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Acute myeloid leukemia (AML) is an aggressive blood cancer characterized by poor survival outcomes. Further, due to the extreme molecular heterogeneity of the disease, drug treatment response varies from patient to patient. The variability of drug response can cause unnecessary treatment in more than half of the patients with no or partial therapy responses leading to severe side effects, monetary as well as time loss. Understanding the genetic risk factors underlying the drug response in AML can help with improved prediction of treatment responses and identification of biomarkers in addition to mechanistic insights to monitor treatment response. Here, we report the results of the first Exome-Wide Association Study (EWAS) of ex-vivo drug response performed to date with 175 AML cases and 47 drugs. We used information from 55,423 germline exonic SNPs to perform the analysis. We identified exome-wide significant ( p  < 9.02 × 10 − 7 ) associations for rs113985677 in CCIN with tamoxifen response, rs115400838 in TRMT5 with idelalisib response, rs11878277 in HDGFL2 with entinostat, and rs2229092 in LTA associated with vorinostat response. Further, using multivariate genome-wide association analysis, we identified the association of rs11556165 in ATRAID , and rs11236938 in TSKU with the combined response of all 47 drugs and 29 nonchemotherapy drugs at the genome-wide significance level ( p  < 5 × 10 − 8 ). Additionally, a significant association of rs35704242 in NIBAN1 was associated with the combined response for nonchemotherapy medicines ( p  = 2.51 × 10 − 8 ), and BI.2536, gefitinib, and belinostat were identified as the central traits. Our study represents the first EWAS to date on ex-vivo drug response in AML and reports 7 new associated loci that help to understand the anticancer drug response in AML patients.

Aim: To report symptoms and findings of lacrimal duct malfunction after topical mitomycin C (MMC) for conjunctival neoplasia. Methods: 14 consecutive patients treated with 1–6 cycles of topical 0.04% MMC four times daily for periods of 2 weeks were interviewed about symptoms of lacrimal duct malfunction. Patients who complained of tearing had examination of the puncta and canaliculi including probing and lacrimal duct irrigation. Results: Nine patients complained of epiphora after topical MMC. Three of these patients had normal puncta and canaliculi, patent to irrigation. In these patients epiphora ceased spontaneously after probing and irrigation. The additional six patients had stenosis of the punctum (n = 3), the common canaliculus (n = 1), both puncta and both canaliculi (n = 1) and complete occlusion of the lower canaliculus (n = 1). Conclusion: Obstruction of the puncta or canaliculi is not an infrequent event after topical 0.04% MMC.