Another interesting study is called, Immunohistochemical Analysis of the p16INK4 Cyclin-Dependent Kinase Inhibitor in Malignant Mesothelioma – JNCI J Natl Cancer Inst (1995) 87 (24): 1870-1875 by Robert A. Kratzke, Gregory A. Otterson, Clint E. Lincoln, Stephen Ewing, Herbert Oie, Joseph Geradts and Frederic J. Kaye. Here is an excerpt: Abstract – Background: The identification in 1994 of the CDKN2 gene as a target for mutations in a wide range of human cancers, including malignant mesothelioma, has been controversial because subsequent studies have detected a lower frequency of CDKN2 gene mutations in primary tumors than in cultured cell lines. These reports raised the hypothesis that another gene, distinct from CDKN2, might be the target of the chromosome 9p21 deletions frequently observed in these tumors. Purpose: To address whether inactivation of CDKN2 function is an essential event in the etiology of malignant mesothelioma, we examined p16INK4 protein expression in primary thoracic mesotheliomas, in nonmalignant pleural tissues, and in independent mesothelioma cell lines. We also studied the growth rate of tumor cell lines following stable transfection of CDKN2 gene. Methods: Retinoblastoma (Rb) and p16INK4 protein expression was determined by immunohistochemical analysis from archival paraffin specimens of 12 primary thoracic mesotheliomas and a nonmalignant pleural biopsy specimen. In addition, protein immunoblot analysis for Rb and p16INK4 expression was conducted on 15 independent mesothelioma cell lines, and the ability of a transfected CDKN2 gene to suppress the growth of the mesothelioma cell lines H2373 and H2461 in vitro was examined. Results: We demonstrated abnormal p16INK4 expression in 12 of 12 primary mesothelioma specimens and in 15 of 15 mesothelioma cell lines. All tumor specimens and the tumor cell lines showed expression of wild-type Rb protein. In addition, we have confirmed the ability of a transfected CDKN2 gene to suppress growth of two independent mesothelioma cell lines. Conclusions: Immunohistochemical analysis of the p16INK4 gene product is feasible in archival biopsy samples. With this analysis, CDKN2 gene inactivation can be determined in tumors that are contaminated with nonmalignant cells. Furthermore, since loss of p16INK4 protein expression can result from both genetic (gene mutations) and epigenetic (abnormal DNA hypermethylation) mechanisms, as we and others have shown recently, examination of protein expression is a highly sensitive method for analyzing the CDKN2 status in large numbers of tumor samples.
Another interesting study is called, Phase I Clinical and Pharmacokinetic Study of Pemetrexed and Carboplatin in Patients With Malignant Pleural Mesothelioma By Andy Hughes, Paula Calvert, Ashraf Azzabi, Ruth Plummer, Rob Johnson, Jim Rusthoven, Melanie Griffin, Kevin Fishwick, Alan V Boddy, Mark Verrill, Hilary Calvert – Journal of Clinical Oncology, Vol 20, Issue 16 (August), 2002: 3533-3544. Here is an excerpt: ABSTRACT – PURPOSE: To determine the maximum tolerated dose (MTD) of pemetrexed and carboplatin given in combination, to derive a recommended dose for phase II studies, and to explore its efficacy. We assessed toxicities and explored the activity of the drug combination exclusively in patients with malignant pleural mesothelioma (MPM). The pharmacokinetics of both agents was investigated.

PATIENTS AND METHODS: Twenty-seven patients (23 male, four female) with MPM were treated on five escalating dose levels. Doses ranged from pemetrexed 400 mg/m2 (as a 10-minute intravenous infusion), followed by carboplatin area under the plasma concentration-time curve (AUC) 4 mg/mLmin (as a 30-minute intravenous infusion) to pemetrexed 500 mg/m2, carboplatin AUC 6 mg/mLmin. All patients had a World Health Organization performance status of 1. A total of 163 courses of treatment were administered (median, six; range, one to 10).

RESULTS: The main toxicity was hematologic, particularly neutropenia, although this was characteristically short-lived and caused few clinical problems. The MTD was pemetrexed 500 mg/m2, carboplatin AUC 6, because three of the five patients treated at this dose level experienced a dose-limiting toxicity. Eight partial responses (in 25 assessable patients) were observed for a response rate of 32%. Seventy percent of patients noticed an improvement in symptoms, usually (84%) after only two courses. Median time to progression was 305 days, and median survival time was 451 days.

We all owe a debt of gratitude to these fine researchers. If you found any of these excerpts interesting, please read the studies in their entirety.

