M Murai

Publications (121)219.42 Total impact

• Article: Autocrine growth promotion by multiple hematopoietic growth factors in the established renal cell carcinoma line KU-19-20.

  M Tachibana, A Miyakawa, J Nakashima, M Murai, K Nakamura, A Kubo, J Hata
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  ABSTRACT: Increasing evidence suggests that paraneoplastic syndrome may be mediated by tumor-related cytokine release, although the specific factors involved remain to be clearly defined. The cancer cells used in the present study were obtained from a 67-year-old man with metastatic renal cell carcinoma in the subcutaneous space who demonstrated marked leukocytosis (37,800/mm3). The primary tumor of the kidney was pathologically diagnosed as renal cell carcinoma consistent with the sarcomatoid type. On microscopic observation, the cultured cells exhibited an epithelial appearance with vacuole formation in their cytoplasm. Ultrastructural observations revealed relatively marked microvilli and a tight junction. Significant amounts of GM-CSF, G-CSF, IL-6, and IL-8 concentrations in the culture media were identified by an enzyme-linked immunosorbent assay. Reverse transcriptase polymerase chain reaction (RT-PCR) significantly exhibited marker protein m-RNA expression in cancer cells. In addition, GM-CSF receptor and IL-6 receptor mRNA expression was also demonstrated by RT-PCR. The administration of both IL-6 and GM-CSF induced cell-proliferation activities estimated by both [3H]-thymidine and bromodeoxyuridine labeling. Anti-IL-6 antibody and anti-GM-CSF antibody neutralized the enhanced proliferative activities generated by these cytokines. Our findings indicate that the established renal cancer cell line can be demonstrated by both the production of multiple cytokines and by their promotion of autocrine growth. These cells are thus considered to be useful as an effective model for multipotent differentiated renal cell carcinoma, as well as for studying the mechanisms of action of autocrine growth.
  Cell and Tissue Research 10/2000; 301(3):353-67. · 3.11 Impact Factor
• Article: Prostate specific antigen adjusted for transition zone volume: the most powerful method for detecting prostate carcinoma.

  E Kikuchi, J Nakashima, M Ishibashi, T Ohigashi, H Asakura, M Tachibana, M Murai
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  ABSTRACT: Several methods for the identification of patients with prostate carcinoma have been proposed to enhance the clinical usefulness of prostate specific antigen (PSA). However, it remains unclear which method is superior in practical use. The authors attempted prospectively to identify the most powerful method with which to detect prostate carcinoma, especially among patients with intermediate PSA levels. Between October 1997 and August 1999, systematic sextant biopsies were performed on 281 patients, including 147 with PSA levels between 4.1 ng/mL and 10.0 ng/mL. The clinical values of PSA, the free PSA to total PSA ratio (free/total PSA ratio), alpha-1-antichymotrypsin-PSA complex (PSA-ACT), the calculated derivatives, PSA density (PSAD), and PSA density of the transition zone (PSATZD) for the detection of prostate carcinoma were compared by using receiver operating characteristic (ROC) curves and logistic regression analyses. According to ROC curve analysis, PSATZD had the greatest area under the curve in the overall patient population and in patients with intermediate PSA levels. In patients with intermediate PSA levels, at the sensitivity of 90%, PSATZD would have prevented unnecessary biopsies in 68 of 117 patients who were without prostate carcinoma, whereas PSA, free/total PSA ratio, and PSA-ACT would have prevented unnecessary biopsies in 25, 28, and 25 patients, respectively. Stepwise logistic regression analysis showed that PSATZD and findings on digital rectal examination were significant independent predictors. PSATZD had the most useful validity in the differentiation between prostate carcinoma and benign prostatic enlargement in the overall patient population and in patients with intermediate PSA levels.
  Cancer 09/2000; 89(4):842-9. · 4.77 Impact Factor
• Article: Intravesical and intravenous therapy of human bladder cancer by the herpes vector G207.

