National Cancer Institute®
Last Modified: July 1, 2002
UI - 12015746
AU - Strizzi L; Muraro R; Vianale G; Natoli C; Talone L; Catalano A; Mutti L;
TI - Tassi G; Procopio A Expression of glycoprotein 90K in human malignant pleural mesothelioma: correlation with patient survival.
SO - J Pathol 2002 Jun;197(2):218-23
AD - Department of Oncology and Neurosciences, G. D'Annunzio University, Chieti, Italy. email@example.com
The expression of the tumour-associated glycoprotein 90K in patients with malignant pleural mesothelioma (MM) has not been described. This study used enzyme-linked immunoassay (ELISA) to measure 90K in pleural effusions (PEs) and sera from patients with MM (n=28), lung cancer (LC) (n=14) and benign pleural disease (BPD) (n=15). Immunohistochemistry was used to investigate 90K expression in MM and LC tissue sections. The expression of 90K was further evaluated in vitro by ELISA and western blot analysis of conditioned media and cellular extracts of MM, LC and normal human mesothelial (NHM) cell cultures. Finally, the relationships between 90K expression in MM and patient age and survival were studied. The mean 90K level was significantly higher (p<0.05) in PEs of MM patients (11.0+/-6.6 microg/ml) than in LC (6.1+/-3.2 microg/ml) or BPD (6.2+/-5.0 microg/ml) patients. Immunohistochemistry showed a positive reaction for 90K in MM biopsy sections and positive staining limited to inflammatory infiltrates in LC sections. The level of 90K was significantly higher in cell culture media of MM than of LC or NHM (p<0.001). Bands representing proteins with molecular weight of approximately 90 kDa were detected by western blot in MM cellular extracts. An inverse correlation between PE 90K levels and MM patient age (r=-0.45; p=0.017) and a positive correlation between serum 90K levels and MM patient survival (r=0.62; p=0.006) were detected by linear regression analysis. Kaplan-Meier univariate analysis showed increased survival probability for MM patients with serum 90K level >7.3 microg/ml (log rank, p<0.05). This is the first report in MM of the expression of 90K and of its potential diagnostic and prognostic application. Copyright 2002 John Wiley & Sons, Ltd.
UI - 11977485
AU - Jimborean G; Gabor M; Szilai D
TI - [Considerations upon diagnosis and treatment of lung and pleural tumors in Mures county]
SO - Pneumologia 2001 Jul-Sep;50(3):148-53
AD - Clinica Pneumologie Targu-Mures.
We studied 171 patients with pulmonary and pleural tumours, in 1999. Within this group we had 87.7% primary lung cancers, 8.8% pulmonary methastatic tumors and 3.5% pleural mesothelioma. The primary lung cancer is more frequent in men (male-female ratio = 8.4) and in patients living in rural area; it involved persons over 40 years only. The chronic tobacco use is the main risk factor we found among these patients (80%). All the patients showed symptoms linked to delayed diagnosis. Radiology was characteristic in 100% of the cases, showing typical aspects of lung tumours and complications and contributed to staging. The bronchoscopy was the main procedure in diagnosis (80.1%), allowing the microscopic confirmation and contributing in staging. The thoracic computed thomography was performed in 30.4% of the cases. We had a late case finding (56.7% in the stage III, 26% in the stage IV) allowing the surgical treatment in only 15.2% of the cases. The early diagnosis of lung cancers would be possible by "oncological screening", combining clinical aspects with data from radiology and bronchoscopy in high-risk persons (heavy smokers, contacts with cancer producing substances). Performing bronchoscopy and computed tomography in all patients with lung cancer would allow the histological diagnosis and the proper staging for a proper treatment. The education against smoking will allow the decrease of the lung cancer in the future.
UI - 11824875
AU - Adlard JW; Joseph J; Brammer CV; Gerrard GE
TI - Open access follow-up for lung cancer: patient and staff satisfaction.
