RESUMO
In this study, we generated induced pluripotent stem cells (iPSC) from normal human small airway epithelial cells (SAEC) to investigate epigenetic mechanisms of stemness and pluripotency in lung cancers. We documented key hallmarks of reprogramming in lung iPSCs (Lu-iPSC) that coincided with modulation of more than 15,000 genes relative to parental SAECs. Of particular novelty, we identified the PRC2-associated protein, ASXL3, which was markedly upregulated in Lu-iPSCs and small cell lung cancer (SCLC) lines and clinical specimens. ASXL3 overexpression correlated with increased genomic copy number in SCLC lines. ASXL3 silencing inhibited proliferation, clonogenicity, and teratoma formation by Lu-iPSCs, and diminished clonogenicity and malignant growth of SCLC cells in vivo Collectively, our studies validate the utility of the Lu-iPSC model for elucidating epigenetic mechanisms contributing to pulmonary carcinogenesis and highlight ASXL3 as a novel candidate target for SCLC therapy. Cancer Res; 77(22); 6267-81. ©2017 AACR.
Assuntos
Células Epiteliais/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Fatores de Transcrição/genética , Animais , Linhagem Celular Tumoral , Células Cultivadas , Reprogramação Celular , Epigênese Genética , Perfilação da Expressão Gênica/métodos , Humanos , Células-Tronco Pluripotentes Induzidas/transplante , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Mucosa Respiratória/citologia , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Teratoma/genética , Teratoma/metabolismo , Fatores de Transcrição/metabolismo , Transplante HeterólogoRESUMO
Malignant pleural mesotheliomas (MPM) are notoriously refractory to conventional treatment modalities. Recent insights regarding epigenetic alterations in MPM provide the preclinical rationale for the evaluation of novel combinatorial regimens targeting the epigenome in these neoplasms.
RESUMO
BACKGROUND: Postoperative urinary retention (POUR) is a common entity following surgery, particularly after laparoscopic inguinal hernia repair. Here the intent is to investigate the incidence of POUR in all comers at a single institution following laparoscopic inguinal hernia repair. METHODS: A retrospective chart review of all patients who underwent laparoscopic hernia repair at our institution from January 2010 through December 2013 was performed. POUR was defined as the inability to spontaneously urinate following surgery, requiring straight catheterization or placement of a Foley catheter. Perioperative data including narcotic use, operative time, type of mesh, and intraoperative fluid use were also recorded for each patient. RESULTS: A total of 346 patients underwent laparoscopic inguinal hernia repair in the specified time period, 340 patients were included in this study. The incidence of POUR after laparoscopic inguinal hernia repair at our institution was 8.2 % (n = 28) with the most common presentation of POUR being failure to void (n = 23). Postoperative narcotic use of 6.5 mg or greater of morphine or morphine equivalent was associated with higher risk of POUR via ROC analysis (OR 2.5, 95 % CI 1.2-5.6, p = 0.025). In univariate analysis, age greater than 50 years was also a risk factor for developing POUR (OR 2.8, 95 % CI 1.2-6.4, p = 0.02). Factors not found to be significant included intraoperative IV fluids, history of BPH, unilateral versus bilateral repair, and preoperative void time in relation to surgery start. CONCLUSIONS: Minimizing postoperative narcotic medications may reduce the risk of developing POUR after laparoscopic inguinal hernia repairs. If possible surgeons should consider non-steroidal anti-inflammatory drugs, acetaminophen, or regional anesthetic blocks to minimize postoperative narcotic requirements.
Assuntos
Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Laparoscopia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Retenção Urinária/etiologia , Adolescente , Adulto , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Retenção Urinária/epidemiologia , Adulto JovemRESUMO
The increase in frequency of bariatric surgery has been accompanied by an increase in litigation involving patients and practitioners in this emerging field. With much being written about the medical aspects of bariatric surgery, the legal and risk management perspective of these procedures is now getting increased attention. This article examines from a legal and risk management perspective the issue of patient selection, informed consent, postoperative management, the use of promotional materials and other issues that can result in a doctor or facility being sued.
