HDAC4 Inhibits NMDA Receptor-mediated Stimulation of Neurogranin Expression.

The coordination of neuronal wiring and activity within the central nervous system (CNS) is crucial for cognitive function, particularly in the context of aging and neurological disorders. Neurogranin (Ng), an abundant forebrain protein, modulates calmodulin (CaM) activity and deeply influences synaptic plasticity and neuronal processing. This study investigates the regulatory mechanisms of Ng expression, a critical but underexplored area for combating cognitive impairment.

Association between missense variants of uncertain significance in the gene and hereditary breast cancer: a cosegregation and bioinformatics analysis.

Inherited mutations in the gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain.

[Risk factors for cancer-related cognitive impairment in breast and colorectal cancer patients who undergo chemotherapy].

Background: Our study aims to evaluate the impact of different factors on cancer-related cognitive impairment in patients who undergo chemotherapy.

Methodology: Prospective longitudinal single-centre study that included patients with breast and colon carcinoma who underwent chemotherapy as part of their treatment. Clinical and genetic characteristics of the patients (single nucleotide polymorphisms, SNPs) were collected.

Long-term outcomes of high-risk HR-positive and HER2-negative early breast cancer patients from GEICAM adjuvant studies and El Álamo IV registry.

Purpose: The monarchE trial showed that the addition of abemaciclib improves efficacy in patients with high-risk early breast cancer (EBC). We analyzed the long-term outcomes of a population similar to the monarchE trial to put into context the potential benefit of abemaciclib.

Methods: HR-positive/HER2-negative EBC patients eligible for the monarchE study were selected from 3 adjuvant clinical trials and a breast cancer registry.

Impact of the 21-Gene Assay in Patients with High-Clinical Risk ER-Positive and HER2-Negative Early Breast Cancer: Results of the KARMA Dx Study.

Background: The 21-gene Oncotype DX Breast Recurrence Score assay is prognostic and predictive of chemotherapy benefit for patients with estrogen receptor-positive, HER2- early breast cancer (EBC). The KARMA Dx study evaluated the impact of the Recurrence Score results (RS) on the treatment decision for patients with EBC and high-risk clinicopathological characteristics for whom chemotherapy (CT) was considered.

Methods: Eligible patients with EBC were candidates for the study if CT was considered standard recommendation by local guidelines.

Facilitating Factors and Barriers in the Return to Work of Working Women Survivors of Breast Cancer: A Qualitative Study.

Several studies have identified the main barriers and facilitators that breast cancer survivors experience in the return to work (RTW). The authors conducted a qualitative study using focus group discussions with a group of female non-metastatic breast cancer survivors (n = 6), a group of health professionals from different medical specialties (n = 8), and a third group of company managers mainly composed of human resources managers (n = 7). The study was carried out between March and December 2021 in Zaragoza (Spain).

Pembrolizumab Plus Gemcitabine in the Subset of Triple-Negative Advanced Breast Cancer Patients in the GEICAM/2015-04 (PANGEA-Breast) Study.

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR).

Palbociclib combined with endocrine therapy in heavily pretreated HR/HER2 advanced breast cancer patients: Results from the compassionate use program in Spain (PALBOCOMP).

Background: This study evaluated efficacy and safety of palbociclib, a CDK4/6 inhibitor, in heavily-pretreated hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR/HER2) metastatic breast cancer (mBC) patients during the compassionate use program in Spain from February 2015 to November 2017.

Patients And Methods: Patient data were collected retrospectively from 35 hospitals in Spain. Patients with HR/HER2 mBC who had progressed on ≥4 treatments for advanced disease were eligible.

Serum Phospholipids Fatty Acids and Breast Cancer Risk by Pathological Subtype.

This study evaluates whether serum phospholipids fatty acids (PL-FAs) and markers of their endogenous metabolism are associated with breast cancer (BC) subtypes. EpiGEICAM is a Spanish multicenter matched case-control study. A lifestyle and food frequency questionnaire was completed by 1017 BC cases and healthy women pairs.

Double heterozygous mutation in the BRCA1 and ATM genes involved in development of primary metachronous tumours: a case report.

Purpose: Between 5 and 10% of cases of breast cancer (BC) are attributable to a genetic susceptibility. The BRCA1 and BRCA2 genes described in the late 1990s are associated with an increased risk of breast and ovarian cancer, and the clinical management of carriers of pathogenic variants in these genes is defined in several clinical guidelines (Paluch-Shimon et al. in Ann Oncol 27(suppl 5):v103-v110, 2016; Llort et al.

