RESUMEN
Attempts to furnish antitumor structural templates that can prevent the occurrence of drug-induced hyperuricemia spurred us to generate xanthine oxidase inhibitor-based hydroxamic acids and anilides. Specifically, the design strategy involved the insertion of febuxostat (xanthine oxidase inhibitor) as a surface recognition part of the HDAC inhibitor pharmacophore model. Investigation outcomes revealed that hydroxamic acid 4 elicited remarkable antileukemic effects mediated via HDAC isoform inhibition. Delightfully, the adduct retained xanthine oxidase inhibitory activity, though xanthine oxidase inhibition was not the underlying mechanism of its cell growth inhibitory effects. Also, compound 4 demonstrated significant in-vivo anti-hyperuricemic (PO-induced hyperuricemia model) and antitumor activity in an HL-60 xenograft mice model. Compound 4 was conjugated with poly (ethylene glycol) poly(aspartic acid) block copolymer to furnish pH-responsive nanoparticles (NPs) in pursuit of circumventing its cytotoxicity towards the normal cell lines. SEM analysis revealed that NPs had uniform size distributions, while TEM analysis ascertained the spherical shape of NPs, indicating their ability to undergo self-assembly. HDAC inhibitor 4 was liberated from the matrix due to the polymeric nanoformulation's pH-responsiveness, and the NPs demonstrated selective cancer cell targeting ability.
RESUMEN
RATIONALE: Primary cardiac angiosarcoma (PCA) is a rare and fatal disease with a poor prognosis. Whether the survival of PCA patients can be prolonged with additional treatment following complete surgical excision is controversial. PATIENT CONCERNS: In this case study, a 52-year-old male complained of chest tightness and pain for 7 days before admission into the hospital. Subsequently, he revisited the hospital because of dizziness and headache. DIAGNOSES: Initially, the patient was diagnosed with PCA in the right atrium by thoracic computed tomography (CT). Palliative resection identified brain, lung, and liver metastases. INTERVENTION: The patient accepted multimodal combination therapy, including first-line chemotherapy and then second-line anlotinib concurrent with brain radiotherapy and immunotherapy. OUTCOME: Although anlotinib combined with brain radiotherapy controlled the growth of intracranial lesions, progression-free survival (PFS) was only 5 months, and the overall survival (OS) was only 12 months. LESSON: The treatment for metastatic PCA needs an in-depth exploration.