tbuckley/cabot-search huggingface dataset:
Bayesian Network Inference Modeling Identifies TRIB1 as a Novel Regulator of Cell-Cycle Progression and Survival in Cancer Cells
Authors: Rina Gendelman, Heming Xing, Olga K. Mirzoeva, Preeti Sarde, Christina Curtis, Heidi S. Feiler, Paul McDonagh, Joe W. Gray, Iya Khalil, W. Michael Korn
Journal: Cancer Research (2017)

Molecular networks governing responses to targeted therapies in cancer cells are complex dynamic systems that demonstrate nonintuitive behaviors. We applied a novel computational strategy to infer probabilistic causal relationships between network components based on gene expression. We constructed a model comprised of an ensemble of networks using multidimensional data from cell line models of cell-cycle arrest caused by inhibition of MEK1/2. Through simulation of a reverse-engineered Bayesian network model, we generated predictions of G1-S transition. The model identified known components of the cell-cycle machinery, such as CCND1, CCNE2, and CDC25A, as well as revealed novel regulators of G1-S transition, IER2, TRIB1, TRIM27. Experimental validation of model predictions confirmed 10 of 12 predicted genes to have a role in G1-S progression. Further analysis showed that TRIB1 regulated the cyclin D1 promoter via NFκB and AP-1 sites and sensitized cells to TRAIL-induced apoptosis. In clinical specimens of breast cancer, TRIB1 levels correlated with expression of NFκB and its target genes (IL8, CSF2), and TRIB1 copy number and expression were predictive of clinical outcome. Together, our results establish a critical role of TRIB1 in cell cycle and survival that is mediated via the modulation of NFκB signaling. Cancer Res; 77(7); 1575-85. ©2017 AACR.
Specific MiRNA Silencing by Lentivirus Mediated Antagomir Expression in Chronic Myeloid Leukemia (CML) Cells.
Authors: Michaela Scherr, Letizia Venturini, Karin Battmer, Michael Schaller-Schoenitz, Daniel Schaefer, Iris Dallmann, Arnold Ganser, Matthias Eder
Journal: Blood (2007)
Tailored Approaches to Induction Therapy for Acute Promyelocytic Leukemia
Authors: Daniel J. DeAngelo
Journal: Journal of Clinical Oncology (2017)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Proteomic Studies Identify Citron Rho Interacting Kinase (CRIK), a Novel Protein That Regulates Proliferation and Survival In Multiple Myeloma Cells
Authors: Hai T Ngo, Aldo M. Roccaro, Alexey Leontovich, Yang Liu, Yong Zhang, Abdel Kareem A. Azab, Antonio Sacco, Eric Still, Brittany Morgan, Kenneth C. Anderson, Irene Ghobrial
Journal: Blood (2010)
Unrelated Donor Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies.
Authors: Chunji Gao, Wanming Da, Bolong Zhang, Xiaoping Han, Jing Yu, Yizhuo Zhang, Honghua Li, Jian Bo, Haiyan Zhu, Haijie Jin, Xiaoxiong Wu, Quanshun Wang, Suxia Li, Wenrong Huang, Li Yu
Journal: Blood (2005)
B-Cell Lymphoma Cells Overexpressing BMI-1 Are Correlated with Drug Resistance through Enhanced Expression of Survivin and Are Effectively Eliminated by T Cells with Anti-CD38 Chimeric Receptor
Authors: Joyeeta Bhattacharyya, Keichiro Mihara, Motoaki Ohtsubo, Shin'ichiro Yasunaga, Yoshihiro Takihara, Masaharu Hoshi, Akiro Kimura
Journal: Blood (2010)
ABCB1 Overexpression May Predispose Imatinib Treated CML Patients to the Development of Abl Kinase Domain Mutations, and May Be an Important Contributor to Acquired Resistance.
Authors: Deborah White, Phuong Dang, Amity Venables, Verity Saunders, Stephanie Zrim, Andrew Zannettino, Peter Diamond, Steven Quinn, Luen Bik To, Timothy Hughes
Journal: Blood (2006)
Prospective Randomized Comparison of Reduced Intensity (FLU-BU-ATG) and Non-Myeloablative (FLU-TBI) Conditioning for Genoidentical Allo-SCT: a Clinical and economical Multicenter Itac Study.
