Fear of Cancer Recurrence and associated factors among breast cancer survivors in South India.

OBJECTIVE: Fear of Cancer Recurrence (FCR) is a universal phenomenon widely reported as an unmet need among cancer survivors. The present study aims to determine the patterns of FCR and its associated factors among breast cancer survivors in South India. METHODS: A longitudinal study was carried out with pre and post-assessment. RESULTS: Two hundred and forty eight breast cancer survivors (BCSv) were included in the study. The main finding for the pre versus post-study was the pattern of mean scores. It is observed that in all factors, the pre-mean scores were steadily higher than the post-mean scores the predictors for FCR scores were decrease of age (p = 0.016), BCSv living in joint family (p = 0.008) and who were self-funded (p = 0.031). CONCLUSIONS: FCR was a relatively common symptom reported by BCSv. The predictors for FCR were younger age, BCSv living in a joint family and who were self-funding for their treatment. In the pre and post-assessment, it could be concluded that BCSv has reported that the overall FCR and on other variables higher FCR mean scores were reported during the preassessment period.

Synergistic effect of metformin and vemurufenib (PLX4032) as a molecular targeted therapy in anaplastic thyroid cancer: an in vitro study.

BACKGROUND: Survival rate of patients affected with anaplastic thyroid carcinoma (ATC) is less than 5% with current treatment. In ATC, BRAFV600E mutation is the major mutation that results in the transformation of normal cells in to an undifferentiated cancer cells via aberrant molecular signaling mechanisms. Although vemurufenib is a selective oral drug for the BRAFV600E mutant kinase with a response rate of nearly 50% in metastatic melanoma, our study has showed resistance to this drug in ATC. Hence the rationale of the study is to explore combinational therapeutic effect to improve the efficacy of vemurafenib along with metformin. Metformin, a diabetic drug is an AMPK activator and has recently proved to be involved in preventing or treating several types of cancer. METHODS AND RESULTS: Using iGEMDock software, a protein-ligand interaction was successful between Metformin and TSHR (receptor present in the thyroid follicular cells). Our study demonstrates that combination of vemurufenib with metformin has synergistic anti-cancer effects which was evaluated through MTT assay (cytotoxicity), colony formation assay (antiproliferation evaluation) and suppressed the progression of ATC cells growth by inducing significant apoptosis, proven by Annexin V-FITC assay (Early Apoptosis Detection). Downregulation of ERK signaling, upregulation of AMPK pathway and precision in epithelial-mesenchymal transition (EMT) pathway which were assessed by RT-PCR and Western blot provide the evidence that the combination of drugs involved in the precision of altered molecular signaling Further our results suggest that Metformin act as a demethylating agent in anaplastic thyroid cancer cells by inducing the expression of NIS and TSHR. Our study for the first time explored cAMP signaling in ATC wherein cAMP signaling is downregulated due to decrease in intracellular cAMP level upon metformin treatment. CONCLUSION: To conclude, our findings demonstrate novel therapeutic targets and treatment strategies for undifferentiated ATC.

A facile gold nanoparticle-based ELISA system for detection of osteopontin in saliva: Towards oral cancer diagnostics.

In the current study, we emphasize that osteopontin is overexpressed in oral squamous cell carcinoma. Overexpression of osteopontin levels was confirmed by mRNA quantification studies and immunohistochemistry analysis. Based on this, a gold nanoparticle-based ELISA system was developed for non-invasive osteopontin detection. The incorporation of AuNRs (Gold nanorods) or AuNSs (Gold nanospheres) in the conventional ELISA improved the sensitivity of analyses. A considerably lowered detection limit in case of AuNR (detection limit: 0.02ngmL-1) and AuNS (detection limit: 0.03ngmL-1) modified assay was obtained as compared to commercially available OPN ELISA kit (detection limit: 0.14ngmL-1). The modified ELISA had a wide linear detection range (0.31-20ngmL-1), good reproducibility, and specificity against the tested interferents in the saliva. Finally, the nanoELISA was validated with osteopontin spiked in artificial and normal saliva samples and observed to show good recovery (95.4-97.85%), which indicates the application potential of the developed kit for real sample analysis.

