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Biomedical subjects

O Maeda

Publications and source records attributed to O Maeda.

At least 55 records · Page 3Linked to original sources
PubMed1995

Establishment and characterization of acquired resistance to platinum anticancer drugs in human ovarian carcinoma cells.

To investigate differences in resistance to cis-diamminedichloroplatinum(II) (CDDP) and diammine (1,1-cyclobutanecarboxylato)platinum(II) (CBDCA), and their newly developed derivative, ((-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum (II) (DWA2114R), four types of resistant cell lines were established from a parental cell line (NOS2) of a serous cystadenocarcinoma of the ovary. The cross-resistance of CDDP-resistant cells (NOS2CR1 and NOS2CR2) to DWA2114R was slight (only 25% of the resistance to CDDP), and no cross-resistance was observed to anticancer drugs other than the CDDP derivative, except to camptothecin (CPT-11) in the case of NOS2CR2 cells. The cross-resistance of CBDCA-resistant cells (NOS2CBR) to DWA2114R was slight (only about 1/3 of the resistance to CBDCA), and no cross-resistance was observed among anticancer drugs other than the CDDP derivative. On the other hand, DWA2114R-resistant cells (NOS2DR) showed a high cross-resistance to CDDP, CBDCA, etoposide (VP-16), and CPT-11. Intracellular accumulations of CDDP and CBDCA were markedly reduced in NOS2CR1, NOS2CR2, and NOS2CBR cells compared to those in NOS2 cells, but were reduced only slightly in NOS2DR cells. Intracellular accumulation of DWA2114R was reduced somewhat in the four types of resistant cells. Glutathione S-transferase activity was not increased in any of the four types of resistant cells, and intracellular GSH concentration was increased only in NOS2CR2 cells (by 2.6 fold). From these results, we consider that the resistance mechanisms against CDDP and CDBCA are similar, and reduction of intracellular drug accumulations is a significant factor. Resistance to DWA2114R differed from resistance to CDDP and CBDCA in both cross-resistance spectrum and resistance mechanism, indicating that reduction in intracellular drug accumulation is not the major resistance mechanism.

Camptothecin↗
PubMed1995

[Multicentricity and concomitant tumors in renal cell carcinoma: analysis by serial section of resected kidneys].

Nephron-sparing surgery was initially limited to the patients with localized renal cancer (RCC) present bilaterally or in a solitary kidney. Recently there is controversy in the indication for partial nephrectomy or enucleation to incidentally defined small RCC with normal opposite kidney. We examined the incidence of multicentricity in 43 kidneys removed for RCC with a diameter of less than 80 mm. The mean diameter of the predominant tumors was 45 mm (range 12 to 80 mm). The kidneys were serially sectioned at 5 mm intervals. Three of 43 kidneys (7%) had multiple RCC. The size of the concomitant tumors ranged from 2 to 15 mm. The multicentricity had no relation to pathological grade, stage, vascular invasion or infiltration pattern. In addition, the other 4 kidneys had 2 adenomas, 1 angiomyolipoma and 1 fibroma. Therefore we observed a 16% incidence of small renal nodules and a 7% multicentricity of RCC in the nephrectomized kidneys with normal opposite kidney.

Adenoma↗
PubMed1995

Preoperative endocrine therapy in patients with locally advanced prostate cancer.

Recently, there has been increased interest in the application of preoperative endocrine therapy prior to radical prostatectomy for locally advanced cancer in order to enhance surgical curability and increase survival. Between 1986 and 1993, 40 patients with prostate cancer were given endocrine therapy before radical prostatectomy. Fifteen patients had stage B2 disease and 25 stage C. The median duration of preoperative endocrine therapy was 3.8 months, and all the patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was an average 25.5% (0-71.8%) decreases in the maximal cross-sectional area of the prostate gland as determined by transrectal ultrasonography. Twenty-four of 25 patients with elevated levels of serum prostate-specific antigen (PSA) showed normal values after preoperative endocrine therapy. Evaluation of treatment-related histological effects, divided into three grades, revealed that 17 patients had pronounced, 11 moderate and 12 poor or no regression. Thirteen of the 40 patients (33%) demonstrated pathological downstaging of disease status from the diagnosis made at the initial clinical examination. After a median follow-up period of 36 months (3-100 months), 36 of the 40 patients are disease-free; two died of cancer 43 and 50 months after surgery, respectively. These results suggest that preoperative endocrine therapy may play an important role in the management of locally advanced prostatic cancer.