Authors: Didier Blaise, Reza Tabrizi, Anne-Gaelle Le Corroller-Soriano, Mauricette Michallet, Jacques-Olivier Bay, Mohamad Mohty, Catherine Faucher, Sabine Furst, Noel Milpied, Luca Castagna, Christian Chabannon, Agnes Boyer, Jean-Marie Boher
Journal: Blood (2009)
Phosphoproteomic analysis reveals hyperactivation of mTOR/STAT3 and LCK/Calcineurin axes in pediatric early T-cell precursor ALL
Authors: V Serafin, V Lissandron, B Buldini, S Bresolin, M Paganin, F Grillo, N Andriano, C Palmi, G Cazzaniga, S Marmiroli, V Conter, G Basso, B Accordi
Journal: Leukemia (2017)
The Urine Preservative Acetic Acid Degrades Urine Protein: Implications for Urine Biorepositories and the AASK Cohort Study
Authors: Salem Almaani, Lee A. Hebert, Brad H. Rovin, Daniel J. Birmingham
Journal: Journal of the American Society of Nephrology (2017)

Patients enrolled in the African American Study of Kidney Disease and Hypertension (AASK) Cohort Study who exhibited overt proteinuria have been reported to show high nonalbumin proteinuria (NAP), which is characteristic of a tubulopathy. To determine whether African American Study of Kidney Disease and Hypertension nephropathy (AASK-N) is a tubulopathy, we obtained urine samples of 37 patients with AASK-N, with 24-hour protein-to-creatinine ratios (milligrams per milligram) ranging from 0.2 to 1.0, from the National Institute of Diabetes and Digestive Kidney Diseases repository and tested for seven markers of tubular proteinuria. By protocol, each sample had been collected in acetic acid (0.5%; mean final concentration). Compared with samples from patients with lupus nephritis or healthy black controls, AASK-N samples had lower amounts of six markers. Four markers (albumin, β-2-microglobulin, cystatin C, and osteopontin) were undetectable in most AASK-N samples. Examination by SDS-PAGE followed by protein staining revealed protein profiles indicative of severe protein degradation in 34 of 37 AASK-N urine samples. Treatment of lupus nephritis urine samples with 0.5% acetic acid produced the same protein degradation profile as that of AASK-N urine. We conclude that the increased NAP in AASK-N is an artifact of acetic acid-mediated degradation of albumin. The AASK-N repository urine samples have been compromised by the acetic acid preservative.
Establishment of a New Immunodeficient Mouse Line Harboring NOD-Type Sirpa with Highly-Efficient Human Hematopoietic Cell Engraftment.
Authors: Takuji Yamauchi, Katsuto Takenaka, Shingo Urata, Takahiro Shima, Yoshikane Kikushige, Takahito Tokuyama, Chika Iwamoto, Toshihiro Miyamoto, Koichi Akashi
Journal: Blood (2012)
Survival Is Poorer in Patients with Secondary Core Binding Factor Acute Myelogenous Leukemia Compared with De Novo Core Binding Factor Leukemia.
Authors: Gautam Borthakur, Nitin Jain, Hagop Kantarjian, E. Lin, Farhad Ravandi, Sherry Pierce, Elihu Estey
Journal: Blood (2007)
Outcomes of Unrelated Cord Blood and Haploidentical Stem Cell Transplantation in Adults with Acute Leukaemia.
Authors: Vanderson Rocha, Franco Aversa, Myriam Labopin, Guillermo Sanz, Fabio Ciceri, William Arcese, Donald Bunjes, Jacob M. Rowe, Paolo Di Bartolomeo, Francesco Frassoni, Massimo F. Martelli, Eliane Gluckman
Journal: Blood (2005)
Compression hosiery versus compression bandages in treatment of venous leg ulcers (Venous leg Ulcer Study IV, VenUS IV): a randomised controlled trial
Authors: RL Ashby, R Gabe, S Ali, U Adderley, JM Bland, NA Cullum, JC Dumville, CP Iglesias, AR Kang’ombe, MO Soares, NC Stubbs, DJ Torgerson
Journal: The Lancet (2014)
Human Placental Derived Mesenchymal Stromal Cells (MSC) Grown in 3D-Culture (PLX-I), Promotes Engraftment of Human Umbilical Cord Blood (hUCB) Derived CD34+ Cells in NOD/SCID Mice.
