mitoxantrone

P1, N=49, Completed, Wake Forest University Health Sciences | Phase classification: P2 --> P1

These results indicate that melatonin negatively modulates the cell survival of spheres derived from CF41.Mg cells, in a way that is independent of its MT1 receptor. These effects did not counteract the resistance to doxorubicin and mitoxantrone, even though the hormone negatively regulates the gene expression of MDR1 and ABCG2.

P2, N=41, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed

Moreover, marein can significantly sensitize the ABCG2-expressing tumor cells to chemotherapeutic drugs such as topotecan, mitoxantrone, and Olaparib. This study reveals a novel role and mechanism of marein in modulating drug resistance, and may have important implications in treatment of cancers that are resistant to chemotherapeutic drugs that belong to the substrates of ABCG2 transporters.

P2, N=16, Active, not recruiting, Robert Redner, MD | Completed --> Active, not recruiting | Trial completion date: Feb 2023 --> Dec 2028

P1, N=130, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1

P1, N=50, Recruiting, Shanghai Jiao Tong University School of Medicine | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2026

The intensification of induction therapy with risk stratification on the basis of response to induction and hSCT for high-risk patients led to improved outcomes. Mitoxantrone had a superior anti-leukemic effect than liposomal daunorubicin.

In a murine wound infection with vancomycin-resistant Enterococcus faecalis, a single intraperitoneal bosutinib injection or multiple topical applications on the wound reduce the bacterial load by approximately 10-fold, which is abolished by macrophage depletion...Other Src kinase inhibitors such as DMAT and tirbanibulin also upregulate expression of bacterial uptake markers in macrophages and enhance intracellular bacterial killing. Finally, cotreatment with bosutinib and mitoxantrone, another chemotherapeutic in clinical use, results in an additive effect on bacterial clearance in vitro and in vivo. These results show that bosutinib stimulates macrophage clearance of bacterial infections through multiple mechanisms and could be used to boost the host innate immunity to combat drug-resistant bacterial infections.

EGFR-Erbitux receptor targeted EnGeneIC Dream Vector with mitoxantrone can be safely delivered in paediatric patients aged 2-21 years with solid or CNS tumours harbouring EGFR expression. The discovery of EGFR expression in a high proportion of paediatric gliomas means that EGFR may be useful as a target for other treatment strategies. Targeted therapeutic-loaded EDVs may be worth exploring further for their role in stimulating an anti-tumour immune response.

The complexes were simulated for 100 ns to study the stability by computing the deviation, fluctuations, and intermolecular interactions formed during the simulation. This study produced promising results, satisfying the criteria that Mitoxantrone 2HCl can be a multitargeted inhibitor against cervical cancer proteins-however, experimental validation is a must before human use.Communicated by Ramaswamy H. Sarma.

P2, N=54, Completed, Gilead Sciences | Active, not recruiting --> Completed

A docking study showed that 11 did not share the same binding site with ABCG2 substrate mitoxantrone. Finally, 11 could revert the chemoresistance to SN-38 mediated by ABCG2.

Edited clones were partially resistant to mitoxantrone and XK469, while lacking cross-resistance to etoposide and mAMSA. Results demonstrated the import of TOP2ß/180 in drug sensitivity/resistance in K562 cells and revealed differential paralog activity of TOP2-targeted agents.

P3, N=1400, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting

Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.

P1/2, N=41, Active, not recruiting, Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea | Trial completion date: Oct 2023 --> Oct 2024

Overall, our results suggest that foretinib can target MDR-linked ABCB1 and ABCG2 transporters in clinical cancer therapy.

USP11 exacerbated RIP by triggering an inflammatory response in endothelial cell both in vitro and in vivo, and OTUD5-STING pathway was involved in USP11 promotes RIP. This study provided experimental support for the development of precision intervention strategies targeting USP11 to mitigate RIP.

