tbuckley/cabot-search huggingface dataset:
PDTB-05. DEVELOPING A NONINVASIVE IMAGING MARKER FOR ASSESSING THE RESPONSE OF DIFFUSE INTRINSIC PONTINE GLIOMA TO PANOBINOSTAT USING HYPERPOLARIZED CARBON-13 MR METABOLIC IMAGING
Authors: Ilwoo Park, Adam Elkhaled, Xiaodong Yang, Yuying Zhai, Renuka Sriram, Dave Korenchan, John Kurhanewicz, Sarah Nelson, Sabine Mueller
Journal: Neuro-Oncology (2016)

One of the challenges in managing children with diffuse intrinsic pontine glioma (DIPG) is the lack of non-invasive imaging biomarkers for monitoring response to therapy. This study aimed to develop noninvasive imaging markers for assessing the response of DIPG to histone deacetylase inhibitor, panobinostat, which has shown potent anti-tumor effect in a recent study (Grasso et al, Nat Med. 2015). We hypothesized that the down-regulation of HIF1α with panobinostat treatment and the consequent decrease in LDHA activity in DIPG can be monitored by evaluating pyruvate to lactate conversion using HP 13C metabolic imaging in responding DIPG. Vehicle- (n=3) and panobinostat-treated (4nM for 72hr, n=2) K27M.H3 mutant DIPG cells were imaged in a perfusion bioreactor system. Following an injection of [1-13C]-pyruvate that was pre-polarized using a HyperSense (Ardenkjaer-Larsen et al, PNAS. 2003), 13C spectra were acquired every 3s for a total of 5min in a 500 MHz spectrometer using a 30° flip angle. Lactate levels were estimated by normalizing the lactate area-under-the-curve (AUC) to the pyruvate AUC and the level of cell viability that was assessed by estimating β-NTP from 31P spectra. The levels of HIF1α and LDHA activity in vehicle- and panobinostat-treated DIPG cells were assessed by Western blotting and spectrophotometric assay, respectively. HP 13C pyruvate to lactate conversion was reduced in the treated cells compared to control. Normalized lactate for treated group (1.22 ± 0.44) was smaller than normalized lactate for control (4.02 ± 0.93, p=0.03). The reduced lactate signal observed in the treated cells was associated with decreased levels of HIF1α and LDHA activity compared to control. The results from this study suggest that the modulation in pyruvate metabolism induced by panobinostat treatment can be monitored by HP 13C imaging and this novel metabolic imaging method may provide a non-invasive biomarker of response to panobinostat in DIPG.
IV Busulfan (Bu) with Fludarabine (Flu) or Cyclophosphamide (Cy) - Comparing Ablative Conditioning Regimens for Allogeneic Transplantation in AML/MDS.
Authors: Marcos de Lima, Daniel Couriel, Munir Shahjahan, Jorge Alamo, Peter F. Thall, James Russell, Paolo Anderlini, Sergio Giralt, Elizabeth J. Shpall, Roy B. Jones, Richard E. Champlin, Borje S. Andersson
Journal: Blood (2004)
CXCR4 Up-Regulation by Imatinib Mesylate Induces CML Cell Migration to Bone Marrow Stroma and Promotes Survival of Chemoresistant Quiescent CML Cells.
