[On the role of ribonucleic acid in benign and malignant neoplasms of the colon].
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Colonic Diseases↗
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[Dietary factors and risk of colon cancer].
Epidemiological and experimental studies indicate that certain dietary habits are associated with increased frequency of cancer in the large bowel. The article presents recent studies on the effects of fiber, fat and calcium on risk of cancer of the large bowel. A low fiber/high fat diet seems to enhance the risk of developing a colonic neoplasm. Increased intake of calcium may be beneficial in high-risk populations.
Carcinogens↗
Neoplasia and ureterosigmoidostomy: a colonoscopy survey.
Patients who have undergone implantation of ureters into the sigmoid colon (ureterosigmoidostomy) are known to be at high risk of developing cancer of the colon many years later. The operation is often performed in infancy for congenital abnormalities of the bladder, thus creating a long term surveillance problem. Six of 34 patients (17.6 per cent) who had undergone ureterosigmoidostomy were found at a screening fibresigmoidoscopy to have adenomas of the left colon or severe dysplasia of the stoma, a mean interval of 22 years after their urinary diversion. Four other patients had previously had a sigmoid adenoma or cancer; thus, 29 per cent overall had developed colonic neoplasms, almost all closely related to their stomas. Another patient who, by error, was excluded from the surveillance, died of metastatic cancer of the sigmoid colon within the study period. Regular surveillance by fibresigmoidoscopy of patients who have had urinary diversion affords the opportunity to detect and remove potentially malignant sigmoid lesions. In addition to its clinical importance, it allows a closer study of this unique model of colon carcinogenesis.
Adenoma↗
Dietary administration with prenyloxycoumarins, auraptene and collinin, inhibits colitis-related colon carcinogenesis in mice.
We previously reported the chemopreventive ability of a prenyloxycoumarin auraptene in chemically induced carcinogenesis in digestive tract, liver and urinary bladder of rodents. The current study was designed to determine whether dietary feeding of auraptene and its related prenyloxycoumarin collinin can inhibit colitis-related mouse colon carcinogenesis. The experimental diets, containing the compounds at 2 dose levels (0.01 and 0.05%), were fed for 17 weeks to male CD-1 (ICR) mice that were initiated with a single intraperitoneal injection of azoxymethane (AOM, 10 mg/kg body weight) and promoted by 1% (w/v) DSS in drinking water for 7 days. Their tumor inhibitory effects were assessed at week 20 by counting the incidence and multiplicity of colonic neoplasms and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA)-labeling index, apoptotic index, cyclooxygenase (COX)-2, inducible nitric oxide (iNOS) and nitrotyrosine in colonic epithelial malignancy. Feeding with auraptene or collinin, at both doses, significantly inhibited the occurrence of colonic adenocarcinoma. In addition, feeding with auraptene or collinin significantly lowered the positive rates of PCNA, COX-2, iNOS and nitrotyrosine in adenocarcinomas, while the treatment increased the apoptotic index in colonic malignancies. Our findings may suggest that certain prenyloxycoumarins, such as auraptene and collinin, could serve as an effective agent against colitis-related colon cancer development in rodents.
Animals↗
[Importance of the analysis of the carcinoembryonic antigen in clinical oncology].
330 patients (126 with gastric neoplasms, 204 with large bowel carcinoma) were submitted to serial assays to evaluate the possible relations between C.E.A. levels, pathologic stage and histologictype of the neoplasm and to define the usefulness of the C.E.A. test in monitoring the followup of the patients with gastrointestinal neoplasms. From our experience it ensues that C.E.A. test positivity (C.E.A. greater than or equal to 5 ng/ml, according to the method employed) is higher in colon neoplasms in comparison with gastric neoplasms, in the adenocarcinomas compared with the anaplastic forms. Besides, the study of the relationship with the pathologic stage points out the scanty usefulness of the C.E.A. test in the early diagnosis of gastroenteric neoplasms (Dukes A-B-C1 = 29.2%; CH stage = 88.1%). The use of C.E.A. test during the follow up seemed us of fundamental importance. We observed that: a) after radical surgery, 72% of the patients showed a normalization of C.E.A. values; b) there is a significant relationship between clinical course and C.E.A. as it can predict, sometimes several months earlier, the occurrence of relapses and metastases; c) there is also a close relationship (P less than 0.001) between the modifications of the antigen under chemotherapy and the clinical response. At present, C.E.A. seems to play, above all, fundamental role in choosing a correct treatment after radical surgery or in modifying the chemotherapeutic treatment in non surgical cases or in non radically resected patients.
