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.

Effect of angiotensin II induced hypertension on tumor blood flow and interstitial fluid pressure.

Abstract: The effect of angiotensin II-induced hypertension on tumor interstitial fluid pressure (TIFP) and tumor blood flow (TBF) was investigated to examine blood flow and pressure regulation in solid tumors. TIFP measurements were made before and after administration of angiotensin II using the wick-in-needle method in s.c. tumor implants. Relative TBF was continuously monitored by laser doppler velocimetry. The effect of host strain on TIFP was evaluated in MCA-IV mammary carcinoma, transplanted in C3H and SCID mice, and showed no significant difference. The effects of tumor types were evaluated by comparing two murine tumors, MCA-IV mammary carcinoma and FSaII fibrosarcoma, and a human tumor xenograft, LS174T adenocarcinoma, transplanted in SCID mice. Baseline TIFP was elevated in all three tumor lines to significantly different pressures. AII-induced hypertension (approximately 150 mm Hg) had a variable but tumor line-specific effect on TIFP and TBF. The increase in TIFP was correlated with the baseline TIFP (r2 = 0.853) (increasing from 6.9 to 8.7 mm Hg, 10.5 to 15.8 mm Hg, and 21.7 to 29.4 mm Hg in FSaII, MCA-IV, and LS174T, respectively). These data suggest that in addition to blood flow redistribution due to the steal phenomenon, arterial control of TBF and TIFP exists within these solid tumors; however, the extent of control is tumor line dependent and less than that in normal tissues. Moreover, parallel increases in TIFP and TBF do not support the hypothesis that elevated TIFP causes vascular collapse and thus decreases TBF.

Chemotaxis of Ralstonia sp. SJ98 towards p-nitrophenol in soil.

Abstract: Bioremediation of contaminated sites has been accepted as an efficient and cheaper alternative to physicochemical means of remediation in several cases. Although chemotactic behaviour of many bacteria has been studied earlier and assays have been developed to study bacterial chemotaxis in semi-solid media, this phenomenon has never been demonstrated in soil. For bioremediation application it is important to know whether bacteria actually migrate through the heterogenous soil medium towards a gradient of a particular chemoattractant. In the present study we have successfully demonstrated bacterial chemotaxis of a Ralstonia sp. SJ98 in soil microcosm using qualitative and quantitative plate and tray assays. The migration of bacteria has been established using several methods such as plate counting, vital staining and flow cytometry and slot blot hybridization. A non-chemotactic p-nitrophenol utilizing strain Burkholderia cepacia RKJ200 has been used as negative control. Our work clearly substantiates the hypothesis that chemotactic bacteria may enhance in situ bioremediation of toxic pollutants from soils and sediments.

Development of a recombinase polymerase amplification assay for the diagnosis of banana bunchy top virus in different banana cultivars

Abstract: Recombinase polymerase amplification (RPA) is a rapid, isothermal amplification method with high specificity and sensitivity. In this study, an assay was developed and evaluated for the detection of banana bunchy top virus (BBTV) in infected banana plants. Three oligonucleotide primer pairs were designed from the replicase initiator protein gene sequences of BBTV to function both in RPA as well as in polymerase chain reaction (PCR). A total of 133 symptomatic as well as asymptomatic banana leaf samples from various cultivars were collected from the different regions of India and evaluated for BBTV infection using the RPA assay. BBTV was efficiently detected using crude leaf sap in RPA and the results obtained were consistent with PCR-based detection using purified DNA as template. To our knowledge, this is the first report of reliable diagnosis of BBTV infection by RPA using crude leaf sap as a template.

Biomarkers of Antiangiogenic Therapy: How Do We Move From Candidate Biomarkers to Valid Biomarkers?

