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National Cancer Institute®
Ultima Vez Modificado: 1 de abril del 2002
UI - 11423790
AU - Melloni G; Puglisi A; Ferraroli GM; Carretta A; Ceresoli G; Calori G;
TI - Zannini P [Treatment of malignant pleural mesothelioma]
SO - Minerva Chir 2001 Jun;56(3):243-50
AD - Universita Vita-Salute San Raffaele, Divisione e Cattedra di Chirurgia Toracica, Ospedale San Raffaele, Milan, Italy. analyzed in order to describe the impact of treatment modality on survival. METHODS: Medical records of 56 patients with MPM (44 male, 12 female, median age = 59 yrs) were reviewed. In 34 cases the histotype was epithelial, in 4 sarcomatoid, in 4 mixed, in 3 desmoplastic, and in 11 not specified. Four treatment modalities were identified: 1) Surgery (subtotal pleurectomy) = 20 patients; 2) Chemotherapy = 19 patients; 3) Surgery+Chemo-therapy = 8 patients; 4) Supportive care = 9 patients. RESULTS: The median survival was: 1) Surgery = 12.4 months; 2) Chemotherapy = 7.5 months; 3) Surgery+Chemotherapy = 12 months; 4) Supportive care = 11.4 months. Using univariate analysis, 8 prognostic factors were studied (age, sex, asbestos exposure, side, histotype, performance status, stage, treatment). Among these, only the stage and the performance status had shown a prognostic value on survival (p<0.05), while the treatment modality had not significantly influenced the prognosis. Using multivariate analysis only performance status showed to be significatively associated with survival (p=0.01 and odds ratio = 1.9, I.C. 1.2-3.2). CONCLUSIONS: Despite the limits of a retrospective study, personal experience confirms the ineffectiveness of current therapeutical approaches to MPM. A better understanding of MPM is required to develop new therapeutical approaches and alter the dismal prognosis of this disease.
UI - 11515151
AU - Merler E; Gioffre F; Rozio L; Bizzotto R; Mion M; Sarto F
TI - [Pleural mesothelioma in women in the Veneto Region who used to work as rag sorters for textile recycling and paper production]
SO - Med Lav 2001 May-Jun;92(3):181-6
AD - Servizio per la Prevenzione Igiene e Sicurezza nei Luoghi Lavoro, Unita Locale Socio Sanitaria n. 16, Padova. firstname.lastname@example.org
The paper reports 9 cases of mesothelioma diagnosed by means of histology or cytology that were observed among women resident in the Veneto Region, Northern Italy, whose only activity that could involve exposure to asbestos was as rag sorter. These cases are part of a group of about 260 subjects with mesothelioma whose entire working and residential history has been collected. The women worked as rag sorters between the 1940's and 1960's in textile recycling (8 cases) or (one case) at a paper mill where cotton was used for paper production. The work as rag sorter helps to explain the high proportion of mesotheliomas among women with an occupational exposure to asbestos.
UI - 11201579
AU - Garcia-Lopez MP; Barrera-Rodriguez R
TI - [Malignant mesothelioma: clinical and radiological description of 45 cases with and without asbestos exposure]
SO - Salud Publica Mex 2000 Nov-Dec;42(6):511-9
AD - Instituto Nacional de Enfermedades Respiratorias, Secretaria de Salud, Mexico.
OBJECTIVE: Our aim was to identify and describe the main symptoms, clinical presentation, and radiographic changes in malignant mesothelioma (MM) patients. MATERIAL AND METHODS: We reviewed the medical and X-ray records of all patients diagnosed with MM, admitted between 1991 and 1998 to the National Institute of Respiratory Diseases (INER), which is a governmental institution specialized in chest disease in Mexico City. The following data were collected: Age, occupation, asbestos exposure, latency, family history of cancer, clinical symptoms, and X-ray changes. Data are presented as percentages by sex and age group. RESULTS: We found 45 cases of MM; in 80% of them a history of asbestos exposure could not be documented. The 51-60 years age group had the highest frequency of MM. Dispnea and chest pain were the presenting symptoms in most patients. Pleural effusion and pleural thickening were the X-ray abnormalities observed in 75% of the patients. CONCLUSIONS: The clinical and radiographic findings among patients with MM without asbestos exposure were similar to those with a history of asbestos exposure.
