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1.
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.

2.
J Surg Oncol ; 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129330

RESUMO

BACKGROUND: Cutaneous melanoma (CM) is a malignancy with a variable incidence worldwide and a poor advanced-stage prognosis. Melanoma growth is closely associated with the immune system. METHODS: A cross-sectional study was performed on CM patients admitted at the Hospital de Cancer de Pernambuco (HCP) between 2015 and 2018. Fifty-one CM patients were included, and 30 healthy individuals. The study aimed to evaluate the association of platelet activation mechanisms and inflammatory response in patients with cutaneous melanoma. RESULTS: Elevated serum IL10 and low serum TNF levels in CM patients compared to controls (p < 0.05). High IL6 levels in patients with negative lymph nodes LN (-) compared to positive lymph nodes group (LN +, p = 0.0005). Low RANTES levels in patients compared to controls (p < 0.05). Elevated levels of platelet-lymphocyte (PLA), platelet-monocytes (PMA), and platelet-neutrophils (PNA) aggregates were observed in patients compared to controls (p < 0.05). CM patients with stage II had lower PMA levels than stages I and III (p < 0.05). High PMA levels were observed in patients with LN (+) compared to the LN (-) group (p < 0.0001). Patients with SSM had high levels of sCD40L and sCD62P compared to controls (p < 0.05)). High sCD40L levels in stage II compared to the stage III group, and sCD62P in stages I and II compared to the stage III group (p < 0.05). High sCD62P levels in patients with LN (-) compared to the group LN (+) (p < 0.05). CONCLUSION: It was observed the immunosuppressive profile in CM may favor tumor progression. High levels of platelet-leukocyte aggregates, sCD40L, and sCD62P may be associated with the worst prognosis.

3.
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
4.
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
5.
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
6.
Int J Mol Sci ; 25(18)2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39337362

RESUMO

Prostate cancer (PC) is one of the most commonly diagnosed tumours among men. Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone acetate (AbA) and enzalutamide (ENZ), are currently used in the management of metastatic castration-resistant PC (mCRPC). However, the treatment is challenging due to the lack of prognostic biomarkers. Meanwhile, single-nucleotide polymorphisms (SNPs) have emerged as potential prognostic indicators of mCRPC. Thus, this study evaluated the impact of relevant SNPs on the treatment outcomes of 123 mCRPC patients enrolled in a hospital-based cohort study. The CYP17A1 rs2486758 C allele was associated with a 50% reduction in the risk of developing castration resistance (hazard ratio (HR) = 0.55; p = 0.003). Among patients without metastasis at tumour diagnosis and under AbA, a marginal association between YBX1 rs10493112 and progression-free survival was detected (log-rank test, p = 0.056). In the same subgroup, significant associations of HSD3B1 rs1047303 (CC/CA vs. AA; HR = 3.41; p = 0.025), YBX1 rs12030724 (AT vs. AA; HR = 3.54; p = 0.039) and YBX1 rs10493112 (log-rank test, p = 0.041; CC vs. AA/AC; HR = 3.22; p = 0.053) with overall survival were also observed, which were confirmed by multivariate Cox analyses. Although validation with larger cohorts is required, these findings suggest that SNPs could enhance the prognosis assessment of mCRPC patients, leading to a more personalised treatment.


Assuntos
Acetato de Abiraterona , Polimorfismo de Nucleotídeo Único , Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Idoso , Receptores Androgênicos/genética , Acetato de Abiraterona/uso terapêutico , Pessoa de Meia-Idade , Feniltioidantoína/uso terapêutico , Resultado do Tratamento , Nitrilas/uso terapêutico , Benzamidas/uso terapêutico , Esteroide 17-alfa-Hidroxilase/genética , Idoso de 80 Anos ou mais , Prognóstico , Proteína 1 de Ligação a Y-Box/genética , Proteína 1 de Ligação a Y-Box/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Metástase Neoplásica , Biomarcadores Tumorais/genética
7.
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
8.
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
9.
Mol Cell Probes ; 70: 101917, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37364690

