Biomedical subjects
Publications and source records attributed to J Bier.
The well-known cytotoxic mode of action of bleomycin up to now has been clarified exclusively by intracellular processes. Our findings however indicate that an immunologic effect induced by bleomycin can also lead to the destruction of tumor cells.
Using a mouse tumor model, an attempt was made to determine whether demonstrable differences could be established for the excretion and organ distribution of labeled bleomycin, whereby the tumor and local lymph node concentration were given special consideration. No significant differences could be established for the excretory behavior with different methods of application (i.t., i.v.). Organ distribution studies however showed that the blood and organ load after intravenous administration of 57Co bleomycin was higher and the tumor concentration significantly lower than after injection directly into the tumor. The lower organ load following injection directly into the tumor was investigated with a toxicity test.
The cell-specific absorption mechanism for 57Co bleomycin and the transport behavior was examined under various parameters in an in vitro tumor cell system. The 57Co bleomycin absorption of vital Ehrlich-ascites tumor cells showed a positive time-dose-temperature correlation plus a definite indication of an active intracellular transport mechanism. Because erythrocytes, as compared to Ehrlich-ascites tumor cells, absorb almost no 57Co bleomycin, it could be concluded indirectly that active transport of 57Co bleomycin into the intracellular space is controlled by endocytosis. The additional 57Co bleomycin absorption in membrane structures was also demonstrated in examinations of an Ehrlich-ascites tumor cell membrane preparation.
Observations of the development of nonspecific immunity parameters in patients with squamous cell carcinoma of the buccal cavity showed, on the one hand, that there is a significant difference between normal control subjects and tumor patients in all stages before and after therapy. On the other, however, it was established that continuous controls are not suitable for controlling the clinical course or determining the prognostic significance. On the basis of these findings, we have suspended our observations of the development of these nonspecific immunity parameters.
A qualitative histologic examination of squamous cell carcinoma of the buccal cavity was made before and after the injection of BCG cell walls directly into the tumor. The density of the inflammatory infiltrate in and at the tumor site differed significantly. The distribution pattern of the cells involved in the infiltrate showed an increased number of lymphocytes and histiocytes. Lymphocytes, the largest cell group represented, were more frequently demonstrated in the tumor than outside it. The injection of BCG cell walls directly into the tumor primarily causes a shift in the total number of cells and only secondarily an alteration in the distribution pattern of the cells involved in the infiltrate.
Three groups of tumor systems in animals must be differentiated: 1) xenogeneic, 2) allogeneic, 3) syngeneic systems. While the tumor is not genetically identical with the tumor host in xenogeneic and allogeneic systems, syngeneic models are distinguished by a homogeneous genetic background of tumor and host organism. Xenogeneic, allogeneic, and syngeneic inbred animal models, on the one hand, and spontaneously tumor development in outbred animals on the other, were introduced with which oncologic questions can be handled.
Oral tumors with associated cervical lymph node metastases developed after injection of tumor cells into buccal pads of inbred guinea pigs. Intralesional injection of living BCG or BCG cell walls (CW) caused regression of established tumors, prevented the development of cervical lymph node metastases and led to the development of host resistance to the growth of subsequent tumor transplant.
In tumor-free and tumor-bearing mice the body clearance and organ distribution of 57Co-BLM was measured in different time intervals after iv, sc, and it administration of the drug. No significant differences could be demonstrated in body clearances following different doses and routes of application of labeled BLM in tumor-free and tumor-bearing mice. The organ distribution studies showed higher concentrations following iv compared to sc or it application of 57Co-BLM; however, the activity in the ipsilateral injection sites were significantly increased after sc and it injection. In tumor-bearing mice the activity in the draining lymph nodes of the injection site were as high as that seen in draining lymph nodes following iv injection. However, on the contralateral side, the lymph node concentration was significantly reduced after it injection. These results indicate on the basis of organ distribution of 57Co-BLM a rational basis for it treatment of malignant tumors.
The cytostatic drugs Chlorambucil and Bleomycin were labeled with 131I and with 57Co, respectively: Ruthenocenealdehyde-(N-methyl-N-beta-chlorethyl)-hydrazone and Ruthenocene-3-phenyl-prop.1-en-3-one were labeled with the gamma emitter 103Ru. In tumor-bearing mice the elimination and organ distribution of these radioactive substances were tested after intravenous (i.v.) and intratumoral (i.t.) injection of the drugs. The organ load showed lower values after i.t. than after i.v. application, while the radioactivity concentrations in the tumor were considerably increased after i.t. injection. The integrals of the concentration-time curves showed 10--80 times higher concentrations in the tumor after i.t. compared to i.v. injection of the drugs.
In tumour-free and tumour-bearing mice the body clearance and organ distribution of 57Co-BLM was measured at different time intervals after iv., sc., and it. administration of the drug. No significant difference could be demonstrated in body clearance following different doses and routes of application of labelled BLM in tumour-free and tumour-bearing mice. The organ distribution studies showed higher concentrations following iv. compared to sc. or it. of 57Co-BLM; however, the activity in the ipsilateral injection sites was significantly increased after sc. and it. injection. In tumour-bearing mice the activity in the lymph nodes draining injection site was as high as that seen in the draining lymph nodes following iv. injection. However, on the contralateral side, the lymph node concentration was significantly reduced after it. injection. These results indicate on the basis or organ distribution of 57Co-BLM a rational basis for it. treatment of malignant tumours.
An introduction to the role of lymphocytes in immunological reactions is given. Two fundamental categories of immunological response are described which are mediated by two distinct subpopulations of lymphocytes: B-lymphocytes are responsible for humoral immune reactions and T-lymphocytes are involved in cell-mediated immunity. Information is given on the role of the immune system in generation of anti-tumour activities and of mechanisms leading to an acceleration of tumour growth. Several pathways of cytotoxic and blocking reactions against target cells are mentioned. Furthermore, methods are described for monitoring the non-specific immune reactivity of the host. These nonspecific cellular immune responses in 30 patients with squamous cell carcinoma of the head and neck were compared with those in 30 healthy controls. Assays were performed in vitro to evaluate the blastogenic response of lymphocytes to the mitogens PHA (phytohaemagglutinin) and PWM (pokeweed mitogen) and to quantify T-rosetteforming lymphocytes in the peripheral blood. The in vivo assays used were the delayed cutaneous hypersensitivity reaction to the primary stimulus of DNCB (dinitro-chloro-benzene) and the recall reaction to PPD (purified protein derivate). The carcinoma patients demonstrated significant impairment of lymphocyte blastogenesis reactions to PHA but not to PWM. The percentage and absolute counts of T-rosettes was significantly reduced in cancer patients compared with normal controls. Skin test reactivity to de-novo sensitation with DNCB was significantly abnormal in patients with head and neck cancer. However, delayed type hypersensitivity evaluated with PPD (recall antigen) was not significantly reduced. After subdividing the cancer patients according to their clinical stage of disease and subsequent analysis, they showed no correlation between clinical stage and immune reactivity. These data indicate that PHA induced lymphocyte blastogenesis, enumeration of T-rosette levels and evaluation of delayed hypersensitivity reaction to DNCB are potentially useful for the study of squamous cell carcinoma of head and neck to monitor effects of tumour treatment and perhaps to evaluate a correlation between immunocompetence and prognosis.
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Considerable importance for the elimination of malignant cells has been attributed to the cellular immune system. Cytostatic drugs however are known to be immunosuppressive. The transformation response of peripheral lymphocytes to bleomycin and methotrexate was determined before and after treatment in patients with squamous cell carcinoma of the head and neck region. The transformation response was interpreted as an indication of the potential for the nonspecific cellular immune reaction. The cellular reaction was significantly suppressed during therapy; this suppression was then followed by an excessive reaction in some patients. The immunosuppressive effect of bleomycin was substantiated in in vitro studies of isolated lymphocytes from healthy doners. Low concentrations of methotrexate however produce excessive reactions while higher concentrations tend to have an immunosuppressive effect.
The acute intermittent porphyria is mainly a porphyrimmetabolism disorder inheritable through autosomes. This disorder is characterized by intermittent abdominal pains, neurological symptoms of central as well as peripheral genesis, and by psychotic syndromes. An acute attack is fatal in many cases. Among others, it can be induced by numerous factors, such as local anesthetics, analgetics and sedatives. Thus, it is important that the dentist is aware of this rare disease should he find himself in a position where treatment of this type of patient is imminent.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.