Our findings suggest that up-regulation of Anxa2 may play an important role in modulating proliferation and invasion of breast cancer MCF-7 cells through regulation of many relevant downstream target genes.

Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3), a pro-apoptosis protein regulated by the methylation status of its promoter, has been implicated in inducing autophagy. However, the roles of BNIP3 and BNIP3-induced autophagy under hypoxia remain uncertain in esophageal squamous cell carcinoma (ESCC). Two esophageal squamous cancer cell lines, CAES17 and KYSE140, were selected on the basis of the expression and methylation status of BNIP3 to investigate the features of BNIP3 under hypoxia. Hypoxia increased cell death and the expression of BNIP3, whose promoter status was lower methylation, in a time-dependent manner. BNIP3 knockdown by RNA interference downregulated cell death. These studies demonstrated that the exposure of ESCC cells to hypoxia increased the autophagic punctate distribution of MDC staining and GFP-LC3 and that autophagy rate could be inhibited by BNIP3-siRNA. In addition, under hypoxia, cells transfected with BNIP3-siRNA exhibited a lower apoptosis rate than the control, and the apoptosis induced by BNIP3 exhibited a caspase-independent manner. Furthermore, the administration of the autophagic inhibitor 3-methyladenine (3-MA) could augment BNIP3-induced cell apoptosis and death, suggesting that autophagy plays a protective role under hypoxia. Together, our studies indicated that BNIP3 exerts prodeath effects through the induction of caspase-independent apoptosis under hypoxia in ESCC, though BNIP3-induced autophagy acting as a survival mechanism.

followed by Obinutuzumab maintenance for 3 years then Obinutuzumab on-demand for MRD positive patients. The LYMA-101 primary objective was the MRD negativity rate after 4 cycles of O-DHAP. MRD in the BM was assessed by IGH clonospecific or bcl1-JH PCR, and quantification with a sensitivity of at least 10 -4 was reach by dd-PCR following Euro-MRD lymphoma group recommendations. We hypothesized that O-DHAP would be considered as an effective induction chemotherapy regimen if MRD negativity was ≥ 70%. We calculated that a minimum of 83 patients should be included (α risk of 0.05 and β of 0.20 one-sided test). Results:We enrolled 86 patients between Nov 2016 and May 2018.One patient withdrew consent before starting treatment. Sixty-three patients (73.3%) were male and median age was 55.5 years ). MIPI and MIPI-b risk scores were low in 47 (54.7%) and 9 (10.5%) cases, intermediate in 24 (27.9%) and 38 (44.2%) cases and high in 14 (16.3%) and 21 (24.4%) cases. Fifteen patients (17.4%) presented with a blastoid variant. At the time of analysis, median FU was 14 months (3.8-24.4). Twelve patients out of 85 were not evaluable for MRD, essentially due to purely nodal disease and no detectableMCL clone in PB or BM. Among the 73 MRD-informative patients, 62 reached MRD negativity in the BM (84.9%) while 6 were MRD positive after O-DHAP. The remaining 5 patients were not evaluated because 4 stopped treatment during induction due to AEs and one progressed then died. 72 patients underwent ASCT and 68 started Obinutuzumab maintenance. Twelve patients stopped treatment before ASCT (including disease progression in 2 cases and AE in 7 cases), 3 before maintenance (2 because of AE, one died during ASCT), and 9 during maintenance (including disease progression in one case, death in another, AE in 4 cases or other malignancies in 2 cases). In the whole population (n=85), 3 patients progressed, three died. At one year, PFS is 93.4% (IC95%, 84.7-97.2) and OS is 96% (IC95%, 88.1-98.7). Conclusion: The Lyma-101 trial successfully achieved its primary endpoint (84.9% of MRD BM negativity after induction) and demonstrates the high efficacy of O-DHAP as induction chemotherapy regimen before ASCT with an unprecedented high level of MRD negativity, which predict better PFS and OS. Longer FU is needed to evaluate patient outcome after O-DHAP/ASCT/Obinutuzumab on-demand maintenance. However, both PFS and OS are highly encouraging at one year. Introduction: Zanubrutinib is a selective and irreversible BTK inhibitor that has demonstrated potent inhibition of BTK in prior studies, with minimal, off-target inhibition of other kinases. We present updated safety and efficacy results from a phase 2 study of zanubrutinib in patients with R/R MCL. Methods: In this single-arm, multicenter phase 2 study (ClinicalTrials. gov NCT03206970), oral zanubrutinib (160 mg BID) was given to R/R MCL patients until disease progression (PD) or unacceptable toxicity. Primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC) acco...

Our findings indicate that targeting OCT4 could improve cisplatin effect in NSCLC, confirming their role in modulating cisplatin sensitivity.

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