Objective:To study the mechanisms of pancreatic cancer treatment with Kanglaite combined Gemcitabine by investigating the relationship between the apoptosis and the expression of bcl-2, Bax and VEGF in pancreatic canc...Objective:To study the mechanisms of pancreatic cancer treatment with Kanglaite combined Gemcitabine by investigating the relationship between the apoptosis and the expression of bcl-2, Bax and VEGF in pancreatic cancer cells.Methods:Nude mouse subcutaneous transplantation tumor model of Human PC-3 pancreatic cancer was established; the expressions of bcl-2, Bax and VEGF of transplantation tumor cell were determined; the earlier apoptosis rate of pancreatic cancer cell and the gross tumor volume were determined. Results:Kanglaite combined Gemcitabine remarkably decreased the protein expression of bcl-2,raised the expression of Bax,increased the apoptosis rate of the pancreatic cancer and contract the gross tumor volume. Kanglaite greatly decreased the protein expression of VEGF of the tumor cell. Conclusion:Therapeutic efficacy of Kanglaite combined Gemcitabine is far better than separate use of the two medicines in the pancreatic cancer transplantation tumor treatment.展开更多
Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse panc...Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse pancreas,animal models can recapitulate human disease.Pancreas epithelium-specific endogenous Kras activation develops murine pancreatic intraepithelial neoplasia(mPanIN).Additional inactivation of p16,p53,or transforming growth factor-βsignaling,in the context of Kras activation,dramatically accelerates mPanIN progression to invasive pancreatic ductal adenocarcinoma(PDAC)with abundant stromal expansion and marked fibrosis(desmoplasia).The autochthonous cancer models retain tumor progression processes from pre-cancer to cancer as well as the intact tumor microenvironment,which is superior to xenograft models,although there are some limitations and differences from human PDAC.By fully studying GEM models,we can understand the mechanisms of PDAC formation and progression more precisely,which will lead us to a breakthrough in novel diagnostic and therapeutic methods as well as identification of the origin of PDAC.展开更多
Emerging evidence points to the existence of pan-creatic cancer stem cells (CSC) as the culprit in the initiation, maintenance, metastasis, and treatment resistance of pancreatic cancer. The existence of such a cell p...Emerging evidence points to the existence of pan-creatic cancer stem cells (CSC) as the culprit in the initiation, maintenance, metastasis, and treatment resistance of pancreatic cancer. The existence of such a cell population would have an important im-pact on the design of novel therapies against this devastating disease. However, no in vivo validation or rebuttal of the pancreatic CSC hypothesis exists. Major backlashes in the discussion on CSC are firstly, the confusion between the terms CSC and cell of origin of pancreatic ductal adenocarcinoma (PDAC), secondly the ambiguity of the cell of origin itself and thirdly, the fact that the CSC hypothesis is based on cell sorting and xenografting experiments; the latter of which often precludes solid conclusions because of the lack of a natural microenvironment and differences in drug delivery. Nonetheless, recent studies in other cancers partially support the CSC hypothesis by demonstrating a link between epithelial-to-mesenchymal transdifferentiation/transition (EMT) and CSC properties. Such a link is again open to dispute as EMT is a reversible process which is highly dependent on major oncogenic pathways in PDAC [e.g. K-Ras, transforming growth factor-β (TGF-β)] rather than on presumed cancer stem cell pathways. Hence, the available evidence does not robustly support the CSC concept in PDAC and a thorough validation of this hypothesis in well-defined genetically engineered mouse models of pancreatic cancer is required.展开更多
文摘Objective:To study the mechanisms of pancreatic cancer treatment with Kanglaite combined Gemcitabine by investigating the relationship between the apoptosis and the expression of bcl-2, Bax and VEGF in pancreatic cancer cells.Methods:Nude mouse subcutaneous transplantation tumor model of Human PC-3 pancreatic cancer was established; the expressions of bcl-2, Bax and VEGF of transplantation tumor cell were determined; the earlier apoptosis rate of pancreatic cancer cell and the gross tumor volume were determined. Results:Kanglaite combined Gemcitabine remarkably decreased the protein expression of bcl-2,raised the expression of Bax,increased the apoptosis rate of the pancreatic cancer and contract the gross tumor volume. Kanglaite greatly decreased the protein expression of VEGF of the tumor cell. Conclusion:Therapeutic efficacy of Kanglaite combined Gemcitabine is far better than separate use of the two medicines in the pancreatic cancer transplantation tumor treatment.
文摘Recently,there has been significant progress in the development of genetically-engineered mouse(GEM)models.By introducing genetic alterations and/or signaling alterations of human pancreatic cancer into the mouse pancreas,animal models can recapitulate human disease.Pancreas epithelium-specific endogenous Kras activation develops murine pancreatic intraepithelial neoplasia(mPanIN).Additional inactivation of p16,p53,or transforming growth factor-βsignaling,in the context of Kras activation,dramatically accelerates mPanIN progression to invasive pancreatic ductal adenocarcinoma(PDAC)with abundant stromal expansion and marked fibrosis(desmoplasia).The autochthonous cancer models retain tumor progression processes from pre-cancer to cancer as well as the intact tumor microenvironment,which is superior to xenograft models,although there are some limitations and differences from human PDAC.By fully studying GEM models,we can understand the mechanisms of PDAC formation and progression more precisely,which will lead us to a breakthrough in novel diagnostic and therapeutic methods as well as identification of the origin of PDAC.
文摘Emerging evidence points to the existence of pan-creatic cancer stem cells (CSC) as the culprit in the initiation, maintenance, metastasis, and treatment resistance of pancreatic cancer. The existence of such a cell population would have an important im-pact on the design of novel therapies against this devastating disease. However, no in vivo validation or rebuttal of the pancreatic CSC hypothesis exists. Major backlashes in the discussion on CSC are firstly, the confusion between the terms CSC and cell of origin of pancreatic ductal adenocarcinoma (PDAC), secondly the ambiguity of the cell of origin itself and thirdly, the fact that the CSC hypothesis is based on cell sorting and xenografting experiments; the latter of which often precludes solid conclusions because of the lack of a natural microenvironment and differences in drug delivery. Nonetheless, recent studies in other cancers partially support the CSC hypothesis by demonstrating a link between epithelial-to-mesenchymal transdifferentiation/transition (EMT) and CSC properties. Such a link is again open to dispute as EMT is a reversible process which is highly dependent on major oncogenic pathways in PDAC [e.g. K-Ras, transforming growth factor-β (TGF-β)] rather than on presumed cancer stem cell pathways. Hence, the available evidence does not robustly support the CSC concept in PDAC and a thorough validation of this hypothesis in well-defined genetically engineered mouse models of pancreatic cancer is required.
