Combined Inhibition of KIF11 and KIF15 as an Effective Therapeutic Strategy for Gastric Cancer.

BACKGROUND: Novel therapeutic 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.

Present and Future Prospects of the Anti-cancer Activities of Saikosaponins.

Since their discovery, saikosaponins (SSs) have been found to play an important role in treating a variety of cancers via diverse mechanisms of action. This review summarizes the current research status and prospects of the anti-cancer activities of SSs, providing novel insights into the limitations of current studies. In addition, it discusses whether SSs can be applied in immunotherapy and the possible mechanisms by which SSs may facilitate immunotherapy. The research is significant to understanding the anti-cancer potents of SSs in the development of SSs-based therapeutic strategies and clinical practice.

Improving therapeutic resistance: beginning with targeting the tumor microenvironment.

Cancer is a serious threat to human health and life. The tumor microenvironment (TME) not only plays a key role in the occurrence, development and metastasis of cancer, but also has a profound impact on treatment resistance. To improve and solve this problem, an increasing number of strategies targeting the TME have been proposed, and great progress has been made in recent years. This article reviews the characteristics and functions of the main matrix components of the TME and the mechanisms by which each component affects drug resistance. Furthermore, this article elaborates on targeting the TME as a strategy to treat acquired drug resistance, reduce tumor metastasis, recurrence, and improve efficacy.

The role of the primary cilium in cancer.

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.

Non-operative Treatment of Gastric Fistula after Splenectomy Combined with Pericardial Devascularisation in Portal Hypertension.

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.

Effect of KIF22 on promoting proliferation and migration of gastric cancer cells via MAPK-ERK pathways.

BACKGROUND: Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms. METHODS: Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogen-activated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests. RESULTS: The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways. CONCLUSIONS: KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.

The Role of Shcbp1 in Signaling and Disease.

Src homolog and collagen homolog (Shc) proteins have been identified as adapter proteins associated with cell surface receptors and have been shown to play important roles in signaling and disease. Shcbp1 acts as a Shc SH2-domain binding protein 1 and is involved in the regulation of signaling pathways, such as FGF, NF-κB, MAPK/ERK, PI3K/AKT, TGF-ß1/Smad and ß -catenin signaling. Shcbp1 participates in T cell development, the regulation of downstream signal transduction pathways, and cytokinesis during mitosis and meiosis. In addition, Shcbp1 has been demonstrated to correlate with Burkitt-like lymphoma, breast cancer, lung cancer, gliomas, synovial sarcoma, human hepatocellular carcinoma and other diseases. Shcbp1 may play an important role in tumorigenesis and progression. Accordingly, recent studies are reviewed herein to discuss and interpret the role of Shcbp1 in normal cell proliferation and differentiation, tumorigenesis and progression, as well as its interactions with proteins.

Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) as preoperative and postoperative chemotherapy compared with surgery followed by chemotherapy for patients with locally advanced gastric cancer: a propensity score-based analysis.

Introduction: Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) may improve overall survival (OS) in patients with locally advanced gastric cancer (LAGC); however, evidence for its use as a standard treatment has not been established in China. The aim of this study was to investigate the effectiveness, safety, and feasibility of the FLOT regimen as neoadjuvant chemotherapy in Chinese patients with resectable LAGC. Methods: We conducted an observational study to compare the effectiveness of FLOT regimen consisting of docetaxel (60 mg/m2), oxaliplatin (85 mg/m2), leucovorin (200 mg/m2), and 5-fluorouracil (2,600 mg/m2 as a 24 hr infusion), all given on day 1 and administered every 2 weeks versus initial surgery followed by chemotherapy in patients with clinical T3-4 LAGC. OS was compared by using the Cox proportional hazards regression model and the Kaplan-Meier curve adjusted by inverse probability of treatment weighting (IPTW) and propensity score-matched (PSM) analysis. In addition, we performed subgroup analyses to determine the effectiveness of the FLOT regimen in clinically relevant patient subsets. Results: Overall, 47 patients who received initial FLOT chemotherapy and 269 patients who received initial surgery were enrolled in this study. In the PSM analysis, the FLOT-first group showed favorable OS compared with the surgery-first group (41 vs 41 [HR, 0.416; 95% CI, 0.218-0.794; P=0.008]), and 3-year survival rates were 58.7% and 30.9% in the FLOT-first group and surgery-first group, respectively. IPTW analysis showed similar results. However, the effect of FLOT was low (HR, 0.868; 95 CI%, 0.215-3.504) in patients without lymph node metastasis. Conclusion: Our study suggests that preoperative FLOT chemotherapy is safe and feasible. In terms of OS, FLOT may be superior to initial surgery followed by chemotherapy in reducing morbidity with resectable LAGC.

A Competing Endogenous RNA Network Reveals Novel Potential lncRNA, miRNA, and mRNA Biomarkers in the Prognosis of Human Colon Adenocarcinoma.

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 < 0.01. Subsequently, a colon adenocarcinoma-specific ceRNA network was successfully established with133 DElncRNAs, 29 DEmiRNAs, and 55 DEmRNAs. Among ceRNA network, seven DElncRNAs (AL590483.1, AP004609.1, ARHGEF26-AS1, HOX transcript antisense RNA (HOTAIR), ITCH-IT1, KCNQ1OT1, and LINC00491), four DEmiRNAs (hsa-mir-143, hsa-mir-183, hsa-mir-216a, and hsa-mir-424), and six DEmRNAs (FJX1, TPM2, ULBP2, PDCD4, PLAU, and SERPINE1) significantly correlated with OS (all P-value < 0.05). Notably, several interactions were highlighted in the ceRNA network, such as "KCNQ1OT1-hsa-mir-183-PDCD4", "KCNQ1OT1-hsa-mir-424-TPM2", "HOTAIR-hsa-mir-143-SERPINE1", and "ARHGEF26-AS1-hsa-mir-143-SERPINE1". 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.

A propensity score-matched comparison of laparoscopic distal versus total gastrectomy for middle-third advanced gastric cancer.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ±â€¯28.0 vs. 259.1 ±â€¯30.1, P < 0.0001), less operative blood loss (142.9 ±â€¯50.9 vs. 157.8 ±â€¯54.1, P = 0.006), earlier day of first flatus (2.6 ±â€¯0.8 vs. 2.9 ±â€¯0.9, P = 0.014), fewer number of retrieved lymph nodes (36.5 ±â€¯7.9 vs. 41.4 ±â€¯9.8, P < 0.0001), and shorter postoperative hospital stay (9.7 ±â€¯1.3 vs. 10.7 ±â€¯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. CONCLUSIONS: 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.

Identification of key genes and associated pathways in KIT/PDGFRA wild­type gastrointestinal stromal tumors through bioinformatics analysis.

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 v­kit Hardy­Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet­derived growth factor receptor α (PDGFRA) wild­type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild­type 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 Orthology­Based Annotation System (KOBAS) online tools, respectively. Protein­protein interaction (PPI) networks of the DEGs were constructed using Search Tool for the Retrieval of Interacting Genes online tool and Cytoscape, and divided into sub­networks using the Molecular Complex Detection (MCODE) plug­in. 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', 'cell­cell signaling', 'PI3K­Akt signaling pathway' and 'ECM­receptor 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 sub­networks also revealed these genes were primarily involved in significant pathways, including 'PI3K­Akt signaling pathway', 'proteoglycans in cancer', 'pathways in cancer', 'Rap1 signaling pathway', 'ECM­receptor interaction', 'phospholipase D signaling pathway', 'ras signaling pathway' and 'cGMP­PKG signaling pathway'. These results suggested that several key hub DEGs may serve as potential candidate biomarkers for wild­type GISTs, including phosphatidylinositol­4,5­bisphosphate 3­kinase, catalytic subunit γ, insulin like growth factor 1 receptor, hepatocyte growth factor, thrombospondin 1, Erb­B2 receptor tyrosine kinase 2 and matrix metallopeptidase 2. However, further experiments are required to confirm these results.

Robotic versus conventional laparoscopic gastrectomy for gastric cancer: A retrospective cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 ±â€¯13.1 vs. 35.4 ±â€¯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. CONCLUSIONS: 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.

A systematic review and network meta-analysis protocol of neoadjuvant treatments for patients with gastric cancer.

