Biomedical subjects

B Wollenberg

Publications and source records attributed to B Wollenberg.

47 records · Page 3Linked to original sources

PubMed1994

[Micrometastases in bone marrow of patients with cancers in the head and neck area].

Individual disseminated epithelial tumour cells were detected in bone marrow aspirates in 41 of 108 patients (37%) with squamous cell cancer of the head and neck region by an immunocytochemical technique based on monoclonal antibodies raised against the cytokeratin No. 19. In the clinical stage I (T1N0M0) tumour cells were detected only in 26.3% of the patients, whereas in stage IV (T4N0M0, T(all)N2-3M0, T(all)N(all)M1) almost twice as many patients (47.7%) presented with tumour cells in the bone marrow. Apparently, grade of differentiation of the tumour (grading) had no influence on the spread of single tumour cells. An influence of the different localisations of the primary tumour on tumour cell spread or the rate of tumour recurrence cannot as yet be discovered. Cytokeratin No. 19 expressing cells were not detectable in the bone marrow of 18 patients with non-malignant disease. Seventy-three patients were included in a follow-up study with a mean observation time of 25 months (range: 4-52 months). The presence of epithelial cells at the time of primary treatment appears to indicate a significantly higher risk of development of local or distant tumour recurrences (p = 0.01). Of 46 patients initially exhibiting no tumour cells in the bone marrow, only 14 had a clinical recurrence. Whereas 17 of 27 patients who presented with tumour cells in the bone marrow developed either a local tumour recurrence or distant metastases in different organs. Patients presenting with bone marrow tumour cells showed a significantly shorter disease-free survival than those without (p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

PubMed1993

[Leiomyosarcoma of the tongue].

We report on a 48-year old female patient presenting with a spherical firm tumour that developed within a period of about three weeks. No causative trauma could be assessed. The tumour was surgically removed and turned out to be a leiomyosarcoma of the tongue. Probably the tumour originated from the vascular smooth muscle cells. Clinically this very rare tumour of the tongue must be differentiated from various benign and malignant mesenchymal neoplasms. Therapeutic considerations and differential diagnosis are discussed in reviewing the literature.

Brachytherapy↗

PubMed1993

[Incidence of Doppler ultrasound detectable stenoses of cervical arteries in patients with cochlear-vestibular symptoms].

Doppler ultrasound examination is an easy and non-invasive examination technique to image the anatomical and functional situation of cervical vessels. An increasing number of ENT-specialists has been using Doppler sonography in the diagnosis of cochlear and vestibular disorders. We analysed the frequency of pathological Doppler examination results of 150 patients with vertigo, hearing loss and tinnitus. Especially patients with vertigo bear a greater risk for stenosis of the extracranial arteries (28%) compared to an asymptomatical population (1%). Patients with hearing loss and tinnitus showed a different degree of artery disorders (23% of the patients with hearing loss; 18% of the patients with tinnitus). Patients bearing no risk for atherosclerosis showed in 13% (vertigo) and 8% (hearing loss and tinnitus) stenosis of the cervical arteries. Thus we found by Doppler ultrasound examination more stenoses in patients with cochlear or vestibular symptoms than in an asymptomatical population. The early attribution of stenosis to a malfunction of the inner ear helps to avoid invasive examinations of cervical vessels. In addition to this, imminent cerebral ischaemia can be revealed at an early stage.

Aged↗

PubMed1992

[Does the otorhinolaryngologist need Doppler sonography?].

Doppler sonography has not only proved to be a non invasive but also a highly sensitive diagnostic tool for imaging of functional vascular disorders. The otorhinolaryngologist who in future will have to deal with an increasing number of neurootological problems, such as tinnitus, vertigo and hearing loss, should cover the Doppler sonographic examination of the vertebral and carotid artery and its branches. Ultrasound examination of these vessels should be performed in all patients suffering from cochlear or vestibular disorders and bearing risks for arteriostenosis. Early diagnosis does not only point out causative vascular changes but also helps to prevent the patients from invalidising or lethal cerebral events. The combination of (Doppler- and B-mode-sonography Duplex sonography) enables the ENT specialist not only to rule out functional vessel disorders but also to look for morphological vascular changes. Duplex scan imaging is far less risky than angiographic procedures and in many cases it is superior to these invasive techniques too.

Blood Flow Velocity↗

PubMedDate not supplied

Ep-CAM--a marker for the detection of disseminated tumor cells in patients suffering from SCCHN.

Disseminated tumor cells are considered as the origin of metastases. Since the number of circulating tumor cells in the bone marrow or the peripheral blood of patients correlates well with the tumor stage, their early detection is an important feature for the identification of high risk patients. We therefore investigated the pan-carcinoma antigen Ep-CAM for its suitability to serve as a specific marker for disseminated tumor cells in patient with squamous cell carcinoma of the head and neck (SCCHN). In order to detect small numbers of tumor cells in early tumor stages, we developed and describe here a RT-PCR assay that detects a single tumor cell within 10(5) normal cells. We examined bone marrows from patients and healthy donors and demonstrate that Ep-CAM can be used as a tumor marker for the diagnosis of single tumor cells in patients with SCCHN.

Antigens, Neoplasm↗

PubMedDate not supplied

Targeting head and neck cancer by GM-CSF-mediated gene therapy in vitro.

BACKGROUND: The prognosis for patients with squamous cell carcinoma of the head and neck (SCCHN) has remained poor during the last decades, emphasizing the need for new treatment modalities. Consequently, the objective of our study was to evaluate the feasibility and efficacy of cytokine-mediated gene therapy in SCCHN in vitro. MATERIALS AND METHODS/RESULTS: The SCCHN cell line PCI-1 was transduced by lipofection with a plasmid encoding the human granulocytemacrophage colony-stimulating factor (GM-CSF). Transfection of PCI-1 resulted in the production of significant amounts of GM-CSF as tested by ELISA. Enhanced proliferation of a GM-CSF sensitive cell line, TF-1, after incubation with supernatants of GM-CSF-transduced tumor cells demonstrated the release of biological active GM-CSF from these PCI-1 cells. In addition, GM-CSF-secreting PCI-1 cells enhanced antitumor cytotoxicity of allogeneic peripheral blood mononuclear cells, as tested in 24h-MTT-cytotoxicity assays. CONCLUSIONS: Our data demonstrate the feasibility and efficacy of GM-CSF-mediated stimulation of the antitumor immune response against SCCHN in vitro and may help to define new strategies in the treatment of this malignancy.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

TNFalpha contributes to the antitumor activity of a bispecific, trifunctional antibody.

Immunological cancer therapies focus on the activation of immune effector cells yielding a specific antitumor activity. Disseminated tumor cells are regarded as the origin of metastases and consequently their elimination is the central objective of adjuvant immune therapies. The use of bispecific antibodies is an approach that is regarded as promising in order to fight those disseminated tumor cells. Unfortunately, the efficiency of these antibodies is limited by the fact that they usually activate a single class of effector cell, thus not yielding optimal immune response. In addition, tumor cells may down-regulate the antibody's target molecule and escape recognition. We have recently described results with an intact bispecific molecule, BiUII, that represents a new class of intact antibodies. These antibodies, termed "triomab", provide an excellent antitumor activity in vitro, a fact that most probably is attributable to the simultaneous activation of different classes of immune effector cells. We have now investigated this antitumor activity in more detail and demonstrate here that at least a dual mechanism accounts for triomab-mediated killing of tumor cells: besides direct cell-mediated killing, triomab induces the production of TNFalpha in PBMCs at concentrations that induce apoptosis in target cells. This bystander effect may be of special interest for the clinical application of triomab in terms of killing of target antigen-negative tumor cells.

Antibodies, Bispecific↗

PubMedDate not supplied

The significance of Tenascin-C serum level as tumor marker in squamous cell carcinoma of the head and neck.

BACKGROUND: Tenascin, an extracellular matrix glycoprotein, is transiently present in embryonic tissue, in benign granulation tissue, but also in several highly anaplastic tumors like fibrosarcoma, melanoma and squamous cell carcinoma of the skin. This study was performed to validate elevated Tenascin serum levels as a possible marker for head and neck squamous cell carcinomas (HNSCC). PATIENTS AND METHODS: Tenascin serum levels were evaluated in patients with primary (n = 92) and with recurrent (n = 28) HNSCC. Patients with benign, non inflammatory ear, nose and throat diseases (n = 16) served as the control. The Tenascin serum levels were measured by ELISA (Aventis). RESULTS: Serum Tenascin concentrations of patients with benign ENT diseases ranged between 0.37 and 2.19 micrograms/ml (n = 16, mean +/- SD: 1.23 +/- 0.59 micrograms/ml), of patients with HNSCC (primary diagnosis) between 0.05 and 8.75 micrograms/ml (n = 92, mean +/- SD: 1.81 (1.36 micrograms/ml) and of patients with recurrent HNSCC between 0.53 and 10.0 micrograms/ml (n = 28, mean +/- SD: 2.78 +/- 2.2 micrograms/ml). CONCLUSION: We found a significant elevation of Tenascin serum levels only in patients with higher tumor stages (T4/UICC4) (p < 0.01/p < 0.1) or recurrent disease compared to Tenascin serum levels in healthy controls. Thereby Tenascin serum levels cannot be used clinically as a routine serum marker for the control of head and neck cancer. Further investigations are necessary to evaluate whether the measurement of Tenascin levels as tumor markers could offer additional information to the clinical outcome of patients with HNSCC.

