Pub Date : 2020-01-01DOI: 10.35248/2157-2518.20.11.351
T. B. Henriques, Di, ra Zipinotti dos Santos, Mariam F. Hakeem-Sanni, I. V. Silva, L. B. Rangel
The epithelial-mesenchymal transition (EMT) plays an important role in the progression of cancer, metastasis and drug resistance. Several factors are known to mediate EMT-driven drug resistance in cancer cells, among them the tumor microenvironment (TME). This phenomenon has gained attention in the field of cancer biology for its potential contribution to in the progression of carcinomas. It is also known that tumor cells experiencing EMT increases the secretion of specific factors in the TME, including cytokines, chemokines and growth factors, which can play an important role in tumor progression. The main event in EMT is the repression of E-cadherin driven by transcriptional factors including SNAIL, SLUG and ZEB1. Chemokines function as growth factors, activating, through its receptor CXCR2 and transcription factors such as SNAIL, thus inducing the EMT phenotype, contributing to the progression of the disease. Studies have investigated how the acquisition of mesenchymal characteristics could contribute to the development of a tumor microenvironment, and point to a possible link between the CXCR2 pathway and EMT. This review describes the mechanism by which CXCR2 is involved in EMT through SNAIL, contributing to progression of cancer and summarizes new advances in the research of EMTassociated CXCR2.
{"title":"The CXCR2-SNAIL Axis: Is this a Novel Anti-Tumor Therapeutical Target for Cancer Cells Undergoing Epithelial-Mesenchimal Transition Process?","authors":"T. B. Henriques, Di, ra Zipinotti dos Santos, Mariam F. Hakeem-Sanni, I. V. Silva, L. B. Rangel","doi":"10.35248/2157-2518.20.11.351","DOIUrl":"https://doi.org/10.35248/2157-2518.20.11.351","url":null,"abstract":"The epithelial-mesenchymal transition (EMT) plays an important role in the progression of cancer, metastasis and drug resistance. Several factors are known to mediate EMT-driven drug resistance in cancer cells, among them the tumor microenvironment (TME). This phenomenon has gained attention in the field of cancer biology for its potential contribution to in the progression of carcinomas. It is also known that tumor cells experiencing EMT increases the secretion of specific factors in the TME, including cytokines, chemokines and growth factors, which can play an important role in tumor progression. The main event in EMT is the repression of E-cadherin driven by transcriptional factors including SNAIL, SLUG and ZEB1. Chemokines function as growth factors, activating, through its receptor CXCR2 and transcription factors such as SNAIL, thus inducing the EMT phenotype, contributing to the progression of the disease. Studies have investigated how the acquisition of mesenchymal characteristics could contribute to the development of a tumor microenvironment, and point to a possible link between the CXCR2 pathway and EMT. This review describes the mechanism by which CXCR2 is involved in EMT through SNAIL, contributing to progression of cancer and summarizes new advances in the research of EMTassociated CXCR2.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"84 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89911113","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 : 2020-01-01DOI: 10.35248/2157-2518.20.11.345
Michelle Bilbao, D. Warshal, O. Ostrovsky
This review highlights the ability of epigenetic drugs to target ovarian cancer cells while preserving and modifying surrounding normal tissue to resist serving as a soil for tumor growth. Ovarian cancer exhibits aberrant epigenetics. Normal tissue has its own epigenetic expression which can be controlled with epigenetic therapy, reversing the ability of cells like those in the omentum to support ovarian cancer. Consequently, epigenetic therapy may be particularly actionable at the tumor microenvironment level in tissues like the omentum. We are calling on the scientific community to continue to study epigenetic therapy in relation to metastatic ovarian cancer.
