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Article ; Online: Pharmacokinetics and pharmacodynamics of antibody-drug conjugates for the treatment of patients with breast cancer.

Cherifi, François / Da Silva, Angélique / Martins-Branco, Diogo / Awada, Ahmad / Nader-Marta, Guilherme

Expert opinion on drug metabolism & toxicology

2024 Volume 20, Issue 1-2, Page(s) 45–59

Abstract: Introduction: Currently three antibody-drug-conjugates (ADC) are approved by the European Medicines Agency (EMA) for treatment of breast cancer (BC) patient: trastuzumab-emtansine, trastuzumab-deruxtecan and sacituzumab-govitecan. ADC are composed of a ... ...

Abstract	Introduction: Currently three antibody-drug-conjugates (ADC) are approved by the European Medicines Agency (EMA) for treatment of breast cancer (BC) patient: trastuzumab-emtansine, trastuzumab-deruxtecan and sacituzumab-govitecan. ADC are composed of a monoclonal antibody (mAb) targeting a specific antigen, a cytotoxic payload and a linker. Pharmacokinetics (PK) and pharmacodynamics (PD) distinguish ADC from conventional chemotherapy and must be understood by clinicians. Areas covered: Our review delineates the PK/PD profiles of ADC approved for the treatment of BC with insight for future development. This is an expert opinion literature review based on the EMA's Assessment Reports, enriched by a comprehensive literature search performed on Medline in August 2023. Expert opinion: All three ADC distributions are described by a two-compartment structure: tissue and serum. Payload concentration peak is immediate but remains at low concentration. The distribution varied for all ADC only with body weight. mAb will be metabolised firstly by the saturable complex formation of ADC/Tumour-Receptor and secondly by binding of FcgRs in immune cells. They are all excreted in the bile and faeces with minimal urine elimination. Dose adjustments, apart from weight, are not recommended. Novel ADC are composed of cleavable linkers with various targets/payloads with the same PK/PD properties, but novel structures of ADC are in development.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/drug therapy ; Trastuzumab ; Ado-Trastuzumab Emtansine/therapeutic use ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/metabolism ; Immunoconjugates/pharmacokinetics ; Immunoconjugates/therapeutic use ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use
Chemical Substances	Trastuzumab (P188ANX8CK) ; Ado-Trastuzumab Emtansine (SE2KH7T06F) ; Antineoplastic Agents ; Immunoconjugates ; Antibodies, Monoclonal
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2214462-6
ISSN	1744-7607 ; 1742-5255
ISSN (online)	1744-7607
ISSN	1742-5255
DOI	10.1080/17425255.2024.2302460
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Article: Brain Hemispheric Asymmetry in Schizophrenia and Bipolar Disorder.

Pinto, Diogo / Martins, Ricardo / Macedo, António / Castelo Branco, Miguel / Valente Duarte, João / Madeira, Nuno

Journal of clinical medicine

2023 Volume 12, Issue 10

Abstract: Background: This study aimed to compare brain asymmetry in patients with schizophrenia (SCZ), bipolar disorder (BPD), and healthy controls to test whether asymmetry patterns could discriminate and set boundaries between two partially overlapping severe ... ...

Abstract	Background: This study aimed to compare brain asymmetry in patients with schizophrenia (SCZ), bipolar disorder (BPD), and healthy controls to test whether asymmetry patterns could discriminate and set boundaries between two partially overlapping severe mental disorders. Methods: We applied a fully automated voxel-based morphometry (VBM) approach to assess structural brain hemispheric asymmetry in magnetic resonance imaging (MRI) anatomical scans in 60 participants (SCZ = 20; BP = 20; healthy controls = 20), all right-handed and matched for gender, age, and education. Results: Significant differences in gray matter asymmetry were found between patients with SCZ and BPD, between SCZ patients and healthy controls (HC), and between BPD patients and HC. We found a higher asymmetry index (AI) in BPD patients when compared to SCZ in Brodmann areas 6, 11, and 37 and anterior cingulate cortex and an AI higher in SCZ patients when compared to BPD in the cerebellum. Conclusion: Our study found significant differences in brain asymmetry between patients with SCZ and BPD. These promising results could be translated to clinical practice, given that structural brain changes detected by MRI are good candidates for exploration as biological markers for differential diagnosis, besides helping to understand disease-specific abnormalities.
Language	English
Publishing date	2023-05-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12103421
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Article: FLUORO-CT GUIDED BIOPSY OF LUNG NODULES: A STEP BY STEP REVISION.

