Biomedical subjects

G Kajiyama

Publications and source records attributed to G Kajiyama.

At least 109 records · Page 6Linked to original sources

PubMed1999

Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct.

OBJECTIVE: In this study, we examined the mutational spectrum of K-ras in cases of gallbladder and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct (AJPBD). METHODS: We examined 35 gallbladders with AJPBD (20 with hyperplasia, 15 with carcinoma) and 38 gallbladders without AJPBD (four normal gallbladders, four with hyperplasia, six with adenoma, 24 with carcinoma). Polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to detect mutations in codon 12 or 13 of K-ras. RESULTS: In the cases with AJPBD, the prevalences of K-ras mutation were 15% (3/20) in hyperplasia, 60% (6/10) in stage I carcinoma, and 100% (5/5) in stage II-IV carcinoma. In the cases without AJPBD, the prevalences of K-ras mutation were 0% (0/4) in normal gallbladder, 0% (0/4) in hyperplasia, 17% (1/6) in adenoma, 7% (1/16) in stage I carcinoma, and 38% (3/8) in stage II-IV carcinoma. Prevalences of K-ras mutation in hyperplasia and carcinoma with AJPBD were greater than those without AJPBD (p < 0.05). The point mutation of GGT to GAT in codon 12 was frequently observed in the cases with AJPBD. CONCLUSION: These results suggest that the specific K-ras mutation in codon 12 (GGT to GAT) may contribute to the early stage of carcinogenesis in the gallbladder with AJPBD.

Adenoma↗

PubMed1999

MUC1 expression in intramucosal colorectal neoplasms. Possible involvement in histogenesis and progression.

PURPOSE: The mucin core peptide MUC1 often is detectable in colorectal carcinoma (CRC) tissue and cell lines. However, whether MUC1 in CRC correlates with tumor histogenesis and progression is unclear. We studied the relationship between MUC1 expression in intramucosal CRC and clinicopathologic features, expression of Ki-67, and p53 protein, and apoptosis. METHODS: The intramucosal CRC we studied included 140 endoscopically or surgically resected lesions, including 106 low-grade carcinomas and 34 high-grade carcinomas. De novo carcinoma, defined as carcinoma with no adenomatous component, represented 9 of 140 tumors. Three macroscopic types were identified: 57 lesions were polypoid, 55 were superficial and flat, and 28 were granular-type laterally spreading tumors (G-LST). MUC1, Ki-67, and p53 expression were examined immunohistochemically. Apoptotic cells were identified by in situ DNA nick end labeling. RESULTS: MUC1 expression in high-grade carcinomas was significantly more frequent (p < 0.01) than in low-grade carcinomas; expression in adenomas was almost nil. MUC1 expression in polypoid carcinomas was significantly more frequent (p < 0.05) than in superficial carcinomas or G-LST. MUC1 expression in carcinomas with p53 expression was significantly more frequent (p < 0.01) than in carcinomas not expressing p53. No significant correlation was found between expression of MUC1 and Ki-67 labeling index. MUC1 was expressed more frequently in carcinomas with relatively high apoptotic index (p < 0.01). MUC1 expression did not differ between de novo carcinomas and those developing from adenomas. CONCLUSIONS: The results suggest that MUC1 is likely to be expressed in the course of colorectal carcinoma development when p53 protein is overexpressed and apoptosis is prominent.

Apoptosis↗

PubMed1999

Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension.

