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1.
Cells Tissues Organs ; 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38194935

RESUMO

TEMTIA X, the tenth symposium organized by the EMT international Association (TEMTIA) took place in Paris on November 7th-10th, 2022. Similarly to the previous meetings, it reviewed most recent aspects of the epithelial-mesenchymal transition, a cellular process involved during distinct stages of development, but also during wound healing and fibrosis to some level. EMT steps are likewise typically described with various extents during tumor cell progression and metastasis. The meeting emphasized the intermediate stages involved in the process and their potential physiological or pathological importance, taking advantage of the expansion of molecular methods at single cell level. It also introduced new descriptions of EMT occurrences during early embryogenesis. In addition, sessions explored how EMT reflects cell metabolism and how the process can mingle with immune response, particularly during tumor progression, providing new targets, that were discussed, among others, for cancer therapy. Finally, it introduced a new perception of EMT biological meaning based on an evolutionary perspective. The meeting integrated the TEMTIA general assembly , allowing general discussion about the future of the association, starting with the site of the next meeting, now decided to take place in Seattle (US), late 2024.

2.
Eur J Contracept Reprod Health Care ; 29(4): 177-181, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38721704

RESUMO

BACKGROUND: Emergency contraception reduces the risk of unintended pregnancy, after unprotected sexual intercourse or contraceptive failure. In Belgium, emergency contraception is available without a prescription and pharmacists play therefore a crucial role in dispensing emergency contraception. AIM: This study assesses the dispensing practices of emergency contraception by pharmacists in two regions of Belgium. METHOD AND DESIGN: Simulated patient study, using a predefined scenario, evaluating a request for emergency contraception. The scenario involves a 25-year-old woman not using contraception, who had unprotected sexual intercourse 84 h (3.5 days) ago. Her last menstrual period was 10 days ago. POPULATION: 260 pharmacies were randomly selected. Principal outcome: proportion of pharmacists who deliver the adequate emergency contraception. We considered the following responses as adequate: Prescribing ulipristal acetate or redirecting to another pharmacy, in case of unavailability, or referring for a copper IUD. RESULTS: We analysed the data obtained in 216 pharmacies (216/260 = 83.1%). In 64% of cases, adequate dispensing of emergency contraception (dispensing of ulipristal acetate or referral for intrauterine device insertion) occurred. There was an association between correct dispensing and asking appropriate questions, such as the date of the last menstrual period and the date of the risky sexual intercourse. CONCLUSION: More than one-third of visited pharmacies did not distribute appropriate emergency contraception, underlining the need for improvement. We hypothesise that this may be achieved with appropriate training, use a dispensing checklist.


We assesses the dispensing of emergency contraception by pharmacists using a simulated patient. More than one-third of visited pharmacies did not distribute appropriate emergency contraception, underlining the need for improvement.


Assuntos
Anticoncepção Pós-Coito , Norpregnadienos , Simulação de Paciente , Farmacêuticos , Humanos , Feminino , Bélgica , Anticoncepção Pós-Coito/estatística & dados numéricos , Adulto , Norpregnadienos/uso terapêutico , Padrões de Prática dos Farmacêuticos/estatística & dados numéricos , Dispositivos Intrauterinos de Cobre/estatística & dados numéricos , Anticoncepcionais Pós-Coito/uso terapêutico , Gravidez
3.
HIV Med ; 24(8): 877-892, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37062862

RESUMO

BACKGROUND: Women with HIV are more often infected with human papillomavirus (HPV) and are more prone to develop precancerous cervical lesions (squamous intraepithelial lesions, SIL) and invasive cervical cancer (ICC) than HIV-negative women. OBJECTIVE: This scoping-review analyses the impact of HIV on HPV prevalence, incidence and evolution to SIL and ICC. METHODS: We selected all PubMed systematic reviews and meta-analyses published between January 2000 and July 2021 reporting data about HPV, cervical intraepithelial neoplasia (CIN), SIL and ICC prevalence, incidence and evolution in women with HIV. A hypothetical model comparing the history of HPV infection in HIV-negative, combined antiretroviral therapy (cART)-treated and -untreated women with HIV was built. RESULTS: Data from 11 meta-analyses and 10 systematic reviews were selected, which included between 770 and 236 127 women with HIV. Women with HIV have a 3 to 6 times higher risk of being infected by HPV, of progression to high-grade SIL (HSIL) and to ICC. These risks are exacerbated when the CD4 cell counts are low and when they are not using cART, whereas these risks are reduced by 20%-30% when they are optimally treated with cART and have had a suppressed HIV viral load for at least 2 years. In our model, we illustrated that optimal HIV treatment and preventing HIV reduce the number of ICC cases by 2.5 and 6 times, respectively. CONCLUSIONS: Optimal treatment and care of HIV patients are essential to reduce their prevalence of ICC, as are preventive strategies which include HPV vaccination, cervical cancer screening strategies and treatment of HSIL.


