Lineamientos para la gestión del Repositorio en material de ciencia, tecnología e innovación del Instituto Nacional de Enfermedades Neoplásicas

Políticas del repositori

LncRNA-mRNA integrated networks in the neuroendocrine system of bisphenol a-treated mice induce cellular dysfunctions by disrupting transcriptional homeostasis

Bisphenol A (BPA) is a widely used xenoestrogen that can disrupt neuroendocrine and immune regulation through multiple hormone receptors. This study investigated BPAinduced long non-coding RNA (lncRNA)-mRNA interactions in the cerebral cortex and hypothalamic-pituitary-thyroid (HPT) axis of adult male mice. Transcriptome sequencing and comprehensive lncRNA annotation identified 14,858 novel lncRNA transcripts. Integrated network analysis using weighted gene co-expression network analysis (WGCNA) revealed four distinct tissue-specific modules: neuronal signaling alterations (Tac1, Htr1b, Npy), RNA splicing modifications (Srsf5), PI3K/Akt-mediated cellular dysfunction (Creb5, Cdkn1a), and immune receptor signaling disruptions (Trbv15, Fcrla). These findings suggest that BPA reprograms transcriptional networks in a tissue-specific manner, potentially disrupting hormone-related neurotransmission, metabolic regulation, and immune signaling via lncRNA-mediated mechanisms. Such systems-level reprogramming of the immune-neuroendocrine network (INEN) provides novel mechanistic insights and biomarker candidates for assessing and mitigating the health impacts of environmental endocrine disruptors

Impact of diorites and feldspars on soil radioactivity: Evidence from university city of the Universidad Nacional Mayor de San Marcos and the National Institute of Neoplastic Diseases

This study represents the first systematic measurement of environmental radiation in the University City of the Universidad Nacional Mayor de San Marcos (UNMSM) and the National Institute of Neoplastic Diseases (INEN) in the city of Lima, Peru, conducted between July, December 2022, and January 2023. Natural radioactivity levels and absorbed dose rates in soil samples were determined by using gamma spectroscopy with a high purity germanium detector (HPGe) semiconductor detector with 150 % efficiency. At UNMSM, the following results were obtained for the activity concentrations (A) of the four main naturally occurring radioactive materials NORM (238U, 226Ra, 232Th, and 40K): AU238 = 24.2 ± 3.4 Bq kg 1, ARa226 = 28.8 ± 0.7 Bq kg 1, ATh232 = 39.4 ± 1.2 Bq kg 1 and AK40 = 539 ± 7 Bq kg 1. We find the absorbed dose rate of 57.5 nGy h 1 and an annual effective dose equivalent of 0.28 mSv y 1. On the other hand, at INEN, the following activity concentrations of NORM were found: AU238 = 26.0 ± 3.4 Bq kg 1, ARa226 = 27.9 ± 0.8 Bq kg 1, ATh232 = 42.1 ± 1.6 Bq kg 1 and AK40 = 559 ± 7.8 Bq kg 1. We found the annual absorbed dose rate of 60.7 nGy h 1 and an annual effective dose equivalent of 0.30 mSv y 1. Additionally, the equivalent activity in radium (Req) and the risk indices for both indoor and outdoor environments were also determined. The higher than global average values of 40K activity concentrations are due to the greater presence of diorites and feldspars in the alluvial soils of Lima. These findings highlight the geological influence on local environmental radioactivity and are essential for future risk assessments. Nonetheless, the levels of environmental radioactivity found in this study are safe for the population in urban areas of academic and medical importance

Validating a Target-Enrichment Design for CapturingUniparental Haplotypes in Ancient Domesticated Animals

This work was supported by H2020 Marie Skłodowska-Curie Actions (897931-PALEOS, 895107-ARAUCANA, 101062645-ZEPHYRUS, and 101032990-PALEOQUINOA), Zone Atelier PYGAR, the Agence Nationale de la Recherche (ANR) through the CoproDNA project (ANR-17- CE27- 0004), the Knut and Alice Wallenberg Foundation and the European Research Council (ERC) under the projects Horsepower (101071707), anthropYXX (101117101), PEGASUS (681605), and DEATHREVOL (949330). Additional support was provided by the PrimiGenomes project (101054984), the Fondo Social Europeo and Agencia Estatal de Investigación (MCIN/AEI/10.13039/501100011033, RYC2020-029656- I), and the Centro Nacional de Investigación sobre la Evolución Humana. Institutional funding was received from the Science for Life Laboratory, the Swedish Research Council (2021-00625), Université de Toulouse (PhD Fellowship) and the Centre National de la Recherche Scientifique (CNRS) through the AnimalFarm project. Further support came from the Junta de Comunidades de Castilla-La Mancha (SBPLY/24/180801/000019)

