Matthieu Talagas - Academia.edu (original) (raw)

Papers by Matthieu Talagas

The Journal of Allergy and Clinical Immunology, May 1, 2023

Oncology Reports, Jul 21, 2016

Lung Cancer, 2016

ALK-rearrangements are mainly encountered in lung adenocarcinomas and allow treating patients wit... more ALK-rearrangements are mainly encountered in lung adenocarcinomas and allow treating patients with anti-ALK targeted therapy. ALK-rearranged squamous cell lung carcinomas are rare tumors that can also respond to anti-ALK-targeted therapy. Nevertheless, ALK screening is not always performed in patients with squamous cell lung carcinomas making the identification and treatment of this molecular tumor subtype challenging. We intend to report a rare case of ALK-rearranged lung squamous cell carcinoma with response to crizotinib therapy. We report clinical, pathological, immunohistochemical and fluorescent in situ hybridization data concerning a patient having an ALK-rearranged squamous cell lung cancer diagnosed in our institution. The patient was a 58-year old woman with a metastatic-stage lung cancer. Histopathological and immunohistochemical analyses were performed on a bronchial biopsy sample and concluded in a non-keratinizing squamous cell lung carcinoma expressing strongly cytokeratin 5/6, p63 and p40, which are classic hallmarks of lung squamous cell carcinomas, but also cytokeratin 7 which is more commonly expressed in lung adenocarcinomas. The tumor did not express thyroid transcription factor-1. ALK rearrangement was searched because of the never-smoker status of the patient and resulted in strong positive fluorescent in situ hybridization test and ALK/p80 immunohistochemistry. The patient responded to crizotinib therapy during 213 days. Our observation points out the interest of considering ALK screening in patients with metastatic lung squamous cell carcinomas, especially in patients lacking a usual heavy-smoker clinical history. The histopathological and immunohistochemical features of this particular tumor highlighting the overlapping criteria between lung adenocarcinomas and rare ALK-rearranged squamous cell lung carcinomas could also be relevant to extend ALK screening to tumors with intermediate phenotypes between squamous cell carcinomas and adenocarcinomas and/or arising in non-smokers.

Itch, Oct 1, 2020

Introduction: Ciguatera fish poisoning (CFP), the most common seafood poisoning worldwide, is cau... more Introduction: Ciguatera fish poisoning (CFP), the most common seafood poisoning worldwide, is caused by the consumption of seafood contaminated with ciguatoxins (CTXs). Pruritus is one of the most distressing symptoms, associated with other cutaneous sensory disorders, including paresthesia and cold dysesthesia. No specific treatment exists. CTXs are known to primarily activate voltage-gated sodium channels, but the downstream molecular events that lead to sensory disturbances remain poorly defined. Peptidergic sensory neurons were recently identified as major players in CFP sensory disturbances. Methods: In this study, we examined the role of molecular actors in 2 effects induced by Pacific CTX-2 (P-CTX-2): the increase in cytosolic calcium levels in rat primary sensory neurons; and the release of the neuropeptide substance P (SP) in sensory neurons co-cultured with keratinocytes. Results: Our results (i) rule out the involvement of the Na+/Ca2+ exchanger (NCX) and the transient receptor potential channels transient receptor potential ankyrin 1 and and transient receptor potential vanilloid 1; (ii) show that N-type voltage-gated calcium (Cav) channels contribute to the initiation of the calcium signal elicited by P-CTX-2 in rat sensory neurons, while N-type and L-type Cav channels play equal parts in the SP release in the co-culture; and (iii) identify store-operated calcium entry supported by Orai calcium release-activated calcium modulator 1 (ORAI1) as a critical effector of the late phase of the calcium signal and the subsequent SP release elicited by P-CTX-2. Discussion: Our in vitro findings indicate that Cav and ORAI1 channels may be promising pharmacological targets for specifically relieving the sensory effects of CTXs.

British Journal of Pharmacology, Oct 15, 2021

Until recently, itch pathophysiology was poorly understood, and treatments were poorly effective ... more Until recently, itch pathophysiology was poorly understood, and treatments were poorly effective in relieving itch. Current progress in knowledge on itch processing and the numerous mediators and receptors involved has led to a large variety of possible therapeutic pathways. Currently, anti-IL31, anti-IL4/13, anti-NK1, opioids, cannabinoids, anti-Jak, anti-phosphodiesterase-4, or anti-TRP are the main compounds in clinical trials. However, many expected, such as MRGPRs, and unexpected new pathways should also be explored.

