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Hitoshi Takayama

Publications and source records attributed to Hitoshi Takayama.

12 recordsLinked to original sources
PubMed2006

[The growing teratoma syndrome report of a case].

A 26-year-old man presented with a swelling of the right scrotal content, lumbago and exertional dyspnea. He underwent high inguinal orchiectomy. Histopathological examination of the specimen revealed yolk sac tumor and mature teratoma. Further evaluation revealed mediastinal and retroperitoneal lymph node metastases (stage IIIA). A single course of BEP (bleomysin, etoposide and cisplatin), two courses of chemotherapy consisting of nedaplatin and irinotecan, and three courses of TIP (paclitaxel, ifosfamide and cisplatin) were delivered. The previous abnormally elevated serum biomarkers (AFP, beta-hCG and LDH) returned to normal levels, but the mediastinal and retroperitoneal masses continued to enlarge slowly. The CT-guided biopsy of the mediastinal mass was performed, and histologic study revealed no evidence of malignancy. He underwent excision of the mediastinal masses and retroperitoneal lymph node dissection. Histologic examination of the resected specimens revealed mature teratoma without malignant components. These results were compatible with growing teratoma syndrome. 30 months after the first excision of mediastinal mass, he underwent the second excision of recurrent mediastinal mass in the absence of biomarker elevation. The resected specimens revealed mature teratoma without malignant components. He is alive for 49 months after high inguinal orchiectomy and free of carcinoma.

Adult↗
PubMed2006

[Molecular-targeted therapy for hormone-refractory prostate cancer].

Molecular-targeted therapy is to treat pathologic pathways specifically in tumor cell or tumor microenvironment. Specific molecular-targeted therapeutic agents for hormone-refractory prostate cancer (HRPC) include endothelin-A receptor antagonist, EGF receptor (EGFR) inhibitor, platelet derived growth factor receptor (PDGFR) inhibitor, nuclear factor of kappaB (NF-kappaB) inhibitor, cyclooxygenase-2 (COX2) inhibitor, and active form of Vitamin D. These agents have been investigated in clinical trials. So far, none of the above-mentioned agent has shown a sufficient clinical efficacy alone. However, docetaxel-based combinations with thalidomide or calcitriol have promising clinical activities. Further investigations are needed to optimize the molecular-targeted agents in the combinations with chemotherapeutic agents for the treatment of HRPC.

Angiotensin Receptor Antagonists↗
PubMed2004

In situ shortening of CAG repeat length within the androgen receptor gene in prostatic cancer and its possible precursors.

BACKGROUND: The amino-terminal transcriptional activation domain of the androgen receptor (AR) gene contains two polymorphic trinucleotide repeat segments that encode polyglutamine (CAG)n and polyglycine (GGC)n tracts. Shorter CAG repeat lengths are associated with higher transcriptional activity. The previous studies using peripheral blood leukocytes showed the relationship between shorter CAG repeat length and risk for prostate cancer (PCA). METHODS: Prostatic cancer (PCA), its possible precursors [high grade prostatic intraepithelial neoplasia (HGPIN) and postatrophic hyperplasia (PAH)], and non-neoplastic epithelium were microdissected from a whole-mount prostatectomy specimen from 34 cases with PCA. DNA extracted from each lesion was processed for PCR-based electrophoresis on 6% denaturing polyacrylamide gels, followed by direct sequencing. To examine whether the in situ shortening of CAG repeat was confined to the CAG repeat or was a part of phenomenon induced by microsatelite instability (MSI), BAT-25 and BAT-26, effective markers for detection of MSI, were also examined. RESULTS: All non-neoplastic epithelial lesions had identical numbers of CAG repeat in the same prostate. CAG repeat lengths were identical in lesions in 25 cases. Two distinct products were found in 9 of 34 cases (26.5%); one product identical to that of non-neoplastic epithelium and another smaller one. In situ shortening of CAG repeat lengths in PCA, HGPIN, and PAH was found in 3 of 34 (8.8%), 6 of 34 (17.6%), and 3 of 10 (30%) cases, respectively. Frequency of CAG shortening was significantly higher in PAH than in PCA lesions (P < 0.05). The length of GGC repeats, BAT-25 and -26 was identical among all lesions in the same case. There was no significant correlation between shortening of CAG repeat length and the clinicopathologic parameters. CONCLUSION: Shortening of CAG repeat length was found in in situ lesions of PCA and its possible precursors.

