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Pesquisa : D02.691.800 [Categoria DeCS]
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[PMID]:29274491
[Au] Autor:Srivastava P; Singh K; Verma M; Sivakumar S; Patra AK
[Ad] Endereço:Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, Uttar Pradesh, India.
[Ti] Título:Photoactive platinum(II) complexes of nonsteroidal anti-inflammatory drug naproxen: Interaction with biological targets, antioxidant activity and cytotoxicity.
[So] Source:Eur J Med Chem;144:243-254, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The effect on the therapeutic efficacy of Pt(II) complexes on combining non-steroidal anti-inflammatory drugs (NSAIDs) is an attractive strategy to circumvent chronic inflammation mediated by cancer and metastasis. Two square-planar platinum(II) complexes: [Pt(dach)(nap)Cl] (1) and [Pt(dach)(nap) ] (2), where dach = (1R,2R)-dichloro(cyclohexane-1,2-diamine) and NSAID drug naproxen (nap), have been designed for studying their biological activity. The naproxen bound to the Pt(II) centre get released upon photoirradiation with low-power UV-A light as confirmed by the significant enhancement in emission intensities of the complexes. The compounds were evaluated for their photophysical properties, photostability, reactivity with 5'-guanosine monophophosphate (5'-GMP), interactions with CT-DNA and BSA, antioxidant activity and reactive oxygen species mediated photo-induced DNA damage properties. ESI-MS studies demonstrated the formation of bis-adduct with 5'-GMP and the formation of Pt -DNA crosslinks by gel electrophoretic mobility shift assay and ITC studies. The interaction of the complexes 1 and 2 with the CT-DNA exhibits potential binding affinity (K âˆ¼ 10 M , K ∼ 10 M ), implying intercalation to CT-DNA through planar naphthyl ring of the complexes. Both the complexes also exhibit strong binding affinity towards BSA (K ∼ 10 M ). The complexes exhibit efficient DNA damage activity on irradiation at 365 nm via formation of singlet oxygen ( O ) and hydroxyl radical ( OH) under physiological conditions. Both the complexes were cytotoxic in dark and exhibit significant enhancement of cytotoxicity upon photo-exposure against HeLa and HepG2 cancer cells giving IC values ranging from 8 to 12 µM for 1 and 2. The cellular internalization data showed cytosolic and nuclear localization of the complexes in the HeLa cells.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/química
Antineoplásicos/química
Antioxidantes/química
Naproxeno/análogos & derivados
Compostos Organoplatínicos/química
[Mh] Termos MeSH secundário: Anti-Inflamatórios não Esteroides/farmacologia
Antineoplásicos/farmacologia
Antioxidantes/farmacologia
Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos da radiação
Dano ao DNA/efeitos dos fármacos
Dano ao DNA/efeitos da radiação
Células HeLa
Células Hep G2
Seres Humanos
Naproxeno/farmacologia
Neoplasias/tratamento farmacológico
Neoplasias/genética
Compostos Organoplatínicos/farmacologia
Fármacos Fotossensibilizantes/química
Fármacos Fotossensibilizantes/farmacologia
Raios Ultravioleta
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antineoplastic Agents); 0 (Antioxidants); 0 (Organoplatinum Compounds); 0 (Photosensitizing Agents); 57Y76R9ATQ (Naproxen)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171224
[St] Status:MEDLINE


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[PMID]:28461099
[Au] Autor:Alaaeldin E; Abu Lila AS; Ando H; Fukushima M; Huang CL; Wada H; Sarhan HA; Khaled KA; Ishida T
[Ad] Endereço:Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia 61519, Egypt.
[Ti] Título:Co-administration of liposomal l-OHP and PEGylated TS shRNA-lipoplex: A novel approach to enhance anti-tumor efficacy and reduce the immunogenic response to RNAi molecules.
