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Biomedical subjects

M Oya

Publications and source records attributed to M Oya.

At least 19 recordsLinked to original sources
PubMed2005

Akt activation in renal cell carcinoma: contribution of a decreased PTEN expression and the induction of apoptosis by an Akt inhibitor.

BACKGROUND: Akt has been implicated in the oncogenesis of human malignant tumors, because Akt regulates many key effector molecules involved in cell survival. PTEN (phosphatase and tensin homolog deleted on chromosome 10) negatively regulates Akt activation. MATERIALS AND METHODS: The expression of phosphorylated Akt (p-Akt), total Akt and PTEN was analyzed by Western blotting in 45 renal cell carcinoma (RCC) patients. The Bad and phosphorylated Bad (p-Bad) statuses were analyzed in 20 RCC patients. A phosphatidylinositol ether analog was used as an Akt inhibitor to treat four RCC cell lines, namely Caki-1, KU19-20, SW839 and Caki-2. RESULTS: The PTEN expression in RCC was observed to decrease and p-Akt expression to increase significantly in comparison with that in the corresponding normal kidney tissue. The PTEN expression inversely correlated with the p-Akt expression. These alterations were specific for clear cell type RCC, but not for papillary or chromophobe type RCC. Alterations in Bad phosphorylation were also specifically observed in clear cell type. The Akt inhibitor induced apoptosis in KU19-20 and Caki-2 cells with a high Akt activity. CONCLUSIONS: A decreased expression of PTEN may be an underlying mechanism for Akt activation. An Akt inhibitor may be a therapeutic option for a subset of RCC with an elevated Akt activity.

Apoptosis↗
PubMed2005

Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer.

BACKGROUND: Lateral lymph node metastases occur in some patients with low rectal cancer and may cause local recurrence after total mesorectal excision. The aims of this study were to identify risk factors for lateral node metastases in patients with pathological tumour (pT) stage 3 or pT4 low rectal adenocarcinoma, and to evaluate the prognostic significance of lateral node metastases. METHODS: A retrospective analysis was performed of the outcome of 237 patients with pT3 or pT4 low rectal adenocarcinoma who underwent R0 resection with systematic lateral node dissection. RESULTS: Lateral lymph node metastases were found in 41 patients (17.3 per cent). Increased risk of lateral lymph node metastases was associated with a distal tumour margin close to the anal margin, histological type other than well or moderately differentiated adenocarcinoma, and the presence of mesenteric lymph node metastases. Patients with lateral node metastases had a significantly shorter postoperative survival (5-year survival rate 42 versus 71.6 per cent; P < 0.001) and an increased risk of local recurrence (44 versus 11.7 per cent; P < 0.001) compared with those without lateral node metastases. CONCLUSION: Tumour site, histological type and the presence of mesenteric lymph node metastasis are factors predicting the risk of lateral node metastasis. The poor prognosis of patients with lateral lymph node metastases after systematic lateral dissection suggests the need for adjuvant therapy.

Adenocarcinoma↗
PubMed2005

Colonic muco-submucosal elongated polyp: diagnosis with endoscopic ultrasound.

Colonic muco-submucosal elongated polyp is a new clinical entity first reported in 1998. The purpose of this report is to determine the value of endoscopic ultrasound in the diagnosis of this condition. We reviewed the endosonographic and histological findings of seven colonic muco-submucosal elongated polyps that were removed completely by endoscopic resection or surgery. The lesions appeared as pedunculated submucosal tumours, measuring 1-4 cm in maximal diameter. Endosonographically, all lesions consisted of mucosal and submucosal layers, and microcystic components were found in the submucosal layer. There were no echogenic masses or muscularis propria within the polyps. These endosonographic features corresponded to histological findings of this type of polyp which was covered with normal mucosa and composed of submucosal layer alone. The submucosal layer consisted of oedematous, loose, connective tissue and/or fibrous tissue, accompanied by dilated blood vessels and lymphatics. Endoscopic ultrasound enabled differentiation of colonic muco-submucosal elongated polyp from other submucosal lesions.

Adult↗
PubMed2003

Effects of an aldose reductase inhibitor on gastroenteropathy in streptozotocin-diabetic rats.