Aged↗
PubMed2004

Fas gene mutations in mycosis fungoides: analysis of laser capture-microdissected specimens from cutaneous lesions.

Fas (APO-1/CD95) is a transmembrane protein which mediates programmed cell death (apoptosis). Cells with a mutated Fas gene are resistant to apoptosis and thus accumulate in lesional tissues. This might provide a basis for the development of neoplasias. Genomic DNA selectively obtained from Pautrier's microabscesses in 16 cases of mycosis fungoides (MF) using a laser capture microdissection method was analyzed. Fas gene mutations were detected in 3 of 16 cases of MF (18.8%); 1 was silent and 2 were missense mutations located in exon 9. One of the 2 missense mutations involved the death domain of the Fas gene, which is essential for apoptotic signal transduction. The missense mutations resulted in the substitution of Ala with Asp at codon 220 and Ile with Thr at codon 314. Mouse T cell lymphoma cells transfected with mutant genes were resistant to apoptosis induced by the anti-Fas antibody, indicating that the missense mutations found in MF were loss-of-function mutations, thus causing the accumulation of cells in the cutaneous lesions. These findings suggest that the accumulation of lymphoid cells with Fas mutations provides, in part, a basis for the development or maintenance of MF.

Adaptor Proteins, Signal Transducing↗
PubMed2003

[Leydig cell tumor of the testis presenting male infertility: a case report].

A 33-year-old male was referred to our hospital for male infertility with painless swelling of the left scrotal content. Left high orchiectomy was performed under the diagnosis of left testicular tumor. Histologically, this testicular mass was a Leydig cell tumor. We reviewed 55 cases of Leydig cell tumor of the testis previously reported in Japan, and reported the hormonal profile in our case before and after surgery.

Adult↗
PubMed2002

Postatrophic hyperplasia of the prostate in Japan: histologic and immunohistochemical features and p53 gene mutation analysis.

BACKGROUND: Postatrophic hyperplasia (PAH) is one of the patterns of prostatic atrophy but has been regarded as a precursor of prostatic cancer (PCA) because of its possible increase in proliferative activity compared with simple atrophy and morphologic mimicry of PCA. METHODS: Radical prostatectomy specimens obtained from 28 patients with PCA were analyzed by histologic and immunohistochemical methods by using 34 beta E12 and Ki-67 as primary antibodies. Tissue from PAH, PCA, high-grade prostatic intraepithelial neoplasia (HGPIN), a possible precursor of PCA, and benign hyperplasia were microdissected and p53 gene mutations were examined by the polymerase chain reaction-single strand conformation polymorphism method followed by direct sequencing. RESULTS: Histologically, PAH consists of compactly arranged small acini with irregular atrophic-appearing contours, mimicking PCA. PAH lesions were detected in 7 (25%) of 28 cases with PCA: multifocal in 6 of 7 (85.7%) cases, maximum size of lesions ranged from 0.3 to 2.3 mm. Mild nuclear enlargement and small nucleoli were observed in all cases. Capsular or perineural invasion, crystalloids, and mitotic figures were not found in any case. Inflammatory changes and fibrosis near PAH were found in 100% and 71% of cases, respectively. PAH involved non-transition zone in all cases and occasionally involved transition zone. Forty-three percent of PAH lesions were in proximity (<2 mm) to PCA. None of the clinical and pathologic factors examined were correlated with the presence of PAH. Immunohistochemical analysis by using 34 beta E12 revealed intact basal cells. Proliferative activity defined by positive rate for labeling with MIB-1 antibody was intermediate between benign prostatic hyperplasia and HGPIN. The frequency of p53 mutations in PAH lesions was 5.3%, which was similar to that in HGPIN lesions (4.2%). Benign glands never showed mutations. CONCLUSION: These findings suggested that PAH might be a precursor for PCA.