Carcinoembryonic Antigen↗
Comparison of immune status and 1,2-dimethylhydrazine induced tumorigenesis in brown--Norway and Fischer rats. Emphasis on splenic and colonic lymphocyte function.
Sym 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis was studied in immunologically different strains of rat: the Brown--Norway which is known to be immunologically a low-responder and the Fischer a high-responder. Brown--Norway rats received a total dose of 75, 150 or 225 mg DMH/kg or vehicle and Fischer rats received 150 mg DMH/kg or vehicle over a 3-week period. Rats were killed 5 months after the final treatment. Lymphocytes were isolated from the spleen and colon from rats treated with 150 mg DMH/kg or vehicle. Natural killer (NK) cell activity and the autologous mixed lymphocyte response (AMLR) as well as colon tumor incidence were compared between the two strains. Splenic and colonic intraperithelial lymphocytes (IEL) from the Brown--Norway strain demonstrated low NK activity and reduced splenic T lymphocyte proliferation in response to autologous non-T lymphocytes. As well, colonic lamina propria lymphocyte (LPL) proliferation was low and Brown--Norway rats had a low incidence of DMH-induced colon neoplasms (7%). In comparison, the Fischer rats had more effective splenic and IEL NK killing, enhanced splenic AMLR, enhanced LPL proliferation and a higher incidence of colon tumors (20%).
1,2-Dimethylhydrazine↗
CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48.
CDX2 is a Drosophila caudal-related homeobox transcription factor that is important for the establishment and maintenance of intestinal epithelial cells. CDX2 is a marker of colon cancer, with strong staining in up to 90% of colonic adenocarcinomas. CDX2 heterozygous-null mice develop colonic neoplasms, which have suggested that CDX2 is a tumor suppressor. However, CDX2 has not been reported to affect xenograft growth. Furthermore, CDX2 is rarely mutated in colon cancer, which has led to suggestions that it may play only a minor role as a tumor suppressor in colon cancer. To understand the functional contributions of CDX2 to colon cancer, we disrupted CDX2 in LOVO and SW48 human colon cancer cell lines by targeted homologous recombination. Consistent with the literature, disruption of CDX2 enhanced anchorage-dependent cell proliferation. However, homozygous loss of CDX2 led to significant inhibition of anchorage-independent growth in LOVO cells, and cell lethality in SW48 cells. Further analyses revealed that disruption of CDX2 led to anchorage-independent G1 to S growth arrest and anoikis. In vivo xenograft studies confirmed that disruption of CDX2 inhibited LOVO tumor growth. These data demonstrate that CDX2 mediates anchorage-independent growth and survival. Thus, CDX2 has tumorigenic potential in the human colon cancer cell lines LOVO and SW48.
Animals↗
Faecal mutagens and intestinal tumours in the dimethylhydrazine-injected rat.
The relationship between the development of colonic tumours and the presence of faecal mutagens has been investigated in the dimethylhydrazine (DMH) injected rat model. Subcutaneous DMH 20 mg/kg for 6 weeks in 10 rats produced colonic tumours in 8 animals and duodenal tumours in 2. Faeces were collected 6, 10, 14, 20 and 25 weeks after commencing DMH injections and were assayed using the Ames test system with both aqueous and ether extracts. All faeces were initially negative for mutagens, but all became positive at some stage following DMH injections, There was no consistent pattern of mutagen excretion or of the strain of Salmonella typhimurium detecting a positive extract. Early positive extracts tended to be with aqueous extracts, whereas later extracts (20 and 25 weeks) were predominantly with ether extracts. DMH produces a metabolic change in the rat resulting in the production of faecal mutagens. This change precedes the appearance of colonic neoplasms and persists after the withdrawal of DMH injections.
Animals↗
Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells.
Overexpression of the ornithine decarboxylase (ODC) gene may be important to the development and maintenance of colonic neoplasms, as well as tumors in general. In this study, we examined the promoter elements governing constitutive expression of the human ODC gene in HCT 116 human colon carcinoma cells and, for comparison, K562 human erythro-leukemia cells. It was determined by functional analysis that the promoter elements responsible reside within the 378 bp immediately upstream from the transcription start site. Within this sequence, there are at least three regions that modulate the efficiency of the ODC promoter cooperatively. Both DNA bandshift and footprint assays demonstrated all three regions to be rich in sites that bind to nuclear proteins isolated from HCT 116 and K562 cells; the protein binding pattern of non-transformed, diploid fibroblasts was found to be much less complex. Several of the protein binding sequences have little or no homology to common regulatory elements. We suggest that the constitutive activity of the ODC gene in HCT 116 colon carcinoma cells, and perhaps transformed cells in general, involves a complex interaction of multiple regulatory sequences and their associated nuclear proteins. Finally, the saturation of the promoter in these transformed cell lines suggests that high levels of protein binding in the ODC promoter may contribute to elevated constitutive expression of this gene.
