ASCL1 antibody - N-terminal region (ARP32355_T100)
- Known as:
- ASCL1 (anti-) - N-terminal region (ARP32355_T100)
- Catalog number:
- arp32355_t100
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Aviva Systems Biology
- Gene target:
- ASCL1 antibody - N-terminal region (ARP32355_T100)
Related genes to: ASCL1 antibody - N-terminal region (ARP32355_T100)
- Gene:
- ASCL1 NIH gene
- Name:
- achaete-scute family bHLH transcription factor 1
- Previous symbol:
- -
- Synonyms:
- ASH1, HASH1, bHLHa46
- Chromosome:
- 12q23.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-12-09
- Date modifiied:
- 2016-01-15
Related products to: ASCL1 antibody - N-terminal region (ARP32355_T100)
Related articles to: ASCL1 antibody - N-terminal region (ARP32355_T100)
- Although small cell lung cancer (SCLC) comprises transcription factor (TF)-defined molecular subtypes (ASCL1, NEUROD1, POU2F3), the extent to which these subtypes predict response to clinically effective therapy in patients-and whether therapy can select for subtype switching-remains unknown. The recent approval of the DLL3×CD3 bispecific T-cell engager tarlatamab represents one of the first meaningful advances in relapsed small cell lung cancer (SCLC) in decades, yet responses remain heterogeneous and resistance is inevitable. Here, we inferred SCLC gene expression from circulating chromatin in prospectively collected patient plasma (46 patients; 167 samples), enabling interrogation of response and acquired resistance to tarlatamab. Parallel development of the first immunocompetent syngeneic mouse model to study tarlatamab response and resistance enabled functional validation. Across species, findings converged on a central principle: TF subtype governs both initial response and acquired resistance. Therapeutic response was significantly associated with ASCL1-subtype tumors, whereas NEUROD1-subtype tumors exhibited inferior responses and POU2F3-subtype tumors were uniformly resistant, consistent with DLL3 being a direct ASCL1 transcriptional target and most highly expressed in ASCL1-positive tumors. Strikingly, one mode of acquired resistance revealed therapeutic selection for a NEUROD1-high state with concomitant DLL3 downregulation. Other resistant tumors exhibited enrichment of regulatory and exhausted T-cell programs, highlighting tarlatamab's dual-targeting mechanism of action. Together, these results reveal that tarlatamab exerts selective pressure against ASCL1-driven lineages, facilitating resistance through loss of an antigen intrinsically linked to that state. These findings underscore the clinical relevance of TF-defined molecular subtypes in human SCLC. More broadly, they highlight the power of integrating longitudinal plasma transcriptional profiling from patient plasma with functional mouse modeling to uncover clinical and biological mechanisms of response and resistance to cell-surface-targeted therapies. - Source: PubMed
Publication date: 2026/04/08
Vasseur DamienSaito ShinGulati Gunsagar SLee Garyoung GaryLaimon Yasmin NSimsek BerkayLerner MaddieCho HyeonseoLi YixiangWang TianchuSeo Ji-HeuiSavignano HunterJames BradyZhang ZeSemaan KarlJin ZhenjieDaoud Khatoun WassimNafeh GaelleNawfal RashadCooper Alissa JMiller KathrynSeager Maxwell DBrea Elliott JSmith EricChang JonathanPelletier MarcCosta CarlottaChoueiri Toni KSignoretti SabinaSands JacobBaca Sylvan CFreedman Matthew LOser Matthew G - Neuroblastoma is a heterogeneous paediatric cancer arising from developmentally arrested neuronal precursors, where restoring differentiation offers therapeutic promise. ASCL1, a pro-neural transcription factor, is widely expressed in neuroblastoma and can drive either proliferation or differentiation depending on the cellular context. Here, we show that distinct MYCN-amplified neuroblastoma cell lines exhibit differing differentiation responses to ASCL1 overexpression. By comparing genome-wide ASCL1 chromatin binding, transcriptional changes, and protein-protein interactions, we found that ASCL1 binds more extensively to neuronal proteins in a cell line that is more susceptible to ASCL1-driven differentiation, but associates with cell cycle regulators in less responsive cells. We show that CDK2-Cyclin A2 bind ASCL1 in less responsive cells, with CDK-mediated phosphorylation of ASCL1 limiting the ability of ASCL1 to drive differentiation. Implications: Our study reveals that context-dependent interactions of ASCL1 with protein partners on the chromatin control its ability to re-engage a differentiation program in neuroblastoma. - Source: PubMed
Publication date: 2026/04/14
Mykhaylechko LidiyaGomez Roshna LWoods Laura MPapachristou Evangelia KRamachandran RevathyLundie-Brown JethroDrummond RosalindMarcos DanielAbou Grealy Fiona M YIbragimova ShakhzadaAli Fahad RCarroll JasonPhilpott Anna - Vascular dementia, which is considered the second most common cause of dementia, has consistently remained a worldwide health concern. One possible approach to improving vascular dementia is by inducing neurogenesis. The asymmetric carotid artery stenosis (ACAS) model was employed and viral vectors were administered to induce an astrocytes-to-neuron conversion, including the Ptbp1 knockdown (KD) or transduction of Ascl1, NeuroD1, and Sox2 (ANS), with the aim of assessing their therapeutic effects. Mice were sacrificed 2 months after ACAS surgery and administration of the viral vector, followed by an immunohistochemical analysis that evaluated CA1 preservation, the inflammatory response and neurogenesis. CA1 was significantly thicker in the ACAS + ANS group than in the ACAS + Ptbp1 KD group. The inflammatory response in the hippocampus was suppressed in both the ACAS + ANS and ACAS + Ptbp1 KD groups. In the dentate gyrus, NeuN/mCherry double-positive cells were observed in both the ACAS + Ptbp1 KD and ACAS + ANS groups. On the other hand, in CA1, they were only found in the ACAS + ANS group. In conclusion, AAV-pGFAP-ANS efficiently induced glia-to-neuron reprogramming and suppressed hippocampal inflammation in the ACAS-induced microinfarction model. - Source: PubMed
Publication date: 2026/04/11
Ota-Elliott Ricardo SatoshiFukui YusukeHu XinranBian YutingSun HongmingAn HangpingLiu HongzhiMorihara RyutaIshiura HiroyukiYamashita Toru - First-void urine (FVU) collection for high-risk human papillomavirus (HPV) testing may reach un(der)-screened women in cervical cancer screening programs. This cross-sectional study investigated the clinical performance of DNA methylation markers ASCL1 and LHX8 in HPV-positive FVU for detecting high-grade cervical intraepithelial neoplasia and cancer (CIN2+ and CIN3+). Additionally, results were compared with paired HPV-positive clinician-collected cervical samples (CS) and HPV genotyping. - Source: PubMed
Publication date: 2026/04/10
Tranberg MetteVan Keer SeverienHesselink Albertus TNørgaard PiaBrøndum RikkeWu ChunsenGustafson Line WintherHammer AnneBor PinarBinderup Karen OmannBlach ChristinaVorsters AlexSteenbergen Renske - Parkinson's disease (PD) is a progressive neurodegenerative disorder marked by degeneration of dopaminergic neurons and associated motor impairments. Current pharmacotherapies only offer symptomatic relief hampered by multiple adverse effects. Herein, pharmacologic, molecular and histopathologic studies were employed to determine whether valsartan (VAL) has functional neurorestorative potential in PD male rat model induced by intraperitoneal (IP) injection of haloperidol (HALO) (1.5 mg/kg/day, for 42 days). Administration of VAL (40 mg/kg PO) for 21 days markedly improved motor functions as revealed by i) reduced muscle rigidity in catalepsy bar test, ii) increase in performance in rotarod and beam walking tests, iii) increased total distance travelled, grooming duration, rearing duration, and maximum speed in open field test. Western blot analysis revealed that VAL restored the markers of dopaminergic neuronal degeneration as indicated by increased protein expression of dopaminergic-specific transcription factors (Nurr1, ASCL1) and mRNA expression of Nurr1 regulatory proteins (PIN1, CoREST), the dopamine (DA) neurons detoxifier ALDH1A1, and markers for dopaminergic transmission (D2 receptor, tyrosine hydroxylase (TH), DA transporter (DAT). Histopathological analyses confirmed neuronal integrity in the substantia nigra (SN). Furthermore, VAL exerted epigenetic modulation by downregulating histone deacetylases HDAC1/5 and upregulating sirtuin 1 (SIRT1), decreased α-synuclein (α-syn) and restored ApoA1. Co-administration of Nurr1 inhibitor meloxicam (MLX; 3 mg/Kg/day PO) significantly attenuated VAL's neuroprotective effects, confirming Nurr1's central role, but did not fully reverse its epigenetic actions. In conclusion, VAL demonstrated potent neuroprotective, restorative of neuronal function, and epigenetic modulatory effects in PD, highlighting its promising role as a novel disease-modifying therapeutic candidate and warranting further investigation. - Source: PubMed
Publication date: 2026/04/03
Gowied Hadeer GEl-Mezayen Nesrine SAfify Elham A