Molecular binary classification of NSCLC: miR-375 is a potential biomarker to differentiate SQCC from ADCC in Indian NSCLC patients

Background: Current developments in the targeted therapies of non-small-cell lung carcinoma demand accurate classification to dodge the adverse drug response and to yield maximum therapeutic outcome. Accurate classification depends on the classical hematoxylin and eosin staining and immunohistochemistry techniques. In selected critical cases, inter-observer variability, lack of standardization, tumor heterogeneity, and degree of differentiation makes it difficult to classify NSCLC. During the last decade, microRNAs (miRNAs) have been proven to be a promising biomarker in the field of oncology from diagnosis to therapy. The present study developed a binary classification method based on the expression of three well-known miRNAs: miR-205, miR-196b, miR-375, since it is the most demanding criteria to the clinicians trying to provide better therapy to the patients. Methods: Quantitative real-time polymerase chain reaction was performed for 90 NSCLC samples. Receiver-Operator Characteristic Curve and Discriminant Function Analysis was done to classify the NSCLC. A discriminant formula was developed to calculate the Z-score of miR-375 (Z3 = −0.637 + (0.439 x NCt miR-375) + (−0.245 x NCt miR-21). Results: The miR-375 classified NSCLC into SQCC and ADCC with higher accuracy. miR-375 appeared to differentiate SQCC from ADCC accurately in the test and validation set, signifying a sensitivity and specificity of 96.7% and 93.1%, respectively. Discussion: miR-375 is over-expressed in ADCC and suppressed in SQCC. This evidence accentuated the oncogenic and tumor suppressor nature in ADCC and SQCC respectively. Conclusion: miR-375 was proven to be the prominent biomarker of accurate NSCLC classification. The current study developed a molecular binary classification method in adjunctive of IHC which will help the clinicians in better classifying NSCLC and designing therapy (AU)

Modulatory Effect of a Unani Formulation (Jawarish amla sada) on Cyclophosphamide-induced Toxicity in Tumour Bearing Mice.

Aims: Our aim was to study the modulatory effect of a Unani herbal formulation Jawarish amla sada against cyclophosphamide-induced toxicity in tumour bearing mice. Study Design: Non randomized control study. Place and Duration of Study: The study was conducted at the Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi during 2008-10. Methodology: Study was conducted in Swiss albino mice divided in five groups (n=6). Animals were challenged with Ehrlich’s ascites tumour cells (1x106 cells). Cyclophosphamide (50 mg/kg body weight), an alkylating anticancer drug that especially affects humoral immune functions, was injected intraperitoneally in a single dose. The protective effect of Unani drug Jawarish amla sada (250 mg/kg body weight) was studied in tumour bearing animals treated with cyclophosphamide. Immune function assessment test such as plaque forming cell assay (PFC) and biochemical parameters such as activities of antioxidant enzymes and reduced glutathione were measured in mice. Results: Jawarish amla sada significantly modulated the immunosuppressive effect of cyclophosphamide as compared to the group treated with cyclophosphamide. Jawarish amla sada also protected activities of antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase and significantly restored level of reduced glutathione in liver and kidney of tumour bearing mice exposed to cyclophosphamide. Similar protective effect of Jawarish amla sada was observed against elevated lipid peroxidation in these tissues. Conclusion: Jawarish amla sada showed potential to provide protection against toxic effects of cyclophosphamide in tumour bearing mice. The mechanism of action of the drug may be attributed to various antioxidants fortified in this herbal Unani formulation, which is used in the traditional system of medicine in Indian subcontinent against several liver ailments.

Cytogenetic investigation in chronic myeloid leukemia: study from an Indian population.

Chronic myeloid leukemia (CML) is a malignant neoplasm of hematopoietic cells characterized by abnormal proliferation of myeloid precursors, decreased rates of self destruction and an arrest in cellular differentiation. The bone marrow and peripheral blood accumulates all forms of mature and immature granulocytes, primarily blast cells. It is the most common type of leukemia seen in India, accounting for 30% of all leukemias. Cytogenetic analysis plays a vital and important role in the diagnosis of CML patients. The present study consists of cytogenetic evaluation of 175 CML cases from the Indian population with ages ranging from 6-86 years (mean of 42.8). The study population included 115 males (65.72%) and 60 females (34.28%) with a Male: Female ratio 1.9:1. Out of the 175 cases, 164 (93.7%) were successfully karyotyped while culture failure was observed for 11 (6.3%). Among the 164 reported cases, 53 (32.3%) showed a normal karyotype while within the 111 (67.7%) abnormal cases, 96 cases (86.5%) showed the presence of Philadelphia (Ph') chromosome with standard translocation t(9;22); Ph'+ve along with secondary aberrations was detected in 9 (8.1%) cases. Variants of Ph' chromosome were detected in only one case (0.9%). Ph'-ve CML with other chromosomal aberrations were detected in 5 (4.5%) cases, including +8, del 20q, del 11q and marker chromosome. Furthermore, we believe that availability of more advanced molecular techniques can be used as a supportive tool in CML diagnosis even though it cannot fully replace cytogenetics, which remains the backbone for laboratory investigation of the disease.