SO - Clin Oncol (R Coll Radiol) 2001;13(6):404-8
AD - Yorkshire Regional Centre for Cancer Treatment, Cookridge Hospital, Leeds, UK.
The majority of patients with lung cancer have incurable disease from presentation and a survival measured in months. Treatments offered to these patients are aimed at the palliation of symptoms with either radiotherapy or chemotherapy, or with supportive measures. It has been traditional to offer regular outpatient follow-up after initial palliative treatment. Further treatment options, which may be limited, are usually reserved for the recurrence of troublesome symptoms. A pilot 'open access' lung cancer clinic has been set up. Rather than have regular follow-up at the hospital, patients who have completed initial palliative treatments are discharged to the community with follow-up by their general practitioner and Macmillan nurse. Review at the open access clinic can be arranged at short notice if requested by the patient, carers, general practitioner or Macmillan nurse. The outcomes and level of satisfaction of patients, their relatives and staff to this method of follow-up were found to be positive. Open access follow-up may be useful for many patients after the completion of initial palliative treatment.
UI - 12063468
AU - Smythe WR; Mohuiddin I; Ozveran M; Cao XX
TI - Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product.
SO - J Thorac Cardiovasc Surg 2002 Jun;123(6):1191-8
AD - Department of Thoracic and Cardiovascular Surgery, Section of Thoracic Molecular Oncology, University of Texas M.D. Anderson Cancer Center, Houston, 77030, USA. firstname.lastname@example.org
OBJECTIVE: Malignant pleural mesothelioma is resistant to conventional therapies and to apoptosis. The bcl-2 family genes are major determinants of apoptotic homeostasis. Malignant pleural mesothelioma lines and tumors rarely express the antiapoptotic Bcl-2 protein but routinely express the antiapoptotic protein Bcl-xl and the proapoptotic proteins Bax and Bak. We have previously shown pharmacologic inhibition of bcl-xl expression in malignant pleural mesothelioma can lead to apoptosis, so we sought to determine whether antisense oligonucleotides directed at bcl-xl messenger RNA would engender apoptosis, possibly through a "forced imbalance" of bcl-2 family proteins. METHODS: Malignant pleural mesothelioma lines REN (epithelial) and I-45 (sarcomatous) were exposed to modified bcl-xl antissense oligonecleotides directed near the messenger RNA initiation sequence with and without a liposomal delivery system. Untreated cells and bcl-xl sense oligonucleotides were controls. Cell viability was measured by colorimetric assay, and apoptosis was evaluated with Hoechst staining and sub-G(1) fluorescence-activated cell sorter analysis. RESULTS: Bcl-xl protein expression after antisense oligonucleotides was downwardly regulated in both cell lines relative to sense oligonucleotides (>65%). Significant cellular killing in both the I-45 and REN cell lines was achieved with antisense oligonucleotides (compared with sense oligonucleotides) without (P =.003 and.006, respectively) and with (P =.006 and.0005, respectively) liposomal delivery. Hoechst staining and sub-G(1) fluorescence-activated cell sorter analysis demonstrated apoptosis to be the mechanism of cellular death. Use of a liposomal delivery system increased therapeutic effect and allowed lower doses of antisense oligonucleotides. CONCLUSION: Antisense oligonucleotides directed at the bcl-xl gene product engender apoptosis in mesothelioma cell lines. The therapeutic potential of inhibiting expression of this protein in mesothelioma should be evaluated.
UI - 12057100
AU - Hahn SM; Smith RP; Friedberg J
TI - Photodynamic therapy for mesothelioma.
