Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Fahreignung bei Epilepsie und assoziierten Störungen

Ohne Zusammenfassung     

Permeability of human brain tumor to 99mTc-gluco-heptonate and 99mTc-albumin. Implications for monoclonal antibody therapy

The variable penetration of chemotherapeutic drugs into brain and tumor is more dependent upon lipid solubility than upon size. In contrast, the molecular weight of virus- and tumor-specific monoclonal antibodies appears to limit uptake. The authors have studied eight patients with malignant brain tumors in order to compare tumor uptake of an iodinated contrast agent evaluated by computerized tomography scanning with uptake of the low and high molecular weight imaging agents technetium-99m (99mTc)-glucoheptonate and 99mTc-albumin, respectively, measured by radionuclide brain scanning. The agent 99mTc-labeled albumin was chosen for evaluation because its molecular weight (68,000) is similar to that of the most clinically promising monoclonal antibody fragment, the immunoglobulin (Ig) G Fab monomeric fragment. The radionuclide brain scans in the eight patients showed highly variable permeability of brain tumor to these markers, with uptake of the high molecular weight marker in the tumor being much less than that of the low molecular weight radionuclide. A clinical implication of these studies is that the success of monoclonal antibody therapy in the treatment of malignant brain tumors may require techniques to increase permeability of the blood-brain barrier and blood-tumor barrier to protein.     

Retrorenal colon: implications for percutaneous diskectomy

It has been recommended that computed tomography (CT) with the patient prone be performed in every patient undergoing percutaneous diskectomy; this would enable detection of a retrorenal location of the colon, which could interfere with the percutaneous procedure. In this evaluation of 346 prone CT studies, only one patient (0.29%) was found to have retrorenal or retropsoas bowel that would have been perforated at diskectomy. Because of this extremely low prevalence, the performance of prone CT in every patient undergoing percutaneous lumbar diskectomy is not believed to be necessary.     

Interferon modulation of 5-fluorouracil: use in neoadjuvant therapy inhibits experimental liver metastases in nude mice.

Experimental liver metastasis was studied in 4-5 week old athymic nude mice that were injected intrasplenically with a human colorectal tumor cell line (LoVo). A treatment schedule combining 5-fluorouracil and interferon (IFN) was previously shown to inhibit liver metastases. When this treatment was delayed until after splenectomy at 1, 2 and 3 weeks after tumor cell injections, liver metastases were not inhibited. However, when IFN was given during the interval between tumor cell injections and splenectomy (as neoadjuvant therapy), liver metastases were inhibited in the 2 and 3 week groups, but not in the 1 week group.