{"title":"Epigenetic Therapy should be in the Tool Box for Recurrent Ovarian Cancer","authors":"Michelle Bilbao, D. Warshal, O. Ostrovsky","doi":"10.35248/2157-2518.20.11.345","DOIUrl":"https://doi.org/10.35248/2157-2518.20.11.345","url":null,"abstract":"This review highlights the ability of epigenetic drugs to target ovarian cancer cells while preserving and modifying surrounding normal tissue to resist serving as a soil for tumor growth. Ovarian cancer exhibits aberrant epigenetics. Normal tissue has its own epigenetic expression which can be controlled with epigenetic therapy, reversing the ability of cells like those in the omentum to support ovarian cancer. Consequently, epigenetic therapy may be particularly actionable at the tumor microenvironment level in tissues like the omentum. We are calling on the scientific community to continue to study epigenetic therapy in relation to metastatic ovarian cancer.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"5 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87557592","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 : 2020-01-01DOI: 10.35248/2157-2518.20.11.357
T. Iizuka
Progress in endoscopic technologies, such as magnifying endoscopy and narrow band imaging, has increased endoscopists’ ability to detect superficial Pharyngeal Squamous Cell Carcinoma (PSCC), leading to an increase in reported cases. At the same time, new Endoscopic Submucosal Dissection (ESD) techniques enabling lesions to be removed en bloc regardless of their size are now available to treat lesions not only in the stomach but also in the esophagus and colon.
{"title":"Endoscopic Submucosal Dissection for the Treatment of Superficial Pharyngeal Squamous Cell Carcinoma","authors":"T. Iizuka","doi":"10.35248/2157-2518.20.11.357","DOIUrl":"https://doi.org/10.35248/2157-2518.20.11.357","url":null,"abstract":"Progress in endoscopic technologies, such as magnifying endoscopy and narrow band imaging, has increased endoscopists’ ability to detect superficial Pharyngeal Squamous Cell Carcinoma (PSCC), leading to an increase in reported cases. At the same time, new Endoscopic Submucosal Dissection (ESD) techniques enabling lesions to be removed en bloc regardless of their size are now available to treat lesions not only in the stomach but also in the esophagus and colon.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"76 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85652917","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 : 2020-01-01DOI: 10.35248/21572518.20.11.346
M. A. Pereira
Flower or floral cells are multilobulated/petal-like nuclei, medium to large size cells usually present in cases of adult T-cell leukemia (ATL). However, since 2008, four cases of these cells, previously "restricted" to adult T leukemia, have been reported in B-cells lymphomas, many of them highly aggressive. Thus, this brief article aims to show how should be the assessment of these atypical cells in B lineage lymphomas and instigate more robust studies on the subject.
{"title":"Reflections about the Detection of Flower Cells in B-Cells Lymphomas","authors":"M. A. Pereira","doi":"10.35248/21572518.20.11.346","DOIUrl":"https://doi.org/10.35248/21572518.20.11.346","url":null,"abstract":"Flower or floral cells are multilobulated/petal-like nuclei, medium to large size cells usually present in cases of adult T-cell leukemia (ATL). However, since 2008, four cases of these cells, previously \"restricted\" to adult T leukemia, have been reported in B-cells lymphomas, many of them highly aggressive. Thus, this brief article aims to show how should be the assessment of these atypical cells in B lineage lymphomas and instigate more robust studies on the subject.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"6 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76432799","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 : 2020-01-01DOI: 10.35248/2157-2518.20.11.344
Keiji Kuwabara, H. Ichihara, Y. Matsumoto
The inhibitory activity of hybrid liposomes (HLs), composed of 90 mol% L-α-dimyristoyl-phosphatidylcholine (DMPC) and 10 mol% polyoxyethylene (25) dodecyl ether (C12(EO)25), was investigated in human glioma NP2 cells. HLs with a hydrodynamic diameter below 100 nm persisted for 4 weeks. The inhibitory effect of HLs on the proliferation of NP2 cells was evaluated. Induction of apoptosis in NP2 cells treated with HL was measured through a PI assay and the TUNEL method. HLs caused apoptosis in NP2 cells through the mitochondrial pathway. An increase of AIF protein expression was observed in HL-treated cells. Cellular membrane fluidity of NP2 cells was also increased as revealed by the fluorescence depolarization method. Enhanced HL accumulation in the membrane of NP2 cells was observed.
{"title":"Inhibitory Effect of Hybrid Liposomes on the Growth of NP2 Glioma Cells","authors":"Keiji Kuwabara, H. Ichihara, Y. Matsumoto","doi":"10.35248/2157-2518.20.11.344","DOIUrl":"https://doi.org/10.35248/2157-2518.20.11.344","url":null,"abstract":"The inhibitory activity of hybrid liposomes (HLs), composed of 90 mol% L-α-dimyristoyl-phosphatidylcholine (DMPC) and 10 mol% polyoxyethylene (25) dodecyl ether (C12(EO)25), was investigated in human glioma NP2 cells. HLs with a hydrodynamic diameter below 100 nm persisted for 4 weeks. The inhibitory effect of HLs on the proliferation of NP2 cells was evaluated. Induction of apoptosis in NP2 cells treated with HL was measured through a PI assay and the TUNEL method. HLs caused apoptosis in NP2 cells through the mitochondrial pathway. An increase of AIF protein expression was observed in HL-treated cells. Cellular membrane fluidity of NP2 cells was also increased as revealed by the fluorescence depolarization method. Enhanced HL accumulation in the membrane of NP2 cells was observed.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"15 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85221978","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 : 2019-01-01DOI: 10.4172/2157-2518.1000329
I. Soto-Cruz, Octavio Zerecero-Carreón, Francisco Trejo-Islas, J. L. Ventura-Gallegos, Alej, ro Zentella-Dehesa, B. Weiss-Steider, J. Mendoza-Rincón
NKG2D receptor engages ligands such as MICA and MICB, which activates cytotoxicity in NK cells leading to the destruction of tumour cells expressing these ligands. In normal human lymphoid cells the association of DAP10 with NKG2D is essential for signalling and important for its cell surface expression. However, the mechanism of the NKG2D/DAP10 complex upregulation is not completely understood in cancer. Also, the role of DAP10 in the activation of the PI3/AKT signaling pathway in cervical cancer has not been fully elucidated. In the present study, we investigated the role of MICA in the regulation of DAP10 in cervical cancer cells. First, we demonstrate the presence of the NKG2D/DAP10 complex in different tumour cell lines by flow cytometry. Also, we demonstrate that MICA upregulates the expression of DAP10 in cervical cancer cells in a time dependent manner by immunoblotting. We found that the AKT kinase is constitutively phosphorylated and MICA induced an increase in tyrosine phosphorylation. Furthermore, this activation is independent of the PI3K in cervical cancer cell lines as determined by immunoblotting and flow cytometry. Our results provide evidence supporting the notion that MICA functions as a stimulatory molecule to regulate the expression of the receptor adapter DAP10 in cervical cancer cells and thus may contribute to their proliferation and survival. The possibility that the NKG2D-DAP10 complex is widely expressed in different types of cancer may confer an advantage to transformed cells to survive in the tumour microenvironment and escape from the immune surveillance.
{"title":"MICA Regulates the Expression of DAP10 and Signals through an Independent PI3K Pathway in NKG2D Positive Cervical Cancer Cells","authors":"I. Soto-Cruz, Octavio Zerecero-Carreón, Francisco Trejo-Islas, J. L. Ventura-Gallegos, Alej, ro Zentella-Dehesa, B. Weiss-Steider, J. Mendoza-Rincón","doi":"10.4172/2157-2518.1000329","DOIUrl":"https://doi.org/10.4172/2157-2518.1000329","url":null,"abstract":"NKG2D receptor engages ligands such as MICA and MICB, which activates cytotoxicity in NK cells leading to the destruction of tumour cells expressing these ligands. In normal human lymphoid cells the association of DAP10 with NKG2D is essential for signalling and important for its cell surface expression. However, the mechanism of the NKG2D/DAP10 