Publications by authors named "Manuel Rodrigues"

108 Publications

The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival.

Oncogene 2021 Sep 10. Epub 2021 Sep 10.

OncoRNALab, Center for Medical Genetics (CMGG), Ghent University, Ghent, Belgium.

Long non-coding RNAs (lncRNAs) can exhibit cell-type and cancer-type specific expression profiles, making them highly attractive as therapeutic targets. Pan-cancer RNA sequencing data revealed broad expression of the SAMMSON lncRNA in uveal melanoma (UM), the most common primary intraocular malignancy in adults. Currently, there are no effective treatments for UM patients with metastatic disease, resulting in a median survival time of 6-12 months. We aimed to investigate the therapeutic potential of SAMMSON inhibition in UM. Antisense oligonucleotide (ASO)-mediated SAMMSON inhibition impaired the growth and viability of a genetically diverse panel of uveal melanoma cell lines. These effects were accompanied by an induction of apoptosis and were recapitulated in two uveal melanoma patient derived xenograft (PDX) models through subcutaneous ASO delivery. SAMMSON pulldown revealed several candidate interaction partners, including various proteins involved in mitochondrial translation. Consequently, inhibition of SAMMSON impaired global, mitochondrial and cytosolic protein translation levels and mitochondrial function in uveal melanoma cells. The present study demonstrates that SAMMSON expression is essential for uveal melanoma cell survival. ASO-mediated silencing of SAMMSON may provide an effective treatment strategy to treat primary and metastatic uveal melanoma patients.
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http://dx.doi.org/10.1038/s41388-021-02006-xDOI Listing
September 2021

Different Pigmentation Risk Loci for High-Risk Monosomy 3 and Low-Risk Disomy 3 Uveal Melanomas.

J Natl Cancer Inst 2021 Aug 23. Epub 2021 Aug 23.

Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, Paris, 75005, France.

Background: Uveal melanoma (UM), a rare malignant tumor of the eye, is predominantly observed in populations of European ancestry. UMs carrying a monosomy 3 (M3) frequently relapse mainly in the liver, whereas UMs with disomy 3 (D3) are associated with more favorable outcome. Here, we explored the UM genetic predisposition factors in a large genome-wide association study (GWAS) of 1,142 European UM patients and 882 healthy controls.

Methods: We combined two independent datasets (GSA array) with the dataset described in a previously published GWAS in UM (Omni5 array), which were imputed separately and subsequently merged. Patients were stratified according to their chromosome 3 status and identified UM risk loci were tested for differential association with M3 or D3 subgroups. All statistical tests were two-sided.

Results: We recapitulated the previously identified risk locus on chromosome 5 on CLPTM1L (rs421284: odds ratio [OR] =1.58, 95% confidence interval [CI] = 1.35-1.86; P=1.98 × 10-8) and identified two additional risk loci involved in eye pigmentation: IRF4 locus on chromosome 6 (rs12203592: OR = 1.76, 95% CI = 1.44-2.16; P =3.55 × 10-8) and HERC locus on chromosome 15 (rs12913832: OR = 0.57, 95% CI = 0.48-0.67; P =1.88 × 10-11). The IRF4 rs12203592 SNP was found to be exclusively associated with risk for the D3 UM subtype (ORD3 = 2.73, 95% CI = 1.87-3.97; P =1.78 × 10-7), and the HERC2 rs12913832 SNP was exclusively associated with risk for the M3 UM subtype (ORM3 = 2.43, 95% CI = 1.79-3.29; P =1.13 × 10-8). However, the CLPTM1L risk locus was equally statistically significant in both subgroups.

Conclusion: This work identified two additional UM risk loci known for their role in pigmentation. Importantly, we demonstrate that UM tumor biology and metastatic potential are influenced by patients' genetic backgrounds.
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http://dx.doi.org/10.1093/jnci/djab167DOI Listing
August 2021

Definition of Biologically Distinct Groups of Conjunctival Melanomas According to Etiological Factors and Implications for Precision Medicine.

Cancers (Basel) 2021 Jul 30;13(15). Epub 2021 Jul 30.

INSERM U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée par la Ligue Nationale Contre le Cancer, Department of Genetics, Institut Curie, PSL Research University, F-75005 Paris, France.

