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Background: Novel tuppherapeutic strategies are urgently required to improve clinical outcomes of gastric cancer (GC). KIF15 cooperates with KIF11 to promote bipolar spindle assembly and formation, which is essential for proper sister chromatid segregation. Therefore, we speculated that the combined inhibition of KIF11 and KIF15 might be an effective strategy for GC treatment. Hence, to test this hypothesis, we aimed to evaluate the combined therapeutic effect of KIF15 inhibitor KIF15-IN-1 and KIF11 inhibitor ispinesib in GC. Methods: We validated the expression of KIF11 and KIF15 in GC tissues using immunohistochemistry and immunoblotting. Next, we determined the effects of KIF11 or KIF15 knockout on the proliferation of GC cell lines. Finally, we investigated the combined effects of the KIF11 and KIF15 inhibitors both in vitro and in vivo. Results: KIF11 and KIF15 were overexpressed in GC tissues than in the adjacent normal tissues. Knockout of either KIF11 or KIF15 inhibited the proliferative and clonogenic abilities of GC cells. We found that the KIF15 knockout significantly increased ispinesib sensitivity in GC cells, while its overexpression showed the opposite effect. Further, using KIF15-IN-1 and ispinesib together had a synergistic effect on the antitumor proliferation of GC both in vitro and in vivo. Conclusion: This study shows that the combination therapy of inhibiting KIF11 and KIF15 might be an effective therapeutic strategy against gastric cancer.

Portal hypertension may gradually lead to esophagogastric varices and splenomegaly in the decompensated stage of liver cirrhosis, which requires surgical treatment, if the disease worsens. Splenectomy with pericardial devascularisation is the routine surgery. One complex complication after splenectomy is upper gastric fistula which can seriously affect the perioperative recovery. Here, we present a case of a 51-year female patient, who recovered completely from non-operative treatment for gastric fistula after splenectomy and pericardial devascularisation. The occurrence of gastric fistula may be strongly related to preoperative preparation, intra-operative procedure and postoperative management. Therefore, personalised management is important for avoiding gastric fistula. Key Words: Gastric fistula, Splenectomy, Pericardial devascularisation, Portal hypertension.

Background: α-Aryl substituted nitroalkanes are important synthetic intermediates for the preparation of pharmaceutical molecules, natural products, and functional materials. Due to their scare existence in Nature, synthesis of these compounds has attracted the attention of synthetic and medicinal chemists, rendering α-arylation of nitroalkanes of an important research topic. This article summarizes the important advances of α- arylation of nitroalkanes since 1963. Results: After a brief introduction of the synthetic application and the reactions of nitroalkanes, this article reviewed the synthetic methods for the α-arylated aliphatic nitro compound. The amount of research on α-arylation of nitroalkanes using various arylation reagents and the discovery of elegant synthetic approaches towards such skeleton have been discussed. This review described these advances in two sections. One is the arylation of non-activated nitroalkanes, with an emphasis on the application of diverse arylation reagents; the other focuses on the arylation of activated nitroalkanes, including dinitroalkanes, trinitroalkanes, α-nitrosulfones, α-nitroesters, α-nitrotoluenes, and α-nitroketones. The synthetic application of these methods has also been presented in some cases. Conclusion: In this review, we described the progress of α-arylation of nitroalkanes. Although the immense amount of research on α-arylation of aliphatic nitro compounds has been achieved, many potential issues still need to be addressed, especially the asymmetric transformation and its wide application in organic synthesis.

Background Accumulating evidence indicated that long noncoding RNAs (lncRNAs) have a wide range of biological functions and may play significant roles in tumorigenesis and progression. However, the understanding of its functions and related competitive endogenous RNAs (ceRNAs) networks is much less than that of protein-coding genes, particularly in colon adenocarcinoma. Methods We comprehensively analyzed the sequencing data of protein-coding and noncoding RNAs in colon adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database. Next, we constructed colon adenocarcinoma-specific ceRNA network and evaluated the effect of these RNAs on overall survival (OS) for colon adenocarcinoma patients. Results Totally, 1138 differentially expressed lncRNAs (DElncRNAs), 245 microRNAs (DEmiRNAs), and 2081 mRNAs (DEmRNAs) were identified using a threshold of |log2FoldChange| >2.0 and adjusted P-value Conclusions These findings reveal several molecules might be novel important prognostic factors and potential treatment targets for colon adenocarcinoma. In addition, these observations contribute to a more comprehensive understanding of lncRNA-related ceRNA network and provide novel strategies for subsequent functional studies of lncRNAs in colon adenocarcinoma.