Assuntos
Infecções por HIV , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/epidemiologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Papillomavirus Humano , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Detecção Precoce de Câncer , Displasia do Colo do Útero/epidemiologia , Papillomaviridae , Prevalência
4.
Cells Tissues Organs ; 211(2): 91-109, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32750701

RESUMO

Lung cancer is one of the most common solid cancers and represents the leading cause of cancer death worldwide. Over the last decade, research on the epithelial-mesenchymal transition (EMT) in lung cancer has gained increasing attention. Here, we review clinical and histological features of non-small-cell lung cancer associated with EMT. We then aimed to establish potential clinical implications of EMT in current therapeutic options, including surgery, radiation, targeted therapy against oncogenic drivers, and immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Biomarcadores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Humanos , Imunoterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
5.
Sex Transm Infect ; 97(5): 329-333, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33106437

RESUMO

BACKGROUND: Postexposure prophylaxis (PEP) is a recommended public health intervention after a sexual assault to prevent HIV infection. METHODS: We conducted a retrospective case-control study on how use of a single-tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild) affected adherence to PEP and attendance of a follow-up visit to the STI clinic compared with those who received a multitablet regimen (MTR). Data from sexual assault victims consulting for PEP were prospectively recorded between January 2011 and December 2017. Data were systematically collected on patient demographics, time of medical contact, source risk factors, type of exposure, attendance to follow-up visit, reported completion of PEP and adherence based on pharmacy records. RESULTS: A total of 422 patients received PEP following a sexual assault, of whom 52% had documented completion of a 28-day PEP regimen and 71% attended a follow-up clinic visit. Patients who received an elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/COBI/FTC/TDF)-based STR had a similar likelihood of attending their first follow-up visit (OR: 0.97; 95% CI: 0.64 to 1.48, p=0.90) but were more likely to complete the PEP regimen (OR: 1.70; 95% CI: 1.16 to 2.50, p=0.007). After adjusting for confounders, those who were prescribed an STR regimen were more likely to complete the PEP regimen (OR: 1.66, 95% CI: 1.09 to 2.53, p=0.019) than those who were prescribed an MTR such as stavudine/lamivudine/lopinavir/ritonavir or zidovudine/lamivudine/indinavir/ritonavir. CONCLUSIONS: Sexual assault victims who were prescribed an STR based on EVG/COBI/FTC/TDF were more likely to complete PEP than those who were prescribed an MTR.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Vítimas de Crime/psicologia , Combinação Elvitegravir, Cobicistat, Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Infecções por HIV/prevenção & controle , Adesão à Medicação/estatística & dados numéricos , Profilaxia Pós-Exposição/métodos , Delitos Sexuais/psicologia , Adulto , Bélgica/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
6.
AIDS Res Ther ; 18(1): 44, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301269

