PubMed Health⌕ Search

Biomedical subjects

N Van Zandwijk

Publications and source records attributed to N Van Zandwijk.

At least 19 recordsLinked to original sources
PubMed1998

Differences in aromatic-DNA adduct levels between alveolar macrophages and subpopulations of white blood cells from smokers.

The 32P-post-labelling assay for DNA adduct quantification gives the opportunity to examine endogenous exposure to DNA reactive compounds. Most human biomonitoring studies applied white blood cells (WBC) or cells obtained by broncho-alveolar lavages (BAL) as source of DNA, but still it is not clear what cell type represents the most reliable indicator for exposure to cigarette smoke-associated genotoxins. At first, we examined DNA adduct levels by means of nuclease P1 (NP1) enriched 32P-post-labelling in separated WBC subpopulations after in vitro incubations for 18 h with 10 microM benzo[a]pyrene (B[a]P). DNA adduct levels were highest in monocytes (10.7 +/- 2.9 adducts/10(8) nucleotides, n = 8), followed by lymphocytes (5.9 +/- 1.7, n = 8), and granulocytes (0.5 +/- 0.2, n = 8). Secondly, aromatic-DNA adduct levels were determined in BAL cells and WBC-subsets from (non-)smoking volunteers. In smoking individuals, adduct levels were in the ranking order: BAL cells (3.7 +/- 1.0, n = 5) > monocytes (2.0 +/- 0.5, n = 8) > or = lymphocytes (1.6 +/- 0.4, n = 8) > granulocytes (0.8 +/- 0.2, n = 8) by NP1-enrichment and monocytes (9.0 +/- 3.2, n = 5) > or = lymphocytes (8.0 +/- 2.1, n = 6) > granulocytes (2.1 +/- 0.3, n = 7) by butanol-enriched 32P-post-labelling. Aromatic-DNA adduct levels were significantly higher in WBC-subsets of smokers as compared with non-smokers, except for DNA adducts in granulocytes using butanol enrichment. Thirdly, dose-response relationships were investigated in mononuclear white blood cells (MNC, i.e. monocytes plus lymphocytes) and BAL-cells of a larger group of smoking individuals (n = 78). Adduct levels in MNC were related to daily exposure to cigarette-tar (r = 0.31, P < 0.01). Adduct levels in BAL cells seemed to be correlated with pack-years, but after correction for age this relationship was lost. Butanol extraction resulted in 5-6-fold higher DNA adduct levels in MNC, whereas butanol extraction of BAL-DNA of the same individuals yielded only 2-fold higher adduct levels. The two enrichment procedures of 32P-post-labelling were correlated in BAL cells (r = 0.86, P < 0.001, n = 12). We conclude that particularly MNC are good surrogates for the detection of smoking-related DNA adducts.

Adult↗
PubMed1998

The role of prognostic factors and oncogenes in the detection and management of non-small-cell lung cancer.

Like other epithelial tumors, non-small-cell lung cancer (NSCLC) is a result of a series of genetic and epigenetic changes that eventually progress to invasive cancer. The order and timing of these changes, involving specific chromosomal locations, oncogenes, and tumor-suppressor genes, have become important areas of translational research. It is hoped that this research will lead to "very early" diagnosis and "very early" treatment of non-small-cell lung cancer, and to the identification of patients with poor prognostic tumor characteristics who may be helped by additional treatment. The recognition of persons with inherited predisposition to lung cancer is also on the horizon, and, together with the molecular characterization of lung cancer, brings with it a promise of improved treatment results.

Biomarkers↗
PubMed1997

32P-postlabelling of aromatic DNA adducts in white blood cells and alveolar macrophages of smokers: saturation at high exposures.

