J. Valliant, K. Gulenchyn","doi":"10.4137/BIC.S31805","DOIUrl":"https://doi.org/10.4137/BIC.S31805","url":null,"abstract":"Immune-based therapies have been in use for decades but recent work with immune checkpoint inhibitors has now changed the landscape of cancer treatment as a whole. While these advances are encouraging, clinicians still do not have a consistent biomarker they can rely on that can accurately select patients or monitor response. Molecular imaging technology provides a noninvasive mechanism to evaluate tumors and may be an ideal candidate for these purposes. This review provides an overview of the mechanism of action of varied immunotherapies and the current strategies for monitoring patients with imaging. We then describe some of the key researches in the preclinical and clinical literature on the current uses of molecular imaging of the immune system and cancer.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S31805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686462","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}
E. Croteau, J. Renaud, M. Richard, T. Ruddy, F. Bénard, R. deKemp
The body's main fuel sources are fats, carbohydrates (glucose), proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET) imaging using the glucose analog 18F-fluorodeoxyglucose (18F-FDG) has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.
{"title":"PET Metabolic Biomarkers for Cancer","authors":"E. Croteau, J. Renaud, M. Richard, T. Ruddy, F. Bénard, R. deKemp","doi":"10.4137/BIC.S27483","DOIUrl":"https://doi.org/10.4137/BIC.S27483","url":null,"abstract":"The body's main fuel sources are fats, carbohydrates (glucose), proteins, and ketone bodies. It is well known that an important hallmark of cancer cells is the overconsumption of glucose. Positron emission tomography (PET) imaging using the glucose analog 18F-fluorodeoxyglucose (18F-FDG) has been a powerful cancer diagnostic tool for many decades. Apart from surgery, chemotherapy and radiotherapy represent the two main domains for cancer therapy, targeting tumor proliferation, cell division, and DNA replication–-all processes that require a large amount of energy. Currently, in vivo clinical imaging of metabolism is performed almost exclusively using PET radiotracers that assess oxygen consumption and mechanisms of energy substrate consumption. This paper reviews the utility of PET imaging biomarkers for the detection of cancer proliferation, vascularization, metabolism, treatment response, and follow-up after radiation therapy, chemotherapy, and chemotherapy-related side effects.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S27483","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686486","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}
Peripheral neutrophils are the predominant circulating leukocytes and an important component of innate and adaptive immune systems, which is a primary defense against cancer. MicroRNAs (miRNAs) can modulate neutrophil functions and play important roles in cancer pathogenesis by regulating neutrophil gene expression. To investigate if assessment of differential miRNA levels of peripheral neutrophils has the potential for diagnosis of non-small-cell lung cancer (NSCLC), we examine neutrophils of 15 patients with stage I NSCLC and 15 smokers without cancer. We identify five neutrophil miRNAs that have an abnormal level in patients with NSCLC versus smokers without cancer. In a training set of 82 patients with lung cancer and 73 controls, a set of two genes (miRs-26a-2-3p and 574-3p) are developed, producing 77.8% sensitivity and 78.1% specificity for NSCLC detection. Furthermore, in a testing set of 60 patients with lung cancer and 58 smokers, the performance of analyzing the two miRNAs for lung cancer detection is confirmed. This study for the first time shows that a neutrophil miRNA profile may serve as a new category of circulating biomarkers for the detection of NSCLC.
{"title":"Circulating Neutrophil MicroRNAs as Biomarkers for the Detection of Lung Cancer","authors":"Jie Ma, Ning Li, Yanli Lin, C. Gupta, F. Jiang","doi":"10.4137/BIC.S37333","DOIUrl":"https://doi.org/10.4137/BIC.S37333","url":null,"abstract":"Peripheral neutrophils are the predominant circulating leukocytes and an important component of innate and adaptive immune systems, which is a primary defense against cancer. MicroRNAs (miRNAs) can modulate neutrophil functions and play important roles in cancer pathogenesis by regulating neutrophil gene expression. To investigate if assessment of differential miRNA levels of peripheral neutrophils has the potential for diagnosis of non-small-cell lung cancer (NSCLC), we examine neutrophils of 15 patients with stage I NSCLC and 15 smokers without cancer. We identify five neutrophil miRNAs that have an abnormal level in patients with NSCLC versus smokers without cancer. In a training set of 82 patients with lung cancer and 73 controls, a set of two genes (miRs-26a-2-3p and 574-3p) are developed, producing 77.8% sensitivity and 78.1% specificity for NSCLC detection. Furthermore, in a testing set of 60 patients with lung cancer and 58 smokers, the performance of analyzing the two miRNAs for lung cancer detection is confirmed. This study for the first time shows that a neutrophil miRNA profile may serve as a new category of circulating biomarkers for the detection of NSCLC.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S37333","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686761","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}
M. Waseem, Syed Rizwan Hussain, Shashank Kumar, M. Serajuddin, F. Mahdi, S. Sonkar, C. Bansal, M. Ahmad
Background Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population. Materials and Methods Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. Results The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P = 0.007 and P = 0.005, respectively) between the control and the case subjects. Conclusion This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women.