We investigated the effects of epalrestat, an aldose reductase inhibitor (ARI), on gastric emptying, fecal water content, and electrolyte transport in distal colon in streptozotocin (STZ)-induced diabetic rats. We measured gastric emptying time by acetaminophen method and short-circuit-current (Isc) in colonic mucosa using an Ussing chamber. The Isc in response to electric-field-stimulation (EFS) was decreased in untreated rats due to suppression by Cl- secretion. ARI treatment alleviated this suppression (2.7 +/- 0.6 vs. 7.4 +/- 1.1 microA/0.38 cm2 at 8 weeks after treatment, 1.1 +/- 0.2 vs. 7.0 +/- 1.0 at 12 weeks after treatment, P<0.05). In addition, the percentage of fecal water content in untreated rats was significantly lower than in ARI-treated rats (58.0 +/- 2.0 vs. 67.6 +/- 0.8% at 8 weeks, 56.9 +/- 2.1 vs. 63.4 +/- 1.4 at 12 weeks, P<0.05). From STZ injection to 8 weeks, the serum levels of acetaminophen in the diabetic rats were significantly lower than in controls, indicating delayed gastric emptying. At 12 weeks in the diabetic rats treated with ARI, the serum levels of acetaminophen were significantly higher than in the untreated diabetic rats (6.6 +/- 0.4 vs. 3.5 +/- 0.5 microg/ml, P<0.05). ARI-treatment ameliorated delayed gastric emptying without improving glycemic control. These findings show that ARI partially prevented progression of impaired gastric emptying, ion transport, and water transport, and suggest that epalrestat might be useful in the treatment of diabetic gastroenteropathy.

Acetaminophen↗
PubMed2001

Constitutive activation of nuclear factor-kappaB prevents TRAIL-induced apoptosis in renal cancer cells.

TRAIL has gained much attention for its specific induction of apoptosis in cancer cells but not in normal cells. This phenomenon has been explained thus: that cancer cells dominantly express death receptors while normal cells express decoy receptors. However, recent reports have shown that some cancer cell lines are resistant to TRAIL-induced apoptosis despite the absence of decoy receptors and the presence of death receptors. This suggested the existance of an inhibitory factor. We herein showed that NF-kappaB is a key molecule underlying the TRAIL-resistant mechanism in renal cell carcinoma (RCC) cell lines. We observed that NF-kappaB is constitutively activated in resistant cell lines. Forced expression of antisense cDNA of IkappaBalpha, a specific inhibitor of NF-kappaB, in TRAIL-sensitive cell lines with a low NF-kappaB activity result in constitutive activation of NF-kappaB and resistance to TRAIL-induced apoptosis. Adenoviral expression of a stable form of IkappaBalpha in the TRAIL-resistant cell lines induced apoptosis. These data suggest that RCC can be classified into two subsets: TRAIL-sensitive RCC with a low NF-kappaB activity and TRAIL-resistant RCC with constitutively activated NF-kappaB. In the former group TRAIL can be a treatment option, while in the latter group a molecular approach targeting NF-kappaB appears to be a promising therapy.

Antineoplastic Agents↗
PubMed2001

Isolated splenic metastasis of sigmoid colon cancer: a case report.

We report the case of a 62-year-old man who developed isolated splenic metastasis of sigmoid colon cancer. The patient underwent left hemicolectomy for Dukes C sigmoid colon cancer in February 1997. In March 1999, an abdominal CT scan revealed a tumor 3 cm in size at the inferior pole of the spleen. The tumor was hyperechoic on ultrasonography. The serum carcinoembryonic antigen level was normal. Since no other site of recurrence was identified, a splenectomy was performed with a curative intent. At laparotomy, neither hepatic metastasis, peritoneal dissemination, lymph node metastasis nor local recurrence was detected. Histological findings of the splenic tumor were compatible with metastasis of the previously resected sigmoid colon adenocarcinoma. The patient has been disease-free for 19 postoperative months. Immunohistochemical staining for urokinase-type plasminogen activator was positive in primary sigmoid colon cancer and splenic metastasis, but negative in lymph node metastasis; results that possibly reflect the difference in progenitor cells between splenic metastasis and lymph node metastasis or the difference in the microenvironment of cancer cells between the spleen and lymph nodes. Based on the present case, we recommend that clinicians pay close attention to the spleen for the early diagnosis of isolated splenic metastasis when routinely evaluating abdominal CT scans and abdominal ultrasonography following curative resection of primary colorectal cancer.

