Combined expression of BUB1B, DLGAP5, and PINK1 as predictors of poor outcome in adrenocortical tumors: validation in a Brazilian cohort of adult and pediatric patients

Background: A recent microarray study identified a set of genes whose combined expression patterns were predictive of poor outcome in a cohort of adult adrenocortical tumors (ACTs). The difference between the expression values measured by qRT-PCR of DLGAP5 and PINK1 genes was the best molecular predictor of recurrence and malignancy. Among the adrenocortical carcinomas, the combined expression of BUB1B and PINK1 genes was the most reliable predictor of overall survival. The prognostic and molecular heterogeneity of ACTs raises the need to study the applicability of these molecular markers in other cohorts. Objective: To validate the combined expression of BUB1B, DLGAP5, and PINK1 as outcome predictor in ACTs from a Brazilian cohort of adult and pediatric patients. Patients and methods: BUB1B, DLGAP5, and PINK1 expression was assessed by quantitative PCR in 53 ACTs from 52 patients - 24 pediatric and 28 adults (one pediatric patient presented a bilateral asynchronous ACT). Results: DLGAP5 PINK1 and BUB1B PINK1 were strong predictors of disease-free survival and overall survival, respectively, among adult patients with ACT. In the pediatric cohort, these molecular predictors were only marginally associated with disease-free survival but not with overall survival. Conclusion: This study confirms the prognostic value of the combined expression of BUB1B, DLGAP5, and PINK1 genes in a Brazilian group of adult ACTs. Among pediatric ACTs, other molecular predictors of outcome are required.

HER-2, p53, p21 and hormonal receptors proteins expression as predictive factors of response and prognosis in locally advanced breast cancer treated with neoadjuvant docetaxel plus epirubicin combination

Abstract Background Neoadjuvant chemotherapy has been considered the standard care in locally advanced breast cancer. However, about 20% of the patients do not benefit from this clinical treatment and, predictive factors of response were not defined yet. This study was designed to evaluate the importance of biological markers to predict response and prognosis in stage II and III breast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting. Methods Sixty patients received preoperative docetaxel (75 mg/m2) in combination with epirubicin (50 mg/m2) in i.v. infusion in D1 every 3 weeks after incisional biopsy. They received adjuvant chemotherapy with CMF or FEC, attaining axillary status following definitive breast surgery. Clinical and pathologic response rates were measured after preoperative therapy. We evaluated the response rate to neoadjuvant chemotherapy and the prognostic significance of clinicopathological and immunohistochemical parameters (ER, PR, p51, p21 and HER-2 protein expression). The median patient age was 50.5 years with a median follow up time 48 months after the time of diagnosis. Results Preoperative treatment achieved clinical response in 76.6% of patients and complete pathologic response in 5%. The clinical, pathological and immunohistochemical parameters were not able to predict response to therapy and, only HER2 protein overexpression was associated with a decrease in disease free and overall survival (P = 0.0007 and P = 0.003) as shown by multivariate analysis. Conclusion Immunohistochemical phenotypes were not able to predict response to neoadjuvant chemotherapy. Clinical response is inversely correlated with a risk of death in patients submitted to neoadjuvant chemotherapy and HER2 overexpression is the major prognostic factor in stage II and III breast cancer patients treated with a neoadjuvant docetaxel and epirubicin combination.

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients

Abstract Background To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). Patients and Methods We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 oropharynx and 4 hypopharynx SCC and 65 matched adjacent mucosa, available for study, were also included. For survival analysis, patients were categorized as positive or negative for each Smad, according to median mRNA expression. We also performed real-time quantitative PCR (QRTPCR) to asses the pattern of TGFβ1, TGFβ2, TGFβ3 in oral SCC. Results Our results showed that Smad2 and Smad6 mRNA expression were both associated with survival in Oral SCC patients. Cox Multivariate analysis revealed that Smad6 positivity and Smad2 negativity were both predictive of good prognosis for oral SCC patients, independent of lymph nodal status (P = 0.003 and P = 0.029, respectively). In addition, simultaneously Smad2- and Smad6+ oral SCC group of patients did not reach median overall survival (mOS) whereas the mOS of Smad2+/Smad6- subgroup was 11.6 months (P = 0.004, univariate analysis). Regarding to TGFβ isoforms, we found that Smad2 mRNA and TGFβ1 mRNA were inversely correlated (p = 0.05, R = -0.33), and that seven of the eight TGFβ1+ patients were Smad2-. In larynx SCC, Smad7- patients did not reach mOS whereas mOS of Smad7+ patients were only 7.0 months (P = 0.04). No other correlations were found among Smad expression, clinico-pathological characteristics and survival in oral, larynx, hypopharynx, oropharynx or the entire head and neck SCC population. Conclusion Smad6 together with Smad2 may be prognostic factors, independent of nodal status in oral SCC after curative resection. The underlying mechanism which involves aberrant TGFβ signaling should be better clarified in the future.

Demographic and clinical predictors of depressive symptoms among incarcerated women

Abstract Background Imprisonment may lead to the development of mental illness, especially depression. This study examines the clinical and sociodemographic profiles of imprisoned women, identifies indicative signs of depression, and relates these indicators to other variables. Methods This study took the form of descriptive exploratory research with a psychometric evaluation. A total of 100 of 300 women in a female penitentiary were interviewed. A questionnaire with sociodemographic, clinical and penal situation information was used, along with the Beck Depression Inventory. The authors performed bivariate and multivariate analysis regarding depression. Results In all, 82 women presented signs of depression (light = 33, mild = 29 and severe = 20). Comorbidities, lack of religious practice, absence of visitors and presence of eating disorders were risk factors for depression (P = 0.03, 0.03, 0.02, 0.04, and 0.01). Being older was a protection factor against severe depression; for women over 30, the risk of depression was multiplied by 0.12. The rate of depression among women prisoners was high. Conclusions Comorbidities, the lack of religious practice, not having visitors and eating disorders are significant risk factors for depression, while age is a protective factor, among incarcerated women.

Predictors of long-term survival among first-ever ischemic and hemorrhagic stroke in a Brazilian stroke cohort

Abstract Background Few studies have examined both ischemic and hemorrhagic stroke to identify prognostic factors associated to long-term stroke survival. We investigated long-term survival and predictors that could adversely influence ischemic and hemorrhagic first-ever stroke prognosis. Methods We prospectively ascertained 665 consecutive first-ever ischemic and hemorrhagic stroke cases from “The Study of Stroke Mortality and Morbidity” (The EMMA Study) in a community hospital in São Paulo, Brazil. We evaluated cardiovascular risk factors and sociodemographic characteristics (age, gender, race and educational level). Results We found a lower survival rate among hemorrhagic cases compared to ischemic stroke cases at the end of 4 years of follow-up (52% vs. 44%, p = 0.04). The risk of death was two times higher among people with ischemic stroke without formal education. Also, we found consistently higher risk of death for diabetics with ischemic stroke (HR = 1.45; 95% CI = 1.07-1.97) compared to no diabetics. As expected, age equally influenced on the high risk of poor survival, regardless of stroke subtype. Conclusions For ischemic stroke, the lack of formal education and diabetes were significant independent predictors of poor long-term survival.

Socioeconomic and psychosocial predictors of dental healthcare use among Brazilian preschool children

Abstract Background Disparities in utilization of oral healthcare services have been attributed to socioeconomic and individual behavioral factors. Parents’ socioeconomic status, demographics, schooling, and perceptions of oral health may influence their children’s use of dental services. This cross-sectional study assessed the relationships between socioeconomic and psychosocial factors and the utilization of dental health services by children aged 1–5 years. Methods Data were collected through clinical exams and a structured questionnaire administered during the National Day of Children’s Vaccination. A Poisson regression model was used to estimate prevalence ratios and 95% confidence intervals. Results Data were collected from a total of 478 children. Only 112 (23.68%) were found to have visited a dentist; 67.77% of those had seen the dentist for preventive care. Most (63.11%) used public rather than private services. The use of dental services varied according to parental socioeconomic status; children from low socioeconomic backgrounds and those whose parents rated their oral health as “poor” used dental services less frequently. The reason for visiting the dentist also varied with socioeconomic status, in that children of parents with poor socioeconomic status and who reported their child’s oral health as “fair/poor” were less likely to have visited the dentist for preventive care. Conclusion This study demonstrated that psychosocial and socioeconomic factors are important predictors of the utilization of dental care services.

IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population

Background: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. Aims: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. Methods: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. Results: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 x 10(-5)). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/ relapse (NR/R) (P = 8.00 x 10(-3)). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 x 10(-3)), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 x 10(-3) and P = 2.16 x 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 x 10(-3)); Amerindian and European ancestry genetic contribution were greater in the SVR group. Conclusion: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

ABCB1 haplotype is associated with major molecular response in chronic myeloid leukemia patients treated with standard-dose of imatinib

Background: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor used for treating chronic myeloid leukemia (CML). IM has high efficacy, however some individuals develop a resistance due to impaired bio-availability. Polymorphisms in genes encoding membrane transporters such as ABCB1 have been associated with differences in protein expression and function that influence the response to several drugs. Aim: To investigate the relationship of ABCB1 polymorphisms with markers of response to IM in patients with CML Methods: One hundred eighteen CML patients initially treated with a standard dose of IM (400 mg/day) for 18 months were selected at two health centers in Sao Paulo City, Brazil. The response criteria were based on the European LeukemiaNet recommendations. ABCB1 polymorphisms c.1236C>T (rs1128503), c.3435C>T (rs1045642) and c.2677G>T/A (rs2032582) were evaluated by PCR-RFLP. Results: ABCB1 polymorphisms were not related with a risk for CML in this sample population (p<0.05). In the CML group, frequencies of ABCB1 SNPs were similar between responder and non-responder patients (p>0.05). In the responder group, the frequency of ABCB11236CT/2677GT/3435CT haplotype was higher in patients with major molecular response (MMR) (51.7%) than in patients without MMR (8.3%, p = 0.010). Furthermore, carriers of this haplotype had increased the probability of reaching the MMR compared with the non-carriers (OR: 11.8; 95% CI: 1.43-97.3, p = 0.022). Conclusions: The ABCB1 1236CT/2677GT/3435CT haplotype is positively associated with the major molecular response to IM in CML patients. (C) 2011 Elsevier Inc. All rights reserved.

New Equation for Prediction of Reverse Remodeling after Cardiac Resynchronization Therapy

Objectives: To integrate data from two-dimensional echocardiography (2D ECHO), three-dimensional echocardiography (3D ECHO), and tissue Doppler imaging (TDI) for prediction of left ventricular (LV) reverse remodeling (LVRR) after cardiac resynchronization therapy (CRT). It was also compared the evaluation of cardiac dyssynchrony by TDI and 3D ECHO. Methods: Twenty-four consecutive patients with heart failure, sinus rhythm, QRS = 120 msec, functional class III or IV and LV ejection fraction (LVEF) = 0.35 underwent CRT. 2D ECHO, 3D ECHO with systolic dyssynchrony index (SDI) analysis, and TDI were performed before, 3 and 6 months after CRT. Cardiac dyssynchrony analyses by TDI and SDI were compared with the Pearson's correlation test. Before CRT, a univariate analysis of baseline characteristics was performed for the construction of a logistic regression model to identify the best predictors of LVRR. Results: After 3 months of CRT, there was a moderate correlation between TDI and SDI (r = 0.52). At other time points, there was no strong correlation. Nine of twenty-four (38%) patients presented with LVRR 6 months after CRT. After logistic regression analysis, SDI (SDI > 11%) was the only independent factor in the prediction of LVRR 6 months of CRT (sensitivity = 0.89 and specificity = 0.73). After construction of receiver operator characteristic (ROC) curves, an equation was established to predict LVRR: LVRR =-0.4LVDD (mm) + 0.5LVEF (%) + 1.1SDI (%), with responders presenting values >0 (sensitivity = 0.67 and specificity = 0.87). Conclusions: In this study, there was no strong correlation between TDI and SDI. An equation is proposed for the prediction of LVRR after CRT. Although larger trials are needed to validate these findings, this equation may be useful to candidates for CRT. (Echocardiography 2012;29:678-687)