Cancer interception is a preventative approach aiming to reduce cancer incidence by targeting precancers and early-stage cancers. Lynch syndrome (LS) is a prevalent hereditary cancer syndrome affecting 1 in 300 individuals, with an overall lifetime cancer risk as high as 80 NCT05078866 ). In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.
Prostate cancer (PCA) is the second leading cause of cancer-related death among men in the US. Early-onset prostate cancer (EOPCa) accounts for ∼10% of all PCA diagnoses, with an ∼58,694 new cases reported worldwide in 2021. Although EOPCa accounts for a growing proportion of cases, it remains underexplored. Younger patients often present with distinct clinical features, hereditary predispositions, and long-term survivorship challenges. Hispanic/Latino men, particularly those from Puerto Rico, experience disparities in incidence and outcomes, yet remain underrepresented in PCA research. A better understanding of the epidemiological, clinical, and germline genetic profile of Puerto Rican men with EOPCa is essential to guide risk stratification and inform precision medicine strategies. This study retrospectively identified 80 cases of EOPCa of 9,393 patients treated for PCA between 2020–2025 in a tertiary hospital in southern PR. Demographic, clinicopathological variables were collected, including age, PSA, BMI, Gleason score (GS), tumor stage, family history, lifestyle factors, and treatments. Germline genetic testing results were analyzed and variants classified as pathogenic, variants of uncertain significance (VUS), or benign. Frequencies of recurrent alterations were calculated. Eighty patients were identified; 39 met the inclusion criteria. Age ranged 37–49 years (mean 45.7). PSA at diagnosis ranged 1.7–25.4 ng/mL (mean 6.2). Nearly half (48.7%) were obese (BMI ≥30). At biopsy, GS 6 was most frequent (56.4%); following prostatectomy (87.2% of cases), GS 6 remained most common (50.0%), followed by GS 8 (23.5%). Stage T2 (55.9%) and T3 (23.5%) predominated. Family history of PCA was reported by 38.0%. Most patients consumed alcohol (76.9%) but denied smoking (71.8%). Germline testing identified 10.3% pathogenic variants, 35.9% VUS, and 5.1% carriers, with the remainder negative. In total, 21 alterations were detected: 15 VUS, 5 pathogenic, and 1 benign. Alterations were distributed across 15 genes, with recurrent findings in RECQL4 (n=3), POLD1 (n=3), ATM (n=2), and TMEM127 (n=2). This study provides the first characterization of the epidemiological, clinical, and germline genetic profile of EOPCa in Puerto Rico. Findings highlight a notable burden of germline alterations and underscore the importance of incorporating genetic testing into clinical management. Expanding research among underrepresented populations is critical to guide early detection, refine prognostication, and reduce PCA disparities. Gustavo Alayón-Rosario, Sebastián Bernaschina-Rivera, Natalia Yordán-Fernández, Juliana Meléndez-Ojeda, Gabriela Castro-Morales, Lenin Godoy-Muñoz, Fabiola A. Benitez-Ríos, Laura F. Rodríguez-Fernández, Carmen Ortiz-Sánchez, Gilberto Ruiz-Deyá. Genetic and clinical profiles of early-onset prostate cancer in Puerto Rican men: A preliminary characterization [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(2_Suppl):Abstract nr B001.
The pathophysiology of depression involves multiple biological processes, including circuit dysfunction and impaired neuroplasticity, yet an integrative view linking these processes remains elusive. Here, we identify a convergent circuit for antidepressant response and plasticity modulation. We demonstrate that chemogenetic activation of the infralimbic cortex (IL) exerts rapid antidepressant-like effects across multiple behavioral domains in a mouse model of stress-induced depression. IL stimulation exerts top-down control over the hippocampus, enhancing structural plasticity, restoring long-term potentiation deficits and improving state-dependent network dynamics in the ventral hippocampus (vHIPP). We identify the thalamic nucleus reuniens (RE) as a necessary mediator of these effects. Notably, direct inhibition of RE, its inputs from IL or projections to vHIPP, blocks both IL stimulation-induced antidepressant response and the therapeutic and neuroplastic effects of ketamine. Our findings demonstrate that the functional IL → RE→vHIPP circuit plays a central role in the antidepressant response, linking circuit activity, hippocampal plasticity, and depressive-like behaviors.
In the late 1990s, Pieprzyk and Qu introduced rotation symmetric Boolean functions. They showed that these functions have efficient and secure cryptographic implementations. In recent years, examples of dihedral symmetric Boolean functions, a subclass of rotation symmetric Boolean functions, have been found to exceed the bent concatenation bound for an odd number of variables. In this work, we present a study of dihedral symmetric Boolean functions. In particular, we give an explicit representation of generators of monomial dihedral symmetric Boolean functions. We also present a method for finding recurrences that some families of dihedral symmetric Boolean functions' exponential sum sequences satisfy and show how these recurrences can be used to obtain some cryptographic properties for the underlying functions. (c) 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Abstract Background & Objectives: Colibactin is a genotoxin encoded by the pks genomic island in pathogenic Gram-negative bacteria and has been implicated in colorectal cancer. Colibactin synthesis and activation occur in a two-step process in which pre-colibactin is produced in the bacterial cytoplasm and subsequently activated into colibactin within the periplasmic space. However, the mechanism by which pks+ bacteria export colibactin to host cells remains unclear. We hypothesize that outer membrane vesicles (OMVs), nanosized proteoliposomes released by Gram-negative bacteria capable of transporting diverse biomolecules, serve as a delivery system for this toxin to host cells. Methods: To investigate this, OMVs were isolated from pks+ NC101 and pks- DH10B E. coli strains using the exoEasy Maxi Kit and quantified with a BSA-based protein assay on a Synergy H1 microplate reader. Results: Yielding concentrations consistent with typical OMV preparations. The stability and morphological characteristics of the extracted OMVs will be evaluated using dynamic light scattering (DLS). Metabolites extracted from OMVs will be examined via mass spectrometry to confirm the presence of known colibactin-related intermediates. Additionally, OMVs will undergo proteomic analysis to identify proteins involved in OMV-host interaction mechanisms. Finally, we aim to assess the effects of OMV exposure on large intestinal epithelial cells to better understand their contribution to colibactin-associated toxicity and colorectal cancer development. Conclusion: Ultimately, this research seeks to clarify how OMVs mediate colibactin transport and cytotoxicity, providing new insights into bacterial factors that promote colorectal carcinogenesis. Acknowledgements: This research was funded by the National Institute of Allergy and Infectious Diseases (NIAID) Grant #5R25AI183304-02. Citation Format: Lissette Marie Perez-Rovira, Grace Enid Velez Crespo, Luis A. Prieto-Costas, Jeremy J. Colon-Morales, Abel Baerga-Ortiz. Characterization of outer membrane vesicles (OMVs) from pks+ NC101 and pks-DH10B E. coli strands [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7668.