UI - 11750145
AU - Metintas M; Ucgun I; Elbek O; Erginel S; Metintas S; Kolsuz M; Harmanci
TI - E; Alatas F; Hillerdal G; Ozkan R; Kaya T Computed tomography features in malignant pleural mesothelioma and other commonly seen pleural diseases.
SO - Eur J Radiol 2002 Jan;41(1):1-9
AD - Department of Chest Diseases, Osmangazi University Medical Faculty, Eskisehir, Turkey. email@example.com
OBJECTIVE: To investigate the computed tomography (CT) features of malignant pleural mesothelioma (MPM) cases, comparing them to those in other malignant and benign pleural diseases. MATERIALS AND METHODS: We reviewed the CT findings of 215 patients; 99 with MPM, 39 with metastatic pleural disease (MPD), and 77 with benign pleural disease. The findings were evaluated in univariate and multivariate analysis for differentiation of pleural diseases. RESULTS: In patients with MPM, the most common CT features were circumferential lung encasement by multiple nodules (28%); pleural thickening with irregular pleuropulmonary margins (26%); and pleural thickening with superimposed nodules (20%). In the majority (70%) of cases, there was rind-like extension of tumor on the pleural surfaces. In multivariate analysis, the CT findings of "rind-like pleural involvement", "mediastinal pleural involvement", and "pleural thickness more than 1 cm" were independent findings in differentiating MPM from MPD with the sensitivity/specificity values of 70/85, 85/67, and 59/82, respectively. "Rind-like pleural involvement", "mediastinal pleural involvement", "pleural nodularity" and "pleural thickness more than 1 cm" were independent findings for differentiation of malignant pleural diseases (MPM+MPD) from benign pleural disease with the sensitivity/specificity values of 54/95, 70/83, 38/96, and 47/64, respectively. Invasion of thoracic structures such as pericardium, chest wall, diaphragm, mediastinum, with pleural disease and nodular involvement of fissures, was detected infrequently; however, since these invasions were not seen in benign pleural diseases, it was concluded these invasions, if detected on a CT scan, directly suggested malignancy. CONCLUSION: A patient has extremely high probability of malignant pleural disease if one or more of these CT findings are found and the possibility of MPM is high. These findings may be important for patients in bad state or patients who do not want any invasive biopsy procedures. It is also possible to identify cases with a low probability of malignant disease.
UI - 11846639
AU - Walker AM; Maxim LD; Utell M
TI - Risk analysis for mortality from respiratory tumors in a cohort of refractory ceramic fiber workers.
SO - Regul Toxicol Pharmacol 2002 Feb;35(1):95-104
AD - Epidemiology Division, Ingenix Pharmaceutical Services, One Newton Executive Park, Newton Lower Falls, Massachusetts 02462-9669, USA. AlecWalker@Epidemiology.com
Although workers in refractory ceramic fibers (RCF) manufacturing facilities have experienced no elevations in lung cancer or mesothelioma rates, the historical experience of asbestos together with animal studies of RCF have led to ongoing studies of the respiratory health of RCF workers. We have compared lung cancer and mesothelioma in the accumulated mortality experience of a cohort of male RCF production workers (Lemasters et al., 2001, submitted for publication) to that which would have been expected if RCF had a carcinogenic potency similar to that of various forms of asbestos. To accomplish this, we used risk models recently formalized by Hodgson and Darnton (2000, Ann. Occup. Hyg. 41, 13-36) for asbestos cohorts together with the RCF exposure measurements and historical reconstructions of Rice and colleagues (1997, Appl. Occup. Environ. Hyg. 12, 54-61). Deaths from lung cancer in the RCF cohort are statistically significantly below that which would be expected if RCF had the potency of either crocidolite or amosite. The mortality is also lower than would be expected if RCF had the potency of chrysotile, but the difference is not statistically significant. For mesothelioma, the anticipated numbers of deaths under hypotheses of asbestos-like potency are too small to be rejected by the zero cases seen in the RCF cohorts. The current epidemiologic studies do not rule out risk, but they clearly do rule out lung cancer risks like those of crocidolite or amosite. The residual uncertainty justifies ongoing workplace surveillance. B) 2002 Elsevier Science (USA).
UI - 11862420
AU - Bright RK; Kimchi ET; Shearer MH; Kennedy RC; Pass HI
TI - SV40 Tag-specific cytotoxic T lymphocytes generated from the peripheral blood of malignant pleural mesothelioma patients.
