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Biomedical subjects

R Saitoh

Publications and source records attributed to R Saitoh.

At least 19 recordsLinked to original sources
PubMed2001

A phase I study of weekly docetaxel and cisplatin in advanced non-small cell lung cancer.

This phase I study was designed to determine the maximum tolerated dose (MTD) and toxicity of a weekly docetaxel (TXT) and cisplatin (CDDP) combination regimen in advanced non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC who were previously untreated were eligible. Docetaxel, at a starting dose of 20 mg m(-2) per week on days 1, 8 and 15, was combined with a fixed dose of cisplatin 80 mg m(-2) on day 1. Docetaxel was increased in 5 mg m(-2) per week steps. Chemotherapy was given in a 4-weeks cycle. Dose-limiting toxicities (DLTs) were defined as grade 3-4 leukopenia, thrombocytopenia, anemia, fever with grade 4 neutropenia and more than grade 2 non-hematologic toxicity, with the exception of nausea, vomiting, and alopecia. Omission of chemotherapy on day 8 and/or 15 was also considered DLT. Eighteen patients were enrolled in this study. Leukopenia, anemia and fatigue were the DLTs. No grade 4 toxicities were seen in any patients. The overall response rate was 44.4% (95% confidence interval, 21.5-67.4%). The recommended dose of TXT to be combined with CDDP 80 mg m(-2) on day 1 is 35 mg m(-2) per week on days 1, 8 and 15. This is a promising regimen, therefore a multicenter phase II study is now under way.

Aged↗
PubMed1999

Effects of cyclopiazonic acid on contraction and intracellular Ca2+ in oesophageal striated muscle of normotensive and spontaneously hypertensive rats.

1. The effects of cyclopiazonic acid (CPA), a selective inhibitor of sarcoplasmic reticulum (SR) Ca2+-ATPase, on twitch contraction and on the resting state of tension and intracellular Ca2+ level ([Ca2+]i) of the oesophageal striated muscle of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) were compared. 2. CPA (10 micronM) augmented the twitch contraction of oesophageal striated muscle preparations from both SHRSP and WKY, reducing the rate of relaxation (-dT/dt), and thus resulting in the prolongation of the time to 80% relaxation. The effect was significantly smaller in the SHRSP preparations. 3. In the resting state, CPA caused a sustained elevation of [Ca2+]i. The elevation was greater in the WKY preparations. Tension development accompanied by the elevation was observed in WKY preparations, but not in SHRSP preparations. 4. The sustained elevation of [Ca2+]i induced by CPA was eliminated by the removal of extracellular Ca2+. Both the elevated [Ca2+]i and tension in the preparations from WKY were reduced by flufenamic acid (100 micronM), mefenamic acid (100 micronM), lanthanum (La3+, 100 micronM), gadolinium (Gd3+, 100 micronM) and SK&F 96365 (100 micronM) but not by verapamil (10 micronM). 5. Thapsigargin (3 micronM), another SR Ca2+-ATPase inhibitor, produced similar effects on basal tension to those of CPA, although it reduced the amplitude of twitch contraction. 6. These results suggest that in the rat oesophageal striated muscle, (1) CPA extends the sequestrating time of Ca2+ into the SR, (2) CPA induces a Ca2+ influx mediated through verapamil-insensitive pathways, possibly nonselective cation channels, and (3) the mechanism of [Ca2+](i) modulation due to CPA-sensitive SR Ca2+-ATPase is deteriorated in the oesophageal striated muscle from SHRSP as compared with WKY preparations.

Animals↗
PubMed1999

Risk factors for severe radiation pneumonitis in lung cancer.

BACKGROUND: Risk factors for severe radiation pneumonitis, which often spreads beyond treatment portals and may even be bilateral, have not been fully investigated. The purpose of this study was to identify important factors associated with severe radiation pneumonitis. METHODS: 111 cases of primary lung cancer, treated with radiotherapy or chemoradiotherapy, were retrospectively analyzed. RESULTS: Severe radiation pneumonitis occurred in 17 cases (15.3%). The ratio of interstitial change in lungs before radiotherapy and radiotherapy to the contralateral mediastinum with > 40 Gy in the radiation pneumonitis group (RP group) was significantly higher than in patients without radiation pneumonitis (control group) (47.1% vs 5.3%; P < 0.001 and 58.8% vs 27.7%; P = 0.037, respectively). Using logistic regression analysis, interstitial changes before radiotherapy and radiotherapy to the contralateral mediastinum of > 40 Gy were significant risk factors associated with severe radiation pneumonitis. CONCLUSIONS: These data suggest that pre-existing interstitial changes detected by chest radiography or computed tomography and radiotherapy to the contralateral mediastinum (> 40 Gy) may predict the development of severe radiation pneumonitis.

Adult↗
PubMed1998

Quantitative differences in telomerase activity among malignant, premalignant, and benign ovarian lesions.

Telomerase activation has been demonstrated in both cancers and some noncancerous lesions. However, few studies have determined levels of telomerase activity in these lesions. In the present study, using a recently developed stretch PCR assay, telomerase activity was quantitatively determined in a variety of ovarian lesions including 36 ovarian cancers, 5 ovarian low potential malignancy (LPM) lesions, 10 ovarian cysts, and 12 normal ovaries. Telomerase activity was normalized to control activity (100 units) in C33A cell line and given in relative units. Telomerase activity in ovarian cancer (51 +/- 7 units, mean +/- SE) was significantly higher than that in LPM lesions, ovarian cysts, and normal ovaries (7 +/- 3, 10 +/- 2, and 10 +/- 2 units, respectively; P < 0.001). Interestingly, all LPMs, ovarian cysts, and normal ovaries exhibited low telomerase activity less than 30 units, and no significant difference in level of telomerase activity was found among them. We also found a significant correlation between the level of telomerase activity and the clinical stage of ovarian cancer. Our quantitative telomerase assay thus clearly distinguished telomerase activity in ovarian cancers from that in LPM lesions and ovarian cysts. Significant levels of telomerase activation frequently occurred in cancer but rarely occurred in premalignant and benign lesions, suggesting that telomerase activation is a critical step in cancer development.

Female↗
PubMed1997

A phase II study of carboplatin-cisplatin-etoposide combination chemotherapy in advanced non-small-cell lung cancer.

It is reported that the combination of cisplatin (CDDP) and carboplatin (CBDCA) is synergistic in vitro. The objective of this study was to evaluate the therapeutic effect and safety of the two platinum compounds in combination with etoposide in the treatment of non-small-cell lung cancer (NSLC). Forty patients were registered. Based on the results of a phase I study, patients were treated with CDDP (80 mg/m2 i.v. on day 1), CBDCA (280 mg/m2 i.v. on day 1), and etoposide (80 mg/m2 i.v. on days 1-3). Of the 40 patients, 30 were men and 10 women. Histology revealed adenocarcinoma(AC) (n = 20), squamous cell carcinoma(SCC) (n = 18), and large cell carcinoma(LCC) (n = 2). Staging: IIIA (n = 3); IIIB (n = 17); and IV (n = 20). A 32.5% overall response rate [13 of 40; 95% confidence interval (CI) 18-47%] was achieved. The response rates in patients with SCC and AC were 55.6 and 10.0% (p < 0.005), respectively. The median duration of response was 47.1 weeks and the overall median survival time was 57.1 weeks. Leukopenia and thrombocytopenia--World Health Organization (WHO) grade IV--occurred in nine and 11 patients, respectively. Nonhematological toxicities were mainly nausea, vomiting, and alopecia. In conclusion, further investigations of this regimen are warranted in the treatment of NSLC.

Adult↗
PubMed1997

[Removal of bronchial foreign bodies by suction with a bronchoscope].

