Histone acetylation: a key determinant of acquired cisplatin resistance in cancer.

Cisplatin is an alkylating class of chemotherapeutic drugs used to treat cancer patients. However, cisplatin fails in long-term treatment, and drug resistance is the primary reason for tumor recurrence. Hence, understanding the mechanism of acquirement of chemoresistance is essential for developing novel combination therapeutic approaches.

An increase in polyadenylation of histone isoforms, Hist1h2ah and Hist2h3c2, is governed by 3'-UTR in de-differentiated and undifferentiated hepatocyte.

Replication-dependent histones have a stem-loop structure at the 3' end of messenger RNA (mRNA) and are stabilized by stem-loop binding protein (SLBP). Moreover, loss of SLBP and imbalance in the level of ARE (adenylate-uridylate-rich elements)-binding proteins, HuR, and BRF1 are associated with the polyadenylation of canonical histone mRNAs under different physiological conditions. Previous studies from the lab have shown increased protein levels of H2A1H and H3.

Combinatorial cetuximab targeted polymeric nanocomplexes reduce PRC1 level and abrogate growth of metastatic hepatocellular carcinoma in vivo with efficient radionuclide uptake.

Hepatocellular carcinoma (HCC) is the most aggressive form of cancer with poor drug responses. Developing an effective drug treatment remains a major unmet clinical need for HCC. We report a comprehensive study of combinatorial Cetuximab (Cet) targeted polymeric poly(D, L-lactide-co-glycolide)-b-poly(ethylene glycol) nanocomplexes delivery of Combretastatin A4 (CA4) and 2-Methoxyestradiol (2ME) (Cet-PLGA-b-PEG-CA4 NP + Cet-PLGA-b-PEG-2ME NP) against metastatic HCC in SCID mice.

Histone deacetylase inhibitor pre-treatment enhances the efficacy of DNA-interacting chemotherapeutic drugs in gastric cancer.

Background: The prognosis of gastric cancer continues to remain poor, and epigenetic drugs like histone deacetylase inhibitors (HDACi) have been envisaged as potential therapeutic agents. Nevertheless, clinical trials are facing issues with toxicity and efficacy against solid tumors, which may be partly due to the lack of patient stratification for effective treatments.

Aim: To study the need of patient stratification before HDACi treatment, and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.

Establishing a correlation between RIN and A along with the multivariate evaluation of factors affecting the quality of RNA in cryopreserved cancer bio-specimen.

Biomarkers are biological characteristic to measure and evaluate normal and pathological states. To define expression-based molecular biomarkers, high-quality tissue samples are a prerequisite for the preparation of standard RNA. It is already known that RIN number defines the RNA quality, however its relation with A ratio and Ct value is not defined clearly; therefore, understanding an association will provide a reliable method for describing RNA quality.

Repositioning of Difluorinated Propanediones as Inhibitors of Histone Methyltransferases and their Biological Evaluation in Human Leukemic Cell Lines.

Background: At present, 'pharmaco-epigenomics' constitutes the hope in cancer treatment owing to epigenetic deregulation- a reversible process and playing a role in malignancy.

Objective: Chemotherapy has many limitations like host-tissue toxicity, drug resistance. Hence, it is imperative to unearth targets to better treat cancer.

A novel method for isolation of histones from serum and its implications in therapeutics and prognosis of solid tumours.

Background: Dysregulation in post-translational modifications of histones and their modifiers are now well-recognized as a hallmark of cancer and can be used as biomarkers and potential therapeutic targets for disease progression and prognosis. In most solid tumours, a biopsy is challenging, costly, painful or potentially risky for the patient. Therefore, non-invasive methods like 'liquid biopsy' for analysis of histone modifications and their modifiers if possible will be helpful in the better clinical management of cancer patients.

p38-MAPK/MSK1-mediated overexpression of histone H3 serine 10 phosphorylation defines distance-dependent prognostic value of negative resection margin in gastric cancer.

Background: Alterations in histone modifications are now well known to result in epigenetic heterogeneity in tumor tissues; however, their prognostic value and association with resection margins still remain poorly understood and controversial. Further, histopathologically negative resection margins in several cancers have been associated with better prognosis of the disease. However, in gastric cancer, despite a high rate of R0 resection, a considerably high incidence of loco-regional recurrence is observed.

sPLA2 -IIA Overexpression in Mice Epidermis Depletes Hair Follicle Stem Cells and Induces Differentiation Mediated Through Enhanced JNK/c-Jun Activation.

Secretory phospholipase A2 Group-IIA (sPLA2 -IIA) catalyzes the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. sPLA2 -IIA is deregulated in various cancers; however, its role in hair follicle stem cell (HFSC) regulation is obscure. Here we report a transgenic mice overexpressing sPLA2 -IIA (K14-sPLA2 -IIA) showed depletion of HFSC pool.

Brief Communication: Featured Article: Histone H2A mono-ubiquitination and cellular transformation are inversely related in N-nitrosodiethylamine-induced hepatocellular carcinoma.

Aberrant changes in histone post-translational modifications are encountered frequently in diseases like cancer. Although histone H3 post-translational modifications have been extensively studied in context of diseases, the functionally important histone H2A PTM H2A119ub (H2Aub) has not gained much attention. In this study, we report that H2Aub markedly decreases in hepatocellular carcinoma.

Dynamic alteration in H3 serine 10 phosphorylation is G1-phase specific during ionization radiation induced DNA damage response in human cells.

Chromatin acts as a natural barrier in DNA-damage recognition and repair. Histones undergo differential post-translational modification(s) to facilitate DNA damage response (DDR). Importance of modifications like phosphorylation of histone variant H2A.

Techniques to access histone modifications and variants in cancer.

Recent years have witnessed an explosion of epigenetic research on the role of histone variants and modifications in cancer. To understand the global dynamics of chromatin structure and function, analysis of histone variants incorporated into the nucleosome and their covalent modifications, is required. The nucleosome is the fundamental structural unit of chromatin, contains an octamer of core histones H3, H4, H2A, and H2B.

Expression of histone variant, H2A.1 is associated with the undifferentiated state of hepatocyte.

Recent studies suggest the incorporation of histone variants into the chromatin regulate cellular proliferation, differentiation, and de-differentiation. We have earlier reported the increase of H2A.1 variant during sequential de-differentiation of hepatocyte to hepato-cellular carcinoma.

Chemopreventive and hepatoprotective effects of embelin on N-nitrosodiethylamine and carbon tetrachloride induced preneoplasia and toxicity in rat liver.

Embelin, an active constituent isolated from the fruits of Embelia tsjeriam cottam was investigated for its chemopreventive and hepatoprotective effects against N-nitrosodiethylamine (NDEA) induced liver preneoplasia or carbon tetrachloride (CCl4) induced liver damage. Rats received NDEA, 1 ppm/g b.w.

Mass spectrometry-compatible silver staining of histones resolved on acetic acid-urea-Triton PAGE.

Acetic acid-Urea-Triton (AUT) PAGE is commonly used method to separate histone variants and their post-translationally modified forms. Coomassie staining is the preferred method for protein visualization; however, its sensitivity is less than that of silver staining. Though silver staining of histones in AUT-PAGE has been reported, the method is time-consuming, dependent on prior staining by Amido black and has not been reported suitable for mass spectrometry.

Sida rhombifolia ssp. retusa seed extract inhibits DEN induced murine hepatic preneoplasia and carbon tetrachloride hepatotoxicity.

Sida rhombifolia ssp. retusa is a well established drug in the Ayurvedic system of medicine used for antirheumatism and antiasthmatism. Inhibitory effects of S.