Novel Anthraquinone-based Derivatives as Potent Inhibitors for Receptor Tyrosine Kinases

The influence of new derivatives of 9,10-anthraquinone with benzoylthiourea, thiazole, triazole and amino acid fragments on the activity of membrane-associated tyrosine kinases was investigated. Inhibitors of protein tyrosine kinase activity of the membrane fraction, as promising agents to search for new potential anticancer agents among the studied compounds, were discovered.     

The role of palliative radiotherapy in locally advanced non-small cell lung cancer

The aim of this study was to evaluate retrospectively the treatment results of non-small cell lung cancer (NSCLC) patients treated with palliative intent in Dokuz Eylul University Hospital, Radiation Oncology Department. One hundred and fifteen inoperable, non-metastatic and symptomatic NSCLC patients were treated with palliative radiotherapy (PRT) between July 1991 and May 2000. PRT was used in patients with low performance status, weight loss more than 10% within last 6 months, secondary malignancies, co-morbid diseases and socio-economic problems. Parallelly opposed isocentric antero-posterior fields including both the parenchymal and mediastinal masses were used. 10-55 Gy total doses were delivered in 1-23 fractions with a median of 30 Gy. Nineteen patients received systemic chemotherapy before PRT. Survival analysis was made from the treatment beginning date, and subjective palliation rates were assessed according to clinical improvements in symptomatology evaluated 1-6 weeks after PRT. The median follow-up time was 28 weeks (1-234 weeks). Totally, 245 disease-related symptoms were detected in 115 patients. Overall "improvement" in symptomatology was found to be 90% (221/245) with a "near-total response" rate of 46% (113/245). Hemoptysis was the best palliated symptom. Median survival time was 30 weeks. Karnofsky performance status (KPS) (p=0.015), weight loss (p=0.0015), histologic tumor type (p=0.0024) and tumor size (p=0.02) were found to effect overall survival rates significantly in uni-variant analysis. Multi-variant analysis revealed statistically significant effect with histological tumor type and weight loss status. Only 16% of patients (3/19) showed partial and 5% (1/19) complete response to systemic treatment. Median survival time was 46 weeks in this group. In conclusion, this retrospective study of patients with poor prognostic factors confirms that PRT is an effective treatment modality in symptomatic locally advanced NSCLC patients resulting in 90% symptomatic improvement rate and a median survival of 30 weeks.     

The postviral fatigue syndrome — an analysis of the findings in 50 cases

The clinical, pathological, electrophysiological, immunological and virological abnormalities in 50 patients with the postviral fatigue syndrome are recorded. These findings confirm the organic nature of the disease. A metabolic disorder, caused by persistent virus infection and associated with defective immunoregulation, is suggested as the pathogenetic mechanism.     

Stimulation of rat peritoneal mast cells enhances uptake of low density lipoproteins by rat peritoneal macrophages in vivo

The effect of mast cell stimulation on the uptake of low density lipoproteins (LDL) by macrophages was tested in vivo in the peritoneal cavity of the rat, a site known to contain both macrophages and mast cells. The concentration of LDL in the peritoneal cavity was raised by injecting [14C]sucrose-labeled LDL ([14C]sucrose-LDL). In the treated rats, in the absence of mast cell stimulation, the uptake of LDL by the peritoneal macrophages was low. But when the peritoneal mast cells were concomitantly stimulated by intraperitoneal administration of compound 48/80, an agent known to induce mast cell degranulation, the rate of uptake of labeled LDL by macrophages rose by 7-24-fold. The reason for this rise was that exocytosed mast cell granules bound LDL and carried it into macrophages when phagocytosed. Thus, cyclohexanedione treatment of LDL, or injection of avidin along with LDL, 2 measures known to inhibit binding of LDL to mast cell granules, totally prevented the mast cell-dependent uptake of LDL. Furthermore transmission electron microscopic studies with gold-labeled LDL disclosed phagocytosis of LDL-bearing granules by the peritoneal macrophages. This is the first demonstration of a natural proteoglycan being able to enhance the rate of LDL uptake by macrophages in vivo. These observations on the relation between stimulation of mast cells and uptake of LDL by macrophages in vivo may have relevance in other sites where mast cells and macrophages coexist, such as the arterial intima.     

Renal function and morphology in Sudanese patients with advanced hepatosplenic schistosomiasis and portal hypertension

The association between glomerular disease and hepatosplenic schistosomiasis is well documented in reports from South America. During the present hospital investigation in Sudan, 58 patients admitted for intercurrent complications of advanced hepatosplenic schistosomiasis were studied. The patients, median age 35 years, had no concurrent Schistosoma haematobium infection. Diagnostic criteria included an enlarged spleen (n = 58), at least 1 episode of hematemesis (n = 55) and/or melena (n = 36), endoscopical demonstration of gastroesophageal varices (29/29 studied), ultrasonographical imaging of hepatic periportal fibrosis (18/18 studied), and intraoperative liver biopsy with characteristic histological findings (11/16 biopsied). Serum creatinine, urea, electrolytes, cholesterol, total protein, and electrophoresis were within normal limits. Median urinary protein/creatinine ratio was 0.06 and thereby not significantly different from European reference values. Only 1 patient had proteinuria of 1.7 g/l. Minimal hematuria was found in 5 patients. Ten kidney biopsies were taken intraoperatively during a portal decompression procedure (Hassab operation). Light, immunofluorescence, and electron microscopy produced no evidence of glomerulonephritis. These findings indicate that S. mansoni induced nephrotic syndrome may be less frequent in Sudan than in South America. Renal involvement due to S. mansoni infection may therefore encompass geographical variances.