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Biomedical subjects

S Takeda

Publications and source records attributed to S Takeda.

At least 991 records · Page 55Linked to original sources
PubMedDate not supplied

Lipid peroxidation in human breast cancer cells in response to gamma-linolenic acid and iron.

Lipid peroxidation in human breast cancer (ZR-75-1) cells and cancer cell killing were confirmed by using ultraviolet (UV)-spectrophotometry and mass spectrometry (MS). ZR-75-1 cells and human normal fibroblast CCD-41-SK (41Sk) cells were cultured with gamma-linolenic acid (GLA) and ferrous iron Fe (II) combinations. Formation of lipid peroxide and cytotoxic effect were highest in ZR-75-1 cells treated with GLA + Fe (II), though 41Sk cells showed little evidence of either lipid peroxidation or cytotoxity. These results indicate a cancer-cell-specific lipid peroxidation mechanism in association with the selective cancer cell killing effect in response to GLA.

Antineoplastic Agents↗
PubMedDate not supplied

Changes in hepatic lobe volume in hepatocellular carcinoma after transcatheter arterial and percutaneous transhepatic portal embolization.

BACKGROUND/AIMS: Determining changes in liver volume after preoperative percutaneous transhepatic portal embolization (PTPE) for hepatocellular carcinoma (HCC) is essential in managing the operation safely. We evaluated the alterations in liver volume by means of ultrasonography (US) and computed tomography (CT). METHODOLOGY: We studied 12 patients scheduled for hepatectomy with HCC. Transcatheter arterial embolization (TAE) and PTPE of the right portal vein were performed preoperatively. Liver volume was evaluated before and after PTPE. RESULTS: The volume of the right lobe measured by CT significantly decreased from 709+/-266 cm3 before PTPE to 589+/-209 cm3 18 days after PTPE (P=0.0021). The volume of the left lobe significantly increased from 382+/-97 cm3 to 477+/-84 cm3 (P=0.0008). US volume measurement of the left lateral segment revealed a temporary volume increase 2 days after PTPE and a significant linear correlation between the hypertrophy ratios from 2 to 18 days after PTPE (r=0.946, P<0.0001). CONCLUSIONS: Preoperative PTPE allowed a compensatory volume increase in the remnant liver. A sonographic estimation is useful in confirming the dynamic alteration of liver hypertrophy. Care must be taken for appropriate timing of a CT scan for volume measurements, considering the drawbacks associated with irradiation.

Adult↗
PubMedDate not supplied

Imipenem/cilastatin as secondary therapy for bacterial infections.

Imipenem/cilastatin (IPM/CS) was used to treat 39 documented infections in patients who had failed to respond to other antibiotic regimens. The overall response rating was 76.9%. Respiratory infections responded less frequently (efficacy rating, 55.6%) to IPM/CS than abdominal infections, urinary tract infections, or sepsis. Methicillin-resistant Staphylococcus aureus, Xanthomonas maltophilia, and Acinetobacter calcoaceticus were less sensitive to IPM/CS therapy than the other bacterial strains encountered. Respiratory tract infections were though to be less responsive to IPM/CS, probably because imipenem-resistant strains of S aureus were present in most of those cases. It is concluded that IPM/CS is well tolerated and effective in the treatment of various bacterial infections.

Adult↗
PubMedDate not supplied

Cytologic detection of malignant mesothelioma of the pericardium.

We have reported a very rare case, malignant mesothelioma of the pericardium, with the initial diagnosis made by cytology from the smears of the pericardial fluid. There were numerous large clusters in the smears, in which two types of cells were mixed: adenocarcinoma-like round cells and fibrosarcoma-like spindly cells. Some round cells very much resembled benign mesothelial cells. Central collagenous stalks and brush borders with long microvilli in the round cell aggregates were specific for carcinomatous mesothelioma and differentiated the round cells from adenocarcinoma cells. On the other hand, the spindly and pleomorphic tumor cells, present both singly and in clusters, implied malignancy. Therefore, a preliminary cytologic diagnosis of probable mixed malignant mesothelioma was made. Histopathologic and electron microscopic examinations confirmed the cytologic description that this tumor was a malignant mesothelioma.

Adolescent↗
PubMedDate not supplied

Progressive supranuclear palsy with limbic system involvement: report of a case with ultrastructural investigation of neurofibrillary tangles in various locations.

An autopsied case of a 65-year-old woman with progressive supranuclear palsy (PSP) characterized by dementia, hallucination and delirium is described. On neuropathologic examination, widespread neurofibrillary tangles (NFTs) associated with neuronal cell loss and gliosis were observed in the basal ganglia, subthalamic nucleus and various brain stem nuclei, corresponding to the well-established pathology of PSP. In addition, a large number of NFTs with neuronal cell loss were shown in the hippocampus, parahippocampal gyrus, amygdaloid nucleus, subcallosal area, anterior perforated substance, cingulate gyrus and anterior olfactory nucleus. Ultrastructurally, NFTs observed in the periaqueductal central grey, locus ceruleus and hippocampus were composed almost exclusively of straight tubules. On the other hand, those in the amygdaloid and anterior olfactory nuclei were composed mainly of twisted tubules of Alzheimer type. NFTs composed of twisted tubules alone were not observed. The present case was considered as a rare peculiar type of PSP which showed massive systemic appearance of NFTs in the so-called limbic system.

Female↗
PubMedDate not supplied

Protective effect of pacing on reperfusion-induced ventricular arrhythmias in isolated rat hearts.

OBJECTIVES: To determine whether pacing would have a protective effect similar to preconditioning on reperfusion-induced ventricular arrhythmias and whether this protective effect would be induced by pacing-induced myocardial ischemia. DESIGN: Isolated rat hearts (n = 36) were perfused by the Langendorff technique and the working heart mode. Global ischemia was induced for 10 mins followed by reperfusion for 15 mins. The control group had no pacing, while in the other groups, the hearts were electrically paced three times at 300, 400 and 600 beats/min, respectively, for 5 mins with 1 min intervals between pacings. MAIN RESULTS: The incidence of reperfusion-induced ventricular fibrillation in controls was 100%, whereas that in the 300, 400 and 600 beats/min groups was reduced to 67% (not significant), 50% (P < 0.03) and 30% (P < 0.01), respectively. The mean duration of reperfusion-induced ventricular fibrillation was also significantly reduced in the 300, 400 and 600 beats/min groups compared with the control group. Coronary flow during pacing in the 400 and 600 beats/min groups, but not the 300 beats/min group, was reduced significantly compared with controls. In the 300 beats/min group, oxygen tension of the coronary effluent during pacing was decreased significantly, and proton production and lactate release of coronary effluent during pacing were increased significantly compared with the control group. CONCLUSIONS: Pacing exerted a protective effect similar to preconditioning against reperfusion-induced ventricular arrhythmias. Pacing-induced mild myocardial ischemia, in which coronary flow was maintained, may be involved in the mechanism of this protective effect.

Animals↗
PubMedDate not supplied

Cytotoxicity of CPT-11 and SN-38 for gastrointestinal and recurrent carcinomas cultured on contact-sensitive plates.

CPT-11 is a derivative of camptothecin, a topoisomerase-I inhibitor with marked cytotoxic activity. We examined the cytotoxicity of CPT-11 and its metabolite SN-38 for primary gastrointestinal carcinoma and various recurrent carcinomas which were cultured on contact-sensitive plates (CSPs). The response rate of seven gastrointestinal carcinomas for either CPT-11 or SN-38 was 71% (5/7). The response was higher than those for other anticancer agents, including adriamycin (ADM), cisplatinum (CDDP) and 5-fluorouracil (5-FU). The mean percent survival of these tumor cells was 69% when incubated with 25 ng/ml of SN-38, which was the lowest survival for all the anticancer drugs tested. IN the case of recurrent carcinomas, the response rate to either CPT-11 or SN-38 was 60% (3/5), and was higher than the rates for MMC, CDDP or 5-FU. The mean percent survival of the recurrent carcinoma cells was 76% in the presence of 25 ng/ml SN-38, and this was once again the lowest survival rate. CPT-11 had a stronger inhibitory effect against one carcinoma than SN-38 when a clinical drug concentration was added to the culture medium, suggesting that CPT-11 itself was cytotoxic. IN addition, one carcinoma with a low response to CDDP also showed no response to CPT-11, but was very occurred because of decreased conversion of CPT-11 to SN-38. Our results suggest that CPT-11 may be a useful agent for the treatment of both primary gastrointestinal cancer and various recurrent carcinomas.

3T3 Cells↗
PubMedDate not supplied

Mechanism of lipid peroxidation in cancer cells in response to gamma-linolenic acid (GLA) analyzed by GC-MS(I): Conjugated dienes with peroxyl (or hydroperoxyl) groups and cell-killing effects.

We have investigated the nature of lipid peroxidation occurring in association with cancer-killing produced by gamma-linolenic acid (GLA) and iron (Fe) in cultured human breast cancer cells (ZR-75-1: ZR). UV-spectrophotometry, high performance liquid chromatography (HPLC) and gas chromatography (GC) or gas chromatography-mass spectrometry (GC-MS) have been used to analyze lipid peroxides and their derivatives. Formation of conjugated dienes (CD), the conversion of triphenylphosphine (TPP) to its oxide (TPPO), and the simultaneous production of hydroxy polyunsaturated fatty acids (PUFA-OHs) from these corresponding PUFAs hydroperoxides (PUFA-OOHs) were analyzed in the total lipid extract of ZR cells and of normal human skin fibroblasts (CCD-41Sk:Sk). Fe enhanced the formation of both the CD and TPPO and increased the percentage of dead cells, while vitamin E inhibited these effects. Neither of these events was observed at any significant level in Sk cells. Identity of PUFA-OHs was confirmed by determining the regional positions of the hydroxyl group by GC-MS analysis of hydrogenated methyl ester tert-butyldimethylsilyl ether alcohol derivatives (Me-H2-PUFA-O-TBDMS). The regional isomers identified were 15-, 12- and 8-OH 20 carbon and 13-OH 18 carbon fatty acid derivatives. These results suggest that the increased formation of conjugated dienes and/or hydroperoxyl (or peroxyl) groups in PUFA molecules is relevant to the cancer cell-killing effect of GLA+Fe.

Breast Neoplasms↗
PubMedDate not supplied

Antitumor activity of menogaril alone, and in combination against human mammary cancer models in mice and rats.

Menogaril is an antitumor agent different from other anthracyclines in being active after oral administration. To predict its clinical effectiveness by this route against human breast cancer, we compared its antitumor activity against breast cancer in experimental animals with that of injected Adriamycin. Menogaril had half the much antitumor activity of Adriamycin against human mammary cancer cell lines. Menogaril given orally also had a antitumor activity against mammary cancer caused by 7,12-dimethyl-benz[a]anthracene in rats comparable with that of Adriamycin. The high concentration of menogaril in tumor tissue seemed to contribute to its effectiveness. Of several combinations of cyclophosphamide, Adriamycin, menogaril, and 5-fluorouracil, the combination of cyclophosphamide, menogaril, and 5-fluorouracil was most effective against mouse leukemia L1210 and human breast cancer xenografts in mice. This combination might have antitumor activity against breast cancer superior to that of the therapy currently of first choice (cyclophosphamide, Adriamycin, and 5-fluorouracil) in the clinic.

9,10-Dimethyl-1,2-benzanthracene↗
PubMedDate not supplied

Acute eosinophilic pneumonia accompanied by Guillain-Barré syndrome.

A 74-year-old man presented with chest pain, dry cough, progressive respiratory distress and infiltrative lung shadow. Diagnosis of acute eosinophilic pneumonia was confirmed by histological examination as well as clinical features. On the 8th day post-admission, he developed progressive generalised muscle weakness that required mechanical ventilation. Clinical investigations revealed features concurring with the accepted diagnostic criteria for Guillain-Barré syndrome. Although precise aetiologies for the disorders suffered by this case were unknown, a common cause of allergic nature was speculated. This is the first report of acute eosinophilic pneumonia accompanied by Guillain-Barré syndrome.

Aged↗
PubMedDate not supplied

Prediction of the optimum clinical dosing schedule for menogaril from results with tumor-bearing mice.

