Biomedical subjects

Shuji Terao

Publications and source records attributed to Shuji Terao.

6 recordsLinked to original sources

PubMed2006

Progress report on phase I/II clinical trial of Ad-OC-TK plus VAL therapy for metastatic or locally recurrent prostate cancer: Initial experience at Kobe University.

There is no effective therapy for hormone-refractory prostate cancer and a novel therapeutic modality, such as a gene therapy, should be actively pursued. Previously, Gardner and Chung conducted a phase I clinical trial of Ad-OC-TK (recombinant adenoviral vector containing osteocalcin promoter-driven herpes simplex virus thymidine kinase gene) plus VAL (valacyclovir) for the treatment of hormone-refractory prostate cancer at the University of Virginia. We report on our ongoing phase I/II clinical trial of Ad-OC-TK plus VAL for the treatment of advanced prostate cancer at the Kobe University Hospital, Japan.

Acyclovir↗

PubMed2005

EGFR mRNA is upregulated, but somatic mutations of the gene are hardly found in renal cell carcinoma in Japanese patients.

PURPOSE: Heterozygous somatic mutations of epidermal growth factor receptor (EGFR) in exons 18, 19, and 21 were recently reported to be associated with response to gefitinib in patients having nonsmall cell lung cancer. Such mutations are more frequently found among Japanese than Europeans. In this work, the frequency of mutations was investigated in renal cell carcinoma (RCC) samples obtained from Japanese subjects to examine the potential of gefitinib as a therapeutic agent for RCC. METHODS: Nineteen patients with RCC, who gave written informed consent, were enrolled in this study. mRNA expression levels of EGFR were measured in RCC and its adjacent noncancerous renal tissue via the real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) method. Somatic mutations were determined using genomic DNA extracted from RCC by direct sequencing method. RESULTS: mRNA expression was confirmed to be about 19 times higher in RCC than in adjacent noncancerous renal tissues, but no such mutations were detected in both. CONCLUSION: Results from this study do not support the validity of further clinical trials on gefitinib for RCC with genotyping even in Japanese patients, although EGFR plays a key role in tumor progression.

Carcinoma, Renal Cell↗

PubMed2005

Granulocyte-colony stimulating factor producing urothelial carcinoma of renal pelvis.

We report a case of granulocyte-colony stimulating factor (G-CSF) producing urothelial carcinoma of the renal pelvis in a 39-year old man. The patient was admitted to Kobe University Hospital, Kobe, Japan, complaining of macrohematuria and a 6-month history of left abdominal swelling. Abdominal computed tomography showed a large mass in the left kidney and para-aortic lymph node enlargement. A remarkable degree of leukocytosis was detected without any acute infectious disease. Enzyme immunoassay of the serum demonstrated a remarkable high concentration of G-CSF. The patient underwent left nephroureterectomy and para-aortic lymphadenectomy. Histochemical examination revealed urothelial carcinoma. Immunohistochemical staining with an anti-G-CSF antibody demonstrated G-CSF secreting cells. The patient died 8 weeks after the surgical operation. To our knowledge, this is the second case of G-CSF producing urothelial carcinoma of renal pelvis reported in the English literature.

Adult↗

PubMed2005

[Gene therapy].

We selected bone-metastatic prostate cancer as the target form of recurrent prostate cancer and developed a suicide-gene therapy based on an adenovirus vector with an organ-specific osteocalcin promoter. Related clinical studies have already been conducted in the United States at the University of Virginia, where results so far have established the safety of this therapy. In the present paper, in addition to presenting the results of these gene-therapy studies from the basic research to the clinical stage, we discuss the clinical studies begun by our group in August 2003. In the 21st century, therapeutic systems in use are undergoing major changes. Gene therapy is likely to become an important therapeutic option in recurrent prostate cancer. In terms of theory and technology however, this form of treatment is still at a very immature stage of development. We look forward to evolution in this field to provide an established treatment for recurrent prostate cancer and are committed to actively continuing with the development of gene therapy through translational research.

Adenoviridae↗

PubMedDate not supplied

Effects of nafamostat mesilate on ADP-induced platelet aggregation and disaggregation in hemodialysis patients.

Nafamostat mesilate (NM), a synthetic protease inhibitor, is the most commonly used anticoagulant in the setting of extracorporeal circulation (ECC) in patients with bleeding tendency. It inhibits both platelet aggregation and activation of coagulation factors. Although it has been reported that NM disaggregates aggregated platelets, little is known about such an effect in the setting of hemodialysis therapy (HD). We examined the effects of NM on adenosine 5'-diphosphate (ADP)-induced platelet aggregation and disaggregation using platelet-rich plasma obtained from 6 HD patients. The platelet aggregation was stimulated by 3 microM ADP and change of aggregation was monitored by an aggregometer. NM adjusted to the final concentrations of 0.1 (1.9 x 10(-7)), 1.0 (1.9 x 10(-6)), 10, (1.9 x 10(-5)), and 100 (1.9 x 10(-4)) microg/ml (M) or veronal-buffered saline (VBS) as control was added before or after to the stimulation of ADP. NM not only inhibited platelet aggregation, but also disaggregated already aggregated platelets at concentrations of 1.0 microg/mln or higher. Moreover, NM almost completely disaggregated at 100 microg/ml. This NM concentration of 1.0 microg/ml was lower than the therapeutic concentration in ECC of HD (i.e., 10 M(-5)). Both inhibitory and disaggregatory effects of NM expressed a dose-related dependency. Our results suggest that NM can exert both aggregation inhibitory and disaggregatory effects on platelets of HD patients within the therapeutic concentration.

Adenosine Diphosphate↗

PubMedDate not supplied

Recombinant interleukin-2 enhanced the antitumor effect of ADV/RSV-HSV-tk/ACV therapy in a murine bladder cancer model.

BACKGROUND: Previous studies demonstrated the antitumor effects of IL-2 and ADV/RSV-HSV-tk in bladder tumor models. In our study, we employed the intramuscular injection of recombinant IL-2 combined with ADV/RSV-HSV-tk gene therapy in the MBT-2 murine bladder tumor model. MATERIALS AND METHODS: In the in vitro study, after adenoviral gene transduction efficiency had been assessed, the cytotoxicity of ADV/RSV-HSV-tk/ACV was examined. In the in vivo study, ADV/RSV-HSV-tk was injected into MBT-2 subcutaneous tumors, ACV was injected intraperitoneally daily for 13 days and recombinant IL-2 was injected intramuscularly daily for 10 days. RESULTS: The X-gal staining of MBT-2 cells infected with 125 multiplicity of injection (MOI) indicated > 20% adenoviral gene transduction efficiency. The cell growth of MBT-2 infected with 125 MOI was significantly inhibited by 40 microM of ACV. In the in vivo study, the combination therapy significantly inhibited tumor growth in the MBT-2 tumor model. CONCLUSION: The systemic administration of recombinant IL-2 in combination with HSV-tk gene therapy exhibited an enhanced antitumor effect.

Acyclovir↗