ALK inhibitors suppress HCC and synergize with anti-PD-1 therapy and ABT-263 in preclinical models
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA737761 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14813853_1.fastq.gz | Fastqsanger.gz | |||
| SRR14813853_2.fastq.gz | Fastqsanger.gz | |||
| SRR14813854_1.fastq.gz | Fastqsanger.gz | |||
| SRR14813854_2.fastq.gz | Fastqsanger.gz | |||
| SRR14813855_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
Similar Datasets
Project description:Hepatocellular carcinoma (HCC) currently lacks effective therapies, leaving a critical need for new treatment options. A previous study identified the Anaplastic Lymphoma Kinase (ALK) amplification in HCC patients, raising the question of whether ALK inhibitors could be a viable treatment. Here, we showed that both ALK inhibitors and ALK knockout effectively halted HCC growth in cell cultures. Lorlatinib, a potent ALK inhibitor, suppressed HCC tumor growth and metastasis across various mouse models. Additionally, in an advanced immunocompetent humanized mouse model, when combined with an anti-PD-1 antibody, lorlatinib more potently suppressed HCC tumor growth, surpassing individual drug efficacy. Lorlatinib induced apoptosis and senescence in HCC cells, and the senolytic agent ABT-263 enhanced the efficacy of lorlatinib. Additional studies identified that the apoptosis-inducing effect of lorlatinib was mediated via GGN and NRG4. These findings establish ALK inhibitors as promising HCC treatments, either alone or in combination with immunotherapies or senolytic agents.
2024-04-29 | GSE178211 | GEO
Project description:Senescent cells accumulate in aging tissues, impairing their ability to undergo repair and regeneration following injury. Previous research has demonstrated that targeting tissue senescence with senolytics can enhance tissue regeneration and repair by selectively eliminating senescent cells in specific aged tissues. In this study, we focused on eliminating senescent skin cells in aged mice to assess the effects on subsequent wound healing. We applied ABT-263 (Navitoclax) and a DMSO control directly to the skin of 24-month-old mice over a 5-day period. Following ABT-263 treatment, aged skin showed decreased gene expression of senescent markers p16 and p21, accompanied by reductions in SA-β-gal and p21-positive cells compared to the DMSO-treated skin. However, ABT-263 treatment also triggered a temporary inflammatory response and macrophage infiltration in the skin. Bulk RNA sequencing of ABT-263-treated skin revealed prompt upregulation of genes associated with wound healing pathways, including hemostasis, inflammation, cell proliferation, angiogenesis, collagen synthesis, and extracellular matrix organization. Aged mice treated with ABT-263 exhibited accelerated wound closure compared to the DMSO control group. In conclusion, topical ABT-263 effectively reduced several senescence markers in aged skin, thereby priming the skin for improved subsequent wound healing. This enhancement may be attributed to ABT-263-induced senolysis and the resulting inflammation, which in turn stimulated the expression of genes involved in extracellular matrix remodeling and wound repair pathways.