Another interesting study is called, “Immunohistochemical Analysis of the p16INK4 Cyclin-Dependent Kinase Inhibitor in Malignant Mesothelioma” – JNCI J Natl Cancer Inst (1995) 87 (24): 1870-1875 by Robert A. Kratzke, Gregory A. Otterson, Clint E. Lincoln, Stephen Ewing, Herbert Oie, Joseph Geradts and Frederic J. Kaye.  Here is an excerpt: “Abstract – Background: The identification in 1994 of the CDKN2 gene as a target for mutations in a wide range of human cancers, including malignant mesothelioma, has been controversial because subsequent studies have detected a lower frequency of CDKN2 gene mutations in primary tumors than in cultured cell lines. These reports raised the hypothesis that another gene, distinct from CDKN2, might be the target of the chromosome 9p21 deletions frequently observed in these tumors.  Purpose: To address whether inactivation of CDKN2 function is an essential event in the etiology of malignant mesothelioma, we examined p16INK4 protein expression in primary thoracic mesotheliomas, in nonmalignant pleural tissues, and in independent mesothelioma cell lines.

We also studied the growth rate of tumor cell lines following stable transfection of CDKN2 gene. Methods: Retinoblastoma (Rb) and p16INK4 protein expression was determined by immunohistochemical analysis from archival paraffin specimens of 12 primary thoracic mesotheliomas and a nonmalignant pleural biopsy specimen. In addition, protein immunoblot analysis for Rb and p16INK4 expression was conducted on 15 independent mesothelioma cell lines, and the ability of a transfected CDKN2 gene to suppress the growth of the mesothelioma cell lines H2373 and H2461 in vitro was examined. Results: We demonstrated abnormal p16INK4 expression in 12 of 12 primary mesothelioma specimens and in 15 of 15 mesothelioma cell lines. All tumor specimens and the tumor cell lines showed expression of wild-type Rb protein. In addition, we have confirmed the ability of a transfected CDKN2 gene to suppress growth of two independent mesothelioma cell lines.  Conclusions: Immunohistochemical analysis of the p16INK4 gene product is feasible in archival biopsy samples. With this analysis, CDKN2 gene inactivation can be determined in tumors that are contaminated with nonmalignant cells. Furthermore, since loss of p16INK4 protein expression can result from both genetic (gene mutations) and epigenetic (abnormal DNA hypermethylation) mechanisms, as we and others have shown recently, examination of protein expression is a highly sensitive method for analyzing the CDKN2 status in large numbers of tumor samples.”
Another interesting study is called, “Phase I Clinical and Pharmacokinetic Study of Pemetrexed and Carboplatin in Patients With Malignant Pleural Mesothelioma” 
By Andy Hughes, Paula Calvert, Ashraf Azzabi, Ruth Plummer, Rob Johnson, Jim Rusthoven, Melanie Griffin, Kevin Fishwick, Alan V Boddy, Mark Verrill, Hilary Calvert – Journal of Clinical Oncology, Vol 20, Issue 16 (August), 2002: 3533-3544.  Here is an excerpt: “ABSTRACT – PURPOSE: To determine the maximum tolerated dose (MTD) of pemetrexed and carboplatin given in combination, to derive a recommended dose for phase II studies, and to explore its efficacy. We assessed toxicities and explored the activity of the drug combination exclusively in patients with malignant pleural mesothelioma (MPM). The pharmacokinetics of both agents was investigated.

PATIENTS AND METHODS: Twenty-seven patients (23 male, four female) with MPM were treated on five escalating dose levels. Doses ranged from pemetrexed 400 mg/m2 (as a 10-minute intravenous infusion), followed by carboplatin area under the plasma concentration-time curve (AUC) 4 mg/mL•min (as a 30-minute intravenous infusion) to pemetrexed 500 mg/m2, carboplatin AUC 6 mg/mL•min. All patients had a World Health Organization performance status of 1. A total of 163 courses of treatment were administered (median, six; range, one to 10).

RESULTS: The main toxicity was hematologic, particularly neutropenia, although this was characteristically short-lived and caused few clinical problems. The MTD was pemetrexed 500 mg/m2, carboplatin AUC 6, because three of the five patients treated at this dose level experienced a dose-limiting toxicity. Eight partial responses (in 25 assessable patients) were observed for a response rate of 32%. Seventy percent of patients noticed an improvement in symptoms, usually (84%) after only two courses. Median time to progression was 305 days, and median survival time was 451 days.”

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.

Another interesting study is called, “Induction of mesothelioma in p53 mouse by intraperitoneal application of multi-wall carbon nanotube” by Atsuya Takagi, Akihiko Hirose, Tetsuji Nishimura, Nobutaka Fukumori, Akio Ogata, Norio Ohashi, Satoshi Kitajima and Jun Kanno – The Journal of Toxicological Sciences Vol. 33 (2008) , No. 1 February 105-116.  Here is an excerpt: “ABSTRACT-  Nanomaterials of carbon origin tend to form various shapes of particles in micrometer dimensions. Among them, multi-wall carbon nanotubes (MWCNT) form fibrous or rod-shaped particles of length around 10 to 20 micrometers with an aspect ratio of more than three. Fibrous particles of this dimension including asbestos and some man-made fibers are reported to be carcinogenic, typically inducing mesothelioma. Here we report that MWCNT induces mesothelioma along with a positive control, crocidolite (blue asbestos), when administered intraperitoneally to p53 heterozygous mice that have been reported to be sensitive to asbestos.

