Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 1.098
Filtrer
1.
Cureus ; 16(8): e66635, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-39258099

RÉSUMÉ

Rheumatoid arthritis is a multisystemic inflammatory disease that can involve the respiratory system, including the pleural space. Most rheumatoid pleural effusions (PE) are incidentally found and do not require any treatment. Very rarely, however, they can become symptomatic and loculated, leading to lung entrapment or trapped lung. Surgical decortication remains the mainstay of management in such circumstances, although recent studies showed comparable efficacy of intrapleural fibrinolytics (alteplase and dornase alfa) in non-rheumatoid complicated effusions. We present a case of rheumatoid PE leading to lung entrapment successfully treated with intrapleural fibrinolytics without complications and good clinical status at six-month follow-up.

2.
Sci Rep ; 14(1): 20877, 2024 09 06.
Article de Anglais | MEDLINE | ID: mdl-39242741

RÉSUMÉ

The study of social interactions lies at the core of several disciplines such as psychiatry, psychology and ethology, just to name a few. In this context, understanding the temporal patterns underlying interactive behaviors is of crucial importance. Here, we employed T-pattern detection and analysis to study social interactions in ten pairs of Wistar rats tested in an Open-Field environment. We found four different categories of interactive behaviors. One of them was of particular interest to us because it consisted of behavioral events that, taken individually, should not underlie an interaction of any kind; however, they were included in T-patterns, which is suggestive of a dyadic temporal coordination in the behavioral expression of two individuals. Within this category, we described for the first time a new subcategory of apparent interaction patterns characterized by events that one of the two rats repeats only if previously produced by the partner (i.e., behavioral mirroring). These findings are discussed in functional terms for rodents and in light of our current understanding of social interactions in humans.


Sujet(s)
Comportement animal , Rat Wistar , Animaux , Comportement animal/physiologie , Rats , Mâle , Interaction sociale , Comportement social
3.
Cureus ; 16(7): e65124, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-39171037

RÉSUMÉ

Cardiocerebral infarction (CCI), the simultaneous occurrence of acute ischemic stroke and acute myocardial infarction (AMI), is a rare but critical condition. However, the optimal treatment strategy, particularly regarding the use of tissue plasminogen activator (t-PA), remains unclear. This case report describes a patient with CCI diagnosed during a neurosurgical emergency. A 67-year-old man with a history of hypertension presented with sudden right hemiparesis and sensory aphasia 30 minutes prior to hospital arrival. Diffusion-weighted magnetic resonance imaging revealed acute cerebral infarction in the left middle cerebral artery territory but without large-vessel occlusion. Routine electrocardiography (ECG) showed ST-T elevation in leads V1, V2, II, III, and aVF (augmented vector foot). Subsequent blood tests confirmed positive troponin T and elevated creatine kinase levels. Despite the absence of reported AMI symptoms, the patient received a diagnosis of CCI. Due to the uncertain time of AMI onset and to expedite transfer to the percutaneous coronary intervention (PCI) unit, t-PA administration was withheld. Upon transfer, dual antiplatelet therapy with aspirin (200 mg) and clopidogrel (300 mg) was initiated. Emergency coronary angioplasty successfully treated a 99% stenosis of the left anterior descending artery (#7). The patient's post-procedure course was uneventful. After 18 days, he was transferred to a rehabilitation hospital with a modified Rankin Scale score of 3. This case highlights the importance of routine 12-lead ECG in neurosurgical emergencies, regardless of presenting symptoms like chest pain. While guidelines support the use of t-PA in CCI, its administration requires careful consideration due to specific risks, including cardiac rupture and limitations on antithrombotic therapy within the first 24 hours.

4.
BMC Public Health ; 24(1): 2208, 2024 Aug 13.
Article de Anglais | MEDLINE | ID: mdl-39138572

RÉSUMÉ

BACKGROUND: YouTube™ has a great role in providing information, which includes educational videos, to more than 2 billion users, making it the second most popular application in the world. BE-FAST is a modified version of the FAST mnemonic and is used to detect acute ischemic stroke by the patients or their relatives. The purpose of this study is to assess the overall usefulness of the information of YouTube in patients to realize an acute stroke attack. METHODS: YouTube was searched for the following five terms: "stroke", ''stroke diagnosis", "stroke signs", "brain attack" and "what is stroke" in November 2021 and May 2023, separately. Two independent neurology specialists scored each video by using Global Quality Scale (GQS). RESULTS: Among the total of 150 videos, the number that met inclusion criteria was 91 for the November 2021 search and 104 for the May 2023 search. For the 2021 search, in 30 videos (33%), the FAST mnemonic or its contents were noticed, whereas BE-FAST was mentioned in only four videos (4.4%). For the 2023 search, the FAST mnemonic or its contents were noticed in 36 videos (34.6%) and BE-FAST was mentioned in 11 videos (10.6%). Among the 2021 and 2023 searches, the mean GQS values were 3.09 and 2.96 points, 50 (54.8%) vs. 56 (53.8%) videos rated 3.5 points or higher (high quality), respectively. GQS scores of the videos mentioning balance, eyes, face, arms, speech, and time, the basic and advanced information about radiology and treatment, and mentioning FAST, BE-FAST, and TPA were significantly higher. CONCLUSION: We conclude that YouTube is not yet a very useful tool for patients to realize that they may have acute ischemic stroke, though over the years; information available on social media for healthcare information and education has improved.


Sujet(s)
Médias sociaux , Accident vasculaire cérébral , Enregistrement sur magnétoscope , Humains , Accident vasculaire cérébral/diagnostic , Éducation du patient comme sujet/méthodes
5.
J Clin Med ; 13(15)2024 Jul 25.
Article de Anglais | MEDLINE | ID: mdl-39124612

RÉSUMÉ

Pleural effusion is the most common manifestation of pleural disease, and chest ultrasound is crucial for diagnostic workup and post-treatment monitoring. Ultrasound helps distinguish the various types of pleural effusion and enables the detection of typical manifestations of empyema, which presents as a complicated, septated effusion. This may benefit from drainage and the use of intrapleural enzyme therapy or may require more invasive approaches, such as medical or surgical thoracoscopy. The mechanism of action of intrapleural enzymatic therapy (IPET) is the activation of plasminogen to plasmin, which breaks down fibrin clots that form septa or the loculation of effusions and promotes their removal. In addition, IPET has anti-inflammatory properties and can modulate the immune response in the pleural space, resulting in reduced pleural inflammation and improved fluid reabsorption. In this article, we briefly review the literature on the efficacy of IPET and describe a case series in which most practical applications of IPET are demonstrated, i.e., as a curative treatment but also as an alternative, propaedeutic, or subsequent treatment to surgery.

6.
Int J Biol Macromol ; 278(Pt 3): 134751, 2024 Aug 22.
Article de Anglais | MEDLINE | ID: mdl-39173801

RÉSUMÉ

The aim of this study was to investigate the effect of varying concentrations of furcellaran (FUR) and safflower (Carthamus Tinctorius) oil on the functional properties of emulgels as potential carriers of bioactive substances. The textural, mechanical, thermal and structural properties of twenty different formulations were characterised. The pH stability and zeta-potential of the emulgels was also examined. It was found clear correlation between gelling agent and oil fraction content and investigated properties. The hardness, strength, thermal stability expressed as melting point of the investigated systems increased with increasing concentration of the furcellaran and decreasing proportion of safflower oil, which indicated a significant weakening of the structure as a result of the addition of the oil fraction. Stored under refrigeration, emulgels appeared to be relatively stable showing a slight decrease in pH values after 7 days. Swelling ratio (SW) of emulgels increased with increasing both, polysaccharide and oil content, in emulgels. Based on the microstructure analyses, it can also be concluded that only part of the added safflower oil chemically bound to the functional groups of the polysaccharide, while the vast majority of it was only physically immobilized in the furcellaran matrix. Colour of furcellaran - safflower oil emulsion gels depended largely on the amount of oil fraction. The presented research demonstrating the wide spectrum of functional properties of polysaccharide-oil systems is a first step to developing a carrier composition for lipophilic compounds at further stages of research.

