Identification of potential histone deacetylase1 (HDAC1) inhibitors using multistep virtual screening approach including SVM model, pharmacophore modeling, molecular docking and biological evaluation.

Histone Deacetylases (HDACs) play a significant role in the regulation of gene expression by modifying histones and non-histone substrates. Since they are key regulators in the reversible epigenetic mechanism, they are considered as promising drug targets for the treatment of various cancers. In the present study, we have developed a workflow for identification of HDAC1 inhibitors using a multistage virtual screening approach from Maybridge and Chembridge chemical library.

A model to study the inhibition of nsP2B-nsP3 protease of dengue virus with imidazole, oxazole, triazole thiadiazole, and thiazolidine based scaffolds.

A theoretical model was developed to allosterically inhibit the biological activity of dengue virus (DENV) by targeting the non-structural protein ns2B-nsP3 protease based on the studies. The imidazole, oxazole, triazole, thiadiazole, and thiazolidine based scaffolds were imported from the ZINC database, reported by various research group with different biological activity. They were found biologically active as they contain heterocyclic fragments.

Clinical Genomic Sequencing of Pediatric and Adult Osteosarcoma Reveals Distinct Molecular Subsets with Potentially Targetable Alterations.

Purpose: Although multimodal chemotherapy has improved outcomes for patients with osteosarcoma, the prognosis for patients who present with metastatic and/or recurrent disease remains poor. In this study, we sought to define how often clinical genomic sequencing of osteosarcoma samples could identify potentially actionable alterations. We analyzed genomic data from 71 osteosarcoma samples from 66 pediatric and adult patients sequenced using MSK-IMPACT, a hybridization capture-based large panel next-generation sequencing assay.

Immunogenic neoantigens derived from gene fusions stimulate T cell responses.

Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy.

Attributes of alternatively activated (M2) macrophages.

Macrophages are cells of innate immunity and are derived from circulating monocytes and embryonic yolk sac. They exhibit high plasticity and polarize functionally in response to stimulus triggering it into classically activated M1 macrophages and alternatively activated M2 macrophages. This review summarizes markers of M2 macrophages like transmembrane surface receptors and signaling cascades initiated on their activation; cytokine and chemokine repertoires along with their receptors; and genetic markers and their involvement in immunomodulation.

Patient-Driven Discovery, Therapeutic Targeting, and Post-Clinical Validation of a Novel Fusion-Driven Cancer.

Despite the important role of the PI3K/AKT/mTOR axis in the pathogenesis of cancer, to date there have been few functional oncogenic fusions identified involving the genes. A 12-year-old female with a histopathologically indeterminate epithelioid neoplasm was found to harbor a novel fusion between the and genes. Through expanded use access, she became the first pediatric patient to be treated with the oral ATP-competitive pan-AKT inhibitor ipatasertib.

Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors.

Glypican 3 (GPC3) is a heparan sulfate proteoglycan and cell surface oncofetal protein which is highly expressed on a variety of pediatric solid embryonal tumors including the majority of hepatoblastomas, Wilms tumors, rhabdoid tumors, certain germ cell tumor subtypes, and a minority of rhabdomyosarcomas. Via both its core protein and heparan sulfate side chains, GPC3 activates the canonical Wnt/β-catenin pathway, which is frequently overexpressed in these malignancies. Loss of function mutations in lead to Simpson-Golabi-Behmel Syndrome, an X-linked overgrowth condition with a predisposition to GPC3-expressing cancers including hepatoblastoma and Wilms tumor.

Multimodality management of incidentally detected gall bladder cancer: long term results from a tertiary care cancer centre.

Background: Gall bladder cancer (GBC) is the most common biliary tract malignancy in India. GBC present either with incidental diagnosis after simple cholecystectomy (SC) or with a primary gall bladder mass. Incidentally detected gall bladder cancer (ICGB) has traditionally been thought to be a relatively early stage disease but there are controversies associated with various aspects of its management.

Factors Associated with Depression among School-going Adolescent Girls in a District of Northern India: A Cross-sectional Study.

Context: Depression among adolescents, especially among girls, is a rising public health problem worldwide. It has been associated with a profound negative impact on their physical, social, and mental well-being.

Aim Of The Study: To ascertain the factors associated with depression among school-going adolescent girls in district Barabanki of Uttar Pradesh.

Gene Expression, Epigenetics and Ageing.

As the popular adage goes, all diseases run into old age and almost all physiological changes are associated with alterations in gene expression, irrespective of whether they are causal or consequential. Therefore, the quest for mechanisms that delay ageing and decrease age-associated diseases has propelled researchers to unravel regulatory factors that lead to changes in chromatin structure and function, which ultimately results in deregulated gene expression. It is therefore essential to bring together literature, which until recently has investigated gene expression and chromatin independently.

Clinicopathological profile of breast cancer: An institutional experience.

Introduction: This study was undertaken to evaluate the clinicopathological characteristics of patients with breast cancer at our institute, a tertiary-care cancer center in northern India.

Materials And Methods: This retrospective study included all patients with breast cancer registered at our institute from January 1, 2014 to December 31, 2016. We retrieved data (demographic, baseline clinical characteristics, pathology, and treatment details) from prospectively maintained clinical case records.

Optimal control of HCV transmission under liquoring.

Chronic hepatitis C virus (HCV) and alcohol are common causes of chronic liver diseases and both are recognized as major causes of liver disease worldwide. Each poses a major public and economic burden to society, and when the two co-exist they appear to have a synergistic effect in the progression of chronic liver disease. In this research, we developed a SIRS model of transmission of the hepatitis C virus (HCV) under effect of liquoring in six compartments: Susceptible, Low liquoring, High liquoring, Acute, Chronic and Recovered Individuals.

Double burden of malnutrition among school-going adolescent girls in North India: A cross-sectional study.

Context: Double burden of malnutrition comprising both undernutrition and overnutrition is nowadays emerging as a major public health concern among adolescent girls in India.

Aim: The present study was conducted to determine the prevalence of underweight, overweight, and obesity among school-going adolescent girls along with dietary and physical activity-related factors associated with them.

Settings And Design: The present cross-sectional survey was conducted among 2400 school-going adolescent girls (10-19 years) in Barabanki district of Uttar Pradesh.

Recent Advances and Perspectives in Small-molecule TLR Ligands and Their Modulators.

Activation of Toll-like receptors (TLRs) located on immune cells leads to induction of immune responses that can be useful in vaccines for infectious diseases, cancer immunotherapy, and autoimmune diseases. Novel TLR signaling pathway modulators can further enhance the efficacy of TLR ligands.

A recurrent novel fusion identifies a new subtype of high-grade spindle cell sarcoma.

-rearranged tumors are defined by the presence of a gene fusion between and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. -rearranged tumors display histologic features of a poorly differentiated carcinoma with areas of focal squamous differentiation and typically express the fusion gene defining a distinct clinicopathologic entity-NUT carcinoma (NC). NCs with mesenchymal differentiation have rarely been described in the literature.

Functional Characterization of SMG7 Paralogs in .

SMG7 proteins are evolutionary conserved across eukaryotes and primarily known for their function in nonsense mediated RNA decay (NMD). In contrast to other NMD factors, SMG7 proteins underwent independent expansions during evolution indicating their propensity to adopt novel functions. Here we characterized SMG7 and SMG7-like (SMG7L) paralogs in .

A case of fusion-associated acute megakaryoblastic leukemia.

Acute megakaryoblastic leukemia (AMKL) constitutes ∼5%-15% of cases of non-Down syndrome AML in children, and in the majority of cases, chimeric oncogenes resulting from recurrent gene rearrangements are identified. Based on these rearrangements, several molecular subsets have been characterized providing important prognostic information. One such subset includes a group of patients with translocations involving the gene, which has been associated with various fusion partners in patients with AMKL.

Discovery of a Novel Microtubule Targeting Agent as an Adjuvant for Cancer Immunotherapy.

For an activating immunotherapy such as adjuvants, a compound that can prolong immune stimulation may enhance efficacy. We leveraged data from two prior high throughput screens with NF-B and interferon reporter cell lines to identify 4-chromene-3-carbonitriles as a class of compounds that prolonged activation in both screens. We repurchased 23 of the most promising candidates.

Maintenance chemotherapy to reduce the risk of a metachronous Wilms tumor in children with bilateral nephroblastomatosis.

From 2009 to 2018, 10 consecutive patients with Wilms tumors and bilateral nephroblastomatosis, who had completed standard therapy, were provided a maintenance chemotherapy regimen consisting of vincristine and dactinomycin every 3 months for 12 months in order to prevent an early metachronous Wilms tumor. One patient (10%) with Beckwith-Wiedemann syndrome developed a new tumor, without anaplasia. There were no significant toxicities reported during maintenance.

Gallbladder cancer incidence in Delhi urban: A 25-year trend analysis.

Introduction: Gallbladder cancer (GBC) falls into the top ten leading cancer sites in urban Delhi. The incidence of GBC in females is more than that among males worldwide. The present study evaluates the temporal variation of GBC incidence in an urban Delhi population.