There are indirect evidences to suggest that 80% of colorectal cancers (CRC) develop from adenomatous polyps and that, on average, it takes 10 years for a small polyp to transform into invasive CRC. In multiple cohort studies, colonoscopic polypectomy has been shown to significantly reduce the expected incidence of CRC by 76% to 90%. Colonoscopic polypectomy is performed frequently in primary, secondary and tertiary and medical centers in Korea. However, there are no evidence-based, procedural guidelines for the appropriate performance of this procedure, including the technical aspects. For the guideline presented here, Pubmed, Medline, and Cochrane Library literature searches were performed. When little or no data from well-designed prospective trials were available, an emphasis was placed on the results from large series and reports from recognized experts. Thus, these guidelines for colonoscopic polypectomy are based on a critical review of the available data as well as expert consensus. Further controlled clinical studies are needed to clarify aspects of this statement, and revision may be necessary as new data become available. This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions for any particular case involve a complex analysis of the patient's condition and the available courses of action.
Adenoma/diagnosis/*surgery ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Aspirin/therapeutic use ; Colonic Polyps/pathology/*surgery ; Colonoscopy ; Colorectal Neoplasms/diagnosis/*surgery ; Databases, Factual ; Epinephrine/therapeutic use ; Gastrointestinal Hemorrhage/prevention & control ; Humans ; Lymphatic Metastasis ; Republic of Korea ; Surgical Instruments ; Thrombosis/drug therapy ; Vasoconstrictor Agents/therapeutic use

KITENIN (KAI1 C-terminal interacting tetraspanin) promotes invasion and metastasis in mouse colon cancer models. In the present study, we evaluated the effects of KITENIN knockdown by intravenous administration of short hairpin RNAs (shRNAs) in an orthotopic mouse colon cancer model, simulating a primary or adjuvant treatment setting. We established orthotopic models for colon cancer using BALB/c mice and firefly luciferase-expressing CT-26 (CT26/Fluc) cells. Tumor progression and response to therapy were monitored by bioluminescence imaging (BLI). In the primary therapy model, treatment with KITENIN shRNA substantially delayed tumor growth (P = 0.028) and reduced the incidence of hepatic metastasis (P = 0.046). In the adjuvant therapy model, KITENIN shRNA significantly reduced the extent of tumor recurrence (P = 0.044). Mice treated with KITENIN shRNA showed a better survival tendency than the control mice (P = 0.074). Our results suggest that shRNA targeting KITENIN has the potential to be an effective tool for the treatment of colon cancer in both adjuvant and metastatic setting.
Animals ; Carrier Proteins/*genetics/metabolism ; Cell Line, Tumor ; Colonic Neoplasms/genetics/mortality/pathology/*therapy ; Disease Progression ; Liver Neoplasms/prevention & control/*secondary ; Membrane Proteins/*genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis/*prevention & control ; Neoplasm Recurrence, Local/genetics/*prevention & control ; RNA Interference ; RNA, Small Interfering/*therapeutic use ; Tumor Markers, Biological/genetics

OBJECTIVETo develop a colon-specific prodrug of Indomethacin microbially triggered, carry out in vitro/in vivo evaluation of drug release, and appraise its inhibitory effect on liver metastasis from colon cancer.

METHODSIndomethacin prodrugs were synthesized and characterized by FTIR and NMR, and dissolution test simulating gastrointestinal tract was employed to screen the colon-specific prodrug. Then, the pharmacokinetic profile of portal vein and peripheral blood in Sprague-Dawley rats was studied. Lastly, the inhibitory effect on liver metastasis from colon cancer in nude mice was observed.

RESULTSThe chemical structure characterized by FTIR and NMR demonstrated that six kinds of indomethacin-block-amylose with different drug loading (IDM-AM-1-6) were synthesized, among which IDM-AM-3 was degraded 1.3%, 9.3% and 95.3%, respectively, in simulated gastric fluid for 4 h, small intestine for 6 h, and colon for 36 h. The pharmacokinetic test of IDM-AM-3 showed that absorption was delayed significantly (P < 0.01), peak time [(11.35 + or - 2.45) h], elimination half-life [(16.74 + or - 4.04) h] and mean residence time [(22.27 + or - 0.52) h] were significantly prolonged (P < 0.01), as well as peak serum concentrations [(9.69 + or - 2.40) mg/L] and AUC(0-t) [(236.7 + or - 13.1) mg x L(-1) x h] were decreased markedly (P < 0.01) as compared with those of IDM regarding to portal vein. Additionally, its AUC(0-t) in peripheral blood was remarkably lower than that in Portal vein (P < 0.01). The tumor suppression observation showed that it could remarkably reduce the number of liver metastases in contrast to IDM (P < 0.05).

CONCLUSIONColon-specific IDM-AM-3 possesses advantage of sustained release in portal vein providing some experimental basis for colon-specific delivery system applied to sustained release in the portal vein.

Amylose ; administration & dosage ; chemical synthesis ; pharmacokinetics ; therapeutic use ; Animals ; Colon ; metabolism ; Colonic Neoplasms ; pathology ; Delayed-Action Preparations ; Drug Delivery Systems ; HT29 Cells ; Humans ; Indomethacin ; administration & dosage ; chemical synthesis ; pharmacokinetics ; therapeutic use ; Liver Neoplasms ; prevention & control ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Prodrugs ; administration & dosage ; chemical synthesis ; pharmacokinetics ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the impact of arsenic trioxide (As2O3) on human colorectal carcinoma LS-174T cells and their activity of telomerase.

METHODSLS-174T cells and xenograft model of nude mice were treated with As2O3. The inhibitory effect of As2O3 on survival of LS-174T cells was determined by MTT assay. Apoptosis was determined by electron microscopy and fluorescence microscopy. Cell cycle was assessed by flow cytometry. Telomerase activity in LS-174T cells was determined by PCR-ELISA kit.

RESULTSWith the increasing concentration of As2O3, the ratio of living cells to dead cells decreased significantly, and the IC50 value was 5.23 micromol/L. Apoptosis curve appeared after 24 h and cells turned to apoptosis in a time-dependent manner. As2O3 inhibited the telomerase activity in cell extraction, obviously in a concentration-dependent and time-dependent manner. Inhibitiory effect of As2O3 on xenograft model of nude mice was observed by tumor volume and weight measurement, showing a significant difference between As2O3 and control groups (P < 0.05).

CONCLUSIONBoth the experiments in vitro and in vivo showed an inhibitory effect of As2O3 on colonrectal cancer S-174T cell growth, probably by induction of apoptosis and inhibition of telomerase activity.

Animals ; Apoptosis ; drug effects ; Arsenicals ; administration & dosage ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Colonic Neoplasms ; pathology ; prevention & control ; ultrastructure ; Dose-Response Relationship, Drug ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Inhibitory Concentration 50 ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microscopy, Electron ; Microscopy, Fluorescence ; Oxides ; administration & dosage ; pharmacology ; Polymerase Chain Reaction ; methods ; Random Allocation ; Telomerase ; antagonists & inhibitors ; genetics ; metabolism ; Time Factors ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

BACKGROUND/AIMS: Warfarin and aspirin are commonly used to prevent cardiovascular diseases. Aspirin was recently found to have chemopreventive effects on colon cancer and polyps by inhibiting cyclooxygenase-2. Therefore, we evaluated whether the symptoms of bleeding related with aspirin or warfarin could be a clue in early detection of colon cancer. We also assessed the effect of aspirin on the development of synchronous polyps. METHODS: A total of forty-one and 16 patients diagnosed as colon cancer, taking aspirin or warfarin respectively were enrolled. In addition, 171 patients with colon cancers were age and gender matched as a control group. We investigated the difference of clinical features and laboratory findings among three groups. RESULTS: The incidence of bleeding was 81.3% (warfarin), 53.7% (aspirin), 40.4% (control). Among three groups, location and size of cancer, number of lymph nodes involvement and stages were not different, but the number of patients in Duke stage D in warfarin group (n=1, 6.3%) were less than that of the control (n=44, 25.7%) (p=0.049). The extent of circumferencial involvement by cancer was lower in aspirin group (67%) than in the control group (80%) (p=0.035). The percentage of patients with synchronous polyps and mean number of synchronous polyps in aspirin group (34.1%, 0.68, respectively) was lower than that of control group (53.6%, 1.69, respectively) (p=0.029, 0.008, respectively). CONCLUSIONS: Bleeding related with aspirin or warfarin usage had no effect on the early diagnosis of colon cancer. However, lower incidence of Duke stage D in warfarin group might be related to anti-metastatic effect of warfarin. In addition, aspirin may have a role in suppressing the development of synchronous polyps.
Aged ; Anticoagulants/adverse effects/therapeutic use ; Aspirin/adverse effects/*therapeutic use ; Cardiovascular Diseases/prevention & control ; Colonic Neoplasms/*diagnosis/pathology ; English Abstract ; Female ; Gastrointestinal Hemorrhage/chemically induced ; Humans ; Male ; Middle Aged ; Platelet Aggregation Inhibitors/adverse effects/*therapeutic use ; Warfarin/adverse effects/*therapeutic use

OBJECTIVETo investigate the effect of cytosine deaminase (CD) gene plus 5-fluorocytosine (5-Fc) on the growth of human colon cancer xenograftin nude mice.

METHODSRetroviral vector expressing CD gene was transfected into human colon cancer SW1116 cells. Expression of the transfected CD gene in SW1116 (SWCD(2)) was confirmed by RT-PCR. The cytotoxicity of 5-Fc on SW1116 was determined by MTT assay in vitro. In vivo, the CD gene expression vector was injected intratumorally and 5-Fc was given by ip injections.

RESULTSIn vitro, SWCD(2) cells were killed by 5-Fc with an IC(50) of 66 micromol/L while the nontrasfected SW1116 cells needed an IC(50) of 16 000 micromol/L to be killed. The growth of SWCD(2) xenografts was significantly inhibited by systemic administration of 5-Fc.

CONCLUSIONCD gene/5-Fc system is a potential gene therapy strategy for human colon cancer.

