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benigno valdez

Yago Nieto, Peter F Thall, Junsheng Ma, Benigno C Valdez, Sairah Ahmed, Paolo Anderlini, Uday Popat, Roy B Jones, Elizabeth J Shpall, Chitra Hosing, Muzaffar Qazilbash, Partow Kebriaei, Amin Alousi, Melissa Timmons, Alison Gulbis, Alan Myers, Yasuhiro Oki, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Sarah Milgrom, Richard Champlin, Borje S Andersson
We conducted a prospective phase 2 trial of gemcitabine, busulfan and melphalan (Gem/Bu/Mel) with autologous stem cell transplantation (ASCT) in patients with primary refractory or poor-risk relapsed Hodgkin lymphoma (HL) (ie, extranodal relapse or within 1 year of frontline therapy). The trial was powered to detect an improvement in 2-year progression-free survival (PFS) from a historical 50% using a BEAM regimen (carmustine/etoposide/cytarabine/melphalan) to 65%. We compared the study population with all other concurrent patients who were eligible for the trial but instead received the BEAM regimen at our center...
March 2, 2018: Biology of Blood and Marrow Transplantation
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
Combination of drugs that target different aspects of aberrant cellular processes is an efficacious treatment for hematological malignancies. Hypomethylating agents (HMAs) and inhibitors of poly(ADP-ribose) polymerases (PARPis) and histone deacetylases (HDACis) are clinically active anti-tumor drugs. We hypothesized that their combination would be synergistically cytotoxic to leukemia and lymphoma cells. Exposure of AML and lymphoma cell lines to the combination of the PARPi niraparib (Npb), the HMA decitabine (DAC) and the HDACi romidepsin (Rom) or panobinostat (Pano) synergistically inhibited cell proliferation by up to 70% via activation of the ATM pathway, increased production of reactive oxygen species, decreased mitochondrial membrane potential, and activated apoptosis...
January 9, 2018: Oncotarget
Yago Nieto, Benigno C Valdez, Sai R Pingali, Roland Bassett, Ruby Delgado, John Nguyen, Nina Shah, Uday Popat, Roy B Jones, Borje S Andersson, Alison Gulbis, Sairah Ahmed, Qaiser Bashir, Simrit Parmar, Krina Patel, Alan Myers, Gabriela Rondon, Robert Z Orlowski, Richard Champlin, Muzaffar Qazilbash
BACKGROUND: High-dose melphalan is of little benefit as a regimen for patients with relapsed or refractory myeloma undergoing an autologous stem-cell transplant (ASCT). The poor performance of single-agent melphalan in this setting prompted us to study a new high-dose combination of infused gemcitabine, busulfan, and melphalan. METHODS: We did a phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). We enrolled patients with primary refractory or relapsed myeloma who had received treatment with bortezomib, an immunomodulatory drug, or both, or who were receiving a salvage ASCT...
June 2017: Lancet Haematology
Benigno C Valdez, Moustapha Hassan, Borje S Andersson
Drug interactions may dictate the failure or success of a treatment. Patients undergoing hematopoietic stem cell transplantation (HSCT) are exposed to various types of drugs, and understanding how these drugs interact is of the utmost importance. The pharmacokinetics of busulfan, melphalan, and cyclophosphamide, drugs commonly used for HSCT, are known to be affected by a variety of other drugs with differing molecular structures. We hypothesized that these structurally unrelated drugs affect the transport of DNA-alkylating agents...
August 2017: Experimental Hematology
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
The combination of gemcitabine (Gem), busulfan (Bu), and melphalan (Mel) is a promising regimen for autologous stem-cell transplantation (SCT) for lymphomas. To further improve the efficacy of [Gem + Bu + Mel], we added poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (Ola). We hypothesized that Ola would inhibit the repair of damaged DNA caused by [Gem + Bu + Mel]. Exposure of J45.01 and Toledo cell lines to IC10-20 of individual drug inhibited proliferation by 6-16%; [Gem + Bu + Mel] by 20-27%; and [Gem + Bu + Mel + Ola] by 61-67%...
November 2017: Leukemia & Lymphoma
Guiyun Song, Daniel Banov, August S Bassani, Benigno C Valdez
The efficacy of active pharmaceutical ingredients (API) in compounded medications for oral mucosa greatly depends on the composition of the base. Here, we assessed the safety, facilitation of cell migration, and mucoadhesive properties of a newly developed mucoadhesive polymer blend (MPB) which contains pullulan, tamarindus indica polysaccharide, and sodium hyaluronate. No cell death was observed when human oral keratinocyte (HOK) and fibroblast (HOrF) cells were exposed to 1% MPB for 24 h. Epithelial cells in a 3D buccal tissue model (EpiOral) were unaffected when exposed to 50% MPB for 20 h whereas 1% Triton X-100 killed 93% cells after 4...
July 2017: AAPS PharmSciTech
Cristóbal Chaidez, Juan R Ibarra-Rodríguez, José Benigno Valdez-Torres, Marcela Soto, Charles P Gerba, Nohelia Castro-Del Campo
OBJECTIVE: In developing countries, rural communities often face the lack of potable water infrastructure and must rely on untreated sources for drinking, which are often contaminated with waterborne pathogens. The use of home water treatment devices is seen as one means of reducing the risk of exposure to waterborne pathogens. The aim of this study was to evaluate the microbiological and physicochemical performance of a simple in-home point-of-use device based on gravity ultrafiltration through an ultrafilter membrane...
September 2016: Wilderness & Environmental Medicine
Benigno C Valdez, Yang Li, David Murray, Jonathan E Brammer, Yan Liu, Chitra Hosing, Yago Nieto, Richard E Champlin, Borje S Andersson
HDAC inhibitors, DNA alkylators and nucleoside analogs are effective components of combination chemotherapy. To determine a possible mechanism of their synergism, we analyzed the effects of HDAC inhibitors on the expression of drug transporters which export DNA alkylators. Exposure of PEER lymphoma T-cells to 15 nM romidepsin (Rom) resulted in 40%-50% reduction in mRNA for the drug transporter MRP1 and up to ~500-fold increase in the MDR1 mRNA within 32-48 hrs. MRP1 protein levels concomitantly decreased while MDR1 increased...
September 27, 2016: Oncotarget
Gheath Alatrash, Peter F Thall, Benigno C Valdez, Patricia S Fox, Jing Ning, Haven R Garber, Selma Janbey, Laura L Worth, Uday Popat, Chitra Hosing, Amin M Alousi, Partow Kebriaei, Elizabeth J Shpall, Roy B Jones, Marcos de Lima, Gabriela Rondon, Julianne Chen, Richard E Champlin, Borje S Andersson
Pretransplant conditioning regimens critically determine outcomes in the setting of allogeneic stem cell transplantation (allo-SCT). The use of nucleoside analogs such as fludarabine (Flu) in combination with i.v. busulfan (Bu) has been shown to be highly effective as a pretransplant conditioning regimen in acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS). Because leukemia relapse remains the leading cause of death after allo-SCT, we studied whether clofarabine (Clo), a nucleoside analog with potent antileukemia activity, can be used to complement Flu...
October 2016: Biology of Blood and Marrow Transplantation
Benigno C Valdez, Jonathan E Brammer, Yang Li, David Murray, Esmeralda C Teo, Yan Liu, Chitra Hosing, Yago Nieto, Richard E Champlin, Borje S Andersson
Novel approaches to pre-transplant conditioning are needed to improve treatment of advanced T-cell malignancies. We investigated the synergism of fludarabine (Flu), clofarabine (Clo), busulfan (Bu), and romidepsin (Rom) in T-cell lines and patient-derived cell samples. [Flu+Clo+Bu+Rom] had combination indexes of 0.4-0.5 at ∼50% cytotoxicity in PEER and SUPT1 cells, suggesting synergism. Drug exposure resulted in histone modifications, DNA-damage response (DDR), increased reactive oxygen species (ROS), decreased glutathione (GSH) and mitochondrial membrane (MM) potential, and apoptosis...
August 2016: Leukemia Research
Yago Nieto, Benigno C Valdez, Peter F Thall, Roy B Jones, Wei Wei, Alan Myers, Chitra Hosing, Sairah Ahmed, Uday Popat, Elizabeth J Shpall, Muzaffar Qazilbash, Alison Gulbis, Paolo Anderlini, Nina Shah, Qaiser Bashir, Amin Alousi, Yasuhiro Oki, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Richard Champlin, Borje S Andersson
BACKGROUND: More active high-dose chemotherapy (HDC) regimens are needed for refractory lymphomas. The authors previously combined infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel) pursuing DNA damage repair inhibition. Subsequently, they combined Gem/Bu/Mel with vorinostat, which facilitates chemotherapy access to DNA. The resulting regimen was safe and synergistic. However, vorinostat induced DNA methyltransferase up-regulation, which could be preclinically abrogated by azacitidine, increasing tumor-cell kill...
September 1, 2016: Cancer
Esmeralda C Teo, Benigno C Valdez, Jie Ji, Yang Li, Yan Liu, Jonathan E Brammer, Chitra Hosing, Yago Nieto, Richard E Champlin, Borje S Andersson
DNA alkylators busulfan (B) and melphalan (M) act synergistically with gemcitabine (G) against lymphoma cells. To further improve the cytotoxicity, we combined them with the histone deacetylase inhibitor panobinostat (P) and proteasome inhibitor bortezomib (V). Lymphoma cell lines U937 and J45.01, and patient-derived cell samples were exposed to these drugs and the effects on cell proliferation and apoptosis were quantified. The combination BMGPV was found to exert strong synergistic cytotoxicity. Drug exposure to these cells activated the ATM pathway and modified histones at the epigenetic level...
November 2016: Leukemia & Lymphoma
Jie Ji, Benigno C Valdez, Yang Li, Yan Liu, Esmeralda C Teo, Yago Nieto, Richard E Champlin, Borje S Andersson
Hematopoietic stem cell transplantation (HSCT) is an effective treatment for patients with refractory lymphomas. Nucleoside analogs (NAs) and DNA alkylating agents are efficacious in treating hematologic malignancies. To design an efficacious and more economical pretransplant regimen for lymphoma patients, we analyzed the cytotoxicity of cladribine (Clad), gemcitabine (Gem), busulfan (Bu), and suberoylanilide hydroxamic acid (SAHA) in lymphoma cell lines. J45.01 and U937 lymphoma cell lines were exposed to drugs, alone or in combination, for 48 hours and analyzed with the MTT and annexin V assays, Western blotting, and flow cytometry...
June 2016: Experimental Hematology
Dalmira Félix-Urquídez, Melina Pérez-Urquiza, José-Benigno Valdez Torres, Josefina León-Félix, Raymundo García-Estrada, Abraham Acatzi-Silva
Certified reference materials (CRMs) are required to guarantee the reliability of analytical measurements. The CRMs available in the field of genetically modified organisms (GMOs) are characterized using real-time polymerase chain reaction (qPCR). This technology has limited application, because of its dependence on a calibrant. The objective of this study was to obtain a method with higher metrological quality, to characterize the CRMs for their contents of T-nos/hmg copy number ratio in maize. A duplex droplet digital PCR (ddPCR) assay was developed and optimized by a central composite design...
January 5, 2016: Analytical Chemistry
Yago Nieto, Benigno C Valdez, Peter F Thall, Sairah Ahmed, Roy B Jones, Chitra Hosing, Uday Popat, Elizabeth J Shpall, Muzaffar Qazilbash, Alison Gulbis, Paolo Anderlini, Amin Alousi, Nina Shah, Qaiser Bashir, Yan Liu, Yasuhiro Oki, Frederick Hagemeister, Michelle Fanale, Bouthaina Dabaja, Chelsea Pinnix, Richard Champlin, Borje S Andersson
More active high-dose regimens are needed for refractory/poor-risk relapsed lymphomas. We previously developed a regimen of infusional gemcitabine/busulfan/melphalan, exploiting the synergistic interaction. Its encouraging activity in refractory lymphomas led us to further enhance its use as a platform for epigenetic modulation. We previously observed increased cytotoxicity in refractory lymphoma cell lines when the histone deacetylase inhibitor vorinostat was added to gemcitabine/busulfan/melphalan, which prompted us to clinically study this four-drug combination...
