Molecular Staging of Surgical Margins in Oral Squamous Cell Carcinoma Using Promoter Methylation of p16INK4A, Cytoglobin, E-cadherin, and TMEFF2

Background

Local recurrence in oral squamous cell carcinoma (OSCC) despite clear surgical margins may indicate the presence of residual, sub-microscopic disease. Molecular assessment of surgical margins may provide a greater prognostic sensitivity compared to histopathology. We aimed to determine whether promoter methylation in deep and mucosal resection margins can predict recurrence in OSCC.

Methods

Forty-eight consecutive OSCC cases were recruited and a 5 mm³ tumor sample plus 5 deep and 5 mucosal margin samples were snap frozen. Clinical, pathological, adjuvant therapy, and outcome data were recorded. Tumors were informative if >5 % promoter methylation was found for ≥1 of 4 genes using qMSP. Margins were declared molecularly positive if >1 % promoter methylation was found in any margin.

Results

Thirty (63 %) of 48 cases were methylation informative. Mucosal margin samples were largely positive for methylation (26 of 30, 87 %), indicating the presence of field cancerization. Methylation at ≥1 gene promoters in ≥1 deep margin correlated with the presence of close/involved mucosal margins (P = 0.027) and increased pT status (P = 0.027) but not the status of deep margins, recurrence, or survival.

Conclusions

The current gene panel did not add prognostic information to histopathological reporting of resection margins. Future efforts should concentrate on improving gene selection, informativity, and assay performance in the patient group with intermediate indications for adjuvant therapy.     

Eulophia Nuda: A Review of Its Traditional Uses,Phytochemistry and Pharmacology

Pharmaceutical Chemistry Journal - Eulophia nuda Lindl. (Orchidaceae) is a small perennial terrestrial herb found in central and Southeast Asian regions usually known for its ethnomedicinal uses by...     

Synthesis,biological activities,and pharmacokinetics studies of a mutual prodrug of aceclofenac and paracetamol

An ester-based mutual prodrug (aceclofenac–paracetamol; AC-PR) was synthesized (one-pot method) with an aim of improving the therapeutic index through prevention of gastrointestinal irritation and bleeding that is associated with aceclofenac. The release of aceclofenac and paracetamol from the ester prodrug (AC-PR) was studied by reverse phase HPLC in hydrochloric acid buffer (pH 1.2), phosphate buffer (pH 7.4), 80 % v/v human plasma, 10 % w/v rat intestinal homogenate and 10 % w/v rat liver homogenate (pH 7.4). The prodrug showed negligible hydrolysis at pH 1.2 as compared to pH 7.4, suggesting that very less of the prodrug would hydrolyze in stomach, but would release the parent drugs at pH 7.4 in adequate amounts. The prodrug showed enhanced anti-inflammatory activity and significant protection against acetic acid-induced writhings (analgesic activity) as compared to that of aceclofenac. Further, the prodrug produced reduced number of ulcers as compared to that of the parent drug. These results suggest that the synthesized mutual prodrug (AC-PR) is better in terms of activity and GIT toxicity than the parent drug.     

Pre-pubertal exposure of cytarabine-induced testicular atrophy,impaired spermatogenesis and germ cell DNA damage in SD rats

Context: Cytarabine (Ara-C) is an effective chemotherapeutic drug for the treatment of acute leukaemias. It inhibits the DNA synthesis and repair, thereby causes cytotoxicity in the proliferating cells.

Objective: This study was aimed to investigate the effects of pre-pubertal exposure of Ara-C on testesticular development in juvenile SD rats and their function at puberty.

Materials and methods: Ara-C was injected at the doses of 50, 100 and 200?mg/kg/day from postnatal day (PND) 29–42 (14 days) by intraperitoneal (i.p.) route. Half of the animals were sacrificed on PND 43 and remaining on PND 70. End points of the evaluation included gross pathological examination, histomorphometric analysis, sperm count and sperm head morphology, cell proliferation and DNA damage as well as apoptosis analysis.

Results: Ara-C treatment significantly decreased food and water intake, weight gain, testes and epididymis weight and increased histological alterations in the seminiferous tubule. Furthermore, Ara-C treatment significantly decreased the PCNA-positive cells and sperm count in a dose-dependent manner. Ara-C treatment also increased the DNA damage and apoptosis in testes and sperm as evident from the comet and TUNEL assays results.

Discussion: The present study results clearly indicated that Ara-C treatment impaired spermatogenesis and adversely affects the testicular development and its function in rats by reducing the germ cell proliferation and the inducing DNA damage and apoptosis.