Mukherjee S.,Chittaranjan National Cancer Institute
Asian Pacific Journal of Cancer Prevention | Year: 2014
Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone SiHaR (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and SiHaR, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in SiHaR due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.
Hui S.P.,University of Calcutta |
Dutta A.,Chittaranjan National Cancer Institute |
Ghosh S.,University of Calcutta
Developmental Dynamics | Year: 2010
Zebrafish proves to be an excellent model system to study spinal cord regeneration because it can repair its disengaged axons and replace lost cells after injury, allowing the animal to make functional recovery. We have characterized injury response following crush injury, which is comparable to the mammalian mode of injury. Infiltrations of blood cells during early phases involve macrophages that are important in debris clearance and probably in suppression of inflammatory response. Unlike mammals where secondary injury mechanisms lead to apoptotic death of both neurons and glia, here we observe a beneficial role of apoptotic cell death. Injury-induced proliferation, presence of radial glia cells, and their role as progenitor all contribute to cellular replacement and successful neurogenesis after injury in adult zebrafish. Together with cell replacement phenomenon, there is creation of a permissive environment that includes the absence or clearance of myelin debris, presence of Schwann cells, and absence of inflammatory response. © 2010 Wiley-Liss, Inc.
News Article | August 22, 2016
Glimpses of blue sky are becoming a rare sight in Delhi, India’s capital, particularly in wintertime, when a thick white haze smothers the city. David Hagan, an MIT PhD candidate studying atmospheric chemistry and a Fellow in the MIT Tata Center for Technology and Design, says that the city’s air quality is now quantifiably among the worst in the world. “Beijing has bad episodes, but Delhi is worse because of the meteorology,” says Hagan. “It’s hot, it’s humid, and in the winter an inversion layer settles in. Delhi is a perfect reactor of anthropogenic and biogenic particulates.” Meanwhile, a lack of specific data has frustrated scientists and governments hoping to understand the complex environments of megacities in India and China, where air quality is inextricably linked to energy systems. Emissions in megacities such as Delhi can be traced to a wide variety of sources, including automobiles, fossil fuel-driven power plants, and open burning of biomass for warmth and cooking, each producing different kinds of particles. Hagan and his advisor, Associate Professor Jesse Kroll of the Department of Civil and Environmental Engineering, saw this complexity as motivation to design a compact, low-cost air quality sensor that they hope will be deployed in dense networks across cities like Delhi, logging accurate, real-time data on the chemistry of the air. “Air quality monitoring is often discussed as an either-or situation,” says Kroll. “One can have expensive, regulatory-grade monitors or else distributed, low-cost sensors. But in reality it’s a continuum, with a tradeoff between cost, size, and power on one hand, and accuracy, precision, and sensitivity on the other. We’re somewhere in the middle of the continuum, with enough accuracy and precision to provide quantitative measurements.” “If we can generate a better data set,” Hagan adds, “it could lead to a sustainable public good.” The production of particulate matter less than 2.5 microns across, known as PM2.5, is a particular area of concern for epidemiologists. These fine particulates are largely generated by fuel combustion, and when they’re inhaled, they can have dire health effects, including asthma, lung disease, and heart attack. In fact, a recent study by the Chittaranjan National Cancer Institute estimated that half of Delhi’s schoolchildren have suffered irreversible lung damage. “In Manhattan the highest level of PM2.5 you’ll see is about 12 micrograms per cubic meter,” Hagan says. “Delhi can be anywhere from 150 to 1,000 micrograms per cubic meter, so the levels are dozens of times higher. However, there is no safe level of PM2.5. We all have a long way to go to make it better.” Kroll and Hagan already have several prototypes on the ground in India, reporting data to a remote server every 30 seconds. Two units are located at Nehru Place in south Delhi, and four are near Connaught Place in central Delhi, co-located with a regulatory-grade sensor for calibration. Two are in the city of Pune, near Mumbai, and one is mobile — Hagan can frequently be seen taking it on rickshaw rides around Delhi. A regulatory-grade sensor, of which there are roughly 20 in Delhi, costs between $50,000 and $100,000. Kroll and Hagan’s sensor costs “on the order of $1,000” per unit, says Hagan, and offers comparable performance, measuring six types of gases (O , NO, NO , SO , CO, and volatile organic compounds) and 16 size groups, or “bins,” of particles, ranging from coarse to fine. The lower cost makes it feasible for these sensors to be deployed in large volumes, creating an opportunity to map pollutant distribution at greater levels of detail. There are several low-cost and do-it-yourself devices on the market already, but the sensitivity of Hagan’s design, including its ability to measure particles as small as 380 nanometers across, sets it apart. “Most low-cost sensors only measure one size bin of particulate — coarse,” he says. “I’m very interested in both the atmospheric chemistry and the user experience, which is why my sensor is different. There hasn’t been a low-cost sensor made with a good mix of quality components and a well-engineered interface.” Kroll adds: “We’re interested in measurements with reasonably good spatial coverage, but that are also directly comparable to those from regulatory-grade monitors and that provide insight into the chemical changes that