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Biomedical subjects

G J Hordijk

Publications and source records attributed to G J Hordijk.

At least 19 recordsLinked to original sources
PubMed1996

Radioresistance and p53 status of T2 laryngeal carcinoma. Analysis by immunohistochemistry and denaturing gradient gel electrophoresis.

BACKGROUND: Animal experiments and tumor cell line studies have shown that p53 alterations can cause radioresistance. This has not yet been demonstrated in patient groups. METHODS: We report p53 status in 20 patients with T2 laryngeal carcinoma and recurrent disease after curative therapy. The control group consisted of 16 patients with T2 laryngeal carcinoma without recurrent disease. The p53 gene (exons 5 to 9) was analyzed by Denaturing Gradient Gel Electrophoresis (DGGE). Expression of p53 in biopsy material was visualized by immunohistochemistry (monoclonal antibody BP 53-12-1). RESULTS: The group with recurrent disease showed a mutation in 9 cases (45%) and overexpression in 14 cases (70%). In 17 cases (85%) either mutation or overexpression was found. The control group showed a mutation in 7 cases (44%) and overexpression in 14 cases (88%). In 14 cases (88%) either mutation or overexpression was found. Adding up both groups a discordance of 50% was found between both detection techniques. The same mutated exon was found in 6 patients (66%) in both primary and recurrent tumors. CONCLUSIONS: A discordance between immunohistochemistry and DGGE exists in 50% of the cases. Assuming that both p53 mutation and p53 overexpression are indicative of a disturbed p53 checkpoint system, 31 cases (86%) in both groups show an alteration of the p53 system. No significant difference in p53 status in patients with or without recurrent disease exists. Analysis of the p53 status is not of prognostic significance for irradiation as primary treatment.

Adult↗
PubMed1996

Optimal regimes for local IL-2 tumour therapy.

In this report we present studies on optimal regimes for regional IL-2 therapy, focused on dose, schedule and site of injection. Original data obtained in 2 murine tumour models show that all 3 factors are of importance. Anti-tumour responses were most effective when IL-2 was administered regionally 5 to 10 times, at doses ranging from 7,000 to 33,000 IU/day every day or every other day. This resulted in cure rates of more than 40% in mice bearing ascitic tumour that had also disseminated to liver and lungs. The importance of these data is discussed in the light of previous results of our group. These results illustrate that the doses and schedules used in this study are not effective exclusively in these 2 tumour models but may have a more general applicability.

Animals↗
PubMed1996

Discordance of p53 status in matched primary tumours and metastases in head and neck squamous cell carcinoma patients.

To study the use of p53 as a diagnostic tool in head and neck squamous cell carcinoma (HNSCC), we analysed 15 primary tumours (PT) and matched lymph node metastases (LNM) for overexpression and mutations of p53. The primary goal was to study whether differentiation between primary and metastatic disease through their p53 status would be possible. Immunohistochemistry for p53 protein (antibody BP 53-12-1) was performed. Mutations of the p53 gene were detected by exon-specific amplification of DNA (exons 4-9), followed by exon analysis using denaturing gradient gel electrophoresis (DGGE). Mutant exons were sequenced. p53 overexpression was detected in seven (47%) of the PT and in seven (47%) of the LNM. 6 patients (40%) exhibited p53 protein overexpression in both PT and LNM. 2 patients had a different p53 protein expression in each sample. Mutations in the p53 gene were detected in 6 patients (40%) in the PT and in 7 patients (47%) in the LNM. In 2 patients (13%), the same mutation was found in the PT and in the LNM. 9 patients (60%) had a different mutation in each sample. We conclude that a poor correlation exists between p53 protein overexpression and p53 gene mutation in HNSCC. Also, a poor correlation for both detection techniques exists, when PT and LNM are compared. The p53 status may seem to differ between PT and LNM because of polyclonality in the PT. More sensitive detection techniques could be promising.

Base Sequence↗
PubMed1996

Autopsy findings in patients with head and neck squamous cell cancer and their therapeutic relevance.