SO - Cancer Immunol Immunother 2002 Feb;50(12):682-90
AD - Laboratory of Prostate Cancer Biology, Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, and the Oregon Cancer Center, 4805 NE Glisan Street, Portland, OR 97213, USA. firstname.lastname@example.org
Malignant pleural mesothelioma (MPM) is an aggressive cancer, with survival of less than one year following diagnosis and treatment with current protocols. Recent studies have demonstrated the presence of the simian virus 40 (SV40)-like, large tumor antigen (Tag) in nearly 60% of MPMs. SV40 Tag is a viral-encoded tumor-specific antigen, and thus a potential target for the induction of anti-tumor immunity and the development of therapeutic vaccines. We describe here evidence for the existence of SV40 Tag-specific immune responses in patients with MPM whose tumors express Tag. Humoral immunity was demonstrated by the detection of IgG titers against Tag in serum samples from 1/3 of patients examined. CTLs were generated from the peripheral blood of an HLA-A2(+) MPM patient with a synthetic peptide representing an HLA-A2 binding epitope in SV40 Tag. The CTLs demonstrated epitope fine specificity, in that other peptides from SV40 Tag and a peptide from influenza virus were not recognized in the context of HLA-A2. Moreover, the CTLs were capable of recognizing mesothelioma tumor cells that expressed SV40 Tag, in an MHC class I restricted manner.
UI - 11905410
AU - Kerrigan SA; Turnnir RT; Clement PB; Young RH; Churg A
TI - Diffuse malignant epithelial mesotheliomas of the peritoneum in women: a clinicopathologic study of 25 patients.
SO - Cancer 2002 Jan 15;94(2):378-85
AD - Department of Pathology, Vancouver Hospital and Health Sciences Center, British Columbia, Canada.
BACKGROUND: The behavior of diffuse peritoneal mesotheliomas in women and the possible relation between tumor morphology and outcome are uncertain. Reported survival has ranged from < 1 month to > 14 years, and a previous study found that tumor morphology could not be used reliably for predicting outcome. The authors examined the behavior of diffuse epithelial peritoneal mesotheliomas in women and the possible relation between pathologic features and outcome. METHODS: Twenty-five female patients with diffuse peritoneal epithelial malignant mesotheliomas were divided into two groups: those who survived for < 4 years (60%) and those who survived for > 4 years (40%). Both groups were compared in terms of age, presentation, treatment, survival, tumor architecture, mitotic rate, necrosis, nuclear grade, and immunohistochemical profile. RESULTS: Patients in the two groups were similar in terms of age at diagnosis (median ages, 50.7 years and 49.9 years), presentation, initial tumor burden, and treatment. In both groups, the most common initial clinical presenting features were ascites and abdominal pain. The tumors typically took the form of multiple nodules measuring < 1.5 cm in greatest dimension. Slightly less than 50% of patients in both groups received some form of chemotherapy or radiation therapy after undergoing tumor-reductive surgery or biopsy. Overall survival ranged from 1 month to 15 years. The median survival was 12 months in the group of women who survived for < 4 years and 7 years in the group of women who survived for > 4 years. Overall, 10 of 25 patients survived for > or = 5 years. One patient was alive with disease 15 years after diagnosis. Although there was a suggestion that the tumors in patients with short survival more often had solid architecture and high-grade nuclei, these findings were not significant statistically. The frequency of necrosis and the mitotic activity were the same in both groups. CONCLUSIONS: The spectrum of diffuse epithelial peritoneal mesotheliomas in women includes tumors that are highly aggressive and behave much like pleural mesotheliomas, although a sizeable number of tumors, unlike the pleural tumors, are relatively indolent. However, because there do not appear to be morphologic features that reliably identify favorable tumors versus unfavorable tumors, aggressive therapy for all women with diffuse peritoneal mesotheliomas may be warranted.
UI - 11875694
AU - Mendes R; O'Brien ME; Mitra A; Norton A; Gregory RK; Padhani AR;
TI - Bromelow KV; Winkley AR; Ashley S; Smith IE; Souberbielle BE Clinical and immunological assessment of Mycobacterium vaccae (SRL172) with chemotherapy in patients with malignant mesothelioma.
SO - Br J Cancer 2002 Feb 1;86(3):336-41
AD - Lung Unit, Department of Haematology, The Royal Marsden Hospital NHS Trust, Downs Road, Sutton, SM2 5PT, UK.