Abdomen↗
PubMed2001

High preoperative plasma D-dimer level is associated with advanced tumor stage and short survival after curative resection in patients with colorectal cancer.

BACKGROUND: An elevated plasma D-dimer level indicates activation of coagulation and fibrinolysis. Previous studies demonstrated that the preoperative plasma D-dimer level correlates with tumor stage in patients with colorectal cancer. This study examined the relationship between preoperative plasma D-dimer level and both pathological findings and TNM classification and examined the prognostic significance of preoperative plasma D-dimer level. METHODS: Preoperative plasma D-dimer levels were measured in 93 patients who underwent curative resection of colorectal cancer and 40 patients with benign colorectal diseases other than inflammatory bowel disease. The results were analyzed for correlations between preoperative plasma D-dimer levels in patients with colorectal cancer and pathological findings, TNM classification and postoperative survival. RESULTS: Preoperative plasma D-dimer levels were significantly higher in patients with colorectal cancer than in patients with benign colorectal diseases. Plasma D-dimer levels were higher in patients with tumors that were relatively large, had relatively deep wall penetration and were at a relatively advanced TNM stage. Higher preoperative plasma D-dimer levels were significantly associated with shorter postoperative overall survival. Results of analysis with a multivariate proportional hazard model suggested that preoperative plasma D-dimer level was the third strongest prognostic factor; exceeded in importance only by lymph node status and preoperative carcinoembryonic antigen level. CONCLUSIONS: Elevated plasma D-dimer levels in patients with colorectal cancer are associated with relatively advanced tumor stage and short postoperative survival after curative resection. It appears that measurement of preoperative D-dimer level would be useful in the preoperative diagnosis of tumor stage and prediction of postoperative survival.

Colectomy↗
PubMed2001

Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma.

Pleomorphic leiomyosarcoma (PLMS) was recently described as a morphologic variant of leiomyosarcoma; however, its diagnostic criteria, as shown by morphologic features and biologic behavior, remain controversial. We describe 28 cases of pleomorphic sarcoma with pleomorphic areas in more than two thirds of the tumor and an ordinary leiomyosarcomatous fascicular area covering less than one third as PLMS. PLMS comprised 8.6% of all the leiomyosarcomas (322 cases) registered in our institute. Patients ranged in age from 31 to 89 years (average, 57.9 years). Seventeen patients (60.7%) were male and 11 were female. Tumor location was as follows: the extremities in 17 cases, the retroperitoneum or abdominal cavity in 7 cases, the chest/abdominal wall in 3 cases, and the scalp in 1 case. Histologically, all cases showed at least small foci of fascicles consisting of smooth muscle tumor cells, in addition to pleomorphic areas mimicking storiform-pleomorphic malignant fibrous histiocytoma. The border between pleomorphic and leiomyosarcomatous fascicular areas was sharp in 3 cases, gradual in 2 cases, and blending in 23 cases. Sixteen cases (57.1%) showed a typical storiform pattern, 6 cases revealed extensive stromal hyalinization, 6 cases showed a chronic inflammatory infiltrate, 2 cases had the foci of foamy xanthomatous cells, and 7 cases contained myxoid malignant fibrous histiocytoma-like areas covering less than 50% of the tumor. The tumors had a tendency to be of a morphologically higher grade (10 tumors were French Federation of Cancer Centers grade 2, 18 were grade 3). Five of 28 cases (18%) showed rhabdoid features. Immunohistochemically, all of the 28 tumors examined showed a positive reactivity for at least one smooth muscle marker (desmin, muscle-specific actin, and alpha-smooth muscle actin) in the leiomyosarcomatous fascicular areas. In the pleomorphic areas the expression of smooth muscle markers (desmin 10 of 28, muscle-specific actin 13 of 28, and alpha-smooth muscle actin 14 of 28) was significantly reduced, compared with that in leiomyosarcomatous fascicular area (desmin 18 of 28, muscle-specific actin 26 of 28, and alpha-smooth muscle actin 24 of 28). No significant difference was observed between the MIB-1 labeling index in the leiomyosarcomatous fascicular areas (26.10 on average) and that in the pleomorphic areas (26.17 on average). However, the MIB-1 labeling index in PLMS was significantly higher than that in ordinary leiomyosarcoma (n = 20, 12.86 on average) or storiform-pleomorphic malignant fibrous histiocytoma (n = 16, 16.63 on average). In 23 patients follow-up data were available with a duration of 1-239 months. Eleven patients developed metastases, and lung accounted for the most common site of metastasis (9 cases). Fifteen of 23 patients (65.2%) died of disease. Our results indicate that PLMS should be differentiated from ordinary leiomyosarcoma because of its high proliferative activities and rather aggressive biologic behavior.

