PubMed HealthSearch

Biomedical subjects

R Saitoh

Publications and source records attributed to R Saitoh.

At least 19 recordsLinked to original sources

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

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

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

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

[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

[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

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

[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

[A case of spindle cell (squamous) carcinoma (WHO) of the lung].

A 76-year-old man with spindle cell (squamous) carcinoma of the lung developed fatal respiratory failure after limited thoracic irradiation at a total dose of 18 Gy. He developed severe pulmonary toxicity, which presented as dry cough, dyspnea, and pulmonary infiltrates extending beyond the radiation field. Microscopically, a transitional form of squamous to spindle-shaped cells was observed in the primary tumor, located at right S8. Immunohistochemical examination showed positive staining of spindle cells for keratin, vimentin, and EMA, but not for desmin. These results indicate that the spindle cells had characteristics of squamous epithelial cells, and differed from carcinosarcoma. Distant metastatic lesions were composed of only the spindle cell component.

Aged

Modulation of c-myc expression by transforming growth factor beta 1 in human hepatoma cell lines.

The effects of transforming growth factor beta 1 (TGF-beta 1) on cell proliferation of human hepatoma cell lines, PLC/PRF/5 and Mahlavu, were investigated under serum-free conditions. DNA synthesis was strongly inhibited in the PLC/PRF/5 cells by addition of TGF-beta 1 (0.5 to 4.0 ng/ml), but remained unchanged in the Mahlavu cells. Also the expression of c-myc mRNA was suppressed by the addition of TGF-beta 1 in the PLC/PRF/5 cells but not in the Mahlavu cells. These results indicate that TGF-beta 1 might regulate cell growth, in part, by modulating c-myc expression, although there is no direct proof that c-myc expression is really relevant to DNA synthesis mediated by TGF-beta 1.

Carcinoma, Hepatocellular

[Lung transplantation as a treatment method in terminal respiratory failure].

Lung transplantation is the last treatment for terminal respiratory failure due to irreversible pulmonary disease such as fibrosis and emphysema. In this paper we reported the results of our studies on three major problems for conducting clinical lung transplantation sefely, including lung preservation, early diagnosis of lung allograft rejection and bronchial anastomotic healing. We have developed a method for 48- and 96-hour lung preservation. Under simple hypothermic preservation using phosphate buffered solution resembling extracellular fluid, 48-hour storage of the lung becomes possible. Immunologic monitoring is feasible for early detection of postoperative rejection of the lung transplant. In this study subset and spontaneous blastogenesis of lymphocyte obtained from bronchoalveolar lavage fluid were measured in orthotopic rat lung allotransplantation. Lung allograft rejection is closely connected with wound healing of the bronchial anastomosis in lung transplantation. It seems that clinical applications of single and double lung transplantation is now possible for patients with terminal respiratory disease in our country.

Bronchoalveolar Lavage Fluid

The inhibitory effect of forskolin on antibody-dependent cell-mediated cytotoxicity using Chang liver cells as target cells.

The effect of forskolin, a unique adenylate cyclase activator, on antibody-dependent cell-mediated cytotoxicity (ADCC) was examined. ADCC was assayed using Chang liver cells as the target cells, immuned rabbit serum as the antibody and healthy human peripheral blood mononuclear cells (PBMNC) as the effector cells. Forskolin at concentrations ranging from 1 to 20 microM significantly inhibited ADCC in a dose-dependent manner. By the addition of forskolin, cyclic AMP levels did not change in Chang liver cells but increased in PBMNC. Therefore, it appears that forskolin exerted an inhibitory effect on ADCC by increasing the intracellular cyclic AMP levels in PBMNC, the effector cells.

Antibody-Dependent Cell Cytotoxicity

Changes in hepatic functional reserve after transcatheter embolization of hepatocellular carcinoma. Assessment by maximal removal rate of indocyanine green.

To clarify the influence of transcatheter arterial embolization (TAE) on hepatic function, the maximal removal rate of indocyanine green (ICG-Rmax), which represents the hepatic functional reserve, and the plasma disappearance rate of indocyanine green (k-ICG) were measured serially before and after 15 TAE procedures performed on 13 hepatocellular carcinoma (HCC) patients with underlying hepatic diseases. Compared to the values before TAE, ICG-Rmax values did not change or gradually decreased during 4 weeks in seven of the 13 patients but markedly decreased in the remaining six by as much as 50% during the first week. k-ICG values remained almost unchanged at any time after TAE. Albumin and prothrombin time were serially measured before and after 24 TAE procedures performed on 21 HCC patients with underlying hepatic diseases in whom no plasma products had been used for therapy. Albumin decreased by up to 75% in one of the 21 patients during the first week but did not change or gradually decreased in 20 of the 21 patients. Prothrombin time showed no obvious changes. This study showed that prominent changes occurred in ICG-Rmax, i.e., in the hepatic functional reserve, after TAE.

Aged

Hepatic conversion of 1-(tetrahydro-2-furanyl)-5-fluorouracil into 5-fluorouracil in patients with hepatocellular carcinoma.

The pharmacokinetics of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT) and its conversion into 5-fluorouracil (FUra) in liver tissue were studied in ten patients with hepatocellular carcinoma (HCC). The plasma concentration of FT after its intravenous injection (dosage: 800 mg) was computerfitted to a bi-exponential function (C = Ae-alpha t + Be-beta t), indicating a two-compartment disposition. The pharmacokinetic parameters did not significantly differ between the five patients with, and the five without cirrhosis of the liver. The plasma concentrations of FUra likewise showed no significant difference between the two groups. The rates of FT degradation in the liver tissue homogenate were similar for four of the patients with cirrhosis (0.10 +/- 0.05 mumol/g liver protein/30 min) and four of those without it (0.13 +/- 0.05). The rates of cytochrome P-450-dependent FUra formation in the microsomal fraction of liver tissue from two patients (1.1 and 1.3 nmol/mg microsomal protein/30 min) were dramatically reduced to less than half of those of two control subjects (2.4 and 2.7). The estimated rates of FUra formation in the soluble fraction (105,000 X g supernatant fraction) from the two patients (0.1 and 0.13 nmol/mg protein/30 min) were almost identical to those from the controls (0.12 and 0.14), suggesting that the rate in the soluble fraction from HCC patients may not be as strongly affected as the rate in the microsomal fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged