Ulcerative colitis (UC) is an inflammatory bowel disease and a chronic gastrointestinal disorder. Rubi Fructus (RF), the fruit of Rubus coreanus Miquel, is known to exert several pharmacological effects including anti-oxidative, anti-obesity and anti-inflammatory properties. However, the improving effect and mechanism of RF on intestinal inflammation is not been fully understood. The purpose of this study was to investigate the regulatory effect of RF on dextran sulfate sodium (DSS)-induced colitis in mice. We evaluated the effects of RF on DSS-induced clinical signs by analyzing weight loss and colon length. The inhibitory effects of RF on inflammatory mediators such as prostaglandin E2 (PGE2), cyclooxygenase (COX)-2, as well as the activation of nuclear factor-κB (NF-κB), were determined in colitis tissue. Our data indicated that mice treated with DSS showed clinical symptoms of colitis, including weight loss, colon length decrease and diarrhea. However, we observed that RF treatment significantly improved these clinical symptoms of weight loss, colon length decrease and diarrhea induced by DSS. RF inhibited the enhanced levels of COX-2 and PGE2 caused by DSS. We also showed that the anti-inflammatory mechanism of RF by suppressing the activation of NF-kB in DSS-treated colon tissues. Collectively, the findings of this study indicate the prospect of developing new drugs from RF for UC treatment.
Park, Sung-Ki;Moon, Dae-Hyuk;Lee, Myung-Chul;Cho, Bo-Youn;Kim, Byoung-Kook;Kim, Noe-Kyeong;Koh, Chang-Soon;Lee, Mun-Ho
The Korean Journal of Nuclear Medicine
/
v.18
no.1
/
pp.1-8
/
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.
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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v.34
no.6
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pp.286-291
/
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.
Kucukzeybek, Yuksel;Dirican, Ahmet;Demir, Lutfiye;Yildirim, Serkan;Akyol, Murat;Yildiz, Yasar;Bayoglu, Ibrahim Vedat;Alacacioglu, Ahmet;Varol, Umut;Salman, Tarik;Yildiz, Ibrahim;Can, Huseyin;Tarhan, Mustafa Oktay
Asian Pacific Journal of Cancer Prevention
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v.16
no.6
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pp.2413-2418
/
2015
Background: Although adjuvant chemotherapy is a standard treatment in stage III colon cancer, its benefit is not as clear for stage II patients. In this retrospective analysis, we aimed to evaluate the survival of patients with low-risk stage II colon cancer, the efficacy of adjuvant chemotherapy in high-risk stage II colon cancer patients, and prognostic factors in stage II disease. Materials and Methods: One hundred and seventeen patients who were diagnosed with stage II colon cancer between January 2006 and December 2011 were included in the study. Patients were stratified into two groups as being low-risk and high-risk according to risk factors for stage II disease. Adjuvant 5-fluorouracil-based chemotherapy were administered to the patients with risk factors. Results: Ninety-four patients were treated with adjuvant chemotherapy due to high risk factors and 23 were monitored without treatment. Median follow-up time was 43 months. In terms of disease free survival and overall survival, adjuvant chemotherapy did not provide a statistically significant difference. Univariate analysis demonstrated that bowel obstruction was the major risk factor for shortened disease-free survival, while bowel perforation and perineural invasion were both negative prognostic factors for overall survival. Conclusions: The recommendation of adjuvant chemotherapy for stage II colon cancer is not clear. In our study, it was found that adjuvant chemotherapy did not contribute to survival in high-risk stage II patients. Due to the fact that prognosis of stage II patients is good, many more patients will be needed for statistically significant differences in survival. Adjuvant chemotherapy containing 5 fluorouracil is being used to high-risk stage II patients although it is not a standard treatment approach.
Christudoss, Pamela;Selvakumar, R.;Pulimood, Anna B.;Fleming, Jude Joseph;Mathew, George
Asian Pacific Journal of Cancer Prevention
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v.13
no.2
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pp.487-492
/
2012
Trace element zinc deficiency or excess is implicated in the development or progression of some cancers. The exact role of zinc in the etiology of colon cancer is unclear. To cast light on this question, an experimental model of colon carcinogenesis was applied here. Six week old rats were given sub cutaneous injections of DMH (30 mg/kg body weight) twice a week for three months and sacrificed after 4 months (precancer model) and 6 months (cancer model). Plasma zinc levels showed a significant decrease (p<0.05) at 4 months and a greater significant decrease at 6 months (p<0.01) as compared with controls. In the large intestine there was a significant decrease in tissue zinc levels (p<0.005) and in CuZnSOD, and alkaline phosphatase activity (p<0.05) in the pre-cancerous model and a greater significant decrease in tissue zinc (p<0.0001), and in CuZnSOD and alkaline phosphatase activity (p<0.001), in the carcinoma model. The tissue zinc levels showed a significant decrease in the small intestine and stomach (p<0.005) and in liver (p<0.05) in the cancer model. 87% of the rats in the precancer group and 92% rats in the cancer group showed histological evidence of precancerous lesions and carcinomas respectively in the colon mucosa. This study suggests that the decrease in plasma zinc, tissue zinc and activity of zinc related enzymes are associated with the development of preneoplastic lesions and these biochemical parameters further decrease with progression to carcinoma in the colon.
Colon cancer is the third most common malignant neoplasm in the world and it remains an important cause of death, especially in western countries. The toxic environmental pollutant, 1, 2-dimethylhydrazine (DMH), is also a colon-specific carcinogen. Tannic acid (TA) is reported to be effective against various types of chemically induced toxicity and also carcinogenesis. In the present study, we evaluated the chemopreventive efficacy of TA against DMH induced colon toxicity in a rat model. Efficacy of TA against the colon toxicity was evaluated in terms of biochemical estimation of antioxidant enzyme activities, lipid peroxidation, histopathological changes and expression of early molecular markers of inflammation and tumor promotion. DMH treatment induced oxidative stress enzymes (p<0.001) and an early inflammatory and tumor promotion response in the colons of Wistar rats. TA treatment prevented deteriorative effects induced by DMH through a protective mechanism that involved reduction of oxidative stress as well as COX-2, i-NOS, PCNA protein expression levels and TNF-${\alpha}$ (p<0.001) release. It could be concluded from our results that TA markedly protects against chemically induced colon toxicity and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.
Structural differences in various divisions of the rabbit colon were investigated using light and scanning electron microscopy. For light microscopic study, various Portions of the colon from seven rabbits (2.5 kg body weight) were fixed in 10% neutral buffered formalin, and paraffin sections were stained with hematoxylin-eosin. Tissues for scanning electron microscopy were fixed in 1% glutaraldehyde-1.5% paraformaldehyde and postfixed in 1% $OsO_4$, dehydrated to 100% alcohol, transfered to isoamilacetate and dried by the critical point method. Subsequently, specimens were coated with gold and viewed with a JSM-35C scanning electron microscope. The colon displays a morphological diversity along its proximo-distal axis. Five regions can be discerned based on the macroscopic and microscopic characteristics. 1) The first segment immediately distal to the cecocolical junction possessing three teniae is approximately 5 cm ($4{\sim}6cm$) in length, and displays irregular folds of the mucosa oriented transversely similar to those of the cecum. 2) The second segment possessing three teniae is about 7 cm ($5{\sim}8cm$) in length, and is characterized by the papilla-like protrusions on the mucosal surface. 3) The third segment, possessing a single tenia is about 16 cm ($12{\sim}20cm$) in length, and also displays the papilla-like protrusions similar to the aforegoing segment. 4) Fusus coli, approximately 4 cm ($3{\sim}5cm$) in length, is free of teniae and exhibits longitudinal folds on the mucosal surface. These four portions together constitute the proximal colon. 5) The distal colon reaches a length of about 58 cm ($53{\sim}55cm$) and shows a pattern of surface irregularities with minor ridges on the mucosal folds.
In order to evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against Colon-26(Murine Rectum Carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to Colon-26 cell lines. Soonkiwhajungtang has only mimic direct anti-tumor effect against to Colon-26 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Soonkiwhajungtang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubidn and Soonkiwhajungtang extracts.
The differences between luminal microbiota (LM) and mucosal microbiota (MAM) were little known, especially in duodenum. In this study, LM and MAM in colon and duodenum of mice were investigated through 16S rRNA high-throughput sequencing. The lowest bacterial diversity and evenness were observed in duodenal LM (D_LM), followed by duodenal MAM (D_MAM). Meanwhile, the bacterial diversity and evenness were obviously increased in D_MAM than these in D_LM, while no significant difference was observed between colonic MAM (C_MAM) and colonic LM (C_LM). PCoA analysis also showed that bacterial communities of LM and MAM in duodenum were completely separated, while these in colon overlapped partly. The ratio of Firmicutes to Bacteroidetes (F/B) in D_MAM was significantly higher than that in D_LM. Lactobacillus was largely enriched and was the characteristic bacteria in D_LM. The characteristic bacteria in D_MAM were Turicibacter, Parasutterella, Marvinbryantia and Bifidobacterium, while in C_LM they were Ruminiclostridium_6, Ruminiclostridium_9, Ruminococcaceae_UCG_007 and Lachnospiraceae_UCG_010, and in C_MAM they were Lachnospiraceae_NK4A136, Mucispirillum, Alistipes, Ruminiclostridium and Odoribacter. The networks showed that more interactions existed in colonic microbiota (24 nodes and 74 edges) than in duodenal microbiota (17 nodes and 29 edges). The 16S rDNA function prediction results indicated that bigger differences of function exist between LM and MAM in duodenum than these in colon. In conclusion, microbiota from intestinal luminal content and mucosa were different both in colon and in duodenum, and bacteria in colon interacted with each other much more closely than those in duodenum.
This study was designed to observe the effect of dietary fiber and fat on colon tumor incidence and cell proliferation. Male Sqraue Dawley rats(n=225) at 7 weeks of age, were divided into 3 groups depending on the type of fat b(beef tallow, corn oil and DHA-rich fish oil) and each group was again divided into 3 groups depending on type of fiber(fiber-free, perctin and cellulose) . The experimental diet containing dietary fat at 15%(w/w) and fiber at 6%(w/w) levels was fed for 25 weeks. At the same time, each rats was intramuscularly injected with DMH two times a week for 6 weeks to geive total dose of 180mg/kg body weight. Cell proliferation was measured by in vivo incroporation of bromodeoxyuridine (BrdU) into DNA. Fish oil decreased the tumor incidence (9.67%) compared with beef talow (33.39%) and corn oil (21.21%). Tumor incidence was decreased in all groups that fed cellulose (11.67%) compared with those of fiber-free(21.74%) and pectic(19.70%). Most of tumors was distributed at the site of the distal colon. The rats fed both fish oil and cellulose significantly decreased th enumber of tumors and tumor incidence compared to other groups. Fish oil was more effective in preventing cell prolofieration by decreasing crypt length and labeling index(LI) compared with beef tallow(p<0.05). Cell proliferation in distal colon was more developed to the upper part of the crypt compared to proximal colon. Overall tumor incidence and cell proliferation were more affected by dietary fat. But the effect of dietary fiber was different depending on type of fat in the experimental diet. These results suggest that a DHA -rich fish oil may has more decisive effect in inhibiting the cell proliferation in colon.
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