OBJECTIVETo study the effect of hyperlipidemia on the prognosis and therapeutic response for colorectal cancer and to explore the associated mechanism.

METHODSThe hyperlipidemic subcutaneous heterotopic colorectal cancer orthotopic transplant model of nude mice was established by feeding high fat diet and performing transplantation. Seventy mice were divided into 7 groups with 10 mice in each group. Two groups were used as pre-experiment. The remaining 5 groups included 4 high-fat groups (G1 to G4), and 1 normal-diet control group (G5). G1, G2, G3, G4, and G5 received normal saline, capecitabine, simvastatin, capecitabine plus simvastatin and capecitabine respectively for 3 weeks. Changes of tumor volume, tumor weight, tumor growth rate and blood lipid parameters (TC, TG, HDL, LDL, Lpa, apoA and apoB) were observed.

RESULTSIn G1 to G4, TC, HDL, apoA, TG, LDL, Lpa, apoB increased, but only TC, HDL, apoA were significantly different as compared with G5 (P=0.020, P=0.001, P=0.001, P=0.911, P=0.249, P=0.681, P=0.053). The tumor in G1 grew fastest, and its growth rate was significantly different as compared with G2, G4, G5 except G3 (P=0.001, P=0.806, P=0.001, P=0.010). The tumor growth rate of G3 was lower than group G1, but higher than G2, G4, G5 with significant difference (P=0.001, P=0.002, P=0.016). The tumor of G5 grew faster than G2 and G4, but without significant differences (P=0.051, P=0.070). The tumor of G4 grew slowest without significant difference as compared to G2 (P=0.438). Compared with pre-administration, at the third week, the TC of G1 was increased [(3.8±0.4) mmol/L], while the other 4 groups decreased [G2 (2.8±1.8) mmol/L, G3 (2.9±0.7) mmol/L, G4 (1.4±0.9) mmol/L, G5 (2.1±0.2) mmol/L]. G4 decreased significantly (P=0.004). At the fifth week, the TC of all the 5 groups decreased, while the lipids of G4 were higher as compared to those at the third week. The TG, Lpa, ApoA were significantly decreased at the third week (all P<0.05), while no significant differences were found in HDL and apoB.

CONCLUSIONSA hyperlipidemia colon tumor model involving subcutaneous colon translocation and orthotopic transplantation of nude mice is successfully established. This model is an ideal research model for hyperlipidemia and colorectal cancer. The effect of capecitabine on tumors in hyperlipidemia groups is better as compared to normal diet group. The proliferation of tumor cells can increase serum total serum cholesterol.

Animals ; Antineoplastic Agents ; therapeutic use ; Colorectal Neoplasms ; blood ; complications ; drug therapy ; Disease Models, Animal ; Female ; Hyperlipidemias ; complications ; Lipids ; blood ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation

OBJECTIVETo study the expression of JAG1 and DLL1 in colorectal cancer and its clinical significance.

METHODSPatients with colorectal cancer were treated in the Center of Colorectal Surgery of the Third Affiliated Hospital of Nanjing University of TCM were collected prospectively and followed up. A tissue microarray was made and expressions of JAG1 and DLL1 were detected by immunohistochemical staining.

RESULTSA total of 146 cases with colorectal cancer were included. The differences in JAG1 expression were significant among different tumor differentiation types and the differences in DLL1 expression were significant among different tumor locations(all P<0.05). There were no significant differences in the expression of the two genes and microsatellite instability(MSI)(P>0.05). One hundred and thirty-four (91.8%) cases were followed up and the mean follow-up time was (42.3±13.3) months. Tumor-free survival was noticed in 86 patients. The overall survival was 93% at 1 year, 74% in 3 years, and 67% in 5 years. Multivariate analysis showed that long-term survival rate was related to TMN stage, pathology types, MSI status and expression of JAG1. The prognosis of patients with high expression of JAG1 was better than those with low and negative expression(P<0.05).

CONCLUSIONSThe expressions of JAG1 and DLL1 are related to tumor differentiation and tumor location. The expression of JAG1 gene is associated with long-term survival.

Adult ; Aged ; Aged, 80 and over ; Calcium-Binding Proteins ; genetics ; metabolism ; Colorectal Neoplasms ; genetics ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Jagged-1 Protein ; Male ; Membrane Proteins ; genetics ; metabolism ; Microsatellite Instability ; Middle Aged ; Prognosis ; Retrospective Studies ; Serrate-Jagged Proteins ; Survival Analysis ; Young Adult

OBJECTIVETo study the inhibitory effect of (-)-epigallocatechin-3-gallate (EGCG) on cancer cells line HCT-8 and HT29 and its influence on the expression of HES1 and JAG1.

