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1.
Geroscience ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954129

RESUMO

Canine mammary tumors (CMTs) represent a significant health concern in dogs, with a high incidence among intact female dogs. CMTs are a promising comparative model for human breast cancer, due to sharing several pathophysiological features. Additionally, CMTs have a strong genetic correlation with their human counterpart, including the expression of microRNAs (miRNAs). MiRNAs are a class of non-coding RNAs that play important roles in post-translational regulation of gene expression, being implicated in carcinogenesis, tumor progression, and metastasis. Moreover, miRNAs hold promise as diagnostic, prognostic, and metastatic biomarkers. Understanding the molecular mechanisms underlying CMTs is crucial for improving diagnosis, prognosis, and monitoring of treatments. Herein, we provide a comprehensive overview of the current knowledge on miRNAs in CMTs, highlighting their roles in carcinogenesis and their potential as biomarkers. Additionally, we highlight the current limitations and critically discuss the overarching challenges in this field, emphasizing the need for future research to translate miRNA findings into veterinary clinical practice.

2.
Cancers (Basel) ; 16(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39001418

RESUMO

Ovarian cancer (OC) is the deadliest gynaecological malignancy. Identifying new prognostic biomarkers is an important research field. Haemostatic components together with leukocytes can drive cancer progression while increasing the susceptibility to venous thromboembolism (VTE) through immunothrombosis. Unravelling the underlying complex interactions offers the prospect of uncovering relevant OC prognostic biomarkers, predictors of cancer-associated thrombosis (CAT), and even potential targets for cancer therapy. Thus, this study evaluated the expression of F3, F5, F8, F13A1, TFPI1, and THBD in peripheral blood cells (PBCs) of 52 OC patients. Those with VTE after tumour diagnosis had a worse overall survival (OS) compared to their counterparts (mean OS of 13.8 ± 4.1 months and 47.9 ± 5.7 months, respectively; log-rank test, p = 0.001). Low pre-chemotherapy F3 and F8 expression levels were associated with a higher susceptibility for OC-related VTE after tumour diagnosis (χ2, p < 0.05). Regardless of thrombogenesis, patients with low baseline F8 expression had a shorter progression-free survival (PFS) than their counterparts (adjusted hazard ratio (aHR) = 2.54; p = 0.021). Among those who were not under platelet anti-aggregation therapy, low F8 levels were also associated with a shorter OS (aHR = 6.16; p = 0.006). Moving forward, efforts should focus on external validation in larger cohorts.

3.
Porto Biomed J ; 9(3): 254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835655

RESUMO

Background: This literature review explores the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-lymphocyte-to-platelet ratio (NLPR) biomarkers, as potential indicators for predicting bacteremia and sepsis in patients with cancer. Objective: Tracing the evolution of interest in this area since 2001, the aim of this review was to report a comprehensive overview of current knowledge and gaps, particularly in patients undergoing immunosuppression. Summary of Findings: The literature research indicates the potential of NLR, PLR, and other biomarkers in diagnosing and predicting sepsis, with some studies emphasizing their value in mortality prediction. A specific focus on bacteremia shows the effectiveness of NLR and PLR as early indicators and prognostic tools, though mostly in noncancer patient populations. While NLR and PLR are promising in general cancer patient populations, the review addresses the challenges in applying these biomarkers to patients with neutropenic and lymphopenic cancer. The NLPR could be considered a significant biomarker for inflammation and mortality risk in various medical conditions, yet its diagnostic accuracy in patients with immunosuppressed cancer is not extensively validated. Conclusion: This review offers a snapshot of the current research on biomarkers in patients with immunocompromised cancer in the sepsis and bacteremia area. More focused research on their application is necessary. This gap underscores an opportunity for future studies to enhance diagnostic and prognostic capabilities in this high-risk group.

4.
Vet World ; 17(5): 1052-1072, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38911075

RESUMO

Chronic inflammation plays a crucial role in carcinogenesis. High levels of serum prostaglandin E2 and tissue overexpression of cyclooxygenase-2 (COX-2) have been described in breast, urinary, colorectal, prostate, and lung cancers as being involved in tumor initiation, promotion, progression, angiogenesis, and immunosuppression. Non-steroidal anti-inflammatory drugs (NSAIDs) are prescribed for several medical conditions to not only decrease pain and fever but also reduce inflammation by inhibiting COX and its product synthesis. To date, significant efforts have been made to better understand and clarify the interplay between cancer development, inflammation, and NSAIDs with a view toward addressing their potential for cancer management. This review provides readers with an overview of the potential use of NSAIDs and selective COX-2 inhibitors for breast cancer treatment, highlighting pre-clinical in vitro and in vivo studies employed to evaluate the efficacy of NSAIDs and their use in combination with other antineoplastic drugs.

5.
Int J Mol Sci ; 25(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38791254

RESUMO

Mycoses are one of the major causes of morbidity/mortality among immunocompromised individuals. Considering the importance of these infections, the World Health Organization (WHO) defined a priority list of fungi for health in 2022 that include Candida albicans as belonging to the critical priority group and Pichia kudriavzevii (Candida krusei) to the medium priority group. The existence of few available antifungal drugs, their high toxicity, the acquired fungal resistance, and the appearance of new species with a broader spectrum of resistance, points out the need for searching for new antifungals, preferably with new and multiple mechanisms of action. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 was previously tested against several fungi and revealed an interesting activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans. The main objective of the present work was to deeply understand the mechanisms involved in its antifungal activity. The effects of the cyclam salt on yeast metabolic viability (resazurin reduction assay), yeast mitochondrial function (JC-1 probe), production of reactive oxygen species (DCFH-DA probe) and on intracellular ATP levels (luciferin/luciferase assay) were evaluated. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 induced a significant decrease in the metabolic activity of both C. albicans and C. krusei, an increase in Reactive Oxygen Species (ROS) production, and an impaired mitochondrial function. The latter was observed by the depolarization of the mitochondrial membrane and decrease in ATP intracellular levels, mechanisms that seems to be involved in the antifungal activity of H4[H2(4-CF3PhCH2)2Cyclam]Cl4. The interference of the cyclam salt with human cells revealed a CC50 value against HEK-293 embryonic kidney cells of 1.1 µg/mL and a HC10 value against human red blood cells of 0.8 µg/mL.


Assuntos
Antifúngicos , Candida albicans , Candida , Testes de Sensibilidade Microbiana , Espécies Reativas de Oxigênio , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Candida/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pichia
6.
Curr Issues Mol Biol ; 46(5): 4845-4873, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38785560

RESUMO

Venous thromboembolism (VTE) is a challenging clinical obstacle in oncological settings, marked by elevated incidence rates and resulting morbidity and mortality. In the context of cancer-associated thrombosis (CAT), endothelial dysfunction (ED) plays a crucial role in promoting a pro-thrombotic environment as endothelial cells lose their ability to regulate blood flow and coagulation. Moreover, emerging research suggests that this disorder may not only contribute to CAT but also impact tumorigenesis itself. Indeed, a dysfunctional endothelium may promote resistance to therapy and favour tumour progression and dissemination. While extensive research has elucidated the multifaceted mechanisms of ED pathogenesis, the genetic component remains a focal point of investigation. This comprehensive narrative review thus delves into the genetic landscape of ED and its potential ramifications on cancer progression. A thorough examination of genetic variants, specifically polymorphisms, within key genes involved in ED pathogenesis, namely eNOS, EDN1, ACE, AGT, F2, SELP, SELE, VWF, ICAM1, and VCAM1, was conducted. Overall, these polymorphisms seem to play a context-dependent role, exerting both oncogenic and tumour suppressor effects depending on the tumour and other environmental factors. In-depth studies are needed to uncover the mechanisms connecting these DNA variations to the pathogenesis of malignant diseases.

