breast cancer prevention

Malaria drug may prevent Zika virus from infecting fetus

Studying pregnant mice, researchers at Washington University School of Medicine in St. Louis found that Zika virus manipulates the body's normal barrier to infection, and that hydroxychloroquine, a malaria drug related to chloroquine, interferes with this process, protecting the fetus from viral infection.Zika virus infects the fetus by manipulating the body’s normal barrier to infection, according to a new study of pregnant mice. Moreover, the study showed that a drug that interferes with this process protects the fetus from viral infection. That drug is already approved for use in pregnant women for other medical purposes.
Devastating consequences of Zika virus infection are suffered in the womb, where the virus can cause brain damage and sometimes death.

Studying pregnant mice, researchers at Washington University School of Medicine in St. Louis have learned that the Zika virus infects the fetus by manipulating the body’s normal barrier to infection. Moreover, they showed that a malaria drug that interferes with this process protects the fetus from viral infection. That drug already is approved for use in pregnant women for other medical purposes.

“We found that the malaria drug hydroxychloroquine effectively blocks viral transmission to the fetus,” said senior author Indira Mysorekar, PhD, an associate professor of obstetrics and gynecology, and of pathology and immunology. “This drug already is used in pregnant women to treat malaria, and we suggest that it warrants evaluation in primates and women to diminish the risks of Zika infection and disease in developing fetuses.”

The findings are published July 10 in The Journal of Experimental Medicine.

In late 2015, doctors in Brazil began to notice a surge in the number of babies born with microcephaly, or unusually small heads, an indicator of neurological damage. The epidemic soon was linked to the mosquito-borne Zika virus, which was spreading through the tropical parts of the Americas. Doctors advised pregnant women to avoid mosquito bites by wearing bug spray and long-sleeved clothing, but had little other advice to offer. There were, and still are, no drugs or vaccines approved for use in pregnant women to protect them or their fetuses from Zika infection.

The developing fetus is uniquely vulnerable to damage from infection, so the body mobilizes robust defenses to keep microbes from ever reaching the fetus in the first place. The placenta is the last line of defense. Mysorekar and others have shown that a process known as autophagy — the cellular waste-disposal pathway by which cells grind up debris, unwanted organelles and invading microbes — is an important part of the formidable placental barrier to infection. However, previous studies by Mysorekar and others have shown that Zika not only can invade the placenta, but multiply there.

To learn more about how Zika breaches the placenta, Mysorekar, postdoctoral fellow Bin Cao, PhD, and colleagues infected human placental cells with Zika virus. They found that exposure to the virus activated genes related to autophagy.

However, when the researchers treated the cells with drugs to ramp up the autophagy pathway, the number of cells infected with Zika virus increased. Drugs that suppressed autophagy resulted in fewer placental cells infected with Zika virus. In other words, the virus multiplied and spread more effectively when the researchers dialed up the barrier response, and performed more sluggishly when they dialed it down. The virus seemed to be doing a form of microbial martial arts, turning the body’s weapons to its own advantage.

Mysorekar and colleagues verified these findings using mice whose autophagy response was hobbled by low levels of a key autophagy protein. They infected two groups of pregnant mice with Zika: one in which the autophagy process was disrupted and the other in which it worked normally.

Five days after infection, the mothers with a weak autophagy response had about the same amount of virus in their bloodstreams as the mice with a normal response. However, in mice with a weak autophagy response, the researchers found 10 times fewer viruses in the placenta and the heads of the fetuses and less damage to the placentas.

“It appears that Zika virus takes advantage of the autophagy process in the placenta to promote its survival and infection of placental cells,” Cao said.

Since hydroxychloroquine suppresses the autophagy response, the researchers questioned whether it also could protect fetuses against Zika.

To find out, they repeated the mouse experiment using only mice with a normal autophagy response. Female mice at day nine of pregnancy were infected with Zika and then dosed with hydroxychloroquine or placebo every day for the next five days.

Following treatment, the researchers found significantly less virus in the fetuses and placentas from the mice that had received hydroxychloroquine. In addition, these placentas showed less damage and the fetuses regained normal growth. Both the untreated and the treated mothers had about the same amount of Zika virus in their bloodstreams, indicating that hydroxychloroquine was able to protect fetuses even when the virus was circulating through the mother.

Although hydroxychloroquine has been used safely in pregnant women for short periods of time, the researchers caution that further studies are needed before it can be used in pregnant women to fend off Zika. Pregnant women living in areas where Zika circulates may need to take the drug for the duration of their pregnancies, and the safety of hydroxychloroquine for long-term use is unknown.

