Biomedical subjects
Publications and source records attributed to H Bier.
A brief description of the anatomical relationship between the orbit and the paranasal sinus system is given. Sinus infections, celes, and tumors which can lead to orbital complications are described.
The success of antineoplastic chemotherapy in head and neck carcinoma is limited by the insufficient primary chemosensitivity of the tumor and/or the decrease of drug efficacy in the course of treatment. As regards cisplatin (CDDP) this phenomenon of chemoresistance may be closely associated with glutathione (GSH) metabolism since GSH is responsible for the detoxication of active CDDP hydrolysates. In the human squamous carcinoma cell line HLac 79, selective inhibition of GSH synthesis by buthionine sulfoximine (BSO) led to enhanced CDDP chemosensitivity both in vitro and in vivo. Using the colony-forming assay GSH depletion of HLac 79 tumor cells of more than 90% (Table 1) resulted in a dose modifying factor of 2 (Table 2). Combined treatment of HLac 79 tumor-bearing nude mice with BSO and CDDP brought about significant increase in mean survival time (p less than 0.001) as compared to the CDDP-treated group. The possible role of BSO as chemosensitizer is discussed.
In an 8 week trial period six black and white dairy cows were injected with Optiflex, a slow release formulation of recombinantly derived bovine somatotropin (BST). Three cows each were injected at two-weeks (BST-14) or four weeks (BST-28) intervals. The dosage was 640 mg BST per injection. Average milk yield increased by 18.3% and 13.8% in groups BST-14 and BST-28 respectively. Blood plasma levels of bSTH and IGF-I increased till day 10 post-injection; thereafter they declined, except IGF-I levels in group BST-14 which persisted continuously elevated with minor variations. No bSTH above detection level could be assayed in the milk of treated animals. The IGF-I level in milk was slightly elevated after BST-application but stayed within the normal range.
A radioreceptor assay was used to determine the number and affinity of epidermal growth factor (EGF) receptors in a human squamous carcinoma cell line of the larynx (HLac 79) after exposure to cisplatin (DDP). Cells exposed to high concentrations of cisplatin showed about 30% fewer receptors compared to untreated and low-dose-treated cells. This reduction in the number of receptors might be responsible for the decreased growth when stimulated by EGF. Cisplatin appears to lower the concentration of EGF receptors on carcinoma cells, which might result in additional antiproliferative activity especially in carcinomas with high EGF receptor expression.
High intrinsic chemoresistance contributes to the dismal outcome of patients with disseminated renal cell carcinoma (RCC). In experimental cell lines, two defined defence mechanisms, P-170 glycoprotein and glutathione metabolism, have been established in multidrug resistance, a cross-resistance to cytotoxic compounds without functional or structural similarities. In 21 primary human RCCs, P-170 expression was examined, glutathione content and activities of related enzymes determined and the results were correlated to the degree of in vitro chemoresistance. P-170 was found in 10 of 17 resistant tumors but in none of the sensitive cases. The glutathione content was significantly higher and the related enzyme distinctively enhanced in resistant RCCs. Both mechanisms occurred independently and may well explain the multidrug resistance of RCC. Therefore, reversal of one or both systems may have a clinical impact on the chemotherapy of RCCs.
Representative tumor samples and mucosal samples were taken from three different groups of patients and were stained immunohistochemically for their expressions of epidermal growth factor receptors (EGFR). Patients in group 1 had oral squamous carcinoma, with specimens taken from the tumor as well as from the mucosa without tumor invasion. Patients in group 2 had no evidence of tumor but had heavy drinking and smoking habits. Tumor-free patients who do not drink or smoke served as the control group. The findings in the present study showed that the tumor and mucosal samples from groups 1 and 2 had increased EGFR expression while the control group showed significantly less EGFR. These results suggest that EGFR may play a role in the development of premalignant tissue changes, which are probably influenced by chronic toxic irritation.
