oci.soholaunch.com

Reception: September 8, 2004, 2 p.m.
Petit Biotechnology Building, 315 Ferst Street
The Georgia Institute of Technology
Atlanta, GA

Ovarian Cancer Institute Laboratory Opens at Georgia Tech

- Network of researchers from major Georgia universities and colleges working to develop early diagnostic test and more effective new therapies -

ATLANTA (August 30, 2004) Every year more than 27,000 women are diagnosed with ovarian cancer. Approximately one third of them will survive more than five years.

There is no diagnostic test for ovarian cancer and no obvious symptoms until late in its development. As a result, about 75 percent of ovarian cancers are detected at Stages III and IV when it has spread throughout a woman's abdomen. At those late stages, extensive surgery and chemotherapy are required, with no assurance of lasting success.

Gilda Radner, Madeline Kahn and ?Driving Miss Daisy's? Jessica Tandy are a few familiar women who fell victim to this stealthy and often deadly disease.

However, if ovarian cancer is diagnosed and treated at Stage I when it is confined to the ovaries, the survival rate skyrockets to more than 85 percent. This startling statistic is one of the factors driving the doctors and researchers of the Ovarian Cancer Institute (OCI) to dramatically raise survival rates by developing a simple diagnostic blood test to detect ovarian cancer in its earliest stages, as well as develop more effective therapies to treat the cancer and diminish its rate of reoccurrence.

To rapidly advance the science about ovarian cancer, OCI has opened a new research laboratory at the Georgia Institute of Technology. OCI is headed by John McDonald, Ph.D., professor and chair of the School of Biology at the Georgia Institute of Technology, and Benedict B. Benigno, M.D., noted Atlanta gynecologic oncologist of the Southeastern Gynecologic Oncology Group.

This partnership between a major research university and a large medical practice provides scientists and researchers with access to a significant number of high quality tissue samples, complete with medical histories.

Benigno commented, ?On average our practice performs at least one surgery each day for ovarian cancer. The result is a continual stream of high-quality and documented tissue samples for our broad research agenda. We are searching for ?markers' that will lead to an affordable diagnostic test, as well as developing much more refined chemotherapy approaches based on new molecular profiles of ovarian cancer subtypes that may respond differently to treatment.?

Armed with these well-documented samples, the OCI Laboratory draws on the combined expertise of preeminent scientists and bioinformaticists from major Georgia universities and colleges. This multidisciplinary approach means that researchers with different backgrounds and approaches can apply their expertise to the same sample and compare results to rapidly gain new insights and understanding.

OCI researchers are from the Georgia Institute of Technology, University of Georgia, Georgia State University, Emory University, the Medical College of Georgia in Augusta and Clark Atlanta University. The diverse team includes members from the disciplines of bio- and medical chemistry; molecular biology and medicine, genetics; food and nutrition; statistics, mathematics, bioinformatics, and computer science; and veterinary medicine.

McDonald notes, ?By weaving together a variety of disciplines into a tight network of world-class researchers we have the opportunity to rapidly advance the science associated with ovarian cancer. Our laboratory-based insights will be further clarified by statistically correlating our experimental results with detailed patient histories to identify the potential impacts of a variety of factors including heredity, age and lifestyle.?

Among related research efforts, OCI scientists are learning more about the origins of various types of ovarian cancer. This knowledge will lead to a greater understanding of why some tumors become resistant to chemotherapy, new insights into what causes a cancer to spread, and ultimately, to the development of innovative and much more effective therapies.

OCI research is funded by the Georgia Cancer Coalition, various federal grants and private donations.

September is designated as Ovarian Cancer Awareness Month.

About Georgia Tech
The Georgia Institute of Technology is one of the nation's premiere research universities. Ranked among U.S. New & World Report's top 10 public universities, Georgia Tech educates nearly 17,000 students every year through its Colleges of Engineering, Management, Computing, Science, Architecture and Liberal Arts. Georgia Tech maintains a diverse campus and is among the nation's top producers of women and African-American engineers. The Institute offers research opportunities to both undergraduate and graduate students and is home to more than 80 interdisciplinary units plus the Georgia Tech Research Institute. During the 2003-2004 academic year, Georgia Tech totaled more than $341.9 million in research awards and expenditures.

