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.

Conventional and High-Speed Intravital Multiphoton Laser Scanning Microscopy of Microvasculature, Lymphatics, and Leukocyte- Endothelial Interactions

Abstract: The ability to determine various functions of genes in an intact host will be an important advance in the postgenomic era. Intravital imaging of gene regulation and the physiological effect of the gene products can play a powerful role in this pursuit. Intravital epifluorescence microscopy has provided powerful insight into gene expression, tissue pH, tissue pO2, angiogenesis, blood vessel permeability, leukocyte-endothelial (L-E) interaction, molecular diffusion, convection and binding, and barriers to the delivery of molecular and cellular medicine. Multiphoton laser scanning microscopy (MPLSM) has recently been applied in vivo to overcome three drawbacks associated with traditional epifluorescence microscopy: (i) limited depth of imaging due to scattering of excitation and emission light; (ii) projection of three-dimensional structures onto a two-dimensional plane; and (iii) phototoxicity. Here, we use MPLSM for the first time to obtain high-resolution images of deep tissue lymphatic vessels and show an increased accuracy in quantifying lymphatic size. We also demonstrate the use of MPLSM to perform accurate calculations of the volume density of angiogenic vessels and discuss how this technique may be used to assess the potential of antiangiogenic treatments. Finally, high-speed MPLSM, applied for the first time in vivo, is used to compare L-E interactions in normal tissue and a rhabdomyosarcoma tumor. Our work demonstrates the potential of MPLSM to noninvasively monitor physiology and pathophysiology both at the tissue and cellular level. Future applications will include the use of MPLSM in combination with fluorescent reporters to give novel insight into the regulation and function of genes.

Tretinoin peels versus glycolic acid peels in the treatment of Melasma in dark-skinned patients

Abstract: Background. Chemical peels have become a popular method for treating melasma. Although daily topical 0.05 and 0.1% tretinoin have been used for melasma, the therapy takes at least 4 to 6 months to produce clinically significant lightening. In a recent trial, 1% tretinoin peel has shown good clinical and histologic results after biweekly applications in 2.5 weeks only in the treatment of melasma. Objective. Because there is a paucity of studies evaluating the efficacy and safety of 1% tretinoin peel in the treatment of melasma in dark-skinned Asian population, we conducted a pilot study to evaluate the efficacy and side effects of this potentially new peeling agent versus a standard peeling agent, 70% glycolic acid, in the treatment of melasma in Indian women. Methods. Ten female patients of melasma, after written consent, were taken up for an open left–right comparison pilot study of 12 weeks. One percent tretinoin peel was applied on one-half of the face, whereas 70% glycolic acid was applied on the other at weekly intervals. The results were evaluated by a clinical investigator by using the modified Melasma Area and Severity Index and with photographs at baseline and 6 and 12 weeks. Results. A significant decrease in the modified Melasma Area and Severity Index from baseline to 6 weeks and then from 6 to 12 weeks was observed on both facial sides (p<0.001). Nevertheless, there was no statistically significant difference between the right and the left sides. Side effects were minimal and 1% tretinoin peel appeared to be well tolerated by the patients. Conclusions. It was concluded from the present trial that serial 1% tretinoin peel is a well tolerated and as effective a therapy for melasma in dark-skinned individuals as a standard and well-tried chemical peel, 70% glycolic acid, although larger trials over longer periods may be necessary to substantiate such findings.

Targeting Tumor Vasculature and Cancer Cells in Orthotopic Breast Tumor by Fractionated Photosensitizer Dosing Photodynamic Therapy

Abstract: Photodynamic therapy (PDT) is a locally administered therapy currently being investigated in various clinical and preclinical settings. Tumor-host interaction is an important determinant of tumor biology and response to treatments. Here we report for the first time the effects of PDT on an orthotopic, murine mammary tumor model. PDT utilizes two individually nontoxic components: (a) the localization in the target site of a photosensitizing drug; and (b) the activation of the photosensitizer by light of an appropriate wavelength and energy. PDT after a single dose of the photosensitizer MV6401 induced drug dose-dependent, long-term blood flow shut down and tumor growth delay in the MCaIV tumor, grown in the mammary fat pad. The plasma half-life of MV6401 was approximately 20 min, and the drug was confined to the vascular compartment shortly after administration. However, it accumulated in the interstitial compartment at 2-6 h after the administration. Two equal MV6401 doses injected 4 h and 15 min before the light administration allowed the photosensitizer to localize in both vascular and tumor cell compartments. The fractionated drug dose PDT more effectively induced tumor growth delay than the same total dose given as a single dose either at 4 h or at 15 min before light administration. The long-term effect of the fractionated drug PDT on blood flow was also more extensive than single-dose PDT. Fractionated photosensitizer dosing PDT offers a new strategy to optimize PDT therapy.

Cancer, angiogenesis and fractals.

Abstract: To the editor—The recent commentary by Coffey emphasizes the value of nonlinear dynamics and fractals as tools for studying aspects of biological pattern formation that are not readily accessible to strictly molecular methods. Our studies of the vascular architecture in tumors support Coffey’s points about the delicate interplay among gradients in diffusible cytokines, heterogeneity of cell pheno-

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.