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Hiroyoshi Suzuki

Publications and source records attributed to Hiroyoshi Suzuki.

At least 55 records · Page 3Linked to original sources
PubMed2004

Clinical usefulness of serum antip53 antibodies for prostate cancer detection: a comparative study with prostate specific antigen parameters.

PURPOSE: Alterations in the p53 tumor suppressor gene located on human chromosome 17p13.1 are currently the most common genetic abnormalities associated with many different types of human malignancies. Recently serum p53 antibodies (p53-Abs) have been detected in the serum of patients with various cancers. To evaluate the clinical usefulness of serum p53-Abs we compared p53-Abs with prostate specific antigen (PSA) parameters in patients with benign prostatic disease (BPD) and prostate cancer. MATERIALS AND METHODS: Serum samples were obtained from 50 patients with BPD and 103 with histologically diagnosed prostate cancer, including T1c/2N0M0 in 50, T3N0M0 in 29 and TxNxM1 in 24. The serum p53-Abs titer was assessed by enzyme-linked immunoabsorbent assay using a MESCUP Kit II (Medical and Biological Laboratories Co., Ltd., Nagoya, Japan) antip53 test. Free and total PSA was measured using an Architect (Dinabott, Chicago, Illinois) PSA kit. The clinical values of p53-Abs were compared with total PSA, PSA density (PSAD), PSA density of the transition zone (PSATZD) and the free-to-total PSA ratio using ROC curves. RESULTS: All patients with prostate cancer had significantly higher total PSA, PSAD, PSATZD and p53-Abs than patients with BPD. While total PSA, PSAD, PSATZD and free-to-total PSA ratios were associated with stage progression, serum p53-Abs were not related to clinical stage. The Gleason sum 5 or less group had a higher level of p53-Abs than higher Gleason sum groups. Patients with T1c cancer had significantly higher p53-Abs than those with BPD. According to ROC curve analysis to distinguish prostate cancer from BPD the p53-Abs titer had the greatest AUC in the overall patient population and in patients without digital rectal examination findings. CONCLUSIONS: These results suggest that p53-Abs might be helpful in the clinical decision to perform prostate biopsy. In the current study the serum p53-Abs titer had the most useful validity in discriminating between prostate cancer and BPD in the overall patient population and in patients with normal digital rectal examination.

Aged↗
PubMed2004

Alternative antiandrogens to treat prostate cancer relapse after initial hormone therapy.

PURPOSE: We studied the efficiency of second or third line hormonal therapy for prostate cancer relapse after hormone therapy. MATERIALS AND METHODS: The study included 70 patients with advanced prostate cancer treated with hormonal therapy, androgen deprivation monotherapy or maximum androgen blockade including surgical or medical castration combined with steroidal antiandrogen, 100 mg chlormadinone acetate daily or nonsteroidal antiandrogens, 375 mg flutamide (FLT) daily or 80 mg bicalutamide (BCL) daily. When the disease relapsed, we discontinued the antiandrogen and evaluated the patient for the antiandrogen withdrawal syndrome (AWS). Thereafter we administrated an alternative antiandrogen and evaluated its effect. RESULTS: The incidence of the AWS after first, second and third line hormonal therapy was 35.8%, 8.0% and 0%, respectively. The efficiency of subsequent hormonal therapy was not related to the occurrence of the AWS. Nonsteroidal antiandrogens as alternative therapies for disease relapse from primary therapy were effective in second line (FLT 38.1%, BCL 44.4%) or in third line (FLT 30.0%, BCL 28.6%) hormonal therapy. Of 5 (80%) patients who responded to second line therapy 4 (80%) had effective third line therapy, while only 1 of 12 (8.3%) second line nonresponders had effective third line therapy (p = 0.003). The survival of second line responders was significantly better than that of nonresponders (5-year survival rate 92.3% vs 23.9%, p <0.001), indicating a potential predictive value for second line responsiveness. No significant clinical factor identified second line responsiveness. CONCLUSIONS: Subsequent nonsteroidal antiandrogen therapies were effective against prostate cancer relapse after hormonal therapy. The response to third line therapy was more effective and survival was improved from the time of first line therapy relapse among second line responders than that in nonresponders. Our data support the notion that second line responders are androgen independent but still hormonally sensitive.