DNA adducts may serve as a molecular dosimeter of exposure to cigarette smoke-associated carcinogens such as polycyclic aromatic hydrocarbons (PAH). Target tissues for cigarette smoke-induced carcinogenesis are rarely accessible; therefore, peripheral blood cells or cells obtained by bronchoalveolar lavage (BAL) may be used as surrogate sources of exposed DNA. However, the relationship between cigarette smoke exposure and aromatic-DNA adducts in white blood cells and BAL cells is still unclear. In this study, we examined DNA adduct formation in lymphocytes and BAL cells in several populations of smoking individuals by means of 32P-postlabelling. Significant correlations between the amount of cigarettes smoked per day and the level of aromatic-DNA adducts were found in lymphocytes. In BAL cells, DNA adduct levels were associated with age (p = 0.05) and gender (p = 0.10) after adjustment for smoking behaviour. Adduct formation levelled off at higher exposure levels, suggesting less efficient adduct formation; decreases in the formation of adducts per unit of exposure were found in lymphocytes (r(s) = -0.80, p < 0.001) and BAL cells (r(s) = -0.72, p < 0.001). To assess intra-individual variation in adduct levels at constant smoking behaviour, sampling was repeated after a period of 2 and 6 months. In lymphocytes, repeated measurements with an interval of 2 months were highly correlated (r = 0.84, p = 0.009, n = 8), whereas repeated measurements with an interval of 6 months showed no correlation (r = 0.30, p = 0.27, n = 16). Repeated measurements in BAL cells showed a significant correlation after 6 months (r = 0.68, p = 0.03, n = 10). Furthermore, in a group of occupationally exposed aluminium workers, adduct levels in total white blood cells were correlated with the average concentrations of PAH in the ambient air of workers who smoked cigarettes, whereas in non-smokers, no such relationship was found. We conclude that cigarette smoking may directly or indirectly influence DNA adduct levels and saturation of DNA adduct formation may occur, leading to non-linear dose-response relationships.

Adult↗
PubMed1997

Cisplatin/paclitaxel vs cisplatin/teniposide for advanced non-small-cell lung cancer. The EORTC Lung Cancer Cooperative Group. The European Organization for Research and Treatment of Cancer.

A total of 332 patients with advanced non-small-cell lung cancer were randomized by the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC) to receive one of two cisplatin (Platinol)-based chemotherapy regimens: Paclitaxel (Taxol) 175 mg/m2 given by 3-hour infusion followed by cisplatin 80 mg/m2 on day 1; Or cisplatin 80 mg/m2 on day 1, followed by teniposide (Vumon) 100 mg/m2 given on days 1, 3, and 5. Cycles were repeated every 3 weeks. Preliminary analysis of the results of this phase III trial shows that hematologic toxicity was decidedly more severe in the group treated with cisplatin/teniposide than in those given paclitaxel/cisplatin. Of 264 patients evaluable so far, responses have been observed in 47% of those given paclitaxel and in 29% of those treated with teniposide. However, extramural radiologic response evaluation is still under way, so these figures are expected to change somewhat. It appears clear that the paclitaxel-based therapy affords a benefit in terms of response and toxicity, but survival results are premature and any definite conclusions await final analysis.

Adolescent↗
PubMed1995

Heat and moisture exchangers as a treatment option in the post-operative rehabilitation of laryngectomized patients.

A multi-institutional, prospective clinical study was undertaken to investigate whether the use of a heat and moisture exchanger (HME) in the period following total laryngectomy could prevent the development or reduce the severity of respiratory symptoms. Fifty-nine patients from three hospitals were provided with HMEs, either immediately post-surgery or, in the case of post-surgical radiotherapy, upon completion of the radiotherapy. For the total sample (n = 59) statistically significant improvements over time (between 3 and 6 months) could be found in forced expectoration (P < 0.05), in the perceived voice quality (P < 0.001), social anxiety (P < 0.001), social interactions (P < 0.001) and in feelings of anxiety and depression (P < 0.05). Repeated measures analysis of variance indicated statistically significant group differences over time in forced expectoration and stoma cleaning (P < 0.05). No statistically significant differences over time were noted between the regular and non(regular) HME user groups in voice quality or in various aspects of daily living.

Humans↗
PubMed1995

Long-term pulmonary function after total laryngectomy.

In 58 laryngectomized patients pulmonary function tests were performed during a routine visit to the outpatient clinic. The assessment of pulmonary function with an extratracheal device could easily and reliably be accomplished in all instances. The results show that in long-term follow-up post-laryngectomy expiratory lung function values are significantly lower than predicted. Of the various subjective respiratory complaints, only a higher frequency of coughing was statistically significantly associated with decreased lung function values (P < 0.01). Neither time since surgery (> 1 year vs < 1 year), nor radiation therapy seemed to be correlated with the pulmonary function outcomes. In contrast, the age of the patient did have a significant influence. Although an age-related decline in pulmonary function is a well documented phenomenon, an additional adverse effect was suggested by the present series in the group who was over 65 years of age. Bronchodilator treatment was found to significantly ameliorate several pulmonary function parameters in a sub-group of 18 patients. It may be concluded, that after total laryngectomy significant abnormalities in pulmonary function have to be anticipated. We have found that these disturbances seem to be more pronounced with increasing age.

Age Factors↗
PubMed1991

Activity of intrapleural recombinant gamma-interferon in malignant mesothelioma.

Twenty-two consecutive patients with malignant diffuse pleural mesothelioma were treated with recombinant gamma-interferon by the intrapleural route. Diagnosis was made by thoracoscopic examination and all cases were confirmed by the French Mesothelioma Panel of Pathologist. Patients were staged based on thoracoscopic examination and computed tomography (CT) scan: 12 patients were classified as Stage I and 10 were Stage II. A solution of gamma-interferon (40 X 106 U) was infused twice a week over 2 months. Every patient experienced fever. One patient had a Grade 2 leukopenia and one patient suffered from pleural empyema. Response evaluation was based on the following: (1) CT scan performed 2 weeks after treatment ended, and (2) repeat thoracoscopic examination with histopathologic verification in nine patients who had demonstrated a stabilization or a regression of the disease on CT scan. From the original group, 19 patients could be evaluated. Four complete thoracoscopic histopathologic responses and one partial response were observed in Stage I patients (56%). One partial response was observed in Stage II patients.

Alkaline Phosphatase↗
PubMed1991

Neural cell adhesion molecule expression, neuroendocrine differentiation and prognosis in lung carcinoma.

We investigated the expression of the neural cell adhesion molecule (NCAM) in a series of surgically resected lung carcinomas of various histological subtypes by means of a panel of monoclonal antibodies recognising different N-CAM epitopes. In a subgroup of 56 tumours, the results of immunostaining with MAb 123C3--the antibody studied most extensively in our material--were compared to the ultrastructure, and in 231 radically resected non-small cell carcinomas, with histological tumour type and with clinical follow-up data. N-CAM expression was not limited to neuroendocrine tumours, as assessed ultrastructurally. Non-small cell lung carcinomas positive for MAb 123C3 showed post-operative overall and disease-free survival times significantly shorter than 123C3-negative non-small cell carcinomas.

Antibodies, Monoclonal↗
PubMed1990

Physical and psychosocial consequences of total laryngectomy.

The incidence and severity of respiratory symptoms after total laryngectomy and their influence on daily living were studied in 59 laryngectomized patients. Daily sputum production was the principal complaint of these patients (98%), followed by coughing (64%) and the need for frequent forced expectoration (more than 5 times a day) in order to clear the airway (57%). Frequent stoma cleaning (more than 5 times a day) was required by 37% of the patients. Significant correlation was found between respiratory symptoms, voice rehabilitation and several aspects of daily living, including fatigue, sleep problems, social contacts and psychological distress. These findings indicate that respiratory symptoms after total laryngectomy are both frequent and troublesome. The development of effective methods for minimizing and/or preventing such respiratory problems would contribute significantly to improving the quality of life of laryngectomized patients.

Aged↗
PubMed1986

Prevalence of neuroendocrine granules in small cell lung carcinoma. Usefulness of electron microscopy in lung cancer classification.

Fifty-four lung carcinomas submitted for routine electron microscopy under the light microscopical diagnosis of small cell carcinoma were investigated. In 42 or of 45 evaluable cases, neuroendocrine granules were considered definitely or probably present, the modification 'probably' being necessary in suboptimal material. In three cases, squamous cell differentiation was seen, but no neuroendocrine granules were found. On revision of these three cases, the light microscopical diagnosis was changed to squamous cell carcinoma in one instance, and neither of the other two cases was considered classical for small cell carcinoma. Patient follow-up of these three cases showed tumour behaviour indicative of non-small cell carcinoma in two evaluable cases, the third case yielding no significant data. These results indicate that neuroendocrine granules can generally be found in small cell lung carcinomas, provided the material is sufficient for evaluation. When these granules are absent, and other differentiation is found on electron microscopy, the final classification of the tumour should incorporate this finding, to warn the clinician that the tumour will not necessarily behave as a small cell carcinoma.

Carcinoma, Small Cell↗
PubMed1986

The 'grey area' between small cell and non-small cell lung carcinomas. Light and electron microscopy versus clinical data in 14 cases.

We studied 14 lung tumours which on light microscopy had posed difficulties on classification as either small cell or non-small cell carcinomas. The light and electron microscopical features were compared with patient follow-up data. Electron microscopy showed neuroendocrine granules in 12 cases, and adeno- and squamous cell differentiation but no neuroendocrine granules in the remaining two cases. The latter two cases showed prolonged patient survival (both patients alive after 2 1/2 and 2 years, respectively). Ten of the cases with neuroendocrine granules showed a rapid course of disease (death between 2 1/2 weeks and 15 months after diagnosis) and marked initial response to multiagent chemotherapy. Thus, the clinical impression of these cases was that of small cell carcinoma. The remaining two cases with neuroendocrine granules showed a more protracted course, with death after 1 1/2 and 2 1/2 years. These two tumours did not show the light microscopical features of atypical carcinoid. The results illustrate the value of electron microscopy in predicting clinical behaviour of carcinomas difficult to place into small cell or non-small cell carcinoma groups. They also point to the existence of neuroendocrine carcinomas other than carcinoids with a more protracted course than small cell carcinomas.

Adult↗
PubMed1986

N-isopropyl-p[123I]iodoamphetamine, a new agent for lung imaging studies.

N-isopropyl-p[123I]iodoamphetamine, originally designed for brain scintigraphy, has been found to be retained by the normal lung and to produce excellent camera images. Ten patients with gross abnormalities on their chest radiographs due to lung cancer have been studied with this drug. The diseased parts of the lung consistently showed less uptake and these defects matched those obtained with microspheres labelled with technetium-99m, indicating that 123I-iodoamphetamine has the characteristics of a perfusion tracer. In five out of the 10 patients studied sequential studies showed that improved iodoamphetamine uptake was encountered shortly after a favourable response to radiotherapy and reduced uptake was seen in congruence with the radiation field at a later stage. This first clinical demonstration indicates that the retention of 123I-iodoamphetamine could be a sensitive marker for pulmonary vascular integrity and a useful new tool to identify the extent of disease where the pulmonary circulation is the initial site of the disorder.

Adult↗
PubMedDate not supplied

Are we moving towards continuous treatment in small cell lung cancer (SCLC)?

In the late sixties the first randomized placebo controlled study with cyclophosphamide demonstrated improved survival in patients with extensive small cell lung cancer (SCLC). Since then chemotherapy has become the mainstay of treatment of SCLC. A number of active combination chemotherapy programs for SCLC were developed during the 1970s and early 1980s. Administration of three or four effective drugs simultaneously appeared to be required for optimal results, but the particular regimen selected was of less importance than the delivery of doses that induced moderately severe but not life-threatening myelosuppression. The drugs chosen for a combination were justified on the basis of single agent activity, difference in mechanism of action and non-overlapping toxic effects. The actual doses were usually the result of feasibility studies in which the doses of all except one drug were held constant. Certain combinations became popular quickly, long before it was appreciated that one of the drugs in the combination added more toxicity than benefit. It is therefore not surprising that the old concept that two drugs in combination are better than one, or three drugs in combination are better than two, is being increasingly criticized. There is recognition that at the time of diagnosis SCLC may already be partially resistant to multiple chemotherapeutic agents and that the strategy simulated by Goldie and Coldman may only partly be applicable to SCLC. Moreover, the development of hematopoietic growth factors has provided a reason to re-evaluate the doses of individual cytostatic agents in current combination regimes and to combine drugs that previously were thought to be incompatible. But even without growth factors, recent investigations with the single agent etoposide and the combination of etoposide and cisplatin have provided arguments against the old theories of "more is better". Drug combinations must preferably be selected on the basis of pharmacokinetic studies. Dose intensity has to be revised and fascinating opportunities will arrive as soon as efficient oral formulations of active drugs, such as platinum, ifosfamide and etoposide become available.

Antineoplastic Combined Chemotherapy Protocols↗