Death-related gastric necrosis after Laparoscopic Adjustable Gastric Banding in the early post-operative period

We report a case of a rare complication of Laparoscopic Adjustable Gastric Banding (LAGB) as a cause of death in the immediate post-operative period. The number of relevant reports and postmortem images presented in the literature is extremely restricted. Gastric necrosis may constitute a cause of death after LAGB in the early post-operative period. Postmortem examination reveals the extension of gastric ischemia and necrosis, responsible for the lethal outcome. To date, only one case of gastric necrosis after LAGB in the immediate post-operative period leading to death has been reported, according to authors' knowledge. The diagnosis of this complication may be delayed on the grounds of its rarity. In our opinion, surgeons should be aware of the clinical state implying gastric ischemia early after LAGB, so as to recognize and, in turn, to treat it promptly

A comparison of the provisional clinical diagnosis of death with autopsy findings

Abstract: Autopsy rates have been in decline for the last half of the century. On the other hand, advanced technology does not seem to have reduced clinical errors. Autopsy retains a role in the evaluation of clinical practice, but its value is under consideration. The aim of the study was to determine the rates of disparity between clinical diagnosis and autopsy findings. Key Words: autopsy findings; clinical diagnosis of death; postmortem; clinical accuracy; hospital; cause of death T he word "autopsy" is from Greek (meaning to see oneself) and has come to refer to the systematic examination of a dead person for medical, legal and/or scientific purposes Clinical autopsy rates have been in decrease for the last half of the century. The autopsy rates in American and European hospitals have been progressively declining, from approximately 60% in the 1960s to 10% or less toda

Critical roles of protein methyltransferases and demethylases in the regulation of embryonic stem cell fate

Accumulating evidence has recently shown that protein methyltransferases and demethylases are crucial regulators in either maintaining pluripotent states or inducing differentiation of embryonic stem cells. These enzymes control pluripotent signatures by mediating activation or repression of histone marks, or through direct methylation of non-histone proteins. Importantly, chromatin modifiers can influence the fate of many differentiation-related genes by loosening chromatin and allowing for transcriptional activation of lineage-specific genes. Genome-wide studies have unraveled diverse changes in methylation patterns following embryonic stem cell differentiation, with redistribution of heterochromatic and euchromatic marks, underlying the importance of chromatin modifiers in governing the fate of embryonic stemness. Furthermore, the development of small molecule inhibitors targeting these agents may shed light in potential clinical implementation to reprogram embryonic stem cells for biomedical therapeutics. Ever since the pioneering introduction of induced pluripotent stem cells, the challenge for application in regenerative medicine and broader medical therapeutics has commenced

Abstract 4041: SUV39H2 inhibition enhances sensitivity of breast cancer cells to doxorubicin through downregulation of γ-H2AX production

Abstract Accumulating evidence has demonstrated the biological importance of protein methyltransferases in human tumorigenesis, and several small molecular inhibitors targeting these enzymes have been developed. Moreover, inhibiting pathways involved in DNA repair has been shown to enhance the cytotoxicity of DNA-damaging agents. Herein, we report the development of a potent SUV39H2 inhibitor (OTS193320) that decreases global histone H3 lysine 9 tri-methylation (H3K9me3) levels in cancer cells and attenuates cancer cell proliferation, and suppresses the tumor growth in mouse xenograft models. SUV39H2 (Suppressor of variegation 3-9 homolog 2), is a protein methyltransferase known to methylate histone H3 at lysine 9 (H3K9), and recently reported to methylate histone H2AX at lysine 134, which enhances the accumulation of phosphorylated H2AX (γ-H2AX) and regulates the DNA repair pathway in human cancer. SUV39H2 is highly expressed in many cancer types, including lung and breast cancers, while its expression levels are restricted to testis in normal adult tissues. Exposure of OTS193320 to two triple negative breast cancer cell lines attenuated H3K9me3 levels in a dose-dependent manner and triggered apoptotic cell death. Combination of OTS193320 and doxorubicin (DOX) resulted in reduction of γ-H2AX levels compared to single agent DOX, as visualized on western blot and immunocytochemical analysis. Furthermore, combination therapy attenuated the levels of p53-binding protein 1, which is reported to co-localize with γ-H2AX foci, compared to single agent DOX. Cell viability assays demonstrated a significant growth suppressive effect when OTS193320 was combined with DOX, compared to single agent treatment of either drug, suggesting chemosensitization to DOX. Importantly, in a mouse xenograft model of A549 lung cancer cells, we observed a tumor growth inhibition of 60.8% at day 14 with 25mg/kg intravenous administration of the inhibitor, without significant body weight loss or toxicity. Immunohistochemical staining of tumors treated with the inhibitor demonstrated a significantly lower number of Ki-67 positive cells and attenuated distribution patterns of H3K9me3 compared to the control tumors. Collectively, our results demonstrate that SUV39H2 inhibition may be a promising approach to develop a novel class of anti-cancer treatment. Citation Format: Theodore Vougiouklakis, Vassiliki Saloura, Yo Matsuo, Yusuke Nakamura. SUV39H2 inhibition enhances sensitivity of breast cancer cells to doxorubicin through downregulation of γ-H2AX production [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4041. doi:10.1158/1538-7445.AM2017-4041</jats:p