complex upregulation is not completely understood in cancer. Also, the role of DAP10 in the activation of the PI3/AKT signaling pathway in cervical cancer has not been fully elucidated. In the present study, we investigated the role of MICA in the regulation of DAP10 in cervical cancer cells. First, we demonstrate the presence of the NKG2D/DAP10 complex in different tumour cell lines by flow cytometry. Also, we demonstrate that MICA upregulates the expression of DAP10 in cervical cancer cells in a time dependent manner by immunoblotting. We found that the AKT kinase is constitutively phosphorylated and MICA induced an increase in tyrosine phosphorylation. Furthermore, this activation is independent of the PI3K in cervical cancer cell lines as determined by immunoblotting and flow cytometry. Our results provide evidence supporting the notion that MICA functions as a stimulatory molecule to regulate the expression of the receptor adapter DAP10 in cervical cancer cells and thus may contribute to their proliferation and survival. The possibility that the NKG2D-DAP10 complex is widely expressed in different types of cancer may confer an advantage to transformed cells to survive in the tumour microenvironment and escape from the immune surveillance.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80234307","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 : 2019-01-01DOI: 10.4172/2157-2518.1000330
C. D. Fava, L. Okuda, M. Vicente, M. Lara, E. Villalobos, E. Mori, T. P. C. Moura, Waleska Villas Boas Loiacono, Dirlene Marques Justino, E. M. Pituco
Bovine papillomavirus (BPV) infection is endemic in Brazilian herds. Papillomaviruses are oncogenic, with a trophic response in squamous epithelial and mucosal tissues, and are associated with asymptomatic infections, proliferative benign skin lesions (papillomas), and malignant epithelial lesions (carcinomas). The presence and expression of BPV in the blood of healthy and papillomatosis-affected cattle has been demonstrated. Experimental inoculation of Bovine papillomavirus (BPV) into calf meninges can result in meningiomas and papillomatosis, but it´s not known if its natural infection causes neoplasia and neurological syndrome in cattle. We assessed the frequency of BPV in 300 Central Nervous System (CNS) samples from cattle with neurological syndrome from several Brazilian regions obtained from surveillance of neurological syndrome. Samples were negative for rabies, Neospora caninum, BoHV-1 and BoHV-5, bovine leukemia virus, and catarrhal malignant fever (PCR). Samples were fixed in 10% buffered formalin and submitted to macroscopic examination. For histological analysis, slides were submitted to a staining protocol using hematoxylin and eosin. PCR for BPV detection was applied in CNS frozen samples using generic primers FAP59 and FAP64 (L1 gene). Thirteen (4.3%) samples were positive for BPV by PCR, with 11 of these showing no pathological changes in microscopy, and two exhibiting nonspecific non-purulent meningoencephalitis. No CNS samples showed neoplasia. Nine of the 13 BPV positive samples (69.2%) came from females and four (30.8%) from males. The 13 positive animals were age 5 to 168 months with seven over 36 months (53.8%). Five were dairy cattle, four crossbred, and three beef cattle. Only one of the 13 positive samples provided sufficient BPV DNA for sequencing, which emonstrated 99% identity to samples of BPV-1 obtained from cutaneous papillomas in cattle in Brazil. The small quantity of BPV DNA in the CNS and the low number of PCR-positive samples may be associated with low neurotropism, unspecific inflammation, or BPV-infected lymphocytes in CNS tissues or bloodstream. Natural BPV-1 infection was not associated with cerebral neoplasia or neurological syndrome.