Authors: Yoko Tabe, Linhua Jin, Clinton E. Leysath, Shinya Kimura, Hagop Kantarjian, Michael Andreeff, Marina Konopleva
Journal: Blood (2006)
Updated phase II study results of capecitabine (X) + irinotecan (I) + bevacizumab (A) as first-line therapy for metastatic colorectal cancer (MCRC)
Authors: S. Beslija, M. Banjin, S. Jungic, N. Obralic, G. Kecman-Malcic, I. Rakita, B. Salkic, A. Pasic, L. Tinjic, V. Smoljanovic
Journal: Journal of Clinical Oncology (2009)

e15064 Background: The oral fluoropyrimidine X has improved efficacy, safety, and convenience vs. 5-FU/LV in MCRC [Van Cutsem et al. Br J Cancer 2004] and early-stage colon cancer [Twelves et al. NEJM 2005]. A recent study showed that I + X q2w is active and well tolerated [Garcia-Alfonso et al. ESMO 2006]. The humanized monoclonal antibody A targets VEGF and limits tumor angiogenesis. The addition of A to 5-FU/LV/I (IFL regimen) improves survival significantly in patients (pts) with MCRC [Hurwitz et al. NEJM 2004]. Replacing 5-FU/LV with X in this combination is a logical step forward. Here we report data from an open-label phase II trial of XIA in MCRC. Methods: Pts with untreated, histologically confirmed MCRC received I 175mg/m 2 i.v. d1, X 1,000 mg/m 2 orally bid d2–8, and A 5 mg/m 2 d1. Treatment was repeated q2w x 12 cycles in the absence of progressive disease (PD) or unacceptable toxicity. Pts without PD after 12 cycles of XIA continued on the same dose of A + X 1,500 mg/m 2 bid d2–8, q2w. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall response rate (ORR, RECIST), overall survival (OS), safety, and quality of life. Results: 57 pts have been enrolled. Baseline characteristics: M/F 44%/56%; median age 52 years (range 30–70); disease stage at initial diagnosis II/III/IV 16%/9%/75%; no. of metastatic sites 1/&gt;1 47%/53%; most common metastatic site liver. Pts received a median 12 cycles (range 1–12) of XIA. All 57 pts are evaluable for safety and 56 for efficacy. ORR is 46% (3 CR, 13 PR); 5 pts (22%) have stable disease and 35 have PD. Median PFS and OS are 14.9 months (range 1.7–39.2) and 18.3 months (range 2.9–39.2), respectively. Grade 3 adverse events occurring in more than 1 pt are diarrhea (9%), hypertension (9%), hand-foot syndrome (7%), ileus (4%), and hypertriglyceridemia (4%); there is one report of grade 4 leucopenia. Conclusions: The XIA combination appears to be highly active and well tolerated as first-line treatment for MCRC; further studies of XIA are warranted. [Table: see text]
Identification of a New Subclass of ALK Negative Anaplastic Large Cell Lymphoma Expressing Aberrant Levels of ERBB4 Transcripts
Authors: Irene Scarfò, Elisa Pellegrino, Ivo Kwee, Luca Agnelli, Elisabetta Mereu, Elisa Bergaggio, Francesco Abate, Rodolfo Machiorlatti, Katia Messana, Andrea Rinaldi, Enrico Tiacci, Sara Serra, Silvia Deaglio, Antonino Neri, Brunangelo Falini, Raul Rabadan, Francesco Bertoni, Giorgio Inghirami, Roberto Piva
Journal: Blood (2014)
Alvocidib Potentiates the Activity of Azacytidine in an MCL-1-Dependent Fashion
Authors: Wontak Kim, Katherine K. Soh, Jeremiah J. Bearss, Ye Sol Lee, Peter Peterson, Clifford J. Whatcott, Adam Siddiqui-Jain, Steven Weitman, James M Bogenberger, Raoul Tibes, David J. Bearss, Steven L. Warner
Journal: Blood (2015)
Assessment for residual nodal disease after neoadjuvant chemotherapy with image-guided surgery.