BACKGROUND: National Comprehensive Cancer Network (NCCN) guidelines recommend surgery, chemotherapy, and radiation therapy for gastric cancer patients. Neoadjuvant treatments as the administration of therapeutic agents before a main treatment gained in more and more attention. However, the role of neoadjuvant treatments is still controversial. The main aim of this systematic review and network meta-analysis is to assess the relative efficacy of different neoadjuvant treatment regimens for gastric cancer using network meta-analysis method. METHODS: We will search 5 electronic databases to identify randomized controlled trials (RCTs) and non-RCTs compared the efficacy differences of surgery alone (S), preoperative chemotherapy follow by surgery (CTS), preoperative radiotherapy follow by surgery (RTS), and preoperative chemoradiotherapy follow by surgery (CRTS) for patients with gastric cancer. The risk of bias tool from the Cochrane Handbook version 5.1.0 will be used to assess the risk of bias of RCTs, and the risk of bias in nonrandomized studies of interventions (ROBINS-I) for non-RCTs. Data will be analyzed using R-3.4.1 software. RESULTS AND CONCLUSION: The results of present network meta-analysis will estimate the relative efficacy among all interventions and rank the interventions even if head-to-head comparisons are lacking and will provide more evidence for clinicians, researchers, and patients in the management of gastric cancer.Protocol registration number: CRD42017074956.

Clinical epidemiological survey of gallbladder carcinoma in northwestern China, 2009-2013: 2379 cases in 17 centers.

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 "Questionnaire for Gallbladder Carcinoma Patients in Northwestern Area of China." 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 (P < 0.001). (2) Gallbladder carcinoma was more prone to occur in elderly women. The male:female incidence ratio was 1.0:2.1, the average age of onset of disease was 63.7 ± 11.3 years, and the incidence was higher in farmers than in other occupational groups. (3) A total of 57.2% (1360/2379) of patients with gallbladder carcinoma also had gallstones. (4) Abdominal pain (1796/2379, 75.5%) and jaundice (727/2379, 30.6%) were the most common clinical manifestations, 81.2% (1527/1881) were positive in those receiving B ultrasound examinations and 90.7% (1567/1727) were positive in those undergoing computed tomography, and 64.5% (1124/1742) of patients with gallbladder carcinoma were positive for carbohydrate antigen (CA) 19-9. (5) The pathological type of gallbladder carcinoma was mainly moderately and poorly differentiated adenocarcinoma with a high degree of malignancy. At admission, 55.1% (1091/1981) of patients had stage IV cancer among patients with TNM staging information; 55.9% (1331/2379) had lymphatic metastasis, 29.7% (706/2379) had bile duct metastasis, and 53.1% (1263/2379) had liver metastasis. (6) A total of 283 patients (283/2379, 11.9%) had incidentally detected gallbladder carcinoma. (7) The rate of radical surgical resection was 30.4% (723/2379). CONCLUSION: The proportion of gallbladder carcinoma in biliary tract diseases in the northwestern area of China was significantly higher from 2009 to 2013 than from 1986 to 1998. Gallbladder carcinoma was common in older women and mainly diagnosed at an advanced stage. Compared with other surveys in different regions, the rate of metastasis in this survey was high, leading to a low resection rate. Populations at high risk should undergo B-ultrasound examinations at regular follow-up intervals to increase the rate of early diagnosis of gallbladder carcinoma.

[Small intestinal cavernous hemangioma causing chronic hemorrhage: a case report].

Small intestinal hemangioma is a rare condition that can be divided histologically into capillary, cavernous or mixed types, among which the cavernous type is the most common. Here we report a case of small intestinal cavernous hemangioma with chronic hemorrhage in 44-year-old man. The patient complained of weakness and dizziness for 2 years that aggravated 1 month before admission accompanied by intermittent melena. Laboratory tests suggest severe anemia, and computed tomography, gastroscopy and colonoscopy all revealed signs of anemia. Capsule endoscopy detected small intestinal erosions, bleeding lesions and prominent neoplasms. An exploratory laparotomy was performed, in which the segment of the jejunum with lesions was resected. Pathological examination of the resected jejunum identified the neoplasm as cavernous hemangioma of the small intestine, which was the cause of severe anemia.

Duodenal Bulb Adenocarcinoma Benefitted from Neoadjuvant Chemotherapy: A Case Report.

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.

Possible Role of Cancer Stem Cells in Colorectal Cancer Metastasizing to the Liver.

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.

Effect of tissue factor on invasion inhibition and apoptosis inducing effect of oxaliplatin in human gastric cancer cell.

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 double- staining 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.