Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease.

Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (F) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans.

The Chilean COVID-19 Genomics Network Biorepository: A Resource for Multi-Omics Studies of COVID-19 and Long COVID in a Latin American Population.

Although a lack of diversity in genetic studies is an acknowledged obstacle for personalized medicine and precision public health, Latin American populations remain particularly understudied despite their heterogeneity and mixed ancestry. This gap extends to COVID-19 despite its variability in susceptibility and clinical course, where ethnic background appears to influence disease severity, with non-Europeans facing higher hospitalization rates. In addition, access to high-quality samples and data is a critical issue for personalized and precision medicine, and it has become clear that the solution lies in biobanks.

Quadruple therapies show a higher eradication rate compared to standard triple therapy for Helicobacter pylori infection within the LEGACy consortium. A multicenter observational study in European and Latin American countries.

Introduction: Gastric cancer (GC) is one of the most lethal malignancies worldwide. Helicobacter pylori is the primary cause of GC; therefore, its eradication reduces the risk of developing this neoplasia. There is extensive evidence regarding quadruple therapy with relevance to the European population.

Fibroblast growth factor receptor signaling in estrogen receptor-positive breast cancer: mechanisms and role in endocrine resistance.

Fibroblast Growth Factor Receptors (FGFRs) play a significant role in Estrogen Receptor-positive (ER+) breast cancer by contributing to tumorigenesis and endocrine resistance. This review explores the structure, signaling pathways, and implications of FGFRs, particularly FGFR1, FGFR2, FGFR3, and FGFR4, in ER+ breast cancer. FGFR1 is frequently amplified, especially in aggressive Luminal B-like tumors, and its amplification is associated with poor prognosis and treatment resistance.

Biomarkers in Thyroid Cancer: Emerging Opportunities from Non-Coding RNAs and Mitochondrial Space.

Thyroid cancer diagnosis primarily relies on imaging techniques and cytological analyses. In cases where the diagnosis is uncertain, the quantification of molecular markers has been incorporated after cytological examination. This approach helps physicians to make surgical decisions, estimate cancer aggressiveness, and monitor the response to treatments.

Assessing the Occurrence and Influence of Cancer Chemotherapy-Related Pharmacogenetic Alleles in the Chilean Population.

Background: Pharmacogenomic knowledge as a biomarker for cancer care has transformed clinical practice, however, as current guidelines are primarily derived from Eurocentric populations, this limits their application in Latin America, particularly among Hispanic or Latino groups. Despite advancements, systemic chemotherapy still poses challenges in drug toxicity and suboptimal response. This study explores pharmacogenetic markers related to anticancer drugs in a Chilean cohort, filling a gap in Latin American research.

Exploring the impact of MiR-92a-3p on FOLFOX chemoresistance biomarker genes in colon cancer cell lines.

One of the primary obstacles faced by individuals with advanced colorectal cancer (CRC) is the potential development of acquired chemoresistance as the disease advances. Studies have indicated a direct association between elevated levels of miR-92a-3p and the progression, metastasis, and chemoresistance observed in CRC. We proposed that miR-92a-3p impairs FOLFOX (fluorouracil/oxaliplatin) chemotherapy response by upregulating the expression of chemoresistance biomarker genes through the activation of β-catenin and epithelial-mesenchymal transition (EMT).

Overexpression of REST Represses the Epithelial-Mesenchymal Transition Process and Decreases the Aggressiveness of Prostate Cancer Cells.

The RE-1 silencing transcription factor (REST) is a repressor factor related to neuroendocrine prostate cancer (PCa) (NEPC), a poor prognostic stage mainly associated with castration-resistant PCa (CRPC). NEPC is associated with cell transdifferentiation and the epithelial-mesenchymal transition (EMT) in cells undergoing androgen deprivation therapy (ADT) and enzalutamide (ENZ). The effect of REST overexpression in the 22rv1 cell line (xenograft-derived prostate cancer) on EMT, migration, invasion, and the viability for ENZ was evaluated.

Oxidative damage associated with exposure to heavy metals present in topsoils in central Chile.

Exposure to heavy metals may cause the overproduction of reactive oxygen species, generating oxidative stress and consequently, various harms to human health. The soil surrounding the Ventanas Industrial Complex, in Puchuncaví and Quintero municipal districts on the central Chilean coast, contains heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed the maximum permissible levels established by Italian soil standards (used as a reference). This study aimed to investigate the potential association between heavy metal exposure in humans and the levels of oxidative stress biomarkers in inhabitants of these locations.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association.

Acquired Secondary HER2 Mutations Enhance HER2/MAPK Signaling and Promote Resistance to HER2 Kinase Inhibition in Breast Cancer.

Unlabelled: HER2 mutations drive the growth of a subset of breast cancers and are targeted with HER2 tyrosine kinase inhibitors (TKI) such as neratinib. However, acquired resistance is common and limits the durability of clinical responses. Most HER2-mutant breast cancers progressing on neratinib-based therapy acquire secondary mutations in HER2.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models.

Oxidative Stress Parameters and Morphological Changes in Japanese Medaka () after Acute Exposure to OA-Group Toxins.

