Tryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy

PurposeA relatively low response to chemotherapy has been reported for hormone receptor (HR)-positive breast cancer. In this study, we investigated the role of tryptophanyl-transfer RNA synthetase (WARS) in the chemotherapeutic response of HR-positive breast cancer.MethodsPre-chemotherapeutic needle biopsy samples of 45 HR-positive breast cancer patients undergoing the same chemotherapeutic regimen were subjected to immunohistochemistry. To investigate the biological functions of WARS in HR-positive breast cancer, we conducted cell viability assay, flow cytometry analysis, caspase activity assay, Quantitative real-time polymerase chain reaction, and western blotting using WARS gene-modulated HR-positive breast cancer cells (T47D, ZR-75-1, and MCF7).ResultsWARS overexpression in HR-positive breast cancer patients showed a significant correlation with favorable chemotherapy response. Downregulation of WARS increased cell viability following docetaxel treatment in tumor cell lines. On the other hand, WARS overexpression sensitized the therapeutic response to docetaxel. Additionally, downregulation of WARS caused a decrease in the number of apoptotic cell populations by docetaxel. Poly (ADP-ribose) polymerase cleavage and caspase 3/7 activity were increased in docetaxel-treated tumor cells with WARS overexpression.ConclusionOur results suggest that WARS might be a potential predictor for chemotherapy response in patients with HR-positive breast cancer as well as a novel molecular target to improve chemosensitivity.     

β-blocker therapy for infantile hemangioma

ABSTRACT

Introduction

Fifteen percent of proliferating infantile hemangioma (IH) require intervention because of the threat to function or life, ulceration, or tissue distortion. Propranolol is the mainstay treatment for problematic proliferating IH. Other β-blockers and angiotensin-converting enzyme (ACE) inhibitors have been explored as alternative treatments.     

First experience with robotic pancreatoduodenectomy in Singapore

INTRODUCTIONRecent studies reported that laparoscopic pancreatoduodenectomy (LPD) is associated with superior perioperative outcomes compared to the open approach. However, concerns have been raised about the safety of LPD, especially during the learning phase. Robotic pancreatoduodenectomy (RPD) has been reported to be associated with a shorter learning curve compared to LPD. We herein present our initial experience with RPD.METHODSA retrospective review of a single-institution prospective robotic hepatopancreaticobiliary (HPB) surgery database of 70 patients identified seven consecutive RPDs performed by a single surgeon in 2016–2017. These were matched at a 1:2 ratio with 14 open pancreatoduodenectomies (OPDs) selected from 77 consecutive pancreatoduodenectomies performed by the same surgeon between 2011 and 2017.RESULTSSeven patients underwent RPD, of which five were hybrid procedures with open reconstruction. There were no open conversions. Median operative time was 710.0 (range 560.0–930.0) minutes. Two major morbidities (> Grade 2) occurred: one gastrojejunostomy bleed requiring endoscopic haemostasis and one delayed gastric emptying requiring feeding tube placement. There were no pancreatic fistulas, reoperations or 90-day/in-hospital mortalities in the RPD group. Comparison between RPD and OPD demonstrated that RPD was associated with a significantly longer operative time. Compared to open surgery, there was no significant difference in estimated blood loss, blood transfusion, postoperative stay, pancreatic fistula rates, morbidity and mortality rates, R0 resection rates, and lymph node harvest rates.CONCLUSIONOur initial experience demonstrates that RPD is feasible and safe in selected patients. It can be safely adopted without any compromise in patient outcomes compared to the open approach.     

MicroRNA‐361‐3p is a potent therapeutic target for oral squamous cell carcinoma

MicroRNAs (miRNAs) can act not only as tumor suppressor genes but also as oncogenes. Oncogenic miRNAs (oncomiRs) could therefore provide opportunities for the treatment of human malignancies. Here, we aimed to identify oncomiRs present in oral squamous cell carcinoma (OSCC) and addressed whether targeting these miRNAs might be useful in treatment for cancer. Functional screening for oncomiRs in a human OSCC cell line (GFP‐SAS) was carried out using the miRCURY LNA microRNA Knockdown Library – Human version 12.0. We identified a locked nucleic acid (LNA)/DNA antisense oligonucleotide against miR‐361‐3p (LNA‐miR‐361‐3p) which showed the largest degree of growth inhibition of GFP‐SAS cells. Transfection with a synthetic mimic of mature miR‐361‐3p resulted in an approximately 20% increase in the growth of GFP‐SAS cells. We identified odd‐skipped related 2 (OSR2) as a miR‐361‐3p target gene. Transfection of GFP‐SAS cells with LNA‐miR‐361‐3p caused a significant increase in the expression levels of OSR2. Cotransfection of a OSR2 3′‐UTR luciferase reporter plasmid and LNA‐miR‐361‐3p into GFP‐SAS cells produced higher levels of luciferase activity than in cells cotransfected with the LNA‐nontarget. We assessed the effect of LNA‐miR‐361‐3p on the in vivo growth of GFP‐SAS cells. We found that LNA‐miR‐361‐3p significantly reduced the size of s.c. xenografted GFP‐SAS tumors, compared to the control group treated with LNA‐NT. Finally, we observed that miR‐361‐3p is overexpressed in OSCC tissues. These results suggest that miR‐361‐3p supports the growth of human OSCC cells both in vitro and in vivo and that targeting miR‐361‐3p could be a useful therapeutic approach for patients with OSCC.