tbuckley/cabot-search huggingface dataset:
Related Versus Unrelated Donor Transplantation for High Risk (HiRi) Acute Myeloid Leukemia (AML) in First Complete Remission (CR1).
Authors: Joachim Kienast, Hans-Jochem Kolb, Dietrich W. Beelen, Maria Cristina Sauerland, Björna Berning, Albrecht Reichle, Ernst Holler, Renate Arnold, Karin Kolbe, Peter Staib, Rainer Schwerdtfeger, Matthias Stelljes, Christoph Schmid, Claudia Haferlach, Wolfgang E. Berdel, Wolfgang Hiddemann, Thomas Buchner
Journal: Blood (2007)
Stathmin 1 Silencing Amplifies Ruxolitinib-Induced Apoptosis in JAK2V617F Cells
Authors: João Agostinho Machado-Neto, Paula de Melo Campos, Patricia Favaro, Mariana Lazarini, Adriana Silva Santos Duarte, Irene Lorand-Metze, Sara Teresinha Olalla Saad, Fabiola Traina
Journal: Blood (2014)
TMIC-13. QUANTITATIVE ANALYSIS ON THE ISOLATION OF TUMOR MESENCHYMAL STEM-LIKE CELLS FROM HIGH GRADE GLIOMAS
Authors: Seon-Jin Yoon, Soon Haeng Kong, Ji-Hyun Lee, Sohyong Moon, Jiwong Oh, Kyoung Su Sung, Se Hoon Kim, Sohee Park, Jin-Kyong Shim, Ju Hyung Moon, Junseong Park, Eui Hyun Kim, Sun Ho Kim, Su-Jae Lee, Yong-Min Huh, Sahng Wook Park, Jong Hee Chang, Seok-Gu Kang
Journal: Neuro-Oncology (2016)

Tumor mesenchymal stem-like cells (tMSLCs) can be isolated from high grade gliomas and also play a role in a glioma progression as a participant in the tumor microenvironment. tMSLCs were known to have an effect on the overall survival of primary glioblastoma patients. However, Isolation rate of tMSLCs from surgical specimen was inconstant and the yield was not guaranteed. With a presumption that a relationship might exists between the weight of the sample and the yield rate, we assessed fifty-one fresh high grade glioma specimens and allocated them into two groups by the success or failure of isolation of the cells. As a result, we found there is no significant difference in the weights of specimens between two groups, and calculated the optimal weight of samples for tMSLCs isolation of 180mg. Furthermore, we obtained the results of no significant differences between two groups in other characteristics; patient age, sex, pathologic diagnosis, tumor types, molecular markers. Consequently, in contrast with our conjecture, a yield rate of tMSLCs from high grade gliomas does not have a correlation with the weight of surgical specimens.
Community resource centres to improve the health of women and children in informal settlements in Mumbai: a cluster-randomised, controlled trial
Authors: Neena Shah More, Sushmita Das, Ujwala Bapat, Glyn Alcock, Shreya Manjrekar, Vikas Kamble, Rijuta Sawant, Sushma Shende, Nayreen Daruwalla, Shanti Pantvaidya, David Osrin
Journal: The Lancet Global Health (2017)

<h2>Summary</h2><h3>Background</h3> Around 105 million people in India will be living in informal settlements by 2017. We investigated the effects of local resource centres delivering integrated activities to improve women's and children's health in urban informal settlements. <h3>Methods</h3> In a cluster-randomised controlled trial in 40 clusters, each containing around 600 households, 20 were randomly allocated to have a resource centre (intervention group) and 20 no centre (control group). Community organisers in the intervention centres addressed maternal and neonatal health, child health and nutrition, reproductive health, and prevention of violence against women and children through home visits, group meetings, day care, community events, service provision, and liaison. The primary endpoints were met need for family planning in women aged 15–49 years, proportion of children aged 12–23 months fully immunised, and proportion of children younger than 5 years with anthropometric wasting. Census interviews with women aged 15–49 years were done before and 2 years after the intervention was implemented. The primary intention-to-treat analysis compared cluster allocation groups after the intervention. We also analysed the per-protocol population (all women with data from both censuses) and assessed cluster-level changes. This study is registered with ISRCTN, number ISRCTN56183183, and Clinical Trials Registry of India, number CTRI/2012/09/003004. <h3>Findings</h3> 12 614 households were allocated to the intervention and 12 239 to control. Postintervention data were available for 8271 women and 5371 children younger than 5 years in the intervention group, and 7965 women and 5180 children in the control group. Met need for family planning was greater in the intervention clusters than in the control clusters (odds ratio [OR] 1·31, 95% CI 1·11–1·53). The proportions of fully immunised children were similar in the intervention and control groups in the intention-to-treat analysis (OR 1·30, 95% CI 0·84–2·01), but were greater in the intervention group when assessed per protocol (1·73, 1·05–2·86). Childhood wasting did not differ between groups (OR 0·92, 95% CI 0·75–1·12), although improvement was seen at the cluster level in the intervention group (p=0·020). <h3>Interpretation</h3> This community resource model seems feasible and replicable and may be protocolised for expansion. <h3>Funding</h3> Wellcome Trust, CRY, Cipla.
