CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Did quality of life for older cancer survivors improve with the turn of the century in the United States?

ObjectivesAlthough survival after a cancer diagnosis has improved considerably over the past 20 years, little is known about trends in health-related quality-of-life (HRQOL) for older prostate, breast, and lung cancer survivors.MethodsUsing a population-based registry with longitudinal patient reported outcomes (the National Cancer Institute Surveillance, Epidemiology and End Results database linked to Medicare Health Outcomes Survey), we analyzed Medicare Advantage patients diagnosed with cancer during 1998–2011, who completed surveys regarding HRQOL through 2013. ‘Early Era’ patients were treated during 1998–2003; ‘Late Era’ patients were treated during 2006–2011. After propensity score matching, post-diagnosis changes in health utility (HU), Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were calculated and compared between the two eras.ResultWe identified 208 older patients with prostate, 276 with breast and 76 with lung cancer who were treated in the ‘Early Era’ and matched to equal numbers in the ‘Late Era’. Mean age of patients in early and late era was 72 and 73 years, respectively. The mean post-diagnosis decline in health utility for patients treated in the ‘Late Era’ was not significantly different from the ‘Early Era’ for any cancer (Prostate [early vs. late]: ?0.06 vs. -0.03, p = .09; Breast: ?0.03 vs. ?0.04, p = .65; Lung: ?0.07 vs. ?0.07, p = .95); nor for Physical Component Summary or Mental Component Summary scores.ConclusionOlder patients treated for prostate, breast or lung cancer in the later era reported similar outcomes of changes in HRQOL compared to earlier era patients.     

Smartphone Addiction and Its Relationship with Indices of Social-Emotional Distress and Personality

International Journal of Mental Health and Addiction - We examined the relationships among smartphone addiction, social-emotional distress (e.g., anxiety, depression, sleep quality, and...     

IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer

Preclinical studies indicate that activated IGF-1R can drive endocrine resistance in ER-positive (ER+) breast cancer, but its clinical relevance is unknown. We studied the effect of IGF-1R signaling on tamoxifen benefit in patients and we searched for approaches to overcome IGF-1R-mediated tamoxifen failure in cell lines. Primary tumor blocks from postmenopausal ER+ breast cancer patients randomized between adjuvant tamoxifen versus nil were recollected. Immunohistochemistry for IGF-1R, p-IGF-1R/InsR, p-ERα(Ser118), p-ERα(Ser167) and PI3K/MAPK pathway proteins was performed. Multivariate Cox models were employed to assess tamoxifen efficacy. The association between p-IGF-1R/InsR and PI3K/MAPK pathway activation in MCF-7 and T47D cells was analyzed with Western blots. Cell proliferation experiments were performed under various growth-stimulating and -inhibiting conditions. Patients with ER+, IGF-1R-positive breast cancer without p-IGF-1R/InsR staining (n = 242) had tamoxifen benefit (HR 0.41, p = 0.0038), while the results for p-IGF-1R/InsR-positive patients (n = 125) were not significant (HR 0.95, p = 0.3). High p-ERα(Ser118) or p-ERα(Ser167) expression was associated with less tamoxifen benefit. In MCF-7 cells, IGF-1R stimulation increased phosphorylation of PI3K/MAPK proteins and ERα(Ser167) regardless of IGF-1R overexpression. This could be abrogated by the dual IGF-1R/InsR inhibitor linsitinib, but not by the IGF-IR-selective antibody 1H7. In MCF-7 and T47D cells, stimulation of the IGF-1R/InsR pathway resulted in cell proliferation regardless of tamoxifen. Abrogation of cell growth was regained by addition of linsitinib. In conclusion, p-IGF-1R/InsR positivity in ER+ breast cancer is associated with reduced benefit from adjuvant tamoxifen in postmenopausal patients. In cell lines, stimulation rather than overexpression of IGF-1R is driving tamoxifen resistance to be abrogated by linsitinib.