Aged↗
PubMed2002

Frequent Fas gene mutations in testicular germ cell tumors.

The Fas (Apo-1/CD95)/Fas ligand (L) system is involved in cell death signaling, and has been suggested to be important for the regulation of germ cell apoptosis in the testis. Mutations of the Fas gene may result in accumulation of germ cells and thus might contribute to testicular carcinogenesis. The open reading frame of Fas cDNA was examined in 24 cases of testicular germ cell tumors (TGCTs), comprised of 19 pure histological type (15 seminomas, 3 embryonal carcinomas, 1 immature teratoma) and 5 mixed-type tumors. Mutations of the Fas gene were found in nine (37.5%) of these cases. Each lesion with a homogeneous histological picture was selectively microdissected using a laser capture microdissection method: samples consisted of 18 lesions from seminomas, 7 embryonal carcinomas, 4 immature teratomas, 2 choriocarcinomas, and 1 from a yolk sac tumor. Microdissected genomic DNA was examined to determine which mutations were derived from which kind of histological lesion. Eleven mutations were detected in 10 TGCT lesions from nine cases, but none were found in benign lesions. All were point mutations, and eight missense mutations occurred in exon 9 encoding the core protein of the death domain essential for apoptotic signal transduction. Three were silent mutations. Mutations were found in the seminoma (27.8%) and embryonal carcinoma lesions (62.5%), but none were found in the one yolk sac tumor, two choriocarcinomas, or four immature teratoma lesions. Each seminoma and embryonal carcinoma lesion found in the same case had a different type of Fas mutation from the others. Mouse T-cell lymphoma cells transfected with missense mutated genes were resistant to apoptosis induced by anti-Fas antibody, indicating these to be loss-of-function mutations. These findings suggested a role of Fas gene mutations in the pathogenesis of TGCTs.

Adult↗
PubMed2002

Changes in extent and zonal distribution of prostatic adenocarcinoma in patients preoperatively treated with neoadjuvant endocrine therapy: analysis on whole-mounted prostatectomy specimens.

BACKGROUND: An increasing number of pharmacologic agents that induce reversible androgen deprivation are available for neoadjuvant endocrine therapy (NET) for prostatic adenocarcinoma (PCA). If information about the regression pattern of PCA after NET is recognized, more effective decision-making for subsequent therapies such as prostatectomy and radiotherapy, will be possible. METHODS: The extent and zonal distribution of PCA with or without NET were examined in totally embedded radical prostatectomy specimens obtained from 103 patients with PCA. Seventy-nine of the 103 patients received androgen deprivation therapy (castrated). The zonal location of PCA lesions (non-transition vs transition zone), was identified in three slices from the inferior, middle and superior parts of the prostate. The area of the PCA lesions in these zones was measured. RESULTS: Prostatic adenocarcinoma was identified in 94 of 103 cases: 24 of 24 cases (100%) and 70 of 79 cases (87%) in the non-castrated and castrated groups, respectively. The NET induced a mean of 21% reduction of the prostate volume and lowered the serum PSA level by one eighth. The frequency of capsular penetration in the castrated cases (57%) was lower than in the non-castrated cases (83%) and confinement of the PCA lesion was found in 32% of the castrated and 17% of the non-castrated cases. The reduction rate of the extent of the PCA lesions in the non-transition and transition zone was 33% and 28%, respectively. The extent of the PCA lesions were smaller in the anterior parts, especially at the superior portion of the prostate. CONCLUSION: Neoadjuvant endocrine therapy induced involutional changes of the PCA evenly across both the non-transition and transition zones. The density of the PCA lesions was low in the anterior part of the prostate. This information is useful for decision-making in post-NET.

