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1.
Chinese Medical Journal ; (24): 949-956, 2013.
Article in English | WPRIM | ID: wpr-342268

ABSTRACT

<p><b>OBJECTIVE</b>This review discusses the current status and progress in studies on fulminant Clostridium difficile colitis (FCDC), including the definition, risk factor, diagnostic role of CT, surgical treatment, postoperative mortality, and new therapeutic strategy.</p><p><b>DATA SOURCES</b>A literature search was conducted mainly in Medline and PubMed published in English between January 2000 and May 2011. The search terms were "ulminant Clostridium difficile colitis" "reatment", "urgery" and "ortality"</p><p><b>RESULTS</b>Recent studies show that the overall mortality rate for FCDC remains high despite early surgical intervention. It has been difficult to identify the real value for surgical intervention in patients with FCDC due to the absence of prospective, randomized studies. Early recognition of patients with FCDC will help a clinician decide the need for treatment in an intensive care setting, multi-disciplinary consultation, and appropriate therapeutic selection. Some studies emphasize the importance of early recognition and emergent surgery at a less severe stage. Monoclonal antibody therapy and intravenous immunoglobulin treatment may be useful for the treatment of FCDC.</p><p><b>CONCLUSIONS</b>Present studies do not provide strong evidence for guiding the surgical treatment of FCDC; hence, creation of collaborative research networks is crucial in order to undertake large prospective multi-center studies for improvement in overall survival.</p>


Subject(s)
Humans , Antibodies, Monoclonal , Therapeutic Uses , Clostridium Infections , Drug Therapy , General Surgery , Clostridioides difficile , Virulence , Immunoglobulins , Therapeutic Uses
2.
Chinese Journal of Gastrointestinal Surgery ; (12): 1256-1260, 2012.
Article in Chinese | WPRIM | ID: wpr-312312

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the feasibility of bone marrow mesenchymal stem cells(MSC)with the acellular dermal matrix(ADM) biological patch for the treatment of external anal sphincter injury on the animal models.</p><p><b>METHODS</b>Thirty Wistar rats with sphincter injury were randomly divided into three groups. Group A underwent end to end sphincteric repair directly, group B underwent end to end repair and then covered by ADM patch, and group C underwent end to end repair and then covered by ADM which was previously seeded with MSC. After six weeks, the whole ring specimens including anal canal and lower rectum were removed. The hematoxylin and eosin stain and Masson trichrome stain were performed to observe the change of histomorphology.</p><p><b>RESULTS</b>Two weeks later, the majority of rat models presented with moist anus and crissum with loose stools, which indicated that the model was established successfully. Six weeks after repair, in group A and B, the suffusion of fibrous connective tissue and the infiltration of inflammatory cells were observed at the repair site of sphincter. And lots of collagen fiber which was stained into blue deposited dispersedly at the site of repair with no obvious proliferation of capillaries. However, in group C, the blue collagenous fiber which deposited at the sphincter injury site was less than that in groups A and B. Muscle fibers were observed to be stained into red distributed dispersedly at the repair site of sphincter in group C.</p><p><b>CONCLUSIONS</b>Transplantation of ADM biological patch rich in bone MSC can partly improve the regeneration of rat injured anal sphincter and lessen the formation of cicatrix.</p>


Subject(s)
Animals , Rats , Acellular Dermis , Anal Canal , Wounds and Injuries , General Surgery , Bone Marrow , Mesenchymal Stem Cell Transplantation , Rats, Wistar , Wound Healing
3.
Chinese Journal of Surgery ; (12): 346-350, 2011.
Article in Chinese | WPRIM | ID: wpr-346307