7.
Int J Mol Sci ; 25(10)2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38791151

RESUMO

P-glycoprotein (P-GP) is a transporter molecule expressed on the apical surface of capillary endothelial cells of the Blood-Brain Barrier (BBB), whose activity heavily influences drug distribution, including antidepressants. This transporter is encoded by ABCB1 gene, and genetic variations within ABCB1 gene have been proposed to affect drug efflux and have been previously associated with depression. In this context, we aimed to evaluate the role of C1236T, G2677TA and C3435T ABCB1 genetic polymorphisms in antidepressant treatment phenotypes from a cohort of patients harboring Major Depressive Disorder. Patients enrolled in the study consisted of 80 individuals with Major Depressive Disorder, who took part in a 27-month follow-up study at HML, Portugal. To investigate the correlation between ABCB1 polymorphisms and antidepressant response phenotypes, DNA was extracted from peripheral blood, and C1236T, C3435T and G2677TA polymorphisms were genotyped with TaqMan® SNP Genotyping Assays. Despite the fact that the evaluated polymorphisms (C1236T, C3435T and G2677TA) were not associated with treatment resistant depression, or relapse, we observed that patients carrying TT genotype of the C3435T polymorphism remit earlier than the ones carrying CC or CT genotypes (10.2 weeks vs. 14.9 and 21.3, respectively, p = 0.028, Log-rank test). Since we found an association with C3435T and time to remission, and not to the absence of remission, we suggest that this polymorphism could have an impact on antidepressant drug distribution, and thus influence on the time to remission will occur, without influencing the risk of remission itself.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP , Antidepressivos , Transtorno Depressivo Maior , Polimorfismo de Nucleotídeo Único , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Feminino , Antidepressivos/uso terapêutico , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Masculino , Pessoa de Meia-Idade , Adulto , Portugal , Fenótipo , Genótipo , Estudos de Coortes , Idoso
8.
Biochim Biophys Acta Rev Cancer ; 1879(3): 189103, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679401

RESUMO

Cancer-associated cachexia (CAC) is a complex multiple organ syndrome that significantly contributes to reduced quality of life and increased mortality among many cancer patients. Its multifactorial nature makes its early diagnosis and effective therapeutic interventions challenging. Adipose tissue is particularly impacted by cachexia, typically through increased lipolysis, browning and thermogenesis, mainly at the onset of the disease. These processes lead to depletion of fat mass and contribute to the dysfunction of other organs. The ß-adrenergic signalling pathways are classical players in the regulation of adipose tissue metabolism. They are activated upon sympathetic stimulation inducing lipolysis, browning and thermogenesis, therefore contributing to energy expenditure. Despite accumulating evidence suggesting that ß3-adrenergic receptor stimulation may be crucial to the adipose tissue remodelling during cachexia, the literature remains controversial. Moreover, there is limited knowledge regarding sexual dimorphism of adipose tissue in the context of cachexia. This review paper aims to present the current knowledge regarding adipose tissue wasting during CAC, with a specific focus on the role of the ß3-adrenergic receptor, placing it as a potential therapeutic target against cachexia.


Assuntos
Tecido Adiposo , Caquexia , Lipólise , Neoplasias , Receptores Adrenérgicos beta 3 , Transdução de Sinais , Caquexia/metabolismo , Caquexia/patologia , Caquexia/etiologia , Humanos , Neoplasias/complicações , Neoplasias/metabolismo , Neoplasias/patologia , Receptores Adrenérgicos beta 3/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Metabolismo Energético , Termogênese , Animais
9.
J Thromb Thrombolysis ; 57(5): 805-814, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643312

