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Biomedical subjects

K Koshida

Publications and source records attributed to K Koshida.

At least 37 records · Page 2Linked to original sources

Chemotherapy of metastatic testicular germ cell tumors: relationship of histologic response to size reduction and changes in tumor markers.

BACKGROUND: Although testicular germ cell tumor is one of the most curable cancers, approximately 20% of advanced cases remain incurable. In this study we investigate factors that may predict a poor response to standard chemotherapeutic regimens and thus allow earlier initiation of more aggressive measures. METHODS: We analyzed the records of 19 patients with metastatic testicular germ cell tumors (8 seminomas and 11 nonseminomas). Sixteen patients underwent surgical exploration for residual tumors following chemotherapy, and the histological findings on the resulting specimens were correlated with reductions in tumor size observed on computed tomography and with changes in tumor marker levels. RESULTS: Complete necrosis was obtained in 10 of 12 lesions that shrank by at least 80%, while continued existence of teratoma or cancer was confirmed in 9 of 11 lesions with smaller size reductions. An initial human chorionic gonadotropin-beta subunit (HCG-beta) level more than 100 times the upper limit of normal appeared to predict poor histological response (teratoma/cancer) to chemotherapy. Slow fall (prolonged half-life) of tumor markers during chemotherapy also correlated with poor histological response. CONCLUSION: Factors which predict poor histological response of tumors to chemotherapy include size reduction less than 80%, initial HCG-beta levels more than 100 times the upper limit of normal, and prolonged half-life of tumor markers (placental alkaline phosphatase, alpha-fetoprotein and HCG-beta).

Antineoplastic Combined Chemotherapy Protocols↗

A chick embryo model for metastatic human prostate cancer.

OBJECTIVE: To establish a suitable experimental model of bone and liver micrometastases from human prostate cancer for evaluating antitumor agents. METHODS: PC-3 cells, an androgen-independent prostate cancer cell line, were inoculated into the chorioallantoic membrane vein of 10-day-old chick embryos (10(6) cells/egg). The polymerase chain reaction product for the human beta-globin gene in chick embryo femur and liver was quantified at various time points after inoculation, when immunohistochemical staining was done for Ki-67 antigen and cytokeratin. The antitumor effect of suramin was evaluated using the model, as was regional blood flow after thallium injection. RESULTS: Micrometastases were identified in bone and liver 1 day after inoculation and grew to form established metastatic foci in all embryos. Suramin showed significant antitumor effect for liver metastases, but not for those in bone where blood flow was relatively low. CONCLUSION: The chick embryo system provides a highly reproducible model for bone and liver micrometastases from human prostate cancer, suitable for evaluating antineoplastic agents at an early stage of the metastatic process.

Animals↗

Detection of human telomerase reverse transcriptase messenger RNA in voided urine samples as a useful diagnostic tool for bladder cancer.

Activation of telomerase and stabilization of telomeres are thought to be required for cellular immortality and oncogenesis. Telomerase activity is detected in >90% of various cancers, including urothelial cancers. Of the three subunits comprising telomerase complex, human telomerase reverse transcriptase (hTERT) is a rate-limiting determinant of the enzymatic activity of telomerase. In the present study, spontaneously voided urine specimens from 33 patients with bladder cancer and 26 without bladder lesions were examined for the expression of hTERT mRNA, and the usefulness of detecting hTERT mRNA in urine samples for screening of bladder cancer was evaluated. RT-PCR analysis revealed that approximately 80% of urinary sediments from patients with bladder cancer expressed hTERT mRNA, regardless of clinical stage or pathological grade, whereas only 4% of sediments from patients without urothelial lesions did. Interestingly, hTERT mRNA expression was observed, even in some urine samples from bladder cancer patients with negative urinary cytology. These findings suggest that the expression of hTERT in urine sample may be a useful diagnostic marker for bladder cancer.

Aged↗

Factors contributing to imaging of xenografts using anti-placental alkaline phosphatase monoclonal antibody.

