Twenty years of EMT: A state of the field from TEMTIA X.

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.

Mental health of sexual assault victims and predictors of their use of support from in-house psychologists at Belgian sexual assault care centres.

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.

Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors.

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.

The recent natural history of human papillomavirus cervical infection in women living with HIV: A scoping review of meta-analyses and systematic reviews and the construction of a hypothetical model.

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.

HPV genotyping in biopsies of HSIL and invasive cervical cancers in women living with HIV: A cohort- and a nested -case control study.

OBJECTIVE: To characterize HPV genotype distribution in HSIL and ICC- biopsies, of WLWH, in Europe, as compared to HIV-negative women. DESIGN: Cohort- and nested -case control study. METHOD: We characterized HPV genotype distribution by performing PCR on HSIL and ICC biopsies from WLWH (n = 170); 85 cases were compared to 85 HIV-negative matched controls. The proportion of patients that might be protected by HPV vaccines was estimated. RESULTS: Among WLWH (median age 36 years-old, median duration of HIV infection 70,5 months, 79% under cART): the most frequently detected HPV were HPV16 (30%), HPV35 (16%), HPV58 (14,7%), HPV31 (13,5%), and HPV52 (11,7%). HPV16 was less frequently found in WLWH, originating from Central Africa (20,5%) compared to other African regions (35,5%) (p = 0,05) or world regions (38,8%) (p = 0,007). Multiple versus single high-risk HPV infections were associated with younger age (≤35 years)(odds ratio (OR) 2,65 (95%IC: 1,3-5,2,p = 0,002), lymphocyte CD4 count < 350 cells / µL (OR 2,7 (95%IC: 2-8,5; p = 0,005), use of cART for < 18 month OR 2,2 (95%IC: 1,1-4,5),p = 0,04) or a cumulative time with undetectable HIV viral load of less than 12 months (OR 4,2 (95%IC: 2-8.5,p = 0,001). HPV 31, 33 and 35 were more frequently detected in samples from WLWH than in HIV-negative controls (p < 0,05). The 9-valent vaccine would increase HPV protection, in HIV-positive and negative women (p < 0,001). CONCLUSION: WLWH are more frequently infected with high-risk HPV other than 16 and 18 than HIV-negative ones. The use of 9-valent vaccine may prevent HSIL or ICC in up to 85% of the women. Adding HPV 35 to the HPV vaccine panel, might improve vaccine effectiveness in WLWH.

Regulation of Tissue Factor by CD44 Supports Coagulant Activity in Breast Tumor Cells.

Previous work identified Tissue Factor (TF), a key activator of the coagulation cascade, as a gene induced in cellular contexts of Epithelial-Mesenchymal Transitions (EMTs), providing EMT+ Circulating Tumor Cells (CTCs) with coagulant properties that facilitate their metastatic seeding. Deciphering further molecular aspects of TF regulation in tumor cells, we report here that CD44 and TF coexpress in EMT contexts, and that CD44 acts as a regulator of TF expression supporting procoagulant properties and metastatic seeding. A transcriptional regulatory mechanism bridging CD44 to TF expression was further evidenced. Comparing different TF -promoter luciferase reporter constructs, we indeed found that the shortest -111 pb TF promoter fragment harboring three Specificity Protein 1 (Sp1) binding sites is still responsive to CD44 silencing. The observation that (i) mutation within Sp1 binding sites decreased the basal activity of the -111 pb TF promoter construct, (ii) CD44 silencing decreased Sp1 protein and mRNA levels and (iii) Sp1 silencing diminished TF expression further points to Sp1 as a key mediator linking CD44 to TF regulation. All together, these data thus report a transcriptional regulatory mechanism of TF expression by CD44 supporting procoagulant activity and metastatic competence of CTCs.

Unified European support framework to sustain the HIV cascade of care for people living with HIV including in displaced populations of war-struck Ukraine.

Ukraine is one of the countries in Europe most affected by HIV. The escalation of open war on the European continent has affected HIV care in Ukraine in an unprecedented way. Treating physicians in Europe have little experience on how to handle HIV-specific care under these circumstances. A framework is urgently needed that both defines and sets out strategies to handle the specific challenges for emergency support for people living with HIV, both those staying in Ukraine and those becoming displaced. The optimal allocation of the few available medical resources, primarily antiretroviral therapy, is necessary to best prevent individual morbidity and achieve population transmission control. Professional HIV networks play a central role to create, optimise, and execute support strategies. Through a rapid literature review we identified the key strategies needed to create a support framework, adapted to Ukraine's HIV epidemiology. We produce a unified support framework aiming to reduce the inevitable impact on Ukraine's HIV care cascade now, and when rebuilding it after the war.

Clinical Impact of the Epithelial-Mesenchymal Transition in Lung Cancer as a Biomarker Assisting in Therapeutic Decisions.

