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Biomedical subjects

T Kotake

Publications and source records attributed to T Kotake.

At least 55 records · Page 3Linked to original sources

[Clinical staging and management of prostate cancer].

Through the use of digital rectal examination, prostate-specific antigen and improved biopsy technique, it is possible to diagnose early stage prostate cancer. The management of this disease, however, has generated considerable controversy. The decision whether to treat actively or conservatively must be made on the basis of accurate staging and grading technique, a patient's life expectancy and performance status. This article will show the current staging and management of prostate cancer as practiced in Japan.

Humans↗

[Application of radical prostatectomy for prostate cancer and its outcome].

The proportion of patients with localized prostate cancer treated by radical prostatectomy is increasing rapidly in Japan. As for the qualifications of patient candidates for radical surgery, various clinical and pathological findings to predict tumor extent and disease-free outcome must be considered carefully. There has been increased interest in the application of neoadjuvant or adjuvant therapy for locally advanced tumor group in order to improve disease-free survival and overall survival. The new anatomical approach to radical prostatectomy with its nerve sparing option assures preservation of erection. This procedure achieves excellent cancer control for patients with a definite organ-confined tumor preoperatively. Finally, more time is needed to obtain information on the long-term outcome after radical prostatectomy.

Aged↗

[Clinical significance of prostate specific antigen (PSA) and PSA density in the detection of T1a and T1b prostate cancer].

The clinical significance of preoperative prostate specific antigen (PSA) and PSA density (PSAD) in distinguishing stage T1a and T1b prostate cancer from benign prostatic hyperplasia (BPH) was studied retrospectively in men who had undergone surgery for BPH. A total of 202 clinically BPH patients underwent transurethral resection of prostate (TURP) or retropubic prostatectomy, and histopathological findings were BPH in 179 patients, T1a cancer in 10 patients and T1b cancer in 13 patients. The T1a cancer group was similar to the BPH group in all parameters. The PSA and PSAD values in the T1b cancer group were significantly higher than those in the BPH group (P < 0.001). Prostate volume and amount of tissue resected in the T1b cancer group were significantly smaller than those in the BPH group (p < 0.001). The cut-off values of PSA and PSAD were examined with T1a and T1b cancer as a positive control and histologically proven BPH as a negative control. When 8.0 ng/ml was used as the PSA cut-off value, the sensitivity was 65% and specificity was 70%. When 0.25 ng/ml/ml was used as the PSAD cut-off value, the sensitivity and specificity were 65% and 75%, respectively. PSAD was useful for improving the specificity. Almost all the cases undetected by using both cut-off values were of T1a cancer. The receiver operating characteristics curve demonstrated that at any point, PSAD was a better detector for distinguishing T1a, T1b cancer from BPH, focusing especially in the range of PSA level between 6.0 and 10.0 ng/ml. These findings suggest that PSA and PSAD are useful parameters in distinguishing T1b cancer from BPH before surgery.

Aged↗

[Phase I study of raltitrexed (ZD-1694)].

