Genomic landscapes of ovarian clear cell carcinoma from latin countries reveal aberrations linked to survival and progression.

BACKGROUND: Ovarian clear cell carcinomas (OCCCs) are rare, aggressive and chemoresistant tumors. Geographical and ethnic differences in the incidence of OCCC have been reported with a higher incidence in Asiatic countries. There is a paucity of information regarding OCCC in Latin America (LA) and other countries. METHODS: Here, we characterized two cohorts of 33 patients with OCCC from LA (24 from Brazil and 9 from Costa Rica) and a cohort of 27 patients from Spain. Genomic analysis was performed for 26 OCCC using the OncoScan platform. Tumors were classified according to their genomic landscapes into subgroups. Clinical parameters were related to the frequency of genomic aberrations. RESULTS: The median overall survival (OS) was not significantly different between the cohorts. Genomic landscapes were characterized by different homologous recombination deficiency (HRD) levels. No difference in the distribution of genomic landscapes profiles was detected between patients from the different cohorts. OCCCs with MYC-amplified tumors harboring a concomitant loss of a region in chromosome 13q12-q13 that includes the BRCA2 gene had the longest OS. In contrast, patients carrying a high number (> 30) of total copy number (CN) aberrations with no concomitant alterations in MYC and BRCA2 genes presented the shortest OS. Furthermore, amplification of the ASH1L gene was also associated with a shorter OS. Initial-stage OCCCs with early progression were characterized by gains in the JNK1 and MKL1 genes. CONCLUSIONS: Our results provide new data from understudied OCCC populations and reveal new potential markers for OCCCs.

Filling gaps in experiences religious understanding of people living with cancer in palliative care: a phenomenological qualitative study.

BACKGROUND: According to a phenomenology of contemporary religion, the analysis of religious experiences finds that they are part of an individual's search for something powerful that overcomes him seeking not only a need, but the meaning of all existence. The present study aims to contribute to a deeper understanding of the religious experiences of people living with cancer in palliative care (PC) and fill gaps in access to experience, with regard to how it was properly lived. METHODS: A qualitative, phenomenological, cross-sectional study was conducted with 14 people living with cancer undergoing PC at two outpatient clinics of a public hospital. The experiences were accessed through in-depth interviews and the results were analysed according to the principles of classical phenomenology. RESULTS: The patients confidently surrendered to the divine, attributing to it the power of continuity of life or not, which sustained them and launched them into horizons of hope, directing them to possibilities of achieving meaning in life, which it fed back their faith and to continue living, opening them up to an intense perception of the value of life. CONCLUSIONS: The religious positions of confident surrender to the divine, to his will and a belief in his intervention, regardless of the outcome, opened possibilities to patients for the belief in the continuity of life by the power of faith. This position allowed the patients in this study to visualize achievements in the present and in the future, opening a horizon of hope, meaning and value of living. This study showed how this elements are presented and sustained, providing subsidies to health professionals seeking to provide more holistic care.

Personal positioning of oncology patients in palliative care: a mixed-methods study.

BACKGROUND: Advanced oncological disease requires comprehensive health care, although attention is predominantly paid to the physical dimension of care. The consideration of personal positioning encompasses other dimensions of patients' management of their illness, such as existential management and expanding forms of care. The objective of this study was to understand the personal positioning of cancer patients in palliative care. METHODS: This was a cross-sectional study using the mixed convergent parallel method. The sample consisted of 71 cancer patients in palliative care, of whom 14 participated in the qualitative and quantitative portions and 57 participated in only the quantitative portion. Phenomenological interviews were performed, and qualitative and quantitative methods were used to collect meaning of life (PIL-Test), quality of life (EORTC QLQ C-30), anxiety and depression (HADS) and sociodemographic data. The interview results were analysed according to the principles of classical phenomenology, and the quantitative data were analysed using the generalized structural equations model. RESULTS: The results showed that the patients turned to living, focusing on their possibilities and distancing themselves from the impact of the illness and the factuality of death, which the patients themselves associated with not succumbing to depression, a condition whose signs were exhibited by 21% of the sample. Sustaining this positioning required a tenacious fight, which feeds on sensitivity to life. Linked to this position was the belief in the continuation of life through religious faith, together with the patients' realization of the meaning of their lives. In this same direction, there was a direct association between awareness of the meaning of life and increased scores on the functional scales (p <  0.01) and decreased scores for symptoms (p <  0.01), anxiety (p = 0.02) and depression (p < 0.01). The last element that emerged and structured this experience was the intense will to live and a sense of the value of life. CONCLUSIONS: Through the use of mixed methods, the present study recognized the existential positioning of cancer patients in palliative care. This understanding can aid in the realization of more comprehensive and meaningful treatment plans and can contribute to the goal of achieving humanization in this area of treatment.