The effects of long-term aerobic exercise on endothelial function in patients with essential hypertension remain unclear. To determine whether endothelial function relating to forearm hemodynamics in these patients differs from normotensive subjects and whether endothelial function can be modified by continued physical exercise, we randomized patients with essential hypertension into a group that engaged in 30 minutes of brisk walking 5 to 7 times weekly for 12 weeks (n=20) or a group that underwent no activity modifications (control group, n=7). Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test for endothelium-dependent vasodilation and after sublingual nitroglycerin administration to test endothelium-independent vasodilation. Forearm blood flow in hypertensive patients during reactive hyperemia was significantly less than that in normotensive subjects (n=17). Increases in forearm blood flow after nitroglycerin were similar between hypertensive and normotensive subjects. Exercise lowered mean blood pressure from 115.7+/-5.3 to 110.2+/-5.1 mm Hg (P<0.01) and forearm vascular resistance from 25.6+/-3.2 to 23. 2+/-2.8 mm Hg/mL per minute per 100 mL tissue (P<0.01); no change occurred in controls. Basal forearm blood flow, body weight, and heart rate did not differ with exercise. After 12 weeks of exercise, maximal forearm blood flow response during reactive hyperemia increased significantly, from 38.4+/-4.6 to 47.1+/-4.9 mL/min per 100 mL tissue (P<0.05); this increase was not seen in controls. Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of exercise. Intra-arterial infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine abolished the enhancement of reactive hyperemia induced by 12 weeks of exercise. These findings suggest that through increased release of nitric oxide, continued physical exercise alleviates impairment of reactive hyperemia in patients with essential hypertension.

Analysis of Variance↗

PubMed1999

Difference in the incidence of cough induced by angiotensin converting enzyme inhibitors: a comparative study using imidapril hydrochloride and enalapril maleate.

To compare the incidence of cough between two angiotensin converting enzyme (ACE) inhibitors, imidapril and enalapril, comparative crossover study was performed in 489 patients (228 men and 261 females) with essential or renal parenchymal hypertension. Patients were randomly assigned to one of two treatment groups, a group receiving imidapril for 12 wk (Period I) followed by enalapril for 12 wk (Period II), and a group in which the order of drugs was reversed. The occurrence of cough during treatment was monitored by questionnaire in all cases. There were no differences in background characteristics between the two groups. The incidence of cough during Period I was 15.2% (32/210) in the group initially treated with imidapril (Group IE) and 38.6% (85/220) in the group initially treated with enalapril (Group EI), the difference being statistically significant (p < 0.001). During Period I, decrease in blood pressure was observed in 63.9% (115/180) of Group IE and 64.6% (115/178) of Group EI patients. In approximately half of the patients in Group EI who developed cough during Period I and in whom the treatment was subsequently switched to imidapril, cough subsequently disappeared. It was concluded that the incidence of cough was significantly less under imidapril than under enalapril treatment, while there was no difference in the antihypertensive effects of the two ACE inhibitors.

Administration, Oral↗

PubMed1999

Adenosine 5'-triphosphate induced dilation of human coronary microvessels in vivo.

OBJECT: This study was performed to compare the coronary microvascular response to adenosine 5'-triphosphate (ATP) with the response to adenosine in humans. METHODS: Coronary blood flow velocity was determined using a Doppler flow wire. After intracoronary nitroglycerin infusion, intracoronary bolus injections of adenosine (20 microg) and ATP (20 microg) were performed to induce reactive hyperemia. PATIENTS: Twenty-nine patients (23 men and 6 women, mean age: 63+/-9 years) with coronary artery disease and risk factors for coronary atherosclerosis were studied. RESULTS: Coronary flow reserve in response to ATP was similar to that for adenosine (2.7+/-0.7 vs. 2.7+/-0.7). However, the duration of ATP-induced vasodilation was longer than that of adenosine-induced dilation (39+/-25 seconds vs. 26+/-12 seconds, p<0.0001). The coronary flow reserve obtained with either ATP or adenosine was significantly reduced in the interventioned arteries compared with non-stenosed arteries. The coronary flow reserve obtained with ATP was similar to that obtained with adenosine in both artery groups. The duration of the vasodilator effect of ATP was significantly greater than that of adenosine in both artery groups. CONCLUSION: These results suggest that ATP induces maximal dilation of coronary microvessels, most likely through an endothelium-independent mechanism. The degradation of ATP to adenosine 5'-monophosphate (AMP) and adenosine, as well as the direct action of ATP on A2-adenosine receptors may be responsible for the dilation. We conclude that coronary flow reserve can be determined safely with intracoronary ATP administration.

