Mesothelioma:
Asbestos or other mineral fibers and pleural contamination has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are potent carcinogens than "feather fibers" (chrysotile or white asbestos fibers). However, the evidence is there now indicating that it is a danger more than the larger fibers small particles. They are floating remaining in the air that can be inhaled, into the lungs, it may penetrate more easily and deeply. "We probably will find more about the health aspects of asbestos from the World Trade Center attack], unfortunately," Dr. Alan Fein, of the North Shore-Long Island Jewish Health System in pulmonary and critical care medicine chief said.
Development of mesothelioma in rats has been demonstrated after vaccination in the pleura of phosphorylated chrysotile fibers. In humans, transport of fibers to the pleura are to be important in the pathogenesis of mesothelioma is suggested. This is supported by other significant number of observation mobilization of cells of macrophages and the immune system of the lesions localized cumulative asbestos fibers in the pleural and peritoneal cavity of rats. These lesions, to attract, as the disease progresses, continue to accumulate the macrophage, changes in the cells in the lesions, culminated in a morphologically malignant tumor.
Experimental evidence has suggested that acts as a complete carcinogen with the onset of mesothelioma asbestos occurs in successive stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers, (the next - see paragraph However -1), despite the demonstration of its carcinogenic ability, is still unknown. However, not been fully achieved yet in the transformation of the in vitro of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibers. In general, asbestos fibers are thought to act through direct physical interaction with cells of mesothelial with respect to interaction following indirect effects of the inflammatory cells such as macrophages.
Analysis of the interaction between asbestos fibers and DNA is often while entangled attached or chromosome chromatin fibers, phagocytosis fiber shows that it is possible to make contact with chromosomes. This contact between the chromosomes or structural proteins of asbestos fibers and spindle device, you can induce an abnormality of the complex. The most common abnormalities 22 other frequent abnormalities relocation of the structure 1P, 3P, a monosomy of chromosome containing the 9P and 6Q chromosome arm.
Common gene abnormalities in mesothelioma cell lines, including the deletion of the tumor suppressor gene:
Asbestos has been shown to mediate the entry of foreign DNA into target cells. This of foreign DNA uptake, mutated by some of the possible mechanisms, may lead to carcinogenesis.
Inactivation of tumor suppressor gene
Oncogene activation
Activation of proto-oncogenes due to the foreign DNA uptake, including the promoter region
Activation of DNA repair enzymes may be error-prone
Activation of telomerase
Prevention of apoptosis
Some of the genes are commonly mutated in mesothelioma, and you may be a prognostic factor. These include epidermal growth factor receptor (EGFR) and the C-Met, and include kinasesoverexpressed receptor tyrosine in mesothelioma many. Some of the association, has been discovered in EGFR and epithelioid histology, a clear association has not been found between overexpression and the overall survival of EGFR. Expression of AXL receptor tyrosine kinase is a negative prognostic factor. Expression of PDGFRB is a positive prognostic factor. Generally, mesothelioma, rather than the tumor suppressor gene, the acquisition of over-expression or function in cancer gene, characterized by loss of function.
Asbestos fibers, eventually creating favorable conditions for the development of mesothelioma, have been shown to alter the function and secretion properties of macrophages. After asbestos phagocytosis, macrophages increased amounts of the normal hydroxyl radical of anaerobic metabolism of byproducts cells, will generate. However, these free radicals also known clastogenic, membrane active agent is thought to promote asbestos carcinogenicity. These oxidizing agents, either directly or indirectly membrane-associated cellular events, including the perturbation of activation and antioxidant defense of cells of a cancer gene, modification, can participate in carcinogenic process by interacting with DNA you.
Asbestos is also, you can have immunosuppressive properties. For example, chrysotile fibers, the growth in vitro phytohemagglutinin stimulated peripheral blood lymphocytes to suppress the dissolution of inhibiting natural killer cells, it has been shown to reduce the survival and recovery of significant lymphokine-activated killer cells. Furthermore, genetic alterations in asbestos-activated macrophages, in turn, may induce chronic irritation, such powerful as platelet-derived growth factor (PDGF) and transforming growth factor � (TGF-�) mesothelium proliferation of mesothelial cells after injury by can we asbestos fibers can lead to release of mitogenic factor.
