Preservation mission: UC graduate helps kids connect to nature
Wed, July 17, 2019
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Marlene Harris-Ride Cincinnati has continued its support of University of Cincinnati Cancer Institute scientists with the annual award of seven grants, totaling $200,000, to continue promising breast cancer research.
Ride Cincinnati, a cycling event for all ages and abilities, was founded in 2007 by Harvey Harris, DDS, his family and two friends in memory of his late wife, Marlene Harris.
Ride Cincinnati has contributed over $2 million directly to the university since August 2007. In addition, the Western & Southern Foundation has earmarked funds from its gifts to the UC Health Barrett Cancer Center to support the Ride Cincinnati annual cycling event.
In addition to the research projects (described below), a $20,000 grant will be awarded to the REDCap program within the UC Cancer Institute, to assist with breast cancer data collection.
Mechanism and pharmacological control of human ADP-ribosyl-acceptor hydrolase 3:
In-Kwon Kim, PhD, assistant professor of chemistry, McMicken College of Arts and Sciences; $35,000
About the study: A team led by Kim is hoping to discover ARH3 (ADP-ribosyl-acceptor hydrolase 3) inhibitors as a way to target and treat certain breast cancers. ARH3 is an enzyme that regulates poly(ADP-ribose) polymerases (PARPs), whose inhibition by small molecules has shown promise in selective killing of certain breast cancers. However, PARP inhibitors can cause drug resistance and harmful side effects in patients. Researchers in this study are aiming to develop safe and effective alternatives to PARP inhibitors by focusing on ARH3.
Mechanisms of mutant HER3 signaling and therapeutic potential in breast cancer:
Joan Garrett, PhD, assistant professor of pharmaceutical sciences, James L. Winkle College of Pharmacy; $35,000
About the study: HER3 mutations can be oncogenic in thousands of cancer patients. Researchers will investigate the molecular mechanisms by which mutant HER3 promotes breast cancer progression and identify the best treatment strategies for patients with HER3-mutant breast cancer. HER3 mutations occur in about 2.5 percent of all solid tumors; these findings could result in enhanced treatment strategies to improve outcomes for patients with HER3-mutant cancer.
Breast Papilloma: A unique opportunity to investigate risk factors and outcomes:
Benjamin Hinrichs, MD, assistant professor of pathology and laboratory medicine; Elizabeth Shaughnessy, MD, PhD, professor of surgery; Susan Pinney, PhD, professor of environmental health, all UC College of Medicine; $35,000
About the study: Using a combination of data in the UC Health Electronic Health Records and the Fernald Community Cohort, researchers in this study will look at breast papilloma risk factors and outcomes to assess if breast papillomas may be related to the development of breast cancer. While most breast papillomas are benign, some are atypical, and over the last 10 years, there has been an increase in UC Health pathology examinations noting breast papilloma. After completing the study, researchers will have validated the breast papilloma diagnoses and identified risk factors in a one of the largest case-control studies ever conducted and will use preliminary data in a R01 grant application to the National Cancer Institutes and the National Institute of Environmental Health Studies.
Targeting RON-dependent glutamine metabolism in breast cancer:
Susan Waltz, PhD, professor of cancer biology; Tom Cunningham, PhD, assistant professor of cancer biology; Elyse Lower, MD, professor of medicine, director, UC Cancer Institute Breast Cancer Center, all UC College of Medicine; $20,000
About the study: Researchers hope to find the mechanism by which RON signaling raises glutamine metabolism within the tumor, which could be a potential target for disrupting the process and shrinking tumors. The metabolism of glutamine, an amino acid that is used in the biosynthesis of proteins, in the context of RON signaling (RON is a cancer causing enzyme) is seen to be overproduced in breast cancer cells, and reduced breast cancer cell sustainability is seen when glutamine is inhibited by blocking the activity of Gln synthetase (or GS, the enzyme responsible for glutamine production). These studies will help researchers gain additional knowledge of tumor metabolism, uncover potentially translatable therapeutic strategies for patients and generate a deeper basis for study of RON-mediated metabolic reprogramming.
Enhancer RNAs in breast cancer metastasis and therapeutic resistance:
Xiaoting Zhang, PhD, associate professor of cancer biology, UC College of Medicine; $35,000
About the study: A team led by Zhang will work to further understand the role and molecular workings behind MED1(a protein coding gene) and its regulation of certain RNAs using animal models and human samples. A key part of the study will involve nanotechnology. MED1 is a coactivator of estrogen receptor and is responsible in part for the development of cancer. It was found in previous studies to be a key mediator in anti-estrogen treatment resistance and spread of breast cancer. Additionally, MED1 is overproduced in 40 to 60 percent of human breast cancers. This study will help provide clarity about how it impacts newly identified small RNAs called enhancer RNAs.
RON expression in breast cancer progression:
Vinita Takiar, MD, PhD, assistant professor of radiation oncology; Susan Waltz, PhD, professor of cancer biology; and Elyse Lower, MD, professor of medicine and director of the UC Cancer Institute Breast Cancer Center, all UC College of Medicine; $20,000
About the study: Metastatic breast cancer kills 40,000 patients each year. RON is an enzyme that has been associated with breast cancer recurrence, the development of metastases and relatively worse survival. However, it is unclear whether the expression level of RON in the breast tumor tissue predicts for the development of metastasis or whether there is any relationship between RON expression within the breast tumor and the metastatic site. Researchers will analyze RON expression in primary breast tumors and in areas of metastatic spread in the same patient and correlate with clinical outcomes. This will improve understanding of the relationship between RON levels and breast cancer progression.
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CINCINNATI—Adolescent girls who reach puberty at an earlier age may also have a greater chance of developing migraine headaches, according to new research from investigators at the University of Cincinnati (UC) College of Medicine. “We know that the percentage of girls and boys who have migraine is pretty much the same until menstruation begins,” says Vincent Martin, MD, professor in the Division of General Internal Medicine and director of the Headache and Facial Pain Center at the UC Gardner Neuroscience Institute. “When the menstrual period starts in girls, the prevalence goes way up, but what our data suggests is that it occurs even before that.” The findings will be presented by Martin at the American Headache Society 61st Annual Scientific Meeting Saturday, July 13, in Philadelphia. Nationally, about 10 percent of school age children suffer from migraine, according to the Migraine Research Foundation (MRF). As adolescence approaches, the incidence of migraine increases rapidly in girls, and by age 17, about 8 percent of boys and 23 percent of girls have experienced migraine, the MRF reports. Martin and a team of researchers were part of a longitudinal study looking at 761 adolescent girls from sites in Cincinnati, New York and the San Francisco Bay area. The girls ranged in age from 8 to 20 and study took place over a 10-year period beginning in 2004. Girls enrolled in the study at age 8-10 were examined during study visit every six to 12 months. Researchers determined when they showed initial signs of thelarche (breast development), pubarche (pubic hair growth) and menarche (start of menstrual periods). Girls answered a headache questionnaire to find out if they suffered from migraine headache, no migraine or probable migraine—the latter is defined as meeting all the diagnostic criteria for migraine except one. The average age at which they completed the survey was 16. Of those surveyed, 85 girls (11 percent) were diagnosed with migraine headache while 53 (7 percent) had probable migraine and 623 (82 percent) had no migraine, according to Martin, also a UC Health physician specializing in migraine. Researchers found that girls with migraine had an earlier age of thelarche (breast development) and the onset of menarche (menstrual periods) than those with no migraine. On average breast development occurred four months earlier in those with migraine while menstruation started five months earlier. There was no difference in the age of pubarche (pubic hair development) between those with migraine and no migraine. “There was a 25 percent increase in the chance of having migraine for each year earlier that a girl experienced either thelarche or menarche,” says Susan Pinney, PhD, professor in the UC Department of Environmental Health and lead investigator on the study. “This suggests a strong relationship between early puberty and the development of migraine in adolescent girls.” The age of onset of thelarche, pubarche or menarche did not differ between those with probable migraine and no migraine, says Pinney. Previous research suggests that migraine often starts with the onset of menstrual cycles during menarche in adolescent girls. But this study looks at earlier stages of puberty such as thelarche and pubarche, explains Martin. “To suggest the origins of migraine may occur actually before menstrual periods begin is pretty novel,” says Martin. “At each of these stages, different hormones are starting to appear in girls. During pubarche, testosterone and androgens are present, and during thelarche, there is the very first exposure to estrogen. Menarche is when a more mature hormonal pattern emerges. Our study implies that the very first exposure to estrogen could be the starting point for migraine in some adolescent girls. It may be the Big Bang Theory of migraine.” So is there anything that one can do to prevent an early puberty? “Studies suggest that childhood obesity is associated with early puberty,” says Martin, who is also president of the National Headache Foundation. “Keeping your weight down might prevent the early onset of puberty. Future studies will need to be done to determine if strategy will decrease also the likelihood of developing migraine.” Other co-investigators in the study include Frank Biro, MD, UC professor in the Department of Pediatrics and Cincinnati Children’s pediatrician, Jun Ying, PhD, professor in the UC Department of Environmental Health, and Hao Yu, biostatistician, UC Department of Environmental Health. Funding for this research came grant U01ES026119 from the National Institute of Environmental Health Sciences and grant 1R03HD094236 of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.