Authors: Abigail Suzanne Caudle, Wei Tse Yang, Elizabeth Ann Mittendorf, Dalliah MaShon Black, Michael Gilcrease, Isabelle Bedrosian, Brian P Hobbs, Rosalind P Candelaria, Gildy Babiera, Basak Dogan, Lumarie Santiago, Kelly Hunt, Savitri Krishnamurthy, Henry Mark Kuerer
Journal: Journal of Clinical Oncology (2014)

99 Background: Staging of breast cancer patients is enhanced by axillary ultrasound (US) and needle biopsy of abnormal lymph nodes (LN). When clips are placed in sampled metastatic LNs, they can be evaluated for nodal response to neoadjuvant chemotherapy (NCT). The goals of this study were to determine if pathologic changes in clipped LNs reflect nodal response to NCT and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) in addition to selective localization and removal of clipped LNs, could increase the accuracy of nodal assessment. Methods: This prospective study included patients with US-identified axillary metastases confirmed by needle biopsy with a clip placed in the sampled LN. After NCT, patients underwent axillary lymphadenectomy (ALND) with x-ray of the axillary contents to identify the clip-containing LN. In 38 patients, the clipped LN was selectively removed using wire (n=2) or I 125 seed localization (n=36) before ALND was performed. Five patients did not undergo ALND. The pathologic findings of the clipped LN were reported separately from the other nodes. Results: Ninety node positive patients were enrolled. Forty (44%) had a complete nodal response to NCT and 50 (56%) had residual disease. Pathologic evaluation of the clipped LN revealed metastases in 47/50 patients with residual disease, resulting in a false negative rate (FNR) of 6% (95% CI 1.3-16.6). In 52 patients who underwent SLND, the clipped LN was not a SLN in 23% (n=12). Thirty-one of these patients had residual disease; metastases were not seen in SLNs in 5 cases resulting in a FNR for SLND alone of 16% (95% CI 5.4-34). Evaluation of the clipped LN in addition to SLND improved the FNR to 3% (1/31, 95% CI 0.1-17). Thirty-one patients underwent TAD while an additional 7 had localization and selective removal of the clipped LN without SLND with one false negative result. Conclusions: US-guided marking of LNs with documented metastatic disease allows for their selective removal and improved pathologic evaluation for residual nodal disease. The FNR of SLND can be reduced by ensuring removal and evaluation of the clipped LN. TAD is technically feasible and allows for improved assessment of nodal response after NCT.
Image-guided proton therapy for low- and intermediate-risk prostate cancer: Three-year results of two prospective trials.
Authors: Randal H. Henderson, Bradford S. Hoppe, Romaine Charles Nichols, William M Mendenhall, Robert B Marcus, Zhong Su, Christopher R Williams, Zuofeng Li, Christopher G. Morris, Nancy Price Mendenhall
Journal: Journal of Clinical Oncology (2012)

152 Background: To report outcomes in two prospective proton therapy (PT) trials for localized prostate cancer. Methods: From 2006 to 2007, 171 low- and intermediate-risk prostate cancer patients were treated with PT on prospective trials. Low-risk patients (N=89) were treated on PR01 with 78 CGE/39 fractions to the prostate. Intermediate-risk patients (N=82) were treated on PR02, a dose-escalation trial, with 78-82 CGE to the prostate and proximal seminal vesicles. Based on organ-constraint goals, 57 (69%), 13 (16%), and 12 (15%) PR02 patients received 82 CGE, 80 CGE, and 78 CGE, respectively. Toxicity was scored by CTCAE v3 and biochemical failure defined as nadir + 2 ng/mL. Results: The proportions of PR01 and 02 patients alive with no evidence of disease are 83 (93%) and 73 (89%); alive with disease, 1 (1%) and 1 (1%); and dead of intercurrent disease, 5 (6%) and 8 (10%), respectively. Only 2 patients had disease progression, both isolated pelvic-node recurrences. No patient died of prostate cancer or recurred locally. Grade (GR) 3 genitourinary (GU) and gastrointestinal (GI) complications occurred in 2 of 101 (2%), 0 of 13, and 4 of 57 (7%) patients receiving 78, 80, and 82 CGE, respectively. GR 3 GU toxicity occurred in 1 PR01 and 3 PR02 patients, including hematuria in 1 PR01 patient on anticoagulation; posttreatment TURP in 2 who had pretreatment (pre-tx) TURP; and dysuria in 1 with severe chronic pre-tx prostatitis. Multivariate analysis (MVA) of protocol, dose, age, prostate volume, pre-tx IPSS, pre-tx medical or surgical GU symptom management (SM), anticoagulation, and bladder wall V70 or V30 showed only pre-tx SM (P&lt; .0001) and age (P =.007) to be associated with GR2+ toxicity. GR 3 GI toxicity occurred in 2 PR02 patients, including rectal bleeding in a patient on anticoagulation, and rectal bleeding and proctitis in a patient on anticoagulation who had a transrectal prostate biopsy. MVA of protocol, age, dose, anticoagulation, and rectal wall V70 or rectum V30 showed only rectal wall V70 (.045) and rectum V30 (.027) to be associated with GR 2+ rectal bleeding and proctitis. Conclusions: PT may provide sufficiently reduced toxicity to permit further dose intensification and/or concomitant chemotherapy.
Creatinine &gt; 1.5 Mg/Dl and MDS Diagnosis Predicts Poor Outcome Following HSCT
Authors: Fern Martin, Lekha Mikkilineni, Kinjal Parikh, Dolores Grosso, Benjamin E Leiby, Onder Alpdogan, Matthew Carabasi, Margaret Kasner, Thomas R. Klumpp, Ubaldo Martinez-Outschoorn, Manish Sharma, Mark Weiss, John L. Wagner, Neal Flomenberg, Joanne Filicko-O'Hara
Journal: Blood (2015)
Rituximab Added αIFN+CHVP Improves the Outcome of Follicular Lymphoma Patients with a High Tumor Burden: to First Analysis of the GELA-GOELAMS FL-2000 Randomized Trial in 359 Patients.
Authors: Gilles Andre Salles, Charles Foussard, Mounier Nicolas, Morschhauser Franck, Doyen Chantal, Lamy Thierry, Haioun Corinne, Brice Pauline, Bouabdallah Reda, Rossi Jean-François, Audhuy Bruno, Fermé Christophe, Mahe Béatrice, Feugier Pierre, Sebban Catherine, Colombat Philippe, Xerri Luc
Journal: Blood (2004)
A phase 2 study of LY3023414 and necitumumab after first-line chemotherapy for metastatic squamous non-small cell lung cancer (NSCLC)
Authors: M. Johnson, V. Wacheck, M. Hussein, M. McCleod, D. Daniel, D. Waterhouse, M. Gil, D. Strickland, J.C. Bendell
Journal: Annals of Oncology (2016)
Deferasirox Decreases Liver Iron Concentration (LIC) in Transfusional Iron Overloaded Patients with Myelodysplastic Syndromes (MDS), Aplastic Anemia (AA) and Other Rare Anemias: Results From 1-Year Multi-Center, Open-Label Phase II Study
Authors: Yutaka Kohgo, Akio Urabe, Yurdanur Kilinç, Leyla Agaoglu, Krzysztof Warzocha, Guillermo Sanz, Lay Cheng Lim, Silvia Helou, Dany Habr, Isabelle Malet, Sabine Glaser, Wieslaw Wiktor-Jedrzejczak
Journal: Blood (2011)
Inhibition of TGF-β and CXCR4 Signaling Promotes Cell Cycle Arrest and Apoptosis In Leukemic Cells Co-Cultured with Stromal Cells
Authors: Yixin Zhou, Yoko Tabe, Linhua Jin, Takashi Miida, Zhihong Zeng, Michael Andreeff, Marina Konopleva
Journal: Blood (2010)
Elevated Ferritin Is Associated with Poorer Survival Following Nonablative Allogeneic Transplantation.
