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Biomedical subjects

Masaru Murai

Publications and source records attributed to Masaru Murai.

At least 19 recordsLinked to original sources
PubMed2003

Suppression of hormone-refractory prostate cancer by a novel nuclear factor kappaB inhibitor in nude mice.

We have synthesized and explored the feasibility of using a novel nuclear factor (NF) kappaB inhibitor, a dehydroxymethylepoxyquinomicin designated as DHMEQ, against prostate cancer. The activity of NFkappaB, evaluated by transient transfection of a luciferase reporter DNA containing a specific binding sequence for NFkappaB, was inhibited by DHMEQ in three human hormone-refractory prostate cancer cell lines, DU145, JCA-1, and PC-3. Statistically significant growth inhibition was achieved by 20 micro g/ml of DHMEQ, and marked levels of apoptosis were induced 48 h after DHMEQ administration in vitro. Electrophoretic mobility shift assay showed that DHMEQ completely inhibited NFkappaB DNA binding activity in JCA-1 cells. Furthermore, i.p. administrations of DHMEQ significantly inhibited pre-established JCA-1 s.c. tumor growth in nude mice without any side effects. Our result indicates the possibility of using a novel NFkappaB activation inhibitor, DHMEQ, as a new treatment strategy against hormone-refractory prostate cancer.

Animals↗
PubMed2003

Non-functional adrenocortical adenoma with extensive degeneration.

We report a case of non-functional adrenocortical adenoma of 5.5 x 5.5 x 3.2 cm in size that had an unusual histopathological appearance in two respects. First, the tumor contained small adipose foci with osteogenesis and was suspected of being a myelolipoma based on its appearance on computerized tomography (CT) and magnetic resonance imaging. However, pathologically, the fat element was seen focally and was not accompanied by hematopoietic cells, and the diagnosis of myelolipoma was abandoned. Second, the tumor was suspected of being an adrenal carcinoma based on its appearance on CT scans and showed extensive degeneration: fibrosis, hemorrhage, loss of parenchyma and moderate atypism of the tumor cells. However, as the architecture of the tumor cells was non-diffuse and there were no necrotic foci or mitoses, and vascular or capsular invasion were not present, the tumor was concluded to be an adrenocortical adenoma rather than a carcinoma. We diagnosed the tumor as a non-functional adrenocortical adenoma with extensive degeneration as the extensive areas of fibrosis were particularly remarkable. Furthermore, the extensive areas of degeneration might have been caused not only by an ischemic effect but also by low hormone levels.

Adrenal Cortex↗
PubMed2003

Primary carcinoid tumor in a polycystic kidney.

A case of a primary carcinoid tumor within a polycystic kidney is reported. A 51-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) underwent a bilateral nephrectomy because of an infection in her polycystic kidneys. A tumor (1.5 cm in diameter) was incidentally found close to the hilum of the left kidney. Histologically, the tumor exhibited a predominantly trabecular pattern of cuboidal or columnar cells. Grimelius staining showed numerous silver-stained neurosecretory granules in most of the tumor cells; the tumor cells were also positive for chromogranin, synaptophysin, prostatic acid phosphatase (PAP) and neuron-specific enolase (NSE). The tumor was diagnosed as a primary carcinoid tumor of the kidney. Primary renal carcinoid is a very rare neoplasm, and this is the first report of such a lesion arising in a polycystic kidney.

Biomarkers, Tumor↗
PubMed2003

Incidence and growth pattern of simple cysts of the kidney in patients with asymptomatic microscopic hematuria.

