RESUMO
Cervical cancer is among the most frequently occurring neoplasms worldwide, and it particularly affects individuals in developing countries. Factors such as the low quality of screening tests, the high incidence of locally advanced cancer stages and the intrinsic resistance of certain tumors are the main causes of failure in the treatment of this neoplasm. Due to advances in the understanding of carcinogenic mechanisms and bioengineering research, advanced biological nanomaterials have been manufactured. The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including IGF receptor 1. These receptors are activated by binding to their respective growth factor ligands, IGF-1 and IGF-2, and insulin, and play an important role in the development, maintenance, progression, survival and treatment resistance of cervical cancer. In the present review, the role of the IGF system in cervical cancer and three nanotechnological applications that use elements of this system are described, namely Trap decoys, magnetic iron oxide nanoparticles and protein nanotubes. Their use in the treatment of resistant cervical cancer tumors is also discussed.
RESUMO
Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute-Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and exome sequenced. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.
Assuntos
Variações do Número de Cópias de DNA , Proteínas de Ligação a DNA , Proteínas de Neoplasias , Neoplasias da Bexiga Urinária , Humanos , México , Mutação , Invasividade Neoplásica , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genéticaRESUMO
BACKGROUND: Worldwide prevalence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has increased, affecting mostly young males. OPSCC associated with Human Papillomavirus (HPV) infection exhibits particular characteristics in terms of response to treatment, hence HPV has been proposed as a prognostic factor. The impact of HPV positivity and associated biomarkers on OPSCC in the Mexican population has not been addressed. Therefore, the analysis of OPSCC prognostic markers in the Mexican population is necessary. METHODS: Retrolective study in Mexican OPSCC patients, where HPV prevalence, p16 and EGFR levels were assessed using INNO-LiPA and immunohistochemistry. RESULTS: We found an HPV prevalence of 57.6% in OPSCC cases treated at a reference center in Mexico. HPV and p16 positivity, as well as EGFR, associate with better outcomes in OPSCC patients, and they also promote reduced death risk. Notably, HPV presence and p16 positivity showed a significant association with disease-free survival (DFS), with a HR of 0.15 (p = 0.006) and a HR of 0.17 (p = 0.012), respectively, indicating a possible role as predictive biomarkers in Mexican OPSCC patients. CONCLUSIONS: Our results reflect the clinical utility of p16 analysis to improve overall survival (OS) and to predict recurrence in oropharyngeal cancer. These results position p16 and HPV as predictive biomarkers for OPSCC.
RESUMO
Despite having a favorable response to platinum-based chemotherapies, ~15% of Testicular Germ-Cell Tumor (TGCT) patients are platinum-resistant. Mortality rates among Latin American countries have remained constant over time, which makes the study of this population of particular interest. To gain insight into this phenomenon, we conducted whole-exome sequencing, microarray-based comparative genomic hybridization, and copy number analysis of 32 tumors from a Mexican cohort, of which 18 were platinum-sensitive and 14 were platinum-resistant. We incorporated analyses of mutational burden, driver mutations, and SNV and CNV signatures. DNA breakpoints in genes were also investigated and might represent an interesting research opportunity. We observed that sensitivity to chemotherapy does not seem to be explained by any of the mutations detected. Instead, we uncovered CNVs, particularly amplifications on segment 2q11.1 as a novel variant with chemosensitivity biomarker potential. Our data shed light into understanding platinum resistance in a Latin-origin population.
RESUMO
The heat shock protein 90 kDalpha (Hsp90) subfamily is constituted by five isoforms, among them Hsp90alpha and Hsp90beta are the more abundant cytosolic proteins. These two proteins are molecular chaperons that participate in numerous cellular processes, through interacting with more than 100 proteins known as client proteins of Hsp90. These client proteins include: transcriptional factors, kinase proteins and other proteins that participate in transcriptional and transductional regulation such as steroid hormone receptors and nitric oxide synthases. This review offers a retrospective in the recent information about molecular and cellular functions of Hsp90 in the vascular physiology. In addition, the studies that evaluate Hsp90 role in the renal physiology and pathophysiology are discussed. Finally, the molecular tools developed to manipulate the Hsp90 expression in vitro and in vivo, through its inhibition or over-expression are reviewed. All these studies together have allowed increasing our knowledge regarding the role of Hsp90 during normal and pathophysiological conditions.