Navigation Links
Researchers identify and shut down protein that fuels ovarian cancer

HOUSTON - A protein that stimulates blood vessel growth worsens ovarian cancer, but its production can be stifled by a tiny bit of RNA wrapped in a fatty nanoparticle, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports in the Journal of the National Cancer Institute.

"The protein interleukin-8 (IL-8) is a potential therapeutic target in ovarian cancer," said senior author Anil Sood, M.D., professor in the M. D. Anderson Departments of Gynecologic Oncology and Cancer Biology.

The paper demonstrates that high IL-8 expression in tumors is associated with advanced tumor stage and earlier death for ovarian cancer patients. Lab experiments and research in a mouse model show that short interfering RNA (siRNA) can cut IL-8 expression, reducing tumor size by attacking its blood supply.

"This comprehensive analysis - with human data, animal data and lab experiments to highlight the molecular mechanisms involved - helps us develop the new targets needed for a more effective approach against ovarian cancer," Sood said.

Interleukin-8 is overexpressed in many types of cancer and has previously been shown to promote tumor growth, new blood vessel growth known as angiogenesis, and metastasis, the spread of cancer to other organs. "In the long run, this research will have applications in other cancers as well," Sood said.

His research focuses on ovarian cancer, for example, while senior co-author Menashe Bar-Eli, Ph.D., professor in M. D. Anderson's Department of Cancer Biology, examines IL-8's role in melanoma.

Impact on survival

Ovarian cancer is often detected in late stages. Initial treatment includes surgery and taxane- or platinum-based chemotherapy regimens that keep the cancer at bay for a time in most patients. Recurrence is common and often lethal.

To examine IL-8's role in ovarian cancer, the researchers analyzed tumors from 102 patients diagnosed and treated between 1988 and 2006 at M. D. Anderson and the University of Iowa. Of those, 43 had tumors with high levels of IL-8 and 59 had low levels. The median survival of those with high IL-8 tumors was 1.62 years, compared with 3.79 years for those with low expression of the protein.

All 43 tumors with high expression of IL-8 were of high grade and 42 of 43 were advanced, either stage III or IV tumors. By comparison, 10 of 59 tumors with low IL-8 expression were early stage tumors and six were of low grade.

Shrinking tumors

Genes transcribe single strands of RNA that in turn are "read" by ribosomes to produce proteins. siRNAs are short, double-stranded bits of RNA capable of halting that process. The team confirmed in a lab experiment that a specific siRNA silences IL-8 and then tested it against two lines of ovarian cancer in a mouse model.

Sood, Gabriel Lopez-Berestein, M.D., professor in M. D. Anderson's Department of Experimental Therapeutics, and colleagues are building an arsenal of siRNAs capable of silencing genes that produce cancer-promoting proteins. They packaged siRNA that stymies IL-8 into a small ball of fat known as a liposome, a combination they developed to overcome a problem - siRNA is hard to deliver to tumors.

Tumors shrank by a median of 32 percent and 52 percent in the two cancer lines among mice that received injections of the IL-8 siRNA liposome compared to those receiving control siRNA or empty liposomes.

Mice that got both the IL-8 siRNA plus the taxane-based chemotherapy drug docetaxel had median tumor weight reduction of 90 percent and 98 percent in the two cell lines. Mice with control siRNA plus docetaxel saw reductions of 67 and 84 percent.

Finally, they tested the approach in mice with an ovarian cancer cell line known to be resistant to taxane-based drugs such as docetaxel. IL-8 siRNA alone reduced the size of these tumors by 47 percent, and when combined with docetaxel reduced tumor size by 77 percent, suggesting that the combination re-sensitizes a resistant tumor to taxanes.

The team gauged the impact of IL-8 siRNA on tumor blood supply by measuring the density of blood vessels in the tumor. The IL-8 siRNA alone reduced blood vessel density by 34 percent and 39 percent in two cancer lines.

Clinical Prospects

"These are encouraging results. We want to move one of our siRNA agents into the clinic to test its potential for therapy," Sood said, "and then in the longer term, we'll consider moving additional siRNA agents into the clinical arena."

The IL-8 siRNA liposome is the third developed by Sood's and Lopez-Berestein's team. Two others target the oncoproteins FAK and EphA2. The EphA2 siRNA liposome is closest to Phase I clinical trial, with required toxicology studies nearly complete. A clinical trial could begin within a year.

Methods used to inject siRNA in high volumes for research purposes are impractical for human therapy. Sood and Lopez-Berestein developed the liposomal approach to ensure that the siRNA reaches the cell intact so it can silence the targeted gene. Their research has shown that the liposome penetrates deeply into cells to deliver its siRNA.


Contact: Scott Merville
University of Texas M. D. Anderson Cancer Center

Related medicine news :

1. Stanford researchers find culprit in aging muscles that heal poorly
2. UCLA researchers identify markers that may predict diabetes in still-healthy people
3. Mayo Clinic researchers discover new diagnostic test for detecting infection in prosthetic joints
4. Bipolar disorder relapses halved by Melbourne researchers
5. Cell that triggers symptoms in allergy attacks can also limit damage, Stanford researchers find
6. High and mighty: first common height gene identified by researchers behind obesity gene finding
7. Researchers estimate about 9 percent of US children age 8 to 15 meet criteria for having ADHD
8. Majority of 2.4 Million U.S. Children With ADHD Not Diagnosed or Consistently Treated, According to New Gold Standard Study by Cincinnati Childrens Researchers
9. Researchers develop long-lasting growth hormone
10. Jefferson immunology researchers halt lethal rabies infection in brain
11. Purdue researchers develop technology to detect cancer by scanning surface veins
Post Your Comments:
Related Image:
Researchers identify and shut down protein that fuels ovarian cancer
(Date:11/29/2015)... ... November 29, 2015 , ... Key Housing, a top-rated corporate housing service ... 2015, featured apartment community: Epic. In showcasing this featured apartment community in San Jose, ... Area rental market to efficiently find housing suitable to their needs by showcasing quality ...
(Date:11/28/2015)... PITTSBURGH, PA (PRWEB) , ... November 28, 2015 , ... ... Manalapan, N.J., has created the COUCH BUDDY. "I conceived of this design due to ... more comfort for couch users. It promotes relaxation and convenience, as well as increases ...
(Date:11/27/2015)... (PRWEB) , ... November 28, 2015 , ... There is ... we outperform our billings from last year? , This question has not been an ... are coming to the retirement age and the younger workforce don’t share the same ...
(Date:11/27/2015)... ... ... According to an article published November 15th by ABC News, ... in light of the recent terrorist attacks in Paris, other cities are taking extra ... from reaching U.S. soil. Especially around special events that may be high-profile in nature, ...
(Date:11/27/2015)... ... November 27, 2015 , ... An inventor, from Hopkinsville, ... prescription medications at home, so he invented the patent-pending ELECTRONIC M.D. , The ... medications. In doing so, it could help to prevent potential overdose situations. As ...
Breaking Medicine News(10 mins):
(Date:11/27/2015)... PHILADELPHIA , Nov. 27, 2015  Lannett ... that it has completed the acquisition of Kremers ... pharmaceuticals subsidiary of global biopharmaceuticals company UCB S.A. ... --> Lannett has acquired KU from UCB ... to certain adjustments, including a customary working capital ...
(Date:11/26/2015)... WILMINGTON, North Carolina , 26 november ... Laboratories, Inc. (AAIPharma/CML) kondigt de geplande investering ... de uitbreiding van de laboratoria en het ... . De uitbreiding zal resulteren in ... waarmee wordt voldaan aan de groeiende behoeften ...
(Date:11/26/2015)... -- 3D bioprinting market is expected to ... report by Grand View Research Inc. Rising prevalence of chronic ... transplantation is expected to boost the market growth, as 3D ... --> 3D bioprinting market is expected to ... report by Grand View Research Inc. Rising prevalence of chronic ...
Breaking Medicine Technology: