Publications by authors named "Leticia F Leal"

Introduction: Lung cancer in never-smoker (LCINS) patients accounts for 20% of lung cancer cases, and its biology remains poorly understood, particularly in genetically admixed populations. We elucidated the molecular profile of driver genes in Brazilian LCINS.

Methods: The mutational and gene fusion status of 119 lung adenocarcinomas from self-reported never-smoker patients, was assessed using targeted sequencing (NGS), nCounter, and immunohistochemistry.

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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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Article Synopsis
  • Immune checkpoint inhibitors (ICIs) have transformed treatment for non-small-cell lung cancer (NSCLC), but better methods for selecting patients who will benefit from these therapies are necessary, particularly through gene expression profiling (GEP).
  • In a study involving 135 Brazilian NSCLC patients treated with ICIs, researchers analyzed GEP from tumor tissues and found that certain signatures, such as tumor inflammation signature (TIS) and IFN-γ, were linked to better outcomes.
  • Patients with high TIS levels had significantly longer overall survival after immunotherapy (29.2 months) compared to those with low levels (15.5 months), indicating that TIS and IFN-γ could serve as valuable biomarkers to guide treatment choices
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Background: Gastrointestinal stromal tumors (GIST) represent a significant clinical challenge due to their metastatic potential and limited treatment options. Raf kinase inhibitor protein (RKIP), a suppressor of the MAPK signaling pathway, is downregulated in various cancers and acts as a metastasis suppressor. Our previous studies demonstrated low RKIP expression in GIST and its association with poor outcomes.

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  • - Medulloblastomas, the most common brain tumors in children, are classified into subgroups with WNT-activated cases often linked to specific gene mutations; this study focuses on their occurrence in a Latin-Iberian population.
  • - Analyzing 266 tumor samples from Brazil, Portugal, and Argentina, the researchers found that only 15% were WNT-activated, with 73% of these containing mutations; wild-type cases tended to occur more frequently in females and were associated with poorer outcomes.
  • - The study revealed a lower incidence of mutations in WNT-activated medulloblastomas in the Latin-Iberian cohort than reported elsewhere, suggesting around 30% of these cases might be hereditary due to
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  • A study examined the link between how long patients abstained from smoking before being diagnosed with non-small-cell lung cancer (NSCLC) and their survival rates, aiming to inform public health messaging.
  • Conducted using data from 26 cohorts across various continents, researchers analyzed survival outcomes based on smoking history and demographic factors of nearly 42,087 patients diagnosed with NSCLC.
  • Findings revealed that longer periods of smoking abstinence (1-3 years, 3-5 years, and over 5 years) before diagnosis were correlated with improved overall and NSCLC-specific survival rates, indicating that quitting smoking can enhance cancer outcomes.
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Lung cancer has the highest mortality rate among all cancer types, resulting in over 1.8 million deaths annually. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) has revolutionized the treatment of non-small cell lung cancer (NSCLC).

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Background: Some studies reported that differential gene expression could be used as a biomarker for high-grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid-based cytology (LBC) samples.

Methods: LBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses.

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Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of in a large series of TGCT from a single reference cancer center.

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Introduction: Medulloblastoma is the most common and lethal pediatric malignant brain tumor. It comprises four main molecular subgroups: WNT-activated, SHH-activated, Group 3, and Group 4. Medulloblastoma treatment is surgical resection, craniospinal radiation, and chemotherapy.

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Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a minimally invasive approach to determine biomarkers from body fluids, such as blood, urine, sputum, and saliva.

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Introduction: Glioblastoma (GBM), isocitrate dehydrogenase () wild-type ( ), and grade 4 astrocytomas, mutant ( ), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities.

Objectives: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with GBM and tumors and identify prognostic biomarkers and a gene signature associated with patient survival.

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Introduction: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set.

Methods: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions.

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ERBB2 exon 20 insertions may impact the clinical management of lung cancer patients. However, the frequency of ERBB2 exon 20 insertions in lung cancer patients in Brazil is scarce. Here, we analyzed 722 Brazilian non-small cell lung cancer (NSCLC) patients from Barretos Cancer Hospital that were indicated to require routine lung cancer molecular testing.

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Introduction: Lung cancer is the deadliest cancer worldwide and in Brazil. Despite strong evidence, lung cancer screening by low-dose computed tomography (LDCT) in high-risk individuals is far from a reality in many countries, particularly in Brazil. Brazil has a universal public health system marked with important inequalities.

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Background: Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center.

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Article Synopsis
  • The study aims to assess the therapeutic potential of vitamin D receptor (VDR) signaling in adrenocortical carcinoma (ACC) cells, specifically H295R.
  • Researchers found that VDR was hypermethylated and underexpressed in these cells, but treatments with calcitriol and seocalcitol restored VDR signaling, reduced cell proliferation, and affected other signaling pathways.
  • In animal models, seocalcitol inhibited tumor growth and reduced steroid secretion from tumors without severe side effects, suggesting VDR could be a promising target for ACC therapy and patient management.
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  • Pediatric adrenocortical tumors (pACT) show complex genomic profiles and lack clear prognostic markers and treatment options, prompting research into the Vitamin D3 receptor (VDR) for potential insights.
  • A study involving 108 pediatric patients found that most pACT had low VDR expression and high methylation, particularly in more aggressive carcinomas, suggesting a link between VDR status and disease severity.
  • The findings indicate that VDR hypermethylation and underexpression could serve as important predictive and prognostic biomarkers for pACT, affecting patient outcomes.
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Background: Somatic EGFR mutations define a subset of non-small cell lung cancers (NSCLC) that have clinical impact on NSCLC risk and outcome. However, EGFR-mutation-status is often missing in epidemiologic datasets. We developed and tested pragmatic approaches to account for EGFR-mutation-status based on variables commonly included in epidemiologic datasets and evaluated the clinical utility of these approaches.

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Cetuximab is the sole anti-EGFR monoclonal antibody that is FDA approved to treat head and neck squamous cell carcinoma (HNSCC). However, no predictive biomarkers of cetuximab response are known for HNSCC. Herein, we address the molecular mechanisms underlying cetuximab resistance in an in vitro model.

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New prevention strategies are needed to detect cervical intraepithelial neoplasia (CIN). The microRNA expression analysis has already been reported as molecular biomarkers in the early detection of cervical cancer (CC) through minimally invasive samples, such as liquid biopsy, obtained through collection using liquid-based cytology (LBC). In this study, we aimed to identify molecular signatures of microRNAs in cervical precursor lesions from LBC cervical and the molecular pathways potentially associated with the CC progression.

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Driver mutations in non-small cell lung cancer (NSCLC) have a relevant significance for clinical management. EGFR mutations are the most important predictive biomarkers for NSCLC, although KRAS and BRAF mutations can also be prognostic and predictive biomarkers, respectively. PCR-based approaches followed by sequencing are useful for EGFR, KRAS, and BRAF mutational analysis.

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Background: For non-small cell lung cancer (NSCLC) the most used method for analysing programmed cell death ligand 1 (PD-L1) expression is the Tumor Proportion Score (TPS). Nevertheless, for other tumour types, the Combined Positive Score (CPS) has been the method of choice.

Aim: Evaluate and compare the predictive value of both CPS and TPS as predictors of immunotherapy response in NSCLC, and to evaluate the agreement intra-observer between both methods and inter-observer between two expert lung pathologists.

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