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.

ZO-1 Intracellular Localization Organizes Immune Response in Non-Small Cell Lung Cancer.

Delocalization of zonula occludens-1 (ZO-1) from tight junctions plays a substantial role in epithelial cell plasticity observed during tumor progression. In vitro, we reported an impact of ZO-1 cyto-nuclear content in modulating the secretion of several pro-inflammatory chemokines. In vivo, we demonstrated that it promotes the recruitment of immune cells in mouse ear sponge assays. Examining lung cancers, we showed that a high density of CD8 cytotoxic T cells and Foxp3 immunosuppressive regulatory T cells in the tumor microenvironment correlated with a cyto-nuclear expression of ZO-1. Taken together, our results support that, by affecting tumor cell secretome, the cyto-nuclear ZO-1 pool may recruit immune cells, which could be permissive for tumor progression.

Menopausal hormone therapy and breast cancer risk.

This narrative review analyses the customization of Menopause Hormone Therapy in the context of breast cancer risk in women with premature ovarian insufficiency (POI) and with menopause at a normal age. Women with Idiopathic POI, FMR-1 premutation or Turner syndrome, if left untreated, may have lower breast cancer risk compared to the healthy age-matched female population. These women should be treated with MHT until the age of 50, as the risk of breast cancer is equal to that of normally menstruating women. Carriers of BRCA 1 & 2 mutation after risk-reducing bilateral salpingo-oophorectomy (RRSO), without a personal history of cancer, have an increased breast cancer risk, but may probably be treated with MHT till the age of 50. POI resulting from endometriosis or cancer related treatment is discussed in a separate paper in this issue. In peri- and postmenopausal women with menopausal symptoms and/or risk factors for osteoporosis in need of MHT, the individual breast cancer risk can be evaluated using internet-based calculators. In most women the 5-year-breast cancer risk is low (<3%) and MHT is a safe option. MHT should be prescribed with caution in women who have an intermediate risk (3-6%) and should not be prescribed in those who have a high risk of breast cancer (>6%). Oestrogen-only MHT and oestrogen-progestogen MHT containing micronized progesterone or dydrogesterone are associated with lower breast cancer risk compared to other combined MHT regimens.

Piloting sexual assault care centres in Belgium: who do they reach and what care is offered?

Background: Sexual assault (SA) is highly prevalent in Belgium. In order to mitigate the negative consequences for victims of acute SA, Sexual Assault Care Centres (SACCs) were piloted from October 2017 to October 2018 in three Belgian hospitals. SACCs offer medical and psychological care, forensic examination and the possibility to report to the police at the SACC. Objective: Aiming to improve SACC services, we quantitatively assessed the number and characteristics of victims attending the SACC, the SA they experienced, and the care they received over 12 months upon admission. Method: Data on victims presenting at the SACC were routinely collected in electronic patient files by the SACC personnel between 25 October 2017 and 31 October 2019. These data were analysed in IBM SPSS Statistics 25. Results: Within the first year 931 victims attended the SACCs. Mean age was 24.5 years (SD = 12.8), and one-third were under 18. The majority were female (90.5%) and 63.1% presented for rape. About one-third of the victims were considered vulnerable due to previous SA (35.6%), prior psychiatric consultation (38.7%) or disability (8.5%). The assailant was known to the victim in 59.2% of the cases. Of all SACC presentations, 35.2% self-referred to the SACC while 40.9% were referred by the police. Two out of three victims attended the SACC within 72 h post-assault. Respectively 74.7% of victims received medical care, 60.6% a forensic examination, 50.2% psychological care, and 68.7% reported to the police. Conclusion: Despite the absence of promotion campaigns, the SACCs received a high number of victims during the pilot year. Use of acute and follow-up services was high, although new approaches to offer more accessible psychological support should be explored. The big proportion of vulnerable victims warrants careful monitoring and adaptation of care pathways.