Our results point out the possibility that carbon-made fibrous or rod-shaped micrometer particles may share the carcinogenic mechanisms postulated for asbestos. To maintain sound activity of industrialization of nanomaterials, it would be prudent to implement strategies to keep good control of exposure to fibrous or rod-shaped carbon materials both in the workplace and in the future market until the biological/ carcinogenic properties, especially of their long-term biodurability, are fully assessed.”

One interesting study is called, “Inactivation of p16INK4a expression in malignant mesothelioma by methylation.” By Wong L, Zhou J, Anderson D, Kratzke RA. -
Research Service, Minneapolis VA Medical Center, Minneapolis, MN, USA -
Lung Cancer. 2002 Nov;38(2):131-6.  Here is an excerpt: “Abstract – The molecular mechanisms of oncogenesis in mesothelioma involve the loss of negative regulators of cell growth including p16(INK4a). Absence of expression of the p16(INK4a) gene product is exhibited in virtually all mesothelioma tumors and cell lines examined to date. Loss of p16(INK4a) expression has also been frequently observed in more common neoplasms such as lung cancer as well. In a wide variety of these malignancies, including lung cancer, p16(INK4a) expression is known to be inactivated by hypermethylation of the first exon. In a survey of ten mesothelioma cell lines, one cell line (NCI-H2596) was identified as possessing loss of p16(INK4a) gene product following gene methylation. This methylation in these mesothelioma cells could be reversed, resulting in re-expression of p16(INK4a) protein, following the treatment of the cells with cytidine analogs, which are known inhibitors of DNA methylation. In previous clinical trials in mesothelioma, the cytidine analog dihydro-5-azacytidine (DHAC) has been found to induce clinical responses in approximately 17% of patients with mesothelioma treated with this drug, including prolonged complete responses. In addition, we identified evidence for methylation of p16(INK4a) in three of 11 resected mesothelioma tumor samples. When both cell lines and tumors are combined, inactivation of p16(INK4a) gene product expression following DNA hypermethylation was found in four of 21 samples (19%). We are further exploring the clinical significance of inhibition of methylation in mesothelioma by cytidine analogs. This may provide a potential treatment target in some mesothelioma tumors by inhibition of methylation.”

One interesting study is called, “Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies” by A S Abutaily, B J Addis, W R Roche – J Clin Pathol 2002;55:662-668
Here is an excerpt: “Abstract – Aim: The value of immunohistochemical staining in differentiating between malignant mesothelioma and pulmonary adenocarcinoma was re-examined using newly available commercial antibodies, with the aim of increasing the sensitivity and specificity of diagnosis, and simplifying the antibody panel required.
Methods: Forty one malignant mesotheliomas and 35 lung adenocarcinomas were studied. Commercial antibodies to calretinin, E-cadherin, N-cadherin, surfactant apoprotein A (SP-A), thyroid transcription factor 1 (TTF-1), thrombomodulin, and cytokeratin 5/6 were applied using the streptavidin–biotin–peroxidase complex procedure on formalin fixed, paraffin wax embedded tissue. Results: E-cadherin was expressed in all adenocarcinomas and in 22% of the mesotheliomas. TTF-1 expression was detected in 69% of the adenocarcinomas and none of the mesotheliomas. Positive staining with polyclonal anticalretinin was detected in 80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed in 6% of the adenocarcinomas and in 53% of the mesotheliomas. Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and 63% of the mesotheliomas. The results were compared with the standard laboratory panel for mesothelioma diagnosis: anticarcinoembryonic antigen (anti-CEA), LeuM1, BerEP4, and HBME-1.

Conclusion: Of the antibodies used in this study, E-cadherin was 100% sensitive for pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary adenocarcinoma. The application of these two antibodies alone was adequate for the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TTF-1 is negative and E-cadherin is positive, a secondary panel of antibodies, including BerEP4 and LeuM1 (CD15) and antibodies directed against CEA, calretinin, cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation between malignant mesothelioma and pulmonary adenocarcinoma.”

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.

Mesothelioma is a form of cancer which is caused due to asbestos exposure. It is a cancer of the mesothelium membrane which covers and protects most of our internal organs. It is a disease where the mesothelium cells become abnormal and divide without control, leading to damage of the nearby tissues and organs. This normally affects the lungs, abdomen and the heart.

What Are the Symptoms of Mesothelioma?

Symptoms of Mesothelioma include coughing up blood, shortness in breath, troubled breathing, similar to symptoms of aging and hence normally mistaken for other forms of disease.

What is Asbestos?

It is a group of minerals in fibrous bundle occurring naturally and which is used as insulation in engineering, scientific and construction industries. Release of microscopic fibers from asbestos lead to health complications.

What are the dangers behind Asbestos Exposure?

Asbestos exposure leads to a number of minute asbestos particles that lingering in the air and settle on clothing, which becomes easily inhalable.

Once inhaled it begins to damage the cellular structure of internal organs, more often the lungs.

Who Are Exposed To Risk Of Contracting Mesothelioma?

People working in places like shipping industries, construction sites and renovation sites where asbestos is used to the maximum are usually subject to exposure. The exposure to asbestos is hardly considered due to the long gap between exposure and onset of Mesothelioma.

Different Types of Mesothelioma?

Pleural Mesothelioma condition affecting lungs and chest cavity.
Peritoneal Mesothelioma condition affecting the abdomen.
Pericardial Mesothelioma affecting the heart.
What are the available treatments for Mesothelioma Cancer?

There is no particular cure for Mesothelioma or Asbestosis, but yes with medical advancements anything may be possible.

Do Mesothelioma victims have a legal recourse?

Subject to law of limitation the victims can initiate legal action through their attorney.

Another interesting study is called, Expression of c-sis (PDGF B-chain) and PDGF A-chain genes in ten human malignant mesothelioma cell lines derived from primary and metastatic tumors. By Versnel MA, Hagemeijer A, Bouts MJ, van der Kwast TH, Hoogsteden HC. – Department of Cell Biology, Immunology and Genetics, Erasmus University, Rotterdam, The Netherlands. Oncogene. 1988 Jun;2(6):601-5. Here is an excerpt: Abstract – Ten human malignant mesothelioma cell lines from primary and metastatic sites were studied for the expression of c-sis (PDGF B-chain) and PDGF A-chain genes. Malignant mesothelioma cell lines expressed strongly the c-sis oncogene which is barely detectable in normal mesothelial cells. The PDGF A-chain gene expression was slightly elevated in malignant mesothelioma cell lines compared to the expression in normal mesothelial cells. Cytogenic and Southern blot analysis did not provide evidence for genomic amplification or rearrangement of the c-sis oncogene. These results suggest that malignant mesothelioma cell lines show constitutively enhanced expression of the c-sis and PDGF A-chain genes that could play a role in the etiology of this type of malignancy.

Another interesting study is called, Detection and Quantitation of Serum Mesothelin, a Tumor Marker for Patients with Mesothelioma and Ovarian Cancer by Raffit Hassan, Alan T. Remaley, Maureen L. Sampson, Jingli Zhang, Derrick D. Cox, James Pingpank, Richard Alexander, Mark Willingham, Ira Pastan and Masanori Onda – Clinical Cancer Research January 2006 12; 447. Here is an excerpt: Abstract – Purpose: To determine whether mesothelin, a cell surface protein highly expressed in mesothelioma and ovarian cancer, is shed into serum and if so to accurately measure it.

Experimental Design: We developed a sandwich ELISA using antibodies reacting with two different epitopes on human mesothelin. To quantitate serum mesothelin levels, a standard curve was generated using a mesothelin-Fc fusion protein. Sera from 24 healthy volunteers, 95 random hospital patients, 56 patients with mesothelioma, and 21 patients with ovarian cancer were analyzed. Serum mesothelin levels were also measured before and after surgical cytoreduction in six patients with peritoneal mesothelioma.

Results: Elevated serum mesothelin levels were noted in 40 of 56 (71%) patients with mesothelioma and in 14 of 21 (67%) patients with ovarian cancer. Serum mesothelin levels were increased in 80% and 75% of the cases of mesothelioma and ovarian cancer, respectively, in which the tumors expressed mesothelin by immunohistochemistry. Out of the six patients with peritoneal mesothelioma who underwent surgery, four had elevated serum mesothelin levels before surgery. Out of these four patients, three had cytoreductive surgery and the serum mesothelin level decreased by 71% on postoperative day 1 and was undetectable by postoperative day 7.

Conclusions: We developed a serum mesothelin assay that shows that mesothelin is elevated in patients with mesothelioma and ovarian cancer. The rapid decrease in mesothelin levels after surgery in patients with peritoneal mesothelioma suggests that serum mesothelin may be a useful test to monitor treatment response in mesothelin-expressing cancers.

