Breast cancer (BC) is a highly heterogeneous disease. The treatment of BC is complicated owing to intratumoral complexity. Tissue biopsy and immunohistochemistry are the current gold standard ...techniques to guide breast cancer therapy; however, these techniques do not assess tumoral molecular heterogeneity. Personalized medicine aims to overcome these biological and clinical complexities. Advances in techniques and computational analyses have enabled increasingly sensitive, specific, and accurate application of liquid biopsy. Such progress has ushered in a new era in precision medicine, where the objective is personalized treatment of breast cancer, early screening, accurate diagnosis and prognosis, relapse detection, longitudinal monitoring, and drug selection. Liquid biopsy can be defined as the sampling of components of tumor cells that are released from a tumor and/or metastatic deposits into the blood, urine, feces, saliva, and other biological substances. Such components include circulating tumor cells (CTCs), circulating tumor DNA (ctDNA) or circulating tumor RNA (ctRNA), platelets, and exosomes. This review aims to highlight the role of liquid biopsy in breast cancer and precision medicine.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Background Although the clinical signs of inflammatory breast cancer (IBC) resemble acute inflammation, the role played by infiltrating immune and stromal cells in this aggressive disease is ...uncharted. The tumor microenvironment (TME) presents molecular alterations, such as epimutations, prior to morphological abnormalities. These changes affect the distribution and the intricate communication between the TME components related to cancer prognosis and therapy response. Herein, we explored the global DNA methylation profile of IBC and surrounding tissues to estimate the microenvironment cellular composition and identify epigenetically dysregulated markers. Methods We used the HiTIMED algorithm to deconvolve the bulk DNA methylation data of 24 IBC and six surrounding non-tumoral tissues (SNT) (GSE238092) and determine their cellular composition. The prognostic relevance of cell types infiltrating IBC and their relationship with clinicopathological variables were investigated. CD34 (endothelial cell marker) and CD68 (macrophage marker) immunofluorescence staining was evaluated in an independent set of 17 IBC and 16 non-IBC samples. Results We found lower infiltration of endothelial, stromal, memory B, dendritic, and natural killer cells in IBC than in SNT samples. Higher endothelial cell (EC) and stromal cell content were related to better overall survival. EC proportions positively correlated with memory B and memory CD8 + T infiltration in IBC. Immune and EC markers exhibited distinct DNA methylation profiles between IBC and SNT samples, revealing hypermethylated regions mapped to six genes ( CD40 , CD34 , EMCN , HLA-G , PDPN , and TEK ). We identified significantly higher CD34 and CD68 protein expression in IBC compared to non-IBC. Conclusions Our findings underscored cell subsets that distinguished patients with better survival and dysregulated markers potentially actionable through combinations of immunotherapy and epigenetic drugs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This exploratory analysis of the Neoadjuvant Carboplatin in Triple Negative Breast Cancer (NACATRINE) study aimed to identify the biomarkers of pathological complete response (pCR) in patients with ...triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC) within the context of a clinical trial. The NACATRINE trial is a phase II, single-center, randomized, open-label clinical trial that investigated the addition of carboplatin to sequential anthracycline- and taxane-based NAC for TNBC. We evaluated the gene expression in untreated samples to investigate its association with pCR, overall survival (OS), and disease-free survival (DFS). RNA was extracted from the tissue biopsy, and the nCounter Breast Cancer panel was used to analyze gene expression. Of the 66 patients included in the gene expression profiling analysis, 24 (36.4%) achieved pCR and 42 (63.6%) had residual disease. In unsupervised hierarchical clustering analyses, differentially expressed genes between patients with and without pCR were identified irrespective of the treatment (24 genes), carboplatin (37 genes), and non-carboplatin (27 genes) arms. In receiver operating characteristic (ROC) curve analysis, 10 genes in the carboplatin arm (area under the ROC curve AUC, 0.936) and three genes in the non-carboplatin arm (AUC, 0.939) were considered to be potential pCR-associated biomarkers. We identified genes that were associated with improvements in OS and DFS in addition to being related to pCR. We successfully identified gene expression signatures associated with pCR in pretreatment samples of patients with TNBC treated with NAC. Further investigation of these biomarkers is warranted.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Liquid biopsy is increasingly vital in monitoring neoadjuvant breast cancer treatment. This study collected plasma samples at three time points from participants in the Neoadjuvant Carboplatin in ...Triple Negative Breast Cancer (NACATRINE), analyzing miRNA expression with NanoString's nCounter
Human v3 miRNA assay. In the carboplatin arm, four ct-miRNAs exhibited dynamic changes linked to pathologic complete response, with a combined area under the curve of 0.811. Similarly, the non-carboplatin arm featured four ct-miRNAs with an area under the curve of 0.843. These findings underscore the potential of ct-miRNAs as personalized tools in breast cancer treatment, assisting in predicting treatment response and assessing the risk of relapse. Integrating ct-miRNA analysis into clinical practice can optimize decisions and enhance patient outcomes.
