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  • 1
    Language: English
    In: Leukemia, 2018-11, Vol.32 (11), p.2316-2325
    Description: The survival of pediatric patients with multiply relapsed and/or refractory (R/R) B-cell acute lymphoblastic leukemia has historically been very poor; however, data are limited in the current era. We conducted a retrospective study to determine the outcome of multiply R/R childhood B-ALL treated at 24 TACL institutions between 2005 and 2013. Patient information, treatment, and response were collected. Prognostic factors influencing the complete remission (CR) rate and event-free survival (EFS) were analyzed. The analytic set included 578 salvage treatment attempts among 325 patients. CR rates (mean ± SE) were 51 ± 4% for patients with bone marrow R/R B-ALL who underwent a second salvage attempt, 37 ± 6% for a third attempt, and 31 ± 6% for the fourth through eighth attempts combined. For patients achieving a CR after their second, third, and fourth through eighth attempts, the 2 year EFS was 41 ± 6%, 13 ± 7%, and 27 ± 13% respectively. Our results showed slight improvement when compared to previous studies. This is the largest and most recent study to date that evaluates the outcome of this patient population. Our data will provide detailed reference for the evaluation of new agents being developed for childhood B-ALL.
    ISSN: 0887-6924
    E-ISSN: 1476-5551
    Source: Nature Open Access
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Journal of chemical education, 2007-08, Vol.84 (8), p.1328
    Description: This exercise combines conformational analysis and 1-D and 2-D NMR spectroscopy to correctly assign the proton and carbon NMR spectra of 2,3-epoxy-1-propanol (glycidol). In the process, students learn how to read DEPT-135, HETCOR, and COSY spectra. One set of diastereotopic protons is assigned using dihedral angles and the Karplus relationship. The assignment of the other set of diastereotopic protons requires that conformational modeling be done to complete the assignment of protons to signals.
    Subject(s): Education ; Analysis ; Epoxy compounds ; Nuclear magnetic resonance spectroscopy ; Spectra ; College students ; Chemical properties ; Alcohols ; Science experiments ; Organic chemistry ; Science education ; Nuclear magnetic resonance--NMR ; Spectrum analysis ; Spectrometers ; Two dimensional models ; Experiments ; Scientific apparatus & instruments
    ISSN: 0021-9584
    E-ISSN: 1938-1328
    Source: Hellenic Academic Libraries Link
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: Child's nervous system, 2019-11, Vol.35 (11), p.2043-2046
    Description: Radiation-induced injury is a well-described toxicity in children receiving radiation therapy for tumors of the central nervous system. Standard therapy has historically consisted primarily of high-dose corticosteroids, which carry significant side effects. Preclinical models suggest that radiation necrosis may be mediated in part through vascular endothelial growth factor (VEGF) overexpression, providing the rationale for use of VEGF inhibitors in the treatment of CNS radiation necrosis. We present the first prospective experience examining the safety, feasibility, neurologic outcomes, and imaging characteristics of bevacizumab therapy for CNS radiation necrosis in children.Seven patients between 1 and 25 years of age with neurologic deterioration and MRI findings consistent with radiation injury or necrosis were enrolled on an IRB-approved pilot feasibility study. Patients received bevacizumab at a dose of 10 mg/kg intravenously every 2 weeks for up to 6 total doses.Five patients (83%) were able to wean off corticosteroid therapy during the study period and 4 patients (57%) demonstrated improvement in serial neurologic exams. All patients demonstrated a decrease in T1-weighted post-gadolinium enhancement on MRI, while 5 (71%) showed a decrease in FLAIR signal. Four patients developed a progressive disease of their underlying tumor during bevacizumab therapy.Our experience lends support to the safety and feasibility of bevacizumab administration for the treatment of radiation necrosis for appropriately selected patients within the pediatric population.
