Search results for "Piperazines"
showing 10 items of 135 documents
Synthesis and cytotoxic activity of a new potential DNA bisintercalator: 1,4-Bis{3-[N-(4-chlorobenzo[g]phthalazin-1-yl)aminopropyl]}piperazine
2010
The synthesis of new 1,4-bisalkylamino (2-4) and 1-alkylamino-4-chloro (5-6) substituted benzo[g]phthalazines is reported. Compounds 2-4 and 6 were prepared both in the free and heteroaromatic ring protonated forms. Bifunctional 6 contains the 1,4-bisaminopropylpiperazine chain as a linker between the two heteroaromatic units, whereas 5 is its monofunctional analogue. The in vitro antitumour activity of the synthesized compounds has been tested against human colon, breast and lung carcinoma cells, and also against human glioblastoma cells. Results obtained show that all of them are active in all cases, but bifunctional 6·2HCl is remarkably effective against the four cell lines tested, exhib…
Mass spectrometric studies on small open-chain piperazine-containing ligands and their transition metal complexes
2001
Electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry was used to characterize the complexes formed between open-chain piperazine-containing ligands and transition metal salts (Cobalt, Copper, Zinc, and Cadmium as chlorides, nitrates, and acetates). Only single-charged complexes were observed, formed of one ligand (L) and mainly one metal ion (M). Since the net charge of the complexes was one, a counterion (X) was attached to some of the complexes, with formation of [L + M + X]+ complexes, and a proton was lost from others, as in [L − H + M]+ complexes. In most cases the composition of the complexes was more dependent on the ligand than the metal salt. Collisio…
Effects of the MDM2 inhibitor Nutlin-3a on sensitivity of pancreatic cancer cells to berberine and modified berberines in the presence and absence of…
2021
Abstract Approaches to improve pancreatic cancer therapy are essential as this disease has a very bleak outcome. Approximately 80% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDAC). A key regulatory gene frequently mutated (∼75%) in PDAC is the TP53 tumor suppressor gene which controls the transcription of multiple genes involved in cell cycle progression, apoptosis, cancer progression and other growth regulatory processes. The mouse double minute 2 homolog (MDM2) gene product is a nuclear-localized E3 ubiquitin ligase and negatively regulates the TP53 protein which results in its proteasomal degradation. Various MDM2 inhibitors have been isolated and examined in clinical t…
The GiSAS study: Rationale and design of a pragmatic randomized controlled trial on aripiprazole, olanzapine and haloperidol in the long-term treatme…
2011
Given the controversy about the comparative efficacy of first- compared with second-generation antipsychotics in the treatment of schizophrenia, more large-scale evidence is needed to guide clinicians in their prescriptions. Most randomized controlled trials (RCTs) were conducted in centers of excellence on highly selected samples, poorly representative of real-world patients, and often suffered conflicts of interest as they were sponsored by drug companies. The primary aim of the present study is to compare the effectiveness of haloperidol, olanzapine and aripiprazole in a representative sample of schizophrenia patients. The GiSAS trial is an open-label, independent, pragmatic RCT in Itali…
Functional polymorphisms in SOCS1 and PTPN22 genes correlate with the response to imatinib treatment in newly diagnosed chronic-phase chronic myeloid…
2011
a b s t r a c t The function of the natural modulators of BCR-ABL-induced signaling pathways could influence the results to imatinib treatment. We assessed the association between single nucleotide polymorphisms (SNPs) on genes of the phosphatase family and the suppressors of cytokine signaling and the response to imatinib in 105 patients newly diagnosed with chronic-phase CML. SNPs in SOCS1 (rs243327) and PTPN22 (rs2476601) genes correlated with the risk of primary resistance to imatinib. A high-risk Sokal score, the T allele in PTPN22 SNP, and each copy of the C allele in SOCS1 SNP were adverse prognostic factors for failure-free survival (FFS). Based on such parameters, three risk groups…
Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid …
2007
BACKGROUND Despite advances in drug therapy and allogeneic stem cell transplantation (allo-SCT), the prognosis of patients with chronic myeloid leukemia (CML) in blast crisis remains poor. Imatinib has demonstrated synergistic effects in vitro with mitoxantrone, etoposide, and cytarabine. METHODS A Phase I/II trial was performed in patients with CML myeloid blast crisis. Patients were treated with imatinib + mitoxantrone/etoposide in four cohorts: mitoxantrone 10 mg/m2/day and etoposide 100 mg/m2/day for 2 or 3 consecutive days and imatinib 600 mg/day from Day 15 (cohorts 1 and 2) or from Day 1 (cohorts 3 and 4). After hematologic reconstitution after the cytopenic phase, cytarabine was giv…
Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.
2003
Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML.We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression.Afte…
The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in philadelphia chromosome-negative cells.
2007
BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-…
Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, mu…
2013
Contains fulltext : 118365.pdf (Publisher’s version ) (Closed access) BACKGROUND: Until now, only imatinib and sunitinib have proven clinical benefit in patients with gastrointestinal stromal tumours (GIST), but almost all metastatic GIST eventually develop resistance to these agents, resulting in fatal disease progression. We aimed to assess efficacy and safety of regorafenib in patients with metastatic or unresectable GIST progressing after failure of at least imatinib and sunitinib. METHODS: We did this phase 3 trial at 57 hospitals in 17 countries. Patients with histologically confirmed, metastatic or unresectable GIST, with failure of at least previous imatinib and sunitinib were rando…
Lack of everolimus diffusion in pleural fluid during pleural progression of breast cancer: A case report
2020
Background We report here a case where no everolimus pleural diffusion was evidenced at the same time of pleural progression of a metastatic breast cancer treated with everolimus and exemestane. Case description A 69-year-old woman was diagnosed in October 2006 with stage III invasive ductal breast adenocarcinoma. After nine months of everolimus and exemestane treatment, she presented with a pleural progression. Everolimus concentration was measured in blood and in pleural fluid. Residual blood concentration was at 9.1 ng/mL, while no everolimus was observed in the pleural fluid. Management and outcome Due to inefficacy of everolimus in this patient, she was switched to palbociclib and fulv…