{"title":"Bovine Papillomavirus Type 1 in Brains of Cattle with a Neurological Syndrome: Pathological and Molecular Study","authors":"C. D. Fava, L. Okuda, M. Vicente, M. Lara, E. Villalobos, E. Mori, T. P. C. Moura, Waleska Villas Boas Loiacono, Dirlene Marques Justino, E. M. Pituco","doi":"10.4172/2157-2518.1000330","DOIUrl":"https://doi.org/10.4172/2157-2518.1000330","url":null,"abstract":"Bovine papillomavirus (BPV) infection is endemic in Brazilian herds. Papillomaviruses are oncogenic, with a trophic response in squamous epithelial and mucosal tissues, and are associated with asymptomatic infections, proliferative benign skin lesions (papillomas), and malignant epithelial lesions (carcinomas). The presence and expression of BPV in the blood of healthy and papillomatosis-affected cattle has been demonstrated. Experimental inoculation of Bovine papillomavirus (BPV) into calf meninges can result in meningiomas and papillomatosis, but it´s not known if its natural infection causes neoplasia and neurological syndrome in cattle. We assessed the frequency of BPV in 300 Central Nervous System (CNS) samples from cattle with neurological syndrome from several Brazilian regions obtained from surveillance of neurological syndrome. Samples were negative for rabies, Neospora caninum, BoHV-1 and BoHV-5, bovine leukemia virus, and catarrhal malignant fever (PCR). Samples were fixed in 10% buffered formalin and submitted to macroscopic examination. For histological analysis, slides were submitted to a staining protocol using hematoxylin and eosin. PCR for BPV detection was applied in CNS frozen samples using generic primers FAP59 and FAP64 (L1 gene). Thirteen (4.3%) samples were positive for BPV by PCR, with 11 of these showing no pathological changes in microscopy, and two exhibiting nonspecific non-purulent meningoencephalitis. No CNS samples showed neoplasia. Nine of the 13 BPV positive samples (69.2%) came from females and four (30.8%) from males. The 13 positive animals were age 5 to 168 months with seven over 36 months (53.8%). Five were dairy cattle, four crossbred, and three beef cattle. Only one of the 13 positive samples provided sufficient BPV DNA for sequencing, which emonstrated 99% identity to samples of BPV-1 obtained from cutaneous papillomas in cattle in Brazil. The small quantity of BPV DNA in the CNS and the low number of PCR-positive samples may be associated with low neurotropism, unspecific inflammation, or BPV-infected lymphocytes in CNS tissues or bloodstream. Natural BPV-1 infection was not associated with cerebral neoplasia or neurological syndrome.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85749496","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 : 2019-01-01DOI: 10.4172/2157-2518.1000332
Jeetendar Paryani, Sameer Gupta, A. Chaturvedi, Vijay Kumar, N. Akhtar, P. Suryavanshi, S. Pawar
{"title":"Paraneoplastic Leukemoid Reaction in a Case of Carcinoma Gall Bladder: A Rare Scenario","authors":"Jeetendar Paryani, Sameer Gupta, A. Chaturvedi, Vijay Kumar, N. Akhtar, P. Suryavanshi, S. Pawar","doi":"10.4172/2157-2518.1000332","DOIUrl":"https://doi.org/10.4172/2157-2518.1000332","url":null,"abstract":"","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74921205","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 : 2019-01-01DOI: 10.4172/2157-2518.1000331
O. Tehrani, H. Abdulhaq, C. Delozier
Objective: Identifying the potential of germline CDKN2A I49T (also known as p.I49T: ATC>ACC) in familial cancer and its potential as a targetable driver mutation in carcinogenesis. Method: Germline mutational analysis was done using commercially available next generation sequencing (NGS) in kindred affected by cancers of lung, throat, gastrointestinal stromal tumor (GIST) and osteosarcoma using. Treatment of chemo-refractory osteosarcoma was done with CDK4/6 inhibitor palbociclib. Monitoring of response was done by serial computed tomography (CT) imaging. Results: Two affected members in the kindred, one with GIST and one with osteosarcoma were tested and proven positive for germline CDKN2A I49T alteration. The patient with osteosarcoma experienced progression of the disease despite multiple surgical resections and combination chemotherapy. Patient had a sustainable response to CDK4/6 inhibitor palbociclib, with disease controlled for more than a year. Conclusion: These findings suggested a familial cancer syndrome associated with germline CDKN2A I49T and showed its potential as a targetable driver mutation.
