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.

Evaluation of potential ferromagnetic coupling units: the bis(TMM) [bis(trimethylenemethane)] approach to high-spin organic molecules

Abstract: Four new hydrocarbon tetraradicals, 1-4, each composed of two triplet trimethylenemethane (TMM) subunits linked by a potential ferromagnetic coupling unit (FC), were synthesized and characterized by variable-temperature electron paramagnetic resonance (EPR) spectroscopy. Simulation of the EPR powder spectra and a priori calculation of the zero-field splitting parameters aided spectral assignment. The Heisenberg Hamiltonian appears to quantitatively model relative spin-state energies in 1-4. In three cases ferromagnetic coupling was achieved, as evidenced by quintet ground states in the resulting tetraradicals. In one case, strong evidence for antiferromagnetic coupling was obtained.

Phase II Study of Neoadjuvant Bevacizumab and Radiotherapy for Resectable Soft Tissue Sarcomas

Abstract: Purpose Numerous preclinical studies have demonstrated that angiogenesis inhibitors can increase the efficacy of radiotherapy (RT). We sought to examine the safety and efficacy of bevacizumab (BV) and RT in soft tissue sarcomas and explore biomarkers to help determine the treatment response. Methods and Materials Patients with ≥5 cm, intermediate- or high-grade soft tissue sarcomas at significant risk of local recurrence received neoadjuvant BV alone followed by BV plus RT before surgical resection. Correlative science studies included analysis of the serial blood and tumor samples and serial perfusion computed tomography scans. Results The 20 patients had a median tumor size of 8.25 cm, with 13 extremity, 1 trunk, and 6 retroperitoneal/pelvis tumors. The neoadjuvant treatment was well tolerated, with only 4 patients having Grade 3 toxicities (hypertension, liver function test elevation). BV plus RT resulted in ≥80% pathologic necrosis in 9 (45%) of 20 tumors, more than double the historical rate seen with RT alone. Three patients had a complete pathologic response. The median microvessel density decreased 53% after BV alone ( p p p Conclusions The results from the present exploratory study indicated that BV increases the efficacy of RT against soft tissue sarcomas and might reduce the incidence of local recurrence. Thus, this regimen warrants additional investigation. Gene expression profiles and other tissue and circulating biomarkers showed promising correlations with treatment response.

Blood Flow and Venous pH of Tissue-isolated Walker 256 Carcinoma during Hyperglycemia

Abstract: Hemodynamic (blood flow rate, hematocrit, hemoglobin concentration, and blood viscosity) and pH responses to glucose (6 g/kg, i.p.) injections were studied in ten Walker 256 carcinoma tumors (0.5–1.8 g) grown in the “tissue-isolated” tumor preparation. A maximum blood flow reduction of 57 ± 19% (SD) occurred concurrently with an increase in tumor arterial-venous blood pH difference 20–30 min after glucose administration. Tumor venous blood pH dropped significantly by 0.15 ± 0.07 pH unit to 7.15 ± 0.01, while systemic blood pH dropped by 0.06 ± 0.02 pH unit to 7.38 ± 0.03. Arteriovenous blood pH differences were found to correlate with blood flow rates; however, both the small magnitude of the pH reduction and the immediate blood flow response argue against the hypothesis of increased resistance to flow caused by low pH-stiffened RBC membranes. Significant increases in systemic and tumor efferent whole blood viscosities at 2.25 and 4.5s-1 occurred after glucose administration, while hemoglobin concentrations of systemic and tumor efferent blood increased by as much as 11 ± 1 and 16 ± 2%, respectively. Venous to arterial hematocrit and hemoglobin ratios remained unchanged with glucose administration. These data suggest local tumor blood flow reductions are caused by increased viscous resistance to flow within the tortuous microvasculature of tumor, not as a result of low pH RBC rigidity, but rather from other mechanisms such as glucose-mediated RBC rigidity and systemic hemoconcentration.

Preferential localization of human adherent lymphokine-activated killer cells in tumor microcirculation.

Abstract: The efficacy of adoptive immunotherapy for solid tumors with lymphokine-activated effector cells presumably depends on the ability of these cells to localize adequately in tumor tissues. We present here the first quantitative study of the in vivo movement of fluorescently labeled adherent lymphokine-activated killer (A-LAK) cells. These cells were injected intra-arterially along with low-dose interleukin-2 into normal (mature granulation) tissue and an implant of VX2 carcinoma grown in the rabbit ear chamber. A small proportion of A-LAK cells accumulated preferentially in the tumor microcirculation in vivo because of an increased frequency of long-term adhesive interactions with the tumor vasculature. Stasis of blood flow in the tumor vasculature was observed 1 to 2 days after injection. Subsequent necrosis of the tumors was observed, along with diffuse infiltrates of lymphocytes, monocytes, and granulocytes in the interstitial space within the tumor. Development of necrosis despite low ratios of effector cells to target cells suggests that in addition to direct cytotoxicity, the response to adoptive immunotherapy is mediated via the tumor vasculature. This novel mechanism for adoptive immunotherapy must be taken into account in the development of improved strategies for cancer treatment.

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.