A series of 63 autopsied patients with a history of head and neck squamous cell cancer (HNSCC) is reported with emphasis on the importance of locoregional disease (LRD) versus distant metastasis (DM) in the terminal course of the disease. There were 49 males and 14 females; mean age 64.9 years (range 35-94 years). Locoregional disease was present in 39 patients (62%), in 25 (40%) without tumour at other body sites outside the head and neck region. Distant metastasis was observed in 15 patients (24%); in 12 (19%), it occurred with concomitant LRD. Second primary tumours (SPT) were observed in 20 patients (32%). They occurred in the head and neck region (n = 7; 11%), the lung (n = 9; 14%) and at miscellaneous other sites (n = 4; 6%). Of the 13 patients with SPT outside the head and neck region, 2 had concomitant LRD. 11 patients (17%) died due to other causes, no tumour being found at autopsy. These figures indicate that still a major part of HNSCC patients die with LRD as the single tumour manifestation, which means that improvement of local tumour control will result in a significant therapeutic gain.

Adult↗
PubMed1995

Clinical relevance of protein-tyrosine (de-)phosphorylation in head and neck cancer.

Previous studies have shown that protein tyrosine (de)phosphorylation plays an important role in head and neck cancer. Protein-tyrosine kinases (PTK) and protein-tyrosine phosphatases (PTPase) activities in the cytosol of tumor tissue were significantly increased compared to normal tissue of cancer patients as well as controls. Additionally, the enzyme activities in normal tissue of tumor patients were significantly higher than enzyme activities in normal tissue of the control group. In this paper, we have correlated the cytosolic and membranous PTK and PTPase activity of tumor and nontumor tissue with several clinical and histological parameters known to influence the clinical outcome. Furthermore, we have analyzed the value of the enzyme activities as an independent predictor of clinical behavior and occurrence of second primary tumors. We confirmed our earlier observations that cytosolic and membranous PTK activities and cytosolic PTPase activities in tumor tissues are increased compared to activities in nontumor tissues and controls. Moreover, we also confirmed the findings of increased enzyme activities in nontumor tissues compared to findings in control tissues. This finding in histologically proven healthy mucosa is highly interesting because it indicates that these biochemical changes are obviously not (yet) translated into morphological changes. Significant differences were found in membranous PTK activity when the patients were grouped by sex, tumor localization, lymph node metastasis, and previous radiotherapy. During the follow-up period, no relation could be found between enzyme activities in tumor and/or nontumor tissues and disease-free interval or occurrence of second primary tumors.

Adult↗
PubMed1995

Aberrant tyrosine phosphorylation in head and neck tumours and potentially premalignant tissues.

Protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTPase) activity in tumor tissue, obtained from 107 patients with squamous cell carcinoma of the upper aerodigestive tract, was determined. In 79 patients samples were also taken from a histologically proven non-tumourous part of the mucosa. In this extensive study we confirmed our previous findings of increased enzyme activities (cytosol PTK, membranes PTK, cytosol PTPase) in non-tumour tissues compared with control tissues. These biochemical changes suggesting a premalignant mucosa could not be correlated to a higher probability of secondary tumours.

Carcinoma, Squamous Cell↗
PubMed1995

Microbiology of chronic maxillary sinusitis in adults: isolated aerobic and anaerobic bacteria and their susceptibility to twenty antibiotics.

In a comparative study on the efficacy of two surgical treatment procedures, 90 patients diagnosed with chronic maxillary sinusitis received antimicrobial prophylaxis. Maxillary sinus fluid samples were taken from these 90 patients before the initiation of antimicrobial prophylaxis, and were cultured for aerobic and anaerobic bacteria. In 81% of all samples, bacterial growth was present. Anaerobic bacteria were present in 29% of the cases (5% pure anaerobic and 24% mixed aerobic and anaerobic). Predominant aerobic bacteria were staphylococci, in 42% of all samples (mainly coagulase-negative), and streptococci (32%). Predominant anaerobic bacteria were Propionibacterium species (18%) and Gram-negative rods (9%). The antimicrobial susceptibility was determined for 20 antibiotics, and the beta-lactamase production was investigated. The prevalence of beta-lactamase-producing bacteria was unexpectedly high (isolated from 36% of all patients). The findings in this study indicate that not all antimicrobial agents used against upper respiratory tract infections are suitable for treatment of this group of patients when the susceptibility of bacteria present in sinus fluid is taken into account. The high prevalence of beta-lactamase-producing bacteria could influence the course of the disease, due to the breakdown of antibiotics by such strains. Recommendations are given for criteria to use when choosing antimicrobial agents to treat bacterial infections it) patients with chronic maxillary sinusitis.

Adolescent↗
PubMed1995

Degree of tumour differentiation as a prognostic factor in advanced laryngeal cancer.

