• 제목/요약/키워드: colon

검색결과 2,166건 처리시간 0.026초

Expression of Smoothened Protein in Colon Cancer and its Prognostic Value for Postoperative Liver Metastasis

  • Ding, Yin-Lu;Wang, Qi-San;Zhao, Wei-Min;Xiang, Lei
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.4001-4005
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    • 2012
  • Backgrouds: The hedgehog (Hh) signaling pathway is composed of patched (PTCH) and smoothened (SMO), two transmembrane proteins, and downstream glioma-associated oncogene homolog (Gli) transcription factors. Hh signaling plays a pathological role in the occurrence and development of various cancers. Methods: To investigate the expression of SMO protein in colon cancer and its association with clinicopathological parameters and postoperative liver metastasis, immunohistochemistry was performed with paraffin-embedded specimens of 96 cases. Relationships between SMO protein expression and clinicopathological parameters, postoperative liver metastasis were analyzed. Results: IHC examination showed that SMO protein expression was significantly increased in colon cancer tissues compared to normal colon tissues (P = 0.042), positively related to lymph node metastases (P = 0.018) and higher T stages (P = 0.026). Postoperative live metastasis-free survival was significantly longer in the low SMO expression group than in those with high SMO expression ($48.7{\pm}8.02$ months vs $28.0{\pm}6.86$ months, P=0.036). Multivariate analysis showed SMO expression level to be an independent prognostic factor for postoperative live metastasis-free survival (95% confidence interval [CI] =1.46-2.82, P = 0.008). Conclusions: Our results suggest that in patients with colon cancer, the SMO expression level is an independent biomarker for postoperative liver metastasis, and SMO might play an important role in colon cancer progression.

Polymorphisms in the Thymidylate Synthase Gene and Risk of Colorectal Cancer

  • Gao, Chang-Ming;Ding, Jian-Hua;Li, Su-Ping;Liu, Yan-Ting;Cao, Hai-Xia;Wu, Jian-Zhong;Tajima, Kazuo
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권8호
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    • pp.4087-4091
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    • 2012
  • To evaluate the relationship between polymorphisms (28 bp repeated sequences in 5'-UTR and 6-bp ins/del in 3'-UTR) in then thymidylate synthetase gene (TS) and risk of colorectal, colon and rectal cancers, we conducted a case-control study with 315 cases of colorectal cancer and 439 population-based controls in Jiangsu province, China. TS genotypes were identified using PCR.RFLP (restriction fragment length polymorphism) methods. Odds ratios (ORs) were estimated with an unconditional logistic regression model. We found that the distributions of 5'-UTR genotypes in TS were significantly different between controls and male colon cases (${\chi}^2$=8.25, P = 0.016). Compared with 3R/3R genotype, individuals with the 2R allele were at an increased risk of colon cancer (age-, BMI-, smoking- and alcohol drinking-adjusted OR=1.98, 95%CI: 1.11-3.53) among men. In ccontrast, the 6-bp ins/del polymorphism at the TS 3'- UTR did not influence risk of the colorectal, colon and rectal cancers. When combined genotypes for both TS 5'-UTR and 3'-UTR polymorphisms were evaluated, individuals with the 5'-UTR 2R allele had a OR of 3.61 (95%CI: 1.38-9.49) for colon cancer among men with the 3'-UTR .6bp/-6bp genotype. These results show that the polymorphism of the 28 bp repeated sequences in TS 5'-UTR could influence susceptibility to colon cancer and that there was a coordinated effect between TS 3'-UTR and 5'-UTR polymorphisms in increasing risk of colon cancer among Chinese men.