[So] Source:J Control Release;255:210-217, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Many therapeutic strategies have been applied in efforts to conquer the development and/or progression of cancer. The combination of chemotherapy and an RNAi-based approach has proven to be an efficient anticancer therapy. However, the feasibility of such a therapeutic strategy has been substantially restricted either by the failure to achieve the efficient delivery of RNAi molecules to tumor tissue or by the immunostimulatory response triggered by RNAi molecules. In this study, therefore, we intended to investigate the efficacy of using liposomal oxaliplatin (liposomal l-OHP) to guarantee the efficient delivery of RNAi molecules, namely shRNA against thymidylate synthase (TS shRNA) complexed with cationic liposome (TS shRNA-lipoplex), to solid tumors, and to suppress the immunostimulatory effect of RNAi molecules, TS shRNA, following intravenous administration. Herein, we describe how liposomal l-OHP enhanced the intra-tumor accumulation of TS shRNA-lipoplex and significantly reduced the immunostimulatory response triggered by TS shRNA. Consequently, such enhanced accumulation of TS shRNA-lipoplex along with the cytotoxic effect of liposomal l-OHP led to a remarkable tumor growth suppression (compared to mono-therapy) following systemic administration. Our results, therefore, may have important implications for the provision of a safer and more applicable combination therapy of RNAi molecules and anti-cancer agents that can produce a more reliable anti-tumor effect.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Neoplasias/terapia
Compostos Organoplatínicos/administração & dosagem
RNA Interferente Pequeno/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/química
Antineoplásicos/farmacocinética
Antineoplásicos/uso terapêutico
Linhagem Celular Tumoral
Citocinas/metabolismo
Seres Humanos
Lipossomos
Masculino
Camundongos Endogâmicos BALB C
Camundongos Nus
Neoplasias/genética
Neoplasias/metabolismo
Compostos Organoplatínicos/química
Compostos Organoplatínicos/farmacocinética
Compostos Organoplatínicos/uso terapêutico
Polietilenoglicóis/química
Interferência de RNA
RNA Interferente Pequeno/química
RNA Interferente Pequeno/farmacocinética
RNA Interferente Pequeno/uso terapêutico
Timidilato Sintase/genética
Distribuição Tecidual
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Cytokines); 0 (Liposomes); 0 (Organoplatinum Compounds); 0 (RNA, Small Interfering); 04ZR38536J (oxaliplatin); 30IQX730WE (Polyethylene Glycols); EC 2.1.1.45 (Thymidylate Synthase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29206996
[Au] Autor:Fokas E; Ströbel P; Fietkau R; Ghadimi M; Liersch T; Grabenbauer GG; Hartmann A; Kaufmann M; Sauer R; Graeven U; Hoffmanns H; Raab HR; Hothorn T; Wittekind C; Rödel C; German Rectal Cancer Study Group
[Ad] Endereço:Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany.
[Ti] Título:Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer.
[So] Source:J Natl Cancer Inst;109(12), 2017 Dec 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: We investigated tumor regression grading (TRG) as a prognostic marker and individual-level surrogate for disease-free survival (DFS) in patients with rectal carcinoma treated within the Chirurgische Arbeitsgemeinschaft fur Onkologie/Arbeitsgemeinschaft Radiologische Onkologie/Arbeitsgemeinschaft Internistische Onkologie (CAO/ARO/AIO)-04 randomized trial. Methods: TRG was recorded prospectively using the Dworak classification in 1179 patients after preoperative fluorouracil-based chemoradiotherapy (CRT) with or without oxaliplatin. Multivariable analysis was performed using Cox regression models adjusted for treatment arm, resection status, and pathologic stage. Individual-level surrogacy of TRG for DFS was examined using the four Prentice criteria (PC1-4). All statistical tests were two-sided. Results: With a median follow-up of 50 months, the addition of oxaliplatin to fluorouracil-based CRT led to statistically significantly improved three-year DFS (75.9%, 95% CI = 72.3 to 79.5, vs 71.3%, 95% CI = 67.6 to 74.9, P = .04, PC 1) and a shift toward more advanced TRG groups ( P < .001, PC 2) compared with CRT with fluorouracil alone. The three-year DFS was 64.6% (95% CI = 57.3 to 71.9), 77.6% (95% CI = 74.5 to 80.7), and 92.3% (95% CI = 88.4 to 96.2) for TRG 0 + 1 (poor regression), TRG 2 + 3 (intermediate regression), and TRG 4 (complete regression), respectively ( P < .001, PC 3). TRG constituted an independent prognostic factor for DFS (TRG 2 + 3 vs TRG 0 + 1, HR = 0.68, 95% CI = 0.51 to 0.90, P = .007). Due to multicollinearity, TRG 4 and pathologic stage could not be tested within the same model. The treatment effect on DFS was captured by TRG, satisfying individual-level PC4. Conclusions: Higher TRG after preoperative CRT predicted a favorable long-term outcome. At the individual patient level, TRG was a surrogate marker for DFS. Further phase III trials are needed to validate TRG as a surrogate at trial level.
[Mh] Termos MeSH primário: Carcinoma/secundário
Carcinoma/terapia
Recidiva Local de Neoplasia
Neoplasias Retais/patologia
Neoplasias Retais/terapia
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Quimiorradioterapia Adjuvante
Intervalo Livre de Doença
Feminino
Fluoruracila/administração & dosagem
Seguimentos
Seres Humanos
Masculino
Margens de Excisão
Gradação de Tumores
Recidiva Local de Neoplasia/patologia
Neoplasia Residual
Compostos Organoplatínicos/administração & dosagem
Período Pré-Operatório
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Organoplatinum Compounds); 04ZR38536J (oxaliplatin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171206
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx095


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[PMID]:29335202
[Au] Autor:Wei ZZ; Qin QP; Meng T; Deng CX; Liang H; Chen ZF
[Ad] Endereço:State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, 15 Yucai Road, Guilin 541004, PR China.
[Ti] Título:5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA and mitochondrial functions.
[So] Source:Eur J Med Chem;145:360-369, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Two platinum(II) complexes [Pt(L)(DMSO)Cl] (1) and [Pt(L)(pn)]Cl (2) with 5-bromo-oxoisoaporphine (H-L) were synthesized. We found that the two new platinum(II) complexes were more selective for Hep-G2 tumor cells than for normal cells (HL-7702, WI-38 and L-o2 cell lines). 5-Bromine-oxoisoaporphine platinum(II) complex 2 was a telomerase inhibitor targeting c-myc G4, and it triggered Hep-G2 cell apoptosis more potently than complex 1. Moreover, they induced cell apoptosis via disruption of mitochondrial functions. Significantly increased ROS level, loss of Δψ, decrease of bcl-2 level, and increase of some of the mitochondria-initiated apoptosis protein levels (including bax, Cyt C, caspase-3, caspase-9, and apaf-1) were observed in Hep-G2 cells. In brief, complexes 1 and 2 triggered Hep-G2 cell apoptosis mainly through inhibiting telomerase activity by interacting with c-myc promoter elements and disruption of mitochondrial pathway. Our results also showed the effects of second ligands on the in vitro antitumor activity in the order of pn > Cl and DMSO.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Quadruplex G/efeitos dos fármacos
Mitocôndrias/efeitos dos fármacos
Compostos Organoplatínicos/farmacologia
Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores
Telomerase/antagonistas & inibidores
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Mitocôndrias/metabolismo
Estrutura Molecular
Compostos Organoplatínicos/síntese química
Compostos Organoplatínicos/química
Proteínas Proto-Oncogênicas c-myc/metabolismo
Relação Estrutura-Atividade
Telomerase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Organoplatinum Compounds); 0 (Proto-Oncogene Proteins c-myc); EC 2.7.7.49 (Telomerase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


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[PMID]:28448662
[Au] Autor:Al-Batran SE; Homann N; Pauligk C; Illerhaus G; Martens UM; Stoehlmacher J; Schmalenberg H; Luley KB; Prasnikar N; Egger M; Probst S; Messmann H; Moehler M; Fischbach W; Hartmann JT; Mayer F; Höffkes HG; Koenigsmann M; Arnold D; Kraus TW; Grimm K; Berkhoff S; Post S; Jäger E; Bechstein W; Ronellenfitsch U; Mönig S; Hofheinz RD
[Ad] Endereço:Institute of Clinical Cancer Research, Krankenhaus Nordwest, Universitären University Cancer Center, Frankfurt, Germany.
