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Objective To evaluate the clinical efficacy of comprehensive treatment for synchronous primary advanced gastric and esophageal cancer by propensity score matching (PSM). Methods A total of 2 551 patients with advanced gastric cancer admitted to Jiangsu Province Hospital of Chinese Medicine from January 2013 to December 2022 were retrospectively analyzed. Among them, 45 patients with synchronous primary esophageal cancer were distributed to the observation group, and 2 506 patients without esophageal cancer were distributed to the control group. Through the PSM method, the control group was matched with the observation group and the equilibrium samples of covariates between two groups were obtained. The overall survival(OS) between the two groups were compared. Results Both observation and control group contained 45 patients in this study. According to the treatment regimen, the patients in the observation group was divided into radical resection treatment subgroup (n=22) and chemoradiotherapy (CRT) subgroup (n=23). In the radical resection subgroup, 4 patients underwent the simultaneous surgical resection of gastric and esophageal tumors through proximal gastrectomy with the Ivor Lewis operation. Eighteen patients underwent endoscopic submucosal dissection(ESD) of their esophageal tumors and gastric cancer radical resection. Radical resection of gastric cancer combined with preoperative chemoradiotherapy of esophageal cancer was performed in the CRT subgroup. Survival analysis showed that OS in the observation group was significantly shorter than that in the control group (P=0.042) and there was no significant difference in OS between the radical resection subgroup and the control group (P=0.799). The 1 -, 3 -, and 5-year survival rates of the patients in the CRT subgroup were significantly lower than those of the control group (P=0.003). While the 1 -, 3 -, and 5-year survival rates of the patients in the radical resection subgroup were not statistically significant, compared to those of the CRT subgroup (P=0.071).Conclusions Multidisciplinary and comprehensive treatment can significantly improve the prognosis of patients with synchronous primary advanced gastric and esophageal cancer. Radical resection of gastric cancer combined with ESD of esophageal cancer is an optional treatment for patients with gastric cancer complicated with early esophageal cancer. Radical resection of gastric cancer combined with CRT of esophageal cancer can improve the prognosis of patients with advanced gastric cancer complicated with unresectable esophageal cancer.

DNA replication checkpoint (Mec1-Mrc1-Rad53 in budding yeast) is an evolutionarily conserved surveillance system to ensure proper DNA replication and genome stability in all eukaryotes. Compared to its well-known function as a mediator of replication checkpoint, the exact role of Mrc1 as a component of normal replication forks remains relatively unclear. In this study, we provide in vitro biochemical evidence to support that yeast Mrc1 is able to enhance the activity of DNA polymerase ε (Pol ε), the major leading strand replicase. Mrc1 can selectively bind avidly to primer/template DNA bearing a single-stranded region, but not to double-stranded DNA (dsDNA). Mutations of the lysine residues within basic patch 1 (BP1) compromise both DNA binding and polymerase stimulatory activities. Interestingly, Mrc1-3D, a mutant mimicking phosphorylation by the Hog1/MAPK kinase during the osmotic stress response, retains DNA binding but not polymerase stimulation. The stimulatory effect is also abrogated in Mrc1 purified from cells treated with hydroxyurea (HU), which elicits replication checkpoint activation. Taken together with previous findings, these results imply that under unperturbed condition, Mrc1 has a DNA synthesis stimulatory activity, which can be eliminated via Mrc1 phosphorylation in response to replication and/or osmotic stresses. [ABSTRACT FROM AUTHOR]

Background: Recent studies have implicated that members of the DICKKOPF (DKK) were causally involved in large number of human cancers. This study was designed to investigate the relationship between the genetic variations of DKK family genes and the risk of gastric cancer (GC).Methods: Six SNPs (single nucleotide polymorphisms) of DKK family genes, including rs2241529 in DKK1, rs3733635, rs17037102 and rs419764 in DKK2, rs3206824 in DKK3 and rs2073664 in DKK4, were selected and genotyped by restriction fragment length polymorphism (RFLP) and TaqMan SNP genotyping methods in 409 GC cases and 554 cancer-free controls in the Han population in eastern China.Results: None of the six SNPs achieved significant association with the overall GC risk and stratified analysis by age, gender, smoking status, drinking status, tumor location and pathological classification confirmed these non-significant associations.Conclusions: Our study indicated that the studied six SNPs of DKKs would not be the risk factors for GC in this Han Chinese population. Studies of larger population for different ethnicities will be needed to warrant our findings. [ABSTRACT FROM AUTHOR]

Methanogenesis and its key small-molecule methyltransferase Mtr complex are poorly understood despite their pivotal role in Earth's global carbon cycle. Mtr complex is encoded by a conserved mtrEDCBAFGH operon in most methanogens. Here we report that two discrete lineages, Methanococcales and Methanomicrobiales, have a noncanonical mtr operon carrying two copies of mtrA resulting from an ancient duplication. Compared to mtrA-1, mtrA-2 acquires a distinct transmembrane domain through domain shuffling and gene fusion. However, the nontransmembrane domains (MtrA domain) of mtrA-1 and mtrA-2 are homogenized by gene conversion events lasting throughout the long history of these extant methanogens (over 2410 million years). Furthermore, we identified a possible recruitment of ancient nonmethanogenic methyltransferase genes to establish the methanogenesis pathway. These results not only provide novel evolutionary insight into the methanogenesis pathway and methyltransferase superfamily but also suggest an unanticipated long-lasting effect of gene conversion on gene evolution in a convergent pattern., (Copyright © 2015 Wang et al.)

Objective: To explore the feasibility of short-term neoadjuvant chemotherapy (NACT) in patients with advanced gastric cancer (AGC), and to compare clinical efficacy of short-term neoadjuvant chemotherapy with different ways., Methods: Clinical data of 310 AGC patients treated with one course of NACT using EOF regimen(epirubicin, oxaliplatin and fluorouracil plus calcium folinate) in our hospital from January 2008 to December 2011 were retrospectively analyzes. Efficacy was compared between regional arterial infusion chemotherapy and intravenously chemotherapy., Results: All the 310 AGC patients completed one course of NACT and none was interrupted by adverse events. Postoperative pathological remission rate was 33.9% (105/310) and 5 patients (1.6%) had complete pathological remission. The pathologic response rate in the regional arterial infusion chemotherapy group was higher than that in the intravenously chemotherapy group(42.4% vs. 23.6%, P = 0.001). Multivariate analysis revealed that chemotherapy method(HR=1.827, 95% CI:1.006-3.316, P = 0.048) was associated with significantly higher pathologic response., Conclusions: Pathological response rate is quite low following short-term NACT. Regional arterial infusion chemotherapy with short-term NACT can improve the pathological response rate of advanced gastric cancer.