Degree of tumour differentiation as a prognostic factor in advanced laryngeal cancer. As part of a retrospective analysis on treatment results in 139 patients with advanced laryngeal squamous cell carcinoma (T3-4) differentiation grade of the tumour was analyzed as a prognostic factor. Univariate analysis differentiation grade was related to tumour size, presence of neck node metastasis and conversion of N-stage during follow-up. For statistical analysis, patients with G1-G2 and G3-G4 were grouped. Prognosis for G3-G4 carcinomas is significantly worse for disease specific survival (p < 0.025), due to significantly more regional recurrence (p = 0.05). At multivariate analysis it turned out that regional control and disease specific survival in patients with no palpable neck nodes were adversely affected by the histological degree of differentiation of the diagnostic biopsy. For this group of patients extensive treatment of neck nodes is recommended.

Adult↗
PubMed1994

Treatment of localized non-Hodgkin's lymphomas of the head and neck.

BACKGROUND: Localized non-Hodgkin's lymphomas of the head and neck are generally treated with radiotherapy with or without chemotherapy, although the results of treatment of localized non-Hodgkin's lymphomas with of treatment of localized non-Hodgkin's lymphomas with chemotherapy alone appear to be favorable. It is unclear if and when combined modality therapy should be used. METHODS: The authors reviewed the records of 53 patients with Stage I or II non-Hodgkin's lymphoma of the head and neck, who were treated with radiotherapy alone (13 patients), chemotherapy according to the cyclophosphamide, doxorubicin, vincristine, prednisone- (CHOP) regimen (27 patients), or a combination of both treatments (13 patients). RESULTS: A complete remission was achieved in 43 (81%) patients. The 5-year survival for all patients was 78%. A significant difference (P = 0.03) in 5-year relapse-free survival was observed between Stages I and II disease, of 92 and 60%, respectively. Extensive tumor was a significantly poor prognostic factor (P = 0.04) with a 5-year relapse-free survival of 52 versus 84% for patients with nonextensive lymphoma. Eight relapses occurred; in five patients, a local relapse was the first presentation. Although salvage radiotherapy was successful in these five patients, a distant relapse developed in three. No relapses were observed in previously irradiated areas. CONCLUSIONS: Our results suggest that radiotherapy alone is the appropriate treatment for nonextensive Stage I intermediate grade non-Hodgkin's lymphoma of the head and neck. For extensive Stage I or II non-Hodgkin's lymphomas, chemotherapy is preferable. The value of combined modality therapy remains unclear.

Adult↗
PubMed1994

Protein tyrosine (de-)phosphorylation in head and neck squamous cell carcinoma.

Protein phosphorylation plays an important role in signal transduction of both normal and neoplastic cells. Since increased protein tyrosine phosphorylation may be associated with malignant transformation, we studied the activities of protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTPase) in patients with various head and neck tumors. Furthermore, we determined the patterns of tyrosine phosphorylated protein (P-tyr) in tissues by western blotting. Enzyme activities were studied in tumor and histologically normal, non-tumorous tissues of 54 patients and in 11 controls. P-tyr patterns were determined in 3 patients and 2 controls. PTK and PTPase activities were greater in tumor tissues than in normal tissue of the cancer patients as well as controls. P-tyr levels in tumors were also higher than in normal tissues. Additionally, PTK activity in normal tissue of tumor patients was significantly higher than in normal tissue of the control group. The same trend was observed for the PTPase activity and P-tyr levels.

Adult↗
PubMed1994

The presence of p53 protein in relation to Ki-67 as cellular proliferation marker in head and neck squamous cell carcinoma and adjacent dysplastic mucosa.

Paraffin embedded material from 15 patients suffering from head and neck squamous cell carcinoma (HNSCC) bordered by dysplastic mucosal areas was immunohistochemically investigated for the presence of p53 protein and Ki-67 proliferation marker. p53 protein was present in 9 cases (60%), invariably in invasive cancer areas as well as in adjacent non-invasive dysplastic mucosa. Only cells exhibiting atypia contained p53 protein. Ki-67 proliferation marker was present in the basal cells of the normal epithelium and more extensive in dysplasias and HNSCC. The presence of Ki-67 closely coincided with p53 protein in the 9 cases exhibiting this. No differences in Ki-67 expression were found between p53 positive and negative cases. It is concluded that the appearance of p53 protein occurs early in carcinogenesis but that cells also may show increased proliferation without involving immunohistochemically detectable alterations in the p53 gene.

