Search PubMed⌕ Search

Biomedical subjects

M Monden

Publications and source records attributed to M Monden.

501 records · Page 28Linked to original sources
PubMedDate not supplied

Microchimerism and hyporesponsiveness induced by intraportal injection of donor spleen cells in rats.

It is controversial whether or not microchimerism (MC) is responsible for the induction and maintenance of donor-specific tolerance. We have shown that intraportal injection (i.p.) of donor splenocytes induces a long-term graft survival of liver and heart in rats. In this study, we examined by polymerase chain reaction (PCR) the status of MC in the liver, spleen, and blood of rat cardiac recipients following i.p. or intravenous injection (i.v.) of donor splenocytes. Male DA (RT1a) and Wistar (RT1k) rats were used as donors and recipients, respectively. Heterotopic heart transplantation was performed 10 days after i.p. or i.v. injection of 5 x 10(7) DA spleen cells. DA cardiac allografts were rejected with a mean survival time (MST) of 11.9 +/- 1.6 (n = 10) days in nontreated recipients. Injections (i.v.) led to no significant prolongation of graft survival (MST: 11.2 +/- 1.9 days, n = 6), while i.p. or i.v. injection alone resulted in significant MC in these organs throughout the observation time over 60 days. MC was detected in the spleen, liver, and blood of cardiac recipients 7 days after transplantation and also even after cessation of cardiac heartbeat 21 days after transplantation. This was the case with either i.p. or i.v. group, which showed MC on day 7 after transplantation and persistent MC after cessation of the heartbeat. These data suggests that the presence of MC in the liver, spleen and blood of transplant recipients may not be responsible for immunological unresponsiveness to donor antigens.

Animals↗
PubMedDate not supplied

Pretreatment of crude pancreatic islets with mitomycin C (MMC) prolongs islet graft survival in a xenogeneic rat-to-mouse model.

In this study, we examined the effect of mitomycin C (MMC) treatment on graft survival and evaluated its efficacy in immunomodulation of islet graft for transplantation. Male WS rats were used as islet donors and streptozotocin-induced diabetic C57BL/6 mice as recipients. The isolated islets were treated with MMC at concentrations of 0, 0.1, 1, 3.2, 10, 32, 100, 320, and 1000 microg/mL for 30 min, and were cultured for 20 h. Then, 300-400 islets were transplanted into the renal subcapsular space of diabetic mice. Significant prolongation of graft survival was obtained when the islets were treated with MMC at a concentration of 10, 32, or 100 microg/mL (MST 23 +/- 7.4, 17.5 +/- 5.4, 29.6 +/- 9.7 days: p < 0.003, p < 0.012, p < 0.001, respectively, vs. 12.3 +/- 2.7 days for culturing alone). Islets treated with MMC at a concentration of 320 microg/mL or more failed to restore normoglycemia in the diabetic recipient mice after transplantation. Viability of islets incubated with doses up to 100 microg/mL, assessed under the confocal microscope after propidium iodide and Hoechst 33342 staining, was maintained well comparable to that of freshly isolated islets, while those treated at 320 microg/mL was significantly decreased. Thus, a therapeutic window for MMC efficacy was found at concentrations from 10 microg/mL to 100 microg/mL. This modality is simple and effective and underlying molecular mechanisms need to be determined in the future.

Animals↗
PubMedDate not supplied

Identification of a 7-cM region of frequent allelic loss on chromosome band 16p13.3 that is specifically associated with anaplastic thyroid carcinoma.

A total of 17 primary thyroid cancer specimens including seven anaplastic cancers, two papillary cancers adjacent to the anaplastic cancers, and eight papillary cancers were analyzed for loss of heterozygosity (LOH) on chromosome arm 16p. All tumors of anaplastic cancer showed LOHs at one or more loci, and a 7-cM region of the smallest deleted region was found on 16p13.3 between D16S423 and D16S406. This LOH was specifically found in the anaplastic cancer and not in the papillary thyroid cancer. Our present results suggest localization of the putative tumor suppressor gene on 16p13.3, which is likely to play an important role in the anaplastic transformation of thyroid cancer.

Adult↗
PubMedDate not supplied

Selection of mRNA markers for detection of lymph node micrometastases in breast cancer patients.

The aim of this study was to search for specific and sensitive mRNA markers or a combination of markers for RT-PCR detection of micrometastases in axillary lymph nodes (LNs) from patients with breast cancer. LNs (n=177) from 17 patients were examined with Cytokeratin20 (CK20), melanoma-associated genes (MAGE1, MAGE3), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), mammaglobin (MGB1) and mammaglobin B (MGB2) as molecular markers. CK20, MAGE1 and MAGE3 were slightly positive in primary tumors and CEA, PSA, MGB1 and MGB2 were highly positive. MGB1 and MGB2 were 100% positive in HE-positive LNs while CEA and PSA were only 35.7% and 57.1% positive. MGB1 and MGB2 were also 30.1% and 17.8% positive in HE-negative nodes. Thus, MGB1 and MGB2 are specific and a combination of the two should be useful for detection of micrometastases in axillary LNs of breast cancer patients.

Biomarkers, Tumor↗
PubMedDate not supplied

Prognostic factors for recurrence in stage II and III gastric cancer patients receiving a curative resection and postoperative adjuvant chemotherapy.

Prognostic value of clinicopathologic factors and biologic markers was analyzed in 185 patients who received a curative resection and adjuvant chemotherapy of pathologically confirmed stage II or III gastric cancer. No difference was found between the chemotherapeutic regimens according to the frequency of recurrence, but tumor type, histology, depth of invasion, nodal metastasis, and lymphatic and venous invasion were significantly different between recurrent (n=62) and non-recurrent (n=123) patients. However, the degree of lymphatic dissection and the patterns of biological markers (DNA ploidy, p53 staining and PCNA labeling) were not different. Hepatic metastasis and venous invasion were more frequent on patients recurring within one year, compared to those who recurred later. Multivariate analyses showed that depth of invasion, level 2 lymph node metastasis and tumor histology were risk factors for recurrence. Pathologic factors were more important for predicting recurrence than biological markers.

Adenocarcinoma↗
PubMedDate not supplied

Expression of heparin binding epidermal growth factor-like growth factor in hepatocellular carcinoma: an immunohistochemical study.

Previous studies have demonstrated an elevated level of heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA in hepatocarcinogenesis in a rodent model and of its protein as well as mRNA in human hepatocellular carcinoma (HCC). In order to elucidate the clinical significance of HB-EGF in human HCC, we immunohistochemically investigated its expression in 100 HCC cases with different characteristics. HB-EGF was not or only faintly expressed in non-cancerous hepatocytes. On the other hand, 59% of the HCC cases were classified as positive for HB-EGF, and its expression was more frequently observed in cases with low proliferating activity, at an early stage, of small size, without portal invasion, low alpha-fetoprotein level, without satellite nodules (borderline significance), and well or moderate differentiation. Furthermore, HB-EGF expression showed prognostic significance in both univariate and multivariate analyses and can be regarded as an independent prognostic factor of disease-free survival. These results strongly suggest the involvement of HB-EGF in early stage of HCC.

Adult↗
PubMedDate not supplied

Expression and clinical significance of the G1-S modulators in carcinoma of the extrahepatic bile duct.

Expression of cell cycle modulators at the G1-S boundary, the retinoblastoma gene product (pRb), p21, p16, p27, p53, cyclin D1 as well as Ki-67 was investigated with 39 extrahepatic bile duct carcinomas (BDC). The Ki-67 labeling index (LI) was higher in cases with poor differentiation, lymph node metastasis and stage III or IV. Cyclin D1 overexpression was seen in 14 cases (35.8%). This phenomenon could be observed more frequently in cases of hilar carcinoma and with poor differentiation, perineural invasion, lymphatic invasion and lymph node metastasis. Furthermore, Ki-67 LI was higher in cyclin D1 overexpressing cases. p27 expression showed inverse relationships with Ki-67 LI, lymph node metastasis and aberrant p53 expression. Although p16 and p21 expression significantly correlated with lymph node metastasis and cyclin D1 overexpression, respectively, they were not related to Ki-67 LI. pRb expression was observed in all cases. Although the LI was lower in carcinoma of upper and middle bile ducts, no correlation was established between pRb expression and other clinicopathological parameters including Ki-67 LI. Aberrant p53 expression was observed in 13 cases (33.3%) and Ki-67 LI was significantly higher in these cases. These findings suggest that p27 and cyclin D1 strongly correlate with BDC proliferation and reflect the biological aggressiveness of this carcinoma.

Aged↗
PubMedDate not supplied

Gastric carcinoma associated with dermatomyositis. Case report.

A case of gastric carcinoma associated with dermatomyositis is reported. Total gastrectomy was performed and subsequently excision of hepatic metastasis. Although the cause-effect relationship between dermatomyositis and internal malignancy remains controversial, the obvious dependence of the clinical course of dermatomyositis on that of the gastric carcinoma in this case suggests a causal involvement.

Adenocarcinoma↗
PubMedDate not supplied

The prognostic significance of macroscopic growth pattern of hepatocellular carcinoma.

The relationship between macroscopic growth pattern of main tumor and postoperative survival was retrospectively investigated in 155 patients with resectable hepatocellular carcinoma. The survival of single nodular type (type I, n = 75) was significantly better than that of single nodular type with proliferation into the surrounding area (type II, n = 53) or massive type (type V, n = 13). The frequency of intrahepatic metastasis or portal tumor thrombus in the resected specimens was significantly lower in patients with type I than in those with type II or V (p < 0.05). Patients with type I undergoing segmentectomy (Hr1) had better survival than those with hepatic resections of less than 1 segment (Hr0, p < 0.05). However, such difference was not observed in patients with either type II or V. Moreover, the presence of a cancer-free surgical margin (1 cm or more) significantly affected the long-term prognosis (5-7 years after surgery) in type I but not in type II, suggesting that the intrahepatic spread of tumor might be localized around the main tumor in type I. On the other hand, intrahepatic metastasis and portal involvement were frequently observed in type V and the prognosis was extremely poor even when major hepatic resections were performed. These results indicate that the macroscopic growth pattern of main tumor is an important predictor for hepatocellular carcinoma.

Adult↗
PubMedDate not supplied

Plasminogen activation system in active even in thyroid tumors; an immunohistochemical study.

The plasminogen activation system is one of the prominent factors in tumour progression since it enhances both distant metastasis and direct invasion. In this study we investigated the expression and localization of this system in clinical thyroid tumours. It was found that urokinase-type plasminogen activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor type 1 (PAI-1) were expressed diffusely in most thyroid carcinomas. The lesions positive for the latter two were equal to or sometimes even a litter more extensive than those positive for uPA. The immunoreactivity of plasminogen activator inhibitor type 2 (PAI-2), however, was often partially or even entirely absent, and only 56% of the carcinomas expressed it diffusely, indicating that the two types of inhibitors in this carcinoma have quite different characteristics. No relationship between the expression of these proteins and clinicopathological parameters could be determined. THese findings suggest that the plasminogen activation system is functionally active in thyroid carcinoma but that is has hardly any effect on its general characteristics, that is, slow growth and excellent prognosis of usual types and the exceptionally sudden progression of the anaplastic type. In benign tissues, too, this system was often expressed and appeared to enhance their growth to some extent.

Antibodies, Monoclonal↗
PubMedDate not supplied

Nonpalpable breast cancer with nipple discharge: how should it be treated?

