Plasma microRNA levels following resection of metastatic melanoma

Melanoma remains the leading cause of skin cancer–related deaths. Surgical resection and adjuvant therapies can result in disease-free intervals for stage III and stage IV disease; however, recurrence is common. Understanding microRNA (miR) dynamics following surgical resection of melanomas is critical to accurately interpret miR changes suggestive of melanoma recurrence. Plasma of 6 patients with stage III (n = 2) and stage IV (n = 4) melanoma was evaluated using the NanoString platform to determine pre- and postsurgical miR expression profiles, enabling analysis of more than 800 miRs simultaneously in 12 samples. Principal component analysis detected underlying patterns of miR expression between pre- vs postsurgical patients. Group A contained 3 of 4 patients with stage IV disease (pre- and postsurgical samples) and 2 patients with stage III disease (postsurgical samples only). The corresponding preoperative samples to both individuals with stage III disease were contained in group B along with 1 individual with stage IV disease (pre- and postsurgical samples). Group A was distinguished from group B by statistically significant analysis of variance changes in miR expression ( P < .0001). This analysis revealed that group A vs group B had downregulation of let-7b-5p, miR-520f, miR-720, miR-4454, miR-21-5p, miR-22-3p, miR-151a-3p, miR-378e, and miR-1283 and upregulation of miR-126-3p, miR-223-3p, miR-451a, let-7a-5p, let-7g-5p, miR-15b-5p, miR-16-5p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-26a-5p, miR-106a-5p, miR-17-5p, miR-130a-3p, miR-142-3p, miR-150-5p, miR-191-5p, miR-199a-3p, miR-199b-3p, and miR-1976. Changes in miR expression were not readily evident in individuals with distant metastatic disease (stage IV) as these individuals may have prolonged inflammatory responses. Thus, inflammatory-driven miRs coinciding with tumor-derived miRs can blunt anticipated changes in expression profiles following surgical resection

GN and C Subsystem Concept for Safe Precision Landing of the Proposed Lunar MARE Robotic Science Mission

The Lunar MARE (Moon Age and Regolith Explorer) Discovery Mission concept targets delivery of a science payload to the lunar surface for sample collection and dating. The mission science is within a 100-meter radius region of smooth lunar maria terrain near Aristarchus crater. The location has several small, sharp craters and rocks that present landing hazards to the spacecraft. For successful delivery of the science payload to the surface, the vehicle Guidance, Navigation and Control (GN&C) subsystem requires safe and precise landing capability, so design infuses the NASA Autonomous precision Landing and Hazard Avoidance Technology (ALHAT) and a gimbaled, throttleable LOX/LCH4 main engine. The ALHAT system implemented for Lunar MARE is a specialization of prototype technologies in work within NASA for the past two decades, including a passive optical Terrain Relative Navigation (TRN) sensor, a Navigation Doppler Lidar (NDL) velocity and range sensor, and a Lidar-based Hazard Detection (HD) sensor. The landing descent profile is from a retrograde orbit over lighted terrain with landing near lunar dawn. The GN&C subsystem with ALHAT capabilities will deliver the science payload to the lunar surface within a 20-meter landing ellipse of the target location and at a site having greater than 99% safety probability, which minimizes risk to safe landing and delivery of the MARE science payload to the intended terrain region

Cognitive problems among breast cancer survivors: loneliness enhances risk

Abstract Background: Cancer survivors often experience cognitive difficulties after treatment completion. Although chemotherapy enhances risk for cognitive problems, it is likely only one piece of a complex puzzle that explains survivors&apos; cognitive functioning. Loneliness may be one psychosocial risk factor. The current studies included both subjective and objective cognitive measures and tested whether lonelier breast cancer survivors would have more concentration and memory complaints and experience more concentration difficulties than their less lonely counterparts. Methods: The relationship between loneliness and cognitive function was tested among three samples of breast cancer survivors. Study 1 was a sample of breast cancer survivors (n = 200) who reported their concentration and memory problems. Study 2a was a sample of breast cancer survivors (n = 185) and noncancer controls (n = 93) who reported their concentration and memory problems. Study 2b was a subsample of Study 2a breast cancer survivors (n = 22) and noncancer controls (n = 21) who completed a standardized neuropsychological test assessing concentration. Results: Studies 1 and 2a revealed that lonelier women reported more concentration and memory problems than less lonely women. Study 2b utilized a standardized neuropsychological continuous performance test and demonstrated that lonelier women experienced more concentration problems than their less lonely counterparts. Conclusions: These studies demonstrated that loneliness is linked to concentration and memory complaints and the experience of concentration problems among breast cancer survivors. The results were also highly consistent across three samples of breast cancer survivors. These data suggest that loneliness may be a risk factor for cognitive difficulties among cancer survivors

Precancerous Stem Cells Have the Potential for both Benign and Malignant Differentiation