We report two cases in which intrabronchial foreign bodies were removed with a fiberoptic bronchoscope. In both cases the foreign body was a seed of a small Japanese apricot. Atelectasis or obstructive pneumonia was seen on chest roentgenograms. The foreign bodies were associated with slight inflammation and polyps on the bronchial epithelium. The foreign bodies were removed by applying suction with a fiberoptic bronchoscope. This method may also be useful for removing other large, hard, uneven, and ball-like foreign bodies.

Aged↗
PubMed1997

[Malignant hemangioendothelioma associated with chronic pyothorax].

A 67-year-old man was admitted to the hospital because of a fever. A chest CT scan showed multilobular heterogeneous shadows on the right side in the chest wall and the lung, but clinical examinations and examination of a biopsy specimen did not lead to a diagnosis. At autopsy, a hemorrhagic tumor was found on the right side in the chest wall. Microscopical examination showed that large atypical cells had proliferated and formed vascular structures, which were stained positively with anti-factor VIII antibody. The histological findings led to the diagnosis of malignant hemangioendothelioma. Chronic empyema-associated malignant hemangioendothelioma is rare.

Aged↗
PubMed1997

Nonlinear intestinal absorption of 5-hydroxytryptamine receptor antagonist caused by absorptive and secretory transporters.

The mechanism of the nonlinear concentration dependence of intestinal absorption of the 5-hydroxytryptamine receptor antagonist azasetron was studied by use of rat in situ intestinal perfusion, as well as an in vitro Ussing-type chamber method mounted with rat intestinal tissue and cultured monolayers of human adenocarcinoma Caco-2 cells. The intestinal absorption rate constant of azasetron evaluated by the Doluisio method increased significantly with increasing concentration of azasetron up to 10 mM in a nonlinear fashion and tended to decrease at higher concentrations. Mucosal-to-serosal directed permeation of [14C]azasetron across rat ileal sheets evaluated by the in vitro Ussing-type chamber method also increased in a nonlinear fashion in a low concentration range, followed by a decrease as the concentration was further increased, whereas serosal-to-mucosal directed permeation decreased in a concentration-dependent manner. Vectorial transport of [14C]azasetron across a Caco-2 cell monolayer was observed, with higher transport in the basolateral-to-apical direction at a trace concentration of azasetron. When the initial uptake rate of azasetron by Caco-2 cells was measured, it was saturable with an apparent half-saturation concentration of 15 mM and was reduced in the presence of several cationic compounds. These observations suggest that azasetron is taken up by a carrier-mediated transport mechanism across the intestinal epithelial cells. When the steady-state uptake of [14C]azasetron was measured, it was increased in the presence of unlabeled azasetron and ondansetron. In addition, the steady-state uptake was enhanced in the presence of a P-glycoprotein inhibitor, cyclosporin A, and by ATP-depletion of the cells, although these treatments had no effect on the initial uptake of [14C]azasetron. Furthermore, the multidrug-resistant cancer cell line K562/ADM that overexpresses P-glycoprotein accumulated azasetron less extensively than did the parental drug-sensitive K562 cells. These results strongly suggest that azasetron is secreted into the intestinal lumen predominantly by P-glycoprotein. We conclude that intestinal transport of azasetron involves specialized transporters in both the absorptive and secretory directions, and the complex nonlinear intestinal absorption characteristics can be ascribed to the participation of multiple transport mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Elimination rate of fat emulsion particles from plasma in Japanese subjects as determined by a triglyceride clamp technique.

