Prevención de la infección neonatal precoz por estreptococo del grupo B

El estreptococo del grupo B (EGB) constituye la principal causa de morbimortalidad neonatal y de morbilidad materna durante el embarazo y el posparto. Coloniza el aparato digestivo y el genitourinario en un 10-30% de las gestantes, con una tasa de transmisión vertical del 50%. De entre los recién nacidos colonizados, un 1-2% desarrollará una sepsis grave precoz. Se ha realizado una revisión bibliográfica con el objetivo de conocer las estrategias de prevención de la infección neonatal por EGB. Los resultados ponen de manifiesto que las recomendaciones para su prevención consisten en el cribado universal prenatal de colonización por EGB mediante cultivo vaginorrectal a las 35-37 semanas, y la administración de profilaxis antibiótica intraparto a todas las embarazadas portadoras

Preservation of fertility in patients with cancer (Review)

Survival rates in oncological patients have been steadily increasing in recent years due to the greater effectiveness of novel oncological treatments, such as radio‑ and chemotherapy. However, these treatments impair the reproductive ability of patients, and may cause premature ovarian failure in females and azoospermia in males. Fertility preservation in both female and male oncological patients is nowadays possible and should be integrated as part of the oncological healthcare. The main objective of this review was to describe the different existing options of fertility preservation in patients undergoing gonadotoxic cancer treatments, as well as the differences in success rates that may appear in the different techniques evaluated. Emerging techniques are promising, such as the cryopreservation in orthotopic models of ovarian or testicle tissues, artificial ovaries, or in vitro culture prior to the autotransplantation of cryopreserved tissues. However, oocyte vitrification for female patients and sperm banking for male patients are considered the first line fertility preservation option at the present time for cancer patients undergoing treatment. Certainly, new fertility preservation techniques will continue to develop in the following years. However, despite the growing advances in the subject, optimal counselling from healthcare professionals should always be present

Risk factors associated with the colonization of group b streptococcus during pregnancy: preliminary results

In Spain, the rate of colonization with GBS in pregnant women is 11%-18.2% and in Catalonia between 13-16%. The vertical transmission rate is 50%, and in the absence of avoidance manoeuvres, between 1-2% of new-borns develop GBS infection, which is the main bacterial agent in neonatal sepsis precocious

Full-term pregnancy in breast cancer survivor with fertility preservation: A case report and review of literature

A 43-year-old woman with an associated history of gynecological pathology and breast cancer with only one cryopreserved embryo wished to be a mother. Several factors that influenced the success of the pregnancy in this case were analyzed. Favorable factors included: triple positive breast cancer [positive hormone receptors and positive human epidermal growth factor receptor 2], which is more hormosensitive and chemosensitive; absence of metastasis; correct endometrium preparation; and the patient's optimistic attitude and strict health habits. In contrast, the factors against success were: breast cancer; adjuvant breast cancer therapy gonadotoxicity; the age of the patient (> 40-year-old); endometriosis; ovarian cyst; hydrosalpinx; submucosal fibroids and the respective associated surgery done for the above-mentioned pathology (all resolved prior to the embryo transfer); and a low quantity of ovules (low ovarian reserve) after ovarian stimulation. This is a very special clinical case of a patient with theoretically low pregnancy success probability due to the consecutive accumulation of gynecological and oncological pathologies, who nonetheless became pregnant and delivered a full-term infant and was able to provide adequate breastfeeding

Multidrug resistance protein 1 localization in lipid raft domains and prostasomes in prostate cancer cell lines

Background: One of the problems in prostate cancer (CaP) treatment is the appearance of the multidrug resistance phenotype, in which ATP-binding cassette transporters such as multidrug resistance protein 1 (MRP1) play a role. Different localizations of the transporter have been reported, some of them related to the chemoresistant phenotype. Aim: This study aimed to compare the localization of MRP1 in three prostate cell lines (normal, androgen-sensitive, and androgen-independent) in order to understand its possible role in CaP chemoresistance. Methods: MRP1 and caveolae protein markers were detected using confocal microscopy, performing colocalization techniques. Lipid raft isolation made it possible to detect these proteins by Western blot analysis. Caveolae and prostasomes were identified by electron microscopy. Results: We show that MRP1 is found in lipid raft fractions of tumor cells and that the number of caveolae increases with malignancy acquisition. MRP1 is found not only in the plasma membrane associated with lipid rafts but also in cytoplasmic accumulations colocalizing with the prostasome markers Caveolin-1 and CD59, suggesting that in CaP cells, MRP1 is localized in prostasomes. Conclusion: We hypothesize that the presence of MRP1 in prostasomes could serve as a reservoir of MRP1; thus, taking advantage of the release of their content, MRP1 could be translocated to the plasma membrane contributing to the chemoresistant phenotype. The presence of MRP1 in prostasomes could serve as a predictor of malignancy in Ca

Activation of p53 by nutlin-3a induces apoptosis and cellular senescence in human glioblastoma multiforme