Authors: Anuj Mahindra, Ronald Sobecks, Lisa Rybicki, Stacey Brown, Brad Pohlman, Matt Kalaycio, Robert Dean, Steve Andresen, John Sweetenham, Brian Bolwell, Edward Copelan
Journal: Blood (2007)
69P Cisplatin based preoperative chemotherapy regimens for basal-like breast cancer potentially improve prognosis even in patients without pCR: A retrospective analysis from a single-institution
Authors: A. Yamaguchi, H. Ishiguro, M. Torii, M. Takada, E. Suzuki, M. Takeuchi, F. Sato, M. Toi
Journal: Annals of Oncology (2016)
breast cancer, locally advanced and metastatic First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC)
Authors: G.N. Hortobagyi, S.M. Stemmer, H.A. Burris, Y.S. Yap, G.S. Sonke, S. Paluch-Shimon, M. Campone, K. Blackwell, F. André, E.P. Winer, W. Janni, S. Verma, P. Conte, C.L. Arteaga, D. Cameron, F. Xuan, F. Souami, M. Miller, C. Germa, J. O'Shaughnessy
Journal: Annals of Oncology (2016)
Cost-effectiveness of Intensive Blood Pressure Management—Is There an Additional Price to Pay?—Reply
Authors: Ilana B. Richman, Douglas K. Owens, Jeremy Goldhaber-Fiebert
Journal: JAMA Cardiology (2017)

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NIMG-73. ACCURATE 3D GBM SEGMENTATION IN 30 SECONDS
Authors: Ross Mitchell, Wenzhe Xue, Kristin Swanson
Journal: Neuro-Oncology (2016)

Many clinical trials of Glioblastoma (GBM) therapies use changes in tumor burden to determine treatment response. Often, tumor size is estimated from bi-orthogonal lines placed to cover the largest cross-sectional extent of the lesion. This method is simple, rapid, and widely used. However, it is plagued by low accuracy. Consequently, many are developing more accurate algorithms to directly label, or “segment” the 3D extent of GBM tumors in MRI exams. The BRain Tumor Segmentation (BRATS) challenge allows objective comparison of these algorithms. BRATS includes anonymized MRI exams from patients with GBMs. Each exam includes a “true” tumor boundary determined from manual outlining by experts. A “leader board” of the most accurate algorithms is maintained on the BRATS website. However, leading algorithms often require long computation times (> 80 minutes in at least one case). We present a new method to segment brain tumors from multi-spectral MRI exams. Our approach leverages the speed of a graphical processing unit (GPU) level set algorithm to allow rapid and simple brain tumor segmentation. We implement a new data term in the level set speed function. This term eliminates the need to store MR exams on the GPU memory, as in prior approaches. Instead, a fixed size data and seed dependent lookup table is employed. This allows multi-spectral MR exams that are too large to fit on the GPU memory to be processed efficiently. We evaluated our method on the BRATS 2013 data. Our algorithm achieved an overall accuracy (Dice coefficient) on whole GBM segmentation of 83.5%. This is comparable to top performing algorithms. The average segmentation time was 30.8 seconds. Current limitations include the need for a user to place seed regions in each exam. Future work will focus on automating this step using machine-learning based approaches.
A phase 1b dose-escalation study of TRC105 (endoglin antibody) in combination with axitinib in patients with metastatic renal cell carcinoma (mRCC)
Authors: T. Choueiri, M.D. Michaelson, E. Posadas, G. Sonpavde, D. McDermott, B. Seon, M. Jivani, R. Shazer, B. Adams, C. Theuer
Journal: Annals of Oncology (2016)
A systematic review of the safety profile of bolus, continuous infusion of 5-fu and capecitabine in combination with oxaliplatin in the treatment of colorectal cancer patients
Authors: B. Chiara, C. Zichi, M. Di Maio, C. Sonetto, M.P. Brizzi, G.V. Scagliotti, M. Tampellini
Journal: Annals of Oncology (2016)
Final Analysis of Phase II Study of CHOP/CHOEP-14 Followed by Consolidation with Alemtuzumab in Untreated Aggressive T-Cell Lymphomas (DSHNHL 2003–1).
