Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma

The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.     

First Indications of Omsk Haemorrhagic Fever Virus beyond Russia

Omsk haemorrhagic fever virus (OHFV) is the agent leading to Omsk haemorrhagic fever (OHF), a viral disease currently only known in Western Siberia in Russia. The symptoms include fever, headache, nausea, muscle pain, cough and haemorrhages. The transmission cycle of OHFV is complex. Tick bites or contact with infected small mammals are the main source of infection. The Republic of Kazakhstan is adjacent to the endemic areas of OHFV in Russia and febrile diseases with haemorrhages occur throughout the country—often with unclear aetiology. In this study, we examined human cerebrospinal fluid samples of patients with suspected meningitis or meningoencephalitis with unknown origins for the presence of OHFV RNA. Further, reservoir hosts such as rodents and ticks from four Kazakhstan regions were screened for OHFV RNA to clarify if this virus could be the causative agent for many undiagnosed cases of febrile diseases in humans in Kazakhstan. Out of 130 cerebrospinal fluid samples, two patients (1.53%) originating from Almaty city were positive for OHFV RNA. Screening of tick samples revealed positive pools from different areas in the Akmola region. Of the caught rodents, 1.1% out of 621 were positive for OHFV at four trapping areas from the West Kazakhstan region. In this paper, we present a broad investigation of the spread of OHFV in Kazakhstan in human cerebrospinal fluid samples, rodents and ticks. Our study shows for the first time that OHFV can not only be found in the area of Western Siberia in Russia, but can also be detected up to 1.600 km away in the Almaty region in patients and natural foci.     

Epidemiological aspects of morbidity and mortality from cervical cancer in Kazakhstan

Epidemiological studies of cancer incidence in Kazakhstan have revealed an uneven distribution for cervical cancer. Incidence and mortality rates were calculated for different regions of the republic, including the two major cities of Almaty and Astana, in 1999-2008. Defined levels for cartograms for incidence were low (up to 12.8/100,000), medium (12.8 to 15.9) and high (above 15.9) and for mortality were up to 7.1, 7.1 to 10.8 and above 10.8, respectively. Basically high incidence rates were identified in the eastern, central and northern parts of the country and in Almaty. Such difference in cervical cancer data, and also variation in mortality/incidence ratios from a low of 0.4 in Almaty to a high of 0.71 in Zhambyl, point to variation in demographic and medical features which impact on risk and prognistic factors for cervical cancer in the country. Further research is necessary to highlight areas for emphasis in cancer control programs for this important cancer.     

犬用吡喹酮缓释药棒预防人、畜包虫病效果的流行病学评价

目的　评价大规模现场应用SRPⅢ型犬用吡喹酮缓释药棒预防人、畜包虫病的流行病学效果。方法　在新疆北部包虫病流行的农牧区有代表性的乡村 ,对 90 %以上的家犬皮下埋植吡喹酮缓释药棒 ,作为唯一的干预措施。以家犬细粒棘球绦虫感染率、小学新生血清抗体阳性率、7～ 16岁学生包虫病的患病率和 1岁龄绵羊包虫病患病率为指标 ,连续观察 4年 ,做出预防效果的评价。结果　家犬细粒棘球绦虫感染率实验前为 4 1 2 % ,埋植药棒后第二和第三年末均为零 ,第四年末为 2 98% ;小学新生血清抗体阳性率实验前为 4 1 2 3% ,以后逐年下降 ,至第四年末为 5 36 % ,同年对照区为 30 6 % ;7～ 16岁学生包虫病患病率实验前两个乡各为 1 6 9%和 1 89% ,三年后未检出新发患者 ;1岁龄绵羊包虫病患病率实验前为 4 4 77% ,第三年末为 10 6 6 % ,同期对照区为 4 6 38%。结论　SRPⅢ型犬用吡喹酮缓释药棒在家犬皮下埋植后的有效缓释时间可达 3年。流行病学监测结果证实以埋植这种药棒作为惟一的干预措施 ,在按规定的技术方案实施的条件下 ,可以完全控制人畜包虫病的传播。