Conjunctival melanoma (ConjMel) is a potentially deadly ocular melanoma, originating from partially sunlight-exposed mucosa. We explored the mutational landscape of ConjMel and studied the correlation with etiological factors. We collected 47 primary ConjMel samples and performed next-generation sequencing of 400 genes. Hotspot mutations in , , , and were observed in 16 (34%), 5 (11%), 2, and 2 cases, respectively. Patients with and -mutated ConjMel tended to be younger while the -mutated one tended to be older. The eight tumors arising from nevi were enriched in mutations (63% vs. 8%; Fisher's exact -test = 0.001) compared to non-nevi ConjMel and five were devoid of , , , or mutations, suggesting a specific oncogenic process in these tumors. The two -mutated cases carried mutations and were located on sun-protected mucosa, a genotype shared with genital and anorectal mucosal melanomas. Targetable mutations were observed in , , , and (one occurrence each). Mutational landscape of ConjMel characterizes distinct molecular subtypes with oncogenic drivers common with mucosal and skin melanomas. mutations were associated with nevus-derived ConjMel. Concomitant / mutations in sun-protected cases suggest a common tumorigenic process with genital and anorectal mucosal melanomas.
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http://dx.doi.org/10.3390/cancers13153836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345091PMC
July 2021

Prognostic nomogram for progression-free survival in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer on maintenance olaparib therapy following response to chemotherapy.

Eur J Cancer 2021 Sep 19;154:190-200. Epub 2021 Jul 19.

National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, NSW 2050, Australia; Department of Medical Oncology, St George Hospital, Kogarah, NSW 2217, Australia; Australia New Zealand Gynecological Oncology Group, Camperdown, New South Wales, Australia.

Background: The impact of maintenance therapy with PARP inhibitors (PARPi) on progression-free survival (PFS) in patients with BRCA mutations and platinum-sensitive recurrent ovarian cancer (PSROC) varies widely. Individual prognostic factors do not reliably distinguish patients who progress early from those who have durable benefit. We developed and validated a prognostic nomogram to predict PFS in these patients.

Methods: The nomogram was developed using data from a training patient cohort with BRCA mutations and high-grade serous PSROC on the placebo arm of two maintenance therapy trials, Study 19 and SOLO2/ENGOT-ov21. We performed multivariable Cox regression analysis based on pre-treatment characteristics to develop a nomogram that predicts PFS. We assessed the discrimination and validation of the nomogram in independent validation patient cohorts treated with maintenance olaparib.

Results: The nomogram includes four PFS predictors: CA-125 at randomisation, platinum-free interval, presence of measurable disease and number of prior lines of platinum therapy. In the training (placebo) cohort (internal validation C-index 0.64), median PFS in the model-predicted good, intermediate and poor-risk groups was: 7.7 (95% CI 5.3-11.3), 5.4 (4.8-5.8) and 2.9 (2.8-4.4) months, respectively. In the validation (olaparib) cohort (C-index 0.71), median PFS in the model-predicted good, intermediate and poor-risk groups was: not reached, 16.6 (13.1-22.4) and 8.3 (7.1-10.8) months, respectively. The nomogram showed good calibration in the validation cohort (calibration plot).

Conclusions: This nomogram can be used to predict PFS and counsel patients with BRCA mutations and PSROC prior to maintenance olaparib and for stratification of patients in trials of maintenance therapies.
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http://dx.doi.org/10.1016/j.ejca.2021.06.024DOI Listing
September 2021

Influence of the COVID-19 Pandemic in Higher Education Courses in the Health Field.

Invest Educ Enferm 2021 Jun;39(2)

School of Health, University of Trás-os-Montes e Alto Douro, Portugal,

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http://dx.doi.org/10.17533/udea.iee.v39n2e01DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253522PMC
June 2021

Nursing educators' and undergraduate nursing students' beliefs and perceptions on evidence-based practice, evidence implementation, organizational readiness and culture: An exploratory cross-sectional study.

Nurse Educ Pract 2021 Jul 17;54:103122. Epub 2021 Jun 17.

Health Sciences Research Unit, Nursing, Nursing School of Coimbra, P.O. Box 7001, 3046-851 Coimbra, Portugal; Nursing School of Coimbra, P.O. Box 7001, 3046-851 Coimbra, Portugal; Portugal Centre for Evidence-Based Practice: A JBI Centre of Excellence, Health Sciences Research Unit, Nursing, Nursing School of Coimbra, P.O. Box 7001, 3046-851 Coimbra, Portugal. Electronic address:

Aims: To describe the undergraduate nursing students' and nursing educators' evidence-based practice beliefs, their extent of evidence-based practice implementation and their perspectives regarding organizational culture for evidence-based practice. To identify any relationship between the mentioned variables.

