Hamid Fiuji - Academia.edu (original) (raw)
Papers by Hamid Fiuji
Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2014
Ribonucleotide reductase subunit M2 (RRM2) is located in chromosome-2 p25-p24, converts ribonucle... more Ribonucleotide reductase subunit M2 (RRM2) is located in chromosome-2 p25-p24, converts ribonucleotides to deoxynucleotides which is required for DNA polymerization and repair. It has been shown that RMM2 plays a key role in DNA synthesis, cell growth, and drug resistance of cancer cells. There is accumulating evidence that alteration in the expression level of RRM2 can have a substantial impact on the biological characteristics of cancer cells, including tumor initiation and progression, suggesting its role as a prognostic factor and a possible therapeutic target for cancer therapy. Therefore, this review highlights several recent and clinically relevant aspects of the expression and function of RRM2 in human cancer.
Nucleosides, Nucleotides and Nucleic Acids, 2014
Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from... more Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from gemcitabine-based chemotherapy, thus the identification of novel prognostic factors is essential. In a high-throughput, microRNA (miRNA) array, miR-211 emerged as the best discriminating miRNA, with high expression associated with long survival. Here, we further explored the biological role of miRNA-211 in gemcitabine activity in the human PDAC cells (SUIT-2) subclones SUIT2-007 and SUIT2-028. Our results showed that miR-211 was expressed differentially in PDAC cells characterized by differential metastatic capability. In particular, S2-028 with lower metastatic ability had a higher expression of miR-211, compared to the S2-007 with higher metastatic capacity. Enforced expression of miR-211 via pre-miR-211 significantly reduced cell migration and invasion (e.g., 40% reduction of invasion of SUIT2 cells, compared to control; p<.05). Moreover, we demonstrated that induction of the miR-211 expression in the cells increased the sensitivity to gemcitabine and reduced the expression of its target ribonucleotide reductase subunit 2 (RRM2). In conclusion, miR-211 functional analyses suggested the role of RRM2 as a target of miR-211 in the modulation of gemcitabine sensitivity. Moreover, inhibition of cell migration and invasion might explain the less aggressive behavior of pancreatic cancer cells with higher expression levels of miR-211.
Current Drug Targets, 2014
Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with ... more Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properties and invasive-phenotype has gained substantial attention, suggesting its role as an intriguing-target for cancer-therapy. In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement. However several important questions remain to be answered on the molecular mechanisms underlying the antitumor effects of crizotinib, as well as on its possible role in the treatment of different tumor types, including uppergastrointestinal- cancers. The aim of this review is to give an overview on critical role of the c-Met/HGF pathway in cancer, and the preclinical/clinical studies on c-Met inhibitors. There are accumulating evidences on therapeutic potential of c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. However, further investigations are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic/ environmental alterations affecting c-Met and parallel pro-cancer pathways; mechanisms result in developing resistance to anti-c-Met agents; and selection of patients that might benefit from therapy. These studies will be essential to improve the selectivity/efficacy of future anticancer strategies of c-Met targeted-therapies in the treatment of upper gastrointestinal- cancers.
Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2014
Ribonucleotide reductase subunit M2 (RRM2) is located in chromosome-2 p25-p24, converts ribonucle... more Ribonucleotide reductase subunit M2 (RRM2) is located in chromosome-2 p25-p24, converts ribonucleotides to deoxynucleotides which is required for DNA polymerization and repair. It has been shown that RMM2 plays a key role in DNA synthesis, cell growth, and drug resistance of cancer cells. There is accumulating evidence that alteration in the expression level of RRM2 can have a substantial impact on the biological characteristics of cancer cells, including tumor initiation and progression, suggesting its role as a prognostic factor and a possible therapeutic target for cancer therapy. Therefore, this review highlights several recent and clinically relevant aspects of the expression and function of RRM2 in human cancer.
Nucleosides, Nucleotides and Nucleic Acids, 2014
Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from... more Only a subset of radically-resected pancreatic ductal adenocarcinoma (PDAC) patients benefit from gemcitabine-based chemotherapy, thus the identification of novel prognostic factors is essential. In a high-throughput, microRNA (miRNA) array, miR-211 emerged as the best discriminating miRNA, with high expression associated with long survival. Here, we further explored the biological role of miRNA-211 in gemcitabine activity in the human PDAC cells (SUIT-2) subclones SUIT2-007 and SUIT2-028. Our results showed that miR-211 was expressed differentially in PDAC cells characterized by differential metastatic capability. In particular, S2-028 with lower metastatic ability had a higher expression of miR-211, compared to the S2-007 with higher metastatic capacity. Enforced expression of miR-211 via pre-miR-211 significantly reduced cell migration and invasion (e.g., 40% reduction of invasion of SUIT2 cells, compared to control; p<.05). Moreover, we demonstrated that induction of the miR-211 expression in the cells increased the sensitivity to gemcitabine and reduced the expression of its target ribonucleotide reductase subunit 2 (RRM2). In conclusion, miR-211 functional analyses suggested the role of RRM2 as a target of miR-211 in the modulation of gemcitabine sensitivity. Moreover, inhibition of cell migration and invasion might explain the less aggressive behavior of pancreatic cancer cells with higher expression levels of miR-211.
Current Drug Targets, 2014
Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with ... more Aberrant activation of receptor-tyrosine kinase c-Met/HGF pathway is shown to be associated with cell proliferation, invasion, metastasis and poor-prognosis in several tumor types, including upper gastrointestinal-malignancies. The interaction of c-Met with multiple signalling-pathways involved in tumorigenic-properties and invasive-phenotype has gained substantial attention, suggesting its role as an intriguing-target for cancer-therapy. In recent years, there have been considerable efforts in the development of effective c-Met inhibitors with potential clinical-applications and one of them, crizotinib (dual c-Met/ALK inhibitor), has recently been approved for lung-cancers with ALKrearrangement. However several important questions remain to be answered on the molecular mechanisms underlying the antitumor effects of crizotinib, as well as on its possible role in the treatment of different tumor types, including uppergastrointestinal- cancers. The aim of this review is to give an overview on critical role of the c-Met/HGF pathway in cancer, and the preclinical/clinical studies on c-Met inhibitors. There are accumulating evidences on therapeutic potential of c-Met inhibitors for the treatment of other malignancies, such as gastric and pancreatic cancers. However, further investigations are needed to identify determinants of the activity of c-Met inhibitors, through the analysis of genetic/ environmental alterations affecting c-Met and parallel pro-cancer pathways; mechanisms result in developing resistance to anti-c-Met agents; and selection of patients that might benefit from therapy. These studies will be essential to improve the selectivity/efficacy of future anticancer strategies of c-Met targeted-therapies in the treatment of upper gastrointestinal- cancers.