Yannick Romero

Union for International Cancer Control | UICC

Growing premature mortality because of cancer is an increasing public health concern in all countries. This article reviews 10 years of the International Cancer Control Partnership (ICCP) considering the themes of National Cancer Control Plan (NCCP) support, technical assistance, governance, and the renewed momentum of global calls to action. ICCP...

With the advent of innovative therapeutics for and the rising costs of cancer management, low-income and middle-income countries face increasing challenges to deliver effective and sustainable health care. Understanding of how countries are selecting and prioritising essential cancer interventions is poor, including in the formulation of policies f...

In order to understand the structure and effectiveness of national cancer control systems, the International Cancer Control Partnership, the World Health Organization, the National Cancer Institute and the Union for International Cancer Control underwent a review of available national cancer health plans (NCCPs) and noncommunicable diseases plans (...

When developed and implemented effectively, national cancer control plans (NCCPs) improve cancer outcomes at the population level. However, many countries do not have a high-quality, operational NCCP, contributing to disparate cancer outcomes globally. Until now, a standard reference of NCCP core elements has not been available to guide development...

There is increasing global recognition that national cancer plans are crucial to effectively address the cancer burden and to prioritise and coordinate programmes. We did a global analysis of available national cancer-related health plans using a standardised assessment questionnaire to assess their inclusion of elements that characterise an effect...

Objective miR-21 is an oncomir highly upregulated in hepatocellular carcinoma and in early stages of liver diseases characterised by the presence of steatosis. Whether upregulation of miR-21 contributes to hepatic metabolic disorders and their progression towards cancer is unknown. This study aims at investigating the role of miR-21/miR-21* in earl...

Small non-coding RNAs act as critical regulators of gene expression and are essential for male germ cell development and spermatogenesis. Previously, we showed that germ cell-specific inactivation of Dicer1, an endonuclease essential for the biogenesis of micro-RNAs (miRNAs) and endogenous small interfering RNAs (endo-siRNAs), led to complete male...

Mouse sex determination provides an attractive model to study how regulatory genetic networks and signaling pathways control cell specification and cell fate decisions. This study characterizes in detail the essential role played by the insulin receptor (INSR) and the IGF type I receptor (IGF1R) in adrenogenital development and primary sex determin...

Absence of testicular markers in XX dko gonads. The expression of key testicular markers was assessed in control and dko XX gonads at E12.5, E12.5 and E16.5 with double immunofluorescence using either the Sertoli cell marker SOX9 (A–F, in green) or the Leydig cell marker P450SCC (G–L, in green) along with E–cadherin (red). (PDF)

Reduced proliferation rates in somites, mesonephroi and heart of dko embryos at E10.5 and E11.5. (A) Cell proliferation in the developing somites, mesonephroi and heart was evaluated by immunofluorescence using the proliferating marker KI67 (green). In somites and heart, proliferating cells are positive for KI67 (green) and DAPI (blue), whereas in...

Representation of the 397 probesets being differentially expressed in dko SF1+ cells. (A) Graphic representations of the number of probesets found up- (green) or down-regulated (red) for each of the pairwise comparisons performed between the 4 analyzed samples. (B) Heatmap representation of the probesets exhibiting an altered signal in mutant SF1+...

Genes from known biological processes are affected in dko gonads. Selection of a set of Gene Ontology (GO) terms found enriched within the two groups of up- and down-regulated genes. Each cluster is matched with enriched GO terms from the ontologies “biological process”, “molecular function” and “cellular component”, and the numbers of genes (Entre...

GFP fluorescence of SF1+ cells was not affected by the genetic sex and the genotype of developing embryos. Representative FACS graphs showing the typical and identical pattern of Sf1/eGFP+ cell distribution from control (A) or dko (B) XY genital ridges at E11.5. FL1H axis represents the levels of fluorescence (arbitrary units) while the x axis refl...

3-ways ANOVA analysis of the sources of gene expression variation for 65 selected genes measured by the Nanostring Ncounter system. (PDF)

Alteration of genes involved in the MAPK pathway. Transcript levels were assessed in XY and XX control and dko gonads at E11.5 and E12.5 by Affymetrix analyses or by qRT-PCR. Values are expressed as means ± SEM, **p<0.01, ***p<0.001 vs control. (PDF)

Primer sequences used for Real-Time PCR. (PDF)

Expression profiles of known female dimorphic genes within the dko gonads. Probeset intensities between XX and XY control and dko mutant SF1+ cells at E11.5 were pairwise compared and submitted to an unpaired t-test to evaluate the relevance of differences between samples, *p<0.05, **p<0.01, ***p<0.001 vs control. Graphs illustrating the expression...

Alteration of genes involved in the glycogen synthesis pathway. Pathway for conversion of glucose monomers to polymeric glycogen including relevant enzymes. Transcript levels for these enzymes were assessed in XY and XX control and dko gonads at E11.5 and E12.5 by Affymetrix analyses or by qRT-PCR. Values are expressed as means ± SEM, **p<0.01, ***...

Markers of both somatic progenitors and germ cells are normally present in dko gonads at E10.5 and E11.5. The presence of both somatic precursors and germ cells in control and dko gonads at E10.5 and E11.5 was assessed by immunofluorescence using either the somatic progenitor cell marker GATA4 (A,B, in red) or the germ cell marker OCT4 (C,D, in red...

Expression profiles of known male dimorphic genes in dko gonads. Probeset intensities between XX and XY control and dko mutant SF1+ cells at E11.5 were pairwise compared and submitted to an unpaired t-test to evaluate the significance of differences between samples, *p<0.05, **p<0.01, ***p<0.001 vs control. Graphs illustrating the expression profil...

Expression profiles of 65 genes as determined by NanoString Multiplex Assays. (A) Analysis of the sources of variation (ANOVA) revealed that the main sources of variations are genotype, sex and time. (B) The set of selected genes includes classical genes involved in the testicular program, the ovarian program, adrenogonadal development and insulin/...

Validation of the RMA normalization process. (A) Box plot representation of expression data before and after RMA normalization. Scale bar indicates Log2-transformed probeset intensities. WT = control; Mut = dko. (B) Correlation matrix for sample duplicates. High and low degrees of similarity between two samples are displayed in black and white, res...

List of Affymetrix mouse 430.2 microarray probesets differentially expressed between control and dko gonads at E11.5. We provide for each probeset: the characteristics of the corresponding genes (probeset IDs, Entrez gene, homologene, GeneName, and expression group); the log2-transformed expression values and fold changes associated to each of the...

Reagents and antibodies. (PDF)

Spermatogenesis relies on the precise regulation of the self-renewal and differentiation of spermatogonia to provide a continuous supply of differentiating germ cells. The understanding of the cellular pathways regulating this equilibrium remains unfortunately incomplete. This investigation aimed to elucidate the testicular and ovarian functions of...

The continuous production of spermatozoa is a tightly regulated biological process, both at the transcriptional and post-transcriptional levels. Recently, different classes of small non-coding RNAs have emerged as important regulators of spermatogenesis. Available molecular and genetic data, although still fragmented, underscore their crucial role...

La production continue de spermatozoïdes est un processus biologique strictement régulé, tant au niveau transcriptionnel que post-transcrip-tionnel. Récemment, les petits ARN non codants ont été identifiés dans la lignée germinale mâle et dans les cellules somatiques testiculaires et se sont avérés essentiels à la fertilité mascu-line. Cette revue...

Accumulation of metaphasic-like cell population in Ddx4-Cre;Dcr1 fx/fx (−/−)tubules. At P60, undergoing metaphasic cells are more abundant in Dicer1 mutant as shown by Histone H3Ser-10 phosphorylated (pH 3) positive cells (green, A and B). (C) shows a 2.5-fold increase of pH 3 positive tubules in −/− versus +/+ individuals. Cross-sections were coun...

The early spermatogenic phase is not affected in Ddx4-Cre;Dcr1fx/fx (−/−) individuals. H&E staining of P5 (A&B) and P10 (C&D) cross-sections from control (A&C) and −/− (B&D) seminiferous tubules. At these stages, no histological differences were observed between mutant and control testes. (TIF)

Sertoli cells organization and number are not affected in testes lacking Dicer1 in the germinal compartment. Gata-4 immunostaining (red) revealed the presence of Sertoli cells nuclei at the edge of tubules in Dcr1fx/fx (+/+) control individuals (A) as well as in Ddx4-Cre;Dcr1fx/fx mutant mice (−/−) (B), indicating that Sertoli cells organization is...

Apoptotic cell population display pachytene spermatocytes localisation in Ddx4-Cre;Dcr1fx/fx (−/−) tubules. At P60, TUNEL-positive cells (green) are found near late prophase I spermatocytes in Dicer1 mutant as shown by γH2AX staining of the XY body (red foci, white arrowheads in A and B). C and D show the localization of prophase I cells at the edg...

Frequency of Ddx4-Cre;Dcr1fx/fx obtained is lower than expected. Ddx4-Cre;Dcr1 fx/wt males were mated with Dcr1fx/fx females in order to produce Ddx4-Cre;Dcr1fx/fx (−/−) as well as Dcr1fx/fx (+/+) and Ddx4-Cre;Dcr1fx/wt (+/−) control littermates. The genetic background of these mice is mixed. The expected Mendelian ratio should be 25% for each geno...

Table comparing reproductive and endocrine measurements between Ddx4-Cre;Dcr1fx/fx (−/−) individuals compared to Dcr1fx/fx (+/+) and Ddx4-Cre;Dcr1fx/wt (+/−) control littermates. (TIF)

Spermatogenesis is a complex biological process that requires a highly specialized control of gene expression. In the past decade, small non-coding RNAs have emerged as critical regulators of gene expression both at the transcriptional and post-transcriptional level. DICER1, an RNAse III endonuclease, is essential for the biogenesis of several clas...

PAS staining of adult testis sections. Bouin's-fixed and paraffin embedded Dcr(fx/fx) and Dcr(fx/fx);Ngn3Cre testes were sectioned and stained with Periodic-Acid-Schiff. Staging of the seminiferous epithelial cycle of the tubule cross sections was done on the basis of the presence and organization of different types of spermatids. Stages of the sem...

Tubular organization in knockout testes is normal. Anti-DDX4/MVH (A) and anti-GATA4 (B) immunofluorescence on Dcr(fx/fx), Dcr(fx/wt);Ngn3Cre and Dcr(fx/fx);Ngn3Cre testis sections (60 dpp and 120 dpp) revealed the normal localization of germ (DDX4/MVH) and Sertoli (GATA4) cells within the heterozygous and knockout seminiferous tubules. Scale bar: 5...

Electron microscopic analysis. A) Synaptonemal complexes (arrows) were detected in knockout pachytene spermatocytes. B) Fragmented acrosomes and abnormal acrosomal structures were frequently observed (asterisk), and Golgi complexes appeared unusually prominent (arrows) in knockout round spermatids. C) The chromatoid body (arrows) of Dicer1 knockout...

HE staining of testis sections. Bouin's-fixed and paraffin-embedded Dcr(fx/fx) and Dcr(fx/fx);Ngn3Cre testes section at 21 and 35 dpp were stained by hematoxylin and eosin. Staging of the seminiferous epithelial cycle was done on the basis of the presence and organization of different types of spermatogonia, and on the basis of the presence, organi...

Heterochromatin patterns in Dicer1 knockout male germ cells. Immunofluorescence staining of control and knockout testis sections with antibodies against dimethylated H3 Lysine 9 (A) and CENP-A (B) demonstrated no gross abnormalities in the heterochromatin patterns of knockout testes. Nuclei are stained with DAPI (blue). Stages of the seminiferous e...

The RNase III endonuclease Dicer is an important regulator of gene expression that processes microRNAs (miRNAs) and small interfering RNAs (siRNAs). The best-characterized function of miRNAs is gene repression at the post-transcriptional level through the pairing with mRNAs of protein-encoding genes. Small RNAs can also act at the transcriptional l...

We have previously identified a mutation in the mouse hairless locus-hairless rhino bald Mill Hill (Hr(rhbmh)). The genetic alteration in these mice consists in a large 296 bp deletion at the 3' part of the hairless gene (ID:MGI:3039558; J:89321). Here, we show that this deletion removes the stop codon and creates a new reading frame at the C termi...

The hairless gene in mammals encodes a nuclear factor that is highly expressed in skin and appears to control hair follicle integrity and cycling. In the absence of a normal and functional Hairless (Hr) protein, the hair bulb undergoes premature apoptosis during the first catagen stage of the hair cycle. The most striking effects of the mutation ar...