The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis ...The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the γc in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-γc monoclonal antibodies (mAbs) injection, and those in control group were not given anti-γc mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografts over 30 days, and two of them accepted allografts without rejection until sacrifice on the 120 day. Animals only receiving DST rejected grafts within 5 days, and the mice receiving cardiac transplantation alone rejected grafts within 9 days. Our study showed that blockade of γc signaling combined with DST significantly prolonged allograft survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.展开更多
AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of ...AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.展开更多
Despite improvements in surgical techniques and adjuvant chemotherapy,the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%.Thi...Despite improvements in surgical techniques and adjuvant chemotherapy,the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%.This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes,proteins,microRNAs or epigenetic modifications.However,there are still major hurdles when translating investigational biomarkers into routine clinical practice.Furthermore,novel ways of secondary screening in high-risk individuals,such as artificial neural networks and modern imaging,will be discussed.Drug resistance is ubiquitous in pancreatic cancer.Several mechanisms of drug resistance have already been revealed,including human equilibrative nucleoside transporter-1 status,multidrug resistance proteins,aberrant signaling pathways,microRNAs,stromal influence,epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells.These factors must be considered when developing more customized types of intervention("personalized medicine").In the future,multifunctional nanoparticles that combine a specific targeting agent,an imaging probe,a cell-penetrating agent,a biocompatible polymer and an anticancer drug may become valuable for the management of patients with pancreatic cancer.展开更多
基金supported by grants from the National Natural Sciences Foundation of China (No. 30500468 and 30700768)
文摘The γc cytokines play an important role in proliferation and survival of T cells. Blocking the γc signals can cause the activated donor-reactive T cells losing the ability to proliferate, and getting into apoptosis pathway, which contributes to induction of the peripheral tolerance. In this study, we induced the transplant tolerance through blocking the γc in combination with donor-specific transfusion (DST) in the cardiac transplantation. Following DST, on the day 2, 4 and 6, C57BL/6 recipients received anti-γc monoclonal antibodies (mAbs) injection, and those in control group were not given anti-γc mAbs. On the day 7, Balb/c cardiac allografts were transplanted. All recipients in experimental group accepted cardiac allografts over 30 days, and two of them accepted allografts without rejection until sacrifice on the 120 day. Animals only receiving DST rejected grafts within 5 days, and the mice receiving cardiac transplantation alone rejected grafts within 9 days. Our study showed that blockade of γc signaling combined with DST significantly prolonged allograft survival, which was probably associated with inhibition of antigen-specific T-cell proliferation and induction of apoptosis.
基金Supported by Zhejiang provincial top key discipline in surgery
文摘AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.
文摘Despite improvements in surgical techniques and adjuvant chemotherapy,the overall mortality rates in pancreatic cancer have generally remained relatively unchanged and the 5-year survival rate is actually below 2%.This paper will address the importance of achieving an early diagnosis and identifying markers for prognosis and response to therapy such as genes,proteins,microRNAs or epigenetic modifications.However,there are still major hurdles when translating investigational biomarkers into routine clinical practice.Furthermore,novel ways of secondary screening in high-risk individuals,such as artificial neural networks and modern imaging,will be discussed.Drug resistance is ubiquitous in pancreatic cancer.Several mechanisms of drug resistance have already been revealed,including human equilibrative nucleoside transporter-1 status,multidrug resistance proteins,aberrant signaling pathways,microRNAs,stromal influence,epithelial-mesenchymal transition-type cells and recently the presence of cancer stem cells/cancer-initiating cells.These factors must be considered when developing more customized types of intervention("personalized medicine").In the future,multifunctional nanoparticles that combine a specific targeting agent,an imaging probe,a cell-penetrating agent,a biocompatible polymer and an anticancer drug may become valuable for the management of patients with pancreatic cancer.
基金This work was supported by the National Basic Research 973 Program of China （No. 2009CB522407） and the National Natural Science Foundation of China （No. 30500468 and No. 30700768）.