RESUMO

BACKGROUND: This study compares the management and outcome of high grade squamous intraepithelial lesions (HSIL) in HIV-positive and -negative women and identifies risk factors for treatment failure. METHODS: This retrospective, controlled study includes 146 HIV-positive women, matched for HSIL, age and year of diagnosis, with 146 HIV-negative women. Differences were analysed using parametric and non-parametric tests and Kaplan-Meier survival curves. A binary logistic regression was used to assess risk factors for treatment failure. RESULTS: Persistence of cervical disease was observed most frequently in HIV-positive women (42 versus 17%) (p < 0.001) and the cone biopsy margins were more often invaded in HIV-positive-women than in HIV-negative ones. (37 versus 16%; p < 0.05). HIV-positive women, with successful cervical treatment had better HIV disease control: with significantly longer periods of undetectable HIV viral loads (VL) (19 versus 5 months; p < 0.001) and higher CD4 counts (491 versus 320 cells/mm3; p < 0.001). HIV-positive women with detectable VL at the time of dysplasia had 3.5 times (95% IC: 1.5-8.3) increased risk of treatment failure. Being treated through ablative therapy was associated with a 7.4, four-fold (95% IC: 3.2-17.3) increased risk of treatment failure compared to conization CONCLUSION: HIV-positive women have a higher risk of treatment failure of HSIL than do HIV-negative women, especially when ablative therapy is used and in women with poor control of their HIV infection. The management and the follow- up of HSIL's guidelines in this high-risk population should be adapted consequently: for HIV-positive women with uncontrolled viral load, excisional treatment should be the preferred therapy, whereas for women with undetectable viral load, CD4 + lymphocytes higher than 500 cells/mm3 and with a desire of pregnancy, ablative therapy may be considered.


Assuntos
Infecções por HIV , Lesões Intraepiteliais Escamosas , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Gravidez , Estudos Retrospectivos , Neoplasias do Colo do Útero/epidemiologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/terapia
7.
Adv Exp Med Biol ; 1220: 11-34, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32304077

RESUMO

Circulating tumor cells offer an unprecedented window into the metastatic cascade, and to some extent can be considered as intermediates in the process of metastasis. They exhibit dynamic oscillations in epithelial to mesenchymal plasticity and provide important opportunities for prognosis, therapy response monitoring, and targeting of metastatic disease. In this manuscript, we review the involvement of epithelial-mesenchymal plasticity in the early steps of metastasis and what we have learned about its contribution to genomic instability and genetic diversity, tumor progression and therapeutic responses using cell culture, mouse models and circulating tumor cells enriched from patients.


Assuntos
Transição Epitelial-Mesenquimal , Metástase Neoplásica/patologia , Células Neoplásicas Circulantes/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Humanos , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/genética
8.
Thorax ; 74(8): 768-779, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31142617

RESUMO

BACKGROUND: Air pollution, including particulates and gazes such as ozone (O3), is detrimental for patient's health and has repeatedly been correlated to increased morbidity and mortality in industrialised countries. Although studies have described a link between ambient particulate matter and increased lung cancer morbidity, no direct relation has yet been established between O3 exposure and metastatic dissemination to lungs. OBJECTIVES: To outline the mechanisms through which pulmonary O3 exposure modulates metastasis kinetics in an experimental mouse model of O3 exposure. METHODS: Metastatic responses to pulmonary O3 exposure were assessed using a reliable experimental mouse model of concomitant pulmonary O3 exposure and tumour cell injection. Roles of neutrophils in O3-induced lung metastasis were highlighted using blocking anti-Ly6G antibodies; moreover, the implication of neutrophil extracellular traps (NETs) in metastatic processes was evaluated using MRP8cre-Pad4lox/lox mice or by treating mice with DNase I. RESULTS: Pulmonary O3 exposure strongly facilitates the establishment of lung metastasis by (1) Inducing a pulmonary injury and neutrophilic inflammation, (2) Influencing very early steps of metastasis, (3) Priming neutrophils' phenotype to release NETs that favour tumour cell colonisation in lungs. The ability of O3-primed neutrophils to enhance lung colonisation by tumour cells was proven after their adoptive transfer in Balb/c mice unexposed to O3. CONCLUSIONS: Pulmonary neutrophils induced by O3 promote metastatic dissemination to lungs by producing NETs. These findings open new perspectives to improve treatment and prevention strategies in patients affected by metastatic diseases.


Assuntos
Neoplasias da Mama/patologia , Armadilhas Extracelulares , Neoplasias Pulmonares/secundário , Melanoma/patologia , Metástase Neoplásica , Neutrófilos/patologia , Ozônio/toxicidade , Animais , Anticorpos/farmacologia , Antígenos Ly/imunologia , Bronquite/induzido quimicamente , Bronquite/patologia , Líquido da Lavagem Broncoalveolar/citologia , Linhagem Celular Tumoral , Desoxirribonuclease I/farmacologia , Modelos Animais de Doenças , Contagem de Leucócitos , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/genética , Transplante de Neoplasias , Neutrófilos/efeitos dos fármacos , Pneumonia/induzido quimicamente , Pneumonia/patologia , Proteína-Arginina Desiminase do Tipo 4/genética
9.
BMC Int Health Hum Rights ; 19(1): 21, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31248413

