• Title/Summary/Keyword: colorectal cancer

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Effect of Cimetidine on the Transport of Quinolone Antibiotics in Caco-2 Cell monolayers

  • Kim, Seon-Hwa;Jung, Seo-Jeong;Um, So-Young;Na, Mi-Ae;Choi, Min-Jin;Chung, Myeon-Woo;Oh, Hye-Young
    • Biomolecules & Therapeutics
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    • v.15 no.2
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    • pp.102-107
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    • 2007
  • Cimetidine, a substrate for P-glycoprotein (P-gp), is a well known drug interacting with a variety of drugs and results in alteration of pharmacokinetic parameters by concomitant administration. The aim of present study was to investigate whether cimetidine affects the transport of various quinolone antibiotics in human colorectal cancer cell line (Caco-2) system which has been typically used to investigate drug transport via P-gp. The apparent permeability coefficients (P$_{app}$) value of 9 quinolone antibiotics in the co-treatment with cimetidine was examined. Apical to basolateral (AP-to-BL) transport of fleroxacin in the co-treatment with cimetidine was increased to 1.5-fold (p<0.01) compared with that of fleroxacin alone, whereas basolateral to apical (BL-to-AP) transport of fleroxacin was decreased to 0.83-fold significantly (p<0.05). Ofloxacin was decreased to 0.8-fold (p<0.01) and 0.72-fold (p<0.01) significantly in AP-to-BL and BL-to-AP direction, respectively by cimetidine cotreatment. The P$_{app}$ values of gatifloxacin, moxifloxacin, ciprofloxacin and rufloxacin also were changed by cimetidine. These results have a potential that cimetidine influences on the pharmacokinetics of quinolone antibiotics. It suggests that careful drug monitoring and dosage adjustment may be necessary during the co-administration of quinolone antibiotics with cimetidine.

Fecal Microbiota Transplantation (FMT) Alleviates Experimental Colitis in Mice by Gut Microbiota Regulation

  • Zhang, Wanying;Zou, Guiling;Li, Bin;Du, Xuefei;Sun, Zhe;Sun, Yu;Jiang, Xiaofeng
    • Journal of Microbiology and Biotechnology
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    • v.30 no.8
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    • pp.1132-1141
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    • 2020
  • Inflammatory bowel disease (IBD) is an increasing global burden and a predisposing factor to colorectal cancer. Although a number of treatment options are available, the side effects could be considerable. Studies on fecal microbiota transplantation (FMT) as an IBD intervention protocol require further validation as the underlying mechanisms for its attenuating effects remain unclear. This study aims to demonstrate the ameliorative role of FMT in an ulcerative colitis (UC) model induced by dextran sulfate sodium (DSS) and elucidate its relative mechanisms in a mouse model. It was shown that FMT intervention decreased disease activity index (DAI) levels and increased the body weight, colon weight and colon length of experimental animals. It also alleviated histopathological changes, reduced key cytokine expression and oxidative status in the colon. A down-regulated expression level of genes associated with NF-κB signaling pathway was also observed. The results of 16S rRNA gene sequencing showed that FMT intervention restored the gut microbiota to the pattern of the control group by increasing the relative abundance of Firmicutes and decreasing the abundances of Bacteroidetes and Proteobacteria. The relative abundances of the genera Lactobacillus, Butyricicoccus, Lachnoclostridium, Olsenella and Odoribacter were upregulated but Helicobacter, Bacteroides and Clostridium were reduced after FMT administration. Furthermore, FMT administration elevated the concentrations of SCFAs in the colon. In conclusion, FMT intervention could be suitable for UC control, but further validations via clinical trials are recommended.

Distinct Cellular Calcium Metabolism in Radiation-sensitive RKO Human Colorectal Cancer Cells

  • Kim, Yun Tai;Jo, Soo Shin;Park, Young Jun;Lee, Myung Za;Suh, Chang Kook
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.6
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    • pp.509-516
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    • 2014
  • Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive $Ca^{2+}$ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of $Ca^{2+}$ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular $Ca^{2+}$ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (${\gamma}$)-irradiation. In irradiated RKO cells, $Ca^{2+}$ influx via activation of NCX reverse mode was enhanced and a decline of $[Ca^{2+}]_i$ via forward mode was accelerated. The amount of $Ca^{2+}$ released from the ER in RKO cells by the activation of $IP_3$ receptor was also enhanced by irradiation. An increase in $[Ca^{2+}]_i$ via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that ${\gamma}$-irradiation elicits enhancement of cellular $Ca^{2+}$ metabolism in radiation-sensitive RKO cells yielding programmed cell death.

Microsatellite Instability and p53, k-ras c-myc Oncoprotein Expression in Non-Small Cell Lung Carcinoma (비소세포 폐암에서의 Microsatellite Instability와 p53. K-ras, c-myc 암단백의 발현)

  • 나석주;곽문섭
    • Journal of Chest Surgery
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    • v.33 no.1
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    • pp.60-67
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    • 2000
  • Background: Microsatellites are short-tandem repeated uncleotide sequences present throughout the human genome. Alterations of microsatellites have been termed microsatellite instability(MI). It has been generally known that microsatellite instability detected in hereditary non-polyposis colorectal cancer (HNPCC) reflects genetic instability that is caused by impairments of DNA mismatch repair system regarding as a novel tumorigenic mechanism. A number of studies reported that MI occurred at varying frequencies in non-small cell lung carcinoma (NSCLC). However It has been unproven whether MI could be a useful market of genetic instability and have a clinical significance in NSCLC. Material and Method : We have examined whether MI can be observed in thirty NCSLC using polymerase chain reaction whether such alterations are associated with other molecular changes such as p53, K-ras and c-myc oncoproteins expression detected by immunohistochemical stain,. Result: MI(+) was observed in 16.6%(5/30) and MI(-) was 83.3% (25/30) Average age was 50$\pm$7.5 year-old in MI(+) group and 57$\pm$6.6 year-old in MI(-) group. Two year survival rate in MI(=) group (20% 1/5) was worse than MI(-) group (64% 16/25) with a statistic difference. (P=0.04) The positive rate of K-ras oncoprotein expression and simultaneous expression of 2 or 3 oncoproteins expression were higher in MI(+) group than MI(-) group with a statistic difference(P=0.05, P=0.01) Conclusion: From, these results the authors can conclude that MI is found in some NSCLC and it may be a novel tumorigenic mechanism in some NSCLC. We also conclude that MI could be used as another poor prognostic factor in NSCLS.

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Effect of Dietary Folate on Hyperhomocysteinemia and Cellular Toxicity Induced Alcohol Administration in Rat Liver

  • Kim, Chung-Hyeon;Kim, Ki-Nam;Kim, Yeon-Soo;Chang, Nam-Soo
    • Molecular & Cellular Toxicology
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    • v.1 no.2
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    • pp.137-141
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    • 2005
  • The critical role of folate in the remethylation pathway for methionine synthesis from homocysteine has been well documented. Hyperhomocysteinemia resulting from inadequate folate nutrition has been implicated in increased incidence of macrovascular diseases, colorectal cancer, neural tube defects, etc. Chronic exposure to ethanol impairs folate nutrition and one-carbon metabolism in the liver, which often results in fatty liver due to a defective remetylation process. This study was carried out to investigate the chronic effects of moderate levels of alcohol and dietary folate on plasma homocysteine levels, and on histopathology and biochemical functions of the liver. Rats were raised on experimental diets with three levels of folate (0, 2, 8 mg/kg diet), and 50% ethanol (1.8 ml/kg body weight) was administered intragastically by intubation tubes three times a week for 10 weeks. Plasma homocysteine concentrations were found to be significantly influenced by dietary folate intake and alcohol administration. Among all treatment groups, plasma homocysteine levels were the highest in the animals receiving a combined treatment of folate deficient diet and alcohol administration. Plasma homocysteine concentrations were negatively correlated with folate concentration in the plasma (p<0.01) and liver (p<0.05). Among alcohol treated rats, increase in plasma homocysteine values due to macrovascular and microvascular fatty changes and spotted necrosis were observed more frequently in folate-deficient animals diet than those on folate-adequate and folate supplemented diets in alcohol-treated rats. These results indicate that folate supplementation above the recommended level might be beneficial in the prevention of alcohol-related hyperhomocysteinemia and abnormal histologic changes in the liver.

