Peritoneal carcinomatosis (PC) is a common pattern of recurrence in gastric cancer patients and is associated with a poor prognosis. This study aimed to evaluate the predictive value of the albumin-fibrinogen ratio (AFR) for PC in patients with gastric cancer and to develop two preoperative prediction models. A total of 745 gastric cancer patients were included in this study. Preoperative AFR, along with other serum markers and clinical tumor characteristics, was assessed. Univariate and multivariate logistic regression analyses were performed to determine the odds ratios (ORs) and 95

Gastric cancer is a prevalent gastrointestinal tumor. In the classical cascade of gastric cancer development, the gradual progression from non-atrophic gastritis, atrophic gastritis, intestinal metaplasia, to intraepithelial neoplasia eventually leads to early gastric cancer. We investigated the proteomic characteristics of chronic gastritis (CG), low-grade intraepithelial neoplasia (low-grade LGIN), and early gastric cancer (EGC). Additionally, we utilized transcriptomic databases to explore the expression patterns of ITGB2 across different stages of gastric tissue and its correlation with the prognosis of gastric cancer. The expression of ITGB2 was confirmed in cytological experiments, revealing that ITGB2 can influence the onset and progression of gastric cancer via the CXCL1-CXCR2 axis. This finding suggests that ITGB2 represents a novel biomarker for gastric cancer, making it a potential target for accurate diagnosis and treatment.

Acyl-CoA Synthetase long-chain family member 4 (ACSL4) is a member of acyl-CoA synthetase protein long-chain family, which is associated with amino acid synthesis, lipid synthesis and lipid peroxidation dependent iron death. However, the role of ACSL4 in generalized carcinoma remains unclear. We aim to analyze the expression and prognostic value of ACSL4 in pan-cancer, and further explore the correlation between ACSL4 and immune infiltration. Through ONCOMINE, TIMER (Tumor Immune Estimation Resource), GEPIA (Gene expression Profiling Interactive), UALCAN and HPA, ACSL4 expression patterns of in pan-cancer were analyzed. The prognostic value of ACSL4 was analyzed using PrognoScan and Kaplan-Meier Plotter databases. Furthermore, gene variation and epigenetic modification of ACSL4 were analyzed by cBioPortal and GSCA databases. Meanwhile, GEPIA and TIMER databases applied to evaluate the relationship between ACSL4 expression and immune infiltration. These results indicate that ACSL4 expression is down-regulated and associated with prognosis in most tumors. In general, lower ACSL4 expression shows more beneficial prognosis. The most common genetic alteration of ACSL4 is point mutation. ACSL4 is negatively correlated with DNA methylation levels in most cancers. ACSL4 mutations or hypomethylation are associated with poor prognosis. In addition, ACSL4 is positively correlated with immune infiltration in cancers. ACSL4 and immune infiltration are strongly associated with prognosis in BRCA (Breast invasive carcinoma) and SKCM (Skin Cutaneous Melanoma). ACSL4 mutation caused significant changes of immune infiltration in UCEC (Uterine Corpus Endometrial Carcinoma) and SARC (Sarcoma). ACSL4 may be a promising prognostic biomarker for pan-cancer and is closely associated with immune infiltration in the tumor microenvironment.

