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Hiroyoshi Suzuki

Publications and source records attributed to Hiroyoshi Suzuki.

72 records · Page 4Linked to original sources
PubMed2002

CAG polymorphic repeat lengths in androgen receptor gene among Japanese prostate cancer patients: potential predictor of prognosis after endocrine therapy.

BACKGROUND: Several investigators have examined the clinical significance of the length of the CAG repeat at the N-terminal region of the androgen receptor in the pathogenesis of prostate cancer. Because the clinical significance of CAG repeat length during the course of prostate cancer in Japanese patients is unknown, the present study analyzed CAG repeat length in relation to several potential clinical factors. MATERIALS AND METHODS: A total of 88 Japanese patients with prostate cancer and a control group of 53 patients with benign prostatic disease were enrolled in this study. The length of the CAG repeat was determined by PCR sequencing and analyzed in relation to several clinical factors. RESULTS: The length of the CAG repeat did not significantly differ between prostate cancer and benign prostatic disease. Although not statistically different with regard to clinical stage and serum PSA level, the CAG repeat length was associated with histological grade and age at diagnosis. In addition, the CAG repeat length in CR and in non CR patients significantly differed at 22.1 +/- 2.4 and 24.4 +/- 3.0, respectively (P = 0.0264), suggesting that the CAG repeat length can act as a molecular marker with which to predict response to endocrine therapy in stage D prostate cancer patients. CONCLUSIONS: A shorter CAG repeat length appears to predict a response to endocrine therapy, showing a positive prognostic value and indicating good prognosis in the metastatic stage of prostate cancer patients.

Aged↗
PubMed2002

Tumor-associated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity.

CTCF is a widely expressed 11-zinc finger (ZF) transcription factor that is involved in different aspects of gene regulation including promoter activation or repression, hormone-responsive gene silencing, methylation-dependent chromatin insulation, and genomic imprinting. Because CTCF targets include oncogenes and tumor suppressor genes, we screened over 100 human tumor samples for mutations that might disrupt CTCF activity. We did not observe any CTCF mutations leading to truncations/premature stops. Rather, in breast, prostate, and Wilms' tumors, we observed four different CTCF somatic missense mutations involving amino acids within the ZF domain. Each ZF mutation abrogated CTCF binding to a subset of target sites within the promoters/insulators of certain genes involved in regulating cell proliferation but did not alter binding to the regulatory sequences of other genes. These observations suggest that CTCF may represent a novel tumor suppressor gene that displays tumor-specific "change of function" rather than complete "loss of function."

Amino Acid Sequence↗
PubMed2002

A case of angioglioma composed of astrocytoma with a papillary growth pattern: immunohistochemical and ultrastructural studies.

We report a case of a large cystic astrocytoma associated with arteriovenous malformation in the right cerebral hemisphere of a 16-year-old boy. Neuroimaging showed large abnormal vessels with flow voids and arteriovenous shunt around the cystic lesion. Histologically, the cyst wall was formed by abnormal vasculature and clusters of glial cells forming a papillary growth pattern. The abnormal vasculature consisted of dilated vein-like vessels and medium-sized arteries with incomplete media, and was diagnosed as an arteriovenous malformation. Immunohistochemically, glial fibrillary acidic protein (GFAP) decorated both the perikaryon and the processes of the glial tumor cells. They were negative for epithelial membrane antigen (EMA), cytokeratin, and S-100 protein. Ultrastructurally, the tumor cells were rich in intermediate filaments, and neither cilia, microvilli, nor ependymal rosettes were verified. Based on these morphological features and the low MIB-1 labeling index of 0.8%, the glial tumor was diagnosed as astrocytoma, Grade II, according to the World Health Organization (WHO) tumor classification. An association of glioma with various types of vascular anomalies has been designated as angioglioma. A unique feature of the present case, however, is a papillary growth pattern, which is not listed in the current WHO classification of brain tumors. The recognition of the occurrence of such cases would be important in differential diagnosis of papillary ependymoma and choroid plexus papilloma.

Adolescent↗
PubMed2002

Minute pancreatic carcinoma with initial symptom of acute pancreatitis.

We experienced a case of minute pancreatic carcinoma in a 59-year-old man who complained of upper abdominal pain after drinking alcohol. Abdominal ultrasonography (US) revealed dilatation of the main pancreatic duct (MPD). Abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) showed slight dilatation of the MPD and its obstruction near the portal vein. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated occlusion of the MPD, and cytology of aspirated pancreatic juice was negative for malignancy. With the diagnosis of benign localized obstruction of the MPD, the patient underwent surgery. There was a clear demarcation of hardness and color of the pancreas on the left margin of the superior mesenteric vein, and the caudal pancreas was hard and fibrotic. Intraoperative US revealed slight dilatation of the MPD, and the aspiration cytology result was class IV. First, segmental resection of the pancreas was performed, but pathological examination of frozen section showed neither malignancy nor stenotic lesion. An additional small portion of the proximal pancreas was resected. The specimen included a ductal carcinoma, 5 mm in diameter. Accordingly, a pylorus-preserving pancreatoduodenectomy was performed. Microscopically, the minute carcinoma had already penetrated the duct wall and infiltrated lymph vessels and veins. The patient has been under close observation at our outpatient clinic, and so far there have been no signs of recurrence. To improve the poor prognosis of pancreatic cancer, we should be alert to the occurrence of acute pancreatitis as an initial symptom.

Acute Disease↗
PubMed2002

Chromogranin a concentration as a serum marker to predict prognosis after endocrine therapy for prostate cancer.

PURPOSE: Chromogranin A is gaining acceptance as a serum marker of neuroendocrine tumors and the concentration is thought to be elevated in relation to neuroendocrine differentiation of prostate cancer. We examined the significance of the chromogranin A level as a serum marker for prostate cancer. MATERIALS AND METHODS: Serum chromogranin A values were determined by monoclonal immunoradiometric assay in 108 patients with prostate cancer before treatment and in 66 with benign prostatic hyperplasia. In those with prostate cancer clinicopathological parameters, the response to endocrine therapy and the prognosis were evaluated in relation to serum chromogranin A. RESULTS: Mean serum chromogranin A plus or minus standard deviation in prostate cancer and benign prostatic hyperplasia cases was 59.4 +/- 52.5 and 59.3 +/- 44.3 ng./ml., respectively (not significant). Poorly differentiated adenocarcinoma was associated with higher chromogranin A than well differentiated disease (p = 0.044). Of the stage D cases with a median prostate specific antigen (PSA) of 172.1 ng./ml. or less those with higher chromogranin A had a poorer prognosis than those with lower chromogranin A. In contrast, in stage D cases with a PSA of greater than 172.1 ng./ml. there was no difference in the prognosis between the higher and lower chromogranin A groups. CONCLUSIONS: Serum chromogranin A tends to be elevated in patients with high grade prostate cancer. When combined with PSA, this marker may effectively predict a poor prognosis after endocrine therapy.

Adenocarcinoma↗
PubMed2002

Clinical characteristics of prostate cancer in elderly Japanese patients 80 years of age or older.

OBJECTIVE: Prostate adenocarcinoma is predominantly a disease of elderly men. This study retrospectively examined prostate adenocarcinoma in Japanese patients 80 years of age or older to determine the natural history and prognosis of this malignancy in the elderly population. METHODS: The medical records of 593 patients were reviewed, with respect to age, histologic grade, clinical and pathological stage, treatment modality and clinical outcome. A variety of possible clinical factors were compared between patient groups > or = 80 and < 80 years old. RESULTS: No significant difference in clinical stage, tumor grade, and performance status (PS) was found between two age groups of patients with prostate cancer. A significant stage migration between pre-PSA era and PSA era was found only in the group < 80 years old. In the series of stage D2 cancer patients, while there was no significant difference in cause-specific and progression-free survival rates between the two groups, the younger group < 80 years old had a better marker response at 3 months from the start of endocrine therapy compared with the older group (P = 0.0048, chi2 analysis). CONCLUSION: These data suggest that patients > or = 80 years with prostate cancer present with similar histologic grade and disease stage as younger patients, although the younger group with stage D2 had a better marker response to endocrine therapy.

Adenocarcinoma↗
PubMed2002

Anaplastic ganglioglioma with sarcomatous component: an immunohistochemical study and molecular analysis of p53 tumor suppressor gene.

The present case report describes a case of ganglioglioma with a distinct sarcomatous component in the left temporal lobe of a 59-year-old Japanese man. Neoplastic neuroglial tissue contained both benign and anaplastic glial components with a MIB-1 labeling index of 0.1% and 12.0%, respectively. Sarcomatous tissue adjacent to the anaplastic glial tissue was dominated by pleomorphic fibroblastic cells with a MIB-1 labeling index of 10.8%. They were immunoreactive for smooth muscle actin, type IV collagen, and alpha 1 antitrypsin, but not for desmin and CD34. Interestingly, some of the sarcomatous cells were double-positive for smooth muscle actin and GFAP. The p53 protein had accumulated in the anaplastic astrocytes and sarcomatous cells, but direct DNA sequencing of PCR products failed to detect any mutation in the p53 gene (from exon 4 to exon 10).