Medulloblastoma and Familial Adenomatous Polyposis in a 24-year-old Female Patient: A Case Report of Turcot Syndrome (뇌수모세포종 및 가족성 선종성 용종증으로 발현한 Turcot 증후군 1예)

  • Jeong, Soo-In;Suh, Jung-Min;Lee, Ji-Hyuk;Lee, Hae-Jung;Lee, Jee-Hyun;Sung, Ki-Woong;Song, Hye-Jung;Choe, Yon-Ho
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.10 no.2
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    • pp.206-210
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    • 2007
  • Turcot syndrome is characterized by the concurrence of a primary neuroepithelial brain tumor and multiple colorectal polyposis. We report a case of a 24-year-old woman diagnosed with Turcot syndrome. At first, the patient was diagnosed as having a medulloblastoma after a tumorectomy of the 4th ventricle mass. The patient underwent radiotherapy and chemotherapy. After high-dose chemotherapy, neutropenic fever and severe mucositis developed. For an evaluation of the persistent hematochezia and diarrhea, a colonoscopy was performed. It revealed pseudomembranous colitis and multiple polyps in the entire colon. According to the family history, her father had undergone a total colectomy due to colon cancer and polyposis of the entire colon. Her brother also was found to have multiple polyps in the colon by a colonoscopy. The patient was diagnosed with Turcot syndrome.

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Toxicogenomics Study on TK6 Human Lymphoblast Cells Treated with Mitomycin C

  • Kim, Joo-Hwan;Koo, Ye-Mo;Lee, Woo-Sun;Suh, Soo-Kyung;Kang, Jin-Seok;Han, Eui-Sik;Kim, Seung-Hee;Park, Sue-N.
    • Molecular & Cellular Toxicology
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    • v.3 no.3
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    • pp.165-171
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    • 2007
  • Mitomycin C (MMC), an antitumor antibiotic isolated from Streptomyces caespitosus, is used in chemotherapy of gastric, bladder and colorectal cancer. MMC is activated in vivo to alkylate and crosslink DNA, via G-G interstrand bonds, thereby inhibiting DNA synthesis and transcription. This study investigates gene expression changes in response to MMC treatment in order to elucidate the mechanisms of MMC-induced toxicity. MMC was admistered with single dose (0.32 and 1.6 ${\mu}M$) to TK6 cells. Applied Biosystem's DNA chips were used for identifying the gene expression profile by MMC-induced toxicity. We identified up- or down-regulated 90 genes including cyclin M2, cyclin-dependent kinase inhibitor 1A (p21, cip1), programmed cell death 1, tumor necrosis factor (ligand) superfamily, member 9, et al. The regulated genes by MMC associated with the biological pathways apoptosis signaling pathway. Further characterization of these candidate markers related to the toxicity will be useful to understand the detailed mechanism of action of MMC.

The Levels of Health Literacy and Related Factors among Middle-aged Adults in Seoul, Korea (서울 지역 일부 중년 성인의 건강정보이해능력(health literacy) 실태와 관련 요인에 대한 연구)

  • Kang, Soo-Jin;Lee, Tae-Wha;Kim, Gwang-Suk;Lee, Ju-Hee
    • Korean Journal of Health Education and Promotion
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    • v.29 no.3
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    • pp.75-89
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    • 2012
  • Objectives: This study was performed to identify the level of health literacy and to investigate the relationship between the health literacy and preventive health care use in middle-aged adults in Korea. Methods: A total of 315 adults aged 40 to 64 years living in Seoul participated in the study. Data were collected from December 15-24, 2010 from outpatient hospitals, clinics, workplaces and other locations in the community. Health literacy was measured using the Functional Health Literacy and Self-rated Health Literacy Questionnaires. Preventive health service use was defined as receiving screening (general health checkups, gastric and colorectal cancer, mammogram, and pap smear) and influenza vaccination. Descriptive analysis, t-test, and ANOVA were used. Results: The mean of functional health literacy was 3.87 (score range 0-6) and the self-rated health literacy was 60.08 (score range 16-80). The most difficult items of the self-rated questionnaires were patient educational materials provided by health care providers and medical forms. The most difficult items of functional health literacy were information-based, including nutritional facts and clinical schedules. Association between health literacy and preventive health service use was not found. Conclusions: Further study is necessary with larger samples and with considerations for their education level, age, and preventive health care use.

