RESUMEN
Six pyrazolopyrimidine rhodium(III) or palladium(II) complexes, [Rh(L1)(H2O)Cl3] (1), [Rh(L2)(CH3OH)Cl3] (2), [Rh(L3)(H2O)Cl3] (3), [Rh2(L4)Cl6]·CH3OH (4), [Rh(L5)(CH3CN)Cl3]·0.5CH3CN (5), and [Pd(L5)Cl2] (6), were synthesized and characterized. These complexes showed high cytotoxicity against six tested cancer cell lines. Most of the complexes showed higher cytotoxicity to T-24 cells in vitro than cisplatin. Mechanism studies indicated that complexes 5 and 6 induced G2/M phase cell cycle arrest through DNA damage, and induced apoptosis via endoplasmic reticulum stress response. In addition, complex 5 also induced cell apoptosis via mitochondrial dysfunction. Complexes 5 and 6 showed low in vivo toxicity and high tumor growth inhibitory activity in mouse tumor models. The inhibitory effect of rhodium complex 5 on tumor growth in vivo was more pronounced than that of palladium complex 6.
Asunto(s)
Antineoplásicos , Complejos de Coordinación , Neoplasias , Rodio , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/metabolismo , Rodio/farmacología , Paladio/farmacología , Línea Celular , Neoplasias/tratamiento farmacológico , Apoptosis , Complejos de Coordinación/farmacología , Línea Celular TumoralRESUMEN
8p11 myeloproliferative syndrome (EMS) is a rare and aggressive hematological malignancy, characterized by myeloproliferative neoplasms, and associated with eosinophilia and T- or B-cell lineage lymphoblastic lymphoma. The pathogenesis is defined by the presence of chromosomal translocations associated with the fibroblast growth factor-1 (FGFR1) gene, located in the 8p11-12.1 chromosomal locus. At present, only ~100 cases have been reported globally. At least 15 partner genes have been identified, including the most common, the zinc finger MYM-type containing 2 (ZNF198)-FGFR1 fusion gene formed by t(8;13)(p11;q12). Different fusion genes determine the clinical manifestations and prognosis of the disease. Patients with EMS with t(8;13)(p11;q12) commonly present with lymphadenopathy and T-lymphoblastic lymphoma, which usually converts to acute myeloid leukemia (AML) with the progression of the disease. The present study describes the case of an elderly female patient with EMS with t(8;13)(p11;q12), presenting with myeloid/lymphoid syndrome (myeloproliferative neoplasms and T lymphoblastic lymphoma). The patient received the CHOPE regimen combined with tyrosine kinase inhibitor (dasatin) treatment and obtained short-term complete remission. However, 6 months later, the disease progressed from EMS to AML and the patient died due to ineffective induction therapy. The present study also reviews the relevant literature about this unusual entity to enhance the understanding of EMS.
RESUMEN
This study aimed to determine the expression levels of the autophagy markers Beclin-1 and p62 in patients with diffuse large B-cell lymphoma (DLBCL) and explore the association between autophagy and disease prognosis. The expression of Beclin-1 and p62 was investigated in patients with DLBCL (n=60) and patients with reactive lymphoproliferative disease (RLD; n=20) using immunohistochemistry. The association between the clinical characteristics of patients with DLBCL and autophagy status was further analyzed. Beclin-1 levels were increased in patients with RLD compared to those with DLBCL, but the difference was not statistically significant (P>0.05). p62 levels in patients with DLBCL were significantly higher than those in patients with RLD (P<0.05). Beclin-1 expression was associated only with the Ann Arbor stage (P<0.05), whereas p62 expression was associated with the Ann Arbor stage, International Prognostic Index score, extranodal involvement, and Ki-67 index (P<0.05). Beclin-1 and p62 levels were not associated with short-term treatment efficacy in patients with DLBCL. Survival analysis showed that Beclin-1 expression had no significant effect on 2-year progression-free survival (PFS) or overall survival (OS) (P>0.05). However, high p62 expression in patients with DLBCL was associated with reduced 2-year PFS compared with that of patients with low p62 expression (P<0.05); the 2-year OS was not affected (P>0.05). Our results demonstrate that autophagic activity affects the prognosis of patients with DLBCL; the lower the autophagic activity, the shorter the PFS. Targeted p62 knockout may be a novel therapeutic strategy for the treatment of patients with DLBCL.
RESUMEN
As a continuation of our endeavors in discovering metal-based drugs with cytotoxic and antimetastatic activities, herein, we reported the syntheses of 11 new rhodium(III)-picolinamide complexes and the exploration of their potential anticancer activities. These Rh(III) complexes showed high antiproliferative activity against the tested cancer cell lines in vitro. The mechanism study indicated that Rh1 ([Rh(3a)(CH3CN)Cl2]) and Rh2 ([Rh(3b)(CH3CN)Cl2]) inhibited cell proliferation by multiple modes of action via cell cycle arrest, apoptosis, and autophagy and inhibited cell metastasis via FAK-regulated integrin ß1-mediated suppression of EGFR expression. Furthermore, Rh1 and Rh2 significantly inhibited bladder cancer growth and breast cancer metastasis in a xenograft model. These rhodium(III) complexes could be developed as potential anticancer agents with antitumor growth and antimetastasis activity.