Search results for "Hedgehog"

How to make a tongue: Cellular and molecular regulation of muscle and connective tissue formation during mammalian tongue development

2018

IF 6.614 (2016); International audience; The vertebrate tongue is a complex muscular organ situated in the oral cavity and involved in multiple functions including mastication, taste sensation, articulation and the maintenance of oral health. Although the gross embryological contributions to tongue formation have been known for many years, it is only relatively recently that the molecular pathways regulating these processes have begun to be discovered. In particular, there is now evidence that the Hedgehog, TGF-Beta, Wnt and Notch signaling pathways all play an important role in mediating appropriate signaling interactions between the epithelial, cranial neural crest and mesodermal cell pop…

Pivotal roles of glycogen synthase-3 in hepatocellular carcinoma

2017

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and represents the second most frequently cancer and third most common cause of death from cancer worldwide. At advanced stage, HCC is a highly aggressive tumor with a poor prognosis and with very limited response to common therapies. Therefore, there is still the need for new effective and well-tolerated therapeutic strategies. Molecular-targeted therapies hold promise for HCC treatment. One promising molecular target is the multifunctional serine/threonine kinase glycogen synthase kinase 3 (GSK-3). The roles of GSK-3β in HCC remain controversial, several studies suggested a possible role of GSK-3β as a tumor …

2016

AbstractStem cells control their mitotic activity to decide whether to proliferate or to stay in quiescence. Drosophila neural stem cells (NSCs) are quiescent at early larval stages, when they are reactivated in response to metabolic changes. Here we report that cell-contact inhibition of growth through the canonical Hippo signalling pathway maintains NSC quiescence. Loss of the core kinases hippo or warts leads to premature nuclear localization of the transcriptional co-activator Yorkie and initiation of growth and proliferation in NSCs. Yorkie is necessary and sufficient for NSC reactivation, growth and proliferation. The Hippo pathway activity is modulated via inter-cellular transmembran…

Inhibition of GLI2 with antisense-oligonucleotides: A potential therapy for the treatment of bladder cancer.

2019

The sonic hedgehog (SHH) signaling pathway plays an integral role in the maintenance and progression of bladder cancer (BCa) and SHH inhibition may be an efficacious strategy for BCa treatment. We assessed an in-house human BCa tissue microarray and found that the SHH transcription factors, GLI1 and GLI2, were increased in disease progression. A panel of BCa cell lines show that two invasive lines, UM-UC-3 and 253J-BV, both express these transcription factors but UM-UC-3 produces more SHH ligand and is less responsive in viability to pathway stimulation by recombinant human SHH or smoothened agonist, and less responsive to inhibitors including the smoothened inhibitors cyclopamine and SANT-…

ceRNA Network Regulation of TGF-β, WNT, FOXO, Hedgehog Pathways in the Pharynx of Ciona robusta

2021

The transforming growth factor-β (TGF-β) family of cytokines performs a multifunctional signaling, which is integrated and coordinated in a signaling network that involves other pathways, such as Wintless, Forkhead box-O (FOXO) and Hedgehog and regulates pivotal functions related to cell fate in all tissues. In the hematopoietic system, TGF-β signaling controls a wide spectrum of biological processes, from immune system homeostasis to the quiescence and self-renewal of hematopoietic stem cells (HSCs). Recently an important role in post-transcription regulation has been attributed to two type of ncRNAs: microRNAs and pseudogenes. Ciona robusta, due to its philogenetic position close to verte…

Non-coding RNAs Functioning in Colorectal Cancer Stem Cells

2016

In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main…

Interfering with MIF-CD74 signalling on macrophages and dendritic cells with a peptide-based approach restores the immune response against metastatic…

2018

ABSTRACTMounting an effective immune response against cancer requires the activation of innate and adaptive immune cells. Metastatic melanoma is the most aggressive form of skin cancer. Immunotherapies that boost the activity of effector T cells have shown a remarkable success in melanoma treatment. Patients, however, can develop resistance to such therapies by mechanisms that include the establishment of an immune suppressive tumour microenvironment. Understanding how metastatic melanoma cells suppress the immune system is vital to develop effective immunotherapies against this disease. In this study, we find that the innate immune cells, macrophages and dendritic cells are suppressed in m…

TCTN3 Mutations Cause Mohr-Majewski Syndrome

2012

Orofaciodigital syndromes (OFDSs) consist of a group of heterogeneous disorders characterized by abnormalities in the oral cavity, face, and digits and associated phenotypic abnormalities that lead to the delineation of 13 OFDS subtypes. Here, by a combined approach of homozygozity mapping and exome ciliary sequencing, we identified truncating TCTN3 mutations as the cause of an extreme form of OFD associated with bone dysplasia, tibial defect, cystic kidneys, and brain anomalies (OFD IV, Mohr-Majewski syndrome). Analysis of 184 individuals with various ciliopathies (OFD, Meckel, Joubert, and short rib polydactyly syndromes) led us to identify four additional truncating TCTN3 mutations in un…

Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial.

2021

Summary Background Before February, 2021, there was no standard treatment regimen for locally advanced basal cell carcinoma after first-line hedgehog inhibitor (HHI) therapy. Cemiplimab, a PD-1 antibody, is approved for treatment of advanced cutaneous squamous cell carcinoma and has shown clinical activity as monotherapy in first-line non-small-cell lung cancer. Here, we present the primary analysis data of cemiplimab in patients with locally advanced basal cell carcinoma after HHI therapy. Methods We did an open-label, multicentre, single-arm, phase 2 trial across 38 outpatient clinics, primarily at academic medical centres, in Canada, Europe, and the USA. Eligible patients (aged ≥18 years…

Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind…

2019

Background: Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. Objectives: This is the final 42-month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib. Methods: Adults with no prior hedgehog pathway inhibitor therapy were randomized in a 1 : 2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termin…