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Biomedical subjects

B J Folz

Publications and source records attributed to B J Folz.

49 records · Page 3Linked to original sources

p53 serum antibodies as prognostic indicator in head and neck cancer.

p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients. The mechanism underlying the immunization process is still unclear. We investigated the incidence of p53 serum antibodies in 143 head and neck cancer patients with an enzyme-linked immunosorbent assay. The posttherapy course of two matched study groups (n = 38 each), one p53-antibody-seropositive and one p53-antibody-seronegative, was followed up for 24 months. Thirty-nine head and neck cancer patients (27.3%) were seropositive for p53 antibodies. During the follow-up, the p53-antibody-seropositive patients accounted for more local tumor recurrences (n = 12 versus n = 8) and more tumor-related deaths (n = 11 versus n = 5) than did seronegative patients, and second primary tumors (n = 9 versus n = 0) occurred exclusively in seropositive patients. In total, therapy failures (recurrences, tumor-related deaths, second primaries) were observed in 17/38 cases (44.7%) in the p53-antibody-seropositive group and in 8/38 cases (21.1%) in the p53-antibody-seronegative group. These results, after a follow-up of 2 years, seem to indicate a prognostic value of p53 serum antibodies for therapy failure in patients with head and neck cancer.

Adult↗

[Reproducibility of nonradioactive DDRT-PCR method for detection of gene expression in squamous epithelial carcinoma cells of the upper aerodigestive tract].

BACKGROUND: The analysis of the gene spectrum in tumor and normal cells may provide information about genes involved in the differentiation or in the genesis of tumors. Differential Display Reverse Transcriptase Polymerase Chain Reaction (DDRT-PCR) is an innovative method that enables quick analysis of almost all mRNA molecules expressed in the cells. METHODS: In the trials, the mRNAs of keratinocytes and tumor cells were amplified by a number of oligonucleotide pairs after reverse transcription and resolved on polyacrylamide gel. A modified protocol for the amplification of cDNA probes was devised for detecting PCR products with silver nitrate. RESULTS: After reverse transcription of mRNAs, all cDNA samples were successfully amplified using the protocol devised for the silver nitrate DDRT-PCR, and the differentially expressed fragments were reproducibly demonstrated. CONCLUSIONS: The high reproducibility and feasibility of silver nitrate DDRT-PCR expand the alternatives for analyzing gene expression and detecting selectively expressed genes in different kinds of cells.

Carcinoma, Squamous Cell↗

[Mucous membrane melanomas of the upper aerodigestive tract. An analysis of 34 cases].

BACKGROUND: Malignant mucosal melanoma of the upper aerodigestive tract is a rare disease. The prognosis is expected to be significantly worse than the prognosis of cutaneous melanoma and so far no uniform therapeutic concept exists. Publications about mucosal melanoma are scarce and reported patient groups are usually small. PATIENTS: Thirty-four patients have been registered at the ENT Department of the University of Kiel Medical Center with the diagnosis mentioned above. Clinical data were obtained from the patient's charts, the minimum follow-up was three years. RESULTS: Most common site of the tumor was the nasal cavity and paranasal sinuses with 28 of 34 patients. Less frequently affected was the nasopharynx (three cases), oropharynx, larynx, and middle ear (one case each). All patients were caucasians and most of them were of an advanced age (66.9 years +/- 12.3). Treatment of choice was surgical resection in 27 cases, in four cases it was combined with radiation therapy, in one case with radiation therapy and chemotherapy, and in three cases with chemotherapy. Six patients received solely radiation therapy, one patient was only treated by chemotherapy. Patients who were treated by a combined approach had a more favourable outcome than patients who were treated by a monotherapy of surgery, radiation therapy, or chemotherapy. A high number of recurrences were observed, which occurred on an average of 16.6 months after the diagnosis of the primary tumor. Overall 5-year survival was 45.8%, the 10-year survival rate was 22.3%. CONCLUSIONS: Optimized combined therapeutical approaches might possibly improve the prognosis of mucosal melanoma of the upper aerodigestive tract. Intervals between follow-ups should be short to render detection of relapses at an early stage. Repeated therapy of recurrent disease might lengthen survival.

Combined Modality Therapy↗

[Detection of differentially expressed genes in head-neck carcinomas].

BACKGROUND: Carcinogenesis is generally considered a multistage process based on many alterations of the genetic substance. These alterations lead to many qualitative and quantitative changes in gene expression with subsequent malignant transformation of the cell. Only a few of these genetic alterations are identified yet. METHODS: The differential display reverse transcriptase polymerase chain reaction was employed to detect differentially expressed genes in head and neck cancer. The mRNA expression of cultivated keratinocytes of the upper aerodigestive tract was compared to the one of cultivated squamous cell carcinoma cells of the larynx, hypopharynx, and floor of the mouth. RESULTS: A total of 116 differentially expressed gene fragments were identified. They were either solely expressed by the malignant cells or the keratinocytes or in just one carcinoma cell entity. Forty-three of the 116 DNA fragments were sequenced successfully. In four cases the specific differential expression was confirmed by Northern blot hybridisation in comparison to keratinocytes, normal mucosa, and 3 benign tumors from the head and neck region. A gene bank search revealed in three cases a homology of less than 20% to already known human, animal, bacterial or viral gene sequences and in one case a homology of 98% with a human gene sequence. CONCLUSIONS: The detected for squamous cell carcinoma of the head and neck specific genes or gene fragments are the basis for further investigations to better understand carcinogenesis.

Carcinoma, Squamous Cell↗

[Detection of serum soluble fragments of cytokeratins 8 and 18 in patients with squamous epithelial carcinomas of the upper aerodigestive tract].

BACKGROUND: During the development of squamous cell carcinomas of the head and neck (SCCHN), cytokeratin (CK) 18 and 19, which are typical for simple epithelia, show an elevated expression in tumor tissues. CK 8 was found to be overexpressed in cell lines of SCCHN. Epithelial tumors like normal epithelia express characteristic "pairs" of CK. The smallest of these pairs comprises CK 8 and 18. Therefore, the aim of this study was to serologically detect fragments of CK 8 and 18 (cyfra 8/18) in SCCHN patients. METHODS: Sera of 151 patients with SCCHN were tested for cyfra 8/18 (cyfra 8/18 ELISA medac, Hamburg) before treatment. Thirty sera of healthy volunteers and 43 sera of patients with benign diseases of the head and neck region served as control and reference group, respectively. Thirteen patients were followed-up clinically and serologically after surgery. The serum cyfra 8/18 concentrations of those 13 patients were compared to their clinical run. RESULTS: The cut-off value for cyfra 8/18 was determined with a 95% specificity of the reference group and was fixed at 1.1 ng/ml. The sensitivity was 7%. No correlation was found between cyfra 8/18 and clinical parameters like tumor stage, grading, and tumor location. Cyfra 8/18 concentrations could be correlated to the clinical run of 5 of 13 followed-up patients. CONCLUSIONS: Because of its low sensitivity, the serological detection of cyfra 8/18 must not be seen as a sufficient tumor marker for SCCHN. Its clinical applicability for regular post-surgical controls seems to be restricted and appears inferior to the clinical usefulness of cyfra 21-1.

Biomarkers, Tumor↗

Expression of a novel mRNA in human head and neck squamous cell carcinoma cells.

AIMS: The differential display reverse transcription polymerase chain reaction (DDRT-PCR) technique was used to search for differences between the mRNA expression profiles of squamous cell carcinoma (SCC) cell lines established from head and neck tumours and normal keratinocytes from the mucosa of the upper aerodigestive tract. METHODS: Total RNA prepared from both cell types was reverse transcribed into cDNA then amplified in a PCR mixture. To compare the electrophoretic patterns, mRNAs were amplified by nested PCR using specific oligonucleotides. Additionally, using labelled cDNA probes, northern hybridisation was carried out on three cancer cell lines of different origin, a biopsy from a parotid gland pleomorphic adenoma, healthy mucosa, and keratinocytes. RESULTS: Comparison of the separated bands revealed a fragment with a differential expression pattern in the SCC cells. This cloned sequence of a 336 base pair mRNA fragment exhibited no significant homology with known transcripts. Additionally, after amplification and sequencing of the 3' end of the fragment no homology with a known human gene sequence was found. However, low homology with a genomic sequence of a nematode was found. Northern hybridisation confirmed the selective expression of this fragment in SCC cells versus the cancer cell lines of different origin, the biopsy of the pleomorphic adenoma, keratinocytes, and healthy mucosa. CONCLUSIONS: This is the first differentially expressed human genome transcript of squamous cell carcinoma of the head and neck identified by DDRT-PCR. It may prove useful, in the future, to characterise this tumour type.

Base Sequence↗

Optimized differential display and reamplification parameters for silver staining.

Differential display (DD) is a powerful instrument to detect differences in gene expression of malignant and normal cells. An optimized silver staining protocol was used to compare mRNA expression of keratinocytes and squamous cell carcinoma cells of the head and neck. Optimal concentration for upstream and downstream primer was 0.2 microM. Best primer concentrations for reamplification were between 40 and 60 pM. With this optimized protocol nearly 50 differentially expressed transcripts have been identified and differential display can be applied safer, easier, and faster, than by radioactive labeling.

Carcinoma, Squamous Cell↗

[Monoclonal antibodies against squamous epithelial carcinomas of the upper aerodigestive tract].

BACKGROUND: Squamous cell carcinoma is the most common cancer of the head and neck. The application of monoclonal hybridoma technology to the identification and characterization of molecules preferentially expressed in carcinoma cells may provide potentially important diagnostic and therapeutic tools. METHODS: After immunization of mice with viable squamous cell carcinoma cells derived from human tumors of the upper aerodigestive tract hybridomas were selectively grown for production of monoclonal antibodies. Monoclonal antibodies produced by 690 hybridoma clones were tested on immunoreactions with frozen sections of human squamous cell carcinoma and reactive tonsils. RESULTS: Immunohistochemical trials showed that monoclonal antibodies produced by hybridoma clone K-640 are strongly accumulated at the plasma membrane whereas no immunoreaction in squamous epithelium of the tonsil could be detected. By means of ELISA it could be shown that these antibodies belong to the class of IgM. Immunoblotting revealed that the antibodies recognize antigenes with approximate molecular weights of 52 and 54 kD. CONCLUSIONS: The experiments suggest that the hybridoma clone K-640 produces antibodies which bind to the plasmamembrane of the tumor cells. Further recloning steps of this hybridoma clone could possibly enhance the specificity of these antibodies for squamous cell carcinoma.

Animals↗

CYFRA 8/18 in head and neck cancer.

BACKGROUND: Cytokeratins (Ck) 8, 18 and 19 that are normally expressed in head and neck tissue in only small amounts, become overexpressed in head and neck squamous cell cancerous tissue. It was questioned whether Ck 8 and 18, which occur together, were also detectable and of value as a tumor markers for this cancer entity. MATERIALS AND METHODS: One hundred forty-nine sera from patients with squamous cell carcinoma of the head and neck (SCCHN) were investigated with a novel ELISA kit for the detection of fragments of Ck 8 and 18. Twenty-five sera from healthy volunteers and 39 patients with benign diseases of the head and neck region served as controls. RESULTS: It was found that CYFRA 8/18 had a sensitivity of 7%. CYFRA 8/18 values did not show a correlation with clinical parameters. CONCLUSIONS: Because of a low sensitivity CYFRA 8/18 seems not to be of value as a tumor marker for SCCHN.

Biomarkers, Tumor↗

A new prognostic indicator for head and neck cancer--p53 serum antibodies?

BACKGROUND: p53 antibodies are a new serological parameter of unknown potential in patients with malignancies. Their occurrence has been described in various types of cancer patients and several studies in head and neck cancer patients and other cancer patient groups have indicated its prognostic value. MATERIAL AND METHODS: We investigated the incidence of p53 serum antibodies in 271 head and neck cancer patients with an ELISA and investigated a possible correlation with clinical parameters like tumor staging and grading. RESULTS: Sixty-seven head and neck cancer patients (24.7%) were seropositive for p53 antibodies. No correlation between p53 antibody status, tumor staging and grading was found. CONCLUSIONS: These results indicate that the occurrence of p53 antibodies does not correlate with the most relevant prognostic factors, rate of regional metastasis and primary tumor size, in patients with head and neck cancer.

Autoantibodies↗

The influence of differing dissection techniques on p53 as a possible indicator for local recurrences in carcinomas of the upper aerodigestive tract.

BACKGROUND: A correlation between the occurrence of p53 protein in margins after tumor resection has been proposed as indicator for recurrence. This study should clarify whether differences occur in p53 protein detection after laser surgery as opposed to surgery with the scalpel. MATERIAL AND METHODS: Healthy mucosa of the oropharynx (n = 28) and squamous cell carcinoma of the head and neck (SCCHN) (n = 19) were excised with scalpel, CO2 and Nd:YAG laser and then examined for the presence of p53 protein with immunohistochemistry and ELISA. RESULTS: The occurrence of p53 protein in SCCHN was dependent on the applied resection technique. In lasersurgically excised tissue only a small zone adjacent to the cutting edge was found to be negative for p53. This zone of necrosis was smaller in margins after CO2 than after Nd:YAG laser resection. CONCLUSIONS: Lasersurgical excision does only inhibit the detection of p53 in the zone of necrosis.

Adult↗

Bipolar radiofrequency induced thermotherapeutic volumetric reduction of VX2 metastases in an animal model.

BACKGROUND: Radiofrequency-induced thermotherapy has shown promising results in the palliative treatment of various tumor entities. The purpose of this study was to investigate the effectiveness of bipolar radiofrequency volumetric tissue reduction (VTR) on lymph node (LN) metastases in the VX2 SCC model. MATERIALS AND METHODS: Six male New Zealand white rabbits, with palpable metastatic disease within the parotid lymph nodes, were treated using the Celon-ProSurge probe, needle length 10 mm, diameter of 2.3 mm. The animals were sacrificed on the 4th, 8th, 11th, 14th, 18th and 22nd postoperative days respectively. RESULTS AND CONCLUSION: Bipolar radiofrequency VTR could prevent progression of local metastatic disease in one-third of the animals compared to the control group of untreated VX2 carcinoma rabbits. These results encourage further studies, directed at whether this treatment modality could play a role in the palliative therapy of metastatic LN. Future studies should concentrate on the refinement of the treatment parameters and optimization of the treatment duration.

Animals↗

The soluble interleukin-2 receptor--a marker for squamous cell carcinoma of the upper aerodigestive tract.

Various studies indicate that the soluble interleukin-2 receptor (sIL-2R) is of value as marker in chronic and malignant disorders. No data are available on sIL-2R levels in head and neck cancer. The serum of 86 patients with squamous cell carcinoma of the head and neck (SCCHN) prior to any therapy and of 25 healthy controls was taken. Six month later the serum of 49 patients was taken again. sIL-2R levels were determined with ELISA. Patients with SCCHN prior to therapy had significantly elevated sIL-2R serum levels (895 U/ml) compared to controls (437 U/ml). After an eight month follow up 78.4% of the SCCHN patients with tumor recurrence had increased and 80% of the carcinoma patients without recurrence had decreased sIL-2R levels compared to prior to therapy. sIL-2R seems to be an unspecific marker for SCCHN and may be of prognostic value.

Biomarkers, Tumor↗