Susan K. Lutgendorf

Metabolic Effects of Healing Touch During Cervical Cancer Treatment: An Exploratory Analysis

Introduction: Cancer treatment with chemotherapy frequently leads to side effects such as fatigue, pain, nausea, and anxiety. Healing Touch is a non-invasive complementary therapy often used by cancer patients to address side effects of treatment. To better inform the use of complementary therapies, there is a need to understand the biological mechanisms underlying the effects of such treatments. Methods: This study included 44 patients with cervical cancer undergoing chemoradiation randomized into a Healing Touch (HT), a relaxation training (RT) and a usual care (UC) group. An exploratory metabolomics analysis was conducted on plasma samples taken at baseline, 4, and 6 weeks of ongoing treatment (4 sessions per week). Results: A multivariate data analysis revealed no significant separation in metabolites between the 3 groups. Univariate data analysis revealed changes in metabolites between baseline and week 6 within each group. The main findings were lower levels of acylcarnitines, bile acids and proline in the HT group, higher levels of fatty acids in the HT and RT groups, and lower levels of kynurenine and quinolate in the UC group. The network of correlations between metabolites shows clear differences in correlations between steroids, fatty acids, sphyngomyelins, amino acids, and γ glutamyl peptides between the 3 groups, suggesting a more flexible and resilient metabolism in the HT and RT groups compared with UC. Conclusion: This first exploratory study investigating metabolic effects of Healing Touch in cancer patients indicated suggestive differences in metabolic signatures which need further investigation in a larger study.

The biology of hope: Inflammatory and neuroendocrine profiles in ovarian cancer patients

Although the concept of hope is highly relevant for cancer patients, little is known about its association with cancer-relevant biomarkers. Here we examined how hope was related to diurnal cortisol and interleukin-6 (IL-6), a pro-inflammatory cytokine previously associated with tumor biology and survival in ovarian cancer. Secondly, we examined whether hope and hopelessness are distinctly associated with these biomarkers. Participants were 292 high-grade ovarian cancer patients who completed surveys and provided saliva samples 4x/daily for 3 days pre-surgery to assess diurnal cortisol. Blood (pre-surgery) and ascites were assessed for IL-6. Hope and hopelessness were assessed using standardized survey items from established scales (Center for Epidemiological Studies Depression Scale; Profile of Mood States, Functional Assessment of Cancer Therapy). Two hopeless items were z-scored and combined into a composite for analysis. Regression models related these variables to nocturnal cortisol, cortisol slope, plasma and ascites IL-6, adjusting for cancer stage, BMI, age, and depression. Greater hope was significantly related to a steeper cortisol slope, β = -0.193, p = 0.046, and lower night cortisol, β = -0.227, p = 0.018, plasma IL-6, β = -0.142, p = 0.033, and ascites IL-6, β = -0.290, p = 0.002. Secondary analyses including both hope and hopelessness showed similar patterns, with distinct relationships of hope with significantly lower nocturnal cortisol β = -0.233,p = 0.017 and ascites IL-6, β = -0.282,p = 0.003, and between hopelessness and a flatter cortisol slope, β = 0.211, p = 0.031. These data suggest a biological signature of hope associated with less inflammation and more normalized diurnal cortisol in ovarian cancer. These findings have potential clinical utility but need replication with more diverse samples and validated assessments of hope.

Epithelial‐mesenchymal transition polarization in ovarian carcinomas from patients with high social isolation