P2, N=60, Recruiting, Princess Maxima Center for Pediatric Oncology

This study proposes FDA-approved drugs with ALK inhibitory characteristics. Moreover, we identified pharmacophores sites that can be tested with other pharmacological libraries.

P3, N=281, Completed, DKMS gemeinnützige GmbH

However, the substrate mitoxantrone occupies a different site, binding to the F436 region, closer to the L554/L555 plug...See also the Graphical abstract(Fig. 1).

P1, N=120, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2025

This study confirmed a novel mechanism by which E2F3/CDC25B mediated DNA damage to promote mitoxantrone resistance in STAD cells, providing a new therapeutic target for STAD treatment.

EGF stimulation of MCF-7/MX cells showed the downregulaton of N-cadherin and β-catenin. Our results suggest that decreased NMIIA heavy phosphorylation at S1943 increases BCRP expression and promotes MX resistance in breast cancer cells via upregulating N-cadherin expression.

P1/2, N=90, Recruiting, Tanja Andrea Gruber | Not yet recruiting --> Recruiting

P1, N=26, Active, not recruiting, Medical College of Wisconsin

P1, N=36, Not yet recruiting, Medical College of Wisconsin

High-risk patients were more sensitive to some small molecules compounds like camptothecin_1003, cisplatin_1005, cytarabine_1006, nutlin-3a (-)_1047, gemcitabine_1190, WZ4003_1614, selumetinib_1736 and mitoxantrone_1810. In summary, our study comprehensively explored the role of NETosis-related genes in gastric cancer, which can provide direction for relevant studies.

At non-toxic concentrations, CRYO markedly reduced BCRP-induced resistance to known substrate drugs (mitoxantrone and SN-38) and cisplatin, gemcitabine, sorafenib, and 5-FU but not oxaliplatin...In contrast, intratumor drug content was enhanced when administered together, and tumor growth was inhibited. In sum, the combined treatment of drugs exported by BCRP with CRYO can improve the response to chemotherapy in CCA patients.

P1, N=48, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Potential therapeutic chemicals are alvocidib, AT-7519, kenpaullone, PHA-793887, JNJ-7706621, danusertibe, doxorubicin and analogues, mitoxantrone, podofilox, teniposide, and amonafide. This multi-omic study offers a comprehensive view of DEGs in HCC, shedding light on potential therapeutic targets and drug repurposing opportunities.

Herein, we first prepare chemodrug-gene nanoparticles (Mito-Her2 NPs) by the electrostatic interaction coself-assembly of mitoxantrone hydrochloride (Mito) and human epidermal growth factor receptor-2 antisense oligonucleotide (Her2 ASO)...Mito-Her2@RSHM NPs also show a high tumor suppression rate of 83.33 ± 4.16% in vivo without significant damage to normal tissues. In summary, Mito-Her2@RSHM NPs would be expected as a versatile and safe nanodrug delivery platform with high efficiency for chemo-gene combined cancer treatment.

He began maintenance BCNU/cytoxan, then several cycles 6-MP/MTX/vincristine. On day +554 after diagnosis, he relapsed and started decitabine/venetoclax, then decadron + dasatinib, then MVP, followed by 3 cycles of inotuzumab...As his condition worsened he was put on ponatinib, then asciminib before expiring on day +940...On day +447 he started blinatumomab + IT MTX + nilotinib...The patient underwent leukapheresis and started HiDAC + mitoxantrone + etoposide + dasatinib...Likewise, many undocumented adults are the parents of US citizen minors who would benefit economically from their survival. For consideration we will explore cost analysis to further elucidate the potential benefit of allowing coverage of HSCT.

Our findings showed the combination regimen CLAG(M)/Ven is feasible in pts with AML. It also provided better characterization in terms of early mortality and survivals in these pts, which can help inform future clinical trial design. ORR was similar to what was previously reported with CLAG(M); however, it is encouraging that those who achieved CR/CRi and had MRD testing also achieved MRD negativity.