As a common lethal disease, cancer is now responsible for the majority of deaths worldwide and has been the single most important barrier to increasing life expectancy in the world. The pathogenesis of cancer has been the key point of cancer therapeutics research. The primary cilium, a solitary microtubule-based organelle, is considered to be an important sensor for receiving mechanical and chemical stimulation from other cells and environments; it plays an important role in a variety of signal transduction and disease processes. More importantly, the primary cilium can also function as an elaborate structure to regulate cell proliferation because ciliogenesis regulates cell division by sequestering the centriole. Recently, many new findings have suggested that the length and incidence of the primary cilium are closely connected to carcinogenesis and responses to cancer therapy. Here, we review relevant evidences proving that the primary cilium plays a key role in the occurrence and treatment of cancer. We also summarize the primary cilium-associated signaling pathways in cancer, including Wnt signaling, Hedgehog signaling, PDGFR signaling, and Notch signaling, and anticipate that targeting proteins localized in the primary cilium may be a potential anti-cancer strategy.

The optimal resection extent for middle-third advanced gastric cancer (AGC) still remains controversial. This study aimed to assess the long-term oncologic outcomes of laparoscopy-assisted distal gastrectomy (LADG) versus laparoscopy-assisted total gastrectomy (LATG) for middle-third AGC.A retrospective cohort study was conducted using data from 464 patients who underwent LADG or LATG between September 2007 and March 2013. Propensity score matching (PSM) were used for reducing the confounding effects to compare the long-term oncologic outcomes between two groups. Cox regression analysis was performed to clarify the prognostic factors.After PSM was performed, a well-balanced cohort of 376 patients (188 LADG and 188 LATG) was further analyzed. Of interest, the LADG group had a significantly shorter operative time (244.6 ± 28.0 vs. 259.1 ± 30.1, P 0.0001), less operative blood loss (142.9 ± 50.9 vs. 157.8 ± 54.1, P = 0.006), earlier day of first flatus (2.6 ± 0.8 vs. 2.9 ± 0.9, P = 0.014), fewer number of retrieved lymph nodes (36.5 ± 7.9 vs. 41.4 ± 9.8, P 0.0001), and shorter postoperative hospital stay (9.7 ± 1.3 vs. 10.7 ± 1.4, P 0.0001) than the LATG group. However, no significant differences were observed in days of eating liquid diet (P = 0.626) and days of eating soft diet (P = 0.353). The incidence of overall and severe postoperative complications (Clavien-Dindo grade ≥ IIIa) following the LADG group were significantly fewer than the LATG group (overall, 24.5% vs. 34.6%, P = 0.032; severe, 4.8% vs. 11.2%, P = 0.022). In addition, the LADG group had significantly more favorable overall survival (OS) and disease-free survival (DFS) rates than the LATG group (5-year OS rate, 55.6% vs. 41.8%, P = 0.002; 5-year DFS rate, 45.9% vs. 32.8%, P 0.001). In multivariate analyses, resection extent was not an independent prognostic factor for OS and DFS.This PSM cohort analysis has indicated LADG with D2 lymphadenectomy appeared to be safe and reasonable option for patients with middle-third AGC in general. LADG could contribute to improved survival.