NSAIDs offer little benefit for spinal pain, review finds
Authors: Anne Gulland
Journal: BMJ (2017)

Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen offer little more clinical benefit to patients with spinal pain than a placebo, a systematic review and meta-analysis has found.

The review of 35 randomised placebo controlled trials involving 6065 people, published in the Annals of the Rheumatic Diseases ,1 found that NSAIDs did provide some relief from pain and disability but found little evidence that they were more effective than placebo. Researchers found that, in every six patients treated …
Erratum: Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord (Nature Medicine (2000) 6 (521-528))
Authors: P. Honore, N. M. Luger, M. A.C. Sabino, M. J. Schwei, S. D. Rogers, D. B. Mach, P. F. O'Keefe, M. I. Ramnaraine, D. R. Clohisy, P. W. Mantyh
Journal: Nature Medicine (2000)
Brigatinib (BRG) in patients (Pts) with anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) in a phase 1/2 trial
Authors: L. Bazhenova, S. Gettinger, C. Langer, R. Salgia, K. Gold, R. Rosell, A. Shaw, G. Weiss, J. Haney, V. Rivera, F. Haluska, D. Kerstein, D.R. Camidge
Journal: Annals of Oncology (2016)
OS4.5 Magnetic resonance spectroscopy for in vivo detection of 2-hydroxyglutarate in lower-grade gliomas
Authors: E. Anghileri, V. Cuccarini
Journal: Neuro-Oncology (2016)

Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are detected in up to 75% grade II-III (lower-grade) gliomas (LGG). IDH1/2 mutations result in 2-hydroxyglutarate (2HG) synthesis. 2HG screening is a useful marker to detect the presence of IDH1/2 mutations. Magnetic resonance spectroscopy (MRS) of 2HG are under investigation by others, and pre-clinical MRS was already performed on phantoms by our group. To investigate the accuracy of MRS for in vivo detection of 2HG on treatment-naïve suspect LGG patients, in a clinical setting. Spectra from suspect LGG patients were respectively acquired with a 1H-MRS single-voxel PRESS sequence with TE=30 ms (group 1) and a tailored PRESS sequence with TE=97 ms (group 2). The Magnetic Resonance (MR) protocol included two MRS acquisitions for each subject: a voxel within the tumor and one contralateral. The voxel size was 2x1.5x1.5 cm 3 for group 1 (n=13 patients) and group 2A (n=14) and 2x2x2 cm 3 for group 2B (n=28). MR 3T scanner with a 32 channel head coil was used. Metabolite concentrations were estimated by linear combination analysis and a simulated basis set using LCModel software. IDH1/2 analysis were performed by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR). Spectra at TE=30 showed low specificity: 2 false positive (FP) and 4 false negative (FN) were identified out of the 12 LGG patients (10 IDH mut and 3 IDH wt). Group 2A correctly identified 4 mutated and 2 wt LGG, but also 2 FP and 6 FN out of the 14 patients (10 IDH mut and 4 IDH wt). The larger voxel TE97 sequence resulted in higher specificity: 3 FN (including two with technical issues: one suboptimal spectrum and one including 40% normal tissue; the three all with relative apparent diffusion coefficient (rADC)>1.5, suggesting low cellularity) were detected within 17 IDH mut and 11 IDH wt. In one tumor, MRS analysis showed a 2HG value of 2.2 mM (though with CRLB 42%, thus over the reliability superior limit), while IHC resulted negative for IDH mutations: the lesion was very small and excided tissue was insufficient to allow PCR analysis, in order to detect IDH mutations other than IDH1 R132H, thus this case was considered apart from the others gaining unequivocal molecular diagnosis. Besides, TE30 sequence detected 2HG in the contralateral region in 5 cases, while TE=97 sequences did not. Our data suggest that MRS TE97 is rather specific for 2HG detection and the 2x2x2 cm 3 voxel bring to highest specificity and sensitivity than a smaller one. Main limits of the technique are small tumor volume and low cellularity. The detection of 2HG could help for a non-invasive diagnosis, clinical follow-up, and possibly patient screening for targeted anti IDH1mut therapy.