Base Sequence↗
Gemella endocarditis: consider the colon.
Gemella species, including Gemella morbillorum, are part of the normal flora of the human oropharynx, upper respiratory tract and gastrointestinal tract. Differentiation of Gemella from viridans streptococci in the laboratory may be difficult. Although uncommonly pathogenic, they have been implicated in a variety of human infections, most notably infective endocarditis. Dental instrumentation appears to be the usual source of infection. The case is reported of Gemella morbillorum native valve endocarditis, which was associated with an underlying colonic carcinoma. An association with colonic neoplasm has been described in three previous cases of endocarditis attributed to Gemella. It is well documented that Streptococcus bovis endocarditis may occur in the setting of colonic neoplasia. It is suggested that colonic investigation should be considered in patients with Gemella endocarditis, in whom no other source is apparent.
Colonic Neoplasms↗
[The washout in emergency surgery of the colon. A technical note].
The authors report their experience in the treatment of 179 cases of colonic neoplasm between January 1985 and August 1992. Particularly, they emphasize the advantages of one-stage colectomy with anastomosis because of an obstructing carcinoma of the left colon, used on 41 cases. This treatment can be practicable by using the intraoperative "wash-out" technique. The one-stage colectomy with anastomosis can be advisable because the long survival can be compared to that deriving from the non obstructing carcinoma. Moreover this technique offers several advantages such as the one-stage treatment, the absence of colostomy, the improvement of the cost-benefit relationship, etc. On 41 cases treated by this technique, the authors lament only one decease caused by a total dehiscence of the anastomosis, notwithstanding reintervention. Moreover, 9 cases of partial dehiscence were treated by NPT (Total Parenteral Nutrition) except one which demanded a reintervention.
Adult↗
Omeprazole-induced hypergastrinemia does not influence growth of colon carcinoma.
Colonic mucosa and adenocarcinoma are known to possess gastrin receptors. Recent studies have suggested that some patients with large intestinal cancers and polyps have elevated serum gastrin levels and that gastrin may stimulate growth of colonic neoplasms. The aim of the present investigation was to determine whether endogenous hypergastrinemia--induced by the proton pump inhibitor omeprazole--would influence growth in a subcutaneously implanted murine colonic cancer. The results show that despite a fivefold increase in serum gastrin levels (193 pg/ml median value, range 186-252, in the omeprazole-treated group vs 36 pg/ml median value, range 28-37 in controls), there were no differences in tumor size or survival of tumor-bearing animals. Additionally, there were no differences in serum gastrin values between tumor- (29 pg/ml, range 25-38) and non-tumor- (34 pg/ml, range 25-30) bearing, untreated animals. Endogenous elevation of the serum gastrin hormone to five times the normal level does not demonstrate trophic effects on the murine colon tumor MC-26.
Adenocarcinoma↗
Latent adenocarcinoma of the colon discovered during or after laparoscopic cholecystectomy.
BACKGROUND: The wide acceptance of laparoscopic cholecystectomy has resulted in the performance of increased numbers of cholecystectomies, hence increasing the number of patients discovered with concomitant malignancy or other pathological states. PATIENTS AND METHODS: A total of 3751 patients who underwent laparoscopic cholecystectomy between January 1995 and December 2000 were included in this study. Nine cases of coexisting malignant colonic neoplasm were discovered. All of these patients but one underwent therapeutic resection. RESULTS: The survival rate of these nine patients was the same as that of 62 consecutive colonic cancer patients who were treated in our department over the same period. The rate of postoperative complications in the study group was higher than in the control group (21 % vs. 9.5 %). The hospital stay in these patients was also greater (17 days vs. 10 days). CONCLUSION: The rate of incidental discovery of colorectal carcinomas during laparoscopic cholecystectomy in our department was 0.24 %. These patients had higher complication rates and a longer hospital stay.
Adenocarcinoma↗
[Giant renal angiomyolipoma. Presentation of a case].
A case of large sized angiomyolipoma with atypical clinical presentation is reported. The retroperitoneal mass, showed by ultrasonography, was mainly made by fat tissue, as showed by CT and MRI, and it was associated with focal, probably metastatic, liver lesions. The diagnostic hypothesis of retroperitoneal liposarcoma with liver metastases was made. In the same time a colon neoplasm was found and US-guided biopsies of both the liver lesions and the retroperitoneal mass were carried out. The former were found to be metastases from colon cancer while the latter was a renal angiomyolipoma. The reported case underlines that renal angiomyolipoma if large sized and with atypical clinical presentation may be difficult to differentiate from retroperitoneal, even malignant masses. The hystological evaluation by means of needle biopsy or surgical resection becomes therefore mandatory.