Animals ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; metabolism ; pathology ; prevention & control ; Combined Modality Therapy ; Cytosine Deaminase ; genetics ; metabolism ; Female ; Flucytosine ; pharmacology ; therapeutic use ; Genetic Therapy ; Genetic Vectors ; Humans ; Inhibitory Concentration 50 ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Retroviridae ; genetics ; Transfection

Animals ; Coculture Techniques ; Colonic Neoplasms ; pathology ; therapy ; Cytokines ; pharmacology ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; Female ; Immunophenotyping ; Immunotherapy, Adoptive ; Interferon-gamma ; biosynthesis ; Interleukin-12 ; biosynthesis ; Killer Cells, Natural ; immunology ; Lung Neoplasms ; prevention & control ; secondary ; Lymphocyte Activation ; Mice ; Mice, Inbred BALB C

OBJECTIVETo study the influence of Kai1/CD82 transfection on the growth, adherence, separation and invasion potential of LoVo colon carcinoma cell line.

METHODSKai1/CD82 cDNA was transfected into LoVo cells, and a stable expressing clone was established. In vitro methodology was used to obtain the growth curve and also to detect the adherence, separation and invasion potential of the transfected LoVo cells, in comparison with those of control cells without transfection.

RESULTSCompared with the control, no change was observed in the growth pattern of transfected LoVo cells. The numbers of adherent cells in the two groups were 0.08, 0.63, 0.83, 0.91 (x 10(5)) for the transfected cells and 0.04, 0.48, 0.71, 0.82 (x 10(5)) for the control cells respectively after 10, 20, 30, 40 minutes culture with shaking. The difference at 20, 30 and 40 minutes was statistically significant (P < 0.05). The separation rates of each group were 13%, 20%, 53% for the transfected cells and 11%, 28%, 60% for the control cells, respectively after 5, 10, 15 minutes culture with shaking. The difference at 10 and 15 minutes was statistically significant (P < 0.05). The aggregation rate of the transfected cells was higher than that of the control cells after culture with mild shaking for 5 hours (64.8% vs. 58.6%, P < 0.05). After co-incubation with endothelium cells ECV304, the number of invading cells decreased more in the transfected cells than that in the control cells (6.33/field and 17.67/field, P < 0.05).

CONCLUSIONTransfection expression of Kail/CD82 into LoVo cell line results in an increase of cell adherence and aggregation, but a diminished capability of separation and invasion, suggesting that the expression of Kai1/CD82 gene may inhibit the metastatic potential of colon carcinoma.

Antigens, CD ; Cell Adhesion ; Cell Division ; Colonic Neoplasms ; genetics ; pathology ; prevention & control ; Genes, Tumor Suppressor ; Humans ; Kangai-1 Protein ; Membrane Glycoproteins ; genetics ; Neoplasm Invasiveness ; Proto-Oncogene Proteins ; Transfection

Animals ; Colonic Neoplasms ; pathology ; Disease Models, Animal ; Humans ; Kupffer Cells ; cytology ; metabolism ; physiology ; Liver Neoplasms ; prevention & control ; secondary ; Mice ; Mice, Nude ; Neoplasm Metastasis ; Phagocytosis ; physiology ; Reactive Oxygen Species ; metabolism ; Splenectomy ; methods

Colorectal cancer is becoming increasingly common in Asian countries and still remains the second leading cause of cancer deaths in the United States. Efforts to prevent colon cancer have targeted early detection through screening and chemoprevention. For the last ten years our laboratory has utilized an in vivo screening assay for the testing of potential cancer preventives for colon cancer. We have conducted investigations on over 150 compounds including many with botanical or herbal origins. As part of our program on natural products we have examined a number of herbal and botanical products in the aberrant crypt foci (ACF) assay including Korean red ginseng powder, green tea catechins, curcumin from the Indian culinary spice, tumeric, compounds from garlic and onion, resveratrol from red grapes, among others. In the ginseng experiments groups of 10 F344 rats were fed ginseng powder at a dose of 0.5 g/kg or 2 mg/kg for 5 weeks. During weeks 2 and 3 rats were injected with 10 mg/kg azoxymethane to induce ACF. Controls (n=10) did not receive azoxymethane (AOM). Rats were killed by CO2 overdose and ACF counted in the rat colon. In 8 week post-initiation experiments ginseng powder inhibited the progression of established ACF, indicating a cytostatic effect. This may be due to an anti-inflammatory effect. There is a body of literature that suggests that compounds in wine, tumeric, and tea inhibit cyclooxygenases, thus reducing prostaglandin-mediated effects on the colon. As colon tumors have been shown to highly express COX-2 protein, and given, that many NSAID drugs also suppress COX-1, it is tempting to speculate that herbal products that inhibit one or both forms of the COX enzyme will be effective agents for the prevention of cancer in man.
Animal ; Anticarcinogenic Agents/*pharmacology ; Colonic Neoplasms/pathology/*prevention & control ; Disease Models, Animal ; Human ; Korea ; *Panax ; Precancerous Conditions/pathology/*prevention & control ; Rats ; Rats, Inbred F344