Nora Berois

Reliable circulating biomarkers for prognosis and treatment monitoring in non-small cell lung cancer (NSCLC) remain limited. Liquid biopsy offers a minimally invasive approach to identify clinically informative tumour-derived markers. Given the emerging role of GalNAc-transferases in cancer biology, we evaluated GALNT13 expression in peripheral blood as a potential biomarker for prognosis and disease monitoring in lung cancer patients. Sensitive molecular assays (nested and digital RT-PCR) were developed to detect GALNT13 mRNA in circulating tumour cells (CTCs). These methods were applied to peripheral blood samples from non-small cell lung cancer patients to assess prognostic value and enable longitudinal monitoring. A cohort of 143 NSCLC patients was analysed, of whom 60% were GALNT13-positive in peripheral blood at baseline. During a five-year follow-up, GALNT13 positivity was significantly associated with reduced overall survival. In several patients, increases in GALNT13 levels preceded radiologic evidence of disease progression. GALNT13 expression in CTCs emerges as a promising biomarker for prognosis and treatment monitoring in NSCLC. Prospective studies in larger cohorts are warranted to validate its clinical utility.

Introducción: El cáncer de tiroides constituye la neoplasia endocrina más frecuente, con un incremento en el diagnóstico de nódulos tiroideos debido al uso generalizado de la ecografía. En este contexto, la mutación BRAF V600E emerge como un marcador molecular clave en el carcinoma papilar, aunque su prevalencia muestra variaciones geográficas y carece de estudios locales. Este estudio tuvo como objetivo determinar la frecuencia de BRAF V600E en nuestra población y evaluar su utilidad como herramienta diagnóstica complementaria. Metodología: Se realizó un estudio transversal, analítico, que incluyó 155 pacientes de citopunción evaluados en el Hospital Maciel entre octubre del 2020 y setiembre del 2022 y 33 muestras de piezas en parafina. Las muestras fueron analizadas mediante PCR aleloespecífica para BRAF V600E. Se recopilaron variables clínicas, ecográficas, citológicas (clasificación Bethesda) e histopatológicas. Resultados: Los resultados demostraron una prevalencia de BRAF V600E del 75.9% (22/29) en carcinomas papilares, con sólo un 2.2% (4/180) en lesiones benignas (p<0.001). La prueba mostró una sensibilidad del 73.3% y una especificidad del 95.4%, con valores predictivos positivo y negativo de 75.9% y 94.7%, respectivamente. La mutación se asoció significativamente con categorías Bethesda V-VI (p<0.001), hipoecogenicidad (p=0.01) y carcinoma papilar en el estudio histopatológico (p=0.039). No se observaron diferencias con otras características anatomopatológicas. Conclusiones: La prevalencia de la mutación BRAF V600 fue del 75.9% en los carcinomas papilares, concordante con reportes internacionales de mayor incidencia. Se demostró adecuado rendimiento de la prueba diagnóstica pudiendo ser de utilidad para la toma de decisiones terapéuticas.

Background/Objectives: The focus of this study was to prepare and characterize docetaxel (DCX)-loaded lipid/polymer hybrid nanoparticles (LPHNps) functionalized with the monoclonal antibody (mAb) Chi-Tn for a potential active targeting approach in lung cancer treatment. Methods: We synthesized DOTAP-PLGA hybrid nanoparticles loaded with DCX and functionalized them with Chi-Tn mAb through a biotin–avidin approach. The physicochemical characterization involved dynamic light scattering, transmission electron microscopy, Raman spectroscopy, and atomic force microscopy. The in vitro and in vivo evaluations encompassed uptake studies, cell viability tests, and the assessment of tumor growth control in a lung cancer model. Results: The nanoparticles featured a hydrophobic PLGA core with 99.9% DCX encapsulation efficiency, surrounded by a DOTAP lipid shell ensuring colloidal stability with a high positive surface charge. The incorporation of PEGylated lipids on their surface helps evade the immune system and facilitate Chi-Tn mAb attachment. The resulting nanoparticles exhibit a spherical shape with monodisperse particle sizes averaging 250 nm, and demonstrate sustained drug release. In vitro uptake studies and viability assays conducted in A549 cancer cells show that the Chi-Tn mAb enhances nanoparticle internalization and significantly reduces cell viability. In vivo studies demonstrate a notable reduction in tumor volume and an increased survival rate in the A549 tumor xenograft mice model when DCX was encapsulated in nanoparticles and targeted with Chi-Tn mAb in comparison to the free drug. Conclusions: Therefore, Chi-Tn-functionalized LPHNps hold promise as carriers for actively targeting DCX to Tn-expressing carcinomas.

Aberrant glycosylation is a hallmark of cancer and can lead to changes that influence tumor behavior. Glycans can serve as a source of novel clinical biomarker developments, providing a set of specific targets for therapeutic intervention. Different mechanisms of aberrant glycosylation lead to the formation of tumor-associated carbohydrate antigens (TACAs) suitable for selective cancer-targeting therapy. The best characterized TACAs are truncated O-glycans (Tn, TF, and sialyl-Tn antigens), gangliosides (GD2, GD3, GM2, GM3, fucosyl-GM1), globo-serie glycans (Globo-H, SSEA-3, SSEA-4), Lewis antigens, and polysialic acid. In this review, we analyze strategies for cancer immunotherapy targeting TACAs, including different antibody developments, the production of vaccines, and the generation of CAR-T cells. Some approaches have been approved for clinical use, such as anti-GD2 antibodies. Moreover, in terms of the antitumor mechanisms against different TACAs, we show results of selected clinical trials, considering the horizons that have opened up as a result of recent developments in technologies used for cancer control.

