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Biomedical subjects

H Bier

Publications and source records attributed to H Bier.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dual role of fibroblasts in tumor cell growth.

Vast experience with cultivating biopsies from human tumors indicates that in most cases the admixture of fibroblasts has a negative effect on growth of tumor cells. Only rarely is observed help provided by the fibroblasts. It has also long been known that fibroblasts can inhibit by contact themselves and also produce growth factor(s) promoting cell proliferation. We have used three permanent squamous cell carcinoma lines and fibroblasts derived from biopsies of trachea to study this paradox. The inhibitory activity of fibroblasts is contact-dependent in a cell membrane-bound factor, which is trypsin sensitive. We prepared microsomal fractions (MF) from aged (more than 40 passages) fibroblasts and followed their effect on proliferation of the tumor cell lines in MTT assay. MF from all three fibroblast lines inhibited the tumor cells. Most regularly was this phenomenon observed with line UM-SCC 22B. Not all tumor cells are immortal. On the contrary, a large portion of them undergoes terminal differentiation. With the line UM-SCC 22B we tested the possibility that MF from fibroblasts can increase the portion of tumor cells which will senescence after few mitoses. The immortal cells were defined as cells capable in 8 or 13 days of forming colonies of more than 50 or 200 cells. The senescent cells were defined as cells not capable of producing within the same period of time colonies of more than 12 or 30 cells. The MF was able to increase the number of small colonies, i.e. the number of senescent tumor cells. The fibroblasts of the same passage level were releasing soluble growth factor(s) promoting growth of cells. Fibroblasts can apparently simultaneously inhibit growth by contact and release factor(s) promoting growth of cells. The final outcome is a result of the balance between these two forces. This balance is regulated by many intrinsic and extrinsic forces.

Carcinoma, Squamous Cell↗
PubMed1994

[Immunohistochemical studies of advanced laryngeal and hypopharyngeal carcinomas 3 days after administration of monoclonal antibody against epidermal growth factor receptor].

Sixteen consecutive patients with stage III/IV laryngeal or hypopharyngeal cancer received 0, 20, 100 or 400 mg i.v. of the murine anti EGF-R IgG2a mab EMD 55900 three days before laryngectomy and neck dissection. Presence of macrophages, T-cells (CD3) and T-cell subpopulations (CD4/CD8), NK-cells, complement factors (iC3b, C1q, C4c), and expression of MHC class I, MHC class II, ICAM-1 and IL-2-R were determined in cryostat sections of the surgical specimens and compared to normal tissue of the same patient. The antibody showed good binding to EGF-R of malignant and normal tissue. However, no signs of strong inflammatory reactions were noticed. Infiltration with macrophages was directly correlated with the dose of the administered antibody, even in the basal layer of the normal mucosa. No morphological signs of direct destruction of normal and malignant tissue infiltrated by macrophages or other immunocytes were noticed. This finding was underlined by random infiltration with HLA-DR positive-, T- and NK-cells. Possible long-term effects of this antibody--e.g. non-specific stimulation or improved antigenic processing--must be evaluated in further studies.

Adolescent↗
PubMed1994

Intratumoral PEG-interleukin-2 therapy in patients with locoregionally recurrent head and neck squamous-cell carcinoma.

BACKGROUND: An enhanced efficacy of local as compared to systemic administration of interleukin-2 (IL-2) has been demonstrated in several experimental tumors. We previously reported that guinea pigs with palpable tumors and regional micrometastases could be cured by intratumoral injections of polyethylene glycol-modified IL-2 (PEG-IL-2). In the present study this treatment schedule was applied in a clinical situation. PATIENTS AND METHODS: Nineteen patients with 11 local and 11 regional recurrences of head and neck squamous cell carcinoma (HNSCC) were treated with intratumoral injections of 200,000 U of PEG-IL-2 3 times weekly in courses of 4 weeks. RESULTS: Treatment was given on an out-patient basis, and was well tolerated. Temporary regional swelling and redness developed in 10 patients, and in 9 of them systemic eosinophilia was documented. Median duration of treatment was 4 weeks (range 2-14 weeks). Seventeen patients were evaluable for response. One complete response (CR; 6%; duration 91 weeks), and 6 stable diseases (SDs; duration 8-57+ weeks) were recorded. The CR and the 3 best SDs (23, 40, 57+ weeks) occurred in patients with a single regional tumor recurrence of relatively small size. During treatment, all 4 developed locoregional edema and redness, and high levels of circulating eosinophils. Median survival was 23 weeks for all patients, and 45+ weeks for the patients with SD. CONCLUSION: Intratumoral injection of PEG-IL-2 in patients with HNSCC is feasible. This treatment appears beneficial for highly selected patients. The objective response rate is insufficient to justify wide clinical application.