“We would urge caution but nevertheless feel our study provides new avenues for feasible therapeutic interventions,” said Mysorekar, who is also co-director of the university’s Center for Reproductive Health Sciences. “Our study suggests that an autophagy-based therapeutic intervention against Zika may be warranted in pregnant women infected with Zika virus.”

The Women’s OB/GYN Medical Group strives to better the lives of all women with a holistic approach to women’s health. Call for an appointment today: (707) 579-1102. Visit our website: www.womensobgynmed.com


Story Source:

Materials provided by Washington University School of Medicine. Original written by Tamara Bhandari. Note: Content may be edited for style and length.


Journal Reference:

  1. Indira Mysorekar et al. Inhibition of autophagy limits vertical transmission of Zika virus in pregnant mice. The Journal of Experimental Medicine, July 2017 DOI: 10.1084/jem.20170957

Read this article on ScienceDaily: Washington University School of Medicine. “Malaria drug protects fetuses from Zika infection: Treatment prevents virus from crossing placenta to infect fetus, mouse study shows.” ScienceDaily. ScienceDaily, 10 July 2017. www.sciencedaily.com/releases/2017/07/170710091702.htm.

Recent Studies Underscore the Importance of Eating Healthy to Lower the Risk of Breast Cancer

The Women’s OB/GYN Medical Group of Santa Rosa discusses the results of two recent studies that help to empower women to make healthy food choices.

broccoli-1328937According to the latest national trends for women in the U.S., breast cancer death rates continue to be higher than those for any other cancer, except for lung cancer. About 1 in 8 women will develop invasive breast cancer over the course of a lifetime, and approximately 85 percent of those breast cancers will occur in women who have no family history of the disease. This is thought to occur due to genetic mutations as a result of the aging process combined unknown factors of life.

Statistics such as these only serve to demonstrate the importance of taking steps to reduce the risk of developing breast cancer in the first place. Two studies out this month help to provide important clues as to what women can do to improve the likelihood of long term breast health, namely eating healthy, and knowing what to eat.

The Correlation Between High Fiber Diet and Lower Breast Cancer Risk

Women who eat more high-fiber foods during adolescence and young adulthood may have a lower breast cancer risk than those who don’t eat as many fruits and vegetables when young, according to a new large-scale study led by researchers at Harvard T.H. Chan School of Public Health. Similar studies conducted recently have clearly demonstrated that breast tissue is highly susceptible to carcinogens, especially during childhood and adolescence. The study released just this month, helped to provide evidence that the types of foods children get during this period of life is also an important factor in a woman’s lifetime risk of developing cancer.

In another exciting study that correlates nutrition and breast cancer risk was conducted by researchers at Oregon State University (OSU) and the Oregon Health and Science University. This group was focused on the particular anti-cancer properties of sulforophane, a sulfur-containing compound found primarily in leafy green vegetables, including broccoli. Following up on previous evidence that seemed to show that sulforaphane might help prevent cancer the OSU research team also determined that sulforophane containing vegetables have the potential to actually slow breast cancer cell growth, especially at early stages.

The OSU group focused on broccoli but studies in the past have also established an association between a high intake of cruciferous vegetables, such as cauliflower, brussel sprouts, cabbage, broccoli, or kale and a decreased risk of breast cancer. Researchers speculated that eating more fiber-rich foods may also lessen breast cancer risk partly by helping to reduce high estrogen levels in the blood, which are strongly linked with breast cancer development.

The Big-Picture Approach to Breast Health

Lela Emad, MDThe Women’s OB/GYN Medical Group of Santa Rosa have long advocated to patients the importance of taking a dietary approach to maintaining overall health. “With studies like these we can only stress the importance of making lifestyle changes that support breast health,” says Dr. Lela Emad, MD. “A healthy approach to nutrition combined with routine breast exams and general awareness of how to maintain breast health are important elements in living a healthy lifestyle.”

Screening methods such as regular self-breast exams, breast checks during routine gynecologic exams, and screening mammographies can all help to detect breast problems early-on. Early treatment of breast problems can contribute to the success of any treatment that is needed.

Self-check breast exams are easy to perform at home and should be conducted monthly in addition to scheduling an annual breast exam with an OB/GYN healthcare provider. Depending on a woman’s age and individual health, a more frequent interval of regular check-ups may be recommended. “Self-care is important but we also recommend that patients who suspect a breast health problem contact a provider immediately,” added Dr. Emad.

About Women’s OBGYN Medical Group

The provider team of expert OB/GYN physicians, certified nurse midwives, family nurse practitioners, and medical assistants provides unmatched care to patients in our region. As women proudly serving women, we understand the needs and expectations of our patients. For more information, visit our website or call (707) 579-1102. We urge you to contact our office to schedule an appointment with one of our physicians if you suspect that you may have any breast health problems.