About the Ovarian Cancer Institute
The Ovarian Cancer Institute is a non-profit organization dedicated to the development of an early and widely-available diagnostic test and more effective, non-surgical therapies. Donations to the Ovarian Cancer Institute may be sent to 980 Johnson Ferry Road, Suite 900, Atlanta, GA, 30342-1609, or call 404-843-6001 for more information. Learn more about OCI at www.ovariancancerinstitute.org

August 27, 2004
Ovarian cancer unit moving from UGA to Tech
Megan Woolhouse

Georgia Tech has hired one of the University of Georgia's top geneticists, who will officially relocate the Ovarian Cancer Institute from Athens to Tech's Midtown campus in Atlanta on Sept. 8.

The switch occurred shortly after former UGA geneticist John McDonald, head of research at the Ovarian Cancer Institute, was named chairman of Georgia Tech's school of biology. He took the post a few weeks ago, bringing the research institute with him.

The institute is part of a mission spearheaded by Atlanta surgeon Dr. Benedict B. Benigno to create a way to diagnose ovarian cancer. A "silent killer" among women that caused the deaths of celebrities Gilda Radner and Madeline Kahn, the cancer often goes undetected until its late and lethal stages. Even then, its symptoms can be deceiving.

"When a patient develops symptoms secondary to cancer of the ovary, it takes them four to six weeks to reach me," Benigno said.

Benigno said the move to Georgia Tech "opens up vast new research horizons" for the institute's researchers. The institute's monetary horizons also are brighter today.

The institute received more than $377,342 in contributions, but operated at a net loss of more than $64,000, according to 2002 tax reports. The center still operates largely on donations from individuals and pharmaceutical companies, but has received additional funding in 2004 from the Georgia Cancer Coalition, a state agency that allocates tobacco-settlement and cancer-awareness funds.

McDonald received a one-time grant earlier this year of $55,000 from the coalition. The coalition had already agreed to fund the work of two other researchers in its "Distinguished Cancer Clinicians and Scientists Program." Erin Dickerson will receive $250,000 for her research at the institute through 2009 and Nathan Bowen will receive $200,000 in funding from the coalition through 2006.

Benigno, a surgeon who practices primarily at Northside Hospital, sends surgical specimens to the institute's labs so they can be tested and entered into a database. The lab has tested nearly 350 real and suspected ovarian cancer tumors. Benigno said he needs as many as 1,000 to qualify for federal funding from the National Institutes of Health, but the equipment and testing is expensive. He receives no compensation for his part, and has donated his own money to keep the institute afloat.

The program will also benefit from its new location. Georgia Tech will hire more than 20 new full-time researchers in the biology department, many of whom will work within the institute.

Sentinel Against Ovarian Cancer
Basic research on the organic molecule LPA could lead to new diagnostic tools and drugs to treat ovarian cancer.
Jane M. Sanders

One member of a family of fat-like molecules called lysophospholipids strongly promotes ovarian and uterine cancer tumor cell growth and metastasis. This compound ?called lysophophatidic acid, or LPA ? is being studied by researchers at Georgia Tech.

Its role is important to scientists searching for an early detection marker and new drugs to treat the often-lethal ovarian cancer, which has few or no symptoms in its early stage.

The Georgia Cancer Coalition is funding Harish Radhakrishna, an assistant professor of biology who began a one-year pilot study on LPA last year, to gather more data on his recent findings.
Radhakrishna's investigation was prompted by a 1999 Cleveland Clinic study comparing LPA levels in the blood and body cavity fluid of ovarian cancer patients at varying stages of the disease. Researchers found that, at all stages of the cancer, patients had elevated levels of LPA compared to healthy individuals. They further discovered that LPA stimulates growth and metastasis of various tumor cell types, including lung, breast, prostate and ovarian.

