Elucidating the Role of miRNA-326 Modulating Hedgehog Signaling in Pancreatic Carcinoma.

Background And Aim: Pancreatic ductal adenocarcinoma (PDAC) is one of the lethal malignancies worldwide characterized by poor prognosis. MicroRNAs (miRNAs) function as the key regulators in carcinogenesis and may act as noninvasive biomarkers in various malignancies including PDAC. The present study aimed to elucidate the role of miR-326, a known modulator of hedgehog (Hh) pathway in PDAC.

NFκB (RelA) mediates transactivation of hnRNPD in oral cancer cells.

Heterogeneous Ribonucleoprotein D (hnRNPD) is an RNA binding protein involved in post-transcriptional regulation of multiple mediators of carcinogenesis. We previously demonstrated a strong association of hnRNPD over expression with poor outcome in Oral Squamous Cell Carcinoma (OSCC). However, hitherto the precise molecular mechanism of its overexpression in oral cancer was not clear.

Pleiotropic role of PARP1: an overview.

Poly (ADP-ribose) polymerase 1 (PARP1) protein is encoded by the gene located on chromosome 1 (1q42.12) in human cells. It plays a crucial role in post-translational modification by adding poly (ADP-ribose) (PAR) groups to various proteins and PARP1 itself by utilizing nicotinamide adenine dinucleotide (NAD +) as a substrate.

Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma.

Early-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas.

Influence of different forms and materials (zirconia or titanium) of abutments in peri-implant soft-tissue healing using matrix metalloproteinase-8: A randomized pilot study.

Statement Of Problem: It is unclear how pathogenic bacteria adhere to different implant materials and whether biomarker matrix metalloproteinase-8 (MMP-8) level provides a reliable method of evaluating the connective tissue status of peri-implant tissues.

Purpose: The purpose of this pilot clinical study was to evaluate peri-implant connective tissue response by assessing the MMP-8 levels in peri-implant crevicular fluid around titanium and zirconia abutments.

Material And Methods: The study was designed as a prospective, within-subject comparison with left-right randomization low.

End Binding 1 (EB1) overexpression in oral lesions and cancer: A biomarker of tumor progression and poor prognosis.

Introduction: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and despite the improvement in treatment strategy, 5-year survival rates are about 50%. Identification of patients at high risk of recurrence may enable rigorous personalized post-treatment management. In an earlier proteomics study we observed overexpression of End Binding Protein (EB1) in OSCC.

Nuclear heterogeneous nuclear ribonucleoprotein D is associated with poor prognosis and interactome analysis reveals its novel binding partners in oral cancer.

Background: Post-transcriptional regulation by heterogeneous ribonucleoproteins (hnRNPs) is an important regulatory paradigm in cancer development. Our proteomic analysis revealed hnRNPD overexpression in oral dysplasia as compared with normal mucosa; its role in oral carcinogenesis remains unknown. Here in we determined the hnRNPD associated protein networks and its clinical significance in oral squamous cell carcinoma (OSCC).

Prognostic significance of cytoplasmic S100A2 overexpression in oral cancer patients.

Background: Oral squamous cell carcinoma (OSCC) patients are at high risk of loco-regional recurrence and 5-year survival rates are about 50%. Identification of patients at high risk of recurrence will enable rigorous personalized post-treatment management. Most novel biomarkers have failed translation for clinical use because of their limited successful validation in external patient cohorts.

The rational design of specific peptide inhibitor against p38α MAPK at allosteric-site: a therapeutic modality for HNSCC.

p38α is a significant target for drug designing against cancer. The overproduction of p38α MAPK promotes tumorigenesis in head and neck squamous cell carcinoma (HNSCC). The ATP binding and an allosteric site referred as DFG are the key sites of the p38α mitogen activated protein kinase (MAPK) exploited for the design of inhibitors.

siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin.

Aim: To determine the functional significance of TC21 in esophageal squamous cell carcinoma (ESCC).

Methods: TC21 siRNA transfection was carried out using Hyperfectamine to knock down TC21, and transcripts were analyzed by reverse transcription-polymerase chain reaction and protein by Western blotting. We demonstrated the effect of TC21 downregulation of cell signaling in esophageal cancer cells by assessing the phosphorylation status of its downstream targets, phosphoinositide 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), protein kinase B (pAkt), nuclear factor-κB (NF-κB) and cyclinD1 using specific antibodies.

Prevalence, distribution and functional significance of the -237C to T polymorphism in the IL-12Rβ2 promoter in Indian tuberculosis patients.

Cytokine/cytokine receptor gene polymorphisms related to structure/expression could impact immune response. Hence, the -237 polymorphic site in the 5' promoter region of the IL-12Rβ2 (SNP ID: rs11810249) gene associated with the AP-4 transcription motif GAGCTG, was examined. Amplicons encompassing the polymorphism were generated from 46 pulmonary tuberculosis patients, 35 family contacts and 28 miscellaneous volunteers and sequenced.

Structure based design and synthesis of peptide inhibitor of human LOX-12: in vitro and in vivo analysis of a novel therapeutic agent for breast cancer.

