CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid–base homeostasis. Cftr has been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping Beauty DNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated ApcMin mice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftr is a tumor suppressor gene in the intestinal tract as Cftr mutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc+/+ mice aged to ~ 1 year, Cftr deficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftr mutant mice compared with wild-type controls, suggesting a potential role of Cftr in regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc+/+ Cftr knockout mice and identified sets of genes dysregulated in tumors including altered Wnt β-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease-free survival.

Dermatomyositis is a chronic inflammatory disease involving the skin and muscles. It most commonly occurs in adults with preponderance in females, but pediatric occurrence is also possible. The risk of malignancy in adult patients with dermatomyositis was reported to be 4.66-fold higher compared to that in the general population. A significantly increased risk of malignancy was reported within the first 12 months following the diagnosis of dermatomyositis (standardized incidence ratio equaled 17). One of the characteristic laboratory findings associated with dermatomyositis is the presence of circulating autoantibodies which are classified into two subgroups: myositis-specific and myositis-associated autoantibodies. It was shown that specific types of antibodies might be associated with an increased risk of malignancy. Current literature data indicate that the strongest correlation with malignant diseases was reported in anti-TIF1-γ-positive patients who were at a 9.37-fold higher risk of cancer. A 3.68-fold increase in the risk of cancer was also reported among patients with anti-NXP2 antibodies. Malignant diseases were reported in 14–57% of patients with anti-SAE antibodies. The presence of other autoantibodies may also be associated with an increased risk of malignancy. These data indicate that patients with circulating anti-TIF1-γ, anti-NXP2, and anti-SAE should be very closely monitored for dermatomyositis-associated malignant comorbidities. The aim of this review is to summarize the current data regarding the link between malignancy and the presence of specific antibodies in patients with dermatomyositis.

Scleroderma (morphea) en coup de sabre is a localized subtype restricted to the frontoparietal region of the head. Current treatment paradigms rely on low levels of evidence, primarily case reports and case series-supported by expert opinions. The aim of this article was to systematically analyze current data related to the treatment of localized scleroderma en coup de sabre. The databases Scopus, PubMed, and EBSCO were searched for all reports discussing the treatment of localized scleroderma en coup de sabre. The keywords en coup de sabre, “facial linear scleroderma”, and “morphea linearis”, combined with “treatment” or “therapy” were used as search terms. A total of 34 articles analyzed treatment outcomes for patients with localized scleroderma en coup de sabre including 4 retrospective cohort studies, 2 prospective cohort studies, 4 case series, and 24 case reports, representing a total of 69 patients (38 children and 31 adults). Methotrexate was the most commonly investigated treatment (26 patients) with a highest response rate (26/26, 100%). Other treatments included systemic glucocorticosteroids (nine patients), followed by UVA1 (four patients), mycophenolate mofetil (two patients), hydroxychloroquine (five patients), abatacept (two patients), tocilizumab (three patients), cyclosporine (one patient), interferon gamma (one patient), PUVA therapy (two patients), NB-UVB therapy (one patient), and pulsed dye laser (one patient). Reconstructive and surgery treatment was successfully used for lesions with settled disease activity to improve the cosmetic aspect of the lesions. Conclusion: methotrexate is the most often-studied treatment and reported good clinical outcomes in children and adults with localized scleroderma en coup de sabre.

Alopecia areata is an autoimmune, inflammatory form of non-scarring hair loss that may affect any hair-bearing area. Recently, an increased risk of cardiovascular disorders has been described in patients with alopecia areata. The aim of the study was to evaluate the serum concentrations of proinflammatory proteins associated with atherosclerosis (chemokine C-C motif ligand 4; CCL4, chemokine C-C motif ligand 7, CCL7; and sortilin, SORT1), and cardiovascular risk (myeloperoxidase, MPO; interleukin 1 receptor-like 1, IL1RL1; and growth differentiation factor 15, GDF15) in patients with alopecia areata without symptoms or prior cardiovascular disease in comparison with healthy controls. Sixty otherwise healthy patients with alopecia areata and twenty control subjects matched for age, gender, and body mass index (BMI) were enrolled in the study. No significant differences in the serum levels of MPO, IL1RL1, CCL4, CCL7, SORT1, and GDF15 were detected between patients with alopecia areata and healthy controls. A positive correlation was found between the serum concentration of CCL7 and the severity of alopecia areata (r = 0.281, p = 0.03), while GDF15 correlated with age at the disease onset (r = 0.509, p < 0.0001). The results of the present study suggest that the severity of alopecia areata may be associated with an increased risk of atherosclerosis.

Background Alopecia areata (AA) is an autoimmune form of hair loss, which may affect any hair‐bearing area. It has been suggested that AA is associated with an increased risk of metabolic and cardiovascular comorbidities. Aim To evaluate the early predictors of cardiovascular disease [endothelial function (EF) and arterial stiffness (AS)] in patients with AA without prior cardiovascular disease, and compare with healthy controls (HCs). Methods In total, 52 patients with AA (38 women and 14 men; mean age 41 years, range 30–52 years) and 34 HCs, matched for age, sex and body mass index, were enrolled in the study. EF, expressed as reactive hyperaemia index (RHI), and AS, identified by augmentation index at 75 beats/min (AI@75) were assessed with the use of the Endo‐PAT 2000 device. Endothelial dysfunction (ED) was defined as RHI value ≤1.67. Results ED was observed in 22 of 52 patients with AA (42%) and in 4 of 34 HCs (12%) (P < 0.01). Moreover, mean RHI was lower in patients with AA compared with HCs (1.90 ± 0.31 vs. 2.11 ± 0.45; P = 0.03). There was no significant difference in AI@75 between patients with AA and HCs. Conclusions Patients with AA show abnormalities in early predictors of cardiovascular diseases. Regular cardiovascular screening might be appropriate for patients with AA.