Aged↗
PubMed2004

In situ gelatinolytic activity correlates with tumor progression and prognosis in patients with bladder cancer.

PURPOSE: Degradation of the extracellular matrix by malignant tumor cells has an essential role in the process of tumor invasion and metastasis. The 2 gelatinolytic matrix metalloproteinases (MMPs) MMP-2 and MMP-9 are believed to be key enzymes in this process. We investigated the possible relationship between in situ gelatinolytic activity of MMPs and clinicopathological factors in patients with bladder cancer to clarify whether these proteins would be critical for tumor advancement in this disease. MATERIALS AND METHODS: We evaluated the intensity of gelatinolytic activity in 25 bladder cancer tissues by film in situ zymography (FIZ). To clarify the MMP(s) responsible for gelatinolytic activity in bladder cancer tissues we examined MMP-2 and MMP-9 expression in bladder tissues by gelatin zymography. MMP expression was also confirmed by reverse transcriptase-polymerase chain reaction and Western blotting. We then investigated the association between MMP expression detected by gelatin zymography and the intensity of gelatinolytic activity determined by FIZ. RESULTS: FIZ demonstrated that all tumor tissues had in situ gelatinolytic activities. There was a statistically significant correlation between the intensity of gelatinolytic activity, and tumor grade, stage, vessel invasion and cause specific survival (p <0.05). Stronger in situ gelatinolytic patterns were documented in cases with higher pro and active MMP-2 expression. CONCLUSIONS: FIZ enables the direct assessment of in situ gelatinolytic activity in bladder cancer tissues. The intensity of activity appears to affect the biology of carcinoma tissues. Our results indicate a major role for MMP-2 in in situ gelatinolysis in bladder cancer.

Adult↗
PubMed2004

[A case of peripheral-type primitive neuroectodermal tumor arising in the dura mater at the frontal base].

A 7-year-old boy was admitted to our hospital because of headache and frequent vomiting. The patient was noted to have papilloedema and mild palsy of the right abducent nerve. Magnetic resonance image (MRI) revealed a large tumor in the frontal base with tumoral hemorrhage. Angiography showed the tumor was fed by anterior meningeal arteries. At surgery, the tumor was arising in the dura mater at the frontal base, and was removed totally. Histological examination showed the tumor to be composed of small cells with uniform round nuclei and minimal cytoplasm. Immunohistochemical studies were positive for MIC-2, NSE, C-KIT, vimentin, Class III-beta tublin and glycogen, but negative for NFP, synaptophysin, chromogranin A and GFAP. MIB-1 labeling index was 40-50%. The tumor was histologically confirmed to be peripheral-type primitive neuroectodermal tumor(pPNET). Following surgery, he underwent whole brain, whole spine and local radiation therapy(30 Gy in total respectively) and received two 5-day cycles of chemotherapy, consisting of intravenous administration of cisplatin 20 mg/m2/day, etoposide 60 mg/m2/day and IFOS 900 mg/m2/day. After these therapies, follow-up radiological examination showed there was no recurrence of the tumor for 24 months. Intracranial pPNET is rare. Ewing sarcoma and pPNET(ES/pPNET) is the designation given to a family of small round cell tumor arising in bone or soft tissues. Intracranial PNETs are devided into central nervous system PNET(cPNET) and pPNET. It is necessary that intracranial PNETs are divided into two types of PNETs because of different prognosis between these tumors. MIC-2 is a specific marker for pPNET/ES family and is useful in the differential diagnosis of these two types of tumors.

12E7 Antigen↗
PubMed2004

[Hemangioblastoma of the optic nerve growing like a dumbbell through the optic canal: case report].

