Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer

BACKGROUND As the primary microtubule organizing center in animal cells,centrosome abnormalities are involved in human colon cancer.AIM To explore the role of centrosome-related genes(CRGs)in colon cancer.METHODS CRGs were collected from public databases.Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort.Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature(CRS)to score colon cancer patients.A nomogram was developed to evaluate the CRS risk in colon cancer patients.An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy,chemotherapy,and targeted therapy.Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes.RESULTS A total of 726 CRGs were collected from public databases.A CRS was constructed,which consisted of the following four genes:TSC1,AXIN2,COPS7A,and MTUS1.Colon cancer patients with a high-risk signature had poor survival.Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+T cells.Regarding treatment response,patients with a high-risk signature were resistant to immunotherapy,chemotherapy,and targeted therapy.COPS7A expression was relatively high in endothelial cells and fibroblasts.MTUS1 expression was high in endothelial cells,fibroblasts,and malignant cells.CONCLUSION We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients,contributing to the development of individualized treatment for colon cancer.

Nanomedicine-based multimodal therapies:Recent progress and perspectives in colon cancer

Colon cancer has attracted much attention due to its annually increasing incidence.Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic side effects.In the past decade,nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention,high accumulation at tumor sites,co-loading with different drugs,and combination of various therapies.This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy,radiotherapy,phototherapy(photothermal therapy and photodynamic therapy),chemodynamic therapy,gas therapy,and immunotherapy.Additionally,the therapeutic mechanisms,limitations,improvements,and future of the above therapies are discussed.

Benefit of Targeted Therapies in Metastatic Colon Cancer in the Ivorian Context

In our daily practice, the use of targeted therapies (Bevacizumab and rarely Cetuximab) in metastatic colic cancers is recent. Very few patients benefit from these therapies because of their high cost. In a cohort of 68 patients who received these therapies, a retrospective and prospective study was conducted over three years period (1 January 2013 to 31 December 2015) to evaluate their benefit in terms of quality of life, tolerance and overall survival. These targeted therapies provided a significant clinical and biological gain with acceptable toxicities (most often resolving spontaneously). Moreover, they have allowed a significant improvement in overall survival in first line metastatic treatment. The limiting factor remains their extremely high cost and therefore inaccessibility to the majority of our patients.

Colon cancer stem cells:Controversies and perspectives

Tumors have long been viewed as a population in which all cells have the equal propensity to form new tumors,the so called conventional stochastic model.The cutting-edge theory on tumor origin and progression,tends to consider cancer as a stem cell disease.Stem cells are actively involved in the onset and maintenance of colon cancer.This review is intended to examine the state of the art on colon cancer stem cells(CSCs),with regard to the recent achievements of basic research and to the corresponding translational consequences.Specific prominence is given to the hypothesized origin of CSCs and to the methods for their identification.The growing understanding of CSC biology is driving the optimization of novel anti-cancer targeted drugs.

Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases

Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several protooncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and microRNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be selected for combined regiments. However, due to its context-dependent cellular function, it is clinically essential to consider which cytotoxic drugs are used in combination with c-MYC targeted agents in various tissues. Increasing our knowledge about MYCdependent pathways might provide direction to novel anti-inflammatory and colorectal cancer therapies.

Therapeutic implications of colon cancer stem cells

Colorectal cancer is the second most common cause of cancer-related death in many industrialized countries and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, the concept that cancer might arise from a rare population of cells with stem cell-like properties has received support with regard to several solid tumors, including colorectal cancer. According to the cancer stem cell hypothesis, cancer can be considered a disease in which mutations either convert normal stem cells into aberrant counterparts or cause a more differentiated cell to revert toward a stem cell-like behaviour; either way these cells are thought to be responsible for tumor generation and propagation. The statement that only a subset of cells drives tumor formation has major implications for the development of new targeted therapeutic strategies aimed at eradicating the tumor stem cell population. This review will focus on the biology of normal and malignant colonic stem cells, which might contribute to our understanding of the mechanisms responsible for tumor development and resistance to therapy.

