Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity.

Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors.     

Effects of Helicobacter pylori on histamine and carbachol stimulated acid secretion by human parietal cells.

Helicobacter pylori (H pylori) infection is associated with hypo, normal, and hypersecretory disorders of the gastric mucosa. Pathophysiological pathways by which H pylori interacts with acid secretion are still unclear. The effects of H pylori on (14C) aminopyrine uptake by human parietal cells were examined as an indirect assay for acid secretion. Isolated oxyntic glands were stimulated with submaximal concentrations of histamine or carbachol and incubated with sonicates of different H pylori strains. Omeprazole and sonicates of Campylobacter jejuni served as positive and negative controls, respectively. Two of four H pylori strains reduced hydrochloric acid sequestration within the parietal cells significantly and in a dose dependent manner in up to 80%. Interaction with acid secretion may therefore constitute a factor contributing to a distinct pathogenicity of H pylori strains.     

Veränderungen von α-Ketoglutarsäure,Brenztraubensäure und Diphosphopyridinnucleotid bei chronischen Leberkranken

Zusammenfassung Bei 41 Kranken mit Lebercirrhose wurden die -Ketoglutarsäure, die Brenztraubensäure und das Diphosphopyridinnucleotid enzymatisch bestimmt. — Als Normalwerte wurden gefunden für -KGS=0,14 mg-%±0,05, für BTS=0,77 mg-%±0,19 und für DPN=1,57 mg-%±0,14.Die Leberkranken wurden nach ihrer klinischen Symptomatologie in Schweregrade eingeteilt und eine Zuordnung von klinischem Schweregrad und biochemischen Werten vorgenommen.Dabei zeigt sich, daß die Werte für -KGS gut der klinischen Symptomatologie entsprechen. Diese Werte betrugen für Grad 0=0,21 mg-%±0,08, für Grad 1=0,37 mg-%±0,09, für Grad 2=0,48 mg-%±0,13 und für Grad 3=0,61 mg-%±0,27.Die Werte für BTS zeigten keine so gute Übereinstimmung mit der klinischen Symptomatologie.Die Werte für DPN lagen für alle klinischen Grade mit wenigen Ausnahmen im Normalbereich.Auszugsweise vorgetragen auf der Tagung der Deutschen Gesellschaft für Physiologische Chemie, Hamburg, 28. 9. 56²⁷ und (G. A. M.) auf dem Jahrestreffen der American Association for the Study of the Liver, Chicago, 8. 11. 56³².In dieser Arbeit wurden folgende Abkürzungen benutzt: -Ketoglutarsäure (-KGS); Brenztraubensäure (BTS); Diphosphopyridinnucleotid (DPN); Glutaminsäuredehydrogenase (GluDH); Milchsäuredehydrogenase (MDH); Alkoholdehydrogenase (ADH).     

5-Fluorouracil plus leucovorin is an effective adjuvant chemotherapy in curatively resected stage III colon cancer: long-term follow-up results of the adjCCA-01 trial.

BACKGROUND: Adjuvant postoperative treatment with 5-fluorouracil (5-FU) and leucovorin in curatively resected stage III colon cancer significantly reduces the risk of cancer recurrences and improves survival. The impact of 5-FU plus leucovorin on survival and tumor recurrence was analyzed in a long-term follow-up study in comparison with the effects of 5-FU plus levamisole in the prospective multicenter trial adjCCA-01. PATIENTS AND METHODS: Patients with a curatively resected stage III (International Union Against Cancer) colon cancer were stratified according to tumor, node and grading category and randomly assigned to receive one of the two adjuvant treatment schemes: 5-FU 400 mg/m2 body surface area intravenously in the first chemotherapy course, then 450 mg/m2 x 5 days, plus leucovorin 100 mg/m2, 12 cycles (arm A), or 5-FU plus levamisole (Moertel scheme; arm B). RESULTS: Six hundred and eighty (96.9%) of 702 patients enrolled into this study were eligible. To date, 261 patients have died, 117 on arm A and 144 on arm B (P = 0.007). After a median follow-up time of 82 months, the 5-FU plus leucovorin combination significantly improved disease-free survival [79.8 months in arm A versus 69.3 months in arm B (P = 0.012)] and significantly increased median overall survival (88.9 months in arm A versus 78.6 months in arm B; P = 0.003). Adjuvant treatment with 5-FU plus levamisole as well as 5-FU plus leucovorin was generally well tolerated; only a minority of patients experienced grade 3 and 4 toxicities. CONCLUSIONS: After curative resection of a stage III colon cancer, adjuvant treatment with 5-FU plus leucovorin is generally well tolerated. This long-term follow-up study demonstrates that adjuvant treatment with 5-FU plus leucovorin given for 12 cycles is significantly more effective than 5-FU plus levamisole (Moertel scheme) in reducing tumor relapse and improving survival.     

Immunostaining of p53 protein in ovarian carcinoma: correlation with histopathological data and clinical outcome

Objective: The objective of this study was to analyze the incidence of immunohistochemically detectable p53 protein accumulation in epithelial ovarian carcinomas and to correlate these data with the clinical outcome so as to clarify further the role of p53 mutations in prognosis with these patients.Methods: Tumor tissues from 179 patients with epithelial ovarian carcinoma were used for immuno-histochemical analysis with monoclonal antibody DO1 and BP 53-12-1 on formalin-fixed, paraffin-embedded tissue.Results: A total of 78 cases (44%) showed positive nuclear p53 staining. The p53-positive cases were found in all histological types of epithelial ovarian tumors. p53 staining was found in tumors of all stages with a higher percentage of positive cases in stage IV ovarian carcinomas (not significant). Poorly differentiated carcinomas showed a significantly higher percentage of p53 protein expression than did highly differentiated tumors (P=0.0002). Clinical follow-up of up to 14 years (median 25 months) showed a slightly but not significantly shortened disease-free and overall survival time for patients with p53-positive epithelial ovarian carcinomas.Conclusions: We conclude from our data that p53 expression in ovarian carcinoma is associated with poor differentiation but not with the disease being in an advanced stage. There was a tendency for shortened disease-free and overall survival for patients with p53-positive tumors.     

Pancreatic pseudocysts. Actual diagnostic and therapeutic approaches. Surgical treatment (author's transl)

The development of modern diagnostic technics (ultrasound and CT) has facilitated diagnosis of pancreatic pseudocysts. The subsequent demonstration of spontaneous resolution (in 25-50%) has however produced new controversies on the optimal therapeutic strategy. In spite of the progress in the area of diagnosis important questions regarding the evaluation of the percutaneous fine needle puncture, the indication for surgical treatment in relationship to the size of the pseudocysts and the optimal timing of surgical measures are still be open to discussion. To clarify these problems a prospective controlled study should be begun. According to most reports operative intervention is indicated if after a period of 6 weeks no spontaneous resolution has been observed. The optimal surgical treatment is thought to be internal drainage, for instance a cystojejunostomy.     

Does dopamine predispose to gastroesophageal reflux?

In the American opossum dopamine causes a dose-dependant fall in the lower esophageal sphincter (LES) pressure. The effect in man is unknown. Therefore, the effect of two dosages of dopamine (1 mcg.kg-1 body weight.minute-1 and 5 mcg.kg-1 body weight.minute-1) was studied in ten healthy volunteers by pullthrough manometry. The results show that neither dopamine nor normal saline solution as a control changed LES pressure which is an important determinant of gastroesophageal sphincter competence. Thus, dopamine in clinically used doses does not appear to predispose to gastroesophageal reflux.