Bardet-Biedl syndrome 4 is the key protein to control cilia formation. In this study, bioinformatics method was used to screen the core genes related to the prognosis of breast cancer by analyzing the gene chip data of gene expression omnibus and the cancer genome atlas database, so as to provide a new candidate target for the treatment of breast cancer. Data were downloaded from the cancer genome atlas, gene expression omnibus to evaluate Bardet-Biedl syndrome 4 expression levels in breast cancer. Differentially expressed genes were screened by R package. Gene ontology and Kyoto encyclopedia of Genes and Genomes pathway enrichment analysis was used to explore the biological functions of differentially expressed genes. The correlation of differentially expressed genes used was, "corrplot" for visual analysis. The proteinprotein interaction relationship was constructed based on search tool for the retrieval of interacting genes/ proteins database and Cytoscape software and the key genes were obtained by module analysis with Cytoscape software molecular complex detection plugin and the prognostic value and survival of BardetBiedl syndrome 4 were evaluated by R package. Finally, the correlation between Bardet-Biedl syndrome 4 and clinicopathological parameters was also visualized by R package. These differentially expressed genes were mainly involved in response to peptide hormone, nuclear division, hormone secretion and transport and extracellular matrix. Genes were mainly involved in the Kyoto encyclopedia of genes and genomes pathway called Interleukin-17 signaling pathway. Bardet-Biedl syndrome 4 levels were found to be down regulated in breast cancer tissues compared with normal tissues. Survival analysis showed that low Bardet-Biedl syndrome 4 expression was associated with poor prognosis. These results were verified in clinical specimens, where in the Bardet-Biedl syndrome 4 protein levels were significantly down regulated in breast cancer tissues compared with non-breast cancer tissues. This study confirmed that Bardet-Biedl syndrome 4 can be used as an independent prognostic factor for the prognosis of breast cancer, which provides a basis for exploring a new target for the treatment of breast cancer.

Transcriptomes and DNA methylation of colon cancer at the single-cell level are used to identify marker genes and improve diagnoses and therapies. Seven colon cancer subtypes are recognized based on the single-cell RNA sequence, and the differentially expressed genes regulated by dysregulated methylation are identified as marker genes for different types of colon cancer. Compared with normal colon cells, marker genes of different types show very obvious specificity, especially upregulated genes in tumors. Functional enrichment analysis for marker genes indicates a possible relation between colon cancer and nervous system disease, moreover, the weak immune system is verified in colon cancer. The heightened expression of markers and the reduction of methylation in colon cancer promote tumor development in an extensive mechanism so that there is no biological process that can be enriched in different types.

目的:应用RNAi技术阻断VEGF基因表达后,观察结肠癌细胞系LS-174T细胞增殖和对结肠癌组织增殖的影响,探讨VEGF基因在结肠癌生长过程中的作用.方法:应用免疫组化法验证结肠癌细胞系表达VEGF蛋白;应用RNAi技术沉默结肠癌细胞系LS-174T中VEGF基因,并通过Western-Blot、RT-PCR等方法,观察沉默VEGF基因对结肠癌细胞生长的影响.结果:人的结肠癌细胞系中有不同程度的VEGF蛋白表达;沉默VEGF基因后,实验组结肠癌细胞系LS-174T的增殖和凋亡有显著的降低.因此,在肿瘤组织中的VEGF可能是通过调控肿瘤增值率和新生血管的生成,进而促进肿瘤的生长.

为了探究增强子介导的核内miRNA在结肠癌发生中的作用,本研究筛选了结肠癌中的差异表达的miRNA数据、结肠的特异性增强子数据、结肠癌中差异表达基因数据,利用细胞核内miRNA靶向增强子预测算法,筛选miRNA调控的结肠特异性增强子;利用增强子靶基因预测数据,筛选核内miRNA调控的差异表达靶基因,并且构建核内miRNA-靶基因网络,并通过网络的分析和筛选获得结肠癌中关键的致病基因,同时对网络中的靶基因进行GO的功能注释.结果表明,我们所构建的核内miRNA-激活调控靶基因网络包含miRNA-靶基因关系对2121个,259个节点,其中包含34个下调基因、183个上调的基因,7个下调的miRNA,35个上调的miRNA.而后我们分析了网络进行的节点度的整体分布情况,发现网络中大部分的节点的度都是小于10的,仅有少量miRNA结合和部分的差异表达基因节点的度大于10.核内miRNA主要通过激活调控了一些应激反应相关的功能和,同时,抑制调控了细胞周期、细胞凋亡、细胞死亡巨噬细胞代谢等相关功能,通过激活和抑制相关功能诱发结肠癌的发生.从核内miRNA的激活调控角度研究结肠癌的发病机制,是对原有细胞浆中miRNA抑制调控机制的补充,也为结肠癌的系统研究提供了新的视野.

