Biomedical subjects

M Imamura

Publications and source records attributed to M Imamura.

850 records · Page 48Linked to original sources

PubMedDate not supplied

Anticancer chemosensitivity and growth rate of freshly separated human colorectal cancer cells assessed by in vitro DNA synthesis inhibition assay.

The present study was designed to assess the chemosensitivity profile of freshly separated colorectal cancer cells and to screen effective agents for the design of new combination regimens. The DNA synthesis and chemosensitivity (% inhibition of DNA synthesis by the anticancer agent) were successfully assessed in 184 samples (107 primary and 77 metastatic or recurrent lesions) from 152 patients with colorectal cancer using an 3H-thymidine incorporation assay, and the correlations between these two measures and various clinicopathological factors were analysed. DNA synthesis was highest in nodal metastasis followed by malignant effusion, primary lesion, liver metastasis, and local recurrence. DNA synthesis liver metastasis and local recurrence were significantly lower than in other lesions. The results of the chemosensitivity assay are as follows: 5-FU seems to be the most beneficial for primary colorectal cancer; carboquone (CQ), etoposide (VP-16), 5-FU, and mitomycin-C (MMC) for nodal metastasis; CQ, cisplatin (CDDP), 5-FU, adriamycin (ADR) and VP-16 for malignant effusion; and VP-16, CDDP and CQ for liver metastasis. However, the present results showing the chemosensitivity profiles in different lesions suggest that regimens including 5-FU with VP-16 and CQ in addition to MMC or ADR may be applicable for all kinds of colorectal cancer lesions. These results demonstrated the heterogeneity in the chemosensitivity of colorectal cancer, which suggests not only the necessity of patient-specific chemotherapy dependent on the sensitivity assay, but also the usefulness of the present results in the choice of agents for widely applicable combination regimens for colorectal cancer.

Antineoplastic Agents↗

PubMedDate not supplied

Intracellular Ca2+ response of pancreatic acini in cerulein-induced acute pancreatitis in rats.

BACKGROUND/AIMS: To approach the mechanism of impaired signal transduction in cerulein-induced pancreatitis, in vitro acinar cell responses including the intracellular Ca2+ dynamics were evaluated. METHODOLOGY: Rats were infused with 10 micrograms/kg/h of cerulein for 4 hours, and the pancreas was dispersed. A binding study for 125I-CCK, intracellular Ca2+ measurement, and an amylase secretion analysis were performed in dispersed pancreatic acini. RESULTS: The binding study for 125I-CCK revealed that the CCK-binding capacity (Bmax) was decreased, although the binding affinities (Kd high and Kd low) were not altered. An in vitro amylase secretion analysis evoked higher basal secretion but little response. In the control acini, the in vitro application of a physiological dose of CCK (10 pM) evoked intracellular Ca2+ oscillations, and a higher dose of CCK (100 pM, 1 nM) evoked a large transient rise in the intracellular Ca2+ concentration. In cerulein-treated acini, 10 pM CCK evoked no intracellular Ca2+ release, and 100 pM CCK evoked only oscillated Ca2+ concentrations. A higher dose (1 nM) of CCK evoked a transient rise, but the peak Ca2+ level was significantly lower than that in the control (p < 0.05). CONCLUSIONS: These data suggest that both CCK receptors and intracellular Ca2+ mobilizations are similarly desensitized. The attenuation of amylase secretion is partly due to impaired signal transduction, including impaired intracellular Ca2+ release.

Amylases↗

PubMedDate not supplied

An exogenous cdk inhibitor, butyrolactone-I, induces apoptosis with increased Bax/Bcl-2 ratio in p53-mutated pancreatic cancer cells.

We investigated the effects of an exogenous cdk inhibitor, butyrolactone-I, on cell growth inhibition, apoptosis induction, and the regulation of apoptosis in pancreatic cancer cells with mutated p53. Cell growth was dose-dependently inhibited by Butyrolactone-I in PANC-1 and AsPC-1 cells. Phosphorylation of pRb and Cyclin A expression were significantly inhibited in Butyrolactone-I-treated cells. Apoptotic cell death was detected by both Hoechst staining and TUNEL assay. In butyrolactone-I-treated PANC-1 cells, expression of p53 protein was unchanged, but Bax expression was slightly upregulated and Bcl-2 expression was predominantly down-regulated. Bax/Bcl-2 ratio reached 9.6-fold increase compared to the control at the maximum. The time course of changes in Bax/Bcl-2 ratio was similar to that in the TUNEL-positive ratio. These data, suggest that dynamic changes of the Bax/Bcl-2 ratio might be important in determining point of apoptosis induction in pancreatic cancer cells with p53 mutation.

4-Butyrolactone↗

PubMedDate not supplied

Effects of right hemithoracic irradiation on ceftazidime penetration into the alveolar space in rats.

The effect of thoracic irradiation on antibiotic penetration into the alveolar space was determined in a hemithoracic irradiation rat model to evaluate radiation-induced acute alveolar injury at various time intervals. The results of this investigation may be summarized as follows: (1) The transfer of ceftazidime (CAZ: Modacin) from blood to lung tissue, that is, the permeability of pulmonary capillary epithelium, and the transfer of ceftazidime from lung tissue to bronchoalveolar lavage fluid, that is, the permeability of the alveolar epithelium, peaked at 4 to 5 weeks after thoracic irradiation; (2) the time course of change in the absolute concentration of ceftazidime in lung tissue showed a significant increase not only in the irradiated lung but also in the contralateral non-irradiated lung 3 days or more after irradiation. The finding that the administration of antibiotics may cause a significant increase in drug concentration in lung tissue even in the contralateral lung at 3 days after irradiation suggests that the change induced at the alveolar level immediately after irradiation affects the non-irradiated lung field through an as yet unknown mechanism.

Acute Disease↗