The elimination rate of emulsion triglyceride (TG) from plasma was investigated in Japanese subjects by a plasma TG clamp technique. Two different studies were performed. In Study 1, a lipid emulsion (20% long-chain triglyceride emulsion: LCT) was infused into a healthy research associate to achieve a certain concentration of TG in the plasma. Thereafter, the infusion rate was adjusted to maintain the chosen concentrations of TG in plasma (namely, 4-5 mmol/L, 3-4 mmol/L, and approximately 2 mmol/L) over a period of 160 min by measuring plasma TG concentrations at 10-min intervals. Concentrations of TG in plasma were clamped within 2.13 +/- 0.13 mmol/L by an infusion rate of 0.10 g.kg-1.h-1, within 3.34 +/- 0.20 mmol/L by an infusion rate of 0.14 g.kg-1.h-1, and within 4.46 +/- 0.22 mmol/L by an infusion rate of 0.11 g.kg-1.h-1. The mean rate of infusion of emulsified TG that had maintained the steady concentrations of TG in plasma was limited to the very narrow range of 0.12 +/- 0.02 g of TG.kg-1.h-1 regardless of the chosen concentration of TG in plasma. Concentrations of nonesterified fatty acids (NEFA) also remained at a fixed level of 1.378 +/- 0.103 mEq/L regardless of the chosen concentration of TG in the plasma. Study 2 was undertaken to determine whether plasma TG concentration reached a plateau during a period when emulsion TG was infused into three different subjects at a rate of 0.12 g.kg-1.h-1. The plasma TG concentrations were steady at a level of 2.04 +/- 0.32 mmol/L, and the plasma NEFA concentrations remained at a fixed level of 1.33 +/- 0.13 mEq/L, over a period of 160 min after 50-min priming infusion. These results indicate that the plasma TG elimination rate was limited to the narrow range of 0.12 +/- 0.02 g.kg-1.h-1 when the fat emulsion was infused into Japanese subjects in a steady state. However, the plasma TG elimination rate in Japanese subjects appeared to be lower than that of Europeans. This may be due to a difference in lipoprotein lipase activity caused by different dietary habits, namely, a lower fat intake.

Adult↗
PubMed1996

Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 in human breast carcinoma.

The in situ formation of estradiol plays an important role in the development and biological behavior of human breast cancer Aromatase and 17 beta-hydroxysteroid dehydrogenase type 1 (17 beta-HSD type 1) are two principal enzymes involved in in situ estradiol production. We evaluated the expression of aromatase and 17 beta-HSD type 1 by immunohistochemistry in 41 cases of invasive breast carcinoma (19 lobular and 22 ductal). We then examined the correlation among the expression of these enzymes, estrogen (ER) and progesterone (PR) receptor status, Ki67 labeling index of carcinoma cells, age, and the clinical stage of the patients. Marked aromatase immunoreactivity was observed in stromal cells around carcinomatous glands in 32 of 41 cases (78%), and 17 beta-HSD type 1 immunoreactivity was detected in carcinoma cells in 23 of 41 cases (56%). There was a significant correlation observed between expression of 17 beta-HSD type 1 and aromatase in invasive lobular carcinoma (P = 0.0119), but not in invasive ductal carcinoma. There was an inverse correlation between aromatase and ER status in invasive ductal carcinoma (P = 0.0213), but not in invasive lobular carcinoma. No other correlations were observed among 17 beta-HSD type 1, aromatase, PR, ER, clinical stage, age, and Ki67 labeling indexes. Aromatase and 17 beta-HSD are not always expressed simultaneously in human breast carcinoma, but their simultaneous expression is more frequent in invasive lobular carcinoma than invasive ductal carcinoma. Consequently, different mechanisms may be involved in the regulation of expression of these two enzymes in human breast carcinoma.

17-Hydroxysteroid Dehydrogenases↗
PubMed1996

Embolization for ruptured superior mesenteric artery aneurysms.

Superior mesenteric artery (SMA) aneurysms are very uncommon. They are difficult to detect until they rupture and cause hypovolaemic shock. We performed embolization in four cases of aneurysm of branches of the superior mesenteric artery, succeeding in three cases without the need for surgical treatment. In the first case, the aneurysm was excised because of migration of a microcoil into the left hepatic artery. It was not retrieved because sufficient blood flow to the liver was shown on angiography after migration and no ischaemic change of liver was detected on laparotomy. In the second case, the aneurysm arose from the anterior pancreaticoduodenal artery. In the third case, the patient had two SMA aneurysms; one had been resected at surgery, another was revealed on follow-up angiography and embolized with microcoils. The fourth patient had a jejunal artery aneurysm with extravasation; haemostasis was achieved by packing it. In all four cases, no major complications were observed in the clinical course after embolization. Microcoils were considered to be the desirable embolic material, in order to prevent post-therapeutic ischaemic change. Embolization should be the treatment of choice for SMA aneurysms, because it is less invasive and takes less time than surgical treatment.

Adult↗
PubMed1996

[A case of asymptomatic extra-adrenal pheochromocytoma].

A 46-year-old female first presented to our clinic with a chief complaint of an abdominal mass. A computerized tomographic (CT) scan revealed a 6 cm retroperitoneal mass below the left kidney. Preoperative hormonal examinations showed elevation of catecholamines and vanillymandelic acid (VMA) in her 24-hour urine, although she had no hypertension. Therefore, the tumor was uneventfully removed and histologically diagnosed as pheochromocytoma. It is difficult to preoperatively diagnose normotensive extra-adrenal pheochromocytoma without any considerations of the possibilities. However, it may be hazardous to treat pheochromocytoma surgically without any preparations. In the present case, we emphasized the importance of preoperative accurate diagnosis of extra-adrenal pheochromocytoma and discussed briefly the clinical features in the literature.

Biomarkers, Tumor↗
PubMed1995

[Primary lung cancer in young patients].

We studied the clinical characteristics and prognosis of patients, 40 years old or younger, in whom primary lung cancer was diagnosed and treated at National Nishigunma Hospital between 1982 and 1993, and compared them with those of 978 patients more than 40 years old. Younger patients numbered 30 (3.0%). Females accounted for 16 of the 30 cases (53.3%), a proportion higher than the female: male ratio for the older patients (27.8%). There were more smokers among the older patients (72.8%) than among the younger patients (53.3%) (p < 0.01). Adenocarcinoma was significantly more common (19/30, 63.3% vs 43.8%, p < 0.05) and squamous cell carcinoma was less common (3.30, 10.0% vs 34.3%, p < 0.05) in the younger patients than in the older patients. Median survival time in younger patients was 30.0 months, and in older patients it was 14.6 months, but we found no significant difference in survival between younger and older patients. In the younger group, all the cases of stage I or II disease were discovered during mass screening.

Adenocarcinoma↗
PubMed1994

von Recklinghausen's disease with lung cancer derived from the wall of emphysematous bullae.

A 53-year-old male with von Recklinghausen's disease, diagnosed to have metastatic large cell carcinoma in the left supraclavicular lymph node, was admitted for radiotherapy. No other primary lesions were found. Emphysematous bullae in both upper lung fields were seen on chest roentgenograph, and the leucocyte count and G-CSF level were extremely elevated. Later, when metastases appeared, systemic chemotherapy was supplemented, but in vain. An autopsy showed large cell carcinoma of the lung derived from the wall of emphysematous bullae in left lung along with multiple metastases. The presence of von Recklinghausen's disease, emphysematous bullae and lung cancer together are noteworthy.

Carcinoma, Large Cell↗
PubMed1993

[Clinical study of intrapleural administration of pirarubicin (THP-ADM) in the treatment of malignant pleural effusion secondary to lung cancer].

The efficacy of intrathoracic administration of pirarubicin (THP-ADM), a derivative of adriamycin, was evaluated in 20 patients with malignant effusion due to lung cancer. All 20 patients had no previous intrapleural therapy. According to the criteria of ECOG, eight patients were at performance status 1 (P.S.1), nine were P.S.2, and three were P.S.3. Fourteen patients were clinical stage IIIB, and six stage IV. The effusions were first completely drained by thoracocentesis or tube thoracostomy drainage, and 30 mg/m2 THP-ADM was instilled. Overall response rate was 50.0%. The response rate for treatment with tube thoracostomy drainage was 69.2%, which was significantly higher than that for treatment with thoracocentesis (14.3%). Significant difference in survival was not seen between the tube thoracostomy drainage group and the thoracocentesis group. There were no severe side effects. In conclusion, intrapleural administration of THP-ADM with tube thoracostomy drainage was considered to be useful for the control of malignant pleural effusion due to lung cancer.

Adult↗