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate and compare the efficiency and safety of laparoscopic surgery (LS) and open surgery (OS) in the treatment of colorectal carcinoma.</p><p><b>METHODS</b>Randomized controlled trials on laparoscopic surgery and open surgery for colorectal carcinoma from January 2000 to October 2010 were searched in the databases of EMbase, PubMed, Cochrane Library, Sciencedirect, Springer, VIP, CNKI, CBMdisc. The methodological quality was assessed according to the standard of Cochrane systematic review. For homogeneous studies, RevMan5.0 software was used for meta-analysis.</p><p><b>RESULTS</b>A total of 13 RCTs involving 4603 patients were included in this study, and among those 6 were multi-center randomized controlled trials. The meta-analysis showed that: the operation time of the LS group was longer than that of the OS group (WMD = 38.91, 95%CI: 33.89 - 43.93, P < 0.001), the blood loss (WMD = -138.14, 95%CI: -195.79 - -80.50, P < 0.001) and the length of hospital stay (WMD = 2.91, 95%CI: -4.65 - -1.17, P = 0.001) of the LS group was less than those in OS group. There was no significant differences between the two groups in the number of dissected lymph nodes (WMD = -0.62, 95%CI: -1.47 - 0.23, P = 0.150). There was no significant differences between the two groups in terms of the postoperative complications (30 days) (RR = 0.78, 95%CI: 0.59 - 1.01, P = 0.06). There was no significant differences between the two groups in 3-year overall survival (RR = 1.00, 95%CI: 0.96 - 1.04, P = 0.970). There was no significant differences between the two groups in 5-year overall survival (RR = 1.03, 95%CI: 0.99 - 1.08, P = 0.140). There was no significant differences between the two groups in 5-year overall recurrence (RR = 0.89, 95%CI: 0.74 - 1.07, P = 0.200).</p><p><b>CONCLUSIONS</b>Laparoscopic surgery for colorectal carcinoma is a safe and effective therapy as open surgery in the short term or long term outcomes. It could be an acceptable alternative to open surgery for colorectal carcinoma.</p>


Subject(s)
Humans , Colorectal Neoplasms , General Surgery , Laparoscopy , Randomized Controlled Trials as Topic , Treatment Outcome
4.
Chinese Journal of Gastrointestinal Surgery ; (12): 419-421, 2011.
Article in Chinese | WPRIM | ID: wpr-237107

ABSTRACT

<p><b>OBJECTIVE</b>To explore the feasibility and functional outcome of antiperistaltic cecoproctostomy in colorectal reconstruction.</p><p><b>METHODS</b>Fifty-six patients who underwent antiperistaltic cecoproctostomy were retrospectively studied. Indications for antiperistaltic cecoproctostomy included slow transit constipation(n=44), synchronous colon cancer or colonic polyps(n=5), acute obstructing left colon carcinoma(n=4), and adult megacolon(n=3).</p><p><b>RESULTS</b>Short-term postoperative complications included wound infections(n=5), 3 lymphatic leakages(n=3), and inflammatory small bowel obstruction(n=1). One month after antiperistaltic cecoproctostomy, the median frequency of daily bowel movement was 4.0(range, 2-6). After a median follow-up of 4 years(range, 1 month to 7 years), the median daily bowel frequency was 2.5(range, 0.5-4.0). Five patients suffered from long-term postoperative complications including small bowel obstruction(n=3), incision hernia(n=1), and mild cecal dilatation(n=1). The mean Wexner incontinence score was 4.2±1.1.</p><p><b>CONCLUSION</b>Antiperistaltic cecoproctostomy is safe and effective for colorectal reconstruction.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Anastomosis, Surgical , Methods , Cecum , General Surgery , Digestive System Surgical Procedures , Methods , Rectum , General Surgery , Retrospective Studies , Treatment Outcome
5.
Chinese Journal of Gastrointestinal Surgery ; (12): 286-288, 2010.
Article in Chinese | WPRIM | ID: wpr-266355

