Abstract # 3157 Elucidating the mechanisms of post-treatment cancer-related fatigue using a preclinical model

2019 ◽  
Vol 76 ◽  
pp. e32
Author(s):  
E.G. Vichaya ◽  
A.J. Grossberg ◽  
J. Molkentine ◽  
D.J. Estrada ◽  
P.S. Gross ◽  
...  
Keyword(s):  
Post Treatment ◽  
Preclinical Model ◽  
Cancer Related Fatigue

A window of opportunity trial of atorvastatin in p53-mutant and p53 wild type malignancies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS3165-TPS3165 ◽  
Author(s):  
Mohammad Telfah ◽  
Tomoo Iwakuma ◽  
Andres Bur ◽  
Lisa Shnayder ◽  
Terry Tsue ◽  
...  
Keyword(s):  
Pilot Trial ◽  
Xenograft Model ◽  
Post Treatment ◽  
Rational Approach ◽  
Cancer Center ◽  
Preclinical Model ◽  
Window Of Opportunity ◽  
Wild Type ◽  
P53 Expression ◽  
Pre Treatment

TPS3165 Background: Mutations in p53 contribute to tumor progression. A rational approach is to destabilize mutant (m) p53. The group at the University of Kansas Cancer Center screened compounds that suppress m p53 in a preclinical model. Luciferase-based reporter assay identified statins as suppressors of m p53 expression. In vitro validation assay demonstrated atorvastatin (A) suppressed m p53 level and cell growth selectively; and depletion of mevalonic acid lead to degradation of m p53. These effects were limited to mutations in the conformation of p53, while wild-type and DNA contact mutations were not as sensitive to statin-induced degradation of p53. M p53 xenograft model confirmed that A could suppress tumor growth at a concentration that can decrease LDL level. The primary objective of this trial is to determine if A decreases the level of conformational m p53. The secondary objective is to assess the effects of A on Ki-67 and caspase-3 in conformational m p53 tumors. Methods: This is an open-label, window of opportunity pilot trial to see if A given for 1 to 4 weeks at a dose of 80 mg/day is sufficient to reduce the levels of conformational m p53 in the tumor tissues. Subjects with new diagnosis of malignancy with a planned surgical therapy, and subjects with previously treated AML, in between treatment regimens, are eligible. Tissues from solid tumors, and bone marrow or peripheral blood samples from AML will be used to screen for m p53 by immunohistochemistry (IHC). Subjects will receive A at 80 mg/day po for 1 to 4 weeks. Pharmacokinetics at pre-dose and 1-hour post-dose on Day 1 and on the day of surgery will be done. Mutational analysis using exome sequencing technique will be done on m p53. Using IHC, the amount of p53 in pre-treatment and post-treatment samples will be measured and compared simultaneously. The levels of Ki67 and caspace-3 will be tested and compared between pre-treatment and post-treatment samples in subjects with conformational m p53, between conformational and non-conformational m p53, and in wild-type p53 tumors. The trial is actively enrolling subjects. The results of this trial will determine further investigations on the role of atorvastatin in tumors with p53 mutations in a placebo-controlled, randomized trial. Clinical trial information: NCT03560882.

Prevalence of cancer-related fatigue in a population-based sample of colorectal, breast, and prostate cancer survivors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9131-9131
Author(s):  
Jennifer M Jones ◽  
Doris Howell ◽  
Karin Lou Olson ◽  
Haiyan Jiang ◽  
Charles N Catton ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cancer Survivors ◽  
Negative Impact ◽  
Population Sample ◽  
Metastatic Breast ◽  
Post Treatment ◽  
Trend Test ◽  
Time Points ◽  
Cancer Related Fatigue

9131 Background: Cancer-related fatigue (CRF) is the most prevalent and distressing cancer-related symptom and has a greater negative impact on patients' daily activities and quality of life than other cancer-related symptoms, including pain and depression. However, the prevalence and severity of persistent CRF and related disability in the post-treatment survivorship period has seldom been examined in populations other than breast cancer. The primary objective of the study was to describe the prevalence of significant CRF and associated levels of disability in a mixed cancer population sample at 3 time points in the post-treatment survivorship trajectory. Methods: Based on cancer registry data, a self-administered mail based questionnaire using Dillman's Tailored Design Method was sent to 3 cohorts of disease-free cancer survivors (6-18 months; 2-3 years; and 5-6 years post-treatment) previously treated for non-metastatic breast, prostate or colorectal cancer. Fatigue was measured using the FACT-F and disability was measured with the WHO-Disability Assessment Schedule. Clinical information was extracted from chart review. Frequencies of significant fatigue by disease sites and time points were studied and compared using chi-square test. Disability between those with and without CRF was also compared using Cochran-Armitage trend test. Results: 1294 questionnaire packages were completed (63% response rate). The FACT-F score was 39.1+10.9; 29% (95% CI: [27%, 32%]) of the sample reported significant fatigue (FACT-F≤34) and this was associated with much higher levels of disability (p<0.0001). Breast (40% [35%, 44%]) and colorectal (33% [27%, 38%]) survivors had significantly higher rates of fatigue (≤34) compared to the prostate group (17% [14%, 21%]) (p<0.0001). Fatigue levels remained relatively stable across the 3 time points. Conclusions: CRF was a significant and debilitating symptom for a substantial minority of the respondents across all 3 time points. Effective CRF management strategies are needed and have the potential to significantly reduce morbidity associated with cancer and its treatments and to improve quality of life for the growing population of cancer survivors.