METHODSColorectal cancer cells line HCT-8 and HT29 were cultured in vitro and treated with different concentrations of EGCG(10 mg/L, 20 mg/L, 35 mg/L). The inhibition of proliferation was tested by MTT analysis. Influence of EGCG on the cell apoptosis and cell cycle of HCT-8 and HT29 were detected with flow cytometry, and gene expression of HCT-8 and HT29 after EGCG treatment with real-time polymerase chain reaction.

RESULTSEGCG affected the proliferation and apoptosis of HCT-8 and HT29. The inhibition rates of the three different concentrations of EGCG were(28.894±5.076)%, (34.903±1.794)%, and (39.028±0.105)% on HCT-8, and (14.682±4.244)%, (22.429±3.847)%, and (29.840±5.076)% on HT29. EGCG caused G(2)/M phase arrest and M phase transition in HCT-8 cell line, and S phase arrest and G2 phase transition in HT29 cell line. EGCG down-regulated HES1 gene expression in both cell lines, however, the differences were not statistically significant(both P>0.05). EGCG upregulated JAG1 gene expression in both cell lines, however only the difference in HCT-8 was statistically significant(0.201±0.018 vs. 0.440±0.077, P=0.029).

CONCLUSIONSEGCG can significantly inhibit the proliferation of HT29 cells and HCT-8 cells by changing cell cycle and inducing cell apoptosis. The mechanism may be related to the upregulation of JAG1 gene expression.

Apoptosis ; drug effects ; Basic Helix-Loop-Helix Transcription Factors ; metabolism ; Calcium-Binding Proteins ; metabolism ; Catechin ; analogs & derivatives ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colorectal Neoplasms ; pathology ; Flow Cytometry ; HT29 Cells ; Homeodomain Proteins ; metabolism ; Humans ; Intercellular Signaling Peptides and Proteins ; metabolism ; Jagged-1 Protein ; Membrane Proteins ; metabolism ; Serrate-Jagged Proteins ; Transcription Factor HES-1

OBJECTIVETo study the distribution characteristics of colorectal neoplasm and evaluate the implication for colorectal cancer screening.

METHODSA total of 17,939 colonoscopies were performed in the National Center of Colorectal Surgery between October 2004 and June 2009. Characteristics of colorectal neoplasm including anatomical distribution, sex, and age were investigated.

RESULTSColorectal neoplasm was found in 24.8% (4450/17,939) of the patients during colonoscopy, including adenomatous polyp (n=3410, 19.0%) and adenocarcinoma (n=1040, 5.8%). The prevalence of colorectal neoplasm was higher in male and significantly increased in patients older than 40 years. 63.3% of the lesions located at the distal colon (sigmoid colon and rectum) and 36.7% at the proximal colon (36.7%). In patients with adenomatous polyp, 52.8% (1802/3410) of the lesions were at the distal colon, 30.8% (1049/3410) at the proximal colon, and 16.4% (559/3410) at both distal and proximal colon. In patients with carcinoma (n=1040), 921 (88.6%) lesions located at the distal colon, 118 (11.3%) at the proximal colon, and 1 (0.1%) at both segments.

CONCLUSIONSigmoidoscopy is inadequate for colorectal cancer screening as compared to colonoscopy.

Adult ; Age Distribution ; Aged ; Colonoscopy ; Colorectal Neoplasms ; diagnosis ; pathology ; Early Detection of Cancer ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sex Distribution

OBJECTIVETo explore the indications for colonoscopy examination and the distribution of diagnostic diseases.

METHODFrom Jan. 2000 to Dec. 2004, 5960 patients received colonoscopy examination in our colorectal center. The indications for colonoscopy examination and the distribution of its diagnostic diseases were analyzed.

RESULTSThere were 3096 males and 2594 females,and the mean age was (52+/-15) years. The reasons for colonoscopy included hemafecia (26.9%), atypical abdominal pain (25.8%), diarrhea or increased frequency of stool (11.1%), anal tenesmus or discomfort (7.6%), constipation (7.0%),mucous or bloody purulent stool (3.0%), intra-rectal mass or abdominal mass on physical examination (0.9%), re- examination after colonoscopic polypectomy (10.9%), re-examination after operation for colorectal cancer(1.5%), simple health examination (2.2%). Colonoscope reached the cecum in 97.7% of the cases,and at least one disease was found in 2283 cases (40.1%). Among them,colorectal cancer accounted for 10.3%, colorectal polyps 19.6%, ulcerative colitis 4.3%, and Crohn's disease 0.5% respectively.