Overcoming 5-Fu Resistance of Colon Cells through Inhibition of Glut1 by the Specific Inhibitor WZB117

  • Liu, Wei;Fang, Yong;Wang, Xiao-Tong;Liu, Ju;Dan, Xing;Sun, Lu-Lu
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권17호
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    • pp.7037-7041
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    • 2014
  • Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

Pseudorabies 바이러스를 이용한 랫드 결장을 지배하는 중추신경핵의 동정 (Localization of the central nuclei innervating the rat colon using pseudorabies virus)

  • 이성준;이봉희;김진상;강태천;이흥식
    • 대한수의학회지
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    • 제37권3호
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    • pp.479-487
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    • 1997
  • The present study was carried out to localize the central nuclei innervating the rat colon using pseudorabies virus-Bartha strain which has been known as a very useful neurotracer. The results were as follows. The central nuclei innervating the proximal colon were premotor area, subfornical organ, preoptic area in telencephalon, and paraventricular nucleus, bed nucleus of stria terminalis, retrochiasmatic area in the diencephalon, and periaqueductal gray, Edinger-Westphal nucleus, tegmental nucleus in the mesencephalon, and parabrachial nucleus, locus ceruleus, A5 area, $K{\ddot{o}}lliker$-Fuse nucleus, magnocellular reticular nucleus in the metencephalon, and nucleus tractus solitarius, A1 noradrenergic cell group, dorsal motor nucleus of vagus nerve, nucleus ambiguus, area postrema in the myelencephalon. In the spinal cord, the thoracic division had some nuclei innervating the proximal colon. The nuclei innervating the distal colon were paraventricular nucleus of the diencephalon, Edinger-Westphal nucleus of midbrain, and parabrachial nucleus, locus ceruleus, A5 area, $K{\ddot{o}}lliker$-Fuse nucleus, magnocellular reticular nucleus of the metencephalon, and nucleus tractus solitarius, dorsal motor nucleus of vagus nerve, nucleus ambiguus, area postrema in the myelencephalon. In the spinal cord, thoracic, lumbar and sacral division innervated the distal colon.

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Gene Expression Profiling of Doxifluridine Treated Liver, Small and Large Intestine in Cynomolgus (Macaca fascicularis) Monkeys

  • Jeong, Sun-Young;Park, Han-Jin;Oh, Jung-Hwa;Kim, Choong-Yong;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • 제3권2호
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    • pp.137-144
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    • 2007
  • The mechanism of cytotoxicity of doxifluridine, a prodrug fluorouracil (5-FU), has been ascribed to the misincorporation of fluoropyrimidine into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase. Increased understanding of the mechanism of 5-FU has led to the development of strategies that increases its anticancer activity or predicts its sensitivity to patients. Using GeneChip?? Rhesus Macaque Genome arrays, we analyzed gene expression profiles of doxifluridine after two weeks repeated administration in cynomolgus monkey. Kegg pathway analysis suggested that cytoskeletal rearrangement and cell adhesion remodeling were commonly occurred in colon, jejunum, and liver. However, expression of genes encoding extracellular matrix was distinguished colon from others. In colon, COL6A2, COL18A1, ELN, and LAMA5 were over-expressed. In contrast, genes included in same category were down-regulated in jejunum and liver. Interestingly, MMP7 and TIMP1, the key enzymes responsible for ECM regulation, were overexpressed in colon. Several studies were reported that both gene reduced cell sensitivity to chemotherapy-induced apoptosis. Therefore, we suggest they have potential as target for modulation of 5-FU action. In addition, the expression of genes which have been previously known to involve in 5-FU pathway, were examined in three organs. Particularly, there were more remarkable changes in colon than in others. In colon, ECGF1, DYPD, TYMS, DHFR, FPGS, DUT, BCL2, BAX, and BAK1 except CAD were expressed in the direction that was good response to doxifluridine. These results may provide that colon is a prominent target of doxifluridine and transcriptional profiling is useful to find new targets affecting the response to the drug.