Adult↗
PubMed1994

Persistence of middle ear dysfunction after recurrent acute otitis media.

The presence of otitis media with effusion (OME) and high negative pressure (-200 to -400 mm H2O), were investigated in the follow-up of a randomized double-blind placebo-controlled trial on the efficacy of amoxicillin/clavulanic acid in the treatment of acute otitis media. All children in this study were recruited from a general practice population. Tympanometry results 1 month from the start of an episode of acute otitis media were taken as outcome criteria. Bilateral middle ear dysfunction was defined as bilateral OME, unilateral OME and contralateral or bilateral high negative pressure. Bilateral middle ear dysfunction was present in 47.9% of the patients. Of all the investigated factors of possible influence (age, sex, season, laterality of acute otitis media, therapy, and clinical course of acute otitis media), only season showed a statistically significant influence on the persistence of OME/high negative pressure (P = 0.001). Bilateral middle ear dysfunction was shown to be of prognostic value for the risk of a recurrence of acute otitis media (odds ratio 3.75).

Acoustic Impedance Tests↗
PubMed1994

Is antibiotic treatment of chronic sinusitis effective in children?

A double-blind randomized controlled trial on 79 patients aged between 2 and 12 years with chronic sinusitis showed no significant advantage of adding antibiotics to the treatment by sinus lavage. The prognosis after both 6 and 12 weeks was worse for patients with bilateral opaque sinus radiographs. Half of the Branhanmella catarrhalis cultured in this study were beta-lactamase producing organisms, therefore antibiotics prescribed for this group of children should be chosen bearing this in mind.

Cefaclor↗
PubMed1993

Protein tyrosine kinase activity in laryngeal squamous cell carcinoma.

Oncogenes play an important role in the process of malignant transformation. Since many of the protein tyrosine kinases (PTK) are products of oncogenes, the aim of this study was to demonstrate whether an increased PTK activity could be found in head and neck tumors. By using a non-radioactive dot-blot assay, PTK activity was measured in tumor and normal tissues of 38 patients with laryngeal cancer. The control group consisted of 19 healthy persons. PTK activity in tumor cells was significantly higher (P < 0.001) than in normal cells of the tumor patients and normal controls. Additionally, the PTK activity in the normal mucosa of the tumor patients was significantly higher than in the normal mucosa of the control group.

Carcinoma, Squamous Cell↗
PubMed1993

The value of twice yearly bronchoscopy in the work-up and follow-up of patients with laryngeal cancer.

The aim of this retrospective study was to investigate the usefulness and feasibility of twice-yearly bronchoscopy and sputum cytology in patients with laryngeal cancer. In 170 selected patients, 500 (both initial and during follow-up) bronchoscopies were performed. There was a maximum follow-up of 34 months. 5 (2.8%) male patients developed lung cancer. In only 2 of them was the diagnosis based on bronchoscopy alone. After treatment with curative intent, both patients developed a recurrent lung carcinoma. According to most patients' experience, regular bronchoscopy is unpleasant. It is concluded that twice-yearly bronchoscopy and sputum cytology in patients with laryngeal cancer is not useful as a routine procedure. At present, chemoprevention of second primary tumours seems the most promising adjunctive treatment modality.

Adult↗
PubMed1993

Uni- and multivariate analysis of eight indications for post-operative radiotherapy and their significance for local-regional cure in advanced head and neck cancer.

Eighty consecutive patients with advanced head and neck cancer were treated with combined therapy of radical surgery and post-operative radiotherapy. Indications for post-operative radiotherapy were pathological staging of the primary tumour (pT3 or pT4), poorly differentiated or undifferentiated carcinoma (G3, G4), tumour thickness, tumour invasion in the surrounding tissues with slender tumour strands and solitary tumour cells, perineural spread, lymphangio-invasive tumour growth, multiple positive neck nodes or extranodal spread, and microscopical irradicality of the surgical margins. The contribution for prognosis of these indications for post-operative radiotherapy were retrospectively calculated in an univariate and multivariate analysis. Of all investigated parameters, the mode of tumour invasion and lymphangio-invasive growth were independent prognostic factors. If these unfavourable prognostic signs are present, post-operative radiotherapy has to be intensified to at least curative doses of 66 Gy or more to the areas at risk.

Combined Modality Therapy↗