Human Pathology, Nov 1, 2015

NRAS and BRAF mutational status has become mandatory to treat patients with metastatic melanomas.... more NRAS and BRAF mutational status has become mandatory to treat patients with metastatic melanomas. Mutation-specific immunohistochemistry (IHC) can help analyze challenging tumor samples. We report our experience integrating NRASQ61R (SP174) and BRAFV600E (VE1) IHC in routine practice in a cancer molecular genetic platform. All samples screened for BRAF and NRAS mutations during the year 2014 were analyzed by IHC and pyrosequencing, with an independent analysis of the 2 methods. Cases with first-line discordant results benefited from a complementary second-round IHC and next-generation sequencing (NGS) with a final interpretation taking into account the results of pyrosequencing, IHC, NGS, and quantification of the tumor cells. We analyzed 111 consecutive formalin-fixed and paraffin-embedded melanoma samples from 101 patients. Twenty-two and 11 samples were concordant for BRAFV600E and NRASQ61R mutations, respectively. Second-round analyses of 9 discordant and 1 molecularly inconclusive samples allowed conclusion in 4 further mutated samples (2 BRAFV600E and 2 NRASQ61R). A sample remained NRASQ61R IHC negative but NRASQ61R mutated with molecular methods. Overall, BRAFV600 and NRASQ61 mutation frequencies were 31.7% and 30.7%, respectively. When compared to molecular results, the sensitivity and specificity of IHC were 100% for BRAFV600E IHC and 92.3% and 98.9% for NRASQ61R IHC, respectively. IHC interpretation required a more stringent cutoff for BRAFV600E IHC than NRASQ61R to minimize false results. We conclude that NRASQ61R and BRAFV600E IHC coupled with NGS allow detection of mutations in melanoma challenging samples.

Acta Dermato-venereologica, Sep 1, 2017

Elsevier eBooks, 2018

The skin is densely innervated to transmit all sensations (touch, temperature, pressure, pain, an... more The skin is densely innervated to transmit all sensations (touch, temperature, pressure, pain, and pruritus) but not only it. Indeed, innervation plays a major role in the structuration of the epidermis, in its renewal, and in the process as wound healing. There are increasing evidences that skin cells and cutaneous nerve endings are in close interactions each other. So, to study them is an important issue to better understand the behavior of the skin and its both physiological and pathological processes. However, due to scientific, technical, ethical, or economic reasons, the study of these interactions in human or animals in vivo remains quite impossible. So, the development of in vitro models is crucial to better understand them. Since several years, all the actors of these interactions, skin cells such as keratinocytes, fibroblasts, melanocytes, Merkel cells or stem cells, and sensory neurons, could be extracted and cultured independently or together so named 2-D cocultures. Other cocultures, the 3-D cocultures, could also be considered by the use of the epidermis or dermis or whole portions of native or reconstructed skin. These 3-D models offer also an alternative by the use of compartmented cocultures to only analyze the biochemical communication between the different types of cells. After a description of the different models available, this chapter will give some clues to define the best model(s) depending of the applications and, finally, will discuss of the advantages and the limitations of these types of cultures to study cutaneous innervation mechanisms.

Annales De Dermatologie Et De Venereologie, Dec 1, 2016

Cells

Merkel cells (MCs) are rare multimodal epidermal sensory cells. Due to their interactions with sl... more Merkel cells (MCs) are rare multimodal epidermal sensory cells. Due to their interactions with slowly adapting type 1 (SA1) Aβ low-threshold mechanoreceptor (Aβ-LTMRs) afferents neurons to form Merkel complexes, they are considered to be part of the main tactile terminal organ involved in the light touch sensation. This function has been explored over time by ex vivo, in vivo, in vitro, and in silico approaches. Ex vivo studies have made it possible to characterize the topography, morphology, and cellular environment of these cells. The interactions of MCs with surrounding cells continue to be studied by ex vivo but also in vitro approaches. Indeed, in vitro models have improved the understanding of communication of MCs with other cells present in the skin at the cellular and molecular levels. As for in vivo methods, the sensory role of MC complexes can be demonstrated by observing physiological or pathological behavior after genetic modification in mouse models. In silico models ar...

Itch, 2020

Skin Tissue Models for Regenerative Medicine, 2018

Cells, 2020

Ciguatera fish poisoning (CFP), the most prevalent seafood poisoning worldwide, is caused by the ... more Ciguatera fish poisoning (CFP), the most prevalent seafood poisoning worldwide, is caused by the consumption of tropical and subtropical fish contaminated with potent neurotoxins called ciguatoxins (CTXs). Ciguatera is a complex clinical syndrome in which peripheral neurological signs predominate in the acute phase of the intoxication but also persist or reoccur long afterward. Their recognition is of particular importance in establishing the diagnosis, which is clinically-based and can be a challenge for physicians unfamiliar with CFP. To date, no specific treatment exists. Physiopathologically, the primary targets of CTXs are well identified, as are the secondary events that may contribute to CFP symptomatology. This review describes the clinical features, focusing on the sensory disturbances, and then reports on the neuronal targets and effects of CTXs, as well as the neurophysiological and histological studies that have contributed to existing knowledge of CFP neuropathophysiolo...

Annales de Dermatologie et de Vénéréologie, 2020

La temperature, la douleur et le prurit sont classiquement considerees comme etant exclusivement ... more La temperature, la douleur et le prurit sont classiquement considerees comme etant exclusivement percus par les fibres nerveuses intra-epidermiques. Alors qu’il a recemment ete demontre que les keratinocytes epidermiques participent egalement a la transduction sensorielle cutanee, le mecanisme qui sous-tend la communication entre les keratinocytes et les fibres nerveuses intra-epidermiques reste meconnu. Nous demontrons, dans notre etude, que les kerationocytes dialoguent avec les neurones sensoriels par l’intermediaire de contacts « en passant » de type synaptique. Ces contacts ont les caracteristiques ultrastructurales et moleculaires de synapses chimiques, vehiculant des informations sensorielles des keratinocytes vers les neurones sensoriels par l’intermediaire d’une exocytose mediee par des complexes SNAREs. Le renouvellement permanent de l’epiderme, qui implique une grande plasticite, pourrait avoir retarde leur identification, contribuant par consequent a perenniser le concept de fibres nerveuses intra-epidermiques cheminant librement entre les keratinocytes. En assurant une communication selective entre les keratinocytes et les neurones sensoriels, ces contacts pourraient etre le pivot d’un recepteur a deux sites, l’un keratinocytaire, l’autre neuronal. La decouverte de ces contacts pourrait amener a une reconsideration des concepts etablis au sujet de la perception sensorielle cutanee, invitant a porter un regard nouveau sur la physiopathologie de la douleur et du prurit.

Annals of Neurology, 2020

ObjectivePain, temperature, and itch are conventionally thought to be exclusively transduced by t... more ObjectivePain, temperature, and itch are conventionally thought to be exclusively transduced by the intraepidermal nerve endings. Although recent studies have shown that epidermal keratinocytes also participate in sensory transduction, the mechanism underlying keratinocyte communication with intraepidermal nerve endings remains poorly understood. We sought to demonstrate the synaptic character of the contacts between keratinocytes and sensory neurons and their involvement in sensory communication between keratinocytes and sensory neurons.MethodsContacts were explored by morphological, molecular, and functional approaches in cocultures of epidermal keratinocytes and sensory neurons. To interrogate whether structures observed in vitro were also present in the human epidermis, in situ correlative light electron microscopy was performed on human skin biopsies.ResultsEpidermal keratinocytes dialogue with sensory neurons through en passant synaptic‐like contacts. These contacts have the u...

Journal of Investigative Dermatology, 2020

Experimental Dermatology, 2019

Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous noc... more Recent years have brought an enhanced understanding of keratinocyte contribution to cutaneous nociception. While intra‐epidermal nerve endings were classically considered as the exclusive transducers of cutaneous noxious stimuli, it has now been demonstrated that epidermal keratinocytes can initiate nociceptive responses, like Merkel cells do for the innocuous mechanotransduction. In the light of recent in vivo findings, this article outlines this paradigm shift that points to a not yet considered population of sensory epidermal cells.