Biomedical subjects

I Okayasu

Publications and source records attributed to I Okayasu.

At least 73 records · Page 4Linked to original sources

PubMed1999

K-ras point mutations in the supernatants of pancreatic juice and bile are reliable for diagnosis of pancreas and biliary tract carcinomas complementary to cytologic examination.

In order to clarify whether DNA analysis for K-ras mutation can be used to diagnose cancers in supernatants of pancreatic juice and bile, samples from 29 cases of pancreatic, biliary tract, gastric, and neuroendocrine carcinomas, 1 malignant lymphoma case, 2 cases of pancreatic adenoma, 9 cases of chronic pancreatitis and 21 other non-cancer cases were examined. Polymerase chain reaction (PCR) products for K-ras gene codons 2 to 97 of exons 1 and 2 were generated with 33/33 (100%) pancreatic juice and 41/41 (100%) bile samples. By the single strand conformation polymorphism (SSCP) method, point mutations were detected in the pancreatic juice or bile supernatants of 13/13 (100%) pancreas cancer cases, 5/14 (35.7%) biliary tract cancer cases, 1/2 (50.0%) pancreatic adenoma cases and 3/9 (33.3%) chronic pancreatitis cases. Direct sequencing confirmed identical point mutations in the supernatants, malignant cells of cytologic smears of pancreatic juice or bile and cancer tissues. The DNA analysis demonstrated the presence of K-ras point mutations in 3 cases of pancreatic carcinomas with false-negative cytologic diagnoses. This novel method allows simultaneous testing for genetic abnormalities in supernatants of pancreatic juice and bile, after removing cells for cytologic diagnosis and screening for pancreatic and biliary tract tumors.

Bile↗

PubMed1999

An aggressive desmoid tumor in a patient with familial adenomatous polyposis: immunohistochemical findings.

A case of an aggressive desmoid tumor in a patient with familial adenomatous polyposis is described. The lesion rapidlyenlarged with compression of adjacent structures including the ureter and small bowel, and the patient died because of small bowel perforation and hydronephrosis 3 years after detection of small desmoid tumors at the time of a prophylactic coloproctectomy for a colon carcinoma. Immunohistochemically, proliferating cell nuclear antigen (PCNA), p21WAF1/CIP1 and cathepsin D indices, but not the bcl-2 index, which were defined as the numbers of immunoreactive tumor cells per 1000 tumor cells, increased in line with tumor progression. The tumor did not show staining for collagen IV, but was characterized by intense staining for basic fibroblast growth factor (bFGF). Accordingly, tumor aggression was related to increases in both cell proliferation and protease activity, as well as an enhanced expression of bFGF. In addition, the desmoid tumor showed deregulation between PCNA and p21WAF1/CIP1 because the normal inverse relation between these two was not apparent.

Adenomatous Polyposis Coli↗

PubMed1999

Prediction of response to 5'-deoxy-5-fluorouridine (5'-DFUR) in patients with inoperable advanced gastric cancer by immunostaining of thymidine phosphorylase/platelet-derived endothelial cell growth factor.

BACKGROUND: No reliable method is available for predicting the response to chemotherapy in patients with gastric cancer. The anticancer drug 5'-deoxy-5-fluorouridine (5'-DFUR) is converted into 5-fluorouracil (5-FU) by thymidine phosphorylase (dThdPase). We studied the relation between the expression of dThdPase in tumor tissue and the response to treatment with 5'-DFUR to determine if this enzyme can be used to predict the response to chemotherapy. METHODS AND MATERIALS: We performed endoscopic biopsy and studied the expression of dThdPase by immunostaining with anti-dThdPase monoclonal antibody in 41 patients with inoperable advanced gastric carcinomas before they received multiple-drug chemotherapy, including 5'-DFUR. The relation between the expression of dThdPase and the response to chemotherapy was studied. We also studied the characteristics of positive cells against anti-dThdPase monoclonal antibody. RESULTS: The response rate among patients whose tumors were positive for dThdPase expression (56.8%, 21/37) was higher than that among patients whose tumors were negative for dThdPase expression (0%, 0/4; p = 0.048). Spindle-shaped cells darkly expressing dThdPase were sporadically seen surrounding cancer nests in some patients. Multiple-antibody immunostaining suggested that these spindle-shaped cells were perivascular mesenchymal cells. The response rate was 82.4% (14/17) among patients with spindle-shaped cells strongly positive for dThdPase, as compared with 29.2% (7/24) among those with spindle-shaped cells weakly positive or negative for dThdPase (p = 0.00131). The expression of spindle-shaped cells darkly stained with dThdPase was the factor most strongly related to the response to chemotherapy (odds ratio = 35.513, p = 0.0027). CONCLUSIONS: The expression of dThdPase in stromal spindle-shaped cells may be a useful index in predicting the response to 5'-DFUR in patients with gastric cancer.

Adult↗

PubMed1999

In vitro toxicity of gallium arsenide in alveolar macrophages evaluated by magnetometry, cytochemistry and morphology.

Gallium arsenide (GaAs), a chemical compound of gallium and arsenic, causes various toxic effects including pulmonary diseases in animals. Since the toxicity is not completely investigated, GaAs has been used in workplaces as the material of various semiconductor products. The present study was conducted to clarify the toxicity of GaAs particles in the alveolar macrophages of hamsters using magnetometry, enzyme release assays and morphological examinations. Alveolar macrophages obtained from hamsters by tracheobronchial lavage and adhered to the disks in the bottom of wells were exposed to ferrosoferric oxide and GaAs particles. Ferrosoferric oxide particles were magnetized externally and the remanent magnetic field was measured. Relaxation, a fast decline of the remanent magnetic fields radiated from the alveolar macrophages, was delayed and decay constants were decreased dose-dependently due to exposure to GaAs. Because the relaxation is thought to be associated with cytoskeleton, the exposure of GaAs may have impaired the motor function of them. Enzyme release assay and morphological findings indicated the damage to the macrophages. Thus the cytotoxicity causes cytostructural changes and cell death. According to DNA electrophoresis and the TUNEL method, necrotic changes occur more frequently than apoptotic changes.

Animals↗

PubMed1999

Enhanced epithelial cell turnover associated with p53 accumulation and high p21WAF1/CIP1 expression in ulcerative colitis.

To cast light on accelerated epithelial cell turnover as an important risk factor of dysplasia and carcinoma development in patients with long-standing ulcerative colitis (UC), we examined cell proliferation and cell death, as well as expression of apoptosis-related markers, including p53 and p21WAF1/CIP1, in a series of cases. Biopsy specimens (n = 176; 84, active phase; 92, remission) were endoscopically obtained from 25 Japanese patients with UC. As controls, 68 biopsy specimens of normal mucosa were also examined from 27 Japanese patients with colon polyps. We counted the numbers of mitoses, apoptotic bodies, Ki-67-immunoreactive cells, and p21WAF1/CIP1-immunoreactive cells per 1000 crypt cells and the numbers of p53-positive cells per crypt. All of the indices in active UC were significantly higher than in either remitting UC cases or normal cases (mean mitotic index = 0.52, 0.28, and 0.15%, respectively; apoptotic index = 5.40, 2.91, and 1.30%, respectively; Ki-67 labeling index = 39.5, 28.3, and 26.8%, respectively; p21WAF1/CIP1 labeling index = 33.6, 20.0, and 19.0%, respectively; p53 labeling index = 0.66, 0.13, 0.13 per crypt, respectively). In addition, the mitotic, apoptotic, and Ki-67 labeling indices were increased in remitting UC of more than 10 years' duration, in comparison with those of less than 10 years' duration or the normal group. Immunostaining of serial sections revealed a small number of crypt cells coexpressing p53 and p21WAF1/CIP1. Increases in both epithelial cell proliferation and cell death, partially associated with p53 accumulation and high p21WAF1/CIP1 expression, are thus characteristic of active phase UC, as well as in remission of long-standing UC. Accelerated epithelial cell turnover caused by chronic inflammation and epithelial damage might predispose the mucosa to DNA damage, resulting in an elevated risk of mutation in line with dysplasia and carcinoma development in patients with UC.

Adult↗

PubMed1998

Progesterone therapy for endometrial carcinoma reduces cell proliferation but does not alter apoptosis.

BACKGROUND: Although the anticancer effects of progesterone therapy for patients with endometrial carcinoma are widely acknowledged, a detailed assessment of the resultant morphologic alterations in tumor tissue kinetics has hitherto been lacking. METHODS: Biopsy and hysterectomy specimens of 14 endometrial carcinomas (endometrioid-type) before and during progesterone therapy were studied to clarify changes in apoptosis and cell proliferation and their relation to morphologic alterations. The extent of squamous differentiation within tumor lesions was also examined. RESULTS: In the good-response group, tumor cells took on characteristics of normal endometrial gland cells in the secretory phase. A positive correlation between reduction in the mitotic index and the degree of morphologic alterations during hormone therapy was observed, but the frequency of apoptotic cells did not vary. In both the good-response and poor-response groups, development or enlargement of squamous areas was observed, in comparison with the initial biopsy specimens. CONCLUSIONS: These results suggest that prolonged progesterone administration can suppress cell proliferation in endometrial carcinomas through tumor cell differentiation without altering apoptosis, resulting in a shift in tissue kinetics toward a relative predominance of cell deletion. In addition, increases in the occurrence of squamous areas within tumors do not always appear to be related to treatment efficacy.

Adult↗

PubMed1998

CD44 expression in normal, hyperplastic, and malignant endometrium.

A total of 140 endometrial carcinomas (endometrioid type), as well as 72 hyperplasias (41 of simple or complex and 31 of atypical type) and 141 normal endometria (35 in the proliferative and 106 in the secretory phase), were immunohistochemically investigated for expression of the standard and variant-3 and -6 isoforms of CD44, and the results compared with several known prognostic factors. A combination of the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization (SBH) for CD44 mRNA levels was also carried out on 27 endometrial carcinomas. In normal endometrium, the expression of standard and variant CD44 forms was remarkably higher in the secretory than in the proliferative phase, with immunoreactivity scores being inversely correlated with numbers of oestrogen and progesterone receptors. Significantly elevated levels of CD44 expression in endometrial carcinomas compared with the proliferative phase and hyperplasia were also revealed by both the immunohistochemical and the RT-PCR/SBH assays, while no association was noted with any prognostic factors. The results indicate that CD44 expression in the normal menstrual cycle is closely related to the secretory differentiation of the glandular epithelium. Moreover, detection of aberrant expression may be useful for the early diagnosis of endometrial carcinoma, but not as an indicator of tumour progression.

Antigens, Neoplasm↗

PubMed1998

p53 and p21(WAF1) expression in lymphocytic thyroiditis and thyroid tumors.

To clarify the roles of increased apoptosis and cell proliferation in chronic autoimmune lymphocytic thyroiditis and thyroid tumorigenesis, expression of p53 and p21(WAF1) proteins was immunohistochemically investigated in a series of 158 cases. Positive epithelial cells were quantified to give numbers per unit square and to score for distribution. They were found scattered in nontumorous thyroid tissue, their numbers increasing with the severity of thyroiditis and the correlation between expression of the two proteins, regardless of the presence or absence of thyroid neoplasms. Simultaneous expression of both proteins was occasionally found in the same cells by analysis of serial histologic sections. In thyroid tumors, increased expression was found to be diffuse, focal, or scattered for the distribution of p53- or p21(WAF1)-immunopositive cells in accordance with tumor cell dedifferentiation, showing significant correlation between expression of the two proteins. Correlated with these findings, enhanced apoptosis along with decreased Bcl-2 expression and increased Ki-67 labeling in lymphocytic thyroiditis and thyroid tumors was also confirmed in the same series, using in situ DNA nick-end labeling and immunohistochemical methods. Increased expression of p53 and/or p21(WAF1) proteins was thus suggestive of possible DNA damage and increased apoptosis in autoimmune thyroiditis. In addition, a significant correlation between protein overexpression and dedifferentiation of thyroid tumor cells was apparent.

Antibodies↗

PubMed1998

Involvement of interleukin-1 in the development of ulcerative colitis induced by dextran sulfate sodium in mice.