Expression of microRNAs miR-21 and miR-326 associated with HIF-1α regulation in neurospheres of glioblastoma submitted to ionizing radiation treatment.

Background: Glioblastoma is an incurable neoplasm. Its hypoxia mechanism associated with cancer stem cells (CSCs) demonstrates hypoxia-inducible factor 1α (HIF-1α) expression regulation, which is directly related to tumor malignancy. The aim of this study was to identify a possible tumor malignancy signature associated with regulation of HIF-1α by microRNAs miR-21 and miR-326 in the subpopulation of tumor stem cells which were irradiated by ion in primary culture of patients diagnosed with glioblastoma. Materials and methods: We used cellular cultures from surgery biopsies of ten patients with glioblastoma. MicroRNA expressions were analyzed through real-time polymerase chain reaction (PCR ) and correlated with mortality and recurrence. The ROC curve displayed the cutoff point of the respective microRNAs in relation to the clinical prognosis, separating them by group. Results: The miR-21 addressed high level of expression in the irradiated neurosphere group (p = 0.0028). However, miR-21 was not associated with recurrence and mortality. miR-326 can be associated with tumoral recurrence (p = 0.032) in both groups; every 0.5 units of miR-326 increased the chances of recurrence by 1,024 (2.4%). Conclusion: The high expression of miR-21 in the irradiated group suggests its role in the regulation of HIF-1α and in the radioresistant neurospheres. miR-326 increased the chances of recurrence in both groups, also demonstrating that positive regulation from miR-326 does not depend on ionizing radiation treatment.

ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition. METHODS: Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients. RESULTS: Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples. CONCLUSION: Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration.

Apoptosis related microRNAs and MGMT in glioblastoma cell lines submitted to treatments with ionizing radiation and temozolomide.

AIM: To evaluate the effect of radiotherapy and temozolomide on the expression of miRNAs apoptotic (miRNAs-21, -221, -222 (anti-apoptotic) and miRNAs-15a, -16 (pro-apoptotic)) and the gene MGMT in glioblastoma cell lines. BACKGROUND: The limited knowledge of the molecular biology of malignant gliomas may hinder the development of therapeutic modalities. In this scenario, one of the greatest advances of recent years was the identification of microRNAs. These molecules have an important role in biological processes involving cancer, including glioblastoma. MATERIALS AND METHODS: Trypan blue was used to verify the cell viability, and real time PCR to quantify the expression of microRNAs and gene 24, 48 and 120 h after exposure to treatments. RESULTS: There was a statistically significant decrease of expression of miR-15a between 48 and 120 h in line T98 G treated with radiation, increased expression of miR-15a between 24 and 120 h in line U251 treated with radiation and temozolomide, and increased expression of miR-16 between 24 and 120 h in line U251 treated with radiation alone and when combined with temozolomide. There was a decrease in MGMT gene expression, between 24 and 48 h in U343 cells treated with temozolomide. CONCLUSIONS: Ionizing radiation and temozolomide modified the expression of miRNAs studied and MGMT.

Elevated serum levels of proinflammatory cytokines potentially correlate with depression and anxiety in colorectal cancer patients in different stages of the antitumor therapy.

Depression and anxiety, the most important psychological disorders in cancer patients, have now been considered as psychoneuroimmunological disorders, in which peripheral immune activation, through the release of proinflammatory cytokines, is implicated in the variety of behavioral, neuroendocrine and neurochemical alterations associated with these disorders. Along with the tumor itself, cancer treatment can also contribute to exacerbate the production of proinflammatory cytokines. This study aimed to investigate whether proinflammatory cytokine levels are related to depression and anxiety in CRC patients in different stages of the antitumor therapy We evaluated 60 patients in three stages of antitumor therapy (Pre-chemotherapy, Under-chemotherapy and Post-chemotherapy, n=20 in each group) and 20 healthy volunteers by the Hospital Anxiety and Depression Scale (HADS). Serum levels of cytokines were measured by CBA. Depression and/or anxiety were found at clinically relevant levels in CRC patients during all antitumor therapy. Patients in pre-chemotherapy group exhibited the highest concentrations of pro-inflammatory cytokines and the lowest levels of IL-10. In latter stages of treatment, cytokines reached levels similar to the control group. Correlation analysis between HADS score and cytokine serum levels revealed positive associations of anxiety and/or depression with IL-1ß, IL-6, IL-8, and TNF-α, and a negative correlation with IL-10, suggesting that cytokines are involved in the pathophysiology of these psychological disorders in CRC patients. A better understanding of the molecular mechanisms involved in these psychological disorders will allow the design of new therapeutic strategies to assist in alleviating such symptoms in cancer patients.

Cost-effectiveness analysis of XELOX versus XELOX plus bevacizumab for metastatic colorectal cancer in a public hospital school.

BACKGROUND: Metastatic colorectal cancer imposes a substantial burden on patients and society. Over the last years, progresses in the treatment have been made especially due to the introduction of monoclonal antibodies, such as bevacizumab which, on the other hand, has considerably increased the costs of treatment. We performed a cost-effectiveness analysis of bevacizumab plus XELOX in comparison with XELOX alone in metastatic colorectal cancer in first-line therapy, from the perspective of a public hospital school in Brazil. METHODS: This was a cost-effectiveness analysis performed by a decision tree and Markov models. Costs were expressed in local currency and outcomes were expressed in months of life gained. The model was constructed using the TreeAge Pro 2013® software. RESULTS: The incremental difference in years of life gained was 2.25 months, with an extra cost of 47,833.57 BRL, resulting in an incremental cost-effectiveness of 21,231.43 BRL per month of life gained. CONCLUSIONS: Although the XELOX plus bevacizumab regimen is a more expensive and more effective treatment than XELOX, it does not fit the reimbursement values fixed by the public healthcare system in Brazil.

Assessment of the integration between oncology and palliative care in advanced stage cancer patients.

PURPOSE: Chemotherapy is indicated for patients with metastatic malignancy in order to improve quality of life and in some cases to increase survival. However, the greatest difficulty regarding the choice of treatment is to evaluate the clinical benefit and intrinsic toxicity of each procedure. The best strategy is the integration between oncology and palliative care, which is still mostly insufficient. The main objective of this study was to assess time to palliative care referral for cancer patients with advanced local or metastatic disease and to investigate the impact of covariates on this relationship. METHODS: A retrospective, cross-sectional, observational pilot study was conducted on 286 patients divided into two groups, one consisting of metastatic patients and the other of non-metastatic patients at diagnosis. Karnofsky Performance Scale (KPS), setting, and survival time were evaluated. RESULTS: One hundred eighteen patients (41.25%) were metastatic and 168 (58.74%) had locally advanced malignant disease. The median time of metastatic patient referral to the group of palliative care (GPC) was 5.3 months, with 39.8% referred earlier and 60.2% referred late (≥3 months). 60.2% of metastatic patients were referred to the GPC with a KPS <70% and 56% of non-metastatic patients were referred earlier and 44% after 3 months. There was improved survival only in metastatic patients referred to the GPC with a KPS ≥70% (p = 0.02). CONCLUSIONS: Many oncology patients were referred late to the GPC. A higher KPS was a risk factor for late referral because only severe patients were referred earlier. Metastatic patients referred with a KPS ≥70% had a longer survival.