A phase II trial of cabazitaxel in patients with metastatic NSCLC progressing after docetaxel-based treatment.
Authors: Athanasios Kotsakis, Nikolaos K. Kentepozidis, Ioannis I. Varthalitis, Vasilios Karavasilis, Epaminontas Samantas, Charalampos Christophyllakis, Eleftheria- Kleio Dermitzaki, Nikolaos Ziras, Sofia Agelaki, Haralambos P. Kalofonos, Dimitrios Mavroudis, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2014)

8102 Background: Cabazitaxel, a semi-synthetic microtubule inhibitor has shown antitumor activity in models resistant to paclitaxel and docetaxel. It has been approved for the treatment of docetaxel-resistant prostate cancer. We investigated its activity in patients with metastatic NSCLC progressing under or after docetaxel-based regimens. Methods: Pre-treated patients with documented, measurable, stage IV NSCLC, with an ECOG performance status 0-2 were enrolled; patients had to have up to 2 prior chemotherapy regimens for the treatment of metastatic disease from which one containing docetaxel. Treatment consisted of cabazitaxel (25 mg/m2 iv, every 21 days) until disease progression. G-CSF was administered to the physician’s discretion. Primary endpoint was the objective response rate. A 2-stage design was followed. Results: Among the 46 evaluable patients, 28% had squamous cell carcinoma, 54% adenocarcinoma and 18% low differentiated carcinoma. Eight (17.4%) patients had received one and 38 (82.6%) two prior chemotherapy regimens. Treatment compliance was 95%; 26 (16%) cycles were delayed because of toxicity (n=13) or other reasons (n=13); dose reduction was required in 6 (13%) patients because of hematologic toxicity. Six (13%) patients achieved partial response and 17 (39.5%) stable disease [Disease Control Rate of 52.5%; 95% CI: 3.6- 24.3%]. The median response duration was 2.9 months. The median PFS and OS were 2.1 (95% CI: 1.0- 3.2) and 7.8 (95% CI: 5.3- 10.3) months, respectively. Grade 4 adverse events (AEs) included: neutropenia (n=8pts; 17%), febrile neutropenia (n=6; 13%); thrombocytopenia (n=3; 6.5%); anemia (n=4; 9%); infection (n=3; 6.5%) and fatigue (n=2; 4%). One patient experienced bowel obstruction and another hemorrhagic cystitis; both resolved with conservative treatment. There was no treatment-related death. Conclusions: Cabazitaxel monotherapy is an active agent in NSCLC patients pre-treated with docetaxel-based chemotherapy. The toxicity profile of the drug was acceptable and manageable. Further development of cabazitaxel in this indication is needed. Clinical trial information: NCT01852578.
217TiP Dose-finding phase Ib study of FOLFOXIRI plus ramucirumabas first-line therapy for patients with metastatic colorectal cancer
Authors: K. Yamazaki, Y. Kito, T. Esaki, H. Satake, H. Taniguchi, T. Tsuda, T. Denda, T. Moriwaki, K. Mori
Journal: Annals of Oncology (2016)
The AML1-ETO Fusion Gene and the FLT3 Length Mutation Collaborate in Inducing Acute Leukemia in a Murine Bone Marrow Transplantation Model.
Authors: Christina Schessl, Vijay P.S. Rawat, Monica Cusan, Aniruddha Deshpande, Tobias M. Kohl, Patricia M. Rosten, Karsten Spiekermann, R.Keith Humphries, Susanne Schnittger, Wolfgang Kern, Wolfgang Hiddemann, Leticia Quintanilla-Martinez, Stefan K. Bohlander, Michaela Feuring-Buske, Christian Buske
Journal: Blood (2005)
Allogeneic BMT Followed by Substrate Deprivation Therapy with N-butyldeoxynojirimycin in a Child with Tay-Sachs Disease.
Authors: Hans J.F.M. Jacobs, Michel M.A.A.P. Willemsen, Jacqueline J.J. Groot-Loonen, Ron R.A. Wevers, Peter P.M. Hoogerbrugge
Journal: Blood (2004)
Reduction of nodal micrometastases in patients with histological node-negative esophageal cancer after neoadjuvant treatment.
Authors: D. Wang, J. K. Smit, H. Hollema, J. T. Plukker
Journal: Journal of Clinical Oncology (2011)

73 Background: Neoadjuvant chemoradiation (CRT) is important in the treatment ofesophageal cancer. Rationales are tumor-downstaging and elimination of micrometastases improving resectability and curability rate. In this study we evaluated the effect of neo-adjuvant CRT on nodal micrometastases (NMM) in pN0 esophageal cancer patients. Methods: From a prospective database, we selected a matched group of patients on cT-stage, histological type and treatment without (group 1) or with neo-adjuvant CRT (group 2). Patients were staged by EUS, PET-scan, CT-scan and EUS guided cytology. CRT was given in a randomized clinical trial and consisted of paclitaxel 50 mg/m 2 and carboplatin AUC = 2 for 5 weeks and concurrent radiotherapy (41.4 Gy/23 frs). All patients (n = 19) underwent a curative intended transthoracic esophagectomy with extended 2-field nodal dissection. After reviewing routine pathological examination all tumors were confirmed as stage pN0. Four sections of every examined lymph node (n = 261) were made at different levels according to a sentinel node protocol and further analyzed immunohistochemically with anti-CK8/18 (CAM 5.2) to detect NMM. Results: Patients characteristics were equally distributed. All patients had a microscopically radical (R0) resection. In group 2 (n = 9) the response rate was 55% which was complete (CR) in 33%. The median number of resected nodes was comparable: 15 ± 6.5 and 15 ± 5.6 in both groups. Thirtheen of the 261 (5%) pN0 nodes in these 19 pts contained NMM. In group 1 (n = 10); 12 of the 136 (9%) examined pN0 lymph nodes were positive and in group 2 only one of the 125 (0.8%) examined pN0 nodes was positive (p = 0.003). NMM were found in 7 pts (70%) in group 1 and in only one patient (11%) in group 2 (p = 0.02). Interestingly, this last patient had responded well to CRT. Conclusions: Neo-adjuvant CRT seems to have a significant impact on the numbers of NMMs in esophageal cancer. Based on the presence of NMM even in patients with good responses, we still advocate a curatively intended nodal dissection. No significant financial relationships to disclose.
Tumor regression and growth rates determined in two intramural NCI prostate cancer trials: The growth rate constant as an indicator of therapeutic efficacy.
