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Objective:Research in Eastern India especially among children and adolescents for acute lymphoblastic leukemia (ALL) have not been well documented until recently when it was conducted at a cancer institute of tertiary care with primary objectives of examining and correlating different cell surface markers involved with respect to disease surveillance thereby highlighting it as a strong prognostic marker for future diagnosis and treatment.Materials and Methods:A total of 500 consecutively selected ALL patients were diagnosed and treated according to National Cancer Institute protocol (MCP 841) for a period of 24-88 months during this hospital-based study.Results:Of the total, 50.4% had a higher incidence of T-ALL and 47.6% had pro-B, B-cell precursor ALL. Disease free survival and event free survival were remarkably higher in B-ALL adolescent patients as compared to T-ALL, who had significantly lower overall survival ratio. Prevalence of T-ALL was also observed in relapse cases for adolescent patients.Conclusions:We conclude that there is an increased prevalence of T-ALL among adolescents in Eastern India. Immunophenotypic analysis might help in proper evaluation and prediction of treatment outcomes with an increased thrust on studying age-specific incident rates enabling well planned future treatments for improved and better outcome.

Methylphophorbide a (MPa) has been isolated from the ethanol extract of the wheat grass plant. Its antioxidative efficacy is evaluated by hydroxyl radical scavenging activities and reducing capacity which are significantly up regulated in comparison with aqueous extract of the plant. The compound shows iron-binding capacity where the Fe(2+) binds with MPa by two types of binding patterns with dissociation constants 157.17 and 27.89. It has antioxidative and cytotoxic effects on HeLa and Hep G2 cells. The cancerous cell survivability decreases with increasing concentration of MPa. These findings have provided evidence for the traditional use of the wheat grass plant in the treatment of cancers, oxidative stress and iron overloaded disorders.

Endocrine resistance is a major clinical issue. AP-1 is a transcription factor downstream of different growth factor receptors (GFR) and stress-related signaling cascades implicated in endocrine resistance. We have previously shown that acquired endocrine resistance is associated with increased AP-1 activity. Moreover, AP-1 modulates the estrogen receptor (ER) transcriptional program, especially upon high GFR signaling. We therefore hypothesized that interfering with AP-1 could circumvent endocrine resistance. Methods and results: AP-1 was genetically inhibited by siRNA or by stable expression of an inducible dominant-negative (DN) c-Jun in MCF7 cells. In vitro, siRNA c-Jun significantly inhibited the growth of acquired tamoxifen resistant (TamR) MCF7 derivatives (>95% inhibition, p = .001) but not of parental cells ( p = .06). Xenografts of two inducible DN c-Jun clones were established in nude mice. Mice were randomized to continued estrogen (E2) supplementation or to either estrogen deprivation (ED) or Tam, all in the presence or absence of DN c-Jun. AP-1 blockade significantly reduced time to tumor response ( p = .014 and p = .006 for the two clones) and time to tumor disappearance ( p = .001 and p = .0034) in the Tam group, with similar results in the ED group. In addition, AP-1 blockade significantly delayed TamR by increasing time to tumor doubling ( p = .002). Furthermore, induction of DN c-Jun resulted in dramatic tumor shrinkage after long-term Tam treatment, suggesting reversal of endocrine resistance with AP-1 blockade. Interestingly, no significant effect was observed on E2-stimulated tumor growth. Immunohystochemistry showed that AP-1 blockade reduced proliferation and induced apoptosis. A gene signature of our TamR MCF7 xenografts significantly overlapped ( p < 2E-16) with a putative gene list associated with EGF-induced ER-DNA binding sites that mostly contain the AP-1 motif. Pathway analysis of these genes identified the AP-1 member c-Fos as the most represented transcription factor. Conclusions: We show that AP-1 blockade increases tumor sensitivity and circumvents resistance to endocrine therapy. We suggest that AP-1 is critical in a switch in the ER transcriptional program and may be a new hallmark of endocrine resistance. Disclosure: All authors have declared no conflicts of interest. Background: Triple negative breast cancer (TNBC), defined by estrogen, progesterone and HER2 negativity, is a heterogeneous disease with limited targeted therapy. Molecular and immunohistochemical stratification have already identified several TNBC subgroups, characterised by different biological processes with possible implication for therapy. A clear picture of the various TNBC entities and their relationship(s), however, is still missing. Aim: To shed light on this problem we have analysed a collection of 111 needle-macrodissected, clinically-annotated TNBCs using an approach based on the integration of DNA copy-number aberrations, transcriptional data and publically available gene signatures. Methods: Allel...