"Burnout in Medical Oncology Fellows: a Prospective Multicenter Cohort Study in Brazilian Institutions".

Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in residency programs in clinical oncology are exposed to similar risk factors; however, few data are available in this population. This study assessed the occurrence of burnout and associated factors among first-year residents at Brazilian institutions. The present prospective, multicenter, cohort study was conducted with doctors enrolled in residency programs in clinical oncology at Brazilian institutions affiliated with the public health system. The participants answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI), Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission to the program and 6 and 12 months later. Of 37 eligible residency programs in 2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents, representing 100 % of new admissions to the participating institutions, were included. Most of the participants met the criteria for severe burnout upon admission to the residency programs (emotional exhaustion in 49.0 % and depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and depersonalization increased significantly (p < 0.01) during the first year of residency, and the prevalence of burnout increased to 88 % at the end of that first year. The present study found a high prevalence of burnout among doctors enrolled in residency programs in clinical oncology at Brazilian institutions. A large fraction of the participants met the criteria for burnout syndrome upon admission to the program, which suggests that the problem began during the course of the previous residency program in internal medicine.

Effect of Zinc Supplementation on Serological Response to Vaccination Against Streptococcus Pneumoniae in Patients Undergoing Chemotherapy for Colorectal Cancer.

The aim of the study was to evaluate the effect of zinc supplementation on the antibody titer and the 23-valent pneumococcal seroconversion after vaccination in patients undergoing chemotherapy for colorectal cancer. The study included 25 patients undergoing postsurgery chemotherapy for colorectal adenocarcinoma (chemo group). Subjects were assessed in the perioperative period (prevaccination), before chemotherapy (4th wk) and after 3 cycles of chemotherapy (16th wk). Thirty-two healthy volunteers (control group) were included in the study. Participants received the 23-valent pneumococcal conjugate vaccine, and capsules containing zinc (Zn) sulfate (70 mg daily) or identical placebo capsules (containing wheat starch with no added Zn) for 16 wk and were randomly allocated on one of the following groups: chemo-Zn (n = 10), chemo-placebo (n = 15), control-Zn (n = 21), and control-placebo (n = 11). The antipneumococcal antibody titer against 6 polysaccharides was analyzed by ELISA and compared using linear mixed models. The seroconversion rate was compared using Fisher's exact test. An immune response to the vaccination against pneumococcus was observed in all participants. In the 16th wk, the polysaccharide 6 concentration was lower in the chemo-Zn group [2.96 (1.74-5.03) µg/mL] compared with the Chemo-Placebo group [10.75 (5.37-21.54) µg/mL] and the seroconversion rate was lower in the chemo-placebo (36%) compared with the control-placebo (85%) (P = 0.027). Zinc supplementation did not change the antibody titer after vaccination. However, the lower seroconversion rate observed in the chemo-placebo suggests an influence of zinc in the vaccinal protection.

A mechanistic breast cancer survival modelling through the axillary lymph node chain.

In this paper, we proposed a mechanistic breast cancer survival model based on the axillary lymph node chain structure, considering lymph nodes as a potential dissemination arrangement. We assume a naive breast cancer treatment protocol consisting of exposing patients first to a chemotherapy treatment on r intervals at k-cycles separated by equal time intervals, and then they proceed to surgery. Our model, different from former ones, accommodates a quantity of contaminated lymph nodes, which is observed during surgery. We assume a generalised negative binomial survival distribution for the unknown number of contaminated lymph nodes after surgery, which, during an unknown period, may potentially propagate the disease. Estimation is based on a maximum likelihood approach. A simulation study assesses the coverage probability of asymptotic confidence intervals when small or moderate samples are considered. A Brazilian breast cancer data illustrate the applicability of our modelling.