Adenocarcinoma↗
PubMed1994

Differential diagnosis of ovarian tumors by transvaginal color-pulse Doppler sonography.

To investigate the clinical significance of transvaginal color-pulse Doppler sonography in ovarian tumors, 109 patients were examined at Nagoya University Hospital. Ultrasonographic patterns were classified and the levels of three circulating tumor markers, CA125, CA72-4, and CA19-9, were simultaneously evaluated. In differentiating benign and malignant ovarian tumors, transvaginal color-pulse Doppler and ultrasonographic pattern classification were superior to the tumor markers. Of 49 cases with benign pattern, 45 were benign (91.8%). Of 60 cases with malignant pattern, 24 (40%) were benign and 36 (60%) were malignant or borderline malignant. In this group color-pulse Doppler sonography was the most useful procedure, and sensitivity, specificity, and accuracy were 75.0, 79.2, and 76.7%, respectively. Menopausal status and site of the arterial wave form in the tumor were also important. Transvaginal color-pulse Doppler sonography was a reliable diagnostic method for differentiating ovarian tumors.

Adenocarcinoma↗
PubMed1994

Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer.

A total of 20 patients with primary invasive bladder cancer who underwent radical cystectomy received postoperative adjuvant chemotherapy using a CAP (cyclophosphamide, doxorubicin, and cisplatin) or modified M-VAC (methotrexate, vinblastine, pirarubicin, and cisplatin) regimen. In all, 16 of the patients were treated with CAP and 4 received the modified M-VAC regimen. Of the 20 patients, 17 had transitional-cell carcinoma with or without non-transitional-cell elements. All of the patients had tumors with a histological grade of G2 (6 cases) or G3 (14 cases). As for lymph-node metastasis, there were ten N0 cases, three N1 cases, six N2 cases, and one N3 case. Adjuvant chemotherapy was usually commenced 2 weeks after the surgery and was given every 3-4 weeks for two or three cycles. The 5-year survival rate of these 20 patients was 65.9%, whereas that of 49 patients who did not receive any adjuvant chemotherapy was 30.2%. Regarding toxicity, both of the adjuvant chemotherapy regimens used in this study were generally well tolerated. The most common toxic effects were gastrointestinal symptoms, alopecia, and myelosuppression. Another 19 patients with invasive transitional-cell carcinoma of the bladder received 2 or 3 cycles of neoadjuvant chemotherapy using the modified M-VAC or MEC (methotrexate, epirubicin, and cisplatin) regimen. Of 18 pathologically evaluable patients who underwent radical cystectomy or partial cystectomy, the stage was pT0 in 3 cases (17%), pTis in 3 (17%), pT1 in 3 (17%), and pT2 or higher in 9 (50%). The 4-year survival rate of 18 patients who received neoadjuvant chemotherapy was 71.5%. Regarding toxicity, one patient died of a bowel complication after surgery, and the complication was suggested to be drug-induced.

Adenocarcinoma↗
PubMed1994

Different pattern of zymography between human gynecologic normal and malignant tissues.

OBJECTIVE: Our purpose was to evaluate type IV collagenase in ovarian and endometrial cancer tissues. STUDY DESIGN: Tissue specimens were obtained from patients with ovarian and endometrial cancer and uterine myoma. Gelatinase activity was detected by zymography and quantitated by densitometer. RESULTS: Four dominant gelatinases were detected in ovarian and endometrial cancer tissues: 200, 130, 92, and 72 kd gelatinase. Other forms observed were 83 kd gelatinase, which is an active form of 92 kd gelatinase, and 66 kd gelatinase, which is an active form of 72 kd gelatinase. Densitometric analysis showed that the 92 kd/72 kd ratio in ovarian cancer tissues was significantly higher than in normal ovarian tissues (p < 0.05) and that the 66 kd/72 kd ratio was higher in ovarian cancer tissues (p = 0.07). Both ratios in endometrial cancer tissues were significantly higher than in normal endometrial tissues (p < 0.05). CONCLUSION: Gelatinase activity was remarkably higher in ovarian and endometrial cancer tissues. Especially, 92, 83, and 66 kd gelatinases were clearly detected in cancer tissues, suggesting that these gelatinases were related to the malignant phenotype, because degradation of the components of the basement membrane such as type IV collagen is necessary for cancer cells to metastasize.

