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Biomedical subjects

T Iba

Publications and source records attributed to T Iba.

At least 19 recordsLinked to original sources
PubMed1999

[Comparison between continuous intravenous and oral administration of 5-FU with LV].

UNLABELLED: In case of 5-fluorouracil (5-FU)/leucovorin (LV) treatment, which is one of the most effective forms of chemotherapy for colorectal carcinoma, 5-FU is usually continuously infused from the venous route. However, since this continuous infusion limits the patients' active daily life, oral administration is preferable. In the present study, we evaluated the efficacy and side effects of orally administered 5-FU/LV. MATERIAL AND METHODS: In the continuous intravenous infusion group (civ group), colon 26 bearing mice were cannulated into central vein from external jugular vein. From this route, either 5, 10, or 20 mg/kg of 5-FU was continuously infused for 7 days (n = 6). In another group, either 10, 20, 40 mg/kg of 5-FU was infused orally (po group, n = 6). The other 6 animals were used for the non-treatment group. In the next series, 100 mg/kg of LV was added for each group above. Tumor volume, thymidylate synthase inhibition rate (TSIR) and body weight were measured at the end of infusion. During the experimental period, mice had free access to chow and water. RESULTS: The tumor/control (T/C) volumes ratio showed that approximately twice the orally administered 5-FU dose had an anti-tumor effect equal to that of 5-FU administered intravenously. Synergic antitumor effects by LV were only revealed in the civ group. Significant body weight loss was recognized only in the po group at a 5-FU dose of more than 20 mg/kg. In summary, since the modulation effect of LV was recognized only with continuously intravenous infusion of 5-FU, further improvement of oral administration is required in the LV/5-FU combination therapy.

Administration, Oral↗
PubMed1998

Total parenteral nutrition supplemented with medium-chain triacylglycerols prevents atrophy of the intestinal mucosa in septic rats.

Total parenteral nutrition (TPN) is associated with an increased incidence of bacterial translocation (BT) compared with enteral nutrition because of the disuse atrophy of the intestine. In this study, we assessed the effect of adding medium-chain triacylglycerols (MCT) to TPN for the prevention of mucosal atrophy in the intestine. Rats were subjected to either fat-free TPN, TPN with long-chain triacylglycerols (LCT), or TPN with MCT for 5 d and nutrition parameters were evaluated. In another set of rats receiving the same TPN regimen, 0.8 or 0.05 mg/kg endotoxin was administered on day 4. Survival was evaluated and BT to the mesenteric lymph nodes, liver, and systemic blood was measured 24 h later. The mucosal heights of the jejunum and ileum were evaluated concurrently. The survival rate was significantly improved in the MCT group (P < 0.05) at the endotoxin dose of 0.8 mg/kg. The nutrition condition presented by phospholipid, total cholesterol, and total ketone body levels was the best in the MCT group compared to the other groups. The intestinal villous height in the ileum was significantly greater in the MCT group. However, the improvement of BT in MCT group was not statistically significant. In this endotoxin-challenged rat model, survival rate was improved by the supplementation of MCT. This effect may be presented in some part by the improvement in nutrition condition and by the prevention of mucosal atrophy in the intestine.

Animals↗
PubMed1998

[The intratumoral levels of thymidylate synthetase and folate in gastric and colon cancer].

Currently, biochemical modulation for 5-fluorouracil (5-FU) is one of the most successful chemotherapy for both colo-rectal and gastric cancer. The purpose of this study is to evaluate the significance of measuring intratumoral thymidylate synthetase (TS) and folate (FH4) levels as predictive parameters for the successful treatment. Samples were collected from 16 advanced colo-rectal and 21 advanced gastric cancer. TS and tetrahydrofolate levels in the specimens were measured by binding assay. Results showed that there were no significant difference in TS levels between the different pathologic types of carcinoma. On the other hand, well (3.94 +/- 1.75 p mol/g) and moderately (5.95 +/- 2.69 p mol/g) differentiated carcinoma showed lower FH4 levels compared to poorly differentiated carcinoma (9.58 +/- 5.27 p mol/g). In conclusion, biochemical modulation by cisplatin or leucovorin, which elevates intratumoral folate levels, is more needed for well and moderately differentiated carcinoma. Finally, measuring TS levels can also be important because two cases who responded to cisplatin/5-FU chemotherapy showed low TS levels compared to the others who had lower response.

Adenocarcinoma↗
PubMed1996

Alterations in coagulation and fibrinolysis during sepsis.

Circulating levels of thrombin-antithrombin III complex (TAT) and plasmin-alpha 2 plasmin inhibitor complex (PIC) in 49 septic patients (23 patients with organ dysfunction (OD), 26 without OD) and 11 postgastrectomy patients were measured to determine the significance of the coagulation-fibrinolytic systems in the development of OD. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and thrombomodulin were also measured. The mean level of TAT on the day when OD occurred was significantly higher compared with the maximum level of TAT in septic patients without OD (P < .01) or postoperative patients (P < .01). There was no difference in PIC levels between the three groups. The TAT/PIC ratio was significantly higher in septic patients with OD compared with the other groups (P < .001). Septic patients with OD showed higher levels of PAI-1 (P < .001) but not of t-PA. Thrombomodulin levels were significantly higher in the septic patients with OD compared with the others (P < .001). We conclude that suppression of the fibrinolytic system contributes to the imbalance between coagulation and fibrinolysis, and that this hypercoagulable millieu on the endothelial surface leads to the onset of OD.

Adult↗
PubMed1996

[Changes in folate levels after cisplatin treatment of gastric cancer].

Currently, biochemical modulation for 5-fluorouracil (5-FU) by cisplatin (CDDP) is one of the most successful forms of chemotherapy for gastric cancer. Although the mechanism of this modulation is thought to increase intracellular folate levels, it is still unknown how much CDDP is needed to elevate folate levels. The purpose of this study is to determine the appropriate volume of CDDP as a modulator for 5-FU. Either 5, 20, 100 mg/body of CDDP was administered intravenously to advanced gastric cancer patients just before operation. Four hrs later, the stomach was resected and folate levels were measured in the tumor and normal mucosa by thymidylate synthase binding assay. The results showed folate elevation only after administration of 100 mg/body of CDDP, both in the tumor and mucosa (p < 0.01). In conclusion, if CDDP is infused as a bolus, a relatively large amount is needed to modulate the intratumor folate level.

Adult↗
PubMed1995

Increased plasma levels of soluble thrombomodulin in patients with sepsis and organ failure.

The fact that thrombomodulin (TM) is released into the bloodstream from damaged vascular endothelial cells led us to hypothesize that plasma levels of soluble TM could be an indicator of the development of organ failure. In this study, we examined the changes in plasma levels of TM in 60 septic patients and 13 postsurgical patients, and investigated the circulating levels of interleukin 6 (IL-6) and polymorphonuclear leukocyte elastase (PMN-E) to determine the mechanism causing the excess liberation of TM. The arterial ketone body ratio (AKBR) was also measured as an indicator of the hepatocyte energy state. Of the 60 septic patients, 26 developed organ failure, 10 of whom died. In contrast, none of the postsurgical patients developed organ failure. The mean plasma level of TM was significantly higher in the septic patients who developed organ failure compared to those without organ failure (P < 0.001) or the postsurgical patients (P < 0.001). Furthermore, those patients whose plasma TM values became elevated over 6.0 ng/ml frequently developed complications. A positive correlation was also observed between the plasma TM levels and the IL-6 (P < 0.01) and PMN-E levels (P < 0.01). In contrast, a negative correlation was seen between the plasma TM levels and the AKBR (P < 0.01). These findings show that plasma TM could be a useful indicator of impending organ failure during sepsis.

Adult↗
PubMed1995

[Efficacy of combination chemotherapy with mitoxantrone, vincristine, prednisolone (MVP) for recurrence of breast cancer].

Fourteen patients with recurrent breast cancer were treated with a combination of mitoxantrone (10 mg/m2 iv, day 1), vincristine (1 mg/m2 iv, day 1) and prednisolone (30 mg/day day 1-7). Cycles were repeated every 4 weeks and all patients received more than 3 cycles. The objective response rate was 70.0% (7 of 10). In two patients, the treatment has been continued now for more than one year. In these 2 patients, the duration of response is more than 40 weeks. The toxicity was primarily myelosuppression. Five of 14 patients (35.7%) had leukopenia of Grade 3 and 4. These patients received G-CSF therapy and recovered well from leukopenia. Nausea and vomiting were well tolerated, probably by prednisolone. This regimen was especially superior in the maintenance of quality of life because hair loss was much less compared to CAF (cyclophosphamide, ADM, 5-fluorouracil) treatment. In conclusion, MVP treatment is highly effective and safe for the treatment of recurrent breast cancer.

Adult↗
PubMed1994

[The mechanism of biochemical modulation in methotrexate/5-fluorouracil sequential chemotherapy].

5-fluorouracil (5-FU)/methotrexate (MTX) sequential chemotherapy is one of the standard regimen for the treatment of gastric cancer. Though this combination therapy is highly effective, the mechanism is still unclear. In this study, we investigated the relationship between antitumor activity and the inhibition of thymidylate synthase and between antitumor activity and incorporation of 5-FU into RNA (F-RNA) in mice bearing Sarcoma-180 treated by tegafur alone (100 mg/kg) or by the combination of MTX (42 mg/kg) and tegafur (100 mg/kg). A new method for the determination of F-RNA of tumor tissue samples was used. Briefly, RNA fractions containing incorporated 5-FU were extracted by KOH hydrolysis. FUra in RNA fractions was released by HCl hydrolysis and its levels were determined by GC-MS. The results showed that the F-RNA levels were significantly elevated by the pretreatment of MTX. According to this result, it is suggested that the measurement of F-RNA levels together with the determination of FUra concentration and the inhibition rate of thymidylate synthase were considered as a good means for the evaluation of antitumor efficacy of FUra. We concluded that the impairment of RNA metabolism played a major role in the antitumor activity of MTX/5-FU combination.

Animals↗
PubMed1993

[Four cases of advanced adenocarcinoma showing marked response to EAP (etoposide, ADM, CDDP) treatment].

Four cases of unresectable adenocarcinoma due to multiple metastasis were treated by EAP (etoposide, ADM, CDDP). The first was a 49-year-old male with gall bladder cancer, who was admitted to the hospital with metastatic umbilical tumor and intraabdominal dissemination. After 2 courses of treatment, the tumor was significantly decreased and the dissemination was diminished. The second was a 42-year-old female of breast cancer, involving lung, adrenal gland and bone metastasis. After 2 courses of treatment, all metastasis responded remarkably. Case 3 was a 42-year-old female with recurrent rectal cancer. Her lung metastasis completely disappeared after EAP treatment. Case 4 was a 42-year-old breast cancer patient with multiple liver metastasis, who also exhibited a remarkable response. In spite of severe side effects, EAP treatment was remarkably effective in all four cases of unresectable advanced adenocarcinoma.

Adenocarcinoma↗
PubMed1993

[Comparison between leucovorin and cisplatin as a modulator of 5-fluorouracil].

Currently, biochemical modulation for 5-fluorouracil (5-FU) by leucovorin (LV) and cisplatin (CDDP) seems one of the most successful chemotherapy for gastro-intestinal tract cancers. The mechanism of the modulation is thought to increase intracellular 5, 10-methylenetetrahydrofolate (CH2-H4 folate) levels. The purpose of this study is to examine the effect of LV and CDDP as a modulator of 5-FU. Either 10, 200, 400 mg/kg of LV or 2, 4, 6 mg/kg of CDDP were administered intravenously to mice bearing Sarcoma-180. Two hrs. later, CH2-FH4 folate levels were measured in tumor, muscle and intestine by thymidylate synthase (TS) binding assay. As the results, after administration of 200, 400 mg/kg of LV or 4, 6 mg/kg of CDDP, CH2-H4 folate level was elevated. This elevation was dose-dependent in LV. In contrast, no more elevation was observed after 6 mg/kg of CDDP injection. There was much smaller increase of CH2-H4 folate level was observed in the muscle and intestine. We conclude that the elevation of CH2-H4 folate levels depends on the organ and this leads to the tumor specificity in these chemotherapy.

Animals↗
PubMed1992

Intracellular cyclic AMP levels in endothelial cells subjected to cyclic strain in vitro.

Human saphenous vein endothelial cells (EC) were grown to confluence in fibronectin-coated culture plates with flexible membrane bottoms and maintained in M-199 supplemented with substrates. One hour prior to experimentation 5 mM IBMX, a phosphodiesterase inhibitor, was added. Vacuum was used to deform the membrane bottoms to 24% strain at 60 cycles/min (0.5 sec elongation alternating with 0.5 sec relaxation). After 10-60 min of cyclic strain, or upon exposure of EC to 100 microM forskolin or 0.1 microM galanin, intracellular cyclic AMP (cAMP) was measured by radioimmunoassay. In parallel experiments, tissue plasminogen activator (tPA) secretion was determined after 24 hr of cyclic strain in the absence or presence of forskolin or galanin. The results demonstrate that exposure of EC to cyclic strain led to no change in cAMP levels and confirmed our previous observation that tPA secretion was enhanced with cyclic strain. Addition of forskolin, which led to an almost 10-fold increase in cAMP levels, or galanin, which led to a 34% decrease in cAMP levels, did not significantly alter the rise in tPA induced by cyclic strain.

Cells, Cultured↗
PubMed1992

Tissue plasminogen activator expression in endothelial cells exposed to cyclic strain in vitro.

The effects of cyclic strain on the production of tissue plasminogen activator (tPA) and type 1 plasminogen activator inhibitor (PAI-1) by cultured endothelial cells (EC) were examined. Human saphenous vein EC were seeded in selective areas of culture plates with flexible membrane bottoms (corresponding to specific strain regions) and grown to confluence. Membranes were deformed by vacuum (-20 kPa) at 60 cycles/min (0.5 s strain alternating with 0.5 s relaxation in the neutral position) for 5 days. EC grown in the periphery were subjected to 7-24% strain, while cells grown in the center experienced less than 7% strain. The results show a significant increase in immunoreactive tPA production on days 1, 3 and 5 compared to day 0 in EC subjected to more than 7% cyclic strain. There was no significant elevation of tPA in the medium of EC subjected to less than 7% strain. tPA activity could only be detected in the medium of EC subjected to more than 7% cyclic strain. PAI-1 levels in the medium were not significantly different in either group. In addition, immunocytochemical detection of intracellular tPA and messenger ribonucleic acid (mRNA) expression of tPA (assessed by the reverse transcriptase polymerase chain reaction utilizing tPA specific sense and antisense primers) was significantly increased in EC subjected to more than 7% cyclic strain. We conclude that a 60 cycles/min regimen of strain that is greater than 7% can selectively stimulate tPA production by EC in vitro and may contribute to the relative nonthrombogenicity of the endothelium in vivo.

Adult↗
PubMed1992

[A case of gallbladder cancer with marked response to EAP treatment].

A case of unresectable gall bladder cancer due to multiple metastasis was dealt with EAP (VP-16, ADM, CDDP) treatment. The case was a 49-year-old male who was admitted to the hospital with a 3 cm sized umbilical tumor. After 2 cycles of the treatment, the tumor size significantly decreased and the symptoms diminished. In parallel, the symptoms from bone metastasis and dissemination also disappeared. As for tumor markers, CA 19-9 indicated 5151 U/ml, fell down to the normal range after the treatment. In this case, the efficacy of EAP treatment to the primary gall bladder carcinoma was undetectable, because of the difficulty of elucidation of the primary site by diagnostic images. However, all data suggested that EAP treatment was effective to the advanced unresectable gallbladder cancer, at least to its metastatic sites.

Adenocarcinoma↗
PubMed1991

Stimulation of endothelial secretion of tissue-type plasminogen activator by repetitive stretch.

Endothelial cells (EC) synthesize many of the fibrinolytic components and anticoagulants present in plasma. EC have been demonstrated to release tissue type plasminogen activator (t-PA) and its rapid inhibitor type 1 plasminogen activator inhibitor (PAI-1). In vivo, EC lining a blood vessel are exposed to the forces of the circulation, predominantly shear stress and pulsatile stretch. We have previously reported that repetitive stretch of EC in culture will stimulate prostacyclin secretion. In this study, the effects of cyclic stretch on the production of t-PA and PAI-1 by cultured EC were examined. EC harvested from human saphenous vein were seeded in culture plates with flexible membrane bottoms and grown to confluence. Vacuum (-20 kPa) was used to deform the membrane bottoms to 24% maximum strain. EC in the experimental group were subjected to 24% maximum strain at 60 cycles/min (0.5 sec elongation alternating with 0.5 sec relaxation), while control EC were grown on the same membranes but kept stationary in the same incubator. After 1, 3, and 5 days, the cell numbers were counted and the media were collected and analyzed for t-PA and PAI-1 by ELISA. The result shows a significant increase in t-PA production with the cyclic stretch on Days 3 and 5. There was no significant difference in PAI-1 levels in stretched versus stationary EC. We concluded that cyclic stretch of EC in vitro can selectively stimulate t-PA production and may account for the relative nonthrombogenicity of the endothelium in vivo.

Cells, Cultured↗
PubMed1991

Morphological response of human endothelial cells subjected to cyclic strain in vitro.

Endothelial cells (EC) are subjected to hemodynamic forces in vivo. However, most in vitro studies of EC biology have been performed utilizing stationary culture conditions. To study the morphology and cytoskeletal features of EC under dynamic culture conditions, we utilize a system capable of exerting repetitive strain on cells in culture. Human saphenous vein EC were plated to a subconfluent density in 25-mm wells with a thin flexible bottom and a rat collagen, Type I surface. A -20 kPascals vacuum applied to the bottoms led to a maximum deformation of 24%. EC were exposed to 0.5 sec deformation alternating with 0.5 sec relaxation (60 cycles/min) for 24 hr. EC were fixed with formalin at different time intervals and stained with crystal violet. Actin filaments were stained with rhodamine phalloidin, an F-actin marker, while beta-tubulin and vimentin were visualized by immunofluorescent antibody techniques. Within 15 min after initiation of cyclic strain, actin stress fibers were aligned perpendicular to the force vector. By 12 hr of cyclic strain EC were elongated and oriented in the same direction as the actin filaments. EC elongation and alignment were inhibited by cytochalasin B. Even up to 24 hr of cyclic strain, beta-tubulin and vimentin distributions were unaltered. We propose that cyclic strain of EC in vitro influences cell alignment and elongation by a mechanism dependent on the actin filament system.

Cells, Cultured↗