Hybrid volatilomics in cancer diagnosis by HS-GC-FID fingerprinting.

Assessing volatile organic compounds (VOCs) as cancer signatures is one of the most promising techniques toward developing non-invasive, simple, and affordable diagnosis. Here, we have evaluated the feasibility of employing static headspace extraction (HS) followed by gas chromatography with flame ionization detector (GC-FID) as a screening tool to discriminate between cancer patients (head and neck-HNC,n= 15; and gastrointestinal cancer-GIC,n= 19) and healthy controls (n= 37) on the basis of a non-target (fingerprinting) analysis of oral fluid and urine. We evaluated the discrimination considering a single bodily fluid and adopting the hybrid approach, in which the oral fluid and urinary VOCs profiles were combined through data fusion. We used supervised orthogonal partial least squares discriminant analysis for classification, and we assessed the prediction power of the models by analyzing the values of goodness of prediction (Q2Y), area under the curve (AUC), sensitivity, and specificity. The individual models HNC urine, HNC oral fluid, and GIC oral fluid successfully discriminated between healthy controls and positive samples (Q2Y = 0.560, 0.525, and 0.559; AUC = 0.814, 0.850, and 0.926; sensitivity = 84.8, 70.2, and 78.6%; and specificity = 82.3; 81.5; 87.5%, respectively), whereas GIC urine was not adequate (Q2Y = 0.292, AUC = 0.694, sensitivity = 66.1%, and specificity = 77.0%). Compared to the respective individual models, Q2Y for the hybrid models increased (0.623 for hybrid HNC and 0.562 for hybrid GIC). However, sensitivity was higher for HNC urine and GIC oral fluid than for hybrid HNC (75.6%) and hybrid GIC (69.8%), respectively. These results suggested that HS-GC-FID fingerprinting is suitable and holds great potential for cancer screening. Additionally, the hybrid approach tends to increase the predictive power if the individual models present suitable quality parameter values. Otherwise, it is more advantageous to use a single body fluid for analysis.

Mirtazapine versus Megestrol in the Treatment of Anorexia-Cachexia Syndrome in Patients with Advanced Cancer: A Randomized, Double-Blind, Controlled Phase II Clinical Trial.

This study compared mirtazapine with megestrol in the management of cancer-related anorexia-cachexia syndrome in patients with advanced cancer. A randomized, double-blind, controlled clinical trial involving patients with advanced cancer and anorexia-cachexia syndrome was performed. Participants received mirtazapine 30 mg/day or megestrol 320 mg/day for eight weeks. The primary endpoint was the effect of mirtazapine on weight gain and the secondary endpoints were its effect on appetite, muscle strength, physical performance, body composition, adverse events, and medication adherence. Linear regression model with mixed effects was applied and a significance level of 5% was adopted. Fifty-two patients were randomized. Mean age was 65.8 ± 8.4 years. There was weight gain in 52% of the participants in the megestrol group and in 38% in the mirtazapine group after four weeks (p = 0.040). Appetite improved in 92% of the participants in the megestrol group and in 56% in the mirtazapine group after eight weeks (p = 0.007). In the sub-analysis by sex, women showed improvement in appetite (p < 0.001) and weight gain (p < 0.005) in the mirtazapine group, which was not observed in men. Mirtazapine appears to be inferior to megestrol in weight and appetite improvement. However, there may be a difference in the therapeutic response between sexes.

Radiotherapy for Brain Metastases Near the End of Life: Characterizing Patients and Tumor Features.

PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

COSTS ANALYSIS OF SPINAL COLUMN METASTASES SURGICAL TREATMENT.

