Colorectal carcinoma is common,particularly on the left side.In 20%of patients,obstruction and ileus may be the first clinical manifestations of a carcinoma that has advanced(stage II,III or even IV).Diagnosis is base...Colorectal carcinoma is common,particularly on the left side.In 20%of patients,obstruction and ileus may be the first clinical manifestations of a carcinoma that has advanced(stage II,III or even IV).Diagnosis is based on clinical presentation,plain abdominal radiogram,computed tomography(CT),CT colonography and positron emission tomography/CT.The best management strategy in terms of short-term operative or interventional and long-term oncological outcomes re-mains unknown.For the most common left-sided obstruction,the first choice should be either emergency surgery or endoscopic decompression by self-expen-dable metal stents or tubes.The operative plan should be either one-stage or two-stage resection.One-stage resection with on-table bowel decompression and irrigation can be accompanied or not accompanied by proximal defunctioning stoma(colostomy or ileostomy).Primary anastomosis is more convenient but has increased risks of anastomotic leakage and morbidity.Two-stage resection(Hart-mann’s procedure)is safer and the most widely used despite temporally affecting quality of life.Damage control surgery in high-risk frail patients is less frequently performed since it can be successfully substituted with endoscopic stenting or tubing.For the less common right-sided obstruction,one-stage surgical resection is more beneficial than endoscopic decompression.The role of minimally invasive surgery(laparoscopic or robotic)is a subject of debate.Emergency laparoscopic-assisted management is advantageous to some extent but requires much expertise due to inherent difficulties in dissecting the distended colon and the risk of rup-ture and subsequent septic complications.The decompressing stent as a bridge to elective surgery more substantially decreases the risks of morbidity and mortality than emergency surgery for decompression and has equivalent medium-term overall survival and disease-free survival rates.Its combination with neoadjuvant chemotherapy or radiation may have a positive effect on long-term oncological outcomes.Management plans are crucial and must be individualized to better fit each case.Core Tip:Acute obstruction is common in patients with more advanced colorectal carcinoma and may be the first manifestation mainly of left-sided obstruction and in elderly individuals.Emergency decompression is mandatory.Emergency surgical resection and primary anastomosis accompanied or not accompanied by proximal defunctioning stoma must be the first treatment choice for fit patients under 70 years.Hartmann’s two-stage procedure,although more preferable,must be the second alternative choice.Emergency endoscopic self-expendable metal stents must be preferred in unfit patients as a bridge to surgery and for palliative treatment in all inoperable cases.However,these basic management principles constitute a general direction.Decision-making is important and should be individualized.展开更多
BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more releva...BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.展开更多
BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perio...BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.展开更多
AIM： To investigate the expression of B7-H1 in human colorectal carcinoma （CRC） to define its regulating ef- fects on T cells in tumor microenvironment.
AIM： To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer.METHODS： E-cadherin expression was detected by immunohistochemistry and two indices of expres...AIM： To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer.METHODS： E-cadherin expression was detected by immunohistochemistry and two indices of expression were calculated which reflected the level of expression and the locations （membrane and cytoplasm）. Univariate and multivariate survival analyses were used to assess the value of these two E-cadherin indices as predictors of both disease-free （DFS） and disease-specific （DSS） survival. RESULTS： E-cadherin membrane index （MI）, but not cytoplasmic index （CI）, was significantly higher in primary tumors than their metastases （P = 0.0001）. Furthermore, both primary tumor MI and CI were higher among the patients who developed subsequent metastasis （P = 0.022 and P = 0.007, respectively）. Interestingly, both indices were higher in liver metastase compared to other anatomic sites （MI, P = 0.034 and CI, P = 0.022）. The CI of the primary tumors was a significant predictor of DFS （P = 0.042, univariate analysis）, with a strong inverse correlation between CI and DFS （P = 0.006, multivariate analysis）. Finally, the MI of primary tumor proved to be a significant independent predictor of DSS, with higher indices being associated with a more favorable outcome （P = 0.016）. CONCLUSION： Examination of E-cadherin expression and distribution in colorectal tumors can be extremely valuable in predicting disease recurrence. The observation that aberrant cytoplasmic expression of E-cadherin can predict disease recurrence is obviously of great importance for both patients and clinicians, and significantly affects decisions concerning the therapy and management of the patients.展开更多
AIM： To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS： Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （T...AIM： To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS： Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNE） were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma. RESULTS： The survivin positive unit （PU） was higher in cancerous tissues （38.76±5.14） than in para-cancerous （25.17±7.26） or normal tissues （0.57±0.03） （P〈0.05）. The apoptosis index （AI） of para-cancerous tissues was （7.51±2.63%） higher than cancerous tissues （4.65±1.76%）. The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma. CONCLUSION： Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.展开更多