Adenosine↗

PubMed1999

Idiopathic verapamil-sensitive left ventricular tachycardia complicated by right ventricular outflow tract ventricular tachycardia and ventricular fibrillation.

Idiopathic ventricular tachycardias (VTs) are generally divided into those arising from the right ventricle and those arising from the left ventricle. There has been few reports of two morphologically distinct VT occurring in patients with no apparent structural heart disease. We report a patient with verapamil-sensitive left VT with a right bundle branch block pattern that spontaneously changed to VT with a left bundle branch block pattern. Ventricular fibrillation was induced by the application of programmed stimulation. Although it is unclear if our patient with pleomorphic VT has ventricular vulnerability, it is necessary to investigate further and follow him carefully.

Adult↗

PubMed1999

The role of nitric oxide in bradykinin-induced dilation of coronary resistance vessels in patients with hypercholesterolemia.

OBJECT: In hypercholesterolemic patients, acetylcholine- and substance P-mediated endothelium-dependent dilation of the coronary resistance vessels is impaired due to decreased nitric oxide production. However, it is not clear if bradykinin-induced coronary vasodilation is impaired in these patients. We investigated whether the endothelium-dependent dilation of coronary resistance vessels mediated by bradykinin is impaired in patients with hypercholesterolemia and, if so, whether this impairment is caused by a decreased production of nitric oxide. METHODS: We examined the coronary vascular responses to acetylcholine and bradykinin. The vascular responses to bradykinin were also assessed after N(G)-monomethyl-L-arginine was infused to inhibit nitric oxide production. Drugs were infused into the left coronary ostium and coronary blood flow (CBF) and coronary vascular resistance were evaluated by quantitative angiography and Doppler flow velocity measurements. PATIENTS: Twelve hypercholesterolemic patients and 11 control patients with angiographically normal coronary arteries were studied. RESULTS: The vasodilator responses to acetylcholine and bradykinin were reduced in hypercholesterolemic patients compared with control patients (p<0.005 and p<0.04, respectively, by two-way analysis of variance (ANOVA)). The CBF responses to acetylcholine and bradykinin were significantly correlated (r=0.56; p<0.01). Bradykinin-induced dilation was similar in hypercholesterolemic patients and control patients after inhibition of nitric oxide. CONCLUSION: These results suggest that the bradykinin-mediated endothelium-dependent dilation of coronary resistance vessels may be impaired due to depressed nitric oxide production in patients with hypercholesterolemia.

Acetylcholine↗

PubMed1999

Cholecystokinin regulates the invasiveness of human pancreatic cancer cell lines via protein kinase C pathway.

We have previously reported that cholecystokinin (CCK) plays an important role in the invasiveness and the production of matrix metalloproteinase-9 (MMP-9) in two human pancreatic cancer cell lines. In this study we investigated the pathway of the invasiveness associated with MMP-9 of those lines regulated by CCK. Two human pancreatic cancer cell lines were treated with CCK-8 alone, CCK-8 and staurosporine, or CCK-8 and indomethacine. The invasiveness and the production of MMP-9 were decreased with staurosporine but not indomethacine. These results suggest that CCK may regulate the invasiveness and the production of MMP-9 via protein kinase C in human pancreatic cancer cell lines.

Blotting, Western↗

PubMed1999

[Magnesium (Mg) status in patients with cardiovascular diseases].

Mg is the fourth most abundant total cation in the human body and the second most abundant intracellular cation. Moreover, Mg is an important cofactor for many enzymes especially those involved in phosphate transfer reactions. Mg is therefore essential in the regulation of the metabolism of other ions and cellular functions. Mg deficiency has been shown to be associated with fatal cardiovascular diseases such as cardiac arrhythmias and coronary heart disease, as well as with risk factors for these diseases, such as hypertension, and diabetes mellitus. Clinical evaluation of Mg status has been limited by the lack of suitable technology for measuring this cation. Although the measurement of serum total Mg is routinely available, ionized Mg is physiologically active. Furthermore, most of the body's Mg is present in the intracellular space. Our findings showed that serum total Mg was similar in all groups, but patients with arrhythmias and diabetes mellitus revealed lower levels of serum ionized Mg. On the other hand, patients with essential hypertension exhibited higher intraerythrocyte Mg concentrations than healthy controls. The measurement of serum total Mg may obscure the diagnosis of an abnormality in Mg metabolism in patients with arrhythmias and diabetes mellitus. Furthermore, the intracellular accumulation of Mg does not support the hypothesis of Mg deficiency in patients with essential hypertension.

Calcium↗

PubMed1999

Enhanced expression of inducible nitric oxide synthase and nitrotyrosine in gastric mucosa of gastric cancer patients.

Recent studies (K. Komoto et al., Am. J. Gastroenterol., 93: 1271-1276, 1998) have shown that Helicobacter pylori infection is associated with gastric cancer. However, the mechanism of H. pylori in carcinogenesis has not been clarified. H. pylori infection leads to a sustained production of reactive nitrogen species that may contribute to cause DNA damage. In this study, we examined the expression of inducible nitric oxide synthase (iNOS) and nitrotyrosine in gastric mucosa. The expression of iNOS and nitrotyrosine was examined by immunohistochemistry in 93 patients who initially underwent gastric biopsies between 1975 and 1992. Thirty-four individuals were later found to have gastric cancer at least 2 years after the initial biopsies (group A). The other 59 subjects have shown no evidence of gastric cancer during long-term follow-up. Fifty-one of these patients were positive for H. pylori (group B), and eight were negative for H. pylori (group C). The expression of iNOS and nitrotyrosine in the gastric mucosa was significantly higher in H. pylori-positive groups A and B than in H. pylori-negative group C. Among the H. pylori-positive patients, the expression of iNOS and nitrotyrosine was significantly higher in group A than in group B. These results suggest that high production of iNOS and nitrotyrosine in the gastric mucosa infected with H. pylori may contribute to the carcinogenesis of gastric cancer.

Adult↗

PubMed1998

Quantitative assessment of comparative potencies of cholesterol-crystal-promoting factors: relation to mechanistic characterization.

The crystallization of cholesterol is affected by various factors in bile. The present study evaluated the relative importance of cholesterol-nucleation-promoting factors and partially characterized the mechanisms of their action. Model biles with an identical relative composition of cholesterol, egg-yolk phosphatidylcholine and taurocholate, except for replacing phosphatidylcholine (5-20%) with dilinoleoyl-phosphatidylcholine or taurocholate (10-30%) with taurodeoxycholate. Cholesterol crystallization was quantitatively assessed spectrophotometrically and morphologically estimated by the laser-scattering diffraction analyser and video-enhanced microscopy in the absence and presence of concanavalin A-binding glycoprotein isolated from human bile. In a series of experiments, lipid distribution among particulate species was determined after isolation by FPLC. In all experiments, cholesterol crystallization was dose-dependently enhanced with a rank order of: concanavalin A-binding glycoprotein > dilinoleoyl - phosphatidyl choline> taurodeoxycholate. No morphological alteration was evident for vesicles and crystals, but the cholesterol/phospholipid ratio in vesicles was increased significantly by replacement with dilinoleoyl-phosphatidylcholine and excess cholesterol. A high proportion of relatively hydrophilic phosphatidylcholine species such as dilinoleoyl-phosphatidylcholine and excess cholesterol in bile cause a redistribution of cholesterol to increase a vesicular cholesterol/phospholipid ratio, eventually promoting cholesterol crystallization, whereas concanavalin A-binding glycoprotein acts via differing mechanisms.