INTRODUCTION:Controversies persist between associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and conventional staged hepatectomy. This meta-analysis aims to compare completion, regeneration capacity, and surgical outcomes between the two strategies.EVIDENCE ACQUISITION:We systematically searched PubMed, EMBASE, Cochrane Library, Medline. The main endpoints consisted of completion rate, future liver remnant (FLR) hypertrophy ratio, morbidity, major complication, minor complication, post-hepatectomy liver failure (PHLF) and mortality. Pooled data was assessed by the use of a random-effects model. Odds ratios (OR) were calculated for dichotomous outcomes and mean differences (MD) for continuous outcomes.EVIDENCE SYNTHESIS:Of the 124 identified studies, 7 were eligible and were included in our analysis (N.=525 participants). In the two groups, there was no statistical difference in morbidity (OR=1.62; 95% CI: 0.81-3.20; Z=1.37; P=0.17), minor complication rate (OR=1.27; 95% CI: 0.50-3.21; Z=0.51; P=0.61), PHLF rate (OR=0.87; 95% CI: 0.34-2.22; Z=0.30; P=0.76), mortality (OR=1.68; 95% CI: 0.59-4.83; Z=0.97; P=0.33). Meanwhile, statistical significance was showed in the completion rate (OR=8.29; 95% CI: 2.49-27.53; Z=3.45; P=0.0006), FLR hypertrophy ratio (MD=28.00; 95% CI: 16.06-39.93; Z=4.60; P<0.00001) and major complication rate (OR=1.83; 95% CI: 1.08-3.10; Z=2.26; P=0.02).CONCLUSIONS:Compared with conventional staged hepatectomy, ALPPS provides a higher completion rate and FLR hypertrophy ratio. However, it results in more major complications. Conventional staged hepatectomy is not better than ALPPS in the aspects of minor complication, PHLF, morbidity and mortality.

Overexpression of histone deacetylases (HDACs) is associated with higher metastatic rates and a poor prognosis in gastric cancer. However, the underlying mechanisms involved remain unclear. The present study aimed to investigate the molecular pathways that are involved in HDAC1-mediated metastatic activities in gastric cancer cells. First we used a microRNA (miRNA or miR) microarray to screen potential miRNAs whose expression can be altered by HDAC1 depletion. Of these miRNAs, miR-34a is important as it is often inactivated in cancer cells and acts as a tumor suppressor for various types of cancer. The reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) results confirmed that miR-34a was upregulated by HDAC1 knockdown. Cells depleted of HDAC1 had lower abilities to migrate, invade and adhere, which were restored by a miR-34a antagomiR. Depletion of HDAC1 also resulted in impaired microfilaments and microtubules, while co-transfection of the miR-34a antagomiR attenuated these changes in the cellular cytoskeleton. The HDAC1/miR-34a axis regulated the expression and activation of CD44 and its downstream factors including Bcl-2, Ras homolog family member A (RhoA), LIM domain kinase 1 (LIMK-1) and matrix metalloproteinase (MMP)-2. The latter three proteins were responsible for the organization of tubulin and actin cytoskeleton and the formation of cellular pseudopodia. In conclusion, results of the present study indicated that HDAC1 depletion inhibits the metastatic abilities of gastric cancer cells by regulating the miRNA-34a/CD44 pathway, which may be a potential target for the treatment of gastric cancer.