Vieites Branco, Inês / Martins, Sara / Monteiro, João Pedro / Rocha, Diogo / Pereira, Tiago

Portuguese journal of cardiac thoracic and vascular surgery

2022 Volume 28, Issue 4, Page(s) 43–46

Abstract: Introduction: Transthoracic biopsies under fluoro-computer tomography (CT) guidance play an important role on the diagnosis and management of lung nodules, permitting histological examination and differentiation between benign and malignant lesions(1). ... ...

Abstract	Introduction: Transthoracic biopsies under fluoro-computer tomography (CT) guidance play an important role on the diagnosis and management of lung nodules, permitting histological examination and differentiation between benign and malignant lesions(1). Furthermore, with recent advances in target therapy, it is increasingly necessary to obtain tumor tissue for the analysis of molecular fingerprints allowing personalized treatment(1). Although many studies report low complication rates for this procedure, they are not negligible, urging the need for a structured and reproducible guide to reduce technique-related complications(1,2).
MeSH term(s)	Biopsy, Needle/methods ; Computers ; Image-Guided Biopsy/methods ; Lung/diagnostic imaging ; Tomography, X-Ray Computed/methods
Language	English
Publishing date	2022-01-04
Publishing country	Portugal
Document type	Journal Article ; Review
ISSN	2184-9927
ISSN	2184-9927
DOI	10.48729/pjctvs.223
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Article ; Online: Automatic segmentation and classification of mice ultrasonic vocalizations.

Pessoa, Diogo / Petrella, Lorena / Martins, Pedro / Castelo-Branco, Miguel / Teixeira, César

The Journal of the Acoustical Society of America

2022 Volume 152, Issue 1, Page(s) 266

Abstract: This paper addresses the development of a system for classifying mouse ultrasonic vocalizations (USVs) present in audio recordings. The automatic labeling process for USVs is usually divided into two main steps: USV segmentation followed by the matching ... ...

Abstract	This paper addresses the development of a system for classifying mouse ultrasonic vocalizations (USVs) present in audio recordings. The automatic labeling process for USVs is usually divided into two main steps: USV segmentation followed by the matching classification. Three main contributions can be highlighted: (i) a new segmentation algorithm, (ii) a new set of features, and (iii) the discrimination of a higher number of classes when compared to similar studies. The developed segmentation algorithm is based on spectral entropy analysis. This novel segmentation approach can detect USVs with 94% and 74% recall and precision, respectively. When compared to other methods/software, our segmentation algorithm achieves a higher recall. Regarding the classification phase, besides the traditional features from time, frequency, and time-frequency domains, a new set of contour-based features were extracted and used as inputs of shallow machine learning classification models. The contour-based features were obtained from the time-frequency ridge representation of USVs. The classification methods can differentiate among ten different syllable types with 81.1% accuracy and 80.5% weighted F1-score. The algorithms were developed and evaluated based on a large dataset, acquired on diverse social interaction conditions between the animals, to stimulate a varied vocal repertoire.
MeSH term(s)	Algorithms ; Animals ; Machine Learning ; Mice ; Software ; Ultrasonics ; Vocalization, Animal
Language	English
Publishing date	2022-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219231-7
ISSN	1520-8524 ; 0001-4966
ISSN (online)	1520-8524
ISSN	0001-4966
DOI	10.1121/10.0012350
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Article: Antibody-drug conjugates: the evolving field of targeted chemotherapy for breast cancer treatment.

Nader-Marta, Guilherme / Molinelli, Chiara / Debien, Véronique / Martins-Branco, Diogo / Aftimos, Philippe / de Azambuja, Evandro / Awada, Ahmad

Therapeutic advances in medical oncology

2023 Volume 15, Page(s) 17588359231183679

Abstract: Antibody-drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the ... ...

Abstract	Antibody-drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the payload. By combining the specificity of mABs with the high potency of the payloads, ADCs constitute a smart drug delivery system with improved therapeutic index. After recognition and binding of the mAB to its target surface antigen, ADCs are internalized by endocytosis by the tumor cell, releasing the payloads into the cytoplasm, where they exert their cytotoxic activity, eventually leading to cell death. The composition of some of the new ADCs confers additional functional properties that allow expanding their activity to neighboring cells not expressing the target antigen, constituting a valuable strategy to overcome tumor heterogeneity. Some of these 'off-target effects', such as the bystander effect, are possibly the mechanism underlying the antitumor activity demonstrated in patients with low expression of the target antigens, which represents an important paradigm shift in anticancer targeted therapy. Three ADCs are currently approved for the treatment of breast cancer (BC); two anti-HER2 (human epidermal growth factor receptor 2) ADCs (trastuzumab emtansine and trastuzumab deruxtecan); and one Trop-2-targeted ADC (sacituzumab govitecan). Based on the unprecedented efficacy data demonstrated by these agents, ADCs have been incorporated as part of standard regimens for all subtypes of advanced BC, as well as for high-risk early HER2-positive BC. Despite the remarkable advances, several hurdles still remain to overcome, including the development of reliable biomarkers for patient selection, prevention, and management of potentially severe toxicities, ADC resistance mechanisms, post-ADC resistance patterns, and optimal treatment sequencing and combinations. In this review, we will summarize the currently available evidence related to the use of these agents, as well as explore the current landscape of ADC development for BC treatment.
Language	English
Publishing date	2023-07-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2503443-1
ISSN	1758-8359 ; 1758-8340
ISSN (online)	1758-8359
ISSN	1758-8340
DOI	10.1177/17588359231183679
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Article ; Online: Brewer's Spent Yeast Cell Wall Polysaccharides as Vegan and Clean Label Additives for Mayonnaise Formulation.

Reis, Sofia F / Fernandes, Pedro A R / Martins, Vítor J / Gonçalves, Sara / Ferreira, Luís P / Gaspar, Vítor M / Figueira, Diogo / Castelo-Branco, Diogo / Mano, João F / Coimbra, Manuel A / Coelho, Elisabete

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 8

Abstract: Brewer's spent yeast (BSY) mannoproteins have been reported to possess thickening and emulsifying properties. The commercial interest in yeast mannoproteins might be boosted considering the consolidation of their properties supported by structure/ ... ...

Abstract	Brewer's spent yeast (BSY) mannoproteins have been reported to possess thickening and emulsifying properties. The commercial interest in yeast mannoproteins might be boosted considering the consolidation of their properties supported by structure/function relationships. This work aimed to attest the use of extracted BSY mannoproteins as a clean label and vegan source of ingredients for the replacement of food additives and protein from animal sources. To achieve this, structure/function relationships were performed by isolating polysaccharides with distinct structural features from BSY, either by using alkaline extraction (mild treatment) or subcritical water extraction (SWE) using microwave technology (hard treatment), and assessment of their emulsifying properties. Alkaline extractions solubilized mostly highly branched mannoproteins (
MeSH term(s)	Animals ; Humans ; Saccharomyces cerevisiae/metabolism ; Emulsions/metabolism ; Vegans ; Polysaccharides/chemistry ; Mannans/metabolism ; Water/analysis ; Cell Wall/chemistry ; beta-Glucans/metabolism ; Plant Extracts/analysis
Chemical Substances	Emulsions ; Polysaccharides ; Mannans ; Water (059QF0KO0R) ; beta-Glucans ; Plant Extracts
Language	English
Publishing date	2023-04-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28083540
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Article ; Online: Adjuvant Chemotherapy De-Escalation with Genomic Assay Protocol in Patients with Early Breast Cancer: A Single-Centre Prospective Cohort Study.