We report a case of optic nerve hemangioblastoma in a 29-year-old man without a family history of von Hippel-Lindau disease or the other organ symptoms. He had progressive loss of vision and proptosis with a dull pain in his right eye. Magnetic resonance image (MRI) showed a gadolinium (Gd) enhancing solid tumor involving the prechiasmal right optic nerve with intraorbital extension. The tumor contained many signal voids of vessels and grew like a dumbbell through the right optic canal. Digital subtraction angiography demonstrated that the hypervascular tumor was fed by the ophthalmic artery and the orbital ramus of the middle meningeal artery. We succeeded in total resection of this hypervascular tumor by orbito-zygomatic approach. This tumor grew unusually like a dumbbell because it occurred in the optic nerve at the part of the optic canal. Histological examination revealed the tumor to be a characteristic hemangioblastoma. The postoperative course was uneventful. Supratentorial hemangioblastomas, especially optic nerve hemangioblastoma are extremely rare. This paper reviews the previous published cases and discusses their findings.

Adult↗
PubMed2003

Ser217Leu polymorphism of the HPC2/ELAC2 gene associated with prostatic cancer risk in Japanese men.

The HPC2/ELAC2 gene may be associated with hereditary/familial prostate cancer (PCa). Two common missense variants (Ser217Leu and Ala541Thr) have been reported in the gene. We performed mutational, allelotyping and expression analyses and a molecular epidemiological study to clarify the relations between this gene and prostatic diseases, including PCa and benign prostatic hyperplasia (BPH) in Japanese men. We screened for mutations in 109 patients with PCa including 11 patients from 1 hereditary and 9 familial PCa. Loss of heterozygosity and expression were analyzed. An epidemiological study was done in sporadic PCa (n=98) and BPH (n=143) using 1 novel (Ser627Leu) and 2 previously described polymorphisms of the HPC2/ELAC2 gene. Somatic or germline mutations were not confirmed in any cases of PCa. Loss of heterozygosity at 2 microsatellites, D17S1289 and D17S520, was detected in 1 of 38 and 1 of 35 cases, respectively. Expression analysis revealed decreased or absent mRNA expression in 6 of 38 tumors. Epidemiologic analysis showed that a Leu allele at codon 217 was significantly more frequent in patients with PCa than in controls (10.2% vs. 3.5%, odds ratio = 3.11; 95% confidence interval, 1.22-7.90). At codon 541, all patients with PCa or BPH and all control subjects had the Ala/Ala genotype. At codon 627, the incidence of the Leu variant was slightly, but not significantly, higher in patients with BPH than in controls (7.0% vs. 2.8%, odds ratio = 2.59, 95% confidence interval, 0.94-7.13, not statistically significant). We concluded that germline/somatic mutations of HPC2/ELAC2 are uncommon in PCa. Similarly, allelic imbalances at the gene locus and changes in expression are rare. Although no difference in allele frequency at Ser217Leu between patients with PCa and controls has been reported in a Western population, this polymorphism is a potential indicator of PCa risk in Japanese men and it should be examined in other ethnic groups.

Aged↗
PubMed2003

Increased in situ gelatinolytic activity in renal cell tumor tissues correlates with tumor size, grade and vessel invasion.

Degradation of collagen, or gelatinolysis, by tumor cells is one of the most important events in tumorigenesis. We investigate the possible relationship between the in situ gelatinolytic activities exerted by matrix metalloproteinases (MMPs) and clinico-pathological factors in renal cell tumor (RCT) patients. Using the film in situ zymography (FIZ) method, we determined in situ localization of MMP-like gelatinolytic activities in cancerous and normal tissues in the kidney (n = 51). To clarify the MMP(s) responsible for the gelatinolytic activity in RCTs, we examined the expressions of MMP-2 and MMP-9 in the kidney tissues by means of gelatin zymography (GZG). MMP expression was also detected by RT-PCR and Western blotting analysis. We then investigated the associations of MMP expression, as detected by GZG, with the intensity of gelatinolytic activity, as determined by FIZ. We analyzed the possible relationship of FIZ findings to several clinico-pathological factors such as tumor size, grade, vessel invasion, histologic type, stage and metastasis. FIZ demonstrated that all tumor and normal kidney tissues showed in situ gelatinase activities, and that gelatinolytic activities in RCTs were much stronger than those of normal kidney tissues. There was a statistically significant correlation between the intensity of MMP-like gelatinolytic activity and tumor size, tumor grade and vessel invasion (p < 0.05), but not between it and histological type, tumor stage or metastatic status. FIZ showed that tumor tissues in 5 of the 6 patients with fatal outcome exhibited the intense gelatinolytic pattern. Stronger in situ gelatinolytic patterns were documented in cases with higher MMP-2 expression. The molecular species of MMPs detected by GZG were confirmed by RT-PCR and Western blotting analysis. The FIZ technique enables a direct assessment of in situ gelatinolytic activity in RCT tissues. The intensity of the activity seems to affect the biology of RCT tissues. Our results also indicate a major role for MMP-2 in in situ gelatinolysis in RCT tissues.

