Publications by authors named "Rui M Reis"

Colorectal cancer incidence rates vary geographically and have changed over time. Notably, in the past two decades, the incidence of early-onset colorectal cancer, affecting individuals under the age of 50 years, has doubled in many countries. The reasons for this increase are unknown.

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Homeobox A9 promoter methylation (HOXA9) has been reported as a biomarker for early lung adenocarcinoma patients' prognosis. We aim to evaluate its prognostic value, regardless of disease stage. Using droplet digital PCR, we measured HOXA9 methylation in a cohort comprising 161 Brazilian patients.

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Background: The molecular non-genetic changes of resistance to sotorasib are currently uncertain. The aim of this study was to generate a sotorasib-resistant cell line via selective pressure and systematically examine the molecular and phenotypic alterations caused by resistance.

Methods: Mutant NCI-H358 (KRAS) were exposed to incremental doses (2-512 nM) of sotorasib.

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Purpose: Molecular classification of endometrial cancer (EC) has emerged as a key approach to individualize therapy and define prognostic outcomes. This study aimed to implement the traditional ProMisE classification in a Brazilian population, compared with a molecular setting of ProMisE biomarkers, and evaluate its impact on patients' prognosis.

Patient And Methods: A prospective cohort of 114 patients with primary EC treated at Barretos Cancer Hospital (BCH) between October 2020 and December 2022 was conducted.

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Background: Colorectal cancer (CRC) is the second leading cause of cancer death worldwide. Early detection of precursor lesions or early-stage cancer could hamper cancer development or improve survival rates. Liquid biopsy, which detects tumor biomarkers, such as mutations, in blood, is a promising avenue for cancer screening.

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Article Synopsis
  • Glioblastoma (GBM) is a tough brain cancer to treat, but researchers are exploring the nose-to-brain drug delivery method as a potential solution.
  • Nanoengineering has led to the creation of a specialized nanostructure (NP-MB) that combines a polymer core with Temozolomide (TMZ) and glioma cell membranes, enhancing drug delivery.
  • The study shows that NP-MB effectively releases TMZ, is more toxic to glioma cells than conventional methods, reduces tumor size, and successfully reaches the brain, indicating its potential for advancing GBM therapy in clinical settings.
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Background: Photodynamic Therapy (PDT) is a therapeutic modality that combines the application of a photoactive compound (photosensitizer, PS) with low-power light to generate reactive oxygen species in the target tissue, resulting in cytotoxic damage and cell death, while sparing adjacent tissues. The objective of this study was to evaluate the phototoxicity of a cyanine dye with two chromophores (biscyanines, BCD) in systems with varying levels of cellular organization, and we used the Photogem® (a photosensitizer approved by the Brazilian ANVISA agency for clinical use in Photodynamic Therapy) as a positive control.

Materials And Methods: The cytotoxicity of the compounds was assessed in vitro in 2D monolayers, 3D spheroid cultures, and artificial skin models.

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Background: The role of microbiome, particularly Fusobacterium nucleatum (Fn), in periodontal disease and oral squamous cell carcinoma (OSCC) has been recently explored. This study aimed to evaluate the Fn presence and its levels in oral rinse samples from Brazilian OSCC patients and healthy individuals and its association with sociodemographic, clinical, and oral health features.

Methods: In this case-control study, 80 participants were included, 31 OSCC patients and 49 individuals without a cancer history.

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Germ cell tumors (GCTs) constitute diverse neoplasms arising in the gonads or extragonadal locations. Testicular GCTs (TGCTs) are the predominant solid tumors in adolescents and young men. Despite cisplatin serving as the primary therapeutic intervention for TGCTs, 10‑20% of patients with advanced disease demonstrate resistance to cisplatin‑based chemotherapy, and epithelial‑mesenchymal transition (EMT) is a potential contributor to this resistance.

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Background: Extracellular vesicles (EVs), ubiquitously released by blood cells, facilitate intercellular communication. In cancer, tumor-derived EVs profoundly affect the microenvironment, promoting tumor progression and raising the risk of recurrence. These EVs contain miRNAs (EV-miRNAs), promising cancer biomarkers.