[Ti] Título:Effect of Neoadjuvant Chemotherapy Followed by Surgical Resection on Survival in Patients With Limited Metastatic Gastric or Gastroesophageal Junction Cancer: The AIO-FLOT3 Trial.
[So] Source:JAMA Oncol;3(9):1237-1244, 2017 Sep 01.
[Is] ISSN:2374-2445
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Importance: Surgical resection has a potential benefit for patients with metastatic adenocarcinoma of the stomach and gastroesophageal junction. Objective: To evaluate outcome in patients with limited metastatic disease who receive chemotherapy first and proceed to surgical resection. Design, Setting, and Participants: The AIO-FLOT3 (Arbeitsgemeinschaft Internistische Onkologie-fluorouracil, leucovorin, oxaliplatin, and docetaxel) trial is a prospective, phase 2 trial of 252 patients with resectable or metastatic gastric or gastroesophageal junction adenocarcinoma. Patients were enrolled from 52 cancer care centers in Germany between February 1, 2009, and January 31, 2010, and stratified to 1 of 3 groups: resectable (arm A), limited metastatic (arm B), or extensive metastatic (arm C). Data cutoff was January 2012, and the analysis was performed in March 2013. Interventions: Patients in arm A received 4 preoperative cycles of fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) followed by surgery and 4 postoperative cycles. Patients in arm B received at least 4 cycles of neoadjuvant FLOT and proceeded to surgical resection if restaging (using computed tomography and magnetic resonance imaging) showed a chance of margin-free (R0) resection of the primary tumor and at least a macroscopic complete resection of the metastatic lesions. Patients in arm C were offered FLOT chemotherapy and surgery only if required for palliation. Patients received a median (range) of 8 (1-15) cycles of FLOT. Main Outcomes and Measures: The primary end point was overall survival. Results: In total, 238 of 252 patients (94.4%) were eligible to participate. The median (range) age of participants was 66 (36-79) years in arm A (n = 51), 63 (28-79) years in arm B (n = 60), and 65 (23-83) years in arm C (n = 127). Patients in arm B (n = 60) had only retroperitoneal lymph node involvement (27 patients [45%]), liver involvement (11 [18.3%]), lung involvement (10 [16.7%]), localized peritoneal involvement (4 [6.7%]), or other (8 [13.3%]) incurable sites. Median overall survival was 22.9 months (95% CI, 16.5 to upper level not achieved) for arm B, compared with 10.7 months (95% CI, 9.1-12.8) for arm C (hazard ratio, 0.37; 95% CI, 0.25-0.55) (P < .001). The response rate for arm B was 60% (complete, 10%; partial, 50%), which is higher than the 43.3% for arm C. In arm B, 36 of 60 patients (60%) proceeded to surgery. The median overall survival was 31.3 months (95% CI, 18.9-upper level not achieved) for patients who proceeded to surgery and 15.9 months (95% CI, 7.1-22.9) for the other patients. Conclusions and Relevance: Patients with limited metastatic disease who received neoadjuvant chemotherapy and proceeded to surgery showed a favorable survival. The AIO-FLOT3 trial provides a rationale for further randomized clinical trials. Trial Registration: clinicaltrials.gov identifier: NCT00849615.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Junção Esofagogástrica
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Peritoneais/tratamento farmacológico
Neoplasias Gástricas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adenocarcinoma/secundário
Adenocarcinoma/cirurgia
Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Quimioterapia Adjuvante
Fluoruracila/administração & dosagem
Gastrectomia
Seres Humanos
Leucovorina/administração & dosagem
Neoplasias Hepáticas/secundário
Neoplasias Hepáticas/cirurgia
Neoplasias Pulmonares/secundário
Neoplasias Pulmonares/cirurgia
Metástase Linfática
Metastasectomia
Meia-Idade
Terapia Neoadjuvante
Estadiamento de Neoplasias
Compostos Organoplatínicos/administração & dosagem
Neoplasias Peritoneais/secundário
Neoplasias Peritoneais/cirurgia
Estudos Prospectivos
Neoplasias Gástricas/patologia
Neoplasias Gástricas/cirurgia
Taxa de Sobrevida
Taxoides/administração & dosagem
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Organoplatinum Compounds); 0 (Taxoids); 04ZR38536J (oxaliplatin); 15H5577CQD (docetaxel); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1001/jamaoncol.2017.0515


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[PMID]:28452475
[Au] Autor:Ritacco I; Al Assy M; Abd El-Rahman MK; Fahmy SA; Russo N; Shoeib T; Sicilia E
[Ad] Endereço:Department of Chemistry and Chemical Technologies, University of Calabria , Arcavacata di Rende 87036, Italy.
