Similarities and differences in the transcriptional regulation of the leptin gene promoter in gastric and adipose cells

AbstractThe stomach was reported to synthesize and secrete leptin mainly in the gastric lumen. Gastric leptin release is markedly increased after food intake, by vagal cholinergic stimulation and by cholecystokinin and secretin. Here we show that human gastric MKN-74 cells produce leptin that increases upon challenge with cholecystokinin, insulin, glucocorticoids and all-trans retinoic acid through activation of the leptin gene promoter. In addition, we demonstrate that forskolin and BRL37344 which increased cAMP levels, fail to affect the activity of leptin gene promoter in MKN74 expressing β3-adrenoceptor cells but, induce a 2-fold decrease in this activity in adipose 3T3-L1 cells. These data described for the first time, similarities and more interestingly, differences in the regulation of the leptin gene promoter in gastric cells as compared to adipocytes

Laparoscopic vs. open surgery for the treatment of iatrogenic colonoscopic perforations: a systematic review and meta-analysis

Quality assessment of the included non-randomized studies based on the Newcastle-Ottawa Scale (NOS). (DOCX 57 kb

Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study

Les adénocarcinomes de l’intestin grêle (AIG) sont des tumeurs rares et de mauvais pronostic à un stade avancé. Les données publiées concernant l’efficacité de la chimiothérapie palliative sont peu nombreuses. Le but de notre étude était d’évaluer l’efficacité et la tolérance de différents protocoles « modernes » de chimiothérapie et de comparer l’efficacité des chimiothérapies à base de sels de platine dans le traitement de première ligne des AIG avancés. Cette étude rétrospective multicentrique a inclus 93 patients (sexe masculin : 53 % ; âge médian : 56 ans ; site primitif duodénal : 53 %) avec un AIG avancé (métastatique : 86 %) traités par LV5FU2 (n = 10), FOLFOX (n = 48), FOLFIRI (n = 19) ou LV5FU2- cisplatine (n = 16). Le taux de toxicité grade 3-4 était significativement plus fréquent dans le groupe de patients traités par LV5FU2-cisplatine (75 %) comparativement aux autres groupes de patients (p = 0,001). Les médianes de survie sans progression (SSP) étaient de 7,7 ; 6,9 ; 6,0 et 4,8 mois (p = 0,16) et les médianes de survie globale (SG) étaient de 13,5 ; 17,8 ; 10,6 et 9,3 mois (p = 0,25) pour les quatre groupes de patients traités par LV5FU2, FOLFOX, FOLFIRI et LV5FU2-cisplatine, respectivement. En analyse multivariée, l’indice de performance OMS à 2 (p < 0,0001) ainsi que des taux élevés d’ACE (p = 0,02) et de CA 19-9 (p = 0,03) avant traitement étaient les seuls facteurs indépendants significativement associés à un mauvais pronostic. Dans le sous-groupe de patients traités par sels de platine, ceux qui ont reçu une chimiothérapie par FOLFOX avaient de meilleures SSP et SG que les patients traités par LV5FU2-cisplatine. En analyse multivariée, le traitement par FOLFOX était un facteur significatif et indépendant de survie prolongée en termes de SSP (p < 0,0001) et SG (p = 0,02). Ainsi, cette étude, la plus grande rapportée à ce jour, suggère d’une part que l’indice de performance OMS et les taux d’ACE et CA 19-9 avant traitement sont des facteurs pronostiques indépendants de survie et, d’autre part que la chimiothérapie par FOLFOX est le traitement de choix en première ligne des AIG avancés

Microbial Dysbiosis in Colorectal Cancer (CRC) Patients

The composition of the human intestinal microbiota is linked to health status. The aim was to analyze the microbiota of normal and colon cancer patients in order to establish cancer-related dysbiosis

Nonsense-Mediated mRNA Decay Impacts MSI-Driven Carcinogenesis and Anti-Tumor Immunity in Colorectal Cancers

Nonsense-mediated mRNA Decay (NMD) degrades mutant mRNAs containing premature termination codon (PTC-mRNAs). Here we evaluate the consequence of NMD activity in colorectal cancers (CRCs) showing microsatellite instability (MSI) whose progression is associated with the accumulation of PTC-mRNAs encoding immunogenic proteins due to frameshift mutations in coding repeat sequences. Inhibition of UPF1, one of the major NMD factors, was achieved by siRNA in the HCT116 MSI CRC cell line and the resulting changes in gene expression were studied using expression microarrays. The impact of NMD activity was also investigated in primary MSI CRCs by quantifying the expression of several mRNAs relative to their mutational status and to endogenous UPF1 and UPF2 expression. Host immunity developed against MSI cancer cells was appreciated by quantifying the number of CD3ε-positive tumor-infiltrating lymphocytes (TILs). UPF1 silencing led to the up-regulation of 1251 genes in HCT116, among which a proportion of them (i.e. 38%) significantly higher than expected by chance contained a coding microsatellite (P<2×10−16). In MSI primary CRCs, UPF1 was significantly over-expressed compared to normal adjacent mucosa (P<0.002). Our data provided evidence for differential decay of PTC-mRNAs compared to wild-type that was positively correlated to UPF1 endogenous expression level (P = 0.02). A negative effect of UPF1 and UPF2 expression on the host's anti-tumor response was observed (P<0.01). Overall, our results show that NMD deeply influences MSI-driven tumorigenesis at the molecular level and indicate a functional negative impact of this system on anti-tumor immunity whose intensity has been recurrently shown to be an independent factor of favorable outcome in CRCs

2020 WSES guidelines for the detection and management of bile duct injury during cholecystectomy.

Bile duct injury (BDI) is a dangerous complication of cholecystectomy, with significant postoperative sequelae for the patient in terms of morbidity, mortality, and long-term quality of life. BDIs have an estimated incidence of 0.4-1.5%, but considering the number of cholecystectomies performed worldwide, mostly by laparoscopy, surgeons must be prepared to manage this surgical challenge. Most BDIs are recognized either during the procedure or in the immediate postoperative period. However, some BDIs may be discovered later during the postoperative period, and this may translate to delayed or inappropriate treatments. Providing a specific diagnosis and a precise description of the BDI will expedite the decision-making process and increase the chance of treatment success. Subsequently, the choice and timing of the appropriate reconstructive strategy have a critical role in long-term prognosis. Currently, a wide spectrum of multidisciplinary interventions with different degrees of invasiveness is indicated for BDI management. These World Society of Emergency Surgery (WSES) guidelines have been produced following an exhaustive review of the current literature and an international expert panel discussion with the aim of providing evidence-based recommendations to facilitate and standardize the detection and management of BDIs during cholecystectomy. In particular, the 2020 WSES guidelines cover the following key aspects: (1) strategies to minimize the risk of BDI during cholecystectomy; (2) BDI rates in general surgery units and review of surgical practice; (3) how to classify, stage, and report BDI once detected; (4) how to manage an intraoperatively detected BDI; (5) indications for antibiotic treatment; (6) indications for clinical, biochemical, and imaging investigations for suspected BDI; and (7) how to manage a postoperatively detected BDI

Helicobacter pylori et cancer gastrique

Le cancer gastrique est observé partout dans le monde. Sa fréquence est particulièrement élevée au Japon et en Amérique du Sud. Son incidence n’a cessé de décroître en France depuis la fin de la Seconde Guerre mondiale et, actuellement, ce cancer n’est responsable que d’environ 10 % des décès. L’infection par Helicobacter pylori, la spécificité génétique et le régime alimentaire de l’hôte sont les principaux facteurs impliqués dans ce cancer. Éradiquer Helicobacter pylori chez les apparentés au premier degré d’un sujet atteint de cancer gastrique et chez tout sujet ayant une gastrite atrophiante et un autre cancer digestif paraît une mesure préventive sage.Gastric cancer is a worldwide cancer especially frequent in Japan and South America. This cancer affects 10 to 70 people per 100 000 according to the countries. Since the end of the Second World War, the incidence of gastric cancer has been decreasing in France and accounts for less than 10 % of mortality. Helicobacter pylori infection, host genetic background, food regimen are known to be involved in this cancer. Helicobacter pylori should be eradicated in selected patients, such as patients’ relatives with documented gastric cancer as well as patients having another gastrointestinal cancer

DNA Methylation Is a Main Key for Bacteria-Related Colon Carcinogenesis

Colorectal cancer (CRC) is the second most common cause of cancer deaths in men and women combined [...