Background: The integration of evidence-based practice in nursing curricula is crucial to educate nursing students to incorporate evidence-based practice in their future clinical practice. Therefore, to promote its integration within nursing education, it is important to deeply understand how prepared academic institutions are for teaching about and supporting evidence-based practice integration.

Design: Cross-sectional study.

Methods: Nursing educators and undergraduate nursing students from nine Portuguese nursing schools were invited to participate in this study through an electronic survey comprising socio-demographic questions and the scales.

Results: Sixty-eight nursing educators replied to the survey. Most were female, have PhD and have evidence-based practice training. They showed mean scores of 88.92 ± 8.18 for evidence-based practice beliefs, 40.20 ± 18.93 for evidence-based practice implementation and 80.59 ± 17.52 for evidence-based practice organizational culture and readiness. Concerning nursing educator sample, there were moderate and statistically significant relationship between: evidence-based practice beliefs and implementation; and evidence-based practice beliefs and organizational culture and readiness for school-wide integration of evidence-based practice. Between evidence-based practice implementation and organizational culture and readiness for school-wide integration of evidence-based practice, there was a small relationship. One hundred and sixty-seven undergraduate nursing students answered the survey. Mostly, they were female and were in third or fourth year of their nursing degree. Similarly, to educators, students showed mean scores of 58.69 ± 6.92 for evidence-based practice beliefs, 32.37 ± 16.97 for evidence-based practice implementation and 84.20 ± 23.48 for evidence-based practice organizational culture and readiness. Regarding undergraduate nursing student sample, there were moderate and statistically significant relationship between the different variables.

Conclusions: Both nursing educators and undergraduate nursing students had strong evidence-based practice beliefs, but low levels of evidence-based practice implementation. In nursing educators' and undergraduate nursing students' perspectives, there were opportunities in their schools for the development of an evidence-based practice culture. Based on results, support for development and testing of interventions, specifically tailored for promoting evidence-based practice implementation in nursing educational contexts, is recommended.
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http://dx.doi.org/10.1016/j.nepr.2021.103122DOI Listing
July 2021

Prognostic Implications of MRI Melanin Quantification and Cytogenetic Abnormalities in Liver Metastases of Uveal Melanoma.

Cancers (Basel) 2021 May 31;13(11). Epub 2021 May 31.

Department of Radiology, Institut Curie, 75005 Paris, France.

To evaluate the prognostic implications of melanin quantification assessed by magnetic resonance imaging (MRI) with respect to the clinical, pathological, and genetic features of liver metastases of uveal melanoma (LMUM). This single-center retrospective cohort study included 63 patients eligible for margin-free resection of LMUM between 2007 and 2018. Comparative genomic hybridization of resected liver metastases on microarrays was performed for genetic risk classification. Metastases exhibiting monosomy 3 with any type of gain of chromosome 8 (M3/8g) were considered high-genetic-risk. MRI melanin quantification using the mean T1 signal (mT1s) in liver metastases was assessed quantitatively on preoperative imaging examination and compared to that of gross pathological evaluation. The association between MRI melanin quantification and overall survival (OS) was assessed by multivariate analysis using the Cox proportional hazards model. Gross pathological assessment of melanin content and MRI melanin quantification were strongly correlated (r = 0.8, < 0.001). Independent prognostic factors associated with OS were disease-free interval ≤ 24 months (HR = 3.1; 95% CI, 1.6-6.0; < 0.001), high-genetic-risk (HR = 2.2; 95% CI, 1.1-4.8; = 0.04), mT1s > 1.1 (HR = 2.3; 95% CI, 1.2-4.7; = 0.019), and complete hepatic resection (HR = 0.3; 95% CI, 0.2-0.7; = 0.004). In patients with high-genetic-risk, mT1s showed a significant association with OS (HR = 3.7; 95% CI, 1.5-9.3; = 0.006). The median OS was 17.5 months vs. 27 months for >1.1 and ≤1.1 mT1s tumors, respectively ( = 0.003). We showed that the level of pigmentation in M3/8g LMUM identified two subsets that were correlated with distinct clinical outcomes.
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http://dx.doi.org/10.3390/cancers13112728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198670PMC
May 2021

[New drug approval: Dostarlimab - second line in advanced MSI endometrial cancer].

Bull Cancer 2021 Jul-Aug;108(7-8):675-676. Epub 2021 May 14.

PSL Research University, Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75248 Paris cedex 05, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2021.04.006DOI Listing
May 2021

[Why and how to assess older people with cancer?]

Bull Cancer 2021 May 6;108(5):513-520. Epub 2021 Apr 6.

Institut Curie, université PSL, département interdisciplinaire de soins de support pour le patient en oncologie (DISSPO) et département d'oncologie médicale, 35, rue Dailly, 92210 Saint-Cloud, France.

The older population accounts for almost 60% of new cancers. Their management is a public health problem and is complex. It raises different questions: Is the patient's prognosis linked to cancer or another pathology? The heterogeneity of this population emphasises the importance of the overall condition assessment, in particular to avoid over-treatment (or under-treatment), and to be able to identify frail or vulnerable elderly patients who are at risk of having more treatment toxicities. Through this article, we will recall the importance of geriatric in-depth evaluation (EGA) by detailing the different factors that impact the therapeutic decision, tolerance to treatments… This EGA is however time-consuming and not all patients can be evaluated. In order to identify the subjects covered by this EGA, screening scales have been developed. Finally, we will develop the place of research in oncogeriatric management.
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http://dx.doi.org/10.1016/j.bulcan.2021.01.011DOI Listing
May 2021

Splicing Patterns in -Mutated Uveal Melanoma Generate Shared Immunogenic Tumor-Specific Neoepitopes.

Cancer Discov 2021 Aug 2;11(8):1938-1951. Epub 2021 Apr 2.

INSERM U932, PSL University, Institut Curie, Paris, France.

Disruption of splicing patterns due to mutations of genes coding splicing factors in tumors represents a potential source of tumor neoantigens, which would be both public (shared between patients) and tumor-specific (not expressed in normal tissues). In this study, we show that mutations of the splicing factor in uveal melanoma generate such immunogenic neoantigens. Memory CD8 T cells specific for these neoantigens are preferentially found in 20% of patients with uveal melanoma bearing -mutated tumors. Single-cell analyses of neoepitope-specific T cells from the blood identified large clonal T-cell expansions, with distinct effector transcription patterns. Some of these expanded T-cell receptors are also present in the corresponding tumors. CD8 T-cell clones specific for the neoepitopes specifically recognize and kill -mutated tumor cells, supporting the use of this new family of neoantigens as therapeutic targets. SIGNIFICANCE: Mutations of the splicing factor in uveal melanoma generate shared neoantigens that are uniquely expressed by tumor cells, leading to recognition and killing by specific CD8 T cells. Mutations in splicing factors can be sources of new therapeutic strategies applicable to diverse tumors..
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http://dx.doi.org/10.1158/2159-8290.CD-20-0555DOI Listing
August 2021

[New drug approval: Olaparib and niraparib - first line in ovarian cancer].

Bull Cancer 2021 Apr 26;108(4):350-351. Epub 2021 Feb 26.

Institut Curie, PSL research university, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France; Institut Curie, PSL research university, Inserm U830, 26, rue d'Ulm, 75005 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2021.01.003DOI Listing
April 2021

[Pembrolizumab as first-line therapy in microsatellite instability metastatic colorectal cancers].

Bull Cancer 2021 Mar 23;108(3):229-231. Epub 2021 Feb 23.

CHU Lille, service d'oncologie médicale, 59000 Lille, France; Université. Lille, CNRS, Inserm, UMR9020-UMR-S 1277, CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000 Lille, France.

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http://dx.doi.org/10.1016/j.bulcan.2021.01.004DOI Listing
March 2021

Ultraviolet radiation drives mutations in a subset of mucosal melanomas.

Nat Commun 2021 01 11;12(1):259. Epub 2021 Jan 11.

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, SK10 4TG, UK.

Although identified as the key environmental driver of common cutaneous melanoma, the role of ultraviolet radiation (UVR)-induced DNA damage in mucosal melanoma is poorly defined. We analyze 10 mucosal melanomas of conjunctival origin by whole genome sequencing and our data shows a predominance of UVR-associated single base substitution signature 7 (SBS7) in the majority of the samples. Our data shows mucosal melanomas with SBS7 dominance have similar genomic patterns to cutaneous melanomas and therefore this subset should not be excluded from treatments currently used for common cutaneous melanoma.
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http://dx.doi.org/10.1038/s41467-020-20432-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801393PMC
January 2021

[What should we remember from 2020?]

Bull Cancer 2021 Jan 6;108(1):55-66. Epub 2021 Jan 6.

Université de Bordeaux, Inserm U1218, 33000 Bordeaux, France.

The editorial committee of the Bulletin du Cancer is proud to comply with his annual analysis of some of the worldwide updates in oncology that emerge in 2020. We know that all new breakthroughs will not be addressed and apologise for not being comprehensive, but we hope that the topics deciphered herein will bring the reader interesting information in his daily practice in gyneco-oncology, uro-oncology, neuro-oncology, digestive oncology, pneumo-oncology, hemato-oncology, pediatric oncology, or in palliative care.
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http://dx.doi.org/10.1016/j.bulcan.2020.12.002DOI Listing
January 2021

The Effectiveness of an Evidence-Based Practice (EBP) Educational Program on Undergraduate Nursing Students' EBP Knowledge and Skills: A Cluster Randomized Control Trial.

Int J Environ Res Public Health 2021 01 3;18(1). Epub 2021 Jan 3.

Health Sciences Research Unit: Nursing, Nursing School of Coimbra, Portugal Centre for Evidence-Based Practice: A Joanna Briggs Institute Centre of Excellence, 3004-011 Coimbra, Portugal.

Evidence-based practice (EBP) prevents unsafe/inefficient practices and improves healthcare quality, but its implementation is challenging due to research and practice gaps. A focused educational program can assist future nurses to minimize these gaps. This study aims to assess the effectiveness of an EBP educational program on undergraduate nursing students' EBP knowledge and skills. A cluster randomized controlled trial was undertaken. Six optional courses in the Bachelor of Nursing final year were randomly assigned to the experimental (EBP educational program) or control group. Nursing students' EBP knowledge and skills were measured at baseline and post-intervention. A qualitative analysis of 18 students' final written work was also performed. Results show a statistically significant interaction between the intervention and time on EBP knowledge and skills ( = 0.002). From pre- to post-intervention, students' knowledge and skills on EBP improved in both groups (intervention group: < 0.001; control group: < 0.001). At the post-intervention, there was a statistically significant difference in EBP knowledge and skills between intervention and control groups ( = 0.011). Students in the intervention group presented monographs with clearer review questions, inclusion/exclusion criteria, and methodology compared to students in the control group. The EBP educational program showed a potential to promote the EBP knowledge and skills of future nurses.
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http://dx.doi.org/10.3390/ijerph18010293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795378PMC
January 2021

Fresno test to measure evidence-based practice knowledge and skills for Portuguese undergraduate nursing students: A translation and adaptation study.

Nurse Educ Today 2021 Feb 24;97:104671. Epub 2020 Nov 24.

Health Sciences Research Unit: Nursing, Nursing School of Coimbra, P.O. Box 7001, 3046-851 Coimbra, Portugal; Nursing School of Coimbra, P.O. Box 7001, 3046-851 Coimbra, Portugal; Portugal Centre for Evidence-Based Practice: A Joanna Briggs Institute Centre of Excellence, Health Sciences Research Unit: Nursing, Nursing School of Coimbra, P.O. Box 7001, 3046-851 Coimbra, Portugal. Electronic address:

Background: The Fresno Test was originally identified as an instrument to assess evidence-based practice knowledge and skills through cognitive testing and performance assessment in medical students. Further studies have been recommended to establish the measurement properties of the Fresno Test in different learner populations.

Objectives: To perform a cross-cultural adaptation of the Fresno Test for Portuguese undergraduate nursing students and to analyze the interrater reliability.

Design: Cross-cultural adaptation study with interrater reliability assessment carried out in two phases during 2017-2018.

Settings: One of the main nursing schools, Portugal.

Participants: Fourth year undergraduate nursing students.

Methods: The study was performed in two phases, firstly the cross-cultural adaptation (performed in five stages) and secondly the analysis of interrater reliability.

Results: Stages I, II, III and IV of the cross-cultural adaptation proceeded smoothly and the expert panel produced and agreed upon the pre-final version of Adapted Fresno Test. In stage V (the pre-test stage), students reported a general understanding of the items, but they reported a lack of knowledge to answer the test. An expert panel subsequently agreed that modifications were needed to ensure the test was within the student's competency level and to decrease risk of assessment bias. For phase II, 50 complete questionnaires were randomly selected to be rated by three independent nurses using the modified rubric to score the test. The overall interrater reliability was 0.826 with a range from 0.271 to 1.000 for each item.

Conclusions: The Adapted Fresno Test presented in this paper is the first instrument translated for European Portuguese and adapted specially for undergraduate nursing students. Despite good interrater reliability, further validation studies with more robust samples are suggested to definitively establish psychometric properties beyond the interrater reliability.
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http://dx.doi.org/10.1016/j.nedt.2020.104671DOI Listing
February 2021

[Drug approval : entrectinib and larotrectinib - cancers with NTRK fusion].

Bull Cancer 2020 Nov 21;107(11):1085-1086. Epub 2020 Oct 21.

PSL Research University, institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France; PSL Research University, institut Curie, Inserm U830, 26, rue d'Ulm, 75005 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.09.009DOI Listing
November 2020

Plasma thymidine kinase 1 activity and outcome of ER+ HER2- metastatic breast cancer patients treated with palbociclib and endocrine therapy.

Breast Cancer Res 2020 09 14;22(1):98. Epub 2020 Sep 14.

Department of Medical Oncology, Institut Curie, Saint-Cloud, 92210, Paris, France.

Purpose: Previous cohort studies have reported plasma TK1 activity (pTKa) as a potential prognostic biomarker in estrogen receptor-positive (ER+) HER2-negative (HER2-) metastatic breast cancer (MBC). In this prospective study, we report here the prognostic impact of pTKa in ER+/HER2- MBC patients treated with endocrine therapy and CDK4/6 inhibitor.

Experimental Design: Patients were included into the prospective, ethics committee-approved ALCINA study (NCT02866149). Eligibility criteria were patients with ER+/HER2- MBC treated at Institut Curie with endocrine therapy and palbociclib. Plasma samples were obtained at baseline and after 4 weeks of treatment. pTKa was quantified by the DiviTum® assay (Biovica, Sweden).

Results: From May 2016 to August 2018, 103 patients treated with endocrine therapy and palbociclib were included. Patients had received a median of two prior systemic therapies for MBC (range 0-14). Median follow-up was 13.8 months (range 6-31), with median PFS and OS of 9.6 months (95%CI [7.0-11.3]) and 28 months (95%CI [23-not reached]), respectively. Median baseline pTKa was 292 Du/L (range 20-27,312 Du/L, IQR [89-853]). After adjusting for other prognostic factors, baseline pTKa remained an independent prognostic factor for both PFS (HR = 1.3 95%CI [1.1-1.4], p = 0.0005) and OS (HR = 1.3 95%CI [1.2-1.6], p < 0.0001), and 4-week pTKa was associated with OS (HR = 1.6 95%CI [1.3-2], p < 0.0001). That survival prediction was significantly improved by the addition of baseline pTKa to clinicopathological characteristics. Adding pTKa changes at 4 weeks to baseline pTKa did not further increase survival prediction.

Conclusion: This study demonstrates the clinical validity of pTKa as a new circulating prognostic marker in ER+/HER2- MBC patients treated with endocrine therapy and palbociclib.
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http://dx.doi.org/10.1186/s13058-020-01334-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489000PMC
September 2020

RISK AND PREVENTIVE FACTORS FOR TRAFFIC ACCIDENTS: ANALYSIS OF CHILDREN'S PERCEPTION USING THE EDUTHERAPEUTIC METHOD.

Rev Paul Pediatr 2020 13;38:e2018281. Epub 2020 Jul 13.

Universidade Federal de Sergipe, Lagarto, SE, Brazil.

Objective: To describe children's perception of risk and preventive factors related to traffic accidents using the Edutherapeutic Method.

Methods: This is a qualitative descriptive study carried out with 173 students from public schools aged seven to 14 years in Lagarto, Sergipe, Brazil. Data were collected in the second half of 2014. The first stage consisted of an activity with drawing/writing sheets in all classes selected by the Nursing undergraduate students. Next, the children answered a questionnaire on sociodemographic data. The qualitative analysis of the expressive language of the children's drawings generated two categories: positive and negative factors for the prevention of traffic accidents and their subcategories.

Results: The children's perception regarding preventive and risk factors for traffic accidents was considered adequate according to other studies found in the literature on the same subject. The drawings and descriptions were used later to provide the students with a better understanding of these factors.

Conclusions: The study lends support to educational activities and interventions about prevention with schoolchildren. This is one of the main goals proposed by Brazil in the National Plan of Action for Road Traffic Safety for the decade 2011-2020.
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http://dx.doi.org/10.1590/1984-0462/2020/38/2018281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357599PMC
August 2021

[AERIO (Young Oncologists French Association) joins BulletinduCancer journal].

Bull Cancer 2020 Jun;107(6):615-616

CHU de Clermont-Ferrand, service de thérapie cellulaire et d'hématologie clinique adulte, UE7453 CHELTER, Inserm CIC-501, site Estaing, Clermont-Ferrand, France.

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http://dx.doi.org/10.1016/j.bulcan.2020.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286238PMC
June 2020

[COVID-19 and cancers. Summary of French guidelines from medical societies and their evolution].

Authors:
Manuel Rodrigues

Bull Cancer 2020 05;107(5):521-523

Institut Curie, PSL research university, département d'oncologie médicale, 75005 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255101PMC
May 2020

[Impact of the COVID-19 epidemic on requests for initial care for breast cancer].

Bull Cancer 2020 Jun 30;107(6):620-622. Epub 2020 Apr 30.

Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France; Institut Curie, département d'oncologie médicale, 26, rue d'Ulm, 75005 Paris, France.

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http://dx.doi.org/10.1016/j.bulcan.2020.04.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190490PMC
June 2020

[Covid-19, the Société française du cancer (SFC) and the BulletinduCancer].

Authors:
Manuel Rodrigues

Bull Cancer 2020 Apr;107(4):393-394

Institut Curie, PSL research university, département d'oncologie médicale, 75005 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2020.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175863PMC
April 2020

Germline MBD4 Mutations and Predisposition to Uveal Melanoma.

J Natl Cancer Inst 2021 01;113(1):80-87

Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe Labellisée Par la Ligue Nationale Contre le Cancer, Paris, France.

Background: Uveal melanoma (UM) arises from malignant transformation of melanocytes in the uveal tract of the eye. This rare tumor has a poor outcome with frequent chemo-resistant liver metastases. BAP1 is the only known predisposing gene for UM. UMs are generally characterized by low tumor mutation burden, but some UMs display a high level of CpG>TpG mutations associated with MBD4 inactivation. Here, we explored the incidence of germline MBD4 variants in a consecutive series of 1093 primary UM case patients and a series of 192 UM tumors with monosomy 3 (M3).

Methods: We performed MBD4 targeted sequencing on pooled germline (n = 1093) and tumor (n = 192) DNA samples of UM patients. MBD4 variants (n = 28) were validated by Sanger sequencing. We performed whole-exome sequencing on available tumor samples harboring MBD4 variants (n = 9). Variants of unknown pathogenicity were further functionally assessed.

Results: We identified 8 deleterious MBD4 mutations in the consecutive UM series, a 9.15-fold (95% confidence interval = 4.24-fold to 19.73-fold) increased incidence compared with the general population (Fisher exact test, P = 2.00 × 10-5, 2-sided), and 4 additional deleterious MBD4 mutations in the M3 cohort, including 3 germline and 1 somatic mutations. Tumors carrying deleterious MBD4 mutations were all associated with high tumor mutation burden and a CpG>TpG hypermutator phenotype.

Conclusions: We demonstrate that MBD4 is a new predisposing gene for UM associated with hypermutated M3 tumors. The tumor spectrum of this predisposing condition will likely expand with the addition of MBD4 to diagnostic panels. Tumors arising in such a context should be recognized because they may respond to immunotherapy.
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http://dx.doi.org/10.1093/jnci/djaa047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781447PMC
January 2021

High-Accuracy Determination of Microsatellite Instability Compatible with Liquid Biopsies.

Clin Chem 2020 04;66(4):606-613

Inserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.) team, Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, Paris, France.

Background: Microsatellite instability (MSI) has recently emerged as a predictive pan-tumor biomarker of immunotherapy efficacy, stimulating the development of diagnostic tools compatible with large-scale screening of patients. In this context, noninvasive detection of MSI from circulating tumor DNA stands as a promising diagnostic and posttreatment monitoring tool.

Methods: We developed drop-off droplet-digital PCR (ddPCR) assays targeting BAT-26, activin A receptor type 2A (ACVR2A), and defensin beta 105A/B (DEFB105A/B) microsatellite markers. Performances of the assays were measured on reconstitution experiments of various mutant allelic fractions, on 185 tumor samples with known MSI status, and on 72 blood samples collected from 42 patients with advanced colorectal or endometrial cancers before and/or during therapy.

Results: The 3 ddPCR assays reached analytical sensitivity <0.1% variant allelic frequency and could reliably detect and quantify MSI in both tumor and body fluid samples. High concordance between MSI status determination by the three-marker ddPCR test and the reference pentaplex method were observed (100% for colorectal tumors and 93% for other tumor types). Moreover, the 3 assays showed correlations with r ≥ 0.99 with other circulating tumor DNA markers and their dynamic during treatment correlated well with clinical response.

Conclusions: This innovative approach for MSI detection provides a noninvasive, cost-effective, and fast diagnostic tool, well suited for large-scale screening of patients that may benefit from immunotherapy agents, as well as for monitoring treatment responses.
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http://dx.doi.org/10.1093/clinchem/hvaa013DOI Listing
April 2020

[2019 international oncology news: A compendium].

Bull Cancer 2020 Feb 10;107(2):148-156. Epub 2020 Feb 10.

Centre hospitalier universitaire Giscard d'Estaing, service thérapie cellulaire et hématologie clinique, 58, rue Montalembert, 63000 Clermont Ferrand, France.

Over the past years, planet oncology has kept changing and moving forward. Recent results of important clinical trials are challenging our daily practices. With modesty, the Editorial Board of BulletinduCancer has selected some clinical trials they consider as "must-know about" even if they go beyond our medical fields.
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http://dx.doi.org/10.1016/j.bulcan.2020.01.010DOI Listing
February 2020

[KRASG12C mutation is not undruggable anymore].

Authors:
Manuel Rodrigues

Bull Cancer 2020 Feb 16;107(2):145. Epub 2020 Jan 16.

DNA Repair and Uveal Melanoma (DRUM), Inserm U830, équipe labellisée par la Ligue nationale contre le cancer, 26, rue d'Ulm, 75005 Paris, France; Institut Curie, PSL research university, département d'oncologie médicale, 75005 Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2019.11.008DOI Listing
February 2020

[PARP inhibitors in first-line of ovarian cancers].

Authors:
Manuel Rodrigues

Bull Cancer 2020 Jan 10;107(1):4-5. Epub 2020 Jan 10.

DNA Repair and Uveal Melanoma (D.R.U.M.), Équipe labellisée par la Ligue Nationale Contre le Cancer, Inserm U830, Paris, France; PSL Research University, institut Curie, département d'oncologie médicale, Paris, France. Electronic address:

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http://dx.doi.org/10.1016/j.bulcan.2019.10.009DOI Listing
January 2020

Association of Partial Chromosome 3 Deletion in Uveal Melanomas With Metastasis-Free Survival.

JAMA Ophthalmol 2020 02;138(2):182-188

Department of Genetics, Institut Curie, PSL Research University, Paris, France.

Importance: Studies on uveal melanomas (UMs) have demonstrated the prognostic value of 8q gain and monosomy 3, but the prognosis of UMs with partial deletion of chromosome 3 remains to be defined.

Objective: To examine the association of partial chromosome 3 deletion in UMs with metastasis-free survival.

Design, Setting, And Participants: This retrospective cohort study of 1088 consecutive comparative genomic hybridization arrays performed from May 1, 2006, to July 31, 2015, assessed patients presenting with UMs with and without partial loss of chromosome 3 at a referral center. Data analysis was performed from September 1, 2017, to November 30, 2017.

Exposure: Uveal melanoma with or without partial loss of chromosome 3.

Main Outcomes And Measures: Metastasis-free survival and overall survival at 60 months.

Results: Of the 1088 consecutive comparative genomic hybridization arrays that were performed, 43 UMs (4.0%) in 43 patients (median age, 58 years [range, 12-79 years]; 22 [51%] female) carried partial deletions of chromosome 3. Median follow-up was 66 months (range, 1.2-126.2 months). Metastasis-free survival at 60 months was 33.6% (95% CI, 15.8%-71.4%) for UMs that carried a deletion of the BAP1 (BRCA1 associated protein 1) locus (BAP1del; 24 tumors) and 80.5% (95% CI, 64.8%-100%) for UMs without the loss of the BAP1 locus (BAP1 normal [BAP1nl]; 19 tumors) (log-rank P = .001). Overall survival at 60 months was 64.5% (95% CI, 43.5%-95.8%) in the BAP1del group vs 84.1% (95% CI, 69.0%-100%) in the BAP1nl group (log-rank P < .001). In these 43 cases, metastasis-free survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 70.0% (95% CI, 50.5%-96.9%) for UMs that carried 1 of these alterations, and 12.5% (95% CI, 2.1%-73.7%) for those that carried both (log-rank P < .001). Similarly, overall survival at 60 months was 100% for UMs without loss of the BAP1 locus or 8q gain, 80.8% (95% CI, 63.3%-100%) for UMs that carried 1 of these alterations, and 46.7% (95% CI, 23.3%-93.6%) for those that carried both (log-rank P < .001).

Conclusions And Relevance: These findings suggest that partial deletion of chromosome 3 encompassing the BAP1 locus is associated with poor prognosis. A cytogenetic classification of UMs could be proposed based on the status of the BAP1 locus instead of the chromosome 3 locus, while also taking chromosome 8q into account.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.5403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6990836PMC
February 2020
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