RESUMO

BACKGROUND: Sexual violence is a global health problem. After ratifying the Convention of Istanbul in 2016, this Belgian study was set up to map the perspective of victims of rape on the current sexual violence care provision in Belgium and to inquire on their need for more specialised and holistic care in future Sexual Assault Care Centres. METHODS: Sixteen rape victims participated in this sub-study. A mixed-method design (questionnaire, in-depth interview or small focus group) was applied depending on the time elapsed between rape and participation. Descriptive Thematic Framework Analysis was performed in duo. RESULTS: The participants thought it of utmost importance that every victim should receive all medical, psychological and forensic care without necessarily having to involve the police first. They stated that the current Belgian sexual violence care provision could be much more patient-centred, specifically the forensic examination and psychological care. Alongside medical and psychological consequences, victims emphasised the high personal financial and relational burden of sexual violence. The holistic care offered in Sexual Assault Care Centres was perceived to enhance the recovery process of victims of sexual violence. Their doors should be open to all victims and their relatives. They should not only provide acute care for the victim, but also improve victims' reintegration into society while reducing their personal costs significantly. CONCLUSION: All care for victims of sexual violence, especially forensic and psychological care, needs drastic improvement in Belgium. All participants agreed that having specialised, multidisciplinary and longitudinal care in a Sexual Assault Care Centre that would be open 24/7 for everyone, victims and their significant others, would be an improvement to the currently available care all over Belgium. TRIAL REGISTRATION: This research was registered on April 1st 2016. Registration number B670201628242.


Assuntos
Vítimas de Crime/reabilitação , Assistência Centrada no Paciente/normas , Estupro/estatística & dados numéricos , Adolescente , Adulto , Bélgica , Vítimas de Crime/psicologia , Prestação Integrada de Cuidados de Saúde/organização & administração , Feminino , Grupos Focais , Pessoal de Saúde/organização & administração , Pessoal de Saúde/psicologia , Hospitais , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente/organização & administração , Polícia , Estupro/psicologia , Apoio Social , Inquéritos e Questionários , Adulto Jovem
10.
Dev Dyn ; 247(3): 432-450, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28407379

RESUMO

Epithelial-mesenchymal transitions (EMTs) associated with metastatic progression may contribute to the generation of hybrid phenotypes capable of plasticity. This cellular plasticity would provide tumor cells with an increased potential to adapt to the different microenvironments encountered during metastatic spread. Understanding how EMT may functionally equip circulating tumor cells (CTCs) with an enhanced competence to survive in the bloodstream and niche in the colonized organs has thus become a major cancer research axis. We summarize here clinical data with CTC endpoints involving EMT. We then review the work functionally linking EMT programs to CTC biology and deciphering molecular EMT-driven mechanisms supporting their metastatic competence. Developmental Dynamics 247:432-450, 2018. © 2017 Wiley Periodicals, Inc.


Assuntos
Plasticidade Celular , Transição Epitelial-Mesenquimal , Células Neoplásicas Circulantes/patologia , Humanos , Metástase Neoplásica/patologia
11.
FASEB J ; 31(4): 1678-1688, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28057697

RESUMO

Zonula occludens-1 (ZO-1) is a submembrane scaffolding protein that may display proinvasive functions when it relocates from tight junctions into the cytonuclear compartment. This article examines the functional involvement of ZO-1 in CXCL8/IL-8 chemokine expression in lung and breast tumor cells. ZO-1 small interfering RNA and cDNA transfection experiments emphasized regulation of CXCL8/IL-8 expression via a cytonuclear pool of ZO-1. Luciferase reporter assays highlighted a 173-bp region of CXCL8/IL-8 promoter that responded to ZO-1. Moreover, by using mutated promoter constructs, we identified a NF-κB site as critical in this activation. Furthermore, NF-κB pathway signaling analysis revealed both IκBα and p65 phosphorylation in ZO-1-overexpressing cells, and subsequent p65 silencing validated its requirement for CXCL8/IL-8 induction. Investigation of the functional implication of this regulatory axis next showed the proangiogenic activity of ZO-1 in both ex vivo and in vivo angiogenesis assays. Finally, we found that non-small-cell lung carcinoma that presented a cytonuclear ZO-1 pattern was significantly more angiogenic that that without detectable cytonuclear ZO-1 expression. Taken together, our results demonstrate that ZO-1 regulates CXCL8/IL-8 expression via the NF-κB signaling pathway and its p65 subunit, which subsequently modulates the transcription of IL-8. We also provide evidence of a newly identified regulatory pathway that could promote angiogenesis. Thus, our results support the concept that the ZO-1 shuttle from the cell junction to the cytonuclear compartment may affect both the intrinsic invasive properties of tumor cells and the establishment of the protumoral microenvironment.-Lesage, J., Suarez-Carmona, M., Neyrinck-Leglantier, D., Grelet, S., Blacher, S., Hunziker, W., Birembaut, P., Noël, A., Nawrocki-Raby, B., Gilles, C., Polette, M. Zonula occludens-1/NF-κB/CXCL8: a new regulatory axis for tumor angiogenesis.


Assuntos
Regulação Neoplásica da Expressão Gênica , Interleucina-8/metabolismo , NF-kappa B/metabolismo , Neovascularização Patológica/genética , Proteína da Zônula de Oclusão-1/metabolismo , Humanos , Interleucina-8/genética , Células MCF-7 , Neovascularização Patológica/metabolismo , Regiões Promotoras Genéticas
12.
Aust N Z J Obstet Gynaecol ; 57(4): 393-399, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28567743

RESUMO

This review discusses the development of selective progestin receptor modulators (SPRMs) for use in women's health and specifically the use of ulipristal acetate (UPA) as emergency contraception (EC) and as a treatment for symptomatic fibroids in women who want to preserve their fertility or avoid a hysterectomy. As an EC, UPA 30 mg should be recommended for women, within 102 h of unprotected intercourse. As a treatment of fibroids, UPA (5 mg daily dose) should be administered for periods of three months as a pre-surgical strategy, reducing bleeding and fibroid size and facilitating surgery. A proportion of these patients may even avoid surgery. Future developments will demonstrate whether UPA can be used for other indications such as endometriosis and breast cancer prevention or treatment.


Assuntos
Anticoncepção Pós-Coito/métodos , Anticoncepcionais Femininos/uso terapêutico , Anticoncepcionais Pós-Coito , Leiomioma/tratamento farmacológico , Norpregnadienos/uso terapêutico , Receptores de Progesterona/antagonistas & inibidores , Neoplasias Uterinas/tratamento farmacológico , Feminino , Humanos
13.
J Pathol ; 237(1): 25-37, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25904364

RESUMO

We have explored the role of the human NANOS3 gene in lung tumour progression. We show that NANOS3 is over-expressed by invasive lung cancer cells and is a prognostic marker for non-small cell lung carcinomas (NSCLCs). NANOS3 gene expression is restricted in testis and brain and is regulated by epigenetic events. It is up-regulated in cultured cells undergoing epithelial - mesenchymal transition (EMT). NANOS3 over-expression in human NSCLC cell lines enhances their invasiveness by up-regulating EMT, whereas its silencing induces mesenchymal - epithelial transition. NANOS3 represses E-cadherin at the transcriptional level and up-regulates vimentin post-transcriptionally. Also, we show that NANOS3 binds mRNAs encoding vimentin and regulates the length of their poly(A) tail. Finally, NANOS3 can also protect vimentin mRNA from microRNA-mediated repression. We thus demonstrate a role for NANOS3 in the acquisition of invasiveness by human lung tumour cells and propose a new mechanism of post-transcriptional regulation of EMT.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Movimento Celular , Transição Epitelial-Mesenquimal , Neoplasias Pulmonares/metabolismo , Proteínas de Ligação a RNA/metabolismo , Vimentina/metabolismo , Antígenos CD , Caderinas/genética , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Epigênese Genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Fatores de Tempo , Transcrição Gênica , Transfecção , Vimentina/genética
14.
J Pathol ; 236(4): 491-504, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25880038