RESUMO

Ischaemic stroke (IS) and venous thromboembolism (VTE) are two forms of thromboembolism that, although distinct, seem to share numerous risk factors. Concerning genetic risk factors, while many VTE genetic markers have been reported, inclusively by genome-wide association studies (GWAS), the identification and validation of genetic determinants underlying IS pathogenesis have been challenging. Considering that IS and VTE shared biological pathways and aetiological factors, the severity of IS might be also influenced by VTE-related genetic variants. Thus, the present study was designed to analyse the impact of six VTE GWAS-identified genetic variants on the clinical outcome of 363 acute IS patients. Results revealed that the single-nucleotide polymorphism (SNP) F11 rs4253417 was an independent predictor of the 5-year risk of death among patients with total anterior circulation infarct (TACI). Namely, the ones carrying the SNP C allele presented a fourfold increase in the 5-year risk of death compared to TT genotype carriers (CC/CT vs. TT; adjusted HR, 4.240; 95% CI, 1.260-14.270; P = 0.020). This SNP is known to be associated with coagulation factor XI (FXI) levels, thus with implications in haemostasis and inflammation. As such, F11 rs4253417 might be a promising prognostic biomarker among TACI patients to aid in clinical decision-making. However, additional investigation is required to confirm the study's results and dissect the underlying mechanisms.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Isquemia Encefálica/genética , Prognóstico , Acidente Vascular Cerebral/genética , Fatores de Risco , Polimorfismo de Nucleotídeo Único/genética
10.
Int J Mol Sci ; 24(10)2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37240449

RESUMO

Prostate cancer (PCa) is one of the most common malignancies among men worldwide. Inevitably, all advanced PCa patients develop metastatic castration-resistant prostate cancer (mCRPC), an aggressive phase of the disease. Treating mCRPC is challenging, and prognostic tools are needed for disease management. MicroRNA (miRNA) deregulation has been reported in PCa, constituting potential non-invasive prognostic biomarkers. As such, this study aimed to evaluate the prognostic potential of nine miRNAs in the liquid biopsies (plasma) of mCRPC patients treated with second-generation androgen receptor axis-targeted (ARAT) agents, abiraterone acetate (AbA) and enzalutamide (ENZ). Low expression levels of miR-16-5p and miR-145-5p in mCRPC patients treated with AbA were significantly associated with lower progression-free survival (PFS). The two miRNAs were the only predictors of the risk of disease progression in AbA-stratified analyses. Low miR-20a-5p levels in mCRPC patients with Gleason scores of <8 were associated with worse overall survival (OS). The transcript seems to predict the risk of death regardless of the ARAT agent. According to the in silico analyses, miR-16-5p, miR-145-5p, and miR-20a-5p seem to be implicated in several processes, namely, cell cycle, proliferation, migration, survival, metabolism, and angiogenesis, suggesting an epigenetic mechanism related to treatment outcome. These miRNAs may represent attractive prognostic tools to be used in mCRPC management, as well as a step further in the identification of new potential therapeutic targets, to use in combination with ARAT for an improved treatment outcome. Despite the promising results, real-world validation is necessary.


Assuntos
MicroRNAs , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Estudos de Coortes , Estudos Retrospectivos , Acetato de Abiraterona/uso terapêutico , Resultado do Tratamento , Nitrilas/uso terapêutico
11.
Int J Mol Sci ; 24(15)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37569483

RESUMO

Venous thromboembolism (VTE), a common condition in Western countries, is a cardiovascular disorder that arises due to haemostatic irregularities, which lead to thrombus generation inside veins. Even with successful treatment, the resulting disease spectrum of complications considerably affects the patient's quality of life, potentially leading to death. Cumulative data indicate that long non-coding RNAs (lncRNAs) may have a role in VTE pathogenesis. However, the clinical usefulness of these RNAs as biomarkers and potential therapeutic targets for VTE management is yet unclear. Thus, this article reviewed the emerging evidence on lncRNAs associated with VTE and with the activity of the coagulation system, which has a central role in disease pathogenesis. Until now, ten lncRNAs have been implicated in VTE pathogenesis, among which MALAT1 is the one with more evidence. Meanwhile, five lncRNAs have been reported to affect the expression of TFPI2, an important anticoagulant protein, but none with a described role in VTE development. More investigation in this field is needed as lncRNAs may help dissect VTE pathways, aiding in disease prediction, prevention and treatment.

12.
Int J Mol Sci ; 25(1)2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38203310

RESUMO

Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann-Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.


Assuntos
Neoplasias Ovarianas , RNA Longo não Codificante , Tromboembolia Venosa , Humanos , Feminino , RNA Longo não Codificante/genética , Tromboembolia Venosa/genética , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/genética , Carcinogênese
13.
Parasitol Res ; 121(11): 3051-3061, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36048267

RESUMO

Pressures from anthropogenic disturbances have triggered a wealth of studies focusing on the assessment and mitigation of the negative impacts of these disturbances on inter and intraspecific ecological interactions, including bats and bat flies in their roosts. The heterogeneity of research methods employed for these studies and the scientific imbalance between countries may constrain advances and the consolidation of the knowledge on this subject. We reviewed the literature regarding bat and bat-ectoparasite interactions in roosts assessing global research trends and patterns of author collaborative work to be able to identify key questions for future studies and potential initiatives to improve the knowledge on this subject. Current information available has mostly come from the Americas and is predominantly focused on the recognition and description of parasite-host interactions between bats and bat flies. Our findings suggest the value of increasing collaboration for future research, as several countries with largely diverse environments and high organismal richness are disconnected from the countries that produce the most publications in this area, and/or have low records of publications. These regions are in the Global South, mostly in South American and African countries. We suggest that more collaborative networks may increase scientific production in the area, and that investing in local research development and enhancing partnerships for publications may strengthen the field. These research programs and collaborations are key for the development of conservation strategies for bats and bat flies, for their roosts, and for understanding bat and bat-ectoparasite interactions.


Assuntos
Quirópteros , Dípteros , África , Animais , Interações Hospedeiro-Parasita
14.
Pharmacogenomics J ; 21(2): 222-232, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33161412

RESUMO

Ovarian cancer (OC) represents the most lethal gynaecological neoplasia. Conversely, venous thromboembolism (VTE) and OC are intricately connected, with many haemostatic components favouring OC progression. In light of this bilateral relationship, genome-wide association studies (GWAS) have reported several single-nucleotide polymorphisms (SNPs) associated with VTE risk that could be used as predictors of OC clinical outcome for better therapeutic management strategies. Thus, the present study aimed to analyse the impact of VTE GWAS-identified SNPs on the clinical outcome of 336 epithelial ovarian cancer (EOC) patients. Polymorphism genotyping was performed using the TaqMan® Allelic Discrimination methodology. Carriers with the ZFPM2 rs4734879 G allele presented a significantly higher 5-year OS, 10-year OS and disease-free survival (DFS) compared to AA genotype patients with FIGO I/II stages (P = 0.009, P = 0.001 and P = 0.003, respectively). Regarding SLC19A2 rs2038024 polymorphism, carriers with the CC genotype presented a significantly lower 5-year OS, 10-year OS and DFS compared to A allele carriers in the same FIGO subgroup (P < 0.001, P = 0.004 and P = 0.005, respectively). As for CNTN6 rs6764623 polymorphism, carriers with the CC genotype presented a significantly lower 5-year OS compared to A allele carriers with FIGO I/II stages (P = 0.015). As for OTUD7A rs7164569, F11 rs4253417 and PROCR rs10747514, no significant impact on EOC patients' survival was observed. However, future studies are required to validate these results and uncover the biological mechanisms underlying our results.


Assuntos
Carcinoma Epitelial do Ovário/genética , Neoplasias Ovarianas/genética , Tromboembolia Venosa/genética , Alelos , Contactinas/genética , Intervalo Livre de Doença , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Proteínas de Membrana Transportadoras/genética , Polimorfismo de Nucleotídeo Único/genética
15.
J Environ Manage ; 232: 37-44, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30468955

RESUMO

Riparian areas around streams are those areas in which biological communites are directly influenced by the stream. The size of protected riparian areas and their conservation has become a controversial topic after changes implemented in the Brazilian Forest Code (BFC): a set of laws that regulates the size of Permanent Protection Areas (PPA). Here, we investigate the influence of distance from water bodies on bat-species and guild composition in a lowland Amazonian rainforest. Our hypotheses were that bat assemblages would change depending on the distance to the water body and that the abundance of herbivorous bats (frugivorous and nectarivorous) would be greater in areas close to water. Bats were captured with mist-nets in 24 riparian and 25 non-riparian plots within a trail grid in an old-growth terra-firme forest, northeast of Manaus, Amazonas, Brazil. Each plot was sampled three times in a total of 7056 net-hours. We captured 1191 bats, comprising 51 species. We used model selection based on AIC (Akaike Information Criterion) to compare linear and piecewise regressions to estimate the ecological thresholds for different bat assemblages. Piecewise models with one breakpoint were more parsimonious than linear models for abundance data, and the species and guild composition of animalivorous and frugivorous bats. Animalivorous-bat abundance increased from the stream to about 181 m, and frugivorous-bat abundance decreased within 50 m of the stream. The patterns of guild abundance suggest that frugivorous bats may need greater access to streams than animalivorous bats. The most conservative model suggests that most of the variation in bat composition occurs close to the stream and extends to up 114 m from the banks. Therefore, the 30 m wide strip of riparian forest protected by Brazilian law would maintain a relatively small fraction of bat-species assemblages in Ducke Reserve, and is insufficient to represent most of the assemblage-composition variation within the riparian zone. The suggestion to reduce the width of the protected riparian zone from 30 to 15 m for streams smaller than 10 m wide, as is under discussion, would likely be prejudicial for bat assemblages.


Assuntos
Quirópteros , Animais , Brasil , Ecossistema , Florestas , Rios
16.
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
17.
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.

18.
Biomolecules ; 14(8)2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39199316

RESUMO

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway-miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p-in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ2, p < 0.05). Regarding patients' prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients' survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Tromboplastina , Humanos , Feminino , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/genética , MicroRNAs/sangue , MicroRNAs/genética , Tromboplastina/metabolismo , Tromboplastina/genética , Pessoa de Meia-Idade , Prognóstico , Idoso , Trombose/sangue , Trombose/etiologia , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/genética , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica
19.
Biodivers Data J ; 12: e133775, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39346621

RESUMO

Biodiversity data, particularly species occurrence and abundance, are indispensable for testing empirical hypothesis in natural sciences. However, datasets built for research programmes do not often meet FAIR (findable, accessible, interoperable and reusable) principles, which raises questions about data quality, accuracy and availability. The 21st century has markedly been a new era for data science and analytics and every effort to aggregate, standardise, filter and share biodiversity data from multiple sources have become increasingly necessary. In this study, we propose a framework for refining and conforming secondary biodiversity data to FAIR standards to make them available for use such as macroecological modelling and other studies. We relied on a Darwin Core base model to standardise and further facilitate the curation and validation of data related including the occurrence and abundance of multiple taxa of a region that encompasses estuarine ecosystems in an ecotonal area bordering the easternmost Amazonia. We further discuss the significance of feeding standardised public data repositories to advance scientific progress and highlight their role in contributing to the biodiversity management and conservation.

20.
Genes (Basel) ; 14(10)2023 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-37895295

RESUMO

Gene variation linked to physiological functions is recognised to affect elite athletic performance by modulating training and competition-enabling behaviour. The fatty acid amide hydrolase (FAAH) has been investigated as a good candidate for drug targeting, and recently, its single-nucleotide polymorphism (SNP) rs324420 was reported to be associated with athletic performance. Given the implications, the biological pathways of this genetic polymorphism linked to elite athletic performance, considering sport type, psychological traits and sports injuries, need to be dissected. Thus, a narrative review of the literature concerning the biological mechanisms of this SNP was undertaken. In addition to its role in athletic performance, FAAH rs324420 is also involved in important mechanisms underlying human psychopathologies, including substance abuse and neural dysfunctions. However, cumulative evidence concerning the C385A variant is inconsistent. Therefore, validation studies considering homogeneous sports modalities are required to better define the role of this SNP in elite athletic performance and its impact on stress coping, pain regulation and inflammation control.


Assuntos
Desempenho Atlético , Medicina Esportiva , Humanos , Polimorfismo de Nucleotídeo Único , Amidoidrolases/genética , Amidoidrolases/metabolismo
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