Another interesting study is called, Expression of colony-stimulating factor genes by normal human mesothelial cells and human malignant mesothelioma cells lines in vitro by GD Demetri, BW Zenzie, JG Rheinwald and JD Griffin – Volume 74, Issue 3, pp. 940-946, 08/15/1989. Here is an excerpt: We investigated normal human mesothelial cells and human malignant mesothelioma cell lines for the ability to produce hematopoietic colony- stimulating factors (CSFs) in culture. Early passage cultures of normal diploid human mesothelial cells spontaneously expressed detectable levels of M-CSF mRNA transcripts, but lacked detectable transcripts for GM-CSF or G-CSF. Exposure of normal mesothelial cells to epidermal growth factor (EGF), lipopolysaccharide (LPS), or tumor necrosis factor (TNF) induced expression of G-CSF mRNA. The combination of EGF and TNF induced threefold more G-CSF transcripts than did either factor alone. GM-CSF transcripts were induced only by the combination of TNF and EGF. Interleukin-1 beta (IL-1 beta) transcripts were induced by EGF, TNF, or LPS and were inhibited by hydrocortisone (HC). All malignant mesothelioma cell lines tested also spontaneously expressed M-CSF transcripts. However, in contrast to normal mesothelial cells, two of four malignant mesothelioma cell lines also autonomously expressed G- CSF and GM-CSF transcripts without TNF, EGF, or LPS stimulation. Secretion of biologically active CSFs was confirmed by testing media conditioned by the various cell types examined. The detection of biologically active CSFs correlated well with the presence of detectable CSF transcripts by Northern analysis. These data indicate that (a) normal human mesothelial cells spontaneously express detectable levels of M-CSF mRNA in culture; (b) EGF is an essential cofactor for optimal induction of G-CSF and GM-CSF expression; (c) exposure of normal mesothelial cells to inflammatory mediators such as LPS and TNF increases the levels of transcripts for CSFs and IL-1 beta; and (d) as compared with normal human mesothelial cells, some cell lines of human malignant mesothelioma exhibit aberrant gene expression for multiple cytokines, including G-CSF, GM-CSF, IL-1 beta, and IL-6.

We all owe a debt of gratitude to these fine researchers. If you found any of these excerpts interesting, please read the studies in their entirety.

The hazards of asbestos are well recognized, with tens of thousands of individuals affected by the disease mesothelioma, asbestosis and linked diseases. For many years, the owners and innocent workers lived and worked around asbestos friable, could do without the know-how of the hazardous and often fatal injuries, breathing in relatively small amounts of asbestos dust. A common problem, among the many people who have had at slightest some exposure to asbestos, the extent to which asbestos causes cancer because you are sick or worse to believe?

The first thing is to know about asbestos exposure, that the negative effects of this exposure have a long latency period. It’s not a person exposed to asbestos do not develop mesothelioma 25-40 years after exposure rarity. Mesothelioma is a cancer of the mesothelium, a shielding layer, which affects most of the security organs of the body covered. Asbestos fibers are inhaled located in the lining of the lungs and ultimately cause cells to change and grow to be malignant. Approximately 70-80% of mesothelioma cases is believed to be caused by varying degrees of exposure to asbestos.

The amount of exposure that caused disease in humans is a subject of debate. Although there were many instances of the factory or other workers, the high burden for the free exhibition, friable many years, the development of the disease, there are also cases where the exhibition was as short as a few months or weeks. Intensity of exposure is more likely to be relevant than the duration of time. If you think you were exposed to asbestos dust a good idea, so much can be reminded how to write, that the duration of time, intensity, where and how they were exposed. Asbestos litigation often done if you can ascertain you worked in an industrial environment or work or live in an environment where it friable asbestos, that was exposed to influences.

One reason why it is so imperative, as much as possible to document the level of exposure to asbestos can, is that the disease mesothelioma very difficult to understand and is often confused with other types of cancer. It is imperative to recognize early signs of asbestos disease, both for early treatment and to obviously identify the cause of a later dispute. The two main types of mesothelioma are pleural (chest) and peritoneal (abdomen). In the pleural membrane thickening of the lung fluid collected. Both problems cause the contraction of the lungs and make breathing hard. In peritoneal-like symptoms, but in the abdominal region, the fluid retention and pain into the region.

Another interesting study is called, Value of the Ber-EP4 antibody in differentiating epithelial pleural mesothelioma from adenocarcinoma : The M.D. Anderson experience and a critical review of the literature – American Society of Clinical Pathologists, Chicago, IL, ETATS-UNIS (1931) (Revue) by ORDONEZ N. G. (1) ; 1998, vol. 109, no1, pp. 85-89 (21 ref.) Here is an excerpt: Abstract – Although most studies have indicated that Ber-EP4 immunostaining can assist in differentiating epithelial pleural mesotheliomas from adenocarcinomas that metastasize to the pleura, the percentage of positive cases has varied greatly among different studies. Authors of a recent publication concluded that Ber-EP4 has no diagnostic utility in separating these conditions. To determine whether Ber-EP4 has any value in distinguishing mesothelioma from adenocarcinoma, 70 formalin-fixed epithelial pleural mesotheliomas, 20 pulmonary adenocarcinomas, 59 nonpulmonary adenocarcinomas, 4 squamous cell carcinomas of the lung, 6 transitional cell carcinomas, and 31 adenocarcinomas of unknown origin that metastasized to the pleura were stained with this antibody. Reactivity was observed in 18 (26%) of 70 mesotheliomas and in all 20 (100%) of the pulmonary adenocarcinomas, in 55 (93%) of the 59 nonpulmonary adenocarcinomas, in 4 (100%) of 4 squamous cell carcinomas of the lung, in 4 (67%) of 6 transitional cell carcinomas, and in 26 (84%) of 31 adenocarcinomas of unknown origin that metastasized to the pleura. The staining in the mesotheliomas was focal and restricted to a limited number of cells, in contrast with staining in the pulmonary adenocarcinomas in which it was invariably diffuse. The extent of the staining in the nonpulmonary adenocarcinomas and the metastatic adenocarcinomas of unknown origin was less consistent-negative or focal in some cases and diffuse in others. Therefore, while Ber-EP4 seems to be helpful in separating epithelial pleural mesotheliomas from lung adenocarcinomas, its value in distinguishing mesotheliomas from other tumors metastatic to the pleura is more limited and depends largely on the site of origin of the metastatic tumor.

Another interesting study is called, Pleurectomy/decortication in the setting of multimodality treatment for diffuse malignant pleural mesothelioma. By Rusch VW. Memorial Sloan-Kettering Cancer Center, Department of Surgery and Cornell University Medical College, New York, NY 10021. Semin Thorac Cardiovasc Surg. 1997 Oct;9(4):367-72. Here is an excerpt: Abstract – Pleurectomy/decortication is a frequently performed operation for patients with diffuse malignant pleural mesothelioma (DMPM). It has a low surgical mortality rate (less than 5%), but is associated with a significant risk of local recurrence. To date, intensive adjuvant radiation or chemotherapy has not diminished that risk. Despite these disappointing results, pleurectomy/decortication may still be the best treatment option for some patients, particularly those with early stage disease whose medical condition precludes pneumonectomy. The role of pleurectomy/decortication in conjunction with newer treatment strategies such as neoadjuvant therapy or gene therapy warrants investigation.

Another interesting study is called, The presence of simian-virus 40 sequences in mesothelioma and mesothelial cells is associated with high levels of vascular endothelial growth factor. By Cacciotti P, Strizzi L, Vianale G, Iaccheri L, Libener R, Porta C, Tognon M, Gaudino G, Mutti L – Am J Respir Cell Mol Biol. 2002 Feb;26(2):189-93. Here is an excerpt: Abstract – The aim of this study was to evaluate whether the presence of simian virus-40 (SV40) is associated with increased release of vascular endothelial growth factor (VEGF) in human malignant mesothelioma (MM) cells. We studied nine cell lines derived from pleural effusion (PE) of patients with MM, and three different cultures of normal human mesothelial cells (NHMC) derived from pleural fluid of patients with congestive heart failure. NHMC were transfected with full length SV40 (NHMC-FL) or large T antigen (NHMC Tag) DNAs. High levels of VEGF were detected in conditioned media of each of two MM cells that tested positive for SV40 by PCR amplification and Southern blot hybridization and for Tag transcript by reverse transcription- polymerase chain reaction (RT-PCR) and immunoprecipitation. We also found that NHMC-FL released high amounts of VEGF. Conditioned media from SV40-positive MM cells and from FL-NHMC increased proliferation of human umbilical vein cells (HUVEC) and this effect was partially abrogated by adding specific blocking antibodies against VEGF. These results offer the first evidence that SV40 can cause VEGF release in SV40-positive MM cells and that entire viral genome is required for this effect.

We all owe a debt of gratitude to these fine researchers for their work. If you found any of these excerpts helpful, please read the studies in their entirety.

Another interesting study is called, “Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product” by W. Roy Smythe, MD, Imran Mohuiddin, MD, Mustafa Ozveran, MD, Xiaobo X. Cao – J Thorac Cardiovasc Surg 2002;123:1191-1198.  Here is an excerpt: “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-G1 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-G1 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 esothelioma cell lines. The therapeutic potential of inhibiting expression of this protein in mesothelioma should be evaluated.”

Another study is called, “Phase III Trial of Pemetrexed Plus Best Supportive Care Compared With Best Supportive Care in Previously Treated Patients With Advanced Malignant Pleural Mesothelioma” by Jacek Jassem, Rodryg Ramlau, Armando Santoro, Wolfgang Schuette, Assad Chemaissani, Shengyan Hong, Johannes Blatter, Susumu Adachi, Axel Hanauske, Christian Manegold  – Journal of Clinical Oncology, Vol 26, No 10 (April 1), 2008: pp. 1698-1704.  Here is an excerpt: “ABSTRACT – Purpose This multicenter, phase III study compared overall survival (OS) of second-line pemetrexed plus best supportive care (BSC) versus BSC alone in patients with advanced malignant pleural mesothelioma (MPM). Secondary end points included response rate, progression-free survival (PFS), time to tumor progression (TTP), time to treatment failure (TTF), and toxicity. Patients and Methods Patients with relapsed MPM after first-line chemotherapy were randomly assigned to receive pemetrexed 500 mg/m2 plus BSC (P+BSC) every 21 days or BSC alone. Results – The study enrolled 243 patients (123 on P+BSC arm and 120 on BSC arm). Median OS time was not significantly different between the arms (8.4 months for P+BSC and 9.7 months for BSC; P = .74). Cox regression modeling suggested a trending survival benefit for patients who responded to first-line therapy. Time-to-event measures significantly favored P+BSC (median PFS, TTP, and TTF). Partial response was achieved in 18.7% and 1.7% of patients in P+BSC and BSC arms, respectively (P

Conclusion Second-line pemetrexed elicited significant tumor response and delayed disease progression compared with BSC alone in patients with advanced MPM. Improvement in OS was not seen in this study, possibly because of the significant imbalance in postdiscontinuation chemotherapy between the arms.”

Another interesting study is called, “Urokinase receptor in human malignant mesothelioma cells: role in tumor cell mitogenesis and proteolysis” by S. Shetty, A. Kumar, A. Johnson, S. Pueblitz and S. Idell – Department of Medicine, University of Texas Health Science Center at Tyler 75710, USA. Am J Physiol Lung Cell Mol Physiol 268: L972-L982, 1995.  Here is an excerpt: “Urokinase (uPA) interacts with its receptor (uPAR) to promote proteolysis and tumor migration, functions of potential importance in the pathogenesis of malignant mesothelioma. Immunohistochemistry of human malignant mesothelioma tissue and mesothelioma cells (MS-1) showed that mesothelioma cells express uPAR. We isolated uPAR from MS-1 cells by metabolic labeling and showed that it could be induced by phorbol myristate acetate (PMA), lipopolysaccharide (LPS), a transforming growth factor-beta (TGF-beta) or tumor necrosis factor-alpha (TNF-alpha). Experiments with MS-1 cells showed that uPA binding was saturable, specific, and reversible with a mean dissociation constant (Kd) of 5.4 +/- 1.1 nM. Binding was inhibited by a blocking antibody to uPAR and by the uPA amino-terminal fragment (ATF), but not by low molecular weight uPA. uPAR expression was regulated transcriptionally and translationally; antisense oligonucleotides blocked expression of uPAR protein. Plasminogen activator inhibitor-1 (PAI-1) inhibited PA activity of preformed uPA/uPAR complexes and increased cycling of the receptor from the cell surface. Stimulation of subconfluent MS-1 cells by high molecular weight or recombinant uPA, but not ATF or low molecular weight fragment, caused concentration-dependent incorporation of [3H]thymidine. These data indicate a novel mechanism by which malignant mesothelioma cells localize pericellular proteolysis and concurrently regulate tumor cell proliferation.”

According to researchers and well known healthcare providers, mesothelioma is a type of cancer which attacks those who use asbestos blended materials randomly. The health of the victim gets destroyed due to over exposure to asbestos. Therefore, proper pre-emptive measures need to be taken to safeguard the body from the onset of this deadly disease. Mesothelioma affected patients must be well taken care of. Researchers have found out that when the disease is in its final stages it can prove to be deadly for the patient. It takes at least 30 years to destroy a person as it spreads very slowly in the body.

Reasons of Occurrence of Mesothelioma

The main reason of onset of mesothelioma is exposure to asbestos. Victims of Meshothelioma have been found to be mainly workers working at construction sites and regularly coming in contact with the use of asbestos. The person’s life span is effected due to over exposure to asbestos. As the disease of Meshothelioma is caused due to over exposure to asbestos so people and workers who come regularly in contact with the material should take all possible precautions. The entire working area remains shaded with asbestos sheet. The air of the work station remains filled with dust particles. As a result workers working in the area are all times exposed to asbestos particles as hey breath them in and further enhance the on set of Meshothelioma with the start of bone erosion.

Precautionary Measures

Gloves covering their hands and masks for their faces are the two simple and important features that should be taken by workers when working with asbestos. Nostrils and cavity of the mouth are the two important paths through which the particles of asbestos enter our body and so if you are to come in contact with asbestos in a regular basis then use masks with visors. Gloves should always be used to cover your hands. The pants and shirts of the workers handling asbestos should be customized as a protective gear for them. Special foot wears must be used to cover the feet. Workers should ensure that every time they return home their hands and feet get cleaned in clear running water.It will be very good if anyone avoids the usage of asbestos. All the employees and workers of a firm should be well taken care of by the company for which they work. The compensation packages provided to the employees of a company dealing with asbestos should be good enough to financially benefit the workers. The company should provide protective uniforms and safety gears for the employees of its company.

