The Experts below are selected from a list of 39705 Experts worldwide ranked by ideXlab platform
Takeo Iwama - One of the best experts on this subject based on the ideXlab platform.
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higher frequency of smad4 gene mutation in human colorectal cancer with Distant Metastasis
1999Co-Authors: Michiko Miyaki, Takeru Iijima, Motoko Konishi, Kimiyo Sakai, Aki Ishii, Masamichi Yasuno, Tsunekazu Hishima, Morio Koike, Nobuyuki Shitara, Takeo IwamaAbstract:Higher frequency of Smad4 gene mutation in human colorectal cancer with Distant Metastasis
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higher frequency of smad4 gene mutation in human colorectal cancer with Distant Metastasis
1999Co-Authors: Michiko Miyaki, Takeru Iijima, Motoko Konishi, Kimiyo Sakai, Aki Ishii, Masamichi Yasuno, Tsunekazu Hishima, Morio Koike, Nobuyuki Shitara, Takeo IwamaAbstract:We have previously detected an increased frequency of loss of heterozygosity (LOH) on chromosome 18q during progression of colorectal carcinomas. To clarify the target of 18qLOH, mutation of Smad4 and Smad2 genes was analysed in 176 colorectal tumors with different stages, including liver Metastasis, from 111 sporadic, 52 familial adenomatous polyposis (FAP) and nine hereditary nonpolyposis colorectal cancer (HNPCC) patients. Mutation of other Smad gene families in the TGF-beta signaling pathway was also examined. Twenty-one Smad4 mutations and one Smad2 mutation were detected, whereas mutation of Smad3, 6 and 7 genes was not detected. Smad4 mutations included seven frameshift, one inframe deletion, four nonsense and nine missense mutations, 95% of which resulted in alteration of Smad4 protein regions included in homo-oligomer and hetero-oligomer formation. Frequencies of tumors with Smad4 mutation were 0/40 (0%) in adenoma, 4/39 (10%) in intramucosal carcinoma, 3/44 (7%) in primary invasive carcinoma without Distant Metastasis, 6/17 (35%) in primary invasive carcinoma with Distant Metastasis, and 11/36 (31%) in Distant Metastasis (metastatic/non-metastatic: P=0.006 approximately 0.01). Loss of the other allele was observed in 19 of 20 (95%) invasive and metastasized carcinomas with Smad4 mutations. In four cases both primary and metastasized carcinomas in the same patients showed the same mutations. The present results suggest that Smad4 gene is one of true targets of 18qLOH, and that its inactivation is involved in advanced stages, such as Distant Metastasis, in human colorectal carcinogenesis.
Oriol Casanovas - One of the best experts on this subject based on the ideXlab platform.
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antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and Distant Metastasis
2009Co-Authors: Marta Paezribes, Elizabeth Allen, James Hudock, Takaaki Takeda, Hiroaki Okuyama, Francesc Vinals, Masahiro Inoue, Gabriele Bergers, Douglas Hanahan, Oriol CasanovasAbstract:Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and Distant Metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and Metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies.
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antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and Distant Metastasis
2009Co-Authors: Marta Paezribes, Elizabeth Allen, James Hudock, Takaaki Takeda, Hiroaki Okuyama, Francesc Vinals, Masahiro Inoue, Gabriele Bergers, Douglas Hanahan, Oriol CasanovasAbstract:Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and Distant Metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and Metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies.
Xiaozhong Chen - One of the best experts on this subject based on the ideXlab platform.
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a prognostic model combining cd4 cd8 ratio and n stage predicts the risk of Distant Metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy
2016Co-Authors: Changjuan Tao, Yuanyuan Chen, Feng Jiang, Xinglai Feng, Qifeng Jin, Ting Jin, Yongfeng Piao, Xiaozhong ChenAbstract:// Chang-Juan Tao 1, * , Yuan-Yuan Chen 1, * , Feng Jiang 1 , Xing-Lai Feng 1 , Qi-Feng Jin 1 , Ting Jin 1 , Yong-Feng Piao 1 , Xiao-Zhong Chen 1 1 Department of Radiation Oncology, Zhejiang Cancer Hospital, Key Laboratory of Radiation Oncology of Zhejiang Province, Hangzhou, Zhejiang Province, People’s Republic of China * These authors contributed equally to this work Correspondence to: Xiao-Zhong Chen, email: chenxz@zjcc.org.cn Keywords: nasopharyngeal carcinoma, lymphocyte subset, CD4/CD8 ratio, Distant Metastasis, survival Received: March 21, 2016 Accepted: April 27, 2016 Published: May 30, 2016 ABSTRACT This study aimed to evaluate the correlation between circulating lymphocyte subsets and clinical variables, and design an effective prognostic model for Distant Metastasis-free survival (DMFS) in NPC. In this study, subsets of circulating lymphocytes were determined in 719 non-metastatic NPC patients before treatment. Overall survival and DMFS was monitored. Significant prognostic factors were identified using univariate and multivariate analyses. Results showed that the percentage of CD19 + lymphocytes correlated negatively with TNM stage (r = –0.082, P = 0.028). Patients with higher CD4/CD8 ratios (≥ 1.77) showed better 5-year DMFS than patients with lower ratios (91.9% vs. 85.4%, P < 0.001). Multivariate analysis revealed that CD4/CD8 ratio (HR, 0.450; 95% confidence interval [CI], 0.266–0.760; P = 0.003) and N classification (HR, 2.294; 95% CI, 1.370–3.839; P = 0.002) were independently prognostic factors for DMFS. The prognostic N-R model was developed and divided patients into three groups: (1) low-risk (early N stage and CD4/CD8 ratio ≥ 1.77); (2) intermediate-risk (advanced N stage or CD4/CD8 ratio < 1.77) and (3) high-risk (advanced N stage and CD4/CD8 ratio < 1.77) of Distant Metastasis. In conclusion our prognostic model, based on clinical N stage and CD4/CD8 ratio, may predict the risk of Distant Metastasis, allowing individualized treatment for NPC.