7.
Int J Mol Sci ; 25(16)2024 Aug 13.
Article de Anglais | MEDLINE | ID: mdl-39201490

RÉSUMÉ

Atherosclerosis is a chronic inflammatory disease that involves modified low-density lipoproteins (LDL) which play a pivotal role in the initiation and progression of the disease. Myeloperoxidase oxidized LDL (Mox-LDL) is considered to be the most patho-physiologically relevant type of modified LDL and has been reported to be ubiquitously present in atheroma plaques of patients with atherosclerosis. Besides its involvement in the latter disease state, Mox-LDL has also been shown to be implicated in the pathogenesis of various illnesses including sleep disorders, which are in turn associated with heart disease and depression in many intricate ways. Meanwhile, we have recently shown that lox-1-mediated Mox-LDL signaling modulates neuroserpin activity in endothelial cells, which could have major implications that go beyond the pathophysiology of stroke and cerebrovascular disease (CD). Of note is that tissue plasminogen activator (tPA), which is the main target of neuroserpin in the brain, has a crucial function in the processing of brain-derived neurotrophic factor (BDNF) into its mature form. This factor is known to be involved in major depressive disorder (MDD) development and pathogenesis. Since tPA is more conventionally recognized as being involved in fibrinolytic mechanisms, and its effect on the BDNF system in the context of MDD is still not extensively studied, we speculate that any Mox-LDL-driven change in the activity of tPA in patients with atherosclerosis may lead to a decrease in the production of mature BDNF, resulting in impaired neural plasticity and depression. Deciphering the mechanisms of interaction between those factors could help in better understanding the potentially overlapping pathological mechanisms that regulate disease processes in CD and MDD, supporting the possibility of novel and common therapeutic opportunities for millions of patients worldwide.


Sujet(s)
Athérosclérose , Lipoprotéines LDL , Myeloperoxidase , Humains , Athérosclérose/métabolisme , Lipoprotéines LDL/métabolisme , Myeloperoxidase/métabolisme , Animaux , Facteur neurotrophique dérivé du cerveau/métabolisme , Dépression/métabolisme , , Récepteurs éboueurs de classe E/métabolisme , Trouble dépressif majeur/métabolisme
8.
EMBO Mol Med ; 16(9): 2146-2169, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39148004

RÉSUMÉ

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.


Sujet(s)
Granulocytes neutrophiles , Activateur tissulaire du plasminogène , Animaux , Granulocytes neutrophiles/métabolisme , Granulocytes neutrophiles/effets des médicaments et des substances chimiques , Granulocytes neutrophiles/immunologie , Humains , Souris , Activateur tissulaire du plasminogène/métabolisme , Activateur tissulaire du plasminogène/effets indésirables , Mâle , Femelle , Sujet âgé , Adulte d'âge moyen , Protéines/métabolisme , Traitement thrombolytique/effets indésirables , Traitement thrombolytique/méthodes , Modèles animaux de maladie humaine , Fibrinolytiques/pharmacologie , Glycoprotéines/métabolisme , Souris de lignée C57BL , Accident vasculaire cérébral ischémique/traitement médicamenteux
9.
Physiol Behav ; 285: 114655, 2024 Oct 15.
Article de Anglais | MEDLINE | ID: mdl-39111642

RÉSUMÉ

This article endeavors to provide a useful perspective for Researchers and Authors within the realm of Behavioral Sciences, particularly those engaged in the study of Behavioral Physiology, namely the discipline focusing on the intricate interplay between physiological processes and the related behavioral manifestations. Alongside the prevailing conservatism that has characterized the progression of behavioral sciences in recent decades, it advocates for an additional approach in the study of Behavioral Physiology that revolves around a more inclusive perspective: beyond the analysis of isolated behavioral events as discrete components, akin to scattered pieces of a larger puzzle, emphasis also is placed on elucidating their interconnectedness. It is within these interrelationships that the governing constraints of behavior, whether exhibited by humans or any other species, manifest as a cohesive and functional structure.


Sujet(s)
Comportement , Humains , Animaux , Comportement/physiologie , Sciences du comportement
10.
Gels ; 10(7)2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-39057478

RÉSUMÉ

Polysaccharides derived from diverse sources exhibit distinct rheological and gel properties, exerting a profound impact on their applicability in the food industry. In this study, we collected five Gracilaria chouae samples from distinct geographical regions, namely Rizhao (RZ), Lianyungang (LYG), Ningde (ND), Beihai (BH), and a wild source from Beihai (BHW). We conducted analyses on the chemical composition, viscosity, and rheological properties, as well as gel properties, to investigate the influence of chemical composition on variations in gel properties. The results revealed that the total sugar, sulfate content, and monosaccharide composition of G. chouae polysaccharides exhibit similarity; however, their anhydrogalactose content varies within a range of 15.31% to 18.98%. The molecular weight distribution of G. chouae polysaccharides ranged from 1.85 to 2.09 × 103 kDa. The apparent viscosity of the LYG and BHW polysaccharides was relatively high, whereas that of RZ and ND was comparatively low. The gel strength displayed a similar trend. BHW and LYG exhibited solid-like behavior, while ND, RZ, and BH demonstrated liquid-like characteristics at low frequencies. The redundancy analysis (RDA) analysis revealed a positive correlation between the texture profile analysis (TPA) characteristics and anhydrogalactose. The study could provide recommendations for the diverse applications of G. chouae polysaccharides derived from different geographical regions.

11.
J Mol Model ; 30(8): 273, 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-39023540

RÉSUMÉ

CONTEXT: Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable plastic. It was introduced to the plastics market in 1998 and since then has been widely used around the world. The main idea of this research is to perform quantum chemical calculations to study the potential toxicity of PBAT and its degradation products. We analyzed the electron transfer capacity to determine its potential toxicity. We found that biodegradable products formed with benzene rings are as good electron acceptors as PBAT and OOH•. Our results indicate that the biodegradation products are potentially as toxic as PBAT. This might explain why biodegradation products alter the photosynthetic system of plants and inhibit their growth. From this and other previous investigations, we can think that biodegradable plastics could represent a potential environmental risk. METHODS: All DFT computations were performed using the Gaussian16 at M062x/6-311 + g(2d,p) level of theory without symmetry constraints. Electro-donating (ω-) and electro-accepting (ω +) powers were used as response functions.


Sujet(s)
Dépollution biologique de l'environnement , Polyesters , Polyesters/composition chimique , Polyesters/métabolisme , Polyesters/toxicité , Matières plastiques biodégradables/composition chimique , Matières plastiques biodégradables/toxicité
12.
Neuroscience ; 550: 21-29, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38964373

RÉSUMÉ

The neurovascular unit (NVU) is assembled by endothelial cells (ECs) and pericytes, and encased by a basement membrane (BM) surveilled by microglia and surrounded by perivascular astrocytes (PVA), which in turn are in contact with synapses. Cerebral ischemia induces the rapid release of the serine proteinase tissue-type plasminogen activator (tPA) from endothelial cells, perivascular astrocytes, microglia and neurons. Owning to its ability to catalyze the conversion of plasminogen into plasmin, in the intravascular space tPA functions as a fibrinolytic enzyme. In contrast, the release of astrocytic, microglial and neuronal tPA have a plethora of effects that not always require the generation of plasmin. In the ischemic brain tPA increases the permeability of the NVU, induces microglial activation, participates in the recycling of glutamate, and has various effects on neuronal survival. These effects are mediated by different receptors, notably subunits of the N-methyl-D-aspartate receptor (NMDAR) and the low-density lipoprotein receptor-related protein-1 (LRP-1). Here we review data on the role of tPA in the NVU under non-ischemic and ischemic conditions, and analyze how this knowledge may lead to the development of potential strategies for the treatment of acute ischemic stroke patients.


Sujet(s)
Encéphalopathie ischémique , Activateur tissulaire du plasminogène , Humains , Activateur tissulaire du plasminogène/métabolisme , Animaux , Encéphalopathie ischémique/métabolisme , Encéphalopathie ischémique/anatomopathologie , Encéphale/métabolisme , Fibrinolyse/physiologie , Neurones/métabolisme
13.
Pathophysiology ; 31(3): 367-375, 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-39051224

