Serologic responses in patients with malignant mesothelioma: evidence for both public and private specificities.

Brain metastasis from malignant mesothelioma--case report.

Taxol inhibits growth of mesothelioma xenografts.

Combined chemotherapy in pleurectomized malignant pleural mesothelioma patients.

A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction.

Intrapleural chemotherapy for patients with incompletely resected malignant mesothelioma: the UCLA experience.

Treatment of malignant mesothelioma with methotrexate and vinblastine, with or without platinum chemotherapy.

Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content.

Mesothelioma as a risk indicator of asbestos exposure: the role of the pathologist.

Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model.

Malignant mesothelioma associated with low pulmonary tissue asbestos burdens: a light and scanning electron microscopic analysis of 18 cases.

Serologic responses in patients with malignant mesothelioma: evidence for both public and private specificities..
Abstract: Malignant mesothelioma (MM) is a pulmonary malignancy that appears to be immunogenic based on a large number of studies in both animals and humans. This notion is supported by our recent demonstration using Western blot analysis of immunoglobulin G antibodies reactive with a variety of autoantigens in many patients with MM. In view of the enormous potential of such antigens in early diagnosis, immunotherapy, and vaccination of at-risk individuals, it was essential to identify these antigens. We therefore applied the SEREX technique (serologic identification by recombinant expression cloning), using a serum pool from six patients as the probe against an expressed complementary DNA library derived from a cloned MM cell line. We screened over one million recombinants and obtained sequence information on eight antigens that had provoked immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition. Six of these antigens were identifiable (U2AF[65], Siah binding protein, topoisomerase IIbeta, ZFM1, mIre1, and pendulin), and of the others, one was found as a single EST from a myotube library (Jemm-1); the other (Jemm-2) was not represented in any EST database even as a weak homolog. Consistent with our previous findings, each of the characterizable antigens would be expected to be associated with the cell nucleus. Each of the autoantibody specificities was uniquely associated with a single patient with the exception of antibodies to TOPIIbeta and U2AF(65). We found 13 of 14 (93%) patients with MM had antibodies to TOPIIbeta and two of 14 (14%) patients had antibodies to U2AF(65). The number of serum reactivities, taken as a measure of the complexity of the immune response, correlates with patient survival and with an index of systemic inflammation. These data suggest that a broader range of serologic reactivities reflects a more active host response to the presence of tumor.
Author: Robinson C, Callow M, Stevenson S, Scott B, Robinson BW, Lake RA.
Address: University Department of Medicine, Western Australian Institute for Medical Research, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia.
Date Of Publication: 2000 May

Brain metastasis from malignant mesothelioma--case report.
Abstract: A 62-year-old male presented with a rare brain metastasis from malignant mesothelioma manifesting as headache and progressive left hemiparesis. He had previously undergone pleurectomy for malignant mesothelioma. Chest x-ray films showed no recurrence of mesothelioma. Computed tomography and magnetic resonance imaging revealed a homogeneously enhanced nodular mass adjacent to the falx in the right frontal lobe. The tumor was totally removed and diagnosed histologically as brain metastasis from malignant mesothelioma. Following surgery, left hemiparesis improved gradually. Brain metastasis from malignant mesothelioma is usually discovered in the terminal stage or at autopsy. Surgical removal and radiotherapy should be considered for isolated lesions.
Author: Kitai R, Kabuto M, Kawano H, Uno H, Kobayashi H, Kubota T
Address: Department of Neurosurgery, Fukui Medical School, Fukui.
Abbreviated Journal Title: Neurol Med Chir (Tokyo) Date Of Publication: 1995 Mar

Taxol inhibits growth of mesothelioma xenografts.
Abstract: BACKGROUND: In vitro tests measuring inhibition of adenosine triphosphate activity predicted three mesothelioma xenografts would be sensitive to taxol. PURPOSE: The in vivo therapeutic efficacy of taxol was tested in nude mice carrying the subcutaneous tumors. METHODS: Once tumor growth reached 100mm3 in size, intraperitoneal taxol, 30 mg/kg, on a day 1, 4, and 8 schedule, was administered to mice bearing subcutaneous mesothelioma xenografts. RESULTS: Taxol inhibits the growth of all three cell lines. It produces actual tumor regression including some complete responses. CONCLUSIONS: Taxol is an active drug against mesothelioma. The in vitro cell lines and the in vivo system are useful tools for screening and developing new treatments for mesothelioma.
Author: Lee JM, Bruckner HW, Szrajer L, Brenne U, Schindelheim G, Andreotti PE
Address: Derald H. Ruttenberg Cancer Center, Mount Sinai Medical Center, New York, NY 10029, USA.
Abbreviated Journal Title: Anticancer Res Date Of Publication: 1995 May-Jun

Combined chemotherapy in pleurectomized malignant pleural mesothelioma patients.
Abstract: A phase II clinical trial of 20 cancer patients who presented with malignant pleural mesothelioma (MPM) between November 1991 and April 1993 was conducted. Of the histologically proven cases, 16 (80%) were epitheloid and 4 (20%) were mixed type MPM. Patients were treated with mitomycin C, cisplatin, and alpha interferon after pleurectomy. Our schedule consisted of 10 mg/m2 mitomycin C i.v. infusion, 50 mg/m2 cisplatin i.v. infusion, 10 mil Ur-alpha interferon i.m. and 10 mil Ur-alpha interferon i.v. infusion on the first day of treatment. Patients were given a mean of 4.5 chemotherapy cycles (range: 2-6). None of the patients showed complete or partial response. Stable disease was observed in 15 patients, while 5 patients had progressive courses. The overall median survival time after chemotherapy was 12 months (range: 3-31 months). Median survival after chemotherapy was 15 months (range: 4-31 months) in the stable disease group (n:15, 75%), and 5 months (range: 3-13 months) in progressive cases (n:5, 25%). The overall survival rates were 55% [95% Confidence Interval (CI):43%-88.8%] at one year and 15% (95% CI:5%-39.1%) at 2 years. Five patients had grade 3 alopecia, three had grade 2 vomiting and nausea, two had grade 2 leukopenia, one had grade 2 cardiotoxicity and another had discoloration on his fingernails. In our multimodal therapy protocol, we found no difference in survival and relapse rates between our combined modal therapy and other single modal therapies in the literature.
Author: Hasturk S, Tastepe I, Unlu M, Cetin G, Baris YI
Address: Department of Chest Diseases, Cukurova University, Adana, Turkey.
Abbreviated Journal Title: J Chemother Date Of Publication: 1996 Apr

A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction.
Abstract: BACKGROUND: The treatment of malignant pleural mesothelioma (MPM) continues to be inadequate with the use of standard techniques, including surgery, radiotherapy and chemotherapy. We initiated a phase II trial of immunochemotherapy with cisplatinum (25 mg/m2 four times weekly), interferon-alpha (5 mU/m2 s.c. three times weekly, and tamoxifen (20 mg orally twice a day for 35 days) (CIT) based on in vitro and in vivo data suggesting interrelating efficacy of this combination. METHODS: Since July 1991, 36 patients have been evaluable for response after receiving one to five cycles of CIT. Ten additional patients had debulking surgery followed by two cycles of postoperative adjuvant CIT commencing a mean of 6 weeks after surgery. RESULTS: Toxicity was acceptable (4% grade III/IV). One treatment-related death (2%) occurred, from myocardial infarction. A 19% partial response rate, objectively quantified using three-dimensional computerized tomographic (CT) measurement of solid disease volume, was recorded. The median survival for the seven responders was 14.7 months, whereas that of the nonresponders was 8 months (p2 = 0.2). Median survival for the entire group was 8.7 months. Preoperative size, platelet count > 360,000/ml, and nonepithelial histology were associated with shortened survival. CONCLUSIONS: The CIT regimen has some activity in MPM and can be delivered after debulking resection. In good-risk patients, as defined by favorable prognostic factors, a randomized trial using this combination may be warranted.
Author: Pass HW, Temeck BK, Kranda K, Steinberg SM, Pass HI
Address: Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abbreviated Journal Title: Ann Surg Oncol Date Of Publication: 1995 May

