Publications by authors named "S C Datta"

2,843 Publications

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Body fatness and breast cancer risk in relation to phosphorylated mTOR expression in a sample of predominately Black women.

Breast Cancer Res 2021 Jul 30;23(1):77. Epub 2021 Jul 30.

Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Background: The mechanistic target of rapamycin (mTOR) pathway promoted by positive energy imbalance and insulin-like growth factors can be a mechanism by which obesity influences breast cancer risk. We evaluated the associations of body fatness with the risk of breast cancer varied with phosphorylated (p)-mTOR protein expression, an indication of the pathway activation.

Methods: Women with newly diagnosed breast cancer (n = 715; 574 [80%] Black and 141 [20%] White) and non-cancer controls (n = 1983; 1280 [64%] Black and 713 [36%] White) were selected from the Women's Circle of Health Study. Surgical tumor samples among the cases were immunostained for p-mTOR (Ser2448) and classified as p-mTOR-overexpressed, if the expression level ≥ 75th percentile, or p-mTOR-negative/low otherwise. Anthropometrics were measured by trained staff, and body composition was determined by bioelectrical impedance analysis. Odds ratios (ORs) of p-mTOR-overexpressed tumors and p-mTOR-negative/low tumors compared to controls were estimated using polytomous logistic regression. The differences in the associations by the p-mTOR expression status were assessed by tests for heterogeneity.

Results: Cases with p-mTOR-overexpressed tumors, but not cases with p-mTOR-negative/low tumors, compared to controls were more likely to have higher body mass index (BMI), percent body fat, and fat mass index (P-heterogeneity < 0.05), although the OR estimates were not significant. For the measurement of central adiposity, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 2.52, 95% CI = 1.46 to 4.34) and Q4 (OR = 1.99, 95% CI = 1.12 to 3.50) of waist circumference (WC) compared to controls. Similarly, cases with p-mTOR overexpressed tumors had a higher odds of being at the Q3 (OR = 1.82, 95% CI = 1.11 to 2.98) and Q4 (OR = 1.81, 95% CI = 1.11 to 2.98) of WHR compared to controls. These associations of WC and waist-to-hip ratio (WHR) did not differ by tumor p-mTOR status (P-heterogeneity = 0.27 and 0.48, respectively).

Conclusions: Our findings suggest that in this population composed of predominately Black women, body fatness is associated with breast cancer differently for p-mTOR overexpression and p-mTOR negative/low expression. Whether mTOR plays a role in the obesity and breast cancer association warrants confirmation by prospective studies.
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http://dx.doi.org/10.1186/s13058-021-01458-zDOI Listing
July 2021

Progress Toward Hepatitis B Control - World Health Organization European Region, 2016-2019.

MMWR Morb Mortal Wkly Rep 2021 Jul 30;70(30):1029-1035. Epub 2021 Jul 30.

In 2019, an estimated 14 million persons in the World Health Organization (WHO) European Region* (EUR) were chronically infected with hepatitis B virus (HBV), and approximately 43,000 of these persons died from complications of chronic HBV infection (1). In 2016, the WHO Regional Office for Europe set hepatitis B control program targets for 2020, including 1) ≥90% coverage with 3 doses of hepatitis B vaccine (HepB3), 2) ≥90% coverage with interventions to prevent mother-to-child transmission (MTCT) of HBV, and 3) ≤0.5% prevalence of HBV surface antigen (HBsAg) in age groups eligible for vaccination with hepatitis B vaccine (HepB) (2-4). This report describes the progress made toward hepatitis B control in EUR during 2016-2019. By December 2019, 50 (94%) of 53 countries in EUR provided routine vaccination with HepB to all infants or children aged 1-12 years (universal HepB), including 23 (43%) countries that offered hepatitis B birth dose (HepB-BD) to all newborns. In addition, 35 (73%) of the 48 countries with universal infant HepB vaccination reached ≥90% HepB3 coverage annually during 2017-2019, and 19 (83%) of the 23 countries with universal birth dose administration achieved ≥90% timely HepB-BD coverage annually during that period. Antenatal hepatitis B screening coverage was ≥90% in 17 (57%) of 30 countries that selectively provided HepB-BD to infants born to mothers with positive HBsAg test results. In January 2020, Italy and the Netherlands became the first counties in EUR to be validated to have achieved the regional hepatitis B control targets. Countries can accelerate progress toward hepatitis B control by improving coverage with HepB and interventions to prevent MTCT and documenting achievement of the HBsAg seroprevalence target through representative serosurveys or, in low-endemicity countries, antenatal screening.
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http://dx.doi.org/10.15585/mmwr.mm7030a1DOI Listing
July 2021

SeqNet: An R Package for Generating Gene-Gene Networks and Simulating RNA-Seq Data.

J Stat Softw 2021 Jul 10;98(12). Epub 2021 Jul 10.

Univeristy of Florida, Department of Biostatistics.

Gene expression data provide an abundant resource for inferring connections in gene regulatory networks. While methodologies developed for this task have shown success, a challenge remains in comparing the performance among methods. Gold-standard datasets are scarce and limited in use. And while tools for simulating expression data are available, they are not designed to resemble the data obtained from RNA-seq experiments. SeqNet is an R package that provides tools for generating a rich variety of gene network structures and simulating RNA-seq data from them. This produces RNA-seq data for benchmarking and assessing gene network inference methods. The package is available on CRAN and on GitHub at https://github.com/tgrimes/SeqNet.
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http://dx.doi.org/10.18637/jss.v098.i12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315007PMC
July 2021

Learnings from past failures: future routes of antimicrobial drug discovery.

Authors:
Santanu Datta

Drug Discov Today 2021 Jul 24. Epub 2021 Jul 24.

Bugworks Research, Bellary Road, NCBS Campus, Hebbal, Bangalore, 560065, India. Electronic address:

Despite the unprecedented unmet need to discover new antibiotics, only a few molecules have been registered for clinical use. This shortage is primarily based on the scientific failure in the postgenomic era of drug discovery. It appears counterintuitive that knowledge of the bacterial genome was followed by the failure to produce new antibiotics using the paradigm of target-driven drug discovery. Here, I discuss the causes of the failures and also describe how small biotech is mitigating these risks and moving forward using new strategies to identify new antibiotics.
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http://dx.doi.org/10.1016/j.drudis.2021.07.017DOI Listing
July 2021

Nrf2 deficiency decreases NADPH from impaired IDH shuttle and pentose phosphate pathway in retinal pigmented epithelial cells to magnify oxidative stress-induced mitochondrial dysfunction.

Aging Cell 2021 Jul 27:e13444. Epub 2021 Jul 27.

Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.

The nuclear factor-erythroid 2-related factor-2 (Nrf2), a major antioxidant transcription factor, is decreased in several age-related diseases including age-related macular degeneration (AMD), the most common cause of blindness among the elderly in western society. Since Nrf2's mito-protective response is understudied, we investigated its antioxidant response on mitochondria. Control and Nrf2-deficient retinal pigmented epithelial (RPE) cells were compared after treating with cigarette smoke extract (CSE). Mitochondrial antioxidant abundance and reactive oxygen species (ROS) were quantified. Mitochondrial function was assessed by TMRM assay, NADPH, electron transport chain activity, and Seahorse. Results were corroborated in Nrf2 mice and relevance to AMD was provided by immunohistochemistry of human globes. CSE induced mitochondrial ROS to impair mitochondrial function. H O increase in particular, was magnified by Nrf2 deficiency, and corresponded with exaggerated mitochondrial dysfunction. While Nrf2 did not affect mitochondrial antioxidant abundance, oxidized PRX3 was magnified by Nrf2 deficiency due to decreased NADPH from decreased expression of IDH2 and pentose phosphate pathway (PPP) genes. With severe CSE stress, intrinsic apoptosis was activated to increase cell death. PPP component TALDO1 immunolabeling was decreased in dysmorphic RPE of human AMD globes. Despite limited regulation of mitochondrial antioxidant expression, Nrf2 influences PPP and IDH shuttle activity that indirectly supplies NADPH for the TRX2 system. These results provide insight into how Nrf2 deficiency impacts the mitochondrial antioxidant response, and its role in AMD pathobiology.
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http://dx.doi.org/10.1111/acel.13444DOI Listing
July 2021
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