Abstract: With the increasing use of antiangiogenic agents for the treatment of cancers, establishing biomarkers of response and resistance has become a priority for oncologists and pharmaceutical companies This urgency comes from the need to select the patients most likely to benefit from these high-cost therapies It also stems from the necessity of identifying new targets to prevent the invariable escape from these therapies, which target specifically or primarily the vascular endothelial growth factor (VEGF) pathway But the much needed biomarkers remain elusive One of the reasons is the still unclear mechanism(s) of action of these drugs Blocking VEGF can have antivascular and normalizing effects on the tumor vasculature, which may not necessarily translate into clinical responses as evaluated by criteria based on tumor size measurements such as the Response Evaluation Criteria in Solid Tumors Moreover, excessive antivascular effects (when using high doses) might induce a transient response, but could lead to severe toxicities, as well as to more aggressive tumors, as seen in mouse models Similarly, vascular normalization alone (with no cytotoxic treatment) might not be sufficient to shrink tumors or halt their growth, as demonstrated in mice Finally, some of the actions of antiangiogenic agents could be systemic For example, antiangiogenic agents could affect trafficking and function of hematopoietic progenitor cells and effector immune cells This could result in promotion or delay in tumor growth depending on the hematopoietic cell type involved Given this complexity, it is most likely that for each cancer and each agent, we might need a specific set of biomarkers for good prediction, and that these biomarkers will be mechanism specific Ideally, these biomarkers should be relatively easy to measure by imaging or in bodily fluids using standardized protocols For plasma or serum biomarkers, this could be achieved readily, given the multiple and reliable options to measure various proteins To date, only a few randomized trials have retrospectively integrated circulating biomarker evaluations, and unfortunately, none have yet identified a valid circulating biomarker candidate In non–small-cell lung cancer (NSCLC), the anti-VEGF antibody bevacizumab was shown to be effective when combined with chemotherapy in two randomized phase III trials In a phase II/III study of bevacizumab with chemotherapy in NSCLC patients, a high baseline circulating plasma VEGF level did not predict patient survival, despite correlating with the response evaluated by Response Evaluation Criteria in Solid Tumors Similarly, baseline soluble intracellular adhesion molecule 1 (sICAM1) was an independent prognostic factor of overall survival in patients treated with chemotherapy with chemotherapy alone or with bevacizumab No correlation was seen with other intuitive biomarker candidates, such as basic fibroblast growth factor or sE-Selectin Therefore, identifying biomarker candidates for prospective evaluation in randomized antiangiogenic trials remains an outstanding challenge in NSCLC and other cancers The comprehensive biomarker study by Hanrahan et al published in this issue of Journal of Clinical Oncology is a step in the right direction These investigators explored a set of 35 plasma biomarkers in NSCLC patients at four time-points after antiangiogenic therapy alone with the VEGF receptor 2 tyrosine kinase inhibitor (TKI) vandetanib, chemotherapy alone, or a combination of the two Vandetanib monotherapy transiently increased the levels of circulating interleukin 8 (IL-8; at day 8) and VEGF (at day 43), and decreased the levels of its soluble receptor VEGF receptor 2 (sVEGFR2; at day 43) In contrast, chemotherapy alone did not change circulating VEGF or IL-8, but transiently decreased sVEGFR2, IL–1 receptor antagonist, matrix metalloproteinase 9, and IL-12, and increased monocyte chemotactic protein-1 plasma levels at day 8 Surprisingly, vandetanib with chemotherapy did not significantly change circulating VEGF, sVEGFR2 or IL-8 levels, but transiently decreased IL-12 and matrix metalloproteinase 9, and increased monocyte chemotactic protein-1 in plasma at day 8 Hanrahan et al also explored possible correlations between the changes in these biomarkers after treatment and the outcome in individual patients They report that lower levels of sICAM1 at day 8 after treatment were significantly associated with poorer treatment outcome in the groups of patients who received vandetanib Although exploratory in nature and with a relatively modest sample size, Hanrahan et al report data from a randomized, threearm trial The study has important implications First, it confirms that pursuing mechanistic biomarkers (ie, circulating proteins with known proor antiangiogenic activity) shortly after treatment initiation might be a fruitful approach, as many of the biomarker changes occur rapidly after the onset of therapy Consistent with this, we have shown JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 28 NUMBER 2 JANUARY 1

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.