Adult↗
PubMed2001

FXIIIA subtypes in Indonesians, Bangladeshis, Tibetans, South African blacks and South African whites.

The polymorphism of FXIIIA was investigated in 105 Indonesians, 141 Bangladeshis, 186 Tibetans, 101 South African Blacks and 100 South African Whites using isoelectric focusing followed by immunoblotting. These population data conformed to the Hardy-Weinberg equilibrium. A circum-pan-Pacific cline in the FXIII*1A (or FXIII*1B) allele frequency appeared to exist among the Mongoloids.

Adult↗
PubMed2000

Prognostic value of alkaline phosphatase flare in patients with metastatic prostate cancer treated with endocrine therapy.

OBJECTIVES: To assess the prognostic significance of alkaline phosphatase (ALP) flare in 114 patients with metastatic prostate cancer treated with endocrine therapy. METHODS: ALP flare was defined as a transient increase of the serum ALP level to 120% or more of the pretreatment value after the initiation of endocrine therapy, followed by a subsequent decrease. RESULTS: Univariate analysis demonstrated that patients with poorly differentiated adenocarcinoma, an extent of disease of 2 or greater, a serum ALP level above twice the upper limit of normal, a serum prostate-specific antigen level greater than 100 ng/mL, an ALP flare, and a hemoglobin level of 12 g/dL or less had a significantly lower survival rate than their respective counterparts. Multivariate Cox's proportional hazards model analysis demonstrated that tumor histologic features and ALP flare were significant prognostic indicators for survival. CONCLUSIONS: The results of the present study suggest that the tumor histologic features and the ALP flare are significant prognostic indicators for survival in patients with metastatic prostate cancer treated with endocrine therapy.

Adenocarcinoma↗
PubMed2000

Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation.

A 70-year-old woman underwent right hemicolectomy and six carcinomas were recognized in the resected colon. These carcinomas were considered to be of a cell lineage common to serrated adenoma (SA) and hyperplastic (metaplastic) polyp (H/MP), because of the occurrence of multiple SAs and H/MPs around the carcinomas, as well as the co-existence of SA and H/MP areas within the carcinomas. These carcinomas had the following common histological and immunohistochemical features: a serrated structure resembling SA; a lace-like structure; infiltrative growth within the muscularis propria, with dedifferentiation at the invasive front; and immunohistochemical expression of pS2 and human gastric mucin. Based on these features, a new subtype of carcinoma is proposed, with a cell lineage common to SA and H/MP. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.

Adenocarcinoma↗
PubMed2000

The tight junction of pancreatic exocrine cells is a morphometrically dynamic structure altered by intraductal hypertension.

The tight junction of pancreatic exocrine cells is thought to regulate paracellular permeability, and is a possible reflux route of pancreatic juice into the blood flow. Morphological changes in the tight junction of canine pancreatic acinar cells following intraductal hypertension and secretin stimulation were morphometrically analyzed to obtain evidence of the control of the paracellular reflux. Pancreatic tissues obtained from 25 dogs after intraductal hypertension, 3 dogs after secretin stimulation, and 5 control dogs were studied. Intraductal pressure was either 20 cmH2O, 30 cmH2O, or 40 cmH2O. Freeze fracture replicas of these pancreatic tissues were observed by electron microscopy. Tight junctions were classified into six morphometric types. Reticular type, parallel type, and mixed type comprised the common types predominantly found in all groups, and three special types were found, infrequently, only after intraductal hypertension. The percentages of the common types were significantly different between the groups. The areas of the tight junctions, and other morphometric parameters, were significantly less after 20 cmH2O intraductal hypertension and secretin stimulation than in the controls. However, these findings after 30 cmH2O or 40 cmH2O intraductal hypertension did not differ from those in the controls. The areas of the three special types of tight junctions were larger than those of the common types. These results suggest that the tight junction of pancreatic exocrine cells is a morphologically dynamic structure that is altered by the extent of intraductal hypertension, and support the hypothesis that paracellular permeability is the mechanism of the reflux of pancreatic juice.

