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NCI CANCERLIT® Search: Malignant Mesothelioma - September 2001
Last Modified: November 1, 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21378028
AU - Catalano A; Romano M; Robuffo I; Strizzi L; Procopio A
TI - Methionine aminopeptidase-2 regulates human mesothelioma cell survival: role of Bcl-2 expression and telomerase activity.
SO - Am J Pathol 2001 Aug;159(2):721-31
AD - Department of Experimental Pathology, University of Ancona, Ancona, Italy.
Methionine aminopeptidase-2 (MetAP2) is the molecular target of the angiogenesis inhibitors, fumagillin and ovalacin. Fumagillin can also inhibit cancer cell proliferation, implying that MetAP2 may play a quite complex role in tumor progression. Here, we examined the expression and function of MetAP2 in an in vitro model of human mesothelioma. We found that mesothelioma cells expressed higher MetAP2 mRNA levels than primary normal mesothelial cells. Consistently, fumagillin induced apoptosis, owing to early mitochondrial damage, in malignant, but not in normal mesothelial cells. Transfection of mesothelioma cells with a MetAP2 anti-sense oligonucleotide determined a time-dependent inhibition of cell survival and induced nucleosome formation. Interestingly, mRNA and protein levels of the anti-apoptotic gene bcl-2 as well as telomerase activity were selectively reduced after MetAP2 inhibition in mesothelioma cells, whereas bcl-2 overexpression counteracted the effect of MetAP2 inhibition on telomerase activity and apoptosis. MetAP2 inhibition also increased caspase activity and the caspase inhibitor, zVAD-fmk, prevented fumagillin-induced apoptosis, but it did not alter telomerase activity. These results indicate that MetAP2 is a main regulator of proliferative and apoptotic pathways in mesothelioma cells and suggest that MetAP2 inhibition may represent a potential target for therapeutic intervention in human mesothelioma.

2
UI - 21385074
AU - Soini Y; Puhakka A; Kahlos K; Saily M; Paakko P; Koistinen P; Kinnula V
TI - Endothelial nitric oxide synthase is strongly expressed in malignant mesothelioma but does not associate with vascular density or the expression of VEGF, FLK1 or FLT1.
SO - Histopathology 2001 Aug;39(2):179-86
AD - Department of Pathology, University Hospital, University of Oulu, PO Box 5000 (Aapistie 5), FIN-90014 Oulu, Finland. msoini@cc.oulu.fi
AIMS: To investigate endothelial nitric oxide synthase (eNOS) expression in malignant mesothelioma and its association with expression of vascular endothelial growth factor (VEGF), its receptors FLK1 and FLT1, and vascular density. METHODS AND RESULTS: eNOS, VEGF, FLK1 and FLT1 were studied in 36 histological mesothelioma samples by immunohistochemistry. Two mesothelioma (M14K, M38K) and one non-neoplastic mesothelial cell line (MET-5A) were studied for eNOS mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR). Vascular density was determined by staining the samples with an antibody to factor VIII. RT-PCR showed that mesothelioma cells synthesize eNOS in vitro. eNOS immunoreactivity was found in 32/36 (89%) tumours. VEGF, FLK1 and FLT1 expression was found in 17 (45%), 24 (69%) and 25 (71%) cases, respectively. FLK1 or FLT1 immunoreactivity was more often seen in epithelioid and biphasic mesotheliomas than in sarcomatoid ones (P=0.007 and P=0.011, respectively). There was a significant association between FLK1 and FLT1 immunoreactivity (P=0.032). No significant association was found between FLK1, FLT1, VEGF and eNOS immunoreactivity and vascular density. CONCLUSIONS: eNOS is strongly expressed in malignant mesothelioma. Since eNOS did not associate with VEGF, FLK1 or FLT1, its synthesis seems not to be regulated through VEGF in malignant mesothelioma as has been shown in non-neoplastic endothelial cells.

3
UI - 21397929
AU - Yang CT; You L; Uematsu K; Yeh CC; McCormick F; Jablons DM
TI - p14(ARF) modulates the cytolytic effect of ONYX-015 in mesothelioma cells with wild-type p53.
SO - Cancer Res 2001 Aug 15;61(16):5959-63
AD - Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
ONYX-015 has been reported to kill selectively tumor cells lacking functional p53. Genetic alterations of INK4a/ARF locus, which is a predominant event in malignant pleural mesothelioma, may result in loss of p14(ARF) and subsequent disruption of p53 pathway in cancer cells. In the present study, ONYX-015 was able to kill three mesothelioma cell lines (H28, H513, and 211H) with wild-type p53 but lacking p14(ARF). In contrast, MS-1 mesothelioma cells, which expressed both p53 and p14(ARF), were resistant to ONYX-015. Introducing p14(ARF) gene into the H28 cell, a mesothelioma cell without p14(ARF) expression, significantly increased the resistance of this cell line to the cytolytic effect of ONYX-015. Our results suggest that human mesotheliomas with wild-type p53 yet lacking p14(ARF) are potential candidates for ONYX-015 therapy.

4
UI - 21363315
AU - Wick MR; Moran CA; Mills SE; Suster S
TI - Immunohistochemical differential diagnosis of pleural effusions, with emphasis on malignant mesothelioma.
SO - Curr Opin Pulm Med 2001 Jul;7(4):187-92
AD - University of Virginia Medical Center, Charlottesville, Virginia, USA. mrw9c@virginia.edu
The immunohistochemical diagnosis of atypical epithelial proliferations in pleural fluid is a challenging topic in cytopathology and surgical pathology. Mesothelioma may be simulated clinically and radiologically by several other nonneoplastic and neoplastic disorders, mandating that strict histologic, histochemical, immunohistochemical, and ultrastructural guidelines be followed for its diagnosis. Because of its availability to most laboratories, immunohistochemistry has emerged as the most commonly used procedure for the diagnosis of pleural malignancies. This review considers the current status of that investigative modality, with particular attention to lesions that are suspected to be mesothelial.

5
UI - 21236683
AU - Jaklitsch MT; Grondin SC; Sugarbaker DJ
TI - Treatment of malignant mesothelioma.
SO - World J Surg 2001 Feb;25(2):210-7
AD - Department of Surgery, Division of Thoracic Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115, USA.
Malignant pleural mesothelioma (MPM) is a rare tumor that predominantly afflicts men over 50 years of age. Nearly 3000 MPMs are reported annually in the United States with the incidence expected to rise into the new millenium. Over the past 40 years, MPM has been unequivocally linked to asbestos exposure worldwide. Recently, however, a new theory on the carcinogenesis of this tumor has been proposed with the isolation of a simian virus (SV 40)-like gene sequence in mesothelioma tumor cells. The clinical presentation of MPM is variable, although most patients typically present with dyspnea, chest pain, or pleural effusion. Obtaining a diagnosis of MPM has been greatly assisted by video-assisted surgery and the use of immunohistochemistry and electron microscopic techniques, which help distinguish MPM from other tumor pathologies such as adenocarcinoma. Computed tomography and magnetic resonance imaging have been also useful for determining tumor burden and resectability. Traditionally, strategies for the treatment of MPM have included supportive care, surgery, radiotherapy, and chemotherapy. Survival with supportive care alone ranges between 4 and 12 months. Single-modality therapy using traditional approaches (surgery, radiotherapy, chemotherapy) alone has failed to improve patient survival significantly. Recently, results using a multimodality approach have been favorable. In particular, cytoreductive surgery (pleuropneumonectomy) followed by sequential chemotherapy and radiotherapy have demonstrated improved survival, especially for patients with epithelial histology, negative resection margins, and no metastases to extrapleural lymph nodes. Innovative therapies such as the use of photodynamic, targeted cytokines and gene therapy are currently being investigated for management of MPM.

6
UI - 21397895
AU - Li Y; Heldin P
TI - Hyaluronan production increases the malignant properties of mesothelioma cells.
SO - Br J Cancer 2001 Aug 17;85(4):600-7
AD - Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala University, Box 575S-751 23 Uppsala, Sweden.
Malignant pleural mesotheliomas is in most cases associated with elevated amounts of hyaluronan. To investigate the importance of hyaluronan for the malignant properties of mesotheliomas, we have expressed murine hyaluronan synthase 2 (HAS2) in the non-hyaluronan producing mesothelioma cell line, Mero-25. We found that upon hyaluronan overproduction the mesothelioma cells changed their epitheloid character to a fibroblastic phenotype and were surrounded by pericellular matrices, the size of which correlated to the amount of synthesized hyaluronan. HAS2-transfected cells with the ability to synthesize about 520 ng hyaluronan/5 x 10(4)cells/24 h exhibited about a 2-fold increase in the expression of the cell surface hyaluronan receptor CD44 and their locomotion increased compared to that of mock-transfected Mero-25 cells. Furthermore, the malignant properties of mesothelioma cell clones as determined by the ability to grow in a soft agar assay correlated to their hyaluronan production. These results provide evidence for an important role of hyaluronan in the aggressive spread of mesotheliomas in adjacent non-cancerous stromal tissues. Copyright 2001 Cancer Research Campaign.

7
UI - 21428490
AU - Ost E; Illiger HJ
TI - [Vinorelbine in patients with malignant pleural mesothelioma--a phase II study]
SO - Strahlenther Onkol 2001 Aug;177(8):440-1

8
UI - 21421802
AU - Olut A; Firat P; Ertugrul D; Gungen Y; Emri S
TI - Ras oncoprotein expression in erionite- and asbestos-induced Turkish malignant pleural mesothelioma patients--a pilot study.
SO - Respir Med 2001 Aug;95(8):697-8
AD - Department of Clinical Microbiology and Infectious Diseases, Hacettepe University School of Medicine, Ankara, Turkey.

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