A multicenter cooperative phase I study of ZD-1694 (raltitrexed), a novel, folate-based thymidylate synthase (TS) inhibitor, was conducted with single and repeated doses in 30 patients with various malignant tumors. ZD-1694 was intravenously infused over 15 minutes. In the single-dose study, the initial dose was fixed at 1.0 mg/m2 (1n), and the dose was escalated stepwise up to 3.5 mg/m2 (3.5 n). Based on the results of the single-dose study, in the repeated-dose study, doses of 2.5 n and 3 n were infused every three weeks (3 weeks/one course). In principle, patients received 2 courses or more. Of the 29 eligible patients, 16 were in the single-dose study and 13 in the repeated-dose study. Adverse reactions were evaluated in all eligible patients. In the single-dose study, neutropenia, nausea/vomiting, diarrhea, and transaminase (GOT, GPT) increases, of grade 3 or higher, occurred at high doses of 3 n and 3.5 n. These were regarded as dose-limiting toxicities (DLT). DLT of grade 3 or higher were observed in 1 of 4 patients given 3 n and 2 of 4 patients given 3.5 n. These results suggested that the maximum tolerated dose (MTD) of ZD-1694 was 3.5 n (3.5 mg/m2). In the repeated-dose study, DLT of grade 3 or higher was observed in no more than one third of each dose group, 2 of the 6 patients given 2.5 n and 2 of the 7 patients given 3 n. These results suggested that 3 n (3.0 mg/m2), a dose nearer to MTD, was the recommended dose for the phase II study. Although transaminase increases were observed in all patients, in 12 of them the increase was grade 2 or lower and reversible. A pharmacokinetic investigation showed the mean elimination half life of ZD-1694 plasma concentration was 91.5 hours in the single-dose group and 119.1 hours in the repeated dose group. It was suggested that ZD-1694 is metabolized to polyglutamates after uptake and retained in the cells for a long duration. However, no accumulation was seen in plasma concentration of ZD-1694 following repeated doses at 3-weekly intervals. One PR was observed in a patient with colorectal cancer receiving 2.5 n in the repeated-dose study. Based on these results, the recommended dosage and administration for the phase II study of ZD-1694 was 3 n (3.0 mg/m2) intravenously infused over 15 minutes every 3 weeks.

Adult↗

[Clinical utility of the free prostate specific antigen (PSA), alpha 1-antichymotrypsin-complexed PSA, and free/total PSA ratio using the specific and sensitive enzyme-linked immunosorbent assay "E-plate EIKEN PSA"].

We studied the clinical significance of serum prostate specific antigen (PSA) ratio: free-PSA/total-PSA and free-PSA/complex-PSA to discriminate between prostate cancer (PC) and prostate benign disease (non-PCa) by using total-PSA, alpha 1-antichymotrypsin complexed (complex)-PSA and free-PSA enzyme-linked immunosorbent assay (ELISA) kits newly developed at EIKEN Chemical Co, Ltd. Fre-PSA and complex-PSA ELISA kits demonstrated high sensitivity and specificity. Total-PSA ELISA kit also demonstrated equimolarity for free-PSA and complex-PSA. On the total-PSA range of 4-10 ng/ml, free-PSA/total-PSA% (f/t%) and free-PSA/complex-PSA% (f/c%) were very useful to discriminate between PCa and non-PCa by receiver operating characteristic curve analysis as well as PSA density (PSA-D) but not free-PSA level. F/t% and f/c% were even useful to discriminate early stage PCa (i.e. A1 or B0) from non-PCa by the Mann-Whitney U-test.

Enzyme-Linked Immunosorbent Assay↗

[TNM classification for urological cancer].

The 5th edition of the new TNM classification for urological cancer has been published by UICC in 1997. Herein, the classification of 4 urological carcinomas (kidney, urinary bladder, renal pelvis and ureter, and urethra) is presented and discussed in comparison with the latest revisions in 1987 and 1992. In the 5th edition, the main revised points are as follows: As for kidney, the primary tumor cut off between T1 and T2 was changed from 2.5 cm to 7.0 cm, and the N classification was simplified as for urinary bladder, all muscle invasive tumors (T2 or T3a in the 1992 classification) are included in the T2 category, which is then subdivided into T2a and T2b; in the urethra, new T categories on transitional cell carcinoma of the prostate and prostatic urethra have been added, and the N classification is simplified; there is no change in the classification for the renal pelvis and ureter. According to these changes, a new system of stage grouping is proposed. There may still be widespread disagreement over the appropriateness of some of the changes introduced in the 5th edition of 1997. It is essential to continue efforts to improve the accuracy of determining the clinical extent of malignant tumors, and to work together in order to achieve our objectives for a unified system of TNM classification.

Female↗

[Bilateral synchronous adrenal myelolipomas: a case report].

A 70-year-old man, who was diagnosed by computed tomographic scan as having bilateral synchronous adrenal myelolipomas 6 years ago during the follow-up of fatty liver, underwent tumor resection at our Department because of growth of bilateral tumors without any subjective symptoms. Histopathological examination revealed mature adipose tissue cells without atypism and areas of hematopoietic tissue, including the myelotic, lymphotic, erythrocytic, and megakaryocytic cells. The diagnosis of myelolipoma was confirmed. The in vivo doubling time of bilateral tumors was 16.1 months and 31.3 months, respectively.

Adrenal Gland Neoplasms↗

[Labial adhesion presenting as urinary incontinence and dysuria in a postmenopausal woman: a case report].

A 68-year-old woman admitted to our hospital complaining of urinary incontinence and dysuria. On examination, the labia were found to be fused extensively, with a pinhole opening at the midline. Under spinal anesthesia, the adhesion was clearly separated with the Hegar's dilator. There remains no recurrence in this patient following therapy. The labial adhesion was considered to be an acquired disease caused by infection, trauma in the genitalia, or sexless life, according to hypoestrogenism.

Aged↗

Differences in the p53 gene mutational spectra of prostate cancers between Japan and Western countries.

Mutations of the p53 gene are related to development of human cancers and their frequencies and spectra, the latter representing fingerprints left by carcinogens, provide information about the molecular epidemiology of the disease. Prostate cancer is the most common neoplasm in American males and although its incidence is still relatively low in Japanese people, it has recently been increasing with the westernization of life style. To assess the frequency and spectrum of p53 gene mutations in Japanese prostate cancers, we examined a series of 90 lesions using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. The patients' mean age was 69.3 years (range 57-87). Of the total, six were well-, 34 moderately- and 50 poorly-differentiated adenocarcinomas, and the median Gleason score was 7.9. Eleven of the 90 cases (12%) had mutations in exons 2-11 of the p53 gene: none of the five clinical-stage A, one of 25 stage B (4%), three of 35 stage C (9%) and seven of 25 stage D (28%) cancers. The correlation with an advanced stage was statistically significant. One insertion and 10 base pair substitutions were encountered, comprising six transversions (55%) and four transitions (36%). Two of the latter involved methylated cytosine-guanine (CpG). These 11 mutations were combined with 18 other mutations in previous reports concerning Japanese prostate cancers to facilitate comparison of the p53 gene mutational spectrum with those reported for American and European prostate cancers. In the latter, 61% were transitions and 33% were transversions. The greater proportion of transversions in the Japanese population suggests that there are different factors responsible for carcinogenesis of the prostate glands in the various countries.

Aged↗

Genetic alterations of androgen receptor gene in Japanese human prostate cancer.

In order to determine the significance of androgen receptor (AR) gene mutations for Japanese prostate cancers, we examined the entire coding region, from exon A to H, in 36 primary lesions. Five in stage A, 12 in stage B, six in stage C and 13 in stage D were subjected to PCR-SSCP analysis for genomic DNA and nucleotide sequencing. Mutations were detected in five samples (14%). Two in stage D and refractory to anti-androgen treatment showed mis-sense mutations. The other three showed changes in the length of the CAG repeat in exon A, with an expansion or a contraction of one repeat unit. However, no association with changes in AR function was indicated because they had not been refractory to hormone therapy. Since these latter three tumors were associated with microsatellite instability, the changes might have been the result of an impairment of mismatch repair. This study indicates that AR gene mutations play a role, in only a subset of prostate cancer patients, in a treatment-refractory state.

Adult↗

Purification and characterization of wall-bound exo-1,3-beta-D-glucanase from barley (Hordeum vulgare L.) seedlings.

A beta-D-glucanase activity hydrolyzing 1,3:1,4-beta-D-glucan was released from the cell walls of barley by 3 M LiCl treatment. It was purified by sequential cation-exchange, gel-filtration and hydrophobic chromatography. The molecular mass of the glucanase was 66 kDa as determined by SDS-polyacrylamide gel electrophoresis. Sequence determination of the first thirty amino acids of the N-terminus revealed a high homology of this enzyme to the Pseudomonas 1,4-beta-D-glucosidase (56.5%). The purified beta-D-glucanase has a pH optimum at 5.0, and hydrolyzes oligosaccharides containing beta-D-1,3 or beta-D-1,4 linkage. The glucanase showed maximum hydrolytic activity toward laminaritetraose, the rate being about two times that of cellotetraose and about four times that of gentiobiose. Polysaccharides such as lichenan, 1,3:1,4-beta-D-glucan (from barley), laminarin and pustulan are also hydrolyzed, but not carboxylmethyl-curdlan, carboxymethyl-cellulose, xyloglucan and maltose. The purified beta-D-glucanase yielded monomeric glucose from laminarihexaose, and exhibited characteristics of an exo-1,3-beta-D-glucanase (EC 3.2.1.58). The activity and biochemical characteristics of this enzyme suggest that it is an exo-1,3-beta-D-glucanase involved in the rapid turnover of 1,3:1,4-beta-D-glucan in barley cell walls during seedling growth.

Amino Acid Sequence↗

Glioblastoma multiforme after radiotherapy for metastatic brain tumor of testicular cancer.

A patient with left testicular cancer and metastases to retroperitoneal lymph nodes, lung, and brain was treated by chemotherapy, radiotherapy and surgery, and obtained the state of no evidence of disease, but 10 years after radiotherapy, a glioblastoma multiforme tumor appeared in the brain. This is the first report of a glioma appearing after radiotherapy in a testicular cancer patient.

Adult↗

Antitumor effect of CPT-11, a camptothecin derivative, on human testicular tumor xenografts in nude mice.

OBJECTIVE: The antitumor effect of CPT-11, a camptothecin derivative, on two human testicular embryonal carcinomas (TTSC-2 and TTSC-3) heterotransplanted into-nude mice was studied. MATERIALS AND METHODS: Tumor-bearing nude mice were given daily intraperitoneal injections of the anticancer drugs in 0.1 ml saline 3 times at 3-day intervals. At the end of the experiments tumors were resected and subjected to light-microscopic observation. RESULTS: When 10, 30 and 50 mg/kg of CPT-11 was administered to tumor-bearing mice intraperitoneally, the antitumor effect of CPT-11 was observed dose-dependently in both TTSC-2 and TTSC-3. When 30 mg/kg of CPT-11 was administered in combination with CDDP, complete tumor regression was observed in both TTSC-2 and TTSC-3 tumors. Histological findings correlated well with the decrease in tumor volume of treated tumors. No mice died after treatment with CPT-11 in a single-agent and combination chemotherapy. CONCLUSION: Chemotherapy with CPT-11 was an effective and safe method against human testicular tumors heterotransplanted in nude mice.

Animals↗

[Urethral recurrence of bladder cancer 16 years after total cystectomy. A case report].

A 74-year-old man was admitted to our hospital. Diagnosis of invasive bladder cancer was made and a total cystectomy was performed on January, 30, 1980. Histological examination showed transitional cell carcinoma, grade 2, pT1 is N0M0. After 16 years, when he suffered left femur, he had right inguinal lymphnode swelling. On the biopsy of the inguinal mass, histology was transitional cell carcinoma. The urethral washing cytology was positive. Lung CT scan dem onstrated multiple lesions. He was diagnosed of the urethral recurrence, right inguinal lymphnode metastasis and lung metastasis of bladder cancer. This case is the 5th case of urethral recurrence of bladder cancer following cystectomy in our hospital.

Aged↗

[Bropirimine (U-54461S) late phase II clinical study for carcinoma in situ of the bladder. Japan Bropirimine Study Group].

Late Phase II clinical study with bropirimine (U-54461S), a novel oral antitumor agent that has interferon inducing and anti-proliferative activities, was conducted in patients with bladder CIS at 38 institutions nationwide. To investigate the efficacy and safety of the treatment, bropirimine was administered to the patients at the dose of 750 mg every two hours, three times a day, for three consecutive days with four-day drug withdrawal, based on the results of the preceding clinical studies up to early phase II. Among the 48 patients registered, 41 patients were evaluable for antitumor efficacy. Complete response (CR) was observed in 17 of them, no change (NC) in 18 patients, and progressive disease (PD) in 6 patients; so the efficacy rate was 41.5%. Classified by patient background, the efficacy rates were 58.3% (7/12) in patients with primary bladder CIS, 34.5% (10/29) in those with secondary bladder CIS, 45.5% (10/22) in those with Grade 3, and 23.8% (5/21) in those previously given chemotherapeutic agents or BCG by intravesical or other routes. Adverse drug reactions frequently observed were influenza-like symptoms such as fever and generalized malaise and gastrointestinal symptoms like anorexia and nausea/vomiting; these symptoms were all Grade 2 or milder. Abnormalities in laboratory tests, such as an elevation in GOT/GPT, neutropenia, and leukopenia were observed. These adverse effects were all tolerated by the patients. From the above results, bropirimine was considered to be a useful oral agent for the treatment of bladder CIS.

Administration, Oral↗

Coexistence of renal cell carcinoma and renal angiomyolipoma developing in a kidney: a case report.

Coexistence of renal cell carcinoma and angiomyolipoma in the same kidney is rare. A 54-year-old woman without tuberous sclerosis was admitted for further examination of incidental renal masses on ultrasonography. Computerized tomography revealed a 17-mm high density mass in the mediolateral portion of the right kidney and a 5-mm low density mass near the right lower pole. Because the former mass showed a typical tumor pattern on selective renal angiography and the latter mass was strongly hyperechoic on ultrasonography, a clinical diagnosis of renal cell carcinoma and angiomyolipoma was made. A right radical nephrectomy confirmed the preoperative diagnosis. She has been followed for 61 months with no recurrence.

Angiomyolipoma↗

Treatment of advanced renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine.

PURPOSE: We examined whether cimetidine could augment the efficacy of interferon-alpha therapy for advanced renal cell carcinoma. MATERIALS AND METHODS: Of 31 male and 6 female patients treated with interferon-alpha and cimetidine 21 had metastases at diagnosis and 15 had a recurrence after nephrectomy. One patient had a primary tumor with thrombus in the inferior vena cava. Lymphoblastoid interferon-alpha was administered at 5 megaunits daily intramuscularly 5 to 7 days a week for at least 8 weeks, and cimetidine was administered orally at 800 mg. daily in 4 divided doses. The evaluable tumors included 30 in the lung, 6 lymph nodes, 5 bone, 4 kidney and 1 inferior vena cava. RESULTS: Combined therapy with interferon-alpha and cimetidine resulted in a complete response in 7 patients, a partial response in 8, stable disease in 12 and progression in 10. The objective response rate was 41%. The lung metastasis showed the best response to combined therapy. The 5-year survival rates for patients with and without response, and overall were 74, 20 and 41%, respectively. Histopathologically, high grade tumors had a better response to combined therapy than did low grade tumors. CONCLUSIONS: Combined therapy with interferon-alpha and cimetidine for advanced renal cell carcinoma resulted in a definitively good response. A prospective randomized trial should be performed to elucidate the efficacy of the combined therapy.

Adult↗

[Clinical investigation for recurrence and progression in Ta grades 1 and 2 bladder cancer].

We treated 107 new patients with stage Ta, grades 1 and 2 transitional cell bladder carcinoma by transurethral resection during the past 23 years. The clinicopathological factors evaluated were grade, size, number and form of tumor. Fifty-five patients (51%) had recurrent tumors after initial resection and progression (muscle invasion or metastasis) occurred in four patients (3.7%). The 5-year and 10-year recurrence free rates were 47.3 and 29.8%, respectively. Seven patients (6.5%) had grade 3 tumor (grade-up) at recurrence. An increase in T category to T1 (stage-up) occurred in 13 patients (12%), only one of whom later developed an invasive tumor (pT4). The size of tumor significantly affected the rate of recurrence (p < 0.01). Sessile tumor were at a significantly greater risk for progression (p < 0.05). Stage-up did not have a significant effect on progression, but grade-up was significantly risky for progression (p < 0.01). Initial grade 2 tumors were highly related to grade-up (p < 0.05).

Adult↗