RÉSUMÉ

Patients undergoing transurethral resection of the prostate (TURP) surgery can develop TURP syndrome and post-TURP bleeding. Post-TURP bleeding can be surgical, from arteries or venous sinuses, or non-surgical, due to coagulopathy preventing clot formation. Non-surgical post-TURP bleeding may be due to high concentrations of urokinase and tissue plasminogen activator (tPA) in the urine that cause fibrinolytic changes and increase bleeding risk. Urine urokinase and tPA may have both local and systemic fibrinolytic effects that may prevent blood clot formation locally at the site of surgery, and cause fibrinolytic changes systemically through leaking into the blood stream. Another post-TURP complication that may happen is TURP syndrome, due to absorption of hypotonic glycine fluid through the prostatic venous plexus. TURP syndrome may present with hyponatremia, bradycardia, and hypotension, which may be preceded by hypertension. In this case report, we had a patient with benign prostatic hyperplasia (BPH) who developed both TURP syndrome and non-surgical post-TURP bleeding. These complications were transient for one day after surgery. The local effect of urine urokinase and tPA explains the non-surgical bleeding after TURP by preventing clot formation and inducing bleeding. Coagulation studies showed fibrinolytic changes that may be explained by urokinase and tPA leakage into the blood stream. In conclusion, non-surgical bleeding after TURP can be explained by the presence of fibrinolytic agents in the urine, including urokinase and tPA. There is a deficiency in existing studies explaining the pathophysiology of the fibrinolytic changes and risk of bleeding after TURP. Herein, we discuss the possible pathophysiology of developing fibrinolytic changes after TURP. More research effort should be directed to explore this area to investigate the appropriate medications to treat and prevent post-TURP bleeding. We suggest monitoring patients' coagulation profiles and electrolytes after TURP because of the risk of developing severe acute hyponatremia, TURP syndrome, fibrinolytic changes, and non-surgical bleeding. In our review of the literature, we discuss current clinical trials testing the use of an antifibrinolytic agent, Tranexamic acid, locally in the irrigation fluid or systemically to prevent post-TURP bleeding by antagonizing the fibrinolytic activity of urine urokinase and tPA.

15.
Cureus ; 16(6): e62280, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-39006622

RÉSUMÉ

Neonatal aortic thrombosis, though rare, is associated with high mortality and is frequently linked to umbilical vessel catheterization, especially in smaller and critically ill infants due to their low levels of natural anticoagulants and increased prothrombotic activity. We report a case of a term neonate with abdominal aortic thrombosis and severe lower limb ischemia, presenting with respiratory distress requiring intubation and subsequent development of thrombosis by day 7. Initial anticoagulation with heparin proved insufficient, necessitating the use of reteplase and intra-arterial thrombolysis, which resulted in clinical improvement despite limited immediate success in Doppler studies. The patient was discharged on low-molecular-weight heparin against medical advice, highlighting the complexities and need for individualized management strategies in neonatal thromboembolism.

17.
Res Pract Thromb Haemost ; 8(4): 102463, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-39026660

RÉSUMÉ

Background: Thrombin activatable fibrinolysis inhibitor (TAFI) is one of the most important physiological fibrinolysis inhibitors. Its inhibitory efficacy under physiological conditions remains uncertain. Objectives: Elucidate the role of soluble thrombomodulin (sTM)/TAFI axis in the regulation of fibrinlysis. Methods: Since thrombin is required to generate activated TAFI (TAFIa) that targets the C-terminal lysine of partially digested fibrin, a clot lysis assay is suitable for evaluating its function. Using tissue-type plasminogen activator-induced plasma clot lysis time (tPA-PCLT) together with TAFIa inhibitor and recombinant sTM (rsTM), we evaluated the specific function of TM/TAFI in the plasma milieu. Results: tPA-PCLT values were significantly shortened by the TAFIa inhibitor. rsTM supplementation prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor to a time similar to that obtained without rsTM and with the TAFIa inhibitor. Plasma obtained from patients treated with rsTM showed prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor but not further prolonged by rsTM. However, no significant correlation was observed between tPA-PCLT and parameters of TM/TAFI system in the plasma. Conclusion: The role of the TM/TAFI system in regulating fibrinolysis was successfully evaluated using TAFIa inhibitor and rsTM. Trace amounts of soluble TM in normal plasma appeared sufficient to activate TAFI and inhibit fibrinolysis. Further, a therapeutic dose of rsTM appeared sufficient to activate TAFI and regulate fibrinolysis in the plasma milieu.

18.
Cureus ; 16(5): e61171, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38933638

RÉSUMÉ

OBJECTIVE: This narrative review aimed to evaluate, based on current evidence, whether the transpalatal arch (TPA) and Nance appliance can effectively reinforce anchorage during fixed orthodontic treatment while also offering a comprehensive and in-depth overview of the existing literature on this subject. MATERIALS AND METHODS: A thorough literature search was performed across multiple electronic databases to identify peer-reviewed articles relevant to the review. RESULTS: Evidence suggests that the Nance appliance does not provide absolute anchorage. Additionally, patients experienced discomfort and inflammation of the palatal tissues. The transpalatal arch is also insufficient for maximum anteroposterior anchorage, and existing studies on its effectiveness in vertical anchorage control are inconsistent with conflicting data. CONCLUSIONS: For patients with critical anchorage demand, mini-screws may be the method of choice, either solely or in combination with Nance or transpalatal arch, though they carry a risk of failure.

