Expression of a peroxisome proliferator-activated receptor gamma 1 splice variant that was identified in human lung cancers suppresses cell death induced by cisplatin and oxidative stress.

PURPOSE: The activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) has been implicated in the inhibition of tumor progression in lung cancers through the induction of differentiation and apoptosis. Recently, we identified a novel splice variant of human PPAR gamma1 (hPPAR gamma1) that exhibits dominant-negative activity in human tumor-derived cell lines. This study aimed to examine the expression and pathophysiologic roles of a truncated splice variant of hPPAR gamma1 (hPPAR gamma1(tr)) in primary human lung cancer tissues. EXPERIMENTAL DESIGN: The expression and localization of hPPAR gamma1(tr) was surveyed in human primary lung cancer tissues using immunohistochemistry and Western blot analysis. Using transfectants stably expressing wild-type hPPAR gamma1 (hPPAR gamma1(wt)) and hPPAR gamma1(tr), we also analyzed the pathophysiologic roles of hPPAR gamma1(tr). RESULTS: We showed that PPAR gamma is expressed predominantly in the nucleus of nontumorous tissues, whereas it is present in both the nucleus and the cytoplasm of tumorous tissues in squamous cell carcinoma (SCC) of the lung. Western blot analysis confirmed the presence of PPAR gamma1(tr) in primary lung SCC tissue but not in nontumorous tissue. Expression of PPAR gamma1(tr) in Chinese hamster ovary cells attenuated their susceptibility to cell death induced by oxidative stress or cisplatin, whereas their susceptibility was completely recovered by down-regulation of PPAR gamma1(tr) with small interfering RNA. CONCLUSIONS: hPPAR gamma1(tr) is expressed strongly in tumorous tissues of primary human lung SCC and its overexpression renders transfected cells more resistant to chemotherapeutic drug- and chemical-induced cell death. These data suggest that the decreased drug sensitivity of PPAR gamma1(tr)-expressing cells may be associated with increased tumor aggressiveness and poor clinical prognosis of patients.     

Caroli's Disease: Scintigraphic and Radiographic Findings

Caroli's disease is a rare congenital anomaly of the liver. Since new diagnostic techniques for the evaluation of hepatic disease have been introduced, the number of reported cases of Caroli's disease has been gradually increasing. This report describes the case of a 13 year old girl with nausea, vomiting, fever and hepatomegaly. The diagnosis of Caroli's disease was established by ultrasonography and CT scan. The complications and management are discussed. The important points in management are to relieve symptoms and to conduct regular examinations by ultrasonography for the early detection of hepatobiliary carcinoma.     

Production of cytokines by thyroid carcinoma cell lines

Five cell lines were established from four undifferentiated carcinomas and one squamous cell carcinoma of the thyroid. The levels of several kinds of cytokines were measured in the conditioned media of these cell lines by enzyme-linked immunosorbent assay (ELISA). Interleukin-6 (IL-6) was produced by four of the five cell lines, interleukin-1α (IL-lα) by three cell lines, and granulocyte-colony stimulating factor (G-CSF) by two cell lines. The mRNA of IL-lα or IL-6 was detected by Northern blot analysis in all the cell lines which secreted these cytokines into culture medium. These results suggest that undifferentiated carcinoma and squamous cell carcinoma of the thyroid frequently produce cytokines. Further studies are needed to clarify the possible clinical effects of these cytokines in patients with thyroid carcinoma. © Wiley-Liss, Inc.     

Detection of c-erbB-2 gene amplification in nipple discharge by means of polymerase chain reaction

Summary In a patient with non-palpable breast carcinoma, c-erbB-2 gene amplification was detected by means of polymerase chain reaction (PCR) in the small number of breast carcinoma cells present in nipple discharge. Amplification of the c-erbB-2 gene is more frequent in carcinoma in situ than in invasive types. Detection by a PCR-based method may help diagnose non-palpable breast carcinoma with nipple discharge. Since this gene amplification is related to high proliferation, it might provide useful preoperative information regarding intraductal carcinoma of comedo type and predict responses to chemotherapy.     

Effects of olprinone hydrochloride on intraocular pressure and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass

BACKGROUND: We evaluated the effect of olprinone hydrochloride on intraocular pressure (IOP) and ocular blood flow in patients after cardiac surgery under cardiopulmonary bypass (CPB). METHODS: Nine patients after cardiac surgery under CPB were investigated. We measured IOP of the left eye using tonometer (Tonopen XL, BIO RAD, Osaka), and mean blood flow velocity in the left ophthalmic artery (Vm) and calculated the pulsatility index in the left ophthalmic artery (PI) using 2 MHz Doppler ultrasound system (Multidop P, DWL, Germany). After baseline measurement, the olprinone hydrochloride loading dosage was increased from 0.15 to 0.3 microgram.kg-1.min-1 every 60 minutes. The intraocular pressure and ocular blood flow were measured at each point. RESULTS: IOP and PI decreased significantly, and Vm increased significantly at the infusion rate of 0.3 microgram.kg-1.min-1 from baseline. There was a significant linear correlations between IOP and Vm. CONCLUSION: We demonstrated that olprinone hydrochloride led to a decrease in IOP and an increase in ocular blood flow in patients after cardiac surgery under CPB.     

Oxidative metabolite of dopamine, 3,4-dihydroxyphenylacetaldehyde, induces dopamine release from PC12 cells by a Ca2+-independent mechanism

3,4-dihydroxyphenylacetaldehyde (DOPALD), an oxidative metabolite of dopamine (DA), induced dose-dependent DA release from pheochromocytoma (PC12) cells without affecting leakage of lactate dehydrogenase from the cells. DOPALD-induced DA release was independent of extracellular Ca2+ concentration and was not blocked by nifedipine, an L-type Ca2+ channel antagonist. These results indicated a novel intrinsic role of DOPALD in dopaminergic nerve terminals that may take part in the activation of dopamine neurons.     

Effect of Mass Screening for Breast Cancer from the Aspect of Psychosocial Assessment of the Quality of Life

To assess the quality of life (QOL) in patients with breast cancer receiving mass screening, a collaborative matched case-control study was conducted in nine hospitals throughout Japan. A total of 122 patients detected by mass screening (study group) and 226 patients found in out-patient clinics (control group) were assessed psychosocially on the basis of questionnaire information. The incidence of patients with early stage breast cancer was significantly higher in the study group than in the control group ( P <0.05). Chest wall pain was observed in 35.2% of the study group and in 46.5% of the control group ( P <0.05). Although control patients were more optimistic than study group patients, disturbed daily life and anxiety about recurrence were a little more frequent in the former group than in the latter. In particular, shoulder stiffness was frequently seen in the control group ( P <0.05). Early detection and information do not create anxiety in mass screening patients ( P <0.01). We should recommend mass screening to patients to detect early stage breast cancer and provide better QOL.     

Resection margin in patients with gastric cancer associated with esophageal invasion: Clinicopathological study

We investigated the correlations between resection margin involvement by carcinoma and a number of clinicopathological features in patients with gastric cancer and esophageal invasion. From January 1968 to December 1988, 1,040 patients with carcinoma of the stomach underwent gastric resection. Thirty-nine patients had tumor infiltration of the esophagus on histological examination of the resected specimens. The patients were divided into two groups on microscopic examination: those in whom the resection margin was less than 5 mm wide, and those in whom it exceeded 5 mm microscopically. There were 6 and 33 patients in the narrow and wide margin groups, respectively. There were statistically significant differences in tumor size, depth of cancer invasion, and macroscopic appearance between the two groups. The risk of resection margin involvement was high in tumors with the following features: large Borrmann type 4 tumor (macroscopic appearance and size) and infiltrative carcinoma (depth of invasion). © 1993 Wiley-Liss, Inc.     

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue

Active specific immunotherapy using the immune reaction of a low-dose irradiated tumor tissue was studied on the transplanted MM46 tumor of female C3H/He mice after radiotherapy. MM46 tumor cells were inoculated into the right hind paws of mice. On the 5th day, irradiation with the dose of 3000 rad was performed. On the 11 th day, tumor cells and mononuclear cells, which were separated from the low-dose irradiated tumor tissue (2000 rad on the fifth day), were injected into the left hind paws of the tumor-bearing mice. Effectiveness of this active specific immunotherapy against tumor was evaluated by the regression of tumor and survival rate of mice. Tumor was markedly regressed and survival rate was significantly increased by the active specific immunotherapy.