Biomedical subjects

Norihiro Hayashi

Publications and source records attributed to Norihiro Hayashi.

8 recordsLinked to original sources

PubMed2005

Adenoviral infection of survivin antisense sensitizes prostate cancer cells to etoposide in vivo.

BACKGROUND: We aimed to investigate whether use of a survivin antisense fragment carried by an adenovirus vector (Ad.survivin-AS) could enhance the therapeutic efficacy of chemotherapy for androgen-independent prostate cancer. METHODS: We used Ad.survivin-AS to promote apoptosis through inhibition of survivin expression. Recombinant adenoviruses alone or in combination with chemotherapeutic agents were tested for anti-cancer activity both in vitro and in vivo. RESULTS: Infection with Ad.survivin-AS strongly inhibited survivin expression in a dose- and time-dependent manner, resulting in significant antitumor activity in vitro and in vivo. Downregulation of survivin expression potentiated induction of apoptosis by the chemotherapeutic agents docetaxel and etoposide in DU145 cells. In particular, the combination of etoposide and Ad.survivin-AS demonstrated dramatic growth inhibition with no tumor regrowth being observed during the experimental period. CONCLUSIONS: The prominent synergy of this combination may provide a basis for clinical application of Ad.survivin-AS as a chemosensitizer of etoposide.

Adenoviridae↗

PubMed2005

Sarcomatoid renal cell carcinoma with a chromophobe component producing beta-human chorionic gonadotropin.

We report a case of sarcomatoid renal cell carcinoma with a chromophobe component showing significant elevation of beta-human chorionic gonadotropin (beta-HCG) in the peripheral blood. A 35-year-old man was hospitalized because of a large tumor of the left kidney and elevated serum levels of beta-HCG. Extended nephrectomy was performed, after which the serum beta-HCG level decreased. However, 3 months later, masses were discovered in the left renal bed and in the lung in association with elevated serum levels of beta-HCG. The patient was rehospitalized and received combination therapy with interferon-alpha and doxorubicin-based multiple chemotherapy (cyclophosphamide, vincristine, doxorubicin, and dacarbazine). The recurrent mass responded extremely well to treatment, and beta-HCG normalized. However, the patient died 14 months after nephrectomy because of eventual resistance to chemotherapy. Sarcomatoid renal cell carcinoma containing beta-HCG positive cells were pathologically diagnosed with immunohistochemical staining in the left kidney. Sarcomatoid renal cell carcinoma is a variant of renal adenocarcinoma which has a poor prognosis. This patient had an extremely rare sarcomatoid renal cell carcinoma associated with serum levels of beta-HCG which were elevated and strongly correlated with morphologic cancer activity. beta-HCG might be a useful serum marker for detecting and monitoring this renal cell carcinoma.

Adult↗

PubMed2005

[New findings on the structure-phototoxicity relationship and photostability of fluoroquinolones].

The present study examined the phototoxicities of a series of 7-(3-aminopyrrolidinyl) quinolones containing various substituents at position 1 by use of a mouse model. For the 7-(3-aminopyrrolidinyl) quinolones with a halogen atom at position 8, well-known substituent groups such as a cyclopropyl, an ethyl, or a difluorophenyl at position 1 were found to be responsible for severe phototoxicity. However, when an aminodifluorophenyl or an isoxazolyl group was placed at position 1, even 8-halogeno quinolones were found to be mildly phototoxic. This is the first report of 8-halogeno quinolones that are not severely phototoxic. Two structurally similar 8-chloro quinolones (the 1-aminodifluorophenyl 8-chloro quinolone and the 1-difluorophenyl 8-chloro quinolone) were investigated further. The former was mildly phototoxic; the latter was severely phototoxic. We demonstrate that these two 8-chloro quinolones have practically the same areas under the concentration-time curves from 0 to 4 h in auricular tissue, suggesting that the mild phototoxicity is not due to pharmacokinetic instability. The rates of UV photodegradation of these compounds were also measured. We found that these two quinolones photodegrade at similar rates, suggesting that the mild phototoxicity is not attained through increased photostability. In conclusion, the phototoxic potentials of fluoroquinolones are influenced not only by the substituent at position 8 but also by that at position 1. We also discovered a mildly phototoxic 8-chloro quinolone which did not have increased photostability.

Animals↗

PubMed2004

New findings on the structure-phototoxicity relationship and photostability of fluoroquinolones with various substituents at position 1.

The present study examined the phototoxicities of a series of 7-(3-aminopyrrolidinyl) quinolones containing various substituents at position 1 (in which the substituent at R8 is a hydrogen or a halogen) by use of a mouse model. For the 7-(3-aminopyrrolidinyl) quinolones with a halogen atom at position 8, well-known substituent groups such as a cyclopropyl, an ethyl, or a difluorophenyl at position 1 were found to be responsible for severe phototoxicity. However, when an aminodifluorophenyl or an isoxazolyl group was placed at position 1, even 8-halogeno quinolones were found to be mildly phototoxic. This is the first report of 8-halogeno quinolones that are not severely phototoxic. Two structurally similar 8-chloro quinolones (the 1-aminodifluorophenyl 8-chloro quinolone and the 1-difluorophenyl 8-chloro quinolone) were investigated further. The former was mildly phototoxic; the latter was severely phototoxic. We demonstrate that these two 8-chloro quinolones have practically the same areas under the concentration-time curves from 0 to 4 h in auricular tissue, suggesting that the mild phototoxicity is not due to pharmacokinetic instability. The rates of UV photodegradation of these compounds were also measured. We found that these two quinolones photodegrade at similar rates, suggesting that the mild phototoxicity is not attained through increased photostability. In conclusion, the phototoxic potentials of fluoroquinolones are influenced not only by the substituent at position 8 but also by that at position 1 (a new finding from this study). We also discovered a mildly phototoxic 8-chloro quinolone which did not have increased photostability.