scholarly journals The Use of Natural Fiber-Rich Food Product Is Safe and Reduces Aberrant Crypt Foci in a Pre-Clinical Model

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2708
Author(s):  
Luane Aparecida do Amaral ◽  
Taina da Silva Fleming de Almeida ◽  
Gabriel Henrique Oliveira de Souza ◽  
Adrivanio Baranoski ◽  
Rafael Souza Maris ◽  
...  
Keyword(s):  
Natural Fiber ◽  
Treatment Protocol ◽  
Food Product ◽  
Negative Control ◽  
Aberrant Crypt Foci ◽  
Post Treatment ◽  
Preclinical Model ◽  
Simultaneous Treatment ◽  
Clinical Model ◽  
Rich Food

Background: Colorectal cancer is a highly prevalent disease, requiring effective strategies for prevention and treatment. The present research aimed to formulate a natural fiber-rich food product (NFRFP) and to evaluate its safety, toxicogenetics, and effects on aberrant crypt foci induced by 1,2-dimethyl-hydrazine in a preclinical model. Methods: A total of 78 male Wistar rats were distributed in six experimental groups: negative control, positive control (1,2-Dimethylhydrazine—40 mg/Kg), and four groups fed with 10% NFRFP: NFRFP, pre-treatment protocol, simultaneous treatment, and post-treatment protocol. Results: The NFRFP was shown to be a good source of fibers and did not change biometric, biochemical, hematological, and inflammatory parameters, and did not induce signs of toxicity and genotoxicity/carcinogenicity. NFRFP exhibited a chemopreventive effect, in all protocols, with damage reduction (% DR) of 75% in the comet test. NFRFP reduced the incidence of aberrant crypt outbreaks by 49.36% in the post-treatment protocol. Conclusions: The results suggest the applicability of NFRFP in the human diet due to potential production at an industrial scale and easy technological application in different products, since it could be incorporated in food without altering or causing small changes in final product sensory characteristics.

scholarly journals Screening, Assessment, and Management of Fatigue in Adult Survivors of Cancer: An American Society of Clinical Oncology Clinical Practice Guideline Adaptation

2014 ◽  
Vol 32 (17) ◽  
pp. 1840-1850 ◽  
Author(s):  
Julienne E. Bower ◽  
Kate Bak ◽  
Ann Berger ◽  
William Breitbart ◽  
Carmelita P. Escalante ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cancer Survivors ◽  
Clinical Practice Guideline ◽  
Practice Guideline ◽  
Primary Treatment ◽  
Post Treatment ◽  
Treatment Approaches ◽  
Nccn Guidelines ◽  
Cancer Related Fatigue ◽  
Screening Assessment

Purpose This guideline presents screening, assessment, and treatment approaches for the management of adult cancer survivors who are experiencing symptoms of fatigue after completion of primary treatment. Methods A systematic search of clinical practice guideline databases, guideline developer Web sites, and published health literature identified the pan-Canadian guideline on screening, assessment, and care of cancer-related fatigue in adults with cancer, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines In Oncology (NCCN Guidelines) for Cancer-Related Fatigue and the NCCN Guidelines for Survivorship. These three guidelines were appraised and selected for adaptation. Results It is recommended that all patients with cancer be evaluated for the presence of fatigue after completion of primary treatment and be offered specific information and strategies for fatigue management. For those who report moderate to severe fatigue, comprehensive assessment should be conducted, and medical and treatable contributing factors should be addressed. In terms of treatment strategies, evidence indicates that physical activity interventions, psychosocial interventions, and mind-body interventions may reduce cancer-related fatigue in post-treatment patients. There is limited evidence for use of psychostimulants in the management of fatigue in patients who are disease free after active treatment. Conclusion Fatigue is prevalent in cancer survivors and often causes significant disruption in functioning and quality of life. Regular screening, assessment, and education and appropriate treatment of fatigue are important in managing this distressing symptom. Given the multiple factors contributing to post-treatment fatigue, interventions should be tailored to each patient's specific needs. In particular, a number of nonpharmacologic treatment approaches have demonstrated efficacy in cancer survivors.

Association between cancer-related fatigue and other symptoms in breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20526-e20526
Author(s):  
Anita Roselyn Peoples ◽  
Charles E. Heckler ◽  
Joseph A. Roscoe ◽  
Charles Stewart Kamen ◽  
Luke Joseph Peppone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Linear Regression ◽  
Cancer Patients ◽  
Post Treatment ◽  
Cancer Therapies ◽  
Breast Cancer Patients ◽  
Cancer Related Fatigue ◽  
Disturbed Sleep ◽  
Delayed Nausea ◽  
Unit Increase

e20526 Background: Cancer-related fatigue (CRF) is one of the most prevalent side effects of cancer treatment and has a detrimental effect on a patient’s normal functioning and quality of life. At present, the underlying pathophysiology of CRF is poorly understood, as it is complex phenomenon involving the interaction of many factors. The relative contributions of the disease itself, different cancer therapies, and comorbid conditions (e.g., sleep disorders, nausea) remain unclear. Therefore, it is important to understand the association between them in order to develop better strategies for the prevention and treatment of CRF. Methods: The purpose of these secondary analyses was to examine the association between post-treatment fatigue with disturbed sleep (on a 0–10 scale), delayed nausea (on a 1–7 scale), age, and baseline fatigue. Analyses were performed on 541 breast cancer patients (mean age 54, 100% female) who completed a four-day diary assessing nausea and sleep following initial chemotherapy. Fatigue as its worst during the prior week (0 = no fatigue to 10 = fatigue as bad as you can imagine) was assessed both prior to chemotherapy and on Day 4. To determine associations between variables, Pearson’s correlation analysis and linear regression were performed. Results: Post-treatment CRF was significantly associated with baseline fatigue (r = 0.40, p < 0.0001), disturbed sleep (r = 0.45, p < 0.0001), delayed nausea (r = 0.37, p < 0.0001), and age (r = -0.22, p < 0.0001). Linear regression showed that a one unit increase in baseline fatigue, disturbed sleep, and delayed nausea was associated with increase in post-treatment CRF by 0.29, 0.37, and 0.42, respectively, all p’s < 0.0001. In addition, every ten years of increased age was associated with a decrease in post-treatment CRF by 0.33 (p < 0.0013). Conclusions: Post-treatment fatigue was found to be significantly correlated with baseline fatigue, disturbed sleep, and delayed nausea while negatively correlated with age in patients with breast cancer. These results demonstrate the importance of further research to better understand the underlying psychological and biological mechanisms for CRF in order to develop effective treatments. Supported by NCI grant CA37420.

scholarly journals Use of a Case Definition Approach to Identify Cancer-Related Fatigue in Women Undergoing Adjuvant Therapy for Breast Cancer

2005 ◽  
Vol 23 (27) ◽  
pp. 6613-6622 ◽  
Author(s):  
Michael A. Andrykowski ◽  
John E. Schmidt ◽  
John M. Salsman ◽  
Abbie O. Beacham ◽  
Paul B. Jacobsen
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Early Stage ◽  
Case Definition ◽  
Clinical Interview ◽  
Post Treatment ◽  
Future Research ◽  
Treatment Assessment ◽  
Cancer Related Fatigue

Purpose Use a proposed case-definition approach to identify the prevalence of cancer-related fatigue (CRF), demographic, clinical and psychosocial predictors of subsequent CRF, and psychosocial factors associated with concurrent CRF. Patients and Methods Women (n = 288) undergoing adjuvant therapy for early-stage breast cancer were recruited from two outpatient clinics. Women completed a baseline assessment before adjuvant therapy and a post-treatment assessment at the conclusion of an initial course of adjuvant chemotherapy or radiotherapy. At both assessments, women completed a clinical interview and measures of fatigue, distress, coping, and quality of life (QOL). The clinical interview consisted of modules from the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) and a diagnostic interview to identify cases of CRF. Results CRF prevalence at the baseline and post-treatment assessments was 10% and 26%, respectively. Multivariate analyses identified factors prospectively associated with greater risk for CRF at the post-treatment assessment, including receipt of adjuvant chemotherapy and a tendency to catastrophize in response to fatigue. Patients with and without CRF differed on a host of concurrent measures of fatigue, depression, functioning, and QOL with mean effect sizes in the range of 1.0 standard deviation. Conclusion CRF is a clinical syndrome experienced before and during adjuvant therapy for breast cancer. Results suggest CRF has a multifactorial etiology and support use of the proposed case definition approach to defining CRF. Future research is necessary to determine the scientific value of these criteria for understanding the etiology and management of fatigue in the oncology setting.

Cancer-related fatigue and associated disability in post-treatment cancer survivors

2015 ◽  
Vol 10 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Jennifer M. Jones ◽  
Karin Olson ◽  
Pamela Catton ◽  
Charles N. Catton ◽  
Neil E. Fleshner ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Post Treatment ◽  
Cancer Related Fatigue

scholarly journals Cancer-Related Fatigue in Post-Treatment Cancer Survivors: Theory-Based Development of a Web-Based Intervention

JMIR Cancer ◽  
2017 ◽  
Vol 3 (2) ◽  
pp. e8
Author(s):  
Teresa Corbett ◽  
Jane C Walsh ◽  
AnnMarie Groarke ◽  
Rona Moss-Morris ◽  
Eimear Morrissey ◽  
...  
Keyword(s):  
Cancer Survivors ◽  
Post Treatment ◽  
Web Based ◽  
Cancer Related Fatigue
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