Gemcitabine is one of the most used anti-neoplastic drugs with documented activity in almost all major localizations of cancer.In pancreatic cancer treatment,gemcitabine occupies a prominent place as a first line chem...Gemcitabine is one of the most used anti-neoplastic drugs with documented activity in almost all major localizations of cancer.In pancreatic cancer treatment,gemcitabine occupies a prominent place as a first line chemotherapy,partly because of the paucity of other efficacious chemotherapy options.In fact,only a minority of pancreatic cancer patients display a response or even stability of disease with the drug.There are currently no clinically applicable means of predicting which patient will derive a clinical benefit from gemcitabine although several proposed markers have been studied. These markers are proteins involved in drug up-take,activation and catabolism or proteins that define the ability of the cell to undergo apoptosis in response to the drug.Several of these markers are reviewed in this paper.We also briefly discuss the possible role of stem cells in drug resistance to gemcitabine.展开更多
The precise and coordinated production of myelin is essential for proper development and function of the nervous system. Diseases that disrupt myelin, including multiple sclerosis, cause significant functional disabil...The precise and coordinated production of myelin is essential for proper development and function of the nervous system. Diseases that disrupt myelin, including multiple sclerosis, cause significant functional disability. Current treatment aims to reduce the inflammatory component of the disease, thereby preventing damage resulting from demyelination. However, therapies are not yet available to improve natural repair processes after damage has already occurred. A thorough understanding of the signaling mechanisms that regulate myelin generation will improve our ability to enhance repair. In this review, we summarize the positive and negative regulators of myelination, focusing primarily on central nervous system myelination. Axon-derived signals, extracellular signals from both diffusible factors and the extracellular matrix, and intracellular signaling pathways within myelinating oligodendrocytes are discussed. Much is known about the positive regulators that drive myelination, while less is known about the negative regulators that shift active myelination to myelin maintenance at the appropriate time. Therefore, we also provide new data on potential negative regulators of CNS myelination.展开更多
Background The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipos...Background The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass. In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized by insulin resistance, and to further identify if variations in this gene have a relationship with type 2 diabetes, we sequenced the entire coding region and splice junctions of Akt2 and made a further case-control study to explore the association between sinclle-nucleotide polvmorphisms （SNPs） in this Qene and type 2 diabetes in the Chinese Han population.Methods We selected 23 probands with a type 2 diabetic pedigree whose family members＇ average onset age was within 25 to 45 years old. The body mass index of all the participants was lower than 28 kg/m2 and all of them were insulin-resistant （the fasting insulin level 〉100 pmol/L or 16 μlU/ml）. The entire coding region and splice junctions of Akt2 were directly sequenced in these 23 probands, SNPs with a frequency of minor allele over 20 percent were selected to be further studied in a case-control study, We chose 743 non-diabetic subjects as the control group and 742 type 2 diabetic patients as the case group, All these subjects were genotyped. A Snapshot Technology Platform （Applied Biosystems） was used for genotyping.Results The Akt2 genes from all 23 subjects were successfully sequenced. We did not identify any mutation in the type 2 diabetic pedigree. Two SNPs were identified, 13010323T〉C and 13007939G〉T. 13010323T〉C was in intron 9, which was the location of rs2304188 reported in Genbank. Its minor allele frequency was 13.04%. 13007939G〉T was in the 3＇-untranslated region （UTR） of exon 14, which was the location of rs2304186 reported in Genbank. Its minor allele frequency was 34.78%. The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported in Ge展开更多
文摘Gemcitabine is one of the most used anti-neoplastic drugs with documented activity in almost all major localizations of cancer.In pancreatic cancer treatment,gemcitabine occupies a prominent place as a first line chemotherapy,partly because of the paucity of other efficacious chemotherapy options.In fact,only a minority of pancreatic cancer patients display a response or even stability of disease with the drug.There are currently no clinically applicable means of predicting which patient will derive a clinical benefit from gemcitabine although several proposed markers have been studied. These markers are proteins involved in drug up-take,activation and catabolism or proteins that define the ability of the cell to undergo apoptosis in response to the drug.Several of these markers are reviewed in this paper.We also briefly discuss the possible role of stem cells in drug resistance to gemcitabine.
文摘The precise and coordinated production of myelin is essential for proper development and function of the nervous system. Diseases that disrupt myelin, including multiple sclerosis, cause significant functional disability. Current treatment aims to reduce the inflammatory component of the disease, thereby preventing damage resulting from demyelination. However, therapies are not yet available to improve natural repair processes after damage has already occurred. A thorough understanding of the signaling mechanisms that regulate myelin generation will improve our ability to enhance repair. In this review, we summarize the positive and negative regulators of myelination, focusing primarily on central nervous system myelination. Axon-derived signals, extracellular signals from both diffusible factors and the extracellular matrix, and intracellular signaling pathways within myelinating oligodendrocytes are discussed. Much is known about the positive regulators that drive myelination, while less is known about the negative regulators that shift active myelination to myelin maintenance at the appropriate time. Therefore, we also provide new data on potential negative regulators of CNS myelination.
文摘Background The Akt2 protein kinase is thought to be a key mediator of the insulin signal transduction process. Akt2 is suggested to play a role in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass. In order to determine whether the Akt2 gene plays a role in the pathogenesis of type 2 diabetes characterized by insulin resistance, and to further identify if variations in this gene have a relationship with type 2 diabetes, we sequenced the entire coding region and splice junctions of Akt2 and made a further case-control study to explore the association between sinclle-nucleotide polvmorphisms （SNPs） in this Qene and type 2 diabetes in the Chinese Han population.Methods We selected 23 probands with a type 2 diabetic pedigree whose family members＇ average onset age was within 25 to 45 years old. The body mass index of all the participants was lower than 28 kg/m2 and all of them were insulin-resistant （the fasting insulin level 〉100 pmol/L or 16 μlU/ml）. The entire coding region and splice junctions of Akt2 were directly sequenced in these 23 probands, SNPs with a frequency of minor allele over 20 percent were selected to be further studied in a case-control study, We chose 743 non-diabetic subjects as the control group and 742 type 2 diabetic patients as the case group, All these subjects were genotyped. A Snapshot Technology Platform （Applied Biosystems） was used for genotyping.Results The Akt2 genes from all 23 subjects were successfully sequenced. We did not identify any mutation in the type 2 diabetic pedigree. Two SNPs were identified, 13010323T〉C and 13007939G〉T. 13010323T〉C was in intron 9, which was the location of rs2304188 reported in Genbank. Its minor allele frequency was 13.04%. 13007939G〉T was in the 3＇-untranslated region （UTR） of exon 14, which was the location of rs2304186 reported in Genbank. Its minor allele frequency was 34.78%. The allele frequency of rs2304188 and rs2304186 were consistent with the frequency reported in Ge