The environmental trigger malignant tumors, tumors of mesothelioma by performing assays based on X inactivation against epithelioid and biphasic tumors obtained from female patients, been found to be polyclonal in origin there. These results, environmental factors, such as asbestos exposure, therefore, the small but results in a population of genetically different tumor cells, damaged, it is possible to convert a group of cells within tissue.
Treatment:
Mesothelioma, there are generally resistant to treatment of radiation and chemotherapy. Long-term survival and treatment is extremely rare. malignancy in the treatment of mesothelioma at an early stage, it has a good prognosis. Clinical behavior of malignant tumors, a series of very long latency period between the development cavity prefer local transition through the pleural peel cell, infiltration to other organs in the organization and the chest cavity at the bottom, and the asbestos exposure are you of the disease that are affected by several factors, including the mesothelial surface. Histological subtype, also the patient's age and health will help to predict the prognosis. Epithelioid histology, respond better to treatment, have a survival advantage in sarcomatoid histology on.Surgery:
Surgery is, by itself, it is a disappointment was found. 1 In a large series, was (including extrapleural pneumonectomy) just 11.7 months median survival with surgery. Radiation therapy and chemotherapy (Duke, 2008), or in, when used in combination with one of the latter, however, research shows various success. Pleurectomy / decortication is the most common surgery for chest lining has been removed. Is very common in the lungs, the inside of the lining of the chest, in a semi-diaphragm and pleural pneumonectomy the pericardium is removed (EPP), is localized pericardial mesothelioma, pericardial resection surgery can be curative. When the tumor has spread, pericardial resection is an option of palliative care. Entire tumor is, in many cases, can not be removed.Radiation:
Localized disease that can withstand the radical surgery, for patients with who, radiation as a consolidation therapy, can be granted after surgery. The entire half the chest of, in many cases, chemotherapy is given at the same time, it has been treated with radiation therapy. Deliver radiation and chemotherapy after radical surgery has led to the average life expectancy has been extended in a patient population that has been selected. Further, it is possible to induce severe side effects, including lethal pneumonia. As part of the curative approach to mesothelioma, radiation therapy is typically applied to the site of the chest drain insertion, chest wall in order to prevent the growth of tumors along the track.Mesothelioma is a generally resistant to therapeutic treatment with radiation therapy alone, palliative treatment regimens, often, occlusion of such major blood vessels, are used to alleviate symptoms resulting from tumor growth you. Radiation therapy given alone with curative purposes are not shown to improve survival rates of mesothelioma. Radiation dose necessary to treat mesothelioma that has not been surgically removed would be very toxic. Radiation therapy is the use of part of the pericardial mesothelioma.
Chemotherapy:
Chemotherapy is the only treatment for mesothelioma is possible to improve the survival rate in a randomized and controlled trials has been demonstrated. In Vogelzang et al by groundbreaking study published in 2003, "In patients who have not received chemotherapy for previously malignant pleural mesothelioma , cisplatin and pemetrexed (trade name Alimta) of chemotherapy to compare the combination with cisplatin monotherapy, more aggressive candidate is was not a person radical "surgery. this study, median survival from 10 months in patients treated with the patient group 13.3 months, with cisplatin alone It showed a statistically significant improvement of the value, in combination with pemetrexed, which was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, treated with cisplatin, who also received a supplement of folic acid and vitamin B12 year. vitamin side effects supplementation pemetrexed related to have been given to most patients in the trial, they also, as compared to patients who received pemetrexed without vitamin supplementation, all of 9 weeks daily oral folic acid 500mcg and intramuscular vitamin B12 It was significantly lower in patients who received pemetrexed when subjected to 1000mcg. the objective response rate, the combination pemetrexed group has increased from 20 percent in the cisplatin group to 46%. such a nausea and vomiting, stomatitis, diarrhea Although some side effects such as were more common in the combination pemetrexed group, to affected only a small number of patients, the combination of pemetrexed and cisplatin when the overall patients received vitamin supplementation tolerated sex was good. been improved in the combination pemetrexed group, to the quality and lung function tests. February 2004 of both of life, the United States food and drug Administration (FDA), the pemetrexed for the treatment of malignant pleural mesothelioma It was approved. However, the optimal use of chemotherapy, including when to start treatment there, the question remains, is the optimal number of cycles of the obtained for. [citation needed] cisplatin and pemetrexed , together to give a median survival of 12.1 months in patients.Cisplatin in combination with raltitrexed showed no similar improvement in survival to those reported for pemetrexed in combination with cisplatin, it is no longer marketed raltitrexed for this indication. Survival benefit is not shown for these drugs, for patients who can not tolerate pemetrexed, cisplatin combined with gemcitabine or vinorelbine, alternatively, or independently vinorelbine. For those patients who can not use cisplatin, it can be substituted for carboplatin, nonrandomized data, although the number of survival similar to patients receiving cisplatin, carboplatin based combination of It shows a lower reaction rate and a high proportion of hematologic toxicity for.
In January 2009, the United States FDA is, I, or II mesothelioma, after studies national survey of Duke University was carried out, using conventional treatments such as surgery in combination with radiation and or chemotherapy on stage on, it signed a nearly 50 point increase in the approved remission rates.
Usually, adriamycin and / or cisplatin pericardial mesothelioma, Chemotherapy, mainly be used to reduce the tumor, there is no curative.
Immunotherapy:
Treatment regimen, including immunotherapy, as a result of the variable has been obtained. For example, it in an attempt to enhance immune responses, intrapleural inoculation of Bacillus Calmette-Guerin (BCG) is, (which might benefit patients with bladder cancer), it is beneficial without the patient It has been found. Mesothelioma cells, sensitive prove to dissolution in vitro by LAK cells after activation by interleukin -2 (IL-2) is, patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the higher level of unacceptable toxicity IL-2, the severity of side effects such as fever and cachexia. Nevertheless, other studies, including interferon-alpha is 20 percent of patients who experienced a reduction of more than 50% tumor mass combined with minimal side effects, it has been demonstrated more encouraging.Heated intraoperative intraperitoneal chemotherapy
This technique , including the patient's malignant pleural mesothelioma, are used in combination with surgery. surgeon was heated from 40 � to 48, followed by the direct administration of the chemotherapeutic agent, to remove as much of possible tumor C, abdominal inch fluid, perfused 60 to 120 minutes, then discharged It will be. High concentration of the selected drug will then be administered to the surface of the abdomen and pelvis. By heating the chemotherapy treatment, it increases the penetration of the drug to the tissue. In addition, damages, a lot of heating yourself than malignant cells than normal cells.
Combined modality therapy
All standards, solid tumors, radiation, approaches to the treatment of chemotherapy and surgery, been studied in patients with malignant pleural mesothelioma who came. Surgery is, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (tri-modal therapy) is a significant prolonged survival among patients with good prognostic factors (3-14 years of age ) was prepared. examine the will, the other large-scale series collection science treatment of demonstrated improvement of slight survival (median 14.5 months and 29.6% only surviving 2-year survival). is the key to extend the reduced survival of the majority of the tumor in the tumor reduction surgery. Two of the surgery have been developed: pleural pneumonectomy and pleurectomy / decortication. Instructions for performing these operations are unique. Selection of operation, i.e., depends on the size of the patient's tumor. Tumor volume, because it is identified as a prognostic factor in mesothelioma, which is an important consideration. pleurectomy / decortication, spare and intent of the underlying lung, tumor of all of the naked eye visible (in the case is to macroscopic completely removed, will be done in patients with early-stage disease resection), relaxation not only. pleural pneumonectomy lung, is the basis of the ipsilateral (same side) diaphragm, and ipsilateral pericardium, is a broader operation involves the excision of the parietal and visceral pleura. This operation can tolerate pneumonectomy, are shown for a subset of patients with more advanced tumors.
Clinical trials:
Clinical trials, prevention, detection, is a research study to test a new method of treating diagnosis, or the disease. People to participate in clinical trials of cancer, we have the opportunity to help the development of scientists knowledge to contribute to the improved treatment of cancer for cancer. For advanced and aggressive cancers, such as such mesothelioma, clinical trials, it might be one of the best choices for treatment. In the case of mesothelioma only, in 78 open research around, you Yes, depending on www.clinicaltrials.gov.Prognosis:
Mesothelioma has a poor prognosis. The median survival period for pleural mesothelioma is 12 months from diagnosis. Women, young people, people with a low-stage cancer and people with epithelioid cancer, is, have a better prognosis. negative prognostic factor is sarcomatoid or biphasic histology, high platelet count (400,000 above), the age of the more than 50-year-old, pleural effusion includes the white blood cell count, low albumin level, and 15.5 above high fibrinogen levels , low glucose level. Some of the markers, is being studied as a prognostic factors, including nuclear grade, and serum C-reactive protein. Long-term survival is rare.During pericardial mesothelioma has a median survival time of 10 months.
In peritoneal mesothelioma, high expression of WT-1 protein is indicative of a poor prognosis.
Epidemiology:
Although reported incidence has increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence, the United Kingdom, Australia, the highest rate in Belgium, Tunisia, from less than one low-rate per 1,000,000 in Morocco, will change things from one country to another. For 30 years per 1,000,000 comparison, the high level of the population smoking can have an incidence of more than 1,000 lung cancer per 1,000,000. The incidence of mesothelioma malignant currently the last few decades, depending on the amount of asbestos exposure of the population is in the range of about 7 40 per 1,000,000 in developed Western countries. Worldwide incidence is estimated at 1,000,000 per 1-6. due to the incidence of mesothelioma, it has been delayed than that of asbestosis in the long time it takes to develop. To stop the use of asbestos in developed countries, the incidence of mesothelioma is expected to diminish. The incidence is due, it is expected to continue to increase in the continuing use and developing countries of asbestos. mesothelioma, occurs more frequently in men than in women, the risk increases with age, this disease at any age, can be displayed in either male or female. Nearly one-fifth to one-third of all mesothelioma is the peritoneum. Less than 5 percent of the mesothelioma There pericardium. The prevalence of pericardial mesothelioma is less than 0.002%. It is men who are more common than women. It is, typically, 50 generations of people, occurs in 70 generations.Between 1940 and 1979, about 27.5 million people in the profession the United States were exposed to asbestos. between 1973 and 1984, the incidence of pleural mesothelioma of the white male were up 300%. In the late 1990s from 1980, mortality from mesothelioma in the United States, than women, and a high more than four times the possibility of man to get it, was increased from 2000 3000 for two years. More than 80% of the mesothelioma is caused by asbestos exposure
UK:
The mesothelioma accounts for less than 1 percent of all cancers diagnosed in the United Kingdom, (2400 people died in 2012 around) (the people around 2600, was diagnosed with the disease in 2011) it is the most common cause of the 17 cancer death.Society and Culture
A notable example
Mesothelioma, although rare, there was a number of patients should be noted:
After he worked for the company, Bernie Banton after the contract mesothelioma, Australian workers' rights activist, fought a long battle for compensation from James Hardie. He claimed that before you start to work with the material to create a heat insulating material for the power plant, James Hardie knew the dangers of asbestos. Mesothelioma, to finally along with his brother James Hardie workers hundreds of people "has been deprived of his life. James Hardy, his mesothelioma is, to have reached its final stage, in the case of that he does not have more than 48 hours that is not alive is expected only, want the reconciliation of private and Banton did. Australian Prime Minister Kevin Rudd, after winning the federal election in Australia in 2007, it said the expansion struggle of Banton in his acceptance speech.
Since the doctor is cancer felt too that it is advanced, diagnostic Steve McQueen, American actor, December 22, he is in 1979, which did not provide surgery and chemotherapy, and peritoneal mesothelioma It has been. McQueen, sought alternative treatment in subsequent Mexican clinic. He is after surgery for cancer, Juarez, Mexico, died of a heart attack in 1980, November 7. He is young adults, while providing the US Marine Corps as asbestos, may have been exposed to asbestos, then, generally (ship McQueen was an avid racing driver and fan piping - it was used to isolate from use as an insulating material or automobile racing suits).