{"title":"Association of MTHFR (C677T) Gene Polymorphism With Breast Cancer in North India","authors":"M. Waseem, Syed Rizwan Hussain, Shashank Kumar, M. Serajuddin, F. Mahdi, S. Sonkar, C. Bansal, M. Ahmad","doi":"10.4137/BIC.S40446","DOIUrl":"https://doi.org/10.4137/BIC.S40446","url":null,"abstract":"Background Breast cancer is one of the most common malignancies in women and is associated with a variety of risk factors. The functional single-nucleotide polymorphism (SNP) C677T in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) may lead to decreased enzyme activity and affect the chemosensitivity of tumor cells. This study was designed to investigate the association of MTHFR gene polymorphism (SNP) in the pathogenesis of breast cancer among the North Indian women population. Materials and Methods Genotyping was performed by polymerase chain reaction (PCR) using genomic DNA, extracted from the peripheral blood of subjects with (275 cases) or without (275 controls) breast cancer. Restriction fragment length polymorphism was used to study C677T polymorphism in the study groups. Results The distribution of MTHFR (C677T) genotype frequencies, ie, CC, TT, and CT, among the patients was 64.7%, 2.18%, and 33.09%, respectively. In the healthy control group, the CC, TT, and CT frequencies were 78.91%, 1.09%, and 20.1%, respectively. The frequencies of C and T alleles were 81.2% and 18.7%, respectively, in the patient subjects, while they were 88.9% and 11.09%, respectively, among the healthy control group. Frequencies of the CT genotype and the T allele were significantly different (P = 0.007 and P = 0.005, respectively) between the control and the case subjects. Conclusion This study shows an association of the CT genotype and the T allele of the MTHFR (C667T) gene with increased genetic risk for breast cancer among Indian women.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S40446","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686923","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}
Yuh Sugii, T. Kasai, Masashi Ikeda, Arun Vaidyanath, Kazuki Kumon, Akifumi Mizutani, Akimasa Seno, H. Tokutaka, Takayuki Kudoh, M. Seno
To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer.
{"title":"A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis","authors":"Yuh Sugii, T. Kasai, Masashi Ikeda, Arun Vaidyanath, Kazuki Kumon, Akifumi Mizutani, Akimasa Seno, H. Tokutaka, Takayuki Kudoh, M. Seno","doi":"10.4137/BIC.S33542","DOIUrl":"https://doi.org/10.4137/BIC.S33542","url":null,"abstract":"To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer.","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S33542","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70686893","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 : 2015-10-04eCollection Date: 2015-01-01DOI: 10.4137/BIC.S29329
Noah A Brown, Bryan L Betz
Ameloblastoma is an odontogenic neoplasm whose molecular pathogenesis has only recently been elucidated. The discovery of recurrent activating mutations in FGFR2, BRAF, and RAS in a large majority of ameloblastomas has implicated dysregulation of MAPK pathway signaling as a critical step in the pathogenesis of this tumor. Some degree of controversy exists regarding the role of mutations affecting the sonic hedgehog (SHH) pathway, specifically Smoothened (SMO), which have been postulated to serve as either an alternative pathogenetic mechanism or secondary mutations. Here, we review recent advances in our understanding of the molecular pathogenesis of ameloblastoma as well as the diagnostic, prognostic, and therapeutic implications of these discoveries.
{"title":"Ameloblastoma: A Review of Recent Molecular Pathogenetic Discoveries.","authors":"Noah A Brown, Bryan L Betz","doi":"10.4137/BIC.S29329","DOIUrl":"https://doi.org/10.4137/BIC.S29329","url":null,"abstract":"<p><p>Ameloblastoma is an odontogenic neoplasm whose molecular pathogenesis has only recently been elucidated. The discovery of recurrent activating mutations in FGFR2, BRAF, and RAS in a large majority of ameloblastomas has implicated dysregulation of MAPK pathway signaling as a critical step in the pathogenesis of this tumor. Some degree of controversy exists regarding the role of mutations affecting the sonic hedgehog (SHH) pathway, specifically Smoothened (SMO), which have been postulated to serve as either an alternative pathogenetic mechanism or secondary mutations. Here, we review recent advances in our understanding of the molecular pathogenesis of ameloblastoma as well as the diagnostic, prognostic, and therapeutic implications of these discoveries. </p>","PeriodicalId":72377,"journal":{"name":"Biomarkers in cancer","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/BIC.S29329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34101859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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