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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.


Papers
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Journal ArticleDOI
TL;DR: In this paper, the plasma pharmacokinetics of sodium fluorescein, conjugated bovine serum albumin and a graded series of dextrans of 19,400 to 71,800 MW were monitored continuously using a noninvasive photometric technique in individual blood vessels of tissue grown in a rabbit ear chamber.
Abstract: Plasma pharmacokinetics of sodium fluorescein, fluorescein isothiocyanate conjugated bovine serum albumin, and a graded series of dextrans of 19,400 to 71,800 MW were monitored continuously using a noninvasive photometric technique in individual blood vessels of tissue grown in a rabbit ear chamber. The data obtained were fitted with a two-compartment open model to obtain an effective permeability and an effective clearance. Both parameters decreased with increasing molecular radius for dextrans. Values for albumin were considerably less than expected on the basis of molecular radius, presumably due to the configuration, charge, and binding characteristics of albumin.

13 citations

Patent
30 Dec 2015
TL;DR: In this paper, a device comprising a semiconductor layer including a plurality of compositional inhomogeneous regions is provided, where the difference between an average band gap for the plurality of inhogeneous regions and an average gap for a remaining portion of the semiconductor layers can be at least thermal energy.
Abstract: A device comprising a semiconductor layer including a plurality of compositional inhomogeneous regions is provided. The difference between an average band gap for the plurality of compositional inhomogeneous regions and an average band gap for a remaining portion of the semiconductor layer can be at least thermal energy. Additionally, a characteristic size of the plurality of compositional inhomogeneous regions can be smaller than an inverse of a dislocation density for the semiconductor layer.

13 citations

Journal ArticleDOI
TL;DR: This model successfully describes the available data during normothermia and whole-body hyperthermia and it is suggested that tumour temperature can be changed by variations in tumour blood flow; however, large modifications of blood flow are necessary to obtain appreciable changes.

13 citations

Journal ArticleDOI
TL;DR: The frequency of microstructural units formed by cancer cells, perivascular macrophages and endothelial cells are associated with the risk of metastatic recurrence and a key role has been proposed for the tumor microenvironment in cancer cell survival and progression to metastasis is proposed.
Abstract: Distant metastasis is the chief cause of cancer mortality. This is particularly true for breast cancer, for which the last decades have brought notable advances in locoregional (surgical, radiation) and systemic (hormonal, chemotherapies) treatment approaches. However, metastatic progression remains a poorly understood process. Therefore, it has been difficult to predict the presence of occult micrometastases in patients and the molecular and cellular mechanisms critical for their formation and progression. As a result, devising novel anti-metastatic therapies has been and remains a great challenge in oncology. Certain gene signatures (eg, MammaPrint, Oncotype DX) have shown statistically significant association with distant disease recurrence and are in clinical use as prognostic markers. These signatures appear to be driven predominately by genes reflecting the level of proliferation and hormone receptors in those tumors. But in addition to intrinsic properties of the cancer cells, a key role has been proposed for the tumor microenvironment in cancer cell survival and progression to metastasis. The contribution of the microenvironment may enhance an otherwise very inefficient process (1,2) and includes angiogenesis and the multi-faceted participation of activated fibroblasts and immune cells. Our understanding of this process is largely based on evidence from mouse models. However, the murine models have several limitations and may not fully reproduce the metastatic cascade in patients. Most metastasis studies have utilized experimental models in which cancer cells are injected as a bolus into the circulation upstream of the metastatic site. The limitation of such an approach is that it overlooks critical events taking place in the primary tumor and systemically prior to metastatic cell colonization. Models featuring spontaneous metastasis from a primary tumor are markedly better; however, these models generally do not metastasize to the same site(s) as the human disease they aim to model. Furthermore, such models are rare, and their metastatic cascade phenomena may represent only a small subset of possible human cases. Both implanted cancer cell models and genetically engineered mouse models—the current gold standard for understanding cancer biology—have these limitations. Finally, although most new agents are first tested in the metastatic setting, more recently there has been considerable interest in evaluating novel therapeutic agents in the neoadjuvant (preoperative) setting for some aggressive subtypes of breast cancer (eg, triple-negative and human epidermal growth factor receptor 2 [HER2]-positive). This approach offers the potential for accelerated Food and Drug Administration approval if the agent demonstrates a substantial increase in the rate of pathological complete response of the primary cancer (3). However, therapeutic effects on the primary cancer may not accurately reflect effects on micrometastatic disease in the setting of a different microenvironment. Preclinical studies often provide little insight in this regard, because most of them are done in primary tumors with no metastasis. This discordance may help explain the observation that drugs that increase pathological complete response rates have failed to decrease rates of metastatic disease. In a report in this issue of the Journal, Rohan et al. examined whether the frequency of microstructural units formed by cancer cells, perivascular macrophages and endothelial cells— termed Tumor MicroEnvironment for Metastasis or TMEM— are associated with the risk of metastatic recurrence (4). The authors identified the cancer cells that comigrate and interact with macrophages at intravasation sites based on the expression of Mena, which is an Ena/VASP protein family member and a

13 citations


Cited by
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Journal ArticleDOI
04 Mar 2011-Cell
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.

51,099 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组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�ly.
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。

18,940 citations

Journal ArticleDOI
TL;DR: Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, rheumatoid arthritis, and ageing.

12,240 citations

Journal ArticleDOI
TL;DR: 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.
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.

10,161 citations

01 Jun 2012
TL;DR: SPAdes as mentioned in this paper is a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler and on popular assemblers Velvet and SoapDeNovo (for multicell data).
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.

10,124 citations