RESUMO

Epithelial-mesenchymal transition (EMT) programmes provide cancer cells with invasive and survival capacities that might favour metastatic dissemination. Whilst signalling cascades triggering EMT have been extensively studied, the impact of EMT on the crosstalk between tumour cells and the tumour microenvironment remains elusive. We aimed to identify EMT-regulated soluble factors that facilitate the recruitment of host cells in the tumour. Our findings indicate that EMT phenotypes relate to the induction of a panel of secreted mediators, namely IL-8, IL-6, sICAM-1, PAI-1 and GM-CSF, and implicate the EMT-transcription factor Snail as a regulator of this process. We further show that EMT-derived soluble factors are pro-angiogenic in vivo (in the mouse ear sponge assay), ex vivo (in the rat aortic ring assay) and in vitro (in a chemotaxis assay). Additionally, conditioned medium from EMT-positive cells stimulates the recruitment of myeloid cells. In a bank of 40 triple-negative breast cancers, tumours presenting features of EMT were significantly more angiogenic and infiltrated by a higher quantity of myeloid cells compared to tumours with little or no EMT. Taken together, our results show that EMT programmes trigger the expression of soluble mediators in cancer cells that stimulate angiogenesis and recruit myeloid cells in vivo, which might in turn favour cancer spread.


Assuntos
Proteínas Angiogênicas/metabolismo , Quimiotaxia , Citocinas/metabolismo , Transição Epitelial-Mesenquimal , Células Mieloides/metabolismo , Neovascularização Patológica , Comunicação Parácrina , Neoplasias de Mama Triplo Negativas/irrigação sanguínea , Neoplasias de Mama Triplo Negativas/metabolismo , Microambiente Tumoral , Proteínas Angiogênicas/genética , Animais , Linhagem Celular Tumoral , Meios de Cultivo Condicionados/metabolismo , Citocinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Camundongos SCID , Células Mieloides/patologia , Fenótipo , Interferência de RNA , Ratos , Transdução de Sinais , Transfecção , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
15.
Mol Cancer ; 13: 108, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24886454

RESUMO

BACKGROUND: DUSP3 phosphatase, also known as Vaccinia-H1 Related (VHR) phosphatase, encoded by DUSP3/Dusp3 gene, is a relatively small member of the dual-specificity protein phosphatases. In vitro studies showed that DUSP3 is a negative regulator of ERK and JNK pathways in several cell lines. On the other hand, DUSP3 is implicated in human cancer. It has been alternatively described as having tumor suppressive and oncogenic properties. Thus, the available data suggest that DUSP3 plays complex and contradictory roles in tumorigenesis that could be cell type-dependent. Since most of these studies were performed using recombinant proteins or in cell-transfection based assays, the physiological function of DUSP3 has remained elusive. RESULTS: Using immunohistochemistry on human cervical sections, we observed a strong expression of DUSP3 in endothelial cells (EC) suggesting a contribution for this phosphatase to EC functions. DUSP3 downregulation, using RNA interference, in human EC reduced significantly in vitro tube formation on Matrigel and spheroid angiogenic sprouting. However, this defect was not associated with an altered phosphorylation of the documented in vitro DUSP3 substrates, ERK1/2, JNK1/2 and EGFR but was associated with an increased PKC phosphorylation. To investigate the physiological function of DUSP3, we generated Dusp3-deficient mice by homologous recombination. The obtained DUSP3-/- mice were healthy, fertile, with no spontaneous phenotype and no vascular defect. However, DUSP3 deficiency prevented neo-vascularization of transplanted b-FGF containing Matrigel and LLC xenograft tumors as evidenced by hemoglobin (Hb) and FITC-dextran quantifications. Furthermore, we found that DUSP3 is required for b-FGF-induced microvessel outgrowth in the aortic ring assay. CONCLUSIONS: All together, our data identify DUSP3 as a new important player in angiogenesis.


Assuntos
Carcinoma Pulmonar de Lewis/genética , Fosfatase 3 de Especificidade Dupla/genética , Neovascularização Fisiológica/genética , Animais , Carcinoma Pulmonar de Lewis/metabolismo , Carcinoma Pulmonar de Lewis/patologia , Movimento Celular , Colo do Útero/irrigação sanguínea , Colo do Útero/metabolismo , Colo do Útero/patologia , Colágeno , Combinação de Medicamentos , Fosfatase 3 de Especificidade Dupla/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fatores de Crescimento de Fibroblastos , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Laminina , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Camundongos , Camundongos Knockout , Neovascularização Patológica/prevenção & controle , Fosforilação , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Proteoglicanas , Transdução de Sinais
16.
J Infect Dis ; 207(11): 1723-9, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23463709

RESUMO

BACKGROUND: Studies analyzing the impact of combination antiretroviral therapy (cART) on cervical infection with high-risk human papillomavirus (HR-HPV) have generated conflicting results. We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months. METHODS: Prospective cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011. RESULTS: At baseline, the median age was 38 years, the race/ethnic origin was sub-Sarahan Africa for 84%, the median CD4(+) T-cell count was 426 cells/µL, 79% were receiving cART, and the HR-HPV prevalence was 43%. The median interval of having had an HIV load of <50 copies/mL was 40.6 months at the time of a HR-HPV-negative test result, compared with 17 months at the time of a HR-HPV-positive test result (P < .0001, by univariate analysis). The median interval of having had a CD4(+) T-cell count of >500 cells/µL was 18.4 months at the time of a HR-HPV-negative test result, compared with 4.45 months at the time of a HR-HPV-positive test result (P < .0001). In multivariate analysis, having had an HIV load of <50 copies/mL for >40 months (odds ratio [OR], 0.81; 95% confidence interval [CI], .76-.86; P < .0001) and having had a CD4(+) T-cell count of >500 cells/µL for >18 months (OR, 0.88; 95% CI, .82-.94; P = .0002) were associated with a significantly decreased risk of HR-HPV infection. CONCLUSION: Sustained HIV suppression for >40 months and a sustained CD4(+) T-cell count of >500 cells/µL for >18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection.


Assuntos
Antirretrovirais/administração & dosagem , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/complicações , Infecções por HIV/imunologia , Infecções por Papillomavirus/epidemiologia , Adulto , África Subsaariana , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Estudos Prospectivos , Medição de Risco , Resultado do Tratamento
17.
Biochem Biophys Res Commun ; 431(4): 652-7, 2013 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-23376074

RESUMO

E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the proximal region of the E-cadherin gene promoter. We have here explored a potential competition between ZEB2 and KLF4 for the binding to the E-cadherin promoter. We show an inverse correlation between ZEB2 expression levels and KLF4 recruitment on the E-cadherin promoter in three breast cancer cell lines and in A431/HA.ZEB2 cells in which ZEB2 expression is induced by doxycycline (DOX). We identified a region of the E-cadherin promoter bound by KLF4 which is necessary for the activation of the E-cadherin promoter activity after KLF4 overexpression. This region is localized between positions -28 and -10 and thus overlaps with one of the ZEB2 binding sites. Deleting the bipartite ZEB2 binding site results in increased KLF4 induced E-cadherin promoter activity. Taken together, our results suggest that E-cadherin expression in cancer cells is controlled by a balance between ZEB2 and KLF4 expression levels.


Assuntos
Caderinas/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas Repressoras/metabolismo , Antígenos CD , Ligação Competitiva , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Transição Epitelial-Mesenquimal/genética , Proteínas de Homeodomínio/genética , Humanos , Fator 4 Semelhante a Kruppel , Regiões Promotoras Genéticas , Proteínas Repressoras/genética , Ativação Transcricional , Homeobox 2 de Ligação a E-box com Dedos de Zinco
18.
Front Immunol ; 14: 1171649, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283751

RESUMO

Lung cancer remains the first cause of cancer-related death despite many therapeutic innovations, including immune checkpoint inhibitors (ICI). ICI are now well used in daily practice at late metastatic stages and locally advanced stages after a chemo-radiation. ICI are also emerging in the peri-operative context. However, all patients do not benefit from ICI and even suffer from additional immune side effects. A current challenge remains to identify patients eligible for ICI and benefiting from these drugs. Currently, the prediction of ICI response is only supported by Programmed death-ligand 1 (PD-L1) tumor expression with perfectible results and limitations inherent to tumor-biopsy specimen analysis. Here, we reviewed alternative markers based on liquid biopsy and focused on the most promising biomarkers to modify clinical practice, including non-tumoral blood cell count such as absolute neutrophil counts, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio. We also discussed soluble-derived immune checkpoint-related products such as sPD-L1, circulating tumor cells (detection, count, and marker expression), and circulating tumor DNA-related products. Finally, we explored perspectives for liquid biopsies in the immune landscape and discussed how they could be implemented into lung cancer management with a potential biological-driven decision.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Biomarcadores Tumorais , Linfócitos/metabolismo
19.
Eur J Psychotraumatol ; 14(2): 2263312, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37819370

RESUMO

BACKGROUND: Sexual assault (SA) can induce a negative impact on victims' mental health. Specialised SA services generally offer medical care and a forensic examination to SA victims. However, there is a large variation in how these services provide mental health support. OBJECTIVE: This study aims to assess mental health problems of SA victims attending the Belgian Sexual Assault Care Centres (SACCs) and identify predictors for victims' use of support from in-house psychologists. METHOD: Health records of victims ≥ 16 years who presented within one week post-SA to one of the three Belgian SACCs between 25 October 2017 and 31 October 2019 were reviewed. An AIC-based stepwise backward binary logistic regression was used to analyse the association between victim, assault, service use and mental health characteristics and follow-up by a SACC-psychologist. RESULTS: Of the 555 victims, more than half had a history of mental health problems. Of those assessed, over 70% showed symptoms of posttraumatic stress disorder (PTSD), depression and/or anxiety disorder. One in two victims consulted a SACC-psychologist. Victims with a mental health history (OR 1.46, p = .04), victims accompanied by a support person during acute care (OR 1.51, p = .04), and victims who were assaulted by an acquaintance in comparison to those assaulted by a stranger (OR 1.60, p = .039) were more likely to attend their appointment with the SACC-psychologist. CONCLUSION: The study reaffirms the high mental health burden among victims attending specialised SA services, stressing the need to provide effective mental health interventions at these services and improve their longer-term use by victims. Prescheduling of appointments with an in-house psychologist in combination with phone reminders may improve the uptake of such services. Health care providers must be vigilant about potential barriers faced by victims without a mental health history or social support in attending appointments with mental health professionals.


The mental health burden is high among victims attending Belgian Sexual Assault Care Centres.Half of the victims use the support of an in-house psychologist. Victims with a history of mental health problems, those accompanied by a support person during acute care, and those assaulted by an acquaintance in comparison to those assaulted by a stranger, are more likely to use this support.Effective mental health support should be recognised as an integral and essential part of care for SA victims. Uptake and longer-term engagement with this mental health support should be improved for those victims diagnosed with PTSD.


Assuntos
Vítimas de Crime , Delitos Sexuais , Transtornos de Estresse Pós-Traumáticos , Humanos , Saúde Mental , Bélgica , Vítimas de Crime/psicologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/terapia , Transtornos de Estresse Pós-Traumáticos/psicologia
20.
Planta ; 236(2): 567-77, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22476292

RESUMO

The impact of Medicago truncatula stress-associated protein gene (MtSAP1) overexpression has been investigated in Nicotiana tabacum transgenic seedlings. Under optimal conditions, transgenic lines overexpressing MtSAP1 revealed better plant development and higher chlorophyll content as compared to wild type seedlings. Interestingly, transgenic lines showed a stronger accumulation of nitric oxide (NO), a signaling molecule involved in growth and development processes. This NO production seemed to be partially nitrate reductase dependent. Due to the fact that NO has been also reported to play a role in tolerance acquisition of plants to abiotic stresses, the responses of MtSAP1 overexpressors to osmotic and salt stress have been studied. Compared to the wild type, transgenic lines were less affected in their growth and development. Moreover, NO content in MtSAP1 overexpressors was always higher than that detected in wild seedlings under stress conditions. It seems that this better tolerance induced by MtSAP1 overexpression could be associated with this higher NO production that would enable seedlings to reach a high protection level to prepare them to cope with abiotic stresses.


Assuntos
Adaptação Fisiológica/fisiologia , Medicago truncatula/genética , Nicotiana/fisiologia , Óxido Nítrico/metabolismo , Proteínas de Plantas/metabolismo , Estresse Fisiológico/fisiologia , Regulação da Expressão Gênica de Plantas , Óxido Nítrico/análise , Osmose/fisiologia , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , RNA de Plantas/genética , Tolerância ao Sal , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/fisiologia , Nicotiana/efeitos dos fármacos , Nicotiana/genética , Nicotiana/crescimento & desenvolvimento
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