Dextran sulfate sodium (DSS)-induced colitis in mice has been recognized as a model for human ulcerative colitis. Using this model, the effects of anti-murine interleukin 1beta (IL-1beta) antibodies (anti-muIL-1beta) and recombinant murine IL-1 receptor type I (rmuIL-1R) on the development of colitis were examined to determine whether IL-1 plays a role in colitis. Furthermore, RT-PCR amplification was used to examine for the presence of mRNAs for IL-1alpha and IL-1beta in the large intestine. In mice with colitis induced by DSS, administration of anti-muIL-1beta (5 mg/kg, once/week, i.p.) significantly suppressed body weight loss and shortening of the large intestine. Administration of rmuIL-1R (0.2 mg/kg or 1.0 mg/kg, once/day, i.v.) significantly suppressed shortening of the large intestine. Expression of mRNAs for IL-1alpha and IL-1beta was observed in the large intestine of mice which received distilled water containing 3% DSS for 5 days. The expression tended to increase in mice which received DSS for 11 days. In contrast, mRNA expression was not observed in mice which received distilled water without DSS. These results clearly demonstrate that IL-1 is involved in the development of DSS-induced colitis in mice and suggest that downregulation of IL-1 might be useful for the treatment of patients with ulcerative colitis.

Animals↗

PubMed1998

Telomerase activity significantly correlates with cell differentiation, proliferation and lymph node metastasis in colorectal carcinomas.

Telomerase activity was examined by the telomeric repeat amplification protocol assay, in a total of 37 colorectal adenocarcinomas, including stages A, B and C according to the Astler and Collier classification, and correlated with clinicopathological features. Of 17 stage C lesions, 13 were positive (76.5%; P<0.01), demonstrating a significant correlation with lymph node metastasis. In contrast, only 6 of 20 stage A and B carcinomas were positive (30.0%), this being significantly lower (P < 0.05). Moderately or poorly differentiated subtypes were more predominant in the telomerase-positive than in the telomerase-negative groups (P< 0.05) with greater elevation of mitotic and Ki-67 labeling indices (P < 0.0001). No significant relation was found between telomerase activity and p53 protein accumulation or Bcl-2 protein expression. The good correlation with tumor staging, lymph node metastasis, differentiation, and mitotic and Ki-67 labeling indices suggests that this parameter might have potential application in estimation of prognosis.

Adenocarcinoma↗

PubMed1998

Autoimmune enteropathy with severe atrophic gastritis and colitis in an adult: proposal of a generalized autoimmune disorder of the alimentary tract.

BACKGROUND: We describe the case of an adult with autoimmune enteropathy consistent with both severe atrophic gastritis accompanying antral stenosis and colitis. METHODS AND RESULTS: The patient, positive for anti-intrinsic factor antibody, had intractable diarrhea and protein-losing enteropathy. In the ileum inflammatory cells were observed infiltrating the lamina propria along with villus atrophy, and similar inflammation was also found in the lamina propria of the colon and stomach, with complete loss of specialized glands. The myenteric ganglion cells of the hypertrophied muscularis propria in the stenosed antrum showed degeneration with surrounding T-lymphocyte infiltration. There were more CD8+ than CD4 lymphocytes in the lamina propria of the stomach and colon. CONCLUSIONS: The CD8+ (suppressor-cytotoxic) T lymphocytes may have played an important role in the production of lesions in the stomach, small intestine, and colon, so we propose this case as an example of a generalized autoimmune disorder of the alimentary tract.

Autoimmune Diseases↗

PubMed1998

Detection of K-ras point mutations in the supernatants of peritoneal and pleural effusions for diagnosis complementary to cytologic examination.

To determine whether DNA analysis can be performed using the supernatants of body fluids after centrifugation at 2,000 rpm for 10 minutes, peritoneal or pleural effusions or bile were examined for K-ras mutations in 34 cases of pancreatic, colorectal, gastric, esophageal, or hepatocellular carcinoma and 15 noncancer cases. The polymerase chain reaction products for K-ras gene codons 2 to 97 of exons 1 and 2 were generated with 41 (93%) of 44 body cavity fluid and 5 (100%) of 5 bile samples. By the single strand conformation polymorphism method, point mutations were detected in the ascites supernatants of 8 (89%) of 9 cases of pancreatic carcinoma. In the remaining case, no point mutation was demonstrated because few malignant cells were present in the ascites fluid. Furthermore, K-ras point mutations were observed in the ascites supernatants of 2 cases of colorectal carcinoma and 1 case of gastric carcinoma. The DNA analysis of the supernatant of ascites fluid showed a K-ras point mutation in 3 cases of false-negative cytologic diagnosis (2 cases of pancreatic carcinoma and 1 case of colorectal carcinoma). Direct sequencing confirmed identical point mutations in the supernatants, whole cell pellets, malignant cells from the cytologic smears of ascites fluid, and cancer tissues. This novel method allows simultaneous testing for genetic abnormalities in supernatants of body fluid, after removing cells for cytologic diagnosis.

