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Biomedical subjects

S Hoshi

Publications and source records attributed to S Hoshi.

At least 19 recordsLinked to original sources
PubMed2001

Glycolipid composition in bladder tumor: a crucial role of GM3 ganglioside in tumor invasion.

Glycolipids were extracted from primary bladder tumors of 14 patients and 2 normal counterparts. Their expression pattern was assessed by thin-layer chromatography (TLC). The most remarkable change was massive accumulation of GM3 in superficial bladder tumors compared with invasive tumors. This change was also confirmed by immunohistochemistry using anti-GM3 monoclonal antibody. The activities of glycosyltransferases responsible for GM3 synthesis (GM3 synthase, Gb3 synthase and GD3 synthase) were consistent with upregulated expression of GM3 in superficial tumors. It was suggested that the marked GM3 accumulation in superficial tumors was caused not only by upregulated GM3 synthase but also by downregulated activities of Gb3 and GD3 synthase. Histopathologic examination revealed an inverse correlation of the amount of GM3 expressed with invasive potential. Exogenously supplemented GM3 suppressed invasion potential in human bladder tumor cell lines (T-24, KK-47). These results indicate that the amount of GM3 expressed may serve as an indicator of the invasion potential of bladder tumor. Furthermore, new antiinvasion therapeutics may be possible by administration of GM3.

Aged↗
PubMed2001

Trans-urethral whole layer core biopsy for detection of residual tumor after neoadjuvant therapy in invasive bladder cancer.

The most essential information necessary for the treatment of bladder cancer is to know its exact staging. We have developed a percutaneous whole layer core biopsy (PC-WLCB) of the bladder tumor and applied it successfully since April 1985 for the staging and evaluation of neoadjuvant therapy in locally invasive bladder cancer. We report here a modified method, the trans-urethral WLCB (TU-WLCB) and present its clinical results. Methods: A 20 F. rigid nephroscope was introduced trans-urethrally and an 18 gauge, 350mm-long biopsy needle or newly developed 450mm-long biopsy needle was advanced to the tumor through the nephroscope. Biopsy was performed under trans-abdominal ultrasound guidance. Results: Specimens of all 20 TU-WLCB cases included the muscle layer and adipose tissue, and demonstrated small focus of residual cancers after neoadjuvant therapy. Serious complications were not observed so far. Conclusion: TU-WLCB may prove to be a reliable method to stage and evaluate neoadjuvant therapy for invasive bladder cancer.

Journal Article↗
PubMed2001

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive and -negative diffuse large B cell lymphoma.

We analyzed nucleotide sequence and intraclonal diversity of the rearranged immunoglobulin heavy chain gene variable region (VH gene) of CD5+ and CD5- diffuse large B cell lymphoma (DLBCL) to clarify the cell origin of de novo CD5+ DLBCL. Ten cases of CD5+ DLBCL and 29 cases of CD5- DLBCL were analyzed. The frequencies of somatic mutation were 0.7 to 12.9% (average, 6.2%) in CD5+ DLBCL and 2.0 to 25.9% (average, 11.1%) in CD5- DLBCL. The ongoing mutation rate was estimated from the number of further single base-substitutions, expressed as a percentage of the total number of nucleotides in 10 cloned PCR products for each case (%). The averages of the ongoing mutation rate of CD5+ DLBCL (four cases) and CD5 DLBCL (seven cases) were 0.051% and 0.197%, respectively. The rate of CD5+ DLBCL was significantly lower than that of CD5- DLBCL (t-test, P = 0.024). These data may indicate that the cell origin of CD5+ DLBCL is different from that of CD5- DLBCL. CD5 is not an activated antigen in DLBCL, but a specific marker of the B1 subset of the B cells, and de novo CD5+ DLBCL may therefore be derived from this unique subset.

Adult↗
PubMed2001

Adenocarcinoma arising from the prostatic duct mimicking transitional cell carcinoma.

