Rakesh K. Jain

Bio: Rakesh K. Jain is an academic researcher from Harvard University. The author has contributed to research in topics: Angiogenesis & Vascular endothelial growth factor. The author has an hindex of 200, co-authored 1467 publications receiving 177727 citations. Previous affiliations of Rakesh K. Jain include Government Medical College, Thiruvananthapuram & University of Oslo.

Pharmacokinetics of methotrexate in solid tumors.

Abstract: The transport of methotrexate (MTX) into Walker 256 carcinoma (W256) and hepatoma 5123 (H5123) transplanted in rats was investigated after a pulse injection and continuous infusion of the drug. A mathematical model was developed which adequately described the distribution and transport of MTX in both solid tumors. In H5123 the uptake was limited by the amount of drug carried by plasma (flow-limited transport), but in W256 MTX uptake was limited by the rate at which the drug crossed the tissue barriers (tissue-limited transport). Relative uptake by the solid tumors was almost eightfold more efficient with low than with high doses. MTX concentration in tumor interstitial fluid equilibrated with that of plasma in about 50 hr using a micropore chamber with a diffusion coefficient of 0.5 microm/min as sampling device. MTX concentration was higher in resistant than in responsive tumors.

Effect of glucose and galactose on red blood cell membrane deformability

Abstract: The effect of glucose and galactose on the membrane deformability of red blood cells (RBC) suspended in isotonic solution was determined using micropipette aspiration technique. In this method, a negative pressure was applied to the RBC membrane via a micropipette and the resulting deformation was analyzed using a Kelvin model to yield a membrane elastic modulus E. When glucose concentration was increased from 0 to 0.3 M/dm3 in the extracellular media, E increased seven-fold (p less than 0.0001) with most increase occurring in the 0-0.05 M/dm3 range. The increase in E due to glucose was not completely reversible. The time constant of increase in E was about 14 minutes. Whereas, galactose had no significant effect on the membrane elasticity up to a concentration of 0.3 M/dm3. Increase in the RBC membrane rigidity in the presence of glucose may be due to binding of glucose to the membrane and intracellular proteins. The results obtained may be important for explanation of decrease in tumor blood flow during hyperglycemia.

Premetastatic lung "niche": is vascular endothelial growth factor receptor 1 activation required?

Abstract: Inflammatory pathways may mediate preparation of the "metastatic soil" in the lungs. Some of these pathways--activation and/or the recruitment of certain inflammatory cells--might depend on vascular endothelial growth factor receptor 1 (VEGFR1) activity. Thus, blocking the activity of VEGFR1 (or the interaction with its ligands) has emerged as a potential antimetastasis strategy to target not only angiogenesis and cancer cell survival and migration, but also the recruitment of tumor growth-promoting bone marrow-derived cells (BMDC). However, inhibition of VEGFR1 activity by blocking antibodies or by genetic deletion of the tyrosine kinase domain neither prevented nor changed the rate of spontaneous metastasis formation after surgical removal of primary tumors. Thus, development of VEGFR1-targeted agents should be pursued in selected tumors (e.g., by identifying cancers that depend on VEGFR1 signaling for survival) or in specific combination therapies. Preventing metastasis will likely require identification and blockade of additional or alternative proinflammatory pathways that mediate the priming of the metastatic soil and the growth of micrometastases.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer

Abstract: background Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy. methods Of 813 patients with previously untreated metastatic colorectal cancer, we randomly assigned 402 to receive irinotecan, bolus fluorouracil, and leucovorin (IFL) plus bevacizumab (5 mg per kilogram of body weight every two weeks) and 411 to receive IFL plus placebo. The primary end point was overall survival. Secondary end points were progression-free survival, the response rate, the duration of the response, safety, and the quality of life. results The median duration of survival was 20.3 months in the group given IFL plus bevacizumab, as compared with 15.6 months in the group given IFL plus placebo, corresponding to a hazard ratio for death of 0.66 (P<0.001). The median duration of progressionfree survival was 10.6 months in the group given IFL plus bevacizumab, as compared with 6.2 months in the group given IFL plus placebo (hazard ratio for disease progression, 0.54; P<0.001); the corresponding rates of response were 44.8 percent and 34.8 percent (P=0.004). The median duration of the response was 10.4 months in the group given IFL plus bevacizumab, as compared with 7.1 months in the group given IFL plus placebo (hazard ratio for progression, 0.62; P=0.001). Grade 3 hypertension was more common during treatment with IFL plus bevacizumab than with IFL plus placebo (11.0 percent vs. 2.3 percent) but was easily managed. conclusions The addition of bevacizumab to fluorouracil-based combination chemotherapy results in statistically significant and clinically meaningful improvement in survival among patients with metastatic colorectal cancer.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.