ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC).
MethodsThe related literatures about the therapeutic targets of PC were reviewed.
ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes.
ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
To study the mechanism of p16,Cyclin D1 and CDK4 and their relationship with pancreatic carcinoma, their expressions were examined by immunchistochemistry methods. Results: overpression of Cyclin D1 and CDK4 was revealed in these samples and p16 was undertectable. There was a negitive correlation between p16 and Cyclin D1 (Ｐ＜0.05), and a positive relation between Cyclin D1 and CDK4 (Ｐ＜0.05). The results indicate that abnormality of p16, Cyclin D1 and CDK4 may be involved in the molecular mechanism of pancreatic carcinoma, p16 lower expression and Cyclin D1 over expression may coexit in the development of pancreatic carcinoma.
ObjectiveTo optimize the culture method of human primary pancreatic ductal adenocarcinoma (PDAC) cells and cancer associated fibroblasts (CAFs) and investigate the effect of CAFs on the growth of primary PDAC cells in vitro and tumor formation in patient-derived xenograft (PDX) model.MethodsThe PDAC specimens were collected and primarily cultured. In order to observe the effect of CAFs on the growth of primary PDAC cells in vitro, the CAFs were co-cultured with primary PDAC cells consistently and the alone cultured primary PDAC cells served as the control. Then, these cells were injected into the shoulder blades of NOG mice in order to develop the PDX model.ResultsWhen the primary PDAC cells separated from the CAFs, the proliferation capacity of the primary PDAC decreased rapidly in the passage culture in vitro, and the most cells were terminated within 5 generations. By contrast, when the CAFs co-cultured with the primary PDAC cells, the proliferation capacity of primary PDAC cells were preserved, which could be stably transferred to at least 10 generations. The tumors of NOG mice were detected during 2–3 weeks after injecting the mixed cells (primary PDAC plus CAFs), while had no tumor formation after injecting CAFs alone. The rate of tumor was 92.9% (13 cases) in the primary PDAC plus CAFs group, which was higher than that of the CAFs alone group (64.3%, 9 cases), but there was no statistical difference because of the small sample size. The volume of tumor in the primary PDAC plus CAFs group at 2, 4, 6, and 8 weeks after the tumor cells injection was significantly larger than that in the CAFs alone group at the corresponding time point, the differences were statistically significant (P<0.01).ConclusionsThe CAFs could promote the growth of primary PDAC cells in vitro. This new method of co-culture CAFs with primary PDAC could improve the success rate of primary PDAC cells culture and improve the success rate of PDX model in NOG mice.
ObjectiveTo study the effects of angiogenesis inhibitor SU5416 on the microvessel density(MVD) of pancreatic cancer and to evaluate its influence on the growth and metastasis of pancreatic cancer. Methods A rat model of pancreatic cancer was established with dimethylbenzanthracine(DMBA). 60 rats with pancreatic cancer were randomly divided into 4 groups: saline group, 5-Fu group, SU5416 group, 5-Fu and SU5416 group. Thirteen weeks after injection, the microvascular density (MVD) of pancreatic cancer was detected.Results The microvascular densities (MVD) were (12.3±3.2)%, (11.4±3.8)%, (2.1±1.5)% and (1.8±1.1)% in the saline group, 5-Fu group, SU5416 group and 5-Fu+SU5416 group respectively. The MVDs in the SU5416 group and 5Fu+SU5416 group were statistically lower than those in the saline group and 5-Fu group(P＜0.05). There was no significant difference between the 5-Fu group and saline group(Pgt;0.05). ConclusionSU5416 can inhibit the microvascular growth in pancreatic cancer. And the inhibition can be enhanced when combined with chemotheraputic drugs.
Objective
To summary the recent progression of imaging methods which mainly applied on the early detection and qualitative diagnosis of pancreatic cancer.
Method
The newest related literatures between home and abroad were collected and reviewed.
Results
Ultrasonic, computed tomography, magnetic resonance imaging and positron emission tomography mostly be used on pancreatic cancer detection and diagnosis.
Conclusion
Each method gets its own advantage even computed tomography seems like dominated on the detection and diagnosis pancreatic cancer, moreover, magnetic resonance imaging has been improved rapidly in recent years which shows its enormous potential.
Objective To study the method of obtaining a large number of dendritic cells （DC）. To study the specific cytotoxicity T lymphocyte (CTL) effect against tumor cells initiated by DC pulsed with peptide of cancer cell. Methods Development of cells with cytologic features of DC in bone marrow cultures supplemented with granulocyte macrophage-colony stimulus factor (GM-CSF) and IL-4. Determining the DC phenotype and the specific structure by electronic microscopy. The CTL effect against pancreatic carcinoma leading by the DC pulsed with tumor cells lysate in vitro was observed. Results A large number of typical DC was proliferated by supplementing with GM-CSF and IL-4 cytokines. DC had specific cell appearance and structure, and highly expressed various cell surface molecules. TNF-α had the ability of stimulating DC mature, the mature DC had the enhancing abilities of antigen presenting and IL-12 self-secreting, as well as, expressed higher levels of CD54， MHC-Ⅱ and CD86 molecules than control group (P＜0.05). T lymphoid cell stimulated by DC without tumor antigen could not recognize and kill the target cells, only if DC pulsed with peptide of cancer cell can lead a b immune response to special tumor cells. The inhibiting ratio of CTL was significantly higher than that in other groups (P＜0.01). Conclusion Bone marrow DC has b ability of inducing special CTL against determined cancer cells after they are pulsed with tumor cell lysate. DC vaccine is probably a new immunotherapeutic method against tumor in the near future.