BackgroundSocial isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. In patients with ovarian cancer, social isolation has been found to be related to decreased survival and multiple biomarkers supporting tumor progression. However, to the authors' knowledge, little is known regarding the relationship between social isolation and the molecular characteristics of ovarian tumors. Herein, the authors have used genome‐wide transcriptional profiling to quantify associations between social isolation and epithelial‐mesenchymal transition (EMT) polarization in ovarian tumors and transcriptome‐driven, promoter‐based bioinformatics analyses to identify gene regulatory pathways that may potentially underlie these changes.MethodsTumor was sampled during primary surgical resection and immediately frozen in liquid nitrogen. After RNA extraction, microarray analysis of the transcriptome was performed and samples were analyzed to assess associations between EMT‐related gene transcripts and social isolation (as indicated by a Social Provisions Scale Attachment subscale score <15). Convergent validation was provided by a promoter‐based bioinformatic analysis of transcription factor activity.ResultsPrimary analyses of 99 women demonstrated a lower average expression of gene transcripts previously associated with epithelial differentiation in women with high social isolation (−0.143 ± 0.048 log2 mRNA abundance; P = .004), but no difference in mesenchymal differentiation as a function of social isolation (+0.007 ± 0.0064 log2 mRNA abundance; P = .900). Upregulated activity was shown for 3 of the 4 targeted EMT‐related transcription factors, including GATA4 (P = .014); SMAD2, SMAD3, and/or SMAD4 (P < .001); and TWIST1 (P < .001). Analyses of SNAIL2/SLUG activity indicated a directional trend toward increased activity that did not reach statistical significance (P = .123).ConclusionsThe findings of the current study demonstrated differential EMT polarization and EMT‐related transcription factor activity according to social isolation, a known socioenvironmental risk factor.Lay Summary Social isolation has shown robust associations with clinical outcomes in the general population and in patients with cancer. Herein, the authors examined the relationship between social isolation and the molecular characteristics of ovarian tumors. The authors investigated the epithelial‐mesenchymal transition (EMT), a process whereby tumor cells lose epithelial characteristics and become more embryonic (mesenchymal), thereby enhancing invasiveness. Primary analyses demonstrated lower expression of genes previously associated with epithelial differentiation and increased activity of specific EMT‐related transcription factors in individuals with high social isolation, indicating increased EMT polarization in these patients. These findings extend the understanding of how socioenvironmental factors may modulate tumor growth.

Chronic difficulties are associated with poorer psychosocial functioning in the first year post‐diagnosis in epithelial ovarian cancer patients

AbstractObjectiveOvarian cancer is characterized by poor prognosis, high levels of distress, disturbed sleep, and compromised quality of life (QOL). Although life stressors have been shown to significantly impact physical and psychological health in cancer populations, no studies have used a high‐resolution stress assessment to differentiate effects of acute versus chronic stressors among women with ovarian cancer. We addressed this issue in the present prospective longitudinal study by examining how acute and chronic stress exposure in the year pre‐diagnosis relate to depressive symptoms, sleep quality, and QOL over the first year post‐diagnosis in women with ovarian cancer.MethodsOne hundred thirty‐seven women completed the Life Events and Difficulties Schedule within a month of initial treatment for suspected ovarian cancer. Depressive symptoms, sleep, and QOL were measured pre‐treatment, at six months, and one‐year post‐diagnosis. Mixed models were used to examine associations of acute and chronic stress pre‐diagnosis with (a) change in psychosocial outcomes over the first year post‐diagnosis and (b) levels of psychosocial outcomes across all time points.ResultsBoth the number and severity of chronic difficulties (but not acute life events) were related to significantly greater depression, and poorer sleep quality and QOL, across all time‐points. In contrast, these stress indices were unrelated to changes in psychosocial functioning over time.ConclusionsChronic but not acute stress exposure predicted average levels of depression, sleep, and QOL in the first year post‐diagnosis among women with ovarian cancer. Assessing stressors and designing interventions for reducing stress may thus be beneficial for ovarian cancer patients.

Biobehavioral factors predict an exosome biomarker of ovarian carcinoma disease progression

AbstractBackgroundBiobehavioral factors such as social isolation and depression have been associated with disease progression in ovarian and other cancers. Here, the authors developed a noninvasive, exosomal RNA profile for predicting ovarian cancer disease progression and subsequently tested whether it increased in association with biobehavioral risk factors.MethodsExosomes were isolated from plasma samples from 100 women taken before primary surgical resection or neoadjuvant (NACT) treatment of ovarian carcinoma and 6 and 12 months later. Biobehavioral measures were sampled at all time points. Plasma from 76 patients was allocated to discovery analyses in which morning presurgical/NACT exosomal RNA profiles were analyzed by elastic net machine learning to identify a biomarker predicting rapid (≤6 months) versus more extended disease‐free intervals following initial treatment. Samples from a second subgroup of 24 patients were analyzed by mixed‐effects linear models to determine whether the progression‐predictive biomarker varied longitudinally as a function of biobehavioral risk factors (social isolation and depressive symptoms).ResultsAn RNA‐based molecular signature was identified that discriminated between individuals who had disease progression in ≤6 months versus >6 months, independent of clinical variables (age, disease stage, and grade). In a second group of patients analyzed longitudinally, social isolation and depressive symptoms were associated with upregulated expression of the disease progression propensity biomarker, adjusting for covariates.ConclusionThese data identified a novel exosome‐derived biomarker indicating propensity of ovarian cancer progression that is sensitive to biobehavioral variables. This derived biomarker may be potentially useful for risk assessment, intervention targeting, and treatment monitoring.