[Pilot study of cisplatin, ifosfamide and irinotecan (CPT-11) with granulocyte colony-stimulating factor support (CIC-regimen) in relapsed small-cell lung cancer].
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Adult↗
Biomedical subjects
K Sekine
Publications and source records attributed to K Sekine.
Inhibition of initiation and early stage development of aberrant crypt foci and enhanced natural killer activity in male rats administered bovine lactoferrin concomitantly with azoxymethane.
The influence of concomitant administration of bovine lactoferrin (bLF) on induction of aberrant crypt foci (ACF) by azoxymethane was investigated in male F344 rats. Two percent bLF and 3% Bifidobacterium longum (B. longum), as a positive control, significantly decreased the numbers of ACF as well as the total numbers of aberrant crypts reproducibly in three independent studies (2% bLF, P < 0.01; 3% B. longum, P < 0.05). Most importantly large size foci composed of four or more crypts were always significantly decreased by 2% bLF (P < 0.05). Additional investigation of the natural killer activity of spleen cells demonstrated enhancement by bLF (P < 0.01) and B. longum (P < 0.01) in line with the levels of influence on foci induction, indicating a possible role for elevated immune cytotoxicity in the observed inhibition.
Animals↗
Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN, MNU and DMH.
An investigation was conducted to assess the chemopreventive potential of lycopene (LP), a naturally occurring hydrocarbon carotenoid found in tomatoes and their products, administered during the post-initiation stage in a multiorgan carcinogenesis model. One hundred eighteen B6C3F1 mice of both sexes were subjected to combined treatment with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU) and 1,2-dimethylhydrazine (DMH) from day 11 after birth to week 9 (DMD treatment) (groups 1 and 2) or their vehicles (group 3). Then group 1 received LP (25 or 50 ppm in drinking water) for 21 weeks from weeks 11 to 32. Group 2 served as a carcinogen alone control and group 3 was given only LP (25 or 50 ppm). All surviving animals were sacrificed at week 32 and the major organs, including the liver, lung, kidney and colon, were histologically examined. The incidences and multiplicities of lung adenomas plus carcinomas combined in male mice in group 1 receiving 50 ppm LP were significantly decreased as compared to the DMD alone or DMD and 25 ppm LP groups (75.0 versus 18.8%, P < 0.02; 0.94 +/- 0.17 versus 0.25 +/- 0.14, P < 0.001). No such effect was observed for females. Although hepatocellular carcinomas were lacking in the DMD and LP groups while two cases were found in the DMD alone group, this difference was not statistically significant. The values for aberrant crypt foci (ACF) and tumors in the colon and kidney did not show any significant variation among the carcinogen-treated subgroups. The results suggest that LP exerts a chemopreventive effect limited to male lung carcinogenesis when given in the post-initiation stage to B6C3F1 mice.
1,2-Dimethylhydrazine↗
Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning.
1 alpha,25-Dihydroxyvitamin D3[1 alpha,25(OH)2D3], an active form of vitamin D, has roles in many biological phenomena such as calcium homeostasis and bone formation, which are thought to be mediated by the 1 alpha,25(OH)2D3 receptor (VDR), a member of the nuclear hormone receptor superfamily. However, the molecular basis for the actions of 1 alpha,25(OH)2D3 in bone formation, its role during development and VDR genetic polymorphisms for predicting bone mineral density are uncertain. To investigate the functional role of VDR, we generated mice deficient in VDR by gene targeting. We report here that in VDR null mutant mice, no defects in development and growth were observed before weaning, irrespective of reduced expression of vitamin D target genes. After weaning, however, mutants failed to thrive, with appearance of alopoecia, hypocalcaemia and infertility, and bone formation was severely impaired as a typical feature of vitamin D-dependent rickets type II (refs 8, 9). Unlike humans with this disease, most of the null mutant mice died within 15 weeks after birth, and uterine hypoplasia with impaired folliculogenesis was found in female reproductive organs. These defects, such as alopoecia and uterine hypoplasia, were not observed in vitamin D-deficient animals. The findings establish a critical role for VDR in growth, bone formation and female reproduction in the post-weaning stage.
Alopecia↗
Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats.
The influence of bovine lactoferrin (bLF) on colon carcinogenesis was investigated in male F344 rats treated with azoxymethane (AOM). Following three weekly injections of AOM, the animals received 2 or 0.2% bLF for 36 weeks. No effects indicative of toxicity were noted, but significant reduction in both the incidence and number of adenocarcinomas of the large intestine was observed with both doses. Thus, the incidences of adenocarcinomas in the groups receiving 2% and 0.2% bLF were 15% and 25%, respectively, in contrast to the 57.5% control value (P < 0.01 and P < 0.05, respectively). The results indicate that bLF might find application for chemoprevention of colon cancer.
Adenocarcinoma↗
Urinary excretion of aquaporin-2 water channel protein in human and rat.
Previous studies by the authors demonstrated that the response of urinary aquaporin-2 (AQP2) excretion to dDAVP (deamino-8-D-arginine vasopressin) infusion is an index of vasopressin action on the kidney (N Engl J Med 332: 1540-1545, 1995). In the study presented here, the characteristics of urinary excretion of AQP2 were examined further. An RIA suitable for AQP2 in the urine was established. Relatively high concentrations of detergent and bovine serum albumin in the RIA buffer allowed analysis of urine samples with a wide range of concentrations and increased the sensitivity of the assay. AQP2 in the urine existed as a high molecular weight form of approximately 190 kD by HPLC analysis. The mean urinary AQP2 concentration corrected for creatinine in spot urine samples of healthy subjects who voided in the morning was 1081 +/- 699 fmol/mg creatinine (mean +/- SD, n = 208). The amount of daily excretion of AQP2 in the urine was the same in men and women. Urinary AQP2 content was not affected by age of the subjects and showed a positive correlation with urine osmolality. Finally, the fraction of AQP2 excreted in the urine compared with whole kidney content was determined in the rat. Approximately 3% of AQP2 in the kidney was excreted daily, and this fraction did not change when rats were dehydrated for 3 d. These data demonstrate the necessity of establishing well-designed protocols to use urinary AQP2 as a marker of AVP action.
Adult↗
[Efficacy of systemic chemotherapy in adenocarcinoma of the lung with pleuritis carcinomatosa].
The efficacy of systemic chemotherapy (CDDP + IFO + 5-FU or CDDP + IFO + CPT-11) was evaluated in 41 patients with malignant pleural effusion secondary to adenocarcinoma of the lung. The overall response rate for measurable disease was 56.1%. The response for pleural effusion was evaluated according to the criteria of the Japan Lung Cancer Society. The overall response for pleural effusion was 53.7% (34.1% CR and 19.5% PR). The median survival time was 361 days. These results suggested that systemic chemotherapy is an effective treatment for pleuritis carcinomatosa.
Adenocarcinoma↗
Expression of Fas antigen on hepatocytes in viral hepatitis patients.
To evaluate the relationship between viral hepatitis and apoptosis, expression of Fas antigen in liver tissue sections of patients with viral hepatitis was investigated by immunohistochemical study using antibody to Fas antigen. A total of 46 liver tissues were obtained from 12 patients with acute viral hepatitis (AH) and 34 patients with chronic hepatitis (CH). Fas antigen was more markedly expressed in hepatocytes of AH patients than of CH patients. The Fas-positive hepatocytes of AH patients was localized rather diffusely in the inter lobular area and they were associated with closely to the area of the inflammatory cell infiltration. In CH patients, Fas antigen was weakly expressed in hepatocytes and was more intense in chronic active hepatitis than in persistent hepatitis patients. These results indicate that apoptosis may occur more frequently in AH than CH and might contributed to death of hepatocytes mainly in viral AH and partly in viral CH.
Adult↗
[Flow cytometric analysis for the activation of peripheral immunoregulatory cells from patients with bronchial asthma].
By use of flow cytometry, we have investigated intracellular activated eosinophil cationic protein (ECP) in eosinophils and mitogen-induced cytokine production of T cells in peripheral blood from children with acute severe asthma. In addition, we measured ECP releasability (serum ECP/lysate ECP) as a maker of activated eosinophils. The monoclonal antibody EG2 (anti-activated ECP/EPX antibody) was used for measuring the amount of intracellular activated ECP. ECP releasability and mean fluorescence intensity (MFI) values of EG2-positive eosinophils increased at the time of asthmatic attack and reduced after treatment with improvement in peak expiratory flow. Furthermore, the frequency of T cells which produced IL-4, IL-5 and IFN-gamma stimulated with phorbol myristate acetate and ionomycin increased and reduced in parallel with MFI of EG2-positive cells. These observations suggest that flow cytometric analysis for intracellular ECP and mitogen-induced cytokine production reflects the activation of T cells in bronchial mucosa, and is useful for monitoring airway inflammation in bronchial asthma.
Adolescent↗
Sequence-specific binding sites in the Taka-amylase A G2 promoter for the CreA repressor mediating carbon catabolite repression.
The N-terminal part of the CreA protein encompassing two zinc fingers was expressed in Escherichia coli as a fusion protein with the maltose binding protein (MalE) of E. coli. Our results show that CreA binds to the promoter of the Taa-G2 gene encoding Taka-amylase A of Aspergillus oryzae. DNase I footprinting experiments showed that CreA bound to three sites with high affinity and to one site with low affinity within the first 401-bp region upstream of the transcription initiation site. All of the sites contained sequences related to the CreA consensus binding site (5'-SYGGRG-3'), and are suggested to participate in repression of the Taa-G2 gene in response to glucose.
Amino Acid Sequence↗
[Evaluation of chemotherapy for stage IV non-small cell lung cancer employing a regression tree type method for quality-adjusted survival analysis to determine prognostic factors].
To evaluate the effect of chemotherapy on QOL, the survival period was categorized by 3 intervals: one in the hospital for chemotherapy (TOX), on an outpatient basis (TWiST Time without Symptom and Toxicity), and in the hospital for conservative therapy (REL). Coefficients showing the QOL level were expressed as ut, uw and ur. If uw was 1 and ut and ur were plotted at less than 1, ut TOX+uwTWiST+urREL could be a quality-adjusted value relative to TWiST (Q-TWiST). One hundred five patients with stage IV non-small cell lung cancer were included. Sixty-five were given chemotherapy, and the other 40 were not. The observation period was 2 years. Q-TWiST values for age, sex, PS, histology and chemotherapy were calculated. Their quantification was performed employing a regression tree type method. Chemotherapy contributed to Q-TWiST when ut approached 1 i.e., no side effect was supposed). When ut was less than 0.5, PS and sex had an appreciable role.
Adult↗
[Phase I study of cisplatin, ifosfamide and CPT11 with granulocyte colony-stimulating factor support in advanced non-small cell lung cancer].
A phase I study was conducted to define the maximal tolerated dose of cisplatin, ifosfamide and CPT-11 with granulocyte colony stimulating factor support in advanced non-small cell lung cancer. CPT-11 was given on days 1, 8 and 15 in combination with a fixed dose of cisplatin (20 mg/m2 i.v. on days 1-4) and ifosfamide (1.5 g/m2 i.v. on days 1-4) every 4 weeks. G-CSF (50 micrograms/m2/day s.c.) was administered on days 5 to 18, except on the days of CPT-11 treatment. The starting dose of CPT-11 was 40 mg/m2, and the dose was escalated in increments of 10 mg/m2. Forty-five patients with stage III or IV, and 35 with no prior chemotherapy, were entered in the study. The dose limiting toxicity of the combination was thrombocytopenia. The maximal tolerated dose of CPT-11 was 70 mg/m2, and the recommended phase II dose is 60 mg/m2. There were 26 partial responses among 45 entered patients for an overall response rate of 57.8%. In 35 chemotherapy-naive patients, the objective response rate was 65.7%, the median response duration was 155 days, and 1 year survival was 62.3%.
Adult↗
[Three cases of resected primary mediastinal yolk sac tumor following six courses of bleomycin, etoposide and cisplatin (BEP) combination chemotherapy].
We experienced three cases of primary mediastinal yolk sac tumor which were resected after 6 courses of BEP chemotherapy with G-CSF support. All cases had high levels of AFP. CT scan revealed an anterior mediastinal tumor infiltrating the surrounding tissue in all cases, and multiple pulmonary nodules in one case. The serum AFP level decreased markedly, but did not return to normal after the chemotherapy was completed. The markedly decreased mediastinal tumor masses were removed with en-bloc resection of the lung and pericardium. Viable tumor cells were not present in the resected tumors. These three cases remain free of disease at present, 3 years, 9 months and 5 months after operation.
Adult↗
Diagnosis of pulmonary lymphangioleiomyomatosis by HMB45 in surgically treated spontaneous pneumothorax.
Pulmonary lymphangioleiomyomatosis (PLAM) is a rare disease with poor prognosis, characterized by an abnormal proliferation of smooth muscle. The patients are females and recurrent pneumothorax is a frequent complication. HMB45 is a monoclonal antibody with specific immunoreactivity for malignant melanoma. Recently, it was reported that some of the smooth muscle cells in PLAM had reactivity for HMB45. The aim of this study was to assess the sensitivity and specificity of HMB45 for the diagnosis of PLAM in cystic pulmonary diseases that cause recurrent pneumothorax. We compared immunoreactivity of the specimens obtained by open lung biopsy at surgical resection of bullae in 72 patients. The specimens of five females with PLAM, one female with suspected PLAM, 49 patients with primary spontaneous pneumothorax (19 females and 30 males), four with pulmonary eosinophilic granuloma (2 females and 2 males), seven with pulmonary emphysema (7 males), and six with idiopathic pulmonary fibrosis with apical bullous change (2 females and 4 males) were stained with HMB45 and anti-smooth muscle actin. All PLAM cases had HMB45 positive cells, which also stained with anti-smooth muscle actin. The biopsy specimens of a PLAM suspected case also stained with HMB45. None of the specimens from other diseases reacted with HMB45. HMB45 appears to provide a highly specific and highly sensitive diagnosis for PLAM in females. It may also be useful in patients with subtle smooth muscle proliferation. where the diagnosis of PLAM is difficult to confirm by conventional histological examination.
Actins↗
Analysis of antitumor properties of effector cells stimulated with a cell wall preparation (WPG) of Bifidobacterium infantis.
Intestinal Bifidobacterium species are thought to be beneficial in animal and human intestines. We studied the mechanisms of Bifidobacteria in antitumor activity using a cell wall preparation (WPG) of B. infantis (Cancer Res., 45, 1300, (1985)). WPG enhanced the in vitro antitumor activities of mouse peritoneal exudate cells elicited with proteose-peptone (P-PEC) and thioglycollate broth (TG-PEC), determined by cytostatic ([3H]thymidine uptake inhibition) and cytolytic ([3H]uridine release) assays. Tumor necrosis factor-alpha (TNF-alpha) and reactive nitrogen intermediates (RNI) play a role in such augmented cytotoxicity, because anti-TNF-alpha antibody almost completely blocked the increased cytolytic activity of P-PEC in the presence of WPG. Moreover, WPG induced RNI in the supernatant of TG-PEC in a dose-dependent manner. The mRNA expression of several cytokines (IL-1 beta, IL-6, IL-10, IFN-alpha and TNF-alpha) was induced in BALB/c mouse peritoneal cells 3 h after an intraperitoneal injection of WPG (3 h WPG-PEC). However, this expression disappeared from 24 h WPG-PEC, except for that of IFN-alpha. IFN-gamma was not induced. Kinetic studies of the tumor neutralizing activities of the WPG-PECs by means of the in vivo Winn assay revealed that the activity emerged at 1.5 h, became maximal at 3 h and disappeared at 24h. These results indicated that Bifidobacterial WPG is a Biological Response Modifier (BRM) with characteristics similar to those of other bacterial BRMs.
Animals↗
Hepatic role in the storage and utilization of fish oil fatty acids in humans: studies on liver surgery patients.
Fish oil fatty acids (FOFA) were analyzed in fresh liver tissue and in subcutaneous and omental adipose tissue obtained from 5 patients who underwent partial hepatectomy. FOFA were also determined in plasma from 5 patients and in 10 healthy subjects. There was a high content of FOFA in the liver phospholipid (PL) fraction (twice that in our previous autopsy study) suggesting that these surgery patients had a hepatic FOFA content of at least 25g. In plasma, FOFA was predominantly found in the PL of high density lipoprotein (HDL) and partly in the PL of other lipoproteins. Since these lipoproteins are produced by the liver, the present findings indicate the role of the liver not only in storage but also in the utilization of FOFA to form the biologically important surface PL component of circulating lipoproteins.
Adipose Tissue↗
Relationship of chlamydial infection to male infertility: sperm parameters / antisperm antibodies.
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Antibodies↗
[A case of primary gastric plasmacytoma showing remarkable changes in endoscopic findings during five month's follow-up].
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Aged↗