A 71-year-old man was first diagnosed with primary transitional cell carcinoma of the prostate with a skip lesion on the distal urethra. The patient received three courses of intra-arterial chemotherapy of cisplatin (CDDP) and pirarubicin (THP-ADM) followed by a radical prostatectomy. Histopathologic examination of the prostatectomy specimen revealed adenocarcinoma invasion along the prostatic duct extending to the peripheral acini, which was diagnosed as ductal adenocarcinoma. The clinical and histopathologic features of this case are entirely different from usual adenocarcinomas of the prostate. This rare histopathologic feature should be recognized as 'ductal carcinoma of the prostate', to distinguish it from papillary adenocarcinoma or adenocarcinoma with endometrioid features. The patient has had no sign of recurrence 14 months after the operation. CDDP-based chemotherapy followed by radical prostatectomy may be one of the promising therapeutic modalities for this rare entity.

Adenocarcinoma↗
PubMed2001

Two patients with N3 bladder cancer successfully treated by internal iliac arterial infusion chemotherapy and irradiation: case reports.

The prognosis of patients with bladder cancer with pelvic lymph node metastasis is poor, and only 30% of them have been reported to achieve 5- and 10-year survival rates. Prognosis of the patients with pelvic lymph node metastasis larger than 5 cm (N3) is especially poor. and no patient has been reported to have survived more than 3 years. The authors report the successful treatment of two patients with pelvic N3 bladder cancer by internal iliac arterial infusion chemotherapy combined with whole-pelvis irradiation.

Aged↗
PubMed2001

PTHrP and PTH/PTHrP receptor expressions in human endometrium.

We investigated menstrual cycle-dependent changes in the expression of PTHrP and PTH/PTHrP receptor in the human endometrium by immunohistochemistry, and competitive reverse transcription and polymerase chain reaction (RT-PCR). Human endometrial tissues were obtained from patients who underwent gynecological surgery due to cervical cancer (carcinoma in situ) or ovarian cancer. The mean age of the 20 patients was 36.5 (range 31-44) years. For analysis of mRNA expression, specimens from proliferative (mid, n=5; late, n=5) and secretory (early, n=4; mid, n=4) phases were used. Immunohistochemical expression of PTHrP and PTH/PTHrP receptor was observed in the cytoplasm of both epithelial and stromal cells. Stronger staining of PTHrP was found in glandular epithelial cells than in stromal cells. The staining during the proliferative phase was stronger than that in the secretory phase and the difference was particularly remarkable when comparing samples from the same patient. PTH/PTHrP receptor was also present in both epithelial and stromal cells of the endometrium. However, no difference was observed in receptor expression between the proliferative and secretory phases. Competitive RT-PCR revealed that the expression of PTHrP mRNA was higher during the proliferative phase than in the secretory phase, although no difference was observed in PTH/PTHrP receptor mRNA expression. The data suggest that endometrial proliferation may be mediated by a local PTHrP autocrine and/or paracrine mechanism.

Adult↗
PubMed2001

Recurrence pattern of metastatic testicular cancers after chemotherapy.

Recurrence pattern of metastatic testicular cancer after the initial treatment was investigated. Seventy-seven patients with metastatic testicular cancer were treated by cisplatin-based chemotherapy. Patients with residual masses after chemotherapy and whose tumor markers were normalized underwent surgical resections. Of the 77 patients, 61 achieved cancer free status and 4 who did not need the study criteria excluded. Recurrences were detected in 12 (21.1%) patients, 2 (7.1%) patients among 28 stage II patients; 10 (34.5%) patients among 29 stage III patients; none (0%) patients among 14 seminoma patients and 12 (27.9%) patients among 43 non-seminoma patients. All recurrences were detected within 17 months (median, 3) after the initial treatment. Of the 12 patients experiencing recurrence, 4 died of cancer. The recurrence rate of the patients in stage III was significantly higher than that in stage II. No recurrence was detected in patients with seminoma. Follow-up studies after treatment should include serum tumor markers and computed tomographic scanning of lung, abdomen and pelvis at defined intervals. Intensive follow-up will be needed especially for the patients in stage III and with non-seminoma. Follow-up within the first two years is especially important in detecting recurrence after chemotherapy.

Antineoplastic Agents↗
PubMed2001

Voltammetric detection of lectin using sugar labeled with electroactive substance.

The voltammetric detection of soybean agglutinin (SBA) was investigated on the basis of an interaction between the lectin and a sugar. Because galactose and lactose combined with SBA, the sugars were labeled by a Schiff base with an electroactive daunomycin. After the labeled sugar and SBA were mixed, measurements were carried out by voltammetry. When SBA-sugar binding occurs, a part of daunomycin of the labeled sugar is taken to the binding sites. As a result, SBA is detected by a change in the peak current of daunomycin, and the SBA-sugar interaction is evaluated. The length of the alkyl chain between daunomycin and the sugar was also considered. The electrode response to the concentration of SBA was linear over the range of 0.04-0.8 microg min(-1). The merits of this procedure are the convenient preparation of labeled sugar and a rapid measurement without separation. On the other hand, the detection of sugar at the 10(-9) mol dm(-3) level was achieved by a competitive reaction to limited binding sites of the lectin between the sugar and the labeled sugar.

Carbohydrates↗
PubMed2001

Enhanced GM3 expression, associated with decreased invasiveness, is induced by brefeldin A in bladder cancer cells.

We reported previously that non-invasive bladder cancer expresses high level of GM3 ganglioside, whereas invasive tumors have low levels. Since glycosphingolipid synthesis in Golgi is modified greatly by a macrocyclic lactone isolated from fungi, brefeldin A (BFA), we studied effects of BFA on expression of glycosphingolipids and on invasiveness of bladder cancer cell lines. Only GM3 synthesis in invasive tumors was greatly enhanced upon treatment with BFA; synthesis of other glycosphingolipids with lacto-series type 2 or globo-series structure in both invasive and non-invasive tumors was not changed. Invasiveness of bladder cancer cells was greatly decreased in association with the great increase of GM3 synthesis induced by BFA treatment. Level of sialyl-Lex expressed in invasive cell line YTS1, which provides the adhesive property of the cells to E-selectin, was unchanged upon BFA treatment. All the bladder cancer cell lines, regardless of invasiveness, highly express tetraspanin CD9. GM3 has been implicated as a co-factor of CD9 in control of tumor cell motility. Down-regulation of CD9 is associated with metastatic properties of tumor cells and survival of patients with colonic cancer. Therefore, enhanced synthesis of GM3 induced by BFA, causing decrease of invasiveness in bladder cancer, is ascribable to the capability of GM3 to interconnect integrin with CD9, in analogy to colonic cancer and perhaps many other types of cancer.

Antibodies, Monoclonal↗
PubMed2000

Regulation of vascular smooth muscle cell proliferation by nuclear factor-kappaB and its inhibitor, I-kappaB.

Proliferation of vascular smooth muscle cells (SMC) is a crucial event in the formation of atherosclerotic tissues and is regulated by nuclear transcriptional factors including nuclear factor-kappaB (NF-kappaB). We constructed a reporter gene assay to measure NF-kappaB-dependent transcriptional activity in SMC. Thrombin receptor-activating peptide (TRAP) and basic fibroblast growth factor (bFGF) stimulated SMC proliferation and rapidly enhanced the NF-kappaB transcriptional activity in a dose-dependent manner. 4-Cyano-5,5-bis-(methoxyphenyl)4-pentenoic acid (E5510) significantly inhibited SMC proliferation and also suppressed NF-kappaB transcription stimulated by TRAP and bFGF. In contrast, although tumor necrosis factor (TNF)-alpha activated NF-kappaB transcription, E5510 had no effect on TNF-alpha-induced activation. NF-kappaB was activated after the stimulation of TRAP, bFGF, and TNF-alpha in electrophoretic mobility shift assay, and E5510 suppressed the NF-kappaB activation induced by TRAP and bFGF but not the activation by TNF-alpha. Western blot analysis of I-kappaBalpha and I-kappaBbeta, inhibitors of NF-kappaB, indicated that I-kappaBalpha degradation, rather than I-kappaBbeta degradation, was important in NF-kappaB activation after the stimulation of TRAP and bFGF. PD98059, an inhibitor of extracellular signal-regulated kinase (ERK) kinase, suppressed NF-kappaB transcriptional activity and SMC proliferation. The phosphorylation of ERK1/2 was rapidly induced by TRAP and bFGF but not by TNF-alpha. These results indicate that TRAP and bFGF induced I-kappaB degradation and NF-kappaB activation through a distinct pathway from TNF-alpha and that ERK1/2 may play an important role in NF-kappaB activation induced by TRAP and bFGF.

Animals↗
PubMed2000

Expression of the SART1 tumor rejection antigen in renal cell carcinoma.

We have previously described the SART1 gene, which encodes both the SART1(259) antigen expressed in the cytosol of the majority of squamous cell carcinomas and some adenocarcinomas and the SART1(800) antigen expressed in the nucleus of the majority of proliferating cells. The SART1(259) antigen is recognized by HLA-A24 and A26-restricted cytotoxic T lymphocytes (CTLs). The present study investigated the expression of these two antigens in renal cell carcinomas (RCCs) in order to identify an appropriate molecule for use in specific immunotherapy for RCC patients. These two antigens were detected in all RCC cell lines and cells of the primary cultures of the RCCs tested. Further, they were detectable in cells of the primary cultures of non-tumorous kidney tissues. In contrast to these cultured cells, SART1(259) was detectable in only a few uncultured RCC tissues (5/20, 25%) and was undetectable in non-tumorous kidney tissues. SART1(800) was also scarcely detectable in uncultured RCC tissues (3/20, 15%) and non-tumorous kidney tissues (4/20, 20%). HLA-A2402-restricted and tumor-specific CTL (KE4-CTL) used for the cloning of the SART1 gene showed significant levels of cytotoxicity to both the cells from the RCC cell line and the cells from the primary cultures of RCC tissues, but did not lyse any normal cells, including cells from the primary cultures of non-tumorous kidney tissues. The SART1-derived peptide at positions 690-698 induced HLA-A24 restricted CTLs cytotoxic to RCC cells from peripheral blood mononuclear cells (PBMCs) of RCC patients. Therefore, the SART1 peptide could be an appropriate molecule for use in peptide-based specific immunotherapy for RCC patients.

Adult↗
PubMed2000

Histone deacetylase inhibitor but not arsenic trioxide differentiates acute promyelocytic leukaemia cells with t(11;17) in combination with all-trans retinoic acid.

Acute promyelocytic leukaemia (APL) with t(11;17)/PLZF-RARalpha responds poorly to all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3), in contrast to APL with t(15;17)/PML-RARalpha. Molecular studies have shown that histone deacetylase (HDAC) recruited by PLZF-RARalpha is associated with the ATRA resistance. Here, we analysed in vitro the differentiation of APL cells with t(11;17) using ATRA, As203, granulocyte colony-stimulating factor (G-CSF), HDAC inhibitor trichostatin A (TSA), or combinations of these. Although 1 microM ATRA, which stimulated the differentiation of APL cells with t(15;17), was insufficient to induce differentiation, 3 microM ATRA induced terminal differentiation into granulocytes. As203 alone or in combination with ATRA induced neither differentiation nor apoptosis. However, the combination of TSA and 1 microM ATRA had a potent differentiating effect, although TSA alone had little effect. The combination of 1 microM ATRA and G-CSF did not induce differentiation. These results indicate that APL cells with t(11;17) need a higher concentration of ATRA than those with t(15;17) to differentiate and suggest that HDAC inhibitor is a promising differentiation enhancer in APL with t(11;17).

Adult↗
PubMed2000

Analysis of the immunoglobulin heavy chain gene of secondary diffuse large B-cell lymphoma that subsequently developed in four cases with B-cell chronic lymphocytic leukemia or lymphoplasmacytoid lymphoma (Richter syndrome).

