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Biomedical subjects

M Sumitomo

Publications and source records attributed to M Sumitomo.

At least 19 recordsLinked to original sources

Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated IkappaBalpha overexpression.

We investigated whether the cell growth and apoptosis of multiple cytokine-producing bladder cancer cells can be regulated by nuclear factor kappaB (NF-kappaB). The bladder cancer cell line KU-19-19, obtained from a 76-year-old man who demonstrated marked leukocytosis, produces multiple cytokines and demonstrates autocrine growth by granulocyte colony-stimulating factor (G-CSF). Electrophoretic mobility shift assay (EMSA) revealed that NF-kappaB was activated in KU-19-19 but not in other bladder cancer cell lines (KU-1, KU-7, or T-24, respectively). The inhibition of NF-kappaB DNA-binding activity with adenovirus vectors expressing the stable form of the NF-kappaB inhibitor IkappaBalpha (multiplicity of infection [MOI] of 10) inhibited growth and induced apoptosis of KU-19-19, but not KU-1, KU-7, or T-24. The production of several cytokines was suppressed significantly in KU-19-19 by this gene delivery. Although dexamethasone (10 microM) could also suppress cytokine production, it did not induce dramatic cell death in KU-19-19 because it could not inhibit NF-kappaB activation stably and strongly. These results suggest that NF-kappaB activation maintains the cell viability as well as regulates cytokine production in cytokine-producing cancer cells and therefore these in vitro experiments support a rationale for preclinical in vivo studies to demonstrate growth inhibition in established tumors.

Adenoviridae

The value of gamma-seminoprotein in combination with prostate specific antigen in detecting prostate cancer.

BACKGROUND: The present study was undertaken to investigate the value of gamma-seminoprotein (gamma-Sm) and the gamma-Sm/prostate specific antigen (PSA) ratio in combination with serum PSA in detecting prostate cancer. METHODS: Prostate specific antigen, gamma-Sm and the gamma-Sm/PSA ratio were evaluated in 112 patients with untreated prostate cancer and 90 patients without prostate cancer who had serum PSA and gamma-Sm levels above their respective detection limits. RESULTS: When data for all of the patients were analyzed, serum PSA and gamma-Sm levels were significantly higher and the gamma-Sm/PSA ratio was significantly lower in patients with prostate cancer than patients without prostate cancer. The serum PSA and gamma-Sm levels significantly increased and the gamma-Sm/PSA ratio significantly decreased with advancing clinical stage in patients with prostate cancer. Among the patients with serum PSA levels ranging from 1.8 to 6 ng/mL, the gamma-Sm/PSA ratio was significantly lower (P < 0.05) and gamma-Sm levels were lower (P = 0.054) in the patients with prostate cancer than in those without prostate cancer, but serum PSA levels were not significantly different (P = 0.53). A receiver operating characteristic (ROC) analysis demonstrated that the areas under the ROC curves were 0.54 for PSA, 0.65 for gamma-Sm and 0.69 for the gamma-Sm/PSA ratio for prediction of prostate cancer in the PSA range from 1.8 to 6 ng/mL, although the ROC analysis suggested that the gamma-Sm/PSA ratio does not provide significant advantage over PSA in detecting prostate cancer when all of the patients were analyzed. CONCLUSIONS: These results suggest that the gamma-Sm/PSA ratio and gamma-Sm may facilitate differentiation between patients with and without prostate cancer who have intermediate PSA levels.

Adenocarcinoma

[A clinical study of recurrence and progression of grade 3 superficial bladder tumor].

Forty-one patients who had grade 3, superficial, transitional cell carcinoma of the bladder were treated with transurethral resection of bladder tumor between January, 1986 and April, 1998. The clinicopathological studies were conducted on intravesical recurrence, disease progression, and prognosis using multivariate analyses. Intravesical recurrence was found in 18 patients (43.9%), and the recurrence-free rate was 77.0% for 1 year. The 3- and 5-year recurrence-free rates were 57.7% and 38.5% for patients with stage pTa disease, and 36.3% and 36.3% for patients with stawe pT1-disease. There was a significant difference between the recurrence-free rates in the patients with stage pTa disease and those with stage pT1 disease (p < 0.01). Disease progression was observed after a mean period of 14.2 months after treatment in 6 patients (14.6%) with pT1 tumors. Three of these patients died of cancer. In the multivariate analyses with clinical and pathological factors, bladder irritability, urine cytology after initial treatment, and tumor multiplicity were the factors contributing to a high risk for recurrence. Intravesical instillation with Calmette-Guerin bacillus was found to prevent recurrence. These results suggest that radical surgery should be performed in a timely manner in patients with G3-stage pT1 tumors because they have a higher risk of recurrence and progression as compared to patients with G3-stage pTa tumors.