Adult↗
PubMed1994

Sensitisation of human ovarian carcinoma cells to cis-diamminedichloroplatinum (II) by amphotericin B in vitro and in vivo.

Human ovarian carcinoma cells (HRA) were sensitised to cis-diamminedichloroplatinum (II) (CDDP) 2.7-, 5.5- and 12.1-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4 and 10.8 microM, respectively. Moreover, intracellular accumulation of platinum after a 2-h exposure to CDDP was increased significantly with AMB treatment. We prepared HRA cell-inoculated nude mice as an experimental therapeutic model for human advanced ovarian carcinoma. Ascites was evident after 7 to 9 days of intra-peritoneal (i.p.) inoculation of HRA cells, and mice died due to intra-abdominal carcinomatosis after 11 to 14 days [mean survival time (MST): 12.4 +/- 1.1 days]. Treatment with AMB (2.0 mg/kg) alone 4 days after inoculation increased MST by only 1.4 days. Simultaneous treatment with CDDP (1.0 to 2.0 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CDDP alone. Maximal MST (30.1 days) was observed by treatment with 2.0 mg/kg CDDP plus 2.0 mg/kg AMB, whereas MST with 2.0 mg/kg CDDP alone was 16.4 days. A further drug accumulation study demonstrated that platinum accumulation in tumour tissues in nude mice treated with CDDP and AMB increased significantly compared to treatment with CDDP alone. These results indicate that intraperitoneal combination chemotherapy with CDDP and AMB is effective in an experimental animal model of advanced ovarian carcinoma.

Amphotericin B↗
PubMed1994

Potentiation of cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) by amphotericin B in BALB/c nude mice bearing human ovarian carcinoma cells.

Human ovarian carcinoma cells (HRA) were sensitized to cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) 1.2-, 2.1- and 3.4-fold by treatment with amphotericin B (AMB) at concentrations of 2.1, 5.4, and 10.8 microM, respectively. Moreover, the intracellular accumulation of platinum after 2-h exposure to CBDCA was increased significantly by AMB treatment. For estimating the enhancing effect of AMB on CBDCA cytotoxicity in vivo, we prepared HRA cell-inoculated nude mice. Ascites was evident 7 to 9 days after intraperitoneal (i.p.) inoculation of HRA cells, and the mice died of intraabdominal carcinomatosis 11 to 14 days (mean survival time (MST): 12.0 +/- 1.0 days) after inoculation. Treatment with AMB (2.0 mg/kg) alone increased the MST by only 1.2 days. Simultaneous treatment with CBDCA (12 or 15 mg/kg) and AMB (0.5 to 2.0 mg/kg) produced a significant increase in MST compared to treatment with CBDCA alone. Maximal MST (38.5 days) was obtained by treatment with 15 mg/kg CBDCA plus 2.0 mg/kg AMB, whereas the MST with 15 mg/kg CBDCA alone was 15.8 days. A drug accumulation study demonstrated that platinum accumulation in tumor tissues after i.p. treatment with CBDCA and AMB in tumor-bearing nude mice was increased significantly compared to treatment with CBDCA alone. These findings indicate that intraperitoneal combination chemotherapy with CBDCA and AMB is useful in nude mice with advanced ovarian carcinoma.

Amphotericin B↗
PubMed1994

Recurrence of epithelial ovarian carcinoma after clinical remission.

One hundred and eighty-eight patients with epithelial ovarian carcinoma were treated with primary cytoreductive surgery and subsequent combination chemotherapy. The first recurrent findings such as sites and disease-free interval were analyzed in 141 patients who were clinically remitted 6 months after operation or chemotherapy. Fifty-seven cases had a recurrence. Five-year disease-free survival rates were 75, 72, 29, and 0% in stage I, II, III, and IV, respectively. Twenty-one of 22 patients with > 2 cm maximum residual tumor died, although they once achieved clinical remission. Significant differences were observed between histologic types, and the disease-free survival rate was lowest for serous cystadenocarcinoma. Nine of 15 stage IV patients with serous histology experienced remission, but none of the 8 in stage IV with other histologies did so, suggesting that serous adenocarcinoma is sensitive to chemotherapy and conducive to clinical remission. However, all stage IV patients in remission encountered a recurrence. Intra-abdominal cavity and lymph node were frequently the initial recurrent sites (38 and 27%, respectively). On the other hand, the incidence of distant recurrence was as high as 27%, and 8 of 16 cases with distant recurrence were stage I. Survival time after recurrence was not different among initial sites of recurrence and mean survival time was 15 months.

Female↗
PubMed1993

A newly synthesized bifunctional inhibitor, W-77, enhances adriamycin activity against human ovarian carcinoma cells.

A newly synthesized calmodulin antagonist, (S)-P-(2-aminoethyloxy)-N-[2-(4-benzyloxy-carbonylpiperazinyl++ +)-1-(P-methoxybenzyl)ethyl]-N-methylbenzenesulfonamide dihydrochloride (W-77), acts as a calcium-independent uncompetitive antagonist which binds to glutathione-S-transferase (GST). We purified GST from human placenta using drug affinity chromatography on a column of W-77 coupled with Sepharose 6B and demonstrated that W-77 bound to GST. A spectrophotometric assay also showed that W-77 inhibited GST activity. We prepared Adriamycin-resistant and -sensitive cells from human ovarian serous cystadenocarcinomas. Immunoblot analysis revealed that GST expression was increased in the Adriamycin-resistant cells. We also purified GST from Adriamycin-resistant cells and found that W-77 bound to the GST obtained from these ovarian carcinoma cells. Adriamycin resistance was partially overcome by the addition of W-77 (10 microM) to the cultured cells. In addition, we investigated the effect of W-77 on P-glycoprotein. Northern blot analysis revealed MDR1 gene expression in Adriamycin-resistant cells. Although W-77 was less potent in increasing the intracellular Adriamycin content than verapamil, it was more effective in overcoming Adriamycin resistance. These results suggest that W-77 enhances the antitumor activity of Adriamycin by inhibiting both GST and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Prognostic significance of bone metastases in patients with metastatic prostate cancer.

BACKGROUND: The distribution of bone metastases on a bone scan has not been duly considered when assessing the prognosis of metastatic prostate cancer. METHODS: The medical records of 76 patients with newly diagnosed, untreated metastatic prostate cancer were reviewed. According to the distribution of bone metastases on the initial bone scan, we divided the patients into three groups: Group I (having bone metastases exclusively within the pelvis and the lumbar spine), Group II (having bone metastases exclusively outside these bones), and Group III (having bone metastases in both areas). RESULTS: Among the responders to androgen deprivation, those in Group I survived significantly longer than did those in Groups II or III. Because the extent of the disease and the distribution of histologic differentiation in Groups I and II were similar, the results indicate that the presence of bone metastases outside the pelvis and the lumbar spine is predictive of short survival time. This prediction was not possible when the extent of disease (EOD) grading system was used. CONCLUSION: The distribution of bone metastases on the initial bone scan should be considered as a variable for the prognostic stratification of patients with metastatic prostate cancer.

Adenocarcinoma↗
PubMed1993

Randomised study of immunotherapy with OK-432 in uterine cervical carcinoma.

OK-432, a streptococcal preparation, was administered to patients with stage Ib and II cervical carcinoma except for adeno- and adenosquamous carcinomas. To evaluate the efficacy of OK-432 precisely, 177 patients were stratified by clinical stage, radiotherapy, and lymph node metastasis after complete radical hysterectomy and pelvic lymphadenectomy. Within each stratum, patients were divided randomly into OK-432 and control groups. 85 patients received OK-432 and 92 patients did not. No significant difference was observed in overall 5-year disease free rates between the OK-432 and the control groups, although the mean diameter of erythema on SU-polysaccharide (SU-PS) skin test was larger in the OK-432 group than in the control group. In stage IIb, a significant difference was observed between the OK-432 and control groups. This difference, however, could be attributed in part to the different incidence of the lymph node metastasis. In stage II without lymph node metastasis, 5-year disease free rate was significantly higher in the OK-432 group.

