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[PMID]:28771889
[Au] Autor:Maruyama D; Nagai H; Maeda Y; Nakane T; Shimoyama T; Nakazato T; Sakai R; Ishikawa T; Izutsu K; Ueda R; Tobinai K
[Ad] Endereço:Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
[Ti] Título:Phase I/II study of pralatrexate in Japanese patients with relapsed or refractory peripheral T-cell lymphoma.
[So] Source:Cancer Sci;108(10):2061-2068, 2017 Oct.
[Is] ISSN:1349-7006
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pralatrexate is a novel antifolate approved in the USA for the treatment of relapsed or refractory peripheral T-cell lymphoma. To assess its safety, efficacy, and pharmacokinetics in Japanese patients with this disease, we undertook a phase I/II study. Pralatrexate was given i.v. weekly for 6 weeks of a 7-week cycle. All patients received concurrent vitamin B and folic acid. In phase I, three patients received pralatrexate 30 mg/m and none experienced a dose-limiting toxicity. In phase II, we treated 22 additional patients with that dose. The median number of treatment cycles was 1 (range, 1-9). Nine of 20 evaluable patients (45%) achieved an objective response by central review, including two complete responses. All responses occurred within the first treatment cycle. At the time of data cut-off, median progression-free survival was 150 days. Median overall survival was not reached. In the total population, the most commonly reported adverse events included mucositis (88%), thrombocytopenia (68%), liver function test abnormality (64%), anemia (60%), and lymphopenia (56%). Grade 3/4 adverse events included lymphopenia (52%), thrombocytopenia (40%), leukopenia (28%), neutropenia (24%), anemia (20%), and mucositis (20%). The pharmacokinetic profile showed no drug accumulation with repeat dosing. These results indicate that pralatrexate is generally well tolerated and effective in Japanese patients with relapsed or refractory peripheral T-cell lymphoma. This trial was registered with ClinicalTrials.gov (NCT02013362).
[Mh] Termos MeSH primário: Aminopterina/análogos & derivados
Ácido Fólico/administração & dosagem
Linfoma de Células T Periférico/tratamento farmacológico
Recidiva Local de Neoplasia/tratamento farmacológico
Vitamina B 12/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Aminopterina/administração & dosagem
Aminopterina/efeitos adversos
Aminopterina/farmacocinética
Esquema de Medicação
Feminino
Ácido Fólico/uso terapêutico
Seres Humanos
Japão
Masculino
Meia-Idade
Análise de Sobrevida
Resultado do Tratamento
Vitamina B 12/uso terapêutico
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); 935E97BOY8 (Folic Acid); JYB41CTM2Q (Aminopterin); P6YC3EG204 (Vitamin B 12)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.1111/cas.13340


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[PMID]:28340883
[Au] Autor:Marchi E; Raufi AG; O'Connor OA
[Ad] Endereço:Columbia University Medical Center, Center for Lymphoid Malignancies, 51 West 51st Street, Suite 200, New York, NY 10019, USA.
[Ti] Título:Novel Agents in the Treatment of Relapsed or Refractory Peripheral T-Cell Lymphoma.
[So] Source:Hematol Oncol Clin North Am;31(2):359-375, 2017 Apr.
[Is] ISSN:1558-1977
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of mature T-cell malignancies associated with exceptionally poor prognoses. Currently, chemotherapy remains the standard of care, but outcomes are suboptimal, with 5-year survival rates ranging from 15% to 25%. In recent years, several novel agents, including pralatrexate, romidepsin, belinostat, and brentuximab vedotin, have been approved for the treatment of relapsed/refractory PTCL. In addition, numerous other therapies with different mechanisms of action and targets are currently under investigation. This article discusses in detail agents currently available, those currently under investigation, and active combination trials.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfoma de Células T Periférico/tratamento farmacológico
[Mh] Termos MeSH secundário: Aminopterina/análogos & derivados
Aminopterina/uso terapêutico
Ensaios Clínicos como Assunto
Depsipeptídeos/uso terapêutico
Intervalo Livre de Doença
Ácidos Hidroxâmicos/uso terapêutico
Imunoconjugados/uso terapêutico
Linfoma de Células T Periférico/mortalidade
Sulfonamidas/uso terapêutico
Taxa de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); 0 (Depsipeptides); 0 (Hydroxamic Acids); 0 (Immunoconjugates); 0 (Sulfonamides); 7XL5ISS668 (brentuximab vedotin); CX3T89XQBK (romidepsin); F4H96P17NZ (belinostat); JYB41CTM2Q (Aminopterin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170529
[Lr] Data última revisão:
170529
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170326
[St] Status:MEDLINE


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[PMID]:27983760
[Au] Autor:Chihara D; Fanale MA; Miranda RN; Noorani M; Westin JR; Nastoupil LJ; Hagemeister FB; Fayad LE; Romaguera JE; Samaniego F; Turturro F; Lee HJ; Neelapu SS; Rodriguez MA; Wang M; Fowler NH; Davis RE; Medeiros LJ; Hosing C; Nieto YL; Oki Y
[Ad] Endereço:Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
[Ti] Título:The survival outcome of patients with relapsed/refractory peripheral T-cell lymphoma-not otherwise specified and angioimmunoblastic T-cell lymphoma.