Adenocarcinoma↗
PubMed2003

Altered methylation of multiple genes in carcinogenesis of the prostate.

The methylation status of 7 genes was examined in four cell lines, 36 samples of benign prostatic hyperplasia (BPH), 20 samples of prostatic intraepithelial neoplasia (PIN) and 109 samples of prostate cancer (PCa), using methylation-specific PCR (MSP): the pi-class glutathione S-transferase (GSTP1), retinoic acid receptor beta 2(RARbeta2), androgen receptor (AR), death-associated protein kinase (DAPK), tissue inhibitor of metalloproteinase-3 (TIMP-3), O(6)-methylguanine DNA methyltransferase (MGMT), and hypermethylated in cancer-1 (HIC-1). The frequencies of methylation in PCa were 88% for GSTP1, 78% for RARbeta2, 36% for DAPK, 15% for AR, 6% for TIMP-3, and 2% for MGMT, whereas the values were 11% for AR and DAPK, 6% for TIMP-3, 3% for GSTP1, and 0 for RARbeta2 and MGMT in BPH. Aberrant methylation of the GSTP1 and RARbeta2 genes was detected in 30% and 20% of PIN, respectively. Most samples of BPH and PCa were positive for HIC-1 methylation. Regarding accumulation of methylated cancer-related genes, there were significant correlations between PCa and BPH as well as PIN and BPH. In the present study, a high frequency of aberrant promoter methylation of the GSTP1 and RARbeta2 genes was noted in PCa. Our findings suggest that methylation of cancer-related genes may be involved in carcinogenesis of the prostate.

Aged↗
PubMed2003

Possible mechanism of dexamethasone therapy for prostate cancer: suppression of circulating level of interleukin-6.

BACKGROUND: Glucocorticoids may have favorable effects on prostate cancer patients showing clinical and/or biochemical failure after androgen ablation. The efficacy and mechanisms of dexamethasone therapy as possible alternative endocrine therapy were investigated. METHODS: Twenty five patients with prostate cancer treated by androgen ablation and showing a steady increase in serum prostate specific antigen (PSA) were treated with low-dose dexamethasone. RESULTS: Of 25 patients, 11 demonstrated 50% or more decline of serum PSA and 9 showed improvement of pain on dexamethasone therapy. Of 8 patients who responded to dexamethasone therapy, 5 had 80% or more decrease in serum interleukin-6 (IL-6). In contrast, none of 8 non-responders showed remarkable IL-6 suppression. Response of PSA was not correlated to the changes in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, or androstendione. CONCLUSIONS: Significant suppression of serum IL-6, probably through inhibition of androgen-independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease.

Adenocarcinoma↗
PubMed2003

Pretreatment serum level of neuron specific enolase (NSE) as a prognostic factor in metastatic prostate cancer patients treated with endocrine therapy.

