IU Indianapolis ScholarWorks :: Browsing by Subject "Oncology"

Browsing by Subject "Oncology"

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Barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients
(Wiley, 2014-07) Mosher, Catherine E.; Winger, Joseph G.; Hanna, Nasser; Jalal, Shadia I.; Fakiris, Achilles J.; Einhorn, Lawrence H.; Birdas, Thomas J.; Kesler, Kenneth A.; Champion, Victoria L.; Psychology, School of Science
OBJECTIVE: This study examined barriers to mental health service use and preferences for addressing emotional concerns among lung cancer patients (N=165) at two medical centers in the Midwestern United States. METHODS: Lung cancer patients completed an assessment of anxiety and depressive symptoms, mental health service use, barriers to using these services, and preferences for addressing emotional concerns. RESULTS: Only 45% of distressed patients received mental health care since their lung cancer diagnosis. The most prevalent patient-reported barriers to mental health service use among non-users of these services (n=110) included the desire to independently manage emotional concerns (58%) and inadequate knowledge of services (19%). In addition, 57% of distressed patients who did not access mental health services did not perceive the need for help. Seventy-five percent of respondents (123/164) preferred to talk to a primary care physician if they were to have an emotional concern. Preferences for counseling, psychiatric medication, peer support, spiritual care, or independently managing emotional concerns also were endorsed by many patients (range=40-50%). Older age was associated with a lower likelihood of preferring to see a counselor. CONCLUSIONS: Findings suggest that many distressed lung cancer patients underuse mental health services and do not perceive the need for such services. Efforts to increase appropriate use of services should address patients' desire for autonomy and lack of awareness of services.
The Cancer Loneliness Scale and Cancer-related Negative Social Expectations Scale: development and validation
(SpringerLink, 2017-07) Adams, Rebecca N.; Mosher, Catherine E.; Rand, Kevin L.; Hirsh, Adam T.; Monahan, Patrick O.; Abonour, Rafat; Kroenke, Kurt; Psychology, School of Science
PURPOSE: Loneliness is a known risk factor for poor mental and physical health outcomes and quality of life in the general population, and preliminary research suggests that loneliness is linked to poorer health outcomes in cancer patients as well. Various aspects of the cancer experience contribute to patients feeling alone and misunderstood. Furthermore, loneliness theory suggests that negative social expectations, which may specifically relate to the cancer experience, precipitate and sustain loneliness. Cancer-specific tools are needed to assess key constructs of this theory. In the current study, we developed and tested measures of (1) loneliness attributed to cancer (i.e., cancer-related loneliness) and (2) negative social expectations related to cancer. METHODS: First, we developed the items for the measures based on theory, prior research, and expert feedback. Next, we assessed the measures' psychometric properties (i.e., internal consistency and construct validity) in a diverse sample of cancer patients. RESULTS: The final products included a 7-item unidimensional Cancer Loneliness Scale and a 5-item unidimensional Cancer-related Negative Social Expectations Scale. Evidence of excellent reliability and validity was found for both measures. CONCLUSIONS: The resulting measures have both clinical and research utility.
Caregiving experiences predict changes in spiritual well-being among family caregivers of cancer patients
(Wiley Online Library, 2014-10) Adams, Rebecca N.; Mosher, Catherine E.; Cannady, Rachel S.; Lucette, Aurelie; Kim, Youngmee; Department of Psychology, School of Science
OBJECTIVE: Although enhanced spiritual well-being has been linked to positive mental health outcomes among family caregivers of cancer patients, little is known regarding predictors of spiritual well-being in this population. The current study aimed to examine caregiving experiences as predictors of change in family caregivers' spiritual well-being during the initial months following the patient's cancer diagnosis. METHODS: Seventy family caregivers of newly diagnosed cancer patients (74% female, mean age = 59 years) participated in this longitudinal survey. Caregivers completed baseline questionnaires shortly before staying with the patient at an American Cancer Society Hope Lodge. Baseline questionnaires assessed caregiving experiences (i.e., self-esteem related to caregiving, family support for providing care, impact of caregiving on finances, and impact of caregiving on one's schedule). In addition, caregivers' spiritual well-being (i.e., meaning in life, peace, and faith) was assessed at baseline and 4-month follow-up. RESULTS: In univariate analyses, all caregiving experiences studied were associated with one or more aspects of spiritual well-being at 4-month follow-up. However, in the multivariate analysis, the only caregiving experience associated with aspects of spiritual well-being at 4-month follow-up was caregivers' perceptions of family support. Specifically, lack of family support was associated with lower levels of meaning and peace. CONCLUSIONS: Findings point to the importance of family support in facilitating the search for meaning and peace shortly after a loved one's cancer diagnosis and suggest that interventions targeting caregivers' support system may enhance their spiritual well-being.
