对于血管标记CD31的免疫组织化学染色法阐述了胰腺肿瘤细胞的结构。
在一项可能为胰腺癌治疗开辟新途径的研究中，据5月22日的《科学》杂志报道说，胰腺肿瘤内血管相对较少，因此化疗药物要在该肿瘤内扩散的途径不多。 这些发现有助于解释为什么胰腺癌是人类最致命的癌症之一。
目前对这种癌症的标准治疗是一种叫做gemcitabin（或译：吉西他滨）的药物，但这种药物只能给病人的生命延长几个星期。 Kenneth Olive及其同僚在一种通过遗传工程而制造出的小鼠胰腺肿瘤模型中发现，在这些小鼠的肿瘤中血管非常稀少，而他们在所分析的人类胰腺肿瘤的标本中也观察到了这种特征。
研究人员对这些小鼠施予了gemcitabine和另外一种化合物（它能够将肿瘤的结构性或“基质”组织减耗）的治疗，其治疗机制是通过抑制由所谓的Hedgehog信号通路所启动的分子信号级联放大反应。 文章的作者报告说，这一组合治疗导致了肿瘤内血管量的增加，从而较好地向肿瘤内输送了gemcitabine 并延迟了肿瘤的进展。（生物谷Bioon.com）
生物谷推荐原始出处：
Science May 21, 2009 DOI: 10.1126/science.1171362
Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer
Kenneth P. Olive 1, Michael A. Jacobetz 1, Christian J. Davidson 2, Aarthi Gopinathan 3, Dominick McIntyre 1, Davina Honess 1, Basetti Madhu 1, Mae A. Goldgraben 1, Meredith E. Caldwell 1, David Allard 1, Kristopher K. Frese 1, Gina DeNicola 3, Christine Feig 1, Chelsea Combs 2, Stephen P. Winter 1, Heather Ireland 1, Stefanie Reichelt 1, William J. Howat 1, Alex Chang 4, Mousumi Dhara 4, Lifu Wang 5, Felix Rückert 6, Robert Grützmann 6, Christian Pilarsky 6, Kamel Izeradjene 7, Sunil R. Hingorani 7, Pearl Huang 8, Susan E. Davies 9, William Plunkett 10, Merrill Egorin 11, Ralph H. Hruban 4, Nigel Whitebread 12, Karen McGovern 12, Julian Adams 12, Christine Iacobuzio-Donahue 4, John Griffiths 1, David A. Tuveson 1*
1 Cancer Research UK, Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE, UK.
2 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
3 Cancer Research UK, Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge, CB2 ORE, UK.; Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
4 Departments of Oncology and Pathology, The Sol Goldman Pancreatic Cancer Research Center, Sidney Cancer Center and Johns Hopkins University, Baltimore, MD 21287, USA.
5 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.; Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
6 Department of Surgery, University Hospital Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
7 Clinical Research and Public Health Sciences Division, Fred Hutchinson Cancer Research Center, and University of Washington, Seattle, WA 98109, USA.
8 Oncology Franchise, Merck and Co, North Wales, PA 19454, USA.
9 Department of Histopathology, Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, CB2 2QQ, UK.
10 Univ. of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
11 Division of Hematology and Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
12 Infinity Pharmaceuticals Inc, Cambridge, MA 01239, USA.
Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers, in part because it is insensitive to many chemotherapeutic drugs. Studying a mouse model of PDA that is refractory to the clinically used drug gemcitabine, we found that the tumors in this model were poorly perfused and poorly vascularized, properties that are shared with human PDA. We tested whether the delivery and efficacy of gemcitabine in the mice could be improved by coadministration of IPI-926, a drug that depletes tumor-associated stromal tissue by inhibiting the Hedgehog cellular signaling pathway. The combination therapy produced a transient increase in intratumoral vascular density and intratumoral concentration of gemcitabine, leading to transient stabilization of disease. Thus, inefficient drug delivery may be an important contributor to chemoresistance in pancreatic cancer.