The objectives of this study were to determine the toxicity of intratumoural/intrapleural SRL172 in addition to intradermal SRL172 and standard chemotherapy (mitomycin-C, vinblastine and cisplatin) in patients with malignant mesothelioma. Patients received chemotherapy (mitomycin-C: 8 mg m(-2), vinblastine: 6 mg m(-2), cisplatin 50 mg m(-2)) on a 3-weekly basis for up to six courses. IP SRL172 injections were given 3-weekly prior to chemotherapy and escalated in groups of three patients from 1 microg to 1 mg bacilli in 10-fold increments. Patients were also given ID SRL172 at a dose of 1 mg bacilli 4-weekly. Patients were assessed for toxicity after each course of chemotherapy and for response by CT imaging. Immuno-haematological parameters were analyzed pre-treatment and 1 month after completion of treatment. There was no dose limiting toxicity with IP SRL172 although there was greater toxicity at the highest dose (n=13). There were six out of 16 partial responses (37.5%). Haemato-immunological parameters, measured in seven patients pre and post-therapy, revealed that response rate correlated with a decrease in platelet count and there was an increase in activation of natural killer cells and a decrease in the percentage of IL-4 producing T cells in all tested patients post-treatment. SRL172 can be given safely into tumour deposits and the pleural cavity in patients with malignant mesothelioma and we have established the dose for phase II testing. Copyright 2002 The Cancer Research Campaign
UI - 11875695
AU - van Haarst JM; Baas P; Manegold Ch; Schouwink JH; Burgers JA; de Bruin
TI - HG; Mooi WJ; van Klaveren RJ; de Jonge MJ; van Meerbeeck JP Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma.
SO - Br J Cancer 2002 Feb 1;86(3):342-5
AD - Rotterdam Oncological Thoracic Studygroup (ROTS), Department of Pulmonology, University Hospital Rotterdam, PO Box 5201, 3008 AE Rotterdam, The Netherlands.
Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma. METHOD: Gemcitabine 1250 mg m(-2) was administered on day 1 and day 8 and cisplatin 80 mg m(-2) was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1-31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5-7 months) with a median survival from registration of 9.6 months (95% CI 8-12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule. Copyright 2002 The Cancer Research Campaign
UI - 11895489
AU - Attanoos RL; Webb R; Dojcinov SD; Gibbs AR
TI - Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum.
SO - Histopathology 2002 Mar;40(3):237-44
AD - Department of Histopathology, Llandough Hospital, Cardiff & Vale NHS Trust, Penarth, Vale of Glamoran, UK.
AIMS: To evaluate the role of mesothelial markers (calretinin, thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal carcinoembryonic antigen, Leu-M1, CA-125 and Ber-EP4) in distinguishing diffuse peritoneal malignant mesothelioma from primary serous papillary adenocarcinoma of the ovary and peritoneum. METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks from 32 diffuse peritoneal mesotheliomas of epithelial subtype (all females), 20 serous papillary ovarian carcinomas and three primary peritoneal serous papillary carcinomas were studied. Calretinin and Ber-EP4 appeared to be the best positive mesothelial and carcinoma marker, respectively. Nuclear calretinin expression was identified in 28 of 32 malignant mesotheliomas with no nuclear immunoreactivity in the cohorts of serous papillary ovarian and peritoneal carcinomas, thus yielding 88% sensitivity and 100% specificity. Ber-EP4 showed 95% sensitivity and 91% specificity for serous papillary ovarian carcinoma. Thrombomodulin, cytokeratin 5/6 and CD44H immunoreactivities were seen in 18 (56%), 17 (53%) and 15 (47%) of peritoneal mesotheliomas, respectively, and in six (30%), five (25%) and five (25%) of the ovarian tumours, respectively. None of the three primary peritoneal serous papillary carcinomas expressed calretinin, thrombomodulin, cytokeratin 5/6 or CD44H. Polyclonal and monoclonal CEA, and Leu-M1 were expressed by two (10%), one (5%) and seven (35%) serous papillary ovarian carcinomas, respectively. None of the serous papillary peritoneal carcinomas expressed polyclonal CEA, monoclonal CEA or Leu-M1. CA-125 was positive in 19 (95%) and two (67%) ovarian and peritoneal carcinomas, respectively, and in eight (25%) peritoneal mesotheliomas. CONCLUSIONS: Calretinin and Ber-EP4 are useful discriminant markers in distinguishing peritoneal mesothelioma in women from serous papillary ovarian and peritoneal carcinoma. The other mesothelial markers (thrombomodulin, cytokeratin 5/6, and CD44H) and carcinoma markers (polyclonal and monoclonal CEA, and Leu-M1) yielded a too low sensitivity for practical use.
UI - 11862475
AU - Ehlers EM; Kuhnel W; Wiedemann GJ
TI - Hyperthermia and mafosfamide in a human-derived malignant pleural mesothelioma cell line.
SO - J Cancer Res Clin Oncol 2002 Feb;128(2):65-72
AD - Department of Anatomy, Medical University of Lubeck, Lubeck, Germany. email@example.com
PURPOSE: Diffuse malignant pleural mesothelioma is the most common primary pleural malignancy. At the beginning of the last century, this tumor was of minor incidence. Meanwhile, the use of asbestos has led to and is still leading to a rise in pleural mesothelioma incidence. There is no standard therapy for this highly aggressive disease and the development of new therapeutic strategies is imperative. METHODS: We, therefore, investigated the morphological and pharmakokinetic effects of a combined thermochemotherapy consisting of the administration of different dosages of mafosfamide with and without the application of a 1-h hyperthermia at 41.7 degrees C on the human biphasic malignant pleural mesothelioma cell line MSTO-211H. After therapy, cells were prepared for light and electron microscopy. BrdU-incorporation for the S-phase fraction, TUNEL-labeling for detection of apoptosis, and quantitative assessments using the MTT assay were performed. RESULTS: Our results demonstrate that the combination of mafosfamide with hyperthermia leads to qualitatively and quantitatively enhanced cellular damage compared to monotherapy. During combined thermochemotherapy, cell damage and death is already induced at lower mafosfamide concentrations than without hyperthermia which suggests an additive effect from hyperthermia to the action of the alkylating drug mafosfamide. Cell death thereby mostly occurs as necrotic cell death rather than as apoptosis, although in a combined thermochemotherapy apoptosis is induced temperature-dependently, when comparing temperatures from 37 degrees C to 43 degrees C. CONCLUSIONS: We suggest that the effect of substances such as ifosfamide and cyclophosfamide which are in clinical use, might be enhanced by the combination of local or regional hyperthermia in order to improve the therapeutical index of these substances in the treatment of pleural mesothelioma.
UI - 11933738
AU - Bard M; Ruffie P
TI - [Malignant pleural mesothelioma. From diagnosis to prognosis]
SO - Presse Med 2002 Mar 9;31(9):406-11
AD - Institut Gustave-Roussy, Departement de Medecine, 39, rue Camille Desmoulins, F94805 Villejuif.
EPIDEMIOLOGY: The incidence of malignant pleural mesothelioma has constantly increased over the past forty years. The recent measures of ban on the use of asbestos and the long latency of this tumor after exposure means that its peak incidence can be foreseen for the years 2010-2020. DIAGNOSIS: Various health professionals are involved in the care of this tumor, which benefits equally from progresses in clinical and fundamental research. Some progress has been made in understanding its oncogenesis as well as its histopathologic analysis. PROGNOSIS: Malignant pleural mesothelioma symptoms are rapidly invalidating and the patient's prognosis is bad at short-term. However, hope may come from the detection of early stages of the disease and from the individualization of good prognosis factors, permitting the selection of patients for whom some curative therapies are in course of evaluation.
UI - 11933739
AU - Bard M; Ruffie P
TI - [Malignant pleural mesothelioma. Present data and perspectives for treatment]
SO - Presse Med 2002 Mar 9;31(9):412-9
AD - Institut Gustave-Roussy, Departement de Medecine, 39, rue Camille Desmoulins, F94805 Villejuif.
CHEMOTHERAPY: With regard to the efficacy of mono-chemotherapy and according to the literature, no cytotoxic substance, apart from methrotrexate at high doses, leads to a response rate of more than 20%. With regard to cyrotoxic associations, the published results show slightly betterresponse rates. IMMUNOTHERAPY: Interleukine 2 as well as various interferons have been tested alone or in association with chemotherapy. Fairly encouraging response rates have been reported. However, the possibility of severe adverse events must be taken into account. RADIOTHERAPY: The interest of prophylactic parietal radiation following invasive thoracic treatment has been demonstrated. Palliative use of radiotherapy is possible for pain, and more rarely for decompression. With curative aim, the results of isolated radiotherapy are disappointing. SURGERY: Palliative surgery is aimed at reducing the tumour and pleural symphysis. Curative surgery consists in wide extrapleural pneumonectomy, permitting total resection of the visceral pleura, or decortication pleurectomy leaving the lung in place. Mean survival of patients having undergone surgery is of 10 to 17 months with rates between 10 and 30% at 2 years ASSOCIATED THERAPY: For the first time, despite high morbidity rates, associated therapy has led to prolonged survival, whereas isolated therapy has not. This is the case with an association of radical surgery, radiotherapy and adjuvant chemotherapy. IN THE FUTURE: In the treatment of malignant pleural mesothelioma, genetic, anti-proliferative and immune therapy, that attempt to use the immune system of the patient to obtain an anti-tumour cytotoxic reaction, appear promising.
UI - 10598561
AU - Thodtmann R; Depenbrock H; Blatter J; Johnson RD; van Oosterom A;
TI - Hanauske AR Preliminary results of a phase I study with MTA (LY231514) in combination with cisplatin in patients with solid tumors.
SO - Semin Oncol 1999 Apr;26(2 Suppl 6):89-93
AD - Universitair Ziekenhuis Gasthuisberg, Katholic University of Leuven, Belgium.
MTA (multitargeted antifolate, LY231514) is a novel antimetabolite resulting from structure/activity studies of the lometrexol-type antifolates. It has been shown to inhibit various enzymes of folate pathways and has broad antitumor activity in a variety of in vitro and in vivo tumor models. Clinical phase 1 studies have been performed using different administration schedules, and subsequently the every-21-days schedule has been selected for further development. We report the preliminary findings from a combination phase I study of MTA and cisplatin administered every 21 days. In the first cohort (34 patients), both agents were administered on day 1 with a starting dose of 300 mg/m2 MTA and 60 mg/m2 cisplatin. In a second cohort (10 patients), MTA (500 or 600 mg/m2) was administered on day 1 followed by cisplatin (75 mg/m2) on day 2. The maximum tolerated doses were reached at 600 mg/m2 MTA/100 mg/m2 cisplatin (cohort 1) and 600 mg/m2 MTA/75 mg/m2 cisplatin (cohort 2). In cohort 1, dose-limiting toxicities consisted of reversible myelosuppression with leukopenia and neutropenia. In addition, delayed fatigue also was of clinical significance. Pharmacokinetic analyses indicated that hydration administered before the administration of cisplatin did not influence the major pharmacokinetic parameters of MTA. Eleven objective remissions were observed, including one complete response in a patient with relapsed squamous cell carcinoma of the head and neck and partial responses in four of seven patients with mesothelioma In contrast, the dose-limiting toxicities in patient cohort 2 consisted of neutropenic sepsis, diarrhea, and skin toxicity with two possibly treatment-related deaths on study. No objective remissions are presently observed in cohort 2. We conclude that the combination of MTA and cisplatin is feasible and clinically active when both agents are administered on day 1 and that it should be pursued for further clinical development.
UI - 10640996
AU - Dhaene K; Wauters J; Weyn B; Timmermans JP; van Marck E
TI - Expression profile of telomerase subunits in human pleural mesothelioma.
SO - J Pathol 2000 Jan;190(1):80-5
AD - Laboratory of Pathology, University of Antwerp (UIA), Department of Medicine, Universiteitsplein 1, B-2610 Wilrijk - Antwerp, Belgium.
Using the TRAP assay, telomerase activity was previously detected in over 90% of human pleural mesotheliomas (MMs), but not in mesothelial cell cultures (MCCs), suggesting that telomerase re-activation occurs during multi-step mesothelioma carcinogenesis. The present study determined the expression of the telomerase RNA template (hTERC), the telomerase-associated protein (hTEP1), and the telomerase catalytic sub-unit (hTERT), in 16 pleural MMs and 4 MM-derived cell lines, in two pleural solitary fibrous tumours and in six MCCs. Reverse transcription-polymerase chain reaction analysis revealed that hTERT mRNA expression parallels the activity status documented by the TRAP assay, whereas hTERC and hTEP1 mRNA are commonly expressed in all malignant and non-malignant serosal cells and tissues. Three alternatively spliced hTERT transcripts were detected in all telomerase-positive samples, whereas neither variant could be detected in the MCCs. Detection of the hTERT protein with a commercially available antibody was not successful. These results indicate that hTERT expression is rate-limiting for human telomerase activity and that re-activation, rather than up-regulation, of hTERT expression can play a critical role in MM carcinogenesis. While waiting suitable anti-hTERT antibodies, these results provide information for the design of hTERT mRNA-specific in situ probes to study telomerase in archived pre-malignant serosal lesions. Copyright 2000 John Wiley & Sons, Ltd.