?Although LPA has a normal physiological function, such as stimulating the contraction of muscles and participating in normal cell growth, cancer cells often subvert that good role,? Radhakrishna explains.
His team's investigation narrowed when Radhakrishna and his Ph.D. student Mandi Murph found that application of LPA to breast and lung cancer cells greatly diminished the activity of a critical ?sentinel? protein, p53, which is mutated in half of all human cancers.

?This is important because all cells have several ?guard posts' set up to ensure that only normal cells can divide,? Radhakrishna explains. ?The p53 protein is one of the most important ?sentinels' in normal cells; it makes sure the cell does not divide if its DNA is damaged.?

If the DNA in a cell is damaged, p53 stops the cell from dividing and triggers a pathway to fix the damage and then lets the cell continue to divide. But if the DNA is damaged beyond repair, p53 triggers the destruction of the cell through a process called programmed cell death or apoptosis.

?If you're a cancer cell, your goal is to bypass these normal ?checkpoints' so that you can divide uncontrollably. One of the best ways to do this is to mutate and inactivate p53. Our finding that LPA decreases p53 function suggests that perhaps this is one of the ways that LPA enhances cancer cell proliferation,? Radhakrishna adds.

For the pharmaceutical industry, this process could be a target for development of an anti-cancer drug, Radhakrishna says. So he and Murph are studying how the LPA signal gets from the receptor at the cell surface to the point of inactivating p53. They have found that LPA enhances the destruction of p53 and are now focusing on the steps it takes to accomplish that task in breast, lung and ovarian cancer cells.

Contact Harish Radhakrishna at 404-385-1312 or harish.radhakrishna@biology.gatech.edu.

Catching Cancer Before it Spreads
Georgia scientists pursue early-stage diagnostic test for ovarian cancer.
Jane M. Sanders

On a quest to develop an early-stage diagnostic test for ovarian cancer is a ?virtual? research institute of Georgia-based academic experts in molecular biology, biochemistry and bioinformatics.

Led by John McDonald, a former University of Georgia professor of genetics who became chairman of the Georgia Tech School of Biology in July 2004, the researchers are studying the same tissue samples from ovarian cancer patients and are comparing their results with each other and with patient data files.
Studying the same tissue samples ? obtained from the non-profit, Atlanta-based Ovarian Cancer Institute (OCI) -- gives the group a distinctive insight, says McDonald. He is the chief scientific officer for OCI, which was founded in 2001 by noted gynecologist Benedict Benigno of the Southeastern Gynecologic Oncology Group.

?We're beginning to establish some correlations now,? McDonald notes. ?We're providing the biologists with high-quality tissue to analyze. They are comparing results, and we hope within a year to see some significant outcomes.?

Ovarian cancer causes almost no symptoms in the early stages and is often misdiagnosed when symptoms ? such as weight gain and digestive problems ? occur. When symptoms become severe, the cancer has usually progressed to Stage 3 and has spread to surrounding organs. The five-year survival rate at that point is only 25 percent. But if caught before it spreads, the survival rate jumps to 95 percent.

Researchers working under the auspices of OCI are funded by various organizations, including the Georgia Cancer Coalition and the National Institutes of Health. McDonald brings funding to ovarian cancer research on several fronts.

First, OCI researchers are exploring the possibility that every type of tissue contains adult stem cells that regenerate damaged tissue. Some evidence exists that these cells are present in ovarian tissue.
?It is possible that malignant cells may be derived from aberrant adult stem cells and not epithelial cells, which are observed when you examine tumors,? McDonald explains. ?If this is true, it's important because chemotherapy is often used to reduce the size of tumors ? some as large as 25 pounds ? before surgery. Chemotherapy kills epithelial cells and is effective, but tumors often recur.

?One hypothesis we're pursuing is that stem cells are not affected by chemotherapy and that they are regenerating more cancer cells after the chemo,? he adds. ?So we want to isolate and characterize the stem cells and then determine their response to chemotherapy. Then perhaps we can design a therapy to inhibit the stem cells.?

In a related research effort, McDonald and his team are using molecular technologies, such as microarray analyses, to create molecular profiles of tumors. This information would assist pathologists as they identify ovarian cancer subtypes and assign a stage to a tumor.

?We hope to find a molecular profile of ovarian cancers and identify subtypes,? McDonald adds. ?Different subtypes may respond differently to chemotherapy. So it's a more refined approach. We already have good preliminary data on this.?

May 17-23, 2002
ATLANTA BUSINESS CHRONICLE

HEALTH-CARE HEROES
"QUICK RESPONSE EASES A HALLOWEEN NIGHTMARE"
By Tom Barry
Contributing Writer

For 19-year-old MariClaire Corica and her parents, this past Halloween was real-life nightmare that mercifully had a happy ending, thanks to Dr. Benedict Benigno, founder of the Ovarian Cancer Institute in Atlanta.

A student at the Savannah College of Art and Design, Corica was at a Halloween party at her parent's home in Marietta when she experienced a sharp stomach cramp.

"We were afraid her appendix was about to burst, so we rushed her to Northside Hospital," said her father, Vince.

But it wasn't appendicitis. Tests were run. And still more tests. The hospital called in Benigno, who diagnosed a rare form of ovarian cancer that strikes young women. The stabbing pains indicated that a tumor was about to burst.

Fortunately, the diagnosis came in time. The surgeon removed a two-pound tumor and one ovary, but left the other intact, meaning MariClaire Corica still will be able to bear children.

Corica's father has no doubt that Benigno's diagnosis, as tense minutes ticked away, saved his daughter's life.

It's a parent's nightmare when a child has surgery, and that nightmare is multiplied when cancer is involved," said Vince Corica, an employee of Equifax Inc. whose nomination led to the naming of Benigno as the winner in the Health-Care Innovations category of Atlanta Business Chronicle's Health-Care Heroes Awards.

Through his practice and his work with the institute which he founded, Benigno battles a deadly, fast-growing cancer that strikes 30,000 American women a year. Most victims are 45 years of age and older.

Although symptoms eventually include swelling and cramping, ovarian cancer defies early detection. No effective screening test exists. By the time pain occurs, ovarian cancer has spread. Fatality rates are 65 percent to 70 percent

A surgeon who heads the six-physician Southeastern Gynecologic Oncology, Benigno is working with Dr. John McDonald, head of genetics at the University of Georgia, to develop a screening test and treatments.

"Dr. Benigno is an outstanding surgeon who's also very interested in the genetic basis of cancer," McDonald said. "It's unique to have a clinician who can communicate so well with researchers. He's always up here learning more about what we're doing."

A native of New York City, Benigno is a former chief of pelvic surgery at Emory University and taught in the medical school there. He now serves as director of gynecologic oncology at Northside Hospital.

At 63, Benigno often goes before women's groups to discuss ovarian cancer and is writing a book on the topic. In 1999, Benigno founded the Ovarian Cancer Institute, which is devoted to research, education and empowering women to demand appropriate diagnostic tests.

An intown resident, Benigno enjoys literature and poetry. He wife, Sheila, is a noted portrait artist. They have three children, ranging in age from 12 to 26.

"He's a true Renaissance man who's as comfortable discussing art and music as he is talking about DNA and surgical procedures," McDonald said.

The piano is another pursuit. "I play badly, but I have a superb teacher," he said with a laugh. "She listens to me because I pay her."

Vince Corica and his wife, DeLynn, always will be grateful that Benigno's quick reading of a dire and potentially fatal situation had a maestro's touch.

"He's a brilliant man," Corica said. "We needed a speedy diagnosis, and got it."

