Last update 21 Mar 2024
Noxa
phorbol-12-myristate-13-acetate-induced protein 1
Last update 21 Mar 2024
Basic Info
Synonyms APR, Immediate-early-response protein APR, NOXA + [4] |
Introduction Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1 (By similarity). Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1. |
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100 Clinical Results associated with Noxa
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100 Translational Medicine associated with Noxa
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0 Patents (Medical) associated with Noxa
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8,389
Literatures (Medical) associated with Noxa24 Feb 2024·Cell death discovery
The interplay of mitophagy, autophagy, and apoptosis in cisplatin-induced kidney injury: involvement of ERK signaling pathway.
Article
Author: Iva Suman ; Lidija Šimić ; Gordana Čanadi Jurešić ; Sunčica Buljević ; Damir Klepac ; Robert Domitrović
AKI induced by CP chemotherapy remains an obstacle during patient treatments. Extracellular signal-regulated protein kinases 1/2 (ERK), key participants in CP-induced nephrotoxicity, are suggested to be involved in the regulation of mitophagy, autophagy, and apoptosis. Human renal proximal tubular cells (HK-2) and BALB/cN mice were used to determine the role of ERK in CP-induced AKI. We found that active ERK is involved in cell viability reduction during apoptotic events but exerts a protective role in the early stages of treatment. Activation of ERK acts as a maintainer of the mitochondrial population and is implicated in mitophagy initiation but has no significant role in its conduction. In the late stages of CP treatment when ATP is deprived, general autophagy that requires ERK activation is initiated as a response, in addition to apoptosis activation. Furthermore, activation of ERK is responsible for the decrease in reserve respiratory capacity and controls glycolysis regulation during CP treatment. Additionally, we found that ERK activation is also required for the induction of NOXA gene and protein expression as well as FoxO3a nuclear translocation, but not for the regular ERK-induced phosphorylation of FoxO3a on Ser294. In summary, this study gives detailed insight into the involvement of ERK activation and its impact on key cellular processes at different time points during CP-induced kidney injury. Inhibitors of ERK activation, including Mirdametinib, are important in the development of new therapeutic strategies for the treatment of AKI in patients receiving CP chemotherapy.
20 Feb 2024·Journal of molecular and cellular cardiology
Cannabidiol protects against acute aortic dissection by inhibiting macrophage infiltration and PMAIP1-induced vascular smooth muscle cell apoptosis.
Article
Author: Yilong Guo ; Yang Che ; Xuelin Zhang ; Zongna Ren ; Yinan Chen ; Liliang Guo ; Lin Mao ; Ren Wei ; Xiang Gao ; Tao Zhang ; Li Wang ; Wei Guo
Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, we performed human AAD single-cell RNA sequencing and mouse AAD bulk RNA sequencing to elucidate the potential underlying mechanism of CBD. Pathological assays and in vitro studies were performed to verify the results of the bioinformatic analysis and explore the pharmacological function of CBD. In a β-aminopropionitrile (BAPN)-induced AAD mouse model, CBD reduced AAD-associated morbidity and mortality, alleviated abnormal enlargement of the ascending aorta and aortic arch, and suppressed macrophage infiltration and vascular smooth muscle cell (VSMC) apoptosis. Bioinformatic analysis revealed that the pro-apoptotic gene PMAIP1 was highly expressed in human and mouse AAD samples, and CBD could inhibit Pmaip1 expression in AAD mice. Using human aortic VSMCs (HAVSMCs) co-cultured with M1 macrophages, we revealed that CBD alleviated HAVSMCs mitochondrial-dependent apoptosis by suppressing the BAPN-induced overexpression of PMAIP1 in M1 macrophages. PMAIP1 potentially mediates HAVSMCs apoptosis by regulating Bax and Bcl2 expression. Accordingly, CBD reduced AAD-associated morbidity and mortality and mitigated the progression of AAD in a mouse model. The CBD-induced effects were potentially mediated by suppressing macrophage infiltration and PMAIP1 (primarily expressed in macrophages)-induced VSMC apoptosis. Our findings offer novel insights into M1 macrophages and HAVSMCs interaction during AAD progression, highlighting the potential of CBD as a therapeutic candidate for AAD treatment.
16 Feb 2024·Aging
PMAIP1, a novel diagnostic and potential therapeutic biomarker in osteoporosis.