[Ti] Título:Hydrolysis in Acidic Environment and Degradation of Satraplatin: A Joint Experimental and Theoretical Investigation.
[So] Source:Inorg Chem;56(10):6013-6026, 2017 May 15.
[Is] ISSN:1520-510X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:For the synthesis and selection of active platinum-based anticancer drugs that perform better than cisplatin and its analogues, six-coordinate octahedral Pt(IV) complexes appear to be promising candidates as, being kinetically more inert and more resistant to ligand substitution than four-coordinate Pt(II) centers, they are able to minimize unwanted side reactions with biomolecules prior to DNA binding. Due to their kinetic inertness, Pt(IV) complexes have also been exploited to bypass inconvenient intravenous administration. The most prominent example is satraplatin (Sat.) which is the first platinum antineoplastic agent reported to have oral activity. The present paper deals with a theoretical DFT investigation of the influence that the acidity of the biological environment can have on the activity of satraplatin and analogous octahedral Pt(IV) complexes having two carboxylates as axial ligands. Moreover, here the outcomes of a joint electrospray ionization mass spectrometry and DFT investigation of the fragmentation pathways of the protonated satraplatin are reported. Calculations show that the simulated acidic environment has an important impact on the satraplatin reactivity causing a significant lowering of the barrier that is necessary to overcome for the hydrolysis of the first acetate ligand to occur. Data from electrospray ionization mass spectrometry, H NMR, and potentiometric experiments strongly suggest that the loss of CH COOH from the protonated satraplatin ion [Sat. + H] takes place almost immediately upon dissolution of satraplatin in methanol-water, D O, and water solutions, respectively, at room temperature.
[Mh] Termos MeSH primário: Antineoplásicos/química
Compostos Organoplatínicos/química
Teoria Quântica
[Mh] Termos MeSH secundário: Concentração de Íons de Hidrogênio
Hidrólise
Espectrometria de Massas
Potenciometria
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Organoplatinum Compounds); 8D7B37T28G (satraplatin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1021/acs.inorgchem.7b00945


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[PMID]:29352306
[Au] Autor:Peraldo-Neia C; Cavalloni G; Fenocchio E; Cagnazzo C; Gammaitoni L; Cereda S; Nasti G; Satolli MA; Aprile G; Reni M; Avallone A; Spadi R; Venesio T; Martin V; Doglioni C; Frattini M; Aglietta M; Leone F
[Ad] Endereço:Medical Oncology, Fondazione del Piemonte per l'Oncologia (FPO), IRCCS-Institute of Candiolo, Candiolo, Italy.
[Ti] Título:Prognostic and predictive role of EGFR pathway alterations in biliary cancer patients treated with chemotherapy and anti-EGFR.
[So] Source:PLoS One;13(1):e0191593, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The association of anti-EGFR to gemcitabine and oxaliplatin (GEMOX) chemotherapy did not improve survival in biliary tract carcinoma (BTC) patients. Multiple mechanisms might be involved in the resistance to anti-EGFR. Here, we explored the mutation profile of EGFR extracellular domain (ECD), of tyrosine kinase domain (TKD), and its amplification status. EGFR mutational status of exons 12, 18-21 was analyzed in 57 tumors by Sanger sequencing. EGFR amplification was evaluated in 37 tumors by Fluorescent In Situ Hybridization (FISH). Kaplan-Meier curves were calculated using the log-rank test. Six patients had mutations in exon 12 of EGFR ECD and 7 in EGFR TKD. Neither EGFR ECD nor TKD mutations affected progression free survival (PFS) or overall survival (OS) in the entire population. In the panitumumab plus GEMOX (P-GEMOX) arm, ECD mutated patients had a worse OS, while EGFR TKD mutated patients had a trend towards shorter PFS and OS. Overall, the presence of mutations in EGFR or in its transducers did not affect PFS or OS, while the extrahepatic cholangiocarcinoma (ECC) mutated patients had a worse prognosis compared to WT. Nineteen out of 37 tumors were EGFR amplified, but the amplification did not correlate with survival. ECC EGFR amplified patients had improved OS, whereas the amplification significantly correlated with poor PFS (p = 0.03) in gallbladder carcinoma patients. The high molecular heterogeneity is a predominant feature of BTC: the alterations found in this work seem to have a prognostic impact rather than a predictive role towards anti-EGFR therapy.
[Mh] Termos MeSH primário: Neoplasias do Sistema Biliar/tratamento farmacológico
Neoplasias do Sistema Biliar/genética
Genes erbB-1
Mutação
Receptor do Fator de Crescimento Epidérmico/genética
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias dos Ductos Biliares/tratamento farmacológico
Neoplasias dos Ductos Biliares/genética
Neoplasias dos Ductos Biliares/metabolismo
Neoplasias do Sistema Biliar/metabolismo
Colangiocarcinoma/tratamento farmacológico
Colangiocarcinoma/genética
Colangiocarcinoma/metabolismo
Análise Mutacional de DNA
Desoxicitidina/administração & dosagem
Desoxicitidina/análogos & derivados
Desoxicitidina/uso terapêutico
Neoplasias da Vesícula Biliar/tratamento farmacológico
Neoplasias da Vesícula Biliar/genética
Neoplasias da Vesícula Biliar/metabolismo
Amplificação de Genes
Seres Humanos
Hibridização in Situ Fluorescente
Estimativa de Kaplan-Meier
Compostos Organoplatínicos/administração & dosagem
Compostos Organoplatínicos/uso terapêutico
Prognóstico
Receptor do Fator de Crescimento Epidérmico/antagonistas & inibidores
Receptor do Fator de Crescimento Epidérmico/metabolismo
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Organoplatinum Compounds); 04ZR38536J (oxaliplatin); 0W860991D6 (Deoxycytidine); 6A901E312A (panitumumab); B76N6SBZ8R (gemcitabine); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Receptor, Epidermal Growth Factor)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191593


  8 / 11031 MEDLINE  
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[PMID]:29311468
[Au] Autor:Shida T; Endo Y; Shiraishi T; Yoshioka T; Suzuki K; Kobayashi Y; Ono Y; Ito T; Inoue T
[Ad] Endereço:Division of Pharmacy, Yamagata University Hospital.
[Ti] Título:[Economic Evaluation of mFOLFOX6-based First-line Regimens for Unresectable Advanced or Recurrent Colorectal Cancer Using Clinical Decision Analysis].
[So] Source:Yakugaku Zasshi;138(1):83-90, 2018.