SO - Curr Treat Options Oncol 2001 Oct;2(5):375-83
AD - Department of Radiation Oncology, University of Pennsylvania, 2 Donner, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA. Hahn@xrt.upenn.edu
Multiple trials of traditional cancer therapies for malignant pleural mesothelioma (including surgery, radiation therapy, and chemotherapy) have not convincingly demonstrated that any one treatment is superior to supportive care alone. Although there have been reports of long-term survivors who were treated with aggressive surgery combined with radiation and aggressive multi-agent chemotherapeutic regimens, these patient populations are highly selected and results cannot be generalized to a larger population. Despite attempts to use aggressive multimodality therapies, disease recurs in most patients. Local failure in particular is a large part of the natural history of mesothelioma, especially after surgery alone. Therefore, one of the major considerations in the development of new treatments is the inclusion of aggressive local therapies. Photodynamic therapy (PDT), a local treatment modality, is being evaluated as an adjuvant therapy to surgical resection. Clinical use of PDT requires the use of a photosensitizing agent and light of a wavelength specific to the absorption characteristics of the sensitizer in the presence of oxygen. The treatment effect of PDT is superficial, mostly because of the limited depth of light absorption in tissues. Therefore, it is theoretically an ideal treatment for tissue surfaces and body cavities after surgical debulking procedures. One theoretical advantage of PDT is that it can be used to treat the lung surface after a pleurectomy; therefore, patients may be treated with a pleurectomy rather than with an extrapleural pneumonectomy. Several studies have evaluated the efficacy of PDT in the treatment of mesothelioma. Clinical studies have not proven convincingly that the use of PDT is superior to the use of other adjuvant therapies or to surgery alone. The advent of newer photosensitizers and improved laser technology has led to a renewed interest in evaluating PDT. Additional studies are necessary to determine the role of PDT in the treatment of mesothelioma.
UI - 12057101
AU - Verschraegen CF
TI - Intracavitary therapies for mesothelioma.
SO - Curr Treat Options Oncol 2001 Oct;2(5):385-94
AD - Section of Gynecologic and Medical Therapeutics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe, Box 401, Houston, TX 77030, USA. email@example.com
The diagnosis of mesothelioma needs to be defined histologically. The staging system has been recently redefined anatomically, but may not be applicable to extrapleural mesothelioma. Further clinicopathologic studies need to be performed to molecularly classify the disease further, according to prognosis. Intracavitary therapy has a definite role in the treatment of mesothelioma. Randomized studies of intracavitary therapies are needed to define the best treatment option. The role of complementary therapeutic modalities such as surgery and radiotherapy needs to be defined by randomized studies. There is an urgent need to better understand the biology of mesothelioma, which may lead to more focus on molecularly relevant therapies.
UI - 12057102
AU - Loggie BW
TI - Malignant peritoneal mesothelioma.
SO - Curr Treat Options Oncol 2001 Oct;2(5):395-9
AD - Department of Surgery, Division of Surgical Oncology, The University of Texas Southwestern Medical Center at Dallas, 1400 Eighth Avenue, Suite 101, Fort Worth, TX 76104, USA. firstname.lastname@example.org
This paper summarizes the author's thoughts about the use of cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy (CS-IPHC) for treatment of peritoneal malignant mesothelioma. Pleural malignant mesotheliomas are by far more common (about ten- to thirty-fold) than the peritoneal variants (2.2 cases per 1 million in the US). Other locations (pericardium, tunica vaginalis) are very rare. It is well known that chemotherapy for mesothelioma is largely unsatisfactory, and measurement of treatment responses can be difficult. Single agent responses are all less than 20% with currently available agents for systemically administered drugs. Multiple drug combinations are typically more toxic, and have yielded little consistent demonstrable benefit with major studies reporting median survivals consistently under a year. There is currently more attention being paid to the response category of "stable" or absence of disease progression in concert with quality of life measurements; all regimens show poor durability. With peritoneal malignant mesothelioma, malignant ascites is a common presentation and a major factor in disease-related morbidity and mortality. Interperitoneal administration of agents is attractive, but drug distribution is an issue, as are response rates and durability. Multiple treatments are required; further, all neoplasms with peritoneal dissemination are typically understaged by current radiologic tests (CT, MRI), and the variable uptake of sugar by the small bowel limits the use of positron-emission tomography (PET) imaging for peritoneal malignant mesothelioma. Also, symptoms of bowel obstruction are not uncommon, and any mechanical component of obstruction will not improve with any form of chemotherapy. The author's approach relies on surgery to achieve the following: 1) accurate staging; 2) tumor debulking, as possible, and treatment of mechanical obstruction as well as prevention of impending obstruction by resection or bypass; and 3) preparation for the use of intra-operative hyperthermic chemotherapy perfusion. This approach has been associated with rapid clinical symptom improvement, as well as a reliable and durable resolution of ascites with a single therapy. Morbidity and mortality have been acceptable with about 27-month median survival. The inability to provide effective systemic therapy to maintain or consolidate these gains is problematic.
UI - 11323795
AU - Merler E; Silvestri S; Mauro L; Campinoti G
TI - Re: mortality among workers in the geothermal power plants at Larderello, Italy. Am. J. Ind. Med. 35:536-539, 2000.
SO - Am J Ind Med 2001 Apr;39(4):436-7; discussion 438
UI - 11414249
AU - Browne K
TI - The quantitative risks of mesothelioma and lung cancer in relation to asbestos exposure.
SO - Ann Occup Hyg 2001 Jun;45(4):327-9; discussion 336-8
UI - 12001992
AU - Tweedale G
TI - Asbestos and its lethal legacy.
SO - Nat Rev Cancer 2002 Apr;2(4):311-5
AD - Centre for Business History, Business School, Manchester Metropolitan University, UK. G.Tweedale@mmu.ac.uk
Asbestos has become the leading cause of occupationally related cancer death, and the second most fatal manufactured carcinogen (after tobacco). In the public's mind, asbestos has been a hazard since the 1960s and 1970s. However, the knowledge that the material was a mortal health hazard dates back at least a century, and its carcinogenic properties have been appreciated for more than 50 years.
UI - 11414250
AU - Liddell D
TI - Asbestos and cancer.
SO - Ann Occup Hyg 2001 Jun;45(4):329-35; discussion 336-8
UI - 12082623
AU - Toyooka S; Carbone M; Toyooka KO; Bocchetta M; Shivapurkar N; Minna JD;
TI - Gazdar AF Progressive aberrant methylation of the RASSF1A gene in simian virus 40 infected human mesothelial cells.
SO - Oncogene 2002 Jun 20;21(27):4340-4
AD - Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, TX 75390, USA.
Mesotheliomas are tumors arising from mesothelial cells and are associated with asbestos exposure and approximately 50% contain simian virus 40 (SV40) DNA sequences. SV40 infection of human mesothelial cells (HM) causes early cellular immortalization and late transformation. Aberrant methylation is a major mech-anism for loss of function of tumor suppressor genes (TSGs). We recently reported that of seven genes frequently methylated in epithelial tumors, only RASSF1A gene was frequently methylated in mesotheliomas, and its methylation was correlated with loss of RASSF1A expression and the presence of SV40. We studied whether SV40 infection of normal HM induces aberrant methylation of the genes previously studied in mesotheliomas. Of six infected foci examined at early passages (passages 8-30) there was no methylation of the seven genes examined. Of two foci examined at late passages (passages 51-86) after the appearance of morphological changes suggestive of transformation, methylation and loss of expression of RASSF1A was detected. Sequencing of the CpG dense region around the transcription start site and semi-quantitative real-time methylation specific PCR (MSP) assay for RASSF1A methylation demonstrated progressive methylation during late passages. Exposure to the demethylating agent 5-aza-2'-deoxycytidine restored RASSF1A expression, while exposure to the histone deacetylation inhibitor trichostatin A had no effect. These data, together with our previous findings, support a causal relationship between SV40 infection, progressive RASSF1A methylation and its silencing, and the pathogenesis of mesothelioma.
UI - 12057155
AU - Vigneswaran WT; Stefanacci PR
TI - Pericardial mesothelioma.
SO - Curr Treat Options Oncol 2000 Oct;1(4):299-302
AD - Loyola University Medical Center Chicago and Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA.