    Subject(s): Neurosciences ; Medicine & Public Health ; Radiation injury ; Neurosurgery ; Pediatric ; Radiation necrosis ; Bevacizumab ; Index Medicus ; radiation necrosis ; radiation injury ; pediatric
    ISSN: 0256-7040
    E-ISSN: 1433-0350
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Neuro-oncology (Charlottesville, Va.), 2018-06-22, Vol.20 (suppl_2), p.i68-i68
    Description: Abstract BACKGROUND Posterior fossa ependymoma (PF EPN) is a pediatric central nervous system malignancy that has poor outcome to standard therapeutic approaches. The majority of PF EPN tumors have increased HER2 expression. Trastuzumab is a monoclonal antibody that targets HER2, and sargramostim (GM-CSF) stimulates hematopoietic progenitor cell proliferation. The combination of trastuzumab and GM-CSF has been shown to trigger antibody-dependent cell cytotoxicity in vitro in PF EPN cell lines. Due to reduced blood-brain barrier penetration of trastuzumab, intrathecal (IT) administration is an attractive method for delivery for treatment of recurrent PF-EPN. METHODS Children aged 1–21 years with relapsed PF EPN and no CSF obstruction on imaging are eligible for the Phase I institutional trial at Children’s Hospital Colorado. Stratum A involves IT trastuzumab and subcutaneous (subQ) GM-CSF prior to standard-of-care surgical resection. Stratum B involves a 3 + 3 phase I design with serial IT trastuzumab doses, each preceded by 3 days of GM-CSF, to establish the MTD for IT trastuzumab. RESULTS Three patients (1:2; male:female) have been enrolled in Stratum A at trastuzumab Dose Level 1 (40 mg). Median age at enrollment is 8.8 years (range, 4.2–20.0 years). 2/3 tumors tested after pre-surgical trastuzumab and GM-CSF had detectable trastuzumab by mass spectroscopy. No adverse events at least possibly related to study therapy have occurred. CONCLUSIONS IT trastuzumab penetrates PF EPN tumor tissue. Stratum A remains open to enrollment for eligible patients who have clinical indication for surgical resection. Based on Stratum A results, Stratum B is now also open to accrual.
    Subject(s): Abstracts
    ISSN: 1522-8517
    E-ISSN: 1523-5866
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: The Journal of immunology (1950), 2016-03-01, Vol.196 (5), p.2239-2248
    Description: We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, bronchoalveolar lavage, and spleens of mice at 24 h postinfection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12 h) in the focal pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TRAIL, and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells. The latter have been shown to facilitate the clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation, and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia.
    Subject(s): Streptococcus pneumoniae - immunology ; Time Factors ; Myeloid Cells - immunology ; Streptococcus pneumoniae - metabolism ; Inflammation Mediators - metabolism ; Streptococcus pneumoniae - genetics ; Female ; Bacterial Proteins - immunology ; Carrier Proteins - immunology ; Macrophages - immunology ; Disease Models, Animal ; Pneumonia, Pneumococcal - immunology ; Pneumonia, Pneumococcal - microbiology ; Macrophages - pathology ; Immunomodulation ; Bacterial Proteins - genetics ; Mice, Transgenic ; Bacterial Load ; Pneumonia, Pneumococcal - mortality ; TNF-Related Apoptosis-Inducing Ligand - metabolism ; Bacteremia ; Carrier Proteins - genetics ; Macrophages - metabolism ; Animals ; Carrier Proteins - metabolism ; Pneumonia, Pneumococcal - pathology ; Myeloid Cells - metabolism ; Bacterial Proteins - metabolism ; Mice ; Mutation ; Gene Expression Regulation, Bacterial ; Cytokines - biosynthesis ; Index Medicus ; Abridged Index Medicus
    ISSN: 0022-1767
    E-ISSN: 1550-6606
    Source: HighWire Press (Free Journals)
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 6
    Language: English
    In: The Journal of immunology (1950), 2016-03-01, Vol.196 (5), p.2239-2248
    Description: We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, BAL and spleens of mice at 24-hrs post infection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12-hrs) in the focal-pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TNF-related apoptosis - inducing ligand (TRAIL) and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells (MDSCs). The latter have been shown to facilitate clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia.
    ISSN: 0022-1767
    E-ISSN: 1550-6606
    Source: HighWire Press (Free Journals)
    Source: Alma/SFX Local Collection
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