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Biomedical subjects

T Watanuki

Publications and source records attributed to T Watanuki.

At least 19 recordsLinked to original sources

An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma.

BACKGROUND: Amplification or overexpression of the c-erbB-2 gene have been reported to correlate with poor patient prognosis in human breast, gastric, and ovarian cancer. Recently, the c-erbB-2 gene product was found to be expressed frequently in the urinary bladder carcinoma. In the current study, the presence of the c-erbB-2 gene product in urinary bladder carcinomas was compared with patient outcome to evaluate whether c-erbB-2 gene product could identify a subset of patients who are destined to have a poor prognosis. METHODS: Immunohistologic study of the c-erbB-2 gene product was done in formaldehyde-fixed paraffin-embedded tissue specimens obtained from 88 transitional cell carcinomas of the human urinary bladder. Eighty-three patients who underwent complete tumor resection by total cystoprostatectomy (30 patients) or by bladder-preserving operations such as transurethral surgery (50 patients) or partial cystectomy (3 patients) entered a follow-up study. The other five patients did not enter the follow-up study because of lost follow-up (2 patients) or distant metastasis at the time of surgery. RESULTS: The c-erbB-2 gene product was expressed in 23 of 88 patients (26%), showing an increase in the expression rate corresponding to the advancement of tumor grade (P < 0.05) and tumor stage (P < 0.2). The 5-year disease-free survival rate was 48.5% for patients with c-erbB-2 negative tumors versus 9.7% for those with c-erbB-2 positive tumors (P < 0.01). The 5-year actuarial survival rate was 65.5% for patients with c-erbB-2 negative tumors versus 41.8% for those with c-erbB-2 positive tumors (P < 0.05). Multivariate analysis using Cox regression model showed that the c-erbB-2 gene product tissue status was a significant prognostic factor independent of grade and stage of the tumor. CONCLUSIONS: The results suggest that the c-erbB-2 gene product could be a tumor marker to identify a malignant subgroup in bladder carcinomas.

Adult

[A retrospective comparison study of patients old and young with non-Hodgkin's lymphoma].

One hundred patients with diffuse non-Hodgkin's lymphoma were treated with combination chemotherapy including adriamycin. Seventy-one patients were under age 70 and 29 were 70 years or older. The clinical characteristics of the two groups were similar, except that the patients showed elevated serum BUN were in the elderly group. The complete remission rate in the elderly patients (66%) was slightly lower than that in the younger patients (75%) (p = NS). The average length of survival in the elderly patients was significantly shorter than in the younger patients (p less than 0.05) (projected 5-year survival: 28 +/- 11% vs 52 +/- 7%). The duration of remission for all patients in the elderly patients did not differ from that in the younger patients (projected 2-year survival: 40 +/- 10% vs 45 +/- 6%). Death during the induction chemotherapy from causes other than lymphoma occurred in 14% of patients over 70-year-old and in one percent of younger patients. At relapse, the response rate was significantly lower in the elderly patients than in the younger patients (CR+PR: 28% vs 78%, p = 0.03). To prevent toxic death in remission induction therapy, drug dose elderly patients should be attenuated according to their general conditions and performance status.

Age Factors

Diffuse large cell lymphoma occurring in a patient with Waldenström's macroglobulinemia. Evidence for the two different clones in Richter's syndrome.

The authors report a 60-year-old man with Richter's syndrome, or diffuse large cell lymphoma (DLCL) occurring in a patient with either chronic lymphocytic leukemia (CLL) or Waldenström's macroglobulinemia (WM). Surface marker analysis revealed that the WM showed mu kappa surface immunoglobulin (Ig) chains, and that the DLCL showed mu lambda Ig chains. Flow cytometric DNA analysis demonstrated DNA content differences between WM and DLCL, the former diploid and the latter aneuploid. The current study suggests that Richter's syndrome derives from two independent B-cell malignancies.

DNA

Expression of c-erbB-2 gene product in urinary bladder cancer.

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.

Antibodies, Monoclonal

Elevated expression of P-glycoprotein in kidney and urinary bladder cancers.

A monoclonal antibody, MRK16, recognizing specifically an epitope of P-glycoprotein (P-GP), a highly active efflux transporter of chemotherapeutic agents, was used to determine the degree of expression of P-GP in the normal human kidney and urinary bladder, and in kidney and urinary bladder cancers. P-glycoprotein was localized in the microvilli of the epithelial cells of the proximal renal tubules by immunoelectron microscopy, and detected immunohistochemically in 6 of 20 untreated kidney cancers and 11 of 31 untreated urinary bladder cancers. Some of the cancerous tissues were further examined with regard to P-GP expression by immunoprecipitation. In urinary bladder cancers, the degree of P-GP expression seemed to be somewhat correlated with tumor grading. These results indicate that our method to detect the degree of expression of P-GP by MRK16 may be applicable for the diagnosis of clinical multidrug resistant urinary cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem

[Electrolyte abnormality and renal insufficiency in malignant lymphoma; clinical and pathological analysis in 123 cases].

The clinical studies about the electrolyte abnormality (EA) in patients with malignant lymphoma (ML) are rarely reported. We analyzed the EA and renal insufficiency in 123 patients with ML between June. 1976 and Jan. 1989; 8 patients with Hodgkin's disease, and 115 patients with non-Hodgkin's lymphoma (NHL). Before treatment, the incidence of the EA was 24.2% and hypercalcemia, hypocalcemia, and hyperkalemia were predominant. After treatment it became to 74.7% and the number of hyponatremia and hypokalemia increased. The incidence of proteinuria and renal insufficiency (serum creatinine above 1.5 mg/dl), were 7.3% and 2.4% before treatment, and became to 26.8% and 26.8% after treatment, respectively. There was a significant difference between two groups with and without the EA before treatment as for serum lactate dehydrogenase (LDH) levels (p less than 0.01), clinical stages (p less than 0.05) and the incidence of bone marrow involvement (p less than 0.01). In 34 autopsied cases, 3 cases showed massive renal involvement and about a half of cases showed various renal changes. The EA before treatment was caused by extrarenal factors, because the incidence of proteinuria and renal insufficiency were almost same to healthy controls. And renal factors play an important role on the E.A after treatment. Above results suggest that the EA before treatment indicates the progress of malignant lymphoma and the EA after treatment means not only the progress of the disease but also therapy-related renal damages.

Adult

[Non-Hodgkin's lymphoma of the nasal cavity and paranasal sinuses: clinicopathologic study of ten cases].

Ten patients with non-Hodgkin's lymphoma originated in the nasal cavity (four patients) and in the paranasal sinuses (six patients) were treated mainly with irradiation and combination chemotherapy including adriamycin. According to the TNM AJC staging system, four patients were in stage T1-T2, and six patients were in stage T3-T4. Nine patients, other than one with stage IV (Ann Arbor) disease, achieved complete remission. Death due to lymphoma occurred in four patients, 4 to 39 months following diagnosis. Three of these patients developed systemic extranodal dissemination, and died in a short time after relapse. Death due to second malignancies occurred in two patients. One died of acute myelogenous leukemia, and the other died of colon cancer, 26 and 53 months after diagnosis, respectively. Four patients were alive and disease-free, from 23 to 68 months following diagnosis (median 40 months). Out of four patients who died of disease, three were in stage T3-T4, and one was in stage T1. Two patients with stage T1 originated in the nasal cavity were both alive and disease-free. Except for lymphomas with stage T1 originated in the nasal cavity, more intensive chemotherapy should be instituted in an attempt to achieve better disease-free survival.

Adult

[Clinical significance of immunophenotype in diffuse non-Hodgkin's lymphoma: with special emphasis on the clinical characteristics of T-cell lymphoma].

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas (NHL) is still controversial. Therefore, we evaluated the prognostic significance of T- and B-cell phenotype in 102 patients having diffuse non-Hodgkin's lymphoma who had been treated in a majority with Adriamycin-containing regimens. The significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of markedly elevated LDH (greater than or equal to X 2 normal) and the lower frequency of decreased cholesterol level in B-NHL (p less than 0.05). Patients with B-NHL had a higher complete remission (CR) rate (77% vs 59%: p = NS), a significantly better overall survival (62% vs 34% at 3-years: p less than 0.05) and longer duration of remission for all patients (50% vs 27% at 3-years: p less than 0.05). Among forty-five patients with stages III and IV disease of nodal origin (excluding those with diffuse small cleaved histology), the B-cell group was associated with a better prognosis; a higher CR rate (68% vs 41%: p = NS) and a longer duration of remission for all patients (44% vs 12% at 2-years: p less than 0.05). Furthermore, for patients with T-cell phenotype, the primary site was the only prognostic factor; the patients whose disease originated from Waldeyer's ring, nasal cavity, and paranasal sinuses, achieved a better CR rate (92% vs 40%: p less than 0.05) and a longer duration of remission for all patients (48% vs 15% at 2-years: p less than 0.05). We conclude that advanced T-cell lymphoma of nodal origin is a subgroup of patients with very poor prognosis if treated with less intensive chemotherapeutic regimens.

Adolescent

Malignant lymphoma of the large intestine--operative results in Japan.

One hundred thirty cases of primary malignant lymphoma of the large intestine in Japan were studied with regard to operative results. The averaged age was 52.6 years and most of the patients were men. Sites of the tumor were the cecum (71.5 per cent), rectum (16.9 per cent) and the ascending colon (6.2 per cent). Surgery was performed for 129 (99.2 per cent) of the 130, of which 71 (55 per cent) were curatively resected. Surgical procedures were mostly Miles operation and the others were anterior resections and hemicolectomies. Postoperative 5 and 10 year survival rates were 34.8 per cent and 33.2 per cent respectively, and the rates after curative resection were 44.2 per cent and 40 per cent respectively. Prognoses were better when the tumor was of 5 cm or less in diameter, intraluminal and without lymph node metastasis. Classified histologically, most of the tumors were of histiocytic type, followed by lymphocytic, mixed type and Hodgkin's disease. Five and ten year survival rates of the curative resection group, by histological type, were both 38.9 per cent for histiocytic type, both 43 per cent for lymphocytic type, 43.8 per cent and 21.9 per cent respectively for mixed type, and both 100 per cent for Hodgkin's disease. Therefore, the operative result of malignant lymphoma in the large intestine was poor compared with results in case of cancer of the large intestine.

Adolescent