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in adults. Despite concerted efforts to improve current therapies and develop novel clinical approaches, patient survival remains poor. As such, increasing attention has focused on developing new therapeutic strategies that specifically target the apoptotic pathway in order to improve treatment responses. Recently, nutlins, small-molecule antagonists of MDM2, have been developed to inhibit p53-MDM2 interaction and activate p53 signaling in cancer cells. Glioma cell lines and primary cultured glioblastoma cells were treated with nutlin-3a. Nutlin-3a induced p53-dependent G1- and G2-M cell cycle arrest and apoptosis in glioma cell lines with normal TP53 status. In addition, nutlin-arrested glioma cells show morphological features of senescence and persistent induction of p21 protein. Furthermore, senescence induced by nutlin-3a might be depending on mTOR pathway activity. In wild-type TP53 primary cultured cells, exposure to nutlin-3a resulted in variable degrees of apoptosis as well as cellular features of senescence. Nutlin-3a-induced apoptosis and senescence were firmly dependent on the presence of functional p53, as revealed by the fact that glioblastoma cells with knockdown p53 with specific siRNA, or cells with mutated or functionally impaired p53 pathway, were completely insensitive to the drug. Finally, we also found that nutlin-3a increased response of glioma cells to radiation therapy. The results provide a basis for the rational use of MDM2 antagonists as a novel treatment option for glioblastoma patients

The impact of the COVID-19 Pandemic on Adherence to Endocrine Therapy for Breast Cancer in Catalonia (Spain)

Purpose. To assess the impact of the COVID-19 pandemic on adherence to oral endocrine therapy in patients diagnosed with breast cancer in the public healthcare system in Catalonia (Spain). Methods. Retrospective cohort study in patients starting endocrine therapy from 2017 to 2021. Adherence was measured during the first year of treatment, and the impact of the pandemic was calculated according to the calendar year and whether the first year of treatment included the peak period of the pandemic in our setting (March-September 2020). Analyses were performed using a chi-square test and multivariable logistic regression, with results stratified by year, age group, and drug type. Results. Mean overall adherence during the first year of treatment was 89.6% from 2017 to 2021. In contrast, the patients who started treatment in 2019 and 2020 and whose treatment included the peak pandemic period presented an adherence of 87.0% and 86.5%, respectively. Young age and tamoxifen or combination therapy were predictors of low adherence. An increase in neoadjuvant therapy was also observed in 2020. Conclusions. The COVID-19 pandemic had only a modest impact on adherence to endocrine therapy (≈3%), despite the enormous disruptions for patients, the healthcare system in general, and cancer care in particular that were occurring in that period

Radioresistance of mesenchymal glioblastoma initiating cells correlates with patient outcome and is associated with activation of inflammatory program

Glioblastoma (GBM) still remains an incurable disease being radiotherapy (RT) the mainstay treatment. Glioblastoma intra-tumoral heterogeneity and GlioblastomaInitiating Cells (GICs) challenge the design of effective therapies. We investigated GICs and non-GICs response to RT in a paired in-vitro model and addressed molecular programs activated in GICs after RT. Established GICs heterogeneously expressed several GICs markers and displayed a mesenchymal signature. Upon fractionated RT, GICs reported higher radioresistance compared to non-GICs and showed lower α- and β-values, according to the Linear Quadratic Model interpretation of the survival curves. Moreover, a significant correlation was observed between GICs radiosensitivity and patient disease-free survival. Transcriptome analysis of GICs after acquisition of a radioresistant phenotype reported significant activation of Proneural-to-Mesenchymal transition (PMT) and pro-inflammatory pathways, being STAT3 and IL6 the major players. Our findings support a leading role of mesenchymal GICs in defining patient response to RT and provide the grounds for targeted therapies based on the blockade of inflammatory pathways to overcome GBM radioresistance

Synchrotron-based fourier-transform infrared micro-spectroscopy (SR-FTIRM) fingerprint of the small anionic molecule cobaltabis(dicarbollide) uptake in glioma stem cells

The anionic cobaltabis (dicarbollide) [3,3'-Co(1,2-C2B9H11)2]-, [o-COSAN]-, is the most studied icosahedral metallacarborane. The sodium salts of [o-COSAN]- could be an ideal candidate for the anti-cancer treatment Boron Neutron Capture Therapy (BNCT) as it possesses the ability to readily cross biological membranes thereby producing cell cycle arrest in cancer cells. BNCT is a cancer therapy based on the potential of 10B atoms to produce α particles that cross tissues in which the 10B is accumulated without damaging the surrounding healthy tissues, after being irradiated with low energy thermal neutrons. Since Na[o-COSAN] displays a strong and characteristic ν(B-H) frequency in the infrared range 2.600-2.500 cm-1, we studied the uptake of Na[o-COSAN] followed by its interaction with biomolecules and its cellular biodistribution in two different glioma initiating cells (GICs), mesenchymal and proneural respectively, by using Synchrotron Radiation-Fourier Transform Infrared (FTIR) micro-spectroscopy (SR-FTIRM) facilities at the MIRAS Beamline of ALBA synchrotron light source. The spectroscopic data analysis from the bands in the regions of DNA, proteins, and lipids permitted to suggest that after its cellular uptake, Na[o-COSAN] strongly interacts with DNA strings, modifies proteins secondary structure and also leads to lipid saturation. The mapping suggests the nuclear localization of [o-COSAN]-, which according to reported Monte Carlo simulations may result in a more efficient cell-killing effect compared to that in a uniform distribution within the entire cell. In conclusion, we show pieces of evidence that at low doses, [o-COSAN]- translocates GIC cells' membranes and it alters the physiology of the cells, suggesting that Na[o-COSAN] is a promising agent to BNCT for glioblastoma cells

Preclinical studies with glioblastoma brain organoid co-cultures show efficient 5-ALA photodynamic therapy

Abstract: Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)- mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100  g/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies