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Factors associated with accepting chemotherapy despite the risk of fertility loss in Latin American breast cancer patients—LACOG 0414 study
No full textBackground: Fertility loss due to chemotherapy is a major concern for young patients with breast cancer (BC), influencing treatment decisions and quality of life. Despite established guidelines recommending fertility counseling, access to fertility preservation remains limited
in Latin America.
Objectives: This study evaluated attitudes and preferences regarding fertility-related concerns and chemotherapy decision-making among young Latin American women with early-stage BC.
Design: A prospective cohort study was conducted at seven institutions in Brazil, Mexico, and Peru.
Methods: Premenopausal women aged 18–40years with stage I–III BC requiring (neo) adjuvant chemotherapy completed a fertility questionnaire before treatment, along with validated quality-of-life assessments (EORTC QLQ-C30 and EORTC QLQ-BR23). One year after
chemotherapy initiation, the patients were reassessed for ovarian function status and quality of life. Factors associated with chemotherapy acceptance despite potential infertility risks were analyzed using univariate and multivariate Poisson regression models.
Results: A total of 270 patients were included (mean age, 33.9years). Prior to diagnosis, 41.5% of the women had children, and 31.1% expressed a desire for future childbearing. Among the participants, 8.5% were unaware of chemotherapy-induced infertility risks, 21.5% would
decline chemotherapy if the infertility risk exceeded 25%, and 20.0% would accept treatment despite a 76%–100% infertility risk. In addition, 44.1% of patients required at least a 20% increase in survival probability to accept chemotherapy. In the multivariate analysis, married
patients were significantly less likely to refuse chemotherapy (risk ratio: 0.88, 95% confidence interval: 0.82–0.94; p<0.01). One year post-treatment, 73.1% of the patients experienced chemotherapy-induced amenorrhea.
Conclusion: Fertility concerns significantly impact chemotherapy decision-making in young Latin American patients with BC. Limited fertility awareness, socioeconomic disparities, and restricted access to fertility preservation contribute to these challenges. Strengthening
fertility counseling and improving access to preservation options are essential for supporting informed treatment decisions in this population
Correction: Desterke et al. Alternative Balance between Transcriptional and Epigenetic Regulation during Developmental Proliferation of Human Cranial Neural Crest Cells. Cells 2024, 13, 1634
No full textIn the original publication [1], the funder “MEAE AMBASS FRANCE AU PEROU FSPI—S-AC23007, Filière Santé Maladie Rare «TeteCou-CRANIOST»” must be modified by
“This research received no external funding” due to the fact that, since it is a computationaldeveloped article, the use of funds was not necessary
Targeting HIF-2α and anemia: A therapeutic breakthrough for clear-cell renal cell carcinoma
No full textRenal 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
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)
No full textAdvanced 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
FOXC1 Expression Predicts Capecitabine Efficacy in Patients with Triple-Negative Breast Cancer from the GEICAM_CIBOMA Trial
No full textPurpose: 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
Lymphoepithelioma epidermoid carcinoma of the uterine cervix: surgical management of an isolated case and review of the literature
No full textCervical cancer is the gynecological malignancy that ranks third worldwide. It consists histologically of multiple subtypes, such as squamous cell carcinoma, which is the most common (65%), then adenocarcinoma (15%) and other types such as neuroendocrine, adenosquamous and carcinosarcoma tumours, which are less common. According to the World Health Organisation, lymphoepithelioma-type carcinoma has been described as an uncommon subtype and a variant of squamous cell carcinoma of the cervix. Its pathogenesis is related to the presence of the human Epstein-Barr virus and human papillomavirus. We present the case of a woman diagnosed with squamous cell lymphoepithelioma-like carcinoma of the cervix that was comprehensively managed with radical hysterectomy alone, presenting a good response and without recurrence
Minocycline Ameliorates Cognitive Impairments Without Modulating Microglial Reactivity in Sporadic Hypercholesterolemia: A Sex-Specific Analysis in Mice
No full textHigh 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
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
No full textThis 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
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
No full textThis 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
LncRNA-mRNA integrated networks in the neuroendocrine system of bisphenol a-treated mice induce cellular dysfunctions by disrupting transcriptional homeostasis
No full textBisphenol 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