Temporal trend analysis of hospitalizations and in-hospital deaths due to female breast cancer in the state of Alagoas from 2009 to 2019: a cross-sectional study.

BACKGROUND: Breast cancer is a common neoplasm in women worldwide. Its varying patterns of incidence and clinical prognosis in Brazil make it an important and complex public health problem that needs to be solved. OBJECTIVES: To analyze the temporal dynamics of hospital admissions and deaths due to female breast cancer in the state of Alagoas, Brazil, from 2009 to 2019. DESIGN AND SETTING: Cross-sectional study including secondary data from hospital admissions and deaths due to female breast cancer in Alagoas. METHODS: A joinpoint regression model was constructed for temporal analysis of hospital admissions and deaths due to female breast cancer in Alagoas, over this period. The hospital information system of the Department of Informatics of the National Health System was used. RESULTS: There were 5,801 hospitalizations and 633 hospital deaths due to neoplasm in Alagoas over the period. The age group from 50 to 59 years old stood out, corresponding to 28.1% of hospitalizations and 31.1% of registered deaths. An increasing trend in the rate of hospital admissions was observed (average annual percentage change, AAPC = 14.0; P-value < 0.001), from 14.9/100,000 inhabitants in 2009 to 53.6 in 2019. There was a growth trend in the in-hospital mortality rate (AAPC = 19.8; P-value < 0.001), from 6.3% in 2009 to 11.0% in 2019. CONCLUSION: The results indicated an increasing trend of hospital admissions and mortality rates in the state of Alagoas, with a higher percentage of hospitalizations and deaths in the 50-59 age group.

Can inflammasomes promote the pathophysiology of glioblastoma multiforme? A view about the potential of the anti-inflammasome therapy as pharmacological target.

Glioblastoma multiforme (GBM) is a malignant brain tumor with one of the worst general survivorship cases among the existing neoplasia. This aggressiveness is due to its complex molecular heterogeneity, immunohistochemistry and genetics. The current therapeutic approach brings little contribution to the improvement of the survival of the patients. Due to that, new forms of treatment have been explored, one of them being immunotherapy. In this aspect, the inflammasome pathway, which induces inflammation and immunosuppressive tumor response, contributing to the progression of the tumor, seems to be a new alternative to improve the treatment efficacy and the survival of the patients.

Temporal trend analysis of hospitalizations and in-hospital deaths due to female breast cancer in the state of Alagoas from 2009 to 2019: a cross-sectional study

ABSTRACT BACKGROUND: Breast cancer is a common neoplasm in women worldwide. Its varying patterns of incidence and clinical prognosis in Brazil make it an important and complex public health problem that needs to be solved. OBJECTIVES: To analyze the temporal dynamics of hospital admissions and deaths due to female breast cancer in the state of Alagoas, Brazil, from 2009 to 2019. DESIGN AND SETTING: Cross-sectional study including secondary data from hospital admissions and deaths due to female breast cancer in Alagoas. METHODS: A joinpoint regression model was constructed for temporal analysis of hospital admissions and deaths due to female breast cancer in Alagoas, over this period. The hospital information system of the Department of Informatics of the National Health System was used. RESULTS: There were 5,801 hospitalizations and 633 hospital deaths due to neoplasm in Alagoas over the period. The age group from 50 to 59 years old stood out, corresponding to 28.1% of hospitalizations and 31.1% of registered deaths. An increasing trend in the rate of hospital admissions was observed (average annual percentage change, AAPC = 14.0; P-value < 0.001), from 14.9/100,000 inhabitants in 2009 to 53.6 in 2019. There was a growth trend in the in-hospital mortality rate (AAPC = 19.8; P-value < 0.001), from 6.3% in 2009 to 11.0% in 2019. CONCLUSION: The results indicated an increasing trend of hospital admissions and mortality rates in the state of Alagoas, with a higher percentage of hospitalizations and deaths in the 50-59 age group.