Ascitic Fluid↗

PubMed1998

Additive effects of medroxyprogesterone acetate and 5-fluorouracil derivative on 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors.

Chronic oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil suppressed thymidylate synthetase (TS) gene expression followed by reduction of TS activity in rat mammary tumors induced with 7,12-dimethylbenz[a]anthracene. Addition of medroxyprogesterone acetate (MPA) to the anticancer drug caused an additional decrease in TS and thymidine kinase activities in the tumor growth and restoration of bone loss. These results suggest that the simultaneous administration of MPA and anticancer drugs causes increased inhibition of mammary tumor growth and also diminishes the bone loss.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1998

Up-regulation of CD44 variant exon expression in endometrial carcinomas: analysis of mRNA and protein isoforms, and relation to clinicopathological factors.

In order to clarify the relation between expression of individual CD44 variant exons and tumor progression, 34 endometrial carcinomas (endometrioid type) were investigated, as well as 27 samples of normal endometrium, using a combination of reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization (SBH). Western blotting was also performed for comparison of protein levels with the results of the RT-PCR/SBH methods. Analysis of gross CD44 splicing patterns demonstrated high-level expression of variant isoforms in endometrial carcinomas as compared with normal endometrium. Exon-specific RT-PCR/SBH assays revealed large, abundant transcripts of individual variant exons in particular v3, v4, and v5, in tumors, but these isoforms were also expressed in normal endometria, suggesting a lack of tumor-specificity. No individual CD44 variant transcripts were associated with any of the prognostic factors investigated. Parallel observations showed variant CD44 transcripts to be more readily detectable than protein isoforms in the same samples. These findings indicate that in endometrial carcinomas, expression of individual variant CD44 exons is markedly up-regulated, but this molecule may not be useful as a consistent indicator of tumor progression.

Endometrial Neoplasms↗

PubMed1998

A prospective randomized study of amoxycillin and omeprazole with and without metronidazole in the eradication treatment of Helicobacter pylori.

A combination of amoxycillin and omeprazole is often used to treat Helicobacter pylori infection. A three-drug regimen comprising metronidazole, amoxycillin and omeprazole has been proposed as an alternative therapy. In a prospective, randomized, comparative study, we evaluated these two regimens with respect to safety and efficacy in patients with H. pylori infection. Sixty patients with peptic ulcer (gastric, 32 patients; duodenal, 28 patients) who had a history of ulcer recurrence were randomly assigned to dual therapy with amoxycillin (500 mg three times daily for 2 weeks) and omeprazole (20 mg once daily for 8 weeks) or to triple therapy with metronidazole (500 mg twice daily for 2 weeks) plus amoxycillin and omeprazole, given in the same dosages as dual therapy. Forty-eight patients completed the protocol; treatment was discontinued because of side effects in nine patients, and three patients dropped out of the study. On the basis of all patients treated, the rate of H. pylori eradication was significantly higher for triple therapy 20/23 cases, 87.0%; 95% confidence interval (CI), 0.664-0.972) than for dual therapy 13/25, 52.0%; 0.313-0.722; P < 0.05). On an intention-to-treat basis, the difference between the groups in the rate of H. pylori eradication was marginally significant (P = 0.06 [0.028-0.512]). Side effects were reported by five patients receiving triple therapy (skin rash, one; nausea, two; headache, one; abdominal pain, one), and four patients receiving dual therapy (skin rash, two; abdominal pain, one; diarrhoea, one). All side effects resolved spontaneously after termination of treatment. There was no significant difference in safety between the two regimens. Triple therapy with metronidazole, amoxycillin, and omeprazole was significantly more effective for the eradication of H. pylori than dual therapy with amoxycillin and omeprazole alone. The safety of these regimens was similar, and triple therapy was found to be clinically acceptable.

Adult↗

PubMed1998

Low levels of apoptosis and proliferative activity in colorectal villous tumors: comparison with tubular tumors.

In order to clarify the cell kinetics of colorectal villous tumors (VT), 21 villous adenomatous areas and 12 carcinomatous areas within villous adenomas were investigated for proliferative activity and apoptosis and compared with a series of 41 tubular tumors (TT), demonstrating elements of intramucosal carcinomas as well as tubular adenomas (so-called carcinoma in tubular adenoma). Proliferation was estimated in terms of Ki-67 labeling indices and mitotic indices, and apoptosis was assessed by DNA nick-end labeling to give apoptotic indices. Apoptotic indices of villous adenomatous and carcinomatous regions were significantly lower than the values for their tubular counterparts. Ki-67 labeling indices were also significantly lower for adenoma components. Apoptotic indices, Ki-67 labeling indices and mitotic indices increased with atypia raised in tubular adenoma components. Correlations of mitotic indices with apoptotic indices, Ki-67 labeling indices with apoptotic indices and mitotic indices with Ki-67 labeling indices were found for each villous tumor group and tubular tumor group, and the apoptosis and proliferation ratios for villous tumors were relatively low, suggesting a tendency for greater growth due to less cell deletion. Although this is only one of the biological features of villous tumor groups, it might play a major role in generation of malignancy.

Adenocarcinoma↗

PubMed1998

The 5D4 antibody (anti-cyclin D1/D2) related antigen: cytoplasmic staining is correlated to the progression of gastric cancer.

In order to clarify the relationship between cyclin D1 and D2 (CD1/CD2) overexpression and progression, 191 gastric cancer cases (81 early and 110 advanced cancers) were investigated using the 5D4 monoclonal antibody for both CD1/CD2 in immunohistochemistry. 5D4 immunoreactivity was noted in 68 (35.6%) cases, staining being restricted to the nucleus in 27 (14.1%) cases, the cytoplasm in 34 (17.8%) cases, and its presence in both the nucleus and cytoplasm in seven (3.7%). Cases demonstrating cytoplasmic positivity, including both positive cases, were significantly more frequent in advanced cancers (P = 0.010), those having lymph node metastasis (P = 0.004) and cases showing cancer invasion of vessels (P = 0.009), although no relation to histological malignant grading was apparent. In contrast, cases of nuclear positivity behaved no differently from 5D4-negative cases. Statistics showed a trend where survival in patients was worse in the cytoplasm-positive cases than the cytoplasm-negative group. However, multivariate analysis revealed no independent statistical significance in the cytoplasmic positivity of prognosis. Additional studies using DCS-6 antibody for CD1 and C-17 antibody for CD2, suggest that nuclear staining of 5D4 indicates the presence of CD1 but cytoplasmic staining is derived from an antigen that is related to CD2. In conclusion, the present results indicate that the accumulation of CD2 in the cytoplasm may play some role in the progression of gastric cancers but not prognosis; however, CD1 overexpression is not linked to either.

Cell Nucleus↗

PubMed1998

Relationship between fecal bile acids and the occurrence of colorectal neoplasia in experimental murine ulcerative colitis.

OBJECTIVE: The possible role of fecal bile acids in colorectal carcinogenesis in ulcerative colitis has been reported. In this study, we investigated the relationship between fecal bile acids and the occurrence of colorectal neoplasia in experimental murine colitis induced by dextran sulfate sodium. METHODS: Colorectal neoplasia in experimental colitis was induced by dextran sulfate sodium subsequent to a single azoxymethane pretreatment. Fecal bile acids were analyzed by gas-liquid chromatography. RESULTS: Multiple high-grade dysplasias (intramucosal adenocarcinoma) and inflammatory changes were seen in all mice administered dextran sulfate sodium and azoxymethane. Inflammatory changes were also observed in all mice given dextran sulfate sodium only, while neither tumor nor inflammatory changes were detected in any of the control mice. Significant increases in cholic acid were observed in the mice of the colorectal tumor and experimental colitis groups during the experimental period, while in the control mice, no significant changes in fecal bile acids were observed. CONCLUSION: It is suggested that fecal cholic acid and colitis may be intimately related to the development of colorectal neoplasia in this experimental model of murine colitis as well as in ulcerative colitis.

Adenocarcinoma↗