  M Oyama, T Ohigashi, M Hoshi, J Nakashima, M Tachibana, M Murai, K Uyemura, T Yazaki
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  ABSTRACT: G207, a conditionally replicating herpes vector, efficiently kills human bladder cancer cells in vitro. To evaluate the therapeutic potential of G207, we have established three in vivo models similar to the clinical situation. In vivo, G207 was intraneoplastically, intravesically, or intravenously inoculated in nude mice. Intraneoplastic inoculation into subcutaneous tumor caused significant tumor growth inhibition. Intravesical inoculation of G207 also caused decreased tumor growth in an orthotopic human bladder cancer model. Furthermore, multiple intravenous inoculation markedly inhibited subcutaneous tumor growth. These results suggest that intravesical therapy with G207 is effective for localized bladder tumor, especially for carcinoma in situ (CIS), and intravenous therapy with G207 is promising for invasive or metastasized bladder tumor.
  Human Gene Therapy 09/2000; 11(12):1683-93. · 4.22 Impact Factor
• Article: Serum interleukin 6 as a prognostic factor in patients with prostate cancer.

  J Nakashima, M Tachibana, Y Horiguchi, M Oya, T Ohigashi, H Asakura, M Murai
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  ABSTRACT: The present study was undertaken to evaluate the prognostic significance of the serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6 levels were measured in 74 patients with prostate cancer. The tumor was stage B in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic significance of tumor histology, performance status (PS), bone metastasis, serum prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level, serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease-specific survival was assessed using univariate and multivariate Cox's proportional hazards model analyses. Serum IL-6 was significantly correlated with the clinical stage of prostate cancer. Univariate analysis of all patients demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated with a significantly lower survival rate than their respective counterparts. In multivariate analysis, however, the only two significant prognostic factors were EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate that the serum IL-6 level is a significant prognostic factor for prostate cancer as well as EOD.
  Clinical Cancer Research 08/2000; 6(7):2702-6. · 7.74 Impact Factor
• Article: [Brachytherapy].

  S Saito, T Momma, T Dokiya, M Murai
  Nippon rinsho. Japanese journal of clinical medicine 08/2000; 58 Suppl:268-72.
• Article: [A case of Collet-Sicard syndrome caused by skull base metastasis of prostate carcinoma].

  H Satoh, T Nishiyama, A Horiguchi, J Nakashima, S Saito, M Murai
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  ABSTRACT: A case of Collet-Sicard Syndrome caused by skull base metastasis of prostate carcinoma is reported. A fifty-five years old man presenting multiple lymph node and bone metastases of prostate carcinoma was treated with LH-RH agonist and Flutamide, which induced transient decrease in serum PSA levels and size of lymph node metastases. After 8 months of the treatment, the patient started complaining headache, dysphagia and dysarthria. Brain CT and MRI demonstrated a soft tissue mass replacing left pyramidal bone and occipital bone around left jugular foramen. The tumor was diagnosed as skull base metastasis of the prostate carcinoma and was treated with 50Gy of radiation. The symptom improved after the radiation but died of the disease in 4 months. The autopsy revealed the skull base metastasis of the prostate carcinoma and the tumor was proved to be poorly differentiated adenocarcinoma, which was positively stained by anti-PSA antibody. The case showed cranial nerve palsy of IX to XII, which is usually called Collet-Sicard syndrome. This is the third case report of Collet-Sicard syndrome caused by the skull base metastasis of prostate carcinoma, and it is the first case in Japan.
  Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 07/2000; 91(6):562-4.
• Article: Current management of incidentally discovered adrenal masses, with a review of Japanese literature.

  M Murai, E Kikuchi, H Yanaihara, J Nakashima
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  ABSTRACT: It is becoming increasingly common to discover adrenal masses incidentally on radiologic imaging studies. We herein present our experience with 61 cases of incidentally discovered and surgically removed adrenal incidentalomas, including 11 pheochromocytomas. Only four were adrenocortical carcinomas. A review of the literature, including Japanese journals, for the prevalence of incidentantally discovered adrenal mass, their differential diagnosis and management are discussed.
  Biomedecine [?] Pharmacotherapy 07/2000; 54 Suppl 1:133s-139s. · 2.00 Impact Factor
• Article: Urinary steroid profile in adrenocortical tumors.