Actins↗
PubMed2002

Expression of thymidine phosphorylase in primary human renal cell carcinoma by ELISA method.

Thymidine phosphorylase (TP) expression in 100 paired samples of renal cell carcinoma (RCC) and normal adjacent tissue was analyzed by an ELISA method. We also investigated whether TP expression correlates with clinicopathological findings and clinical outcomes of these patients. Median TP expression was 9-fold (range, 0.5-56) higher in primary tumor than in non-cancerous renal tissue (P < 0.0001). There was a significant difference with respect to tumor venous invasion. TP expression was significantly higher in patients with such venous invasion than in those without (P = 0.018). However, there was no correlation between TP level and other clinicopathological findings and the survival curves. These results suggest that ELISA is useful for evaluating TP expression of human RCC and may provide a novel approach to therapy for patients with RCC.

Adult↗
PubMed2002

Effect of tumor-infiltrating lymphocyte subsets on prognosis and susceptibility to interferon therapy in patients with renal cell carcinoma.

INTRODUCTION: Immunotherapy effectively treats advanced renal cell carcinoma in only a limited number of patients. However, the predicted prognosis for each patient in relation to immune status and response to immunotherapy remains problematic. We analyzed tumor-infiltrating lymphocyte (TIL) subsets to determine whether these correlated with the prognoses for the patients and the response to alpha-interferon therapy. MATERIALS AND METHODS: TIL subsets from resected specimens of 79 patients were analyzed by two-color flow cytometry and then compared with the patients' long-term clinical courses and responses to interferon therapy. RESULTS: In patients with stages III and IV, an increased infiltration of CD4+ cells and decreased CD8+ cells constituted a fair prognostic factor. In 17 patients with metastatic lesions, 8 of 10 patients who had disease progression after interferon therapy showed an increase in CD8+ cells above 25%, whereas 2 responders and 5 patients who had stable disease showed infiltration of CD8+ cells below 25%. CONCLUSIONS: The TIL subset is a prognostic factor for advanced renal cell carcinoma, and its analysis provides a method to predict the susceptibility to interferon therapy.

Adult↗
PubMed2002

A case of solitary fibrous tumor of the parotid gland: review of the literatures.

We report a rare case of solitary fibrous tumor of the parotid gland. A 47-year-old woman presented with a 3-year-history of left-sided subauricular swelling. Computed tomographic scans and magnetic resonance images revealed a well-defined and dumbbell-shaped mass, measuring about 30 mm in its greatest dimension, in the left parotid gland. Because the tumor occupied both superficial and deep lobes of the gland, she underwent total parotidectomy with preservation of the facial nerve. The microscopic finding showed short-spindle and ovoid cells arranged in a haphazard pattern with interspersed thin collagen fibrils. Immunohistochemically, the tumor cells were strongly positive for CD34, bcl-2 and vimentin, whereas stains for S-100, cytokeratin, smooth muscle actin, collagen type IV and CD117 (KIT) were negative. On the basis of these findings, the tumor was diagnosed as solitary fibrous tumor. Her post-operative course was uneventful, and she is currently free from disease 14 months after surgery. Diagnosis, clinical behavior and treatment of solitary fibrous tumor are reviewed from perusal of the literature.

Antigens, CD34↗
PubMed2002

Intracranial germinoma with syncytiotrophoblastic giant cells in the cerebellopontine angle--case report.

A 23-year-old man presented with a 3-week history of left hearing disturbance and left facial nerve paresis. T1-weighted magnetic resonance (MR) imaging showed an iso-intense mass in the left cerebellopontine angle (CPA), with homogeneous enhancement with gadolinium-diethylenetriaminepenta-acetic acid. T2-weighted MR imaging showed the mass as heterogeneously iso- to hyperintense. Gross total removal of the tumor was achieved. Histological examination revealed that the tumor was a germinoma with syncytiotrophoblastic giant cells. Whole central nervous system irradiation with cisplatin-etoposide chemotherapy was performed postoperatively. He has been in good condition with no sign of recurrence for 7 years. Intracranial germ cell tumors in the CPA are very rare. Total surgical removal followed by irradiation and chemotherapy will provide a good outcome.

Adult↗
PubMed2002

High prevalence of decreased expression of KAI1 metastasis suppressor in human oral carcinogenesis.