Use of Fast Transfer Analysis Cartridges for Cervical Sampling and Real Time PCR Based High Risk HPV Testing in Cervical Cancer Prevention - a Feasibility Study from South India.

BACKGROUND: Molecular testing for human papillomavirus (HPV) is the most objective and reproducible of all cervical cancer screening tests and also less demanding in terms of training and quality assurance. However, there is an impending need for cost effective molecular HPV testing methods with sampling ease, easy storage measures and minimum turn around times suitable for a low resource setting. OBJECTIVE: Our aim was to evaluate the feasibility of using a fast transfer analysis (FTA) mini elute cartridge for cervical sampling to identify high risk HPV by real time PCR and to compare molecular HPV testing and Pap cytology testing to predict histologically confirmed cervical precancer (CIN 2+ lesions) in a cervical cancer prevention program. MATERIALS AND METHODS: This was conducted as a pilot study (n=200) on women sampled using FTA mini elute cartridges, genotyped by two different real time PCR assays, detecting 13 high risk HPV (HR HPV) species, including HPV16 along with its physical DNA status. Results obtained from each of the tests were compared and analysed using suitable statistical tests. RESULTS: With FTA mini elute cartridge samples HR HPV positivity was seen in 48/200 (24%). Of these, presence of HPV 16 DNA was observed in 28/48 (58.3%) women. High risk HPV was positive in 20% (37/185) of women with benign cytology and 73.3% (11/15) of women with abnormal cytology findings. A very significant correlation (χ2 = 22.090 ; p=0.000) was observed between cytology and HR HPV findings showing an increasing trend of HR HPV prevalence in 50% (1/2) of LSIL, 75% (3/4) of HSIL and 100% (3/3) of SCC. Of the CIN 2+ lesions identified by histopathology, 88.9% (8/9) had HR HPV. A significant association (χ2=11.223 ; p=0.001) of HR HPV and histopathologically confirmed CIN 2+ lesions was found. Sensitivity of the two tests were comparable but specificity of Pap testing was better (90.7% vs 70.4%) to predict histopathologically diagnosed cervical precancers. CONCLUSIONS: The current study explored the feasibility of using a FTA mini elute cartridge for cervical sampling for the first time in India as a part of a community based cervical cancer prevention program. We suggest that FTA based sampling is suitable and feasible for real time based HPV testing. Molecular HR HPV testing can be more sensitive and useful to identify high risk women requiring Pap testing which is more specific to detect histologically confirmed cervical precancer.

Molecular docking studies shows tivozanib and lapatinib as potential inhibitors of EML4-ALK translocation mediated fusion protein in non small cell lung cancer.

Identification of activating mutations in non-small cell lung cancers (NSCLC) has been a focus in recent years. This led to successful evidence of using tyrosine kinase inhibitors (TKIs) over the standard platinum doublet based chemotherapy as the first line treatment in the metastatic setting.The rearrangements of fusion protein EML4-ALK in NSCLC lead to the use of crizotinib for this class of tumors. Preclinical and Phase 1 clinical studies show that ceritinib is more effective against both crizotinib sensitive and resistant tumors. Although robust responses to crizotinib are observed in NSCLC harboring ALK mutations, majority of tumors eventually become resistant, posing a major challenge in treatment course. Thus, there is a need for the identification and development of second-generation of ALK inhibitors. Computer aided molecular docking data show Tivozanib and Lapatinib bind EML4-ALK with high score. Tivozanib is in clinical trials for renal cell cancer and Lapatinib is a known dual tyrosine kinase inhibitor effective in breast cancer patients with HER2 over-expression. Additional data on these compounds for use in EML4-ALK positive NSCLC will provide evidence for use in patients treated with crizotinib. Data shows the importance of computer aided molecular docking in developing candidates with improved activity for further consideration in vitro and in vivo validation.