Neurogranin Expression Is Regulated by Synaptic Activity and Promotes Synaptogenesis in Cultured Hippocampal Neurons.

Neurogranin (Ng) is a calmodulin (CaM)-binding protein that is phosphorylated by protein kinase C (PKC) and is highly enriched in the dendrites and spines of telencephalic neurons. It is proposed to be involved in regulating CaM availability in the post-synaptic environment to modulate the efficiency of excitatory synaptic transmission. There is a close relationship between Ng and cognitive performance; its expression peaks in the forebrain coinciding with maximum synaptogenic activity, and it is reduced in several conditions of impaired cognition.

Brugada syndrome trafficking-defective Nav1.5 channels can trap cardiac Kir2.1/2.2 channels.

Cardiac Nav1.5 and Kir2.1-2.

Kir2.1-Nav1.5 Channel Complexes Are Differently Regulated than Kir2.1 and Nav1.5 Channels Alone.

Cardiac Kir2.1 and Nav1.5 channels generate the inward rectifier K (I) and the Na (I) currents, respectively.

Effectiveness of biosimilar filgrastim vs. original granulocyte colony-stimulating factors in febrile neutropenia prevention in breast cancer patients.

Purpose: The purpose of this study is to describe the effectiveness of biosimilar filgrastim and original granulocyte colony-stimulating factors (G-CSFs), lenograstim and pegfilgrastim, in febrile neutropenia (FN) prevention in breast cancer patients receiving docetaxel/doxorubicin/cyclophosphamide (TAC) as adjuvant/neoadjuvant treatment and to analyze their treatment patterns.

Methods: A pharmacoepidemiology cohort study was developed in a university hospital (with 23 healthcare centers) with retrospective data collection (2012-2014). Effectiveness of G-CSFs was assessed by the FN incidence.

Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM "El Álamo III" retrospective study.

Purpose: To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain.

Methods: a retrospective analysis was conducted from 10,638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry "El Álamo III", dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria.

Results: 7,641 patients were evaluable.

Critically short telomeres and toxicity of chemotherapy in early breast cancer.

Cumulative toxicity from weekly paclitaxel (myalgia, peripheral neuropathy, fatigue) compromises long-term administration. Preclinical data suggest that the burden of critically short telomeres (< 3 kilobases, CSTs), but not average telomere length by itself, accounts for limited tissue renewal and turnover capacity. The impact of this parameter (which can be modified with different therapies) in chemotherapy-derived toxicity has not been studied.

F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial.

We previously detected promising efficacy of neoadjuvant nintedanib (a multityrosine kinase inhibitor, TKI) in early HER2-negative breast cancer. In a preclinical study, we monitored stromal hypoxia with F-fluoromisonidazole-positron emission tomography (18F-FMISO-PET); we found that reoxygenation of tumors (or lack of it) during a window-of-opportunity (WoO) treatment with TKIs correlated with the benefit (or lack of it) from TKI-plus-chemotherapy combinations. We studied the predictive role of 18F-FMISO-PET for the TKI nintedanib in the neoadjuvant setting in a phase II WoO randomized trial.

Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study.

Purpose: Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC.

Patients And Methods: Patients with operable node-positive BC (T1-3/N1-3) were eligible.

A mutation in the POT1 gene is responsible for cardiac angiosarcoma in TP53-negative Li-Fraumeni-like families.

Cardiac angiosarcoma (CAS) is a rare malignant tumour whose genetic basis is unknown. Here we show, by whole-exome sequencing of a TP53-negative Li-Fraumeni-like (LFL) family including CAS cases, that a missense variant (p.R117C) in POT1 (protection of telomeres 1) gene is responsible for CAS.

Nab-Paclitaxel in Metastatic Breast Cancer: Defining the Best Patient Profile.

Around 40% of patients with breast cancer will present with a recurrence of the disease. Chemotherapy is recommended for patients with recurrent hormone-independent or hormone-refractory breast cancer and almost all patients with metastatic breast cancer (MBC) receive chemotherapy during their medical history. Nanoparticle albuminbound (nab)-paclitaxel is a solvent-free, 130-nanometer particle formulation of paclitaxel.

Fluorouracil, doxorubicin, and cyclophosphamide (FAC) versus FAC followed by weekly paclitaxel as adjuvant therapy for high-risk, node-negative breast cancer: results from the GEICAM/2003-02 study.

Purpose: Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity.