tbuckley/cabot-search huggingface dataset:
New film‐coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower‐risk MDS: Results of the randomized, phase II ECLIPSE study
Authors: Ali T. Taher, Raffaella Origa, Silverio Perrotta, Alexandra Kourakli, Giovan Battista Ruffo, Antonis Kattamis, Ai‐Sim Goh, Annelore Cortoos, Vicky Huang, Marine Weill, Raquel Merino Herranz, John B. Porter
Journal: American Journal of Hematology (2017)

Once-daily deferasirox dispersible tablets (DT) have a well-defined safety and efficacy profile and, compared with parenteral deferoxamine, provide greater patient adherence, satisfaction, and quality of life. However, barriers still exist to optimal adherence, including gastrointestinal tolerability and palatability, leading to development of a new film-coated tablet (FCT) formulation that can be swallowed with a light meal, without the need to disperse into a suspension prior to consumption. The randomized, open-label, phase II ECLIPSE study evaluated the safety of deferasirox DT and FCT formulations over 24 weeks in chelation-naïve or pre-treated patients aged ≥10 years, with transfusion-dependent thalassemia or IPSS-R very-low-, low-, or intermediate-risk myelodysplastic syndromes. One hundred seventy-three patients were randomized 1:1 to DT (n = 86) or FCT (n = 87). Adverse events (overall), consistent with the known deferasirox safety profile, were reported in similar proportions of patients for each formulation (DT 89.5%; FCT 89.7%), with a lower frequency of severe events observed in patients receiving FCT (19.5% vs. 25.6% DT). Laboratory parameters (serum creatinine, creatinine clearance, alanine aminotransferase, aspartate aminotransferase and urine protein/creatinine ratio) generally remained stable throughout the study. Patient-reported outcomes showed greater adherence and satisfaction, better palatability and fewer concerns with FCT than DT. Treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%). This analysis suggests deferasirox FCT offers an improved formulation with enhanced patient satisfaction, which may improve adherence, thereby reducing frequency and severity of iron overload-related complications.
Long Term Study of the Impact of Quantitative Molecular Monitoring of Bcr-Abl Transcripts on the Risk of Relapse of CML After Allogeneic HSCT.
Authors: Mario Arpinati, Marilina Amabile, maria Teresa Bochicchio, Angela Poerio, Giuseppe Bandini, Francesca Bonifazi, Marta Stanzani, Fausto Castagnetti, Gianantonio Rosti, Giovanni Martinelli, Michele Baccarani
Journal: Blood (2010)
Invasive Fungal Infections in Reduced Intensity Cord Blood Transplantation (RICBT).
Authors: Shigesaburo Miyakoshi, Koichiro Yuji, Eiji Kusumi, Daisuke Kato, Shinsuke Takagi, Tomoko Matsumura, Naoyuki Uchida, Kazuhiro Masuoka, Atsushi Wake, Shuichi Taniguchi
Journal: Blood (2005)
Acute Myeloid Leukemia Patients with an Undefined Genetic Profile at Diagnosis: Clinical and Prognostic Aspects
Authors: Marco Mancini, Teresa Ceglie, Saveria Capria, Anna Maria Testi, Roberto Latagliata, Maria Stefania De Propris, Silvia Trisolini, Massimo Breccia, Clara Minotti, Marta Chisini, Mariella D'Angiò, Federico Vozella, Gioia Colafigli, Adriano Salaroli, Sara Raponi, Caterina Stefanizzi, Daniela Diverio, Francesca Mancini, Anna Guarini, Robin Foà
Journal: Blood (2014)
Thalidomide Based Regimens (TBR) for Relapsed/Refractory Multiple Myeloma Patients: Long Term Follow Up, Unmaintained Remissions and Disease Control after Subsequent Treatments.
Authors: Maria Roussou, Efstathios Kastritis, Athanasios Anagnostopoulos, Evangelos Eleftherakis-Papaiakovou, Charis Matsouka, Despina Barmparousi, Magdalini Migkou, Meletios Athanasios Dimopoulos
Journal: Blood (2007)
Sokal and Hasford Scores Are Able To Predict Cytogenetic Response and Survival in CML Patients Who Failed Prior Therapy and Are Receiving Salvage Therapy with Imatinib or Other Tyrosine Kinase Inhibitors.
Authors: Constantine S. Tam, Hagop M. Kantarjian, Jenny Shan, William G. Wierda, Alessandra Ferrajoli, Charles Asa Koller, Jorge Cortes
Journal: Blood (2006)
Successful Treatment of High-Risk and Refractory Acute Myeloid Leukemia with haploidentical Stem Cell Transplantation Plus NK cell therapy
Authors: Lutz Uharek, Birte Friedrichs, Axel Nogai, Chiara Gentilini, Nadezda Basara, Dietger Niederwieser, Eckhard Thiel
Journal: Blood (2010)
Informed consent and clinical trials: where is the placebo effect?
Authors: C R Blease, F L Bishop, T J Kaptchuk
Journal: BMJ (2017)

Lack of knowledge about placebos affects participants’ understanding of trials and breaches the ethical obligations of researchers, argue <b>C R Blease</b>, <b>F L Bishop</b>, and <b>T J Kaptchuk</b>
Epicardial YAP/TAZ orchestrate an immunosuppressive response following myocardial infarction
Authors: Vimal Ramjee, Deqiang Li, Lauren J. Manderfield, Feiyan Liu, Kurt A. Engleka, Haig Aghajanian, Christopher B. Rodell, Wen Lu, Vivienne Ho, Tao Wang, Li Li, Anamika Singh, Dasan M. Cibi, Jason A. Burdick, Manvendra K. Singh, Rajan Jain, Jonathan A. Epstein
Journal: Journal of Clinical Investigation (2017)

Ischemic heart disease resulting from myocardial infarction (MI) is the most prevalent form of heart disease in the United States. Post-MI cardiac remodeling is a multifaceted process that includes activation of fibroblasts and a complex immune response. T-regulatory cells (Tregs), a subset of CD4+ T cells, have been shown to suppress the innate and adaptive immune response and limit deleterious remodeling following myocardial injury. However, the mechanisms by which injured myocardium recruits suppressive immune cells remain largely unknown. Here, we have shown a role for Hippo signaling in the epicardium in suppressing the post-infarct inflammatory response through recruitment of Tregs. Mice deficient in epicardial YAP and TAZ, two core Hippo pathway effectors, developed profound post-MI pericardial inflammation and myocardial fibrosis, resulting in cardiomyopathy and death. Mutant mice exhibited fewer suppressive Tregs in the injured myocardium and decreased expression of the gene encoding IFN-γ, a known Treg inducer. Furthermore, controlled local delivery of IFN-γ following MI rescued Treg infiltration into the injured myocardium of YAP/TAZ mutants and decreased fibrosis. Collectively, these results suggest that epicardial Hippo signaling plays a key role in adaptive immune regulation during the post-MI recovery phase.
Chromatin Profiling of the Globin Loci of Human ES Cells and ES-Derived Erythroid Cells.
Authors: Xiangdong Fang, Kai-Hsin Chang, Daniel Bates, Morgan Diegel, Richard Sandstrom, Molly Weaver, Michael O. Dorschner, Peter J. Sabo, Thalia Papayannopoulou, George Stamatoyannopoulos, John Stamatoyannopoulos
Journal: Blood (2009)
Human Leukocyte Antigen-G Polymorphisms Influence Clinical Outcome in Diffuse Large B-Cell Lymphoma
Authors: Marta Bielska, Marcin Bojo, Gabriela Klimkiewicz-Wojciechowska, Dorota Jesionek-Kupnicka, Maciej Borowiec, Ewa Kalinka-Warzocha, Monika Prochorec-Sobieszek, Tadeusz Robak, Krzysztof Warzocha, Wojciech Mlynarski, Ewa Lech-Maranda
Journal: Blood (2014)
ATPS-21MONITORING OF LOCAL TREATMENT EFFECTS WITH TEMOZOLOMIDE IN AN ORTHOTOPIC MURINE GLIOBLASTOMA MODEL
Authors: Andrea Faymonville, Marco Timmer, Heike Endepols, Heiko Backes, Roland Goldbrunner
Journal: Neuro-Oncology (2015)

INTRODUCTION: Locally administered agents against malignant gliomas demand sophisticated metabolic imaging to monitor local and systemic treatment effects in animal models. The purpose of this feasibility study was to create an animal model suitable to represent the effect of locally delivered, soluble temozolomide in orthotopically implanted gliomas using micro-[18F] FLT-PET for high quality metabolic information with a distinct resolution for observation of treatment effects. METHODS: U87 glioma cells were stereotactically implanted in 48 female T-cell deficient athymic nude rats (RNU). Tumor existence and proliferation was proven by [18F] FLT-PET and microMRI. Rats were allocated to four treatment groups. Group one and two received a one-time intratumoral stereotactic injection of soluble temozolomide (TMZ) (group 1: 0.03mg; group 2: 0.015mg). Group three was administered systemic TMZ for 2 days (5mg). Group four served as untreated control group. Treatment was performed on day 15 post implantation. FLT-PET and MRI were performed 7 and 14 days after treatment. Animals showing signs of neurological impairment or reduced general health were immediately examined by MRI and sacrificed according to the animal ethical guidelines. RESULTS: The tumor take rate was 100 percent. Characteristically, U87 tumor cell formation was rather solid. Tumor size (MRI) and proliferation rate (PET) were congruent in all groups prior to treatment. Post treatment, FLT-PET was more specific for tumor growth compared to MRI. Tumor proliferation rates were significantly lower in the local treatment groups. MRI confirmed intratumoral TMZ fluid distribution which decreased within 7 days. CONCLUSION: Our orthotopic rat glioma model proved to be feasible and efficient for the performance of local therapy studies. Sophisticated Micro-PET offers distinct monitoring of tumor proliferation and supplements MR tumor imaging very well. The FLT-PET tracer is most suitable for the monitoring of local treatment effects of TMZ.
Randomized Study of Double Cord Blood Transplantation (CBT) with Versus without Ex-Vivo Expansion (EXP).
Authors: Marcos de Lima, J. McMannis, K. Komanduri, L. Worth, S. Karandish, R. Jones, S. Giralt, L. Cooper, L. Padua, P. Patah, D. Petropoulos, P. Thall, W. Zhang, W. Qiao, S. Robinson, S. Qureshi, I. Khouri, C. Hosing, A. Alousi, G. Rondon, B.S. Andersson, R. Champlin, E.J. Shpall
Journal: Blood (2007)
Improvement of painful bortezomib-induced peripheral neuropathy following acupuncture treatment in a case series of patients with multiple myeloma.
Authors: T. Bao, M. Medeiros, R. Zhang, L. Lao, A. Z. Badros
Journal: Journal of Clinical Oncology (2011)

e19569 Background: Peripheral neuropathy is a common and severe dose-limiting side effect of the chemotherapy agent, bortezomib, in multiple myeloma (MM) patients. Treatment with narcotics, antidepressants, and anticonvulsants has limited response and the potential for significant side effects. Acupuncture has been reported to be effective in treating neuropathic pain (Alimi, JCO, 2003). There has been no reporting on the effect of acupuncture in treating bortezomib-induced peripheral neuropathy (BIPN). Here we report a case series of using acupuncture to relieve painful BIPN. Methods: We report the result of a retrospective case series of five MM patients suffering from painful BIPN. Three patients were assessed for severity of BIPN using 0-10 numeric pain scale and the other two were assessed using Clinical Total Neuropathy Score, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity questionnaire or Neuropathy Pain Scale. Acupuncture was planned on a weekly basis with adjustment based on response. The patients were treated with an acupuncture protocol, which included bilateral ear points: shen men, point zero, two additional auricular acupuncture points where electro-dermal signal was detected, and bilateral body acupuncture points: LI4, SJ5, LI11, ST40, and Ba Feng. Each acupuncture session lasted approximately 30 minutes. Results: Five MM patients (3 male, 2 female, age range: 36-57) with moderate to severe BIPN (1 grade 2, 3 grade 3 and 1 grade 4) that received acupuncture treatment for BIPN were included in this study. All patients were African American patients, a population that we have reported to have a higher incidence of painful BIPN (Badros, Cancer, 2007). All five patients experienced immediate pain relief after acupuncture treatment. Two of three patients who had more than four acupuncture treatments experienced long lasting pain relief and improvement of function. There were no adverse events associated with the acupuncture treatment. Conclusions: Acupuncture is a viable treatment option for MM patients experiencing painful BIPN. Further studies on acupuncture for BIPN symptoms are needed.
Selective and Titratable Effects On AML Genome Wide Methylation Patterning, Transcription and Clonogenicity Using Very Low Concentrations of 5-Aza-2'deoxycytidine.
Authors: Elisabeth Heuston, Jason E. Farrar, Timothy Triche, Jonathan Buckley, Poul Sorensen, C. Patrick Reynolds, Gregory Reaman, Vasan Yegnasubramanian, Robert J. Arceci
Journal: Blood (2009)
Quantitative Three-Dimensional Tissue Cytometry to Study Kidney Tissue and Resident Immune Cells
Authors: Seth Winfree, Shehnaz Khan, Radmila Micanovic, Michael T. Eadon, Katherine J. Kelly, Timothy A. Sutton, Carrie L. Phillips, Kenneth W. Dunn, Tarek M. El-Achkar
Journal: Journal of the American Society of Nephrology (2017)

Analysis of the immune system in the kidney relies predominantly on flow cytometry. Although powerful, the process of tissue homogenization necessary for flow cytometry analysis introduces bias and results in the loss of morphologic landmarks needed to determine the spatial distribution of immune cells. An ideal approach would support three-dimensional (3D) tissue cytometry: an automated quantitation of immune cells and associated spatial parameters in 3D image volumes collected from intact kidney tissue. However, widespread application of this approach is limited by the lack of accessible software tools for digital analysis of large 3D microscopy data. Here, we describe Volumetric Tissue Exploration and Analysis (VTEA) image analysis software designed for efficient exploration and quantitative analysis of large, complex 3D microscopy datasets. In analyses of images collected from fixed kidney tissue, VTEA replicated the results of flow cytometry while providing detailed analysis of the spatial distribution of immune cells in different regions of the kidney and in relation to specific renal structures. Unbiased exploration with VTEA enabled us to discover a population of tubular epithelial cells that expresses CD11C, a marker typically expressed on dendritic cells. Finally, we show the use of VTEA for large-scale quantitation of immune cells in entire human kidney biopsies. In summary, we show that VTEA is a simple and effective tool that supports unique digital interrogation and analysis of kidney tissue from animal models or biobanked human kidney biopsies. We have made VTEA freely available to interested investigators via electronic download.
Protein-Based Identification of Inflammatory Signaling Pathways in Graft-Versus-Host-Disease (GVHD): Evidence for STAT1 Pathway as a Key Regulator in GVHD.
Authors: Cuiling Li, Judy Ziegler, Corinna Leng, Anna Lokshin, Suzanne Lentzsch, Markus Y. Mapara
Journal: Blood (2005)
Meta-analysis of behavioral interventions to reduce cancer pain.
Authors: S. S. Gorin, H. Badr, P. B. Jacobsen, E. A. Janke, H. S. Jim, P. Krebs
Journal: Journal of Clinical Oncology (2011)

6069 Background: Pain is among the most common, burdensome, and feared symptoms experienced by cancer patients. American Pain Society standards for cancer pain management recommend both pharmacologic and psychosocial approaches to pain relief. Methods: To obtain a current, stable, and comprehensive estimate of the effect of psychosocial interventions on pain, we conducted a meta-analysis of randomized controlled studies among adult cancer patients published between 1983-2010.Three pairs of raters independently reviewed 1,681 studies, with high inter-rater reliability, yielding 42 papers for meta-analysis. Studies were assessed for quality using an 11-item PEDro coding scheme. Pain severity and interference were primary outcome measures. Results: Study participants (N=3,190) were primarily female (65%), Caucasian (72%); in two-thirds of the studies, patients had mixed cancer stages at baseline. In over half (54%) the studies, patients were receiving chemotherapy at baseline in outpatient settings. The intervention arm averaged 6.83 sessions (SD=12.90) and was most frequently compared with a usual care control group (65%). The weighted averaged effect size (g) for pain severity (k=37) was 0.46 (95% CI = 0.33 - 0.58; p < 0.0001) and for pain interference, (k=4), was 0.41 (CI = 0.21 - 0.60, p < 0.0001). Among studies that measured severity, 19 studies used a skills-based intervention (e.g., Cognitive Behavioral Therapy), which was associated with a significantly larger effect size (g = 0.71) compared to those using an educational approach (k=18; g =0 .31; p = 0.002) . Using the PEDro scale, in less than half of the studies, allocation was concealed, assessors were blinded, and the study had an adequate treatment protocol. Effect size was not related to number of intervention sessions, gender, or percentage of minority participants. Conclusions: A medium-sized effect on pain was found for the psychosocial interventions. Skills–based interventions were more effective than educational approaches. Methodologic quality of the studies varied considerably. The implications for study and intervention design are proposed.
Standardization of cardiac tomographic imaging. From the Committee on Advanced Cardiac Imaging and Technology, Council on Clinical Cardiology, American Heart Association; Cardiovascular Imaging Committee, American College of Cardiology; and Board of Directors, Cardiovascular Council, Society of Nuclear Medicine.
Journal: Circulation (1992)

To facilitate the interpretation and comparison of cardiac tomographic images, the American Heart Asso- ciation, the Society of Nuclear Medicine, and the Amer- ican College of Cardiology recommend that a standard- ized nomenclature and display of these images be adopted by all centers performing single photon emis- sion computed tomographic (SPECT), positron emis- sion tomographic (PET), magnetic resonance (MRI), and cine computed tomographic (CT) imaging.SPECT Images Nomenclature
Sequential active chemotherapy schema in castration-resistant prostate cancer.
Authors: R. Tang, S. G. Groshen, C. I. Piatek, B. B. Desai, J. K. Pinski, F. Acosta, D. Raghavan, T. B. Dorff, D. I. Quinn
Journal: Journal of Clinical Oncology (2011)

e15191 Background: CRPC remains a fatal disease but with improved survival based on the development of novel agents. These developments now allow for sequential therapies. We treated 20 patients in a phase II evaluation with Mitoxantrone (MTX) followed by docetaxel, estramustine, carboplatin (DEC). Methods: Pts with CRPC who progressed on or after prior MTX therapy were given estramustine 280 mg tid po x 5d, docetaxel 60 mg/m2 IV, carboplatin AUC= 5 every 28 days; aspirin 325mg & warfarin 2 mg daily PO. Up to 8 cycles were given. Endpoints: RR > 30% pts with serum PSA fall >30%; with <10% gr 4 toxicity by CTCAE criteria. Results: 20 CRPC pts: Med. age: 66 yrs (53-83), Med BSA 1.96 (1.77-2.48), med. Gleason 8, ECOG PS: 0-1, 12 pts with RP and 8 pts de novo metastasis, Sites: bone (18), lung (3), liver (4), LN (6). Patients received 2-11 MTX cycles. Prior RT: 12 pts. On DEC, 13/20 pts PR by PSA, 5/20: SD, 1: PD and 1: not evaluable. Toxicities: 9 pts gr 3/4 neutropenia, 1 with neutropenic fever, 3 pts: gr 3 neuropathy, 3 pts: grade 3 infection, 6: gr 3/4 anemia, 1: gr 3 thrombocytopenia, 1 DVT. Non-hematologic toxicities: 4 patients with grade 3 fatigue, 3: gr 3 UTI, 1 gr 3 dehydration & diarrhea. Med PFS on MTX: 5.5 months (1.2, 15.3), Med PFS on DEC: 5.3 months (1.2-14.5). OS from MTX start: 20.3 months (9.1-37.5). OS from DEC start: 12.3 months (1.2-31). Interestingly, response to each agent only partially overlapped. Responses measured as >30% drop in PSA to MTX or DEC are as follows: 6 pts responded only to MTX, 10 responded only to DEC, 3 patients responded to both therapies, and 1 patient responded to neither. Med OS for responders to MTX only: 21.6 (6.9-28.9). Median OS for responders to docetaxel only: 14.6 (9.1-43.7). Median OS for responders to both = 30.7 (25.8-37.5) Median OS for response to neither = 12.3. Conclusions: DEC was effective in treating patients with CRPC that had received MTX based chemotherapy. DEC produced a higher PSA response than MTX. Pts benefited if they responded to either or both agents although there was limited overlap in response (15%). A set of biomarkers linked to chemotherapeutic response of individual active agents in CRPC could have great clinical utility by optimizing chemotherapy selection and sequence.
Casein Kinase Iε Downregulates PI3K/Akt Signaling, Followed by Genotoxic Stress-Induced Apoptosis of Hematopoietic Cells.
Authors: Atsuo Okamura, Katsuya Yamamoto, Kimikazu Yakushijin, Norinaga Urahama, Kentaro Minagawa, Akiko Sada, Akio Hato, Shinichiro Nishikawa, Kazuaki Yokoyama, Mitsuhiro Ito, Toshimitsu Matsui
Journal: Blood (2004)
Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome
Authors: Rathi Prasad, Irene Hadjidemetriou, Avinaash Maharaj, Eirini Meimaridou, Federica Buonocore, Moin Saleem, Jenny Hurcombe, Agnieszka Bierzynska, Eliana Barbagelata, Ignacio Bergadá, Hamilton Cassinelli, Urmi Das, Ruth Krone, Bulent Hacihamdioglu, Erkan Sari, Ediz Yesilkaya, Helen L. Storr, Maria Clemente, Monica Fernandez-Cancio, Nuria Camats, Nanik Ram, John C. Achermann, Paul P. Van Veldhoven, Leonardo Guasti, Debora Braslavsky, Tulay Guran, Louise A. Metherell
Journal: Journal of Clinical Investigation (2017)

Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1–/– mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1–/– mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism.
Theoretical Availability of UCBT in High Body Weight Patients Who Received Haplo-SCT for High Risk Haematological Malignancies: Results of the Simulation of Search through BMDW According to International Guidelines
Authors: Maria Teresa Lupo Stanghellini, Annalisa Ruggeri, Jacopo Peccatori, Massimo Bernardi, Consuelo Corti, Chiara Bonini, Claudio Bordignon, Fabio Ciceri
Journal: Blood (2008)
Immunotherapy resistance: the answers lie ahead – not in front – of us
Authors: Miles C. Andrews, Jennifer A. Wargo
Journal: Journal for ImmunoTherapy of Cancer (2017)

Mechanisms of innate and adaptive resistance to checkpoint blockade immunotherapy are under intense investigation with a view to broadening the therapeutic potential of this form of treatment. In a recent manuscript by Zaretsky and colleagues, mutational events were identified that effectively crippled ongoing immunotherapy responses in patients treated with anti-PD-1 therapy. These results are discussed in the light of other recent and ongoing research efforts exploring both mutational and non-mutational resistance mechanisms, highlighting the critical translational importance of longitudinal tumor sampling.