Intrapleural chemotherapy for patients with incompletely resected malignant mesothelioma: the UCLA experience.
Abstract: From 1986 to 1993, 15 patients with malignant pleural mesothelioma were treated by pleurectomy/decortication and intrapleural cisplatin (100 mg/m2) and cytosine arabinoside (1,200 mg). All patients were without known extrathoracic disease and had a mean age of 63 +/- 7.9 years (range 51-78); 13 were male. Histologic subtype of disease were epithelial (47%), sarcomatoid (27%), and mixed-biphasic (27%). The major morbidity and mortality rates were 13% and 0%, respectively. The mean length of hospital stay was 6.5 +/- 2.1 days. Postoperatively, adjuvant chemotherapy and radiation therapy were given to 46% and 73% of the patients respectively. Median survival from date of treatment was 11.5 months. Those patients with an epithelial histologic subtype experienced significantly improved survival compared to those of sarcomatoid subtype (P = 0.024). Whether adjuvant chemotherapy or radiation therapy were given had no significant effect on survival. These data suggest that although this treatment regimen can be administered with very limited morbidity and no mortality, the role of this approach in the treatment of malignant pleural mesothelioma appears limited and cannot currently be recommended.
Author: Lee JD, Perez S, Wang HJ, Figlin RA, Holmes EC
Address: Department of Surgery, University of California, School of Medicine, Los Angeles 90024, USA.
Abbreviated Journal Title: J Surg Oncol Date Of Publication: 1995 Dec

Treatment of malignant mesothelioma with methotrexate and vinblastine, with or without platinum chemotherapy.
Abstract: STUDY OBJECTIVE: To determine the efficacy of methotrexate, vinblastine, and platinum chemotherapy in patients with diffuse unresectable malignant mesothelioma. DESIGN: Patients with histologically confirmed malignant mesothelioma were evaluated for treatment with methotrexate, vinblastine, and cisplatin chemotherapy. If the patient had preexisting hearing loss or neuropathy, or was significantly disabled (eg, spending greater than half of the day in bed or a chair), cisplatin therapy was withheld. SETTING: All patients were initially evaluated at the University of Washington Medical Center and received chemotherapy at the University of Washington or in the community. INTERVENTIONS: Between 1990 and 1994, 17 patients received this chemotherapy. Ten patients received cisplatin, 100 mg/m2 IV on day 1, methotrexate, 30 mg/m2 IV on days 8, 15, and 22, and vinblastine, 3 mg/m2 IV on days 8, 15, and 22, in 28-day cycles. One patient had carboplatin substituted for cisplatin due to preexisting hearing loss. Six patients received weekly methotrexate and vinblastine at the same doses without platinum. MEASUREMENTS AND RESULTS: Nine of the 17 (53%; 95% confidence interval [CI], 28 to 77%) patients responded, including two complete remissions, two partial remissions, and five regressions. Median time to progression is 8 months. The median survival time for all patients is 14 months. Projected 2-year survival is 35% (95% CI, 12 to 60%). CONCLUSIONS: Although the number of the patients in this study is small, the response rate and projected 2-year survival of 35% are better than those typically reported for unresectable malignant mesothelioma. Further investigation is warranted in confirmatory trials.
Author: Hunt KJ, Longton G, Williams MA, Livingston RB
Address: Department of Medicine, University of Washington Medical Center, Seattle, USA.
Abbreviated Journal Title: Chest Date Of Publication: 1996 May

Malignant mesothelioma and duration of asbestos exposure: correlation with tissue mineral fibre content.
Abstract: Among 441 cases of malignant mesothelioma in the author's files, there were 324 for whom reliable information was available regarding the duration of exposure to asbestos. Included were 298 pleural and 26 peritoneal mesotheliomas. The mean duration of exposure to asbestos was 23 +/- 14 years for all cases, and was not different for the pleural and peritoneal groups. Lung tissue was available for analysis of mineral fibre content in 94 cases. Linear regression analysis showed a significant correlation between duration of exposure and asbestos bodies per gramme of wet lung as determined by light microscopy, and between duration of exposure and total uncoated fibres (5 microns or greater in length) as well as commercial amphibole fibres per gramme as determined by scanning electron microscopy.
Author: Roggli VL
Address: Department of Pathology, Durham Veterans Administration, NC 27710, USA.
Abbreviated Journal Title: Ann Occup Hyg Date Of Publication: 1995 Jun

