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Biomedical subjects

S Hoshi

Publications and source records attributed to S Hoshi.

At least 55 records · Page 3Linked to original sources

[High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group].

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.

Adolescent↗

Adjuvant effects of fluoride on oral immunization of chickens.

The present study was conducted to examine the antibody responses of chickens after oral immunization and the influence of sodium fluoride (NaF) on their immunological states. Bovine serum albumin (BSA) was used as an antigen, and the response was measured by enzyme-linked immunosorbent assays of serum samples, bile samples, and lachrymal fluids. Oral immunization of chickens with antigen alone hardly induced antibody responses in sera, bile samples or lachrymal fluids. Moreover, compared to control chickens, these orally immunized chickens exhibited a lower serum IgG response to subsequent parenteral immunization, suggesting that oral immunization induced immunological tolerance in chickens. A mucosal adjuvant, NaF, could abrogate oral tolerance and elicit an increase in antibody responses. Chickens, which received oral administration of antigen and NaF simultaneously, showed a significant rise in serum IgG antibody. Although there were variations among individual chickens and the titers were low, IgA antibodies were detected in bile samples and lachrymal fluids.

Adjuvants, Immunologic↗

Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer.

Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients.

Aged↗

Cell cycle regulation and differentiation in the human podocyte lineage.

Mature podocytes are regarded as growth-arrested cells with characteristic phenotypic features that underlie their function. To determine the relationship between cell cycle regulation and differentiation, the spatiotemporal expression of cyclin A, cyclin B1, cyclin D1, the cyclin-dependent kinase inhibitors (CKIs) p27 and p57, and markers of differentiating podocytes in developing human kidneys was investigated by immunohistochemistry. In S-shaped body stage, Ki-67, a cell proliferation marker that labels the G1/S/G2/M phase, was expressed in the majority (more than 80%) of presumptive podocytes, along with cyclin A (approximately 20% of the Ki-67-positive cells) and cyclin B1 (less than 5% of Ki-67-positive cells) expression. Among these cells), cyclin D1 and CKIs were markedly down-regulated. At the capillary-loop stage, by contrast, CKIs and cyclin D1 were intensely positive in podocytes, whereas no Ki-67, cyclin B1, or cyclin A expression was seen. Moreover, double-immunolabeling and serial-section analysis provided evidence that CKIs and markers specific for differentiating podocytes, namely PHM-5 (podocalyxin-like protein in humans), synaptopodin (a foot process-related protein), and C3b receptor, were co-expressed at the capillary-loop stage. Podocytes were the only cells within the glomeruli that expressed CKIs at immunohistochemically detectable levels. Furthermore, bcl-2 (an apoptosis inhibitory protein) showed a reciprocal expression pattern to that of CKI. These results suggest that 1) the cell cycle of podocytes is regulated by cyclin and CKIs, 2) CKIs may act to arrest the cell cycle in podocytes at the capillary-loop stage, and 3) the specific cell cycle system in podocytes may be closely correlated with their terminal differentiation in humans.

Biomarkers↗

Surveillance study for clinical stage I testicular seminomas and nonseminomatous germ cell tumors.

BACKGROUND: Optimal therapy for stage I testicular tumors is still controversial. This study evaluated the efficacy of a surveillance policy for patients with testicular stage I seminomas and nonseminomatous germ cell tumors (NSGCT). METHODS: From 1984 to 1996, 24 patients with stage I seminoma and 20 with stage INSGCT were followed after radical orchiectomy with tumor markers and imaging studies. All patients were followed for at least 2 years except for those who recurred within 2 years. Recurrent patients were treated with cisplatin-based chemotherapy. RESULTS: The median follow-up periods for seminoma and NSGCT patients were 41 and 54 months, respectively. Recurrences were detected in 2 seminoma (8.3%) and 10 NSGCT (50%) patients. Eleven of the 12 recurrent patients (92%) were detected within 2 years after orchiectomy. The seminoma patients both recurred in the retroperitoneal lymph nodes, while 70% of the NSGCT patients recurred in the lung and/or retroperitoneal lymph nodes. The recurrent seminoma patients were treated with chemotherapy and are alive without disease for 1 7 and 24 months afterorchiectomy. One NSGCT patient died of cancer, but the other 9 recurrent NSGCT patients are alive without disease at 25 to 113 months after orchiectomy. CONCLUSIONS: Surveillance alone is reliable for monitoring patients with stage I testicular seminoma and NSGCT. The majority of recurrences occurred within 2 years, necessitating intensive follow-up for 3 years. As the lung metastatic rates in NSGCT patients were high, a more accurate assessment for lung metastasis is desirable in these patients.

Adolescent↗

Structure of the murine secretory leukoprotease inhibitor (Slpi) gene and chromosomal localization of the human and murine SLPI genes.

