(1/1637) The European mesothelioma epidemic.

Projections for the period 1995-2029 suggest that the number of men dying from mesothelioma in Western Europe each year will almost double over the next 20 years, from 5000 in 1998 to about 9000 around 2018, and then decline, with a total of about a quarter of a million deaths over the next 35 years. The highest risk will be suffered by men born around 1945-50, of whom about 1 in 150 will die of mesothelioma. Asbestos use in Western Europe remained high until 1980, and substantial quantities are still used in several European countries. These projections are based on the fit of a simple age and birth cohort model to male pleural cancer mortality from 1970 to 1989 for six countries (Britain, France, Germany, Italy, The Netherlands and Switzerland) which together account for three-quarters of the population of Western Europe. The model was tested by comparing observed and predicted numbers of deaths for the period 1990-94. The ratio of mesothelioma to recorded pleural cancer mortality has been 1.6:1 in Britain but was assumed to be 1:1 in other countries.  (+info)

(2/1637) An expert system for the evaluation of historical asbestos exposure as diagnostic criterion in asbestos-related diseases.

Compensation schemes for asbestos-related diseases have developed different strategies for attributing a specific disease to occupational exposure to asbestos in the past. In the absence of quantitative exposure information that allows a valid estimate of an individual's historical exposure, general guidelines are required to retrospectively evaluate asbestos exposure. A risk matrix has been developed that contains qualitative information on the proportion of workers exposed and the level of exposure in particular industries over time. Based on this risk matrix, stepwise decision trees were formulated for decisions regarding the decisive role of historical asbestos exposure in case ascertainment of asbestosis and mesothelioma. Application of decision schemes will serve to speed up the process of verifying compensation claims and also contribute to a uniform decision-making process in legal procedures.  (+info)

(3/1637) A historical cohort mortality study of workers exposed to asbestos in a refitting shipyard.

To investigate the risks of developing asbestos-related diseases we conducted a historical cohort mortality study on 249 ship repair workers (90 laggers and 159 boiler repairers) in a single U.S. Navy shipyard in Japan. We successfully identified the vital status of 87 (96.7%) laggers and 150 (94.3%) boiler repairers, and, of these, 49 (56.3%) and 65 (43.3%) died, respectively, during the follow-up period from 1947 till the end of 1996. Our in-person interviews with some of the subjects clarified that asbestos exposure was considered to be substantially high in the 1950-60s, decreased thereafter gradually but remained till 1979 in the shipyard. The laggers, who had handled asbestos materials directly, showed a significantly elevated SMR of 2.75 (95% C.I.: 1.08-6.48) for lung cancer. The risk developing the disease was greater in the laggers after a 20-year latency (SMR = 3.42). Pancreatic cancer yielded a greater SMR than unity (7.78, 90% C.I.: 2.07-25.19) in a longer working years group. Four laggers died from asbestosis. The boiler repairers, who had many chances for secondary exposure to asbestos and a few for direct exposure, showed no elevation of the SMR of lung cancer overall, but there was a borderline statistically significant SMR of 2.41 (90% C.I.: 1.05-5.45) in a longer working years group. One boiler repairer died from mesothelioma and four from asbestosis.  (+info)

(4/1637) Morphological variations in transplanted tumors developed by inoculation of spontaneous mesothelioma cell lines derived from F344 rats.

Morphological and immunohistochemical features of the abdominal mesotheliomas that were developed by inoculation of 3 cell lines (MeET-4, -5 and -6) established from spontaneous abdominal mesotheliomas in male F344 rats. Although the original tumors of three cell lines showed signs of epithelioid growth with a predominantly simple papillary pattern, transplanted tumors revealed a variety of morphologic features including epithelioid with glandular structures, sarcomatous, and a mixture of these components. All tumor cells of transplanted tumors were positive for alpha-smooth muscle actin (ASMA) but almost negative for desmin as were epithelioid cells of the original tumors, and the cell lines were positive for desmin but not for ASMA. These results suggested that mesothelioma in the F344 rat had the potential for wide spectrum differentiation under in vitro conditions. The microenvironmental factors obtained in vivo can modify their potential ability and their morphological aspects. These factors may be related to tumor cell reexpression of ASMA of tumor cells that were masked under in vitro culture conditions.  (+info)

(5/1637) T-cell receptor transgenic analysis of tumor-specific CD8 and CD4 responses in the eradication of solid tumors.

The role of tumor-specific CD8 and CD4 lymphocytes in rejecting solid tumors has been difficult to determine because of the lack of models in which tumor antigen, specific CD8 cells, and specific CD4 cells can be monitored and controlled. To investigate the minimal components required for the induction and maintenance of CTL activity sufficient to reject a solid tumor in vivo, we transfected the influenza hemagglutinin (HA) gene into a nonimmunogenic class I+/class II- murine malignant mesothelioma (MM) tumor line to generate an endogenous tumor antigen and used TCR transgenic mice with class I- or class II-restricted specificities for HA as sources of naive, tumor-specific T cells. The data show that the presence of a strong tumor antigen is not in itself sufficient to induce an effective CTL response, nor does the presence of a high frequency of precursor cells guarantee tumor rejection. We also show that tumor-specific CD4 cells, when CTL numbers are suboptimal, greatly enhance the eradication of tumor, confirming the importance of antigen-presenting cell presentation of tumor antigens to class II-restricted cells. These data confirm that T-cell receptor transgenic cells, combined with nominal tumor antigen transfection, represent powerful tools to analyze tumor-specific T-cell responses.  (+info)

(6/1637) Photodynamic therapy with mTHPC and polyethylene glycol-derived mTHPC: a comparative study on human tumour xenografts.

