Chemoprevention of cancer of the upper respiratory tract of the Syrian golden hamster by aerosol administration of difluoromethylornithine and 5-fluorouracil.
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Research aimed at identifying effective chemopreventive compounds active against carcinogenesis of the upper respiratory tract (URT) has been largely unsuccessful. We are addressing this problem by efforts at agent identification and by using aerosol delivery. Two compounds, difluoromethylornithine (DFMO) and 5-fluorouracil (5-FU) were investigated. DFMO is an irreversible inhibitor of ornithine decarboxylase, an enzyme important in cell proliferation. It has been used widely by oral administration for chemoprevention. 5-FU is a pyrimidine analog used extensively as a chemotherapeutic agent. It is generally administered i.v. and can cause considerable toxicity. However, aerosol administration for therapy of lung cancer in humans has been reported to be without adverse effects (Tatsumura et al., Br J Cancer 1993;68:1146-9). The experimental model used herein entailed six intratracheal administrations of methylnitrosourea (MNU) to hamsters. Each of the test agents was started about 1 week after MNU and was continued for 29 weeks with DFMO. Infiltrating squamous cell carcinomas of the URT occurred in 92% of the controls and were reduced by 50% in animals receiving DFMO (P = 0.0001). The experiment with 5-FU was of shorter duration being terminated 20 weeks after MNU. Thirty percent of the controls had infiltrating carcinomas and were reduced by 60% in animals receiving 5-FU (P = 0.0274). Both compounds resulted in a significant increase in the percent of cancer-free animals. These two agents may have selected use in subjects at high risk of cancer of the URT. (+info)
Intraobserver variability in the MR determination of tumor volume in squamous cell carcinoma of the pharynx.
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BACKGROUND AND PURPOSE: If tumor volumes are to be used for evaluating responses to treatment and long-term outcomes of patients with primary pharyngeal carcinomas, the reproducibility of these measurements must be established. We determined the intraobserver variability of MR imaging-based volume measurements of these cancers and their regional metastases. METHODS: We used an interactive computer program (IDL) that enables the extraction of tumor volumes from 3D MR data to obtain 202 volume measurements in 17 patients with pharyngeal carcinoma (two to five time points each). The primary cancer and largest nodal mass were manually outlined on every T2-weighted image of each MR study. The same neuroradiologist reanalyzed this MR dataset 2-41 weeks later. Measurement error and percentage measurement error (intraobserver variability) were determined. Differences in intraobserver variability between primary lesions and nodes, as well as between stages of treatment were tested with a Wilcoxon rank sum test. RESULTS: The mean and median percentage measurement errors, respectively, were 13% and 12% (range, 0-53%; 95% CI: 10%, 16%) for primary tumors and 9% and 7% (range, 0-37%; 95% CI: 7%, 12%) for nodal metastases. The difference in the percentage measurement error between primary lesions and cervical nodes approached statistical significance (P =.07). Differences in the variation of volume measurements based on the stage of therapy were significant (P =.01). CONCLUSION: Our results suggest that MR imaging-based tumor volumes are reliably reproducible. Such measurements may be important in predicting patient outcome, determining appropriate therapy, and conducting patient follow-up. (+info)
Versican expression in pharyngeal squamous cell carcinoma: an immunohistochemical study.
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AIMS: To study the expression of versican, a large proteoglycan involved in repressing adhesion between cells and the extracellular matrix in pharyngeal squamous cell carcinoma (PSCC), and its relation to the expression of p53 and catenins, histological differentiation, clinical data, and prognosis. METHODS: For the retrospective survey, primary tumours for analyses were obtained from 118 patients diagnosed with PSCC of the oropharynx or hypopharynx. The immunohistochemical expression of versican was studied and was related to the expression pattern of p53 and catenins, in addition to clinical data and survival. RESULTS: In the primary tumours, strong stromal versican expression was graded as low in 59 (50%) and high in 59 (50%) cases. In addition, intracellular versican staining was seen in nine (8%) tumours. In local lymph node metastases, strong stromal versican staining was significantly more frequent compared with the primary tumours (p = 0.018). Strong stromal versican staining was more frequently seen in less advanced tumours (p = 0.015). There was no association between versican expression and the other investigated variables (p53, catenins, TNM status, and histological grade). Neither stromal nor intracellular versican expression predicted overall survival in these patients. CONCLUSIONS: Versican was more strongly expressed in the stroma of local metastases and in the earlier stages of disease in PSCC. However, versican expression was not an independent prognostic factor in this entity. (+info)
Prognostic relevance of cell proliferation in head and neck tumors.
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Cell proliferative activity has been extensively investigated in head and neck tumors. Ki67/MIB-1 immunostaining, tritiated thymidine or bromodeoxyuridine labeling indices, DNA S-phase fraction, proliferating cell nuclear antigen expression, potential doubling time and analysis of the nucleolar organizer region associated proteins (AgNORs) have shown significant correlation with prognosis in 4806 cases of tumors of the oral cavity, salivary glands, pharynx and larynx. However, this was not observed in 2968 other reported cases. Discrepancies may depend on various factors: the heterogeneity of the series, which include tumors from various anatomic sites and patients treated with different therapy, and the lack of standardization of methods for assessing cell proliferation. Furthermore, none of the methods currently applied can by themselves define the actual proliferative activity, as it depends both on the proportion of cells committed to the cycle (growth fraction) and the speed of the cell cycle. Indeed, the actual proliferative activity of a tumor could well be measured by the equation [PA = Ki67 or MIB-1 scores x AgNORs], as we did in pharyngeal carcinoma. Provided that large and homogeneous series are evaluated by standardized methods, cell proliferative activity can still be regarded as an inexpensive and reliable prognostic factor in head and neck tumors. (+info)
Alcohol and cancer.
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Although ethanol has generally not been found to induce cancer in experimental animals, the consumption of alcoholic beverages has been linked to increased risks of several cancers in humans. Risks of oral, pharyngeal, laryngeal, esophageal, and liver cancer are elevated among drinkers, typically in proportion to the amount consumed. Evidence associating colorectal and breast cancer with alcohol drinking is suggestive but awaits confirmation. All types of alcoholic beverages seem to be implicated, pointing to an etiological role for ethanol or its metabolites. The mechanisms, however, by which alcohol induces cancer in humans are not clear. This review summarizes epidemiological studies of alcohol and cancer, focusing primarily on characteristics of the association that may provide clues to causal pathways. (+info)
Case report: greater meningeal inflammation in lumbar than in ventricular region in human bacterial meningitis.
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Differences in the composition of ventricular and lumbar cerebrospinal fluid (CSF) based on single pairs of samples have previously been described. We describe a patient that developed post-surgical recurrent meningitis monitored by daily biochemical and bacteriological CSF analysis, simultaneously withdrawn from lumbar space and ventricles. A 20-year-old Caucasian man was admitted to the ICU after a resection of a chordoma that extended from the sphenoidal sinus to the anterior face of C2. CSF was continuously leaking into the pharyngeal cavity after surgery, and three episodes of recurrent meningitis, all due to Pseudomonas aeruginosa O12, occurred. Our case showed permanent ventricular-to-lumbar CSF gradients of leukocytes, protein and glucose that were increased during the acute phase of meningitis, with the greatest amplitude being observed when bacteria were present in both ventricular and lumbar CSF. This might suggest a greater extent of meningeal inflammation in the lumbar than in the ventricular region. Our case also showed that the increase in intravenous antibiotics (cefepim from 8 to 12 g/day and ciprofloxacine from 1.2 to 2.4 g/day) led to an increase in concentration in plasma but not in CSF. (+info)
The characteristics of human papillomavirus DNA in head and neck cancers and papillomas.
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AIM: To determine the prevalence, type, physical state, and viral load of human papillomavirus (HPV) DNA in cases of head and neck cancer and recurrent respiratory papillomatosis (RRP). METHODS: The prevalence and type of HPV DNA was determined in 27 fresh frozen tissue specimens from patients with head and neck cancers and 16 specimens from 10 patients with RRP by MY09/MY11 and GP5+/GP6+ nested polymerase chain reaction (PCR) and subsequent restriction enzyme cleavage. The physical state of HPV DNA was analysed by E1, E2, and E1E2 specific PCRs and Southern blot hybridisation (SBH). RESULTS: HPV DNA was detected in 13 of 27 cancers and 10 of 10 papillomas. Both low risk HPV-6 and HPV-11 and high risk HPV-16 were present in cancers in low copy numbers, whereas papillomas exclusively harboured low risk HPV-6 and HPV-11. E1E2 PCRs failed to determine the physical state of HPV in cancers except one case where HPV-6 DNA was integrated. In contrast to cancers, all papillomas showed the episomal state of HPV DNA and a relatively higher viral load. CONCLUSIONS: Based on the prevalence, type, physical state, and copy number of HPV DNA, cancers and papillomas tend to show a different HPV DNA profile. The 100% positivity rate of low risk HPV types confirms the role of HPV-6 and HPV-11 in the aetiology of RRP. (+info)
Environmental tobacco smoke and risk of respiratory cancer and chronic obstructive pulmonary disease in former smokers and never smokers in the EPIC prospective study.
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OBJECTIVES: To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death. DESIGN: Nested case-control study within the European prospective investigation into cancer and nutrition (EPIC). PARTICIPANTS: 303,020 people from the EPIC cohort (total 500,000) who had never smoked or who had stopped smoking for at least 10 years, 123,479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment. MAIN OUTCOME MEASURES: Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people. RESULTS: Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours). CONCLUSIONS: This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers. (+info)