Selected Significant Findings
“Incidence of Lymphedema Among Breast Cancer Survivors,” Cancer Epidemiology, Biomarkers and Prevention
“No Risk of Acoustic Neuroma for Occupational Noise,” American Journal of Epidemiology
“Group Randomized Trials Do Not Fully Address Design Issues,” Journal of the National Cancer Institute
“Current Smokers Have Increased Risk for Rectal Cancer,” Journal of the National Cancer Institute
“Despite Cancer Diagnosis, Women Did Not Suffer Sexual Disruption,” Journal of Clinical Oncology
Etiology and Prevention
Among Mexican-American women surveyed in the U.S. National Longitudinal Survey of Youths 1979-2002, researchers found that disadvantaged economic status, both during childhood and midlife, was associated with an increased risk for midlife obesity. (Salsberry PJ and Regan PB. Comparing the influence of childhood and adult economic status on midlife obesity in Mexican-American, white and African-American women. Public Health Nurs 2009 Jan-Feb; 26(1): 14-22).
Among a largely minority and low-income population, those with higher incomes were more likely to talk to family members and physicians about cancer risk (Kelly et al., 2009).
HPV vaccine acceptability in the Appalachian population is related to knowledge, cultural beliefs, acceptability, access and availability (Katz et al 2009).
Survivorship and Quality of Life
Over half of long-term breast cancer survivors reported making positive exercise or diet changes since diagnosis and those who reported increasing exercise also reported lower fatigue. (Alfano CM*, Day JM, Katz ML, Herndon JE, Bittoni MA, Oliveri JM, Donohue K, Paskett ED. Exercise and dietary change after diagnosis and cancer-related symptoms in long-term survivors of breast cancer: CALGB 79804. Psychooncology 2009 Feb;18(2):128-33).
In long-term breast cancer survivors, the frequency of cancer surveillance exams was low (Katz et al., 2009), the most reported side effects were menopausal symptoms, osteoporosis and lymphedema (Paskett et al., 2008), however, many survivors had made positive changes in diet and or exercise (Alfano et al., 2009).
A much more mechanistic approach to the association of stress and immunity and its impact on the genesis of cancer, and quality of life is being undertaken by several CC Program members who founded and play important roles in the OSU Institute of Behavioral Medicine Research (Ronald Glaser, PhD (Director), Janice Kiecolt-Glaser, PhD, William Malarkey, MD, and John Sheridan, PhD), along with 13 other faculty members. The National Institutes of Health named the Institute of Behavioral Medicine Research as one of the five Mind/Body Centers to conduct research on the interactions among the mind and body and wound healing. This center grant was awarded to OSU in 1999 and was supported through September 2004. It was the first such designated group of Centers by the NIH. Drs. Caligiuri, Paskett and Wewers have, over the last several years, provided substantial support to Drs. Ron Glaser and Janet Kiecolt-Glaser, and have worked to integrate the group’s cancer focus within the CC program. The return on this investment has been substantial as evidenced by the large number of cancer-focused publications and several NCI-funded grants from this group. Moreover, this group is becoming well-integrated into the research of other investigators such as Drs. Rob Baiocchi (VO), Electra Paskett, Clay Marsh (IMM), Marshall Williams, Scott Jewell, (IMM) Charles Shapiro, and Stan Lemeshow, thus broadening the scope of their investigations.
Dr Glaser is a tumor virologist who has studied Epstein-Barr Virus (EBV) and cancer for several years. He has focused primarily on viral latency and the replication of EBV in epithelial cells in order to help understand the role that EBV plays in the etiology of nasopharyngeal carcinoma (NPC). He also works closely with Dr. Janice Kiecolt-Glaser studying the interactions between the central nervous system, the immune system and the endocrine system, how stress modulates these systems and the health implications, particularly cancer outcomes, of these interactions. His work has focused on stress and herpesvirus latency, vaccine responses, wound healing and the role that stress may play as a co-factor in the etiology and progression of malignant disease.
In a study published in Cancer Research (Yang EV, Sood AK, Chen M, Li Y, Eubank TD, Marsh CB, Jewell S, Flavahan NA, Morrison C, Yeh PE, Lemeshow S, Glaser R. Norepinephrine up-regulates the expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, and MMP-9 in nasopharyngeal carcinoma tumor cells. Cancer Res. 2006 Nov 1;66(21):10357-64 ), his team showed that nasopharyngeal carcinoma (NPC) tumor cells express beta-adrenergic receptors. When two NPC tumor cell lines were treated with norepinephrine or epinephrine, two stress hormones produced by activation of the sympathetic-adrenal medullary axis, the production of matrix metalloproteinases (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) was up-regulated. Dr. Glaser and his team also showed that this had functional implications for tumor progression and that tumor cells in NPC biopsies express beta adrenergic receptors; these data suggest clinical relevance.
