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Biomedical subjects

J Bier

Publications and source records attributed to J Bier.

At least 73 records · Page 4Linked to original sources

Animal experiments on the role of T lymphocytes in the course of antineoplastic chemotherapy. I. Chemotherapy and tumor-specific immunity.

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.

Animals↗

The doubtful relevance of nonspecific immune reactivity in patients with squamous cell carcinoma of the head and neck region.

Nonspecific immune reactivity (lymphocyte stimulation with PHA, PWM; % T-cells; absolute T-cell levels; skin reactivity to DNCB) was determined in 30 patients with squamous cell carcinoma of the head and neck region and in 30 age- and sex-matched healthy controls. The tests were carried out in each patient at 4-week intervals for at least 1 year. The tumor patients were regularly controlled over a period of 5 years. A reduced nonspecific immune reactivity was detected for tumor patients as compared with healthy controls. However, there was no correlation between the follow-up tests on unspecific immune reactivity and the clinical course of the disease. Moreover it was not possible--on the basis of pretherapeutic unspecific immune reactivity and 5 years' clinical follow-up--to make any prognostic statement for the tumor patients tested.

Carcinoma, Squamous Cell↗

Correlation of intralesional in vivo chemotherapy of line 10 hepatoma with in vitro drug sensitivity.

The effects of intralesional chemotherapy with 7 different drugs on line 10 hepatoma grown in strain 2 guinea pigs were compared with the sensitivity of line 10 tumor cells in vitro, using a micro modification of the tumor stem assay with capillary tubes. A modified method was used to evaluate the in vitro dose-response curves. The correlation for in vivo/in vitro resistance was found to be 100% and for in vivo/in sensitivity it was 80%.

Animals↗

Kinetics of 57Co-bleomycin in sheep after intra-arterial injection in the head and neck region.

Intra-arterial (i.a.) chemotherapy for the treatment of head and neck tumors is performed on the basis of clinical reports. The hypothetical aim of i.a. chemotherapy is to achieve higher drug concentrations in the tumor than are achieved by systemic intravenous (i.v.) administration. Therefore, it is postulated that i.a. chemotherapy leads to an increased therapeutic effect at the tumor site and to a decrease in systemic drug toxicity. The lack of adequate animal experiments and the absence of prospective randomized clinical trials comparing i.a. with i.v. chemotherapy led to the present kinetic study, concerned with various modes of administration of bleomycin with the aim of achieving high cytotoxic concentrations at the required site. Radioactive bleomycin (57Co-bleomycin) was injected locally (buccal plane, group I), intra-arterially (transverse facial artery, group II; superficial temporal artery, group III; external carotid artery, group IV), and intravenously (saphenous vein, group V) in five sheep per group. Between 1 and 360 min after injection of radioactive bleomycin the urine and the systemic blood activities were determined, and the activities in the hypothetical tumor area (buccal plane) were measured continuously. The animals were killed 360 min after injection and the activities in the hypothetical tumor area, in the lymph nodes draining this area (submandibular, parotic, lateral pharyngeal) and in different tissues and organs were determined. For all groups, 70%-80% of the injected bleomycin was eliminated by the kidneys, without any significant differences among the five groups tested. The systemic blood activities measured at 5-min intervals exhibited no differences for the groups injected i.a. (II-IV) and i.v. (V). Only animals which received local injections (group I) showed lower activities for 60 min after injection as compared with the other four groups. The activities of radioactively labeled bleomycin in the hypothetical tumor area during the entire experiment (360 min) were again similar for the groups injected i.a. (II-IV) and those injected i.v. (V). However, only animals injected locally (group I) showed significantly increased activities. After the death of the animals there was again no significant difference between i.a. and i.v. administration. Only local injection led to significantly increased tissue activities. Similar results also obtained for the lymph nodes draining the hypothetical tumor area.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Immunoprophylaxis of an ocular solid malignant tumor in cattle.

Individual Hereford cows bearing benign precursor lesions of ocular squamous cell carcinoma were treated by intralesional injection of mycobacterial cell walls in an oil-in-water emulsion in an attempt to interrupt neoplastic progression. Thirty-one months after treatment, statistical analysis of data indicated that intralesional BCG cell wall vaccine can interrupt this process and provides effective immunoprophylactic prevention of malignant disease.

Animals↗

[Intratumor immunotherapy with BCG cell wall preparations: development of a new therapy approach for head-neck tumors].

The present study deals with the influence of intratumoral injections of BCG cell-wall preparations (CWP) on the development of malignant tumors in the head-neck region. Line 10 tumor cells in strain 2 guinea pigs were used in a first assay. It became evident that intratumoral BCG-CWP injection leads to total tumor regression, a situation which can also be achieved by radical surgery. In contrast to the radically operated animals, those injected intratumorally with BCG-CWP develop a tumor-specific immunity. A second animal system was used to examine the effect of intratumoral BCG-CWP treatment on the development of autochthonous squamous cell carcinomas in cows. In this model, radical surgery leads to a clinical cure in all cases, while intratumoral BCG-CWP therapy leads to a complete clinical cure in 50% of the animals (observation period: 1 year). On the basis of experiments performed with animals systems, a clinical study was initiated to examine the effect of preoperative BCG-CWP injection in patients with squamous cell carcinomas in the head-neck region. At present, the case study involves 24 patients. The cumulative percentage of patients in complete tumor remission is now 69% for BCG-CWP pretreated tumor patients and 39% for patients who underwent surgery only. The hitherto existing life-table analyses of both therapy groups and the small degree of side effects resulting from BCG-CWP seem to justify a continuation of the study until a statistically confirmed statement can be made about the curative effect of BCG-CWP within the framework of a combination therapy in patients with squamous cell carcinomas in the head-neck region.

Aged↗

Immunotherapy by intralesional injection of BCG cell walls or live BCG in bovine ocular squamous cell carcinoma: a preliminary report.

Cows of the Dutch Frisian and Maas-Rijn-IJssel breed with histologically confirmed ocular squamous cell carcinoma showed complete regression of the primary tumor in 70 or 60% of the cases after intralesional injection of a BCG cell wall or live BCG vaccine, respectively. Recurrence of the tumor was observed in 57% of the animals treated with BCG cell walls and in 25% of the animals treated with live BCG vaccine. Spontaneous regression was seen in 20% of the untreated cows. In a second control group, radical surgery, the most successful treatment for primary stage I tumors in humans, resulted in a 90% cure. Influence of immunotherapy on metastases could not yet be fully evaluated. White blood cell counts were not changed after therapy. It was not possible to link a favorable response to BCG therapy with the intensity of the delayed type hypersensitivity (DTH) reaction to purified protein derivative of mycobacteriae (PPD) or the formation of antibodies to BCG as determined by a micro-enzyme-linked immunosorbent assay. However, in animals that showed tumor regression, the DTH reaction to PPD had a tendency to persist for a longer period of time. It was concluded that 1) block resection was the best method of treatment for this tumor, 2) a single intralesional injection of a BCG cell wall vaccine was as effective as live BCG vaccine in the induction of complete regression of the primary tumor, 3) in this preliminary study BCG cell wall vaccine was less effective than live BCG vaccine in the prevention of recurrence, and 4) this naturally occurring tumor model is well suited for the study of the influence of BCG immunotherapy in a primary stage I tumor.

Animals↗

[Investigations of unspecific immune reactivity in patients with head and neck carcinoma (author's transl)].

Unspecific cellular immune reactivity in 30 patients with squamous cell carcinoma of the head and neck was compared with those in 30 healthy controls. Assays were performed in vitro to evaluate the blastogenic response of lymphocytes to the mitogens PHA (phytohemagglutinin), Con A (Concanavalin A) and PWM (pokeweed mitogen) and to quantify T-rosette-forming lymphocytes. The in vivo assay used was the delayed cutaneous hypersensitivity reaction to DNCB (dinitro-chlor-benzene). Tests were performed in all patients every 4 weeks either for a total of 1 year or until death. Tumor patients were followed up to 5 years. Compared to healthy controls tumor patients demonstrated significant impairment of unspecific immune reactivity. Surgery, chemotherapy, and radiotherapy led temporarily to a further decrease of immune reactivity. There was no correlation between unspecific immune reactivity and tumor stage, course of the disease, and prognosis. It was not possible to give any useful statement for patients with squamous cell carcinoma of the head and neck by determining their unspecific immune reactivity.