[Is] ISSN:1347-5231
[Cp] País de publicação:Japan
[La] Idioma:jpn
[Ab] Resumo:We evaluated four representative chemotherapy regimens for unresectable advanced or recurrent KRAS-wild type colorectal cancer: mFOLFOX6, mFOLFOX6+bevacizumab (Bmab), cetuximab (Cmab), or panitumumab (Pmab). We employed a decision analysis method in combination with clinical and economic evidence. The health outcomes of the regimens were analyzed on the basis of overall and progression-free survival. The data were drawn from the literature on randomized controlled clinical trials of the above-mentioned drugs. The total costs of the regimens were calculated on the basis of direct costs obtained from the medical records of patients diagnosed with unresectable advanced or recurrent colorectal cancer at Yamagata University Hospital and Yamagata Prefecture Central Hospital. Cost effectiveness was analyzed using a Markov chain Monte Carlo (MCMC) method. The study was designed from the viewpoint of public medical care. The MCMC analysis revealed that expected life months and expected cost were 20 months/3,527,119 yen for mFOLFOX6, 27 months/8,270,625 yen for mFOLFOX6+Bmab, 29 months/13,174,6297 yen for mFOLFOX6+Cmab, and 6 months/12,613,445 yen for mFOLFOX6+Pmab. Incremental costs per effectiveness ratios per life month against mFOLFOX6 were 637,592 yen for mFOLFOX6+Bmab, 1,075,162 yen for mFOLFOX6+Cmab, and 587,455 yen for mFOLFOX6+Pmab. Compared to the conventional mFOLFOX6 regimen, molecular-targeted drug regimens provide better health outcomes, but the cost increases accordingly. mFOLFOX 6+Pmab is the most cost-effective regimen among those surveyed in this study.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/economia
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias Colorretais/tratamento farmacológico
Neoplasias Colorretais/economia
Análise Custo-Benefício
Técnicas de Apoio para a Decisão
Recidiva Local de Neoplasia/dietoterapia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Anticorpos Monoclonais/administração & dosagem
Anticorpos Monoclonais/economia
Bevacizumab/administração & dosagem
Bevacizumab/economia
Cetuximab/administração & dosagem
Cetuximab/economia
Neoplasias Colorretais/mortalidade
Neoplasias Colorretais/patologia
Feminino
Fluoruracila/economia
Seres Humanos
Leucovorina/economia
Masculino
Cadeias de Markov
Meia-Idade
Estadiamento de Neoplasias
Compostos Organoplatínicos/economia
Taxa de Sobrevida
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Organoplatinum Compounds); 2S9ZZM9Q9V (Bevacizumab); 6A901E312A (panitumumab); PQX0D8J21J (Cetuximab); Q573I9DVLP (Leucovorin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180110
[St] Status:MEDLINE
[do] DOI:10.1248/yakushi.17-00159


  9 / 11031 MEDLINE  
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[PMID]:28448876
[Au] Autor:Sebesta F; Burda JV
[Ad] Endereço:Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, 121 16 Prague 2, Czech Republic.
[Ti] Título:Study on electronic properties, thermodynamic and kinetic parameters of the selected platinum(II) derivatives interacting with guanine.
[So] Source:J Inorg Biochem;172:100-109, 2017 Jul.
[Is] ISSN:1873-3344
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Interaction of hydrated forms of several potential anticancer agents (PtCl (diaminocyclohexane), trans-[PtCl (NH )(thiazole)], cis-[PtCl (NH )(piperidine)], and cis-PtCl (NH )(cyclohexylamine) complexes) with guanine are explored and compared with an analogous interaction of cisplatin. Basic electronic properties, binding and stabilization energies are determined and energy profiles for the aquation reaction are estimated at the B3LYP/6-311++G(2df,2pd) level of theory. It is found that the substitution reaction is an exothermic and exergonic process with ΔG slightly less negative than -20kcal/mol. The largest energy release occurs for PtCl(H O)(diaminocyclohexane) complex. The rate constants for the Pt(II) complexes in the chloro- and hydroxo-form are compared and an impact of the ligand in the trans position to water is discussed.