RESUMO

INTRODUCTION: Cancer-associated thrombosis (CAT) is a significant concern among patients with malignant diseases, leading to increased mortality. While current guidelines recommend primary thromboprophylaxis for venous thromboembolism (VTE) in medium-to-high-risk outpatients, this practice remains controversial. A better understanding of primary thromboprophylaxis is crucial, yet there is a lack of Real-World Evidence (RWE) in Portugal. AIMS: This RWE study aimed to elucidate primary thromboprophylaxis practices among cancer outpatients in Portugal. METHODS: A five-year observational multicentric study in eight Portuguese health institutions enrolled 124 adult cancer outpatients under primary thromboprophylaxis for VTE. The endpoints were CAT, bleeding, cancer progression and death. RESULTS: High thrombotic risk tumours were prevalent, with 57% (71) of the patients presenting with pancreatic and gastric cancers. Regarding primary thromboprophylaxis, 55% (68) received Low-Molecular-Weight Heparin (LMWH). VTE was presented in 11% (14) of the patients and major bleeding in 2% (2). Vascular compression, elevated D-dimer and previous VTE were significantly associated with VTE occurrence under primary thromboprophylaxis. The Onkotev model was shown to be the best risk assessment model (RAM) in this population (p = 0.007). CAT patients exhibited a lower progression-free survival than non-CAT patients (p = 0.021), while thrombosis did not influence overall survival (p = 0.542). CONCLUSION: Primary thromboprophylaxis in medium-to-high-risk cancer outpatients is a safe and effective practice in real-world settings. This study is the first Portuguese RWE on primary thromboprophylaxis, highlighting evidence for improving prophylactic strategies in this population.


Assuntos
Anticoagulantes , Neoplasias , Pacientes Ambulatoriais , Tromboembolia Venosa , Humanos , Neoplasias/complicações , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Portugal/epidemiologia , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Hemorragia/induzido quimicamente , Heparina de Baixo Peso Molecular/uso terapêutico , Heparina de Baixo Peso Molecular/administração & dosagem , Medição de Risco , Adulto , Fatores de Risco
10.
J Thromb Thrombolysis ; 57(5): 815-827, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643313

RESUMO

Venous thromboembolism (VTE) is a life-threatening haemostatic disease frequently diagnosed among the cancer population. The Khorana Score is currently the primal risk assessment model to stratify oncological patients according to their susceptibility to VTE, however, it displays a limited performance. Meanwhile, intensive research on VTE pathophysiology in the general population has uncovered a range of single-nucleotide polymorphisms (SNPs) associated with the condition. Nonetheless, their predictive ability concerning cancer-associated thrombosis (CAT) is controversial. Cervical cancer (CC) patients undergoing chemoradiotherapy often experience VTE, which negatively affects their survival. Thus, aiming for an improvement in thromboprophylaxis, new thrombotic biomarkers, including SNPs, are currently under investigation. In this study, the predictive capability of haemostatic gene SNPs on CC-related VTE and their prognostic value regardless of VTE were explored. Six SNPs in haemostatic genes were evaluated. A total of 401 CC patients undergoing chemoradiotherapy were enrolled in a retrospective cohort study. The implications for the time to VTE occurrence and overall survival (OS) were assessed. CAT considerably impacted the CC patients' OS (log-rank test, P < 0.001). SERPINE1 rs2070682 (T > C) showed a significant association with the risk of CC-related VTE (CC/CT vs. TT, log-rank test, P = 0.002; C allele, Cox model, hazard ratio (HR) = 6.99 and P = 0.009), while F2 rs1799963 (G > A) demonstrated an important prognostic value regardless of VTE (AA/AG vs. GG, log-rank test, P = 0.020; A allele, Cox model, HR = 2.76 and P = 0.026). For the remaining SNPs, no significant associations were detected. The polymorphisms SERPINE1 rs2070682 and F2 rs1799963 could be valuable tools in clinical decision-making, aiding in thromboprophylaxis and CC management, respectively.


