對(duì)于血管標(biāo)記CD31的免疫組織化學(xué)染色法闡述了胰腺腫瘤細(xì)胞的結(jié)構(gòu),。
在一項(xiàng)可能為胰腺癌治療開辟新途徑的研究中,，據(jù)5月22日的《科學(xué)》雜志報(bào)道說,，胰腺腫瘤內(nèi)血管相對(duì)較少,，因此化療藥物要在該腫瘤內(nèi)擴(kuò)散的途徑不多,。 這些發(fā)現(xiàn)有助于解釋為什么胰腺癌是人類最致命的癌癥之一,。
目前對(duì)這種癌癥的標(biāo)準(zhǔn)治療是一種叫做gemcitabin（或譯：吉西他濱）的藥物,，但這種藥物只能給病人的生命延長(zhǎng)幾個(gè)星期,。 Kenneth Olive及其同僚在一種通過遺傳工程而制造出的小鼠胰腺腫瘤模型中發(fā)現(xiàn)，在這些小鼠的腫瘤中血管非常稀少,，而他們?cè)谒治龅娜祟愐认倌[瘤的標(biāo)本中也觀察到了這種特征,。
研究人員對(duì)這些小鼠施予了gemcitabine和另外一種化合物（它能夠?qū)⒛[瘤的結(jié)構(gòu)性或“基質(zhì)”組織減耗）的治療，其治療機(jī)制是通過抑制由所謂的Hedgehog信號(hào)通路所啟動(dòng)的分子信號(hào)級(jí)聯(lián)放大反應(yīng),。 文章的作者報(bào)告說,，這一組合治療導(dǎo)致了腫瘤內(nèi)血管量的增加，從而較好地向腫瘤內(nèi)輸送了gemcitabine 并延遲了腫瘤的進(jìn)展,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