ABSTRACT

<p><b>OBJECTIVE</b>To examine the association between polymorphism of vascular endothelial growth factor(VEGF)1498 C/T,936 C/T and colorectal adenoma genetic susceptibility.</p><p><b>METHODS</b>A case-control study of 224 colorectal adenomas and 200 controls was conducted and VEGF genotypes were determined based on TaqMan-probe assay. The epidemiological factors were collected through questionnaire. Accordingly, the clinicopathological data of each sample were also investigated.</p><p><b>RESULTS</b>The carriage of 936 CT and CT+TT genotypes had significantly higher risk of colorectal adenoma (CT vs. CC, OR=2.00, 95% CI: 1.23-3.25, P=0.006; CT+TT vs. CC, OR=2.04, 95% CI:1.28-3.26, P=0.003). 936-T allele carriage had increased risk of colorectal adenoma (OR=1.91, 95% CI:1.25-2.91, P=0.003). The genotypes of 1498 C/T and the frequency of C/T allele showed no differences between healthy persons and patients (P>0.05). In patients with 936 CT+TT and 936-T allele implied a tendency of villous adenoma category (CT+TT vs. CC, OR=2.54, 95% CI:1.12-5.75, P=0.040; T allele vs. C allele, OR=3.08, 95% CI, 1.64-5.80, P=0.001).</p><p><b>CONCLUSION</b>VEGF 936 C/T polymorphism can influence susceptibility to colorectal adenoma.</p>


Subject(s)
Adult , Female , Humans , Middle Aged , Adenoma , Genetics , Case-Control Studies , Colorectal Neoplasms , Genetics , Genetic Predisposition to Disease , Genotype , Polymorphism, Single Nucleotide , Vascular Endothelial Growth Factor A , Genetics
6.
Journal of Southern Medical University ; (12): 2480-2484, 2009.
Article in Chinese | WPRIM | ID: wpr-325085

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the protective effect of ischemic postconditioning (IPC) against hepatic ischemia-reperfusion injury.</p><p><b>METHODS</b>Twenty-four normal male Wistar rats were randomly divided into sham-operated group, ischemia-reperfusion group (IR) and IPC group, and in the latter two groups, the rats were subjected to acute hepatic ischemia-reperfusion. IPC was achieved by several brief pre-reperfusion and withdrawn before persistent reperfusion. The concentration of malondialdehyde (MDA) and activity of several antioxidant enzymes in the hepatic tissue were measured. The cell apoptosis was detected by TdT-mediated dUTP-biotin nick end labeling (TUNEL) and the expression of Bcl-2 protein measured by immunohistochemistry. The mitochondrial ultrastructural and morphological changes of the hepatic cells were observed by electron microscopy.</p><p><b>RESULTS</b>Compared with IR group, IPC group showed significantly reduced concentration of MDA and the hepatocellular apoptotic index (P<0.05) with markedly enhanced activity of the antioxidant enzymes and Bcl-2 protein expression (P<0.05).The mitochondrial ultrastructural damage was also relieved obviously in IPC group.</p><p><b>CONCLUSION</b>IPC can reduce the hepatocellular apoptosis after reperfusion and offers protection against hepatic IR injury.</p>


Subject(s)
Animals , Male , Rats , Apoptosis , Ischemic Postconditioning , Methods , Liver , Metabolism , Pathology , Malondialdehyde , Metabolism , Mitochondria, Liver , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Random Allocation , Rats, Wistar , Reperfusion Injury
7.
Chinese Journal of Surgery ; (12): 1849-1851, 2009.
Article in Chinese | WPRIM | ID: wpr-291015