Authors: Bamidele Adesunloye, Wilfred Donald Stein, Julia Wilkerson, Xuan Huang, Fatima H Karzai, Ravi A. Madan, Andrea Borghese Apolo, William Douglas Figg, William L. Dahut, Tito Fojo
Journal: Journal of Clinical Oncology (2012)

133 Background: Like ATTP [bevacizumab + thalidomide + docetaxel + prednisone], ARTP [bevacizumab + lenalidomide + docetaxel + prednisone] is active in CRPC and in both the data suggest acquired resistance does not develop, supporting a strategy that continues therapy if tolerable. Discerning amongst new therapies in CRPC would be helped by novel assessment strategies that yield answers from smaller trials and allow comparisons across trials. We have validated a novel assessment method that quantifies tumor regression (d) and growth (g) rate constants using data obtained while pts are treated in a trial. We utilized this method to evaluate a phase II trial of ARTP in CRPC contrasting this with a previous study using thalidomide instead of lenalidomide (ATTP). Methods: Using PSA values and a two-phase mathematical equation we determined d and g. A three-phase equation was used to determine resistant fractions. Results: The median log g value with ARTP (-2.84) was statistically similar (p=0.204) to that observed with ATTP (-3.16). Both therapies had similar effects on log d (ARTP=-2.18; ATTP=-2.64; p=0.404). In a subset of pts with robust data both regimen are highly effective with only 3.01% and 5.46% of tumor resistant to ATTP and ARTP, respectively. In individual pt, statistically valid g and d values could be estimated after the fourth PSA value had been obtained, long before PSA increased - providing an early indicator of treatment failure. In most pts receiving prolonged treatment – as long as 700 d – the growth rate constant did not change, despite rising PSA values, indicating acquired resistance did not develop, and that if tolerable, therapy can be continued for longer periods of time. Conclusions: The substitution of daily thalidomide with lenalidomide 14/21 days in ARTP resulted in a combination statistically as effective as ATTP. As with ATTP majority of pts experienced marked reductions in the tumor’s g, and surprisingly in most, there was no evidence of acquired resistance, g remaining unchanged over prolonged time periods. Given the tolerability of this combination, pts with marked reductions in g may benefit from prolonged ARTP therapy.
Prognostic value of SPINK1 expression in bladder cancer after radical cystectomy.
Authors: Michael Rink, Shahrokh F. Shariat, Kyung Park, Bjoern Volkmer, Eugene K. Cha, Brian D. Robinson, Richard Hautmann, Douglas Scherr, Margit Fisch, Mark A. Rubin, Felix K. Chun, Rainer Kuefer, Juan Miguel Mosquera
Journal: Journal of Clinical Oncology (2012)

274 Background: Serine peptidase inhibitor Kazal type 1 (SPINK1) overexpression has been associated with poor outcomes. In one small study, loss of SPINK1 expression in urothelial carcinoma of the bladder (UCB) was associated with advanced tumor stage. We assessed the expression of SPINK1 in normal urothelium and UCB and analysed the association of SPINK1 with pathological features and clinical outcomes of patients treated with radical cystectomy (RC). Methods: The study used TMAs containing samples from 438 consecutive UCB patients treated with RC. 62 cases of normal urothelium were included as controls. A monoclonal antibody was used for immunohistochemical SPINK1 staining. SPINK1 expression of UCB was evaluated by two pathologists, blind to clinical outcome. Samples demonstrating less than 50% staining extent and 0 to 1 intensity (scale 0 to 3), were considered to have loss of expression. Results: SPINK1 expression was noted in umbrella cells of normal urothelium in 32/62 controls (52%). UCB of 254 patients (57.9%) exhibited loss of SPINK1 expression. Loss of SPINK1 expression was significantly associated with advanced pathological stage (p=0.002) and presence of lymph node (LN) metastasis (p=0.04). Within a median follow-up of 130 month (IQR 98.4), loss of SPINK1 expression was associated with an increased risk of disease recurrence (5-year RFS: 52±3 vs. 61±4 months; p=0.02) and cancer-specific mortality (5-year CSS: 59±3 vs. 68±3 months; p=0.03). In multivariable Cox regression analyses that adjusted for the effects of age, gender, tumor stage and grade, concomitant CIS, LN status and adjuvant chemotherapy, SPINK1 was not associated with disease recurrence (p=0.09) or cancer-specific death (p=0.12). Conclusions: While umbrella cells in normal urothelium commonly expresses SPINK1, more than half of UCB specimen exhibit loss of SPINK1 expression. Loss of SPINK1 expression is strongly correlated with local disease stage and LN metastasis. SPINK1 revealed no independent prognostic value for outcome prognostication, but it is a very promising marker for tumor staging which could be used for tailored follow-up protocols and possibly as a target for therapy as it has similarities with epidermal growth factor.