OBJECTIVE: The serum level of neuron specific enolase (NSE) is gaining acceptance as a marker of neuroendocrine tumors. To clarify the role of NSE in prostate cancer progression, we examined the relationship of NSE to clinicopathological parameters. METHODS: The pretreatment serum NSE level was measured in 104 patients with histologically confirmed prostatic adenocarcinoma (PCa) and 59 patients in whom prostate cancer was not detected (non-PCa). PCa patients consisted of 5 T1N0M0, 20 T2N0M0, 31 T3N0M0, 7 TxN1M0 and 41 TxNxM1 cases. RESULTS: Non-PCa patients had significantly higher serum NSE than PCa patients. Serum NSE in metastatic PCa patients was significantly higher than that in non-metastatic patients, while NSE did not significantly differ with regard to histological grade, or prostate specific antigen (PSA) response to endocrine therapy. In PCa patients, serum NSE was not correlated to serum PSA nor chromogranin A. In metastatic patients who underwent endocrine therapy, the higher NSE group had significantly poorer cause-specific survival. CONCLUSION: The pretreatment serum level of NSE can predict survival of metastatic PCa patients treated with endocrine therapy.

Adenocarcinoma↗
PubMed2003

Epithelial-myoepithelial carcinoma of the parotid gland.

We report a rare case of epithelial-myoepithelial carcinoma (EMC) of the parotid gland. A 70-year-old man presented with a 4-months-history of right-sided subauricular swelling. Computed tomographic scans revealed a well-defined mass with cystic lesion, measuring about 40 mm in diameter, in the right parotid gland. Because the tumor occupied superficial lobe, he underwent superficial parotidectomy with preservation of the facial nerve. On the basis of the histological and immunohistochemical findings, the tumor was diagnosed as EMC. His post-operative course was uneventful, and he is currently free from disease 6 months after surgery. Diagnosis, clinical behavior and treatment of EMC are reviewed from perusal of the literature.

Aged↗
PubMed2003

Non-traumatic recurrent dissection and its spontaneous repair in the circle of Willis: report of two autopsy cases.

Post-mortem examinations of the circle of Willis in two cases of subarachnoid hemorrhage disclosed a wide spectrum of vasculopathy ranging from a minimal tear between the intima and media, and between the media and adventitia, to complete transmural disruption leading to the formation of pseudoaneurysms. The presence of coexistence of the focal lesions with complete replacement of the entire arterial wall with thick fibrous connective tissues and the vasculopathy was suggestive of the spontaneous repair of recurrent non-traumatic dissection of intracranial arteries. The patients were 58-year-old and 43-year-old females. There was no history of injury to the head or neck in either case. They were hypertensive, but the degree of atherosclerotic changes in the circle of Willis was compatible with age. There was no histological evidence of vasculitis. The role of hypertension and medial mucoid degeneration in the genesis of non-traumatic dissection of intracranial arteries was discussed.

Adult↗
PubMed2003

Small cell carcinoma of the prostate expressing prostate-specific antigen and showing syndrome of inappropriate secretion of antidiuretic hormone: an autopsy case report.

An autopsy case of primary small cell carcinoma (SCC) of the prostate in a 68-year-old man is reported. The patient was admitted to hospital because of a bloody stool and suspected rectal cancer. However, a diagnosis of prostate cancer was made on the basis of a digital rectal examination, the serum level of prostate-specific antigen, and a needle biopsy of the prostate. The patient also experienced a syndrome of inappropriate secretion of antidiuretic hormone. He died 29 days after admission. At autopsy, the tumor had invaded the rectum, bladder and pelvic peritoneum. Metastases to the heart, vertebrae and lymph nodes were observed. Microscopically, the tumor was composed of small round cells that showed a solid growth pattern. Rosette formations were observed. Immunohistochemically, the tumor cells were positive for a prostatic epithelial marker and neuroendocrine markers. A high level of antidiuretic hormone was detected in the tumor tissue. To our knowledge, this is the first reported case of SCC of the prostate in which both a prostatic epithelial marker and neuroendocrine markers have been found in the same tumor. This finding supports the hypothesis that SCC of the prostate originates from a multipotential stem cell of the prostatic epithelium.

Aged↗
PubMed2003

Pathologic changes of glial cells in murine model of Niemann-Pick disease type C: immunohistochemical, lectin-histochemical and ultrastructural observations.

