ABSTRACT
Deregulation of Insulin like growth factors (IGF) is an important determinant of breast carcinogenesis. Circulatory IGF-1 (potent breast mitogen) and IGFBP-3 (its regulator) are extensively evaluated; few studies report transcript copy numbers (CN) from ex-vivo samples. This study from 106 patients evaluated mRNA expression (qRT-PCR CN) of IGF-1 and IGFBP-3 for prognostic and predictive utility from tumor, adjacent normal tissues (ANT) and lymph nodes. The differences in IGF-1 and IGFBP-3 mRNA levels (CN/μg RNA) were juxtaposed to clinical and pathologic variables and survival. Tumors expressed lower IGF-1 and higher IGFBP-3 as compared to ANT. Both transcript levels decreased with increasing age. Primary tumors with nodal involvement, Invasive Lobular carcinoma (ILC) histology and stromal involvement showed increased transcript levels than their respective counterparts. Moreover, surviving patients showing no relapse had higher expression of both molecules. Early stage and necrosed tumors expressed higher IGFBP-3 while a trend of lower expression was seen as tumor grade advanced. IGF-1 expression was inversely correlated to stage, histologic grade and. Significantly different Relapse Free Survival (RFS) was seen with IGFBP-3 up-/down-regulation considering progesterone receptor (PR) status but not estrogen receptor (ER) and HER-2 while the Overall Survival (OS) was similar for both these molecules. We conclude that expression of these molecules may aid prognostication and success of anti IGF-1 strategies.
ABSTRACT
Dual role of TGF- signaling in breast tumorigenesis as an inhibitor in early stages and promoter in advanced stages has been well established and known as TGF- switch. However, the biological mechanisms needs to be explored. Aim of the present study was to look for the usefulness of TGF-2 as a predictive marker for breast cancer and to offer a better predictability to identify patients likely to benefit from antiTGF- strategies. Circulatory as well as transcript levels of TGF-2 were estimated from 118 pretherapeutic breast cancer patients using ELISA and q-PCR with ddCt method. Multifactorial analysis was performed to correlate the results to clinico-pathological prognosticators and Kaplan-Meier survival analysis with a median follow-up of 49 months was also evaluated. Circulating TGF-2 was similar in control and breast cancer patients. TGF-2 was significantly upregulated in advanced tumors compared to early tumors. An inverse correlation was observed between TGF-2 protein and mRNA; nevertheless both exhibited significant correlations with clinico-pathological prognosticators. Higher expression of TGF-2 mRNA was connected to an early relapse in advanced stage than early stage patients. It is the first report to evaluate circulatory and transcript levels exhibiting TGF- switch and confirming the utility of TGF-2 as an important predictive marker for breast cancer.
ABSTRACT
Microbiology in-spite of being a crucial subject for understanding the basic principles with their application in infectious disease fails to impress the undergraduate medical students probably because they are taught the subject in isolation without much clinical context. To help students learn important concepts of microbiology by shifting the focus from didactic classroom setting to the patient care setting, we introduced hospital projects focusing on selected concepts of microbiology. The students (n=103) in their 2nd phase of MBBS studying para-clinical subjects were randomly divided in test and control groups. Test group was sent to the hospital with specific objectives for a defined duration. The difference in the level of understanding and knowledge in the selected topics for both the groups was judged by pre and post test. Perception of faculty and students towards the whole process was collected through feedback questionnaires, framed with a four point scale as per the Kirkpatrick's evaluation model. The test group (average pre-test score 9.64 to post-test score 16.28) showed a remarkable improvement in the understanding and knowledge of topics in comparison to the control group (average pre-test score 10.12 to post-test score 12.5). This was highly significant (P value <0.001) by statistical analysis (paired T test). The process of sending the students to hospital for strengthening of the important microbiology concept is a novel idea. Students appreciated the process as they could understand the practical significance and relevance of the theory taught to them in classrooms. Time constraint was perceived as a major limiting factor. [Suman Singh et al. NJIRM 2011; 2(3) : 1-7]
ABSTRACT
Synthetic pyrethroids are the recent major class of broad spectrum, photostable, organic insecticides used in agricultural, domestic and veterinary applications and now account for more than 30% of global insecticide use. Cypermethrin is metabolized and eliminated significantly more slowly by fish than by mammals or birds, which may explain this compound's high toxicity in fish compared to other organisms. The present communication deals with histoanatomical alterations in the gonads of a local fresh water food fish, Channa punctatus exposed to 0.033 ppm (96 hr LC50 X 1/10) concentration of a synthetic pyrethroid, devicyprin (cypermethrin 25%) in aquatic medium of aged tap water for 15, 30 and 45 days respectively. In testis, exposure dependent histological damage has been observed in terms of vacuolization, condensation of spermatogonic cells, distortion of tubular epithelium, shrinkage of interstitial cells and general inflammatory responses. Longest exposure of 45 days has resulted in peculiar starry-sky appearance of the testicular tissue. Gross histo-anatomy of ovarian tissue reveals epithelial lesions, inflammatory responses, stromal hemorrhage, increased interstitium and shrinkage of yolk vesicles towards periphery These findings are quite suggestive of reproductive impairments leading to delayed gonadal maturity and adversely affecting processes of sperm production and ovulation and thus, the fish production.