AIM： To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer （CRC）. METHODS： Archival tumor samples were analyzed for β-catenin using immunohistochemist...AIM： To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer （CRC）. METHODS： Archival tumor samples were analyzed for β-catenin using immunohistochemistry （IHC） in 95 patients with advanced CRC. RESULTS： Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 （58%） cases showed nuclear expression. In univariate （Kaplan-Meier） survival analysis, only the nuclear index （NI） was a significant predictor of disease free survival （DFS） （P = 0.023; n = 35）, with a NI above the median associated with longer DFS （34.2 too） than those with a NI below the median （15.5 too） （P = 0.045, ANOVA）. The other indices were not significant predictors of DFS, and none of the three tested indices （for membranous, cytoplasmic, or nuclear expression） predicted diseasespecific survival （DSS）. However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS （P = 0.041） and DSS （P = 0.046）. CONCLUSION： Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.展开更多
AIM: To investigate the correlation between microvessel density and spiral CT perfusion imaging in colorectal carcinoma. METHODS: Thirty-seven patients, with histologically proven colorectal carcinoma, underwent water...AIM: To investigate the correlation between microvessel density and spiral CT perfusion imaging in colorectal carcinoma. METHODS: Thirty-seven patients, with histologically proven colorectal carcinoma, underwent water enema spiral CT scan. The largest axial surface of the primary tumor was searched on unenhanced spiral CT images. At this level, the enhanced dynamic scan series was acquired. Time-density curves (TDC) were created from the region of interest drawn over the tumor, target artery by Toshiba Xpress/SX spiral CT with perfusion functional software. Then the perfusion was calculated. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and then MVD was correlated with perfusion. RESULTS: MVD of colorectal carcinomas was 33.11-173.44, mean 87.28, and perfusion was 15.60-64.80 mL/min/ 100 g, mean 39.74 mL/min/100 g. MVD and perfusion were not associated with invasive depth, metastasis and disease stage, and they all decreased with increasing Dukes' stage, but no significant correlation was found between them (r=0.18, P=0.29). CONCLUSION: There is no significant correlation between MVD and perfusion. Neovascularizaton and perfusion are highly presented in early colorectal carcinoma. CT perfusion imaging may be more suited for assessing tumorigenesis in colorectal carcinoma than histological MVD technique.展开更多
AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiaml gene in 8 colorectal carcinoma cell lines were detected by reverse transcri...AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiaml gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptase-polymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiaml expression with the invasive ability was also analyzed. RESULTS: Tiaml gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116, LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiaml gene was highly related to the metastatic potential of colorectal carcinoma cells. CONCLUSION: Tiaml gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.展开更多
AIM: To explore the relationship between matrix metallopr- oteinase-2 (MMP-2) and tissue inhibitor of metallopr- oteinase-2 (TIMP-2) in the development of colorectal carcinoma and to provide a valuable marker for clin...AIM: To explore the relationship between matrix metallopr- oteinase-2 (MMP-2) and tissue inhibitor of metallopr- oteinase-2 (TIMP-2) in the development of colorectal carcinoma and to provide a valuable marker for clinical diagnosis. METHODS: Twenty-five patients with colorectal carcinoma underwent surgical resection. Samples were taken from tumor sites and normal tissues. MMP-2 activity was determined by gelatin zymography. Western blot and ABC immunohist-ochemical staining were used to detect the expression levels of MMP-2 and TIMP-2 in normal and colorectal carcinoma tissues. Statistical analyses were performed using the Student's t test and one-way ANOVA. P<0.05 was considered statistically .significant. All the statistical analyses were performed using SPSS 10.0 software. RESULTS: MMP-2 activity could be detected in both normal and colorectal carcinoma tissues. MMP-2 activity in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t=3.916,4.227). MMP-2 activity was positively related to the colorectal carcinoma invasion depth, lymph node metastasis and Duke's stage. Western blot and ABC immunohistochemical staining demonstrated that the expression level of MMP-2 in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t = 9.429), but the expression level of TIMP-2 in colorectal carcinoma tissues was much lower than that in normal tissues (P<0.05, t = 7.329). The MMP-2/TIMP-2 ratio of colorectal carcinoma was much higher than that of normal tissues. With the progression of invasion depth, lymph node metastasis and tumor Duke's stage, the activity and expression level of MMP-2 and TIMP-2 gradually increased, but the MMP-2/TIMP-2 ratio gradually decreased. CONCLUSION: The balance between MMP-2 and TIMP-2 plays a crucial role in the process of colorectal carcinoma invasion and metastasis.展开更多
AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER). METHODS: Multidrug resistance was determined by means o...AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER). METHODS: Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1(+)/ER(+),mdr1(+)/ER(-), mdr1(-) expressions, were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM [15 mg/(kg/d)] was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and t tests. RESULTS: In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group [(39.1±2.29) mg, (31.44±1.61) mm3] and TAM and DOX group [(38.72±2.56) mg, (31.31v1.74) mm3], which were lesser than that of control group [(45.48±3.92) mg, (36.42±2.77) mm3, P= 0.037, P= 0.016 respectively] significantly. In the animal models with mdr1(+)/ER(+) tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group [(425.5±28.58) mg, (340.35±22.28) mm3], they were significantly less than that of control group [(634.23±119.41) mg, (507.45±93.34) mm3, P= 0.022, P = 0.045 respectively], which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments. CONCLUSION: The expression of mdr1 gene corresponds to the sensitivity of colon cancer to anti-tumor drugs in vivo. TAM can reverse the MDR of colorectal carcinoma in nude mice, which is independent of the expression of ER; however, no change was observed in the expressive level of mdr1 mRNA.展开更多
AIM:To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with historically confirmed me...AIM:To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with historically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using X2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables. RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P=0.014). Patients with lower vWF plasma levels (≤160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P= 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P= 0.012), and the performance status (P=0.014) were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.展开更多
AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus ...AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (X2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.展开更多
AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT met...AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.展开更多
Circulating vascular endothelial growth factor-C （VEGF-C） and vascular endothelial growth factor （VEGF） levels in patients with colorectal carcinoma were determined in order to assess their clinical significance a...Circulating vascular endothelial growth factor-C （VEGF-C） and vascular endothelial growth factor （VEGF） levels in patients with colorectal carcinoma were determined in order to assess their clinical significance as a diagnostic tool for monitoring lymph node metastasis. In 66 patients with colorectal carcinoma and 30 healthy controls, circulating VEGF-C and VEGF levels were assessed by using enzyme-linked immunosorbent assay （ELISA）. Serum VEGF-C and VEGF levels were higher in patients with colorectal carcinoma than in healthy controls. Patients with lymph node metastasis had higher serum VEGF-C and VEGF levels than those without lymph node metastasis. The levels of VEGF-C and VEGF were higher in the invasion group than in the non-invasion group. Serum VEGF-C levels reached a sensitivity of 81% and a specificity of 76 % with a cutoff value of 1438.0 pg/mL, whereas VEGF levels reached 72 % sensitivity and 74 % specificity at 240.2 pg/ mL. If 66 patients were divided into 4 groups according to the combined determination of VEGF-C and VEGF levels, the positive predictive value was 85.3 %, the negative predictive value was 94.6 %, and accuracy was 93.7 %. It was suggested that circulating VEGF-C levels might provide additional information for distinguishing the absence from presence of lymph node metastasis in patients with colorectal carcinoma. The combined determination of VEGF-C and VEGF levels could be used as an important index for preoperatively clinical stage of colorectal carcinoma.展开更多
AIM: To investigate the effect of deleted pancreatic cancer locus 4 (DPC4) gene transfection on biological behaviors of human colorectal carcinoma cells and the role of DPC4 gene in colorectal carcinogenesis. METHODS:...AIM: To investigate the effect of deleted pancreatic cancer locus 4 (DPC4) gene transfection on biological behaviors of human colorectal carcinoma cells and the role of DPC4 gene in colorectal carcinogenesis. METHODS: PcDNA3.1-DPC4 plasmid was re-constructed by gene-recombination technology. SW620 cells, a human colorectal carcinoma cell line, were transfected with PcDNA3.1-DPC4 plasmid using lipofectamine transfecting technique. Transfected cells were selected with G418. Expression of Smad4 protein was detected in cells transfected with DPC4 gene by immunohistochemistry and Western blot. Biological characterristics of transfected cells were evaluated by population-doubling time and cloning efficiency. Alterations of percentage of S phage cells (S%) and apoptosis rate were determined by flow-cytometry. RESULTS: PcDNA3.1-DPC4 plasmid was constructed successfully. SW620 cells transfected with PcDNA3.1-DPC4 plasmid (DPC4+-SW620 cells) showed a strong intracellular expression of Smad4 protein, and the positive signal was localized in cytoplasm and nuclei, mainly in cytoplasm, where the expressions of Smad4 protein in SW620 cells transfected with PcDNA3.1 plasmid (PcDNA3.1-SW620 cells) and non-transfected SW620 cells (SW620 cells) were weaker than those in DPC4+-SW620 cells. The population-doubling time in DPC4+-SW620 cells (116 h) was significantly longer than that in SW620 cells (31 h) and PcDNA3.1-Sw620 cells (29 h) (P<0.01). The cloning efficiencies of DPC4+-SW620 cells (12%) were markedly lower than those of SW620 cells (69%) and PcDNA3.1-Sw620 cells (67%) (P<0.01). Compared with SW620 cells and PcDNA3.1-Sw620 cells, the Go-G1% of DPC4+-SW620 cells was obviously higher and the S% was markedly lower (P<0.05). Apoptosis rate of DPC4+-SW620 cells was significantly higher than that of SW620 cells and PcDNA3.1-SW620 cells. CONCLUSION: PcDNA3.1-DPC4 plasmid can be successfully re-constructed and stably transfected into human SW620cells, thereby the cells can steadily express Smad4. DPC4 protein may regulate proliferation of colorectal carcinoma cells by inhibiting cell growth and inducing cell apoptosis.展开更多
The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morpholog...The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.展开更多
Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low ...Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.展开更多
Objective： To investigate the relationship of poly（ADP-ribose）glycohydrolase（PARG） with poly （ADP-ribose） polymerase（PARP）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor（b-FG...Objective： To investigate the relationship of poly（ADP-ribose）glycohydrolase（PARG） with poly （ADP-ribose） polymerase（PARP）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor（b-FGF） in colorectal carcinoma（CRC）. Methods： Immunohistochemical analysis was used to detect PARG, PARP, VEGF and b-FGF in human colorectal carcinoma. Flow cytometry was used to detect PARG and PARP in murine CT26 cell line. Gallotannin （GLTN） was served as PARG inhibitor. Results： The individual positive rates of PARG, PARE VEGF and b-FGF were 55.81%（24/43）, 97.67%（42/43）, 79.07%（34/43） and 81.40%（35/43）, respectively, which were significantly higher than those of control group. The positive PARG was correlated to PARP（r=0.3703, P〈0.05） and b-FGF （r=0.4838, P〈0.05）. The positive PARP was correlated to VEGF （r=0.3968, P〈0.05） and b-FGF （r=0.5610, P〈0.05）. Both PARG and PARP were expressed in CT26 cells. The positive staining rates of PARG and PARP in GLTN-treated group were 7.3% and 52.38%, respectively. They were markedly reduced than those of control group （55.41% and 95.28%, P〈0.01, n=10000）. Conclusion： The data suggest that PARG expression probably plays a role for VEGF and b-FGF expression in colorectal carcinoma.展开更多
AIM： To study the activity of telomerase and the expression of human telomerase reverse transcriptase （hTERT） in colorectal carcinoma and its adjacent tissues, normal mucosa and adenomatoid polyp, and to evaluate t...AIM： To study the activity of telomerase and the expression of human telomerase reverse transcriptase （hTERT） in colorectal carcinoma and its adjacent tissues, normal mucosa and adenomatoid polyp, and to evaluate their relation with carcinogenesis and progression of colorectal carcinoma. METHODS： Telomerase activity and hTERT expression were determined in 30 samples of colorectal carcinoma and its adjacent tissues, normal mucosa and 20 samples of adenomatoid polyp by modified telomeric repeat amplification protocol （TRAP）, enzyme-linked immunosorbent assay （ELISA） and immunohistochemical method. RESULTS： Telomerase activity and hTERT expression were 83.33% （25/30） and 76.67% （23/30） respectively in colorectal carcinoma, which were obviously higher than those in paracancerous tissues （13.33%, 16.67%）, normal mucosa （3.33%, 3.33%） and adenomatoid polyp （10%, 10%）. There was a significant difference between colorectal carcinoma and other tissues （P=0.027）. The telomerase activity and hTERT expression were higher in colorectal carcinoma with lymphatic metastasis than in that without lymphatic metastasis （P=0.034）. When the histological classification and clinical stage were greater, the telomerase activity and hTERT expression increased, but there was no significant difference between them. In colorectal carcinoma, the telomerase activity was correlated with hTERT expression （positive vs negative expression of telomerase activity and hTERT, P=0.021）. CONCLUSION： Telomerase activity is closely correlated with the occurrence, development and metastasis of colorectal carcinoma. Overexpression of hTERT may play a critical role in the regulation of telomerase activity.展开更多
文摘Colorectal carcinoma is common,particularly on the left side.In 20%of patients,obstruction and ileus may be the first clinical manifestations of a carcinoma that has advanced(stage II,III or even IV).Diagnosis is based on clinical presentation,plain abdominal radiogram,computed tomography(CT),CT colonography and positron emission tomography/CT.The best management strategy in terms of short-term operative or interventional and long-term oncological outcomes re-mains unknown.For the most common left-sided obstruction,the first choice should be either emergency surgery or endoscopic decompression by self-expen-dable metal stents or tubes.The operative plan should be either one-stage or two-stage resection.One-stage resection with on-table bowel decompression and irrigation can be accompanied or not accompanied by proximal defunctioning stoma(colostomy or ileostomy).Primary anastomosis is more convenient but has increased risks of anastomotic leakage and morbidity.Two-stage resection(Hart-mann’s procedure)is safer and the most widely used despite temporally affecting quality of life.Damage control surgery in high-risk frail patients is less frequently performed since it can be successfully substituted with endoscopic stenting or tubing.For the less common right-sided obstruction,one-stage surgical resection is more beneficial than endoscopic decompression.The role of minimally invasive surgery(laparoscopic or robotic)is a subject of debate.Emergency laparoscopic-assisted management is advantageous to some extent but requires much expertise due to inherent difficulties in dissecting the distended colon and the risk of rup-ture and subsequent septic complications.The decompressing stent as a bridge to elective surgery more substantially decreases the risks of morbidity and mortality than emergency surgery for decompression and has equivalent medium-term overall survival and disease-free survival rates.Its combination with neoadjuvant chemotherapy or radiation may have a positive effect on long-term oncological outcomes.Management plans are crucial and must be individualized to better fit each case.Core Tip:Acute obstruction is common in patients with more advanced colorectal carcinoma and may be the first manifestation mainly of left-sided obstruction and in elderly individuals.Emergency decompression is mandatory.Emergency surgical resection and primary anastomosis accompanied or not accompanied by proximal defunctioning stoma must be the first treatment choice for fit patients under 70 years.Hartmann’s two-stage procedure,although more preferable,must be the second alternative choice.Emergency endoscopic self-expendable metal stents must be preferred in unfit patients as a bridge to surgery and for palliative treatment in all inoperable cases.However,these basic management principles constitute a general direction.Decision-making is important and should be individualized.
文摘BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.
文摘BACKGROUND Conventional five-port laparoscopic surgery,the current standard treatment for colorectal carcinoma(CRC),has many disadvantages.AIM To assess the influence of reduced-port laparoscopic surgery(RPLS)on perioperative indicators,postoperative recovery,and serum inflammation indexes in patients with CRC.METHODS The study included 115 patients with CRC admitted between December 2019 and May 2023,52 of whom underwent conventional five-port laparoscopic surgery(control group)and 63 of whom underwent RPLS(research group).Comparative analyses were performed on the following dimensions:Perioperative indicators[operation time(OT),incision length,intraoperative blood loss(IBL),and rate of conversion to laparotomy],postoperative recovery(first postoperative exhaust,bowel movement and oral food intake,and bowel sound recovery time),serum inflammation indexes[high-sensitivity C-reactive protein(hs-CRP),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)],postoperative complications(anastomotic leakage,incisional infection,bleeding,ileus),and therapeutic efficacy.RESULTS The two groups had comparable OTs and IBL volumes.However,the research group had a smaller incision length;lower rates of conversion to laparotomy and postoperative total complication;and shorter time of first postoperative exhaust,bowel movement,oral food intake,and bowel sound recovery;all of which were significant.Furthermore,hs-CRP,IL-6,and TNF-αlevels in the research group were significantly lower than the baseline and those of the control group,and the total effective rate was higher.CONCLUSION RPLS exhibited significant therapeutic efficacy in CRC,resulting in a shorter incision length and a lower conversion rate to laparotomy,while also promoting postoperative recovery,effectively inhibiting the inflammatory response,and reducing the risk of postoperative complications.
基金Supported by Grants from the Major State Basic Research Development Program of China 973 Program,No.2007CB512402National Natural Science Foundation of China,No.31100634+1 种基金Natural Science Foundation of Jiangsu Province,No.BK2010161"333" Project of Wuxi City,Jiangsu Province,No.CAE00901-09
文摘AIM： To investigate the expression of B7-H1 in human colorectal carcinoma （CRC） to define its regulating ef- fects on T cells in tumor microenvironment.
基金Supported by grants from the Special Government Funding (EVO) allocated to Turku University Central Hospital
文摘AIM： To investigate the changes that occur in E-cadherin expression during the process of metastasis in colorectal cancer.METHODS： E-cadherin expression was detected by immunohistochemistry and two indices of expression were calculated which reflected the level of expression and the locations （membrane and cytoplasm）. Univariate and multivariate survival analyses were used to assess the value of these two E-cadherin indices as predictors of both disease-free （DFS） and disease-specific （DSS） survival. RESULTS： E-cadherin membrane index （MI）, but not cytoplasmic index （CI）, was significantly higher in primary tumors than their metastases （P = 0.0001）. Furthermore, both primary tumor MI and CI were higher among the patients who developed subsequent metastasis （P = 0.022 and P = 0.007, respectively）. Interestingly, both indices were higher in liver metastase compared to other anatomic sites （MI, P = 0.034 and CI, P = 0.022）. The CI of the primary tumors was a significant predictor of DFS （P = 0.042, univariate analysis）, with a strong inverse correlation between CI and DFS （P = 0.006, multivariate analysis）. Finally, the MI of primary tumor proved to be a significant independent predictor of DSS, with higher indices being associated with a more favorable outcome （P = 0.016）. CONCLUSION： Examination of E-cadherin expression and distribution in colorectal tumors can be extremely valuable in predicting disease recurrence. The observation that aberrant cytoplasmic expression of E-cadherin can predict disease recurrence is obviously of great importance for both patients and clinicians, and significantly affects decisions concerning the therapy and management of the patients.
文摘AIM： To investigate the role of survivin expression in the pathogenesis of colorectal carcinoma. METHODS： Immunohistochemistry S-P method and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNE） were used to detect the expression of survivin and apoptotic cell in situ in colorectal cancerous tissues, para-cancerous tissues and normal tissues of 48 cases of colorectal carcinoma. RESULTS： The survivin positive unit （PU） was higher in cancerous tissues （38.76±5.14） than in para-cancerous （25.17±7.26） or normal tissues （0.57±0.03） （P〈0.05）. The apoptosis index （AI） of para-cancerous tissues was （7.51±2.63%） higher than cancerous tissues （4.65±1.76%）. The expression of survivin was associated with pathological grade, lymph node metastasis and Dukes stage of colorectal carcinoma. CONCLUSION： Survivin expression may play an important role in carcinogenesis of colorectal carcinoma and may be associated with malignant biological behaviors of colorectal carcinoma.
基金Grants from the Special Government Funding (EVO) allocated to Turku University Central Hospital and Cancer Society of South-West Finland (Turku)
文摘AIM： To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer （CRC）. METHODS： Archival tumor samples were analyzed for β-catenin using immunohistochemistry （IHC） in 95 patients with advanced CRC. RESULTS： Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 100% of CRC cases showed membranous and cytoplasmic expression, and 55 （58%） cases showed nuclear expression. In univariate （Kaplan-Meier） survival analysis, only the nuclear index （NI） was a significant predictor of disease free survival （DFS） （P = 0.023; n = 35）, with a NI above the median associated with longer DFS （34.2 too） than those with a NI below the median （15.5 too） （P = 0.045, ANOVA）. The other indices were not significant predictors of DFS, and none of the three tested indices （for membranous, cytoplasmic, or nuclear expression） predicted diseasespecific survival （DSS）. However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS （P = 0.041） and DSS （P = 0.046）. CONCLUSION： Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.