Breast cancer is a public health concern and is currently the fifth cause of mortality worldwide. Identification of different biological subtypes is essential for clinical management; therefore, the role of pathologists is essential and useful tools for immunohistochemistry diagnosis are needed. Polypeptide-GalNAc-transferases are emerging novel biomarkers related to cancer behavior and GalNAc-T13, correlated with aggressiveness in some tumors, is an interesting candidate. Few monoclonal antibodies reacting with native proteins, and not affected by fixation and paraffin embedding, have been reported. The aim of this work was to develop a useful monoclonal antibody anti-GalNAc-T13 and to assess its potential significance in breast cancer diagnosis. We evaluated 6 human breast cancer cell lines, 338 primary breast tumors and 48 metastatic lymph nodes and looked for clinical significance correlating GalNAc-T13 expression with patients’ clinical features and survival. We found high GalNAc-T13 expression in 43.8% of the cases and observed a significant higher expression in metastatic lymph nodes, correlating with worse overall survival. We hypothesized several possible molecular mechanisms and their implications. We conclude that GalNAc-T13 may be a novel biomarker in breast cancer, useful for routine pathological diagnosis. Elucidation of molecular mechanisms related to aggressiveness should contribute to understand the role of GalNAc-T13 in breast cancer biology.

Colorectal carcinoma (CRC) is the second leading cause of cancer mortality worldwide. O‑glycosylated mucins at the cell surface of colonic mucosa exhibit alterations in cancer and are involved in fundamental biological processes, including invasion and metastasis. Certain members of the GalNAc‑transferase family may be responsible for these changes and are being investigated as novel biomarkers of cancer. In the present study the prognostic significance of GalNAc‑T6 was investigated in patients with CRC patients. GalNAc‑T6 expression was observed in all three colon cancer cell lines analyzed by reverse transcription‑polymerase chain reaction, immunofluorescence and flow cytometry. A cohort of 81 colon cancer specimens was analyzed by immunohistochemical staining using MAb T6.3. It was demonstrated that GalNAc‑T6 was expressed in 35/81 (43%) cases of colon cancer but not in the normal colonic mucosa. No association was observed with the clinical‑pathologic parameters. However, patients expressing GalNAc‑T6 had a significantly increased overall survival (median, 58 months; P<0.001) compared with GalNAc‑T6 negative patients, especially those with advanced disease. These results suggest that GalNAc‑T6 expression predicts an improved outcome in patients with CRC. The molecular mechanism underlying the less aggressive behavior of colon cancer cells expressing GalNAc‑T6 remains to be elucidated.

Background. Incorporation of molecular analysis of the epidermal growth factor receptor (EGFR) gene into routine clinical practice represents a milestone for personalized therapy of the non-small-cell lung cancer (NSCLC). However, the genetic testing of EGFR mutations has not yet become a routine clinical practice in developing countries. In view of different prevalence of such mutations among different ethnicities and geographic regions, as well as the limited existing data from Latin America, our aim was to study the frequency of major types of activating mutations of the EGFR gene in NSCLC patients from Uruguay.Methods. We examined EGFR mutations in exons 18 through 21 in 289 NSCLC Uruguayan patients by PCR-direct sequencing.Results. EGFR mutations were detected in 53 of the 289 (18.3%) patients, more frequently in women (23.4%) than in men (14.5%). The distribution by exon was similar to that generally reported in the literature.Conclusions. This first epidemiological study of EGFR mutations in Uruguay reveals a wide spectrum of mutations and an overall prevalence of 18.3%. The background ethnic structure of the Uruguayan population could play an important role in explaining our findings.

The aim of this work was to describe the prevalence of type‐specific Human papillomavirus (HPV) infection in women attending organized cervical cancer screening program in Uruguay. Nine hundred sixty‐five liquid cervical cell samples obtained after collection of cervical smears for cytology were assessed for HPV DNA using the Papillocheck system (Greiner BioOne). The overall prevalence of High‐Risk (HR) HPV infections was 20.8% and increased from 16.5% in women with normal cytology to 93.3% in HSIL. Prevalence of HPV 16 and/or 18 was 6.3% and HPV 16 was the most prevalent genotype in normal cytology (3.6%). The five most prevalent genotypes were HPV 16, 31, 51, 56, and 39. The overall prevalence peaked below age 30. This study provides essential baseline information at national level on type‐specific HPV prevalence in Uruguay before the introduction of HPV vaccination. It documents the current prevalence of each of the oncogenic genotypes in a population attending cervical cancer screening program, suggesting that at least 64.7% of high risk lesions are potentially preventable by available HPV vaccines, and possibly augmentable if cross‐protection against non‐vaccine HPV types 31, 33, and 45 is confirmed. J. Med. Virol. 86:647–652, 2014.