Adult↗
PubMed1993

[Neoadjuvant therapy for prostatic cancer].

Neoadjuvant therapy for prostatic cancer might be important to increase cure rates of the disease and preservability of the organs. There were 43 cases in a period of 1975-1990 in which total prostatectomy were performed after neoadjuvant therapy. According to the clinical stage, there were 14 cases in B, 23 in C, 4 in D1 and 2 in D2. The median duration of neoadjuvant therapy was 4 months. Clinical response of the prostate in 37 evaluable cases was as follows; 6 cases were PR (16%), 12 cases were MR (32%) and 19 cases were NC (52%). Histopathological effect was as follows; 5 cases were grade 0a (12%), 12 cases were grade 0b (28%), 16 cases were grade 1 (37%), 8 cases were grade 2 (19%) and 2 cases were grade 3 (5%). In 2 cases with histopathological effect of grade 3, lymph node metastases were thought to have obviously disappeared. Histopathological effect seemed related to clinical response. In cases given neoadjuvant therapy for less than 2 months, no adequate clinicopathological effect was obtained. Cases that could achieve downstaging were 8; 1 in grade 0a, 2 in grade 1, 3 in grade 2 and 2 in grade 3. These results suggest that neoadjuvant therapy plays an important role in advanced prostatic cancer.

Aged↗
PubMed1993

[Successful interferon therapy of renal cell carcinoma with tumor thrombus extending into the inferior vena cava--a case report].

It is a fact that there are few effective drugs available except for interferon for that treatment of renal cell carcinoma, and the efficacy rate of interferon is less than 10% even if multiple drug regimens are included. We have experienced a case of renal cell carcinoma in whom interferon therapy was successful in reducing the primary lesion and tumor thrombus extending into the inferior vena cava. A 57-year-old man was admitted to our department with a complaint of macroscopic hematuria. Computed tomography and magnetic resonance imaging revealed a right renal tumor and the tumor thrombus. Because of the past history of his myocardial infarction, a radical operation was considered risky. So we started interferon therapy. Four months after the start of interferon therapy, the primary lesion and the tumor thrombus markedly reduced in their size, and the clinical response was evaluated as partial response by response criteria for urological cancer treatment. Therefore, radical nephrectomy and tumor thrombectomy were performed with extracorporeal circulation. Histopathologically, necrosis and lymphocyte infiltration into the cancer cell focus were seen, and these immunologic reactions were considered at the affection of interferon. In some case, interferon therapy is a useful and safe in the treatment of the primary lesion of renal cell carcinoma, and further investigation must be studied.

Carcinoma, Renal Cell↗
PubMed1993

[Tuberculosis of the female urethra: a case report].

A 52-year-old female with the chief complaint of miction pain was referred for the examination of a urethral nodule. Physical inspection revealed the meatus to be reddish and swollen. The painless nodule (1 x 1 x 2 cm) was situated between the urethra and vagina on transvaginal examination. Chest X-ray, drip infusion pyelography (DIP) and urethrocystography (UCG) showed no evidence of tuberculosis. Bladder mucosa was normal on cystoscopy. Mycobacterium tuberculosis was not detected from urine or sputum. The nodule was resected along with a portion of the urethra. Histopathological examination revealed tuberculous granuloma of the urethra.

Drug Therapy, Combination↗
PubMed1992

Calpain II-like proteinase of scallop (Patinopecten yessoensis) striated adductor muscle.

1. A Ca(2+)-dependent cysteine proteinase was purified from scallop striated adductor muscle by ammonium sulfate fractionation and column chromatography on DEAE-cellulose and Sephacryl S-300. 2. The enzyme is of Mr approximately 200,000, composed of two Mr 100,000 subunits. 3. The enzyme is a cysteine proteinase with optimum activity at pH 6.8 and about 18 degrees C. In addition, it requires 1.7 mM Ca2+ for half-maximal activity and more than 10 mM Ca2+ for maximal activity. Thus the enzyme can be classified as calpain II.

Animals↗