CONCLUSIONThe indications for colonoscopy are too strict to screen the early stage colorectal cancer. Colonoscopy should be performed in the cases with symptoms such as bloody stool, diarrhea, abdominal pain, constipation, or with colorectal polyps, after operation for colorectal cancer,or as members of hereditary colorectal cancer family.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Colonic Diseases ; classification ; diagnosis ; Colonoscopy ; Colorectal Neoplasms ; diagnosis ; Early Diagnosis ; Female ; Humans ; Ileocecal Valve ; Male ; Middle Aged ; Young Adult

OBJECTIVETo evaluate the value of magnetic resonance imaging (MRI) in the diagnosis of complex anal fistula.

METHODSThe preoperative digital examination and MRI with the phased-array coil were implemented for 28 patients who were clinically suspected with complex anal fistula. The final diagnosis were based on surgical findings. Outcomes of MRI and digital examination were compared with surgical results.

RESULTSTwenty-five patients were diagnosed as complex anal fistula, 1 presacral cyst and 2 chronic anorectal fistula combined with perianal mucinous adenocarcinoma. All the patients were correctly diagnosed by MRI,while the patients with presacral cyst and perianal mucinous adenocarcinoma could not be diagnosed correctly by digital examination. According to the Parks classification, 3 patients were suffered from trans-sphincteric fistula, 10 intersphincteric, 5 supra- sphincteric and 7 extra-sphincteric. The diagnosis rates of the internal opening with digital examination and MRI were 48% and 84%, the rates of the primary tract were 76% and 100%, and the rates of the secondary extensions were 57.9% and 94.7% respectively. The differences in detection of internal opening, primary tract and secondary extensions between MRI and digital examination were significant (P<0.01).

CONCLUSIONMRI with the phased-array coil can correctly orient the internal opening and direction of the complex anal fistula, and find the relationship between anorectal sphincters and the complex fistula.

Adolescent ; Adult ; Aged ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Rectal Fistula ; diagnosis ; pathology ; Young Adult

OBJECTIVETo evaluate the effects of polyamidoamine dendrimer (PAMAM) liposome as gene carriers on the cellular uptake and its cytotoxicity in colonic cancer cell.

METHODSThe liposome modified PAMAM was synthesized with liposome and polyamidoamine dendrimer. Plasmid PEGFP-N1 was mixed with the liposome-modified PAMAM or unmodified PAMAM to form nanoparticle complexes. The shape and size of the nanoparticle complexes were observed by transmission electron microscope and the zeta potential was measured by analytical tool. The encapsulating efficiency was determined by ultraviolet spectrophotometer in centrifuging method. After the cell lines SW620 (colonic cancer cell), MCF-7 (breast cancer cell), ECV304 (vascular endothelial cell) were transfected by the two kinds of PAMAM nanoparticle complexes, the flow cytometry was used to determine the uptake of enhanced green fluorescent protein (EGFP) gene. The cytotoxicity of PAMAM liposome nanoparticles and PAMAM nanoparticles was evaluated by MTT assay.

RESULTSThe diameter of liposome modified PAMAM complex was (192 ± 16) nm, and that of PAMAM complex was (189 ± 19) nm (P > 0.05); and the zeta potential of liposome modified PAMAM complex was higher than that of PAMAM complex [(42 ± 7) mV vs. (32 ± 7) mV, P < 0.05]. There was no significant difference in envelopment rate between the two groups [(82 ± 7)% vs. (84 ± 6)%, P > 0.05]. After the colonic cancer cell line SW620 was transfected with the two kinds of PAMAM nanoparticle complexes, the cellular uptake of the cells with the liposome-modified PAMAM complex was significantly higher than that of the cell with PAMAM complex (P < 0.05). The cellular survival rate of the cell lines with liposome-modified PAMAM complex was significantly higher than that of cell lines with PAMAM complex (P < 0.05).

CONCLUSIONThe liposome modified PAMAM can improve gene transfection efficiency and suppress its cytotoxicity.