Article
Author: Tao Li ; Jinghong Yuan ; Peichuan Xu ; Jingyu Jia ; Jiangminghao Zhao ; Jian Zhang ; Rui Ding ; Xiaokun Zhao ; Dingwen He ; Tianlong Wu ; Xigao Cheng
BACKGROUND:
Osteoporosis is a common endocrine metabolic bone disease, which may lead to severe consequences. However, the unknown molecular mechanism of osteoporosis, the observable side effects of present treatments and the inability to fundamentally improve bone metabolism seriously restrict the impact of prevention and treatment. The study aims to identify potential biomarkers from osteoclast progenitors, specifically peripheral blood monocytes on predicting the osteoporotic phenotype.
METHODS:
Datasets were obtained from Gene Expression Omnibus (GEO). Based on the differentially expressed genes (DEGs) and GSEA results, GO and KEGG analyses were performed using the DAVID database and Metascape database. PPI network, TF network, drug-gene interaction network, and ceRNA network were established to determine the hub genes. Its osteogenesis, migration, and proliferation abilities in bone marrow mesenchymal stem cells (BMSCs) were validated through RT-qPCR, WB, ALP staining, VK staining, wound healing assay, transwell assay, and CCK-8 assay.
RESULTS:
A total of 63 significant DEGs were screened. Functional and pathway enrichment analysis discovered that the functions of the significant DEGs (SDEGs) are mainly related to immunity and metal ions. A comprehensive evaluation of all the network analyses, PMAIP1 was defined as osteoporosis's core gene. This conclusion was further confirmed in clinical cohort data. A series of experiments demonstrated that the PMAIP1 gene can promote the osteogenesis, migration and proliferation of BMSC cells.
CONCLUSIONS:
All of these outcomes showed a new theoretical basis for further research in the treatment of osteoporosis, and PMAIP1 was identified as a potential biomarker for osteoporosis diagnosis and treatment.
1
News (Medical) associated with Noxa04 Dec 2023
In collaboration with leading cancer centers, research results to be presented from four studies across a breadth of breast tumor types and genomic alterations demonstrating Caris' impact on precision medicine
IRVING, Texas, Dec. 4, 2023 /PRNewswire/ -- Caris Life Sciences®(Caris), the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI, today announced that the company and collaborators within the Caris Precision Oncology Alliance™ (POA) will collectively present findings at the San Antonio Breast Cancer Symposium (SABCS) that illustrate the potential impact of molecular profiling on the treatment of breast cancer. The findings demonstrate the power of Caris' comprehensive clinico-genomic database that enables novel insights into cancer that could have profound effects on a patient's diagnosis, prognosis, care plan, and response to treatment. SABCS is being held December 5-9, 2023 (Booth #1433) in San Antonio, Texas.
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"The San Antonio Breast Cancer Symposium continues to be the premiere conference for breast cancer research," said George W. Sledge, Jr., MD, Executive Vice President and Chief Medical Officer of Caris. "As part of our continuing commitment to the breast cancer community, Caris is proud to share important clinical/translational research created with our academic partners on important breast cancer questions."
The research findings demonstrate the power of Caris' comprehensive clinico-genomic database
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Presentations and posters from Caris include:
Milan Radovich, PhD, Senior Vice President and Chief Scientific Officer of Caris, will participate in a Concurrent Educational Session entitled "Genomics for Clinical Research and Cancer Care" from 3:10 – 5:00 p.m. CT on Thursday, December 7 in the Stars at Night Ballroom 1-2. Dr. Radovich will deliver a presentation on "Emerging approaches to targeting pathways using precision medicine in breast cancer" from 3:10 – 3:40 p.m. before participating in a panel discussion from 4:40 – 5:00 p.m.
"Precision oncology in breast cancer is rapidly evolving with the recent approval of several targeted therapies that rely on the detection of molecular biomarkers to inform selection. On the horizon are novel genomic and AI based approaches that will further shape the future treatment of this disease," said Dr. Radovich. "This education session at SABCS will highlight advances in new drug modalities and targetable pathways; liquid biopsies and clonal hematopoiesis; emerging evidence on treatment resistance; and the forefront of AI-enabled digital pathology for biomarker detection."
A Caris study will be featured in the Concurrent Poster Spotlight Sessions Block 5 in the "PS13 Special Populations: Pregnancy, Male and Geriatric Patients" section on Thursday, December 7, from 5:30 – 6:30 p.m. CT in the Stars at Night Ballroom 3-4. The spotlight poster is titled "Molecular and Immunological Landscape of Sex-Based Differences in Breast Cancer: A Distinct Disease in Men" (Presentation #PS13-09). The study was performed in collaboration with Caris Precision Oncology Alliance™ (POA) members Dana-Farber Cancer Institute and Legorreta Cancer Center at Brown University, as well as others including the Mayo Clinic.
In the featured study, the molecular and immunological landscapes of male and female breast cancer were investigated across 10,728 breast cancer samples (male, n=137; female, n=10,591) using Caris' Next-Generation Sequencing (NGS) technology. The results of this analysis indicate that male breast cancer has differential molecular and immune features compared to female breast cancer. A better understanding of these sex-based differences may help inform disease outcomes, provide a rationale for tailored therapeutic approaches, and guide the design of future treatments.
"The Caris Precision Oncology Alliance™ continues its contribution to advancing breast cancer research by presenting novel findings on the molecular and immunological features of male breast cancer at this year's SABCS," said Chadi Nabhan, MD, MBA, FACP, Chairman of the POA. "By leveraging Caris' expansive real-world clinico-genomic database, our partner academic institutions are able to uncover new insights into the underpinnings of breast cancer biology leading to better therapeutic interventions."
The POA includes 90 cancer centers, academic institutions, research consortia and healthcare systems, including 42 NCI-designated cancer centers, collaborating to advance precision oncology and biomarker-driven research. POA members work together to establish and optimize standards of care for molecular testing through innovative research focused on predictive and prognostic markers that improve the clinical outcomes for cancer patients.
Additional Presentations Reveal Potential Impact of Comprehensive Molecular Profiling
Caris will present additional data from studies demonstrating the critical role of precision medicine and molecular profiling in the treatment of breast cancer. All presentations will be made available online through Caris' website beginning December 7.
Comprehensive Molecular and Immunological Characterization of Invasive Ductal Triple-Negative Breast Cancer (Presentation Number: PO4-24-01)
This investigation of the molecular and immune signatures of invasive ductal (ID) triple-negative breast cancer (TNBC) aimed to improve understanding of TNBC biology to facilitate future identification of novel targets for treatment of this heterogenous disease. The results of this retrospective study of more than 13,000 breast cancer samples indicate that ID TNBC is associated with a distinct mutational and immunological profile compared to ID non-TNBC. ID TNBC is also associated with worse overall survival compared to ID non-TNBC. However, ID TNBC patients have improved survival post-pembrolizumab treatment.
Comprehensive Characterization of BCL2 Family Genes in Metaplastic Triple Negative Breast Cancer (Presentation Number: PO4-24-02)
This study aimed to investigate the expression of BCL2 family genes in metastatic TNBC. Results of this molecular profiling study suggest a strong association between higher expression of PMAIP1 and worse patient survival in this cancer. This association may potentially be attributable to higher immune checkpoint and stem cell-related gene expression, in addition to higher frequency of PD-L1 positivity in PMAIP1-High tumors. Further investigation is needed to prospectively validate PMAIP1 as a potential prognostic biomarker candidate in metaplastic TNBC.
Genomic Landscape of Malignant Phyllodes Tumors Identifies Subsets for Targeted Therapy (Presentation Number: PO4-24-08)
Phyllodes tumors are rare tumors of the breast, a subset of which have considerable malignant potential. This study aimed to identify targetable alterations and enhance understanding of the mutational profiles of malignant phyllodes tumors (MPTs) to potentially enhance treatment options. NGS identified actionable genomic alterations, including an NTRK1 fusion and low HER2 transcriptional expression. These findings highlight the importance of NGS-based profiling, including RNA sequencing, in MPT research to uncover potential targeted treatment options for patients.
About Caris Life Sciences
Caris Life Sciences® (Caris) is the leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition using molecular science and AI. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms, Caris has created the large-scale, clinico-genomic database and computing capability needed to analyze and unravel the molecular complexity of disease. This convergence of sequencing power, big data and AI technologies provides an unmatched platform to deliver the next-generation of precision medicine tools for early detection, diagnosis, monitoring, therapy selection and drug development.
Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S., Europe, Asia and other international markets. To learn more, please visit CarisLifeSciences.com.
Caris Life Sciences Media Contact:
Lisa Burgner
[email protected]
214.294.5606
SOURCE Caris Life Sciences
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