Design, 3D QSAR modeling and docking of TGF-ß type I inhibitors to target cancer.

Transforming growth factor-ß (TGF-ß) family members plays a vital role in regulating hormonal function, bone formation, tissue remodeling, and erythropoiesis, cell growth and apoptosis. TGF-ß super-family members mediate signal transduction via serine/threonine kinase receptors located on the cell membrane. Variation in expression of the TGF-ß type I and II receptors in the cancer cells compromise its tumor suppressor activities which direct to oncogenic functions. The present study was aimed to screen the potent TGF-ß type I inhibitors through atom based 3D-QSAR and pharmacophore modelling. For this purpose, we have chosen known TGF-ß type I inhibitors from the binding database. The PHASE module of Schrodinger identified the best Pharmacophore model which includes three hydrogen bond acceptors (A), one hydrophobic region (H), and one ring (R) as the structural features. The top pharmacophore model AAAHR.27 was chosen with the R2 value of 0.94 and validated externally using molecules of the test set. Moreover the AAAHR.27 model underwent virtual screening using the molecules from the NCI, ZINC and Maybridge database. The screened molecules were further filtered using molecular docking and ADME properties prediction. Additionally, the 7 lead molecules were compared with a newly identified compound "SB431542" (well known TGF-ß type I receptor inhibitor) and Galunisertib, a small molecule inhibitor of TGF-ß type I, under clinical development (phase II trials) using the docking score and other binding properties. Also a top scored screened molecule from our study has been compared and confirmed using molecular dynamic simulation studies. By this way, we have obtained 7 distinct drug-like TGF-ß type I inhibitors which can be beneficial in suppressing cancers reported with up-regulation of TGF-ß type I. This result highlights the guidelines for designing molecules with TGF-ß Type I inhibitory properties.

Assessment of in vitro cytotoxicity and in vivo antitumor activity of Sphaeranthus amaranthoides burm.f.

BACKGROUND: A number of plants have been used in Indian system of medicine such as ayurveda, unani and siddha, but most of these plants were not explored properly. Sphaeranthus amaranthoides (SA) Burm.f., is one such plant used as an energizer in siddha. OBJECTIVE: To evaluate the anticancer effect of chloroform extract of the whole plant of SA Burm.f. against Ehrlich ascites carcinoma bearing Swiss albino mice. MATERIALS AND METHODS: The anticancer effect of chloroform extract was investigated in Swiss albino mice bearing Ehrlich ascites carcinoma at two different dose levels. Acute toxicity studies were also performed to determine the safety of the extract. Mice injected with Ehrlich ascites carcinoma cells were treated with the extract of doses 200 and 400 mg/kg body weight and standard 5-fluorouracil 20 mg/kg body weight for 15 consecutive days. Animals were sacrificed on day 15 for determination of anticancer activity by evaluating tumor volume, nonviable and viable tumor cell count and hematological parameters. RESULTS: Mice treated with the extract showed a significant decrease in tumor volume and viable cell count and an increase in nonviable cell count and mean survival time. The hematological parameters were also found to be restored to a normal level. CONCLUSION: The results indicate that the chloroform extract was producing anticancer activity comparable with that of the standard 5-fluorouracil.

Role of template guided interstitial implants in breast conservation therapy.

Breast conservation therapy is currently considered as a viable alternative to mastectomy in early breast cancer. Radiotherapy by virtue of its ability to reduce local recurrences is an integral component of breast conservation therapy. Apart from irradiating the whole breast, the tumor bed is usually delivered a boost dose in breast conservation therapy to increase the local control rate. One of the methods which has been adopted to selectively boost the tumor bed to high doses is the use of per-operative high dose rate interstitial implants. This particular paper deals with our department's experience with breast conservation therapy using per-operative template guided, High Dose Rate (HDR) interstitial implants in early breast cancer. Local control rates, disease free survival and cosmetic benefit with this technique will be discussed along with literature review.

Passive immunization of rams (Ovis aries) against GnRH: effects on antibody titer, serum concentrations of testosterone, and sexual behavior.

The effect of immunoneutralization of gonadotropin-releasing hormone (GnRH) on serum concentrations of testosterone and sexual behavior was evaluated in sexually mature male sheep. In Experiment 1, GnRH1 rams (n=16) were passively immunized against GnRH (300 ml antiserum), control rams were either passively immunized against keyhole limpet hemocyanin (KLH, n=15) or surgically castrated (Wethers1, n=4). Sexual performance of the rams was assessed weekly for 3 weeks before and 6 weeks after immunization, using ovarihystertomized ewes actively immunized against GnRH. Experiment 2 evaluated the effects of repeated immunization. Rams were immunized with two aliquots (400 and 300 ml, respectively) of anti-GnRH sera (GnRH, n=5) or normal sheep serum (NSS, n=4), 2 weeks apart. Surgically castrated animals were used as a second control group (Wethers2). Administration of anti-GnRH sera, but neither anti-KLH nor NSS sera, resulted in marked reduction (P<0.05) in serum concentrations of testosterone. Sexual behavior was not consistently affected by administration of one aliquot of anti-GnRH sera, however repeated immunizations resulted in more persistent reduction in serum concentrations of testosterone and more consistent suppression of sexual behavior.

Usefulness of imprint and fine needle aspiration cytology (FNAC) in diagnosis of lymphadenopathies and other tumours.

Fifty cases of enlarged lymph nodes and fifteen cases of other tumours were selected and fine needle aspiration cytology (FNAC) and Imprint cytology was performed both as outpatient and pre-operative procedure. The aim of the study was to evaluate the accuracy of these methods of diagnosis. It was found that they are a rapid, easy and dependable method of diagnosis for all practising surgeons especially in semi-urban and small hospitals.