19.
Cureus ; 16(5): e61103, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38919231

RÉSUMÉ

Objective The goal of this study is to evaluate treatment times regarding acute ischemic stroke and identify barriers to implementing stroke care at the Ouachita County Medical Center Emergency Department. Methods A retrospective review of medical records was conducted of patients who presented with acute ischemic stroke to the Ouachita County Medical Center Emergency Department between 2020 and 2023 and received intravenous (IV) r-tPA. The primary focus of this study was to analyze door-to-needle time with IV r-tPA. To determine areas of improvement, this study examined door-to-initial physician evaluation, door-to-CT, door-to-tele neurologist evaluation, and door-to-IV r-tPA administration. Results A total of 26 patients who received treatment with IV r-tPA for acute ischemic stroke were included in this study. Twenty-three patients (88%; n=26) received IV- r-tPA within the recommended 60-minute window with a mean treatment time of 44.5 minutes. The mean door-to-physician evaluation time for patients presenting with acute ischemic stroke was 1.81 minutes. All patients received CT scans within 28 minutes of arrival with the mean time being 5.08 minutes. Teleneurologist evaluation was initiated within 59 minutes of presentation with a mean time of 25.19 minutes. Conclusion Evaluation of treatment times at the Ouachita County Medical Center Emergency Department confirms that stroke care received at this facility adheres to the recommendations outlined by the American Stroke Association. Nevertheless, clinicians should always strive for improvement. Through extensive evaluation of the treatment process, we were able to provide recommendations to further decrease treatment times and improve overall clinical outcomes.

20.
Cancer Sci ; 115(8): 2839-2845, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38898727

RÉSUMÉ

By taking advantage of forward genetic analysis in mice, we have demonstrated that Pak1 plays a crucial role during DMBA/TPA skin carcinogenesis. Although Pak1 has been considered to promote cancer development, its overall function remains poorly understood. To clarify the functional significance of Pak1 in detail, we sought to evaluate the possible effect of an allosteric inhibitor against PAK1 (NVS-PAK1-1) on a syngeneic mouse model. To this end, we established two cell lines, 9AS1 and 19AS1, derived from DMBA/TPA-induced squamous cell carcinoma (SCC) that engrafted in FVB mice. Based on our present results, NVS-PAK1-1 treatment significantly inhibited the growth of tumors derived from 9AS1 and 19AS1 cells in vitro and in vivo. RNA-sequencing analysis on the engrafted tumors indicates that NVS-PAK1-1 markedly potentiates the epidermal cell differentiation and enhances the immune response in the engrafted tumors. Consistent with these observations, we found an expansion of Pan-keratin-positive regions and potentially elevated infiltration of CD8-positive immune cells in NVS-PAK1-1-treated tumors as examined by immunohistochemical analyses. Together, our present findings strongly suggest that PAK1 is tightly linked to the development of SCC, and that its inhibition is a promising therapeutic strategy against SCC.


Sujet(s)
Carcinome épidermoïde , Modèles animaux de maladie humaine , Tumeurs cutanées , p21-Activated Kinases , Animaux , p21-Activated Kinases/métabolisme , p21-Activated Kinases/génétique , p21-Activated Kinases/antagonistes et inhibiteurs , Tumeurs cutanées/traitement médicamenteux , Tumeurs cutanées/anatomopathologie , Tumeurs cutanées/génétique , Tumeurs cutanées/métabolisme , Carcinome épidermoïde/traitement médicamenteux , Carcinome épidermoïde/anatomopathologie , Carcinome épidermoïde/métabolisme , Carcinome épidermoïde/génétique , Souris , Lignée cellulaire tumorale , 7,12-Diméthyl-benzo[a]anthracène/toxicité , Femelle , Différenciation cellulaire/effets des médicaments et des substances chimiques , 12-Myristate-13-acétate de phorbol , Lymphocytes T CD8+/effets des médicaments et des substances chimiques , Lymphocytes T CD8+/métabolisme , Prolifération cellulaire/effets des médicaments et des substances chimiques
SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE