Ask about this productRelated genes to: PTCH1 antibody
- Gene:
- PTCH1 NIH gene
- Name:
- patched 1
- Previous symbol:
- NBCCS, PTCH
- Synonyms:
- BCNS
- Chromosome:
- 9q22.32
- Locus Type:
- gene with protein product
- Date approved:
- 1996-07-19
- Date modifiied:
- 2019-04-23
Related products to: PTCH1 antibody
Related articles to: PTCH1 antibody
- Medulloblastoma (MB) is the most frequent brain malignancy in children, frequently driven by deregulated Sonic Hedgehog (SHH) signaling. We previously identified the antidiabetic drug phenformin (Phen) as a potent Gli1 inhibitor that suppresses SHH-subtype MB growth. Despite its efficacy, systemic administration of Phen is limited by its potential to induce lactic acidosis, primarily through the suppression of hepatic gluconeogenesis. Here, we provide proof-of-concept that phospholipid (liposomes) and non-phospholipid (niosomes) vesicles (<200 nm) can be used to deliver phenformin selectively. Our results show that these vesicle-based delivery systems efficiently entrap Phen (around 50%) and release it into SHH MB cells, reducing proliferation and activating energy stress responses at higher doses. Furthermore, treated cells exhibit marked downregulation of SHH target genes Gli1 and Ptch1. In vivo, phenformin-loaded nanocarriers selectively increased drug accumulation in cerebellar tumors while minimizing systemic and hepatic exposure. Notably, niosomes demonstrated superior brain tumor targeting compared to free drug or liposome administration, as reflected by higher intratumoral concentrations of Phen compared to free drug or liposome administration. Consistent with this targeted delivery, we observed a substantial decline in intratumoral Gli1 and Ptch1 expression, confirming effective SHH pathway modulation. Together, these findings propose a promising nanotechnology-based method to improve phenformin therapeutic index in SHH MB by enhancing tumor specificity and reducing systemic toxicity. - Source: PubMed
Publication date: 2026/05/04
Di Magno LauraRinaldi FedericaCampea LucaDella Rocca GiorgiaForte JacopoD'Intino EleonoraCairoli SaraGoffredo Bianca MariaCarafa MariaDel Favero ElenaMarianecci CarlottaCanettieri Gianluca - This study aimed to identify potential genetic variants and candidate genes associated with feed efficiency (FE), production, and feeding behaviour traits in Canadian purebred Duroc pigs. Genome-wide association studies (GWAS) were conducted using 8,861 individuals and an imputed Affymetrix PigGen Canada 50K panel v2.0 using a linear mixed model (LMM) and a Bayesian B model. This analysis used an adjusted p-value threshold (ranging from 6.6 × 10-5 to 1.3 × 10-4) using false-discovery rate to determine significance. The number of significant SNPs identified for each trait was as follows: average daily gain (ADG, 48), daily feed intake (DFI, 85), feed conversion ratio (FCR, 101), residual feed intake (RFI, 37), residual gain (RG, 64), residual intake and gain (RIG, 55), backfat thickness (BF, 100), loin depth (LD, 6), Keibler ratio (KR, 0), total time spent eating per day (TPD, 7), and number of visits to the feeder per day (NVD, 6). Several traits (BF, DFI, FCR, RFI, RG, and RIG) showed strong overlapping signals on chromosomes 7 and 10 with 24 shared significant SNPs, indicating potential shared genetic mechanisms. These traits also had 71 overlapping candidate genes such as PACSIN1, PTCH1, ADIPOR1 and ITPR3, associated with glucose, lipid and cholesterol metabolism. Well known candidate genes in literature associated with growth and fatness such as MC4R and CDH20 were also identified to be associated with ADG, BF, FCR and DFI in this study. Gene Ontology enrichment analysis revealed a set of the candidate genes were involved in the gonadotropin-releasing hormone (GnRH) and the platelet-derived growth factor (PDGF) signaling pathways. Overall, this study contributed to understating the genetic architecture and provided a biological foundation for improving FE, production and feeding behaviour traits in Canadian Duroc pigs facilitating the selection of more efficient pigs. - Source: PubMed
Publication date: 2026/05/09
Kim BelleDo Duy NgocJafarikia MohsenTulpan DanAdewole DeborahManafiazar GhaderSullivan BrianHoll JustinMiar Younes - Metabolic stress induced by saturated fatty acids such as palmitic acid (PA) disrupts key signalling pathways involved in neuronal survival, differentiation, and plasticity. The Sonic Hedgehog (Shh) pathway, essential for neurogenesis and tissue regeneration, is particularly vulnerable to PA-mediated suppression. In this study, we investigated the therapeutic potential of purmorphamine, a smoothened (SMO) agonist, and lithium chloride (LiCl), a GSK3β inhibitor, in restoring metabolic stress-induced insulin resistance and Shh signalling in Neuro2A cells. For the induction of insulin resistance or metabolic stress model, N2a cells were treated with PA (200 μM) for 24 h and validated by stimulation with insulin (100 nM) for various time periods 0, 5, 15, 30, 60, and 120 min. A blunted response was observed on pAKT and pGSK3β levels, indicating the development of insulin resistance. Cells were co-treated with purmorphamine (1 μM) or LiCl (10 µM) for 24 h alongside PA. PA exposure downregulated Shh components (PTCH1, SMO, Gli1) and transcriptional regulators (CREB, FOXO3), which further leads to reduced expression of neuroplasticity markers (BDNF, profilin1, SOX2) and compromised neurite outgrowth. Co-treatment with purmorphamine or LiCl significantly rescued these deficits, reinstating pathway activity and cellular function. Purmorphamine or LiCl also improved neurite outgrowth and restored the proliferative capacity of N2a cells. These findings highlight the role of GSK-3β and SMO signalling interactions in maintaining neuronal outgrowth and neuroplasticity. - Source: PubMed
Publication date: 2026/05/09
Singh PoojaAmbaliya Shonak VrujlalKumar Gajjar ShivamYadav Shreyash SantoshDatusalia Ashok Kumar - To investigate the clinicopathological and genetic characteristics of mesenchymal tumors with GLI1 gene alterations. Five cases diagnosed at the Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from 2021 to 2025 were collected. HE and immunohistochemical slides were reviewed. Tumor-associated genetic alterations were detected using a next generation sequencing (NGS) panel of pan-solid tumor genes (468 genes, 116 DNA+352 RNA). Fluorescence in situ hybridization (FISH) was performed to detect GLI1 gene translocation and amplification. Clinical and follow-up data were analyzed. There were 3 females and 2 males, aged 48, 16, 47, 47 and 37 years, respectively. The tumor locations were the tongue, small intestine, ovary, and buttock. Histologically, tumor cells arranged in nest and lobular arrangements; within a partially myxoid stroma with necrosis and calcification, surrounded by a rich fibrovascular network around and a pseudocapsule in some cases. The tumor cells were predominantly round to oval, with fewer short spindled forms, showing mild to moderate atypia and distinct nucleoli. Immunohistochemically, tumor cells variably expressed CD56, S-100, and smooth muscle actin, but were negative for broad-spectrum epithelial markers. GLI1 immunohistochemistry showed diffuse, strong positivity (2 cases stained). Ki-67 proliferation index ranged from 1% to 30%. NGS identified PTCH1::GLI1 fusions in three cases and GLI1 amplification in two. All patients underwent complete surgical resection without adjuvant therapy. During the follow-up (4-16 months), one case recurred, while four remained disease-free. Mesenchymal neoplasm with GLI1 gene alterations is a type of tumor with low malignant potential, representing the biological behavior of low-grade sarcoma. However, it is currently not recognized by the World Health Organization classification. Surgical resection is the preferred treatment. While immunophenotyping lacks specificity, and GLI1 immunohistochemistry could aid in its diagnosis. Definitive diagnosis and differential diagnosis of this tumor require characteristic morphological features combined with molecular confirmation of GLI1 gene fusion or amplification. - Source: PubMed
Liu X GWang YLyu Y KAo Q LDuan Y Q - Cutaneous adnexal carcinomas (CACs) comprise a diverse group of malignant tumors that show morphological differentiation toward one of the four main adnexal structures in normal skin: hair follicles, sebaceous glands, sweat-apocrine glands, and sweat-eccrine glands. These tumors can arise sporadically or may be associated with rare genetic syndromes. A total of 276 CACs cases underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of genomic alterations (GA). Sequencing data were used to determine microsatellite instability (MSI) status, tumor mutational burden (TMB), genomic loss of heterozygosity (gLOH), genomic ancestry, and COSMIC mutational signatures. PD-L1 expression was evaluated by immunohistochemistry (TPS; Dako 22C3). Statistical analyses were performed using Fisher's exact test, with false discovery rate correction via the Benjamini-Hochberg method. Sequencing was performed on primary cutaneous tumors in 131 cases (47.4%) and on local recurrence or metastatic site biopsies in 145 cases (52.5%). Across all groups, there was a male predominance (64-81%) and similar mean ages (59-63 years), with apocrine (APO) tumors occurring in older patients than eccrine (ECC) tumors (72 vs. 62 years; = 0.001). Histologically, 173 tumors (62.7%) were sweat gland-derived (SWT), 55 (19.9%) sebaceous gland-derived (SEB), 14 (5.1%) hair follicle-derived (HRF), and 34 (12.3%) unclassified (UNK). Among SWT tumors, 150 (86.7%) were eccrine and 23 (13.3%) apocrine. SWT tumors included digital papillary adenocarcinomas (DPA, 6.9%), mucinous carcinomas (MC, 6.3%), porocarcinomas (POR, 11.0%), spiradenocarcinomas (SPR, 8.1%), syringoadenocarcinomas (SRNG, 5.8%), and 77 (44.5%) unclassified cases. The number of GA per tumor was highest in SEB compared with SWT tumors (7.9 vs. 4.9; = 0.005) and lowest in DPA (2.1 vs. 5.0 in non-DPA; = 0.03). No differences in ancestry distribution were observed. Compared with SWT tumors, SEB tumors exhibited higher frequencies of RB1 (38.2% vs. 8.1%; < 0.0001) and TP53 alterations (76.4% vs. 43.4%; = 0.0002), suggesting potential neuroendocrine differentiation. MC tumors showed significantly higher PTCH1 alterations than non-MC tumors (36.4% vs. 1.8%; = 0.044). MSI-high status was most frequent in SEB tumors compared with all other groups (15.7% vs. 1.2%; = 0.005), and gLOH > 16% was also more common in SEB than SWT tumors (19.6% vs. 7.2%; = 0.081). The MMR signature occurred more frequently in SEB than SWT tumors (32.0% vs. 2.1%; = 0.005). Mean TMB was elevated across most CACs types, ranging from 10.4 mutations/Mb in HRF to 38.8 mutations/Mb in MC, with the exceptions of APO (2.7 mut/Mb; = 0.001) and DPA (1.4 mut/Mb; = 0.003). PD-L1 expression was generally low and did not differ significantly between SWT and SEB tumors (37.0% vs. 33.3%; NS). Given the limited data on CAC treatment, this study provides a catalog of commonly observed GA. SEB tumors exhibited the highest frequency of genomic alterations. Prospective clinical trials are needed to determine the prognostic and predictive value of CAC-specific biomarkers for immune checkpoint inhibitor (ICI) response, which is essential for integrating novel therapies into the evolving treatment landscape. - Source: PubMed
Publication date: 2026/03/30
Bou Zerdan MarounJamouss Kevin TMaalouf AlexandreMoukarzel RitaChhabra TanishqZaccarini Daniel JPavlick DeanDanziger NatalieRoss Jeffrey