Administration, Intravesical

An essential role for nuclear factor kappa B in preventing TNF-alpha-induced cell death in prostate cancer cells.

PURPOSE: Although tumor necrosis factor-alpha (TNF-alpha) induces a strong cytotoxic effect on cell growth, many authors have reported that various cancer cells are resistant to TNF-alpha and the basis for this sensitivity or resistance to TNF-alpha remains to be elucidated. Since nuclear factor kappa B (NF-kappaB) activation has recently been reported to inhibit TNF-alpha-induced cell death, we studied whether NF-kappaB also assumes a protective role in TNF-alpha-induced cell death in prostate cancer cells. MATERIALS AND METHODS: We used two human prostate cancer cell lines of DU145 and PC-3. We prepared two different NF-kappaB inhibitors, pyrrolidine dithiocarbamate (PDTC) and NF-kappaB decoy. NF-kappaB DNA binding activity was detected by electrophoretic mobility shift assay (EMSA). Cell survivals were measured by MTT assay. Induction of apoptosis was detected by nuclear staining and measured by fragmented DNA ELISA. RESULTS: EMSA showed that NF-kappaB inhibitors continuously inhibited TNF-alpha-induced NF-kappaB activation. Cell growth was not inhibited by either TNF-alpha (50 ng./ml. or less) or NF-kappaB inhibitors. However, both PCA cells treated with TNF-alpha (20 ng./ml.) plus NF-kappaB inhibitors showed significant growth inhibition compared with controls (p<0.05). Nuclei of PCA cells appeared severely fragmented by this combination therapy. Furthermore, the levels of DNA fragmentation were significantly elevated in PCA cells treated with TNF-alpha (20 ng./ml.) plus NF-kappaB inhibitors compared with controls (p<0.05). CONCLUSIONS: NF-kappaB activation is suggested to produce the resistance of DU145 and PC-3 to TNF-alpha and that the combination of TNF-alpha and NF-kappaB inhibitors could be constituted an effective therapy to TNF-alpha-resistant human prostate cancer cells.

Apoptosis

Percutaneous endoscopic marsupialization of a pyelocaliceal diverticulum with milk of calcium stones.

Numerous reports have described the management of pyelocaliceal diverticula associated with milk of calcium renal stones. Traditionally, open surgical techniques to manage such diverticula have included marsupialization and fulguration of the diverticulum, or partial/total nephrectomy. Recently, however, these invasive procedures have been replaced by percutaneous techniques. We report a patient with spontaneous rupture of a pyelocaliceal diverticulum with milk of calcium renal stones, who was successfully treated with endourological procedures.

Adult

[Clinical background and treatment of brain metastasis from renal cell carcinoma].

OBJECTIVE: The objective of this study is to evaluate the clinicopathological characteristics and the effect of therapy of brain metastasis from renal cell carcinoma. METHOD: Of 306 cases with renal cell carcinoma treated at Keio University Hospital from June, 1976 to May, 1996, 20 (6.5%) developed brain metastasis. Metastasis-free rate and survival rate were evaluated by Kaplan-Meier's method and tested statistically with Long-rank test. RESULT: As for the time of the brain metastasis, it was already at the time of initial diagnosis in 6 cases, and in the other 14, it was after the diagnosis of original disease. The average interval between the diagnosis of original disease and metastasis was 53.9 months. Only 2 cases have no metastasis without brain, and 17 of 20 cases (85.0%) were complicated by pulmonary metastasis and 10 (50.0%) by bone metastasis. It was considered that the brain metastasis was accompanied with other metastases. As for the treatment, cytokine therapy was performed on 18 cases without efficacy. It was supposed that in cases with pulmonary metastasis, IL-2 therapy may have the possibility of increasing the frequency of brain metastasis. 9 of 20 cases were subjected to surgical treatment with significantly better prognosis than the cases without the operation. Two cases were long-term survivors more than 5 years after the diagnosis of brain metastasis and both underwent surgical treatment to brain metastasis. CONCLUSION: Cytokine therapy was not effective to brain metastasis from renal cell carcinoma. On the other hand, however, it was suggested that surgical treatment could improve prognosis if the metastatic lesions could be resected.

Adult

Invasive thymoma with endobronchial polypoid growth.

A rare case of invasive thymoma with endobronchial polypoid growth is presented. A 68-year-old woman presented with coughing and sputum. The chest X-ray and computed tomography (CT) findings demonstrated a large mass with a calcified lesion in the left hilar region. A bronchoscopic examination showed a polypoid tumor in the left B3b bronchus. The tumor was surgically resected and revealed a unique polypoid endobronchial extension. This tumor was pathologically diagnosed to be invasive thymoma.

Aged

A transient increase in serum procollagen 1 carboxyterminal peptide following effective treatment in prostate cancer patients with bone metastases.

Procollagen 1 carboxyterminal peptide (P1CP) is thought to be an indicator of new bone formation. The present report demonstrates that effective endocrine therapy induced an initial increase followed by a delayed decrease in serum levels of P1CP and alkaline phosphatase in spite of an immediate decrease in serum PSA and PAP and improvement of clinical symptoms in prostate cancer patients with bone metastases. The transient increase in P1CP and alkaline phosphatase is a healing reaction and is followed by apparent improvement. Short-term effects of endocrine therapy on prostate cancer patients with bone metastases should be comprehensively evaluated based upon the entire spectrum of clinical and laboratory findings including serial changes of serum prostate markers and bone markers as well.

Adenocarcinoma

The value of serum carboxyterminal propeptide of type 1 procollagen in predicting bone metastases in prostate cancer.

PURPOSE: Carboxyterminal propeptide of type 1 procollagen (P1CP) is believed to be a marker of new bone formation. We investigated the possible application of serum P1CP as a biochemical marker for bone metastases in patients with prostate cancer. MATERIALS AND METHODS: Prostate specific antigen (PSA), prostatic acid phosphatase (PAP), P1CP and alkaline phosphatase were measured in 136 serum samples from 79 patients with untreated prostate cancer, 29 with stage D2 disease in remission and 28 with progressive stage D2 carcinoma. RESULTS: Serum P1CP and alkaline phosphatase were significantly elevated in untreated patients with a positive bone scan (278.9 +/- 61.9 ng./ml. and 826.5 +/- 176.3 international units per 1., respectively) compared to those with a negative bone scan (104.2 +/- 4.2 and 200.8 +/- 9.1, respectively, p <0.05). The areas under receiver operating characteristics curves were 0.86 for P1CP, 0.87 for alkaline phosphatase, 0.88 for PSA and 0.85 for PAP. The best accuracy rates for P1CP, alkaline phosphatase, PSA and PAP to predict bone lesions were 84, 87, 86 and 84%, respectively. P1CP provided a greater specificity and positive predictive value. These serum markers correlated significantly with the extent of disease on bone scan (p <0.05). The incidence of positive serum P1CP and alkaline phosphatase decreased significantly in response to endocrine therapy in patients with bone metastasis, and increased progressively in association with progression of the tumor (p <0.05) parallel to PSA and PAP. CONCLUSIONS: These findings suggest that serum P1CP is a useful indicator for predicting bone metastases.

Aged

[Serum levels of tumor necrosis factor alpha and soluble tumor necrosis factor-receptor I in asthmatic patients and patients with chronic respiratory tract infection].

In order to investigate the role of tumor necrosis factor alpha (TNF-alpha) in bronchial asthma or chronic respiratory infection, we measured serum levels of TNF-alpha and serum soluble tumor necrosis factor-receptor I (sTNF-RI) in asthmatic patients (n = 11) and patients (n = 10) with chronic respiratory infection by Pseudomonas aeruginosa. We also measured serum levels of eosinophil cationic protein (ECP) in the asthmatic patients. The serum levels of TNF-alpha in the asthmatic patients, patients with chronic respiratory tract infection and control group were 2.864 +/- 0.719 g/ml, 2.564-1.384 pg/ml and 0.681 +/- 0.453 pg/ml respectively. The levels of the former two groups were higher than those of the control group (p < 0.05). The serum levels of sTNF-RI in the asthmatic patients, the patients with chronic respiratory tract infection, and the control group was 758 +/- 268 pg/ml, 999 +/- 242 pg/ml and 909 +/- 268 pg/ml respectively. The levels of the former two groups did not differ significantly from those of the control group. There were significant correlations between TNF-alpha and sTNF-RI in the control group and in the patients with chronic respiratory tract infection, but there was no significant correlation in the asthmatic patients. In the asthmatic patients. TNF-alpha/s TNF-RI correlated with %best of PEF (r = 0.691, n = 9, p 0.0373). The serum levels of ECP correlated significantly with TNF-alpha, but not with sTNF-RI in the asthmatic patients. It is suggested that TNF-alpha plays a significant role in the pathogenesis of bronchial asthma and chronic respiratory tract infection as a factor causing inflammation and that the increase of TNF-alpha/sTNF-RI reflects the activation of eosinophil functions in an asthmatic attack.

Adult

A dose-response relationship between the frequency of p53 mutations and tobacco consumption in lung cancer patients.

Mutations of the p53 tumor suppressor gene are frequent in lung cancers. It is suggested that p53 mutations are associated with smoking-induced lung carcinogenesis. We examined p53 mutations in 53 lung cancers by analyzing reverse transcription-polymerase chain reaction-single strand conformation polymorphism (RT-PCR-SSCP) to ascertain the association between p53 mutations and smoking. Twenty-five (47%) of 53 lung cancers carried p53 mutations. A discriminant analysis showed that the Brinkman index (0.156) and gender (0.140) significantly influenced p53 mutations. Furthermore, there was a dose-response relationship between the quantity of cigarettes consumed and the frequency of p53 mutations in lung cancer patients (P < 0.001). In patients with adenocarcinoma, the frequency of p53 mutations correlated with the amount of the tobacco smoked (P < 0.05). We suggest that the p53 gene is a target of particular carcinogen in tobacco smoke.

Adenocarcinoma

Difference in cytokine production in acute and chronic rejection of rat lung allografts.

In Brown Norway to Lewis rat lung transplantation, short-term administration of cyclosporine produces permanent adoption of allografts; however, the adopted grafts show symptoms of chronic rejection. To clarify the difference in cytokine production in acute an chronic rejection of the allografts, an immunohistochemical study was performed. In acute rejection, positive cells for respective cytokines were observed in infiltrating cells, increasing in number as the days after transplantation passed, and reaching a maximum on the fifth day. The strongest reactivity was observed perivenously. In chronic rejection, TNF-alpha positive cells were observed in the perivascular and peribronchial regions, especially around class II positive epithelia. The number of positive cells was, however, less than that in the vascular phase of acute rejection. Few cells were positive for IL-1 beta, IFN-gamma and, unexpectedly, for IL-4. These facts indicate the functional difference of infiltrating cells between acute and chronic rejection.

Animals

[Hansenula anomala fungemia in a patient undergoing IVH-treatment with ascending colon carcinoma].

A case of catheter-related fungemia due to Hansenula anomala is reported. A 61-year-old male was diagnosed as having stage 3 ascending colon carcinoma stenosing the colon severely and was admitted to our hospital to receive an operation of the carcinoma. Just after admission, an intravenous hyperalimentation (IVH) catheter was inserted and IVH was started to prevent development of ileus and to prepare for laparotomy. Nine days later, he developed a fever. On the next day, the IVH catheter was removed and cultures of blood and the catheter revealed the presence of yeast-like organisms that were identified as H. anomala. Laboratory data showed hypogranulocytemia, slight disturbances of liver and kidney, a prolongation of PT, an increase of FDP and positive reaction of candida antigen by CAND-TEC. He improved after the removal of the catheter, and treatment with intravenous infusion of fluconazole 2 days after the removal was thought to be useful for recovery and to prevent the reappearance of infection though susceptibility to fluconazole was not good. Human infections due to H. anomala are rare and this is the 8th case of H. anomala fungemia in Japan. From this report and a review of the literature, risk factors for developing this fungemia include the use and abuse of central venous catheters such as IVH-catheter. It appears that H. anomala has recently emerged as a potential pathogen in the immunocompromised hosts and patients after insertion of central venous catheters and that these organisms should be added to the growing list of unusual fungal pathogens in these patients.

Colonic Neoplasms

Priming effect of platelet activating factor on leukotriene C4 from stimulated eosinophils of asthmatic patients.

BACKGROUND: Eosinophils from asthmatic patients are known to release greater amounts of leukotrienes than normal eosinophils when stimulated by the calcium ionophore A23187. The effect of platelet activating factor (PAF) in priming eosinophils was investigated. METHODS: Eosinophils were obtained from 18 asthmatic patients and 18 healthy donors. Cells separated by the Percoll gradients were incubated with PAF (C-18) for 30 minutes and then stimulated with the calcium ionophore A23187 (2.5 microM) for 15 minutes. The amount of leukotriene C4 (LTC4) in supernatants was measured using a combination of high pressure liquid chromatography and radioimmunoassay. RESULTS: The mean (SD) amount of LTC4 released by eosinophils from asthmatic patients upon stimulation with the calcium ionophore A23187 alone was 27.9 (9.9) ng/10(6) cells (n = 6). The amount of LTC4 released following stimulation with the calcium ionophore A23187 after pretreatment with PAF (1, 5, and 10 microM) was 57.2 (8.9), 75.1 (14.3), and 52.6 (10.7) ng/10(6) cells (n = 6), respectively. Trace amounts of LTC4 (0.9 (0.02) ng/10(6) cells, n = 6) were detected in the supernatant of the cells after stimulation by PAF alone (5 microM). The amount of LTC4 released upon stimulation by calcium ionophore A23187 alone in eosinophils from healthy donors was 10.3 (3.7) ng/10(6) cells (n = 4). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with PAF at concentrations of 1, 5, and 10 microM were 11.9 (3.5), 17.8 (5.6), and 12.7 (5.1) ng/10(6) cells (n = 4), respectively. Trace amounts of LTC4 (0.6 (0.02) ng/10(6) cells, n = 4) were detected in the supernatant of the cells upon stimulation with PAF alone (5 microM). The amounts of LTC4 released upon stimulation with calcium ionophore A23187 after pretreatment with lyso-PAF at concentrations of 1, 5, and 10 microM (n = 4 or 6) were 30.8 (5.2), 22.9 (5.1), and 27.3 (4.3) ng/10(6) cells (n = 6) from the eosinophils of asthmatic patients and 13.7 (3.3), 15.2 (4.9), and 14.7 (3.8) ng/10(6) cells (n = 4) from the eosinophils of healthy donors. CONCLUSIONS: The results indicated that PAF enhanced LTC4 formation by eosinophils obtained from asthmatic patients stimulated with the calcium ionophore A23187, but not those obtained from normal subjects.

Adult

Clinically safe dosage of felypressin for patients with essential hypertension.

Hemodynamic changes were evaluated in patients with essential hypertension when felypressin of various concentrations was administered. The parameters studied were systolic pressure, diastolic pressure, heart rate, left ventricular systolic phase, and endocardial viability ratio. Results showed that blood pressure tended to increase, and the value of 1/pre-ejection period2 (PEP2) tended to decrease, upon administration of 3 ml of 2% propitocaine containing 0.06 international units/ml (IU/ml) of felypressin. Significant increase of blood pressure and decrease in 1/PEP2 was noted upon administration of 3 ml of anesthetic solution containing 0.13 IU/ml of felypressin. No ischemic change of the myocardium was detected even with the highest felypressin concentration (3 ml of 2% propitocaine containing 0.25 IU/ml of felypressin). These results suggest that the clinically safe dosage of felypressin for patients with essential hypertension is approximately 0.18 IU. This amount is equivalent to 6 ml of 3% propitocaine with 0.03 IU/ml of felypressin, which is a commercially available local anesthetic for dental use. It seems that the decrease in 1/PEP2 that occurred during blood pressure increase was due to the increase in afterload caused by contraction of the arterioles. Although in the present study no ischemic change was noted, special care should be taken to prevent myocardial ischemia in patients with severe hypertension.

Analysis of Variance

In vivo effect of prednisolone on release of leukotriene C4 in eosinophils obtained from asthmatic patients.

We investigated the release of leukotriene C4 from eosinophils of asthmatic patients who were treated with or without intravenous prednisolone. The mean level of LTC4 in the supernatant of A23187-stimulated eosinophils obtained from asthmatic patients during an attack was significantly lower with intravenous prednisolone than without prednisolone treatment. Findings suggest that intravenous prednisolone inhibits the release of LTC4 from the eosinophils of asthmatic patients by acting on these cells in vivo.

Adult