pollutants undergo in the atmosphere.” Part of the learning process for Kroll and Hagan has been understanding how the sensors will respond to a diverse set of environmental circumstances. They, along with other MIT researchers, have subjected different generations of sensors to the seasonal extremes of the Boston area, where two small grids are up and running — one on the MIT campus and the other in Dorchester — and to the highly variable conditions around the Hawaiian volcano Kilauea. Now, with a refined prototype, they’re beginning to see how the intense heat and dirty air of Delhi will affect the sensor’s performance. One of the Nehru Place sensors became so clogged with black grime that air could no longer pass through, and, ironically, it began to record low pollutant numbers. Transparency is vital to the success of the project, Hagan says. “It’s important to be honest about what the sensor is measuring and what its limitations are.” He adds, “The next generation will be much better,” citing a robust filtration system to prevent clogging and a smaller, more energy-efficient design. Hardware is just one part of the equation. Hagan also wrote the algorithms that interpret the sensors’ raw data. He envisions a number of different possible applications for the data in both the public and private sectors. Governments and academic researchers could use it to identify emissions sources and create mitigation strategies, while factories and office buildings could integrate the sensors into their HVAC systems for indoor air quality monitoring. Entrepreneurs might purchase access and use the data in commercial products, such as in-home monitoring systems or smartphone apps that show people real-time information on the air they’re breathing. For millions of Delhi residents who live with the effects of air pollution every day, solutions can’t come soon enough. This research was supported by the MIT Tata Center for Technology and Design. More details can be found at tatacenter.mit.edu/portfolio/air-pollution-sensors. This article appears in the Spring 2016 issue of Energy Futures, the magazine of the MIT Energy Initiative.
Shome S.,Chittaranjan National Cancer Institute |
Dasgupta P.S.,Chittaranjan National Cancer Institute |
Basu S.,Ohio State University
PLoS ONE | Year: 2012
Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by sympathetic nerves which secrete dopamine (DA) and we have recently shown that concentration of DA present in synaptic cleft can significantly inhibit wound tissue neovascularization. As recent reports indicate that MSCs by mobilizing into wound bed play an important role in promoting wound angiogenesis, we therefore investigated the effect of DA on the migration of MSCs in wound tissues. DA acted through its D 2 receptors present in the MSCs to inhibit their mobilization to the wound beds by suppressing Akt phosphorylation and actin polymerization. In contrast, this inhibitory effect of DA was reversed after treatment with specific DA D 2 receptor antagonist. Increased mobilization of MSCs was demonstrated in the wound site following blockade of DA D 2 receptor mediated actions, and this in turn was associated with significantly more angiogenesis in wound tissues. This study is of translational value and indicates use of DA D 2 receptor antagonists to stimulate mobilization of these stem cells for faster regeneration of damaged tissues. © 2012 Shome et al.
Sarkars R.,Chittaranjan National Cancer Institute |
Mukherjee S.,Chittaranjan National Cancer Institute |
Roy M.,Chittaranjan National Cancer Institute
Nutrition and Cancer | Year: 2013
Heat shock proteins (HSPs) are chaperones for several client proteins involved in transcriptional regulation, signal transduction, and cell cycle control. HSPs (27, 70, and 90) are abundantly expressed in a wide range of cancers and are transcriptionally regulated by heat shock factor (HSF1). Most of the synthetic HSP inhibitors exhibit toxicity, therefore, searching for inhibitors with limited or no toxicity will be of help. The objective of the present study was to determine the effect of natural isothiocyanate (phenethyl isothiocyanate; PEITC) on different HSPs (27, 70, and 90) and HSF1 in 2 breast cancer cell lines, namely breast adenocarcinoma MCF-7 (with wild type p53) and highly metastatic breast cancer cell MDA-MB-231 (with mutated p53). PEITC significantly inhibited the expression of HSPs (particularly HSP 90) and HSF1. Molecular consequences due to HSP inhibition were downregulation of cell-cycle regulatory proteins like Cyclin B1, CDK1, Cdc25C, PLK-1, and upregulation of p21 irrespective of p53 status. These modulations were accompanied by cell-cycle arrest at G2/M phase and apoptosis by activation of caspases 3 and 9. PEITC therefore may be regarded as a potent HSP inhibitor and an antitumor agent in the treatment of breast cancer. © 2013 Copyright Taylor and Francis Group, LLC.
Ganguly K.K.,Chittaranjan National Cancer Institute |
Pal S.,Chittaranjan National Cancer Institute |
Moulik S.,Chittaranjan National Cancer Institute |
Chatterjee A.,Chittaranjan National Cancer Institute
Cell Adhesion and Migration | Year: 2013
Metastasis is a combination of biological events that makes the difference between cancer and other diseases. Metastasis requires flow of erroneous but precisely coordinated basic cellular activities like cell migration-invasion, cell survival-apoptosis, cell proliferation, etc. All of these processes require efficient regulation of cell attachment and detachment, which recruit integrin receptors in this flow of events. World literatures are showing several aspects of interrelation of integrins and metastasis. Integrin molecules are being used as prime target to battle metastasis. In this review we are collating the observations showing importance of integrin biology in regulation of metastasis and the strategies where integrin receptors are being used as targets to regulate metastasis. © 2013 Landes Bioscience.
