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Mesothelioma

Disease Details

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Description: Mesothelioma is a rare and aggressive cancer that develops in the lining of the lungs, abdomen, or heart, often due to asbestos exposure.
Type: Mesothelioma is primarily a type of cancer that affects the mesothelium, a thin layer of tissue covering most internal organs. The most common form is pleural mesothelioma, which affects the lining of the lungs.

Regarding genetic transmission, mesothelioma is not typically considered a hereditary disease. Instead, it is most commonly associated with exposure to asbestos. However, there can be genetic factors that influence an individual's susceptibility to developing mesothelioma after asbestos exposure. For example, mutations in the BAP1 gene have been linked to a higher risk of developing mesothelioma.
Signs And Symptoms: Mesothelioma is a type of cancer that affects the mesothelium, a thin layer of tissue that covers most internal organs. The signs and symptoms of mesothelioma can vary depending on the location of the cancer.

**Pleural Mesothelioma (affecting the tissue around the lungs):**
- Chest pain
- Painful coughing
- Shortness of breath
- Unusual lumps of tissue under the skin on the chest
- Unexplained weight loss

**Peritoneal Mesothelioma (affecting the abdominal tissue):**
- Abdominal pain
- Abdominal swelling
- Nausea
- Unexplained weight loss

**Other forms (e.g., pericardial mesothelioma, testicular mesothelioma):**
- Pericardial mesothelioma (around the heart): Chest pain, irregular heartbeats, difficulty breathing
- Testicular mesothelioma: Swelling or lumps in the testicular area

It's important to consult a healthcare provider if you experience persistent symptoms. Early diagnosis and treatment are crucial for better outcomes.
Prognosis: Mesothelioma usually has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses. Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.Pericardial mesothelioma has a 10-month median survival time.In peritoneal mesothelioma, high expression of WT-1 protein indicates a worse prognosis.
Onset: Mesothelioma is a cancer primarily associated with exposure to asbestos. The onset of symptoms can take several decades to appear, typically 20 to 50 years after exposure. Symptoms may include chest pain, shortness of breath, and fatigue.
Prevalence: The prevalence of mesothelioma, a rare cancer linked to asbestos exposure, varies globally but is generally low compared to other cancers. In the United States, about 3,000 new cases are diagnosed annually. Prevalence rates are higher in countries with significant asbestos use or production, as the disease often occurs decades after exposure.
Epidemiology: Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades. Worldwide incidence is estimated at 1-6 per 1,000,000.Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease. Incidence is expected to continue increasing in developing countries due to continuing use of asbestos. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal. Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a person's 50s-70s.Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States. Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. More than 80% of mesotheliomas are caused by asbestos exposure.The incidence of peritoneal mesothelioma is 0.5–3.0 per million per year in men, and 0.2–2.0 per million per year in women.
Intractability: Mesothelioma is often considered intractable, particularly in its advanced stages. It is a rare and aggressive cancer primarily caused by exposure to asbestos. Treatment options such as surgery, chemotherapy, and radiation can sometimes manage symptoms and improve quality of life, but a complete cure is rare. The prognosis for mesothelioma patients is typically poor, with many surviving only a year or two after diagnosis.
Disease Severity: Mesothelioma, a rare and aggressive form of cancer primarily caused by asbestos exposure, is characterized by unpredictable disease severity. It has a long latency period and often presents in advanced stages. Early detection can improve prognosis, but overall survival rates remain low. There is no established nanotechnology treatment (nan) for mesothelioma as of now.
Healthcare Professionals: Disease Ontology ID - DOID:2645
Pathophysiology: Mesothelioma is a malignant tumor primarily caused by inhalation of asbestos fibers, which leads to the development of cancer in the mesothelial cells lining the pleura (lungs), peritoneum (abdomen), pericardium (heart), or tunica vaginalis (testes). The pathophysiology involves:

1. **Asbestos Fiber Inhalation/Exposure:** Asbestos fibers are inhaled or ingested and they become lodged in the mesothelial lining.
2. **Inflammation and Cellular Damage:** The body attempts to eliminate the fibers, leading to chronic inflammation and cellular damage.
3. **Genetic and Cellular Changes:** Continuous irritation and damage from asbestos fibers lead to genetic mutations in mesothelial cells. These mutations can interfere with normal cell growth and apoptosis (programmed cell death), leading to uncontrolled cell proliferation.
4. **Tumor Development:** The accumulation of these genetic mutations causes malignant transformation of the mesothelial cells, resulting in the formation of mesothelioma tumors.
5. **Tumor Spread (Metastasis):** The cancer can metastasize to other parts of the body, complicating treatment and prognosis.