[So] Source:Br J Haematol;176(5):750-758, 2017 Mar.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Survival outcome of patients with peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL) who experience disease progression/relapse remains very poor. A total of 321 patients, newly diagnosed with PTCL-NOS (n = 180) or AITL (n = 141) between 1999 and 2015, were analysed. Failure-free survival (FFS) and overall survival (OS) were calculated from the time of first disease progression (FFS1, OS1), from second disease progression (FFS2, OS2) and from third progression (FFS3, OS3). With a median follow-up duration of 52 months, 240 patients (135 PTCL-NOS, 105 AITL) experienced progression/relapse. In patients with PTCL-NOS, the median durations of FFS1, FFS2 and FFS3 were 3·1, 2·5 and 2·1 months, respectively. In patients with AITL, they were 5·5, 2·9 and 2·3 months, respectively. There was no improvement in FFS1 and OS1 by the time of recurrence during this period (1999-2004, 2005-2009 and 2010-2015). The median FFS after pralatrexate and romidepsin was only 3·0 and 2·5 months, respectively. The 5-year OS rates after salvage autologous and allogeneic transplant were 32% and 52%, respectively; while the 5-year OS rates for patients who did not undergo transplant was 10%. Further research for novel therapeutic approaches with higher efficacy and better safety profile are needed.
[Mh] Termos MeSH primário: Linfadenopatia Imunoblástica/terapia
Linfoma de Células T Periférico/terapia
Linfoma de Células T/terapia
Terapia de Salvação/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Aminopterina/análogos & derivados
Aminopterina/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Depsipeptídeos/uso terapêutico
Intervalo Livre de Doença
Feminino
Seres Humanos
Linfadenopatia Imunoblástica/mortalidade
Linfoma de Células T/mortalidade
Linfoma de Células T Periférico/mortalidade
Masculino
Meia-Idade
Terapia de Salvação/mortalidade
Transplante de Células-Tronco/métodos
Taxa de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); 0 (Depsipeptides); CX3T89XQBK (romidepsin); JYB41CTM2Q (Aminopterin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170523
[Lr] Data última revisão:
170523
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161217
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.14477


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[PMID]:27643862
[Au] Autor:Sastry RVRP; Venkatesan CS; Sastry BS; Mahesh K
[Ad] Endereço:Centre for Chemical Sciences & Technology, Institute of Science & Technology, JNTUH, Kukatpally, Hyderabad-500 085, Telangana, India; Gland Pharma Ltd., Research and Development, D.P.Pally, Hyderabad-500 043, Telangana, India. Electronic address: sastryrvrp@glandpharma.com.
[Ti] Título:Identification and characterization of forced degradation products of pralatrexate injection by LC-PDA and LC-MS.
[So] Source:J Pharm Biomed Anal;131:400-409, 2016 Nov 30.
[Is] ISSN:1873-264X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pralatrexate (PTXT) is an antineoplastic folate analog and the chemical name is (2S)-2-[[4-[(1RS)-1-[(2,4-diaminopteridin-6-yl)methyl]but-3-ynyl] benzoyl] amino] pentanedioic acid. Degradation products of PTXT drug product (DP) under different forced degradation conditions have been studied using LC-PDA and LC-MS techniques. PTXT DP was subjected to forced degradation under the conditions of hydrolysis, photolysis, oxidation, and heat in accordance with ICH guidelines. The LC-MS compatible HPLC method was developed and stressed solutions were chromatographed on reversed phase HPLC. The degradation products were monitored at a wavelength of 242nm. Stress study revealed that PTXT was sensitive towards acid, alkali, peroxide, light and heat. The degradation impurities (I-IX) were identified and characterized using LC-PDA and mass spectral data.
[Mh] Termos MeSH primário: Aminopterina/análogos & derivados
Espectrometria de Massas por Ionização por Electrospray/métodos
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Aminopterina/análise
Aminopterina/metabolismo
Cromatografia Líquida/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); JYB41CTM2Q (Aminopterin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171008
[Lr] Data última revisão:
171008
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160920
[St] Status:MEDLINE


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[PMID]:27638045
[Au] Autor:Kelly KR; Gabrail N; Weitman S; Sarantopoulos J; Olszanski AJ; Edenfield W; Venitz J; Reddy G; Yang A; Hasal SJ; Lockhart AC
[Ad] Endereço:Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California, 1441 Eastlake Ave, NOR 3465, MC 9172, Los Angeles, CA, 90033, USA. kevin.kelly@med.usc.edu.
[Ti] Título:Phase 1 study evaluating the safety and pharmacokinetics of pralatrexate in relapsed/refractory advanced solid tumors and lymphoma patients with mild, moderate, and severe renal impairment.
[So] Source:Cancer Chemother Pharmacol;78(5):929-939, 2016 Nov.
[Is] ISSN:1432-0843
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Pralatrexate is a folate analogue indicated for the treatment of relapsed or refractory peripheral T-cell lymphoma. It has not been formally tested in patients with renal impairment. This study evaluated the pharmacokinetic (PK) profile of pralatrexate in patients with renal impairment and with relapsed/refractory advanced solid tumors and lymphoma. METHODS: This was an open-label, nonrandomized, phase 1 study. Eligible patients received pralatrexate administered as an IV push over 3-5 min once weekly for 6 weeks in 7-week cycles until progressive disease or intolerable toxicity. Four cohorts of 6 patients were planned for a total of 24 patients. Patients with normal renal function (Cohort A), mild (Cohort B), and moderate renal impairment (Cohort C) received 30 mg/m pralatrexate once weekly for 6 weeks in 7-week cycles, and patients with severe renal impairment (Cohort D) were to be administered 20 mg/m once weekly for 6 weeks. Plasma and urine samples were collected at pre-specified time points to determine the PK profile of pralatrexate in each treatment cohort. Patients were followed for safety and tolerability. RESULTS: A total of 29 patients were enrolled and 27 patients (14 male) received at least 1 dose of pralatrexate. Because of a qualifying toxicity in Cohort C, the starting dose for Cohort D was reduced to 15 mg/m . Chronic renal impairment led to a decrease in renal clearance of the pralatrexate diastereomers, PDX-10a and PDX-10b, but systemic exposure to these diastereomers was not dramatically affected by renal impairment. Pralatrexate exposure in Cohort D (15 mg/m ) was similar to the exposure in other cohorts (30 mg/m ). No apparent difference in toxicity between the four treatment cohorts was observed, except for an increase in cytopenias in patients with severe renal impairment. CONCLUSION: Pralatrexate exposure, at a dose of 30 mg/m , in patients with mild or moderate renal impairment was similar to the exposure in patients with normal renal function. For patients with severe renal impairment only, a pralatrexate dose of 15 mg/m is recommended.
[Mh] Termos MeSH primário: Aminopterina/análogos & derivados
Antagonistas do Ácido Fólico/efeitos adversos
Antagonistas do Ácido Fólico/farmacocinética
Linfoma/complicações
Linfoma/tratamento farmacológico
Neoplasias/complicações
Neoplasias/tratamento farmacológico
Insuficiência Renal/complicações
Insuficiência Renal/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Aminopterina/efeitos adversos
Aminopterina/farmacocinética
Aminopterina/uso terapêutico
Resistência a Medicamentos Antineoplásicos
Determinação de Ponto Final
Feminino
Antagonistas do Ácido Fólico/uso terapêutico
Seres Humanos
Falência Renal Crônica/metabolismo
Testes de Função Renal
Linfoma/metabolismo
Masculino
Meia-Idade
Recidiva Local de Neoplasia/tratamento farmacológico
Neoplasias/metabolismo
Estereoisomerismo
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); 0 (Folic Acid Antagonists); JYB41CTM2Q (Aminopterin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160918
[St] Status:MEDLINE


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[PMID]:27421044
[Au] Autor:Del Carmen MG; Supko JG; Horick NK; Rauh-Hain JA; Clark RM; Campos SM; Krasner CN; Atkinson T; Birrer MJ
[Ad] Endereço:Division of Gynecologic Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts. mdelcarmen@partners.org.
[Ti] Título:Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.
[So] Source:Cancer;122(21):3297-3306, 2016 Nov 15.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The objective of this phase 1 and 2 trial was to identify the appropriate dose of combined carboplatin and pralatrexate for patients with recurrent, platinum-sensitive ovarian, fallopian tube, and primary peritoneal cancer. METHODS: In phase 1, patients received carboplatin (at an area under the curve of 5) and increasing doses of pralatrexate until the maximum-tolerated dose (MTD) of pralatrexate was achieved. The primary endpoint was the response rate. Additional endpoints were safety, response duration, progression-free survival, overall survival, and pharmacokinetics. RESULTS: Thirty patients were enrolled in phase 1, and 20 were enrolled in phase 2. Of all 50 patients, 49 completed the study. The mean patient age was 59 years, and patients completed a median of 6 cycles. The MTD for pralatrexate was 105 mg/m . The clinical benefit rate (complete responses plus partial responses plus stable disease) was 86%. Of 26 patients who received the MTD, 12 had a partial response, 11 had stable disease, and 2 had disease progression. The progression-free survival rate at 3 and 6 months was 87% and 79%, respectively; and the overall survival rate was 98% at 6 and 12 months and 66% at 24 months. Of 30 patients, 18 (60%) in phase 1 experienced an adverse event of any grade; and, of those, 4 patients (13%) had a grade 3 or greater adverse event. In phase 2, 12 patients (60%) had an adverse event of any grade, and 4 (20%) had grade 3 or greater toxicity. There was a significant reduction in the total body clearance of pralatrexate when it was received concurrently with carboplatin. CONCLUSIONS: Most patients responded to carboplatin-pralatrexate combination. This regimen is well tolerated and effective in this patient population. Cancer 2016;122:3297-3306. © 2016 American Cancer Society.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Neoplasias das Tubas Uterinas/tratamento farmacológico
Recidiva Local de Neoplasia/tratamento farmacológico
Neoplasias Ovarianas/tratamento farmacológico
Neoplasias Peritoneais/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Idoso
Aminopterina/administração & dosagem
Aminopterina/análogos & derivados
Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética
Carboplatina/administração & dosagem
Carcinoma de Células de Transição/tratamento farmacológico
Carcinoma de Células de Transição/patologia
Carcinossarcoma/tratamento farmacológico
Carcinossarcoma/patologia
Cistadenocarcinoma Seroso/tratamento farmacológico
Cistadenocarcinoma Seroso/patologia
Neoplasias do Endométrio/tratamento farmacológico
Neoplasias do Endométrio/patologia
Neoplasias das Tubas Uterinas/patologia
Feminino
Seguimentos
Seres Humanos
Meia-Idade
Invasividade Neoplásica
Recidiva Local de Neoplasia/patologia
Estadiamento de Neoplasias
Neoplasias Ovarianas/patologia
Neoplasias Peritoneais/patologia
Prognóstico
Taxa de Sobrevida
Distribuição Tecidual
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); BG3F62OND5 (Carboplatin); JYB41CTM2Q (Aminopterin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170525
[Lr] Data última revisão:
170525
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:160716
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30196


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[PMID]:27366017
[Au] Autor:Lee SS; Jung SH; Ahn JS; Kim YK; Cho MS; Jung SY; Lee JJ; Kim HJ; Yang DH
[Ad] Endereço:Department of Hematology and Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea .
[Ti] Título:Pralatrexate in Combination with Bortezomib for Relapsed or Refractory Peripheral T Cell Lymphoma in 5 Elderly Patients.
[So] Source:J Korean Med Sci;31(7):1160-3, 2016 Jul.
[Is] ISSN:1598-6357
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
[Mh] Termos MeSH primário: Aminopterina/análogos & derivados
Antineoplásicos/uso terapêutico
Bortezomib/uso terapêutico
Linfoma de Células T Periférico/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Aminopterina/efeitos adversos
Aminopterina/uso terapêutico
Antineoplásicos/efeitos adversos
Bortezomib/efeitos adversos
Esquema de Medicação
Quimioterapia Combinada
Seres Humanos
Linfoma de Células T Periférico/diagnóstico por imagem
Linfoma de Células T Periférico/patologia
Masculino
Recidiva Local de Neoplasia
Neutropenia/etiologia
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); 0 (Antineoplastic Agents); 69G8BD63PP (Bortezomib); JYB41CTM2Q (Aminopterin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170222
[Lr] Data última revisão:
170222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160702
[St] Status:MEDLINE
[do] DOI:10.3346/jkms.2016.31.7.1160


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[PMID]:27343244
[Au] Autor:Calise SJ; Purich DL; Nguyen T; Saleem DA; Krueger C; Yin JD; Chan EK
[Ad] Endereço:Department of Oral Biology, University of Florida, 1395 Center Drive, Gainesville, FL 32610-0424, USA.
[Ti] Título:'Rod and ring' formation from IMP dehydrogenase is regulated through the one-carbon metabolic pathway.
[So] Source:J Cell Sci;129(15):3042-52, 2016 Aug 01.
[Is] ISSN:1477-9137
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:'Rods and rings' (RRs) are conserved, non-membrane-bound intracellular polymeric structures composed, in part, of inosine monophosphate dehydrogenase (IMPDH), a key enzyme leading to GMP and GTP biosynthesis. RR formation is induced by IMPDH inhibitors as well as glutamine deprivation. They also form upon treatment of cells with glutamine synthetase inhibitors. We now report that depriving cells of serine and glycine promotes RR formation, and we have traced these effects to dihydrofolate reductase (DHFR) and serine hydroxymethyltransferase-2 (SHMT2), pivotal enzymes in one-carbon metabolism and nucleotide biosynthesis. RR assembly is likewise induced upon DHFR inhibition by methotrexate or aminopterin as well as siRNA-mediated knockdown of DHFR or SHMT2. Because RR assembly occurs when guanine nucleotide biosynthesis is inhibited, and because RRs rapidly disassemble after the addition of guanine nucleotide precursors, RR formation might be an adaptive homeostatic mechanism, allowing IMPDH to sense changes in the one-carbon folate pathway.
[Mh] Termos MeSH primário: Carbono/metabolismo
IMP Desidrogenase/metabolismo
Redes e Vias Metabólicas
[Mh] Termos MeSH secundário: Aminopterina/farmacologia
Meios de Cultura/farmacologia
Técnicas de Silenciamento de Genes
Glicina/farmacologia
Glicina Hidroximetiltransferase/metabolismo
Guanosina/farmacologia
Células HeLa
Seres Humanos
Hipoxantina/farmacologia
Redes e Vias Metabólicas/efeitos dos fármacos
Metotrexato/farmacologia
RNA Interferente Pequeno/metabolismo
Serina/deficiência
Tetra-Hidrofolato Desidrogenase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (RNA, Small Interfering); 12133JR80S (Guanosine); 2TN51YD919 (Hypoxanthine); 452VLY9402 (Serine); 7440-44-0 (Carbon); EC 1.1.1.205 (IMP Dehydrogenase); EC 1.5.1.3 (Tetrahydrofolate Dehydrogenase); EC 2.1.2.1 (Glycine Hydroxymethyltransferase); EC 2.1.2.1 (SHMT protein, human); JYB41CTM2Q (Aminopterin); TE7660XO1C (Glycine); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160626
[St] Status:MEDLINE
[do] DOI:10.1242/jcs.183400


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[PMID]:27210892
[Au] Autor:Chen H; Zhang K; Wang S; Xu C; Zou Z; Tao A
[Ad] Endereço:The Second Affiliated Hospital of Guangzhou Medical University, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology.
[Ti] Título:Generation and purification of monoclonal antibodies against Der f 2, a major allergen from Dermatophagoides farinae.
[So] Source:Drug Discov Ther;10(2):103-8, 2016.
