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[PMID]:28467092
[Au] Autor:Wu M; Ye H; Shao C; Zheng X; Li Q; Wang L; Zhao M; Lu G; Chen B; Zhang J; Wang Y; Wang G; Hao H
[Ad] Endereço:Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines and ‡School of Pharmacy, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 210009, China.
[Ti] Título:Metabolomics-Proteomics Combined Approach Identifies Differential Metabolism-Associated Molecular Events between Senescence and Apoptosis.
[So] Source:J Proteome Res;16(6):2250-2261, 2017 Jun 02.
[Is] ISSN:1535-3907
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Apoptosis and senescence are two types of cell fates in response to chemotherapy. Besides canonical pathways that mediate cell fates, cancer cell metabolism has been revealed as a crucial factor affecting cell fate decisions and thus represents a new target for antitumor therapy. Therefore, a comprehensive description of metabolic pathways underlying cell senescence and apoptosis in response to chemotherapy is highly demanded for therapeutic exploitation of both processes. Herein we employed a metabolomics-proteomics combined approach to identify metabolism-associated molecular events that mediate cellular responses to senescence and apoptosis using doxorubicin-treated human breast cancer cells MCF7 as models. Such biomics approach revealed that tricarboxylic acid cycle, pentose phosphate pathway, and nucleotide synthesis pathways were significantly upregulated in the senescent model, whereas fatty acid synthesis was reduced. In apoptotic cells, an overall reduced activity of major metabolic pathways was observed except for the arginine and proline pathway. Combinatorially, these data show the utility of biomics in exploring biochemical mechanism-based differences between apoptosis and senescence and reveal an unprecedented finding of the metabolic events that were induced for survival by facilitating ROS elimination and DNA damage repair in senescent cells, while they were downregulated in apoptotic cells when DNA damage was irreparable.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Senescência Celular/efeitos dos fármacos
Redes e Vias Metabólicas/efeitos dos fármacos
Metabolômica/métodos
Proteômica/métodos
[Mh] Termos MeSH secundário: Ciclo do Ácido Cítrico
Dano ao DNA
Doxorrubicina/farmacologia
Doxorrubicina/uso terapêutico
Ácidos Graxos/biossíntese
Seres Humanos
Células MCF-7
Nucleotídeos/biossíntese
Via de Pentose Fosfato
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Nucleotides); 0 (Reactive Oxygen Species); 80168379AG (Doxorubicin)
[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:170504
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jproteome.7b00111


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[PMID]:28456679
[Au] Autor:Khaliq NU; Oh KS; Sandra FC; Joo Y; Lee J; Byun Y; Kim IS; Kwon IC; Seo JH; Kim SY; Yuk SH
[Ad] Endereço:College of Pharmacy, Korea University, 2511 Sejongro, Sejong 30019, Republic of Korea.
[Ti] Título:Assembly of polymer micelles through the sol-gel transition for effective cancer therapy.
[So] Source:J Control Release;255:258-269, 2017 Jun 10.
[Is] ISSN:1873-4995
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Photo-induced apoptosis-targeted chemotherapy (PIATC) was designed and characterized to propose a new protocol for improved chemotherapy. Intratumoral injection was selected as the mode of administration of the anticancer drug, doxorubicin (DOX). To extend the retention time of DOX at the tumor parenchyma, in-situ gel formation was induced through the sol-gel transition of the Pluronic NPs containing a prodrug of DOX or a photosensitizer. The prodrug (DEVD-S-DOX) was designed to be inactive with a peptide moiety (Aspartic acid-Glutamic acid-Valine-Aspartic acid: DEVD) linked to DOX and to be cleaved into free DOX by caspase-3 expressed with apoptosis. For reactive oxygen species (ROS)-mediated apoptosis, photo-irradiation with methylene blue (MB, photosensitizer) was utilized. The sol-gel transition of the Pluronic NPs containing reactive species, DEVD-S-DOX or MB, was examined by measuring the cloud point and the gel strength in response to temperature change. ROS-mediated apoptosis was observed by measuring the ROS and membrane integrity with induced apoptosis. The in vivo antitumor efficacy of PIATC was measured with a cardiotoxicity assay in tumor-bearing mice.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Doxorrubicina/administração & dosagem
Azul de Metileno/administração & dosagem
Fotoquimioterapia
Fármacos Fotossensibilizantes/administração & dosagem
Poloxâmero/administração & dosagem
Pró-Fármacos/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacocinética
Antineoplásicos/uso terapêutico
Apoptose/efeitos dos fármacos
Caspase 3/metabolismo
Linhagem Celular Tumoral
Doxorrubicina/farmacocinética
Doxorrubicina/uso terapêutico
Liberação Controlada de Fármacos
Géis
Luz
Masculino
Azul de Metileno/uso terapêutico
Camundongos Endogâmicos C3H
Micelas
Neoplasias/tratamento farmacológico
Neoplasias/metabolismo
Fármacos Fotossensibilizantes/uso terapêutico
Poloxâmero/uso terapêutico
Pró-Fármacos/farmacocinética
Pró-Fármacos/uso terapêutico
Espécies Reativas de Oxigênio/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Gels); 0 (Micelles); 0 (Photosensitizing Agents); 0 (Prodrugs); 0 (Reactive Oxygen Species); 106392-12-5 (Poloxamer); 80168379AG (Doxorubicin); EC 3.4.22.- (Caspase 3); T42P99266K (Methylene Blue)
[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:170501
[St] Status:MEDLINE


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[PMID]:29157621
[Au] Autor:Lurain K; Yarchoan R; Uldrick TS
[Ad] Endereço:HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, 10 Center Drive, Bethesda, MD 20892-1868, USA.
[Ti] Título:Treatment of Kaposi Sarcoma Herpesvirus-Associated Multicentric Castleman Disease.
[So] Source:Hematol Oncol Clin North Am;32(1):75-88, 2018 02.
[Is] ISSN:1558-1977
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease (MCD) is a rare, polyclonal lymphoproliferative disorder characterized by flares of inflammatory symptoms, edema, cytopenias, lymphadenopathy, and splenomegaly. Diagnosis requires a lymph node biopsy. Pathogenesis is related to dysregulated inflammatory cytokines, including human and viral interleukin-6. Rituximab alone or in combination with chemotherapy, such as liposomal doxorubicin, has led to an overall survival of over 90% at 5 years. Experimental approaches to treatment include virus activated cytotoxic therapy with high-dose zidovudine and valganciclovir and targeting human interleukin-6 activity. Despite successful treatment of KSHV-MCD, patients remain at high risk for developing non-Hodgkin lymphomas.
[Mh] Termos MeSH primário: Doença de Castleman/tratamento farmacológico
Doxorrubicina/uso terapêutico
Ganciclovir/análogos & derivados
Herpesvirus Humano 8
Rituximab/uso terapêutico
Zidovudina/uso terapêutico
[Mh] Termos MeSH secundário: Biópsia
Doença de Castleman/diagnóstico
Doença de Castleman/metabolismo
Doença de Castleman/patologia
Ganciclovir/uso terapêutico
Seres Humanos
Interleucina-6/antagonistas & inibidores
Interleucina-6/metabolismo
Linfonodos/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (IL6 protein, human); 0 (Interleukin-6); 4B9XT59T7S (Zidovudine); 4F4X42SYQ6 (Rituximab); 80168379AG (Doxorubicin); GCU97FKN3R (valganciclovir); P9G3CKZ4P5 (Ganciclovir)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171122
[St] Status:MEDLINE


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[PMID]:28954297
[Au] Autor:Bandos H; Melnikow J; Rivera DR; Swain SM; Sturtz K; Fehrenbacher L; Wade JL; Brufsky AM; Julian TB; Margolese RG; McCarron EC; Ganz PA
[Ad] Endereço:NRG Oncology and The University of Pittsburgh, Pittsburgh, PA; Center for Healthcare Policy and Research, University of California Davis, Sacramento, CA; Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD; NRG Oncology and The Washington Cancer Institute at
[Ti] Título:Long-term Peripheral Neuropathy in Breast Cancer Patients Treated With Adjuvant Chemotherapy: NRG Oncology/NSABP B-30.
[So] Source:J Natl Cancer Inst;110(2), 2018 Feb 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: The long-term effects of chemotherapy are sparsely reported. Peripheral neuropathy (PN) is one of the most frequent toxicities associated with taxane use for the treatment of early-stage breast cancer. We investigated the impact of the three different docetaxel-based regimens and patient characteristics on long-term, patient-reported outcomes of PN and the impact of PN on long-term quality of life (QOL). Methods: The National Surgical Adjuvant Breast and Bowel Project Protocol B-30 was a randomized trial comparing sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T) (AC→T), concurrent ACT, or AT in women with node-positive, early-stage breast cancer. The AC→T group had a higher cumulative dose of T. PN was one of the symptoms assessed in a QOL substudy. Statistical methods included simple and mixed ordinal logistic regression and general linear models. All statistical tests were two-sided. Results: Of 1512 patients, 41.9% reported PN two years after treatment initiation. Treatment with AT and ACT was associated with less severe long-term PN compared with AC→T (odds ratio [OR] = 0.45, 95% confidence interval [CI] = 0.35 to 0.58; OR = 0.59, 95% CI = 0.46 to 0.75). Preexisting PN, older age, obesity, mastectomy, and greater number of positive nodes were also associated with higher risk of long-term PN. Patients who reported worse PN symptoms at 24 months had statistically significantly worse QOL (Ptrend < .001). Conclusions: The administration of docetaxel is associated with long-term PN. The lower rate of long-term PN in AT and ACT patients might be an important consideration in supporting choosing these therapies for individuals with preexisting neuropathic symptoms or other risk factors for neuropathy.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias da Mama/tratamento farmacológico
Doenças do Sistema Nervoso Periférico/induzido quimicamente
[Mh] Termos MeSH secundário: Quimioterapia Adjuvante
Ciclofosfamida/efeitos adversos
Doxorrubicina/administração & dosagem
Doxorrubicina/efeitos adversos
Esquema de Medicação
Feminino
Seres Humanos
Meia-Idade
Qualidade de Vida
Taxoides/administração & dosagem
Taxoides/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Taxoids); 15H5577CQD (docetaxel); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx162


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[PMID]:28453702
[Au] Autor:Monk BJ; Brady MF; Aghajanian C; Lankes HA; Rizack T; Leach J; Fowler JM; Higgins R; Hanjani P; Morgan M; Edwards R; Bradley W; Kolevska T; Foukas P; Swisher EM; Anderson KS; Gottardo R; Bryan JK; Newkirk M; Manjarrez KL; Mannel RS; Hershberg RM; Coukos G
[Ad] Endereço:Arizona Oncology (US Oncology Network), University of Arizona, College of Medicine, Creighton University School of Medicine at St. Joseph's Hospital, Phoenix.
[Ti] Título:A phase 2, randomized, double-blind, placebo- controlled study of chemo-immunotherapy combination using motolimod with pegylated liposomal doxorubicin in recurrent or persistent ovarian cancer: a Gynecologic Oncology Group partners study.
[So] Source:Ann Oncol;28(5):996-1004, 2017 May 01.
[Is] ISSN:1569-8041
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: A phase 2, randomized, placebo-controlled trial was conducted in women with recurrent epithelial ovarian carcinoma to evaluate the efficacy and safety of motolimod-a Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses-combined with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. Patients and methods: Women with ovarian, fallopian tube, or primary peritoneal carcinoma were randomized 1 : 1 to receive PLD in combination with blinded motolimod or placebo. Randomization was stratified by platinum-free interval (≤6 versus >6-12 months) and Gynecologic Oncology Group (GOG) performance status (0 versus 1). Treatment cycles were repeated every 28 days until disease progression. Results: The addition of motolimod to PLD did not significantly improve overall survival (OS; log rank one-sided P = 0.923, HR = 1.22) or progression-free survival (PFS; log rank one-sided P = 0.943, HR = 1.21). The combination was well tolerated, with no synergistic or unexpected serious toxicity. Most patients experienced adverse events of fatigue, anemia, nausea, decreased white blood cells, and constipation. In pre-specified subgroup analyses, motolimod-treated patients who experienced injection site reactions (ISR) had a lower risk of death compared with those who did not experience ISR. Additionally, pre-treatment in vitro responses of immune biomarkers to TLR8 stimulation predicted OS outcomes in patients receiving motolimod on study. Immune score (tumor infiltrating lymphocytes; TIL), TLR8 single-nucleotide polymorphisms, mutational status in BRCA and other DNA repair genes, and autoantibody biomarkers did not correlate with OS or PFS. Conclusions: The addition of motolimod to PLD did not improve clinical outcomes compared with placebo. However, subset analyses identified statistically significant differences in the OS of motolimod-treated patients on the basis of ISR and in vitro immune responses. Collectively, these data may provide important clues for identifying patients for treatment with immunomodulatory agents in novel combinations and/or delivery approaches. Trial registration: Clinicaltrials.gov, NCT 01666444.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Recidiva Local de Neoplasia/tratamento farmacológico
Neoplasias Epiteliais e Glandulares/tratamento farmacológico
Neoplasias Ovarianas/tratamento farmacológico
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/administração & dosagem
Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
Benzazepinas/administração & dosagem
Intervalo Livre de Doença
Método Duplo-Cego
Doxorrubicina/administração & dosagem
Doxorrubicina/análogos & derivados
Seres Humanos
Imunidade Inata/efeitos dos fármacos
Estimativa de Kaplan-Meier
Meia-Idade
Recidiva Local de Neoplasia/mortalidade
Neoplasias Epiteliais e Glandulares/mortalidade
Neoplasias Ovarianas/mortalidade
Polietilenoglicóis/administração & dosagem
Modelos de Riscos Proporcionais
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Benzazepines); 0 (VTX-2337); 0 (liposomal doxorubicin); 30IQX730WE (Polyethylene Glycols); 80168379AG (Doxorubicin)
[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:170429
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1093/annonc/mdx049


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[PMID]:29184399
[Au] Autor:Wu C; Xu J; Hao Y; Zhao Y; Qiu Y; Jiang J; Yu T; Ji P; Liu Y
[Ad] Endereço:Pharmacy School, Jinzhou Medical University, Jinzhou, China.
[Ti] Título:Application of a lipid-coated hollow calcium phosphate nanoparticle in synergistic co-delivery of doxorubicin and paclitaxel for the treatment of human lung cancer A549 cells.
[So] Source:Int J Nanomedicine;12:7979-7992, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:In this study, we developed a lipid-coated hollow calcium phosphate (LCP) nanoparticle for the combined application of two chemotherapeutic drugs to human lung cancer A549 cells. Hydrophilic doxorubicin (DOX) was incorporated into the hollow structure of hollow calcium phosphate (HCP), and a lipid bilayer containing hydrophobic paclitaxel (PTX) was subsequently coated on the surface of HCP. The study on combinational effects demonstrated that the combination of DOX and PTX at a mass ratio of 12:1 showed a synergistic effect against A549 cells. The particle size, zeta potential, and encapsulation efficiency were measured to obtain optimal values: particle size was 335.0 3.2 nm, zeta potential -41.1 mV, and encapsulation efficiency 80.40%±2.24%. An in vitro release study indicated that LCP produced a sustained drug release. A549 cells had a better uptake of LCP with good biocompatibility. Furthermore, in vitro cytotoxicity experiment, apoptosis analysis, in vivo anti-tumor efficacy and protein expression analysis of Bax, Bcl-2, and Caspase-3 demonstrated that the co-delivery system based on LCP had significant synergistic anti-tumor activity. All conclusions suggested that LCP is a promising platform for co-delivery of multiple anti-tumor drugs.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Sistemas de Liberação de Medicamentos/métodos
Nanopartículas/administração & dosagem
Nanopartículas/química
Fosfolipídeos/química
[Mh] Termos MeSH secundário: Células A549
Animais
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética
Apoptose/efeitos dos fármacos
Fosfatos de Cálcio/química
Caspase 3/metabolismo
Preparações de Ação Retardada/administração & dosagem
Preparações de Ação Retardada/química
Doxorrubicina/administração & dosagem
Doxorrubicina/química
Seres Humanos
Camundongos Nus
Paclitaxel/administração & dosagem
Paclitaxel/química
Tamanho da Partícula
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium Phosphates); 0 (Delayed-Action Preparations); 0 (Phospholipids); 80168379AG (Doxorubicin); 97Z1WI3NDX (calcium phosphate); EC 3.4.22.- (CASP3 protein, human); EC 3.4.22.- (Caspase 3); P88XT4IS4D (Paclitaxel)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171130
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S140957


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[PMID]:29180864
[Au] Autor:Shi J; Su Y; Liu W; Chang J; Zhang Z
[Ad] Endereço:School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou.
[Ti] Título:A nanoliposome-based photoactivable drug delivery system for enhanced cancer therapy and overcoming treatment resistance.
[So] Source:Int J Nanomedicine;12:8257-8275, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Recently, stimuli-responsive drug delivery systems (DDSs) with high spatial/temporal resolution bring many benefits to cancer treatment. However, cancer cells always develop ways to resist and evade treatment, ultimately limit the treatment efficacy of the DDSs. Here, we introduce photo-activated nanoliposomes (PNLs) that impart light-induced cytotoxicity and reversal of drug resistance in synchrony with a photoinitiated and rapid release of antitumor drug. The PNLs consist of a nanoliposome doped with a photosensitizer (hematoporphyrin monomethyl ether [HMME]) in the lipid bilayer and an antitumor drug doxorubicin (DOX) encapsulated inside. PNLs have several distinctive capabilities: 1) carrying high loadings of DOX and HMME and releasing the payloads in a photo-cleavage manner with high spatial/temporal resolution at the site of actions via photocatalysis; 2) reducing drug efflux in MCF-7/multidrug resistance cells via decreasing the level of P-glycoprotein induced by photodynamic therapy (PDT); 3) accumulating in tumor site taking advantage of the enhanced permeability and retention effect; and 4) combining effective chemotherapy and PDT to exert much enhanced anticancer effect and achieving significant tumor regression in a drug-resistant tumor model with little side effects.
[Mh] Termos MeSH primário: Antineoplásicos/administração & dosagem
Sistemas de Liberação de Medicamentos/métodos
Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos
Lipossomos/administração & dosagem
Fotoquimioterapia/métodos
[Mh] Termos MeSH secundário: Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo
Animais
Antineoplásicos/farmacologia
Doxorrubicina/administração & dosagem
Doxorrubicina/farmacologia
Resistência a Múltiplos Medicamentos/efeitos dos fármacos
Feminino
Hematoporfirinas/química
Hematoporfirinas/farmacologia
Seres Humanos
Bicamadas Lipídicas/química
Lipossomos/química
Lipossomos/farmacologia
Células MCF-7
Camundongos Endogâmicos BALB C
Nanoestruturas/administração & dosagem
Nanoestruturas/química
Fármacos Fotossensibilizantes/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ABCB1 protein, human); 0 (ATP Binding Cassette Transporter, Sub-Family B); 0 (Antineoplastic Agents); 0 (Hematoporphyrins); 0 (Lipid Bilayers); 0 (Liposomes); 0 (Photosensitizing Agents); 0 (Reactive Oxygen Species); 0 (hematoporphyrin monomethyl ether); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S143776


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[PMID]:29224502
[Au] Autor:Connors JM; Jurczak W; Straus DJ; Ansell SM; Kim WS; Gallamini A; Younes A; Alekseev S; Illés Á; Picardi M; Lech-Maranda E; Oki Y; Feldman T; Smolewski P; Savage KJ; Bartlett NL; Walewski J; Chen R; Ramchandren R; Zinzani PL; Cunningham D; Rosta A; Josephson NC; Song E; Sachs J; Liu R; Jolin HA; Huebner D; Radford J; ECHELON-1 Study Group
[Ad] Endereço:From the University of British Columbia and the Department of Medical Oncology, British Columbia Cancer Agency Centre for Lymphoid Cancer, Vancouver, Canada (J.M.C., K.J.S.); the Department of Hematology, Jagiellonian University, Krakow (W.J.), the Department of Hematology, Institute of Hematology a
[Ti] Título:Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma.
[So] Source:N Engl J Med;378(4):331-344, 2018 01 25.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma. METHODS: We conducted an open-label, multicenter, randomized phase 3 trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma, in which 664 were assigned to receive brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (A+AVD) and 670 were assigned to receive doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The primary end point was modified progression-free survival (the time to progression, death, or noncomplete response and use of subsequent anticancer therapy) as adjudicated by an independent review committee. The key secondary end point was overall survival. RESULTS: At a median follow-up of 24.6 months, 2-year modified progression-free survival rates in the A+AVD and ABVD groups were 82.1% (95% confidence interval [CI], 78.8 to 85.0) and 77.2% (95% CI, 73.7 to 80.4), respectively, a difference of 4.9 percentage points (hazard ratio for an event of progression, death, or modified progression, 0.77; 95% CI, 0.60 to 0.98; P=0.04). There were 28 deaths with A+AVD and 39 with ABVD (hazard ratio for interim overall survival, 0.73 [95% CI, 0.45 to 1.18]; P=0.20) [corrected]. All secondary efficacy end points trended in favor of A+AVD. Neutropenia occurred in 58% of the patients receiving A+AVD and in 45% of those receiving ABVD; in the A+AVD group, the rate of febrile neutropenia was lower among the 83 patients who received primary prophylaxis with granulocyte colony-stimulating factor than among those who did not (11% vs. 21%). Peripheral neuropathy occurred in 67% of patients in the A+AVD group and in 43% of patients in the ABVD group; 67% of patients in the A+AVD group who had peripheral neuropathy had resolution or improvement at the last follow-up visit. Pulmonary toxicity of grade 3 or higher was reported in less than 1% of patients receiving A+AVD and in 3% of those receiving ABVD. Among the deaths that occurred during treatment, 7 of 9 in the A+AVD group were associated with neutropenia and 11 of 13 in the ABVD group were associated with pulmonary-related toxicity. CONCLUSIONS: A+AVD had superior efficacy to ABVD in the treatment of patients with advanced-stage Hodgkin's lymphoma, with a 4.9 percentage-point lower combined risk of progression, death, or noncomplete response and use of subsequent anticancer therapy at 2 years. (Funded by Millennium Pharmaceuticals and Seattle Genetics; ECHELON-1 ClinicalTrials.gov number, NCT01712490 ; EudraCT number, 2011-005450-60 .).
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Doença de Hodgkin/tratamento farmacológico
Imunoconjugados/administração & dosagem
Fatores Imunológicos/administração & dosagem
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Bleomicina/administração & dosagem
Dacarbazina/administração & dosagem
Intervalo Livre de Doença
Doxorrubicina/administração & dosagem
Feminino
Seguimentos
Doença de Hodgkin/mortalidade
Seres Humanos
Imunoconjugados/efeitos adversos
Fatores Imunológicos/efeitos adversos
Masculino
Meia-Idade
Estadiamento de Neoplasias
Neutropenia/induzido quimicamente
Taxa de Sobrevida
Vimblastina/administração & dosagem
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; COMPARATIVE STUDY; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Immunoconjugates); 0 (Immunologic Factors); 11056-06-7 (Bleomycin); 5V9KLZ54CY (Vinblastine); 7GR28W0FJI (Dacarbazine); 7XL5ISS668 (brentuximab vedotin); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171212
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMoa1708984


  9 / 45979 MEDLINE  
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[PMID]:29390275
[Au] Autor:Li J; Zhou C; Liu W; Sun X; Meng X
[Ad] Endereço:From the Department of Gastroenterology, First Hospital of Jilin University.
[Ti] Título:Synchronous diffuse large B-cell lymphoma of the stomach and small cell lung carcinoma: A case report.
[So] Source:Medicine (Baltimore);96(50):e8873, 2017 Dec.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: The synchronous occurrence of lung cancer in patients with gastric neoplasms is relatively uncommon, especially the cases of synchronous coexistence of small cell lung carcinoma and diffuse large B-cell lymphoma of the stomach. PATIENT CONCERNS: We encountered a case of synchronous primary small cell lung carcinoma and diffuse large B-cell lymphoma of the stomach. A 63-year-old patient with a 7.5 × 5.09 cm mass in the superior lobe of the right lung diagnosed with small cell lung cancer and synchronous diffuse large B-cell lymphoma of the stomach. DIAGNOSES: The diseases were diagnosed by the pathological biopsy and immunohistochemical methods. INTERVENTIONS: As the patient received CHOP chemotherapy, pulmonary function deterioraed. Etoposide was added to the chemotherapy. OUTCOMES: However, after the first treatment, chest computed tomography showed that the mass in the superior lobe of the right lung had increased to 8.5 × 5.2 cm. LESSONS: This report draws attention to the fact that the treatment of synchronous tumors is a challenge.
[Mh] Termos MeSH primário: Carcinoma de Células Pequenas/diagnóstico
Neoplasias Pulmonares/diagnóstico
Linfoma Difuso de Grandes Células B/diagnóstico
Neoplasias Primárias Múltiplas/diagnóstico
Neoplasias Gástricas/diagnóstico
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica
Biópsia
Carcinoma de Células Pequenas/tratamento farmacológico
Carcinoma de Células Pequenas/patologia
Ciclofosfamida
Doxorrubicina
Feminino
Gastroscopia
Seres Humanos
Imuno-Histoquímica
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Pulmonares/patologia
Linfoma Difuso de Grandes Células B/tratamento farmacológico
Linfoma Difuso de Grandes Células B/patologia
Meia-Idade
Neoplasias Primárias Múltiplas/tratamento farmacológico
Neoplasias Primárias Múltiplas/patologia
Prednisona
Neoplasias Gástricas/tratamento farmacológico
Neoplasias Gástricas/patologia
Tomografia Computadorizada por Raios X
Vincristina
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
5J49Q6B70F (Vincristine); 80168379AG (Doxorubicin); 8N3DW7272P (Cyclophosphamide); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180203
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008873


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[PMID]:29346433
[Au] Autor:Chen J; OuYang H; An X; Liu S
[Ad] Endereço:Department of E.N.T., West China Hospital, Sichuan University, Chengdu, China.
[Ti] Título:Vault RNAs partially induces drug resistance of human tumor cells MCF-7 by binding to the RNA/DNA-binding protein PSF and inducing oncogene GAGE6.
[So] Source:PLoS One;13(1):e0191325, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Vault is the largest nonicosahedral cytosolic nucleoprotein particle, which is widely involved in induction of chemoresistance and lead to failure in long-term chemotherapy. Vault contains three different major vault proteins (MVPs) and four vault RNAs paralogues (vtRNAs, vtRNA1-1, vtRNA1-2, vtRNA1-3 and vtRNA2-1). Disruption of the MVPs do not induce hypersensitivity while expression of vtRNAs contributes to cells' drug resistance, indicates that vtRNAs, but not MVPs play an important role in causing drug resistance. Polypyrimidine tract binding protein associated splicing factor (PSF) contributes to cell sensitivity to chemotherapy by its transcriptional activity, promotes us to figure out its potential association with vtRNAs. METHODS: We investigate the interaction between PSF and vtRNAs by electrophoretic mobility shift assays (EMSA) and RNA-immunoprecipitation (IP), and showed the binding between PSF and vtRNAs. Chromatin Immunoprecipitation (ChIP) was performed to detect the effects of vtRNAs on the interaction of PSF with GAGE6 promoter. The role of vtRNAs on chemoresistance in MCF-7 was detected by CCK-8 and EdU staining. The independent role of vtRNAs with MVP is detected by MVP or vtRNAs knockdown. RESULTS: The complex with vtRNA1-1 releases PSF, allowing transcription of GAGE6 to proceed. Then we showed that induction of GAGE6 caused drug resistance by promoting cell proliferation and colony formation in soft agar. Ectopic expression of shRNA targets to vtRNA1-1 further confirmed the role of vtRNA1-1 in regulating PSF transcriptional activity independent with the expression of MVP. By vtRNA1-1 or MVP knockdown, it is revealed that vtRNA1-1 caused chemoresistance independent of MVP. Furthermore, knockdown of GAGE6 does not cause drug resistance, indicates the GAGE6 is directly involved in cell proliferation, but not the drug resistance. CONCLUSION: These results suggest that vtRNAs regulates cell proliferation, drug resistance, and possibly other physiological processes of humans, by complex formation with PSF.
[Mh] Termos MeSH primário: Resistência a Medicamentos Antineoplásicos/genética
Oncogenes/genética
Fator de Processamento Associado a PTB/metabolismo
RNA/genética
RNA/metabolismo
Partículas de Ribonucleoproteínas em Forma de Abóbada/genética
[Mh] Termos MeSH secundário: Proliferação Celular/efeitos dos fármacos
Doxorrubicina/farmacologia
Seres Humanos
Células MCF-7
Fator de Processamento Associado a PTB/química
Regiões Promotoras Genéticas/genética
Ligação Proteica
Domínios Proteicos
Homologia de Sequência do Ácido Nucleico
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (PTB-Associated Splicing Factor); 0 (Vault Ribonucleoprotein Particles); 63231-63-0 (RNA); 80168379AG (Doxorubicin)
[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:180119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191325



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