2024-12-17 | GSE271149 | GEO
Project description:To explore the role played by senescent cells in mice models of pulmonary hypertension we exposed young C57BL6/j mice to 2 days hypoxia or normoxia and treated with senolytic drug ABT-263 (50mg/kg/day) or its vehicule. We then performed lung gene expression profiling analysis using data obtained from RNA-seq of 4 groups of mice (Normoxia+Vehicule; Normoxia+ABT-263; Hypoxia+Vehicule; Hypoxia+ABT-263)
2022-12-16 | GSE207324 | GEO
Project description:To explore the role played by senescent cells in mice models of pulmonary hypertension we exposed young C57BL6/j mice to 8 days hypoxia or normoxia and treated with senolytic drug ABT-263 (50mg/kg/day) or its vehicule. We then performed lung gene expression profiling analysis using data obtained from RNA-seq of 4 groups of mice (Normoxia+Vehicule; Normoxia+ABT-263; Hypoxia+Vehicule; Hypoxia+ABT-263)
2022-12-16 | GSE207256 | GEO
Project description:Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing
| PRJNA1130066 | ENA
Project description:RNA expression analysis was performed to compare patterns to sensitivity to BCL2 inhibitors (ABT-263). Overexpression of the prosurvival Bcl-2 family members (Bcl-2, Bcl-xL and Mcl-1) is commonly associated with tumor maintenance, progression and chemoresistance. We previously reported the discovery of ABT-737, a potent, small molecule Bcl-2 family protein inhibitor. A major limitation of ABT-737 is that it is not orally bioavailable. This may limit its use for chronic single agent treatment and the flexibility to dose in combination with parenteral chemotherapy. Here we report the discovery and biological properties of ABT-263, a potent, orally bioavailable Bad-like BH3 mimetic (Kiâ??s of < 1 nM for Bcl-2, Bcl-xL and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% - 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim) in cells leading to the initiation of apoptosis within 2 hr post-treatment. In human tumor cells, ABT-263 rapidly induces Bax translocation, cytochrome c release and subsequent programmed cell death. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 exhibits modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. These data provide the rationale for clinical trials evaluating ABT-263 in SCLC and B-cell malignancies. The oral efficacy of ABT-263 should provide dosing flexibility to maximize clinical utility as both a single agent and in combination with standard chemotherapeutic regimens. Experiment Overall Design: Naive cell lines were isolated in duplicate or triplicate (only a single for H69AR) to determine RNA expression pattern.
2008-06-19 | E-GEOD-10841 | biostudies-arrayexpress
Project description:RNA expression analysis was performed to compare patterns to sensitivity to BCL2 inhibitors (ABT-263). Overexpression of the prosurvival Bcl-2 family members (Bcl-2, Bcl-xL and Mcl-1) is commonly associated with tumor maintenance, progression and chemoresistance. We previously reported the discovery of ABT-737, a potent, small molecule Bcl-2 family protein inhibitor. A major limitation of ABT-737 is that it is not orally bioavailable. This may limit its use for chronic single agent treatment and the flexibility to dose in combination with parenteral chemotherapy. Here we report the discovery and biological properties of ABT-263, a potent, orally bioavailable Bad-like BH3 mimetic (Kiâ??s of < 1 nM for Bcl-2, Bcl-xL and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% - 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim) in cells leading to the initiation of apoptosis within 2 hr post-treatment. In human tumor cells, ABT-263 rapidly induces Bax translocation, cytochrome c release and subsequent programmed cell death. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 exhibits modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. These data provide the rationale for clinical trials evaluating ABT-263 in SCLC and B-cell malignancies. The oral efficacy of ABT-263 should provide dosing flexibility to maximize clinical utility as both a single agent and in combination with standard chemotherapeutic regimens. Keywords: cell line comparison
2008-05-01 | GSE10841 | GEO
Project description:Genome wide DNA methylation profiling of parental, ABT-199 resistant population, and ABT-199 resistant clones from 3 acute myelogenous leukemia (AML) cell lines (MOLM-13, MV-4-11, OCI-AMLO2). The Illumina Infinium MethylationEPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs from AML cell line samples. Samples include 4 ABT-199 sensitive parental MOLM-13 population samples, 4 ABT-199 resistant MOLM-13 population samples, 3 ABT-199 resistant MOLM-13 S2 clone samples, 3 ABT-199 resistant MOLM-13 S5 clone samples, 4 ABT-199 resistant MOLM-13 S6 clone samples, 3 ABT-199 sensitive parental MV-4-11 population samples, 3 ABT-199 resistant MV-4-11 population samples, 3 ABT-199 sensitive parental OCI-AML2 population samples, 3 ABT-199 resistant OCI-AML2 population samples, 3 ABT-199 resistant OCI-AML2 S1 clone samples, 3 ABT-199 resistant OCI-AML2 S2 clone samples, 3 ABT-199 resistant OCI-AML2 S8 clone samples.
2022-01-12 | GSE193254 | GEO
Project description:To characterize the effects of common ALK fusion genes, we performed a comprehensive RNA-Seq analysis of NL20 cells induced with ALK-EML4-V1, ALK-EML4-V3, ALK-TFG, ALK-KIF5B, using Doxycycline
2022-12-18 | E-MTAB-11304 | biostudies-arrayexpress
Project description:Bacillus altitudinis 263 genome sequence
| PRJEB231 | ENA