Baculovirus vector-mediated transfer of NIS gene into colon tumor cells for radionuclide therapy

AIM:To investigate the feasibility of radionuclide therapy of colon tumor cells by baculovirus vector-mediated transfer of the sodium/iodide symporter(NIS) gene.METHODS:A recombinant baculovirus plasmid carrying the NIS gene was constructed,and the viruses(BacNIS) were prepared using the Bac-to-Bac system.The infection efficiency in the colon cancer cell line SW1116 of a green fluorescent protein(GFP) expressing baculovirus(Bac-GFP) at different multiplicities of infection(MOI) with various concentrations of sodium butyrate was determined by flow cytometry.An in vitro cytotoxicity assay was also conducted after infection of SW1116 cells with Bac-NIS.Iodine uptake of Bac-NIS infected SW1116 cells and inhibition of this uptake by sodium perchlorate was examined,and the effect of Bac-NISmediated 131 I in killing tumor cells was evaluated by cell colony formation tests.RESULTS:Infection and transgene expression in SW1116with Bac-GFP were significantly enhanced by sodium butyrate,as up to 72% of SW1116 cells were infected with the virus at MOI of 400 and sodium butyrate at 0.5 mmol/L.No obvious cytotoxicity was observed under these conditions.Infection of SW1116 with Bac-NIS allowed uptake of 131 I in these tumor cells,which could be inhibited by sodium perchlorate.The viability of SW1116 cells infected with Bac-NIS was significantly lower than with Bac-GFP,suggesting that NIS gene-mediated 131 I uptake could specifically kill tumor cells.CONCLUSION:Baculovirus vector-mediated NIS gene therapy is a potential approach for treatment of colon cancer.

Forward-viewing radial-array echoendoscope for staging of colon cancer beyond the rectum

AIM: To evaluate feasibility of the novel forward-viewing radial-array echoendoscope for staging of colon cancer beyond rectum as the first series.

1,3-Bis(2-chloroethyl)-1-nitrosourea enhances the inhibitory effect of Resveratrol on 5-fluorouracil sensitive/resistant colon cancer cells

AIM:To study the mechanism of 5-fluorouracil(5-FU)resistance in colon cancer cells and to develop strategies for overcoming such resistance by combination treatment.METHODS:We established and characterized a 5-FU resistance(5-FU-R)cell line derived from continuous exposure(25μmol/L)to 5-FU for 20 wk in 5-FU sensitive HCT-116 cells.The proliferation and expression of different representative apoptosis and anti-apoptosis markers in 5-FU sensitive and 5-FU resistance cells were measured by the MTT assay and by Western blotting,respectively,after treatment with Resveratrol(Res)and/or 1,3-Bis(2-chloroethyl)-1-nitrosourea(BCNU).Apoptosis and cell cycle arrest was measured by 4',6'-diamidino-2-phenylindole hydrochloride staining and fluorescence-activated cell sorting analysis,respectively.The extent of DNA damage was measured by the Comet assay.We measured the visible changes in the DNA damage/repair cascade by Western blotting.RESULTS:The widely used chemotherapeutic agents BCNU and Res decreased the growth of 5-FU sensitive HCT-116 cells in a dose dependent manner.Combined application of BCNU and Res caused more apoptosis in5-FU sensitive cells in comparison to individual treatment.In addition,the combined application of BCNU and Res caused a significant decrease of major DNA base excision repair components in 5-FU sensitive cells.We established a 5-FU resistance cell line(5-FU-R)from 5-FU-sensitive HCT-116(mismatch repair deficient)cells that was not resistant to other chemotherapeutic agents(e.g.,BCNU,Res)except 5-FU.The 5-FU resistance of 5-FU-R cells was assessed by exposure to increasing concentrations of 5-FU followed by the MTT assay.There was no significant cell death noted in5-FU-R cells in comparison to 5-FU sensitive cells after5-FU treatment.This resistant cell line overexpressed anti-apoptotic[e.g.,AKT,nuclear factorκB,FLICE-like inhibitory protein),DNA repair(e.g.,DNA polymerase beta(POL-β),DNA polymerase eta(POLH),protein Flap endonuclease 1(FEN1),DNA damage-binding protein 2(DDB2)]and 5-FU-resistance proteins(thymidylate synthase)but under expressed pro-apoptotic proteins(e.g.,DAB2,CK1)in comparison to the parental cells.Increased genotoxicity and apoptosis were observed in resistant cells after combined application of BCNU and Res in comparison to untreated or parental cells.BCNU increased the sensitivity to Res of 5-FU resistant cells compared with parental cells.Fifty percent cell death were noted in parental cells when 18μmol/L of Res was associated with fixed concentration(20μmol/L)of BCNU,but a much lower concentration of Res(8μmol/L)was needed to achieve the same effect in 5-FU resistant cells.Interestingly,increased levels of adenomatous polyposis coli and decreased levels POL-β,POLH,FEN1 and DDB2 were noted after the same combined treatment in resistant cells.CONCLUSION:BCNU combined with Res exerts a synergistic effect that may prove useful for the treatment of colon cancer and to overcome drug resistance.