[Mh] Termos MeSH primário: Fenômenos Eletromagnéticos
Guanina/química
Platina/química
Termodinâmica
[Mh] Termos MeSH secundário: Antineoplásicos/química
Cinética
Compostos Organoplatínicos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Organoplatinum Compounds); 49DFR088MY (Platinum); 5Z93L87A1R (Guanine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170428
[St] Status:MEDLINE


  10 / 11031 MEDLINE  
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[PMID]:29221445
[Au] Autor:Kawamoto Y; Komatsu Y; Yuki S; Sawada K; Muranaka T; Harada K; Nakatsumi H; Fukushima H; Ishiguro A; Dazai M; Hatanaka K; Nakamura M; Iwanaga I; Uebayashi M; Sogabe S; Kobayashi Y; Miyagishima T; Ono K; Sakamoto N; Sakata Y
[Ad] Endereço:Department of Cancer Center, Hokkaido University Hospital, Sapporo, Japan.
[Ti] Título:Study protocol of HGCSG1404 SNOW study: a phase I/II trial of combined chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly to patients with advanced gastric cancer.
[So] Source:BMC Cancer;17(1):837, 2017 12 08.
[Is] ISSN:1471-2407
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In Japan, S-1 plus cisplatin (SP) regimen has become a standard therapy for patients with advanced gastric cancer. Moreover, the S-1 plus oxaliplatin regimen is now a standard treatment. Nab-paclitaxel was developed for chemotherapy of gastric cancer in Japanese clinical practice. Nab-paclitaxel, created with albumin-bound paclitaxel particles, has high transferability to tumour tissues and does not cause hypersensitivity reactions because of a different chemical composition compared with docetaxel and paclitaxel. A combination of S-1, nab-paclitaxel and oxaliplatin (which we named 'SNOW regimen') can be a promising triplet therapy for advanced gastric cancer. Although we have to pay attention to chemotherapy-induced neuropathy, we aim to investigate the recommended dose of this regimen in a phase I study. Furthermore, we will investigate its efficacy and toxicity in a phase II study. METHODS: The phase I study is a dose-escalation study using a standard 3 plus 3 design, followed by expansion cohorts. The SNOW regimen involves 28-day cycles with escalated doses of nab-paclitaxel (100-175 mg/m on days 1 and 15) and fixed doses of oxaliplatin (65 mg/ m on days 1 and 15) and S-1 (80 mg/m /day on day 1 to 14). The primary endpoints are assessment of dose limiting toxicities and determination of maximum tolerated dose to investigate the recommended dose in the subsequent phase II study. In the phase II study, the primary endpoint is objective response rate. Secondary endpoints are assessment of safety, progression-free survival, disease control rate, overall survival and time to treatment failure. Adverse events were monitored and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. DISCUSSION: Triplet therapies for advanced gastric cancer patients have been evaluated in clinical trials. The SNOW regimen can be a promising new triplet therapy. TRIAL REGISTRATION: This study is performed at institutes that participate in Hokkaido Gastrointestinal Cancer Study Group (HGCSG) and registered as UMIN000016788 . Registrated 16 March 2015.
[Mh] Termos MeSH primário: Albuminas
Protocolos de Quimioterapia Combinada Antineoplásica
Compostos Organoplatínicos
Ácido Oxônico
Paclitaxel
Neoplasias Gástricas/tratamento farmacológico
Tegafur
[Mh] Termos MeSH secundário: Adulto
Albuminas/administração & dosagem
Albuminas/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Combinação de Medicamentos
Seres Humanos
Compostos Organoplatínicos/administração & dosagem
Compostos Organoplatínicos/uso terapêutico
Ácido Oxônico/administração & dosagem
Ácido Oxônico/uso terapêutico
Paclitaxel/administração & dosagem
Paclitaxel/uso terapêutico
Neoplasias Gástricas/mortalidade
Tegafur/administração & dosagem
Tegafur/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (130-nm albumin-bound paclitaxel); 0 (Albumins); 0 (Drug Combinations); 0 (Organoplatinum Compounds); 04ZR38536J (oxaliplatin); 150863-82-4 (S 1 (combination)); 1548R74NSZ (Tegafur); 5VT6420TIG (Oxonic Acid); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180217
[Lr] Data última revisão:
180217
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171210
[St] Status:MEDLINE
[do] DOI:10.1186/s12885-017-3850-z



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