基金Supported by the Medical Science Foundation of Guangdong Province, No. A2002185
文摘AIM: To investigate the correlation between microvessel density and spiral CT perfusion imaging in colorectal carcinoma. METHODS: Thirty-seven patients, with histologically proven colorectal carcinoma, underwent water enema spiral CT scan. The largest axial surface of the primary tumor was searched on unenhanced spiral CT images. At this level, the enhanced dynamic scan series was acquired. Time-density curves (TDC) were created from the region of interest drawn over the tumor, target artery by Toshiba Xpress/SX spiral CT with perfusion functional software. Then the perfusion was calculated. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and then MVD was correlated with perfusion. RESULTS: MVD of colorectal carcinomas was 33.11-173.44, mean 87.28, and perfusion was 15.60-64.80 mL/min/ 100 g, mean 39.74 mL/min/100 g. MVD and perfusion were not associated with invasive depth, metastasis and disease stage, and they all decreased with increasing Dukes' stage, but no significant correlation was found between them (r=0.18, P=0.29). CONCLUSION: There is no significant correlation between MVD and perfusion. Neovascularizaton and perfusion are highly presented in early colorectal carcinoma. CT perfusion imaging may be more suited for assessing tumorigenesis in colorectal carcinoma than histological MVD technique.
基金Supported by the National Natural Science Foundation of China, No.30370649
文摘AIM: To explore the expression of Tiam1 gene in colorectal carcinoma and its correlation with tumor metastasis. METHODS: Expressions of Tiaml gene in 8 colorectal carcinoma cell lines were detected by reverse transcriptase-polymerase chain reaction. In vitro invasiveness was determined by means of Matrigel invasion assay. The correlation of Tiaml expression with the invasive ability was also analyzed. RESULTS: Tiaml gene was highly expressed in LoVo and SW620, which were established from metastatic colorectal carcinomas in comparison with LS174T, SW480, HCT116, LST, HRT-18 and Hee8693, which were established from primary colorectal carcinomas. In vitro cell invasivion demonstrated that LoVo and SW620 had a higher invasive ability than LS174T, SW480, HCT116, LST, HRT-18 and Hee8693. The expression of Tiaml gene was highly related to the metastatic potential of colorectal carcinoma cells. CONCLUSION: Tiaml gene may play an important role in invasion and metastasis of colorectal carcinoma and is a metastasis-related gene.
基金Supported by the Natural Science Foundation of Hebei Province,No. C2004000642
文摘AIM: To explore the relationship between matrix metallopr- oteinase-2 (MMP-2) and tissue inhibitor of metallopr- oteinase-2 (TIMP-2) in the development of colorectal carcinoma and to provide a valuable marker for clinical diagnosis. METHODS: Twenty-five patients with colorectal carcinoma underwent surgical resection. Samples were taken from tumor sites and normal tissues. MMP-2 activity was determined by gelatin zymography. Western blot and ABC immunohist-ochemical staining were used to detect the expression levels of MMP-2 and TIMP-2 in normal and colorectal carcinoma tissues. Statistical analyses were performed using the Student's t test and one-way ANOVA. P<0.05 was considered statistically .significant. All the statistical analyses were performed using SPSS 10.0 software. RESULTS: MMP-2 activity could be detected in both normal and colorectal carcinoma tissues. MMP-2 activity in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t=3.916,4.227). MMP-2 activity was positively related to the colorectal carcinoma invasion depth, lymph node metastasis and Duke's stage. Western blot and ABC immunohistochemical staining demonstrated that the expression level of MMP-2 in colorectal carcinoma tissues was much higher than that in normal tissues (P<0.05, t = 9.429), but the expression level of TIMP-2 in colorectal carcinoma tissues was much lower than that in normal tissues (P<0.05, t = 7.329). The MMP-2/TIMP-2 ratio of colorectal carcinoma was much higher than that of normal tissues. With the progression of invasion depth, lymph node metastasis and tumor Duke's stage, the activity and expression level of MMP-2 and TIMP-2 gradually increased, but the MMP-2/TIMP-2 ratio gradually decreased. CONCLUSION: The balance between MMP-2 and TIMP-2 plays a crucial role in the process of colorectal carcinoma invasion and metastasis.
基金Supported by Scientific Foundation of Education Committee of Jiangsu Province. No.96039
文摘AIM: To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER). METHODS: Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1(+)/ER(+),mdr1(+)/ER(-), mdr1(-) expressions, were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM [15 mg/(kg/d)] was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and t tests. RESULTS: In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group [(39.1±2.29) mg, (31.44±1.61) mm3] and TAM and DOX group [(38.72±2.56) mg, (31.31v1.74) mm3], which were lesser than that of control group [(45.48±3.92) mg, (36.42±2.77) mm3, P= 0.037, P= 0.016 respectively] significantly. In the animal models with mdr1(+)/ER(+) tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group [(425.5±28.58) mg, (340.35±22.28) mm3], they were significantly less than that of control group [(634.23±119.41) mg, (507.45±93.34) mm3, P= 0.022, P = 0.045 respectively], which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments. CONCLUSION: The expression of mdr1 gene corresponds to the sensitivity of colon cancer to anti-tumor drugs in vivo. TAM can reverse the MDR of colorectal carcinoma in nude mice, which is independent of the expression of ER; however, no change was observed in the expressive level of mdr1 mRNA.