Cynthia Stelljes, a founding member of the classical quartet Quartetto Gelato oboist and Canada, died of illness on December 29, 2006
Bill Tate, husband of the anti-asbestos activist Nancy Tate of early, spark the subsequent behavior of his wife, he died in the state in 1968.
Bruce Vento, the US House of Representatives lawmakers, Bruce Vento Hopebuilder Award, in order to support the research and advocacy of mesothelioma, given every year by his wife in the MARF symposium to individuals or organizations that have done little, 2000 He died of mesothelioma in the year.
Warren Zevon, American rock singer-songwriter, Jivon refused the treatment that they only him and powerless, due to his last will help you chose to record concerned about the album instead It was was diagnosed with inoperable peritoneal mesothelioma in 2002. He is at home in Los Angeles, at 56 years old, died on September 7, 2003. His album, wind, won the 2, it has been nominated for several Grammy Awards.
People who have lived for some time with mesothelioma
Although life expectancy has been generally limited in this disease, there are notable survivors. In July 1982, Stephen Jay Gould, a reputation of paleontologists, was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould, he statistics are useful abstraction, such as a central value of such survival, argues that it is not fate, "the median is, there is not a message" to write year. Gould, finally succumbed to cancer that has not been linked to mesothelioma he lived another 20 years.
Diagnosed Paul Klaus in 1997, is considered to be a survivor of the world's longest current (as of 2015) living mesothelioma.
Legal issues
Main article: asbestos problem
Some of the people who have been exposed to asbestos, including mesothelioma, was to collect damages for asbestos-related disease. Compensation via asbestos funds and collective action is an important issue of law practices related to mesothelioma.
The first lawsuits against some of the as reported seem to put this (asbestos manufacturers, was in 1929. Since then, a lot of litigation, asbestos, safety measures after the link between asbestos lung implementation to ignore in order to, it has been filed against manufacturers and employers of asbestos, such as the early 1898 that mesothelioma is now to be known). Liability resulting from impact on the vast number of lawsuits and people who received has reached billions of dollars. How to assign the amount of money and compensation reached the US Supreme Court, and has a large number of court cases sources, the government is trying existing and future examples of resolution. However, until today, the United States Congress is not he stepped, there is no federal law governing asbestos compensation. in 2013, "the transparency of the asbestos claims (FACT) proceed with the 2013 law," the United States passes through the House of Representatives, the US Senate, which was called to the Senate Judiciary Committee it was sent. the Senate before the end of the 113th Congress, as did not vote for it, it died in committee. It is, it was still resurrected in the first 114 parliament that had not been raised in front of the house for a vote.
History:
The first lawsuits against asbestos manufacturers, the party that was brought in 1929 settled the lawsuit, as part of the agreement, lawyers have agreed that no further pursue the example. In 1960, a paper published by Wagner et al. It was semen on the establishment of mesothelioma as a disease caused by exposure to asbestos.article referred to as the more than 30 case studies of people who had been suffering from mesothelioma in South Africa. Some of the exposures were transient and some of the miners. Prior to use of the advanced microscopy techniques, malignant mesothelioma was often diagnosed with variant of lung cancer. McNulty in 1962, reported the first diagnostic case of malignant mesothelioma in Australia of asbestos workers. workers of the asbestos mine in Wittenoom from 1948 to 1950 I worked in the millIn the town of Wittenoom, asbestos-containing mine waste was used to cover the schoolyard or playground. Article of the UK magazine industry physician in 1965, has lived in the area of ??asbestos factories and mines, it was in them to establish that the people who did not work had contracted mesothelioma.
Dust associated with the mining and milling of asbestos, despite proof that the cause of asbestos-related diseases, mining begins at Wittenoom in 1943, the first public of the dangers of blue asbestos warning "This is referred to as until 1974, 1966 was published in the cover story we continued killer? "Western Australia state government to letterzine inch 1978 of Australia's in your house, the air sampling results, the evaluation of medical information around the world including, of health department booklet, after the publication of "health hazard in Wittenoom", was the stage that the town of Wittenoom.
1979 CSR and ABA of its subsidiaries, and the first warrant for negligence related to the issued Wittenoom against asbestos disease Society was formed to represent the victims of Wittenoom.
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