In a follow-up study (Yang EV, Kim SJ, Donovan EL, Chen M, Gross AC, Webster Marketon JI, Barsky SH, Glaser R. Norepinephrine upregulates VEGF, IL-8, and IL-6 expression in human melanoma tumor cell lines: implications for stress-related enhancement of tumor progression. Brain Behav Immun. 2009 Feb;23(2):267-75), they found that the C8161 melanoma cell line also expresses beta-adrenergic receptors. When treated with the same stress hormones, VEGF was up-regulated along with two cytokines that play a role in the growth of melanoma tumors in vivo, IL-6 and IL-8. They have also shown that 18 out of 20 melanoma biopsies (both primary and metastatic) express the beta-adrenergic receptors, again supporting the possibility that these data may have clinical relevance.
Similar results were obtained with multiple myeloma tumor cell lines as well. (Eric Yang, Elise Donovan, Don Benson, and Ronald Glaser, Brain, Behavior and Immunity, 2008) This exciting line of research shows that stress hormones can modulate and enhance tumor progression of distinctly different tumor types, such as carcinomas and melanomas. It is clear that other studies need to be done on other tumor cell types as well, but the applicability of using beta-blocker type drugs in patients whose tumors express beta-adrenergic receptors in a clinical setting may be worth exploring.
Dr. Janice Kiecolt-Glaser’s work is in the area of psychoneuroimmunology and primarily examines: 1) the psychological and physiological consequences of chronic stress in older adults; 2) the ability of omega-3 supplementation to alter mood and inflammation; 3) how genetic and environmental influences contribute to depression and immune dysregulation in older adults: 4) the impact of major life stressors on the progression of basal cell carcinoma: 5) the ability of mind-body interventions such as yoga to modulate endocrine and immune responses (Yoga Study for Breast Cancer Patients); and 6) the role that proinflammatory cytokines play in combination with depression among cancer survivors who experience debilitating fatigue. Dr. Kiecolt-Glaser has written about this emerging field of research (Kiecolt-Glaser, JK. Psychoneuroimmunology: Psychology's gateway to the biomedical future. Perspectives on Psychological Science 2009; 4:367-369). Psychological factors such as anger can impact healing process of patients and this has implications for cancer patients who have undergone surgery. Work done by Dr. Kiecolt-Glaser indicates that enhanced levels of cortisol secretion lengthens the healing process. (Gouin JP, Kiecolt-Glaser, JK, Malarkey W B, Glaser R. The influence of anger expression on wound healing. Brain, Behavior, and Immunity 2008; 22: 699-708).
Dr. John Sheridan has also done extensive in psychoneuroimmunology, especially stress. His work compliments the work of Drs. Glaser, Kiecolt-Glaser, and Andersen, in in regards to stress and immunity. His animal model study reveals that social disruption stress can lead to an increase in anxiety-like behaviors, but not depressive-like behaviors, and increase inflammatory responses and a state of glucocorticoid resistance in aplenic CD11B+ monocytes. (Kinsey SG, Bailey MD, Sheridan JF, Padgett DA+, Avitsur R. Repeated social defeat causes increased anxiety-like behavior and alters splenocyte function in C57BL/6 and CD-1 mice. Brain Behav Immun 2007. 21(4);458-66).
Stress and Immunity Breast Cancer Project (PI: Andersen), was a randomized clinic trial that examined behavioral, psychological, immune and endocrine responses in breast cancer patients Results indicated that patients receiving the intervention showed significant lowering of anxiety, improvements in perceived social support, improved dietary habits, and reduction in smoking (all P <.05) [ref]. Results of the immunology analysis revealed that immune responses for the intervention patients paralleled their psychological and behavioral improvements. T-cell proliferation in response to phytohemagglutinin and concanavalin A remained stable or increased for the Intervention patients, whereas both responses declined for Assessment patients; this effect was replicated across three concentrations for each assay (all P <.01) (Andersen BL, Farrar WB, Golden-Kreutz DM, Glaser R, Emery CF, Crespin TR, Shapiro CL, Carson WE. Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial. Journal of Clinical Oncology, Vol 22, No 17 (September 1), 2004: pp. 3570-3580). This type of biobehavioral research compliments the work being done by Drs. Glaser and Kiecolt-Glaser and displays the collaboration within the CC program and with other programs within the OSUCCC.
In 2004, a group of CC Program investigators, supported by a $50,000 investment from the OSUCCC - James, were awarded an NCI P50 Center Grant proposal in response to an RFA entitled “Center for Population Health and Health Disparities.”
The OSUCCC - James application entitled, “Reducing Cervical Cancer in Appalachia,” was one of eight applications in the country to be funded. This Center Grant provides an opportunity for significant interaction among CCRP members and other OSUCCC - James members.
Recognition, Honors and Awards (2008 & 2009)
American Association for the Advancement of Science: Randall Harris, MD, PhD, elected, December 2008
American Association for the Advancement of Science: Rebecca Jackson, MD, elected, December 2008
American Cancer Society, Ohio Division Hero of Hope Research Medal of Honor: Awarded to Mary Ellen Wewers, RN, PhD, MPH, August 2008
American Society of Preventive Oncology: Electra D. Paskett, PhD, elected president, April 2009
Columbus (Ohio) City Council Resolution: Presented to William J. Hicks, MD, recognizing his efforts to end the unequal burden of cancer in minority populations