This study investigated the contribution of survivin and its upstream regulators, AKT and hypoxia‐inducible factor 1α ( HIF –1α), to the resistance of gastric cancer cells to cisplatin ( CDDP ). We found that over‐expression of survivin increased the resistance of SGC 7901 and BGC 823 gastric cancer cells to CDDP . Its over‐expression abrogated CDDP ‐induced inhibition of cell proliferation and CDDP ‐induced cell apoptosis. In contrast, down‐regulation of survivin expression using small hairpin RNA (sh RNA ) vectors and the small‐molecule inhibitor YM 155, or inhibition of survivin function using a recombinant cell‐permeable dominant‐negative survivin protein (d NS ur9), promoted CDDP ‐induced apoptosis. CDDP ‐resistant sub‐lines generated from the parental SGC 7901 and BGC 823 cells by exposure to increasing concentrations of CDDP expressed higher levels of HIF –1α and survivin in response to hypoxia, and higher levels of phosphorylated AKT (p AKT ). Specific inhibition of AKT reduced the expression of HIF –1α and survivin, whereas specific inhibition or depletion of HIF –1α reduced survivin expression but had no effect on the expression of phosphorylated AKT . The expression levels of survivin affected the therapeutic efficacy of CDDP in treating gastric tumors in mice. Specific inhibition of survivin, AKT and HIF –1α enhanced the sensitivity of CDDP ‐resistant cells to CDDP . Specific inhibition of survivin, AKT and HIF‐1α synergized with CDDP to suppress the growth of gastric tumors that had been engineered to overexpress survivin. In summary, the results provide evidence that up‐regulation of survivin by AKT and HIF –1α contributes to CDDP resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer.

Objective To investigate the efficacy and molecular mechanisms of AAV-HO-1 inducing immuno-telorance in rats.Methods An orthotopic liver transplantation model by DA to Lewis was set up using Kamada' s two cuff technique.PBS,empty AAV or purified AAV-HO-1 was injected into the portal vein and incubated for 2 h at the donor liver cold preserved stage,and then OLT was done.The media survival time (MST),serum levels of interleukin (IL)-2 and tumor necrosis factor (TNF)-α,infiltration of CD4 +,CD8 + and Treg (CD4 + CD25 + Foxp3 +) cells into donor livers and percent of Treg in the spleen were examined.A mixed lymphocyte reaction (MLR) was performed.Results Recipients transplanted with AAV-HO-1-perfused liver allografts had a median survival time of 30 days,which was significantly longer than that in the PBS group (11 days) and empty AAV group (12 days) (both P ＜0.01).Overexpression of HO-1 reduced the production of IL-2 and TNF-α,inhibited infiltration of CD4+ and CD8 + cells,and increased infiltration of Treg ceils into donor livers.Splenocytes from the tolerant recipients had higher percentages of Treg cells,and responded poorly to the allogeneic donor splenocytes.Conclusion Persistent expression of HO-1 in the donor livers by intraportal delivery of AAV-HO-1 can prolong the survival by expanding Treg cells,suggesting that AAV-HO-1 can induce immuno-tolerance in liver allograft in rats.

The hypoxic microenvironment inside solid tumors, including hepatocellular carcinoma (HCC), is a major cause of tumor resistance to chemotherapy. The recently identified hypoxia‐inducible factor (HIF)‐2 executes the hypoxia response. Its expression feature and transcriptional targets indicate a possible dominance of HIF‐2 in regulating genes in HCC. The aim of the present study was to determine whether transfection of siRNA targeting HIF‐2α could enhance the efficacy of doxorubicin, the most commonly used drug in the treatment of HCC. Transfection of HIF‐2 siRNA into human HCC cells downregulated the expression of HIF‐2α, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)‐α, and cyclin D1, but had little effect on the expression of HIF‐1α, fms‐related tyrosine kinase‐1 (Flt‐1), the glucose transporter (GLUT)‐1, and lactate dehydrogenase A (LDHA). Doxorubicin itself only downregulated VEGF expression. Furthermore, HIF‐2 siRNA inhibited proliferation, induced cell cycle arrest at the G0/G1 phase, and acted synergistically with doxorubicin to inhibit the growth of human HCC cells in vitro. Transfection of HIF‐2 siRNA also downregulated tumoral expression of HIF‐2α, VEGF, TGF‐α, and cyclin D1 in vivo, and acted synergistically with doxorubicin to suppress the growth of HepG2 tumors established in immunodeficient mice by inhibiting cell proliferation, tumor angiogenesis and microvessel perfusion. The results of the present study suggest that targeting HIF‐2α with siRNA warrants investigation as a potential strategy to enhance the efficacy of doxorubicin in the treatment of HCC. (Cancer Sci 2012; 103: 528–534)

Objective To investigate sensitivity of colon cancer cells to 5-fluorouracil after downregulation of XIAP gene expression. Method Colon cancer cells HCT-8 and HCT116 were transfected with a short hairpin RNA targeted to XIAP by liposome, cells viability were examined.5-fluorouracil was applied into two kinds of colon cancer cells. Tumor cells sensitiviy to chemotherapeutic drug was evaluated. Caspase-3 activity in tumor cells was examined by Western blot. Result After downregulation of XIAP expression, cell growing viability of these two kinds of colon cancer cells was restricted, HCT-8 resistance to 5-fluorouracil was reversed ( P ＜ 0. 01 ), HCT116 sensitivity to 5-fluorouracil was enhanced (P ＜ 0.05), caspase-3 expression in colon cancer cells was highly activated, apoptosis inducing activity of 5-fluorouracil was increased significantly. Conclusions XIAP expression was a important mechanism in colon cancer cells HCT-8 and HCT 116 resistant to 5-fluorouracil, sensitivity to 5-fluorouracil of HCT-8 and HCT-116 was increased by downregulation of XIAP expression.

患者女，48岁。一年前无明显诱因出现持续性上腹部疼痛，伴腹胀，一周左右症状自行缓解，但仍有反复，无恶心及呕吐。4日前疼痛再次加重，当地医院治疗效果不佳，于2009年9月8日入我院。体检：体温36.5℃，脉搏82次/min，血压145/102 mmHg(1 mmHg=0.133 kPa)，呼吸18次/min。心肺正常，腹平软，未触及肿块，上腹部轻压痛，无反跳痛。肝脾肋下未触及。实验室检查：血常规及肝功、肾功未见异常，CA19-9为3.85 U/ml。彩超示胰腺回声欠均匀，胰管偏宽，左上腹囊性占位。CT示胆囊炎，胰尾部占位。

Objective To explore sensitivity changes of colon cancer cells HCT116 to irinotecan after targeted restriction of livin gene expression.Methods A short hairpin RNA(shRNA)of livin gene in vector was transfected into colon cancer cells HCT116,the interference effect was evaluated by Western blot,HCT116 cells were exposed to irinotecan in 0.01,0.1,1,10μg/mL concentration,respectively, and sensitivity to irinotecan was evaluated by MTT,caspase-3 activity also was examined by colorimetric assay.Results Livin gene expression was effectively inhibited by targeted shRNA,sensitivity to irinotecan was increased after inhibition of livin expression,caspase-3 was also activated in tumor cells.Conclusion Apoptosis pathway can be activated by targeted restriction of livin expression,anti-tumor effect of irinotecan on colon cancer cells can be also increased.

由中华医学会外科学分会脾功能与脾外科学组及<中华创伤杂志>、<肝胆外科杂志>编辑部联合主办,哈尔滨医科大学附属第一医院和安徽医科大学附属第一医院承办的"2010国际腹部创伤暨第十届全国脾脏外科学术研讨会"于2010年6月4～6日在合肥市召开.来自国际、国内的30余位著名专家应邀出席会议.美国Roger A.Orsini教授、俄罗斯Dubinkin Vladimir教授、日本Takashi Tajiri教授、韩国Chang Moo Kang博士及黎介寿院士、巴德年院士、夏穗生教授、姜洪池教授等知名专家到会并作精彩的专题报告.参会代表300余人.大会由全国脾功能与脾外科学组副组长乔海泉教授主持.