Primary pericardial mesothelioma is a rare but lethal disease. Altogether there are about 150 cases reported in the literature. In most cases the diagnosis is made at autopsy or postoperatively. Clinical signs and symptoms are typically nonspecific and are similar to compromised cardiac function. Surgical resection remains the main treatment modality. When the disease is localized and completely resected, long-term survival can result. Most often the tumor invades the myocardium or the great vessels and therefore is at best palliative in relieving pericardial tamponade or constriction. Addition of chemotherapy or radiation has been disappointing. Newer therapeutic approaches for malignant pleural mesothelioma are likely to influence the treatment of pericardial mesothelioma in the future.
UI - 12057156
AU - Taub RN; Keohan ML; Chabot JC; Fountain KS; Plitsas M
TI - Peritoneal mesothelioma.
SO - Curr Treat Options Oncol 2000 Oct;1(4):303-12
AD - Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, 161 Fort Washington Avenue, New York, NY 10032, USA.
Malignant peritoneal mesothelioma is an aggressive neoplasm that rapidly spreads within the confines of the abdominal cavity to involve most accessible peritoneal and omental surfaces. Current treatments are unsatisfactory, and new approaches are needed. We have noted prolonged survival in selected patients after intensive multimodality treatment. Our current experimental regimen includes initial laparotomy with omentectomy, resection of peritoneal implants, and placement of bilateral peritoneal Port-a-Caths (Sims Deltec, Inc., St. Paul, MN); repeated courses of intraperitoneal chemotherapy with doxorubicin, cisplatin, and interferon gamma; second-look laparotomy and intraoperative hyperthermic perfusion with mitomycin and cisplatin; and whole abdominal radiation. Patients with peritoneal mesothelioma who are not candidates for this approach can sometimes be palliated with systemic (intravenous) chemotherapy using doxorubicin or mitomycin, alone or in combination with cisplatin or carboplatin. Newer agents such as gemcitabine and multitargeted antifolate (pemetrexed disodium, LY231514) show promise of greater effectiveness.
UI - 12057157
AU - Kindler HL
TI - Malignant pleural mesothelioma.
SO - Curr Treat Options Oncol 2000 Oct;1(4):313-26
AD - Section of Hematology/Oncology, University of Chicago Medical Center, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637, USA.
Despite innumerable trials of surgery, radiotherapy, and countless chemotherapeutic drugs, it is unclear whether any intervention has had a significant impact on more than a few highly selected patients with malignant pleural mesothelioma. Because most patients die of respiratory failure from extensive disease progression in the thorax, treatment usually includes attempts at local control. Unfortunately, radiotherapy is associated with significant complications in pleural mesothelioma, and surgery is feasible in only a small percentage of patients. Although there have been several single-institution reports of combined-modality therapy with extrapleural pneumonectomy, postoperative radiation, and chemotherapy in which prolonged survival has been observed, most patients with malignant pleural mesothelioma have locally advanced disease, advanced age, or comorbid medical illnesses that preclude aggressive surgery. Therefore, the use of a systemic anticancer agent is the only treatment option for most patients with malignant pleural mesothelioma. Evaluation of effective chemotherapy regimens for this disease has been hampered by many factors. Because mesothelioma is an uncommon malignancy, most studies have enrolled small numbers of patients, and few trials have been randomized. The disease is heterogeneous, yet until recently there was no single staging system that could reliably predict survival, nor is there a universally accepted set of prognostic criteria for selecting a uniform group of patients. Response assessment has been limited by the inherent difficulties of reproducibly measuring pleural-based disease. The real impact of systemic chemotherapy on the natural history of malignant mesothelioma is still uncertain because phase III trials comparing chemotherapy with best supportive care have not yet been completed. Although nearly every class of cytotoxic agent has been evaluated in mesothelioma, response rates of greater than 20% have not been consistently demonstrated for any drug. The most active drug classes are the antifolates, the anthracyclines, and the platinums. Doxorubicin has historically been considered the gold-standard chemotherapy, although its true response rate is likely only 15%. The most active commercially available drug for mesothelioma so far appears to be gemcitabine. Although gemcitabine has a limited role as a single agent, it is quite active in combination with a platinating agent. The impressive 48% response rate reported for the combination of gemcitabine with cisplatin in a single phase II study has made this regimen the new standard of care for off-protocol treatment of this disease, although this trial still requires validation. With the recent introduction of several new agents with definite activity in this disease, the therapeutic nihilism previously associated with malignant pleural mesothelioma is gradually being replaced by a cautious optimism. Early trials of angiogenesis inhibitors, gene therapy, and vaccines offer additional avenues for treatment. As we begin to incorporate these active new drugs with each other and in adjuvant and neoadjuvant treatment regimens, there is reason to believe that superior results for patients with malignant pleural mesothelioma can be achieved in the near future.
UI - 12085195
AU - Gorini G; Merler E; Chellini E; Crocetti E; Costantini AS
TI - Is the ratio of pleural mesothelioma mortality to pleural cancer mortality approximately unity for Italy? Considerations from the oldest regional mesothelioma register in Italy.
SO - Br J Cancer 2002 Jun 17;86(12):1970-1
UI - 12082024
AU - Gordon GJ; Appasani K; Parcells JP; Mukhopadhyay NK; Jaklitsch MT;
TI - Richards WG; Sugarbaker DJ; Bueno R Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma.
SO - Carcinogenesis 2002 Jun;23(6):1017-24
AD - Division of Thoracic Surgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
Malignant pleural mesothelioma (MPM) is a highly lethal pleural neoplasm that is often resistant to chemotherapeutic drugs, including cisplatin, and for which little is known regarding carcinogenic pathways. We used differential display to compare gene expression patterns in mesothelioma, normal pleura and normal lung, in order to better understand MPM pathobiology, and to search for genes that may facilitate drug resistance in this cancer. The human inhibitor of apoptosis protein-1 gene (IAP-1/MIHC/cIAP2) was discovered to be highly expressed in MPM. We confirmed overexpression of IAP-1 mRNA and protein in 39 additional human MPM tumor specimens and 3/5 (60%) MPM cell lines by multiple methods, including real time quantitative reverse transcription-PCR and western blot analysis. Using an antisense targeting approach, we found that attenuation of IAP-1 mRNA levels decreases baseline cell viability and increases the sensitivity of MPM cell lines to cisplatin by nearly 20-fold. Reduced IAP-1 gene expression also results in a concordant increase of the pro-apoptotic cleavage product of caspase 9 and a reduction in the number of viable tumor cells. Our observations strongly suggest that IAP-1 is at least partly responsible for promoting carcinogenesis and mediating resistance to cisplatin in many MPM tumors and that further study of this apoptotic pathway is warranted.
UI - 11721205
AU - Rena O; Oliaro A
TI - [Malignant pleural mesothelioma]
SO - Minerva Chir 2001 Dec;56(6):611-41
AD - Cattedra di Chirurgia Toracica, Universita degli Studi, Turin, Italy.
Malignant pleural mesothelioma is a severe disease closely associated with asbestos exposure, at work or environmental. Its incidence has risen for some decades and it's expected to peak between 2010 and 2020. Up today, no treatment has been demonstrated as effective in influencing disease-related survival and the median prognosis ranges between 9 and 17 months after the diagnosis. The epithelial subtype of the disease seems to have a better prognosis when early diagnosed and treated with intrapleural immunotherapy or multimodality therapy. The diagnosis of the disease, often by exclusion, is obtained after macroscopic sampling of the pathological tissue, best accomplished by thoracoscopy, which also allows the intracavitary evaluation of the extension of the disease. Chemotherapy and radiotherapy alone didn't demonstrate any efficacy on the patient survival. For the early-stage disease (stage I) a therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodality treatment combining surgery, radiotherapy and chemotherapy should be proposed. This multimodality protocol has proved to be effective in patients with epithelial subtype, negative margins of resection and negative lymph nodes.
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