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Researchers identify protein ‘protector’ of chemo-resistant ovarian cancer cells.

Ovarian cancer is the most deadly gynecological cancer, claiming the lives of more than 50% of women who are diagnosed with the disease. A study involving the University of Ottawa and National Cheng Kung University researchers provides new insight into why ovarian cancer is often resistant to chemotherapy, as well as a potential way to improve its diagnosis and treatment.  The study is published in the journal Proceedings of the National Academy of Sciences (PNAS).

The key is understanding the role of a protein called gelsolin. The group found that an increased level of this protein is associated with aggressive forms of ovarian cancer that are more likely to be resistant to chemotherapy and lead to death.  The researchers showed how gelsolin works at the molecular level to protect cancer cells against a widely used chemotherapy drug called cisplatin.  What the team has discovered will help clinicians to better treat women with ovarian cancer.

The findings are important because they will help clinicians to determine the most effective treatment plan based on the level of gelsolin. Work still needs to be done to determine exactly how much gelsolin indicates a cancer that is chemo-resistant and would require different treatment options.

In addition, this same protein that makes ovarian cancer cells resistant to chemotherapy can be used to overcome this treatment obstacle. By cutting gelsolin down to a specific fragment and putting it into chemo-resistant cancer cells, the international team discovered they could make these cells susceptible to the cancer-killing effects of cisplatin.

It is estimated that 2,700 Canadian women will be diagnosed with ovarian cancer in 2014 and that 1,750 Canadian women will die from the disease, according to Ovarian Cancer Canada. This cancer is often diagnosed late and develops a resistance to chemotherapy.

The team believe that this discovery is a promising avenue for developing a new therapy to reduce chemo-resistance in women with this deadly disease.

Source:  Ottawa Hospital Research Institute 

 

Immunohistochemical staining of gelsolin (GSN) in ovarian cancer (OVCA) tumors.  Representative H&E-stained pathological sections of OVCA tumor samples show different levels of GSN protein expression (original magnification 400 ×).  Expression levels: 0 and 1, negative; 2, 3, 4, positive (relative stain intensity compared with negative controls).  Cell fate regulation by gelsolin in human gynecologic cancers.  Tsang et al 2014.
Immunohistochemical staining of gelsolin (GSN) in ovarian cancer (OVCA) tumors. Representative H&E-stained pathological sections of OVCA tumor samples
show different levels of GSN protein expression (original magnification 400 ×). Expression levels: 0 and 1, negative; 2, 3, 4, positive (relative stain intensity
compared with negative controls). Cell fate regulation by gelsolin in human gynecologic cancers. Tsang et al 2014.

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