Accuracy of computed tomography in nodal staging of colon cancer patients

AIM: To predict node-positive disease in colon cancer using computed tomography(CT).METHODS: American Joint Committee on Cancer stage Ⅰ-Ⅲ colon cancer patients who underwent curavtiveintent colectomy between 2007-2010 were identified at a single comprehensive cancer center. All patients had preoperative CT scans with original radiology reports from referring institutions. CT images underwent blinded secondary review by a surgeon and a dedicated abdominal radiologist at our institution to identify pericolonic lymph nodes(LNs). Comparison of outside CT reports to our independent imaging review was performed in order to highlight differences in detection in actual clinical practice. CT reviews were compared with final pathology. Results of the outside radiologist review, secondary radiologist review, and surgeon review were compared with the final pathologic exam to determine sensitivity, specificity, positive and negative predictive values, false positive and negative rates, and accuracy of each review. Exclusion criteria included evidenceof metastatic disease on CT, rectal or appendiceal involvement, or absence of accompanying imaging from referring institutions.RESULTS: From 2007 to 2010, 64 stageⅠ-Ⅲ colon cancer patients met the eligibility criteria of our study. The mean age of the cohort was 68 years, and 26(41%) patients were male and 38(59%) patients were female. On final pathology, 26 of 64(40.6%) patients had nodepositive(LN+) disease and 38 of 64(59.4%) patients had node-negative(LN-) disease. Outside radiologic review demonstrated sensitivity of 54%(14 of 26 patients) and specificity of 66%(25 of 38 patients) in predicting LN+ disease, whereas secondary radiologist review demonstrated 88%(23 of 26) sensitivity and 58%(22 of 38) specificity. On surgeon review, sensitivity was 69%(18 of 26) with 66% specificity(25 of 38). Secondary radiology review demonstrated the highest accuracy(70%) and the lowest false negative rate(12%), compared to the surgeon review at 67% accuracy and 31% false negative rate and the outside radiology review at 61% accuracy and 46% false negative rate.CONCLUSION: CT LN staging of colon cancer has moderate accuracy, with administration of NCT based on CT potentially resulting in overtreatment. Active search for LN+ may improve sensitivity at the cost of specificity.