The photosensitizing properties of m-tetrahydroxyphenylchlorin (mTHPC) and polyethylene glycol-derivatized mTHPC (pegylated mTHPC) were compared in nude mice bearing human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts. Laser light (20 J/cm2) at 652 nm was delivered to the tumour (surface irradiance) and to an equal-sized area of the hind leg of the animals after i.p. administration of 0.1 mg/kg body weight mTHPC and an equimolar dose of pegylated mTHPC, respectively. The extent of tumour necrosis and normal tissue injury was assessed by histology. Both mTHPC and pegylated mTHPC catalyse photosensitized necrosis in mesothelioma xenografts at drug-light intervals of 1-4 days. The onset of action of pegylated mTHPC seemed slower but significantly exceeds that of mTHPC by days 3 and 4 with the greatest difference being noted at day 4. Pegylated mTHPC also induced significantly larger photonecrosis than mTHPC in squamous cell xenografts but not in adenocarcinoma at day 4, where mTHPC showed greatest activity. The degree of necrosis induced by pegylated mTHPC was the same for all three xenografts. mTHPC led to necrosis of skin and underlying muscle at a drug-light interval of 1 day but minor histological changes only at drug-light intervals from 2-4 days. In contrast, pegylated mTHPC did not result in histologically detectable changes in normal tissues under the same treatment conditions at any drug-light interval assessed. In this study, pegylated mTHPC had advantages as a photosensitizer compared to mTHPC. Tissue concentrations of mTHPC and pegylated mTHPC were measured by high-performance liquid chromatography in non-irradiated animals 4 days after administration. There was no significant difference in tumour uptake between the two sensitizers in mesothelioma, adenocarcinoma and squamous cell carcinoma xenografts. Tissue concentration measurements were of limited use for predicting photosensitization in this model.  (+info)

(7/1637) Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer.

OBJECTIVE: To evaluate the effectiveness of nursing intervention for breathlessness in patients with lung cancer. DESIGN: Patients diagnosed with lung cancer participated in a multicentre randomised controlled trial where they either attended a nursing clinic offering intervention for their breathlessness or received best supportive care. The intervention consisted of a range of strategies combining breathing control, activity pacing, relaxation techniques, and psychosocial support. Best supportive care involved receiving standard management and treatment available for breathlessness, and breathing assessments. Participants completed a range of self assessment questionnaires at baseline, 4 weeks, and 8 weeks. SETTING: Nursing clinics within 6 hospital settings in the United Kingdom. PARTICIPANTS: 119 patients diagnosed with small cell or non-small cell lung cancer or with mesothelioma who had completed first line treatment for their disease and reported breathlessness. OUTCOME MEASURES: Visual analogue scales measuring distress due to breathlessness, breathlessness at best and worst, WHO performance status scale, hospital anxiety and depression scale, and Rotterdam symptom checklist. RESULTS: The intervention group improved significantly at 8 weeks in 5 of the 11 items assessed: breathlessness at best, WHO performance status, levels of depression, and two Rotterdam symptom checklist measures (physical symptom distress and breathlessness) and showed slight improvement in 3 of the remaining 6 items. CONCLUSION: Most patients who completed the study had a poor prognosis, and breathlessness was typically a symptom of their deteriorating condition. Patients who attended nursing clinics and received the breathlessness intervention experienced improvements in breathlessness, performance status, and physical and emotional states relative to control patients.  (+info)

(8/1637) Telomerase activity in human pleural mesothelioma.

BACKGROUND: Gradual telomere erosion eventually limits the replicative life span of somatic cells and is regarded as an ultimate tumour suppressor mechanism, eliminating cells that have accumulated genetic alterations. Telomerase, which has been found in over 85% of human cancers, elongates telomeres and may be required for tumorigenesis by the process of immortalisation. Malignant mesothelioma is an incurable malignancy with a poor prognosis. The disease becomes symptomatic decades after exposure to carcinogenic asbestos fibres, suggesting the long term survival of pre-malignant cell clones. This study investigated the presence of telomerase in pleural malignant mesothelioma, which may be the target for future anti-telomerase drugs. METHODS: Telomerase activity was semiquantitatively measured in extracts from 22 primary pleural mesotheliomas, two benign solitary fibrous tumours of the pleura, four mesothelioma cell lines, and six short term mesothelial cell cultures from normal pleura using a non-isotopic dilution assay of the telomeric repeat amplification protocol. RESULTS: Twenty of the 22 primary mesotheliomas (91%) and all tumour derived mesothelioma cell lines were telomerase positive. Different levels of enzyme activity were observed in the tumours of different histological subtypes. Telomerase activity could not be detected in the six normal mesothelial cell cultures or in the two mesotheliomas. Both benign solitary fibrous tumours showed strong telomerase activity. CONCLUSIONS: Telomerase activity is found in a high proportion of mesotheliomas and anti-telomerase drugs might therefore be useful clinically. The results are consistent with the hypothesis that telomerase activity may be a feature of carcinogenesis in mesotheliomas and possibly in many other cancers.  (+info)