Biomedical subjects

H Bier

Publications and source records attributed to H Bier.

78 records · Page 5Linked to original sources

PubMedDate not supplied

Intratumoral BCG therapy of transplanted head and neck tumors in strain 2 guinea pigs.

The generally unfavorable prognosis associated with advanced squamous cell carcinoma in the head and neck region in humans led us to immunotherapeutic experiments with bacillus Calmette-Guerin (BCG) in inbred guinea pigs with solid growing and lymphogenous metastasizing tumors. The injection of live BCG or BCG cell wall preparation (CWP) into the planum buccale in the guinea pig led to a pronounced local inflammatory reaction. If live BCG or BCG CWP were injected into the planum buccale together with line 10 tumor cells, no growth of the tumor could be observed. Animals treated in this manner developed a tumor-specific immunity. Guinea pigs treated intratumorally with live BCG or BCG CWP in established, 6-day-old tumors of the planum buccale showed regression of the primary tumor and prevention of the development of lymph node metastases. These cured animals also developed a tumor-specific immunity. Guinea pigs with 6-day-old tumors of the planum buccale remained tumor free after surgical removal of the primary tumor and the draining submandibular and cervical lymph nodes (radical operation) whereas locally operated animals (primary tumor excision) developed lymph node metastases. Animals that were tumor free after radical surgery did not develop tumor-specific immunity. Despite insufficiently clarified mechanisms for the induction and effect of BCG immunotherapy, we can state that, with intratumoral BCG therapy, a tumor experimentally placed in the head and neck region is eliminated, regionally manifest metastases are eliminated, and specific tumor immunity can be demonstrated in successfully treated animals.

Animals↗

PubMedDate not supplied

Preoperative screening for coagulation disorders in children undergoing adenoidectomy (AT) and tonsillectomy (TE): does it prevent bleeding complications?

BACKGROUND: Bleeding remains the most important complication of adenotonsillectomy in children. Preoperative coagulation tests are widely used to detect unknown bleeding disorders. To determine the efficacy of preoperative coagulation screening in preventing bleeding complications. PATIENTS: Study group 1: 148 healthy children referred by the otorhinolaryngology department for preoperative pediatric examination. Study group 2: 124 healthy children sent to the hemostaseologic clinic for preoperative investigation of a prolonged PTT. METHOD: The incidence of relevant coagulation disorders detected by a standardized bleeding history and coagulation screening tests was studied prospectively in 2 study groups planned for AT and/or TE. The frequency of abnormal bleeding was investigated retrospectively in those children who underwent surgery. RESULTS: Bleeding disorders were detected in 7/148 and 15/124 children in study group 1 and 2 respectively. 141/148 and 79/124 children actually underwent surgery, 62 TE +/- AT + 79 AT alone and 26 TE +/- AT + 53 AT alone respectively. Major bleeding occurred in 1/141 patients (1 TE) in study group 1. Preoperatively, this child had shown normal coagulation screening tests. In 4/79 patients (3 TE, 1 AT) in study group 2, surgery was complicated by major bleeding. Despite extensive testing, no relevant bleeding disorder had been diagnosed in these children preoperatively. Sensitivity of coagulation screening tests for major bleeding was 0 in study group 1. CONCLUSIONS: In our study, coagulation screening failed to effectively identify patients at risk of bleeding.

Adenoidectomy↗

PubMedDate not supplied

Regional low-dose interleukin-2 immunotherapy of lymph node micrometastasis in a guinea pig tumor model.

Strain 2 guinea pigs bearing the transplanted intradermally growing line 10 tumor underwent surgical excision of the primary lesion at a time when the tumor had already metastasized to the first draining lymph node. Postoperative perilymphatic immunotherapy with 500 or 5,000 IU of interleukin-2 (IL-2) for 12 consecutive days failed to cure the animals of residual lymphatic micrometastasis. Similarly, intratumoral IL-2 treatment of nonoperated guinea pigs did not alter the natural course of the disease. However, histological serial examination of the tumor-draining lymph nodes at the end of immunotherapy revealed significantly less tumor occupation in all IL-2-treated animals as compared to control animals.

Animals↗

PubMedDate not supplied

Establishment and characterization of cisplatin-resistant sublines of the human squamous carcinoma cell line HLac 79.