Effect of Perilla Oil Rich in $\alpha$-Linolenic Acid on Colon Tumor Incidence, Plasma Thromboxane B2 Level and Fatty Acid Profile of Colonic Mucosal Lipids in Chemical Carcinogen-Treated Rats

  • Park Hyun Suh
    • Journal of Nutrition and Health
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    • v.26 no.7
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    • pp.829-838
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    • 1993
  • This study was designed to compare the effect of different dietary fats on the incidence of colorectal tumor, the level of plasma thromboxane B2(TXB2) and fatty acid profiles of platelet and colonic mucosal lipids in N - methyl - N - nitro - N - nitrosoguanidine(MNNG) - treated rats. Male Sprague Dawley rats, at 8 weeks old, were divided into 2 groups and infused intrarectally with saline(control group) or with 2mg MNNG(carcinogen-treated group) twice a week for 3 weeks. Each group was again divided into 4 groups and fed one of four diets(BT, CO, PO, FO) containing dietary fat at 9%(w/w) level for 37 weeks, Dietary fats were beef tallow(7.2%)+corn oil(1.8%) for BT, corn oil(9.0%) for CO, perilla oil(9.0%) for PO, fish oil (6.5%)+corn oil (2.5%) for FO diets. MNNG-treated rats had colonic tumor, while no tumors(adenocarcinoma and adenoma) than others. Tumor sizes in BT-MNNG rats ranged from 2mm papillary form to 15mm of polypoid. However, the size of tumors in PO-MNNG or FO-MNNG rats could not be measured by gross examination. BT-MNNG and CO-MNNG groups were higher in the level of plasma TXB2 and the ratio of c20 : 4/c20 :5 platelet. PO-MNNG groups were lower in the ratio of c20 : 4/c20 : 5(p<0.05) in fatty acid of colonic mucosal lipids suggesting that perilla oil and fish oil could reduce the level of PGE2 and TXB2 by modifying its precursor content and restrain tumor promotion in colon. Effect of perilla oil rich in $\alpha$-linolenic acid on colon carcinogenesis was similar to that of fish oil and thus perilla oil could have a protective effect against colon cancer possibly by inhibiting the production of arachidonic acid metabolite.

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A Comparison Study: the Risk Factors in the Lifestyles of Colorectal Cancer Patients and Healthy Adults (대장암 환자와 건강인의 생활습관 비교)

  • Yoo, Yang Gyeong
    • Proceedings of the Korea Contents Association Conference
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    • 2014.11a
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    • pp.419-420
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    • 2014
  • 본 연구는 대장암 환자들의 암으로 진단받은 당시의 생활습관 실태를 암 병력이 없는 일반 성인들과 비교해봄으로써 대장암의 발생에 영향을 미치는 위험요인을 규명하고자 실시되었다. 연구 설계: 대장암 환자의 생활습관 실태를 파악하고, 대장암 발생에 영향을 미치는 인자를 확인하기 위하여 대장암 환자와 암 진단을 받지 않은 건강인을 대상으로 시도된 후향적 비교 조사연구(retrospective comparison survey study). 연구 대상자는 2011년 10월부터 2012년 8월까지 대장암으로 진단된지 1년 이내로 J대학교병원 내의 암전문연구센터에 내원한 대장암 환자 107명과 동 시기에 동 병원을 방문한 암환자 아닌 환자의 보호자 중 암진단을 받지 않은 일반 성인을 대상으로 빈도 짝찟기를 통해 연령, 성별 및 배우자 상태 등이 동질한 124명이었다. 연구 도구는 김화영(2011)의 생활습관 측정도구(Content Validity Index [CVI], Mean expert proportion=0.98) 를 저자의 승인 하에 사용하였으며, 관련문헌을 참조하여 수정 보완한 후 식습관, 음주 및 흡연 습관, 휴식 및 활동 습관, 스트레스 관리 및 정기검진습관 등의 5개 하위영역으로 측정하였다. 연구결과 인스턴트식품 섭취여부, 스트레스 해소정도, 육류 익힌정도(살짝 익힘/탈정도로 익힘) 및 평소 주로 먹는 음식(채식/육식 여부)이 대장암 발생에 유의한 영향을 미치는 요인으로 나타났다. 대장암환자군과 건강인군의 생활습관을 비교한 본 연구의 결과를 토대로 하여, 평소 식습관에서 인스턴트식품 등의 가공식품의 섭취를 줄이고, 스트레스가 발생(인지)될 때 이를 효과적으로 조절할 수 있도록 하며, 육류섭취 시 살짝 익혀서 먹는 습관이 실천되어야 할 것이다. 또한 평소에 육류 섭취를 줄이고 섬유질이 많은 채식 위주로 식사하도록 권장해야 할 것이다.

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