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a prognostic model combining cd4 cd8 ratio and n stage predicts the risk of Distant Metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy
2016Co-Authors: Changjuan Tao, Yuanyuan Chen, Feng Jiang, Xinglai Feng, Qifeng Jin, Ting Jin, Yongfeng Piao, Xiaozhong ChenAbstract:6051Background: Distant Metastasis is a poor prognostic factor in nasopharyngeal carcinoma (NPC). We aimed to evaluate the correlation between circulating lymphocyte subsets and clinical variables,...
Michiko Miyaki - One of the best experts on this subject based on the ideXlab platform.
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higher frequency of smad4 gene mutation in human colorectal cancer with Distant Metastasis
1999Co-Authors: Michiko Miyaki, Takeru Iijima, Motoko Konishi, Kimiyo Sakai, Aki Ishii, Masamichi Yasuno, Tsunekazu Hishima, Morio Koike, Nobuyuki Shitara, Takeo IwamaAbstract:Higher frequency of Smad4 gene mutation in human colorectal cancer with Distant Metastasis
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higher frequency of smad4 gene mutation in human colorectal cancer with Distant Metastasis
1999Co-Authors: Michiko Miyaki, Takeru Iijima, Motoko Konishi, Kimiyo Sakai, Aki Ishii, Masamichi Yasuno, Tsunekazu Hishima, Morio Koike, Nobuyuki Shitara, Takeo IwamaAbstract:We have previously detected an increased frequency of loss of heterozygosity (LOH) on chromosome 18q during progression of colorectal carcinomas. To clarify the target of 18qLOH, mutation of Smad4 and Smad2 genes was analysed in 176 colorectal tumors with different stages, including liver Metastasis, from 111 sporadic, 52 familial adenomatous polyposis (FAP) and nine hereditary nonpolyposis colorectal cancer (HNPCC) patients. Mutation of other Smad gene families in the TGF-beta signaling pathway was also examined. Twenty-one Smad4 mutations and one Smad2 mutation were detected, whereas mutation of Smad3, 6 and 7 genes was not detected. Smad4 mutations included seven frameshift, one inframe deletion, four nonsense and nine missense mutations, 95% of which resulted in alteration of Smad4 protein regions included in homo-oligomer and hetero-oligomer formation. Frequencies of tumors with Smad4 mutation were 0/40 (0%) in adenoma, 4/39 (10%) in intramucosal carcinoma, 3/44 (7%) in primary invasive carcinoma without Distant Metastasis, 6/17 (35%) in primary invasive carcinoma with Distant Metastasis, and 11/36 (31%) in Distant Metastasis (metastatic/non-metastatic: P=0.006 approximately 0.01). Loss of the other allele was observed in 19 of 20 (95%) invasive and metastasized carcinomas with Smad4 mutations. In four cases both primary and metastasized carcinomas in the same patients showed the same mutations. The present results suggest that Smad4 gene is one of true targets of 18qLOH, and that its inactivation is involved in advanced stages, such as Distant Metastasis, in human colorectal carcinogenesis.
Marta Paezribes - One of the best experts on this subject based on the ideXlab platform.
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antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and Distant Metastasis
2009Co-Authors: Marta Paezribes, Elizabeth Allen, James Hudock, Takaaki Takeda, Hiroaki Okuyama, Francesc Vinals, Masahiro Inoue, Gabriele Bergers, Douglas Hanahan, Oriol CasanovasAbstract:Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and Distant Metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and Metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies.
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antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and Distant Metastasis
2009Co-Authors: Marta Paezribes, Elizabeth Allen, James Hudock, Takaaki Takeda, Hiroaki Okuyama, Francesc Vinals, Masahiro Inoue, Gabriele Bergers, Douglas Hanahan, Oriol CasanovasAbstract:Multiple angiogenesis inhibitors have been therapeutically validated in preclinical cancer models, and several in clinical trials. Here we report that angiogenesis inhibitors targeting the VEGF pathway demonstrate antitumor effects in mouse models of pancreatic neuroendocrine carcinoma and glioblastoma but concomitantly elicit tumor adaptation and progression to stages of greater malignancy, with heightened invasiveness and in some cases increased lymphatic and Distant Metastasis. Increased invasiveness is also seen by genetic ablation of the Vegf-A gene in both models, substantiating the results of the pharmacological inhibitors. The realization that potent angiogenesis inhibition can alter the natural history of tumors by increasing invasion and Metastasis warrants clinical investigation, as the prospect has important implications for the development of enduring antiangiogenic therapies.