위암 및 대장암의 유발에 영향을 미치는 식이요인에 관한 연구 (A Study on Dietary Factors Related to the Incidence of Stomach Cancer and Colon Cancer in Korea)

  • 양은주
    • Journal of Nutrition and Health
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    • 제26권5호
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    • pp.603-614
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    • 1993
  • This study was undertaken to investigate the dietary factors related to the incidence of stomach and colon cancers in Korean. The subjects were 139 stomach and 52 colon cancer patients recruited from 3 general hospitals in Seoul. Food intake, anthropometric measurement, and blood compositions were studied through personal interview and using medical records. Body weight, body mass index, triceps skinfold thickness, body muscle mass of the subjects were lower than reference values. The body weight was reduced after the onset of the illness, which suggests body waste due to the cancers. The patients showed the lower valuies of hemoglobin and hematocrit. Serum protein and calcium were at lower limit of the normal range. Therefore the untritional status assessed by anthropometry and blood composition should be said to be marginal. The average intake of most of the nutrients except Ca of the subjects met the RDA, but the range was wide and the nutrient intake of large proportion of the subjects feel below 75% of RDA. The food intake of egg, milk, legumes, and fruts were lower than national average, on the other hand the subjects had higher intake of meat, vegetables, and fats. The subjects drank and smoked heavily, stomach cancers being more severs. From this results, dietary risk factors for the stomach and colon cancers in Korean did not agree with the reports of western societies. Even though the intakes of meat and animal food of colon cancer patients can not be classified as high, it was higher than stomach cancer and national average. Therefore it could be concluded that with increasing consumption of animal food, the incidence of colon cancer would be increased in Korea.

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악성종양환자(惡性腫瘍患者)에서 혈청(血淸) Tissue Polypeptide Antigen 치(値)의 임상적(臨床的) 의의(意義)에 관(關)한 연구(硏究) (A Study on the Clinical Significance of Serum Tissue Polypeptide Antigen Levels in Patients with Malignancy)

  • 박성기;문대혁;이명철;조보연;김병국;김노경;고창순;이문호
    • 대한핵의학회지
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    • 제18권1호
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    • pp.1-8
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    • 1984
  • To evaluate the clinical significance of serum tissue polypeptide antigen (TPA) levels in patients with malignancy, serum TP A levels were measured by radioimmunoassay in 49 normal controls, 9 patients of postoperative colon cancer without recurrence and 68 patients with various untreated malignancy, who visited Seoul National University Hospital from February, 1983 to September, 1983. The results were as follows; 1) Serum TPA levels in 49 normal controls were in the range of 22-135 U/L $(74{\pm}28U/L,\;mean{\pm}S.D.)$. There was no sex or age difference. Normal upper limit of serum TPA was defined as 130 U/L (mean+2S.D.). 2) Serum TPA levels in 68 patients with various untreated malignancy (stomach cancer 33 cases, colon cancer 11 cases, lung cancer 10 cases, primary liver cancer 9 cases and metastatic cancer of unknown primary site 5 cases) were in the range of 10-800 U/L $(189{\pm}170U/L,\;mean{\pm}S.D.)$ and significantly elevated, compared with those of normal controls (p<0.005). 3) The sensitivities of serum TPA in various untreated malignancy were 39% in stomach cancer, 55% in colon cancer, 50% in lung cancer, 67% in primary liver cancer and 80% in metastatic cancer of unknown primary site respectively. 4) The sensitivities of serum TPA related to resectability in stomach and colon cancer were 32% in resectable stomach cancer, 50% in unresectable stomach cancer, 29% in resectable colon cancer and 100% in unresectable colon cancer respectively. 5) The mean value of serum TPA levels in 9 patients of postoperative colon cancer without recurrence was $70{\pm}39U/L$ and significantly decreased, compared with that of untreated colon cancer, $180{\pm}150U/L$ U/L (p<0.05). 6) In patients with stomach or colon cancer, there was no significant correlation between serum TP A and serum CEA levels, but simultaneous measurement of serum TPA and serum CEA levels increased sensitivities. From above results, we concluded that serum TPA level is a useful indicator reflecting tumor activity and responses to anticancer treatment in patients with malignancy.

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Female Sex and Right-Sided Tumor Location Are Poor Prognostic Factors for Patients With Stage III Colon Cancer After a Curative Resection

  • Park, Jung Ho;Park, Hyoung-Chul;Park, Sung Chan;Oh, Jae Hwan;Kim, Duck-Woo;Kang, Sung-Bum;Heo, Seung Chul;Kim, Min Jung;Park, Ji Won;Jeong, Seung-Yong;Park, Kyu Joo
    • Annals of Coloproctology
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    • 제34권6호
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    • pp.286-291
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    • 2018
  • Purpose: Stage-IIIC colon cancer is an advanced disease; however, its oncologic outcomes and prognostic factors remain unclear. In this study, we aimed to determine the predictors of disease-free survival (DFS) in patients with stage-IIIC colon cancer. Methods: From a multicenter database, we retrospectively enrolled 611 patients (355 men and 256 women) who had undergone a potentially curative resection for a stage-IIIC colon adenocarcinoma between 2003 and 2011. The primary endpoint was the 5-year DFS. Results: The median age was 62 years; 213 and 398 patients had right-sided colon cancer (RCC) and left-sided colon cancer (LCC), respectively. The 5-year DFS in all patients was 52.0%; median follow-up time was 35 months (range, 1-134 months). A multivariate Cox regression revealed that female sex (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.19-1.90; P < 0.01), right-sided tumor location (HR, 1.65; 95% CI, 1.29-2.11; P < 0.01), lymphatic invasion (HR, 1.52; 95% CI, 1.08-2.15; P < 0.01) and a high (${\geq}0.4$) metastatic lymph node ratio (HR, 3.72; 95% CI, 2.63-5.24; P < 0.01) were independent predictors of worse 5-year DFS. Female patients with RCC were 1.79 fold more likely to experience recurrence than male patients with LCC. Conclusion: Female sex and right-sided tumor location are associated with higher tumor recurrence rates in patients with stage-IIIC colon cancers. Aggressive treatment and close surveillance should be planned for patients in these groups.

Aurora kinase A induces migration and invasion by inducing epithelial-to-mesenchymal transition in colon cancer cells

  • Hong, On-Yu;Kang, Sang Yull;Noh, Eun-Mi;Yu, Hong-Nu;Jang, Hye-Yeon;Kim, Seong-Hun;Hong, Jingyu;Chung, Eun Yong;Kim, Jong-Suk
    • BMB Reports
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    • 제55권2호
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    • pp.87-91
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    • 2022
  • Aurora kinase is a family of serine/threonine kinases intimately associated with mitotic progression and the development of human cancers. Studies have shown that aurora kinases are important for the protein kinase C (PKC)-induced invasion of colon cancer cells. Recent studies have shown that aurora kinase A promotes distant metastasis by inducing epithelial-to-mesenchymal transition (EMT) in colon cancer cells. However, the role of aurora kinase A in colon cancer metastasis remains unclear. In this study, we investigated the effects of aurora kinase A on PKC-induced cell invasion, migration, and EMT in human SW480 colon cancer cells. Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) changed the expression levels of EMT markers, increasing α-SMA, vimentin, and MMP-9 expression and decreasing E-cadherin expression, with changes in cell morphology. TPA treatment induced EMT in a PKC-dependent manner. Moreover, the inhibition of aurora kinase A by siRNAs and inhibitors (reversine and VX-680) suppressed TPA-induced cell invasion, migration, and EMT in SW480 human colon cells. Inhibition of aurora kinase A blocked TPA-induced vimentin and MMP-9 expression, and decreased E-cadherin expression. Furthermore, the knockdown of aurora kinase A decreased the transcriptional activity of NF-κB and AP-1 in PKC-stimulated SW480 cells. These findings indicate that aurora kinase A induces migration and invasion by inducing EMT in SW480 colon cancer cells. To the best of our knowledge, this is the first study that showed aurora kinase A is a key molecule in PKC-induced metastasis in colon cancer cells.

Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation

  • Seok, Ju Hyung;Kim, Dae Hyun;Kim, Hye Jih;Jo, Hang Hyo;Kim, Eun Young;Jeong, Jae-Hwang;Park, Young Seok;Lee, Sang Hun;Kim, Dae Joong;Nam, Sang Yoon;Lee, Beom Jun;Lee, Hyun Jik
    • Journal of Veterinary Science
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    • 제23권5호
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    • pp.74.1-74.16
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    • 2022
  • Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.