Adenocarcinoma↗
PubMed2002

Utility of immunohistochemical detection of prostate-specific Ets for the diagnosis of benign and malignant prostatic epithelial lesions.

BACKGROUND: Human prostate-specific Ets (hPSE) belongs to the Ets family. It regulates the proliferation, differentiation, and development of prostate epithelial cells. A recent study showed that hPSE can be detected in normal glands but not in cell lines established from prostate cancer (PCA), suggesting a translational disorder of hPSE from mRNA to protein in PCA. Immunohistochemical detection of hPSE could therefore be another method of differential diagnosis of PCA from other proliferative conditions in the prostate. METHODS: An immunohistochemical detection of hPSE was carried out on the whole mounted prostatectomy specimen obtained from 19 cases with PCA. RESULTS: Basal and secretory luminar cells showed a diffuse cytoplasmic staining for hPSE in normal glands, hyperplastic glands, and prostate intraepithelial neoplasia lesions. Whereas approximately 30% of PCA lesions showed a negative staining for hPSE, the positive rate for hPSE between PCA and benign glands or prostate intraepithelial neoplasia (PIN), was statistically significant (P < 0.05). Staining intensities in normal glands, hyperplastic glands, and PIN lesions were similar, but generally stronger than those in PCA lesions. CONCLUSIONS: Negative immunoreactivity for hPSE strongly suggests malignancy in the prostate glands. Decreased immunoreactivities of glands for hPSE could suggest PCA.

Aged↗
PubMed2002

Fas and Fas ligand gene mutations in Hashimoto's thyroiditis.

To clarify whether Fas and Fas ligand (FasL) mutations are involved in the pathogenesis of Hashimoto's thyroiditis (HT), we examined the open reading frame of Fas and FasL in 21 cases. Mutations of Fas and FasL genes were detected in 8 (38.1%) and 1 (4.8%) of 21 cases, respectively. All but one of the Fas mutations were frameshift mutations, which affect the cytoplasmic region (death domain) known to be involved in apoptotic signal transduction and thus could be loss-of-function mutations. FasL mutation in one case was a 46-bp deletion from nucleotide 349 to 394, which corresponded to exon 2. Lack of exon 2 results in a frameshift, which generates a stop codon at residue 128. This mutant encodes the protein that contains only a part of the intracellular domain, thus the abnormal protein might not be expressed on the cell surface. The cells with Fas mutations were confined to the mantle zone and the germinal center, as determined by microdissection methods. These findings suggest that the cells with Fas mutations might accumulate in those areas and might be involved in the pathogenesis of Hashimoto's thyroiditis.

Aged↗
PubMed2002

Analysis of Fas gene mutations on laser capture microdissected specimens from renal cell carcinoma.

Renal cell carcinoma (RCC) expresses Fas antigen on the cell surface, and thus could be sensitive to apoptosis induced by the binding of Fas ligand. Fas gene mutations might be involved in the development of RCC. Fas gene mutations were examined in genomic DNA extracted from RCC lesions. With use of laser capture methods, one RCC and one non-neoplastic lesion per case were microdissected from 15 patients with RCC. Polymerase chain reaction-amplified products were directly sequenced. Loss of heterozygosity (LOH) was examined at four sites of known polymorphism. Mutations of the Fas gene were detected in 3 RCC lesions from 3 (20%) of 15 cases. All mutations were point mutations, 2 missense and one silent, in exons 7 and 9. Non-neoplastic tissues never showed Fas gene mutations. Nine of 15 cases (60.0%) were heterozygous for one or more sites of the known biallelic polymorphisms, i.e., at nucleotides -1377, -670, 416, and 836. Two of these 9 cases showed LOH at promoter region -670. Mouse T-cell lymphoma cells transfected with missense mutated genes were resistant to apoptosis induced by anti-Fas antibody, indicating these to be loss-of-function mutations. The results of the present study suggest that Fas gene mutations play a role in the pathogenesis of RCC.

Adult↗