Assessment of the quality of life is an additional, perhaps crucial criterion for deciding on the choice of a palliative therapy. Therefore it is necessary to know what "quality of life" means to the individual patient. We developed a questionnaire in cooperation with patients suffering from cancer of head and neck. With this questionnaire it is possible to judge how the patient rates his own quality of life. The questionnaire helps the physician to develop a palliative therapy schedule taking the psyosocial background into consideration. It improves the practicability of prospective studies concerning palliative therapy schedules.
Strain 2 guinea pigs bearing the transplanted intradermally growing line 10 tumor underwent surgical tumor excision at a time when the tumor had already metastasized to the first draining lymph node. Postoperative active-specific immunotherapy (ASI) consisted of two vaccinations with either Newcastle disease virus (NDV) modified or BCG-admixed line 10 tumor cells. 32% of the animals were cured of residual lymphatic micrometastasis by ASI with NDV-modified tumor cells while ASI with BCG was successful in 45%. No synergistic effect was observed when both ASI procedures were combined. Vaccine preparations with mitomycin C inactivated tumor cells proved to be less (NDV) or noneffective (BCG) compared to those with irradiated tumor cells.
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Drug resistance is a major problem in chemotherapy of squamous cell head and neck cancers (SCHNC). Since glutathione (GSH) plays a crucial role in mediating tumor cell resistance against various toxic insults, GSH metabolism in SCHNC xenografts was investigated. Xenografts from lymph node metastases contained markedly higher GSH concentrations compared with those derived from the corresponding primary lesions. After subcurative chemotherapy with cisplatin (DDP), a significant increase of both GSH levels and gamma-glutamyltranspeptidase activity (gamma-GT) was gained in tumor HT1M. Tumor HT3M showed high concentrations of GSH and gamma-GT, although these latter concentrations did not increase following chemotherapy with DDP. These findings suggest a possible impact of GSH metabolism on both the formation of metastases and the phenomenon of drug resistance in SCHNC.
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Different mechanisms of pain development and strategies of pain treatment are briefly described as an introduction. Since medicaments are preferentially used for the treatment of cancer pain, pharmacology of analgesics and principles of analgetic therapy are pointed out in more detail. Based on own experiences, a stepwise schedule for the treatment of pain in patients with advanced head and neck cancer is presented.
On the basis of aetiology and pathophysiology a rational concept for the treatment of zoster oticus is attempted. The current literature and own experiences favour the simultaneous application of the virostatic acyclovir and glucocorticosteroids.
Strain 2 guinea pigs bearing an intradermally growing already lymphogenetically metastasized line 10 tumor received intralesional chemotherapy with either cisplatin or vincristine. After successful treatment with cisplatin and low-dose vincristine, nearly all animals developed tumor-specific immunity. This phenomenon was not observed in animals treated with high-dose vincristine. Possible mechanisms of generation and alteration of primary T-cell-induced posttherapeutic tumor immunity are discussed.
Inbred 'Strain 2' guinea pigs bearing an intradermally growing and already lymphogenetically metastasized solid tumor ('Line 10') were successfully treated by multiple intralesional chemotherapy. The animals developed tumor-specific immunity. Depression of T lymphocyte function abolished the curative effect of this therapy. After treatment with antilymphocyte serum or cyclosporin A all animals receiving intratumoral chemotherapy with cisplatinum or low-dose vincristine showed progressive tumor growth. Immunosuppression with antilymphocyte serum or cyclosporin A did not interfere with high-dose vincristine treatment.
Chemotherapy of head and neck carcinomas has been the subject of 111 relevant publications reporting on more than 4,500 patients in the international literature of the past five years. Results of similar treatment protocols have been grouped together and tumour remission and survival time determined. Chemotherapy did not result in cure or increased survival times, neither alone nor in combination with irradiation nor when applied as adjuvant treatment. Inductive chemotherapy may result in producing a favourable effect on the prognosis of advanced carcinomas. The beneficial character of palliative chemotherapy is a generally accepted fact. Improvement of treatment results will be achieved only via centrally coordinated, randomised and prospective studies as well as by intensive fundamental research.
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