Biomedical subjects

I Kohno

Publications and source records attributed to I Kohno.

95 records · Page 6Linked to original sources

PubMedDate not supplied

Phase II dose escalation: a novel approach to balancing efficacy and toxicity of anticancer agents. Japanese Docetaxel Ovarian Cancer Study Group.

BACKGROUND: Small patient numbers in phase I trials may result in a safe but ineffective dose being recommended for phase II trials. A phase II dose escalation study may identify a dose that is both safe and effective. The Japanese phase I recommended dose of 60 mg/m2 of docetaxel (Taxotere) had been ineffective in phase II trials in ovarian carcinoma. PATIENTS AND METHODS: Patients previously treated with one platinum-based regimen for ovarian cancer received docetaxel (Taxotere) every 3 weeks. The first dose tested was 70 mg/m2. If none of the first 5 evaluable patients responded, the dose was increased. If at least one patient responded, 10 more patients were enrolled. Also, if fewer than 3 of these first 15 evaluable patients responded, the dose was increased. If at least 3 patients responded, another 15 patients were scheduled to be enrolled to confirm efficacy. Unacceptable toxicity in 4 of 5, or 10 of 15 patients would stop escalation. RESULTS: Dose escalation from 70 mg/m2 was not required because responses were noted with acceptable toxicity levels. Overall response in 25 evaluable patients treated at 70 mg/m2 was 24.0% (95% CI = 9.4-45.1%). CONCLUSION: Docetaxel 70 mg/m2 without premedication was identified as a safe and effective dose. Further testing of the phase II dose escalation design is worthwhile.

Adolescent↗

PubMedDate not supplied

Change in the localization of heat shock protein 27 (HSP 27) in BG-1 human ovarian cancer cells following treatment by the ether lipid ET-18-OCH3.

We have demonstrated a higher nuclear protein content in the hypodiploid fraction of BG-1 human ovarian cancer cells following treatment with one of the ether lipids, ET-18-OCH3. In this study, we have attempted to identify the overexpressed nuclear protein induced in those dying or dead cells in the hypodiploid fraction and its localization before and after ET-18-OCH3 treatment. The pattern of nuclear proteins was analyzed by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) before and after ET-18-OCH3 treatment. The partial amino acid sequence of the most dominantly and consistently up-regulated protein spot after ET-18-OCH3 treatment was determined and it was found to be heat shock protein 27 (HSP27). Immunofluorescence staining disclosed that HSP27 localizes in the cytoplasm of the BG-1 cells before ET-18-OCH3 treatment. Condensation of HSP27 around the nuclei was observed following treatment by ET-18-OCH3. Ultimately, the nuclei of the cells in the hypodiploid fraction were stained by immunofluorescent HSP27. These results indicate that change of the localization of HSP27 may play an important role as a component of the signal transduction pathways affected by ether lipids.

Adenocarcinoma↗

PubMedDate not supplied

Comparison of blood pressure, heart rate and activity between normotensive and spontaneously-hypertensive rats.

Blood pressure, heart rate and physical activity in spontaneously hypertensive rats (SHR) were measured and compared with those of Wistar Kyoto rats (WKY) to see how these parameters vary with age and whether we can find a marker of essential hypertension among these variables. An automatic telemetric system was employed to measure these variables. In SHR, blood pressure and physical activity increased with age, but heart rate decreased. In WKY, neither blood pressure nor physical activity showed significant changes, but heart rate decreased with age. The 24h mean values of blood pressure, heart rate and physical activity were significantly higher in SHR than in WKY. The mean values of blood pressure, heart rate and physical activity were higher during nighttime than during daytime in both SHR and WKY. Circadian MESOR and amplitude of blood pressure increased simultaneously in SHR. These results are compatible with the concept that an increased amplitude of blood pressure may predict subsequent development of essential hypertension.

Aging↗

PubMedDate not supplied

Relationship between activity levels and circadian blood pressure variations.

In 17 healthy Japanese students (14 males and 3 females) an ambulatory activity level monitoring instrument (Actigraph) was attached to the wrist for 48-hour measurement of wrist movement (with 0.01G or higher acceleration). At the same time, an ambulatory blood pressure monitoring apparatus was attached to these subjects to monitor blood pressure (BP) and heart rate (HR) every 30 minutes. Sleeping hours were calculated from the activity levels. The sleeping hours obtained by the Actigraph correlated with those judged from the diary. The correlation was better for the go-to-sleep time than for the awakening time. Activity level, HR and BP showed a similar circadian variation. Activity level differed significantly between the active daytime (4500 counts/hour) and during sleep at night (720 counts/hour). The acrophase of activity level, obtained by the cosinor method, was 235 degrees which did not significantly differ from that of BP and HR. Hourly activity levels correlated with HR and BP at corresponding hours. These results suggest that BP is affected by activity levels even if this rhythm continues to recur in bedrest.

Adult↗

PubMedDate not supplied

Cytokinetic and morphologic differences in ovarian cancer cells treated with ET-18-OCH3 and the DNA-interacting agent, etoposide.

New antineoplastic agents with different cytotoxic mechanisms are of interest for their ability to overcome resistance to conventional DNA-interacting agents. Ether lipids are known to be active against ovarian carcinoma both in vitro and in vivo, and the cell membrane is believed to be the target of their antitumor activity. In this study we have investigated the different cytokinetic and morphologic responses of human ovarian carcinoma cells (BG-1) to one of the ether lipids (ET-18-OCH3) and to etoposide. Etoposide induced a significantly greater G2/M block. However, the proportion of the cycling cell fraction decreased significantly in cells treated by ET-18-OCH3 and induction of the hypodiploid traction was strongly correlated with reduction of the cycling cell fraction. On the other hand, the hyperdiploid fraction was found to correlate with reduction of the cycling cell fraction in etoposide treated cells. Despite the significant appearance of the hypodiploid fraction, apoptosis was not observed by DNA-gel assay. Microscopic study showed that the hyperdiploid fraction represented cells with multiple nuclei. These observations support the unique lethal effect of ET-18-OCH3 on ovarian carcinoma cells, distinguishing it from the action of a typical DNA-interacting agent. The membrane-targeted ether lipids deserve consideration for the future chemotherapy of ovarian carcinoma, perhaps in combination with the appropriate DNA-interacting agent. New antineoplastic agents with different cytotoxic mechanisms are of interest not only for their unique inhibitory properties but also for their potential of overcoming resistance to conventional DNA-interacting agents. Ether lipids are known to be active against ovarian carcinoma both in vitro (1, 2, 3) and in vivo (4, 5), and the cell membrane is believed to be the target of their antitumor activity. Etoposide, a DNA-interacting agent, is also active against human ovarian cancer cells in vitro (6) or in clinical trials either as a single agent (7) or in combination with cisplatin (8). We have reported that a cytotoxic dose of one of the ether lipids, ET-18-OCH3, induces a G2/M block in BG-1 human ovarian cancer cells, and also a hypodiploid fraction as shown on DNA analysis by flow cytometry (FCM) (9). The G2/M block was also observed in BG-1 cells following etoposide treatment (6). In the present study, we have investigated the differences in the cytokinetic and morphologic responses of BG-1 cells to ET-18-OCH3 and to etoposide.

Antineoplastic Agents↗