e18043 Background: Non-small cell lung carcinoma is usually an incurable disease with average overall survival of 7-9 months. But studies in recent years have shown that adenocarcinoma in nonsmokers with epidermal growth factor receptor (EGFR) positivity has shown disease control for longer duration. Female patients with adenocarcinoma where EGFR is positive show higher response rate with EGFR blocker. In eastern India, lung cancer contributes 21.3% of all cancers and female lung cancer contributes about 20% of them. The aim of our study was to see the age at diagnosis, histological type, EGFR status, smoking status and the response rate with Gefitinib, an EGFR tyrosine kinase inhibitor, for the female patients with carcinoma of lung. Methods: We randomly selected 50 female lung cancer patients, who had not previously received chemotherapy, during the period from November, 2006 to November, 2011. The mean age group at diagnosis was 55 years (range 26-85 years). 48 patients (96%) never had smoking habit, 2 (4%) were active smokers and the rest were passive smokers. Results: Twenty six (52%) patients had histological type of adenocarcinoma, 18 (36%) had squamas cell carcinoma, 4 were poorly differentiated and 2 (4%) had large cell carcinoma. Trucut biopsy showed EGFR positivity in 22 patients. All patients were started with single agent Gefitinib therapy at least for 6 months; after that according to response rate, same dose was continued. If there were progression of the disease, they were switched over to other chemotherapeutic agents. The median follow up was 1.5 years; the progression free survival (PFS) was seen in 19 (38%) patients. Adenocarcinoma patients with EGFR positivity had significantly higher PFS than those with non-adenocarcinoma and EGFR negative status. There was no difference of response rate between smokers and nonsmokers (never-smokers). Older patients showed higher response rates. Conclusions: Our data suggested that older patients with adenocarcinoma and EGFR positivity had long term progression free survival. So in developing countries like ours, where molecular diagnosis is not feasible many a times, this result might help clinicians to select a beneficial subgroup in female lung cancer patients.

e13030 Background: Simple BRCA screening is insufficient for ‘event-free survival’ as breast cancer is clinically and pathologically an extremely heterogeneous disease. Targeting Breast Cancer Stem Cells (BCSCs) present in bone marrow and breast tissues is a lucrative alternative. Identification of BCSCs is salient aspect of our research. Invasive and mesenchymal property of BCSCs with CD44+/CD24low/ALDH1+ phenotype has made them a promising target for eliminating metastatic capacity of primary tumors. We hypothesize that ability to therapeutically attack stem cell hinges upon identifying unique targets like cell surface markers and this will decide development of specific target therapies. Methods: A total of 10 early chemo-naive patients with biopsy proven triple-negative metastatic breast cancer in the age group of 18-36 yr.s (mean age 28 yr.s) were selected randomly and tested for CD44/CD24 cell surface markers following immunosorting using magnetic cell sorter and immunophenotyping by flowcytometric analysis. Isolated BCSCs were cultured for in vitro drug sensitivity towards platinum, anthracycline and docetaxel. Correlation was drawn between cell differentiation, % of stem cells and drug response. Accordingly chemotherapy was designed for a particular patient. % of BCSCs in pre- and post-chemotherapeutic condition was further compared. Results: We have detected BCSCs in 90% of cases. Among positive samples, 89% patients showed platinum sensitivity and rest were found to be anthracycline sensitive. No sensitivity to docetaxel was observed. In lieu of this, cisplatin was applied in vivo and % of BCSCs came down to 6.58% from initial 11.16% (for a representative case). Conclusions: Thus primary aim to target BCSCs at the onset of tumors in breast cancer patients to control metastasis and relapse of disease was somewhat obtained. We further plan to correlate ratio of selected markers present in patients in pre- and post-chemotherapeutic condition with time to recurrence, mortality, morbidity and progression-free survival. Finally, if no BCSCs prevail after chemotherapy, then patients would be kept under observation and if traces are found, we would proceed to targeted therapy trial like PARP inhibitor or autologous stem cell replacement.