Biomedical subjects

J Wennerberg

Publications and source records attributed to J Wennerberg.

98 records · Page 6Linked to original sources

PubMedDate not supplied

Circadian variations in cell cycle phase distribution in a squamous cell carcinoma xenograft; effects of cisplatin and fluorouracil treatment.

Tumor tissue sampled at different points during a 24 hour period (08-08) from a xenografted squamous cell carcinoma of the head and neck was analyzed with flow cytometry. Statistically significant variations were found in the mean fraction of cells in the G1, S and G2 phases, the most pronounced variation occurring at 14 and 02 h. Histopathological examination showed no consistent circadian fluctuations in the fraction of cells in mitosis. Treatment with NaCl, cisplatin and fluorouracil was given at the time of most pronounced variation (i.e., 14 and 02 h). Toxicity was low. All animals in all groups survived treatment. All treated animals lost weight, but the initial weight loss was slightly greater and recovery delayed in the groups given cisplatin and fluorouracil at night. Tumor growth inhibition, as defined by the area under the growth curve, did not differ significantly between 14 and 02 h.

Animals↗

PubMedDate not supplied

The effect of continuous bleomycin infusion on the growth and cell kinetics of heterotransplanted squamous cell carcinoma of the head and neck.

The schedule-dependent effect of bleomycin (BLM) on human squamous cell carcinoma (SCC) was investigated using a xenografted SCC line originating from the head and neck region. A total dose of 200 mg BLM/kg was administered according to one of three different schedules: one single i.p. injection; i.p. injection every four hours for seven days; and continuous s.c. administration for seven days via osmotic mini-pump. Both single dose treatment and iterated injections caused significant retardation of tumour growth, and continuous infusion had a more pronounced effect, almost completely retarding increase in tumour volume; these differences in effect in between the treatment schedules were not, however, statistically significant. The effect of continuous BLM infusion on cell cycle phase distribution and histopathological picture was also recorded. During the first three days of infusion, there was an accumulation of cells in Go/G1-phase paralleled by a depletion of cells in S-phase. This was followed by a normalisation during the rest of the infusion period, concomitant with a transient increase of the cells in G2-phase. Histopathologically, there were no changes during the first four days. A swelling of the cytoplasm cold then be seen; and after seven days, scattered groups of necrotic cells were observed which later formed necrotic foci. It is noteworthy that the major perturbances in cell cycle phase distribution preceded both retardation of tumour volume growth and histopathological changes.

Animals↗

PubMedDate not supplied

Regulation and turnover of cellular retinol-binding protein in a xenografted human ovarian tumour.

A human ovarian mesodermal mixed heterologous carcinoma, with a high content of cellular retinol-binding protein (CRBP), was used to study the effects of retinoid and hormonal treatment on tumour CRBP content, tumour growth rate, differentiation and turnover of CRBP. Tumour growth in general was accompanied by an increase in the CRBP concentration of the xenografted tumours. This was related to the appearance of more mature epithelial cells, showing CRBP immunoreactivity. The increase in CRBP concentration was more pronounced in retinyl palmitate-treated tumours than in tumour tissue from etretinate- (an aromatic retinoid) treated mice and controls, suggesting that CRBP synthesis is under the influence of its ligand. Various hormonal treatments had no influence on the CRBP concentration in these tumour cells. The CRBP turnover was similar to that of the bulk of cellular proteins.

Animals↗

PubMedDate not supplied

Plasminogen activators in human xenografted oro-pharyngeal squamous cell carcinomas.

Specimens of squamous cell carcinomas of the head and neck established as xenografted tumour lines on nude mice were examined by the fibrin slide method for the presence of plasminogen activator(s). The fibrinolytic activity was partly quenched by antibodies against the vessel-related tissue plasminogen activator and partly by antibodies against urokinase. The results indicate that inactive pre-urokinase in tumour tissue is to some degree activated when the tumour tissue is transplanted to the nude mice. In organ culture of the tumours, urokinase of both low and high molecular form was secreted into the medium, but only traces of tissue plasminogen activator. Inhibition of urokinase activity might be an approach to hinder tumour growth.

Animals↗

PubMedDate not supplied

Histopathological characteristics predictive for growth of squamous cell carcinomas of the head and neck heterotransplanted to nude mice.

Human tumours heterotransplanted to nude mice vary both with respect to take rate and the rate of tumour line establishment, according to their histological type and between primary and recurrent tumours. The acceptance rate of squamous cell carcinomas of the head and neck is also thought to vary, according to their degree of differentiation and their site of origin. This provided the basis of the present analysis of different tumour characteristics predicting growth of squamous cell carcinomas of the head and neck. Eighty-five attempted heterotransplantations were analysed with respect to T-stage, site of origin, degree of differentiation, and a histopathological malignancy grading score based upon four tumour variables and four tumour-host variables. Of the 85 attempted transplantations, first passage was successful in 24 cases (28%), of which sixteen (19% of 85) resulted in established tumour lines. The frequency of established tumour lines was higher among T4 and poorly differentiated tumours (33% and 22%, respectively), than among less advanced or more differentiated tumours. Tumour size was a more crucial factor than degree of differentiation, and tumours of the oral cavity grew less readily than those from other sites. The take rate was strongly correlated to malignancy grading scores, increasing as they increased. The most predictive information was provided by tumour-host variables, of which vascular invasion and lack of lymphocytic response were the most important in this respect.

Animals↗

PubMedDate not supplied

Bleomycin induced changes in growth and cell kinetics of a heterotransplanted squamous cell carcinoma of the head and neck.

Bleomycin (BLM) is often used against squamous cell carcinomas in combination with other drugs in phase-specific schedules since it has been considered a synchronizing agent. However, the reported effects on the cell cycle are contradictory. In the present study a poorly differentiated squamous cell carcinoma of the head and neck, heterotransplanted to nude mice was used for evaluation of BLM induced suppression of growth, and, measured with flow cytometric technique, cell cycle traverse and cell cycle phase distribution. BLM was administered once daily for four days. The dose-response curve exhibited a plateau-phase beginning at a total dose of 200 mg BLM/kg. A single dose of 75 mg BLM/kg caused a transient accumulation of cells in G0 + G1 phase and was followed by a synchronized passage of cells through the cell cycle. However, the induced perturbations were small. Cell kinetic analysis of tumours treated with repeated doses of BLM did not result in increased cell cycle perturbations. Thus, the present study could not confirm any major cell synchronizing effect of BLM on poorly differentiated heterotransplanted human squamous cell carcinoma.

Animals↗

PubMedDate not supplied

Biochemical modulation of chemotherapy and radiotherapy in head and neck cancer.

In order to improve the treatment of advanced H&N cancer we must consider to adopt new strategies as: new/better cytostatic agents; new combinations of present cytostatic agents and; potentiation of radiotherapy and cytostatic agents by biochemical modulation, which we define as potentiation of therapy by non-chemotherapeutic agents. The list of agents that can potentiate chemotherapy or circumvene resistance is comprehensive. Most of the data are derived from in vitro studies. Much attention has been given to the fact that calcium channel blocker (CCB) agents can circumvene the multi-drug resistance (MDR) phenotype. Cisplatin, 5-fluorouracil, bleomycin and methotrexate, used in the treatment of head and neck cancer, are not part of the MDR phenotype. Still there are a few interesting reports indicating that CCB's could enhanced the antitumour actions of cisplatin, and that this interaction may be: (a) very specific; (b) unique to each species of CCB and (c) is independent of their binding affinity and classical function as inhibitors of the voltage sensitive calcium channels. Metoclopramide (MCA) is a structural analogue of procainamide used worldwide for preventing nausea and vomiting. It has structural resemblance to some of the known inhibitors of the DNA associated enzyme poly ADPRT such as benzamide. Benzamide is however rather toxic. MCA has been shown to enhance the effect of CDDP in vivo as well as in permeabilized cells in vitro, indicating that the DNA damaging effect of MCA is not dependent on cytoplasmatic enzymes or messenger systems. Radiobiologists have pointed out important biologic characteristics about tumour tissue such as hypoxia in relation to tumour radiosensitivity. Nicotinamide can effect tumour radiosensitivity in vivo. Comparing the response of mice in skin and tumour under different gas breathing regimens, a considerable therapeutic gain has been demonstrated for oxygen and carbon dioxide (95% O2 + 5% CO2) breathing mice. The effect of ionizing radiation (RT) on xenografted squamous cell carcinoma can also be enhanced by MCA. The optimal treatment interval is MCA given one hour before RT, which is in concordance with the hypothesis that MCA has to be present at the site of injury when RT is given in order to interact with repair mechanisms. We could not in conventional mice detect any MCA induced enhancement of either acute skin reaction or in LD50/30 after whole body irradiation, which indicates a potential therapeutic gain using MCA in a clinical setting. The above discussed interactions between biochemical modulators and chemo-/radio-therapeutic agents serve to illustrate the fruitful concept of biochemical potentiation of cytotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium Channel Blockers↗

PubMedDate not supplied

Predicting response to therapy of squamous cell carcinoma of the head and neck (review).

The design of treatment for patients with squamous cell carcinoma of the head and neck (SCCHN) is based on prognostic factors, today essentially performance status and TNM status. It becomes increasingly important to optimise treatment and find the appropriate level of treatment and resource consumption for each patient. This can be achieved by means of complementary "biological staging' using predictive factors. A predictive factor contains prognostic information but can also be used to choose between alternative treatments. Candidate variables for prediction of the outcome of chemotherapy are tumour ploidy status, the level of circulating C1q-complexes, the level of p53 expression, and resistance/sensitivity measured by in vitro assays. Several variables and assays capable of predicting response to radiotherapy have been proposed, e.g. the surviving fraction 2 Gy (SF2), potential tumour doubling time (Tpot), and the micronucleus assay. As none of these have yet proved to be of clinical value in a prospective randomised trial, continued studies are well worthwhile.

Carcinoma, Squamous Cell↗