Aged↗
PubMed1994

[The incurable tumor patient].

In patients suffering from advanced or recurrent cancers that are no longer amenable to curative treatment, palliation and symptomatic care have to take the place of cure. In such cases, palliation aims at relief of pain, alleviation of functional disabilities and restoration of mental and social balance. Since the clinicians effort is concentrated on the control of symptoms of uncontrollable disease, decisions have to be made concerning the relative value of the various methods available for treatment and support in the individual patient. Criteria for the physician's decision-making are important parameters in any approach to the patient with incurable cancer and have particular significance in caring for terminal disease.

Humans↗
PubMed1993

Chemotherapeutic drug resistance in the management of head and neck cancer.

Considerable progress has been made in the development of more effective chemotherapy regimens for squamous cell head and neck carcinomas. Unfortunately, increased response rates have not been translated into marked improvements in survival since durations of response have been brief, and the natural history of the disease has ultimately remained unaltered. Since the development of drug resistance is a major obstacle to successful antineoplastic chemotherapy, comprehensive efforts have been focused on understanding the underlying mechanisms. In this review, general and specific aspects of drug resistance related to head and neck cancer are addressed. In particular, mechanisms of resistance towards the most widely used antineoplastic drugs in head and neck malignancies--methotrexate, cisplatin, 5-fluorouracil, bleomycin, and vincristine--are discussed.

Animals↗
PubMed1993

[Hormonal reactions in fattening bulls and cows during a three-week butyric acid exposure].

During a three-week intraruminal butyric acid resp. Na-butyrate load (1 g/kg body weight) we investigated the hormones insulin, cortisol, triiodothyronine (T3) and thyroxin (T4). Distinct effects on insulin concentration were found during the diurnal course which was after butyric acid application in the morning for nine hours depressed followed by a surplus incretion. In the morning the anteprandial concentrations of insulin, cortisol, T3 and T4 were not changed in the whole time. One cow was ill on ketosis and showed strong changes of hormones.

Acid-Base Imbalance↗
PubMed1993

[References for after-care of tumor patients].

Recent publications have questioned the benefit of extensive routine follow-up measures in all patients that have undergone treatment for head and neck cancer. Both the poor detection rate of asymptomatic early tumor lesions and the severe limitations that are encountered with regard to further treatment options require an individual follow-up protocol mainly depending on site, size, and treatment of the respective tumor. The objective is to increase the efficacy of the follow-up in head and neck cancer patients carried out in both clinics and private practice.

Aftercare↗
PubMed1992

Induction of transformation of human respiratory epithelium in vitro. Preliminary investigation.

Malignancy is the result of multistep transformational changes of normal somatic cells. In the case of respiratory epithelial malignancies this process lasts for several years. Many methods have been explored to mimic this process in an extracorporal model. In the present investigation we combined several of these methods. Organ cultures were prepared from tracheal specimens and were then consecutively treated with human papilloma virus, benzo(a)pyrene, methylnitronitrosoguanine and tetradecanoyl phorbol acetate. Identical numbers of organ cultures from the same specimen were maintained without exposure to carcinogens. After 6 weeks these cultures were further cultivated either in mixed cultures (MC) with autologous isotopic fibroblasts or under the kidney capsule of the nude mouse (SRC). These two methods were combined after a few months: MC cells were transplanted under the SRC or SRC transplants were explanted in cell culture. This long-term selection procedure revealed striking differences between control and treated organ cultures. Three-dimensional structures containing epithelial cells were isolated from both organ cultures but survived more than 3 months only from treated cultures. Only MC from treated organ cultures produced nodules under SRC. The incidence and morphology of the nodules in the SRC were directly related to carcinogen treatment, with more nodules with pronounced epithelial cell atypia obtained from treated organ cultures. MC and SRC showed the importance of a time factor for selecting cells with changed growth behavior--increased time increased the incidence of such cells.

Animals↗
PubMed1991

Cross-resistance patterns related to glutathione metabolism in primary human renal cell carcinoma.

In 59 cases of primary human renal cell carcinoma (RCC), cross-resistance and collateral susceptibility patterns were determined in an MTT microculture assay. Concomitantly, the glutathione (GSH) content and the enzymatic activity of gamma-glutamyl transpeptidase (GGT) were measured as distinct resistance characteristics. Resistance or chemoresponse towards Vinca alkaloids and anthracyclines were found to be highly coincident, suggesting that the classical multidrug resistance mechanism is active in human RCC. Strong resistance to platinum complexes combined with relative sensitivity to bleomycin was significantly associated with elevated glutathione levels, providing evidence for another pathway instigating chemoresistance. In contrast, despite substantial enzymatic activity, GGT effects revealed no correlation to the chemoresistance pattern. This result implies that it is the GSH-linked binding and reduction potential rather than the GGT-associated transportation capacity that has an impact on the expression of chemoresistance in human RCC.

Antineoplastic Agents↗
PubMed1991

Circumvention of drug resistance in cisplatin-resistant sublines of the human squamous carcinoma cell line HLac 79 in vitro and in vivo.

In a previous report we have characterized cisplatin (CDDP)-resistant sublines (HLac 79-DDP1 to DDP4) of the recloned squamous cell head and neck cancer (SCHNC) line HLac 79-ML revealing significant alterations of glutathione (GSH) metabolism and drug accumulation. In order to overcome CDDP-resistance in HLac 79 cells we now investigated the effect of buthionine sulfoximine (BSO), a specific inhibitor of GSH synthesis, verapamil (VRP), a calcium channel blocker that has been found to modulate resistance towards a broad spectrum of antineoplastic drugs, cyclosporin A (CSA), an immunosuppressive agent probably affecting drug pharmacokinetics, and aphidicolin (APC), a fungal metabolite interfering with DNA repair through inhibition of DNA polymerase alpha, on HLac 79 CDDP-sensitivity. Using the colorimetric MTT assay, GSH depletion with BSO led to a significant decrease of the 50% inhibitory drug concentration (IC50) in all HLac 79 sublines by dose modifying factors (IC50 CDDP/IC50 BSO + CDDP) ranging from 1.8 to 3.3. VRP, CSA or APC were not effective to overcome CDDP resistance in HLac 79 cells. The potential of BSO to modulate CDDP resistance in vitro was tested in vivo in HLac 79 tumor bearing NMRI nu-nu mice subsequently. Oral administration of BSO 7 days prior and during (days -7 to 8) CDDP treatment (3 mg/kg bw i.p. days 0, 4, 8) produced a significant prolongation of mean survival time mean as compared to chemotherapy alone. This held true for both the maternal line ML in terms of chemosensitization (CDDP: mean = 40.2 +/- 15.9 days vs. CDDP + BSO: mean = 80.3 +/- 30.4 days, p less than 0.001) and the CDDP resistant subline DDP4 in terms of partially overcoming secondary drug resistance (CDDP: mean = 56.5 +/- 13.6 days vs. CDDP + BSO: mean = 72.5 +/- 15.8 days, p less than 0.001). Enhanced toxicity of combined BSO and CDDP treatment manifested by transient 10% reduction of animal mean body weight.

Animals↗
PubMed1991

[Estrus and ovulation synchronization in Merino meat sheep. 1. Effect of Gonavet "Berlin Chemie" after estrus synchronization with prostaglandin F2 alpha in Merino meat sheep].

Oestrus synchronisation by means of PGF2 alpha analogues was followed by injection of Gonavet "Berlin-Chemie" which triggered off an LH peak, 2 to 3 hours from injection. Injection of Gonavet "Berlin-Chemie", 44 hours after PGF2 alpha application, caused synchronisation of all LH peaks. The interval between injection of Gonavet "Berlin-Chemie" and onset of ovulation amounted to 22 hours. The length of ovulation was not accurately determinable. Ovulation was successfully induced to all sheep by application of Gonavet "Berlin-Chemie", 44 or 48 hours after PGF2 alpha injection. Ovulation rates were 1.75 or 1.54. Luteolytic action on sheep of Cloprostenol "Jenapharm", a PGF2 alpha analogue, proved to be just as good as that of Oestrophan (SPOFA).

Animals↗