K. S. Zänker

Beta-adrenoceptors are highly expressed on SW 480 colon carcinoma cells as was assessed by flow cytometry. We investigated the influence of norepinephrine on the migration of these cells using time-lapse videomicroscopy. Norepinephrine-treatment increased the locomotor activity within the population from 25% spontaneously locomoting cells to 65% locomoting cells. The beta1/2-blocker propranolol but not the beta1-blocker atenolol inhibited this increase. The intracellular signaling solely of norepinephrine-induced locomotion involved protein tyrosine kinase activity, whereas both spontaneous and norepinephrine-induced migration were reduced by inhibiting phospholipase Cgamma and protein kinase Calpha activity. In summary, norepinephrine-induced locomotion of SW 480 cells is beta2-adrenoceptor mediated and distinct from spontaneous locomotion concerning the PTK involvement.

Mistletoe is often used as complementary therapy in oncology. The anti-tumor effects of mistletoe (Iscador) are well documented in-vitro in respect to inhibition of cell proliferation, induction of apoptosis, segmental activation of immune competent cells and trapping of chemotherapeutic drugs within cancer cells by modulating the inhibitory potential of P-glycoprotein (P-gp)-mediated transport of cell toxifying substances (cytotoxic drugs). However, the clinical activity of mistletoe treatment remains still controversial. Implementation of mistletoe therapy as supportive care into anti-cancer programs should be based on the best evidence and must continually be evaluated to ensure safety, efficacy, collection of new data, and cost-effectiveness. Useful domains that can be evaluated include symptom control, adherence to conventional treatment protocols, quality of life, individual outcome and potential advantages of a whole-system health approach. Here we report the results of a multicenter, controlled, retrospective and observational pharmaco-epidemiological study in patients suffering from a pancreatic carcinoma. After surgery the patients were treated by adjuvant chemotherapy with gemcitabine supported by Iscador, or with gemcitabine alone, or any other best of care, but not including Iscador. Using a novel methodological pharmaco-epidemiological design and statistical approach it could be shown that Iscador offers benefits--symptom control, overall survival--as supportive care within gemcitabine protocols of patients with surgically resected pancreatic carcinoma.

Whole body hyperthermia was produced in 14 patients with conventionally incurable malignant disease. The technique consisted of arteriovenous shunting involving extracorporeal circulation with heat exchange during general anaesthesia. A temperature of 41.8 degrees C was maintained for periods of 6 hours. After achieving hyperthermic temperatures treatment was enlarged by administration of 5-fluorouracil (1000 mg) in patients with colorectal carcinoma and by dacarazine (200 mg/m2) in patients with malignant melanoma. In 5 out 6 patients with stage IV colorectal carcinoma stabilisation of the disease was seen for an average of 10 months. In contrast, progression of the disease was seen in patients with malignant melanoma and mean survival was only 5 months. These preliminary results in a small number of patients indicate that 1. induction and maintenance of whole body hyperthermia is clinically possible, 2. technical requirements are considerable, however feasible, 3. different tumours react differently to treatment.

In a non-randomized pilot study, 10 patients with histological proof of metastatic colorectal adenocarcinoma were treated by hyperthermia/chemotherapy protocol (41,8 degrees C and 1000 mg 5-FU). Plasma levels of 5-FU were determined after single dose at normothermia and hyperthermia. Plasma concentration time course was consistent with a two-compartment pharmacokinetic open model, with first order kinetic and was significantly altered by hyperthermic treatment. Cytotoxicity of 5-FU was substantially enhanced at hyperthermia (41.8 degrees C) as judged from the clonogenic surviving fractions from established human colon cancer cell lines. Our in vitro and in vivo results suggest that whole body hyperthermia combined with 5-FU is an active combination to develop further in the treatment of colorectal carcinomas.