BACKGROUND: In recent years, morbid states of glial cells have been reported in several neurodegenerative diseases. We studied neuropathologically the glial cells in a murine model of Niemann-Pick disease type C (NPC) to clarify involvement of glias, the most important supportive cells in the central nervous system, by the disease. METHODS: The brains of sphingomyelinosis mice (spm/spm), aged from 5 to 13 weeks, and 15 of their age-matched normal siblings were studied histopathologically, immunohistochemically and electron micro-scopically. RESULTS: Accumulation of ubiquitin-positive materials was found in the cytoplasm of foam cells and ballooned neurons immunohistochemically. In addition to the morphologically abnormal cells, double immunostaining of ubiquitin and glial fibrillary acidic protein (GFAP) revealed the deposition of ubiquitinated substances in the cytoplasm of astrocytes. Ultrastructurally, numerous concentric lamellar inclusions, so-called 'myelin figures', appeared in the neurons and phagocytotic cells. Some oligodendrocytes also contained 'myelin figure' inclusions and multivesicular inclusions. Astrocytes contained abnormal irregularily-shaped electron dense materials. CONCLUSIONS: In the murine model of NPC, astrocytes and oligodendrocytes are also involved in the morbid processes. Thus, it might be relevant to investigate the glial dysfunction to understand the pathological processes of the disease and to prepare an adjunct therapeutic strategy to manage the patients with NPC.

Animals↗
PubMed2003

Aberrant methylation of the vascular endothelial growth factor receptor-1 gene in prostate cancer.

Transcriptional silencing of cancer-related genes by DNA methylation is observed in various cancers. To identify genes controlled by methylation in prostate cancer, we used cDNA microarray analysis to investigate gene expression in prostate cancer cell lines LNCaP and DU145 treated with a methyltransferase inhibitor alone or together with a histone deacetylase inhibitor. We detected significant changes (3.4-5.7%) in gene expression in prostate cancer cell lines with the drug treatments. Among the affected genes, that for the vascular endothelial growth factor receptor 1 (VEGFR-1) was re-expressed in LNCaP and DU145 after the drug treatments. Bisulfite sequencing revealed the promoter and exon 1 of the VEGFR-1 to be hypermethylated in the cell lines. These results support the idea that methylation is associated with loss of VEGFR-1 mRNA expression in prostate cancer cell lines. Combined bisulfite restriction analysis (COBRA) showed the gene to be methylated in 24 (38.1%) of 63 primary local prostate cancer samples, while in all 13 benign prostate samples it was not. These findings indicate that methylation of VEGFR-1 is related with prostatic carcinogenesis.

Antimetabolites, Antineoplastic↗
PubMed2002

Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk.

Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent.

Aged↗
PubMed2002

Loss of heterozygosity at 7q31.1 and 12p13-12 in advanced prostate cancer.

BACKGROUND: Allelic losses on chromosome arms 2q, 3p, 5q, 6q, 7q, 8p, 9p, 10p, 10q, 11p, 11q, 12p, 13q, 16q, 17p, 17q, 18q, and 21q are reportedly associated with progression and/or initiation of prostate cancer. In the present study, we performed a polymerase chain reaction (PCR) analysis of polymorphic microsatellite loci on the human chromosomes 7 and 12p13-12 in prostate cancer tissue to investigate the extent of involvement of these regions, which may contain putative tumor suppressor genes. METHODS: Tissue samples were obtained at autopsy from 17 men who died of hormone-refractory prostate cancer at Chiba University, Japan, and affiliated hospitals between June of 1992 and June of 1995. DNA from normal tumor or metastatic tissue was used as the template for PCR amplification of a set of 16 polymorphic microsatellite loci on human chromosome 7 and 6 loci on the human chromosome region 12p13-12. RESULTS: The frequencies of cases with loss of heterozygosity (LOH) at 7q31.1 were 8% in primary tumor tissue and 11% in metastatic tissue. The frequencies of cases with LOH at 12p13-12 were 12% in primary tumor tissue and 25% in metastatic tumor tissue. CONCLUSIONS: In the present study, the frequencies of LOH at 7q31.1 were lower than in Western patients, suggesting that LOH in this region is not related to progression of prostate cancer in Japanese patients. The frequency of LOH at 12p13-12 was similar to that reported in Western countries, indicating that 12p13-12 may contain a tumor suppressor gene of prostate cancer.

Autopsy↗