Endoscopic Mucosal Resection: Therapy for Early Colorectal Cancer

We review the use of Endoscopic Mucosal Resection in the treatment of early colorectal cancer. Newer endoscopic imaging modalities have lead to earlier detection of advanced lesions thus enabling endoscopic curative therapy of lesions that would otherwise need surgery. Early outcomes data suggest promising results. But further long term prospective studies are needed.

siRNA-targeted inhibition of growth hormone receptor in human colon cancer SW480 cells

AIM:To determine the effects of RNAi-mediated inhibition of the growth hormone receptor(GHR)gene on tumors and colon cancer cells in vivo.METHODS:Construction of a eukaryotic vector for human GHR expression,the pcDNA 6.2-GW/EmGFPsmall interfering RNAs(siRNAs)-GHR plasmid,was used to inhibit GHR expression.Thirty-six BALB/c nude mice were randomly divided into groups and treated with normal saline(NS),recombinant plasmid(G2),growth hormone(GH),5-fluorouracil(FU),G2+FU or G2+FU+GH.Each nude mouse was subcutaneously inoculated with 1×107human colon cancer SW480 cells;the nude mice were weighed before inoculation and on the 2nd,5th,8th,11th,14thand 17thday after inoculation.All nude mice were sacrificed after 17 d.Each subcutaneous tumor was removed and studied.Tumor volume was measured on the 5th,8th,11th,14thand 17thday after inoculation.The expression of GHR protein in the tumor tissue was detected by Western blotting analysis,and the differences in GHR mRNA expression in the tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction.RESULTS:Compared to the control group,the weights of the inoculated nude mice on the 17thday after inoculation were:G2:21.60±0.71 g,GH:21.64±0.45 g,FU:18.94±0.47 g,FU+G2:19.40±0.60 g,G2+FU+GH:21.04±0.78 g vs NS:20.68±0.66 g,P<0.05;the tumor volumes after the subcutaneous inoculation were:G2:9.71±3.82 mm3,FU:11.54±2.42mm3,FU+G2:11.42±1.11 mm3,G2+FU+GH:10.47±1.02 mm3vs NS:116.81±10.61 mm3,P<0.05.Compared to the GH group,the tumor volumes were significantly decreased in the experimental groups.The GHR protein expression(G2:0.39±0.02,FU:0.40±0.02,FU+G2:0.38±0.01,G2+FU+GH:0.39±0.01 vs NS:0.94±0.02,P<0.05)and the GHR mRNA expression(G2:14.12±0.10,FU:15.15±0.44,FU+G2:16.46±0.27,G2+FU+GH:15.37±0.57 vs NS:12.63±0.14,P<0.05)were significantly decreased and increased,respectively,in the experimental groups.CONCLUSION:Inhibition of GHR in human colon cancer SW480 cells resulted in anti-tumor effects in nude mice.

Recent Advances in the Management of Stage IV Colon Cancer

Colon cancer is the second commonest cause of cancer-related death in Canadian men and women, with approximately one-third of patients dying from this disease. One quarter of patients present with metastases initially, and up to half of all colon cancer patients will develop stage IV disease over the course of their life. Despite ongoing advances in the evolution of newer cytotoxic drugs, targeted biological agents and improved metastasectomy techniques, the gain in overall survival in these patients is of low magnitude. This manuscript is a targeted review of the recent advances over the last decade in the management of advanced stage IV colon cancer as available in the published English literature. The two major arms of metastatic colon cancer management that include surgery and systemic chemotherapy and palliative measures as available are discussed. A multi-modality team-based approach involving medical oncologists, surgical oncologists, radiologists, and other health-care providers continues to be critical for ongoing success in the therapeutic management of these patients. Future studies of well-designed prospective, randomized-controlled clinical trials to develop and evaluate newer therapeutic strategies are recommended for continued and improved understanding for optimization of clinical management in advanced colon cancer.

Locally Advanced Colon Cancer with Abdominal Wall Abscess: A Challenging Case Treated by an Innovative Approach

Colon cancer rarely combines with abscess of the abdominal wall. We here describe a case treated by extensive surgery, biological mesh abdominal wall repair and negative pressure therapy. A 58-year-old woman presented with a locally advanced right colon cancer with abdominal wall abscess and no evidence of distant metastasis. Extended right hemicolectomy was performed with en-bloc excision of the bladder dome, the right annex and full thickness removal of the anterior abdominal wall including the abscess. Abdominal wall repair was perfomed by a biological mesh (PermacolTMBiologic Implant) and to facilitate healing the patient was then treated with Vacuum-Assisted Closure (V.A.C.?) Therapy. Histology showed a mucinous moderately differentiated adenocarcinoma without nodal metastases (n = 57). Surgical margins including the abdominal wall was tumor free. The postoperative clinical course was uneventful. VA.C.? Therapy treatment reported excellent results in terms of active promotion of the granulation tissue, this allowing for a subsequent placement of a skin graft. Patient is alive and disease-free one year after surgery. The present case shows some peculiar characteristics such as the size of the initial lesion, the abdominal wall abscess and the use of innovative devices such as biological mesh and V.A.C.? Therapy. We demonstrate that extensive surgery for locally advanced colon cancer, in high-volume centers, provides favorable results in terms of survival and quality of life.

基于机器学习构建新型结肠癌免疫评分模型

目的:基于免疫相关基因,利用机器学习方法构建结肠癌免疫评分模型,用于评估患者的生存状态和免疫治疗效果。方法:使用Lasso+bootstrap+多因素Cox的组合策略,基于1 301个免疫相关基因在结肠癌中的表达情况,对TCGA中的结肠癌患者进行免疫相关基因(IRG)评分,并对高/低分组在功能差异、预后状态、免疫治疗相关等方面进行比较。结果:基于IRG评分的分组在结肠癌患者预后状态方面具有显著差异,并且通过其他独立数据集的验证,IRG评分模型同时能够评估结肠癌患者的免疫治疗效果。结论:本研究能为基于免疫基因的结肠癌免疫治疗和研究提供思路,IRG评分模型可以用于评估结肠癌患者的预后情况。

STAT3抑制剂stattic对小鼠结肠癌CT26细胞增殖和凋亡的影响

目的探讨信号转导和转录激活因子3(STAT3)抑制剂盐酸萘替芬(stattic)对小鼠结肠癌CT26细胞增殖和凋亡的影响和作用机制。方法采用0μmol/L、1μmol/L、5μmol/L、10μmol/L stattic溶液处理小鼠结肠癌CT26细胞,通过CCK-8实验、细胞克隆形成实验、细胞划痕实验、Transwell侵袭实验以及流式细胞术检测细胞活力、增殖、迁移、侵袭、周期和凋亡情况;利用Western blot法检测stattic对小鼠结肠癌细胞磷酸化STAT3(p-STAT3)表达的影响;通过实时荧光定量多聚核苷酶链式反应(RT-qPCR)检测stattic作用后CT26细胞B淋巴细胞瘤-2(Bcl-2)和人跨膜受体蛋白Notch-1(Notch-1)的表达。结果与0μmol/L组相比,stattic溶液组CT26细胞的活力及增殖能力降低(P<0.001)、迁移率和侵袭率降低(P<0.001),细胞凋亡率随浓度增加而增加(P<0.0001);stattic能将CT26细胞周期阻断于G1期,进而阻止CT26细胞的增殖;Western blot结果显示stattic抑制CT26细胞p-STAT3的表达(P<0.05);RT-qPCR检测结果表明stattic下调CT26细胞Bcl-2和Notch1的表达(P<0.05)。结论stattic通过阻断STAT3信号,抑制p-STAT3蛋白的表达,下调下游抗凋亡分子Bcl-2和Notch1信号分子的表达从而抑制CT26细胞增殖促进细胞凋亡。

