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bruce bostrom

Nathan Gossai, Michael Richards, Lara Boman, Yoav Messinger, Sara Gernbacher, Joanna Perkins, Bruce Bostrom
Erwinia chrysanthemi-derived asparaginase is increasingly integral to acute lymphoblastic leukemia therapy. In our series, 16% of patients developed symptomatic hyperammonemia following Erwinia administration with symptoms including refractory nausea, vomiting, profound fatigue, malaise, and coma. This series of patients receiving Erwinia indicates higher than expected incidence of hyperammonemia, correlation between ammonia and asparaginase levels and therapeutic asparaginase activity levels despite dose reduction...
May 2018: Journal of Pediatric Hematology/oncology
Wanda Salzer, Bruce Bostrom, Yoav Messinger, Anthony J Perissinotti, Bernard Marini
Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of acute lymphoblastic leukemia (ALL). Adequate asparagine depletion is believed to be an important factor in achieving optimal therapeutic outcomes. Measurement of asparaginase activity allows practitioners to evaluate the potential effectiveness of therapy in real time. Asparaginase activity levels can be used to identify patients with silent inactivation and modify therapy in these patients. Patients with silent inactivation to asparaginase who are switched to therapy with an immunologically distinct asparaginase exhibit outcomes similar to patients who never developed silent inactivation...
October 18, 2017: Leukemia & Lymphoma
Wendy Landier, Lindsey Hageman, Yanjun Chen, Nancy Kornegay, William E Evans, Bruce C Bostrom, Jacqueline Casillas, David S Dickens, Anne L Angiolillo, Glen Lew, Kelly W Maloney, Leo Mascarenhas, A Kim Ritchey, Amanda M Termuhlen, William L Carroll, Mary V Relling, F Lennie Wong, Smita Bhatia
Purpose Children with acute lymphoblastic leukemia (ALL) are generally instructed to take mercaptopurine (6-MP) in the evening and without food or dairy products. This study examines the association between 6-MP ingestion habits and 6-MP adherence, red cell thioguanine nucleotide (TGN) levels, and risk of relapse in children with TMPT wild-type genotype. Methods Participants included 441 children with ALL receiving oral 6-MP for maintenance. Adherence was monitored over 48,086 patient-days using the Medication Event Monitoring System; nonadherence was defined as adherence rate < 95%...
May 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Wendy Landier, Yanjun Chen, Lindsey Hageman, Heeyoung Kim, Bruce C Bostrom, Jacqueline N Casillas, David S Dickens, William E Evans, Kelly W Maloney, Leo Mascarenhas, A Kim Ritchey, Amanda M Termuhlen, William L Carroll, Mary V Relling, F Lennie Wong, Smita Bhatia
Adequate exposure to oral 6-mercaptopurine (6MP) during maintenance therapy for childhood acute lymphoblastic leukemia (ALL) is critical for sustaining durable remissions; accuracy of self-reported 6MP intake is unknown. We aimed to directly compare self-report to electronic monitoring (Medication Event Monitoring System [MEMS]) and identify predictors of overreporting in a cohort of 416 children with ALL in first remission over 4 study months (1344 patient-months for the cohort) during maintenance therapy...
April 6, 2017: Blood
Lynda Kwon Beaupin, Bruce Bostrom, Matthew J Barth, Irene Franklin, Raven Jaeger, Priyanka Kamath, Brian Schreiber, Archie Bleyer
Pegaspargase is a mainstay in the treatment of acute lymphoblastic leukemia. When intravenous (IV) infusion replaced intramuscular (IM) injection as the standard route of administration, there were early reports suggested an increased hypersensitivity reactions (HSRs) rate with IV administration. There have since been eight published reports comparing the incidence of HSRs occurring with IV versus IM pegaspargase. This review analyzes the reports and summarizes their consistent findings where feasible. For grade 3-4 HSRs, the rates are comparable with IV and IM administration...
April 2017: Leukemia & Lymphoma
Divya Vundamati, Bruce Bostrom
Isolated monosomy-7, a rare cytogenetic abnormality in patients with pediatric acute lymphoblastic leukemia (ALL), portends a worse prognosis. Despite improvements in treatment, outcomes for patients with relapsed ALL remain poor. Novel treatments adopted from the B-cell malignancy multiple myeloma may have a role in treatment of ALL. Bortezomib is one such agent currently in phase III trials for B and T ALL. This study presents a patient with B-cell ALL and monosomy-7 who relapsed off therapy. The combination of bortezomib, lenalidomide, and dexamethasone was used to attain remission before bone marrow transplant after conventional relapse therapy failed...
August 2016: Journal of Pediatric Hematology/oncology
Yousif Matloub, Linda Stork, Barbara Asselin, Stephen P Hunger, Michael Borowitz, Tamekia Jones, Bruce Bostrom, Julie M Gastier-Foster, Nyla A Heerema, Andrew Carroll, Naomi Winick, William L Carroll, Bruce Camitta, Meenakshi Devidas, Paul S Gaynon
BACKGROUND: Children with T-lineage acute lymphoblastic leukemia ALL (T-ALL) historically have had inferior outcomes compared with the children with precursor-B ALL (B-ALL). After 1995, the Children's Cancer Group (CCG) treated patients with B- and T-ALL according to the National Cancer Institute (NCI) risk criteria, basing risk stratification on age and white blood cell (WBC) count regardless of immunophenotype. The Pediatric Oncology Group (POG) treated all the patients with T-ALL on separate, generally more intensive protocols than those used to treat the patients with B-ALL...
February 2016: Pediatric Blood & Cancer
Smita Bhatia, Wendy Landier, Lindsey Hageman, Yanjun Chen, Heeyoung Kim, Can-Lan Sun, Nancy Kornegay, William E Evans, Anne L Angiolillo, Bruce Bostrom, Jacqueline Casillas, Glen Lew, Kelly W Maloney, Leo Mascarenhas, A Kim Ritchey, Amanda M Termuhlen, William L Carroll, F Lennie Wong, Mary V Relling
IMPORTANCE: Variability in prescribed doses of 6-mercaptopurine (6MP) and lack of adherence to a 6MP treatment regimen could result in intra-individual variability in systemic exposure to 6MP (measured as erythrocyte thioguanine nucleotide [TGN] levels) in children with acute lymphoblastic leukemia (ALL). The effect on relapse risk of this variability is unknown. OBJECTIVE: To determine the effect of high intra-individual variability of 6MP systemic exposure on relapse risk in children with ALL...
June 2015: JAMA Oncology
Sven A Forner, Leonel T Takada, Brianne M Bettcher, Iryna V Lobach, Maria Carmela Tartaglia, Charles Torres-Chae, Aissatou Haman, Julie Thai, Paolo Vitali, John Neuhaus, Alan Bostrom, Bruce L Miller, Howard J Rosen, Michael D Geschwind
We assessed the diagnostic utility of 3 CSF biomarkers-14-3-3 protein, total tau (T-tau), and neuron-specific enolase (NSE)-from the same lumbar puncture to distinguish between participants with neuropathologically confirmed sporadic Creutzfeldt-Jakob disease (sCJD, n = 57) and controls with nonprion rapidly progressive dementia (npRPD, n = 41). Measures of diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value, as well as logistic regression and area under the receiver operator curve (AUC), were used to assess the ability of these CSF biomarkers, alone or concomitantly, to predict diagnosis...
April 2015: Neurology. Clinical Practice
Xiaojun Liu, Junjie Xiao, Han Zhu, Xin Wei, Colin Platt, Federico Damilano, Chunyang Xiao, Vassilios Bezzerides, Pontus Boström, Lin Che, Chunxiang Zhang, Bruce M Spiegelman, Anthony Rosenzweig
Exercise induces physiological cardiac growth and protects the heart against pathological remodeling. Recent work suggests exercise also enhances the heart's capacity for repair, which could be important for regenerative therapies. While microRNAs are important in certain cardiac pathologies, less is known about their functional roles in exercise-induced cardiac phenotypes. We profiled cardiac microRNA expression in two distinct models of exercise and found microRNA-222 (miR-222) was upregulated in both. Downstream miR-222 targets modulating cardiomyocyte phenotypes were identified, including HIPK1 and HMBOX1...
April 7, 2015: Cell Metabolism
Susan J Lindemulder, Linda C Stork, Bruce Bostrom, Xiaomin Lu, Meenakshi Devidas, Stephen Hunger, Joseph P Neglia, Nina S Kadan-Lottick
BACKGROUND: We sought to determine whether survivors of standard risk ALL (SR-ALL) treated without cranial radiation have increased risk for obesity by assessing changes in body mass index (BMI) during and after treatment; identifying contributing patient and treatment factors; comparing rates of overweight/obese to national health data. PROCEDURE: Eligibility for this retrospective cohort study included: (i) previous enrollment on legacy therapy trials CCG1922 or CCG1952; (ii) continuous first remission; and (iii) age at follow-up evaluation of 6-16...
June 2015: Pediatric Blood & Cancer
Smita Bhatia, Wendy Landier, Lindsey Hageman, Heeyoung Kim, Yanjun Chen, Kristine R Crews, William E Evans, Bruce Bostrom, Jacqueline Casillas, David S Dickens, Kelly W Maloney, Joseph P Neglia, Yaddanapudi Ravindranath, A Kim Ritchey, F Lennie Wong, Mary V Relling
Durable remissions in children with acute lymphoblastic leukemia (ALL) require a 2-year maintenance phase that includes daily oral 6-mercaptopurine (6MP). Adherence to oral 6MP among Asian-American and African-American children with ALL is unknown. We enrolled 298 children with ALL (71 Asian Americans, 68 African Americans, and 159 non-Hispanic whites) receiving oral 6MP for the maintenance phase. Adherence was measured electronically for 39 803 person-days. Adherence declined from 95.0% (month 1) to 91.8% (month 5, P < ...
October 9, 2014: Blood
Matthew M Moldan, Bruce C Bostrom, Robert J Tibesar, Timothy A Lander, James D Sidman
The epidermal growth factor pathway has been implicated in various tumors, including human papillomavirus (HPV) lesions such as recurrent respiratory papillomatosis (RRP). Due to the presence of epidermal growth factor receptors in RRP, epidermal growth factor receptor (EGFR) inhibitors have been utilized as adjuvant therapy. This case series examines the response to EGFR inhibitors in RRP. Four patients with life-threatening RRP were treated with EGFR inhibitors. Operative frequency and anatomical Derkay scores were calculated prior to, and following EGFR inhibitor treatment via retrospective chart review...
2013: F1000Research
Samyuktha Melachuri, Laura Gandrud, Bruce Bostrom
BACKGROUND: Symptomatic fasting hypoglycemia has been reported as an unusual side effect in patients with acute lymphoblastic leukemia (ALL) on maintenance therapy. We evaluated the relation of the red cell 6-mercaptopurine (6-MP) metabolite 6-methyl-mercaptopurine (6MMP) with hypoglycemia. PROCEDURE: We retrospectively reviewed charts of three patients with ALL and symptomatic hypoglycemia while fasting who were noted to have high levels of 6MMP. All patients had an empiric trial of switching from evening to morning 6-MP administration, and two patients were subsequently switched to twice daily dosing...
June 2014: Pediatric Blood & Cancer
Lee D Roberts, Pontus Boström, John F O'Sullivan, Robert T Schinzel, Gregory D Lewis, Andre Dejam, Youn-Kyoung Lee, Melinda J Palma, Sondra Calhoun, Anastasia Georgiadi, Ming-Huei Chen, Vasan S Ramachandran, Martin G Larson, Claude Bouchard, Tuomo Rankinen, Amanda L Souza, Clary B Clish, Thomas J Wang, Jennifer L Estall, Alexander A Soukas, Chad A Cowan, Bruce M Spiegelman, Robert E Gerszten
The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) regulates metabolic genes in skeletal muscle and contributes to the response of muscle to exercise. Muscle PGC-1α transgenic expression and exercise both increase the expression of thermogenic genes within white adipose. How the PGC-1α-mediated response to exercise in muscle conveys signals to other tissues remains incompletely defined. We employed a metabolomic approach to examine metabolites secreted from myocytes with forced expression of PGC-1α, and identified β-aminoisobutyric acid (BAIBA) as a small molecule myokine...
