Genetics and Malignant Mesothelioma

Kok Siong Chen — Mon, 07 Jun 2010 01:24:54 +0000

This is a guest post submitted by G. Garcia and written by Ben Stillwater. Ben Stillwater is a freelance writer for AsbestosNews.com, an online resource on malignant mesothelioma and asbestos cancer.

There has been some research on the relationship between genetics and the development of malignant mesothelioma. While there is no conclusive body of work, there is some compelling evidence that genetic defects may result in a higher risk for the development of malignant mesothelioma. Research reported in Cancer Genetics and Cytogenetics in 2001 found evidence of chromosomal defects aligned through a family with a history of cancer that included at least one malignant mesothelioma patient.

Frightening Story of Malignant Mesothelioma

There is also an intriguing and frightening story of three villages in Turkey where fifty percent of the deaths are caused by malignant mesothelioma. This is a relatively rare disease, diagnosed perhaps 3,000 times a year in the United States, a nation of 300 million people. The ostensible cause is exposure and inhalation or ingestion of asbestos fibers. In the villages located in the Cappadocian area of Turkey residents were uniformly exposed to a fibrous material called erionite, similar in structure to the six types of fiber categorized as asbestos. Erionite occurs naturally in other areas of Turkey however and the occurrence of malignant mesothelioma is fractional compared to the villages of Tuzkoy, Karain, and Sarihidir.

A cancer study conducted by a collaboration of physicians and scientists from Turkey and the United States looked closely at this epidemic for evidence of genetic predisposition to mesothelioma cancer and reported their findings in the May, 2006 edition of Cancer Research. They found no evidence of a different, more malicious type of erionite fiber among the villages with populations disposed to the development of malignant mesothelioma than in other Cappadocian villages. Further, they found that occurrences of the disease were more frequent in some families than others. And finally, epidemiological research showed that members of families with frequent malignant mesothelioma occurrence who married into families without the history of malignant mesothelioma carried an increased risk of the disease developing for their children and grandchildren. The evidence of genetic predisposition is overwhelming.

Gene Therapy for Malignant Mesothelioma

One of the developments in cytogenetics with regard to malignant mesothelioma and other carcinomas has been the identification of chromosomal damage with the onset of tumor development. Genetic evidence of damage has served as a source of markers for malignant growths. Today the use of gene therapy applying targeted tumor-suppressant genes at malignant cells is in its nascent stage but promising a hopeful path to improved and effective treatment. Gene therapy has been one of the sidelights in mesothelioma news as thoracic oncologists have cast about for more effective ways to target mesothelioma cells. Chemotherapy combinations employing cisplatin, Pemetrexed and Onconase have been tested and retested in various combinations but the difficulty of targeting two distinct types of malignant cells remains.

Malignant mesothelioma is most commonly caused by an epithelial cell, but a sarcomatoid cell is a less frequent possibility and the presence of both occurs in up to twenty percent of all cases. Experimental gene therapy models have been developed for both. The use of gene therapy to slow the reproduction of epithelial cells has shown some effectiveness, while a method of genetic vaccination for sarcomatoid cells has been less conclusive. A summation of recent gene therapy treatment for malignant mesothelioma appeared in the German medical journal Onkologie in 2008, detailing the clinical studies to that point. Oncologists are accustomed to mixing chemotherapy drugs as a treatment option, mixing chemotherapy and radiotherapy for malignant mesothelioma treatment, and now are looking at incorporating gene therapy into treatment protocols for this lethal disease.

Genetics and Malignant Mesothelioma is a post from: Cytogenetics and Cancer Research

9 Steps of Peritoneal Cancer Progression

Kok Siong Chen — Mon, 25 Jan 2010 14:55:05 +0000

Peritoneal cancer is caused by carcinomatosis which occurs at the visceral and parietal peritoneal lining of the abdominal cavity. The tumour cells disseminate from their primary organ of origin to develop metastatic deposits on the visceral and parietal lining of the abdominal cavity. Therefore, it is important to find out the molecular events involved in peritoneal carcinomatosis to design the treatment to deal with the peritoneal cancer.

For better understanding on the events involved in peritoneal carcinomatosis, we need to look deeply on every single process of peritoneal cancer progression. We called this series of steps as “Peritoneal Metastatic Cascade”. Yet, we have to bear in mind that each step in the metastatic cascade does not occur in isolation but occur in a continuous and interdependent process.

Peritoneal Cancer Progression

1. At first, the tumour cells from the primary organ must break away from the primary tumour mass and gain access to the peritoneal cavity.

2. Then, the tumour cells free to disseminate around the peritoneal cavity.

3. There are many factors that determine the final destination of these tumour cells.

i. Gravity

ii. Movement of the abdominal viscera

iii. Flow of ascetic fluid

4. The tumour cells will first enter the innermost layer of peritoneum which is our mesothelium.

5. Next, the tumour cells will attach to the mesothelium.

6. Consequently, the mesothelial monolayer and its basement membrane will penetrate to the submesothelial connective tissue. The penetration provides the chance to the tumour cells to access to the submesothelial connective tissue too.

7. Continuously, the invasion of the underlying connective tissue gives the necessary scaffold for tumour proliferation and provides tumour-stromal interaction.

8. The discrete metastatic tumour deposit starts to establish.

9. Finally, the induction of angiogenesis to sustain tumour proliferation has enabled the further metastatic growth of peritoneal cancer cells.

In conclusion, peritoneal cancer is a rare cancer that still needs a lot of research for further understanding. I decide to write about it in Cytogenetics and Cancer Research blog because it is interesting to look on. I will try to find out more information about peritoneal cancer and write it out here. Stay tuned!

( Resource: Cancer Treatment and Research by Steven T. Rosen)

Have you heard about peritoneal cancer before? Any extra useful information to share with us?

9 Steps of Peritoneal Cancer Progression is a post from: Cytogenetics and Cancer Research

Cytogenetics and Cancer Research » Peritoneal Cancer