Antecedentes: El asalto sexual (SA en si sigla en inglés) es altamente prevalente en Bélgica. Para mitigar las consecuencias negativas para las víctimas de SA agudo, los Centros de Atención de Asalto Sexual (SACCs en su sigla en inglés) fueron piloteados desde octubre de 2017 hasta octubre 2018 en tres hospitales belgas. Los SACCs ofrecen atención médica y psicológica, examen forense y la posibilidad de reportar a la policía en el SACC.Objetivo: Para mejorar los servicios SACC, medimos cuantitativamente el número y las características de las víctimas atendidas por el SACC, el SA que experimentaron y la atención que recibieron a lo largo de los 12 meses desde su admisión.Método: Fueron recolectados rutinariamente los datos en las víctimas que se presentaron en el SACC por el personal de SACC en los archivos electrónicos de los pacientes entre el 25 de octubre 2017 y 31 de octubre de 2019. Estos datos fueron analizados en el Programa Estadístico IBM SPSS 25.Resultados: Dentro del primer año, 931 victimas asistieron a los SCCs. La edad media fue 24,5 (DE = 12.8), y un tercio eran menores de 18 años. La mayoría eran mujeres (90.5%) y 63.1% se presentaron por violación. Alrededor de un tercio de las víctimas fueron consideradas vulnerables debido a SA previos (35.6%), consulta psiquiátrica anterior (38.7%) o discapacidad (8.5%). El asaltante era un conocido de la víctima en 59.2% de los casos. De todas las presentaciones SACC, el 35.2% se autoderivaron a SACC, mientras que 40.9% fueron derivados por la policía. Dos de cada tres víctimas asistieron al SACC dentro de las primeras 72 horas luego del asalto. Respectivamente, el 74.7% de las víctimas recibieron atención médica, el 60.6% un examen forense, el 50.2% atención psicológica, y el 68.7% reportaron a la policía.Conclusión: A pesar de la ausencia de campañas de promoción, los SACCs recibieron un gran número de víctimas durante el año piloto. El uso de servicios agudos y de seguimiento fueron altos, aunque nuevas perspectivas para ofrecer más apoyo psicológico más accesible deberían ser exploradas. La mayor proporción de víctimas vulnerables garantiza un monitoreo cuidadoso y la adaptación de las vías de atención.

Hypoxia in Lung Cancer Management: A Translational Approach.

Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice. Here, we review clinical and pathological features related to hypoxic lung tumours. Secondly, we expound on the main current techniques to evaluate hypoxic status in NSCLC focusing on positive emission tomography. We present existing alternative experimental approaches such as the examination of circulating markers and highlight the interest in non-invasive markers. Finally, we evaluate the relevance of investigating hypoxia in lung cancer management as a companion biomarker at various lung cancer stages. Hypoxia could support the identification of patients with higher risks of NSCLC. Moreover, the presence of hypoxia in treated tumours could help clinicians predict a worse prognosis for patients with resected NSCLC and may help identify patients who would benefit potentially from adjuvant therapies. Globally, the large quantity of translational data incites experimental and clinical studies to implement the characterisation of hypoxia in clinical NSCLC management.

Should the management of high grade cervical squamous intraepithelial lesion (HSIL) be different in HIV-positive women?

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.

Epithelial to Mesenchymal Transition Regulates Surface PD-L1 via CMTM6 and CMTM7 Induction in Breast Cancer.

CMTM6 is a critical regulator of cell surface expression of PD-L1 in tumor cells, but little is known about the transcriptional regulation of CMTM6. Here we report that the expression of CMTM6 positively correlates with the epithelial to mesenchymal transition (EMT) score in breast cancer cell lines and with the major EMT marker Vimentin in triple-negative breast cancers (TNBC). We showed that CMTM6 is concomitantly overexpressed with PD-L1 in breast mesenchymal compared with the epithelial cells. Driving a mesenchymal phenotype in SNAI1-inducible MCF-7 cells (MCF-7Mes cells) increased both PD-L1 and CMTM6. CMTM6 silencing in MCF-7Mes cells partially reduced cell surface expression of PD-L1, indicating that a proportion of the PD-L1 on the surface of MCF-7Mes cells depends on CMTM6. We also found a positive correlation between CMTM3 and CMTM7 expression with EMT score in breast cancer cells, and with Vimentin in TNBC patients. Dual knockdown of CMTM6 and CMTM7 significantly decreased PD-L1 surface expression in MCF-7Mes cells, indicating that both CMTM6 and CMTM7 regulate the expression of PD-L1. This study highlights the importance of CMTM6 and CMTM7 in EMT-induced PD-L1 and suggests that EMT, CMTM6 or CMTM7 modulators can be combined with anti-PD-L1 in patients with highly aggressive breast cancer.

Single-tablet regimen of emtricitabine/tenofovir disoproxil fumarate plus cobicistat-boosted elvitegravir increase adherence for HIV postexposure prophylaxis in sexual assault victims.

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.

EMT-Associated Heterogeneity in Circulating Tumor Cells: Sticky Friends on the Road to Metastasis.

Epithelial-mesenchymal transitions (EMTs) generate hybrid phenotypes with an enhanced ability to adapt to diverse microenvironments encountered during the metastatic spread. Accordingly, EMTs play a crucial role in the biology of circulating tumor cells (CTCs) and contribute to their heterogeneity. Here, we review major EMT-driven properties that may help hybrid Epithelial/Mesenchymal CTCs to survive in the bloodstream and accomplish early phases of metastatic colonization. We then discuss how interrogating EMT in CTCs as a companion biomarker could help refine cancer patient management, further supporting the relevance of CTCs in personalized medicine.

Epithelial-Mesenchymal Plasticity in Circulating Tumor Cells, the Precursors of Metastasis.

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.

Vimentin prevents a miR-dependent negative regulation of tissue factor mRNA during epithelial-mesenchymal transitions and facilitates early metastasis.

Epithelial-mesenchymal transitions (EMTs) are high-profile in the field of circulating tumor cells (CTCs). EMT-shifted CTCs are considered to encompass pre-metastatic subpopulations though underlying molecular mechanisms remain elusive. Our previous work identified tissue factor (TF) as an EMT-induced gene providing tumor cells with coagulant properties and supporting metastatic colonization by CTCs. We here report that vimentin, the type III intermediate filament considered a canonical EMT marker, contributes to TF regulation and positively supports coagulant properties and early metastasis. Different evidence further pointed to a new post-transcriptional regulatory mechanism of TF mRNA by vimentin: (1) vimentin silencing accelerated TF mRNA decay after actinomycin D treatment, reflecting TF mRNA stabilization, (2) RNA immunoprecipitation revealed enriched levels of TF mRNA in vimentin immunoprecipitate, (3) TF 3'-UTR-luciferase reporter vector assays implicated the 3'-UTR of TF mRNA in vimentin-dependent TF regulation, and (4) using different TF 3'UTR-luciferase reporter vectors mutated for potential miR binding sites and specific Target Site Blockers identified a key miR binding site in vimentin-dependent TF mRNA regulation. All together, these data support a novel mechanism by which vimentin interferes with a miR-dependent negative regulation of TF mRNA, thereby promoting coagulant activity and early metastasis of vimentin-expressing CTCs.

Cervical, anal and oral human papillomavirus (HPV) infection in young women: A case control study between women with perinatally HIV infection and women with non-perinatally HIV infection.

OBJECTIVES: HPV infection may differ in women who are HIV-positive since birth (perinatally infected, P-HIV) and those who acquire HIV later in life (non-perinatally infected, NP-HIV). We assessed the HPV prevalence in relation to the HIV acquisition route and HPV vaccination status. STUDY DESIGN: Case control study comparing 22 P-HIV with 22 NP-HIV patients. Cervical, anal and oral specimen were collected for HPV PCRs. The primary outcome was the prevalence of cervical, oral and anal HPV in P-HIV and NP-HIV patients. The secondary outcome was to identify risk factors for HPV infection. Comparative statistics for two independent groups, univariate and multivariable logistic regression analyses were used. RESULTS: There were no differences between perinatally and non-perinatally infected women. Cervical dysplasia was found in 12/44 (27 %) patients and high-risk HPV (hrHPV) in 30 % of cervical (of which 89 % were hrHPV other than 16 and 18), in 3 % of oral and 65 % of anal specimens. All woman were using combined antiretroviral therapy (cART) and 64 % had HIVRNA < 20 cp/ml. A CD4 count <350/mm³ was associated with cytological abnormalities (OR: 13.52, p = 0.002) and with cervical HPV (OR: 6.11; p = 0.04); anal HPV was associated with a previous cervical dysplasia and concomitant cervical HPV infection. None of thirteen vaccinated patients had a 6/11/16/18 HPV infection. CONCLUSION: In this small series of women under cART, we did not observe a difference in HPV infection in relation to the route of HIV acquisition. The high prevalence of hrHPV other than 16 and 18 support the use of a 9-valent vaccine.

Programmed Death-Ligand 1 and Vimentin: A Tandem Marker as Prognostic Factor in NSCLC.

In non-metastatic non-small-cell lung cancer (NSCLC), outcomes remain poor. Adjuvant chemotherapies provide a limited improvement in disease-free survival. Recent exploratory studies on early-stage NSCLC show that immunotherapy given according to Programmed Death-Ligand 1 expression generates variable results, emphasizing a need to improve tumor characterization. We aimed to conjointly assess NSCLC, the expression of PD-L1, and epithelial-mesenchymal transition, frequently involved in tumor aggressiveness. 188 resected NSCLCs were analyzed. Among 188 patients with curatively resected NSCLC, 127 adenocarcinomas and 61 squamous cell carcinomas were stained for PD-L1 and vimentin expression. Overall survival has been compared regarding PD-L1 and vimentin statuses both separately and conjointly in Tumor Cancer Genome Atlas databases. PD-L1 and vimentin higher expressions were strongly associated (OR = 4.682, p < 0.0001). This co-expression occurred preferentially in tumors with lymph node invasion (p = 0.033). PD-L1 was significantly associated with high EMT features. NSCLC harboring both PD-L1high/vimentinhigh expressions were significantly associated with poor overall survival (p = 0.019). A higher co-expression of vimentin and PD-L1 was able to identify patients with worse outcomes. Similar to an important prognostic marker in NSCLC, this tandem marker needs to be further presented to anti-PD-L1 immunotherapies to improve outcome.