Introduction: End-of-life cancer treatment is associated with substantial healthcare costs. Objective: This study aimed to analyze the surgical treatment cost of spinal metastasis and epidural compression patients undergoing surgical treatment. Methods: A retrospective cost analysis of 81 patients with spinal metastasis and epidural compression undergoing surgical treatment. Cost evaluation was defined in the following categories: medications, laboratory and imaging tests, nursery, recovery room, intensive care unit, surgical procedure, and consigned material. The cost of pain improvement, functional activity, and survival was also evaluated. Results: The total cost of surgical treatment for 81 patients was $3,604,334.26, and the average value for each patient was $44,497.95. The highest costs were related to implants (41.1%), followed by hospitalization (27.3%) and surgical procedure (19.7%). Conclusion: The cost of surgical treatment for spinal metastases is one of the most expensive bone complications in cancer patients. The cost of treatment related to outcomes showed differences according to the outcome analyzed. Hospital stay, tests, drugs, and intensive care play an important role in some of the costs related to the specific outcome. Level of Evidence II, Retrospective Study .

Introdução: O tratamento do câncer em fim de vida está associado a custos substanciais em saúde. Objetivo: O objetivo do estudo foi analisar o custo do tratamento cirúrgico de pacientes com metástase espinhal e compressão peridural submetidos ao tratamento cirúrgico. Métodos: Uma análise retrospectiva de custos de 81 pacientes com metástase espinhal e compressão peridural submetidos a tratamento cirúrgico. A avaliação de custos foi definida nas seguintes categorias: medicamentos, exames laboratoriais e de imagem, enfermaria, sala de recuperação, unidade de terapia intensiva, procedimento cirúrgico e material consignado. O custo relacionado à melhora da dor, atividade funcional e sobrevida também foi avaliado. Resultados: O custo total do tratamento cirúrgico de 81 pacientes foi de R $ 3.604.334,26 e o valor médio de cada paciente foi de R $ 44.497,95. Os maiores gastos foram relacionados com implantes (41,1%), seguidos de internação (27,3%) e procedimento cirúrgico (19,7%). Conclusão: O custo do tratamento cirúrgico para metástases espinhais é um dos mais caros entre as complicações ósseas em pacientes com câncer. O custo do tratamento relacionado aos desfechos apresentou diferença de acordo com o desfecho analisado e a permanência hospitalar, exames, medicamentos e terapia intensiva tem papel importante em alguns dos custos relacionados ao desfecho específico. Nível de Evidência II, Estudo retrospectivo .

Modulation of Genes and MicroRNAs in the Neurospheres of Glioblastoma Cell Lines U343 and T98G Induced by Ionizing Radiation and Temozolomide Therapy.

INTRODUCTION: Glioblastoma is the most prevalent primary malignant neoplasm of the central nervous system. It has increased its incidence, while the overall survival remains over 14 months. PURPOSE: The purpose is to evaluate the expression of the genes EGFR, PTEN, MGMT, and IDH1/2, and microRNAs miR-181b, miR-145, miR-149, and miR-128a in adhered cells (AC) and neurospheres (NS) from cell lines (T98G and U343) submitted to temozolomide (TMZ) and ionizing radiation (IR). METHODS: T98G and U343 were treated with TMZ, IR, and TMZ+IR. The analysis of gene expression and miRNAs was performed using real-time PCR. RESULTS: This study demonstrated: a) an improvement in the expression of IDH1 after IR and TMZ + IR in the NS (T98G); b) an increase in the expression of MGMT in NS (T98G) in IR groups and TMZ + IR. The expression of miRNAs results as a) AC (U343) expressed more miR-181b after TMZ, IR, and TMZ + IR; and miR-128a improved after TMZ, IR, and TMZ + IR; b) NS (T98G) after TMZ + IR expressed: miR-181b; miR-149; miR-145 and miR-128a; c) NS (U343) after IR huge expressed miR-149 and miR-145. CONCLUSION: IR was an independent and determining radioresistance factor in NS. However, we observed no complementarity action of oncomiRs regulation.

The Role of MicroRNA 181d as a Possible Biomarker Associated With Tumor Progression in Meningiomas.