  E Kikuchi, H Yanaihara, J Nakashima, K Homma, T Ohigashi, H Asakura, M Tachibana, H Shibata, T Saruta, M Murai
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  ABSTRACT: Determination of the urinary steroid profile has been proposed as a sensitive tool for diagnosing adrenocortical tumors. The urinary steroid profiles were determined for patients with adrenocortical tumors. Urinary steroids were extracted, derivatized to form methyloxime-trimethylsilyl ether and analyzed by gas chromatography/mass spectrometry. Patients with adrenal adenomas from primary hyperaldosteronism had increased metabolites of 18-hydroxycorticosterone and aldosterone, and those with Cushing's syndrome had elevated excretion of 11 -deoxycortisol, cortisol, 18-hydroxycortisol, and cortisone metabolites. In patients with adrenocortical carcinomas, increased levels of metabolites of 11-deoxycortisol or 33-hydroxy-5-ene steroids were observed. The urinary steroid profiles of adrenal adenomas and adrenocortical carcinomas were quite different, suggesting the diagnostic validity for discriminating malignant from benign diseases.
  Biomedecine [?] Pharmacotherapy 07/2000; 54 Suppl 1:194s-197s. · 2.00 Impact Factor
• Article: Complications of laparoscopic and retroperitoneoscopic adrenalectomies in 370 cases in Japan: a multi-institutional study.

  T Terachi, O Yoshida, T Matsuda, S Orikasa, Y Chiba, K Takahashi, M Takeda, E Higashihara, M Murai, S Baba, K Fujita, K Suzuki, S Ohshima, Y Ono, J Kumazawa, S Naito
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  ABSTRACT: A total of 370 laparoscopic adrenalectomies, including 311 transperitoneal (TP) and 59 retroperitoneal (RP) approaches, were performed in nine urologic centers, where the laparoscopic adrenalectomy was first begun independently in Japan, and their affiliated hospitals between January 1992 and September 1996. The clinical diagnoses of those 370 adrenal diseases were primary aldosteronism in 155 patients, Cushing's syndrome in 61. preclinical Cushing's syndrome in 21. pheochromocytoma in 16, nonfunctioning adenoma in 87, complicated cyst in ten, myelolipoma in nine, adrenal cancer in four and other diagnoses in eight (table 1). There was no mortality in this series. Intraoperative complication rate was 33/370 (9%) in total: 26/311(8%) in the TP procedures and 7/59 (12%) in the RP procedures (table 11). Postoperative complication rate was 24/370 (6%) in total: 22/311 (7%) in the TP procedures and 2/59 (3%) in the RP ones (table 111). Conversion rates to open surgery in total, in the TP and in the RP procedures were 13/370 (3.5%), 10/311 (3.2%) and 3/59 (5.1 %). respectively (table IV). Although the RP procedure has a lower morbidity rate compared to the TP procedure, more skill is required to overcome the drawback of the narrow working space and fewer anatomical landmarks.
  Biomedecine [?] Pharmacotherapy 07/2000; 54 Suppl 1:211s-214s. · 2.00 Impact Factor
• Article: [A case of metanephric adenoma treated with partial nephrectomy].

  M Kosugi, H Nagata, J Nakashima, M Murai, J Hata
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  ABSTRACT: A 32-year-old female presented with a right renal mass detected by abdominal ultrasound examination at a routine medical check up. Computed tomography scans and magnetic resonance images revealed a solid tumor in the upper pole of the right kidney measuring 1.5 cm in diameter. Partial nephrectomy was performed on suspicion of the renal cell carcinoma. Histologically, the tumor is composed of small, uniform, epithelial cells with scant cytoplasm and hyperchromatic round nuclei that formed a tubular or glomerular-like structure. The histological diagnosis was metanephric adenoma.
  Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 05/2000; 91(4):489-92.
• Article: Application of conditionally replicating herpes vector for gene therapy treatment of urologic neoplasms.

  M Oyama, T Yazaki, T Ohigashi, M Hoshi, Y Horiguchi, M Oya, H Asakura, J Nakashima, M Tachibana, K Uyemura, M Murai
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  ABSTRACT: Herpes vector has been widely used for experimental gene therapy. We herein review the strategies of such therapy for the treatment of urologic neoplasms. Most experimental studies of genetically altered viruses have employed replication-incompetent vectors. However, such viruses are unable to infect additional cells subsequent to the initial infection event. Therefore, this strategy has relied heavily on the bystander effect because a large number of noninfected tumor cells remain. Conditionally replicating herpes vector G207 has been developed in order to overcome potential problems of safety and tumor specificity for human use. It has been used to treat malignant brain tumors because of its neural tropism. In the last few years, applications of G207 for non-neural tumors have been reported. Because G207 may be useful for the treatment of urologic malignant tumors, we evaluated the antitumor effect against several types of tumor cells both in vitro and in vivo. Our data suggest that G207 may be applicable for the treatment of urologic malignant tumors.
  Molecular Urology 02/2000; 4(2):83-7.
• Article: Tyrosine kinase inhibitors reduce bcl-2 expression and induce apoptosis in androgen-dependent cells.

  T Ohigashi, M Ueno, S Nonaka, T Nakanoma, Y Furukawa, N Deguchi, M Murai
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  ABSTRACT: The signal transduction pathway showing how androgen withdrawal induces apoptosis in androgen-dependent cells has not been clearly understood. In these studies, we focused on the behavior of tyrosine kinases in androgen-dependent cells and investigated its correlation with apoptosis and bcl-2 expression. We used SC2G, an androgen-dependent mouse mammary carcinoma cell line, which had been cloned from Shionogi Carcinoma 115 (SC115). When SC2G cells were cultured with herbimycin A (HMA), a potent tyrosine kinase inhibitor, the number of viable cells decreased significantly after 24 h. Terminal deoxyribonucleotidyltransferase-mediated dUTP-biotin nick end labeling and flow cytometric analysis of annexin V staining showed that HMA induced apoptosis of SC2G cells. The level of bcl-2 mRNA in SC2G cells was suppressed by HMA in a dose-dependent manner on RT-PCR. Preincubation with caspase inhibitors protected HMA-induced apoptosis of SC2G cells. When a human bcl-2 gene was transfected in SC2G cells and overexpressed, SC2G cells seemed to acquire tolerance for HMA. These data indicate that HMA-sensitive tyrosine kinase(s) can regulate apoptosis and inhibit bcl-2 expression in SC2G mouse androgen-dependent cells. Tyrosine kinase(s) seemed to be a member of signal transduction between androgen receptor activation and bcl-2 expression.
  AJP Cell Physiology 02/2000; 278(1):C66-72. · 3.54 Impact Factor
• Article: Antitumor effects of an interferon-loaded silicone formulation in human renal cell carcinoma in nude mice.

  K Marumo, Y Huang, M Murai
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  ABSTRACT: Conventional therapy for renal cell carcinoma using interferon (IFN) has shown limited antitumor action. The IFN-loaded silicone formulation (IFN-SF) is a sustained-release formulation of human lymphoblastoid IFN, with a medical grade silicone elastomer used as the carrier material. We evaluated the antitumor effect of IFN-SF on human renal cell carcinoma cell line (KU-2) transplanted to nude mice. The treatment was started when the tumor nodules had grown 6 to 8 mm in diameter. IFN-SF, on an aqueous solution of IFN, was given by subcutaneous or peritumoral injection. Antitumor effects were evaluated according to tumor weights calculated as (long diameter) x (short diameter)2/2 in 7 groups consisting of 6 mice each. Serum IFN levels remained detectable up to 30 days after subcutaneous injection of IFN-SF. IFN-SF administered by the subcutaneous and peritumor route significantly inhibited growth of the tumor when compared with tumor growth in the untreated mice and mice treated with aqueous IFN solution. IFN-SF had equivalent inhibitory effects on tumor growth by peritumor and subcutaneous injection. Results indicated that the use of IFN-SF could reduce the frequency of injections and provide better treatment of patients with renal cell carcinoma because of its long-acting effect when it is used systemically.
  The Keio Journal of Medicine 01/2000; 48(4):179-83.
• Article: [Effect of aging and diseases on male sexual function assessed by the International Index of Erectile Function].

  K Marumo, K Nagatsuma, M Murai
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  ABSTRACT: Many epidemiological factors contribute to erectile dysfunction (ED). The objective of the present research was to investigate the risk factors of ED and the influence of aging on male sexual function, to obtain some insight into prevention of ED. The study sample consisted of employees, aged from 22 to 59 years old of ten companies in Japan, who responded to the International Index of Erectile Function (IIEF) questionnaire and a survey of health status and related variables. The IIEF sexual activity questionnaire includes 15 items related to male sexual activity organized into five domains (that is erectile function, orgasmic function, sexual desire, intercourse satisfaction, overall satisfaction) to which 967 of the 1,020 subjects (94.8%) provided complete responses. These 967 men constitute the present study sample. For statistical analysis, ANOVA with Scheffe's (post hoc) test was conducted, and statistical significance was set at p < 0.05. Presence of hypertension, heart disease, diabetes and hyperlipidemia was associated with a significantly decreased score for erectile function in subjects in their fifties (p < 0.05), however, it was not significant in the other age groups. In subjects, who were free from risk factors for sexual function, there was significant correlation between age and the scores for erectile function, orgasmic function, sexual desire and intercourse satisfaction. Aging and chronic disorders that have been considered to be putative risk factors for ED, therefore affect male sexual function in the elderly. The IIEF was suggested to be suited for use in studies assessing epidemiology of ED.
  Nippon Hinyōkika Gakkai zasshi. The japanese journal of urology 12/1999; 90(12):911-9.
• Article: Transitional cell carcinoma of ureteral stump after radical nephrectomy for renal cell carcinoma.

  K Nagatsuma, M Tachibana, A Miyakawa, H Asanuma, M Murai
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  ABSTRACT: A 68-year-old male presented with microscopic hematuria during a routine checkup after undergoing a radical nephrectomy for renal cell carcinoma. Retrograde ureterography demonstrated a ureteral stump tumor. The ureteral stump was completely resected with a bladder cuff and histologic diagnosis was grade 2 to 3 transitional cell carcinoma of the ureteral stump. He is doing well and has been tumor-free for 2 years. The ureteral stump must be correctly evaluated using retrograde ureterography in any patient with a prior history of bladder cancer. Even if a patient had no history of ureterial cancer, whenever hematuria is present in the follow-up period after nephrectomy for renal cell carcinoma, a retrograde pyelogram should be performed.
  International Journal of Urology 12/1999; 6(12):627-9. · 1.75 Impact Factor
• Article: Strip biopsy of superficial bladder tumors using an electrosurgical snare.

  M Tachibana, A Miyakawa, Y Horiguchi, K Nakamura, M Murai
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  ABSTRACT: BACKGROUND/METHODS: Transurethral strip biopsy of bladder tumors using an electrosurgical snare was tested to determine whether or not this technique provides any advantage to the histologic examination of bladder cancers and to the management of superficial bladder tumors as a routine treatment. RESULTS/DISCUSSION: Our research results confirm that the strip biopsy technique can be applied as an alternative transurethral management procedure for treatment of superficial bladder tumors. Moreover, the results demonstrate that the procedure can also provide significantly greater histologic diagnostic advantages for bladder cancers than are possible through cold cup biopsy or transurethral resection.
  International Journal of Urology 10/1999; 6(9):463-6. · 1.75 Impact Factor
• Source

  Available from: nih.gov

  Article: Overexpression of IL-1ra gene up-regulates interleukin-1beta converting enzyme (ICE) gene expression: possible mechanism underlying IL-1beta-resistance of cancer cells.

  M Sumitomo, M Tachibana, M Murai, M Hayakawa, H Nakamura, A Takayanagi, N Shimizu
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  ABSTRACT: We investigated the interaction of endogenous interleukin (IL)-1beta, IL-1ra, and interleukin-1beta converting enzyme (ICE) in four human urological cancer cell lines, KU-19-19, KU-1, KU-2 and KU-19-20. Northern blot analysis showed that IL-1beta gene was expressed in all cell lines. On the other hand, in KU-19-19 and KU-19-20, the gene expressions of both IL-1ra and ICE were suppressed. MTT assay revealed that IL-1beta (10 ng ml(-1)) promoted cell growth in KU-19-19 and KU-19-20, while it inhibited in KU-1 and KU-2. An ICE inhibitor, Acetyl-Tyr-Val-Ala-Asp-CHO (YVAD-CHO) blocked IL-1beta-induced growth inhibition in KU-1 and KU-2. Overexpression of the secretory type IL-1ra with adenovirus vector (AxlL-1ra) enhanced ICE gene expression, while exogenous IL-1ra (100 ng ml(-1)) did not enhance it. Furthermore, AxIL-1ra treatment promoted endogenous IL-1beta secretion and induced significant growth inhibition and apoptotic cell death on KU-19-19 and KU-19-20. Treatment with either IL-1ra (100 ng ml(-1)), IL-1beta antibody (100 microg ml(-1)), or YVAD-CHO blocked AxlL-1ra-induced cell death in KU-19-19 and KU-19-20. These results suggest that IL-1beta-sensitivity depends on the level of ICE gene expression, which is regulated by the level of endogenous slL-1ra expression. This is a first report on the intracellular function of slL-1ra and these findings may provide key insights into the mechanism underlying the viability of cancer cells.
  British Journal of Cancer 10/1999; 81(2):277-86. · 5.04 Impact Factor
• Article: N-acetylcysteine modifies cis-dichlorodiammineplatinum-induced effects in bladder cancer cells.

  A Miyajima, J Nakashima, M Tachibana, K Nakamura, M Hayakawa, M Murai
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  ABSTRACT: We previously demonstrated a role of reactive oxygen species (ROS) in cytotoxicity induced by cis-dichlorodiammineplatinum (CDDP) in combination with glutathione (GSH) depletors in bladder cancer cells. However, the relationship between CDDP and ROS is still unclear, although many mechanisms of drug resistance have been well characterized. The present study was undertaken to investigate the effects of N-acetylcysteine (NAC), a GSH precursor, on the CDDP-induced effects in bladder cancer cells (KU1). The cytotoxic effects of CDDP were significantly blunted by NAC (1 mM) in KU1 cells. The IC50 of CDDP only (10.2+/-1.2 microM) is significantly lower than that of CDDP with NAC (IC50: 20.3+/-1.6 microM) in KU1 cells. NAC also significantly increased the intracellular concentration of GSH in KU1 cells (37.2+/-1.6 nmol/10(6) cells), compared to controls (15.9+/-7.6 nmol/10(6) cells). While CDDP produced a significant increase in ROS as measured in terms of dichlorofluorescein (DCF) production in KU1 cells in a time-dependent manner, pretreatment with NAC significantly reduced CDDP-induced intracellular DCF in KU1 cells. Moreover, TdT-mediated dUTP-biotin nick-end labeling (TUNEL) assay showed that CDDP-induced apoptosis (31.1+/-3.8%) was significantly inhibited by pretreatment with NAC in KU1 cells (11.2+/-2.6%). These results demonstrated that NAC scavenges CDDP-induced ROS and inhibits CDDP-induced cytotoxicity, suggesting that ROS mediate the CDDP-induced cytotoxicity in bladder cancer cells.
  Japanese journal of cancer research: Gann 06/1999; 90(5):565-70.
• Article: The value of gamma-seminoprotein in combination with prostate specific antigen in detecting prostate cancer.

  J Nakashima, H Nagata, M Sumitomo, A Miyajima, M Tachibana, S Baba, S Jitsukawa, M Murai
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  ABSTRACT: 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. 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. 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. 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.
  International Journal of Urology 06/1999; 6(6):298-304. · 1.75 Impact Factor
• Article: Application of region-specific immunoassay for human chromogranin A: substantial clue for detection and measurement of chromogranin A in human plasma.

  H Yanaihara, M Hata, Y Nishikawa, M Hoshino, N Yanaihara, M Murai
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  ABSTRACT: Chromogranin A (CgA), a secretory protein, is co-released with catecholamines from storage vesicles. It is known to be elevated in the circulation of patients with neuroendocrine and endocrine tumors. For further investigation of the protein, especially in humans, it is essential to facilitate quantitative analysis of the protein in human biological materials. In order to introduce novel immunological methodology for this purpose, we purposely selected human CgA(344-374) for the synthetic immunogen to produce region-specific CgA antibodies. The anti-synthetic peptide antibody thus obtained made it possible to develop an immunological method for measurement and characterization of CgA in human plasma. The plasma CgA-immunoreactivity (LI) level measured by the method was 0.31+/-0.01 pmol/ml (mean+/-SEM) in normal subjects and 1.55+/-0.29 pmol/ml in pheochromocytoma. On gel chromatography and HPLC analysis of the plasma of patients with pheochromocytoma, the region-specific assay system enabled us to show the presence of N-terminal truncated CgA, besides CgA itself. By following up changes of plasma CgA-LI in a pheochromocytoma patient using samples that were collected consecutively over a two-year period, the present assay system using the region-specific antibody, anti-human CgA (344-374) serum, was confirmed to be extremely valuable for the measurement of CgA-LI in human plasma. The characteristic features and high sensitivity of the present assay system will give us a substantial clue to the detection and measurement of CgA to develop further investigation of the protein in humans.
  Regulatory Peptides 04/1999; 80(1-2):83-90. · 2.11 Impact Factor