BACKGROUND: We examined the incidence and natural history of simple renal cysts found by ultrasonography (US) in patients referred for asymptomatic microscopic hematuria. METHODS: Among the 906 patients aged 18-78 years, 743 patients who had undergone US were included in the present study. The natural history of simple renal cysts was investigated in 55 patients who underwent periodical US examinations for more than 3 years. RESULTS: The incidence of simple renal cysts was 4.3% for ages 29 years or younger, 15.3% for ages 30-39, 21.8% for ages 40-49, 23.3% for ages 50-59 and 32.6% for ages 60 years or older; thus the incidence increased in older age groups (P = 0.0005 for men, P = 0.0020 for women). Men tended to have a higher incidence than women. The degree of hematuria did not influence the incidence of renal cysts (P = 0.9044). The annual growth rate of the mean maximum diameter was 4.2% during a 3-year follow-up period in 55 patients and 5.1% during a 6-year follow-up in 31 patients. CONCLUSION: Since the diameter of a renal cyst may increase by 5% annually, the diameter of the cyst may increase by 1.6 times in 10 years. The scheduling of follow-up examinations depends on the size at the time of disclosure, the effects on calyceal systems, or the suspicion of a concurrent malignant disease. However, the most simple renal cysts may be followed-up at an interval of more than 10 years, once a diagnosis has been established.

Adolescent↗
PubMed2003

Increased nuclear factor-kappa B activation is related to the tumor development of renal cell carcinoma.

Although an aggressive phenotype of renal cell carcinoma (RCC) is known to frequently be associated with inflammatory paraneoplastic syndrome including serum C-reactive protein (CRP) elevation, the molecular mechanism underlying this clinical phenomenon as well as what yields the malignant phenotype leading to the progression of RCC has yet to be elucidated. Based on the increased level of inflammatory cytokines such as interleukin-6 in advanced cases of RCC, a cytokine-inducible transcription factor, namely, nuclear factor-kappa B (NF-kappa B), may thus play a role in the progression of RCC. An electrophoretic mobility shift assay (EMSA) was carried out to determine the activity of NF-kappa B. Out of 45 cases of RCC, 15 cases (33%) showed a >200% increase in the NF-kappa B activity in comparison with that seen in normal renal tissue. In locally advanced cases (> or =pT3), 64% (9/14) showed an increased activity whereas it was only observed in 19% (6/31) of localized cases (< or =pT2). All three cases with metastases showed an increased NF-kappa B activity. The NF-kappa B activity determined by EMSA was further confirmed by an immunohistochemical analysis using an antibody recognizing the nuclear localization signal (NLS) in p65 subunit of NF-kappa B. The serum CRP elevation correlated with the increased NF-kappa B activation, and therefore NF-kappa B may be a causative transcription factor of inflammatory paraneoplastic syndrome. A high NF-kappa B activity was associated with an increased expression of both the p65 and p50 subunits of NF-kappa B and a concomitant decreased expression of I kappa B alpha. No functional mutations of the I kappa B alpha gene were detected. The NF-kappa B activity may therefore be a late event in carcinogenesis related to tumor development, thereby representing a possible molecular target in the treatment of RCC.

Adult↗
PubMed2003

Enhancement of diethylstilbestrol induced cytotoxicity by bcl-2 antisense oligodeoxynucleotides and a glutathione depletor for prostate cancer.

PURPOSE: Bcl-2 has been shown to prolong cancer cell survival by blocking apoptosis and have the function of scavenging reactive oxygen species. We assessed the efficacy of a novel strategy that relies on antisense bcl-2 oligodeoxynucleotides as well as a glutathione depletor combined with diethylstilbestrol (DES) for hormone independent prostate cancer. MATERIALS AND METHODS: The cytotoxic effects of antisense bcl-2 oligodeoxynucleotides and DES on PC-3 cells were determined using spectrophotometry measurement. The expression of Bcl-2 protein was detected by Western blot analysis. Intracellular reactive oxygen species generation was estimated from the amount of intracellular dichlorofluorescein. Apoptosis was determined by the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate-biotin nick end labeling assay. RESULTS: Antisense bcl-2 oligodeoxynucleotides decreased Bcl-2 protein levels and significantly inhibited PC-3 cell growth in a dose dependent manner. Antisense bcl-2 oligodeoxynucleotides significantly enhanced DES induced cytotoxicity. A significant increase in apoptotic cells was induced by the combination of antisense bcl-2 oligodeoxynucleotides and DES compared with the oligodeoxynucleotides alone. The glutathione depletor buthionine sulfoximine significantly decreased the intracellular concentration of glutathione and augmented DES induced cytotoxicity and reactive oxygen species generation in PC-3 cells. Neither the generation of reactive oxygen species nor the intracellular concentration of glutathione was influenced by antisense bcl-2 oligodeoxynucleotide treatment. CONCLUSIONS: Antisense bcl-2 oligodeoxynucleotides significantly enhanced DES induced cytotoxicity in hormone independent prostate cancer cells through the apoptotic pathway independent of augmented reactive oxygen species generation, whereas the glutathione depletor augmented cytotoxicity and reactive oxygen species generation.

Apoptosis↗
PubMed2003

Successful diagnosis of orthotopic rat superficial bladder tumor model by ultrathin cystoscopy.

PURPOSE: In the orthotopic animal bladder tumor model noninvasive evaluation of the tumor establishment and the therapeutic effect has been difficult. To our knowledge we present the first diagnosis of orthotopic rat superficial bladder tumor model by ultrathin cystoscopy. MATERIALS AND METHODS: The established AY-27 rat bladder carcinoma cell line was transplanted orthotopically into 22 female Fischer F344 rats. A cell suspension containing 4 x 10 AY-27 cells was instilled into the bladder, which had been conditioned with mild acid washing. To evaluate tumor growth serial cystoscopy was performed via the urethra with an ultrathin endoscope (diameter 0.75 mm.) 5 to 14 days after tumor cell inoculation. At intervals after cystoscopic tumor detection the rats were sacrificed for autopsy and histological examination. RESULTS: In all 22 rats the orthotopic bladder tumor was established 7 to 10 days after tumor cell implantation and in most it was superficial. Cystoscopy permitted inspection of the urethra and whole bladder surface. We detected all tumors as broad based papillary mass (minimal lesion 1 mm. or less) and inspected its detailed appearance and accurate location. CONCLUSIONS: The orthotopic rat superficial bladder tumor model and the diagnostic procedure by ultrathin cystoscopy would be ideal system for preclinical evaluation of new potential intravesical therapies.

Animals↗
PubMed2003

Elevated Akt activation and its impact on clinicopathological features of renal cell carcinoma.

PURPOSE: Akt has been implicated in the pathogenesis and progression of numerous human malignant tumors because Akt regulates many key effector molecules involved in controlling the balance of survival and apoptosis. Elevated Akt activation has been demonstrated in various types of malignant tumors. In the current study we evaluated Akt activation in renal cell carcinoma and investigated its association with pathological features and clinical outcome. MATERIALS AND METHODS: Akt activation was evaluated by immunohistochemistry using antiphospho-specific Akt antibody, which recognizes only activated Akt, in 48 patients with renal cell carcinoma. High immunostaining tumors were defined as tumors with increased staining intensity compared with adjacent nonneoplastic kidney tissue and low immunostaining tumors were defined as tumors with equivalent or decreased staining intensity. The association of Akt activation status with clinicopathological features was analyzed. RESULTS: Of 48 patients examined 18 (37.5%) demonstrated high antiphospho-specific Akt immunostaining compared with adjacent nonneoplastic kidney tissue, while 30 (62.5%) demonstrated low immunostaining. Elevated immunostaining was significantly associated with tumor grade (p = 0.0354) and metastatic disease (p = 0.0044), while it was not associated with tumor stage or histological subtype. In addition, high antiphospho-specific Akt immunostaining was significantly associated with a poor cancer specific survival rate on univariate analysis (p = 0.0109) but not on multivariate analysis. CONCLUSIONS: Elevated Akt activation could be a common finding, especially in high grade tumor and metastatic disease. It could have an important role in the pathogenesis and progression of renal cell carcinoma.

Adult↗
PubMed2003

Increased activation of CCAAT/enhancer binding protein-beta correlates with the invasiveness of renal cell carcinoma.

Positive inflammatory reactions in an aggressive phenotype are typical features of renal cell carcinoma (RCC). Although a high blood level of inflammatory cytokines, such as interleukin-6, interleukin-8, and tumor necrosis factor-alpha, has been observed in these patients, the mechanisms underlying this clinical phenomenon remain to be elucidated. CCAAT/enhancer binding protein (C/EBP) family are transcription factors which play a role in cell differentiation and inflammatory reactions. Among these, C/EBP-beta induces a variety of cytokines and thus may play a role in the pathogenesis of RCC. We studied the activation of C/EBP-beta determined by electrophoretic mobility shift assay in nine RCC cell lines and 44 tissue samples. Six cell lines showed an activation of C/EBP-beta, whereas three cell lines did not, and two of these three had no expression at all of C/EBP-beta protein. Of 44 tissue samples, 12 (27.3%) showed a >200% increase in the activity compared with the corresponding normal kidney tissues. Locally advanced cases had a significantly higher rate of increased C/EBP-beta activity (5 of 8 = 62.5% in advanced cases versus 7 of 36 = 19.4% in localized cases). Especially, all four cases with renal vein invasion had an increased C/EBP-beta activity. These data suggest that the increased activation of C/EBP-beta may contribute to promote tumor invasiveness and render a malignant phenotype of RCC, although it needs to be validated in a larger series.

Adult↗
PubMed2002

Clinical value of prostate specific antigen based parameters for the detection of prostate cancer on repeat biopsy: the usefulness of complexed prostate specific antigen adjusted for transition zone volume.

PURPOSE: To our knowledge the indications for repeat prostate needle biopsy in men whose previous transrectal ultrasound guided biopsy results revealed no evidence of cancer have not yet been defined. We identified the most effective method for detecting prostate cancer on repeat biopsy. MATERIALS AND METHODS: One or more systematic repeat prostate biopsies were performed in 144 consecutive patients, including 86 with prostate specific antigen (PSA) levels between 4 and 10 ng./ml. at repeat biopsy. Men in whom cancer was detected on repeat biopsies were compared with their counterparts in terms of digital rectal examination findings, PSA based parameters and an atypical prostate on initial prostate biopsy. RESULTS: Prostate cancer was detected on repeat biopsy in 39 of the 144 patients and in 19 on subset analysis of 86. Serum PSA levels at repeat biopsy did not differ significantly in patients with and without prostate cancer. According to receiver operating characteristics analysis the alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume had the greatest area under the curve values, that is 0.756 for all 144 patients and 0.768 for the subset analysis of 86. Multiple logistic regression analysis of the subset of 86 patients showed that alpha1-antichymotrypsin-PSA complex adjusted for transition zone volume was the only significant independent predictor of cancer. CONCLUSIONS: alpha1-Antichymotrypsin-PSA complex adjusted for transition zone volume was the most powerful predictor of cancer in men who had undergone previous negative prostate biopsies. This parameter may be used to avoid more unnecessary repeat biopsies with an acceptable decrease in sensitivity.

Aged↗
PubMed2002

SN-38 induces cell cycle arrest and apoptosis in human testicular cancer.

OBJECTIVE: CPT-11 is one of the most widely used camptothecin analogues and is converted to form the active metabolite SN-38. Clinical trials are ongoing to better characterize its spectra of clinical activity, to determine the optimal schedules of administration, and to define the usage in combination with other chemotherapeutic compounds. MATERIALS AND METHODS: KU-MT, an AFP-producing testicular carcinoma cell line, was exposed to SN-38, etoposide, or cisplatin for 24 h, and the resulting cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay. This paper describes the effects of SN-38 on the cell proliferation and cell cycle of testicular tumor cells in culture. RESULTS: SN-38 was shown to inhibit KU-MT cell growth more potently than either etoposide or cisplatin. A marked decrease in the percentage of S phase cells was accompanied by the enhancement of cyclin E levels. In concentrations of >30 nmol/l, SN-38 arrested the cell cycle in G2 and induced cell death via apoptosis. The apoptosis was promoted by Bax and p53 protein, which were both shown to be present by flow cytometric and Western blot analyses. CONCLUSION: These results suggest that CPT-11, a pro-drug of SN-38, may be clinically useful for the treatment of testicular cancer, and that the mechanism of this agent's cytotoxicity consists of cell cycle arrest and concomitant apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2002

Laparoscopic adrenalectomy: current status with a review of Japanese literature.

A decade has elapsed since laparoscopic adrenalectomy was first performed in 1992. Accumulated experiences of laparoscopic adrenalectomy have shown superior results to treat small functional benign tumors and make the indication expand to large tumors, pheochromocytomas and localized malignant tumors. Following the initially established transperitoneal approach, which includes anterior and lateral approaches, the retroperitoneal lateral flank and posterior lumber approaches have been performed. Each approach has advantages and disadvantages. The transperitoneal approach supplies a large operative field, many anatomical landmarks and easy handling. But it causes post-operative irritability and it is very difficult to perform after previous upper abdominal surgery. The retroperitoneal approach can be performed even after previous abdominal surgery and patients may be more comfortable after the operation. However, the narrow working space and the lack of anatomical landmarks may increase the rate of intra-operative complications and the rate of conversion to open surgery. Although there is no clear preference between transperitoneal and retroperitoneal approaches, the transperitoneal approach is commonly employed and the transperitoneal anterior approach seems to be the easiest one for right adrenal tumors and the transperitoneal lateral approach for left adrenal tumors. The shorter convalescence with laparoscopic adrenalectomy as compared with open adrenalectomy has been accepted and lower morbidity from laparoscopic adrenalectomy has been achieved. The operative time has been shortened to the level of open adrenalectomy. Less blood loss, less pain and better cosmesis are absolute advantages for the patients. Laparoscopic adrenalectomy is now the gold standard for the treatment of adrenal tumors.

Adrenalectomy↗
PubMed2002

Long-term effects of transurethral microwave thermotherapy.

BACKGROUND: To identify the clinical valuables predicting a favorable outcome after transurethral microwave thermotherapy (TUMT) of the prostate with Prostatron. METHODS: One hundred and two patients with lower urinary symptoms were treated with TUMT using a Prostatron device with the low-energy protocol (Prostasoft version 2.0 J). The pre-operative subjective score and objective voiding parameters were collected from the medical record. To test the differences in the risk of the necessity for additional treatments for several subgroups, Kaplan-Meier survival analyses and log-rank tests were used. RESULTS: The Kaplan-Meier analyses showed that 67% of the patients received additional treatment within five years. The median period for receiving additional treatment was 37 months. The patients with a peak flow rate greater than 6.5 mL per second, with a urethral length less than 40 mm, or with an age over 64 years all demonstrated a significantly longer period before receiving additional treatment, when compared with their counterparts. These three factors were also significant in multivariate analysis to predict the long-term outcome. CONCLUSIONS: Overall durability of TUMT was limited. Aged patients with a relatively high peak flow rate or with a short prostatic urethral length resulted in lower risk of receiving additional treatments after TUMT.

Aged↗
PubMed2002

Significance and diagnostic accuracy of renal calculi found by ultrasonography in patients with asymptomatic microscopic hematuria.

BACKGROUND: The purpose of the present study was to evaluate the clinical significance and the accuracy of the diagnosis of renal calculi incidentally found by ultrasonography (US). METHODS: A total of 906 subjects (639 men and 267 women) aged 18-78 years were referred for asymptomatic microscopic hematuria. Of these, 743 patients who underwent US were studied. RESULTS: Hyperechogenic spots in the central echo complex suggesting renal calculi were noted in 195 patients (21.5%). The occurrence of hyperechogenic spots was higher in patients with 20 or more urinary red blood cells per high-power field (chi(2) = 4.896, P = 0.0269) and in men than in women (chi(2) = 7.101, P = 0.0077), but it was lowest in patients who were 29 years old or younger. Of these 195 patients, who were followed up for 1-161 months (average: 33.5 months), 24 patients (12.3%) needed urological management. Extracorporeal shockwave lithotripsy was carried out in eight patients, transureteral lithotripsy was carried out in three patients, spontaneous passage occurred in 11 patients and medication for hyperuricemia was initiated in two patients (1%). Among the patients in whom hyperechogenic spots were found on the kidney by US but calculi were not visible on abdominal plain radiographs, 39 patients underwent computed tomography. Of them, 31 patients were confirmed to have renal calculi. CONCLUSION: The obtained results suggest that US is an effective and reliable means of detecting renal calculi in patients with asymptomatic microscopic hematuria, and in facilitating prompt urological intervention or predicting the natural course of renal calculi.

Adult↗
PubMed2002

STAT3, but not ERKs, mediates the IL-6-induced proliferation of renal cancer cells, ACHN and 769P.

BACKGROUND: Although interleukin-6 (IL-6) has been suggested to function as an autocrine growth factor in renal cell carcinoma (RCC), the underlying mechanism responsible for the IL-6-induced proliferation of RCC has not been defined. The aim of this study was to characterize the signaling cascades mediating IL-6-induced proliferation and to investigate the use of effective novel interventions to block the IL-6-induced autocrine growth of renal cancer cells. METHODS: IL-6-induced proliferation and intracellular signaling cascades were analyzed in four human renal cancer cell lines Caki-1, ACHN, 769P and A498. IL-6-induced activation of STAT3 (signal transducer and activator of transcription-1) and extracellular signal-regulated kinases (ERKs), and the effects of anti-IL-6 neutralizing antibody, Jak inhibitor AG 490, and MEK1 inhibitor PD 98059 were analyzed by Western blotting using phospho-specific antibodies. The DNA-binding activities of STATs were analyzed by EMSA. Apoptosis was determined by using nuclear staining and the TUNEL assay. Changes in the apoptosis-related proteins, bcl-2, bcl-xL, and bax were analyzed by Western blotting. RESULTS: IL-6 induced tyrosine phosphorylation and increased the DNA binding activity of STAT3 and, to a lesser extent, STAT1 in all cell lines except for Caki-1, which did not express the IL-6 receptor subunit gp130. ERKs were constitutively activated in all cell lines and the activation level was not up-regulated further by exogenously added IL-6 nor down-regulated by anti-IL-6 neutralizing antibody. IL-6-induced STAT3 tyrosine phosphorylation and DNA binding activity was inhibited by treatment with Jak specific inhibitor AG 490; however, it was not affected by the MEK1 inhibitor PD 98059. Moreover, treatment with AG 490 inhibited IL-6-induced proliferation of ACHN and 769P cells and induced apoptosis with the down-regulation of bcl-2 and the up-regulation of bax. CONCLUSIONS: This study identified STAT3, but not ERKs, to be a major mediator of IL-6-induced proliferation of renal cancer cells. Although ERKs were constitutively activated, ERKs were not found to be essential for the IL-6-induced proliferation and modulation of the STAT3 activity. Because the Jak specific inhibitor AG 490 effectively inhibited the IL-6-induced STAT3 activity and induced apoptosis, the blockade of the STAT3 signaling pathways is considered to be potentially useful as a novel therapeutic approach for RCC.

Antibodies, Monoclonal↗
PubMed2002

Hypercalcemia and acute renal failure caused by production of parathyroid hormone-related protein from renal cell carcinoma.

A 69-year-old male patient was diagnosed with right-sided renal cell carcinoma and humoral hypercalcemia of malignancy caused by an excessive production of parathyroid hormone-related protein. The hypercalcemia led to acute tubular necrosis, so the patient had to be put on hemodialysis. The renal failure was accompanied by hyponatremic encephalopathy. Rapid correction of the hyponatremia might have initiated central pontine myelinolysis.

Acute Kidney Injury↗
PubMed2002

Bcl-2 and androgen receptor gene expression in androgen-independent subclone derived from mouse androgen-dependent cells.

We investigated bcl-2 and androgen receptor (AR) expression in an androgen-independent subline derived from mouse androgen-dependent mammary carcinoma cells. The androgen-independent SCAI cells were subcloned by cultivating androgen-dependent SC2G cells in serum-free, androgen-free conditions. The growth of the SCAI cells was not affected by testosterone. Western blot analysis showed greater expression of Bcl-2 protein in SCAI cells than in SC2G cells. A four-day culture with 4 microM antisense oligonucleotide complementary to mouse bcl-2 significantly decreased the viability of SCAI cells, when compared with sense control. The amount of the AR-mRNA expression in SCAI cells was slightly weaker. Direct sequence analysis showed no mutations in the AR of either androgen-dependent or -independent cells. These data indicate that the increased expression of Bcl-2 protein plays an important role in acquiring tolerance for the testosterone ablation, although it is not related to AR gene alteration.

Androgens↗