Cancer stem cells (CSCs) have been identified in hematopoietic and solid tumors. However, their precursors—namely, precancerous stem cells (pCSCs) —have not been characterized. Here we experimentally define the pCSCs that have the potential for both benign and malignant differentiation, depending on environmental cues. While clonal pCSCs can develop into various types of tissue cells in immunocompetent mice without developing into cancer, they often develop, however, into leukemic or solid cancers composed of various types of cancer cells in immunodeficient mice. The progress of the pCSCs to cancers is associated with the up-regulation of c-kit and Sca-1, as well as with lineage markers. Mechanistically, the pCSCs are regulated by the PIWI/AGO family gene called piwil2. Our results provide clear evidence that a single clone of pCSCs has the potential for both benign and malignant differentiation, depending on the environmental cues. We anticipate pCSCs to be a novel target for the early detection, prevention, and therapy of cancers

Depression and Anxiety In Colorectal Cancer Patients: Ties To Pain, Fatigue, and Inflammation

Objective: Colorectal cancer poses a significant threat to both psychological and physical health. This study examined relationships between anxiety and depressive symptoms with pain, fatigue, and inflammation among colorectal patients. Methods: Colorectal cancer patients (n = 88, stages 0-IV) completed a laboratory-based study visit before undergoing adjuvant cancer treatment. Patients completed questionnaires assessing depressive, anxiety, pain, and fatigue symptoms. A blood sample was also collected to measure c-reactive protein (CRP). Analyses controlled for age, sex, cancer stage, body mass index (BMI), and menopause status. Results: Multiple linear regression analyses showed colorectal patients with higher depressive and anxiety symptoms had greater pain, fatigue, and CRP (ps \u3c 0.03). Approximately one-third of patients with clinically significant depressive (CESD \u3e16) and anxiety symptoms (BAI \u3e16) also had clinically-elevated levels of CRP (\u3e3 mg/L) (ps = 0.02). Conclusion: These results extend findings from other cancer subgroups showing heightened symptom burden among patients with depression and anxiety. They also highlight the detrimental role that elevated anxiety and depressive symptoms may play in the physical and biological side effects associated with colorectal cancer

Biobehavioral, Immune, and Health Benefits following Recurrence for Psychological Intervention Participants

Abstract Purpose: A clinical trial was designed to test the hypothesis that a psychological intervention could reduce the risk of cancer recurrence. Newly diagnosed regional breast cancer patients (n = 227) were randomized to the intervention-with-assessment or the assessment-only arm. The intervention had positive psychological, social, immune, and health benefits, and after a median of 11 years the intervention arm was found to have reduced the risk of recurrence (hazard ratio, 0.55; P = 0.034). In follow-up, we hypothesized that the intervention arm might also show longer survival after recurrence. If observed, we then would examine potential biobehavioral mechanisms. Experimental Design: All patients were followed; 62 recurred. Survival analyses included all 62. Upon recurrence diagnosis, those available for further biobehavioral study were accrued (n = 41, 23 intervention and 18 assessment). For those 41, psychological, social, adherence, health, and immune (natural killer cell cytotoxicity, T-cell proliferation) data were collected at recurrence diagnosis and 4, 8, and 12 months later. Results: Intent-to-treat analysis revealed reduced risk of death following recurrence for the intervention arm (hazard ratio, 0.41; P = 0.014). Mixed-effects follow-up analyses with biobehavioral data showed that all patients responded with significant psychological distress at recurrence diagnosis, but thereafter only the intervention arm improved (P values &lt; 0.023). Immune indices were significantly higher for the intervention arm at 12 months (P values &lt; 0.017). Conclusions: Hazards analyses augment previous findings in showing improved survival for the intervention arm after recurrence. Follow-up analyses showing biobehavioral advantages for the intervention arm contribute to our understanding of how improved survival was achieved. Clin Cancer Res; 16(12); 3270-8. ©2010 AACR. Meta-analyses suggest that stress-related psychosocial factors (1) and lower health-related quality of life (2) are associated with poorer cancer survival, with a 13% increase in the hazard ratio (HR) in studies of breast cancer patients (1). In 1994 a randomized controlled trial, the Stress and Immunity Breast Cancer Project (SIBCP), was designed to test the hypothesis that newly diagnosed breast cancer patients receiving a psychological intervention would have a reduced risk of recurrence and breast cancer death compared with patients who were only assessed. A conceptual model guided the development of the clinical trial. The Biobehavioral Model of Cancer Stress and Disease Course (3) proposes that psychological stress leads to disruptions in quality of life, health behaviors, and immunity, which in turn contribute to poorer disease outcomes. It was hypothesized that an intervention designed to reduce emotional distress and improve social adjustment, health behaviors, and adherence might also improve immunity and disease course. Analyses showed that positive intervention effects were achieved across the psychological and immune outcomes at 4 months (4) with similar effects and improved health at 12 months (5). Moreover, recent end point analyses show that after a median follow-up of 11 years, the intervention arm had a reduced risk of breast cancer recurrence (HR, 0.55; P = 0.034) and breast cancer death (HR, 0.44; P = 0.016) compared with the assessment-only arm (6). As cancer progresses, the ability of psychological intervention to affect disease course may change. The intervention was hypothesized to reduce the risk of recurrence, and it may have been solely through this reduction in recurrence risk that mortality was affected