Menogaril is an antitumor agent active after oral administration, and unlike other anthracyclines, extravasation cannot occur. When the IC90 values of menogaril were plotted versus exposure time on a double-logarithmic scale, the regression lines had slopes between -0.64 and -0.80. These results showed that the mode of action of menogaril was type lb, dependent on the area under the curve (AUC) of concentration versus time, like Adriamycin. In calculations that simulated pharmacokinetic findings if administration were for three consecutive days (the single dose given was 79 mg/kg) or on days 1 and 8 (the single dose was 238 mg/kg), the peak tumor concentration of menogaril was 1870 and 2985 ng/g and the AUC was 68,363 and 89,352 ng/g hour, respectively. Of the dosing schedules tried, these two dosing schedules were the optimum, with satisfactory antitumor activity against mouse solid tumor Colon 26 and with a wide range of effective dose concentrations. Since menogaril was AUC-dependent, it was possible to predict antitumor activity and to choose optimum dosing schedules on the basis of cell-kill kinetic and pharmacokinetic information.

Animals↗
PubMedDate not supplied

Activity of menogaril against various malignant lymphoma cell lines and a human lymphoma xenograft in mice.

Menogaril is an antitumor agent different from other anthracyclines in that it is active after oral administration; therefore, extravasation is not a side effect. In this basic study, we examined the antitumor activity of menogaril against malignant lymphoma. We compared its activity towards experimental malignant lymphoma with that of Adriamycin, epirubicin, pirarubicin, vincristine, and etoposide, treating mice with each drug at the dose schedule usually used for patients. Menogaril rapidly penetrated lymphoma cells and remained there at least 3 hours after the drug was washed out. Menogaril cleaved more double-stranded DNA in lymphoma cells than Adriamycin, epirubicin, pirarubicin, or etoposide. Menogaril had stronger antitumor activity against experimental malignant lymphoma in mice than Adriamycin, epirubicin, vincristine, and etoposide. Menogaril significantly lengthened the life span of mice bearing one of three lymphoma cell lines resistant to cisplatin, vincristine, or cyclophosphamide. Menogaril had stronger antitumor activity against the human malignant lymphoma xenograft LM-3 than Adriamycin. The strength of the cytotoxic activity of Menogaril might arise from its ready penetration into cells and its cleavage of double-stranded DNA. Therefore, Menogaril might become a useful drug for the treatment of patients with malignant lymphoma by oral administration; 7 days of administration was effective in the in vivo experiments.

Animals↗
PubMedDate not supplied

Augmentation of the chemotherapeutic effectiveness of UFT, a combination of tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil] with uracil, by oral l-leucovorin.

UFT, combination of tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil] with uracil, is widely-used as an anti-neoplastic agent in Japan. We evaluated the anti-tumor efficacy of the combined modality of UFT with oral l-leucovorin. The augmentation of anti-tumor activity of UFT by co-administration of l-leucovorin was observed over a dose of 1.85 mg/kg (5.55 mg/m2) and was significant at a dose of 5.56 mg/kg (16.7 mg/m2). Using ten human tumor xenografts, l-leucovorin significantly enhanced the growth-suppressive ability of UFT against colon carcinoma (KM20C, Col-1) and mammary carcinoma (H-31, MX-1). Among various 5-fluorouracil (FUra) derivatives, such as UFT, 5'-deoxy-5-fluorouridine (5'-DFUR) and FUra, l-leucovorin gave the maximum augmentation to the anti-tumor activity of UFT, due to the prolonged half-life of FUra in plasma. Enhancement of the cytotoxic activity of FUra by l-leucovorin against KM20C colon carcinoma cell line was observed in a time-dependent manner at a concentration of 0.01 microM l-leucovorin. Based on these results, we conclude that the combination of UFT with oral l-leucovorin has significant antitumor activity and represents an interesting regimen to be evaluated in the clinical setting.

Administration, Oral↗
PubMedDate not supplied

Effect of combination therapy with UFT plus cisplatin (UFTP) on the survival of mice in the experimental model for wide-spread metastasis in the peritoneal cavity of gastrointestinal cancer using colon 26 PMF-15 cells.

The prognosis of unresectable advanced gastric cancer patients, especially with wide-spread metastasis in the peritoneal cavity, is very poor. In such cases, only a few treatment methods are available, and chemotherapy as a systemic therapy is often selected. We recently devised an experimental model for wide-spread metastasis in the peritoneal cavity of gastrointestinal cancer, by intraperitoneally implanting colon 26 murine carcinoma PMF-15 cells. When the control mice were autopsied, a number of tumor nodules were formed in their mesenterium, pancreas, liver, etc. and pools of ascites were also occasionally seen. Using this model, oral UFT (combining tegafur and uracil at a molar ratio of 1:4) plus cisplatin (UFTP regimen) prolonged the survival of mice and maintained these mice in relatively better condition than with continuous infusion of 5-fluorouracil plus cisplatin (FP regimen). Since UFT can be used orally, patients receiving UFTP therapy are not required to stay in a hospital for long periods, but rather, are intermittently hospitalized for short periods of time. Better QOL and prolonged survival highlight the potential clinical usefulness of the UFTP therapy.

Animals↗
PubMedDate not supplied

Postoperative delayed emptying in pylorus-preserving pancreatoduodenectomy using pancreaticogastrostomy: comparison of the reconstruction position.

BACKGROUND/AIMS: We frequently use pancreaticogastrostomy after pylorus-preserving pancreatoduodenectomy (PpPD). Although it is a useful and effective technique, it sometimes requires prolonged delayed emptying. We considered the best position for pancreaticogastrostomy in such a way as to reduce this period of delayed emptying. MATERIAL AND METHOD: From 1991 to 1996, 17 patients whose blood sugar was controlled and who were kept on H2 blocker were selected from among 25 patients who underwent PpPD and were reconstructed by pancreaticogastrostomy. We investigated the history of the relationship between reconstruction position and delayed emptying, reconstruction position and minor leakage, minor leakage and delayed emptying, reconstruction position and stomach mobility without leakage. RESULTS: The delayed emptying was shorter for a reconstruction position in the area above the angulus rather than below it. CONCLUSION: The results suggest that the area above the angulus is the preferred site for pancreaticogastrostomy after PpPD.

Adult↗
PubMedDate not supplied

Intraoperative radiotherapy for pancreatic carcinoma with hepatic or peritoneal metastases.

BACKGROUND/AIMS: The purpose of this study was to determine the efficacy of intraoperative radiotherapy (IORT) for unresectable pancreatic carcinoma associated with hepatic or peritoneal metastasis. METHODOLOGY: Between 1991 and 1994, 53 patients with pancreatic carcinoma associated with hepatic or peritoneal metastasis underwent surgery. Twenty-four of these patients received IORT, while 29 received no radiation therapy. The efficacy of IORT on the postoperative survival and pain relief for these patients was retrospectively analyzed. RESULTS: Postoperative survival was lowest in the subgroup of patients (n = 18) with both hepatic and peritoneal metastases, and this group did not benefit from IORT (IORT, n = 6; no IORT, n = 12) in terms of survival. Similarly, there was no significant difference in the survival rates between patients undergoing IORT (n = 10) and patients without IORT (n = 11) in the subgroup of patients with hepatic metastasis but without peritoneal metastasis. However, patients with peritoneal metastasis but without hepatic metastasis benefited significantly from IORT (IORT, n = 8; no IORT, n = 6) (p < 0.05). Pain relief following IORT was observed in 9 out of 10 patients who had experienced pain prior to surgery. CONCLUSION: Pancreatic carcinoma associated with peritoneal metastasis but without hepatic metastasis can be palliated by IORT. In addition, pain palliation in patients who require gastrointestinal or biliary drainage can also be achieved by IORT.

Humans↗
PubMedDate not supplied

Separate histogenesis of combined hepatocellular and cholangiocellular carcinoma in two patients.

Double primary liver carcinomas, i.e. hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) are rare. Two patients in whom double primary liver carcinomas were surgically resected are described herein. Case 1: A 51-year-old Japanese man with chronic type B hepatitis underwent hepatectomy for primary HCC with intrahepatic metastasis. Case 2: A 67-year-old Japanese man with a history of rectal cancer and CCC underwent lateral hepatic segmentectomy for a suspected recurrence of intrahepatic CCC. Lack of direct contact between tumors, no evidence of histological transition and clearly different immunohistochemical staining for cytokeratin support a distinct histogenesis of the tumors in these two patients. The findings indicate that combined HCC and CCC can arise synchronously or metachronously as an intrahepatic double cancer.

Aged↗