Online Medicine

Flu Central: Everything you need to know about H1N1 and seasonal flu

Dipali Pathak
713-798-4710
loriw@bcm.edu

HOUSTON -- (Oct. 16, 2009) -- Dr. Paul Glezen answers questions about the H1N1 vaccine and the virus. The questions fall into six categories: general, symptoms and care, high risk factors, the virus itself, prevention, and the vaccine. You may also read a text version of this Q&A.

General

Dr. Paul Glezen answers general questions. This content requires the Adobe Flash Player. Get Flash

Symptoms and Care

Dr. Paul Glezen answers questions about symptoms and care. This content requires the Adobe Flash Player. Get Flash

High Risk Factors

Dr. Paul Glezen answers questions about high risk factors. This content requires the Adobe Flash Player. Get Flash

The Virus Itself

Dr. Paul Glezen answers questions about the H1N1 virus. This content requires the Adobe Flash Player. Get Flash

Prevention

Dr. Paul Glezen answers questions about flu prevention. This content requires the Adobe Flash Player. Get Flash

The Vaccine

Dr. Paul Glezen answers questions about the H1N1 vaccine. This content requires the Adobe Flash Player. Get Flash

Do you have additional questions? Let us hear from you.

HOUSTON -- (October 15, 2009) -- More women are surviving breast cancer as a result of improvements in early detection methods and more effective, targeted treatment, say experts at Baylor College of Medicine.

"We continue to make great strides in research and patient care," said Dr. Heather West, assistant professor in the Lester and Sue Smith Breast Center at Baylor College of Medicine. "Survival rates have greatly improved the past 10 years."

Early detection

Early detection remains key to survival, West said. Advancements have improved doctors' ability to catch the tumors when they are at a curable stage.

"Yearly screening mammograms have shown to be most effective in women from age 50 to 70," said West. "However, it is recommended that all women begin them at age 40."

Patients with a family history of breast cancer are at a higher risk and should begin screening at age 35, West said.

"Mammograms are not as sensitive in younger women because most have dense breast tissue," West said. "In younger women, we use ultrasounds. Breast magnetic resonance imaging, or MRI, is useful in selected high-risk populations."

Research advancements

Advancements in genetic research have enabled clinicians to evaluate which treatments may work better for a certain patient.

"Now we can look at how the tumors change at the molecular and genetic level with treatment," said West. "This helps clinicians determine how patients may respond to different treatments, and it rationally guides them on the development of new treatment targets."

Common approaches

The most common approaches to breast cancer treatment include:

• For hormone-sensitive tumors (estrogen-receptor positive and progesterone-receptor positive), Tamoxifen (premenopausal) and the newer aromatase inhibitors (postmenopausal)
• For patients with HER-2 gene amplification, anti-HER-2 antibodies (Trastuzumab) in combination with chemotherapy
• For patients that have no hormone sensitivity or HER-2 amplification, or triple negative tumors, chemotherapy

Researchers are currently investigating new agents to treat triple-negative tumors, which are a rare, aggressive subtype of cancer that affects approximately 15 percent of all breast cancer patients.

Some of the most promising research announced in the last year focuses on PARP, or Poly (ADP-ribose) polymerase, inhibitors, which have been shown to be effective in this subtype of breast cancer, West said.

"In certain types of cancer, there is a defect in DNA repair pathways and mutations develop," said West. "PARP is an enzyme involved with DNA damage repair. PARP inhibitors actually impair the tumor's ability to repair damage, thus killing tumors more effectively."

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HOUSTON -- (October 9, 2009) -- A new investigational treatment for breast cancer -- called PARP inhibitors -- holds promise for patients who suffer from triple negative breast cancer, a rare, aggressive form of the disease, said a breast cancer specialist at Baylor College of Medicine.

"This is the most exciting new therapy for triple negative breast cancer and has the potential to work in other types of breast cancer," said Dr. C. Kent Osborne, director of both the NCI-designated Dan L. Duncan Cancer Center and Lester and Sue Smith Breast Center at BCM. "Until now, we have only had chemotherapy available as a treatment for these patients."

PARP hypothesis

Breast Cancer Awareness Month is an opportunity to celebrate the strides that have been made in the identification and treatment of breast cancer. Baylor College of Medicine shares its latest research results and promotes an online program that helps low-health literacy breast cancer patients make informed decisions.

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PARP is an enzyme involved in DNA repair, Osborne said. DNA repair helps the body restore damage caused by genetic mutations that often lead to cancer.

"When there is a defect in one of the DNA repair pathways, our bodies cannot repair damage and mutations develop," said Osborne.

Patients who have mutations in the BRCA1 gene (a common mutation in patients with hereditary breast cancer) are predisposed to DNA damage. Some patients with triple negative breast cancers have tumors similar to BRCA1 – mutant tumors and also have a defect in DNA repair.

PARP inhibitors take advantage of this weakness or inability to repair DNA properly, Osborne said.

"The hypothesis is that if a cancer cell has a defect in one of the four or five DNA repair pathways and if we block one of the other gene pathways, it would be so overwhelming to the cancer cell that it would die," said Osborne. "Previous studies in cell cultures have shown that cancer cells with a defect in one DNA repair pathway die when treated with a PARP inhibitor that blocks a second pathway while normal cells survive."

Survival rates increased

In early human trials involving patients with this subtype, Osborne said, PARP inhibitors had outstanding results. The patients had cancer that spread to other parts of the body and did not respond to multiple other treatments.

"When PARP inhibitors were used in combination with chemotherapy, patients had a doubling in survival rates. Average survival was five months with chemo alone," said Osborne. "With PARP inhibitors and chemotherapy, average survival was nine months. This is a dramatic result when you consider that the patients in the study had tumors that were resistant to all available drugs."

Future studies will focus on using PARP inhibitors in early breast cancer patients.

Targeting pathways

Triple negative breast cancer accounts for 15 percent of all breast cancer cases that occur each year. These patients have tumors that are neither progesterone-receptor positive, estrogen-receptor positive nor HER-2 positive.

The Smith Breast Center received a grant last year to study the DNA of triple negative tumors to identify the proteins that stimulate tumor growth.

"We really do not know the genetic pathways that are causing this kind of cancer to grow and develop," said Osborne. "To develop new treatments that target these pathways, we need a greater understanding of the genetic makeup of these tumors."

Researchers with the Smith Breast Center are trying to develop a gene signature in a tumor sample that would tell which triple negative tumors have defective DNA repair and would likely respond to PARP inhibitors and specific types of chemotherapy, Osborne said.

For more information about clinical trials with PARP inhibitors, visit http://clinicaltrials.gov/.

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HOUSTON -- (October 9, 2009) -- An online program called The Patchwork of Life is helping newly-diagnosed breast cancer patients who have limited understanding of health issues make an informed decision about their surgical treatment by guiding them from diagnosis through after treatment.

The easy-to-understand program provides the information through stories of fictional women going through the same process, helping the real-life women better understand the implications of their decision, said Dr. Maria Jibaja-Weiss, director of the Office of Outreach and Health Disparities in the NCI-designated Dan L. Duncan Cancer Center at Baylor College of Medicine. Segments of the storyline are linked to relevant learning modules.

"A woman facing decisions about her breast cancer surgery will have to analyze many new concepts and interpret a lot of different, hard-to-understand information," said Jibaja-Weiss. "We have developed a tool that is easy to navigate and provides the information to these patients in a realistic, understandable format that helps them make an informed decision."

Four common themes

Breast cancer patients can choose from a variety of characters and then view short stories beginning from diagnosis to after treatment.

There are four common themes to the stories, including providing background on breast cancer, addressing common misconceptions about diagnosis and treatment, providing information about treatments and their outcomes, and walking patients through the steps of making a surgery decision.

For some patients, misinformation and misconceptions may cause them not to seek treatment, said Jibaja-Weiss, thus it is important that they be addressed.

Different scenerios, different outcomes

Ultimately, there may be two surgical options that a patient diagnosed with early stage breast cancer may undergo, Jibaja-Weiss said – the removal of the tumor-containing breast lump (lumpectomy or breasts conserving surgery) or the removal of one or both breasts (mastectomy).

"There are very different medical outcomes associated with each option," Jibaja-Weiss said. "All women must be properly informed so they can discuss this important decision with their doctors."

Program available in English, Spanish

Developed by a multidisciplinary group of breast cancer specialists, surgeons and educators, the program can be viewed in both English and Spanish.

During the program, a narrator reads the information aloud to help women with limited reading capabilities, Jibaja-Weiss said.

There are visual descriptions and question-and-answer sections that allow the patients to interact while watching each story.

"The text is minimal and easy to read," said Jibaja-Weiss. "The stories and scenarios with family members, friends and physicians provide a sensible format for these women to comprehend and learn."

Easy to use computer format

Novice computer users have found the tool easy to navigate, Jibaja-Weiss said.

"They simply click 'next' on each page to go from one screen to the next," said Jibaja-Weiss. "For those who would rather skip around the program, a menu panel is available for exploring the various sections."

The program is updated as new treatment guidelines and practices are adopted, Jibaja-Weiss said.

"This tool has given hope to a lot of women who initially thought of giving up," said Jibaja-Weiss. "Following these stories and adapting the information has allowed them to connect and decide what course is best for them. They have watched these women make decisions and live to see the consequences, and they draw strength from knowing they can too."

In 2008, the program received a silver award from the Web Health Awards, a program that recognizes outstanding web-based health-related content for consumers and professionals.

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HOUSTON -- (October 9, 2009) -- A factor called eIF3 (eukaryotic initiation factor 3) critical to the translation of a gene's message into a protein is in fact only part of a large protein complex called the "translasome" because it contains all the proteins needed to regulate protein synthesis and protein degradation, said a Baylor College of Medicine expert.

"In the broader context, eIF3 may play a role in the control of breast cancer," said Dr. Eric Chang, associate professor of molecular and cellular biology at BCM and a member of the Lester and Sue Smith Breast Center. In mice, the gene encoding one of its subunits, eIF3e/Int6, is the site at which a mouse mammary tumor virus inserts itself to promote the cancer process. In human breast tumors, the expression of the INT6/EIF3E gene is also frequently down regulated, leading to low levels of its protein product in the cell.

Components of protein synthesis

In experiments designed to elucidate eIF3's molecular function, Chang and colleagues from the Burnham Institute for Medical Research in LaJolla, Calif., and the Israel Institute of Technology in Haifa isolated the molecule from yeast cells to look at all the proteins that interact with it. A report on their work appears in the current issue of the journal Molecular Cell.

"We found almost all the proteins needed for protein synthesis form a supercomplex, which we called the translasome," said Chang. "This suggests that all the components of protein synthesis need to be physically linked to work efficiently.

"We also found that the proteins needed to degrade proteins, called proteasomes, also form a complex with those needed to make proteins, a fact that seems counterintuitive," he said.

Not always simple process

However, protein synthesis in the cell is not always a simple or clean process.

"As with any job we might do, a lot of things do not pass quality control. The degradation machinery gives the cells the ability to correct many mistakes. When they can't, they send them to the proteasome to for degradation," said Chang.

The formation of the translasome supercomplex links the making of proteins closely to the disposal process in which the proteasome looks for misfolded or abnormal proteins and removes.

"It's as though the garbage can is right next to the assembly line," said Chang.

In fact, the translasome spatially coordinates steps in the synthesis of proteins, making it more efficient, said Chang and his colleagues in their report. Adding the degradation machinery insures the proteins are made correctly. Those that are not are degraded and discarded.

Activity in nucleus

Protein synthesis is thought to take place in the outer compartment of the cell, called the cytoplasm, as opposed to the nucleus in the center of the cell. However, in this study, they found that the translasome contains proteins that were thought to exist only in the nucleus. Furthermore, the translasome contains proteins whose function is to shuttle proteins into the nucleus. They also found that eIF3 can interact with these import proteins to control nuclear import of proteasomes. If translation proteins go into the nucleus together with proteasomes, this would raise the intriguing possibility that protein synthesis can also occur in the nucleus.

Others who took part in this research include Zhe Sha and Rodrigo Cabrera of BCM, Laurence Brill, Judith S. Scheliga and Dieter A. Wolf of the Burnham Institute for Medical Research in LaJolla, Calif., and Oded Kleifeld and Michael H. Glickman of the Israel Institute of Technology in Haifa.

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