Prevalence of IGFBP3, NOS3 and TCF7L2 polymorphisms and their association with hypertension: a population-based study with Brazilian women of African descent.

OBJECTIVE: African ancestry seems to be a risk factor for hypertension; however, few genetic studies have addressed this issue. This study aimed to investigate the prevalence of polymorphisms NOS3; rs1799983, IGFBP3; rs11977526 and TCF7L2; rs7903146 in Brazilian women of African descent and their association with hypertension. RESULTS: The prevalences of the less frequent genotypes were 26.5% TT genotype of NOS3; rs1799983, 16.7% AA genotype of IGFBP3; rs11977526, and 18.3% TT genotype of TCF7L2; rs7903146. For these conditions, the prevalence of hypertension and PR (adjusted) relatively to the ancestral genotype were, respectively: 52.0% vs 24.5% (PR = 1.54; p < 0.001), 62.0% vs 24.1% (PR = 1.59; p < 0.001), and 38.9% vs 27.9% (PR = 0.86; p = 0.166). Associations with hypertension were statistically significant, except for the TCF7L2; rs7903146 polymorphism, after adjusted analysis. Brazilian Afro-descendant women with the TT genotype for the NOS3 gene and the AA genotype for the IGFBP3 gene are more susceptible to hypertension. The understanding of underlying mechanisms involving the pathogenesis of hypertension can motivate research for the development of new therapeutic targets related to nitric oxide metabolism and the management of oxidative stress.

Correlation between circadian rhythm related genes, type 2 diabetes, and cancer: Insights from metanalysis of transcriptomics data.

Clock genes work as an auto-regulated transcription-translational loop of circadian genes that drives the circadian rhythms in each cell and they are essential to physiological requests. Since metabolism is a dynamic process, it involves several physiological variables that circadian cycling. The clock genes alterations can affect multiple systems concomitantly, because they constitute the promoter factors for relevant metabolic pathways. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of diabetic-associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. In the current study, meta-analysis was performed on type 2 diabetes, circadian rhythm-related genes, and breast, bladder, liver, pancreas, colon and rectum cancer-associated transcriptome data using the integration of gene expression profiles with genome-scale biomolecular networks in diabetes samples. First, we detected downregulated and upregulated DEGs in mouse cortex and hypothalamus samples of mice with sleep deprivation. In summary, upregulated genes active genes associated with oxidative phosphorylation, cancer and diabetes, mainly in hypothalamus specimens. In cortex, we observed mainly downregulation of immune system. DEGs were combined with 214 circadian rhythm related genes to type 2 DM and cancer samples. We observed that several common genes deregulated in both diseases. Klf10, Ntkr3, Igf1, Usp2, Ezh2 were both downregulated in type 2 DM and cancer samples, while Arntl2 and Agrp were upregulated. It seems that the changes in mRNA are contributing to the phenotypic changes in type 2 DM, resulting in phenotypic changes associated with the malignant transformation. Taking those genes to perform a survival analysis, we found only Igf1, Usp2 and Arntl2 genes associated with patient outcomes. While Igf1 and Usp2 downregulation had a negative impact, Arntl2 upregulation was associated with poor survival both in BLCA and BRCA cancer samples. Our data stimulate efforts in news studies to achieve the experimental and clinical validation about these biomolecules.

Correlation between renin-angiotensin system (RAS) related genes, type 2 diabetes, and cancer: Insights from metanalysis of transcriptomics data.

Although studies have provided significant evidence about the role of RAS in mediating cancer risk in type 2 diabetes mellitus (DM), conclusions about the central molecular mechanisms underlying this disease remain to be reached, because this type of information requires an integrative multi-omics approach. In the current study, meta-analysis was performed on type 2 diabetes and breast, bladder, liver, pancreas, colon and rectum cancer-associated transcriptome data, and reporter biomolecules were identified at RNA, protein, and metabolite levels using the integration of gene expression profiles with genome-scale biomolecular networks in diabetes samples. This approach revealed that RAS biomarkers could be associated with cancer initiation and progression, which include metabolites (particularly, aminoacyl-tRNA biosynthesis and ABC transporters) as novel biomarker candidates and potential therapeutic targets. We detected downregulation and upregulation of differentially expressed genes (DEGs) in blood, pancreatic islets, liver and skeletal muscle from normal and diabetic patients. DEGs were combined with 211 renin-angiotensin-system related genes. Upregulated genes were enriched using Pathway analysis of cancer in pancreatic islets, blood and skeletal muscle samples. It seems that the changes in mRNA are contributing to the phenotypic changes in carcinogenesis, or that they are as a result of the phenotypic changes associated with the malignant transformation. Our analyses showed that Ctsg and Ednrb are downregulated in cancer samples. However, by immunohistochemistry experiments we observed that EDNRB protein showed increased expression in tumor samples. It is true that alterations in mRNA expression do not always reflect alterations in protein expression, since post-translational changes can occur in proteins. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in type 2 diabetes and cancer-associated pathways.

Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data.

Schwann cells were identified in the tumor surrounding area prior to initiate the invasion process underlying connective tissue. These cells promote cancer invasion through direct contact, while paracrine signaling and matrix remodeling are not sufficient to proceed. Considering the intertwined structure of signaling, regulatory, and metabolic processes within a cell, we employed a genome-scale biomolecular network. Accordingly, a meta-analysis of Schwann cells associated transcriptomic datasets was performed, and the core information on differentially expressed genes (DEGs) was obtained by statistical analyses. Gene set over-representation analyses was performed on core DEGs to identify significantly functional and pathway enrichment analysis between Schwann cells and, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). DEGs were further integrated with genome-scale human biomolecular networks. miRNAs were proposed by the reconstruction of a transcriptional and post-transcriptional regulatory network. Moreover, microarray-based transcriptome profiling was performed, and the prognostic power of selected dedifferentiated Schwann cell biomolecules was predicted. We observed that pathways associated with Schwann cells dedifferentiation was overexpressed in lung cancer samples. However, genes associated with Schwann cells migration inhibition system were downregulated. Besides, miRNA targeting those pathways were also deregulated. In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in perineural invasion of lung cancer.

Leprosy susceptibility: genetic variations regulate innate and adaptive immunity, and disease outcome.

The past few years have been very productive concerning the identification of genes associated with leprosy. Candidate gene strategies using both case-control and family-based designs, as well as large-scale approaches such as linkage and gene-expression genomic scans and, more recently, genome-wide association studies, have refined and enriched the list of genes highlighting the most important innate and adaptive immune pathways associated with leprosy susceptibility or resistance. During the early events of host-pathogen interaction identified genes are involved in pattern recognition receptors, and mycobacterial uptake (TLRs, NOD2 and MRC1), which modulate autophagy. Another gene, LTA4H, which regulates the levels of lipoxin A4 and possibly interacts with lipid droplet-related events, also plays a role in the early immune responses to Mycobacterium leprae. Together, the activation of these pathways regulates cellular metabolism upon infection, activating cytokine production through NF-κB and vitamin D-vitamin D receptor pathways, while PARK2 and LRRK2 participate in the regulation of host-cell apoptosis. Concomitantly, genes triggered to form and maintain granulomas (TNF, LTA and IFNG) and genes involved in activating and differentiating T-helper cells (HLA, IL10, as well as the TNF/LTA axis and the IFNG/IL12 axis) bridge immunological regulation towards adaptive immunity. Subtle variations in these genes, mostly single nucleotide polymorphisms, alter the risk of developing the disease or the severity of leprosy. Knowing these genes and their role will ultimately lead to better strategies for leprosy prevention, treatment and early diagnosis. Finally, the same genes associated with leprosy were also associated with autoimmune (Crohn's disease, rheumathoid arthritis, psoriasis) or neurodegenerative diseases (Parkinson's and Alzheimer's). Thus, information retrieved using leprosy as a model could be valuable to understanding the pathogenesis of other complex diseases.