Update on Glycosphingolipids Abundance in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Low numbers of HCC patients being suitable for liver resection or transplantation and multidrug resistance development during pharmacotherapy leads to high death rates for HCC patients. Understanding the molecular mechanisms of HCC etiology may contribute to the development of novel therapeutic strategies for prevention and treatment of HCC. UDP-glucose ceramide glycosyltransferase (UGCG), a key enzyme in glycosphingolipid metabolism, generates glucosylceramide (GlcCer), which is the precursor for all glycosphingolipids (GSLs). Since UGCG gene expression is altered in 0.8% of HCC tumors, GSLs may play a role in cellular processes in liver cancer cells. Here, we discuss the current literature about GSLs and their abundance in normal liver cells, Gaucher disease and HCC. Furthermore, we review the involvement of UGCG/GlcCer in multidrug resistance development, globosides as a potential prognostic marker for HCC, gangliosides as a potential liver cancer stem cell marker, and the role of sulfatides in tumor metastasis. Only a limited number of molecular mechanisms executed by GSLs in HCC are known, which we summarize here briefly. Overall, the role GSLs play in HCC progression and their ability to serve as biomarkers or prognostic indicators for HCC, requires further investigation

Predictor variables and screening protocol for depressive and anxiety disorders in cancer outpatients

Background Cancer patients are at increased risk of persistent depressive and anxiety symptoms and disorders compared to the general population. However, these issues are not always identified, which may worsen the prognosis and increase morbidity and mortality. Therefore, the objectives of this study are to identify predictor variables (demographic and clinical) for the development of mood and anxiety disorders in cancer outpatients and to propose a probabilistic screening protocol considering these variables and certain standardized screening instruments. Methods A total of 1,385 adults, of both genders, receiving outpatient cancer care were evaluated using a questionnaire and screening instruments. Thereafter, 400 of these subjects responded to the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (SCID-IV) by telephone to confirm or rule out the presence of a Current Major Depressive Episode (CMDE) or Anxiety Disorder (AD). Results Of the patients surveyed, 64% met the criteria for CMDE and 41% for AD. Female gender was found to be a risk factor for both disorders, and the presence of previous psychiatric history and marital status (divorced and widowed) were risk factors for anxiety disorders. When scoring above the recommended cutoff score, the screening instruments also indicated a risk of the studied disorders. Based on these findings, a screening protocol and nomograms were created for the quantification, combination and probabilistic estimate of risk, with accuracy indicators >0.68. Conclusion The prevalence rates for the disorders under study are extremely high in cancer patients. The use of the proposed protocol and nomogram can facilitate rapid and wide screening, thus refining triage and supporting the establishment of criteria for referral to mental health professionals, so that patients can be properly diagnosed and treated.info:eu-repo/semantics/publishedVersio

Resection of thoracic malignancies infiltrating cardiac structures with use of cardiopulmonary bypass

Background: Only few reports exist on malignant thoracic neoplasms that require cardiopulmonary bypass during resection. We aimed to investigate the early and late clinical outcome of these patients. Methods: Patients with thoracic malignancies that underwent surgery between 2002 and 2014 were analyzed. All patients had cardiopulomonary bypass support during resection. Clinical and perioperative data was retrospectively reviewed for outcome and overall survival. Results: Fifteen patients (12 female, mean age of 55 ± 15 years, range 24 to 80 years) were identified. Eleven (8 female) were diagnosed with primary thoracic malignomas and four with metastases. Three patients died early postoperatively. Patients diagnosed with sarcoma had a significantly worse outcome than non-sarcoma patients (83.3 ± 15.2 % after 1 year, 31.3 ± 24.5 % after 5 years vs. 83.3 ± 15.2 % after 1 year, 0 ± 0 % after 5 years, p = 0.005). Conclusions: Malignancies with extension into cardiac structures or infiltration of great vessels can be resected with cardiopulmonary bypass support and tolerable risk. Carefully selected patients can undergo advanced operative procedures with an acceptable 1-year-survival, but only few patients achieved good long-term outcome

Satisfaction with Life Scale among adolescents and young adults in Portugal: extending evidence of construct validity

The paper presents three empirical studies designed to extend the test of the construct validity of the Satisfaction With Life Scale (SWLS) among Portuguese students. In the first study, the responses of 461 elementary and secondary education students were submitted to a principal component analysis. A solution of one single factor was chosen, accounting for 55.7 % of the total variance, with Cronbach alpha coefficient and inter-item correlation above .70 and .20, respectively. The second study used a sample of 317 undergraduate students and registered a similar factor solution for SWLS (/pq = 0.99), which accounted for 65.6 % of the total variance (Cronbach alpha .89 and inter-item correlation above .20). A test–retest analysis registered coefficients of .70 (T2) and .77 (T3) and no significant statistically differences between T2, T3 and T1. The third study used a sample of 107 foster care youths from elementary and secondary education. Confirmatory factor analysis results indicate adequate fit indexes for the one-factor solution (v2/df = 2.70, GFI = .96, CFI = .96), which showed convergent validity, reliability and homogeneity. In conclusion, there is psychometric evidence for the one-factor structure of the SWLS in Portugal.FCTCOMPET

Differences in the Active Endometrial Microbiota across Body Weight and Cancer in Humans and Mice

Obesity is a risk factor for endometrial cancer. The aim of this study was to determine whether actively replicating microbiota in the endometrium differ between obese vs. lean and cancer vs. benign states. We performed 16S rRNA amplicon sequencing on endometrial tissues from lean and obese women with and without endometrial cancer, and lean and obese mice. Results displayed human endometrial microbiota clustered into three community types (R = 0.363, p = 0.001). Lactobacillus was dominant in community type 1 (C1) while community type 2 (C2) had high levels of Proteobacteria and more cancer samples when compared to C1 (p = 0.007) and C3 (p = 0.0002). A significant increase in the prevalence of the C2 community type was observed across body mass index and cancer (χ2 = 14.24, p = 0.0002). The relative abundance of Lactobacillus was lower in cancer samples (p = 0.0043), and an OTU with 100% similarity to Lactobacillus iners was enriched in control samples (p = 0.0029). Mouse endometrial microbiota also clustered into three community types (R = 0.419, p = 0.001) which were not influenced by obesity. In conclusion, obesity and cancer are associated with community type prevalence in the human endometrium, and Lactobacillus abundance is associated with normal uterine histologies in humans and mice

Increased glucosylceramide production leads to decreased cell energy metabolism and lowered tumor marker expression in non-cancerous liver cells

Hepatocellular carcinoma (HCC) is one of the most difficult cancer types to treat. Liver cancer is often diagnosed at late stages and therapeutic treatment is frequently accompanied by development of multidrug resistance. This leads to poor outcomes for cancer patients. Understanding the fundamental molecular mechanisms leading to liver cancer development is crucial for developing new therapeutic approaches, which are more efficient in treating cancer. Mice with a liver specific UDP-glucose ceramide glucosyltransferase (UGCG) knockout (KO) show delayed diethylnitrosamine (DEN)-induced liver tumor growth. Accordingly, the rationale for our study was to determine whether UGCG overexpression is sufficient to drive cancer phenotypes in liver cells. We investigated the effect of UGCG overexpression (OE) on normal murine liver (NMuLi) cells. Increased UGCG expression results in decreased mitochondrial respiration and glycolysis, which is reversible by treatment with EtDO-P4, an UGCG inhibitor. Furthermore, tumor markers such as FGF21 and EPCAM are lowered following UGCG OE, which could be related to glucosylceramide (GlcCer) and lactosylceramide (LacCer) accumulation in glycosphingolipid-enriched microdomains (GEMs) and subsequently altered signaling protein phosphorylation. These cellular processes lead to decreased proliferation in NMuLi/UGCG OE cells. Our data show that increased UGCG expression itself does not induce pro-cancerous processes in normal liver cells, which indicates that increased GlcCer expression leads to different outcomes in different cancer types. Graphic abstract: [Figure not available: see fulltext.

Cigarette smoking, nicotine dependence and anxiety disorders : a systematic review of population-based, epidemiological studies

Background Multiple studies have demonstrated that rates of smoking and nicotine dependence are increased in individuals with anxiety disorders. However, significant variability exists in the epidemiological literature exploring this relationship, including study design (cross-sectional versus prospective), the population assessed (random sample versus clinical population) and diagnostic instrument utilized.Methods We undertook a systematic review of population-based observational studies that utilized recognized structured clinical diagnostic criteria (Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD)) for anxiety disorder diagnosis to investigate the relationship between cigarette smoking, nicotine dependence and anxiety disorders.Results In total, 47 studies met the predefined inclusion criteria, with 12 studies providing prospective information and 5 studies providing quasiprospective information. The available evidence suggests that some baseline anxiety disorders are a risk factor for initiation of smoking and nicotine dependence, although the evidence is heterogeneous and many studies did not control for the effect of comorbid substance use disorders. The identified evidence however appeared to more consistently support cigarette smoking and nicotine dependence as being a risk factor for development of some anxiety disorders (for example, panic disorder, generalized anxiety disorder), although these findings were not replicated in all studies. A number of inconsistencies in the literature were identified.Conclusions Although many studies have demonstrated increased rates of smoking and nicotine dependence in individuals with anxiety disorders, there is a limited and heterogeneous literature that has prospectively examined this relationship in population studies using validated diagnostic criteria. The most consistent evidence supports smoking and nicotine dependence as increasing the risk of panic disorder and generalized anxiety disorder. The literature assessing anxiety disorders increasing smoking and nicotine dependence is inconsistent. Potential issues with the current literature are discussed and directions for future research are suggested

Dimensionality and measurement invariance in the Satisfaction with Life Scale in Norway

Purpose Results from previous studies examining the dimensionality and factorial invariance of the Satisfaction with Life Scale (SWLS) are inconsistent and often based on small samples. This study examines the factorial structure and factorial invariance of the SWLS in a Norwegian sample. Methods Confirmatory factor analysis (AMOS) was conducted to explore dimensionality and test for measurement invariance in factor structure, factor loadings, intercepts, and residual variance across gender and four age groups in a large (N = 4,984), nationally representative sample of Norwegian men and women (15–79 years). Results The data supported a modified unidimensional structure. Factor loadings could be constrained to equality between the sexes, indicating metric invariance between genders. Further testing indicated invariance also at the strong and strict levels, thus allowing analyses involving group means. The SWLS was shown to be sensitive to age, however, at the strong and strict levels of invariance testing. Conclusion In conclusion, the results in this Norwegian study seem to confirm that a unidimensional structure is acceptable, but that a modified single-factor model with correlations between error terms of items 4 and 5 is preferred. Additionally, comparisons may be made between the genders. Caution must be exerted when comparing age groups