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12d
Piperine Protects Against Arsenic Trioxide-Induced Cardiotoxicity in Rats: A Biochemical and Electrocardiography Study. (PubMed, Curr Cardiol Rev)
This study demonstrated that piperine at 20 mg/kg orally was protective in arsenic trioxide-induced cardiotoxicity in an experimental rat model. This study is the first to combine serum biomarkers and ECG analysis to demonstrate piperine's cardioprotective role. It may have clinical relevance in exploring the potential of piperine to reduce arsenic trioxide-induced cardiotoxicity.
Preclinical • Journal
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IL6 (Interleukin 6) • CAT (Catalase)
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arsenic trioxide
12d
Epigenetic reprogramming by organic arsenic CZ2 elicits potent antitumor responses in DLBCL through TMS1 restoration. (PubMed, Bioorg Chem)
Our study establishes that CZ2, a novel organic arsenical, exhibits superior therapeutic efficacy and high selectivity in DLBCL by targeting DNMT. Our findings suggest that CZ2 represents a promising strategy to overcome epigenetic-mediated resistance, offering a potential therapeutic intervention for relapsed/refractory DLBCL and supporting its further development in rational combination regimens.
Journal
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DNMT3A (DNA methyltransferase 1) • DNMT1 (DNA methyltransferase 1) • CASP9 (Caspase 9) • DNMT3B (DNA Methyltransferase 3 Beta) • ANXA5 (Annexin A5)
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arsenic trioxide
14d
Engineered Peptide Coassembly Enables Precision Delivery of As(III)-Peptide Complexes and Counteracts Inflammation-Dependent Therapeutic Resistance in High-Risk Neuroblastoma. (PubMed, ACS Nano)
While arsenic trioxide (As(III)) demonstrates therapeutic potential through ferroptosis induction, its clinical application is severely constrained by dose-limiting systemic toxicity and consequent inflammation-mediated COX2/PGE2 pathway activation, which confers ferroptosis resistance...TCADS comprises two rationally designed self-assembling peptides incorporating As(III)-binding domains, tumor-selective targeting moieties (MMP9-responsive and Tenascin C-targeting motifs), and the COX2 antagonist naproxen (NPX)...This precision-targeted approach empowers TCADS to effectively disrupt the deleterious inflammation-ferroptosis resistance cycle, thereby successfully overcoming treatment resistance and suppressing tumor progression by 85.0% and 95.4% in subcutaneous and orthotopic tumor models, respectively. This integrated paradigm of precision-targeted delivery coupled with microenvironment modulation establishes a compelling therapeutic framework for chemoresistant HR-NB and potentially other MYCN-amplified malignancies.
Journal
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MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • MMP9 (Matrix metallopeptidase 9)
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MYCN amplification
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arsenic trioxide
26d
Administering Bifidobacterium pseudolongum With Arsenic Trioxide Attenuates Acute Promyelocytic Leukemia in Mice by Restoring Immune Microenvironment and Intestinal Homeostasis. (PubMed, Front Biosci (Landmark Ed))
BP is an effective adjunct to ATO therapy, counteracting gut dysbiosis, intestinal damage, and the immune microenvironment while synergistically improving antileukemic efficacy. Targeting the gut-leukemia axis with BP represents a promising strategy for improving the precision and safety of APL treatment.
Preclinical • Journal
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CD8 (cluster of differentiation 8) • CLDN1 (Claudin 1) • TJP1 (Tight Junction Protein 1) • OCLN (Occludin)
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arsenic trioxide
27d
Differentiation Syndrome in Acute Myeloid Leukemia: Molecular Mechanisms, Clinical Spectrum, and Emerging Therapeutic Paradigms. (PubMed, Int J Mol Sci)
While differentiation therapy revolutionized acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), its extension into non-APL AML has been limited until recent targeted agents...IDH1/2 inhibitors (ivosidenib, enasidenib, olutasidenib) yield overall response rates (ORRs) of 30-94% in AML with DS in 10-19%. Menin inhibitors (revumenib, ziftomenib, enzomenib, bleximenib) achieve ORRs of 33-88% in KMT2A-rearranged or NPM1-mutated AML, with DS in 10-25% and QT prolongation as key toxicities. FLT3 inhibitors (gilteritinib, quizartinib) improve survival in FLT3-mutated AML with DS in 1-5%...Improved recognition of DS and rational combination approaches will be essential to maximize the therapeutic benefit. Future research should address mechanisms of resistance and biomarkers to achieve cures beyond APL.
