Molecular characterization of irinotecan (SN-38) resistant human breast cancer cell lines

Background: Studies in taxane and/or anthracycline refractory metastatic breast cancer (mBC) patients have shown approximately 30% response rates to irinotecan. Hence, a significant number of patients will experience irinotecan-induced side effects without obtaining any benefit. The aim of this study was to lay the groundwork for development of predictive biomarkers for irinotecan treatment in BC. Methods: We established BC cell lines with acquired or de novo resistance to SN-38, by exposing the human BC cell lines MCF-7 and MDA-MB-231 to either stepwise increasing concentrations over 6months or an initial high dose of SN-38 (the active metabolite of irinotecan), respectively. The resistant cell lines were analyzed for cross-resistance to other anti-cancer drugs, global gene expression, growth rates, TOP1 and TOP2A gene copy numbers and protein expression, and inhibition of the breast cancer resistance protein (ABCG2/BCRP) drug efflux pump. Results: We found that the resistant cell lines showed 7-100 fold increased resistance to SN-38 but remained sensitive to docetaxel and the non-camptothecin Top1 inhibitor LMP400. The resistant cell lines were characterized by Top1 down-regulation, changed isoelectric points of Top1 and reduced growth rates. The gene and protein expression of ABCG2/BCRP was up-regulated in the resistant sub-lines and functional assays revealed BCRP as a key mediator of SN-38 resistance. Conclusions: Based on our preclinical results, we suggest analyzing the predictive value of the BCRP in breast cancer patients scheduled for irinotecan treatment. Moreover, LMP400 should be tested in a clinical setting in breast cancer patients with resistance to irinotecan

A new recurring chromosome 13 abnormality in two older patients with de novo acute myeloid leukemia: An Indian experience

We report here two cases of trisomy 13 in acute myeloid leukemia M1 subtype. short-term unstimulated bone marrow and peripheral blood lymphocyte culture showed 47, XY, +13 in all metaphase plates and trisomy 13 was confirmed with whole chromosome paint probes. Trisomy 13 in AML-M1 is a rare numerical abnormality. This is the first Indian report of sole trisomy 13 in AML-M1. Here, we present two cases of elder male patients, which may constitute a distinct subtype

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Not AvailableGNCH-1 a high yielding, wilt and leafhopper resistant castor hybrid was developed by Pulses and Castor Research Station, Navsari Agricultural University,Navsari, Gujarat and released byCentral Sub-Committee onCrop Standards, Notification and Release (CVRC) of Variety for Agricultural Crops in 2017 for commercial cultivation under irrigated situation of Gujarat State, India. The hybrid GNCH-1 was developed by crossing a pistillate line SKP-84 with a male line DCS-94. On an average of 18 trials conducted for five years in south and middle Gujarat, the hybrid GNCH-1 recorded a seed yield of 2545 kg/ha which is 13.8, 35.9 and 31.0 per cent higher yield over the checks GCH-7, DCH-519 and DCH-177, respectively. The hybrid had long primary spike (64.8 cm), more numbers of capsules per primary spike (78.4), matures within 110-112 days and medium height (70-80 cm) which makes it suitable for easy harvesting. The oil content of the hybrid GNCH-1 (47.0 to 48.0 %) revealed that it is at par with the checks. The hybrid screened for wilt at national wilt sick plots showed resistance reactions (< 20%) to wilt. GNCH-1 screened against leafhopper using infester row method during 2014-17 showed resistant reaction to leafhopper (hopper burn grade 0 to 1 on 0-4 scale). The hybrid demonstrated in the farmers fields for two years (2016-18) showed higher seed yield than the existing cultivars. Due to plasticity for sowing time, this new hybrid is a suitable choice for the farmers of south and middle Gujarat under irrigated condition during late kharif and rabi seasons and paddy based cropping systemNot Availabl