{"title":"Potential of Germline CDKN2A I49T as a Targetable Driver Mutation: Prolonged Control of Refractory Osteosarcoma with CDK4/6 Inhibitor in a Familial Cancer","authors":"O. Tehrani, H. Abdulhaq, C. Delozier","doi":"10.4172/2157-2518.1000331","DOIUrl":"https://doi.org/10.4172/2157-2518.1000331","url":null,"abstract":"Objective: Identifying the potential of germline CDKN2A I49T (also known as p.I49T: ATC>ACC) in familial cancer and its potential as a targetable driver mutation in carcinogenesis. Method: Germline mutational analysis was done using commercially available next generation sequencing (NGS) in kindred affected by cancers of lung, throat, gastrointestinal stromal tumor (GIST) and osteosarcoma using. Treatment of chemo-refractory osteosarcoma was done with CDK4/6 inhibitor palbociclib. Monitoring of response was done by serial computed tomography (CT) imaging. Results: Two affected members in the kindred, one with GIST and one with osteosarcoma were tested and proven positive for germline CDKN2A I49T alteration. The patient with osteosarcoma experienced progression of the disease despite multiple surgical resections and combination chemotherapy. Patient had a sustainable response to CDK4/6 inhibitor palbociclib, with disease controlled for more than a year. Conclusion: These findings suggested a familial cancer syndrome associated with germline CDKN2A I49T and showed its potential as a targetable driver mutation.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78374296","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 : 2019-01-01DOI: 10.4172/2157-2518.1000333
A. Kamyab, M. Hashemi, S. Iravani, R. Saeedi
Background: Esophageal cancer is the eighth most common cancer worldwide and the 6th cause of cancer related death. Genetic factors are also responsible in pathogenesis of esophageal cancer. This study aimed to investigate the association between methylenetetrahydrofolate reductase C677T polymorphism and esophageal cancer in Iranian population. Methods and Materials: A cross-sectional study was conducted among patients diagnosed with esophageal cancer in Imam Reza hospital between June 2007 and June 2014, Tehran, Iran. Genotyping was performed using restriction fragment length polymorphism (RFLP)-PCR method using Hinf-1 restriction endonuclease enzyme. Results: The frequencies of various genotypes of MTHFR gene were not statistically significant in cases and controls (P=0.348). There were no statistically significant difference in frequency of C and T alleles in patients with esophageal cancer and controls (P=0.084). Mean survival of patients with esophageal cancer was 31.25 ± 4.25 months in patients with CC genotype, 38.2 ± 4.11 months in CT genotype and 37.2 ± 6.44 months in patients with TT genotype (P=0.459). Allele frequency was not also associated with mean survival in patients and controls (P=0.168). Conclusion: Methylenetetrahydrofolate reductase C677T polymorphism was not associated with esophageal cancer and did not impact on survival in this subset of Iranian patients.
{"title":"The Methylenetetrahydrofolate Reductase C677T Polymorphism in Patients with Esophageal Cancer","authors":"A. Kamyab, M. Hashemi, S. Iravani, R. Saeedi","doi":"10.4172/2157-2518.1000333","DOIUrl":"https://doi.org/10.4172/2157-2518.1000333","url":null,"abstract":"Background: Esophageal cancer is the eighth most common cancer worldwide and the 6th cause of cancer related death. Genetic factors are also responsible in pathogenesis of esophageal cancer. This study aimed to investigate the association between methylenetetrahydrofolate reductase C677T polymorphism and esophageal cancer in Iranian population. Methods and Materials: A cross-sectional study was conducted among patients diagnosed with esophageal cancer in Imam Reza hospital between June 2007 and June 2014, Tehran, Iran. Genotyping was performed using restriction fragment length polymorphism (RFLP)-PCR method using Hinf-1 restriction endonuclease enzyme. Results: The frequencies of various genotypes of MTHFR gene were not statistically significant in cases and controls (P=0.348). There were no statistically significant difference in frequency of C and T alleles in patients with esophageal cancer and controls (P=0.084). Mean survival of patients with esophageal cancer was 31.25 ± 4.25 months in patients with CC genotype, 38.2 ± 4.11 months in CT genotype and 37.2 ± 6.44 months in patients with TT genotype (P=0.459). Allele frequency was not also associated with mean survival in patients and controls (P=0.168). Conclusion: Methylenetetrahydrofolate reductase C677T polymorphism was not associated with esophageal cancer and did not impact on survival in this subset of Iranian patients.","PeriodicalId":15209,"journal":{"name":"Journal of carcinogenesis & mutagenesis","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85622442","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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