Improving equitable access to comprehensive care for people with advanced breast cancer: a global expert review and call-to-action for 2025–2035 (Goal 9)

Advanced breast cancer (ABC) remains an incurable yet treatable disease, requiring lifelong care. While treatment advancements have extended survival for many patients, access to these innovations is far from universal. There remains a critical need to ensure equitable access to proven and established interventions for all individuals with ABC, while continuing to drive progress in care and survival outcomes. This manuscript assesses the evolving economic landscape for and access to comprehensive ABC care since 2015. It describes the persistent access barriers and inequities, and outlines recommendations for the ABC community over the next decade. It summarizes research conducted for the ABC Global Alliance’s Global Decade Report 2.0. The main findings are: a) Disparities in access to ABC care are widening globally; b) Variable access to diagnostic services delays timely and adequate ABC treatment; c) Infrastructure, supply, and reimbursement barriers hinder ABC treatment access; d) High out-of-pocket costs drive severe financial toxicity across all income settings; e) In low-income contexts, multi-stakeholder efforts are improving access to ABC care. The findings from the ABC Global Alliance’s Global Decade Report 2.0 have informed the development of a new ABC Global Charter. The ABC Global Charter 2.0 defines ten new achievable and measurable goals for the decade 2025–2035, aiming at improving the lives of people living with ABC worldwide

Chilean Biobanks: A Snapshot of the Current Landscape

Latin America hosts extraordinary biological diversity but remains underrepresented in global biomedical research, underscoring the need for robust biobanking infrastructures. This work provides an updated snapshot of Chilean biobanks, based on a national survey exploring their current capacities and challenges. Nine active biobanks were identified across 5 of Chile’s 16 regions, the majority concentrated in Santiago. Collectively, they store over 640,000 biospecimens from nearly 49,000 participants, predominantly oncological. While standardized protocols for sample management are broadly implemented by Chilean biobanks, data management practices are not yet well-developed, as only a few centers have adopted internationally recognized standards. Governance structures vary considerably and often lack formal written documentation. Financial sustainability relies mainly on institutional support, competitive grants, and modest cost recovery. Although Chilean biobanks contribute to research and training, measuring productivity remains challenging due to underreported acknowledgments and limited post-transfer traceability. Overall, our analysis suggests a bottom-up development of Chilean biobanks in the absence of dedicated legislation or strategic governmental policies. This overview shows that Chile’s biobanks hold considerable potential for strengthening translational research and health equity, particularly if further support enables expansion into underrepresented regions. By integrating these infrastructures into higher education, clinical care, and broader regional collaborations, biobanks can help leverage Chilean genetic diversity and address health disparities. With greater governmental prioritization, a cohesive regulatory framework, and collaboration as a key strength, biobanks could enhance interaction with global networks and further strengthen Latin America’s overall contribution to biomedical innovatio

Exercise in patients with metastatic prostate cancer: A comprehensive review

Prostate cancer (PC) is one of the most prevalent malignancies worldwide. Metastatic PC remains an incurable disease, with the androgen receptor (AR) pathway being the primary driver of tumor progression and the main target for therapeutic strategies. Thus, patients usually undergo long-term treatments, particularly androgen deprivation therapy (ADT), which can worsen the intrinsic deterioration in quality of life (QoL) caused by the disease burden. Increasing evidence supports the use of physical activity (PA) and structured exercise (EX) as complementary measures to mitigate treatment-related adverse effects and improve clinical outcomes across tumor types. EX has shown benefits across multiple systems and plays a significant role in modulating tumor progression through several cellular pathways. Furthermore, it has confirmed potential to alleviate cancer-related symptoms while enhancing functional capacity and tolerability of treatment. This review gathers the current evidence regarding the impact of PA and EX on patients with metastatic PC, integrating both epidemiological and interventional studies. Despite promising findings, most of the available evidence is documented on non-metastatic populations, highlighting the need for directed studies in advanced disease settings. Future research is needed in metastatic PC patients, in order to assess long-term impacts of EX in this population

FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial

Purpose: In a prespecified GEICAM_CIBOMA trial (NCT00130533) correlative analysis, PAM50 non–basal-like breast cancer (non- BLBC) status distinguished patients with triple-negative breast cancer (TNBC) who are most likely to benefit from adjuvant capecitabine. The standardized forkhead box C1 (FOXC1) IHC test has demonstrated strong reliability in classifying the BLBC subtype throughout TNBC cohorts. This translational analysis aimed to evaluate the prognostic/predictive significance of BLBC classification by FOXC1 IHC in the phase III GEICAM_CIBOMA clinical trial. Experimental Design: Tumor tissues from patients with TNBC randomized to standard (neo)adjuvant chemotherapy followed by capecitabine versus observation were analyzed using the standardized FOXC1 IHC test to assess its BLBC/non-BLBC TNBC subtyping capacity as a distant relapse-free survival clinical outcome predictor of capecitabine benefit (exploratory endpoints: disease-free survival, overall survival, and recurrence-free survival). Results: A total of 705 (80.5%) patients from the GEICAM_ CIBOMA trial were evaluable for FOXC1 expression analysis, with balanced distribution between the trial’s treatments. FOXC1 proportion/intensity (VFOXC1) score–based subtyping demonstrated a strong association [AUC ¼ 0.87; 95% confidence interval (CI), 0.84–0.91] and agreement (κ index ¼ 0.43; P < 0.0001) with PAM50 molecular subtyping. VFOXC1 non-BLBC TNBC subtype was a significant independent predictor of clinical benefit with capecitabine for distant relapse-free survival (HR, 0.44; 95% CI, 0.25–0.76; P ¼ 0.003). This predictive effect of VFOXC1 non-BLBC on capecitabine efficacy was further confirmed at disease-free survival (HR, 0.47; 95% CI, 0.28–0.78; P ¼ 0.003), overall survival (HR, 0.48; 95% CI, 0.24–0.96; P ¼ 0.038), and recurrence-free survival (HR, 0.39; 95% CI, 0.22–0.72; P ¼ 0.002). Conclusions: This ambispective GEICAM_CIBOMA translational analysis validated FOXC1-based basal-like/non–basal-like subtyping as a pragmatic alternative to PAM50 subtyping and independently predicted the benefit of adding capecitabine to standard (neo)adjuvant chemotherapy in TNBC

Targeting HIF-2α and anemia: A therapeutic breakthrough for clear-cell renal cell carcinoma

Renal cell carcinoma (RCC) is a heterogenous disease which the incidence is increasing worldwide. The identification and understanding of the role of the Von Hipple Lindau (VHP) in regulating the hypoxia-inducible factor signaling pathway has revolutionized the treatment of this disease. Belzutifan is an oral hypoxiainducible factor (HIF)-2α inhibitor, which has demonstrated efficacy in treating von Hippel-Lindau (VHL) disease and for the treatment of adults with RCC who experienced disease progression after PD-1/PD-L1– and VEGFR-targeted therapies. One of the most common adverse effect of this drug is anemia; however, it is treatment is not well known. This review summarizes role of the VHL-HIF pathway in ccRCC aroused the interest of targeting HIF activity, the history of belzutifan development and their relationship to anemia as well as propose a management algorith

Minocycline Ameliorates Cognitive Impairments Without Modulating Microglial Reactivity in Sporadic Hypercholesterolemia: A Sex-Specific Analysis in Mice

High blood cholesterol levels have been progressively recognized as an important risk factor for dementia, yet the underlying mechanisms remain poorly understood. Emerging evidence indicates that blood–brain barrier (BBB) dysfunction and microglia-mediated neuroinflammation are key mechanisms contributing to the cognitive decline associated with hypercholesterolemia. In this study, we investigated sex-dependent differences in cognitive impairments, synaptic protein levels, microglial reactivity, and neurovascular changes associated with sporadic hypercholesterolemia, as well as the potential modulatory effects of minocycline. Adult male and female CF-1 mice (3-month-old) were fed either a normal or high-fat high-cholesterol diet for 8 weeks, with daily oral minocycline administered during the final 4 weeks. Mice fed a cholesterol-rich diet exhibited a significant increase in plasma cholesterol levels, which remained unaffected by minocycline treatment. Hypercholesterolemia was associated with memory deficits in the object recognition task, accompanied by decreased claudin-5 expression, reduced numbers of lectin-positive cells, and diminished microglial presence in the hippocampal perivascular area. While minocycline treatment ameliorated cognitive deficits and increased claudin-5 levels and lectin-positive cell numbers in the hippocampus, no significant effects of either diet or treatment were observed on classical microglial reactivity parameters. In addition, diet seemed to impact the content of synaptophysin in the prefrontal cortex and hippocampus. Notably, female mice exhibited greater susceptibility to hypercholesterolemia-induced metabolic and cognitive alterations and showed a more pronounced response to minocycline treatment compared to males. Overall, our findings highlight sex-dependent differences in susceptibility to hypercholesterolemia-induced cognitive dysfunction and in the therapeutic response to minocycline. These results underscore the relevance of BBB alterations and perivascular microglial changes, independent of classical microglial activation, in the pathophysiology of hypercholesterolemia-associated cognitive impairment