Adenocarcinoma↗
Streptococcus bovis brain abscess associated with an occult colonic villous adenoma.
Streptococcus bovis is now recognized as a common cause of bacterial endocarditis. However, infection of the central nervous system by this organism is very rare. Recent studies have demonstrated the association between Streptococcus bovis infections and colonic neoplasms.
Adenoma↗
GROWTH RATE AND MALIGNANT POTENTIAL OF COLONIC POLYPS: EARLY RESULTS.
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Colonic Neoplasms↗
Suppression of azoxymethane-induced colon carcinogenesis in male F344 rats by mandarin juices rich in beta-cryptoxanthin and hesperidin.
We have reported protective effects of dietary administration of a powder "CHRP" containing high amounts of beta-cryptoxanthin and hesperidin prepared from a Satsuma mandarin (Citrus unshiu Marc.) juice on azoxymethane (AOM)-induced rat aberrant crypt foci through suppression of crypt cell proliferation and/or induction of detoxifying enzymes. In the present study, we investigated the modifying effects of a commercial Satsuma mandarin (Citrus unshiu Marc.) juice (MJ) and those of MJ2 and MJ5, which were prepared from MJ and are richer in beta-cryptoxanthin and hesperidin than MJ, on the occurrence of colonic tumors induced by AOM in male F344 rats. Rats were given 2 weekly s.c. injections of AOM (20 mg/kg body weight) to induce colonic neoplasms. They also received MJ, MJ2, or MJ5 as a drinking water at night for 36 weeks, starting 1 week after the last dosing of AOM. AOM exposure produced colonic adenocarcinoma with an incidence of 69% and a multiplicity of 0.76 +/- 0.57/rat at week 38. MJ, MJ2, and MJ5 administration significantly reduced the frequency of colonic carcinoma [MJ: 35% (49% reduction), p < 0.02; MJ2: 20% (64% reduction), p = 0.0028; and MJ5: 15% (78% reduction), p < 0.00021] and multiplicity [MJ: 0.40 +/- 0.58 (47% reduction), p < 0.05; MJ2: 0.25 +/- 0.43 (67% reduction), p < 0.005; and MJ5: 0.15 +/- 0.36 (80% reduction), p < 0.001]. Also, the numbers of cancer cells positive for proliferative cell nuclear antigen (PCNA) and cyclin D1 in colonic tumors were lowered by these treatments. In addition, treatment with MJ, MJ2, or MJ5 significantly increased apoptotic index in colonic adenocarcinoma. These findings might suggest effective chemopreventive ability of MJs, especially MJ5, in colon tumorigenesis.
Adenocarcinoma↗
Claudin-1 is a strong prognostic indicator in stage II colonic cancer: a tissue microarray study.
Tight junction associated proteins are key molecular components governing cellular adhesion, polarity and glandular differentiation. Tight junction proteins also play critical roles in cellular proliferation and neoplastic pathways via their functions as couplers of the extracellular milieu to intracellular signaling pathways and the cytoskeleton. Neoplastic cells frequently exhibit structural and functional deficiencies in the tight junction. The purpose of this study was to determine the pattern of expression and prognostic value of four tight junction associated proteins, claudin-1, claudin-4, occludin and ZO-1 in a cohort of TNM stage II colon cancer using tissue microarray technology. In this study, we retrospectively analyzed, resected and otherwise untreated paraffin embedded specimens from 129 consecutive patients with TNM stage II colonic carcinomas for claudin-1, claudin-4, occludin and ZO-1 protein expression by immunohistochemistry. Seventy-five, 58, 56 and 44% of the tumors exhibited normal to elevated expression levels (+2 and +3 immunopositivity) of claudin-1, claudin-4, occludin and ZO-1 respectively. Low expression levels of claudin-1 and ZO-1 were directly associated with higher tumor grade (P=0.05 and 0.03 respectively). Multivariate analysis indicated that lymphovascular invasion (P=0.01) and low levels of claudin-1 (P=0.0001) expression were independent predictors of recurrence and that reduced claudin-1 expression (P=0.0001) was associated with poor survival. This study is the first to comprehensively examine the expression of several tight junction associated proteins in colonic neoplasms and to correlate their expression with disease progression. Loss of claudin-1 expression proved to be a strong predictor of disease recurrence and poor patient survival in stage II colon cancer.
Adult↗