奥沙利铂与卡培他滨化疗方案联合贝伐珠单抗靶向治疗结肠癌对患者生命质量的影响

目的探讨奥沙利铂与卡培他滨化疗方案联合贝伐珠单抗靶向治疗结肠癌对患者生命质量的影响。方法选取2021年1月至2022年1月抚州市第一人民医院肿瘤内科收治的60例结肠癌患者作为研究对象,随机分为观察组与对照组,每组30例。对照组实施奥沙利铂、卡倍他滨化疗方案,观察组在对照组基础上联合贝伐珠单抗靶向治疗,比较两组临床疗效、治疗前后外周血T淋巴细胞亚群水平、不良反应发生情况及治疗前后卡氏功能状态(KPS)评分。结果观察组总缓解率(OR)、疾病控制率(DCR)均高于对照组,差异有统计学意义(P<0.05)。治疗后,两组CD4^(+)水平及CD4^(+)/CD8^(+)均高于治疗前,CD8^(+)水平均低于治疗前,且观察组CD4^(+)水平及CD4^(+)/CD8^(+)均高于对照组,CD8^(+)水平低于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义;治疗后,两组KPS评分均高于治疗前,且观察组高于对照组,差异有统计学意义(P<0.05)。结论奥沙利铂、卡培他滨化疗方案联合贝伐珠单抗靶向治疗结肠癌疗效显著,不仅可有效控制患者病情进展,还能强化机体免疫功能,维持免疫系统正常状态,且用药安全性较高,能进一步提高患者生命质量。

仙鹤丹皮方结合针刺疗法治疗结肠癌化疗所致骨髓抑制临床效果观察

目的:探讨仙鹤丹皮方结合针刺疗法治疗结肠癌化疗所致骨髓抑制临床效果。方法:将重庆市万州区第一人民医院中医科收治的105例结肠癌化疗所致骨髓抑制患者(2019年2月~2022年2月)根据随机数字表法分为两组,对照组患者(53例)采取西医常规治疗(白介素-11及粒细胞刺激饮食、促红素、输血等),观察组患者(52例)常规治疗同时给予仙鹤丹皮方结合针刺疗法治疗,数据观察:临床疗效、治疗前后中医证候积分(神疲乏力、气短、头晕眼花、面色淡白/萎黄等)变化、治疗前后患者血红蛋白、白细胞及血小板水平变化、化疗不良反应(红细胞减少发生率、血小板减少发生率、白细胞减少发生率等)、治疗后各组患者卡氏生活质量(KPS)评分提升率、化疗通过率及1年生存率、治疗前后免疫指标变化。结果:观察组治疗效果(90.38%)高于比对照组(73.58%)(P<0.05);各组患者治疗后中医证候积分(神疲乏力、气短、头晕眼花、面色淡白/萎黄等)均显著下降,观察组低于对照组(P<0.05);治疗后观察组患者血红蛋白及血小板、白细胞水平下降程度低于对照组(P<0.05);观察组患者治疗后红细胞减少发生率及白细胞减少发生率、血小板减少发生率低于对照组,KPS评分提升率(96.15%)高于对照组患者(81.13%)(P<0.05);观察组患者化疗通过率及1年生存率均高于对照组(P<0.05);对照组患者治疗后免疫指标无明显变化,观察组患者治疗后免疫指标显著改善,且优于对照组(P<0.05)。结论:仙鹤丹皮方结合针刺疗法治疗结肠癌化疗所致骨髓抑制临床效果良好,患者病情好转,生活质量提升,化疗通过率及1年生存率高,免疫力改善,值得应用。

Effect of music on procedure time and sedation during colonoscopy:A meta-analysis

AIM:To integrate results from different studies in examining the effectiveness of music in reducing the procedure time and the amount of sedation used during colonoscopic procedure. METHODS: An electronic search in various databases was performed to identify related articles. Study quality was evaluated by the Jadad’s scale. The random effect model was used to pool the effect from individual trials and the Cohen Q-statistic was used to determine heterogeneity. Egger’s regression was used to detect publication bias. RESULTS: Eight studies with 722 subjects were included in this meta-analysis. The combined mean difference for the time taken for the colonoscopy procedure between the music and control groups was -2.84 with 95% CI (-5.61 to -0.08), implying a short time for the music group. The combined mean difference for the use of sedation was -0.46 with 95%CI (-0.91 to -0.01), showing a significant reduction in the use of sedation in the music group. Heterogeneity was observed in both analyses but no publication bias was detected. CONCLUSION: Listening to music is effective in reducing procedure time and amount of sedation during colonoscopy and should be promoted.