The immunoglobulin heavy chain gene (IgH gene) was analysed in four cases of B-cell Richter syndrome, in order to determine whether a secondary diffuse large B-cell lymphoma (DLBCL) could arise from the same clone as the initial B-cell chronic lymphocytic leukemia (B-CLL) and lymphoplasmacytoid lymphoma (LPL) or be a de novo event, and whether secondary DLBCL shows an intraclonal microheterogeneity. Both the initial B-CLL and secondary DLBCL in two cases expressed CD5 antigen. Both samples of the initial B-CLL or LPL and the secondary DLBCL in three cases were examined for comparison. The polymerase chain reaction-amplified IgH gene of secondary DLBCL in two cases (CD5+ case and CD5- case) were different from those of the initial B-CLL, revealing a new malignant clone. The other case (CD5-) showed that secondary DLBCL had a sequence identical to the initial LPL, indicating the same clonal origin. The variable region of the IgH gene of secondary DLBCL (CD5+ two cases and CD5- two cases) exhibited a 0.5-9.0% somatic mutation range and no intraclonal microheterogeneity.

Aged↗
PubMed2000

Significance of simultaneous determination of serum human chorionic gonadotropin (hCG) and hCG-beta in testicular tumor patients.

BACKGROUND: Simultaneous determinations of human chorionic gonadotropin hormone (hCG) and hCG-beta frequently produce discrepancies, that is when hCG or hCG-beta is normal, the other is elevated. Accordingly, we examined the significance of simultaneous determination of serum hCG and hCG-beta in testicular tumors. METHODS: Simultaneous determination of hCG and hCG-beta was performed in 54 patients with testicular seminoma and 74 with non-seminomatous testicular tumors. RESULTS: For detection of seminoma patients, hCG-beta was more effective than hCG because hCG-beta was positive in 83% (45/54) of the patients and hCG was positive in 50% (27/54). In non-seminomatous testicular tumor cases, hCG-beta was positive in 74% (55/74) and hCG was positive in 82% (61/74). The cases of hCG<1.0 mIU/mL and HCG-beta>0.1 ng/mL were significantly more frequently seen in patients with seminoma than in those with non-seminomatous testicular tumor (P < 0.001). Fourteen patients had recurrent tumor. At recurrence, only hCG was elevated in nine cases, only hCG-beta was elevated in two cases and both in one case. For diagnosis of falsely positive hCG, testosterone administration was effective because after testosterone administration, serum hCG levels became undetectable (< 1.0 mIU/mL) within one week in three examined cases. CONCLUSION: Human chorionic gonadotropin-beta was a better marker of seminoma than hCG. For earlier detection of recurrence, both markers should be examined. For diagnosis of falsely positive hCG, testosterone administration was effective.

Adult↗
PubMed2000

Growth hormone secreting adenoma with unusual extension: coexisting pituitary cyst and its clinical significance.

A 58 year old man showed acromegalic features. The serum growth hormone (GH) level was 7.3 ng/ml and SMC (somatomedin-C) 637 U/ml. Triple stimulation test showed abnormal response compatible with a GH secreting tumour. The conventional enhanced MRI revealed a less enhanced hemisphere-shaped lesion at the right corner of the sella turcica. In addition, dynamic MRI demonstrated an elongated lesion extending to the left beyond the midline. The patient underwent transsphenoidal surgery. Besides the soft and suckable tumour at the right corner, we entered into a small cavity loosely filled with the tumour, which was subsequently also removed. The operative finding corresponded to the lesion shown in dynamic MRI. Postoperative GH and SMC levels became 2.3 ng/ml and 326 U/ml respectively. Incidental pituitary cystic lesions in autopsied cases have been reported to be 6-33%. This case had a GH secreting adenoma with coexisting pituitary cyst. The coexisting pituitary cyst supposedly influenced the unusual shape and extension of the pituitary adenoma. Coexistence of such lesion should be kept in mind for microadenoma on neuroradiological evaluation and on intraoperative inspection surrounding the tumour.

Adenoma↗