ABSTRACT

<p><b>OBJECTIVE</b>To compare clinical outcome and quality of life of subtotal colectomy with antiperistaltic cecoproctostomy and total colectomy with ileorectal anastomosis (TAC-IRA) in patients with severe slow transit constipation (STC).</p><p><b>METHODS</b>Of the 56 patients enrolled in this study from January 1999 to June 2008, 32 cases underwent subtotal colectomy with antiperistaltic cecoproctostomy, and 20 patients underwent TAC-IRA. The patients' clinical characteristics, operative data, postoperative outcome, functional result and gastrointestinal quality of life index (GIQLI) survey were compared between the two groups.</p><p><b>RESULTS</b>All patients were followed up for 1-7 years (median, 4 years). The basic clinical characteristics between the two groups was comparable. During the follow-up period, the number of daily bowel movements in the subtotal colectomy group was significantly fewer than that in TAC-IRA group (2.5+/-0.8 vs. 3.4+/-0.8; P=0.000). The Wexner continence score was significantly lower in subtotal colectomy group (4.4+/-1.6 vs. 5.8+/-1.9; P=0.011), and the GIQLI score in subtotal colectomy group was significantly higher than that in the TAC-IRA group (120.7+/-7.5 vs. 111.1+/-12.0; P=0.005).</p><p><b>CONCLUSION</b>Subtotal colectomy with antiperistaltic cecoproctostomy appeared to be the superior treatment than the TAC-IRA for selected patients with slow transit constipation for improved functional outcomes and quality of life.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Anastomosis, Surgical , Methods , Cecum , General Surgery , Colectomy , Methods , Constipation , General Surgery , Ileum , General Surgery , Quality of Life , Rectum , General Surgery , Retrospective Studies , Treatment Outcome
8.
Chinese Journal of Gastrointestinal Surgery ; (12): 548-550, 2008.
Article in Chinese | WPRIM | ID: wpr-326581

ABSTRACT

<p><b>OBJECTIVE</b>To compare the efficacy between subtotal colectomy with antiperistaltic cecoproctostomy and total colectomy with ileorectal anastomosis (TAC-IRA) for patients with severe refractory slow transit constipation(STC).</p><p><b>METHODS</b>During 1999 to 2002, TAC-IRA was the preferred procedure for 20 STC patients in our department. From 2003 to 2005, 17 STC patients underwent subtotal colectomy plus antiperistaltic cecoproctostomy. Clinical data of the two groups were collected and compared retrospectively.</p><p><b>RESULTS</b>There were no significant differences in basic preoperative clinical data between the two groups. During the follow-up period, the time of daily defecation in the antiperistaltic cecoproctostomy group was less than that of TAC-IRA group (2.4+/-0.9 vs 3.4+/-0.8, P=0.0014), meanwhile the Wexner continence score was significantly lower in the antiperistaltic cecoproctostomy group (4.3+/-1.8 vs 5.8+/-1.9, P=0.0223). Barium enema after subtotal colectomy showed that residual ascending colon and cecum presented a sign of "reservoir".</p><p><b>CONCLUSION</b>Subtotal colectomy with antiperistaltic cecoproctostomy is a better method for appropriately selected patients with STC than TAC-IRA.</p>


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Anastomosis, Surgical , Cecum , General Surgery , Colectomy , Methods , Colon , General Surgery , Constipation , General Surgery , Rectum , General Surgery , Retrospective Studies
9.
Chinese Journal of Surgery ; (12): 1041-1043, 2007.
Article in Chinese | WPRIM | ID: wpr-340865

ABSTRACT

<p><b>OBJECTIVE</b>To assess the long-term results after subtotal colectomy with antiperistaltic cecoproctostomy in idiopathic chronic slow-transit constipation.</p><p><b>METHODS</b>Between January 2003 and February 2004, 14 patients with chronic slow-transit constipation and 2 patients with mixed constipation underwent subtotal colectomy with antiperistaltic cecoproctostomy. The following information was collected during follow-up (mean 3 years): number of bowel movement, stool consistency, complications, quality of life and degree of satisfaction.</p><p><b>RESULTS</b>There was no mortality or major postoperative complications. One month after the operation, bowel frequency was a mean of 4 daily, with a semi-liquid stool consistency. After 3 years, bowel frequency was a mean of 2 daily, with a semi-solid stool consistency. Although no patient used antidiarrheal medicine, laxatives continued to be used by one case with mixed chronic constipation. All patients reported a good or improved quality of life and satisfied with the results. Two patients developed adhesive ileus post operation. There was no diarrhea or incontinence occurred during the follow-up.</p><p><b>CONCLUSIONS</b>Subtotal colectomy with end-to-end antiperistaltic cecoproctostomy for appropriately selected patients with slow-transit constipation results in consistent relief of constipation and satisfactory outcome.</p>