April, 2002
BUSINESS TO BUSINESS
"STALKING THE SILENT KILLER"
An Atlanta non-profit is making major advances in the quest for an early ovarian cancer screening test.
By Michelle M. Havich mhavich@btobmagazine.com

By the end of this year, approximately 27,000 women in the United States will be diagnosed with ovarian cancer. Of those, almost half will die. That chilling statistic has been the same for 25 years. The Atlanta-based Ovarian Cancer Institute (OCI) is fighting to change those odds.

Discouraged by this lack of progress in ovarian cancer research, Dr. Benedict Benigno founded the OCI in 1999 as a not-for-profit organization dedicated to finding an early diagnostic test for ovarian cancer. Benigno is a gynecologic oncologist who has practiced in Atlanta for more than 25 years.

"It occurred to me," says Benigno, "that if I could have access to a basic science laboratory where we could study the molecular genetics and the proteomics of tissue and blood samples from our patients, then we would have a truly extraordinary base from which we could search for a true screening test for ovarian cancer."

As of now, there is no screening test for ovarian cancer. OCI's goal is to develop a blood test to detect the cancer that would be a part of a woman's annual gynecological exam. With the proper funding and support, Benigno predicts they could have a test within two years.

Executive Director Anne Morgan says OCI's mission statement is three-fold. "It's 70 percent research, 15 percent education and 15 percent community outreach. The two parts of the research are finding an early diagnostic test and improving treatments for the disease as well," she says.

On the testing side, OCI has a formal liaison with the molecular genetics division of the University of Georgia, which is chaired by Dr. John McDonald, an international authority on retroviruses. OCI recently purchased a state-of-the-art microarray analyzer, which is in the lab at UGA. "The Ferrari of the molecular genetics laboratory," Benigno calls it.

To test samples with the analyzer, a small tissue sample is removed from a patient here in Atlanta and the RNA is extracted from it. A small amount of serum from the patient's blood is also taken and frozen. The RNA from the sample is converted to DNA and put on a microchip about the size of a thumbnail, then transferred to UGA's molecular genetics laboratory, where the microarray analyzer reads out in quadruplicate all 37,000 genes that make up a patient's cancer. Certain patterns are observed that indicate the abnormal expression of certain genes.

If there is an abnormality, the blood sample is thawed and tested for a marker that may indicate the presence of the abnormal expression from the tissue sample. The presence of these markers will enable the OCI to develop a blood test that can be used as an early diagnostic test for ovarian cancer.

"We are testing three types of cancers - colon, ovarian and breast - to see that it's specific for ovarian cancer," Benigno says.

A Pap smear, traditionally the test for cervical cancer, cannot detect ovarian cancer. In fact, relying on the results of this test could be dangerous.

"In my entire career, an abnormal Pap smear has directed me to the diagnosis of cancer of the ovaries in only six patients," Benigno says. "It lulls the woman into a false sense of security. They'll think, 'If my Pap smear is normal then I can't have cancer,' and nothing could be further from the truth."

Because it is so difficult to detect, Benigno estimates that it takes women six months to come to him because the few symptoms for ovarian cancer that do present themselves are not localized in the pelvic area. Most often, a woman will have a swollen abdomen and cramping and be diagnosed with a GI problem. "That is probably why, in over 70 percent of patients, the cancer is metastatic beyond the pelvis when the (ovarian cancer) diagnosis is first made," he says. OCI is sponsoring seminars, symposia and lectures for physicians on all aspects of ovarian cancer, especially early detection.

The symptoms for ovarian cancer are vague but should not be ignored:

Gastrointestinal complaints that are persistent and unexplained;
Pelvic and/or abdominal swelling and/or pain; feeling of fullness or bloating;
Unexplained change in bowel habits;
Unexplained weight gain or loss;
Frequency and/or urgency of urination;
New unexplained abnormal postmenopausal bleeding.

Women with one or two blood relatives who have had ovarian cancer are at a higher risk, as well as women having the presence of BRCA1 or BRCA2 gene mutations, which are common in women of Ashkenazi (Eastern European)/Jewish decent.