Toxins of the OA-group (okadaic acid, OA; dinophysistoxin-1, DTX-1) are the most prevalent in the fjords of southern Chile, and are characterized by their potential harmful effects on aquatic organisms. The present study was carried out to determine the acute toxicity of OA/DTX-1 on oxidative stress parameters in medaka () larvae. Medaka larvae were exposed to different concentrations (1.

The Transcription Factors Zeb1 and Snail Induce Cell Malignancy and Cancer Stem Cell Phenotype in Prostate Cells, Increasing Androgen Synthesis Capacity and Therapy Resistance.

Prostate cancer (PCa) incidence has increased during the last decades, becoming one of the leading causes of death by cancer in men worldwide. During an extended period of prostate cancer, malignant cells are androgen-sensitive being testosterone the main responsible for tumor growth. Accordingly, treatments blocking production and action of testosterone are mostly used.

Cancer Stemness/Epithelial-Mesenchymal Transition Axis Influences Metastasis and Castration Resistance in Prostate Cancer: Potential Therapeutic Target.

Prostate cancer (PCa) is a leading cause of cancer death in men, worldwide. Mortality is highly related to metastasis and hormone resistance, but the molecular underlying mechanisms are poorly understood. We have studied the presence and role of cancer stem cells (CSCs) and the Epithelial-Mesenchymal transition (EMT) in PCa, using both in vitro and in vivo models, thereby providing evidence that the stemness-mesenchymal axis seems to be a critical process related to relapse, metastasis and resistance.

Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer.

Colorectal cancer (CRC) is a major cause of mortality worldwide, associated with a steadily growing prevalence. Notably, the identification of , , and mutations has markedly improved targeted CRC therapy by affording treatments directed against the epidermal growth factor receptor (EGFR) and other anti-angiogenic therapies. However, the survival benefit conferred by these therapies remains variable and difficult to predict, owing to the high level of molecular heterogeneity among patients with CRC.

SPARC Induces E-Cadherin Repression and Enhances Cell Migration through Integrin αvβ3 and the Transcription Factor ZEB1 in Prostate Cancer Cells.

Secreted protein acidic and rich in cysteine (SPARC), or osteonectin, is a matricellular protein that modulates interactions between cells and their microenvironment. SPARC is expressed during extracellular matrix remodeling and is abundant in bone marrow and high-grade prostate cancer (PCa). In PCa, SPARC induces changes associated with epithelial-mesenchymal transition (EMT), enhancing migration and invasion and increasing the expression of EMT transcriptional factor Zinc finger E-box-binding homeobox 1 (ZEB1), but not Zinc finger protein SNAI1 (Snail) or Zinc finger protein SNAI2 (Slug).

Arsenic concentration in topsoil of central Chile is associated with aberrant methylation of P53 gene in human blood cells: a cross-sectional study.

Gene expression can be modified in people who are chronically exposed to high concentrations of heavy metals. The soil surrounding the Ventanas Industrial Complex, located on the coastal zone of Puchuncaví and Quintero townships (Chile), contain heavy metal concentrations (As, Cu, Pb, Zn, among others) that far exceed international standards. The aim of this study was to determine the potential association of the heavy metals in soils, especially arsenic, with the status of methylation of four tumor suppressor genes in permanent residents in those townships.

Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression.

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer () using robust linear and logistic regression techniques.

Effect of , , and Genetic Polymorphisms in Immunosuppressive Treatment in Chilean Kidney Transplanted Patients.

Cyclosporine (CsA) and tacrolimus (TAC) are immunosuppressant drugs characterized by a narrow therapeutic range and high pharmacokinetic variability. The effect of polymorphisms in genes related to the metabolism and transport of these drugs, namely , , and genes, has been evaluated in diverse populations. However, the impact of these polymorphisms on drug disposition is not well established in Latin American populations.

Validation of an NGS Panel Designed for Detection of Actionable Mutations in Tumors Common in Latin America.

Next-generation sequencing (NGS) is progressively being used in clinical practice. However, several barriers preclude using this technology for precision oncology in most Latin American countries. To overcome some of these barriers, we have designed a 25-gene panel that contains predictive biomarkers for most current and near-future available therapies in Chile and Latin America.

A case-control study of a combination of single nucleotide polymorphisms and clinical parameters to predict clinically relevant toxicity associated with fluoropyrimidine and platinum-based chemotherapy in gastric cancer.

Background: Fluoropyrimidine plus platinum chemotherapy remains the standard first line treatment for gastric cancer (GC). Guidelines exist for the clinical interpretation of four DPYD genotypes related to severe fluoropyrimidine toxicity within European populations. However, the frequency of these single nucleotide polymorphisms (SNPs) in the Latin American population is low (< 0.

Central catheter-associated deep vein thrombosis in cancer: clinical course, prophylaxis, treatment.

The adequate handling of central venous catheters is a key element in the management of patients with cancer. Catheter-associated deep vein thrombosis is frequently observed in patients with malignant diseases; however, despite being a common complication among these patients, objective information concerning its epidemiology, clinical course, prophylaxis and treatment strategies is very limited. The reported incidence of catheter-related thrombosis (CRT) is highly variable, depending on symptomatic events, or if patients are screened for asymptomatic thrombosis.