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Key discovery in the treatment of ovarian cancer

New Delhi, Thu, 23 Feb 2012 NI Wire
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There is a great achievement in the study of ovarian cancer. Researchers have identified a peptide-receptor system, which will help in the understanding the progression and treatment of human ovarian cancer that affects a large population of women worldwide.

For this, researcher conducted this study on immunocompromised mice. They transplanted molecularly engineered human ovarian cancer cells to have a lower expression of opioid growth factor receptor (OGFr). They found that ovarian tumours grew rapidly.

These findings were made by the researchers at The Pennsylvania State University College of Medicine, Hershey, Pennsylvania. Their study brings a fresh insight into the pathogenesis and therapy of a lethal cancer that is the fifth most important cause of cancer-related deaths among women in the USA for over 75 years.

The opioid growth factor (OGF)(also-termed [Met5]-enkephalin)-OGFr axis plays a vital role in cancer as it is related to development, and cellular renewal by regulating cell proliferation.

This study has also answered the requirement of this peptide-receptor system for the development of carcinogenesis.

The study has also found that Human ovarian cancer cell lines that were genetically engineered to underexpress OGFr developed far more faster in tissue culture than control (empty vector/wildtype) cell lines.

Moreover, adding OGF to cultures of these genetically engineered cells did not respond to the inhibitory peptide and change cell number that showed the loss of OGFr interfered with the function of the OGF-OGFr axis with respect to controlling cell proliferation.

Immunocompromised mice in which ovarian cancer cells were transplanted that showed a reduction in OGFr exhibited tumours much earlier than controls, and these tumours developed more rapidly than controls.

With this knowledge that the pathway for OGF-OGFr regulation of cell proliferation in ovarian cancer is by way of escalating the cyclin-dependent inhibitory kinase proteins p16 and p21, it can be said that reducing the quantity of OGFr results in a rise in the number of cells entering the G1/S phase of the cell cycle.

This process has influence on increasing the progression of tumorigenic events.

These results reflects on the critical nature of OGFr in human ovarian cancer, and that the receptor along with its ligand, OGF, is necessary for deciding the course of these neoplasias.

Dr. Ian S. Zagon and Dr. Patricia J. McLaughlin found that endogenous opioids acts as growth factors, and have been pioneers in translating their findings from the bench to the bedside.

"Ovarian cancers frequently have a methylation of p16 that is associated with an increased progression of ovarian cancer and a loss of OGFr in ovarian tumors," Dr. Renee N. Donahue a researcher in the Department of Neural and Behavioral Sciences said.

"The diminished expression of OGFr and its repercussions on tumorigenesis, only adds to the concern about the need for information concerning genetic and epigenetic changes that may impact the course of disease and its treatment.

"Our findings also hold potentially ominous overtones for those individuals taking naltrexone for addictive disorders. The dosage used for treatment of addiction blocks opioid receptors continually. The present findings that diminishing the OGF-OGFr axis by depleting the receptor exacerbates tumorigenesis, could place these patients using naltrexone at risk for accelerating disease processes that involve cell proliferation," Dr. Donahue has been quoted as saying.

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine, opined that this forceful evidence confirmed the absolute requirement for OGFr (and OGF) as a tonically active inhibitory regulatory mechanism in ovarian cancer.

"As a corollary, amplifying the OGF-OGFr pathway is a novel and highly effective biotherapeutic strategy to suppress the progression of these deadly cancers," Dr Goodman stated.

Experimental Biology and Medicine has published this study.

With inputs from ANI

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