Animals↗

PubMed2004

[Invasive squamous cell carcinoma of the bladder: report of 18 cases and review of literature].

PURPOSE: This study was undertaken to determine the most effective treatment for improvement of the prognosis of patients with squamous cell carcinoma of the bladder (SCC). MATERIALS AND METHODS: The subjects included 18 cases of invasive SCC (T2 or worse) we have experienced in the past 10 years. While clarifying the clinical patterns of these cases, the association between stage, therapy, and prognosis was studied. Of the cases of invasive SCC reported in Japan in the recent 20 years, 54 cases in which the stage, therapy, and prognosis were documented were selected, and the association between the therapy and outcome in each stage was studied. RESULTS: In our series, 11 cases are alive without cancer for over 2 years. Of the above patients, 7 underwent cystectomy. Cancer death was experienced in 7 patients. Of these patients, 3 underwent cystectomy, and 6 were classified as stage III or higher. As far as our study of the cases reported in Japan is concerned, the prognosis of the cases having undergone TUR or partial resection of the bladder alone was poor. But, even if patients underwent cystectomy, most of the patients was cancer death in the cases whose cancer was stage III or higher. In the patients receiving some supportive therapy, 4 patients receiving radiation plus cisplatin-based chemotherapy were all alive without for over 2 years. CONCLUSIONS: Total cystectomy is most appropriate as the type of operation for the cases of invasive SCC. But, the cases whose cancer was stage III or higher have high recurrence rate, and must be accompanied with some supportive therapy. We concluded that radiation plus cisplatin-based chemotherapy is a candidate of most effective supportive therapy to improve the prognosis of those patients in the supportive therapy.

Aged↗

PubMed2003

Xanthogranulomatous cystitis.

Xanthogranulomatous cystitis (XC) is a rare benign chronic inflammatory disease of unknown etiology. Herein we report a case of a 70-year-old woman who presented with frequent, postmicturition pain and lower abdominal discomfort. Cystoscopy revealed a mass at the dome of the bladder near the left wall. Enhanced computed tomography (CT) demonstrated a mass with a central cavity. The patient underwent partial cystectomy because the presence of bladder neoplasm could not be ruled out. She had has no recurrence of XC 29 months after the operation. The present case of XC is the 20th to be reported in the world.

Aged↗

PubMed2003

[Decrease in anticoagulant factors in patients with prostate cancer treated with diethylstilbestrol diphosphate].

PURPOSE: Estrogen has been highly evaluated as one of the most potent endocrine agents for the treatment of prostate cancer. Unfortunately, a high risk of cardiovascular complications is a clinically important adverse effect of estrogen therapy, and occasionally the complications are fatal. In recent years a high incidence (55%) of thrombotic events has been reported in patients with congenital protein S (PS) deficiency. The aim of this study is to determine the relationship between cardiovascular complications of estrogen therapy and anticoagulant factor levels in the serum of patients with prostate cancer. MATERIALS AND METHODS: Study 1 employed 99 patients with prostate cancer: 39 were untreated, 25 were treated with LH-RH agonist therapy alone, and 35 were treated with oral diethylstilbestrol diphosphate (DESdP) 300 mg per day. We measured the serum levels of anticoagulant factors, parameters antithrombin III (ATIII), protein C (PC), PS, coagulant and fibrinolytic factors in all patients. In study 2, the adverse effects of DESdP therapy on the serum levels of anticoagulant factors were examined in 8 patients with advanced prostate cancer. RESULTS: In study 1, the ATIII and PS levels of the patients treated with estrogen therapy were significantly lower than those in either the untreated patients or the patients treated with an LHRH agonist alone. Especially, both PS antigen (51.5 +/- 16.0%) and PS activity (42.9 +/- 16.0%) were markedly lower in estrogen-treated patients than in the untreated patients (102 +/- 20.8%, 100.6 +/- 20.7%, respectively) or the patients treated with an LH-RH agonist alone (97.9 +/- 16.8%, 91.5 +/- 17.7%, respectively, both p < 0.0001). PS was decreased to below the normal lower limit of normal in 82% (24/35) of the patients on estrogen therapy. In study 2, all 8 cases showed a significant decrease in PS after DESdP therapy. CONCLUSIONS: Our results showed that the PS levels in the oral DESdP group were almost the same as in patients with congenital PS deficiency. We conclude that decreased PS may play a role in the development of cardiovascular complications in prostate cancer patients on estrogen therapy.

Aged↗

PubMed2002

Allixin accumulation with long-term storage of garlic.

Extremely high accumulation of allxiin, a phytoalexin derived from garlic, was observed in necrotic tissue areas after long-term storage. The allixin produced recrystallized on the surface of the garlic clove. The amount of allixin produced in raw garlic with necrotic tissue areas was 1400 ng/mg wet garlic, which exceeds the minimum exhibitory concentration of allixin. After approximately 2 years of storage, amount of allixin accumulated reached slightly less than 1% of the dry weight of garlic cloves.

Chromatography, High Pressure Liquid↗