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1.
EMBO Rep ; 24(8): e55884, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37366231

RESUMO

Recent studies highlight the importance of baseline functional immunity for immune checkpoint blockade therapies. High-dimensional systemic immune profiling is performed in a cohort of non-small-cell lung cancer patients undergoing PD-L1/PD-1 blockade immunotherapy. Responders show high baseline myeloid phenotypic diversity in peripheral blood. To quantify it, we define a diversity index as a potential biomarker of response. This parameter correlates with elevated activated monocytic cells and decreased granulocytic phenotypes. High-throughput profiling of soluble factors in plasma identifies fractalkine (FKN), a chemokine involved in immune chemotaxis and adhesion, as a biomarker of response to immunotherapy that also correlates with myeloid cell diversity in human patients and murine models. Secreted FKN inhibits lung adenocarcinoma growth in vivo through a prominent contribution of systemic effector NK cells and increased tumor immune infiltration. FKN sensitizes murine lung cancer models refractory to anti-PD-1 treatment to immune checkpoint blockade immunotherapy. Importantly, recombinant FKN and tumor-expressed FKN are efficacious in delaying tumor growth in vivo locally and systemically, indicating a potential therapeutic use of FKN in combination with immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Humanos , Camundongos , Antígeno B7-H1/genética , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimiocina CX3CL1/genética , Quimiocina CX3CL1/uso terapêutico , Neoplasias Pulmonares/genética
2.
Open Respir Arch ; 4(3): 100185, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-37496584

RESUMO

Obstructive sleep apnea (OSA) is defined as the presence of an apnea-hyponea index (AHI)>15/h, predominantly obstructive or AHI greater than 5 with symptoms, the classic symptoms are observed apneas, daytime sleepiness and snoring, however, there are many other associated symptoms. To assess the severity of OSA, classically, only the AHI value was considered, but there is increasing evidence to implicate other factors. The predisposition to develop OSA is determined by anatomical and functional features. Having OSA increases the risk of accidents, high blood pressure (HBP) and is associated with cardiovascular risk, diabetes mellitus (DM), cardiac arrhythmia and neoplasms. To assess the probability of OSA, questionnaires and scales have been developed to assess symptoms, the certain diagnosis is obtained by polysomnography (PSG), which is the gold standard test, or polygraphy, which is a simpler and more accessible diagnostic test for diagnosis validated, the use of one or the other will depend on the suspicion and the associated comorbidities. Treatments for sleep apnea increasingly tend to be more individualized based on the characteristics of the patient and all are complementary. Hygienic-dietary measures should be applied in all patients, continuous positive airway pressure (CPAP) is the most effective treatment and with the most evidence, but other treatments are also available such as mandibular advancement devices (MAD), postural therapy and surgical options among others. Telemedicine is advancing in the follow-up of patients with OSA, both from non-face-to-face consultations and control of equipment via Wi-Fi to assess adherence, efficacy and correct control of therapy.

3.
Oncogene ; 41(28): 3625-3639, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35688943

RESUMO

Given the long-term ineffectiveness of current therapies and late-stage diagnoses, lung cancer is a leading cause of malignant diseases. Tumor progression is influenced by cancer cell interactions with the tumor microenvironment (TME). Insulin-like growth factor 1 receptor (IGF1R) was reported to affect the TME; however, the role of IGF1R in lung TME has not been investigated. First, we assessed IGF1R genomic alterations and expression in NSCLC patient tissue samples, as well as IGF1R serum levels. Next, we performed tumor heterotopic transplantation and pulmonary metastases in IGF1R-deficient mice using melanoma and Lewis lung carcinoma (LLC) cells. Herein we report increased amplification and mRNA expression, as well as increased protein expression (IGF1R/p-IGF1R) and IGF1R levels in tumor samples and serum from NSCLC patients, respectively. Moreover, IGF1R deficiency in mice reduced tumor growth, proliferation, inflammation and vascularization, and increased apoptosis after tumor heterotopic transplantation. Following induction of lung metastasis, IGF1R-deficient lungs also demonstrated a reduced tumor burden, and decreased expression of tumor progression markers, p-IGF1R and p-ERK1/2. Additionally, IGF1R-deficient lungs showed increased apoptosis and diminished proliferation, vascularization, EMT and fibrosis, along with attenuated inflammation and immunosuppression. Accordingly, IGF1R deficiency decreased expression of p-IGF1R in blood vessels, fibroblasts, tumor-associated macrophages and FOXP3+ tumor-infiltrating lymphocytes. Our results demonstrate that IGF1R promotes metastatic tumor initiation and progression in lung TME. Furthermore, our research indicates that IGF1R could be a potential biomarker for early prediction of drug response and clinical evolution in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptor IGF Tipo 1 , Animais , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Inflamação , Neoplasias Pulmonares/patologia , Camundongos , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Microambiente Tumoral
4.
Arch Bronconeumol ; 58(1): 52-68, 2022 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33875282

RESUMO

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

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