tbuckley/cabot-search huggingface dataset:
High field MRI characterization of tumor growth kinetics, vascularity and cellularity in a PDGF-driven RCAS/tv-a mouse model of glioma
Authors: Jonathan B. Moody, Patrick McConville, Richard J. Lister, Alicia R. Kreger, Erin Trachet, William L. Elliott, Bradford A. Moffat, Thomas L. Chenevert, Daniel L. Dexter, Alnawaz Rehemtulla, Brian D. Ross, W. R. Leopold
Journal: Cancer Research (2004)

5115  Introduction: RCAS/tv-a technology provides a promising new platform for development of tissue-, and oncogenic pathway-specific mouse tumor models, for elucidation of mechanisms of neoplatistic transformation, and for development of targeted treatments. The technology relies on somatic gene transfer through infection by RCAS viral vectors derived from the avian retrovirus (ALV-A) in mice expressing the gene for the RCAS receptor (tv-a). We characterized tumor appearance, growth and heterogeneity using high field MRI in a mouse that expresses tv-a under the control of the nestin promoter expressed in glial-progenitors (Ntv-a mouse). Methods: 19 Ntv-a mice that had developed tumors following intracranial injection with RCAS virus encoding PDGF at 3 weeks of age (as determined by MRI) underwent weekly brain MRI to characterize tumor growth and development, until they reached a moribund state and were sacrificed. T2-weighted fast spin-echo MRI was used (3 minute images). At multiple time points, tumors were also evaluated using T1-weighted spin-echo MRI (3 minute images), pre- and post-contrast agent injection, to delineate regions of dense and/or ‘leaky’ microvasculature. Tumor cellularity was also evaluated during the course of the study by diffusion-MRI measurement of the apparent diffusion coefficient (ADC). When signs of illness were apparent, animals were sacrificed, and the brains harvested for histology. Resuts and Discussion: The mean time for tumor appearance was 3.3 ± 0.4 weeks. After appearance, the tumors grew rapidly (2 week doubling time) and invasively, invading one or both ventricles. Tumor cellularity was higher at the outer margins, with ADC similar to that which has been measured in implanted glioma xenografts (∼100-120 cm2/s). Early stage tumors showed little enhancing after contrast injection, but localized enhancing regions were evident in late stage tumors. Histologic sections correlated well with T2-weighted contrast and ADC, confirming localized regions of high cellularity. Conclusion: We have characterized tumor growth, heterogeneity, vasculature and cellularity using high field, high-throughput MRI for the first time in the PDGF-driven Ntv-a mouse model. The MRI-measured tumor characteristics were very similar to those measured clinically in oligodendroglioma, with late stage tumors showing contrast-enhancing regions typical of malignant tissue. This study demonstrates the unique capabilities of MRI in the Ntv-a model, for following tumor appearance and development, showing its potential for pre-clinical efficacy studies in this model. Future use of high field MRI in other RCAS/tv-a models will further highlight this potential.
The Pediatric Research Equity Act Moves Into Adolescence
Authors: Florence T. Bourgeois, Thomas J. Hwang
Journal: JAMA (2017)

This Viewpoint discusses the Pediatric Research Equity Act, a 2003 law authorizing the US Food and Drug Administration to require the study of new therapies for pediatric populations, and proposes improvements to the law as it comes up for reauthorization in 2017.
Arsenic Trioxide (ATO) Interacts Synergistically with MEK Inhibitors to Induce Apoptosis in STI571-Resistant Bcr-Abl Mutants.
Authors: Paolo Lunghi, Laura Mazzera, Attilio Corradi, Anna Maria Cantoni, Stefano Jottini, Guerino Lombardi, Micaela Ricca, Davide Arienti, Vittorio Rizzoli, Michael WN Deininger, Antonio Bonati
Journal: Blood (2009)
Inhibition of Chk1 Kinase Sensitizes Leukemia and Lymphoma Cell Lines with TP53 Mutations to Chemotherapy.
Authors: Jana Zemanova, Ludmila Sebejova, Ondrej Hylse, Kamil Paruch, Sarka Pavlova, Jiri Mayer, Sarka Pospisilova, Martin Trbusek
Journal: Blood (2012)
Systemic Injection of RPE65-Programmed Bone Marrow-Derived Cells Prevents Progression of Chronic Retinal Degeneration
Authors: Xiaoping Qi, S. Louise Pay, Yuanqing Yan, James Thomas, Alfred S. Lewin, Lung-Ji Chang, Maria B. Grant, Michael E. Boulton
Journal: Molecular Therapy (2017)

Bone marrow stem and progenitor cells can differentiate into a range of non-hematopoietic cell types, including retinal pigment epithelium (RPE)-like cells. In this study, we programmed bone marrow-derived cells (BMDCs) ex vivo by inserting a stable RPE65 transgene using a lentiviral vector. We tested the efficacy of systemically administered RPE65-programmed BMDCs to prevent visual loss in the superoxide dismutase 2 knockdown (Sod2 KD) mouse model of age-related macular degeneration. Here, we present evidence that these RPE65-programmed BMDCs are recruited to the subretinal space, where they repopulate the RPE layer, preserve the photoreceptor layer, retain the thickness of the neural retina, reduce lipofuscin granule formation, and suppress microgliosis. Importantly, electroretinography and optokinetic response tests confirmed that visual function was significantly improved. Mice treated with non-modified BMDCs or BMDCs pre-programmed with LacZ did not exhibit significant improvement in visual deficit. RPE65-BMDC administration was most effective in early disease, when visual function and retinal morphology returned to near normal, and less effective in late-stage disease. This experimental paradigm offers a minimally invasive cellular therapy that can be given systemically overcoming the need for invasive ocular surgery and offering the potential to arrest progression in early AMD and other RPE-based diseases.
Nilotinib Inhibits Bcr-Abl Kinase Activity in CML Progenitor Cells More Effectively Than Imatinib but Is Equipotent in Inducing Growth Inhibition.
Authors: Heiko Konig, Melissa Holtz, Hardik Modi, Paul Manley, Tessa L. Holyoake, Stephen J. Forman, Ravi Bhatia
Journal: Blood (2006)
Evaluation of traditional and novel measures of cardiac function to detect anthracycline-induced cardiotoxicity in survivors of childhood cancer.
Authors: A. C. Dietz, S. Sivanandam, C. Kaufman, A. Kelly, J. P. Neglia, P. R. Gaillard, D. A. Mulrooney
Journal: Journal of Clinical Oncology (2011)

9580 Background: Cardiovascular disease is the leading non-cancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures to quantify changes in cardiac function, but these may occur late in the clinical course and reflect advanced myocardial dysfunction. Our aim was to compare traditional and novel echocardiographic measures of systolic (radial strain (ε) vs. EF and FS) and diastolic function (radial strain rate (SR) vs. early/late left ventricular filling ratio (E/A)). Methods: We compared mean radial ε, SR, EF, FS, and E/A ratios among adult survivors of childhood cancer exposed to ≥ 250 mg/m2 of anthracyclines to age, sex-matched healthy controls. Survivors with a history of cardiac directed radiation therapy, known diabetes, or heart disease were excluded. Preliminary data on the first 14 of 36 planned participants are presented. Results: No differences in gender (43% male vs. 43% male, p=1.0) or current age (32.5 yrs (range:19-50) vs. 31.6 yrs (24-50), p=0.86) were identified between survivors and controls, respectively. Among survivors mean age at diagnosis was 15.6 (6-20) yrs, mean survival time 17 (5-30) yrs, and mean anthracycline exposure was 426 (300-645) mg/m2. Diagnoses included osteosarcoma (4), rhabdomyosarcoma (2), and synovial sarcoma (1). Among the echocardiographic measures assessed, only FS was significantly lower in cancer survivors compared to controls (34.1% vs. 41.3%, p < 0.01) (Table). Conclusions: Novel measures of radial ε and SR do not differ between survivors and controls. However this interim analysis suggests traditional FS may be a sufficient echocardiographic metric of cardiac dysfunction among adult survivors of childhood cancer. Further analysis is ongoing. Echocardiographic measures* Survivors (n=7) Controls (n=7) P value EF (%) 53.6 ± 9.5 58.1 ± 6.6 0.32 FS (%) 34.1 ± 4.2 41.3 ± 4.6 <0.01 E/A ratio 1.5 ± 0.2 1.6 ± 0.4 0.61 Systolic radial ε (%) 31.1 ± 18.1 37.6 ± 26 0.60 Diastolic early radial SR (s-1) -3 ± 1.6 -5 ± 5.3 0.35 Diastolic late radial SR (s-1) -1.4 ± 1.4 -3.5 ± 5.1 0.31 * Mean ± standard deviation
Prognostic Factors and Long Term Outcome of 138 Adults with Systemic Anaplastic Large-Cell Lymphoma: a Retrospective Study by the Groupe d'Etude Des Lymphomes De l'Adulte (GELA)
Authors: David Sibon, Marion Fournier, Josette Briere, Laurence Lamant, Corinne Haioun, Bertrand Coiffier, Serge Bologna, Pierre Morel, Jean Gabarre, Olivier Hermine, Anne Sonet, Christian Gisselbrecht, Georges Delsol, Philippe Gaulard, Herve Tilly
Journal: Blood (2010)
A Phase II Study of Intermittent Sunitinib in Previously Untreated Patients With Metastatic Renal Cell Carcinoma
Authors: Moshe C. Ornstein, Laura S. Wood, Paul Elson, Kimberly D. Allman, Jennifer Beach, Allison Martin, Beth R. Zanick, Petros Grivas, Tim Gilligan, Jorge A. Garcia, Brian I. Rini
Journal: Journal of Clinical Oncology (2017)

Purpose Sunitinib is a standard initial therapy in metastatic renal cell carcinoma (mRCC), but chronic dosing requires balancing toxicity with clinical benefit. The feasibility and clinical outcome with intermittent sunitinib dosing in patients with mRCC was explored. Patients and Methods Patients with treatment-naïve, clear cell mRCC were treated with four cycles of sunitinib (50 mg once per day, 4 weeks of receiving treatment followed by 2 weeks of no treatment). Patients with a ≥ 10% reduction in tumor burden (TB) after four cycles had sunitinib held, with restaging scans performed every two cycles. Sunitinib was reinitiated for two cycles in those patients with an increase in TB by ≥ 10%, and again held with ≥ 10% TB reduction. This intermittent sunitinib dosing continued until Response Evaluation Criteria in Solid Tumors-defined disease progression while receiving sunitinib, or unacceptable toxicity occurred. The primary objective was feasibility, defined as the proportion of eligible patients who underwent intermittent therapy. Results Of 37 patients enrolled, 20 were eligible for intermittent therapy and all patients (100%) entered the intermittent phase. Patients were not eligible for intermittent sunitinib because of progressive disease (n = 13), toxicity (n = 1), or consent withdrawal (n = 3) before the end of cycle 4. The objective response rate was 46% after the first four cycles of therapy. The median increase in TB during the periods off sunitinib was 1.6 cm (range, -2.9 to 3.4 cm) compared with the TB immediately before stopping sunitinib. Most patients exhibited a stable sawtooth pattern of TB reduction while receiving sunitinib and TB increase while not receiving sunitinib. Median progression-free survival to date is 22.4 months (95% CI, 5.4 to 37.6 months) and median overall survival is 34.8 months (95% CI, 14.8 months to not applicable). Conclusion Periodic extended sunitinib treatment breaks are feasible and clinical efficacy does not seem to be compromised.
Autologous Stem Cell Transplantation Is Feasible and of Potential Benefit In Very Elderly Patients with Lymphoma and Limited Comorbidities
Authors: Rebecca Elstrom, Peter Martin, Tsiporah B. Shore, Richard R. Furman, Jia Ruan, Tomer M Mark, Roger N Pearse, Morton Coleman, John P. Leonard, Usama Gergis
Journal: Blood (2010)
Retreatment with Alemtuzumab after a First, Successful Alemtuzumab Treatment in B-CLL.
Authors: Michael Fiegl, Florian Falkner, Andreas Falkner, Niklas Zojer, Michael Fridrik, Georg Hopfinger, Reinhard Stauder, Ebehard Gunsilius, Johanna Kantner, Martin Erdel, Inge Tinhofer, Guenther Gastl, Richard Greil
Journal: Blood (2007)
Evaluation of antiproliferative and apoptotic effects of the rational combination of the MEK1/2 inhibitor selumetinib (AZD6244) and inhibitors of the hedgehog pathway in colorectal cancer (CRC) cell lines.
Authors: A. Spreafico, J. J. Tentler, A. Tan, T. M. Pitts, M. I. Kachaeva, H. M. Selby, S. G. Eckhardt
Journal: Journal of Clinical Oncology (2011)

422 Background: The MAPK pathway is a crucial regulator of cell proliferation, survival, and resistance to apoptosis. Hyperactivation of this pathway due to mutations in KRAS have been reported in up to 50% of CRC cases. Clinical trials have shown that KRAS patients do not benefit from therapies targeting EGFR, highlighting the need for new therapeutic options. Utilizing differential gene array analyses, we have identified the hedgehog (HH) signaling pathway as a potential mediator of resistance to AZD6244. Based on these results, we tested the rational combination of selumetinib and the HH inhibitor, cyclopamine against human CRC cell lines. Methods: CRC cell lines were exposed to varying concentrations of selumetinib and cyclopamine. For AZD6244, cell lines with IC 50 ≤ 0.1 μM were considered extremely sensitive (ES) and those with IC 50 ≥ 1μM were deemed extremely resistant (ER). Four KRAS mutant cell lines (2ES, 2ER) were selected for combination studies. The antiproliferative effects were assessed using the sulforhodamine B (SRB) cell viability assay, and potential synergy was evaluated using the Chou and Talalay method. Apoptosis was analyzed using bioluminescent caspase 3/7 detection. Results: In all four cell lines tested, synergistic antiproliferative effects of selumetinib and cyclopamine were observed, including resistant lines to selumetinib. We observed significant induction of apoptosis when cell lines were exposed to the combination treatment, independent of their responsiveness to selumetinib in the SRB assay. Conclusions: Treatment of KRAS mutant CRC cell lines with selumetinib and cyclopamine resulted in synergistic inhibition of proliferation, regardless of sensitivity to selumetinib. Interestingly, a significant increase in apoptosis was observed in response to the combination, which may explain the synergy observed by the combination index (CI). In vivo analyses of this combination in cell lines and human CRC explants are ongoing to further validate these results. These preclinical data may suggest a rational combination strategy for patients with KRAS mutant CRC. No significant financial relationships to disclose.
Will Cardiovascular Outcomes Data on Newer Diabetes Drugs Bury the Older Agents?
Authors: James Flory
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Cancer patients’ use of supportive care services and cancer center services satisfaction
Authors: D. Wolcott, R. Wolosin, J. Macdonald, T. Strouse
Journal: Journal of Clinical Oncology (2008)

20641 Background: Cancer patients undergoing active treatment often need social worker, nutrition, and/or pain management services. Patient satisfaction is a service quality indicator. Few data exist concerning patients’ utilization of social worker, nutrition, and pain management services and levels of satisfaction with cancer center services. Methods: Analysis of 17,077 satisfaction surveys from Aptium Oncology (AO)-managed cancer centers. Selected items from the standard Press-Ganey (PG) Outpatient Oncology Survey were examined. PG mailed and received surveys directly from respondents. Respondents were grouped according to use of social worker, nutrition, and pain services. 10,291 patients used none of these, while 4,018 used 1 and 2,242 used 2, and 526 all three. 9 survey items were analyzed addressing interpersonal aspects of care, billing services, and global satisfaction. A multivariate analysis of covariance (with patient age recoded into larger categories as the covariate) showed a significant effect of the use of support services; t-tests for each different type of support service (pain management, nutritional support, and social work) were then performed for each of the 9 patient satisfaction items. Results: For all items, mean scores increased modestly but significantly in a step-wise fashion with increased self-reported utilization of 1, 2, or 3 services as compared to the “zero services” group. The “3 services group” mean item scores were 4–5 points higher than the zero services group mean scores for all 9 items. These differences remained when patient age range category, gender, and disease status (new vs. recurrent disease) were entered into the multivariate analysis. Conclusions: Self-reported utilization of an increasing number of categories of social worker, nutrition, and pain management services is associated with statistically significant and meaningfully increased levels of patient satisfaction with a broad range of hospital ambulatory cancer center services. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aptium Oncology, Press Ganey Associates, Inc.
Activation of Raf-1 through the Depletion of RKIP by Bcr-Abl Promotes CML Cell Proliferation
Authors: Satoki Nakamura, Tomonari Takemura, Yasuyuki Nagata, Daisuke Yokota, Isao Hirano, Takaaki Ono, Kazuyuki Shigeno, Shinya Fujisawa, Kazunori Ohnishi
Journal: Blood (2010)
First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors
Authors: Y.J. Bang, G. Giaccone, S.A. Im, D.Y. Oh, T.M. Bauer, J.L. Nordstrom, H. Li, G.R. Chichili, P.A. Moore, S. Hong, S.J. Stewart, J.E. Baughman, R.J. Lechleider, H.A. Burris
Journal: Annals of Oncology (2017)
Co-Treatment with Milatuzumab (Anti-CD74 mAb) and Rituximab (Anti-CD20 mAb) Results in the Induction of Mantle Cell Lymphoma Cell Death That Is Dependent On Actin Polymerization and Inhibition of NF-Kb.
Authors: Lapo Alinari, Beth Christian, Bo Yu, Jungook Shin, Erin K Hertlein, Rosa Lapalombella, Fengting Yan, Gregory Lesinski, Xiaoli Zhang, Gerard Lozanski, Natarajan Muthusamy, David M. Goldenberg, John C. Byrd, Robert A. Baiocchi
Journal: Blood (2009)
Frontal fibrosing alopecia in men: an association with facial moisturizers and sunscreens
Authors: A. Debroy Kidambi, K. Dobson, S. Holmes, D. Carauna, V. Del Marmol, A. Vujovic, M.R. Kaur, A. Takwale, P. Farrant, C. Champagne, M. Harries, A.G. Messenger
Journal: British Journal of Dermatology (2017)

fibrosing alopecia in men: an association with leave-on facial cosmetics and sunscreens.
Treatment with Lenalidomide in Myelodysplastic Syndromes with 5q Deletion; Results From the Patient Named Program (PNP) in the Netherlands
Authors: Imane Abouyahya, Canan Alhan, Theresia M Westers, Jan Koedam, Gert Ossenkoppele, Arjan A. Van de Loosdrecht
Journal: Blood (2011)
Band 3 Courcouronne: Homozygous Mutation Ser667Phe Causes Severe Hereditary Spherocytosis and Incomplete Distal Renal Tubular Acidosis.
Authors: Jean Delaunay, Ashley Toye, Rosalind Williamson, Moudji Khanfar, Brigitte Bader-Meunier, Thérèse Cynober, Madeleine Thibault, Gilbert Jean Tchernia, Michèle Déchaux, Lesley Bruce
Journal: Blood (2006)
Enhancing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through pulse zoledronate stimulation
Authors: Mohanad H. Nada, Hong Wang, Grefachew Workalemahu, Yoshimasa Tanaka, Craig T. Morita
Journal: Journal for ImmunoTherapy of Cancer (2017)

Human γδ T cells expressing Vγ2Vδ2 T cell receptors monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Adoptive immunotherapy with Vγ2Vδ2 T cells has been used to treat cancer patients with partial and complete remissions. Most clinical trials and preclinical studies have used continuous zoledronate exposure to expand Vγ2Vδ2 cells where zoledronate is slowly diluted over the course of the culture. Zoledronate inhibits farnesyl diphosphate synthase (FDPS) in monocytes causing isopentenyl pyrophosphate to accumulate that then stimulates Vγ2Vδ2 cells. Because zoledronate inhibition of FDPS is also toxic for T cells, we hypothesized that a short period of exposure would reduce T cell toxicity but still be sufficient for monocytes uptake. Additionally, IL-15 increases the anti-tumor activity of murine αβ T cells in mice but its effect on the in vivo anti-tumor activity of human Vγ2Vδ2 cells has not been assessed.Human Vγ2Vδ2 T cells were expanded by pulse or continuous zoledronate stimulation with IL-2 or IL-15. Expanded Vγ2Vδ2 cells were tested for their expression of effector molecules and killing of tumor cells as well as their in vivo control of human prostate cancer tumors in immunodeficient NSG mice.Pulse zoledronate stimulation with either IL-2 or IL-15 resulted in more uniform expansion of Vγ2Vδ2 cells with higher purity and cell numbers as compared with continuous exposure. The Vγ2Vδ2 cells had higher levels of CD107a and perforin and increased tumor cytotoxicity. Adoptive immunotherapy with Vγ2Vδ2 cells derived by pulse stimulation controlled human PC-3 prostate cancer tumors in NSG mice significantly better than those derived by continuous stimulation, halting tumor growth. Although pulse zoledronate stimulation with IL-15 preserved early memory subsets, adoptive immunotherapy with IL-15-derived Vγ2Vδ2 cells equally inhibited PC-3 tumor growth as those derived with IL-2.Pulse zoledronate stimulation maximizes the purity, quantity, and quality of expanded Vγ2Vδ2 cells for adoptive immunotherapy but there is no advantage to using IL-15 over IL-2 in our humanized mouse model. Pulse zoledronate stimulation is a simple modification to existing protocols that will enhance the effectiveness of adoptively transferred Vγ2Vδ2 cells by increasing their numbers and anti-tumor activity.