Robot-assisted gastrectomy (RAG), as an alternative minimally invasive surgical technique, is gradually being used for the treatment of gastric cancer (GC). This study aimed to assess the feasibility and safety of RAG over conventional Laparoscopy-assisted gastrectomy (LAG) for the treatment of GC.We retrospectively analyzed all procedures (RAG and LAG) performed by one surgeon between 31 January 2017 and 1 December 2017. The short-term of surgical outcomes were compared between two groups and further subgroup analyses were performed.One hundred patients were enrolled in the RAG group and 135 in the LAG group. The demograghics and clinicopathologic characteristics are well matched between two groups. The RAG group had shorter postoperative hospital stay (11 (interquartile range 9-13) vs. 12 (10-14) day; p 0.0001), earlier day of first flatus (2 (2-3) vs. 3 (2.3-3) day; p 0.0001), and larger lymph nodes dissection (40.9 ± 13.1 vs. 35.4 ± 15.8; p = 0.004). Of interest, mean numbers of retrieved lymph nodes from station 6 (p = 0.002), 7 (p = 0.032), 10 (p = 0.025), 11p (p = 0.036), and 14v (p = 0.038) in RAG was significantly larger than LAG. However, no significant differences between two groups were observed in operative time (p = 0.136), operative blood loss (p = 0.434), days of eating liquid diet (p = 0.889), and postoperative complications (p = 0.752). In subgroup analyses, the similar results were observed.RAG for the treatment of GC is a safe and feasible procedure and beneficial for postoperative recovery of GC patients. However, further studies are needed to evaluate long-term and oncologic outcomes of RAG.

Objective: To analyze the clinical epidemiological characteristics of patients with gallbladder carcinoma recruited from 17 hospitals in five northwestern provinces of China (Shaanxi Province, Gansu Province, Qinghai Province, Ningxia Hui Autonomous Region, and Xinjiang Uygur Autonomous Region) from 2009 to 2013, and to summarize the clinical diagnosis and treatment data of gallbladder carcinoma. Methods: Clinical information of 2379 patients with gallbladder carcinoma from 17 hospitals in five northwestern provinces of China was retrospectively collected and analyzed using the âQuestionnaire for Gallbladder Carcinoma Patients in Northwestern Area of China.â All information was verified with EpiData software and analyzed with SPSS 13.0 software. Results: (1) Gallbladder carcinoma accounted for 2.7% (2379/86,609) of all biliary tract diseases during the study period, which was significantly higher than that from 1986 to 1998 (PÂ

Duodenal bulb adenocarcinoma is an extremely rare malignancy in the alimentary tract which has a low incidence rate and nonspecific symptoms. It is difficult to diagnose early, and the misdiagnosis rate is high. CT, MRI, upper gastrointestinal endoscopy, and other advanced imaging modalities should be combined to make a comprehensive evaluation. The diagnostic confirmation of this tumor type mainly depends on the pathological examination. The combination of surgery with other treatment modalities is effective. A review of reports on duodenal bulb adenocarcinoma with chemotherapy revealed 6 cases since 1990. However, there are few reports on neoadjuvant chemotherapy for the disease. In this report, preoperative S-1 in combination with oxaliplatin neoadjuvant chemotherapy achieved a complete pathological response in the treatment of duodenal bulb adenocarcinoma. Neoadjuvant chemotherapy shows a better clinical efficacy in the treatment of duodenal bulb adenocarcinoma, but its value needs to be further verified.

Colorectal cancer (CRC) is one of the most common cancers in the world. In recent decades, drug therapy and surgery have not achieved satisfactory results in curing CRC. The identification of cancer stem cells (CSCs) has provided a possible mechanistic explanation of CRC growth and metastasis. Traditional chemotherapy targets rapidly dividing cells, and since the CSCs can escape these therapies and become circulating cells, CSCs may be responsible for cancer relapse and metastasis. A better understanding of the roles of CSCs in the pathogenesis of primary CRC and its metastasis, as well as how these CSCs are regulated at the molecular level, is of paramount importance. In this review, we summarize the current understanding of the role of colorectal CSCs in CRC liver metastasis, and provide some insights on the potential implication of colorectal CSCs to better design therapeutic regimens and prevent CRC metastasis.

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet‑derived growth factor receptor α (PDGFRA) wild‑type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild‑type GIST samples compared with KIT/PDGFRA mutant GIST samples. Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs was conducted using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology‑Based Annotation System (KOBAS) online tools, respectively. Protein‑protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub‑networks using the Molecular Complex Detection (MCODE) plug‑in. Furthermore, enrichment analysis of DEGs in the modules was analyzed with KOBAS. In total, 546 DEGs were identified, including 238 upregulated genes primarily enriched in 'cell adhesion', 'biological adhesion', 'cell‑cell signaling', 'PI3K‑Akt signaling pathway' and 'ECM‑receptor interaction', while the 308 downregulated genes were predominantly involved in 'inflammatory response', 'sterol metabolic process' and 'fatty acid metabolic process', 'small GTPase mediated signal transduction', 'cAMP signaling pathway' and 'proteoglycans in cancer'. A total of 25 hub genes were obtained and four modules were mined from the PPI network, and sub‑networks also revealed these genes were primarily involved in significant pathways, including 'PI3K‑Akt signaling pathway', 'proteoglycans in cancer', 'pathways in cancer', 'Rap1 signaling pathway', 'ECM‑receptor interaction', 'phospholipase D signaling pathway', 'ras signaling pathway' and 'cGMP‑PKG signaling pathway'. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild‑type GISTs, including phosphatidylinositol‑4,5‑bisphosphate 3‑kinase, catalytic subunit γ, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb‑B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results.

Objective: Tissue factor (TF) is expressed abnormally in certain types of tumor cells, closely related to invasion and metastasis. The aim of this study was to construct a human gastric cancer cell line SGC7901 stably-transfected with human TF, and observe effects on oxaliplatin-dependent inhibition of invasion and the apoptosis induction. Methods: The target gene TF was obtained from human placenta by nested PCR and introduced into the human gastric cell line SGC7901 through transfection mediated by lipofectamine. Stably-transfected cells were screened using G418. Examples successfully transfected with TF-pcDNA3 recombinant (experimental group), and empty vector pcDNA3 (control group) were incubated with oxaliplatin. Transwell chambers were used to show change in invasive ability. Caspase-3 activity was detected using a colorimetric method and annexin-V/PI doublestaining was applied to detect apoptosis. Results: We generated the human gastric cancer cell line SGC7901/TF successfully, expressing TF stably and efficiently. Compared with the control group, invasion increased, whereas caspase-3 activity and apoptosis rate were decreased in the experimental group. Conclusion: TF can enhance the invasive capacity of gastric cancer cells in vitro. Its increased expression may reduce invasion inhibition and apoptosis-inducing effects of oxaliplatin and therefore may warrant targeting for improved chemotherapy.

Aim: Only seven cases of liver transplantation (OLT) with positive serum hepatitis B surface antigen (HBsAg) grafts have been reported in the world till now. Here we report the 4-year follow-up results and clinical pathologic characteristics of two recipients of chronic hepatitis B transplanted with HBsAg-positive cadaveric liver grafts from asymptomatic carriers. Methods: Lamivudine combined with hepatitis B immune globulin were used for the control of hepatitis B virus (HBV) infection in both of the recipients post-OLT. The liver functions, virus status and pathologic characteristics of two recipients were followed up according to the rounte protocol of Liver Transplantation Center of West China Hospital. Results: The serum HBV deoxyribonucleic acid (DNA) turned negative within 30 days post-OLT, but HBsAg remained positive for both of the recipients during follow up. HBV breakthrough occurred in one recipient at the month 12 post-OLT, with detectable serum HBV-DNA (740 copies/mL) and tyrosine-methionine-aspartate-aspartate motif mutation (rtM204I and rtM204V). After the replacement of lamivudine by adefovir dipivoxil 10 mg daily for 2 months, serum HBV-DNA of this recipient became undetectable again and maintained undetectable during follow up. Both of the recipients have survived for more than 4 years post-OLT, with stable liver function and mild hepatitis. Conclusion: Due to extreme scarcity of liver graft, we think that HBsAg-positive liver graft without active HBV-DNA replication and severe pathological manifestation from asymptomatic carriers may deserve consideration when no other graft is available in a bearable waiting time.