Suppression of human colon tumor growth by adenoviral vector-mediated NK4 expression in an athymic mouse model

AIM： To investigate the suppressive effects of adenoviral vector-mediated expression of NK4, an antagonist of hepatocyte growth factor （HGF）, on human colon cancer in an athymic mouse model to explore the possibility of applying NK4 to cancer gene therapy. METHODS： A human colon tumor model was developed by subcutaneous implantation of tumor tissue formed by LS174T cells grown in athymic mice. Fifteen tumorbearing mice were randomized into three groups （n= 5 in each group） at d 3 after tumor implantation and mice were injected intratumorally with phosphate-buffered saline （PBS） or with recombinant adenovirus expressing 13-galactosidase （Ad-LacZ） or NK4 （rvAdCMV/NK4） at a 6-d interval for total 5 injections in each mouse. Tumor sizes were measured during treatment to draw a tumor growth curve. At d 26 after the first treatment, all animals were sacrificed and the tumors were removed to immunohistochemically examine proliferating cell nuclear antigen （PCNA）, microvessel density （represented by CD31）, and apoptotic cells. In a separate experiment, 15 additional athymic mice were employed to develop a tumor metastasis model by intraperitoneal injection （ip） of LS174T cells. These mice were randomized into 3 groups （n = 5 in each group） at d 1 after injection and were treated by ip injection of PBS, or Ad-LacZ, or rvAdCMV/NK4 at a 6-d interval for total two injections in each mouse. All animals were sacrificed at d 14 and the numbers and weights of disseminated tumors within the abdominal cavity were measured. RESULTS： Growth of significantly suppressed human colon tumors were in the athymic mice treatedwith rvAdCMV/NK4 （2537.4± 892.3 mm^3） compared to those treated by either PBS （5175.2 ± 1228.6 mm^3） or Ad-LacZ （5578.8± 1955.7 mm^3） （P 〈 0.05）. The tumor growth inhibition rate was as high as 51%. Immunohistochemical staining revealed a similar PCNA labeling index （75.1% ± 11.2% in PBS group vs 72.8% ± 7.6% in Ad-LacZ group vs 69.3% ± 9.4% in rvAdCMV/ NK4 group） in all groups, but significantly lower microvessel density （10.7 ± 2.4 in rvAdCMV/NK4 group vs 25.6 ± 3.8 in PBS group or 21.3 ± 3.5 in Ad-LacZ group, P 〈 0.05）, and a markedly higher apoptotic index （7.3% ± 2.4% in rvAdCMV/NK4 group vs 2.6 4, 1.1% in PBS group or 2.1% ± 1.5% in Ad-LacZ group, P 〈 0.05） in the rvAdCMV/NK4 group compared to the two control groups. In the tumor metastasis model, the number and weight of disseminated tumors of mice treated with rvAdCMV/NK4 were much lower than those of the control groups （tumor number： 6.2 ± 3.3 in rvAdCMV/ NK4 group vs 22.9 ± 7.6 in PBS group or 19.8 ± 8.5 in Ad-LacZ group, P 〈 0.05; tumor weight： 324 ± 176 mg in rvAdCMV/NK4 group vs 962 ± 382 mg in PBS group or 1116 ± 484 mg in Ad-LacZ group, P 〈 0.05）. CONCLUSION： The recombinant adenovirus, rvAdCMV/ NK4, can attenuate the growth of colon cancer in vivo, probably by suppressing angiogenesis and inducing tumor cell apoptosis, but not by direct suppression of tumor cell proliferation. Moreover, rvAdCMV/NK4 may inhibit peritoneal dissemination of colon cancer cells in a murine tumor metastasis model. These findings indicate that NK4 gene transfer may be an effective tool for the treatment of colon cancer.