Glutathione S-Transferase Alpha 4 Promotes Proliferation and Chemoresistance in Colorectal Cancer Cells.

Glutathione S-transferase alpha 4 (GSTA4) is a phase II detoxifying enzyme that is overexpressed in colorectal cancer (CRC) and regulated by the oncogenic transcription factor AP-1. However, the role of GSTA4 in these CRC cells remains unclear. In this study, we investigated the roles of GSTA4 in the CRC cells by inactivating GSTA4 in HCT116 human CRC cells (Defined as HCT116ΔGSTA4) using the CRISPR/Cas9 gene editing. Cell proliferation, clonogenicity, and susceptibility to chemotherapeutic drugs were analyzed in vitro and in a xenograft model. The results showed that loss of GSTA4 significantly decreased cell proliferation and clonogenicity, whereas it increased intracellular reactive oxygen species and cell susceptibility to 5-fluorouracil (5-FU) and oxaliplatin. Additionally, exposure of HCT116ΔGSTA4 cells to 5-FU increased the expression of γH2AX, a hallmark of double-stranded DNA breaks. In contrast, no remarkably increased γH2AX was noted in oxaliplatin-treated HCT116ΔGSTA4 cells compared with HCT116 cells. Moreover, loss of GSTA4 blocked the AKT and p38 MAPK pathways, leading to proliferative suppression. Finally, the xenograft model showed decreased tumor size for HCT116ΔGSTA4 cells compared with HCT116 cells, confirming in vitro findings. These findings suggest that GSTA4 is capable of promoting proliferation, tumorigenesis, and chemoresistance and is a potential target for CRC therapy.

Medical, Surgical, and Wound Care Management of Ulcerated Infantile Hemangiomas: A Systematic Review [Formula: see text].

Ulcerated infantile hemangiomas may present a therapeutic challenge, especially if there is concurrent hemorrhage or infection. The aim of this study was to systematically review the published evidence on the treatment of ulcerated hemangiomas, focusing on wound healing as the outcome of interest. We searched MEDLINE, Embase, SCOPUS, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science from inception to July 2016. Seventy-seven studies met our inclusion criteria. One study was a randomized controlled trial, 30 were observational studies, and 46 were case reports or case series. There is significant heterogeneity among the methods used. We reviewed 1239 patients in total. Of the 197 treated with oral propranolol, 191 (97.0%) achieved complete ulcer healing. Thirty-one patients failed corticosteroid therapy (oral, intralesional, or topical) and were subsequently successfully treated with other therapies. Surgical resections were typically performed for larger hemangiomas and those causing complications. None of the therapies discussed appear to offer significant advantages over others. Therefore, treatment decisions should be individualized based on location of disease, extent, symptoms, feasibility, cost, and parental preference.

Drug-Induced Pyoderma Gangrenosum: A Review.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that may be caused by an adverse drug reaction. We discuss the clinical presentation and outcomes of 52 cases of drug-induced PG reported to date in the literature. We conducted our literature search for case reports of drug-induced PG using keywords on PubMed and Medical Subject Heading (MeSH) terms on MEDLINE and EMBASE. To assess the probability that each case of PG was related to drug therapy, we used the Naranjo criteria. We identified 44 studies in the literature, with a total of 52 cases of drug-induced PG. The mean Naranjo score for cocaine-induced PG (n = 13) was 9.4, indicating a definite adverse drug reaction, while the mean Naranjo scores for isotretinoin (n = 5), propylthiouracil (n = 5), and sunitinib (n = 5) were 6.2, 6.8, and 7.4, respectively, indicating probable adverse drug reactions. Drugs should be considered as a possible triggering event whenever PG is diagnosed, and clinicians should particularly consider this in patients taking isotretinoin, propylthiouracil, or sunitinib, as well as in patients with a history of cocaine use.

Invasive Rothia infections in children with acute myeloid leukemia: A report from the Canadian infections in AML research group.

Rothia spp. (previously termed Stomatococcus) are normal flora that can cause invasive infections in immunocompromised hosts. The objective of this study was to describe infection characteristics and outcomes of Rothia spp. infections in a large cohort of children with newly diagnosed acute myeloid leukemia (AML). This retrospective chart review is a subanalysis of a larger study in which the aim was to identify factors associated with infection in pediatric patients with AML. Only sterile site infections occurring during chemotherapy were included. Among 578 children with AML, 17 (2.9%) children with at least 1 Rothia spp. infection were identified. All children were neutropenic at the time of infection. Eight (47%) had antecedent colitis or mucositis. Of the 17 infections, 16 were bacteremia and 1 was meningitis. Sepsis occurred in 4 patients, and 1 patient died due to infection. Rothia spp. infections are rare in pediatric AML but can cause significant morbidity and mortality. Future studies should describe trends in incidence and resistance patterns over time.