Expression of hepatocyte growth factor, keratinocyte growth factor and their receptors in experimental chronic pancreatitis.

BACKGROUND: Hepatocyte (HGF) and Keratinocyte growth factors (KGF) are key factors of tissue organization and regeneration. These peptide growth factors and their receptors c-met and keratinocyte growth factor receptor (KGFR) are overexpressed in pancreatic cancer. AIM: Expression and localization of ligands and receptors were investigated during the development of experimental chronic pancreatitis. METHODS: Chronic pancreatitis was induced in rats by intravenous injection of dibutyltin dichloride. One to 60 days after treatment, the expression of growth factors and receptors was analysed by competitive polymerase chain reaction, Western blot analysis and immunohistochemistry. RESULTS: HGF mRNA expression increased (10-fold) until days 7-14 followed by a decrease to control level. Expression of c-met mRNA constantly increased (15-fold). KGF and KGFR mRNA expression were increased after 14-28 days (5-fold) and then returned to control levels. mRNA expression patterns correlated with changes in the protein expression, whereas protein levels of KGF remained unchanged. Ligands were localized in mesenchymal cells and their receptors on epithelial cells. CONCLUSIONS: The significant increase of HGF and c-met expression suggests an essential role of this growth factor in the morphological changes during the development of chronic pancreatitis. Changes in the expression of KGF and KGFR are less pronounced.

[The importance of preoperative chemotherapy and radiotherapy in 373 children with Wilms' tumor]. / Bedeutung der präoperativen Chemotherapie und der Radiotherapie bei 373 Kindern mit Wilms-Tumor.

Between 1980 and 1988, in a prospective study of 373 children with Wilms' tumour throughout the Federal Republic of Germany, the results of various pre- and postoperative treatment schedules were analysed. There were 184 boys and 189 girls, mean age 3 11/12 (0-27) years. One third each was in group I, II or III-V, respectively. In 52% of cases the tumour volume, measured by ultrasound, was more than 400 ml. 218 of the children were called protocol patients, the remaining 155 served as observation patients, because the latter had histological variants or there had been marked treatment deviations. The stage-adapted treatment always included operation, in 30% of children after pre-operative chemo- or radiotherapy. Radiotherapy was given in selected patients in stage II and always to those in stages III, IV or V. Chemotherapy consisted of Actinomycin D and vincristine, adriamycin was added for stages III-V and cyclophosphamide or ifosfamide for histologically highly malignant variants. Of the 218 protocol patients 196 (90%) were alive without recurrence, after a mean observation time of more than 7 years. Radiotherapy was given to only 105 of the 218 protocol patients. The prognosis of the 155 observation patients differed according to the histology: those with clear-cell type had a better prognosis than previously reported. Among the total group of 373 patients 305 (81.8%) have remained without recurrence after more than 6 years.

[The COALL-85 cooperative study for risk patients with acute lymphatic leukemia: initial results]. / Kooperative Studie COALL-85 für Risikopatienten mit akuter lymphatischer Leukämie: Erste Ergebnisse.

A frequent change of non-crossresistant drug combinations might obviate the problem of multiple resistant cell lines in malignant diseases and thus increase cure rates. In a multicenter cooperative study for childhood acute lymphoblastic leukemia (ALL) 109 high-risk patients were randomized to receive 5-6 different drug combinations either in slow rotation (change of drugs every 4-6 weeks) or in rapid rotation (change of drugs every 2-3 weeks) for early intensive treatment. Both groups received the same total amount of drugs within the same period of time. 108/109 patients achieved complete remission. One child failed to enter remission and one was lost in remission due to viral infection. Patients in the rapid rotation arm required 2-3 weeks less time to complete the intensive therapy due to fewer episodes of prolonged myelosuppression. Toxic side effects and infectious complications were comparable in both groups. 9/109 patients relapsed, 6 in the bone marrow and 3 in the central nervous system. As yet none of the 31 patients with an initial white blood count of greater than or equal to 100/nl has relapsed. The probability of relapse-free survival is 88% in the rapid rotation arm and 86% in the slow rotation arm at 2 1/2 years. The results compare favourably with other protocols for high-risk patients but have still to be considered as preliminary because of the short median observation time of 18 months.