Secretory leukoprotease inhibitor (SLPI) is a serine protease inhibitor involved in antineutrophil elastase protection at inflammatory sites. To elucidate both the function and regulation of SLPI in vivo, we isolated and characterized the mouse Slpi gene. An entire 3-kb mouse Slpi gene fragment was sequenced, including an 0. 8-kb 5'-flanking region, the 2.2-kb Slpi gene, and a 0.1-kb 3'-flanking region. The mouse Slpi gene spans 2,222 base pairs containing four exons and three introns. All splicing borders between exons and introns are conserved as predicted by GT-AG rules. Using primer extension analysis, the transcription start site was located 20 nucleotides upstream from the methionine (ATG) initiation codon. At the defined transcription start site, the sequence TCA+1GAGC is present. These results indicate that both mouse and human genomic structure are highly conserved. Using fluorescence in situ hybridization, we confirmed that, consistent with the genomic similarity, the human SLPI gene is localized on chromosome 20q12-13. 2 and the mouse homologue on chromosome 2H, which are syntenic with each other.

Animals↗

[Detection of urogenital malignant cells in the peripheral blood by nested RT-PCR using keratin 19 mRNA].

INTRODUCTION AND OBJECTIVES: It is reported that cytokeratin 19 (CK-19) mRNA is not expressed in the peripheral blood cells of the healthy subjects (Am. J. Pathol. 142: 1111. 1993). Detection of DNA fragments of CK-19 in the peripheral blood suggests the existence of epithelial malignant tumor cells. In this study, we detected CK-19 genes in peripheral blood of patients with urogenital malignancy, and thus clarified the possibility of understanding tumor expansion. METHODS: Mononuclear cells were separated from the peripheral blood of 39 patients with urogenital tumor and 9 controls. Total cellular RNA was extracted according to the method described elsewhere. The CK-19 gene expression was investigated using nested reverse transcription polymerase chain reaction (nested RT-PCR) and confirmed by Southern Blotting. These results were compared to the clinical stages. RESULTS: CK-19 mRNA was not detected in any of 9 controls. CK-19 mRNA was detected in 3 out of the 10 bladder cancer cases. Two had metastases and 1 had muscle invasion without metastasis. One of 6 urothelial cancer case of the upper urinary tract showed positive amplification, and had liver, bone and lymphnode metastases. After one course of chemotherapy, mRNA became negative. In prostate cancer cases, three among 7 were positive and all 3 cases had distant metastases. In renal, testicular and penile cancer cases, the positive ratio were 3/6, 1/8 and 2/2, respectively. All positive cases of renal and testicular cancer had distant metastases, but one case of penile cancer had no metastasis. CONCLUSION: The detection of CK-19 mRNA in the circulating blood by nested RT-PCR makes it possible to detect micrometastasis, to evaluate therapeutic effects and to predict the prognosis.

Adult↗

[Detection of PSA mRNA from the peripheral blood and pelvic lymph nodes in patients with prostatic cancer by means of reverse transcription-polymerase chain reaction (RT-PCR)].

BACKGROUND AND METHODS: To detect prostate cancer cells in the blood circulation and in the lymph nodes by RT-PCR methods, we examined two kinds of prostate specific antigens (PSA) primers and one prostate specific membrane antigen (PSM). PSa primer 1 was established by us, PSA primer 2 by Moreno et al and PSM primer by Israeli et al. RESULTS: Both PSA primers were specific for expression of PSA mRNA because in 12 kinds of urogenital culture cells only LNCaP cells, which produce PSA, expressed PSA mRNA by RT-PCR, PSA 1 was more sensitive than PSA 2 for detection of PSA mRNA in the circulating cells since PSA mRNA was detected in the blood circulating cells in 5 cases of stage D2 prostate cancer using PSA primer 1 but in only one was using PSA primer 2. PSM mRNA was detected in all 12 types of urogenital cancer cells and in the blood circulating cells not of prostate cancer patients but also of renal, bladder, testicular cancer patients and normal volunteers. PSA 1 was used to detect PSA mRNA from the samples of fine needle aspiration biopsy (FNAB) of pelvic lymph node, and PSA mRNA was positive in 10 FNAB samples including not only all 6 cytologically positive and two cytologically class III cases but also 2 of 8 cytologically negative cases. RT-PCR for FNAB samples of all 15 cases of bladder cancer were negative for the detection of PSA mRNA. CONCLUSION: Detection of PSA mRNA by RT-PCR in FNAB samples may be useful to diagnose pelvic lymph node metastasis and to furnish additional information for the cytological diagnosis of prostate cancer.

Aged↗

Megakaryocytopoietic activity of a truncated variant of mouse thrombopoietin.

Thrombopoietin (TPO) is a hemopoietic cytokine that specifically stimulates the growth and development of megakaryocytes. In addition to full-length TPO (corresponding to TPO-1), cDNAs of three truncated variants (TPO-2 to 4) have been isolated. However, whether or not these variants have biological activities has not been clarified presumably because of poor secretion into extracellular milieu. To examine the biological significance of the shortest variants, TPO-4, we prepared two fusion cDNAs of TPO-1 and TPO-4, each of which was combined with the finger-growth factor-kringle 1 (FGK1) domains of tissue plasminogen activator (tPA) as a tag and transfected them into baby hamster kidney (BHK) cells. An immunodetection assay for FGK1 antigen revealed that the amount of secreted TPO-4-FGK1 fusion protein was about 2% of that of TPO-1-FGK1. These fusion proteins after affinity purification had comparable activities on a molar basis in both megakaryocyte colony stimulating activity towards mouse bone marrow cells and growth promotion activity towards the TPO-responsive cell line UT-7/GM. These results indicate that the TPO-4 is biologically active in vitro, although its primary structure of the C-terminal half after the 111th amino acid residues is completely different from authentic TPO-1 due to frame shift.

Animals↗

Endoscopic observation for detection and monitoring of N-butyl-N-(4-hydroxybutyl)nitrosamine--induced bladder tumor in rats.

Recent advances in tumor carbohydrate biochemistry have demonstrated antitumor effects of locally administered GM3 ganglioside on mouse MBT-2 tumor. When intravesical therapy in N-butyl-N(4-hydroxybutyl)nitrosamine (BBN)-induced rat bladder tumor is attempted, it is essential to identify the tumor, to classify its size before therapy and to monitor the effect of the therapy. To establish a more reliable experimental therapeutic system, we assessed the development of BBN-induced rat-bladder tumor by endoscopic observation. BBN-induced bladder tumors in rats were observed serially using a 4.2-F flexible fiberscope. The endoscopic findings were compared with the histopathological findings. Intravesical tumor growth varied greatly between individual rats. The smallest change detected by endoscopy was a small edematous lesion histologically proved to be papilloma. The largest nodular lesion was determined to be a papillary, transitional cell carcinoma. This noninvasive method makes the BBN rat experimental system more reliable by allowing confirmation of tumor formation and classification of the tumor volume prior to therapy.

Animals↗

Hemorrhagic type moyamoya disease.

The clinical picture of hemorrhagic type Moyamoya disease was analyzed in 20 cases. Hematoma at the basal ganglia was noted in 40% of cases, intraventricular hemorrhage (IVH) in 30%, thalamic hemorrhage with ventricular rupture in 15% and subcortical hemorrhage in 5%. The location was undetermined in two cases (10%) due to bleeding in the pre-computed tomography (CT) era. The frequencies shown above were correlated well to previous reports. In magnetic resonance imaging (MRI) performed 1 year or more after IVH, the primary bleeding site was demonstrated at the lateral wall of lateral ventricle, in portion density weighted and T2 weighted images. MRI can detect the site of old bleeding points and its chronological change if the study is repeated. In a follow-up period of 6.2 years, 35% of the cases had rebleeding once or twice. The second bleeding occurred seven times and the third twice. IVH occurred five times and the most common, basal ganglia hematoma three times while thalamic hemorrhage once. As a result, the rate of good outcome was 60% after the first bleeding and 40% after rebleeding. The mortality rate was 5% after the first 25% after rebleedings. Factors related to rebleedings and their poorer outcome are sex (with women being more susceptible), massive ICH and early recurrence. Rebleeding worsened the outcome. Therefore, prevention of rebleeding is important. From a therapeutic viewpoint, although a close relation between rebleeding and untreated hypertension could not be established, blood pressure control is critical at the both acute and chronic stages. Bypass surgery for bleeding type of Moyamoya disease seems to be less promising than ischemic type, even though a definite answer may not be obtained from our small number of cases.

Adolescent↗

Internal iliac arterial infusion chemotherapy for rabbit invasive bladder cancer.

BACKGROUND: Internal iliac arterial infusion (IA) chemotherapy has been used clinically for locally invasive bladder cancer, but there have been no experimental studies to actually demonstrate whether IA is more effective than intravenous infusion (i.v.) chemotherapy in this setting. METHODS: We compared the effects of IA and i.v. using a rabbit invasive bladder cancer model. A 0.2 mL suspension containing 2 x 10(6) VX2 cancer cells was inoculated into the posterior submucosa of the bladder. Two weeks later the rabbits were divided into 3 treatment groups of 8 rabbits each: controls, a group treated with IA consisting of 10 mg/kg carboplatin and 1 mg/kg pirarubicin once a week for 3 weeks (days 14, 21, and 28), and the third treated with the same regimen intravenously. RESULTS: All bladder tumors of the rabbits in the IA group decreased in size, and 3 of the tumors totally disappeared (37.5%). There was also no evidence of lung metastasis. All tumors in the rabbits in the i.v. treatment group increased in size (tumor volume of IA vs. i.v., P = 0.008) and 2 rabbits had lung metastases. All tumors of the control group increased in size and all rabbits had lung metastases. The concentrations of platinum and pirarubicin in the bladder tumors were significantly higher in the IA treatment group than those in the i.v. treatment group at time points from 5 to 10 minutes (P < 0.05) after drug infusion. CONCLUSION: The antitumor effect of IA may be due to higher drug concentrations in the early stage after drug delivery, and the initial circulation of high concentrations of drugs may be the most important factor in suppressing tumor growth.

Animals↗

[Study on the surgical treatment for pulmonary metastasis from renal cell carcinoma].

BACKGROUND: Pulmonary resection for metastatic renal cell carcinoma were studied to assess the indication of surgical management. METHODS: Between January, 1981 and December 1994, 17 consecutive patients (14 men and 3 women) underwent complete pulmonary resection for metastatic renal carcinoma. Median age was 61 years (range, 45 to 73 years). Eleven were appeared lung metastasis after resection of primary tumor. Median time between nephrectomy and pulmonary resection was 32 months (range, 0 to 127 months). RESULTS: There were no operative deaths. One patient had solitary metastasis, 4 had two, 2 had three, 2 had four, one had seven, one had eight and 6 had more than twenty-two. Segmental resection was performed in 12 patients, lobectomy in 2, lobectomy and segmentectomy in 3 and segmentectomy for total lobes in 3. Four patients had another site operation of renal metastasis, brain tumor resection, chest wall and ribs resection, contra-lateral adrenalectomy and contralateral partial nephrectomy. Median follow-up was 44 months (range, 10 to 129 months). The cause specific survival rate and disease free survival after pulmonary resection was 55 and 48 percent at 5 years and 27 and 14 percent at 10 years, respectively. CONCLUSION: Pulmonary resection for metastatic renal cell carcinoma was considered effective in some selected slow-growing cases. Multiple and both lungs metastases is not contraindication and the patients under 10 metastatic focuses had good prognosis.

Aged↗

Plasma chromogranin A in prostatic carcinoma and neuroendocrine tumors.

PURPOSE: Chromogranin A is a good tumor marker for neuroendocrine cells. Whether plasma chromogranin A could be a useful marker for neuroendocrine differentiation of prostatic carcinoma and neuroendocrine tumors was investigated using an enzyme-linked immunosorbent assay. MATERIALS AND METHODS: Plasma levels of chromogranin A were measured by enzyme-linked immunosorbent assay in 33 patients with prostatic carcinoma, 10 with benign prostatic hyperplasia (BPH) and 13 with neuroendocrine tumors (2 medullary thyroid carcinomas, 1 thymic carcinoid, 1 gastrin producing duodenal carcinoid, 3 nonfunctioning pancreatic endocrine tumors, 2 neuroblastomas, 3 pheochromocytomas and 1 carotid body tumor). RESULTS: The normal level of chromogranin A from 40 healthy volunteers was 30 +/- 11 units per 1. (mean plus or minus standard deviation). Mean plasma chromogranin A in patients with BPH and prostatic carcinoma was 52.4 +/- 12.9 and 67.5 +/- 22.9 units per 1., respectively. All patients with neuroendocrine tumors, except 1 with a nonfunctioning pancreatic endocrine tumor, had elevated chromogranin A (mean 401 +/- 409 units per 1.). There were significant differences in plasma chromogranin A level between patients with BPH and neuroendocrine tumors (p < 0.01), prostatic carcinoma and neuroendocrine tumors (p < 0.01), and BPH and prostatic carcinoma (p < 0.05). Of the 33 patients with prostatic carcinoma 5 had elevated chromogranin A, only 1 of whom had elevated prostate specific antigen. CONCLUSIONS: Chromogranin A is an excellent marker for neuroendocrine tumors, particularly nonfunctioning tumors, and measurement of chromogranin A is also useful to detect prostatic carcinoma in patients whose prostate specific antigen is not elevated.

Biomarkers, Tumor↗

[Retrovesical leiomyosarcoma responsive to preoperative chemoradiotherapy: a case report].

A 70-year-old man with dysuria was referred to our hospital. Computed tomography scan and magnetic resonance imaging demonstrated a large solid tumor in the retrovesical space. Transurethral needle biopsy revealed leiomyosarcoma. Since the size of the tumor decreased markedly by intraarterial chemotherapy with cisplatin, methotrexate and pirarubicin, in combination with radiotherapy (40 Gy), surgical extirpation of the tumor was performed. Neither infiltration to the adjacent organs or lymph node metastasis was recognized. The patient had been free of recurrence for 12 months after operation.

Aged↗