基金Supported by a Grant From the Yen Tjing-Ling Medical Foundation
文摘AIM:To evaluate the correlations of plasma von Willebrand factor (vWF) level with the distant metastasis and prognosis of patients with colorectal cancer. METHODS: A total of 86 patients with historically confirmed metastatic colorectal cancers receiving treatment at Taipei Veterans General Hospital were enrolled. All patients had measurable metastatic lesions and life expectancies of more than 3 mo. Plasma vWF levels were measured by immuno-turbidimetric assay and compared with results from 40 non-metastatic colorectal cancer patients and 22 healthy controls. Patients with metastatic colorectal cancer were divided into two groups according to serum vWF levels and the differences between these two groups were analyzed using X2 test. Data on age, gender, performance status, location of primary tumor, extent of metastasis, site of metastases, histological differentiation, serum CEA and plasma vWF levels were analyzed to determine association with survival. Survival curves were constructed by Kaplan-Meier product limit method and the data was analyzed using log-rank test on a microcomputer. Multivariate analysis using the Cox's proportional hazards regression model was then performed to determine the independent prognostic indicators among all of the possible variables. RESULTS: Colorectal cancer patients were identified as having significantly higher plasma vWF concentrations than healthy controls (P<0.05). Moreover, higher vWF plasma levels were associated with advanced tumor stage (P<0.05) and the presence of multiple metastases (P=0.014). Patients with lower vWF plasma levels (≤160%) survived significantly longer than those with a higher plasma vWF level (log-rank test, P= 0.0043). By multivariate analysis, plasma vWF levels (P<0.001), the extent of metastasis (P= 0.012), and the performance status (P=0.014) were identified as independent prognostic factors. CONCLUSION: Our data indicates that high plasma vWF concentrations correlate with advanced diseases and significantly poor prognosis of patients with metastatic colorectal carcinoma. It may serve as a potential biological marker of disease progression in these patients.
文摘AIM: To investigate the killing effect and radiosensitization of double suicide gene mediated by adenovirus on colorectal carcinoma cells. METHODS: Colorectal carcinoma cell line SW480 was transfected with adenovirus expression vector containing cytosine deaminase (CD) and thymidine kinase (TK) fusion gene. The expression of CD-TK fusion gene was detected by reverse transcriptase-polymerase chain reaction. The toxic effect of ganciclovir (GCV) and 5-fluorocytosine (5-FC) on infected cells was determined by MTT assay. The radiosensitization of double suicide gene was evaluated by clonogenic assay. RESULTS: After prodrugs were used, the survival rate of colorectal carcinoma cells was markedly decreased. When GCV and 5-FC were used in combination, the cytotoxicity and bystander effect were markedly superior to a single prodrug (X2 = 30.371, P<0.01). Both GCV and 5-FC could sensitize colorectal carcinoma cells to the toxic effect of radiation, and greater radiosensitization was achieved when both prodrug were used in combination. CONCLUSION: CD-TK double suicide gene can kill and radiosensitize colorectal carcinoma cells.
基金Supported by the grant 143010 from the Ministry of Science and Environment Protection of the Republic of Serbia
文摘AIM: To investigate the significance of p16 and O6- methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p 16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable. CONCLUSION: Our data suggest that comethylation of promoters of p 16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.
文摘Circulating vascular endothelial growth factor-C （VEGF-C） and vascular endothelial growth factor （VEGF） levels in patients with colorectal carcinoma were determined in order to assess their clinical significance as a diagnostic tool for monitoring lymph node metastasis. In 66 patients with colorectal carcinoma and 30 healthy controls, circulating VEGF-C and VEGF levels were assessed by using enzyme-linked immunosorbent assay （ELISA）. Serum VEGF-C and VEGF levels were higher in patients with colorectal carcinoma than in healthy controls. Patients with lymph node metastasis had higher serum VEGF-C and VEGF levels than those without lymph node metastasis. The levels of VEGF-C and VEGF were higher in the invasion group than in the non-invasion group. Serum VEGF-C levels reached a sensitivity of 81% and a specificity of 76 % with a cutoff value of 1438.0 pg/mL, whereas VEGF levels reached 72 % sensitivity and 74 % specificity at 240.2 pg/ mL. If 66 patients were divided into 4 groups according to the combined determination of VEGF-C and VEGF levels, the positive predictive value was 85.3 %, the negative predictive value was 94.6 %, and accuracy was 93.7 %. It was suggested that circulating VEGF-C levels might provide additional information for distinguishing the absence from presence of lymph node metastasis in patients with colorectal carcinoma. The combined determination of VEGF-C and VEGF levels could be used as an important index for preoperatively clinical stage of colorectal carcinoma.
文摘AIM: To investigate the effect of deleted pancreatic cancer locus 4 (DPC4) gene transfection on biological behaviors of human colorectal carcinoma cells and the role of DPC4 gene in colorectal carcinogenesis. METHODS: PcDNA3.1-DPC4 plasmid was re-constructed by gene-recombination technology. SW620 cells, a human colorectal carcinoma cell line, were transfected with PcDNA3.1-DPC4 plasmid using lipofectamine transfecting technique. Transfected cells were selected with G418. Expression of Smad4 protein was detected in cells transfected with DPC4 gene by immunohistochemistry and Western blot. Biological characterristics of transfected cells were evaluated by population-doubling time and cloning efficiency. Alterations of percentage of S phage cells (S%) and apoptosis rate were determined by flow-cytometry. RESULTS: PcDNA3.1-DPC4 plasmid was constructed successfully. SW620 cells transfected with PcDNA3.1-DPC4 plasmid (DPC4+-SW620 cells) showed a strong intracellular expression of Smad4 protein, and the positive signal was localized in cytoplasm and nuclei, mainly in cytoplasm, where the expressions of Smad4 protein in SW620 cells transfected with PcDNA3.1 plasmid (PcDNA3.1-SW620 cells) and non-transfected SW620 cells (SW620 cells) were weaker than those in DPC4+-SW620 cells. The population-doubling time in DPC4+-SW620 cells (116 h) was significantly longer than that in SW620 cells (31 h) and PcDNA3.1-Sw620 cells (29 h) (P<0.01). The cloning efficiencies of DPC4+-SW620 cells (12%) were markedly lower than those of SW620 cells (69%) and PcDNA3.1-Sw620 cells (67%) (P<0.01). Compared with SW620 cells and PcDNA3.1-Sw620 cells, the Go-G1% of DPC4+-SW620 cells was obviously higher and the S% was markedly lower (P<0.05). Apoptosis rate of DPC4+-SW620 cells was significantly higher than that of SW620 cells and PcDNA3.1-SW620 cells. CONCLUSION: PcDNA3.1-DPC4 plasmid can be successfully re-constructed and stably transfected into human SW620cells, thereby the cells can steadily express Smad4. DPC4 protein may regulate proliferation of colorectal carcinoma cells by inhibiting cell growth and inducing cell apoptosis.
文摘The expression of glucose regulated protein 94 (GRP94)during the treatment of human colorectal carcinoma cell lineClone A cells with sodium butyrate was studied. Sodium butyrate (SB) can cause functional and morphological effects on Clone A cells including growth arrest at Go/G1 stage and cell differentiation as observed by morphological changes, MTT and flow cytometry assays, as well as reduced Grp94 gene expression as shown by Northern blot and Western blot assays. The possible mechanism of the correlation between Grp94 gene expression and tumor growth inhibition and cell differentiation is briefly discussed.
文摘Metastatic colorectal cancer to the liver is associated with a uniform poor prognosis without treatment. Advances in therapy over the past decades have now allowed surgical resections of the liver to occur with a low morbidity and mortality. Improvements in chemotherapy regimes have paralleled technical improvements and now allow a new group of patients to become eligible for surgical resection. This chapter will review the recent advances in surgical and chemotherapeutic regimes in metastatic colorectal cancer to the liver.
基金supported by the National Natural Science Foundation of China (No 30870946)Natural Science Foundation of CQ CSTC(CSTC, 2006BB5288)
文摘Objective： To investigate the relationship of poly（ADP-ribose）glycohydrolase（PARG） with poly （ADP-ribose） polymerase（PARP）, vascular endothelial growth factor （VEGF） and basic fibroblast growth factor（b-FGF） in colorectal carcinoma（CRC）. Methods： Immunohistochemical analysis was used to detect PARG, PARP, VEGF and b-FGF in human colorectal carcinoma. Flow cytometry was used to detect PARG and PARP in murine CT26 cell line. Gallotannin （GLTN） was served as PARG inhibitor. Results： The individual positive rates of PARG, PARE VEGF and b-FGF were 55.81%（24/43）, 97.67%（42/43）, 79.07%（34/43） and 81.40%（35/43）, respectively, which were significantly higher than those of control group. The positive PARG was correlated to PARP（r=0.3703, P〈0.05） and b-FGF （r=0.4838, P〈0.05）. The positive PARP was correlated to VEGF （r=0.3968, P〈0.05） and b-FGF （r=0.5610, P〈0.05）. Both PARG and PARP were expressed in CT26 cells. The positive staining rates of PARG and PARP in GLTN-treated group were 7.3% and 52.38%, respectively. They were markedly reduced than those of control group （55.41% and 95.28%, P〈0.01, n=10000）. Conclusion： The data suggest that PARG expression probably plays a role for VEGF and b-FGF expression in colorectal carcinoma.
基金Supported by the Science Foundation of Health Bureau of Guangxi Zhuang Autonomous Region,No.9954
文摘AIM： To study the activity of telomerase and the expression of human telomerase reverse transcriptase （hTERT） in colorectal carcinoma and its adjacent tissues, normal mucosa and adenomatoid polyp, and to evaluate their relation with carcinogenesis and progression of colorectal carcinoma. METHODS： Telomerase activity and hTERT expression were determined in 30 samples of colorectal carcinoma and its adjacent tissues, normal mucosa and 20 samples of adenomatoid polyp by modified telomeric repeat amplification protocol （TRAP）, enzyme-linked immunosorbent assay （ELISA） and immunohistochemical method. RESULTS： Telomerase activity and hTERT expression were 83.33% （25/30） and 76.67% （23/30） respectively in colorectal carcinoma, which were obviously higher than those in paracancerous tissues （13.33%, 16.67%）, normal mucosa （3.33%, 3.33%） and adenomatoid polyp （10%, 10%）. There was a significant difference between colorectal carcinoma and other tissues （P=0.027）. The telomerase activity and hTERT expression were higher in colorectal carcinoma with lymphatic metastasis than in that without lymphatic metastasis （P=0.034）. When the histological classification and clinical stage were greater, the telomerase activity and hTERT expression increased, but there was no significant difference between them. In colorectal carcinoma, the telomerase activity was correlated with hTERT expression （positive vs negative expression of telomerase activity and hTERT, P=0.021）. CONCLUSION： Telomerase activity is closely correlated with the occurrence, development and metastasis of colorectal carcinoma. Overexpression of hTERT may play a critical role in the regulation of telomerase activity.