PURPOSE: KAI1 was originally identified in prostate cancer as a metastasis suppressor gene. Recent studies have shown a frequent down-regulation of KAI1 expression in many tumor types, whereas mutation or hypermethylation of the gene is infrequent. The aim of the present study was to examine whether loss of KAI1 expression that might be caused by genetic or epigenetic alterations could contribute to oral carcinogenesis. EXPERIMENTAL DESIGN: We analyzed mutational and methylation status of the KAI1 gene and both the mRNA and protein level in a series of oral tumors [28 precancerous lesions, 101 primary oral squamous cell carcinomas (OSCCs), and 30 metastatic OSCCs] and OSCC-derived cell lines. We also examined p53 protein expression, which has been reported to be a candidate activator for the KAI1 gene. RESULTS: With the exception of three microsatellite instabilities in the KAI1 gene, we found no mutations in the coding sequence of the KAI1 gene, no loss of heterozygosity, and no hypermethylation of the KAI1 promoter region in all samples investigated. By immunohistochemistry, however, high frequencies of KAI1 down-regulation were evident not only in the metastatic OSCCs [29 of 30 (97%)] but also in the primary OSCCs [83 of 101 (82%)] and in the precancerous lesions [13 of 28 (46%)]. There was a significant relationship between down-regulation of KAI1 protein expression and primary tumors associated with lymph node metastases (P = 0.0115), whereas there was no statistical correlation between p53 status and KAI1 expression. Taken together, reverse transcription-PCR data were consistent with the protein expression status in 16 patients from whom mRNA was available. CONCLUSIONS: Our data suggest that whereas loss of KAI1 protein expression is associated with primary tumors with lymph node metastases, the down-regulation of KAI1 is an early event in the progression of human oral cancer. The down-regulation of KAI1 is not associated with either mutation, allelic loss, methylation of the promoter, or p53 regulation.

Aged↗
PubMed2002

Microdeletions in the Y chromosome of patients with idiopathic azoospermia.

AIM: To evaluate the occurrence and prevalence of microdeletions in the gamma chromosome of patients with azoospermia. METHODS: DNA from 29 men with idiopathic azoospermia was screened by polymerase chain reaction (PCR) analysis with a set of gamma chromosome specific sequence-tagged sites (STSs) to determine microdeletions in the gamma chromosome. RESULTS: Deletions in the DAZ (deleted in azoospermia) loci sgamma254 and sgamma255 were found in three patients with idiopathic azoospermia, resulting in an estimated frequency of deletions of 10.7% in idiopathic azoospermia men. CONCLUSION: We conclude that PCR analysis is useful for the diagnosis of microdeletions in the Y chromosome, which is important when deciding the suitability of a patient for assisted reproductive technology such as testicular sperm extracion-intracytoplasmic sperm injection (TESE-ICSI).

Adult↗
PubMed2002

Mechanisms of metastasis suppression by introduction of human chromosome 10 into rat prostate cancer.

AIM: The metastatic ability of a Dunning R-3327 rat prostate cancer subline (AT6.3) was suppressed by the introduction of human chromosome 10, when these hybrid cancer cells were injected subcutaneously into nude mice (Nihei et al., Genes Chromosomes Cancer 14:112-119, 1995). The present study was undertaken to clarify which step of metastasis was suppressed in the human chromosome 10-containing microcell hybrids (AT 6.3-10 clones). METHODS: Gelatin zymography, an in vitro invasion assay using a Boyden chamber and an intravenous metastasis assay involving the injection of hybrid cells into nude mice were performed. RESULTS: Gelatin zymography revealed that AT6.3-10 microcell hybrid clones expressed the 72 kD type IV collagenase (MMP-2) at an almost equal level as control microcell hybrid clones. Both the invasiveness as measured by the invasion assay and the number of lung metastases as measured by the intravenous metastasis assay of AT6.3-10 hybrid clones were significantly less than those of the AT6.3 parental clone. CONCLUSION: The human chromosome 10 suppresses both the local invasion and the metastatic process after entry into the blood circulation of rat prostate cancer. This decrease in local-invasive ability does not seem to require a decrease in MMP-2 activity.

Animals↗
PubMed2002

Suppression of metastasis of rat prostate cancer by introduction of human chromosome 13.