Dutta S.,Chittaranjan National Cancer Institute
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists | Year: 2012
Despite the high incidence of cervical cancer, population-based data on prevalence of human papillomavirus (HPV) are limited in India. This study aimed to evaluate the prevalence of any HPV type and type-specific prevalence of HPV 16/18 in women without cervical cancer. HPV viral load was measured and correlated with cytologic abnormalities of the cervix. A total of 2501 women between 25 and 65 years of age and without cervical cancer were screened by pap smear cytology. HPV DNA was detected from cervical scrapes by nested polymerase chain reaction. Detection of HPV 16/18 was carried out by polymerase chain reaction using type-specific primers and was confirmed by Southern hybridization. Viral load was determined by absolute real-time polymerase chain reaction. Population prevalence of any HPV was found to be 9.9%. The risk of HPV infection was higher in women aged 25 to 34 years (odds ratio, 1.11), in married women below 20 years of age (odds ratio, 1.80), and in women with parity ≥4 (odds ratio, 1.04). Prevalence of HPV 18 (1.4%) was greater than that of HPV 16 (0.6%) in the overall screened population. High-grade squamous intraepithelial lesion cytology was more frequent in women infected with HPV 16 than in those infected with HPV 18 and other types. A gradual increase in HPV copy numbers was associated with progressive cytologic severity. In this study, HPV prevalence is comparable to HPV prevalence reported by other studies among Indian and Asian women. Although the prevalence of HPV 18 was more than that of HPV 16, type 16 infection was associated with higher oncogenicity.
Sinha D.,Chittaranjan National Cancer Institute |
Biswas J.,Chittaranjan National Cancer Institute |
Bishayee A.,Signal Sciences
Archives of Toxicology | Year: 2013
Arsenic is a ubiquitous toxic metalloid whose natural leaching from geogenic resources of earths crust into groundwater has become a dreadful health hazard to millions of people across the globe. Arsenic has been documented as a top most potent human carcinogen by Agency of Toxic Substances and Disease Registry. There have been a number of schools of opinions regarding the underlying mechanism of arsenic-induced carcinogenicity, but the theory of oxidative stress generated by arsenic has gained much importance. Imbalance in the cellular redox state and its associated complications have been closely associated with nuclear factor-erythroid 2-related factor 2 (Nrf2), a basic-leucine zipper transcription factor that activates the antioxidant responsive element and electrophilic responsive element, thereby upregulating the expression of a variety of downstream genes. This review has been framed on the lines of differential molecular responses of Nrf2 on arsenic exposure as well as the chemopreventive strategy which may be improvised to regulate Nrf2 in order to combat arsenic-induced oxidative stress and its long-term carcinogenic effect. © 2012 Springer-Verlag.
Mondal N.K.,Chittaranjan National Cancer Institute
Toxicologic pathology | Year: 2010
Biomass burning is a major source of indoor air pollution in rural India. The authors investigated in this study whether cumulative exposures to biomass smoke cause activation of the serine/threonine kinase Akt in airway cells and peripheral blood lymphocytes (PBL). For this, the authors enrolled 87 premenopausal (median age 34 years), nonsmoking women who used to cook with biomass (wood, dung, crop wastes) and 85 age-matched control women who cooked with cleaner fuel liquefied petroleum gas. Immunocytochemical and immunoblotting assays revealed significantly higher levels of phosphorylated forms of Akt protein (p-Akt(ser473) and p-Akt(thr308)) in PBL, airway epithelial cells, alveolar macrophages, and neutrophils in sputum of biomass-using women than control. Akt activation in biomass users was associated with marked rise in generation of reactive oxygen species and concomitant depletion of superoxide dismutase. Measurement of particulate matter having a diameter of less than 10 and 2.5 μm in indoor air by real-time aerosol monitor showed 2 to 4 times more particulate pollution in biomass-using households, and Akt activation was positively associated with particulate pollution after controlling potential confounders. The findings suggest that chronic exposure to biomass smoke activates Akt, possibly via generation of oxidative stress.
Basu P.,Chittaranjan National Cancer Institute |
Mittal S.,Child in Need Institute
Journal of Obstetrics and Gynaecology Research | Year: 2011
Aim: The human papillomavirus (HPV) vaccine is recommended for adolescent girls and young women; however, the social structure in India will not permit vaccination of this age-group without parental approval. Our study aimed to explore the attitude of affluent, urban Indian parents towards the HPV vaccine. Methods: Well-to-do married couples with at least one daughter between 9-26 years of age were interviewed using a questionnaire in two parts. The first part was to assess their attitude to vaccination in general and their knowledge of cervical cancer; the second part was to assess their acceptance of the HPV vaccine. An educational fact sheet about cervical cancer and the HPV vaccine was administered in between the two parts. Results: Of the 522 participants, 27% of men and 24% of women agreed to vaccinate their daughters against a cancer initially. After going through the fact sheet, 74% of both men and women were in favor of vaccination. Conclusions: The HPV vaccine seems to be well accepted among this subgroup of population if appropriately educated. © 2011 Japan Society of Obstetrics and Gynecology.