Development of a Tumor-Selective Approach to Treat Metastatic Cancer

BACKGROUND: Patients diagnosed with metastatic cancer have almost uniformly poor prognoses. The treatments available for patients with disseminated disease are usually not curative and have side effects that limit the therapy that can be given. A treatment that is selectively toxic to tumors would maximize the beneficial effects of therapy and minimize side effects, potentially enabling effective treatment to be administered. METHODS AND FINDINGS: We postulated that the tumor-tropic property of stem cells or progenitor cells could be exploited to selectively deliver a therapeutic gene to metastatic solid tumors, and that expression of an appropriate transgene at tumor loci might mediate cures of metastatic disease. To test this hypothesis, we injected HB1.F3.C1 cells transduced to express an enzyme that efficiently activates the anti-cancer prodrug CPT-11 intravenously into mice bearing disseminated neuroblastoma tumors. The HB1.F3.C1 cells migrated selectively to tumor sites regardless of the size or anatomical location of the tumors. Mice were then treated systemically with CPT-11, and the efficacy of treatment was monitored. Mice treated with the combination of HB1.F3.C1 cells expressing the CPT-11-activating enzyme and this prodrug produced tumor-free survival of 100% of the mice for >6 months (P<0.001 compared to control groups). CONCLUSIONS: The novel and significant finding of this study is that it may be possible to exploit the tumor-tropic property of stem or progenitor cells to mediate effective, tumor-selective therapy for metastatic tumors, for which no tolerated curative treatments are currently available

Structural versatility driven by the flexible di(4-pyridyl) sulfide ligand: from cobalt(II) single-ion magnets to sheet-like copper(II) weak antiferromagnets

The reaction between the ligand di(4-pyridyl)sulfide (dps) and two salts of divalent first row transition metals (M = Co2+, and Cu2+) resulted in three new compounds with formula: [Co(dps)(4)(H2O)(2)](ClO4)(2)center dot H2O (1), [Cu(dps)(2)(dmso)(2)](n)(ClO4)(2n) (2) and [{Cu(dps)(2)(dmso)(2)}{Cu(dps)(2)(dmso)(H2O)}](n)(ClO4)(4n)center dot 2nH(2)O center dot n(dmso) (3). Crystal structures of 1-3 were determined using single-crystal X-ray diffraction. Crystal structure of 1 consists of a mononuclear complex, in which the dps ligand acts in a monodentate mode through one of the pyridyl nitrogen atoms. Compounds 2 and 3 present the dps ligands bridging metal centers leading to bidimensional coordination polymers. Magnetic properties in the polycrystalline samples of 1-3 in the 300-2 K temperature range were investigated. Complex 1 exhibits a field-induced slow magnetization behavior and behaves as a single-ion magnet with an effective energy barrier for the reversal of magnetization of 22.9 (1.1) K and tau(0) = 5.3(1.2) x 10(-7) s.171203211CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE MINAS GERAIS - FAPEMIGFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP405199/2016-3; 309687/2018-7; 313068/2017-8Sem informaçãoPPM00508-16; PPM00523-162015/22379-