Biomarkers, Tumor↗

PubMedDate not supplied

MHC-class I antigen expression on micrometastases in bone marrow of patients with head and neck squamous cell cancer.

Although squamous cell carcinoma of the head and neck region very rarely metastasize to the skeleton, epithelial cells have been found in bone marrow aspirates of these patients. This observation reflects the general spread of the disease, indicating a poor clinical prognosis with a much higher risk of developing local or distant recurrences. In a first attempt to characterize the phenotypic properties, the expression of the major histo-compatibility complex (MHC) class I antigens on bone marrow micrometastases was assessed. It has been shown that the down-regulation of these molecules is a potential mechanism to escape from HLA class I restricted lysis by cytotoxic T-cells. The significance of reduced MHC class I expression might be relevant for the survival of residual metastatic cells in the bone marrow of patients with squamous cell carcinoma of the head and neck region. Bone marrow aspirates were screened for individual disseminated epithelial cells using the immunoalkaline phosphatase technique with monoclonal antibodies to the epithelial differentiation marker cytokeratin 19 (CK19), as described previously. Specimens containing CK19-positive cells were colabelled with the monoclonal antibody W6/32. The loss of MHC expression is not related to the tumor stage but clearly to the degree of differentiation: 6 out of 7 patients with low-grade SCCHN, but only 3 out of 13 patients with medium-grade SCCHN showed a complete loss of MHC class I molecules. This finding could indicate the reduced prognosis of undifferentiated SCCHN. The lack of MHC class I expression could encourage the survival of residual tumor cells in the bone marrow of patients with SCCHN that evade immunosurveillance.

Antibodies, Monoclonal↗

PubMedDate not supplied

CYFRA 21-1 is not superior to SCC antigen and CEA in head and neck squamous cell cancer.

CYFRA 21-1 was compared to the most reliable tumor markers for squamous cell carcinoma of the head and neck (HNSCC), SCC antigen and CEA. Sera of 163 patients with primary and 40 patients with recurrent HNSCC were examined. 94 patients with non-malignant ENT-diseases served as the control group. To give a specificity of 95% the cut-off-values were as follows: SCC: 1.9 ng/ml, CEA: 3.8 ng/ml, CYFRA 21-1: 2.9 ng/ml. SCC had the highest sensitivity at the time of primary diagnosis (P) at 43% and 61% at relapse (R), compared to CEA with P: 35%, R: 40% and CYFRA 21-1 with P: 17%, R: 18%. We show that CYFRA 21-1 cannot offer additional information to the clinical outcome of patients with HNSCC, whereas combined analysis of SCC and CEA leads to a markedly increased sensitivity of 60% at primary diagnosis and of 79% in cases of tumor relapse.

Antigens, Neoplasm↗

PubMedDate not supplied

Anti-p53 antibodies in serum of smokers and head and neck cancer patients.

Inactivation of the p53 gene occurs in various tumors favouring the accumulation of genetic aberration. It is assumed that p53 protein can become immunogenic in stimulating the production of circulating anti p53 antibodies. Sera from 97 patients with primary and 30 patients with recurrent squamous cell carcinoma of the head and neck were examined for p53 autoantibodies with an enzyme-linked immunosorbent assay (ELISA). Sera from 42 patients with benign ENT-diseases and 28 healthy smokers served as the control. 38.1% (37/97) of the patients with primary and 36.6% (11/30) with recurrent SCCHN had autoantibodies to p53 in their serum. The evidence of p53 antibodies was not dependent on histological grading, T- or UICC stage of the disease. 24.2% (17/70) of the control group also had autoantibodies to p53 in the serum. The values of the control group and the patient group are so closely related, that p53 autoantibodies can not serve as a marker of malignancy. The indication for p53 measurement by ELISA should be very closely defined and limited.

Autoantibodies↗