Bile↗

PubMed1998

The establishment of a preoperative diagnosis of pancreatic carcinoma using cell specimens from pancreatic duct brushing with special attention to p53 mutations.

BACKGROUND: Previously, the authors reported that 82% of cases of pancreatic carcinoma were positive for p53 in cytologic specimens obtained by selective endoscopic pancreatic duct brushing (SEPB). However, there was an extreme discrepancy between the authors' data of p53 overexpression using cytologic specimens and other reports using surgically resected specimens. In this study, the authors demonstrate that p53 positive cells precisely reflect its gene mutations, and also establish systematic procedures for the preoperative diagnosis of patients with pancreatic carcinoma. METHODS: The authors examined 44 cases of pancreatic carcinoma, 30 cases of chronic pancreatitis, and 9 cases of papillary adenoma. In all cases, pathologic diagnosis was made by surgery or autopsy. The conventional cytology and p53 immunocytology were performed simultaneously in the cell specimens obtained by SEPB. In the cases immunostained for p53, DNA was extracted selectively from p53 immunostained cells using a light microscope. p53 mutations in exons 5 to 8 were examined by direct sequencing. RESULTS: Forty of 44 pancreatic carcinomas (91%) were diagnosed correctly by the methods of conventional cytology associated with p53 immunocytology. p53 mutations were detected in 12 of 14 cases that were positive for p53 (86%). Four of six cases that were inoperable due to massive metastasis or invasion had the mutation at codon 273 (CGT to CAT) in exon 8. CONCLUSIONS: These results suggest that p53 immunocytology reflects its gene mutations precisely, and that the point mutation at codon 273 (CGT to CAT) of p53 may play an important role in the invasive potential and metastasis of pancreatic carcinoma.

Adenocarcinoma↗

PubMed1998

Ergonovine-induced alterations in coronary flow velocity preceding onset of occlusive spasm in patients without significant coronary artery stenoses.

This study examined serial changes in coronary flow velocity to elucidate the dynamic change of coronary circulation during coronary spasm. Twenty patients with variant angina and 27 control patients were studied. Coronary flow velocity was monitored using a Doppler guidewire following intracoronary ergonovine administration. In the control group, diastolic flow velocity either did not change or increased slightly in response to ergonovine. However, in patients with variant angina, 2 patterns of flow velocity alterations were observed. In the first pattern, flow initially increased and then suddenly decreased (16 of 20 patients). In the second pattern, flow gradually decreased (3 of 20 patients). In the remaining patient, the coronary flow alteration could not be detected because of branch spasm. When abnormally high flow velocity was defined as a 100% increase in flow after ergonovine administration within 1 minute, and abnormally low flow velocity was defined as a 50% decrease in flow to diagnose variant angina, sensitivities of 35%, 75%, and 85% were noted if flow was measured 1.0, 2.0, and 3.0 minutes after ergonovine administration, respectively. These abnormal flow velocities were observed before ischemic ST changes appeared. In conclusion, in patients with variant angina, characteristic serial changes in coronary flow velocity occur before occlusive spasm. Variant angina may be diagnosed earlier by monitoring flow velocity rather than by monitoring for ischemic electrocardiographic changes.

Aged↗

PubMed1998

Vasomotility and nitric oxide bioactivity of the bridging segments of the left anterior descending coronary artery.

We compared bridging and nonbridging coronary artery segments with respect to the vasoconstrictor effect of acetylcholine. Bridging segments were hypersensitive to the constrictor effect of acetylcholine, and results suggest that the effect of nitric oxide on the acetylcholine-stimulated condition is decreased, or that the smooth muscle sensitivity to acetylcholine is increased.

Acetylcholine↗

PubMed1998

Frequent p53 gene mutations in serrated adenomas of the colorectum.

