Tankyrase 1 and Tankyrase 2 Are Essential but Redundant for Mouse Embryonic Development

Tankyrases are proteins with poly(ADP-ribose) polymerase activity. Human tankyrases post-translationally modify multiple proteins involved in processes including maintenance of telomere length, sister telomere association, and trafficking of glut4-containing vesicles. To date, however, little is known about in vivo functions for tankyrases. We recently reported that body size was significantly reduced in mice deficient for tankyrase 2, but that these mice otherwise appeared developmentally normal. In the present study, we report generation of tankyrase 1-deficient and tankyrase 1 and 2 double-deficient mice, and use of these mutant strains to systematically assess candidate functions of tankyrase 1 and tankyrase 2 in vivo. No defects were observed in development, telomere length maintenance, or cell cycle regulation in tankyrase 1 or tankyrase 2 knockout mice. In contrast to viability and normal development of mice singly deficient in either tankyrase, deficiency in both tankyrase 1 and tankyrase 2 results in embryonic lethality by day 10, indicating that there is substantial redundancy between tankyrase 1 and tankyrase 2, but that tankyrase function is essential for embryonic development

Cancer-Related Pain and Disability: A Longitudinal Study

Context Although the cross-sectional association between cancer-related pain and disability is well established, their longitudinal relationship has been less studied. Objectives Data from the Indiana Cancer Pain and Depression (INCPAD) trial were analyzed to determine whether baseline cancer-related pain and changes in pain over time predict disability over 12 months. Methods A total of 274 cancer survivors with cancer-related pain were accrued in the INCPAD trial. Data were collected at baseline, one, three, six, and 12 months by interviewers blinded to treatment arm. Disability outcomes included a continuous measure (Sheehan Disability Scale [SDS] score) and a categorical measure (≥14 days in the past four weeks with a ≥50% reduction in usual activities). Predictor variables, operationalized by the Brief Pain Inventory, included baseline pain severity and changes in pain severity scores between each time point. Multivariable analyses were conducted adjusting for treatment group, baseline disability, and selected covariates including depression. Results Baseline pain severity did not predict disability outcomes at 12 months. However, improvement in pain severity predicted less disability over 12 months both in terms of SDS scores (b = −0.17, t = −5.33, P < 0.001) and ≥14 disability days in the past month (odds ratio = 0.85; 95% confidence interval, 0.79–0.93; P < 0.001). Conclusion Disability over 12 months in patients with cancer-related pain is predicted by changes in pain severity over time. Results suggest that effective pain management may reduce subsequent disability among cancer survivors

Predictors of Cancer-related Pain Improvement Over Time

Objective To determine the predictors of pain improvement among patients being treated for cancer-related pain over 12 months. Methods A secondary analysis of the telephone care Indiana Cancer Pain and Depression trial was performed. Patients (n = 274) were interviewed at baseline and after 1, 3, 6, and 12 months. Pain improvement outcomes included both a continuous measure (Brief Pain Inventory score) and a categorical measure (pain improved versus pain not improved). Predictor variables included change in depression, age, sex, race, marital status, socioeconomic disadvantage, medical comorbidity, type of cancer, and phase of cancer. Multivariable repeated measures were conducted, adjusting for intervention group assignment, baseline pain severity, and time in months since baseline assessment. Results Factors significantly predicting both continuous and categorical pain improvement included participating in the intervention group (β = −0.92, p < .001, odds ratio [OR] = 2.53, 95% confidence interval [CI] = 1.65–3.89), greater improvement in depression (β = −0.31, p = .003, OR = 1.84, 95% CI = 1.35–2.51), higher socioeconomic status (Socioeconomic Disadvantage index; β = 0.25, p = .034; OR = 0.73, 95% CI = 0.56–0.94), and fewer comorbid conditions (β = 0.20, p = .002; OR = 0.84, 95% CI = 0.73–0.96). Patients with more severe pain at baseline or with recurrent or progressive cancer were less likely to experience continuous or categorical pain improvement, respectively. Conclusions Effective management of depression and comorbid conditions along with improvement of social services could be critical components of a comprehensive pain management. Patients with more severe pain or with recurrent or progressive cancers may require closer monitoring and adequate treatment of pain

Predictors of Health-related Quality of Life at One Month after Head and Neck Cancer Surgery

poster abstractSignificance: Head and neck cancer (HNC) survivors frequently experience treatment-related complications that may cause decrements in health-related quality of life (HRQOL). Before interventions can be designed to enhance HRQOL in the early postoperative period, descriptive research is needed to determine predictors of HRQOL in this understudied population. Problem and Purpose: The proposed study identified predictors of global HRQOL, and physical, functional, emotional, and social well-being at one month after HNC surgery. Variables examined as potential predictors included shoulder pain, shoulder function, and functional impairments (disfigurement, and eating, speech, and breathing impairments). Theoretical Framework: The University of California, San Francisco School of Nursing Symptom Management Model was modified and used to guide the study. Methods and Analysis: In this exploratory, cross-sectional study, we examined a convenience sample of 29 patients who had undergone HNC surgery with curative intent one month previously. Global HRQOL was measured using the Functional Assessment of Chronic Illness Therapy (FACIT) General Scale, including four well-being subscales. Shoulder pain intensity was measured using the Brief Pain Inventory, shoulder pain distress was measured using a 0-10 numerical rating scale, and functional impairment was measured using the FACIT Head and Neck Subscale. Shoulder function was assessed using a goniometer. Pearson correlations were initially applied to determine correlates (p <0.20) that should be entered in subsequent stepwise regression models. Findings and Implications: The only significant predictor of global HRQOL was eating impairment (B = -0.20, p = 0.02). Predictors of physical well-being were shoulder pain distress (B = -0.10, p = 0.02) and eating impairment (B = 0.27, p = 0.03). Predictors of functional well-being were speech impairment (B = -0.43, p < 0.01) and disfigurement (B = - 0.20, p = 0.02). No significant predictors were found for emotional and social well-being. The findings suggested that patients’ physical and functional well-being can be influenced by eating impairment, shoulder pain distress, speech impairment, or disfigurement at one month after HNC surgery. Nurses need to monitor nutrition intake, provide proper pain management, and collaborate with speech and physical therapists to promote early rehabilitation. A longitudinal study with a larger sample size is warranted to describe needs for multidisciplinary care to improve HQOL after HNC surgery

Targeting SLMAP-ALK—a novel gene fusion in lung adenocarcinoma

Assessment of ALK gene rearrangements is strongly recommended by the Molecular Testing Guideline for Selection of Lung Cancer Patients proposed by IASLC, AMP, and CAP at the time of diagnosis for patients with advanced stage disease. Non- small-cell lung cancer (NSCLC) with ALK gene rearrangements or the resulting fusion pro- teins have been, for the most part, successfully targeted with ALK tyrosine kinase inhibitors (TKIs). The most frequent rearrangement, the EML4-ALK oncogenic fusion, has more than 10 distinct variants, each with a discrete breakpoint in EML4. Recent studies have suggested that EML4-ALK variants may have differential responses to TKIs. Additionally, non-EML4- ALK fusions that result from ALK rearrangements with diverse 5′ partners could possibly have varied biologic and clinical implications in their therapeutic responses and outcomes of patients with NSCLC. Existing literature documents at least 20 non-EML4 fusion partners for ALK, and the clinical responsiveness to crizotinib ranges from increased sensitivity to re- sistance. This underscores the importance of identifying the precise 5′ fusion partner to ALK before initiation of therapy. Herein we report the identification of a novel SLMAP-ALK fusion in a patient with NSCLC

Predictors of stage of adoption for colorectal cancer screening among African American primary care patients

BACKGROUND: Compared with other racial groups, African Americans have the highest colorectal cancer (CRC) incidence and mortality rates coupled with lower screening rates. OBJECTIVE: Our study examined the predictors of stage of adoption for fecal occult blood testing (FOBT) and colonoscopy among African American primary care patients who were nonadherent to published screening guidelines. METHODS: Baseline data (N = 815) in a randomized clinical trial were analyzed. Participants were categorized into precontemplation, contemplation, and preparation stages for FOBT and colonoscopy. Predictor variables were demographics, clinical variables, CRC health beliefs and knowledge, and social support. Hierarchical modeling was to identify significant predictors of stage of adoption. RESULTS: Older, male, Veterans Affairs participants and those with higher perceived self-efficacy, family/friend encouragement, and a provider recommendation had higher odds of being at a more advanced stage of adoption for FOBT. Patients with a history of cancer and higher perceived barriers had higher odds of being at an earlier stage of adoption for FOBT. Predictors of more advanced stage of adoption for colonoscopy included higher perceived benefits, higher perceived self-efficacy, family/friend encouragement, and a provider recommendation for colonoscopy. Higher income (>30 000 vs <15 000) was predictive of earlier stage of adoption for colonoscopy. CONCLUSIONS: Enhancing self-efficacy, encouragement from family and friends, and provider recommendations are important components of interventions to promote CRC screening. IMPLICATIONS FOR PRACTICE: Nurses can use knowledge of the characteristics associated with stage of adoption to educate and motivate their African American primary care patients to complete CRC screening tests