Doctors claim that mesothelioma is a rare type of cancer and the revelation of symptoms takes longer time in the body. When a guy is affected by this disease, malignant or cancerous cells grow rapidly in mesothelium which hoodwink internal parts/organs of a human body. It has been clinically proven that the victims of Meshothelioma have a life span of only one year. In the extreme stage of infection, the disease of Meshothelioma gets incurable and fatal. Survival chances are the least. It is therefore advisable for patients to consult a doctor immediately after the disease starts. The two most essential methods of treatment of the disease is by radiotherapy and chemotherapy.

Another interesting study is called, Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product by W. Roy Smythe, MD, Imran Mohuiddin, MD, Mustafa Ozveran, MD, Xiaobo X. Cao – J Thorac Cardiovasc Surg 2002;123:1191-1198. Here is an excerpt: 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-G1 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-G1 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 esothelioma cell lines. The therapeutic potential of inhibiting expression of this protein in mesothelioma should be evaluated.

Another study is called, Phase III Trial of Pemetrexed Plus Best Supportive Care Compared With Best Supportive Care in Previously Treated Patients With Advanced Malignant Pleural Mesothelioma by Jacek Jassem, Rodryg Ramlau, Armando Santoro, Wolfgang Schuette, Assad Chemaissani, Shengyan Hong, Johannes Blatter, Susumu Adachi, Axel Hanauske, Christian Manegold – Journal of Clinical Oncology, Vol 26, No 10 (April 1), 2008: pp. 1698-1704. Here is an excerpt: ABSTRACT – Purpose This multicenter, phase III study compared overall survival (OS) of second-line pemetrexed plus best supportive care (BSC) versus BSC alone in patients with advanced malignant pleural mesothelioma (MPM). Secondary end points included response rate, progression-free survival (PFS), time to tumor progression (TTP), time to treatment failure (TTF), and toxicity. Patients and Methods Patients with relapsed MPM after first-line chemotherapy were randomly assigned to receive pemetrexed 500 mg/m2 plus BSC (P+BSC) every 21 days or BSC alone. Results – The study enrolled 243 patients (123 on P+BSC arm and 120 on BSC arm). Median OS time was not significantly different between the arms (8.4 months for P+BSC and 9.7 months for BSC; P = .74). Cox regression modeling suggested a trending survival benefit for patients who responded to first-line therapy. Time-to-event measures significantly favored P+BSC (median PFS, TTP, and TTF). Partial response was achieved in 18.7% and 1.7% of patients in P+BSC and BSC arms, respectively (P

Conclusion Second-line pemetrexed elicited significant tumor response and delayed disease progression compared with BSC alone in patients with advanced MPM. Improvement in OS was not seen in this study, possibly because of the significant imbalance in postdiscontinuation chemotherapy between the arms.

Another interesting study is called, Urokinase receptor in human malignant mesothelioma cells: role in tumor cell mitogenesis and proteolysis by S. Shetty, A. Kumar, A. Johnson, S. Pueblitz and S. Idell – Department of Medicine, University of Texas Health Science Center at Tyler 75710, USA. Am J Physiol Lung Cell Mol Physiol 268: L972-L982, 1995. Here is an excerpt: Urokinase (uPA) interacts with its receptor (uPAR) to promote proteolysis and tumor migration, functions of potential importance in the pathogenesis of malignant mesothelioma. Immunohistochemistry of human malignant mesothelioma tissue and mesothelioma cells (MS-1) showed that mesothelioma cells express uPAR. We isolated uPAR from MS-1 cells by metabolic labeling and showed that it could be induced by phorbol myristate acetate (PMA), lipopolysaccharide (LPS), a transforming growth factor-beta (TGF-beta) or tumor necrosis factor-alpha (TNF-alpha). Experiments with MS-1 cells showed that uPA binding was saturable, specific, and reversible with a mean dissociation constant (Kd) of 5.4 +/- 1.1 nM. Binding was inhibited by a blocking antibody to uPAR and by the uPA amino-terminal fragment (ATF), but not by low molecular weight uPA. uPAR expression was regulated transcriptionally and translationally; antisense oligonucleotides blocked expression of uPAR protein. Plasminogen activator inhibitor-1 (PAI-1) inhibited PA activity of preformed uPA/uPAR complexes and increased cycling of the receptor from the cell surface. Stimulation of subconfluent MS-1 cells by high molecular weight or recombinant uPA, but not ATF or low molecular weight fragment, caused concentration-dependent incorporation of [3H]thymidine. These data indicate a novel mechanism by which malignant mesothelioma cells localize pericellular proteolysis and concurrently regulate tumor cell proliferation.