Combination therapy in a xenograft model of glioblastoma: enhancement of the antitumor activity of temozolomide by an MDM2 antagonist
(American Association of Neurological Surgeons, 2017-02) Wang, Haiyan; Cai, Shanbao; Bailey, Barbara J.; Saadatzadeh, M. Reza; Ding, Jixin; Tonsing-Carter, Eva; Georgiadis, Taxiarchis M.; Gunter, T. Zachary; Long, Eric C.; Minto, Robert E.; Gordon, Kevin R.; Sen, Stephanie E.; Cai, Wenjing; Eitel, Jacob A.; Waning, David L.; Bringman, Lauren R.; Wells, Clark D.; Murray, Mary E.; Sarkaria, Jann N.; Gelbert, Lawrence M.; Jones, David R.; Cohen-Gadol, Aaron A.; Mayo, Lindsey D.; Shannon, Harlan E.; Pollok, Karen E.; Pediatrics, School of Medicine
OBJECTIVE Improvement in treatment outcome for patients with glioblastoma multiforme (GBM) requires a multifaceted approach due to dysregulation of numerous signaling pathways. The murine double minute 2 (MDM2) protein may fulfill this requirement because it is involved in the regulation of growth, survival, and invasion. The objective of this study was to investigate the impact of modulating MDM2 function in combination with front-line temozolomide (TMZ) therapy in GBM. METHODS The combination of TMZ with the MDM2 protein-protein interaction inhibitor nutlin3a was evaluated for effects on cell growth, p53 pathway activation, expression of DNA repair proteins, and invasive properties. In vivo efficacy was assessed in xenograft models of human GBM. RESULTS In combination, TMZ/nutlin3a was additive to synergistic in decreasing growth of wild-type p53 GBM cells. Pharmacodynamic studies demonstrated that inhibition of cell growth following exposure to TMZ/nutlin3a correlated with: 1) activation of the p53 pathway, 2) downregulation of DNA repair proteins, 3) persistence of DNA damage, and 4) decreased invasion. Pharmacokinetic studies indicated that nutlin3a was detected in human intracranial tumor xenografts. To assess therapeutic potential, efficacy studies were conducted in a xenograft model of intracranial GBM by using GBM cells derived from a recurrent wild-type p53 GBM that is highly TMZ resistant (GBM10). Three 5-day cycles of TMZ/nutlin3a resulted in a significant increase in the survival of mice with GBM10 intracranial tumors compared with single-agent therapy. CONCLUSIONS Modulation of MDM2/p53-associated signaling pathways is a novel approach for decreasing TMZ resistance in GBM. To the authors' knowledge, this is the first study in a humanized intracranial patient-derived xenograft model to demonstrate the efficacy of combining front-line TMZ therapy and an inhibitor of MDM2 protein-protein interactions.
Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis
(American Society for Clinical Investigation, 2018-07-02) Liao, Chung-Ping; Booker, Reid C.; Brosseau, Jean-Philippe; Chen, Zhiguo; Mo, Juan; Tchegnon, Edem; Wang, Yong; Clapp, D. Wade; Le, Lu Q.; Pediatrics, School of Medicine
Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.
Coping Among Breast Cancer Survivors: A Confirmatory Factor Analysis of the Brief COPE
(Springer, 2019-08-01) Rand, Kevin L.; Cohee, Andrea A.; Monahan, Patrick O.; Wagner, Lynne I.; Champion, Victoria L.; Psychology, School of Science
BACKGROUND AND PURPOSE: Cancer survivors continue to cope with significant stressors after completing treatment. The Brief COPE (Carver, 1997) is frequently used to measure coping; however, its factor structure remains unclear. The purpose of this study was to determine the best factor conceptualization of the Brief COPE for use among breast cancer survivors. METHODS: Breast cancer survivors (N = 1,127) completed the Brief COPE. We conducted confirmatory factor analyses comparing several a priori models based on research in cancer-relevant populations. RESULTS: Of the eight models examined, the 14-factor model of the Brief COPE showed the best fit. CONCLUSIONS: Despite efforts to simplify the structure of the Brief COPE, our results suggest coping among breast cancer survivors is best assessed using Carver's (1997) original 14-factor conceptualization.
The Cost of Complications Following Major Resection of Malignant Neoplasia
(Springer Nature, 2018-11) Zogg, Cheryl K.; Ottesen, Taylor D.; Kebaish, Kareem; Galivanche, Anoop; Murthy, Shilpa; Changoor, Navin R.; Zogg, Donald L.; Pawlik, Timothy M.; Haider, Adil H.; Surgery, School of Medicine
BACKGROUND: Rising healthcare costs have led to increased focus on the need to achieve a higher "value of care." As value-maximization efforts expand to include more complex surgical patients, evidence to support meaningful implementation of complication-based initiatives is lacking. The objective of this study was to compare incremental costs of complications following major gastrointestinal (GI) resections for organ-specific malignant neoplasia using nationally representative data. METHODS: National (Nationwide) Inpatient Sample data, 2001-2014, were queried for adult (≥ 18 years) patients undergoing major resections for malignant neoplasia. Based on system-based complications considered relevant to the long-term treatment of GI disease, stratified differences in risk-adjusted incremental hospital costs and complication probabilities were compared. Differences in surgical outcomes and costs over time were also assessed. RESULTS: A total of 293,967 patients were included, weighted to represent 1,408,117 patients nationwide. One fourth (26.1%; 95% CI, 25.7-26.4%) experienced ≥ 1 pre-discharge complication (range, 45.3% esophagectomy to 24.0% rectal resection). Resultant annual risk-adjusted incremental hospital costs totaled $540 million nationwide (19.5% of the overall cost of care and an average of $20,900 per patient). Costs varied substantially with both cancer/resection type and complication group, ranging from $76.7 million for colectomies with infectious complications to $0.2 million for rectal resections with urinary complications. For each resection type, infectious ($154.7 million), GI ($85.5 million), and pulmonary ($77.9 million) complications were among the most significant drivers of increased hospital cost. CONCLUSIONS: Quantifying and comparing the impact of complications on an indication-specific level in more complex patients offers an important step toward allowing providers/payers to meaningfully prioritize the design of novel and adaptation of existing value-maximization approaches.
Death effector domain-containing protein induces vulnerability to cell cycle inhibition in triple-negative breast cancer
(Springer Nature, 2019-06-28) Ni, Yingjia; Schmidt, Keon R.; Werner, Barnes A.; Koenig, Jenna K.; Guldner, Ian H.; Schnepp, Patricia M.; Tan, Xuejuan; Jiang, Lan; Host, Misha; Sun, Longhua; Howe, Erin N.; Wu, Junmin; Littlepage, Laurie E.; Nakshatri, Harikrishna; Zhang, Siyuan; Surgery, IU School of Medicine
Lacking targetable molecular drivers, triple-negative breast cancer (TNBC) is the most clinically challenging subtype of breast cancer. In this study, we reveal that Death Effector Domain-containing DNA-binding protein (DEDD), which is overexpressed in > 60% of TNBCs, drives a mitogen-independent G1/S cell cycle transition through cytoplasm localization. The gain of cytosolic DEDD enhances cyclin D1 expression by interacting with heat shock 71 kDa protein 8 (HSC70). Concurrently, DEDD interacts with Rb family proteins and promotes their proteasome-mediated degradation. DEDD overexpression renders TNBCs vulnerable to cell cycle inhibition. Patients with TNBC have been excluded from CDK 4/6 inhibitor clinical trials due to the perceived high frequency of Rb-loss in TNBCs. Interestingly, our study demonstrated that, irrespective of Rb status, TNBCs with DEDD overexpression exhibit a DEDD-dependent vulnerability to combinatorial treatment with CDK4/6 inhibitor and EGFR inhibitor in vitro and in vivo. Thus, our study provided a rationale for the clinical application of CDK4/6 inhibitor combinatorial regimens for patients with TNBC.
Developing Bottom-Up, Integrated Omics Methodologies for Big Data Biomarker Discovery
(2020-11) Kechavarzi, Bobak David; Wu, Huanmei; Doman, Thompson; Dow, Ernst; Liu, Yunlong; Liu, Xiaowen; Yan, Jingwen
The availability of highly-distributed computing compliments the proliferation of next generation sequencing (NGS) and genome-wide association studies (GWAS) datasets. These data sets are often complex, poorly annotated or require complex domain knowledge to sensibly manage. These novel datasets provide a rare, multi-dimensional omics (proteomics, transcriptomics, and genomics) view of a single sample or patient. Previously, biologists assumed a strict adherence to the central dogma: replication, transcription and translation. Recent studies in genomics and proteomics emphasize that this is not the case. We must employ big-data methodologies to not only understand the biogenesis of these molecules, but also their disruption in disease states. The Cancer Genome Atlas (TCGA) provides high-dimensional patient data and illustrates the trends that occur in expression profiles and their alteration in many complex disease states. I will ultimately create a bottom-up multi-omics approach to observe biological systems using big data techniques. I hypothesize that big data and systems biology approaches can be applied to public datasets to identify important subsets of genes in cancer phenotypes. By exploring these signatures, we can better understand the role of amplification and transcript alterations in cancer.
Exploring the Nexus of Alzheimer’s Disease and Related Dementias with Cancer and Cancer Therapies
(Elsevier, 2017-03) Snyder, Heather M.; Ahles, Timothy; Calderwood, Stuart; Carrillo, Maria C.; Chen, Honglei; Chang, Chung-Chou; Craft, Suzanne; De Jager, Philip; Driver, Jane A.; Fillet, Howard; Knopman, David; Lotze, Michael; Tierney, Mary C.; Petanceska, Suzana; Saykin, Andrew; Seshadri, Sudha; Shineman, Diana; Ganguli, Mary; Radiology and Imaging Sciences, School of Medicine
Recent population studies suggest an intriguing inverse relationship between several types of cancer and neurodegenerative diseases, including Alzheimer’s disease. Understanding the intersection of the underlying biology for these two distinct families of diseases with one another may offer novel approaches to identify new therapeutic approaches and possible opportunities to repurpose existing drug candidates. The Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation convened a one day workshop to delve into this discussion. Workshop participants outlined research focus areas, potential collaborations and partnerships for future action.

Browsing by Subject "Oncology"

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