Martins-Branco, Diogo / Cristóvão Ferreira, Sofia / Gouveia, Emanuel / André, Saudade / Esteves, Susana / Brito, Margarida / Moreira, António

Acta medica portuguesa

2023 Volume 36, Issue 7-8, Page(s) 487–495

Abstract: Introduction: Genomic assays are useful tools for tailoring adjuvant treatment in early breast cancer. We aimed to analyse the role of an institutional protocol of a genomic assay for chemotherapy de-escalation.: Material and methods: Prospective ... ...

Abstract	Introduction: Genomic assays are useful tools for tailoring adjuvant treatment in early breast cancer. We aimed to analyse the role of an institutional protocol of a genomic assay for chemotherapy de-escalation. Material and methods: Prospective cohort study of all consecutive women diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-negative early breast cancer, tested with the 21-gene Recurrence Score (RS) assay from August 2015 to July 2018 at a Portuguese cancer centre. For being tested, patients should meet at least one of the pre-defined inclusion criteria: i) luminal A-like, pT2pN0; ii) luminal A-like, 1 - 3 positive nodes and comorbidities with higher risk of chemotherapy-induced toxicity; iii) pT1-2pN0, progesterone receptor ≤ 20% and/or Ki67 14% - 40%. Adjuvant treatment was de-escalated to isolated endocrine therapy if RS was less than 18. We measured the reduction in chemotherapy prescribing and its clinical impact, the RS association with pathologic features, and the protocol feasibility. Results: We tested 154 women with a median age of 61 years old (range: 25 - 79), 69% postmenopausal. Tumours were mainly pT1 (55%), pN0 (82%), invasive ductal (73%), G2 (86%), luminal B-like (69%) and stage IA (85%). We obtained a RS less than 18 in 60% of women, with an overall adjuvant chemotherapy reduction of 65%. Seven (95% confidence interval: 5 - 10) patients needed to be screened with the 21-gene RS assay to prevent one clinically relevant adverse event during the first six months of adjuvant treatment. Considering the currently used RS cut-off, only 9% of node-negative and 11% of node-positive patients had RS over 25. We found no relevant associations between RS and pathologic features. The protocol was feasible and did not compromise the adequate timing for adjuvant treatment. Conclusion: These criteria allowed the de-escalation of adjuvant systemic treatment in at least six out of ten women.
MeSH term(s)	Humans ; Female ; Adult ; Middle Aged ; Aged ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Prospective Studies ; Lymphatic Metastasis ; Chemotherapy, Adjuvant ; Genomics ; Neoplasm Recurrence, Local/drug therapy
Language	English
Publishing date	2023-02-06
Publishing country	Portugal
Document type	Journal Article
ZDB-ID	603078-6
ISSN	1646-0758 ; 0870-399X
ISSN (online)	1646-0758
ISSN	0870-399X
DOI	10.20344/amp.18539
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Article ; Online: The Impact of Initial Tumor Response on Survival Outcomes of Patients With HER2-Positive Advanced Breast Cancer Treated With Docetaxel, Trastuzumab, and Pertuzumab: An Exploratory Analysis of the CLEOPATRA Trial.

Debien, Veronique / Agostinetto, Elisa / Bruzzone, Marco / Ceppi, Marcello / Martins-Branco, Diogo / Molinelli, Chiara / Jacobs, Flavia / Nader-Marta, Guilherme / Lambertini, Matteo / de Azambuja, Evandro

Clinical breast cancer

2024

Abstract: Introduction: The CLEOPATRA trial (NCT00567190) established a dual anti-HER2 blockade in combination with docetaxel as the first-line standard of care for patients with metastatic HER2-positive breast cancer. While this treatment is overall associated ... ...

Abstract	Introduction: The CLEOPATRA trial (NCT00567190) established a dual anti-HER2 blockade in combination with docetaxel as the first-line standard of care for patients with metastatic HER2-positive breast cancer. While this treatment is overall associated with significant improvement in progression-free survival (PFS) and overall survival (OS), not all patients respond equally. We hypothesized that a radiological complete response (CR) at week 9 (i.e., first disease re-evaluation) is associated with prolonged OS and PFS compared to radiological partial response (PR) or stable disease (SD). Methods: We performed an exploratory analysis of the CLEOPATRA study to address this question. Results: Out of 362 patients treated with docetaxel, trastuzumab, and pertuzumab eligible for our analysis, 46 (12.7%) had radiological CR at week 9, 243 (67.1%) PR, and 73 (20.2%) SD per central RECIST v1.0. Radiological CR at first tumor re-evaluation was associated with a 60% risk reduction for death compared to SD (adjusted HR = 0.40 95% confidence interval (CI) 0.23-0.70), whereas no significant impact on survival was observed for PR (adjusted HR = 0.85 95% CI 0.60-1.20). The same was observed for PFS with adjusted HR = 0.30 (95% CI 0.18-0.48) for the CR subgroup and adjusted HR = 0.81 (95% CI 0.60-1.09) for the PR subgroup. In multivariate analysis, no variables were associated with radiological CR. Conclusions: Our findings suggest that radiological CR at first disease re-evaluation is associated with more prolonged survival; this might result from stronger dependence on HER2 pathway addiction, supporting the need for further translational research.
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2106734-X
ISSN	1938-0666 ; 1526-8209
ISSN (online)	1938-0666
ISSN	1526-8209
DOI	10.1016/j.clbc.2024.02.012
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Zs.A 5800: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 498: Show issues

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Article ; Online: Atypically Located Solitary Neurofibroma of the Ulnar Nerve as Inaugural Presentation of a New Genetic Variant of Neurofibromatosis Type 1: A Case Report.

Carvalho, Diogo Rocha / Branco, Pedro Martins / Afonso, P Diana / Gerardo, Gonçalo / Baptista, Carolina

Journal of hand surgery global online

2022 Volume 4, Issue 5, Page(s) 283–287

Abstract: We report the case of a 34-year-old woman with hypothenar pain due to a solitary neurofibroma (NF) of the ulnar nerve, with an extrafascicular location, outside Guyon canal, with no clinical evidence of associated neurologic impairment, who was ... ...

Abstract	We report the case of a 34-year-old woman with hypothenar pain due to a solitary neurofibroma (NF) of the ulnar nerve, with an extrafascicular location, outside Guyon canal, with no clinical evidence of associated neurologic impairment, who was successfully treated with surgical resection. The identification of this isolated tumor led to the diagnosis of a new genetic variant of neurofibromatosis type 1 after genome sequencing. At the 1-year follow-up, the patient remains asymptomatic without recurrence or other peripheral nerve sheath tumors. A solitary NF of a deep-seated nerve is extremely rare, especially in the context of neurofibromatosis type 1. To our knowledge, there are no reports of a NF of the ulnar nerve with an extraneural location. In the presence of a solitary NF related to a deep-seated peripheral nerve, neurofibromatosis type 1 should always be excluded.
Language	English
Publishing date	2022-05-20
Publishing country	United States
Document type	Case Reports
ISSN	2589-5141
ISSN (online)	2589-5141
DOI	10.1016/j.jhsg.2022.04.008
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Article ; Online: Correction: Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

Brandão, Mariana / Martins-Branco, Diogo / De Angelis, Claudia / Vuylsteke, Peter / Gelber, Richard D / Van Damme, Nancy / van Walle, Lien / Ferreira, Arlindo R / Lambertini, Matteo / Poggio, Francesca / Verhoeven, Didier / Barbeaux, Annelore / Duhoux, Francois P / Wildiers, Hans / Caballero, Carmela / Awada, Ahmad / Piccart-Gebhart, Martine / Punie, Kevin / de Azambuja, Evandro

Breast cancer research and treatment

2024

Language	English
Publishing date	2024-04-09
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	604563-7
ISSN	1573-7217 ; 0167-6806
ISSN (online)	1573-7217
ISSN	0167-6806
DOI	10.1007/s10549-024-07275-0
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