Subject(s)
Adult , Female , Humans , Male , Middle Aged , Cecum , General Surgery , Colectomy , Methods , Constipation , General Surgery , Follow-Up Studies , Gastroenterostomy , Methods , Rectum , General Surgery , Treatment Outcome
10.
Cancer Research and Clinic ; (6)2006.
Article in Chinese | WPRIM | ID: wpr-676643

ABSTRACT

Objective To study the expression and the relation of vascular endothelial growth factor (VEGF)and matrix metal proteinase-2(MMP-2)in rectal cancer and evaluate their roles in rectal carcinogen- esis and development.Methods The expression of VEGF and MMP-2 in 52 cases of rectal cancer was de- tected by immunohistochemical SP technique.12 cases normal rectal tissue served as the control group.Re- suits The expression of VEGF in rectal carcinoma(67.3 %)was much higher than that in control group(P

11.
Chinese Medical Journal ; (24): 1688-1694, 2005.
Article in English | WPRIM | ID: wpr-320711

ABSTRACT

<p><b>BACKGROUND</b>Thalidomide is reviving for its antiangiogenic effect on corneal neovascularization models. Recently, it has been employed in tumor research in several types of solid carcinomas. However, its effect on hepatocellular carcinoma (HCC) has not yet been clarified.</p><p><b>METHODS</b>A total of 48 nude mice bearing human HCC with a high metastatic potential were randomly divided into 4 groups. Thalidomide (200 mg/kg), paclitaxel (13 mg/kg), or their combination, which was dissolved in 0.5% sodium carboxyl methyl cellulose (CMC) suspension, was intraperitoneally injected in each group since the second day of the establishment of animal model. The group simply administered with 0.5% CMC was set as placebo-control. The mice were sacrificed on the 30th day, for the measurement of tumor size, weight and metastasis in the lungs. The levels of CD34 and endothelial growth factor (VEGF) mRNA in tumor tissues were detected by immunohistochemistry and semiquantitative RT-PCR, respectively, and microvessel density (MVD) was evaluated.</p><p><b>RESULTS</b>No statistical difference was found in tumor weight and volume between the thalidomide group and control (P>0.05). Paclitaxel showed a growth-inhibiting effect on tumors (P<0.05). The value of MVD and VEGF mRNA and metastases to the lungs in each group were lower than those in the placebo-control group (P<0.05); such difference in the combination group was statistically significant (P<0.05).</p><p><b>CONCLUSIONS</b>Paclitaxel, but not thalidomide, has significant growth inhibitory effect on tumors, but both significantly inhibit angiogenesis and metastasis of human HCC in nude mice, such effects of paclitaxel can be amplified by thalidomide.</p>


Subject(s)
Animals , Humans , Male , Mice , Antigens, CD34 , Cell Line, Tumor , Liver Neoplasms, Experimental , Drug Therapy , Lung Neoplasms , Mice, Inbred BALB C , Mice, Nude , Neoplasm Transplantation , Neovascularization, Pathologic , Drug Therapy , Paclitaxel , Therapeutic Uses , Reverse Transcriptase Polymerase Chain Reaction , Thalidomide , Therapeutic Uses , Transplantation, Heterologous
12.
Chinese Journal of Hepatology ; (12): 335-338, 2005.
Article in Chinese | WPRIM | ID: wpr-349117

ABSTRACT

<p><b>OBJECTIVES</b>To investigate the effect of short interfering RNA targeting MAT 2A on growth and apoptosis of hepatoma cells.</p><p><b>METHODS</b>The four siRNA against MAT 2A gene were transcript synthesized intracelluarly by expressed templates of plasmid vector pSilence-2.1-U6. We inserted the target sequence of MAT 2A gene into the upstream of the reporter gene in order to construct the recombinant plasmid vector plucA-MAT 2A. The recombinant plasmid and siRNA-producing plasmid were co-transfected into 293 T cells using this construct via lipofectamine methods. The inhibition effect was detected by measuring luciferase activity in the cell lysate to screen the effective siRNA, and then, the effective siRNA was transfected into Bel-7402 cells. The effect of siRNA treatment on the MAT 2A mRNA level and the MAT activity of hepatoma cells were measured. In order to study the effect of short interfering RNA targeting MAT 2A on growth and apoptosis of hepatoma cells, the tumor cell killing rate was analyzed by MTT method and the rate of apoptosis of hepatoma cells was evaluated by flow cytometry.</p><p><b>RESULTS</b>The two siRNA among the four siRNA displayed inhibitory effect on the lucifermase expression with the inhibitory rates of 81% and 89% respectively. The expression of MAT 2A mRNA in Bel-7402 cells was specifically inhibited and the MAT activity in Bel-7402 cells was decreased. Furthermore, silencing of the MAT 2A gene by RNAi significantly inhibited hepatoma cell growth and led to induction of apoptosis.</p><p><b>CONCLUSION</b>RNA interference-mediated silencing of MAT 2A gene attenuates growth and induces apoptosis of hepatoma cells; MAT 2A is an ideal target of gene-specific therapy for liver cancer.</p>


Subject(s)
Animals , Rats , Apoptosis , Physiology , Carcinoma, Hepatocellular , Pathology , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Gene Silencing , Genetic Therapy , Liver Neoplasms , Pathology , Methionine Adenosyltransferase , Genetics , RNA Interference
13.
Chinese Medical Journal ; (24): 1541-1546, 2004.
Article in English | WPRIM | ID: wpr-291884

ABSTRACT

<p><b>BACKGROUND</b>Hypoxia-inducible factor 1 (HIF-1), a transcription factor, is overexpressed in common human cancers and their metastases. This study aimed at determining the expression levels of HIF-1alpha and vascular endothelial growth factor (VEGF) in SW480 cells and in colorectal adenocarcinoma tissue and ascertaining whether HIF-1alpha and VEGF play important roles in tumor angiogenesis.</p><p><b>METHODS</b>HIF-1alpha mRNA expression was analyzed using in situ hybridization and RT-PCR. HIF-1alpha and VEGF protein were detected in SW480 cells and colorectal adenomas and adenocarcinomas by immunohistochemistry using streptavidin/peroxidase (SP). Western blot was used to detect HIF-1alpha protein extracted from SW480 cells. Microvessel density (MVD) in colorectal carcinomas was determined by anti-CD34 immunostaining in colorectal carcinomas.</p><p><b>RESULTS</b>Optical density values representing HIF-1alpha mRNA expression levels were found to be significantly higher in SW480 cells in hypoxic conditions than in cells under normoxic conditions (P < 0.05) or in hypoxic conditions but treated with genistein (P < 0.05). The levels of HIF-1alpha and VEGF protein expression in SW480 cells were significantly higher in the hypoxia group than in the normoxia group (P < 0.01, P < 0.05, respectively) and hypoxia/genistein group (P < 0.01, P < 0.05, respectively). The positive expression rates of HIF-1alpha mRNA changed dramatically when comparing colorectal adenomas with adenocarcinomas of different Dukes' stages (P < 0.05). HIF-1alpha mRNA was also expressed at higher levels in adenocarcinomas than that in adenomas (P < 0.01). HIF-1alpha protein expression correlated significantly with VEGF protein expression and MVD.</p><p><b>CONCLUSIONS</b>Hypoxia induces the expression of HIF-1alpha and VEGF in colorectal adenocarcinomas. HIF-1alpha may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinomas.</p>


Subject(s)
Adult , Aged , Aged, 80 and over , Humans , Middle Aged , Adenocarcinoma , Pathology , Cell Line, Tumor , Colorectal Neoplasms , Pathology , DNA-Binding Proteins , Genetics , Physiology , Hypoxia-Inducible Factor 1 , Hypoxia-Inducible Factor 1, alpha Subunit , Neovascularization, Pathologic , Nuclear Proteins , Genetics , Physiology , RNA, Messenger , Transcription Factors , Genetics , Physiology , Vascular Endothelial Growth Factor A , Physiology
14.
Chinese Journal of Pathology ; (12): 242-246, 2004.
Article in Chinese | WPRIM | ID: wpr-283538

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the transcription level and protein expression of HIF-1alpha and VEGF in SW480 cell line and colorectal adenocarcinoma, and to determine whether HIF-1alpha plays a role in angiogenesis through its regulation of VEGF.</p><p><b>METHODS</b>HIF-1alpha mRNA expression was analyzed by in situ hybridization. HIF-1alpha and VEGF protein expressions were determined by immunochemical streptavidin/peroxidase (SP) in SW480 cells and colorectal carcinoma tissue samples and Western blot, using proteins extracted from SW480 cells. Tumor tissue microvessel density (MVD) was determined by CD34 immunostaining of colorectal carcinomas.</p><p><b>RESULTS</b>The levels of HIF-1alpha mRNA changed significantly in response to different oxygen concentrations and an addition of genistein in SW480 cells. Immunocytochemistry revealed that the levels of HIF-1alpha, VEGF protein expression in SW480 cells were significantly higher under hypoxia than those in nomoxia (P < 0.01, P < 0.05 respectively). However, addition of genistein, an inhibitor of HIF-1alpha, suppressed such responses to hypoxia. Western blot analysis showed that SW480 cells exposed to hypoxia expressed a high level of HIF-1alpha protein, compared to a weak expression in nomoxia. The addition of genistein in hypoxia suppressed the over-expression of HIF-1alpha. The positive rates of HIF-1alpha mRNA by in situ hybridization in colorectal adenomas and adenocarcinomas were 38.9% (7/18) and 67.7% (42/62), respectively. The percentage of HIF-1alpha mRNA positive cells varied significantly from colorectal adenomas to adenocarcinomas at different Duke stages (P < 0.05), and HIF-1alpha mRNA was higher in adenocarcinomas than in adenomas (P < 0.01). The positive rates of HIF-1alpha and VEGF protein expression in adenocarcinomas were 43.5% (27/62) and 37.1% (23/62), respectively. The expression of VEGF elevated as the Duke tumor staging increased. The conformation rate of HIF-1alpha and VEGF was 74.2% (46/62). MVD was significantly higher in HIF-1alpha and/or VEGF positive tumors than those without (P < 0.01 and P < 0.05 respectively). Among the four groups, i.e. HIF-1alpha+/VEGF+, HIF-1alpha+/VEGF-, HIF-1alpha+/VEGF- and HIF-1alpha-/VEGF-, the difference of MVD was highly significant (P < 0.01). HIF-1alpha expression was correlated significantly with VEGF expression and microvessel density.</p><p><b>CONCLUSIONS</b>These findings suggest hypoxia induces the expression of HIF-1alpha and VEGF in colorectal adenocarcinoma. HIF-1alpha may play an important role in angiogenesis and tumor progression by regulating the expression of VEGF in human colorectal carcinoma.</p>


Subject(s)
Humans , Adenocarcinoma , Metabolism , Pathology , Colorectal Neoplasms , Metabolism , Pathology , Hypoxia-Inducible Factor 1, alpha Subunit , Microcirculation , Pathology , Neovascularization, Pathologic , RNA, Messenger , Genetics , Transcription Factors , Genetics , Tumor Cells, Cultured , Vascular Endothelial Growth Factor A , Genetics
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