PALL-01. PHYSICIAN ASSISTED SUICIDE IN HIGH GRADE GLIOMAS: A UNIVERSITY-BASED PRACTICE PERSPECTIVE
Authors: Marc Chamberlain
Journal: Neuro-Oncology (2016)

Death is inevitable for the overwhelming majority of patients with high-grade gliomas (HGG). Consequently, assisting patients and families with end of life is an integral aspect of neuro-oncology care. In Washington state, physician assisted suicide (PAS) was enacted as law in 2009, modeled and similar to that in Oregon state. During the years 2009 to 2015, 300 patients with HGG were cared for in a university-based practice. 215 patients have died and 14 (6.5%; 10 glioblastoma, 4 anaplastic glioma) requested PAS. As mandated by law, all patients requesting PAS were Washington state residents, acting voluntarily, mentally competent, not depressed, aware of their diagnosis and prognosis and discussed their wish to end life with family in which there was agreement as to the patients' request. Additionally and as required by law, patients made 3 verbal requests (2 to the prescribing physician each separated by a 2-week interval and one to the consulting physician) and a single written request before life ending medication was prescribed (either secobarbital or the combination of morphine sulfate, phenobarbital and chloral hydrate). Ten prescriptions for secobarbital and 4 for the morphine sulfate combination were prescribed. Four patients (29%) elected to proceed with PAS and took the end of life prescribed medicine. Ten patients decided not to use the prescribed medicine. In the four patients taking end of life medication, death ensued on average in 6 minutes (range 4-8 minutes) and in all instances family was with the patient at time of death. Families described death as peaceful with rapid onset sleep, unresponsiveness and respiratory arrest. Notwithstanding the availability of a Washington state PAS program, relatively few terminal HGG patients make a request for PAS and if end of life medication is prescribed only a minority elected to proceed.
CCAAT/Enhancer-Binding Protein ε27 Antagonism of GATA-1 Transcriptional Activity Is Mediated by a Unique N-Terminal Repression Domain, Is Independent of Sumoylation, and Does Not Require but Is Enhanced by DNA-Binding.
Authors: Monika J. Stankiewicz, Jian Du, Steven J. Ackerman
Journal: Blood (2004)
Nucleophosmin-1 and Ribosome-Associated Components Are Constitutively Overexpressed in NOTCH1 Mutated IGHV Unmutated CLL
Authors: Michele Dal Bo, Federico Pozzo, Riccardo Bomben, Antonella Zucchetto, Erika Tissino, Dania Benedetti, Massimo Degan, Francesca Maria Rossi, Pietro Bulian, Tiziana D'Agaro, Sara Dereani, Davide Rossi, Alberto Zamò, Francesco Zaja, Gabriele Pozzato, Francesco Di Raimondo, Gianluca Gaidano, Giovanni Del Poeta, Valter Gattei
Journal: Blood (2012)
Murine Mast Cells Express Mpl, the Thrombopoietin Receptor, and Thrombopoietin Is a Potent Regulator of Mast Cell Differentiation.
Authors: Fabrizio Martelli, Giovanni Amabile, Barbara Ghinassi, Rodolfo Lorenzini, Alessandro M. Vannucchi, Rosa Alba Rana, Mitsuo Nishikawa, Giovanni Migliaccio, Anna Rita Migliaccio
Journal: Blood (2006)
Prognostic Factors and Outcome of Patients with Hematological Malignancies in Phase I Trials: The Gustave Roussy Scoring System
Authors: Lina Benajiba, Capucine Baldini, Laura Faivre, Jean-Marie Michot, Andrea Varga, Rastislav Bahleda, Anas Gazzah, Stéphane de Botton, Jean-Charles Soria, Vincent Ribrag
Journal: Blood (2014)
The JAK2-V617F Mutation Load Remains Stable over Several Years in Most Patients with Myeloproliferative Disorders Analyzed in a Retrospective Single Center Study.
Authors: Alexandre Theocharides, Renate Looser, Hao-Shen Hui, Andreas S. Buser, Alois Gratwohl, Andre Tichelli, Radek C. Skoda
Journal: Blood (2007)