The aim of this study was designed to evaluate the outcomes of liver transplant recipients with chronic hepatitis B (CHB) receiving either lamivudine monotherapy or lamivudine combined with individualized low-dose hepatitis B immunoglobulin (HBIG) therapy.A total of 111 liver transplant recipients with CHB were divided not randomly into two groups according to the availability of HBIG before liver transplantation (LT). Thirty-two patients received lamivudine monotherapy (100 mg/d) and 79 patients received lamivudine (100 mg/d) combined with individualized low-dose HBIG (intramuscular administration) to maintain the titer of antibody to hepatitis B virus (HBV) surface antigen (anti-HBs) not less than 100 U/L. The patients were followed-up for a median time of 32 months (1 to 88 months).In the lamivudine monotherapy group, 5 patients hepatitis B relapsed (3/5 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 7.1%, 14.3% and 17.9% and survival rates of 87.5%, 84.4% and 74.6%. In the lamivudine and HBIG combination therapy group, 2 patients hepatitis B relapsed (2/2 developed YMDD mutants of HBV), with 1-, 2-, and 3-year cumulative recurrence rates of 0, 1.8% and 5.7% (P0.01) and survival rates of 83.5%, 80.9% and 77.6% (P0.05).Compared with lamivudine monotherapy, lamivudine combined with individualized low-dose HBIG can further reduce the recurrence risk of hepatitis B in liver transplant recipients. This combined therapy could be used as a rational strategy for prophylaxis of hepatitis B recurrence in such patients.

Intrahepatic biliary cystadenocarcinoma (IBC) is a rare intrahepatic malignant tumor which is scarcely reported, and there is relatively little experience in the diagnosis and treatment. This study was to analyze the clinicopathologic features, diagnosis, and treatment of IBC.Clinical data of 11 patients with pathologically confirmed papillary IBC, treated between Mar. 1999 and Oct. 2006 with surgical operation in West China Hospital, were analyzed retrospectively. Of the 11 patients, 2 were men and 9 were women, with a median age of 54 (range 45-68).The chief complaints of the IBC patients were pain and distention in the epigastrium. Four cases were determined by immunohistochemistry, and showed cytokeratin 7 (CK7) expression. Four patients showed infiltration of carcinoma cells in the surrounding liver tissues; 3 of them received palliative hepatectomy and 1 received radical excision; they survived for 12-23 months. The rest 7 showed carcinoma cells confined to the cyst wall, and received radical excision; 3 of them survived for over 3 years; of the rest 4 patients, 1 received operation again 10 months later because of tumor recurrence and was still alive 14 months after the second operation, 1 suffered from intrahepatic multi-metastasis 12 months after operation and received expectant treatment, 1 suffered from ascites 15 month after operation and died without further treatment, 1 was lost during follow-up.IBC occurs mainly in elder women, and its malignant degree is lower than that of solid carcinoma. The prognosis of the patients with IBC confined to the cyst wall after complete tumor removal is better than that of the patients with IBC infiltrated into the liver.

Tissue factor (TF), the primary physiologic initiator of coagulation cascade, is involved in the process of angiogenesis of various malignancies. This study was designed to investigate the correlation of TF expression to angiogenesis of gastric carcinoma, and to study its clinical significance.The expression of TF and vascular endothelial growth factor (VEGF) in 80 specimens of gastric carcinoma and 20 specimens of normal gastric tissue was detected by EnVision immunohistochemistry. Tumor microvessel density (MVD) was evaluated using anti-CD34 antibody as an endothelial marker with the same technique as well.Positive rates of TF and VEGF, and the mean value of MVD were significantly higher in gastric carcinoma than in normal gastric tissue (65.00% vs. 5.00%, P0.01; 67.50% vs. 5.00%, P0.05; and 36.14+/-9.94 vs. 12.10+/-3.27, P0.05). TF expression was positively correlated with VEGF expression and MVD value (P0.05). TF expression was correlated to the overall survival times of patients, TNM stage, and liver metastasis (P0.05).Overexpression of TF relates with angiogenesis and prognosis of gastric carcinoma.