[Is] ISSN:1881-7831
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Monoclonal antibodies (mAbs) are needed for the quantitation of environmental allergens for precise diagnosis and immunotherapy. In this study, we produced and purified monoclonal antibodies against Der f 2, one of the major allergens of the house dust mite Dermatophagoides farina, in order to develop an assay for the detection of this allergen. BALB/c mice were immunized four times with the protein Der f 2 together with an adjuvant after which splenocytes were collected and fused with SP2/0 (myeloma cells) in the presence of polyethylene glycol (PEG). The fused cells were selected in the presence of Hypoxanthine-Aminopterin-Thymidine (HAT) and then Hypoxanthine-Thymidine (HT) medium. Positive cells were screened with ELISA and subcloned by limited dilution at least three times to achieve stable mAb-producing clones. Four stable mAb-producing clones were obtained. One clone with IgG1 isotype and another with IgG2b isotype were chosen to produce large amounts of mAb by inoculation of the cells into the abdominal cavity of mice. Ascites were collected and the mAbs were purified using protein A affinity chromatography. Testing of the ascites by ELISA showed the titration of IgG1 and IgG2b to be higher than 1/10(6) dilution. The specificity of both antibodies was confirmed by immunoblotting. Thus, we produced two mAb clones against Der f 2 that can be used to create a precise quantitative method to identify allergen components in dust samples and facilitate further study in Der f 2 component-resolved diagnosis (CRD).
[Mh] Termos MeSH primário: Alérgenos/imunologia
Anticorpos Monoclonais/biossíntese
Antígenos de Dermatophagoides/imunologia
Proteínas de Artrópodes/imunologia
Dermatophagoides farinae/imunologia
Pyroglyphidae/imunologia
[Mh] Termos MeSH secundário: Aminopterina
Animais
Anticorpos Monoclonais/isolamento & purificação
Ascite/imunologia
Fusão Celular
Linhagem Celular
Hibridomas
Hipoxantinas
Imunoglobulina G/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Timidina
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Antibodies, Monoclonal); 0 (Antigens, Dermatophagoides); 0 (Arthropod Proteins); 0 (Dermatophagoides farinae antigen f 2); 0 (Hypoxanthines); 0 (Immunoglobulin G); JYB41CTM2Q (Aminopterin); VC2W18DGKR (Thymidine)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170124
[Lr] Data última revisão:
170124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160524
[St] Status:MEDLINE
[do] DOI:10.5582/ddt.2016.01029


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[PMID]:27040320
[Au] Autor:Dunn TJ; Dinner S; Price E; Coutré SE; Gotlib J; Hao Y; Berube C; Medeiros BC; Liedtke M
[Ad] Endereço:Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
[Ti] Título:A phase 1, open-label, dose-escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma.
[So] Source:Br J Haematol;173(2):253-9, 2016 Apr.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used. Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m(2) and intravenous bortezomib at a dose of 1·3 mg/m(2) on days 1, 8 and 15 of each 4-week cycle. Eleven patients were enrolled and completed a median of two cycles. The maximum tolerated dose was 20 mg/m(2) . Two patients experienced dose-limiting toxicity of mucositis. The most frequent non-haematological toxicities were fatigue (55%) and mucositis (45%). There were three serious adverse events in three patients: rash, sepsis and hypotension. One patient (9%) had a very good partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and two (18%) had progressive disease. The median duration of response was 4 months, the median time to next treatment was 3·4 months and the median time to progression was 4 months. Pralatrexate, in combination with bortezomib, was generally safe and demonstrated modest activity in relapsed or refractory multiple myeloma. Clinicaltrials.gov identifier: NCT01114282.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Mieloma Múltiplo/tratamento farmacológico
Recidiva Local de Neoplasia/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Aminopterina/administração & dosagem
Aminopterina/efeitos adversos
Aminopterina/análogos & derivados
Bortezomib/administração & dosagem
Bortezomib/efeitos adversos
Relação Dose-Resposta a Droga
Feminino
Seres Humanos
Infusões Intravenosas
Masculino
Dose Máxima Tolerável
Meia-Idade
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (10-propargyl-10-deazaaminopterin); 69G8BD63PP (Bortezomib); JYB41CTM2Q (Aminopterin)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160413
[Lr] Data última revisão:
160413
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160405
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.13946



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