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.

Increased CD8+ T-Cell Infiltration and Efficacy for Multikinase Inhibitors after PD-1 Blockade in Hepatocellular Carcinoma.

Abstract: Immune checkpoint blockade combined with anti-angiogenic therapy induces vascular normalization and anti-tumor immunity and is efficacious in hepatocellular carcinoma (HCC). But whether and how initial immunotherapy affects the efficacy of subsequent anti-angiogenic therapy is unknown. We evaluated a cohort of HCC patients (n = 25) who received the pan-VEGF receptor multi-kinase inhibitor sorafenib after initial therapy with an anti-programmed cell death protein (PD)-1 antibody and found superior outcomes in these patients (12% overall response rate to sorafenib and a median OS of 12.1 months). To understand mechanisms of this benefit, we examined the impact of an anti-PD-1 antibody on response to subsequent sorafenib treatment in orthotopic models of murine HCC. Prior anti-PD-1 antibody treatment amplified HCC response to sorafenib therapy and increased survival (n = 8-9 mice per group, HR = 0.28, 95% CI: 0.09-0.91; p = .04). Anti-PD-1 therapy showed angio-protective effects on HCC vessels to subsequent sorafenib treatment, which enhanced the benefit of this therapy sequence in a CD8+ T-cell-dependent manner. This priming approach using immunotherapy provides an immediately translatable strategy for effective HCC treatment while reducing drug exposure.

Temperature distributions and thermal response in humans. I. Simulations of various modes of whole-body hyperthermia in normal subjects.

Abstract: The necessity for a mathematical model of human heat transfer as an aid in determining the clinical effectiveness of whole‐body hyperthermia technique is brought out. A 45‐compartment lumped parameter model of the human thermal system is developed. The model accounts for changes in metabolism, blood flow, and other physiological mechanisms during hyperthermia. Simulations of the model’s projected temperature distributions and responses to six clinical whole‐body techniques are investigated.

Transparent Window Models and Intravital Microscopy

Abstract: The past 30 years have witnessed spectacular advances in our understanding of the molecular origins of cancer and other diseases. These advances have led to the identification of various genes associated with angiogenesis and oncogenesis, and to the development of a vast array of therapeutic agents. The grand challenges now are to relate the expression of these genes to their function in an intact organism, and to deliver these novel therapeutics to their targets in vivo (70). Currently, gene expression, physiological function, and drug delivery are usually measured with techniques that are either destructive or have poor spatial resolution (millimeter to centimeter). The former have limited ability to provide insight into the dynamics, and the latter preclude visualization at the cellular and subcellular levels (1–10 µm).

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.