Serrated adenoma has been recently proposed as a distinct histological lesion of the colorectum. This study examined p53 immunoreactivity, mutations of exons 5-8 of the p53 gene, codon 12 of the Ki-ras gene by PCR-SSCP analyses, and microsatellite instability in 19 serrated adenomas, ten adenocarcinomas in/with serrated adenomas, 23 hyperplastic nodules, four hyperplastic polyps and 29 tubular adenomas of the colorectum. Eleven of 11 (100 per cent) serrated adenomas had p53 immunoreactivity and all six (100 per cent) adenocacinomas in/with serrated adenomas exhibited moderate to severe p53 immunoreactivity. It was confirmed that 9 of 19 (47 per cent) serrated adenomas and 5 of 10 (50 per cent) adenocarcinomas in/with serrated adenomas harboured p53 gene mutations. On the other hand, no p53 gene mutation was detected in the other colorectal lesions. Meanwhile, 11 (58 per cent) serrated adenomas and six (60 per cent) adenocarcinomas in/with serrated adenomas had Ki-ras gene mutations, as also did 9 of 23 (39 per cent) hyperplastic nodules, 3 of 4 (75 per cent) hyperplastic polyps, and 12 of 29 (41 per cent) tubular adenomas. Microsatellite instability was detected in one (5 per cent) serrated adenoma and one (10 per cent) adenocarcinoma in a serrated adenoma. The other lesions did not show microsatellite instability. Serrated adenomas had significantly frequent p53 gene mutations compared with hyperplastic lesions or tubular adenomas (p < 0.005). On the other hand, they did not exhibit significant differences in mutations of the Ki-ras gene or in microsatellite instability. Genetic changes were then examined in small parts of serrated adenomas, such as the upper or lower parts of crypts, to determine the extent of gene mutations by using a microdissection technique. Exon 15 of the APC gene and the DCC gene, in addition to the p53 and Ki-ras genes and microsatellite instability, were analysed. Identical mutations of the p53 gene were found in both invasive adenocarcinomas and adjacent serrated adenomas by direct sequencing, suggesting single clonal origins for those lesions. Mutations of the APC gene and microsatellite instability were heterogeneous in some lesions. No loss of heterozygosity (LOH) of the DCC gene was found. These findings suggest that mutations of the p53 gene are the most characteristic genetic alterations in serrated adenomas, as a relatively early event in a multistep carcinogenic pathway of this type of colorectal lesion, that might be distinct from the ordinary adenoma-carcinoma sequence or from carcinogenesis via mutations of mismatch repair genes.

Adenocarcinoma↗

PubMed1998

Induction and persistence of immune-mediated cholangiohepatitis in neonatally thymectomized mice.

The availability of recombinant autoantigens allows the experimental study of the relationships between primary biliary cirrhosis (PBC) and mitochondrial antigens. We took advantage of these recombinant autoantigens and attempted to induce autoimmune cholangitis by immunizing neonatally thymectomized (NTx) lipopolysaccharide (LPS)-treated A/J mice, known to be prone to organ-specific autoimmune diseases. We employed a recombinant protein containing a dual-headed molecule that coexpresses the immunodominant epitope of the E2 subunits of the pyruvate dehydrogenase complex and the branched-chain keto-acid dehydrogenase complex. We report herein that an immune-mediated cholangiohepatitis was induced by such immunization and the concurrent injection of LPS into NTx mice. The incidence of cholangitis was 79% in the NTx, immunized, LPS group compared to 14% in the NTx, nonimmunized, LPS group. The histopathology ranged from mild to severe and included bile duct damage, focal hepatic necrosis, and endotheliitis, but no granulomas. Moreover, almost all such lesions persisted for 12 weeks after the discontinuation of immunization and LPS injections in the NTx mice. Interestingly, we were successful (89%) in transferring the cholangiohepatitis by injection of liver infiltrating mononuclear cells from the NTx, immunized, LPS mice into congenic nonimmunized NTx mice; such lesions could not be transferred with spleen cells. Although the pathology is not typical of PBC, this model offers a unique venue for the study of immune-mediated hepatobiliary injury.

Adoptive Transfer↗

PubMed1998

Growth patterns in various macroscopic types of noninvasive intramucosal colorectal carcinoma with special reference to apoptosis and cell proliferation.

PURPOSE: Apoptotic cell death and cell proliferation play important roles in the histogenesis and development of colorectal carcinoma. The aim of this study was to examine the relationship between apoptosis and cell proliferation in various macroscopic types of intramucosal colorectal carcinoma in relation to the expression of p53 and bcl-2. METHODS: One hundred forty cases with endoscopically or surgically resected intramucosal colorectal carcinoma were studied. There were 57 cases of polypoid-type carcinomas, 55 cases of superficial-type carcinomas, and 28 cases of granular-type, laterally spreading tumors. Polypoid-type carcinomas were pedunculated, subpedunculated, or sessile polyps. Superficial-type carcinomas were flat lesions with a smooth, even surface. Granular-type, laterally spreading tumors were superficially spreading lesions with aggregates of nodules and a granular surface. Apoptotic cells were identified by the in situ DNA nick end labeling method. Ki-67, p53, and bcl-2 expression were examined immunohistochemically. RESULTS: The superficial-type carcinoma apoptotic index (30.9 percent) was significantly lower than that of polypoid-type carcinoma (54.4 percent) and granular-type, laterally spreading tumor (60.7 percent). The superficial-type carcinoma proliferative index (67.3 percent) was significantly higher than that of polypoid-type carcinoma (42.1 percent) and granular-type, laterally spreading tumor (28.6 percent). In superficial-type carcinomas the proliferative index in p53-positive carcinomas was significantly higher, and the apoptotic index was higher in carcinomas with a lower proliferative index. There was no significant difference in apoptotic index, proliferative index, or p53 protein overexpression between de novo carcinomas and those that had arisen in precursor adenomas. CONCLUSIONS: The pattern of cell death and proliferation may vary with different macroscopic types of intramucosal colorectal carcinoma. Superficial-type colorectal carcinomas especially demonstrate diminished apoptosis and increased cell proliferation. This may be useful in understanding their biologic behavior.

Apoptosis↗

PubMed1998

MUC-1 expression as a predictor of the curative endoscopic treatment of submucosally invasive colorectal carcinoma.

PURPOSE: This study was undertaken to clarify the clinical significance of MUC-1 expression in the endoscopic treatment of colorectal carcinoma with submucosal invasion. METHODS: One hundred eighty-four colorectal carcinomas with submucosal invasion were examined. The depth of submucosal invasion was classified as scanty or massive. The histologic subclassification at the deepest invasive portion was defined as well-differentiated, moderately well-differentiated, moderately to poorly differentiated, poorly differentiated, or mucinous adenocarcinoma. MUC-1 expression was examined immunohistochemically at the deepest invasive portion. In addition, the Ki67 labeling index was also examined immunohistochemically. RESULTS: Lymph node metastases were detected in 28 (15.2 percent) of 184 lesions. Lesions with both scanty submucosal invasion and well-differentiated or moderately well-differentiated adenocarcinomas had no lymph node metastases. MUC-1 expression was detected in 88 (47.8 percent) of 184 lesions and correlated significantly with the presence of lymph node metastases. The Ki67 labeling index also correlated significantly with lymph node metastases. Furthermore, lesions with both MUC-1-negative and low Ki67 labeling index showed no lymph node metastases, even in lesions with massive submucosal invasion. Multivariate analysis indicated that MUC-1 expression was one of the most important risk factors for lymph node metastases and histologic grade among the clinicopathologic factors usually examined. CONCLUSION: MUC-1 expression is one of the accurate predictors of the presence of lymph node metastases among the clinicopathologic factors commonly used. Combined analysis of MUC-1 expression and Ki67 labeling index may be a useful indicator of lymph node metastases and may broaden the indications for the curative endoscopic treatment of carcinoma with massive submucosal invasion.

Adenocarcinoma↗