UI - 11903576
AU - Attanoos RL; Webb R; Dojcinov SD; Gibbs AR
TI - Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern.
SO - Histopathology 2001 Dec;39(6):584-8
AD - Department of Histopathology, Llandough Hospital, Cardiff and Vale NHS Trust, Penarth, Wales, UK.
AIMS: Malignant epithelioid mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how immunoreactivity with mesothelial markers related to histological pattern. METHODS AND RESULTS: Ninety-two cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) were examined and classified as exhibiting tubulopapillary, adenomatoid, solid, small cell or pleomorphic patterns. All cases were immunohistochemically stained with thrombomodulin, calretinin, CD44H, and cytokeratin 5/6. Cases of malignant mesothelioma exhibited a number of different histological forms. Immunohistochemical expression of each mesothelial marker tested was not homogeneous across different histological patterns of malignant epithelioid mesothelioma, even within the same tumour section. Calretinin (with nuclear expression) was identified to show the highest overall sensitivity and lowest range variation in staining (67% sensitivity in small cell areas to 100% expression in pleomorphic areas). Cytokeratin 5/6 and thrombomodulin yielded similar overall sensitivity. Thrombomodulin appeared to demonstrate higher sensitivity for small cell variant tumour (83% sensitivity). A notable advantage with cytokeratin 5/6 was that expression was more diffuse in nature rather than the focal membranous elaboration seen in thrombomodulin. The widest range of staining was seen in small cell mesothelioma (83% sensitivity with thrombomodulin to 17% sensitivity with cytokeratin 5/6) and in tubulopapillary areas (90% sensitivity with calretinin to 38% sensitivity with CD44H). CONCLUSIONS: Calretinin appears most useful and shows the highest overall sensitivity for malignant epithelioid mesothelioma, with good expression in areas displaying a tubulopapillary, adenomatoid, solid and pleomorphic pattern. For small cell mesothelioma, thrombomodulin appears to confer higher sensitivity and is advocated, in this setting, as the first line mesothelial marker. Cytokeratin 5/6 is a useful and easily interpretable mesothelial marker. CD44H is not of particular use in the diagnosis of malignant epithelioid mesothelioma. Accurate interpretation of immunohistochemistry in mesothelioma requires an awareness of the immunophenotypic heterogeneity identified in different histological forms of the tumour, and this is of particular importance in small biopsies.
UI - 11920963
AU - Leigh J; Davidson P; Hendrie L; Berry D
TI - Malignant mesothelioma in Australia, 1945-2000.
SO - Am J Ind Med 2002 Mar;41(3):188-201
AD - Center for Occupational and Environmental Health, Department of Public Health and Community Medicine, University of Sydney, Sydney, NSW, Australia. firstname.lastname@example.org
BACKGROUND: Australia has maintained a total national malignant mesothelioma case register since 1980. There has been a marked increase in the incidence of mesothelioma in the last 20 years. Currently 450-600 cases are notified annually in a population of 20 million. While the history of the Wittenoom (Western Australia) crocidolite mine and its aftermath is well known, these cases comprise only 5% of the total. This study describes the incidence of mesothelioma in Australia from 1945 to 2000. METHODS: Using register data, time trends in mesothelioma incidence were calculated. Analyses of incidence are reported by age, sex, anatomical site, and state of notification. Associations with occupational and environmental asbestos exposure histories are described. Lung fiber content measurements were made on a subset of cases. RESULTS: Australia has had 6,329 cases of mesothelioma from 1 rates for Australia per million population > or = 20 years (1997) were: male, 59.8; female, 10.9; total, 35.4. Incidence rates have been continually increasing and are the highest reported national rates in the world. While Western Australia has the highest rate (1997 total rate, 52.8), most cases arise from the two most populous eastern states, New South Wales and Victoria. In 88% (male 90%, female 61%) of cases, a history of asbestos exposure was obtained. Exposures occurred in a wide variety of occupational and environmental circumstances. In 80% of cases with no history of exposure, TEM lung asbestos fiber counts > 200,000 fibers > 2 microm length per gm dry lung were obtained, suggesting unrecognized exposure. CONCLUSIONS: Australia's high incidence of mesothelioma is related to high past asbestos use, of all fiber types, in a wide variety of occupational and environmental settings. The number of cases in total is expected to be about 18,000 by 2020, with about 11,000 yet to appear. Copyright 2002 Wiley-Liss, Inc.
UI - 11911261
AU - Horita K; Inase N; Miyake S; Formby B; Toyoda H; Yoshizawa Y
TI - Progesterone induces apoptosis in malignant mesothelioma cells.
SO - Anticancer Res 2001 Nov-Dec;21(6A):3871-4
AD - The Pulmonary Medicine, Tokyo Medical and Dental University, Japan.
Progesterone has been used in the treatment of patients with recurrent or metastatic progesterone receptor-positive endometrial carcinoma and breast cancer. In vitro study using a breast cancer cell line, T47D, demonstrated an increase in p53 gene expression and induction of apoptosis by the administration of progesterone. Therefore, we investigated the effect of progesterone administration on the proliferation and apoptosis in a mesothelioma cell line, 211H. The expression of the progesterone receptor gene was detected in this cell line by a nested RT-PCR method. The proliferation of the cell line was suppressed after a 10-day incubation with 30 microM progesterone. In progesterone-treated 211H cells, apoptotic cells were detected by TUNEL assay and nuclear DNA fragmentation analysis. These results clearly demonstrated that progesterone administration suppressed the cell proliferation and induced apoptosis in malignant mesothelioma cells.
UI - 10976692
AU - Churg A; Colby TV; Cagle P; Corson J; Gibbs AR; Gilks B; Grimes M;
TI - Hammar S; Roggli V; Travis WD The separation of benign and malignant mesothelial proliferations.
SO - Am J Surg Pathol 2000 Sep;24(9):1183-200
AD - University of British Columbia, Vancouver, BC, Canada. email@example.com
The separation of benign from malignant mesothelial proliferations has emerged as a major problem in the pathology of the serosal membranes. For both epithelial and spindle cell mesothelial processes, true stromal invasion is the most accurate indicator of malignancy, but stromal invasion is often difficult to assess, especially in small biopsies. In the pleural cavity, deep penetration of a thickened and fibrotic pleura or penetration of mesothelial cells into the fat of the chest wall are good indicators of malignancy; however, superficial entrapment of mesothelial cells and glands by organizing effusions is common in benign reactions and needs to be distinguished from invasion. In the peritoneal cavity, invasion of fat or of organ walls is again the most reliable indicator of malignancy, but entrapment of benign cells in organizing granulation tissue or between fat lobules is frequent and confusing. Proliferations confined to the pleural or peritoneal space, particularly linear arrays of atypical mesothelial cells on the free surface, should not be called malignant in the absence of unequivocal invasion. Cytologic atypia is often not helpful in separating benign from malignant reactions, because benign processes are commonly atypical and mesotheliomas are often deceptively monotonous. Densely packed mesothelial cells within the pleural space are frequent in benign reactions, but densely packed mesothelial cells within the stroma favor a diagnosis of malignancy. Organizing effusions (fibrous pleurisy) typically show zonation with high cellularity and cytologic atypia toward the pleural space and increasing fibrosis with decreasing cellularity and lesser atypia toward the chest wall, whereas sarcomatous (including desmoplastic) mesotheliomas do not demonstrate this type of zonation. Elongated capillaries perpendicular to the pleural surface are seen in organizing effusions but are not a feature of sarcomatous mesotheliomas. The combination of a paucicellular storiform pattern, plus invasion of the stroma (including fat and adjacent tissues), or bland necrosis, overtly sarcomatous foci, or distant metastases, is required for the diagnosis of desmoplastic mesothelioma. Necrosis is usually a sign of malignancy but is occasionally seen in benign mesothelial reactions. Keratin staining is useful in indicating the distribution of mesothelial cells, and particularly in demonstrating penetration of mesothelial cells into the stroma or adjacent structures, but is of no help in separating benign and malignant proliferations because both are keratin-positive. Although both p53 and EMA staining have been proposed as markers of mesothelial malignancy, in our experience they are not helpful for the individual case.
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