Biology subjects

Abal, M.

Publications and source records attributed to Abal, M..

3 recordsLinked to original sources

bioRxiv2026

Patient-derived organoids from malignant pleural effusion to explore for alternative therapies in thoracic tumors

Thoracic malignancies, including lung adenocarcinoma (ADC) and malignant pleural mesothelioma (MPM), remain associated with poor prognosis and limited durable therapeutic responses in advanced stages. Although targeted therapies and immunotherapy have improved outcomes in selected patients, systemic chemotherapy continues to play a central role in routine clinical practice. However, treatment response is highly heterogeneous, and reliable predictive biomarkers of chemotherapy sensitivity are lacking. Both ADC and MPM frequently involve the pleural cavity and are commonly associated with malignant pleural effusion (MPE), which contributes to symptoms such as dyspnea and chest pain and requires therapeutic drainage. Importantly, MPE represents a clinically accessible source of viable tumor cells obtained through minimally invasive procedures. In this study, we established patient-derived organoids (PDOs) from malignant pleural effusion samples obtained from five patients with advanced lung adenocarcinoma and, as an exploratory extension, from one patient with malignant pleural mesothelioma. Organoids were characterized by immunohistochemistry and subjected to systematic chemotherapy drug screening. Inter-model variability in treatment response was assessed, and selected drug sensitivities were further validated through dose-response assays. Pleural effusion-derived organoids successfully recapitulated tumor-specific phenotypic features and revealed marked heterogeneity in chemotherapy sensitivity across models. Secondary validation confirmed the reproducibility of selected responses. Our findings support the feasibility of generating functional organoid models from malignant pleural effusions and highlight their potential as translational platforms for individualized chemotherapy profiling in advanced thoracic malignancies.

cancer biology↗

bioRxiv2025

Conjugates of α-d-Galp-(1->3)-β-d-Galp for the serological diagnosis of Chagas disease.

BackgroundChagas disease (ChD), caused by the parasitic protozoan Trypanosoma cruzi, is a lifelong, neglected tropical disease with substantial medical and socioeconomic impact. Despite this situation, currently available diagnostic and therapeutic methods display serious limitations. A promising strategy to improve ChD serodiagnosis involves targeting parasite carbohydrate antigens, particularly the -galactosyl-rich mucins that coat the surface of bloodstream trypomastigotes (tGPI-mucins). Methods/Principle FindingsHere, we present a concise and efficient protocol for the chemical synthesis of a tGPI-mucin-derived glycotope, the disaccharide -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp, and its functional conjugation to different scaffolds using the squarate method. A neoglycoprotein made upon a bovine serum albumin (BSA) carrier decorated with [~]28 units of the disaccharide, termed BSA-Di, was interrogated with sera of chronic ChD patients and healthy individuals from Argentina using an in-house enzyme-linked immunosorbent assay (ELISA). BSA-Di exhibited excellent sensitivity and effectively discriminated between ChD-positive and negative sera with high accuracy (AUC = 0.905), though its specificity was partially affected by cross-reactivity of some non-ChD sera containing natural -Gal antibodies. Conjugation of -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp to T. cruzi antigenic peptides, instead of BSA, corroborated these findings and enabled the generation of bivalent ChD diagnostic reagents combining glycan- and peptide-based epitopes. Conclusions/SignificanceOverall, our results identify -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp as a robust and reliable biomarker of T. cruzi infection. The methodologies and tools described here, together with optimized derivatives, are expected to positively impact ChD serological applications. AUTHOR SUMMARYDespite the enormous burden imposed by Chagas disease, diagnostic and therapeutic methods still present serious deficiencies. Towards filling this gap, we herein developed a protocol for the chemical synthesis of -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp, a major glycotope present on the Trypanosoma cruzi surface coat. This disaccharide was conjugated with different molecular scaffolds and serologically evaluated using an in-house enzyme-linked immunosorbent assay (ELISA). Our results indicate that -O_SCPLOWDC_SCPLOW-Galp-(1[->]3)-{beta}-O_SCPLOWDC_SCPLOW-Galp provides an overall robust and reliable biomarker of T. cruzi infection, with excellent sensitivity and only minor concerns regarding its potential cross-reactivity with natural -Gal antibodies. These findings indicate that the tools developed here, as well as optimized versions derived from them, should have a positive impact on the diagnosis and clinical management of Chagas disease and on the identification and/or clinical validation of novel drug/vaccine candidates for the treatment of T. cruzi infections.

microbiology↗

bioRxiv2025

Bovine colostrum-derived extracellular vesicles impair cancer cell proliferation through transcriptional repression.

Milk-derived extracellular vesicles (EVs) are a promising source of molecules with therapeutic potential. Bovine colostrum is particularly enriched in EVs, which carry a unique cargo of proteins involved in immune regulation, development, and cellular signaling. However, despite promising bioactive effects in various fields, little is known about their potential as anti-cancer agents. Here, we demonstrate that colostrum-derived EVs (Col-EVs) exert a potent and specific anti-proliferative effect on gastrointestinal cancer cell lines, independent of apoptosis induction. Using a multi-modal approach combining proteomics and functional assays, we show that Col-EVs induce a reversible proliferative arrest through transcriptional repression and chromatin and nuclear remodeling. Col-EV treatment leads to widespread dysregulation of RNA processing and transcriptional machinery, including the downregulation of splicing factors and chromatin regulators essential for cell cycle progression. These molecular changes are accompanied by chromatin compaction, nuclear reorganization, and cytoskeletal remodeling. Notably, these effects do not induce cell death and are reversible upon EV removal, suggesting a modulatory mechanism rather than cytotoxicity. Furthermore, Col-EVs enhance the efficacy of DNA-targeting chemotherapies such as 5-fluorouracil, indicating their potential as adjunctive agents in cancer treatment. Overall, our findings reveal that Col-EVs can selectively and reversibly suppress cancer cell proliferation by reprogramming transcriptional and nuclear architecture, offering a natural, biocompatible strategy for modulating tumor growth and sensitizing cancer cells to conventional therapies.

cancer biology↗