In this study, 26 cases of nonpalpable breast cancer with nipple discharge treated at our department were reviewed. Their discharge was either bloody or serous with a positive hematest, but all except for one were negative for cytology, while CEA value of the discharge was high in 72.7%. Mammograms were found to be unreliable for diagnosis, while abnormal findings were observed in 84.6% by ductography. However, final diagnosis was determined histopathologically from surgical specimens, showing 14 intraductal and 12 invasive ductal cancers, none with components of comedo carcinomas. Seventeen patients underwent mastectomy following duct-lobular segmentectomy and a small remnant of intraductal carcinoma was found microscopically in only one patient. All patients except for one have survived for 98 months on average with no symptoms of metastasis. These findings suggest that duct-lobular segmentectomy with an adequate surgical margin should be adopted as the final operation for selected patients with nonpalpable breast cancer involving nipple discharge.

Adult↗
PubMedDate not supplied

Chemosensitivity of anaplastic thyroid carcinoma and poorly differentiated thyroid carcinoma.

BACKGROUND: The prognosis of anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) is very poor because of their resistance to chemotherapy. MATERIALS AND METHODS: We retrospectively evaluated the response to chemotherapy of 14 patients with ATC and examined the in vitro chemosensitivity of primary cultures of one ATC and five PDTCs from six recent patients. RESULTS: As assessed at one month after treatment, one patient had a partial remission (PR), 3 had no change (NC), and the other 10 progressed (PD). The mean survival of all 14 patients was 3.4 months (PD; 2.3 months, PR or NC; 6 months). Five of the tumors (one ATC and four PDTCs) were resistant to all drugs examined: adriamycin, cisplatin, cyclophosphamide, etoposide, and carboplatin; cells from one PDTC were sensitive to adriamycin alone. Although five patients had administration of anti-cancer agents, none showed a response to chemotherapy. CONCLUSION: most ATCs and PDTCs are very resistant to anti-cancer agents. In vitro chemosensitivity testing may prevent the administration of ineffective chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Fas antigen expression in hepatocellular carcinoma tissues.

Fas antigen belongs to the tumor necrosis factor receptor family and is known to induce apoptosis. This protein is abundantly expressed in hepatocytes, especially in acute and chronic hepatitis. To elucidate the clinical significance of Fas in hepatocellular carcinoma (HCC), we investigated its expression in 50 HCC having various characteristics. Fas was comprehensively expressed in non-cancerous hepatocytes as well as bile ducts. It was moderately expressed in histiocytes in the stroma rather than in infiltrating lymphocytes. In HCC, Fas expression was significantly reduced when there was poor differentiation (p<0.001), portal tumor thrombus and extracapsular invasion (p<0.05) according to univariate analysis. Multivariate analysis revealed statistical significance between Fas expression and the degree of differentiation (p=0.0002). These results suggest that HCC, like non-cancerous hepatocytes, express Fas antigen, when they are well or moderately differentiated but lose this ability when they become poorly differentiated as the carcinoma advances.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Role of urokinase-type plasminogen activator in local immunotherapy.

We have previously reported that intratumoral injection of a mixture of OK-432 and fibrinogen (OK/fbg) is very effective for local immunotherapy of colorectal cancer, but has little influence on breast cancer, while addition of activated macrophages to OK/fbg (OK/fbg/mo) has a marked effect on breast cancer. In this study, we analyzed the role of urokinase-type plasminogen activator (uPA) in local immunotherapy. We found that uPA levels in breast cancer tissue were lower than in colorectal cancer tissue. Injection of OK-432 into breast cancers neither increased the uPA level nor caused tumor regression. Although OK/fbg injection caused an increase of uPA, tumor regression was restricted to the area around the injection site. With OK/fbg/mo however, uPA levels increased much more markedly and extensive tumor necrosis was observed in all cases. These findings suggest that uPA plays an important role in tumor regression during local immunotherapy.

Antineoplastic Agents↗