Treatments for ovarian cancer now almost always start with surgery to remove the cancerous tissues. Then comes chemotherapy every three weeks. These drugs cause a decrease in the bone marrow's ability to produce white and red blood cells and platelets. Hair loss and nausea are common. After six courses of chemotherapy, patients have a laparoscopy, where a small telescope is inserted through the umbilicus (navel) to make sure all of the cancer is gone. After that, varying methods are used to give the patient the best chance of it never coming back, including radiation treatments.

On the treatment side, OCI soon is going to be using the mouse laboratory at UGA. Small tissue samples removed in the operating room will be grafted onto the abdomen of mice whose immune systems have been tampered with so as not to reject the sample.

After that, Benigno says, the mice will be treated every three weeks with the same chemotherapeutic agents that are given to the actual patients every three weeks, and "hopefully be able to use this model as a base for experimenting with the new genetic drugs. It's the best of both worlds. We can experiment on the patient's cancers without experimenting on the living patient."

There is one gigantic possible roadblock to OCI's ultimate goal - all of this research and testing doesn't come cheap, and OCI is not-for-profit. Morgan says, "We will always be dependent on contribution income. We have no source of earned revenue." The long-term goal of OCI is to be self-sufficient by its third year.
St. Joseph's Hospital has been the biggest help in setting up OCI. The organization is currently housed on the hospital's campus near I-285.

"They have been extremely generous with getting us off the ground, helping us out with the laboratory and with certain salary support. The OCI could not have been created without them," Benigno says.

A large chunk of money went to purchase the microarray analyzer for $208,000. "They don't exactly give those things away," Benigno says. The microchips used with the machine cost $1,000 each.

OCI has grant applications out to many foundations and it received a $100,000 outright gift from an Atlanta citizen. plus, it receives numerous gifts from patients who have undergone successful cancer surgery and treatment. Benigno and McDonald met recently with Emory University and representatives from the governor's office to apply for the state's cancer research money.

"Hopefully by the middle of the summer, we will be in a position to apply for federal funding from the NIH (National Institutes of Health) and that will change our financial picture considerably," Morgan says. "The trick is you can't seek federal grants until you have some kind of track record, written a paper, and have some data upon which you can base a federal request. And that could be a sizable amount of money."

OCI is working with the Georgia Cancer Coalition in order to be one of the recipients of their resources. It currently is in the middle of preparing a funding request to the coalition to bring a scientist from Johns Hopkins University to work with OCI.

OCI also is collaborating with the Medical College of Georgia, Emory University, Georgia Tech and any other organization doing similar research.

"The edge we have is the number of patients that Dr. Benigno and his colleagues see with ovarian cancer," Morgan says. "This creates one of the largest tissue banks in the country, and obviously, when you are doing research, the more studies you can do the more valid your work is. There aren't many institutions around that have access to the large tissue bank that we have."

Benigno currently has about 70 tissue samples, mostly from his patients, but with the cooperation of his five partners, The plans to have as many as 200 before long.

"We're also trying to get borderline tumors, midway between cancer and not cancer," he says. "That's where we expect to find the earliest change, which would be of the most help in finding a screening procedure."

OCI has protocols in place to do tissue extractions at numerous hospitals around Atlanta, including Northside Hospital, St. Joseph's, Piedmont Hospital, DeKalb and Southern Regional.

"There is the annual meeting of the Georgia State Obstetrical and Gynecological Society, and I gave a lecture there, and I'll be giving another lecture in September. That's where I generate a great deal of interest and willingness to participate from physicians all over the state," Benigno says.

According to Benigno, the reason ovarian cancer statistics haven't changed in 25 years and the disease has not received the attention of breast cancer is that it's not as common a cancer. "One in 11 American women will get breast cancer and 25-30,000 women each year will get cancer of the ovary," he says. "It's not as common, but people need to realize that it's far more devastating because it's so unlikely to be caught early."