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Little Rock, AR, United States

Chavan S.S.,University of Arkansas for Medical Sciences | Chavan S.S.,Myeloma Institute for Research and Therapy | Shaughnessy Jr. J.D.,Myeloma Institute for Research and Therapy | Edmondson R.D.,Myeloma Institute for Research and Therapy
Human Genomics | Year: 2011

Many primary biological databases are dedicated to providing annotation for a specific type of biological molecule such as a clone, transcript, gene or protein, but often with limited cross-references. Therefore, enhanced mapping is required between these databases to facilitate the correlation of independent experimental datasets. For example, molecular biology experiments conducted on samples (DNA, mRNA or protein) often yield more than one type of 'omics' dataset as an object for analysis (eg a sample can have a genomics as well as proteomics expression dataset available for analysis). Thus, in order to map the two datasets, the identifier type from one dataset is required to be linked to another dataset, so preventing loss of critical information in downstream analysis. This identifier mapping can be performed using identifier converter software relevant to the query and target identifier databases. This review presents the publicly available web-based biological database identifier converters, with comparison of their usage, input and output formats, and the types of available query and target database identifier types. © HENRY STEWART PUBLICATIONS.

Yong K.,University College London | Cavet J.,University of Manchester | Johnson P.,Cancer Research Clinical Center | Morgan G.,Myeloma Institute for Research and Therapy | And 5 more authors.
British Journal of Cancer | Year: 2016

Background:KW-2478 is a novel, non-ansamycin, non-purine heat-shock protein 90 (Hsp90) inhibitor.Methods:In this phase I, multicentre study, KW-2478 was administered intravenously over 1 h at doses ranging from 14 to 176 mg m -2 once daily on days 1-5 of a 14-day cycle in a standard 3+3 design in 27 patients (22 with multiple myeloma and 5 with non-Hodgkin lymphoma). Patients enrolled had relapsed/refractory disease previously treated with ≥2 regimens.Results:There were no dose-limiting toxicities, thus the maximum-tolerated dose was not reached. KW-2478 was well tolerated and did not manifest significant retinal or ocular toxicity. The most common treatment-related adverse events were diarrhoea (33.3%), fatigue (29.6%), headache (25.9%), hypertension (22.2%), nausea (14.8%), vomiting (7.4%), and dizziness (7.4%). Plasma concentrations peaked at the end of infusion and decayed in a biphasic manner with a terminal half-life of ∼6 h. Target inhibition was inferred from the increase in Hsp70 levels in peripheral blood mononuclear cells at doses ≥71 mg m -2. Twenty-four of 25 (96%) evaluable patients showed stable disease, with five being free of disease progression for ≥6 months.Conclusions:Preliminary clinical response data were encouraging and warrant further investigation of KW-2478 in combination regimens for relapsed/refractory B-cell malignancies. © 2016 Cancer Research UK.

Papanikolaou X.,Myeloma Institute for Research and Therapy | Szymonifka J.,Cancer Research and Biostatistics | Rosenthal A.,Cancer Research and Biostatistics | Heuck C.J.,Myeloma Institute for Research and Therapy | And 11 more authors.
Haematologica | Year: 2013

Relapsed/refractory multiple myeloma represents a major challenge in multiple myeloma therapy. For patients with relapsed/refractory multiple myeloma, we developed a treatment schema of metronomically scheduled drug therapy. We identified 186 patients who had been treated with metronomic therapy between March 2004 and January 2012 with a median follow up of 24.2 months. Median age was 61 years (range 36-83). Median number of prior therapies was 14 (range 1-51). Median number of completed metronomic therapy cycles was 1 (range 1- 5), while 45 of 186 (25%) received 2 or more cycles. Responses included complete remission in 11 of 186 patients (6%), very good partial remission in 12 of 186 (7%), partial remission in 65 of 179 (36%), and minimal response in 29 of 186 (16%), for an overall response rate of 63% (117 of 186). Median overall survival and progression-free survival were 11.2 and 3.6 months, respectively. Hematologic toxicity grading was problematic as 146 of 186 (78%) of patients presented with at least grade 2 thrombocytopenia within 90 days prior to starting metronomic therapy. Grade 4 leukopenia, anemia, and/or thrombocytopenia following metronomic therapy occurred in 108 of 186 (58%), 12 of 186 (6%), and 147 of 186 (79%) patients, respectively. Incidence of grade 3-4 neutropenic fever was 4 of 186 (2%). Most patients (177 of 186, 95%) were treated in an outpatient unit and secondary admissions due to regimen-related toxicity occurred in 37 of 186 (20%). Treatment-related mortality was evident in 2 of 186 (1%). In conclusion, metronomic therapy is an effective late salvage treatment in relapsed/refractory multiple myeloma, with a high overall response rate and a favorable toxicity profile.

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