Key features include local invasion of surrounding tissues and organs by the tumor and the formation of pleural effusion, which can impair lung function. The latency period from asbestos exposure to the development of mesothelioma is typically long, often several decades.
Carrier Status: Mesothelioma is not a hereditary disease and does not have a genetic carrier status. It is primarily caused by exposure to asbestos fibers.
Mechanism: Mesothelioma is primarily a cancer of the mesothelium, a thin tissue layer covering most internal organs, often associated with asbestos exposure. Here's a breakdown of its mechanism and molecular mechanisms:

**Mechanism:**
1. **Asbestos Exposure:** Inhalation of asbestos fibers is the primary cause. These fibers lodge in the lung and pleura (lining of the chest cavity).
2. **Inflammation and Scarring:** The trapped fibers cause chronic inflammation and cellular damage, leading to fibrosis and scarring of the tissue.
3. **Cellular Damage and Mutation:** Prolonged inflammation leads to genetic mutations and cellular damage. These changes disrupt normal cell growth and division controls.
4. **Tumor Formation:** Damaged mesothelial cells begin to grow uncontrollably, forming tumors. Mesothelioma can develop in the pleura (pleural mesothelioma), peritoneum (peritoneal mesothelioma), or other mesothelial tissues.

**Molecular Mechanisms:**
1. **Genetic Mutations:** Specific mutations in tumor suppressor genes (like BAP1, NF2, and CDKN2A), and oncogenes are frequently observed in mesothelioma cases. These mutations compromise the cell’s ability to regulate its growth and death.
2. **Inflammatory Cytokines:** Chronic exposure to asbestos fibers leads to the release of growth factors and inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), which further contribute to a pro-carcinogenic environment.
3. **Oxidative Stress:** Asbestos fibers induce the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which cause oxidative damage to DNA, proteins, and cell membranes.
4. **Chromosomal Abnormalities:** Mesothelioma cells often exhibit chromosomal abnormalities, such as deletions, rearrangements, and aneuploidy, contributing to the malignant phenotype.
5. **Epigenetic Changes:** Alterations in DNA methylation and histone modification patterns can lead to the silencing of tumor suppressor genes and activation of oncogenes, aiding in the disease's progression.
6. **MicroRNAs (miRNAs):** Dysregulation of specific miRNAs is implicated in mesothelioma. These small, non-coding RNAs can regulate gene expression post-transcriptionally, influencing key pathways involved in cell proliferation, apoptosis, and metastasis.

Understanding these mechanisms is crucial for developing targeted therapies and improving the prognosis for patients with mesothelioma.
Treatment: Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare. Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.The effectiveness of radiotherapy compared to chemotherapy or surgery for malignant pleural mesothelioma is not known.
Compassionate Use Treatment: For mesothelioma, compassionate use treatment involves providing patients with access to investigational drugs outside clinical trials when no comparable or satisfactory alternative treatments are available. This is typically considered for patients with serious or life-threatening conditions.

Off-label treatments for mesothelioma are those that utilize FDA-approved drugs for purposes not specifically approved by the FDA. Common off-label drugs that might be used in mesothelioma treatment include:

1. **Bevacizumab (Avastin)**: Often combined with chemotherapy to inhibit the growth of blood vessels that supply tumors.
2. **Pemetrexed (Alimta)**: While approved for mesothelioma in specific contexts, it can be used off-label in different therapeutic regimens.

Experimental treatments for mesothelioma are those still being studied in clinical trials. These can include:

1. **Immunotherapy**: Drugs like Keytruda (pembrolizumab) and nivolumab (Opdivo) that help the immune system recognize and attack cancer cells.
2. **Gene Therapy**: Approaches aiming to correct or introduce genetic material within a patient’s cells to fight cancer.
3. **Photodynamic Therapy**: Using light-sensitive drugs and a light source to destroy cancer cells.
4. **Tumor Treating Fields (TTF)**: Electrical fields that disrupt the rapid cell division of cancer cells.

Patients should discuss these options with their healthcare providers to understand the potential benefits and risks associated with each treatment type.
Lifestyle Recommendations: For mesothelioma, lifestyle recommendations mainly focus on improving quality of life and managing symptoms:

1. **Avoid Further Exposure to Asbestos:** If diagnosed with mesothelioma, it's crucial to avoid environments where asbestos exposure might occur.
2. **Healthy Diet:** Consume a balanced diet rich in fruits, vegetables, lean proteins, and whole grains to help maintain energy levels and overall health.
3. **Regular Exercise:** Engage in moderate physical activity as tolerated to maintain muscle strength and reduce fatigue.
4. **Smoking Cessation:** Quit smoking to improve lung function and overall health.
5. **Stress Management:** Incorporate stress-reducing activities such as yoga, meditation, or deep-breathing exercises.
6. **Regular Medical Check-Ups:** Keep up with routine medical appointments to monitor the disease and manage symptoms effectively.
7. **Support Systems:** Engage with support groups or counseling to cope emotionally with the diagnosis.
Medication: Mesothelioma is an aggressive cancer primarily caused by asbestos exposure. Treatment typically involves a combination of therapies, including surgery, radiation, and chemotherapy. Common chemotherapy drugs used for mesothelioma include pemetrexed (Alimta) and cisplatin. Other medications may be used to manage symptoms or side effects. Research is ongoing into new treatments, including nanotechnology-based approaches, but these are not yet standard practice.
Repurposable Drugs: For mesothelioma, certain existing drugs have shown potential for repurposing, including:

1. **Metformin**: Commonly used for diabetes, it has shown potential anti-tumor effects in preclinical studies.
2. **Celecoxib**: A COX-2 inhibitor used for arthritis, it might have anti-cancer properties.
3. **Propranolol**: A beta-blocker for hypertension, which has demonstrated anti-tumor activity in some cancer types.

Research is ongoing, and these drugs are not standard treatments for mesothelioma but are being investigated for their potential benefits.
Metabolites: Mesothelioma is a type of cancer primarily associated with asbestos exposure. The metabolites related to mesothelioma are not well-defined, unlike some other cancers where specific metabolic pathways are clearly implicated. Research is ongoing to better understand the metabolic profile of mesothelioma to identify potential biomarkers and therapeutic targets.
Nutraceuticals: Nutraceuticals, which are food-derived products with potential health benefits, have been investigated for their role in managing mesothelioma, a type of cancer primarily associated with asbestos exposure. Certain compounds like curcumin, found in turmeric, and resveratrol, found in grapes, have shown promise in laboratory studies for their anti-inflammatory and anti-cancer properties. However, these are not yet established as effective treatments in clinical practice and should not replace conventional therapies.

The applications of nanotechnology in mesothelioma treatment are at a research stage. Nanoparticles can be engineered to deliver drugs directly to cancer cells with high precision, potentially reducing side effects and improving the efficacy of treatments. Some studies have explored the use of nanoparticles to deliver chemotherapy drugs or gene therapy directly to mesothelioma cells. While this area shows promising potential, it requires further clinical trials to assess safety and effectiveness before becoming a standard treatment option.
Peptides: In the context of mesothelioma, peptides and nanoparticles (nan) represent promising areas of research and potential therapeutic approaches:

1. **Peptides**: Peptides are short chains of amino acids that can be designed to target specific proteins or receptors on mesothelioma cells. They may be used for diagnostic purposes or as part of targeted therapy to deliver drugs directly to cancer cells, thereby minimizing damage to healthy tissues.

2. **Nanoparticles (nan)**: Nanoparticles are tiny particles that can be engineered to carry drugs, genes, or other therapeutic agents directly to mesothelioma cells. This targeted delivery system aims to improve treatment efficacy while reducing side effects. Nanoparticles can also be used in imaging to better detect and monitor the progression of mesothelioma.

Research in these areas is ongoing, with the goal of developing more effective and less invasive treatments for mesothelioma.