Human breast cancer cell proliferation involves a complex interaction between growth factors, steroid hormones and peptide hormones. The interaction of growth factors, such as epidermal growth factor (EGF), with their receptors on breast cancer cells can lead to the hydrolysis of phospholipids and release of fatty acid such as arachidonic acid, which can be further metabolized by cyclooxygenase (COX) and lipoxygenase (LOX) pathways to produce prostaglandins. The high concentration of prostaglandins has been associated with chronic inflammatory diseases and several types of human cancers.

Loss of DLC1 is an independent prognostic factor in patients with oral squamous cell carcinoma.

Deleted in liver cancer (DLC1), a Rho GTPase-activating protein, was observed to be differentially expressed in oral squamous cell carcinoma in comparison with normal tissues using tissue proteomics. In the current study, we investigated the clinical significance of loss of DLC1 expression in different stages of development of oral squamous cell carcinoma to determine its potential as a biomarker for oral dysplasia and prognosis of oral squamous cell carcinoma. Immunohistochemical analysis of DLC1 expression was carried out in oral squamous cell carcinoma patients (n=214), dysplasia (n=51), hyperplastic squamous mucosa (n=45), and histologically normal oral tissues (n=80), and correlated with clinicopathological parameters and disease prognosis over 91 months for oral squamous cell carcinomas.

Overexpression of prothymosin alpha predicts poor disease outcome in head and neck cancer.

Background: In our recent study, tissue proteomic analysis of oral pre-malignant lesions (OPLs) and normal oral mucosa led to the identification of a panel of biomarkers, including prothymosin alpha (PTMA), to distinguish OPLs from histologically normal oral tissues. This study aimed to determine the clinical significance of PTMA overexpression in oral squamous cell hyperplasia, dysplasia and head and neck squamous cell carcinoma (HNSCC).

Methodology: Immunohistochemistry of PTMA protein was performed in HNSCCs (n = 100), squamous cell hyperplasia (n = 116), dysplasia (n = 50) and histologically normal oral tissues (n = 100).

Guggulsterone targets smokeless tobacco induced PI3K/Akt pathway in head and neck cancer cells.

Background: Epidemiological association of head and neck cancer with smokeless tobacco (ST) emphasizes the need to unravel the molecular mechanisms implicated in cancer development, and identify pharmacologically safe agents for early intervention and prevention of disease recurrence. Guggulsterone (GS), a biosafe nutraceutical, inhibits the PI3K/Akt pathway that plays a critical role in HNSCC development. However, the potential of GS to suppress ST and nicotine (major component of ST) induced HNSCC remains unexplored.

Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers.

Background: We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers.

Methodology And Results: Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies.

Nuclear S100A7 is associated with poor prognosis in head and neck cancer.

Background: Tissue proteomic analysis of head and neck squamous cell carcinoma (HNSCC) and normal oral mucosa using iTRAQ (isobaric tag for relative and absolute quantitation) labeling and liquid chromatography-mass spectrometry, led to the identification of a panel of biomarkers including S100A7. In the multi-step process of head and neck tumorigenesis, the presence of dysplastic areas in the epithelium is proposed to be associated with a likely progression to cancer; however there are no established biomarkers to predict their potential of malignant transformation. This study aimed to determine the clinical significance of S100A7 overexpression in HNSCC.

Antimalarial evaluation of copper(II) nanohybrid solids: inhibition of plasmepsin II, a hemoglobin-degrading malarial aspartic protease from Plasmodium falciparum.

A new class of copper(II) nanohybrid solids, LCu(CH(3)COO)(2) and LCuCl(2), have been synthesized and characterized by transmission electron microscopy, dynamic light scattering, and IR spectroscopy, and have been found to be capped by a bis(benzimidazole) diamide ligand (L). The particle sizes of these nanohybrid solids were found to be in the ranges 5-10 and 60-70 nm, respectively. These nanohybrid solids were evaluated for their in vitro antimalarial activity against a chloroquine-sensitive isolate of Plasmodium falciparum (MRC 2).

Presence and significance of a R110W mutation in the DNA-binding domain of GCM2 gene in patients with isolated hypoparathyroidism and their family members.

Objective: Glial cells missing 2 (GCM2) gene encodes a parathyroid-specific transcription factor. We assessed GCM2 gene sequence in patients with isolated hypoparathyroidism (IH).

Design: Case-control study.

Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma.

Oral leukoplakia is a heterogeneous lesion with risk of cancer development; there are no biomarkers to predict its potential of malignant transformation. Tissue proteomic analysis of oral leukoplakia using iTRAQ labeling liquid chromatography-mass spectrometry showed overexpression of heterogeneous ribonucleoprotein K (hnRNP K), a transformation-related RNA-binding protein, in leukoplakia in comparison with normal tissue. Herein, we investigated the clinical significance of hnRNP K in identification of oral leukoplakic lesions in early stages and as a prognostic marker in head-and-neck/oral squamous cell carcinomas (HNOSCCs).