Biomedical subjects

Yasuhiro Terazaki

Publications and source records attributed to Yasuhiro Terazaki.

8 recordsLinked to original sources

PubMed2005

Expired gas analysis during exercise testing pre-pneumonectomy.

PURPOSE: Expired gas analysis has enabled the successful prediction of postoperative complications in patients undergoing thoracic esophagectomy. We conducted this study to determine whether preoperative expired gas analysis during exercise testing can help identify patients at high risk of postoperative complications after pneumonectomy. METHODS: We measured the vital capacity, percent vital capacity, forced expiratory volume in 1.0 s, percent forced expiratory volume in 1.0 s, maximum oxygen uptake per minute, anaerobic threshold, arterial partial pressure of oxygen, and arterial partial pressure of carbon dioxide in 27 patients scheduled to undergo pneumonectomy. Group A consisted of 18 patients without postoperative cardiopulmonary complications and group B consisted of 9 patients with postoperative cardiopulmonary complications. We compared preoperative cardiopulmonary data between these two groups. RESULTS: Postoperative cardiopulmonary complications developed in 9 of the 27 patients (33.3%), 3 (11%) of whom died. The maximum oxygen uptake and the anaerobic threshold were significantly higher in group A than in group B (P < 0.05), whereas spirometric pulmonary function testing and arterial blood gas analysis showed no intergroup differences. CONCLUSION: Expired gas analysis during exercise testing can help identify patients at high risk of postoperative cardiopulmonary complications after pneumonectomy.

Adult↗

PubMed2005

[A case of advanced breast cancer markedly responding to chemo-endocrine therapy with only slight alopecia].

We report a case of good response to chemo-endocrine therapy with slight alopecia. A 55-year-old woman was diagnosed as advanced breast cancer with T4c, N3, M1, Stage IV, who was left cervical node-positive. She received 4 cycles of CTF (cyclophosphamide 100 mg/body/day 1-14, THP 30 mg/body/days 1,8, and 5-FU 750 mg/body/days 1, 8 4 wq) therapy in addition to oral tamoxifen (20 mg/body) administration. After this treatment, the primary tumor was markedly reduced (PR), and only slight alopecia was observed. Generally, 3 cycles of CAF (CEF) therapy induced severe alopecia (grade 3). But this CTF regimen caused grade 1 alopecia. Most women have strong resistance to alopecia. It seems that the quality of life for breast cancer patients was affected by the extent of the alopecia. Therefore, CTF therapy should be considered effective for advanced breast cancer patients while reducing the extent of alopecia.

Adenocarcinoma, Scirrhous↗

PubMed2005

Adenoviral gene transduction of hepatocyte growth factor elicits inhibitory effects for hepatoma.

Hepatocyte growth factor (HGF) gene therapy may have potential for treating chronic hepatitis (CH) and liver cirrhosis (LC). However, the lack of an HGF gene therapy study on hepatomas that are often associated with CH or LC, together with the stimulatory effects of HGF on many types of cancer, may hamper its application. This study explored the effects of adenoviral HGF gene transduction and their mechanisms on two types of hepatoma cells (hepatoblastoma and hepatocellular carcinoma) in in vitro experiments. Both types of hepatomas were revealed to have higher adenoviral gene transduction efficiencies and more efficient expressions of the HGF transgene, which successfully activated the HGF receptor/c-Met in an autocrine fashion, than those of other types of cancer. Notably, not only HGF, but also adenoviral infection, inhibited DNA synthesis, whereas only HGF but not adenoviral infection exerted a potent apoptotic effect. Moreover, adenoviral HGF gene transduction additively exerted inhibitory effects on cisplatin-treated hepatomas. In conclusion, inhibitory and apoptotic effects of adenoviral HGF gene transduction in hepatomas in contrast to potent mitogenic and antiapoptotic effects of HGF for hepatocytes are not only of biological interest, but also pose clinical benefits for adenoviral HGF gene therapy for CH and LC.

Adenoviridae↗

PubMed2004

Gene therapy eradicating distant disseminated micro-metastases by optimal cytokine expression in the primary lesion only: novel concepts for successful cytokine gene therapy.

The most serious problem in current gene therapy is that clinical applications have often led to unsatisfactory results. Here we show novel concepts and crucial factors that have been missing for successful cytokine gene therapy. A clinically-relevant mouse model of primary and micro-metastatic osteosarcoma was generated by subcutaneously and intravenously injecting murine osteosarcoma LM8 cells, in which adenoviral gene transduction efficiencies were extremely low; current therapies remain less effective for such disseminated micro-metastases. A single injection of adenoviral vector encoding interleukin-2 gene (Ad.IL-2) was given only into the established primary tumor. Notably, antitumoral immunity was successfully elicited by IL-2 secretion from connective tissues adjacent to the primary tumor, and this immunity not only suppressed primary tumor growth but also eradicated disseminated micro-metastases in distant organs. Most importantly, not only minimal side effects but also maximal therapeutic effects were exerted only in the case of injecting the optimal (i.e., not the highest) dose of Ad.IL-2, because spleen injuries caused by excessive levels of circulating IL-2 might diminish the therapeutic effect. Although the narrow range of the optimal therapeutic expression level of IL-2 may be crucial, it was feasibly determined by serum IL-2 levels. Thus, a crucial factor for successful cytokine gene therapy is not the high gene transduction efficiency in the tumor, which has been generally recommended, but the use of the optimal therapeutic expression level. In conclusion, just a single injection of Ad.IL-2 into a primary tumor lesion, which is feasible, not invasive and cost effective, is potently therapeutic for distant disseminated micro-metastases, as long as the optimal therapeutic level is monitored. These novel concepts, which contradict those of previous studies, warn researches about the possible problems with the ongoing clinical cytokine gene therapy.

Adenoviridae↗

PubMed2003

An optimal therapeutic expression level is crucial for suicide gene therapy for hepatic metastatic cancer in mice.

The most serious problem in current gene therapy is discrepancies between experimental data and actual clinical outcomes, which may be due to insufficient analyses and/or inappropriate animal models. We have explored suicide gene therapy by using various clinically relevant animal models and doubt the clinical use of maximal suicide gene expression, which has been generally recommended. To explore this subject further, we studied what expression level of suicide gene and what promoter led to the maximal clinical benefit in the case of hepatic metastatic cancer in mice. Therapeutic and adverse side effects of 4 adenoviral vectors that express herpes simplex virus thymidine kinase (HSV-tk) under different promoters were scrupulously investigated in 2 mouse models of hepatic metastasis of gastric cancer that possess clinical characteristics. Surprisingly, increases in HSV-tk expression beyond a certain point, achieved by the Rous sarcoma virus long terminal repeat promoter, not only enhanced the adverse side effects of lethal hepatotoxicity and ganciclovir-independent cytotoxicity but also failed to further increase therapeutic potential. Moreover, the carcinoembryonic antigen (CEA) tumor-specific promoter, the therapeutic potential of which had been underestimated, was much more useful-even in the case of low CEA-producing cancer-than had been previously reported. In conclusion, the optimal therapeutic expression level of a suicide gene is a novel concept and a crucial factor for successful cancer gene therapy. The present results, which contradict those of previous studies, alert researchers about possible problems with ongoing and future clinical trials that lack this concept.

Adenoviridae↗

PubMed2002

Outcome for malignant tracheobronchial stenoses in esophageal cancer.

OBJECTIVE: Optimal tracheobronchial stenosis treatment in esophageal cancer remains a clinical challenge. METHODS: Subjects were 26 patients with tracheobronchial stenosis due to esophageal cancer treated by modalities such as expandable metallic stent emplacement, laser therapy, radiotherapy, and/or chemotherapy. We assessed patient outcome and modality efficacy, and determined prognostic factors for survival using multivariate analysis. RESULTS: Of the 26, 16 (61%) had improved respiration after treatment. Average posttreatment survival was 140 days (10-1550 days). Multivariate analysis indicated that a Karnofsky performance score of > or = 70% was the most significant prognostic factor, with chemotherapy and laser therapy also significant factors. CONCLUSIONS: Although individual modalities were effective in ameliorating respiratory symptoms, patients with good performance status survived the longest. After a tracheobronchial stenosis diagnosis in esophageal cancer patients, chemotherapy and laser therapy are recommended if the patient is in good general condition.

Aged↗

PubMed2002

Vasoactive peptides in a pulmonary embolism model.

PURPOSE: To investigate changes in atrial natriuretic peptide (ANP) and angiotensin II (AT-II) levels in a canine model of pulmonary embolism (PE), created by embolizing the left posterior pulmonary artery with gelatin powder. METHODS: Pulmonary arterial pressure (PAP) was measured before, immediately after, and 1 day after pulmonary artery embolization. Plasma ANP and AT-II levels were measured by radioimmunoassay (RIA) before and 1, 3, 7, 14, 21, and 28 days after embolization. ANP and AT-II levels were also measured by RIA in both embolized and nonembolized lung tissue 28 days after embolization. RESULTS: No changes in plasma ANP or AT-II were seen within 28 days after embolization. Although the ANP level in the nonembolized lung tissue was significantly increased, the level in the embolized lung tissue was significantly decreased compared with that of sham-operated control lung tissue. The AT-II level in the nonembolized lung tissue was significantly decreased compared with that of the control lung tissue, but the level in the embolized lung tissue did not change. CONCLUSION: Both ANP and AT-II in the nonembolized lung tissue reacted to compensate for vasoconstriction caused by the PE in this model.

Angiotensin II↗

PubMed2002

Minute lung carcinoma associated with focal honeycombed lesion.

We report a case of minute lung carcinoma that developed in a focal honeycombed lesion in the right lung. A 70-year-old man presented hemosputum, and a cytological examination result was at class IV. A right lower lobectomy of the lung was performed. Microscopically, the thickened alveolar wall revealed tumor cells indicating a minute carcinoma, and showed squamous hyperplasia, metaplasia, and dysplasia, with the carcinoma in the distal airway epithelium. This peripheral lung carcinoma in a focal honeycombed lesion demonstrated the various stages of multistep carcinogenesis, which is recognized in hilar type squamous cell carcinoma. To date, the association between a honeycombed lesion and lung cancer has been poorly described. Here we have presented clear evidence of the association of this carcinoma with the honeycombed lesion.

Aged↗