Animals↗
PubMed2000

Expressions of cell-cycle regulatory gene products in conventional gastric adenomas: possible immunohistochemical markers of malignant transformation.

In 54 lesions of gastric adenomas consisting of 31 low-grade adenomas (LGAs) and 23 high-grade adenomas (HGAs), 28 intramucosal carcinomas (IMCs), and 23 carcinomas invading the submucosa (SMCs), the expression of cell-cycle regulatory gene products (p53, p21/waf1, p27/kip1, and Ki-67) was studied using immunohistochemical techniques. Several lesions were also analyzed by the fluorescence in situ hybridization method. The overexpression of p53 was found in no LGAs and in 9% of HGAs, whereas a considerable number of cases showed an overexpression in IMCs (39%) and SMCs (43%). A reduced expression of p21/waf1 was present in only 4% of HGAs. Superficial eccentric positivity was present in all LGAs and 74% of HGAs, whereas it was present in 46% of IMCs and 4% of SMCs. P53-positive and p21/waf1-negative lesions, which were supposed to have a mutated p53 gene, were observed in no LGAs, in 4% of HGAs, in 11% of IMCs, and in 26% of SMCs. The expression of cyclin E was more frequently present in carcinomas than in adenomas. However, no high expression of cyclin E was observed among the adenomas. A reduced expression of p27/kip1 was encountered more frequently in carcinoma than adenoma. By a semiquantitative evaluation comparing adenoma and carcinoma in the same stomach, the increased degrees of both p21/waf1 and cyclin E were highlighted. A chromosome gain was detected among 7% of the adenomas and 85% of the carcinomas. In conclusion, the expressions of p53, p21/waf1, p27/kip1, and cyclin E were considered to be of great value for estimating the dysplastic progression of gastric adenomas. Especially, various aspects of protein expression, including its distribution and semiquantitative evaluation of positive cells, and a combined analysis with several proteins, may thus be useful as possible markers of dysplastic evolution in gastric adenomas.

Adenocarcinoma↗
PubMed2000

Genetic analysis of the STR system D20S161 in Japanese and Bangladeshi.

The allele distributions of the STR locus D20S161 have been investigated in Japanese and Bangladeshi people. No deviation from the Hardy-Weinberg equilibrium was observed in either population. D20S161 was found to be a polymorphic STR with seven alleles in Japanese and with six alleles in Bangladeshi. The distribution of allele frequencies in Japanese was very similar to that in Bangladeshi. The D20S161 system can be a potential marker for medicolegal individualization and paternity testing.

Journal Article↗
PubMed2000

Decreased expression of p57(KIP2)mRNA in human bladder cancer.

To identify targets of genetic and epigenetic alterations on chromosome 11p15.5 in human bladder cancer, expression of the imprinted KIP2, IGF2 and H19 genes was studied by quantitative RT-PCR in 24 paired samples of urothelial carcinomas and morphologically normal mucosa obtained by cystectomy, and in bladder carcinoma cell lines. The most frequent alteration in tumour tissue was decreased expression of KIP2 identified in 9/24 (37%) specimens. Decreased IGF2 and H19 mRNA levels were found in five (21%) and three (13%) tumours, respectively. One tumour each overexpressed IGF2 and H19. Loss of H19 expression was only found associated with loss of KIP2 expression, whereas decreased expression of IGF2 mRNA occurred independently. Almost all bladder carcinoma cell lines showed significant changes in the expression of at least one gene with diminished expression of KIP2 mRNA as the most frequent alteration. IGF2 mRNA levels were diminished in several lines, but increased in others. The KIP2 gene could be an important target of genetic and epigenetic alterations in bladder cancer affecting the maternal chromosome 11p15.5. However, reminiscent of the situation in Wilms' tumours, expression of the IGF2 gene on the paternal chromosome can also be disturbed in bladder cancers.

Aged↗