AIM: Chromosome 13 is one of the most frequently altered chromosomes in prostate cancer. The present study was undertaken to examine the role of human chromosome 13 in the progression of prostate cancer. METHODS: Human chromosome 13 was introduced into highly metastatic rat prostate cancer cells via microcell-mediated chromosome transfer. RESULTS: Microcell hybrid clones containing human chromosome 13 showed suppression of metastasis to the lung without any suppression of tumorigenicity, except for one clone, which contained the smallest sized human chromosome 13 and did not show any suppression on lung metastasis. Expression of two known tumor suppressor genes, BRCA2 and RB1, which map to chromosome 13, was examined by reverse transcription- polymerase chain reaction analysis. BRCA2 was expressed only in the metastasis-suppressed microcell-hybrid clones, whereas RB1 was expressed in all clones. CONCLUSION: Human chromosome 13 contains metastasis suppressor gene(s) for prostate cancer derived from rat. Furthermore, the RB1 gene is unlikely to be involved in the suppression of metastasis evident in this system.

Animals↗
PubMedDate not supplied

Genetic polymorphisms of hormone-related genes and prostate cancer risk in the Japanese population.

Carcinogenesis of the prostate involves androgen influences, and associations between genetic polymorphisms of androgen receptor and metabolizing enzymes and prostate cancer risk have been reported. Roles for non-androgenic hormones are not well defined, but they also may have an impact judging from epidemiological and animal experimental alphalambda zeta of data. The purpose of the study was to determine whether hormone-related polymorphisms are associated with prostate cancer risk. A case-control study was performed with 147 Japanese prostate cancer patients and 266 urological controls. Polymorphisms of target genes [cytochrome P450 (CYP) 1B1, Leu432Val; debrisoquine hydroxylase, (CYP2D6)*4; aromatase (CYP19), Arg264Cys; estrogen receptor (ER)alpha-Xx (Xba I) and Pp (Pvu II); ERbeta-Rr (Rsa I); progesterone receptor (PR) Alu in intron 7] were examined by PCR-based methods. The capital and small letters signify the absence and presence of restriction sites, respectively. Odds ratios (OR) were adjusted for age using multiple logistic regression analysis with SPSS Medical Pack. Among the seven examined genetic polymorphisms, significant associations between CYP1B1 Leu432Val (OR 4.80; 95% confidence interval (CI), 1.21-19.05) and Alu in intron 7 of PR (OR 4.17; 95%CI, 1.26-13.85) were found. As for combined effects, the CYP1B1 polymorphisms (Leu/Val+Val/Val) together with heterozygosity for Alu in the PR were more frequent among prostate cancer patients (1.45%) than controls (0.41%), although without significance (OR, 3.99; 95%CI, 0.36-44.8). The combination of ERalpha (P/p+p/p) polymorphisms with heterozygosity for Alu in the PR demonstrated an OR of 4.56 (95%CI, 1.01-20.6). This pilot study showed that CYP1B1 and PR polymorphisms, alone or in combination, might be associated with prostate cancer risk. They might, therefore, have potential as a tool for identifying high-risk individuals.

Adenocarcinoma↗
PubMedDate not supplied

Interleukin-4 in patients with prostate cancer.

BACKGROUND: Ligand-independent activation of the androgen receptor (AR) by cytokines has been implicated in the progression of androgen-independent prostate cancer (PCa). To determine the potential effects of elevated levels of interleukin-4 (IL-4) in patients with PCa, six different cytokines were examined for their ability to activate the AR. MATERIALS AND METHODS: LNCaP cells were transiently transfected with prostate-specific antigen (PSA) (-630 / +12)-luciferase and treated with R1881, six kinds of cytokines including IL-4, or vehicle. Transactivation assays were also performed in LNCaP cells co-transfected with the 5xGal4UAS-TATA-luciferase and AR-(1-558)-Gal4DBD prior to incubation with R1881, IL-4, IL-6, or vehicle. Seventy-two patients with pre-treatment PCa, 17 patients with hormone-refractory metastatic PCa receiving androgen ablation therapy, 20 patients with benign prostatic hypertrophy and 10 healthy male volunteers were enrolled in this retrospective study. The concentration of serum IL-4 was measured by chemiluminescence enzyme immunoassay. RESULTS: IL-4 induced androgen-response element-driven reporters and activated the AR N-terminal domain (NTD) in a ligand-independent manner in transiently transfected LNCaP cells. Levels of IL-4 in the serum were significantly elevated in patients with hormone-refractory PCa as compared to the levels in pre-treatment PCa. CONCLUSION: IL-4 serum levels were demonstrated to be increased in honnone-refractory PCa and IL-4 was shown to enhance PSA reporter gene activity by the activation of AR NTD in human LNCaP cells. These results suggest that the AR can be activated by cytokines, and that this mechanism may play an important role in the transition from androgen-dependent to androgen-independent PCa after patients receive androgen ablation therapy.

Adult↗