Authors: Claudia Binder, Marita Ziepert, Markus Loeffler, Michael Pfreundschuh, Norbert Schmitz, Ulrich Duehrsen, Hartmut Eimermacher, A. Haas, A. Aldoud, Lorenz H. Truemper
Journal: Blood (2007)
Intraclonal Complexity Of CLL Fractions In Cell Proliferation Rates, Gene Expression Signatures, and Responses To Autologous T-Cell Help In Peripheral blood and Secondary Lymphoid Tissues
Authors: Shih-Shih Chen, Thomas M. Herndon, Claire Emson, John C. Riches, Fabienne McClanahan, Timothy Tong, Xiao-Jie Yan, Piers E.M. Patten, John Gribben, Adrian Wiestner, Nicholas Chiorazzi
Journal: Blood (2013)
STMC-33. DIFFERENTIAL MIGRATION PATHWAYS OF THERAPEUTIC STEM CELL CARRIERS TO GLIOMA AFTER INTRANASAL DELIVERY
Authors: Dou Yu, Nicolas Bonamici, Hsiu-Ming Tsai, Shih-Hsun Cheng, Meijing Wu, Katarzyna Pituch, Yu Han, Chin-Tu Chen, Maciej Lesniak, Irina Balyasnikova
Journal: Neuro-Oncology (2016)

Neural stem cells (NSCs) and mesenchymal stem cells (MSCs) possess natural tropism to brain tumors. The unique stem cell intranasal delivery strategy bypasses the blood brain barrier and was recently demonstrated to convey therapeutic benefits in xenograft mouse models in conjunction with radiation and oncolytic virotherapy. It is imperative to understand the tumor tropism of therapeutic stem cells delivered intranasally to formulate optimal therapeutic strategies. To overcome the limitations of in vivo tracing of small number of stem cells delivered intranasally, we leveraged our mesoporous nanoparticle (MSN)-based radiolabeling technology to analyze NSCs and MSCs with MSN-Zr89 enabled Positron Emission Tomography (PET) with high sensitivity. PET imaging and immunocytochemistry demonstrated striking differences in the primary migration routes of MSCs and NSCs, in that MSCs predominantly migrated toward glioma xenografts through the caudal regions of the mouse brain, such as trigeminal ganglia, whereas NSCs predominantly migrated through the rostral regions of the brain, especially the olfactory bulbs. We hypothesize that the chemotaxic cytokine receptor profiles of NSCs and MSCs are major determinants in the migratory path in response to diverse brain micro-environmental cues, and genetic editing can augment tumor tropism. Mouse cytokine array analysis of brain tissue lysates collected from the olfactory bulbs and trigeminal ganglia showed EGF as a top candidate of responsible environmental cues. Based on the expression differences in EGFR in MSCs and NSCs, we utilized the clustered regularly interspaced palindromic repeats (CRISPR)-based endogenous gene activation to significantly upregulate the EGFR expression levels in NSCs, with improved chemotaxic migration capacity toward EGF in vitro, potentially helpful for enhancements in tumor tropism and therapeutic benefits in survival. Further optimization of tumor tropism via additional cytokine receptor expression profile gene editing offers possibility to enhance the tumor coverage of therapeutic stem cell carriers for brain malignancies of diverse intracranial locations.
Roles of Vascular Oxidative Stress and Nitric Oxide in the Pathogenesis of Atherosclerosis
Authors: Ulrich Förstermann, Ning Xia, Huige Li
Journal: Circulation Research (2017)

Major reactive oxygen species (ROS)–producing systems in vascular wall include NADPH (reduced form of nicotinamide adenine dinucleotide phosphate) oxidase, xanthine oxidase, the mitochondrial electron transport chain, and uncoupled endothelial nitric oxide (NO) synthase. ROS at moderate concentrations have important signaling roles under physiological conditions. Excessive or sustained ROS production, however, when exceeding the available antioxidant defense systems, leads to oxidative stress. Animal studies have provided compelling evidence demonstrating the roles of vascular oxidative stress and NO in atherosclerosis. All established cardiovascular risk factors such as hypercholesterolemia, hypertension, diabetes mellitus, and smoking enhance ROS generation and decrease endothelial NO production. Key molecular events in atherogenesis such as oxidative modification of lipoproteins and phospholipids, endothelial cell activation, and macrophage infiltration/activation are facilitated by vascular oxidative stress and inhibited by endothelial NO. Atherosclerosis develops preferentially in vascular regions with disturbed blood flow (arches, branches, and bifurcations). The fact that these sites are associated with enhanced oxidative stress and reduced endothelial NO production is a further indication for the roles of ROS and NO in atherosclerosis. Therefore, prevention of vascular oxidative stress and improvement of endothelial NO production represent reasonable therapeutic strategies in addition to the treatment of established risk factors (hypercholesterolemia, hypertension, and diabetes mellitus).
Three-Month Cumulative Incidence of Thromboembolism and Bleeding After Periprocedural Anticoagulation Management of Patients with Active Cancer.
Authors: Alfonso J Tafur, Edyta Wolny, Robert McBane, Edyta Sutkowska, Joshua P Slusser, David O Hodge, John A. Heit, Waldemar E Wysokinski
Journal: Blood (2009)