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Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection.

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Article Synopsis
  • LCINS accounts for 20% of lung cancer cases, with the study focusing on the molecular profile of driver genes in Brazilian patients who never smoked.
  • The investigation involved studying mutational and gene fusion status in 119 lung adenocarcinomas using advanced sequencing techniques, alongside genetic ancestry analysis.
  • Results showed high mutation rates in genes like EGFR and TP53, with significant findings on ancestry influencing mutation patterns, and highlighted that a large percentage of patients have potential targets for effective treatment.
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  • RKIP is a tumor suppressor gene whose reduced expression is linked to worse outcomes in different solid tumors, particularly by affecting cellular signaling pathways like MAPK.
  • An analysis of 30 studies showed that in most solid tumors, higher EGFR levels were correlated with lower RKIP levels, especially notable in cervical cancer.
  • Experiments confirmed that reducing RKIP leads to increased EGFR activity, while overactive EGFR decreases RKIP expression, highlighting a significant relationship that could impact cancer prognosis in patients.
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  • * Immunohistochemical analysis revealed that microsatellite instability (MSI) was rare, and PD-L1 expression was low, showing no link to treatment response, while certain immune checkpoint genes had varied expression levels related to BCG responsiveness.
  • * Key findings suggest that PDCD1, CTLA4, TNFRSF14, TIGIT, and CD276 could serve as potential predictive biomarkers for determining BCG treatment outcomes in these patients.
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  • - The study focused on treatment experiences for kids with NTRK-fused tumors, looking at access to care, how they responded to treatment, side effects, and overall health outcomes.
  • - Researchers reviewed data from 17 pediatric cases treated with larotrectinib, identifying six NTRK fusion subtypes and noting that 11 of 14 patients had positive tumor responses, with various levels of adverse effects reported.
  • - The findings suggest that larotrectinib is effective for treating these tumors in children, but challenges still exist in ensuring consistent access to treatment, particularly in countries with limited resources like Brazil.
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Purpose: High-mobility group box 1 protein (HMGB1) is subject to exportin 1 (XPO1)-dependent nuclear export, and it is involved in functions implicated in resistance to immunotherapy. We investigated whether HMGB1 mRNA expression was associated with response to immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC).

Patients And Methods: RNA was isolated from pretreatment biopsies of patients with advanced NSCLC treated with ICI.

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Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, known for its heterogeneity and treatment-associated toxicity, and there is a critical need for new therapeutic targets. We analyzed the somatic mutation profile of 15 driver genes in 69 Latin-Iberian molecularly characterized medulloblastomas using the Illumina TruSight Tumor 15 panel. We classified the variants based on their clinical impact and oncogenicity.

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microRNAs (miRNAs) are small endogenous noncoding RNAs, and alterations in their expression may contribute to oncogenesis. Discovering a unique miRNA pattern holds the potential for early detection and novel treatment possibilities in cancer. This study aimed to evaluate miRNA expression in pediatric patients with gonadal germ cell tumors (GCTs), focusing on characterizing the miRNA profiles of each histological subtype and identifying a distinct histological miRNA signature for a total of 42 samples of pediatric gonadal GCTs.

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International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations.

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Altered glycolytic metabolism has been associated with chemoresistance in acute myeloid leukemia (AML). However, there are still aspects that need clarification, as well as how to explore these metabolic alterations in therapy. In the present study, we aimed to elucidate the role of glucose metabolism in the acquired resistance of AML cells to cytarabine (Ara-C) and to explore it as a therapeutic target.

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Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.

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Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient.

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Background: Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated.

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Background: Glioblastoma is a malignant brain tumor requiring careful clinical monitoring even after primary management. Personalized medicine has suggested the use of various molecular biomarkers as predictors of patient prognosis or factors utilized for clinical decision-making. However, the accessibility of such molecular testing poses a constraint for various institutes requiring identification of low-cost predictive biomarkers to ensure equitable care.

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