Role of epithelial - Stromal interaction protein-1 expression in breast cancer.

BACKGROUND AND AIMS: Epithelial stromal interaction protein-1 (EPSTI-1) is originally identified as stromal-fibroblast - induced gene in breast cancer. It was found to be involved in promotion of EMT, breast cancer invasion, metastasis and anchorage-independent growth in vitro. Strong expression was observed in various tissues as well as higher expression was observed in invasive breast cancer compared to normal breast. EPSTI-1 expression was evaluated from 106 pre-therapeutic breast cancer patients. EPSTI-1 expression was correlated with known clinico-pathological parameters of breast cancer to explore its role in breast carcinogenesis. SUBJECTS AND METHODS: EPSTI-1 expression was analyzed from the collected synchronous tissues [tumors, Malignant Lymph nodes (LN) and adjacent normal tissues (ANT)] of breast carcinoma patients (N = 106). The statistical correlation was performed using SPSS 16.0. RESULTS: In this study EPSTI-1 was significantly higher in LN compared to tumors (P < 0.001), and in tumors compared to ANT (P < 0.01) which is also reflected in ROC curve analysis (P < 0.0001). Further the small tumor size, stage I, grade I and tumors without stromal involvement exhibited significant lower expression compared to their counter parts. CONCLUSION: EPSTI-1 may have significant role in epithelial stromal interaction and disease extension. Moreover, it may be responsible for aggressive tumor behavior and involved in metastatic process which needs to be validated in larger cohort.

Enhancement of the cytotoxic effects of Cytarabine in synergism with Hesperidine and Silibinin in Acute Myeloid Leukemia: An in-vitro approach.

OBJECTIVES: Acute Myeloid Leukemia (AML) therapy continues to be a daunting challenge. Cytosine Arabinoside (Ara-C) is widely used to treat hematological malignancy in humans, but often becomes ineffective because of increased resistance to the drug which may lead to a worse prognosis. Therefore new strategies are needed to understand the mechanism responsible for drug resistance and to develop new therapies to overcome it. Research evidence based on natural compounds used alone or in combination with current chemotherapeutic agents proved their efficacy to treat and prevent cancer. Hesperidin and Silibinin displayed anti-cancer activity against various types of cancers and cell lines and can be used in combination with Cytarabine with the aim to increase cytotoxicy profile and reduction in drug resistance. Experimental Work: Primary cells obtained from AML patient's bone marrow were used to develop in-vitro model and further exposed to various concentration of Cytarabine (10 nM-5000 nM), Hesperidin (0.5 µM-100 µM) and Silibinin (0.5 µM-100 µM) alone and in combination with Cytarabine (Hesperidin-25 µM, Silibinin10 µM) to check cytotoxicity using MTT assay. Synergistic effect was evaluated by Combination Index method. RESULT AND CONCLUSION: In-vitro study of Hesperidin and Silibinin indicated their cytotoxicity at IC 50 value 50.12 µM and 16.2 µM, respectively. Combination Index study revealed Hesperidin and Silibinin both showed synergistic potential and decreased the IC 50 value of Cytarabine by ~5.9 and ~4.5 folds, respectively. Both natural compounds showed potential anti-leukemic activity hence may be used for AML therapy alone or in combination with other chemotherapeutic agents.