BEAT-Breast - Improving Outcomes for Breast Cancer Patients With Brain Metastases: a Pilot Nonrandomised Single Arm Phase 2 Clinical Trial in Patients With Primary Breast Cancer With Brain Metastases Who Are Not Suitable for Stereotactic Radiotherapy

The aim of this study is to demonstrate if it is possible to delivering a novel and modern radiotherapy approach (Dose Escalated internal PTV (DE-iPTV)) and to collect health related quality of life in patients whose breast cancer has spread to the brain (brain metastases) at 8 weeks post enrolling into the study.
The main questions that have been set out to to answer are:
* Is it possible to deliver the novel radiotherapy approach, DE-iPTV?
* Is it possible to measure health -related quality of life?
* What impact does the novel radiotherapy approach have on: patient's quality of life, control of the brain metastasis (control of the lesion) and steroid use?
Participants will:
* Receive 5 doses of radiotherapy
* Complete weekly quality of life (EQ-5D) assessments and medication (steroid) diaries (via telephone/ postal) until 12 weeks post enrolment
* Be reviewed in clinic with up-to-date MRI scans at 8, 12 and 24 weeks post-enrolment
* Complete a more detailed HRQoL panel of assessments will be assessed at baseline, 8 weeks, 12 weeks and 24 weeks post enrolment.

开始日期2025-01-06

申办/合作机构

Imperial College London

[+5]

NCT06590506 / RecruitingN/AIIT

High Definition Medicine: Establishment of a Cohort of Patients With Advanced Cancer for Prospective High-resolution Follow-up

The present study aims to analyze different genetic, phenotypic, environmental, social and lifestyle characteristics of cancer patients who are going to start a first line of cancer treatment with palliative intent and their possible relationship with tumor response or tolerance to treatment. In this way, the aim is to identify a series of variables that allow a better selection of patients and oncological treatments.

开始日期2023-03-02

申办/合作机构

Centro Nacional de Investigaciones Oncologicas CARLOS III

NCT04346147 / Unknown status临床2期IIT

Prospective, Phase II, Randomized, Open-label, Parallel Group Study to Evaluate the Efficacy of Baricitinib, Imatinib or Supportive Treatment in Patients With SARS Cov2 Pneumonia

In absence of vaccine and medications specifically designed to treat SARS-CoV-2 disease, identifying treatment options is critical at this time to control the disease outbreak.
For this, we have designed a phase II trial of efficacy and safety with 3 branches of different combinations of treatment to identify which is the best early treatment option for patients with pneumonia due to SARS-CoV-2 (Covid-19) Identifying treatment options as early as possible is critical to the SARS-CoV-2 outbreak response. Currently, there is no approved vaccine for the disease and the treatments being used are not specifically designed for the SARS-CoV-2 virus, but are different groups of drugs used for other pathologies with mechanisms of action that justify their use because they inhibit entry of the virus into virus cells or proteases.
The study aims to compare Imatinib 400mg, Baricitinib 4mg or supportive treatment, administered for 7 days in the setting of SARS-CoV-2 pneumonia treatment.
Patients who meet inclusion criteria and do not have any exclusion criteria will be randomized to receive open treatment 1:1:1

开始日期2020-05-07

申办/合作机构

Hospital Universitario de Fuenlabrada

[+1]

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2023-01-01·Frontiers in bioengineering and biotechnology

Isolation of goat milk small extracellular vesicles by novel combined bio-physical methodology.

Article

作者: Desco, Manuel ; Aguilera-Jiménez, Elena ; Cortes-Canteli, Marta ; Salinas, Beatriz ; Gallardo, Begoña ; Peinado, Héctor ; González, María Isabel ; Cerón, Carlos

Introduction: Goat milk is notable as a cost-effective source of exosomes, also known as small extracellular vesicles (sEVs). These nanoparticle-like structures are naturally secreted by cells and have emerged as potential diagnostic agents and drug delivery systems, also supported by their proven therapeutic effects. However, the complexity of goat milk and the lack of standardized protocols make it difficult to isolate pure sEVs. This work presents an optimized approach that combines well-established physical isolation methods with the biological treatment of milk with rennet. Methods: sEVs derived from goat milk were purified using a methodology that combines differential ultracentrifugation, rennet, and size-exclusion chromatography. This novel strategy was compared with two of the main methodologies developed for isolating extracellular vesicles from bovine and human milk by means of physico-chemical characterization of collected vesicles using Transmission Electron Microscopy, Western blot, Bradford Coomassie assay, Dynamic Light Scattering, Nanoparticle Tracking Analysis and Zeta Potential. Results: Vesicles isolated with the optimized protocol had sEV-like characteristics and high homogeneity, while samples obtained with the previous methods were highly aggregated, with significant residual protein content. Discussion: This work provides a novel biophysical methodology for isolating highly enriched goat milk sEVs samples with high stability and homogeneity, for their further evaluation in biomedical applications as diagnostic tools or drug delivery systems.

2021-10-01·Seminars in Immunology2区 · 医学

Dimensions of neutrophil life and fate

2区 · 医学

Review

作者: Hidalgo, Andrés ; Casanova-Acebes, María

The earliest reported observations on neutrophils date from 1879 to 1880, when Paul Ehrlich utilized a set of coal tar dyes to interrogate differential staining properties of the granules from white blood cells. While acidic and basic dyes identified eosinophils and basophils respectively, neutrophils were revealed by neutral dyes. Unknowingly, his work staining blood films set the stage for one of the most exciting features of immune cells discovered in the last decade, myeloid heterogeneity. Since then, advances in live imaging and high-resolution sequencing technologies have revolutionized how we analyze and envision those cells that Ehrich fixed in blood smears. Neutrophil plasticity and heterotypic interactions with immune and non-immune compartments are increasingly appreciated as an important part of their biology. In this review, we highlight early and recent work that will help the reader to appreciate our current view of the neutrophil life cycle -from maturation to elimination-, and how neutrophils behave and dynamically modulate tissue immunity, both in steady-state and in disease.

2001-10-01·British Journal of Dermatology1区 · 医学

beta-catenin expression in pilomatrixomas. Relationship with beta-catenin gene mutations and comparison with beta-catenin expression in normal hair follicles

1区 · 医学

Article

作者: Palacios, J. ; Moreno-Bueno, G. ; Contreras, F. ; Gamallo, C. ; Perez-Gallego, L.

BACKGROUNDbeta-catenin functions in signal transduction in the Wnt signalling pathway, which has recently been implicated in hair follicle (HF) morphogenesis. beta-catenin gene mutations affecting exon 3 have been reported in a high percentage of human pilomatrixomas. However, the expression pattern of beta-catenin in human HFs and pilomatrixomas has not been reported.OBJECTIVESTo analyse immunohistochemically the expression pattern of beta-catenin in normal anagen HFs and in 40 human pilomatrixomas.METHODSIn 11 of these tumours we also studied exon 3 beta-catenin gene mutations by polymerase chain reaction and direct sequencing. As these mutations have been related to a replication error (RER) phenotype in other tumour types, we explored whether or not this association also occurs in pilomatrixomas.RESULTSbeta-catenin was expressed in the cell membranes of the outer and inner root sheaths and in matrix cells located at the base and periphery of the HF bulb. However, central matrix cells that differentiate into cortical cells, cortical and cuticular cells expressed beta-catenin in the nucleus, suggesting a role in signal transduction. In addition, some fibroblasts of the dermal papilla also showed nuclear expression of beta-catenin. All 40 analysed pilomatrixomas showed intense nuclear and cytoplasmic beta-catenin expression in proliferating matrix (basaloid) cells. In areas of maturation, transitional cells mainly showed cytoplasmic and membranous expression of beta-catenin, while only a few cells retained nuclear expression. Shadow or ghost cells did not show beta-catenin expression. Three of 11 tumours (26%) had beta-catenin mutations. All three had the same heterozygote mis-sense mutation: a G to T change affecting the first nucleotide at codon 32 (D32Y). None of the 11 tumours studied had a positive RER phenotype.CONCLUSIONSPresent and previous studies suggest that the Wnt/beta-catenin/Tcf-Lef pathway is activated in normal matrix cells of the HF to induce differentiation to the hair shaft. Additionally, the beta-catenin mutation in matrix cells of the HF stabilizes beta-catenin protein, which translocates into the nucleus, where it activates of gene transcription together with lymphoid enhancer factor-1 producing pilomatrixoma. These mutations occur without an underlying defect in DNA mismatch repair.

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100 项与 Centro Nacional de Investigaciones Oncologicas CARLOS III 相关的转化医学

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