The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
Toshiyoshi Fujiwara - One of the best experts on this subject based on the ideXlab platform.
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Telomerase-specific replication-selective virotherapy for Human Cancer.
Clinical Cancer Research, 2004Co-Authors: Takeshi Kawashima, Shunsuke Kagawa, Naoya Kobayashi, Yoshiko Shirakiya, Tatsuo Umeoka, Fuminori Teraishi, Masaki Taki, Satoru Kyo, Noriaki Tanaka, Toshiyoshi FujiwaraAbstract:Purpose: Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with Human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on Human Cancer cells. Experimental Design : We constructed an adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (TRAD)], in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in Human Cancer cells in vitro and in vivo . Results: TRAD induced selective E1A and E1B expression in Human Cancer cells, but not in normal cells such as Human fibroblasts. TRAD replicated efficiently and induced marked cell killing in a panel of Human Cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal Human fibroblasts lacking telomerase activity. In nu/nu mice carrying s.c. Human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, noninjected tumors was demonstrated. Conclusions: Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in Human Cancer cells, an outcome that has important implications for the treatment of Human Cancers.
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Telomerase-specific replication-selective virotherapy for Human Cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2004Co-Authors: Takeshi Kawashima, Shunsuke Kagawa, Naoya Kobayashi, Yoshiko Shirakiya, Tatsuo Umeoka, Fuminori Teraishi, Masaki Taki, Satoru Kyo, Noriaki Tanaka, Toshiyoshi FujiwaraAbstract:Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with Human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on Human Cancer cells. We constructed an adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (TRAD)], in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in Human Cancer cells in vitro and in vivo. TRAD induced selective E1A and E1B expression in Human Cancer cells, but not in normal cells such as Human fibroblasts. TRAD replicated efficiently and induced marked cell killing in a panel of Human Cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal Human fibroblasts lacking telomerase activity. In nu/nu mice carrying s.c. Human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, noninjected tumors was demonstrated. Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in Human Cancer cells, an outcome that has important implications for the treatment of Human Cancers.
Fuyuhiko Tamanoi - One of the best experts on this subject based on the ideXlab platform.
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Single amino-acid changes that confer constitutive activation of mTOR are discovered in Human Cancer
Oncogene, 2010Co-Authors: T. Sato, K. Coffman, Lixin Guo, A. Nakashima, Fuyuhiko TamanoiAbstract:Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates a variety of cellular functions such as growth, proliferation and autophagy. In a variety of Cancer cells, overactivation of mTOR has been reported. In addition, mTOR inhibitors, such as rapamycin and its derivatives, are being evaluated in clinical trials as antiCancer drugs. However, no active mutants of mTOR have been identified in Human Cancer. Here, we report that two different point mutations, S2215Y and R2505P, identified in Human Cancer genome database confer constitutive activation of mTOR signaling even under nutrient starvation conditions. S2215Y was identified in large intestine adenocarcinoma whereas R2505P was identified in renal cell carcinoma. mTOR complex 1 prepared from cells expressing the mutant mTOR after nutrient starvation still retains the activity to phosphorylate 4E-BP1 in vitro. The cells expressing the mTOR mutant show increased percentage of S-phase cells and exhibit resistance to cell size decrease by amino-acid starvation. The activated mutants are still sensitive to rapamycin. However, they show increased resistance to 1-butanol. Our study points to the idea that mTOR activating mutations can be identified in a wide range of Human Cancer.
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mTOR Signaling and Human Cancer
Structure Function and Regulation of Tor Complexes from Yeasts to Mammals Part B, 2010Co-Authors: Naphat Chantaravisoot, Fuyuhiko TamanoiAbstract:Publisher Summary This chapter discusses mammalian target of rapamycin (mTOR) signaling and Human Cancer. Dysregulation of the mTOR signaling is closely associated with Human Cancer. A frequent activation of the mTOR signaling is observed in Human Cancer, as detected by examining tissue samples for the level of phospho-S6K, phospho-S6, or phospho-mTOR. Some of these cases are because of the activation of upstream events such as the activation of Akt. Some genetic disorders associated with benign tumor formation occur when upstream regulators of mTOR are mutated. Activating mutations in mTOR can be identified in Human Cancer. This is possible by mining the Human Cancer genome database. As the Human Cancer genome database is rapidly expanding, it raises the possibility that a large number of activating mTOR mutations will be identified in Human Cancer. Small molecule inhibitors of mTOR have been developed and these inhibitors exhibit efficacy to block tumor growth.
Takeshi Kawashima - One of the best experts on this subject based on the ideXlab platform.
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Telomerase-specific replication-selective virotherapy for Human Cancer.
Clinical Cancer Research, 2004Co-Authors: Takeshi Kawashima, Shunsuke Kagawa, Naoya Kobayashi, Yoshiko Shirakiya, Tatsuo Umeoka, Fuminori Teraishi, Masaki Taki, Satoru Kyo, Noriaki Tanaka, Toshiyoshi FujiwaraAbstract:Purpose: Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with Human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on Human Cancer cells. Experimental Design : We constructed an adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (TRAD)], in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in Human Cancer cells in vitro and in vivo . Results: TRAD induced selective E1A and E1B expression in Human Cancer cells, but not in normal cells such as Human fibroblasts. TRAD replicated efficiently and induced marked cell killing in a panel of Human Cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal Human fibroblasts lacking telomerase activity. In nu/nu mice carrying s.c. Human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, noninjected tumors was demonstrated. Conclusions: Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in Human Cancer cells, an outcome that has important implications for the treatment of Human Cancers.
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Telomerase-specific replication-selective virotherapy for Human Cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research, 2004Co-Authors: Takeshi Kawashima, Shunsuke Kagawa, Naoya Kobayashi, Yoshiko Shirakiya, Tatsuo Umeoka, Fuminori Teraishi, Masaki Taki, Satoru Kyo, Noriaki Tanaka, Toshiyoshi FujiwaraAbstract:Replication-selective tumor-specific viruses present a novel approach for treating neoplastic disease. These vectors are designed to induce virus-mediated lysis of tumor cells after selective viral propagation within the tumor. Telomerase activation is considered to be a critical step in carcinogenesis, and its activity is closely correlated with Human telomerase reverse transcriptase (hTERT) expression. We investigated the antitumor effect of the hTERT-specific replication-competent adenovirus on Human Cancer cells. We constructed an adenovirus 5 vector [tumor- or telomerase-specific replication-competent adenovirus (TRAD)], in which the hTERT promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site, and we examined the selective replication and antitumor effect in Human Cancer cells in vitro and in vivo. TRAD induced selective E1A and E1B expression in Human Cancer cells, but not in normal cells such as Human fibroblasts. TRAD replicated efficiently and induced marked cell killing in a panel of Human Cancer cell lines, whereas replication as well as cytotoxicity was highly attenuated in normal Human fibroblasts lacking telomerase activity. In nu/nu mice carrying s.c. Human lung tumor xenografts, intratumoral injection of TRAD resulted in a significant inhibition of tumor growth. No evidence of TRAD was identified in tissues outside of the tumors, despite the presence of TRAD in the circulation. Moreover, TRAD replication in the distant, noninjected tumors was demonstrated. Our results suggest that the hTERT promoter confers competence for selective replication of TRAD in Human Cancer cells, an outcome that has important implications for the treatment of Human Cancers.
Laura Poliseno - One of the best experts on this subject based on the ideXlab platform.
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Pseudogenes: newly discovered players in Human Cancer.
Science Signaling, 2012Co-Authors: Laura PolisenoAbstract:Because they are generally noncoding and thus considered nonfunctional and unimportant, pseudogenes have long been neglected. Recent advances have established that the DNA of a pseudogene, the RNA transcribed from a pseudogene, or the protein translated from a pseudogene can have multiple, diverse functions and that these functions can affect not only their parental genes but also unrelated genes. Therefore, pseudogenes have emerged as a previously unappreciated class of sophisticated modulators of gene expression, with a multifaceted involvement in the pathogenesis of Human Cancer.
Lin Zhang - One of the best experts on this subject based on the ideXlab platform.
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miRNAs in Human Cancer.
Methods in molecular biology (Clifton N.J.), 2011Co-Authors: Xiaomin Zhong, George Coukos, Lin ZhangAbstract:MicroRNAs (miRNAs) are small (~18–25 nucleotides), endogenous, noncoding RNAs that regulate gene expression in a sequence-specific manner via the degradation of target mRNAs or the inhibition of protein translation. miRNAs are predicted to target up to one-third of all Human mRNAs. Each miRNA can target hundreds of transcripts and proteins directly or indirectly, and more than one miRNA can converge on a single target transcript; thus, the potential regulatory circuitry afforded by miRNAs is enormous. Increasing evidence is revealing that the expression of miRNAs is deregulated in Cancer. High-throughput miRNA quantification technologies provide powerful tools to study global miRNA profiles. It has become progressively more apparent that, although the number of miRNAs (~1,000) is much smaller than the number of protein-coding genes (~22,000), miRNA expression signatures more accurately reflect the developmental lineage and tissue origin of Human Cancers. Large-scale studies in Human Cancer have further demonstrated that miRNA expression signatures are associated not only with specific tumor subtypes but also with clinical outcomes.
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Mechanisms of microRNA deregulation in Human Cancer.
Cell cycle (Georgetown Tex.), 2008Co-Authors: Shan Deng, George A. Calin, Carlo M. Croce, George Coukos, Lin ZhangAbstract:microRNAs (miRNAs) are an abundant class of small non-coding RNAs that function as gene regulators. Although deregulation of miRNA expression is involved in the initiation and progression of tumorigenesis, the underlying mechanisms of miRNA deregulation in Human Cancer are still largely unknown. Increasing evidence indicates that transcriptional deregulations, epigenetic alterations, mutations, DNA copy number abnormalities and defects in the miRNA biogenesis machinery might contribute to miRNA deregulation in Human Cancer. A clearer understanding of the mechanisms involved in miRNA deregulation in Human Cancer will contribute greatly to the development of new miRNA-based strategies in Cancer diagnosis and treatment.
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Apoptosis in Human Cancer cells.
Current opinion in oncology, 2004Co-Authors: Lin ZhangAbstract:Purpose of review Apoptosis, or programmed cell death, is a vital physiologic process to eliminate damaged or unwanted cells. Defects in apoptosis promote tumor formation and make Cancer cells resistant to therapy. This review provides an overview of recent advances in the understanding of apoptosis in Human Cancer cells. Recent findings Recent studies revealed that the apoptotic machinery in Humans consists of a molecular network of a large number of proteins. These proteins regulate a cascade of events in signaling, commitment and execution stages of apoptosis through multiple parallel pathways. Delineation of the basic mechanisms of apoptosis has shed light on how apoptosis is deregulated in Human Cancer cells. Therapeutic strategies based on apoptosis have also been designed to selectively target tumor cells. Summary Understanding the basic mechanisms of apoptosis and determining how Cancer cells evade apoptosis will afford discoveries of new molecular targets and better Cancer therapies.