There is evidence FLAG-IDA may be superior to 7+3 (Solh et al Leuk Res 2020), and that cladribine is superior to fludarabine (Holowiecki et al JCO 2012)...Chemotherapy consisted of cladribine 5 mg/m 2 daily times 5 days, cytarabine 2 gm/m 2 over 4 hrs daily times 5 days (given 2 hours after the completion of each cladribine dose), plus G-CSF 300 ug daily during chemotherapy and then based on weight after that. Patients with adequate cardiac function also received 3 days of mitoxantrone 12 mg/m 2 (CLAG-M) or idarubicin 12 mg/m 2 (CLAG-IDA) on days 1-3 or 2-4... CLAG provides an alternative induction regimen to 7+3. Interestingly, in contrast to 7+3, CR rates did not differ significantly by age or cytogenetic risk group. The older patients treated on this trial were a select group that were considered eligible for intensive chemotherapy.

05 and absolute log2FC>1) in the high-resistance group for one or multiple drugs: amsacrine (ams, n = 10), etoposide (eto, n = 10), tioguanine (thio, n = 8) and mitoxantrone (mito, n = 1). Importantly, our analysis indicates that the differential expression of snoRNAs in the resistance groups cannot be solely attributed to host gene expression, implying that targeting pathways involving host genes might not be the most effective approach. Rather than concentrating on pathways involving host genes, our results suggest that understanding the mechanisms of action of snoRNAs could provide promising avenues for developing novel therapeutic targets to enhance drug response in pediatric ALL.

Recent study showed venetoclax (Ven) added to CLAG+Ida as frontline treatment of AML acquired a good response and well toleration...CLAG±Ida/Mito+Ven: cladribine 5mg/m 2 day 1-5, cytarabine 1-1. 5g/m 2 day 1-5, PEG-G-CSF 6mg day 0, idarubicin 6mg/m 2 day 1-3 or mitoxantrone 6mg/m 2 day 1-3 (lipo-Mito 20mg/m 2 day 1), Ven 400mg day 2-8... CLAG±Ida/Mito+Ven might be a chioce for salvage therapy of RR-AML, with the CR/CRi rate of 66. 7%, MRD-negative rate of 68. 2% and well toleration.

Introduction: Standard induction chemotherapy in newly diagnosed acute myeloid leukemia (AML) includes a combination of standard-dose cytarabine and an anthracycline (idarubicin [IDA], daunorubicin [DNR], or mitoxantrone [MXR]). We are encouraged that our findings mostly agree with previously published studies and that IDA, DNR, and MXR offer comparable survival values in the research and the younger patient groups. In the future, the ever-changing treatment environment in patient groups with targetable mutations makes choosing the optimal anthracycline for induction chemotherapy in AML much more difficult.

Background: Hypomethylating agent (HMA) and venetoclax (Ven) frontline therapy for acute myeloid leukemia (AML) is astandard of care for patients (pts) deemed to be poor candidates for intensive induction due to age or fitness...Fifteen pts (65%) had frontline therapy with azacitidine backbone, 6 pts (26%) with decitabine; some pts received both before intensive therapy...Other regimens included 7+3 (n=2, 9%), FLAG-Ida + Ven (n=2, 9%), HiDAC + Mitoxantrone +/- Ven (n=4, 17%) ( Table 1)... Intensive therapy for R/R AML after prior frontline less-intensive therapy was associated with an ORR rate of 27% and median OS of 5. 8 months in our cohort. This approach may be an appropriate strategy for a subset of pts, particularly those eligible for alloHCT.

The studies showed that the previously described DMQCd, a penta-methoxylated N-carboranyl-2-phenylquinazolin-4-amine, was by far superior to its organic analogues in terms of cytotoxicity, inhibition of the human ABCG2 transporter, as well as the ability to reverse BCRP-mediated mitoxantrone resistance in MDCKII-hABCG2 and HT29 colon cancer cells. Thus, DMQCd is a promising candidate for further studies in combination therapy for ABCG2-overexpressing cancers.