PURPOSE: To investigate factors that influence the imaging of placental alkaline phosphatase (PLAP) producing xenografts using an anti-PLAP monoclonal antibody (MAb). MATERIALS AND METHODS: Three xenografts (human seminoma, HeLa Hep 2 cells, and KK-47 bladder cancer cells) each expressing PLAP to a different degree were used to immunolocalize an anti-PLAP MAb, HPMS-1. RESULTS: Although the highest PLAP level was found in seminoma xenografts, the MAb was not useful for the imaging of seminoma xenografts because of poor accumulation. Fragmentation of the MAb, such as F(ab)2, however, was shown to be efficient for imaging seminoma xenografts. A distribution study with T1-201 revealed the highest blood flow in HeLa cells and the lowest in seminoma. A difference in blood flow may partially explain the disparity between the amount of MAb accumulation and the level of antigen expression in these three xenografts. CONCLUSIONS: Blood flow in targeted tumors was shown to be more critical than their level of antigen expression for the imaging of xenografts with anti-tumor antibody. In addition, fragmentation of the MAb enabled tumor imaging because of a rapid clearance of the fragment from the circulation.

Alkaline Phosphatase↗

Significance of placental alkaline phosphatase (PLAP) in the monitoring of patients with seminoma.

OBJECTIVE: To investigate the significance of placental alkaline phosphatase (PLAP) as a tumour marker for seminoma. PATIENTS AND METHODS: A total of 673 serum samples from 116 patients with testicular germ cell tumours (78 seminomas and 38 non-seminomas) were analysed for several markers including PLAP, total alkaline phosphatase (AL-P), alpha fetoprotein (AFP), beta human chorionic gonadotrophin (HCG-B), and lactic dehydrogenase (LDH). RESULTS: Serum PLAP was increased initially in about 50% of patients with seminoma, and the mean magnitude of elevation was about five times the normal value. There was no significant correlation between PLAP and LDH or between PLAP and HCG-B. Therefore, a combination of these three markers was of value, and resulted in a positive identification rate of 82% of patients with seminoma. False-positive results for PLAP appeared in 1.6% of 673 samples investigated. CONCLUSION: The monitoring of serum PLAP might be of value, as fluctuations in this marker provide information about disease status and prognosis.

Adult↗

Serum and tissue levels of manganese superoxide dismutase in testicular germ cell tumors.

OBJECTIVE: To investigate the potential of manganese superoxide dismutase (MnSOD) as a tumor marker for seminoma. MATERIALS: A total of 44 patients with testicular germ cell tumors were assessed for serum and tissue levels of MnSOD in comparison with levels of placental alkaline phosphatase (PLAP). RESULTS: Positive rates of serum MnSOD were 11% for stage I, 25% for stage II and 80% for stage III. No difference was observed in serum MnSOD between seminoma and NSGCT. No difference was demonstrated in tissue MnSOD level between seminoma and NSGCT, or between tumors and their normal counterparts. CONCLUSION: Since serum MnSOD was shown to have lower sensitivity than PLAP, and MnSOD concentration did not differ significantly between tumors and their normal counterparts, the role of MnSOD as a marker for seminoma appears to be limited.

Alkaline Phosphatase↗

A potential use of a monoclonal antibody to placental alkaline phosphatase (PLAP) to detect lymph node metastases of seminoma.

PURPOSE: To evaluate the ability of monoclonal antibodies against alkaline phosphatase (AL-P) for tumor immunolocalization in nude mice. MATERIALS AND METHODS: Two monoclonal antibodies against placental alkaline phosphatase (PLAP) and liver alkaline phosphatase (LAP) were intravenously administered to nude mice bearing AL-P producing HeLa Hep 2 tumors. Sera and tumors from 65 patients with testicular germ cell tumors were examined for PLAP levels. RESULTS: Levels of PLAP or LAP in the HeLa xenografts were shown to be comparable to levels of PLAP in seminomas, including lymph node metastases, or nonseminomas, respectively. A biodistribution study showed that the percentage of the injected dose of I-125 labelled anti-PLAP in the xenografts was rather constant at around 7% until 7 days after injection, while the percentage of the injected dose of I-125 labelled anti-LAP MAb decreased with time as in other tissues which do not contain significant amounts of PLAP or LAP. On scintiscan, the xenografts in nude mice were distinctly visualized at 7 days after injection of anti-PLAP MAb. CONCLUSIONS: These data may support the potential use of the anti-PLAP MAb for the immunodetection of lymph node metastases of seminoma.