Adult↗

Efficacy of intratumorally administered mycobacterial cell walls in the treatment of cattle with ocular carcinoma.

Individual Hereford cows with naturally occurring ocular squamous cell carcinoma were treated by intralesional injections of mycobacterial cell walls in an oil-in-water emulsion. Six of 23 treated animals were alive (5 free of tumor and 1 with arrested disease) at a minimum of 2.5 years after treatment, as compared to 1 of 18 controls. A necropsy, lymph node metastases were found in most animals with progressive disease. The disease progressed to an advanced stage (which required death of the animals) at a faster rate for control animals than for treated animals.

Animals↗

[Animal experiments for intratumoral chemotherapy with bleomycin (author's transl)].

The intense clinical interest in bleomycin as an anti-tumour agent has led to different methods of administration in an attempt to administer sufficiently high concentrations of the drug to the tumor. Therefore, a study was designed to determine the distribution and the therapeutic effect of a bleomycin emulsion and aqueous bleomycin after different routes of application. The tissue distribution of radioactively labelled bleomycin emulsion and aqueous bleomycin was determined in tumor-free CF 1 and tumor-bearing (EL 4, L 1210) C 57 Bl 6 and DBA 2 mice after local (s.c., i.t.) and systemic (i.v.) injection. The distribution studies for aqueous 57Co-bleomycin showed increased activity in the injection sites and the lymph nodes draining the injection sites after s.c. and i.t. injection compared to i.v. administration of the drug. In comparison to the aqueous local administration, the application of 57Co-bleomycin emulsion resulted in a disproportional increase of the 57Co-bleomycin concentration at the injection sites and in the draining lymph nodes. To prove the therapeutic relevance of the bleomycin tissue distribution tumor-bearing (line 10) strain 2 guinea pigs were treated with different modes of bleomycin. Animals with already lymphogenously metastasized tumors have been cured by means of low i.t. doses of the bleomycin emulsion. Guinea pigs treated with i.t. administration of aqueous bleomycin need, compared to the bleomycin emulsion, five times higher doses for tumor-free survival. Intravenously treated animals died either because of progressive tumor growth or because of toxic bleomycin effects. These findings made by animal experiments favor the i.t. treatment of head and neck carcinomas with a bleomycin emulsion.

Animals↗

[Animal experiments for intra-arterial chemotherapy with bleomycin (author's transl)].

Intra-arterial chemotherapy for treatment of head and neck carcinomas is performed on the basis of clinical reports, which postulate higher effective concentrations at the tumor for this therapeutic method than after systemic administration. This assumption, which has so far not yet been confirmed experimentally, has led to the present study. The study is concerned with different modes of application of bleomycin with the aim to achieve high cytostatic concentrations at the site of action required. In sheep the tissue concentration of 57Co-bleomycin was determined in a hypothetical tumor area, the planum buccale, and in the lymph nodes draining this area, after submucous administration (hypothetical tumor area), intra-arterial administration (A. transversa faciei, A. temporalis superficialis, A. carotis externa) and i.v. administration (V. saphena). Only submucous injection led to significantly increased 57Co-bleomycin activities in the hypothetical tumor area and in the corresponding primary draining lymph nodes. The intra-arterial administration into the A. temporalis superficialis and A. carotis externa did not show any differences compared to the i.v. injection of 57Co-bleomycin. Compared to i.v. administration, injection into the isolated A. transversa faciei led to a slightly increased concentration of radioactively labeled bleomycin, restricted to the hypothetical tumor area. The findings made by animals experiments print out that the clinical application of intra-arterial is not justified and favor intratumoral treatment of head and neck carcinomas with bleomycin.

Animals↗