Introduction Meningiomas are slow-growing intracranial neoplasms that originate from arachnoid meningothelial cells and represent 13-26% of intracranial tumors, thus being the most common. There are numerous technological advances available for a better understanding of the molecular pathways correlated with tumorigenesis and tumor progression of meningiomas. In this context, the role of microRNAs (miRNAs), which are non-coding RNAs (ncRNAs) consisting of 18 to 25 nucleotides whose function is the silencing of mRNA at the posttranscriptional level, has been highlighted. Recent studies suggest that miRNAs may act as possible biomarkers as well as therapeutic targets for various diseases, including brain tumors. Therefore, the objective of our study was to evaluate the tissue and plasma expression of the miRNAs miR-181d, miR-181c, and miR-130a. Methods The miRNAs miR-181d, miR-181c, and miR-130a were selected from our group's prior study by the large-scale microarray analysis technique. In this work, the expression of these miRNAs in the tumor tissue and plasma of patients with grade I (16 patients), II (16 patients), and III (eight patients) meningiomas was evaluated. Results MiR-181d was overexpressed in both tumor tissue and plasma in the studied groups. The level of expression was higher according to the progression of tumor grade. MiR-181c and miR-130a showed no significant difference in the studied groups in either tumor tissue or plasma. Conclusions MiR-181d has potential as a biomarker for meningiomas and is associated with the tumor progression of meningiomas.

Outcomes and survival of spinal metastasis with epidural compression.

OBJECTIVE: The goal of the study was to retrospectively evaluate the demographics, clinical manifestation, outcomes, treatment result, and survival of patients with spinal metastasis with epidural metastasis who underwent surgical treatment. MATERIALS AND METHODS: A retrospective evaluation of 103 patients with spinal metastasis and epidural compression who underwent surgical treatment between 2009 and 2015 was performed. The recorded parameters selected for the study were general demographic data (gender, age, and educational level) and clinical data (primary tumor, performance status according to Karnofsky score, neurological status according to Frankel scale, pain, surgical treatment outcomes, and patient survival). RESULTS: The mean age of the patients was 55.28 ± 15.79 years, and spinal metastasis was more frequent in males (61.7%). The two most frequent tumors were malignant breast cancer (26.21%) and prostate cancer (22.33%). Preoperative pain was presented in 96 (94.12%) patients and improvement was observed in 44 (47.31%) patients. Symptoms of spinal cord compression were the initial clinical manifestation of the primary tumor in 35 (33.98%) patients. Neurological deficit was observed in 66 (64.07%) patients, and improvement was observed in 43 (41.74%) patients. Improvement of functional outcome and pain was observed in 34 (37.38%) patients. The mean survival was 12.26 months. Longer survival (mean 19.13 months) was observed in patients who showed improvement in their ability to walk or kept it preserved (Frankel D or E). CONCLUSIONS: Surgical treatment of spinal metastasis can improve pain and functional activities. Longer survival was observed in patients that keep or recovery the walking ability.

Investigation of sweat VOC profiles in assessment of cancer biomarkers using HS-GC-MS.

Volatile organic compounds (VOCs) have been studied in biological samples in order to be related to the presence of diseases. Sweat can represent substances existing in blood, has less complex composition (compared with other biological matrices) and can be obtained in a non-invasive way. In this work, sweat patches were collected from healthy controls and volunteers with cancer. Static Headspace was used for VOCs extraction, analysis was performed by gas chromatography coupled with mass spectrometry. Principal Components Analysis was used to investigate data distribution. Random Forest was employed to develop classificatory models. Controls and positive cases could be distinguished with maximum sensitivity and specificity (100% of accuracy) in a model based on the incidence of 2-ethyl-1-hexanol, hexanal and octanal. Discrimination between controls, primary tumors and metastasis was achieved using a panel with 11 VOCs. Balanced accuracy of more than 70% was obtained for the classification of a neoplasm site. Total n-aldehydes presented to be strongly correlated with staging of adenocarcinomas, while phenol and 2,6-dimethyl-7-octen-2-ol were correlated with Gleason score. These findings corroborate with the development of accessible screening tools based on VOC analysis and highlight sweat as a promising matrix to be studied in a clinical context for cancer diagnosis.