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Stanford-Led Team Makes Strides Toward Better Endometriosis Diagnosis, Treatment.



News Editors/Health/Medical Writers

STANFORD, Calif.--(BUSINESS WIRE)--June 16, 2003

A Stanford-led team of researchers has opened the way to a new approach for diagnosing and treating endometriosis endometriosis (ĕn'dəmē'trē-ō`sĭs), a condition in which small pieces of the endometrium (the lining of the uterus) migrate to other places in the pelvic area. . The study, in the July issue of Endocrinology, used microarray technology to identify genes likely to contribute to the disease, which affects 10 to 15 percent of women of reproductive age and 35 to 50 percent of women with infertility.

"This new information has great potential to improve diagnosis of endometriosis," said senior author Linda Giudice, M.D., Ph.D., professor of obstetrics and gynecology obstetrics and gynecology

Medical and surgical specialty concerned with the management of pregnancy and childbirth and with the health of the female reproductive system.
 at the Stanford School of Medicine. "The findings suggest targets for new drugs that could minimize the disease," added Giudice, who directs the division of reproductive endocrinology and infertility Reproductive endocrinology and infertility is a subspecialty of the specialty of obstetrics and gynecology dealing with infertility, fertility, contraception and the medicine and surgical procedures related to it.  at the school. Stanford researcher Lee Kao, M.D., Ph.D., led the study, collaborating with Giudice and others at Stanford along with researchers from the University of California-San Francisco, Vanderbilt University and the University of North Carolina-Chapel Hill.

In endometriosis, endometrium endometrium /en·do·me·tri·um/ (-me´tre-um) pl. endome´tria   the mucous membrane lining the uterus.

en·do·me·tri·um
n. pl.
 tissue normally found lining the uterus grows elsewhere, spreading to other areas within a woman's pelvic cavity pelvic cavity
n.
The space bounded by the bones of the pelvis and pelvic girdle.
 and abdomen -- usually the fallopian tubes Fallopian tubes
The narrow ducts leading from a woman's ovaries to the uterus. After an egg is released from the ovary during ovulation, fertilization (the union of sperm and egg) normally occurs in the fallopian tubes.
, ovaries Ovaries
The female sex organs that make eggs and female hormones.

Mentioned in: Choriocarcinoma

ovaries (ō´v
 and intestines. While some women with endometriosis have no symptoms, many experience pelvic pain and severe menstrual cramps menstrual cramps Spasmodic dysmenorrhea Gynecology Painful cramps, spasms, lower abdominal discomfort, generally occurring on the first day of the menstrual period; the pain may extend to the low back, thighs, pelvis, and be accompanied by N&V, dizziness, .

Diagnosing endometriosis usually involves surgery and general anesthesia Anesthesia, General Definition

General anesthesia is the induction of a state of unconsciousness with the absence of pain sensation over the entire body, through the administration of anesthetic drugs.
; treatment typically involves surgical removal of tissue or medication. Both routes pose problems. The condition often relapses after surgery and the medications have undesirable side effects and are sometimes ineffective.

In the study, researchers collected biopsies of endometrium from 15 volunteers, eight with endometriosis and seven without, during the several-day window in a menstrual cycle when a fertile woman's uterus is receptive to an embryo's implantation. Their goal was to uncover differences in gene expression in the two groups of women.

The scientists used a microarray, also known as a gene chip, to simultaneously screen 12,868 genes -- about a third of the predicted number in the human genome. Each gene tells the body how to make RNA RNA: see nucleic acid.
RNA
 in full ribonucleic acid

One of the two main types of nucleic acid (the other being DNA), which functions in cellular protein synthesis in all living cells and replaces DNA as the carrier of genetic
, which in turn makes one or more specific proteins, a process called gene expression. Proteins then carry out specific activities in the body's cells.

The screening revealed 91 genes that had more than a twofold increase in gene expression in women with endometriosis compared to those without the disease, and 115 genes that had more than a twofold decrease.

The researchers next zeroed in on genes that seem especially relevant to endometriosis-related infertility. To do this, they combined their new findings with findings from their earlier study, which used microarray screening to compare gene expression in fertile women during their receptive and non-receptive periods.

Analyzing these findings together revealed 12 genes of particular interest for endometriosis-related infertility. Eight sparked interest because their expression increased during the window of implantation in women without endometriosis but decreased at that time in women with the disease. Three other genes were noteworthy for the opposite reason: their expression decreased in healthy women but increased in women with endometriosis. Another gene, which decreased expression during the window of implantation in healthy women, decreased further in women with the disease.

"These genes are likely to have a role in the development of the disease and its related implantation failure," said Kao. The identified genes make proteins involved in important cellular processes, including embryo attachment, embryo toxicity, immune function, programmed cell death pro·grammed cell death
n.
See apoptosis.



programmed cell death

proposed system of cell death, often including poly(ADP)-ribosylation, ensures that a cell will not survive if it is so badly damaged that its recovery would harm the
, sex hormone regulation and blood vessel development.

Next, the researchers plan to validate their findings and follow new leads. "These are exciting findings and they can potentially lead to new tools for diagnosis and treatment of endometriosis and infertility. This is brand new information," said Kao.

One of the first projects will be to test a microarray designed for diagnosing endometriosis, which could make diagnosis a less-invasive, less-expansive process. Diagnosis with a chip would rely on just a blood test or a biopsy; while it remains unclear which technique would be better, either would represent an improvement over the current method of surgery under general anesthesia. "We have put a diagnostic chip together conceptually and hope to have it made soon," said Giudice, adding that the consortium plans to test the chip's reliability. She estimates it will be available for widespread use in a few years if testing goes well.

More information about endometriosis is available from the government publication Endometriosis, at http://www.nichd.nih.gov/publications/pubs/endometriosis.pdf. For additional information, contact the Endometriosis Association, 8585 North 76th Place, Milwaukee, WI 53223; 414/355-2200; http://www.EndometriosisAssn.org/.

This research was funded by the National Institutes of Health; the National Institute for Child Health and Human Development; the NIH Office of Women's Health Research; the NIH Women's Reproductive Health Research Career Development Program; the German Research Foundation; and the Endometriosis Association.

Stanford University Medical Center Stanford University Medical Center (Stanford Hospital & Clinics) is one of four hospitals affiliated with Stanford University and Stanford University School of Medicine, along with the Lucile Packard Children's Hospital, the Veteran's Administration Hospital in Palo Alto, and Santa  integrates research, medical education and patient care at its three institutions -- Stanford University School of Medicine Stanford University School of Medicine is affiliated with Stanford University and is located at Stanford University Medical Center in Stanford, California, adjacent to Palo Alto and Menlo Park. , Stanford Hospital & Clinics and Lucile Packard Children's Hospital Lucile Packard Children's Hospital (LPCH) is a hospital located on the Stanford University campus in Palo Alto, California. It is staffed by over 650 physicians and 4,750 staff and volunteers.  at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
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