Review • Journal
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FLT3 (Fms-related tyrosine kinase 3) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • KMT2A (Lysine Methyltransferase 2A)
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FLT3 mutation • NPM1 mutation
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Xospata (gilteritinib) • Vanflyta (quizartinib) • Tibsovo (ivosidenib) • Revuforj (revumenib) • Idhifa (enasidenib) • Komzifti (ziftomenib) • Rezlidhia (olutasidenib) • arsenic trioxide • bleximenib (JNJ-6617) • enzomenib (DSP-5336)
1m
Penile Ulcerations in a Patient with Acute Promyelocytic Leukemia. (PubMed, Indian J Hematol Blood Transfus)
After treatment with all-trans retinoic acid and arsenic trioxide, he developed localized penile ulcers resistant to antibiotics. The ulcers improved following chemotherapy with daunorubicin and azacitidine. This case highlights penile ulcerations as a rare manifestation of leukemia cutis in APML, underscoring the importance of considering leukemic infiltration in differential diagnosis of genital ulcers when infectious causes are excluded.
Journal
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CD34 (CD34 molecule) • MME (Membrane Metalloendopeptidase)
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azacitidine • daunorubicin • arsenic trioxide
1m
Primary Indolent Acute Promyelocytic Leukemia. (PubMed, Hematol Rep)
Induction therapy with all-trans-retinoic acid and arsenic trioxide resulted in hematologic remission...Atypical clinical trajectories should prompt careful assessment of marrow morphology and immunophenotypic features. Continued characterization of such cases may refine diagnostic criteria and direct individualized approaches to therapy.
Journal
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TP53 (Tumor protein P53) • ETV6 (ETS Variant Transcription Factor 6)
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TP53 mutation • Chr t(15;17)
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arsenic trioxide
1m
Posaconazole attenuates arsenic trioxide toxicity and enhances safety and efficacy while reducing invasion and metastasis in non-small-cell lung cancer. (PubMed, Pulm Pharmacol Ther)
Furthermore, flow cytometry and colony formation assays revealed that PCZ attenuates and reduces the apoptotic/necrotic effects of ATO. In conclusion, PCZ synergistically and effectively reduces the adverse cytotoxic effects of ATO in lung cancer cells, providing a promising new therapeutic strategy for lung cancer treatment.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • GLI1 (GLI Family Zinc Finger 1) • HMGA2 (High mobility group AT-hook 2) • MMP9 (Matrix metallopeptidase 9)
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arsenic trioxide • Noxafil (posaconazole)
1m
Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia (clinicaltrials.gov)
P3, N=158, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2025 --> Jun 2029
Trial completion date
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RARA (Retinoic Acid Receptor Alpha) • PML (Promyelocytic Leukemia)
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cytarabine • idarubicin hydrochloride • mitoxantrone • Vesanoid (tretinoin) • arsenic trioxide • Hemady (dexamethasone tablets) • Starasid (cytarabine ocfosfate)
1m
Arsenic trioxide-induced acute kidney injury: OPA1- and Drp1-mediated mitochondrial dynamics imbalance, PINK1/Parkin-dependent mitophagy, and Chuanhuang Fang III. (PubMed, Front Mol Biosci)
In vitro experiments using the HK-2 cell line provided further evidence supporting the in vivo findings. The pathogenesis of clinical-dose ATO-induced AKI involves OPA1- and Drp1-mediated mitochondrial dynamics imbalance and PINK1/Parkin-dependent mitophagy in renal tubular epithelial cells, CHF ameliorated this injury by restoring mitochondrial quality control, highlighting its therapeutic potential against AI-AKI.
Journal • IO biomarker
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BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein) • BNIP3 (BCL2 Interacting Protein 3)
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arsenic trioxide
1m
TGFβ-Mediated Overexpression of Podoplanin Serves as a Potential Diagnostic Biomarker in Acute Promyelocytic Leukemia. (PubMed, Mol Carcinog)
Early diagnosis of acute promyelocytic leukemia (APL), driven by PML-RARA oncoprotein, is vital for survival, as delays can cause fatal coagulopathy without prompt therapeutic intervention of all-trans retinoic acid and arsenic trioxide...Pharmacological inhibition of TGF-β1 ligand using luspatercept reduced SMAD phosphorylation and PDPN expression, indicating TGF-β/SMAD transcriptionally regulates PDPN. Additionally, ELISA-based serum profiling showed significantly elevated TGF-β1 levels in APL patients compared to non-APL AML (p < 0.0001). These findings identify PDPN overexpression as a downstream consequence of TGF-β/SMAD signaling and highlight its potential as a diagnostic biomarker for APL.
Journal
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PML (Promyelocytic Leukemia) • TGFB1 (Transforming Growth Factor Beta 1)
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arsenic trioxide • Reblozyl (luspatercept-aamt)