Though various chemotherapy protocols lead to considerable response rates in squamous cell head and neck cancer (SCHNC), the overgrowth of a tumor cell phenotype which no longer responds to clinically achievable drug concentrations regularly impairs definite tumor control. In order to investigate mechanisms of drug resistance towards one of the most active agents in SCHNC we established four Cisplatin (CDDP)-resistant sublines (DDP1-DDP4) of the recloned human SCHNC cell line HLac 79. The 50% inhibitory drug concentration (IC50) of CDDP as determined by the colorimetric MTT-assay was increased by the factors 2.7 (DDP1), 3.3 (DDP2), 5.1 (DDP3), and 6.4 (DDP4) in the respective sublines. Three subpopulations contained significantly elevated glutathione (GSH) levels by the factors 1.4 (DDP3), 1.7 (DDP2), and 2.4 (DDP4) compared to the maternal line (50.2 nM/mg protein). DDP4 showed increased activity of gamma-glutamyl-transpeptidase (1.83 vs. 1.21 mU/mg protein), and DDP2 and DDP4 showed increased activity of GSH-S-transferase (35.6 and 51.9 vs. 25.1 mU/mg protein). Concerning both GSH-peroxidase and GSH-reductase no significant differences between the HLac 79 subpopulations were observed. Intracellular CDDP accumulation determined by neutron activation analysis revealed reduced drug uptake in DDP3 and DDP4 (60% and 76% of control value).

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Establishment and characterization of four cell lines derived from human head and neck squamous cell carcinomas for an autologous tumor-fibroblast in vitro model.

To study interactions between tumor cells and stromal elements, we established carcinoma cell lines as well as tumor-derived and skin fibroblast cultures from four patients with squamous cell carcinoma of the head and neck. For the characterization of the tumor cell lines we a) determined population doubling times, b) assessed morphological features by light and electron microscopy, c) investigated the expression of typical markers by immunohistochemistry, including various intermediate filaments and surface antigens, d) compared these findings with expression patterns in the respective original tumor specimens, e) evaluated p53 mutations in tumor specimens and cell lines, f) performed chromosome analysis, g) investigated the tumorigenicity in athymic mice, and h) tested the formation of both tumor and mixed tumor-fibroblast multicellular spheroids. Tumor cell cultures were considered established cell lines when maintained and passaged over a period of two years after primary explantation. The in vitro morphology of the cell lines showed well preserved characteristics of squamous cell carcinoma, and electron microscopy as well as immunohistochemistry revealed their squamous type of differentiation. All cell lines presented the same p53 genotype as the respective original tumors. Furthermore, they were successfully xenotransplanted into nude mice and formed both pure and mixed three dimensional spheroids. This experimental model allows the in vitro and in vivo investigation of various tumor-fibroblast interactions.

Adult↗

PubMedDate not supplied

Antitumor activity of anti-epidermal growth factor receptor monoclonal antibodies and cisplatin in ten human head and neck squamous cell carcinoma lines.

Head and neck squamous cell carcinomas (HNSCC) frequently display increased levels of epidermal growth factor receptor (EGFR) and since the receptor is located on the cell surface, anti-EGFR antibodies appear to be suitable agents for antitumor therapy. We investigated the effect of murine EMD 55900 and rat ICR 62 monoclonal antibodies (MAb) directed against EGFR both as single agents and in combination with cisplatin. ELISA detection showed the amount of EGFR protein in HNSCC lines UM-SCC-10A, -10B, -11B, -14A, -14B, 14C, -22B and HLac 79, 8029NA, 8029DDP to range between 20 and 8100 fmol/mg protein. Compared to A431 cells, seven HNSCC lines were high and three low receptor expressors. Only low levels of TGF alpha were found in the supernatants of some untreated HNSCC lines, probably due to the consumption of TGF alpha by EGFR. Consequently, occupation of EGFR by MAb led to marked accumulation of TGF alpha in cell supernatants. Colorimetric MTT assay showed both MAbs (0.3-30nM) to have comparable dose-dependent growth inhibition which correlated with the EGFR content of the respective cell lines (p < 0.05). Using 30nM MAb, seven high receptor expressing HNSCC lines were growth inhibited by at least 20% to a maximum of 61% (mean = 38%). Combined treatment with MAb and cisplatin led to a significant decrease in cisplatin IC50 values in 5 cell lines expressing more than 1200 fmol EGFR/mg (dose modification by factor 2.1-4.1). In conclusion, anti-EGFR MAb exert direct antiproliferative activity in HNSCC lines and show additive effects in combination with cisplatin.

Animals↗