November 2015: Biology of Blood and Marrow Transplantation
Benigno C Valdez, Yang Li, David Murray, Jie Ji, Yan Liu, Uday Popat, Richard E Champlin, Borje S Andersson
Clofarabine (Clo), fludarabine (Flu), and busulfan (Bu) combinations are efficacious in hematopoietic stem cell transplantation for myeloid leukemia. We sought to determine whether the more affordable drug cladribine (Clad) can provide a viable alternative to Clo, with or without panobinostat (Pano) and 5-aza-2'-deoxycytidine (DAC). Both Clad+Flu+Bu and Clo+Flu+Bu combinations showed synergistic cytotoxicity in KBM3/Bu250(6), HL60, and OCI-AML3 cell lines. Cell exposure to these drug combinations resulted in 60%-80% inhibition of proliferation; activation of the ATM pathway; increase in histone modifications; decrease in HDAC3, HDAC4, HDAC5 and SirT7 proteins; decrease in mitochondrial membrane potential; activation of apoptosis and stress signaling pathways; and downregulation of the AKT pathway...
June 2015: Experimental Hematology
Guiyun Song, Benigno C Valdez, Yang Li, Yan Liu, Richard E Champlin, Borje S Andersson
Clofarabine (Clo), fludarabine (Flu), and busulfan (Bu) are used in pretransplantation conditioning therapy for patients with myeloid leukemia. To further improve their efficacy in FMS-like tyrosine kinase 3 internal tandem duplications (FLT3-ITD)-positive acute myeloid leukemia (AML), we investigated their synergism with sorafenib (Sor). Exposure of FLT3-ITD-positive MV-4-11 and MOLM 13 cells to Bu+Clo+Flu+Sor resulted in synergistic cytotoxicity; no such synergism was observed in the FLT3-wild type THP-1 and KBM3/Bu250(6) cell lines...
November 2014: Biology of Blood and Marrow Transplantation
Guiyun Song, Benigno C Valdez, Yang Li, Jose R Dominguez, Paul Corn, Richard E Champlin, Borje S Andersson
Fludarabine (Flu), clofarabine (Clo) and busulfan (Bu) are used in allogeneic hematopoietic stem cell transplant (allo-HSCT). We reported that combining [Flu + Clo + Bu] had a synergistic cytotoxicity in AML cells. We hypothesized that combining [Flu + Clo + Bu] with the histone deacetylase inhibitor SAHA will further enhance cytotoxicity. We exposed the acute myeloid leukemia (AML) cell lines KBM3/Bu250(6) and OCI-AML3 to Flu, Clo, Bu and SAHA alone and in various combinations. [Flu + Clo + Bu + SAHA] resulted in synergistic cytotoxicity, which can be attributed to (1) activated DNA-damage response and cell cycle checkpoint activation through the ATM-CHK2-P53 (or P73) pathway or ATM-CHK2-cdc25-cdc2 pathway, (2) histone modifications and (3) activated apoptosis pathway...
July 2014: Leukemia & Lymphoma
Benigno C Valdez, Guiyun Wang, David Murray, Yago Nieto, Yang Li, Jatin Shah, Francesco Turturro, Michael Wang, Donna M Weber, Richard E Champlin, Muzaffar H Qazilbash, Borje S Andersson
Hematopoietic stem cell transplantation (HSCT) is an established treatment for multiple myeloma (MM), a plasma cell malignancy. To identify an improved pretransplant conditioning regimen, we investigated the cytotoxicity of gemcitabine (Gem) and clofarabine (Clo) combinations toward MM cell lines and patient cell samples. A strong synergism of the two nucleoside analogs, when combined at their approximate IC10 concentrations, was observed. This synergism could be partly due to the observed Gem-mediated phosphorylation and activation of deoxycytidine kinase, resulting in enhanced phosphorylation of Gem and Clo...
August 2013: Experimental Hematology
Benigno C Valdez, Yago Nieto, David Murray, Yang Li, Guiyun Wang, Richard E Champlin, Borje S Andersson
Hematopoietic stem cell transplantation is used for treatment of lymphoma. In an attempt to design an efficacious and safe prehematopoietic stem cell transplantation conditioning regimen, we investigated the cytotoxicity of the combination of busulfan (B), melphalan (M), and gemcitabine (G) in lymphoma cell lines in the absence or presence of drugs that induce epigenetic changes. Cells were exposed to drugs individually or in combination and analyzed by the MTT proliferation assay, flow cytometry, and Western blotting...
October 2012: Experimental Hematology
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