ABSTRACT The term Post-Barreiras is a definition for sediments above the deposits of the Barreiras Formation, and the genesis of soils in these environments must be related to sedimentary deposition. ...Our objective was to apply multi-technique analyses to characterize the sediments and soils to understand pedogenesis in these environments. We analysed sedimentological parameters and the geochronology of sediments. Morphological, chemical, and mineralogical analyses allowed the characterization of the soil. Also, these data supported the analysis of lithological discontinuity. We considered the contents of Ti and Zr, uniformity value, the fraction of organic material, morphology, and palynological analysis. The age of Post-Barreiras sediments is from the Pleistocene, and they have a more significant variation of sedimentological parameters concerning Barreiras Formation layers. In general, the soils are sandy, acidic, have a low level of exchangeable cations. Mineralogy has a predominance of quartz and kaolinite minerals. In the region, there are soils with low morphological variation, classified as Quartzipsamments. In other cases, there are soils with apparent spodic morphology, which is conditioned by four aspects: (i) Podzolization in Post-Barreiras sandy sediments without evidence of lithological discontinuity, forming Bs horizon (Spodosols); (ii) contact zones (Post-Barreiras/Barreiras Formation) with physical, chemical, and morphological evidence of discontinuity, forming Quartzipsamments or Ultisols; (iii) layers of the Barreiras Formation buried by Post-Barreiras sediments and the subsequent podzolization process, forming Bhm horizon (Spodosols); and (iv) destruction of Ultisols clay, forming Bs horizon (Spodosols). The sedimentary association (Post-Barreiras/Barreiras Formation) favors the development of different soils. The contact zones generate a morphological aspect similar to the Spodosols, associated or not with podzolization processes.
Abstract Background Inflammatory breast cancer (IBC) is a rare disease characterized by rapid progression, early metastasis, and a high mortality rate. Methods Genome-wide DNA methylation analysis ...(EPIC BeadChip platform, Illumina) and somatic gene variants (105 cancer-related genes) were performed in 24 IBCs selected from a cohort of 140 cases. Results We identified 46,908 DMPs (differentially methylated positions) (66% hypomethylated); CpG islands were predominantly hypermethylated (39.9%). Unsupervised clustering analysis revealed three clusters of DMPs characterized by an enrichment of specific gene mutations and hormone receptor status. The comparison among DNA methylation findings and external datasets (TCGA-BRCA stages III-IV) resulted in 385 shared DMPs mapped in 333 genes (264 hypermethylated). 151 DMPs were associated with 110 genes previously detected as differentially expressed in IBC (GSE45581), and 68 DMPs were negatively correlated with gene expression. We also identified 4369 DMRs (differentially methylated regions) mapped on known genes (2392 hypomethylated). BCAT1, CXCL12, and TBX15 loci were selected and evaluated by bisulfite pyrosequencing in 31 IBC samples. BCAT1 and TBX15 had higher methylation levels in triple-negative compared to non-triple-negative, while CXCL12 had lower methylation levels in triple-negative than non-triple-negative IBC cases. TBX15 methylation level was associated with obesity. Conclusions Our findings revealed a heterogeneous DNA methylation profile with potentially functional DMPs and DMRs. The DNA methylation data provided valuable insights for prognostic stratification and therapy selection to improve patient outcomes. Graphical Abstract
Neoadjuvant chemotherapy (NAC) is often used to treat locally advanced disease for tumor downstaging, thus improving the chances of breast-conserving surgery. From the NAC response, it is possible to ...obtain prognostic information as patients may reach a pathological complete response (pCR). Those who do might have significant advantages in terms of survival rates. Breast cancer (BC) is a heterogeneous disease that requires personalized treatment strategies. The development of targeted therapies depends on identifying biomarkers that can be used to assess treatment efficacy as well as the discovery of new and more accurate therapeutic agents. With the development of new “OMICS” technologies, i.e., genomics, transcriptomics, and proteomics, among others, the discovery of new biomarkers is increasingly being used in the context of clinical practice, bringing us closer to personalized management of BC treatment. The aim of this review is to compile the main biomarkers that predict pCR in BC after NAC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Bitter orange (Citrus aurantium) is an important source of essential oils with high antimicrobial activities, however the composition and antifungal potential of the decoction peels is little ...explored. This study assessed the peel decoction's chemical profile at the secondary metabolism level and its antifungal activity against the melon phytopathogen Fusarium jinanense. The decoction's antifungal potential was investigated using a bioassay-guided fractionation approach based on Solid-Phase Extraction (SPE) and LC-HRMS/MS analysis. Coumarins and flavones were the most abundant classes of compounds in the high-value fractions responsible for up to 61% of the mycelial inhibition of F. jinanense. Overall, this study has presented for the first time the chemical composition, the antifungal potential of the decoction of C. aurantium peels and the compounds associated with these results. This strategy can guide the exploration of under-explored food sources and add value to compounds or fractions enriched with bioactive compounds.
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•C. aurantium peel decoction showed antifungal activity against Fusarium jinanense.•Antifungal activity increased after the SPE fractionation strategy.•LC-MS/MS dereplication annotated 65 compounds of different chemical classes.•The coumarin and polymethoxyflavone fractions showed high antifungal activities.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although ...endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting.
The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%).
Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities.
Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.
ABSTRACT The control of Asian soybean rust depends on fungicide efficacy and the application technology; however, the leaf architecture of soybean cultivars may also interfere in disease control. ...This study aimed to evaluate Asian rust control and fungicide deposition using spray nozzles in three soybean cultivars. A randomized block design was used, with treatments arranged in a split-plot scheme; the plots were three soybean cultivars (SYN 1561 IPRO, M6410 IPRO, and M6210 IPRO) and the subplots three spray nozzles (11002 BD, AIXR 110015 and TTJ60 11002), in addition to a control with no fungicide application, and four replicates. The volume median diameter, droplet coverage, leaf area index, area under the disease progress curve, 1,000-grain weight and crop yield were evaluated. The 11002BD and AIXR11005 nozzles provided better spray deposition in cultivars with lower leaf area indexes at the R1 phenological stage. Nozzles 11002BD, AIXR110015 and TTJ60 ensured better management of Asian rust than that of the control treatment, regardless of leaf area index. Cultivar SYN1561 obtained the largest grain yield and highest leaf area index in the season with the highest rainfall, regardless of the spray nozzle used.
RESUMO O controle da ferrugem asiática da soja depende da eficácia do fungicida e da tecnologia de aplicação empregada, entretanto, a arquitetura foliar de cada cultivar de soja também pode ser um fator a interferir no controle da doença. O objetivo do estudo foi avaliar a deposição de calda fungicida e o controle da ferrugem asiática da soja utilizando pontas de pulverização em três cultivares de soja. O delineamento experimental utilizado foi em blocos ao acaso, com tratamentos arranjados no esquema de parcelas subdivididas, em que as parcelas eram três cultivares de soja (SYN 1561 IPRO, M6410 IPRO e M6210 IPRO) e as subparcelas três pontas de pulverização (11002 BD, AIXR 110015 e TTJ60 11002), e uma testemunha sem aplicação, com quatro repetições. Foram avaliados o diâmetro mediano volumétrico, cobertura de gotas, índice de área foliar (IAF), área abaixo da curva de progresso da doença, massa de 1000 grãos e produtividade da soja. Os bicos 11002BD e AIXR11005 fornecem melhor deposição de calda naquelas cultivares com menores índices de área de foliar, no estágio fenológico da soja R1. Os bicos 11002BD, AIXR110015 e TTJ60 fornecem controle da ferrugem asiática comparada ao tratamento controle, independentemente do índice de área de folha da cultivar. A cultivar SYN1561 apresentou a maior produção de grãos e o maior índice de área de folha, independentemente do bico de pulverização utilizado, na época com a maior precipitação pluviométrica.
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