January 7, 2014: Cell Metabolism
Elizabeth A Raetz, Debra Morrison, Eleny Romanos-Sirakis, Paul Gaynon, Richard Sposto, Deepa Bhojwani, Bruce C Bostrom, Patrick Brown, Elena Eckroth, Jeannette Cassar, Jemily Malvar, Aby Buchbinder, William L Carroll
To address the therapeutic challenges in childhood relapsed ALL, a phase 1 study combining a survivin mRNA antagonist, EZN-3042, with reinduction chemotherapy was developed for pediatric patients with second or greater bone marrow relapses of B-lymphoblastic leukemia. EZN-3042 was administered as a single agent on days -5 and -2 and then in combination with a 4-drug reinduction platform on days 8, 15, 22, and 29. Toxicity and the biological activity of EZN-3042 were assessed. Six patients were enrolled at dose level 1 (EZN-3042 2...
August 2014: Journal of Pediatric Hematology/oncology
Bruce Bostrom, Priya Uppal, Julie Chu, Yoav Messinger, Laura Gandrud, Robert McEvoy
BACKGROUND: Hyperglycemia during corticosteroid and asparaginase therapy for acute lymphoblastic leukemia is a significant side effect that is usually treated with insulin. Metformin is an oral antidiabetic biguanide that may cause metabolic acidosis and liver enzyme abnormalities of possible concern in patients receiving chemotherapy. PROCEDURE: We reviewed patients with acute lymphoblastic leukemia treated with corticosteroids and asparaginase who received metformin for control of hyperglycemia...
October 2013: Journal of Pediatric Hematology/oncology
Kirsty L Spalding, Olaf Bergmann, Kanar Alkass, Samuel Bernard, Mehran Salehpour, Hagen B Huttner, Emil Boström, Isabelle Westerlund, Celine Vial, Bruce A Buchholz, Göran Possnert, Deborah C Mash, Henrik Druid, Jonas Frisén
Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived ¹⁴C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons constituting one-third of the neurons is subject to exchange...
June 6, 2013: Cell
Amanda K Lamarre, Katya Rascovsky, Alan Bostrom, Parnian Toofanian, Sarah Wilkins, Sharon J Sha, David C Perry, Zachary A Miller, Georges Naasan, Robert Laforce, Jayne Hagen, Leonel T Takada, Maria Carmela Tartaglia, Gail Kang, Douglas Galasko, David P Salmon, Sarah Tomaszewski Farias, Berneet Kaur, John M Olichney, Lovingly Quitania Park, Mario F Mendez, Po-Heng Tsai, Edmond Teng, Bradford Clark Dickerson, Kimiko Domoto-Reilly, Scott McGinnis, Bruce L Miller, Joel H Kramer
OBJECTIVE: To evaluate the interrater reliability of the new International Behavioural Variant FTD Criteria Consortium (FTDC) criteria for behavioral variant frontotemporal dementia (bvFTD). METHODS: Twenty standardized clinical case modules were developed for patients with a range of neurodegenerative diagnoses, including bvFTD, primary progressive aphasia (nonfluent, semantic, and logopenic variant), Alzheimer disease, and Lewy body dementia. Eighteen blinded raters reviewed the modules and 1) rated the presence or absence of core diagnostic features for the FTDC criteria, and 2) provided an overall diagnostic rating...
May 21, 2013: Neurology
Li Ye, Sandra Kleiner, Jun Wu, Rajan Sah, Rana K Gupta, Alexander S Banks, Paul Cohen, Melin J Khandekar, Pontus Boström, Rina J Mepani, Dina Laznik, Theodore M Kamenecka, Xinyi Song, Wolfgang Liedtke, Vamsi K Mootha, Pere Puigserver, Patrick R Griffin, David E Clapham, Bruce M Spiegelman
PGC1α is a key transcriptional coregulator of oxidative metabolism and thermogenesis. Through a high-throughput chemical screen, we found that molecules antagonizing the TRPVs (transient receptor potential vanilloid), a family of ion channels, induced PGC1α expression in adipocytes. In particular, TRPV4 negatively regulated the expression of PGC1α, UCP1, and cellular respiration. Additionally, it potently controlled the expression of multiple proinflammatory genes involved in the development of insulin resistance...
September 28, 2012: Cell
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