Cell Line, Tumor ; Cell Survival ; drug effects ; Colonic Neoplasms ; metabolism ; pathology ; Dendrimers ; pharmacokinetics ; toxicity ; Genetic Vectors ; pharmacokinetics ; toxicity ; Humans ; Liposomes ; pharmacokinetics ; toxicity ; Transfection

OBJECTIVETo study the clinicopathological features of the Chinese hereditary non-polyposis colorectal cancer and its germline mutation of hMLH(1) and hMSH(2).

METHODSThirteen typical Chinese hereditary non-polyposis colorectal carcinoma (HNPC)C kindreds and 19 non-typical HNPCC families were registered and followed up. The germline mutation of the hMLH(1) and hMSH(2) of 12 index cases of 6 typical and 6 non-typical HNPCC were screened by PCR-SSCP. Samples with abnormal mobility were sequenced directly.

RESULTSThe average age of typical HNPCC was 47, no difference existed between sexes. Location of the tumors of typical HNPCC represented 44.7% on the right half colon and non-typical HNPCC 65.8% on the rectum. The rate of the metachronos cancer was 11.5%. The 3-, 5-and 10-year survival rate was 64.0%, 45.3% and 31.2% respectively. Among 12 cases, 8 showed abnormal mobility. Except for an intron polymorphism, six exons abnormalities were found in 5 of 12 proband. Sequencing showed 4 missense, 7 insertion and a nonsense mutations.

CONCLUSIONSChinese HNPCC is early onset, more common on proximal colon and better prognosis. Mutation of hMSH(2) is dominant in the Chinese typical HNPCC, but mutation of hMLH(1) is more common in the non-typical group.

Adaptor Proteins, Signal Transducing ; Adult ; Asian Continental Ancestry Group ; genetics ; Carrier Proteins ; genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; pathology ; DNA Mutational Analysis ; Female ; Follow-Up Studies ; Germ-Line Mutation ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; genetics ; Mutation, Missense ; Nuclear Proteins ; genetics ; Pedigree ; Polymerase Chain Reaction

OBJECTIVETo investigate the specificity and sensitivity of the immunohistochemistry for hMLH1 and hMSH2 with detection of microsatellite instability (MSI) to identify the kindreds with hereditary nonpolyposis colorectal cancer and to analyse its value in clinical practice.

METHODSpecimens of 16 cases with HNPCC and 16 cases with sporadic colorectal cancer were detected by immunostaining with hMLH1 and hMSH2 and MSI was also detected.

RESULTSThe specificity and sensitivity of the immunohistochemistry for hMLH1 and hMSH2 were 91.7% and 87.5% respectively. The specificity and sensitivity of MSI were 100% and 75.0%. By combining two methods, the specificity and sensitivity were 91.7% and 93.8% respectively.

CONCLUSIONSBy combination of the immunohistochemistry for hMLH1 and hMSH2 and detection of MSI to identify the kindreds with HNPCC, the specificity and sensitivity are improved which is better than to use either of them alone. And it is very easy and cheap that it can be used in clinics.

Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Carrier Proteins ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; DNA-Binding Proteins ; analysis ; Female ; Genomic Instability ; Humans ; Immunohistochemistry ; Male ; Microsatellite Repeats ; Middle Aged ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Neoplasm Proteins ; analysis ; Nuclear Proteins ; Proto-Oncogene Proteins ; analysis ; Sensitivity and Specificity

OBJECTIVETo investigate the role of microsatellite instability(MSI) in Chinese sporadic coloretal cancer.

METHODSA total of 146 patients with colorectal cancer were treated surgically from August 2004 to September 2006 in the Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine. Data were collected prospectively. Univariate and multivariable analyses were performed for parameters such as age, gender, tumor location, differentiation, MSI, tumor type, lymph node metastasis, TNM stage, and survival.

RESULTSFollow-up was available in 134 patients including telephone call and office visit. MSI(P=0.029), tumor type(P=0.000), TNM stage(P=0.000) were independently associated with survival on Cox regression model. There were 26 patients with MSI, and the 1-, 3-, and 5-year survival rates were 100%, 92.3%, and 92.3%, respectively. The remaining 108 patients had microsatellite stable tumor, and the 1-, 3-, and 5-year survival rates were 96.3%, 72.2%, and 63.5%, respectively. The difference was statistically significant(P=0.016).

CONCLUSIONMicrosatellite instability is an important factor associated with patient survival in Chinese sporadic colorectal cancer.

Aged ; China ; Colorectal Neoplasms ; diagnosis ; genetics ; Female ; Follow-Up Studies ; Humans ; Male ; Microsatellite Instability ; Middle Aged ; Prognosis ; Survival Rate