Assuntos
Inibidor 1 de Ativador de Plasminogênio , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero , Trombose Venosa , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/complicações , Pessoa de Meia-Idade , Inibidor 1 de Ativador de Plasminogênio/genética , Trombose Venosa/genética , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia , Estudos Retrospectivos , Tromboembolia Venosa/genética , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/diagnóstico , Idoso , Adulto , Quimiorradioterapia/efeitos adversos , Prognóstico , Medição de Risco/métodos , Hemostasia/genética
11.
Antibiotics (Basel) ; 13(3)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38534657

RESUMO

The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H4[H2(4-CF3PhCH2)2Cyclam]Cl4 reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.

12.
Int J Mol Sci ; 25(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38542272

RESUMO

Traumatic muscle injuries (TMIs) and muscle pain (MP) negatively impact athletes' performance and quality of life. Both conditions have a complex pathophysiology involving the interplay between genetic and environmental factors. Yet, the existing data are scarce and controversial. To provide more insights, this study aimed to investigate the association of single-nucleotide polymorphisms (SNPs) previously linked to athletic status with TMI and MP after exercise among Brazilian high-performance athletes from different sports modalities (N = 345). The impact of important environmental determinants was also assessed. From the six evaluated SNPs (ACTN3 rs1815739, FAAH rs324420, PPARGC1A rs8192678, ADRB2 rs1042713, NOS3 rs1799983, and VDR rs731236), none was significantly associated with TMI. Regarding MP after exercise, ACTN3 rs1815739 (CC/CT vs. TT; adjusted odds ratio (aOR) = 1.90; 95% confidence interval (95%Cl), 1.01-3.57) and FAAH rs324420 (AA vs. AC/CC; aOR = 2.30; 95%Cl, 1.08-4.91) were independent predictors according to multivariate binomial analyses adjusted for age (≥23 vs. <23 years), sex (male vs. female), and tobacco consumption (yes vs. no). External validation is warranted to assess the predictive value of ACTN3 rs1815739 and FAAH rs324420. This could have implications for prophylactic interventions to improve athletes' quality of life.


Assuntos
Mialgia , Qualidade de Vida , Humanos , Masculino , Feminino , Brasil/epidemiologia , Genótipo , Atletas , Polimorfismo de Nucleotídeo Único , Músculos , Actinina/genética
13.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38339123

RESUMO

Ovarian cancer (OC) is the female genital malignancy with the highest lethality. Patients present a poor prognosis mainly due to the late clinical presentation allied with the common acquisition of chemoresistance and a high rate of tumour recurrence. Effective screening, accurate diagnosis, and personalised multidisciplinary treatments are crucial for improving patients' survival and quality of life. This comprehensive narrative review aims to describe the current knowledge on the aetiology, prevention, diagnosis, and treatment of OC, highlighting the latest significant advancements and future directions. Traditionally, OC treatment involves the combination of cytoreductive surgery and platinum-based chemotherapy. Although more therapeutical approaches have been developed, the lack of established predictive biomarkers to guide disease management has led to only marginal improvements in progression-free survival (PFS) while patients face an increasing level of toxicity. Fortunately, because of a better overall understanding of ovarian tumourigenesis and advancements in the disease's (epi)genetic and molecular profiling, a paradigm shift has emerged with the identification of new disease biomarkers and the proposal of targeted therapeutic approaches to postpone disease recurrence and decrease side effects, while increasing patients' survival. Despite this progress, several challenges in disease management, including disease heterogeneity and drug resistance, still need to be overcome.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Ovarianas , Humanos , Feminino , Qualidade de Vida , Recidiva Local de Neoplasia , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/tratamento farmacológico , Biomarcadores
14.
Tob Control ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378212

RESUMO

Young health advocates have the legitimate aspiration to be masters of their future and are increasingly contributing to public health research and practice worldwide, yet their potential to contribute to the documentation and communication of outputs from public health conferences has not been fully realised. This short communication highlights the Youth Committee of the 2023 European Conference on Tobacco or Health as an example of youth involvement in a major public health conference focused on tobacco control. The authors explore the benefits, practicalities and challenges of incorporating young professionals into conference workflow, including creativity, networking and engagement with broader public health challenges within their communities. This article emphasises the active participation of Youth Committees in public health fora as a model for future conferences and underscores a commitment to achieving a tobacco-free generation.

15.
Biochim Biophys Acta Rev Cancer ; 1879(1): 189053, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38092078

RESUMO

Cancer patients are often diagnosed with venous thromboembolism (VTE), a cardiovascular disease that substantially decreases their quality of life and survival rate. Haemostasis in these patients is deregulated, which is reflected in the common presentation of a blood hypercoagulation state. Despite the inconsistent results, existing evidence suggests that the expression of microRNAs (miRNAs) is deregulated in the context of venous thrombogenesis in the general population. However, few miRNAs are known to be linked to cancer-associated VTE due to the lack of studies with oncological patients. Parallelly, coagulation factor III, also known as tissue factor (TF), tissue factor pathway inhibitor 1 (TFPI1) and tissue factor pathway inhibitor 2 (TFPI2) have been proposed to have a central role in cancer-associated VTE and tumour progression. Yet, contrary to what was expected, the role of miRNAs targeting the TF coagulation pathway (or extrinsic coagulation pathway) is poorly explored in cancer-induced thrombogenesis. In this review, in addition to miRNAs implicated in VTE, TF and TFPI1/2-targeting miRNAs were revised. Future studies should clarify the implications of these non-coding RNAs in tumour coagulome.


Assuntos
MicroRNAs , Neoplasias , Trombose , Tromboembolia Venosa , Trombose Venosa , Humanos , MicroRNAs/genética , Tromboplastina/genética , Tromboplastina/metabolismo , Tromboembolia Venosa/genética , Trombose Venosa/complicações , Qualidade de Vida , Trombose/genética , Trombose/complicações , Neoplasias/complicações , Neoplasias/genética
16.
Biochim Biophys Acta Rev Cancer ; 1879(2): 189067, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38160898

RESUMO

Prostate cancer (PC) is the second most frequently diagnosed cancer and the fifth leading cause of cancer-related deaths in male population worldwide. Since the growth and progression of PC highly depend on the androgen pathway, androgen deprivation therapy (ADT) is the mainstay of systemic treatment. Enzalutamide is a second-generation antiandrogen, which is widely used for the treatment of advanced and metastatic PC. However, treatment failure and disease progression, caused by the emergence of enzalutamide resistant phenotypes, remains an important clinical challenge. MicroRNAs (miRNAs) are key regulators of gene expression and have recently emerged as potential biomarkers for being stable and easily analysed in several biological fluids. Several miRNAs that exhibit dysregulated expression patterns in enzalutamide-resistant PC have recently been identified, including miRNAs that modulate critical signalling pathways and genes involved in PC growth, survival and in the acquisition of enzalutamide phenotype. The understanding of molecular mechanisms by which miRNAs promote the development of enzalutamide resistance can provide valuable insights into the complex interplay between miRNAs, gene regulation, and treatment response in PC. Moreover, these miRNAs could serve as valuable tools for monitoring treatment response and disease progression during enzalutamide administration. This review summarises the miRNAs associated with enzalutamide resistance in PC already described in the literature, focusing on their biological roles and on their potential as biomarkers.


Assuntos
Benzamidas , MicroRNAs , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios/uso terapêutico , MicroRNAs/genética , MicroRNAs/uso terapêutico , Androgênios , Biomarcadores , Progressão da Doença
18.
Antioxidants (Basel) ; 12(12)2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38136171

RESUMO

Nanomedicine's advent has promised to revolutionize different biomedical fields, including oncology. Silver Nanoparticles (AgNPs) showed promising results in different tumor models. Clear cell Renal Cell Carcinoma (ccRCC) is especially challenging due to its late diagnosis, poor prognosis and treatment resistance. Therefore, defining new therapeutic targets and regimens could improve patient management. This study intends to evaluate AgNPs' effect in ccRCC cells and explore their potential combinatory effect with Everolimus and Radiotherapy. AgNPs were synthesized, and their effect was evaluated regarding their entering pathway, cellular proliferation capacity, ROS production, mitochondrial membrane depolarization, cell cycle analysis and apoptosis assessment. AgNPs were combined with Everolimus or used to sensitize cells to radiotherapy. AgNPs are cytotoxic to 786-O cells, a ccRCC cell line, entering through endocytosis, increasing ROS, depolarizing mitochondrial membrane, and blocking the cell cycle, leading to a reduction of proliferation capacity and apoptosis. Combined with Everolimus, AgNPs reduce cell viability and inhibit proliferation capacity. Moreover, 786-O is intrinsically resistant to radiation, but after AgNPs' administration, radiation induces cytotoxicity through mitochondrial membrane depolarization and S phase blockage. These results demonstrate AgNPs' cytotoxic potential against ccRCC and seem promising regarding the combination with Everolimus and sensitization to radiotherapy, which can, in the future, benefit ccRCC patients' management.

19.
Biomarkers ; 28(7): 617-627, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37942654

RESUMO

INTRODUCTION: High-risk human papillomavirus (HPV) is the aetiological agent of cervical cancer, which remains the fourth leading cause of cancer death in women worldwide. K14-HPV16 transgenic mice are a model for HPV-induced cancers, which undergo multistep squamous carcinogenesis at the skin, that is histologically and molecularly similar to carcinogenesis of the human cervix. Previous screens of differentially regulated microRNAs (miRs) using K14-HPV16 mice showed a role for miR-21, miR-155, miR-150, miR-146a, miR-125b and miR-223 during carcinogenesis. METHODS: We now aim to translate these observations into the clinical setting, using data provided by The Cancer Genome Atlas (TCGA) to explore whether those microRNAs can influence the survival of cervical cancer patients. RESULTS: Results showed that low miR-150, miR-155 and miR-146a expression levels in primary tumours were associated with poor overall survival. However, only miR-150 and miR-155 were found to be independent predictors, increasing the risk of death. When patients were stratified by clinical stage, low miR-150, miR-155, miR-146a and miR-125b were associated with poor survival for clinical stages I and II. Only low miR-150 expression increased the death risk. CONCLUSION: We conclude that miR-150 and miR-155 may be potentially applied as prognostic biomarkers in cervical cancer patients. However, further investigation is required to determine their applicability.


Assuntos
MicroRNAs , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Camundongos , Biomarcadores Tumorais/genética , Carcinogênese/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/patologia , Prognóstico , Neoplasias do Colo do Útero/genética
20.
Antioxidants (Basel) ; 12(10)2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891885

RESUMO

Human papillomavirus (HPV) infection is a necessary but not sufficient factor for the development of invasive cervical cancer (ICC) and high-grade intraepithelial lesion (HSIL). Oxidative stress is known to play a crucial role in HPV infection and carcinogenesis. In this study, we comprehensively investigate the modulation of HPV infection, HSIL and ICC, and ICC through an exploration of oxidative stress-related genes: CßS, MTHFR, NOS3, ACE1, CYBA, HAP, ACP1, GSTT1, GSTM1, and CYP1A1. Notably, the ACE1 gene emerges as a prominent factor with the presence of the I allele offering protection against HPV infection. The association of NOS3 with HPV infection is perceived with the 4a allele showing a protective effect. The presence of the GSTT1 null mutant correlates with increased susceptibility to HPV infection, HSIL and ICC, and ICC. This study also uncovers intriguing epistatic interactions among some of the genes that further accentuate their roles in disease modulation. Indeed, the epistatic interactions between the BB genotype (ACP1) and DD genotype (ECA1) were shown to increase the risk of HPV infection, and the interaction between BB (ACP1) and 0.0 (GSTT1) was associated with HPV infection and cervical lesions. These findings underscore the pivotal role of four oxidative stress-related genes in HPV-associated cervical lesions and cancer development, enriching our clinical understanding of the genetic influences on disease manifestation. The awareness of these genetic variations holds potential clinical implications.

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