Mesothelioma as a risk indicator of asbestos exposure: the role of the pathologist.
Abstract: Malignant mesothelioma is an uncommon tumor, which has become an important epidemiological marker for exposure to asbestos. This tumour is characterised by a wide range of microscopic features which may be classified in three histologic patterns: epithelial, mesenchimal and mixed or biphasic. Histochemical staining is often necessary to distinguish mesothelioma from carcinoma. As regards immunohistochemistry, only the use of a combination of antibodies significantly decreases the risk of false-negative results. Analytic electron microscopy techniques may also be useful, permitting the evaluation of the cumulative fiber burden in the target organ.
Author: Zampi G, Comin CE, Dini S
Address: Institute of Pathological Anatomy and Histology, University of Florence, Italy.
Abbreviated Journal Title: Med Lav Date Of Publication: 1995 Sep-Oct

Clinical course of human epithelial-type malignant pleural mesothelioma replicated in an orthotopic-transplant nude mouse model.
Abstract: Malignant pleural mesothelioma is an aggressive tumor that is essentially unresponsive to standard medical and surgical therapies. Little is actually known about its biologic response to therapeutic interventions, in part because of a lack of a "patient-like" animal tumor model. Most experimental models thus far have been derived from inhalation or inoculation of asbestos fibers into animal subjects or by subcutaneous transplantation of human mesothelial cell lines into nude mice. These models are not representative of clinical malignant pleural mesothelioma. In this report, an animal model of human pleural malignant mesothelioma obtained by orthotopic transplantation of intact pleural tumor tissue into athymic nude mice is described. Pleural tumor obtained by thoracolscopy from a patient with epithelial-type malignant pleural mesothelioma was implanted as intact tissue by surgical orthotopic implantation (SOI) into the right pleural cavity of nude mice. Animals were sacrificed when moribund or 6 months after implantation. Tumor growth and regional spread in the mice evaluated at post-mortem examination mimicked the clinical pattern of progression of human disease. Histologic findings and the immunohistochemical profile were similar to those demonstrated on examination of thoracoscopic parietal pleural biopsy specimens and post-mortem examination of the original patient's tumor. This "patient-like" nude mouse model of epithelial-type malignant pleural mesothelioma, phenotypically similar to the original human tumor, should facilitate future investigation of tumorigenesis and metastatic potential of this neoplasm. The model should serve as a basis for assessing the impact of experimental and existing therapy on malignant mesothelioma.
Author: Colt HG, Astoul P, Wang X, Yi ES, Boutin C, Hoffman RM
Address: Division of Pulmonary and Critical Care Medicine, University of California San Diego Medical Center, 92103, USA.
Abbreviated Journal Title: Anticancer Res Date Of Publication: 1996 Mar-Apr

Malignant mesothelioma associated with low pulmonary tissue asbestos burdens: a light and scanning electron microscopic analysis of 18 cases.
Abstract: Most malignant mesothelioma cases are associated with pulmonary asbestos body (AB) counts significantly greater than those of the general population. However, the question remains whether malignant mesothelioma cases associated with "normal" AB counts (i.e., indistinguishable from the general population) represent background incidence levels or are, actually, asbestos related. We performed AB counts (by light microscopy) and mineral fiber analysis (by scanning electron microscopy) in 18 mesothelioma cases with AB counts within our normal range (0 to 20 AB/G wet lung) and in 19 "control" cases. Our study demonstrated that approximately one-third (6 of 18) of the mesothelioma cases have asbestos fiber burdens greater than 95% of the control levels. These results suggest that these six mesothelioma cases may be asbestos related despite AB counts similar to those of the general population. An asbestos etiology was suggested in three additional cases, but too few amphibole fibers were identified in these cases to be certain of a value above background. The remaining nine cases showed no evidence of an asbestos etiology. Electron microscopic analysis of pulmonary mineral fibers may be required to differentiate asbestos-related mesotheliomas from non-asbestos-related cases when AB counts are within the range of background values.
Author: Srebro SH, Roggli Vlk, Samsa GP
Address: Department of Pathology, Durham Veterans' Administration, North Carolina, USA.
Abbreviated Journal Title: Mod Pathol Date Of Publication: 1995 Aug