Alkaline Phosphatase↗

Radiofrequency capacitive hyperthermia combined with irradiation or chemotherapy for patients with invasive bladder cancers.

To assess the immediate therapeutic clinical efficacy and long-term outcome, hyperthermia in combination with irradiation or chemotherapeutic agent was used in 46 patients with invasive bladder cancer. Radiohyperthermia (RH) was employed in 19 cases and chemohyperthermia (CH) in 27 cases. Complete response (CR) was obtained in 5 and partial response (PR) in 15 of the 46 cases. One-year survival rates by the Kaplan-Meier method were 65.0% in the CR/PR group and 46.2% in the no change (NC)/progressive disease (PD) group. Five-year survival rates were 43.8% and 18.3%, showing no difference in survival rate between the CR/PR group and the NC/PD group The overall median survival period for the CR/PR group without metastasis was 61.6 months compared to 32.3 months for the NC/PD group without metastasis (P < 0.05).

Adult↗

Whole bladder wall photodynamic therapy for refractory carcinoma in situ of the bladder.

Whole bladder wall photodynamic therapy (PDT) with haematoporphyrin derivative and an argon dye laser as a light source was performed on 34 patients with refractory carcinoma in situ (CIS) of the bladder. Twenty-five of the 34 patients (73.5%) had achieved a complete response (CR) at 3 months after the treatment. The median follow-up for these CR patients is 49.3 months. Although recurrence within 2 years of follow-up occurred in 14 (77.8%) of the 18 CR patients followed to that point, since most of the recurrent tumours were superficial and low-grade papillary tumours, transurethral resection of the bladder tumours appeared to be sufficient. Of the total of 34 patients, ten were alive with bladder intact with a mean follow-up period of 64.0 months. Skin photosensitivity and transient decrease in bladder capacity were noted as adverse reactions, caused by retention of haematoporphyrin derivative in the skin and normal portion of the bladder. These data suggest that PDT can be an effective form of therapy for CIS of the bladder.

Aged↗

Adjuvant therapy with 5-fluoro-1-(2-tetrahydrofuryl)-2,4 (1H,3H)-pyrimidinedione (UFT) and Bestatin in patients with transitional cell carcinoma of the bladder--comparison between UFT therapy alone and UFT therapy in combination with Bestatin.

To prevent postoperative recurrence a randomized prospective trial was performed on 45 patients with bladder cancers by dividing them into 2 groups given either UFT therapy alone or UFT therapy in combination with Bestatin. In principle, oral administration of these drugs was initiated 4 weeks postoperatively and continued for a period of 1 year. Bestatin was given at the dose of 30 mg/day after breakfast per os, and UFT at the dose of 400 mg/day twice a day per os. After a median follow-up period of 628 days the relapse-free rate was 43.5% for the group given UFT alone and 81.8% for the group given a combination of UFT plus Bestatin, showing a significantly more favorable result in the latter group. In patients with a solitary and papillary tumor the relapse-free rate was significantly better in the UFT plus Bestatin group compared with the group of UFT alone. Accordingly, it was suggested that postoperative administration of UFT in combination with Bestatin is more effective in preventing recurrence of bladder cancer, compared with the administration of UFT alone.

Administration, Oral↗

Possible advantages of aluminum-chloro-tetrasulfonated phthalocyanine over hematoporphyrin derivative as a photosensitizer in photodynamic therapy.

The potency of aluminum-chloro-tetrasulfonated phthalocyanine (AlS4Pc) as a photosensitizer in photodynamic therapy was evaluated in in vitro and in vivo studies. Compared with hematoporphyrin derivative (HpD), the following advantages of AlS4Pc were revealed: (1) AlS4Pc was less toxic than HpD in vitro without light irradiation. (2) AlS4Pc showed more photodynamic-dependent cytotoxicity and anti-tumor effect in the red area of the spectrum (> 660 nm) at which tissue penetration is high. (3) AlS4Pc appeared to be removed more rapidly from normal tissues such as muscle and skin. (4) AlS4Pc showed less photodynamic-dependent cytotoxicity in vitro and milder cutaneous phototoxicity in vivo with UVA irradiation. On the basis of these observations, AlS4Pc shows considerable promise as a photosensitizer for PDT.

Animals↗

Immunopathology of alkaline phosphatase isozymes in seminoma.

An immunohistopathological study using monoclonal antibodies for alkaline phosphatases demonstrated placental alkaline phosphatase (PLAP)-like substance in the tumor cells of 11 pure seminomas, 1 seminoma with embryonal carcinoma and 1 seminoma metastasis. Liver alkaline phosphatase (LAP) could also be demonstrated in all seminomas but a third intestinal alkaline phosphatase (IAP) was not demonstrable in any tumor. The PLAP-like substance and LAP had considerable enzyme activities. This provides two tumor markers of seminomas detectable in histopathological specimens.

Alkaline Phosphatase↗

Percutaneous mitomycin C perfusion of bilateral ureteral carcinoma in situ.

We treated a 61-year-old patient with a diagnosis of bilateral ureteral carcinoma in situ with percutaneous perfusions of mitomycin C. After 16 sessions of mitomycin C therapy instilled through bilateral nephrostomy tubes, the urine cytology results became negative for malignancy. Bilateral ureteroscopy and cold-cup punch biopsies of the ureter revealed no evidence of disease. The patient did not experience side effects. He has remained free of disease during a 12-month follow-up period. Percutaneous perfusion of mitomycin C appears to be one of the effective and safe treatments for the carcinoma in situ of the upper urinary tract.

Antineoplastic Combined Chemotherapy Protocols↗

Studies of temperature rise in bladder cancer and surrounding tissues during radiofrequency hyperthermia.

Temperatures in the tumor on the bladder wall, tumor margin, intravesical urine, rectal cavity and pubic subcutaneous fat tissue (SCFT) were measured in a total of 48 bladder tumor patients during radiofrequency (RF)-capacitive heating of the tumors. There were close correlations (p less than 0.01) between the temperature of the tumor margin and intratumor temperature, between the intravesical temperature and the temperature of the tumor margin, between the RF power applied and the intravesical temperature and also between the thickness and the temperature of SCFT. As long as the thickness of SCFT was 20 mm or less, it was possible to raise the temperature of bladder cancer to 42.5 degrees C or above. The intravesical temperature could be regarded as an indicator for hyperthermia treatment since the intravesical urine temperature of over 42 degrees C implied a therapeutic temperature of 42.5 degrees C or more in the margin of the tumor. Since the intravesical temperature was closely related to the output power, the therapeutic magnitude of the output power could be defined at least as 400 W, by which intravesical urine temperature could exceed 42 degrees C.

Adipose Tissue↗

[A case of retroperitoneal Castleman's disease associated with bladder tumor and a review of 59 cases in Japan].

We present a case of retroperitoneal Castleman's disease associated with bladder tumor. The patient was a 62-year-old man, who underwent partial cystectomy under a diagnosis of bladder tumor in 1989. Subsequently, recurrent bladder tumor was detected and he consulted the outpatient clinic at our University Hospital in November, 1990, at which time computerized tomography (CT) revealed a retroperitoneal tumor. From February, 1991 four courses of combined chemotherapy (methotrexate, vinblastine, pirarubicin, cisplatin) were administered for the tumor. The tumor reduction rate after the chemotherapy was 60% on CT, and retroperitoneal lymph node dissection and left nephroureterectomy were performed in July, 1991. Histological examination revealed Castleman's disease, hyaline-vascular type. Fifty-nine reported cases of retroperitoneal Castleman's disease in Japan are reviewed.

Castleman Disease↗

[Experimental and clinical evaluation of functional electrical stimulation of the anal sphincter].

To determine the most effective parameter of functional electrical stimulation of the anal sphincter (FES), the present study was carried out in female mongrel dogs anesthetized with alpha-chloralose urethane. When spontaneous and rhythmic micturition contractions of the bladder were present, they were more effectively inhibited by the stimulation with low frequency (5 to 10 Hz). Based on the results of this experiment 18 patients with urge incontinence were treated by maximal electrical stimulation with the following parameters. The duration for each stimulus was 0.2 msec, frequency 5 Hz, amplitude 30 to 150 volts. Every patient received ten treatments for two weeks, each lasting for 30 minutes. A clinical cure for urge incontinence was noted in 12 patients. As for urodynamic studies, FES increased significantly the volumes of the first desire to void (FDV) and maximum desire to void (MDV); however, it did not increase significantly the maximum urethral closure pressure or residual urine volume. Eighteen patients were divided into two groups; an unstable bladder group and a neurogenic bladder group. In the latter, the increases in volumes of FDV and MDV were significant. Second, 18 patients were divided into two groups according to the administration of lack of anticholinergic agents. For subjective symptoms, the rate of improvement of urge incontinence was significantly higher in the group administered the agents. These findings suggested that FES was very useful for the treatment of urge incontinence, with its efficacy augmented by the administration of anticholinergic agents.

Aged↗

The role of alkaline phosphatase isoenzymes as tumor markers for testicular germ cell tumors.

The role of serum alkaline phosphatase as a tumor marker for testicular germ cell disease was investigated in 26 patients with testicular seminoma and 13 with nonseminomatous germ cell testis tumors. Placental alkaline phosphatase-like enzyme was elevated in 50% of the stage I seminoma patients and in all patients with stages II to III disease. In addition, liver (tissue unspecific) alkaline phosphatase was elevated in 10 and 83% of the patients, respectively. Lactic dehydrogenase and beta-human chorionic gonadotropin (beta-HCG) were detected in 50 to 60% of the patients with stage I seminoma. By combining placental alkaline phosphatase-like enzyme, lactic dehydrogenase and beta-HCG, 75% of the stage I and 100% of the stages II and III seminoma patients could be identified correctly. Placental alkaline phosphatase-like enzyme in serum also occurred with nonseminomatous germ cell tumor but less frequently, while liver alkaline phosphatase was not detected at all. Thus, placental alkaline phosphatase-like enzyme and liver alkaline phosphatase were predominantly determined in the serum of patients with seminoma. In studies of tumor tissues from 31 of these patients, those with normal serum placental alkaline phosphatase-like enzyme levels had significantly lower tissue placental alkaline phosphatase-like enzyme levels than patients with elevated serum levels (p less than 0.01). Seminoma tissues showed significantly higher levels of placental alkaline phosphatase-like enzyme and liver alkaline phosphatase than nonseminomatous germ cell tumors (p less than 0.01), explaining the infrequent elevation of serum placental alkaline phosphatase-like enzyme and liver alkaline phosphatase found in patients with nonseminomatous germ cell tumors.

Alkaline Phosphatase↗

Identification and characterization of alkaline phosphatase isozymes in human colorectal adenocarcinomas.

Using alkaline phosphatase isozyme-specific immunocatalytical assays, the content of isozymes was determined in normal mucosas and adenocarcinomas from human colon or rectum. Tumor levels of both the tissue (liver)-unspecific and the placental-like alkaline phosphatase (PLAP-like) were elevated compared to normal mucosas of the same patients. Such elevations have been reported previously, particularly in seminomas and ovarian tumors. In several tumors, moreover, the intestinal isozyme was expressed in lesser amounts than in the adjacent mucosa. The present results indicate that the activation of two of the phosphatase isozymes, including expression of the typical germ cell line phosphatase (the PLAP-like isozyme), may occur even in nongonadal tumors. This may reflect an induction pattern of phosphatase isozymes, with implications for malignant transformation also in other tumors.

Adenocarcinoma↗