Authors: Ora Burger, Galit F. Ashtamker, Noam Bercovich, Marina Rusanovsky, Lena Pinzur, Osnat M. Jacov, Nirit D. Carmi, Moran Meiron, Limor Lior, Shai Meretzki, William R. Prather, Avinoam Kadouri, Avi J. Treves, Jacob M. Rowe, Edwin M. Horwitz, Arnon Nagler
Journal: Blood (2007)
Runx2 Transcription Factor Regulates Heparanase-Induced Bone Resorption in Multiple Myeloma
Authors: Li Nan, Haiyan Chen, Jian Ruan, Rebecca S Sollie, Cara Schafer, Francis T Crittenden, Anurag Purushothaman, Ralph D. Sanderson, Amjad Javed, Yang Yang
Journal: Blood (2012)
RNA Nanoparticle-Based Targeted Therapy for Glioblastoma through Inhibition of Oncogenic miR-21
Authors: Tae Jin Lee, Ji Young Yoo, Dan Shu, Hui Li, Jianying Zhang, Jun-Ge Yu, Alena Cristina Jaime-Ramirez, Mario Acunzo, Giulia Romano, Ri Cui, Hui-Lung Sun, Zhenghua Luo, Matthew Old, Balveen Kaur, Peixuan Guo, Carlo M. Croce
Journal: Molecular Therapy (2017)

Targeted inhibition of oncogenic miRNA-21 has been proposed to treat glioblastoma by rescuing tumor suppressors, PTEN and PDCD4. However, systemic delivery of anti-miR-21 sequences requires a robust and efficient delivery platform to successfully inhibit this druggable target. Three-way-junction (3WJ)-based RNA nanoparticles (RNP), artificially derived from pRNA of bacteriophage phi29 DNA packaging motor, was recently shown to target glioblastoma. Here, we report that multi-valent folate (FA)-conjugated 3WJ RNP constructed to harbor anti-miR-21 LNA sequences (FA-3WJ-LNA-miR21) specifically targeted and delivered anti-miR-21 LNA and knocked down miR-21 expression in glioblastoma cells in vitro and in vivo with favorable biodistribution. Systemically injected FA-3WJ-LNA-miR21 RNP efficiently rescued PTEN and PDCD4, resulting in glioblastoma cell apoptosis and tumor growth regression. Overall survival rate was also significantly improved by FA-3WJ-LNA-miR21 RNP. These results are indicative of the clinical benefit of FA-3WJ RNP-based gene therapy for the successful targeted therapy of developing and even recurring glioblastoma. Targeted inhibition of oncogenic miRNA-21 has been proposed to treat glioblastoma by rescuing tumor suppressors, PTEN and PDCD4. However, systemic delivery of anti-miR-21 sequences requires a robust and efficient delivery platform to successfully inhibit this druggable target. Three-way-junction (3WJ)-based RNA nanoparticles (RNP), artificially derived from pRNA of bacteriophage phi29 DNA packaging motor, was recently shown to target glioblastoma. Here, we report that multi-valent folate (FA)-conjugated 3WJ RNP constructed to harbor anti-miR-21 LNA sequences (FA-3WJ-LNA-miR21) specifically targeted and delivered anti-miR-21 LNA and knocked down miR-21 expression in glioblastoma cells in vitro and in vivo with favorable biodistribution. Systemically injected FA-3WJ-LNA-miR21 RNP efficiently rescued PTEN and PDCD4, resulting in glioblastoma cell apoptosis and tumor growth regression. Overall survival rate was also significantly improved by FA-3WJ-LNA-miR21 RNP. These results are indicative of the clinical benefit of FA-3WJ RNP-based gene therapy for the successful targeted therapy of developing and even recurring glioblastoma.
Hemophilia Prophylaxis No Longer Just for Children without Inhibitors - Increasing Use of Prophylaxis in Other Groups (children with inhibitors and adults with and without inhibitors)
Authors: Manuel Carcao, Maria L. Avila, Victor S. Blanchette, Elena Santagostino, Carmen Escuriola-Ettingshausen, Cindy A. Leissinger, Thierry Lambert, Louis M. Aledort
Journal: Blood (2015)
Event-Free Survival at 12 Months and Subsequent Overall Survival in Patients with Peripheral T-Cell Lymphoma
Authors: Matthew J Maurer, Fredrik Ellin, James Cerhan, Stephen Ansell, Brian K Link, Mats Jerkeman, Karin E Smedby, Carrie A. Thompson, William Macon, Sergei Syrbu, Susan L. Slager, Thomas E. Witzig, Thomas M. Habermann, Thomas Relander, Andrew L Feldman
Journal: Blood (2015)
Risk assessment in high grade sarcoma patients during neoadjuvant chemotherapy using multiple tracer PET
Authors: J. F. Eary, E. Conrad, J. Link, A. Cizik, D. Mankoff, K. Krohn
Journal: Journal of Clinical Oncology (2006)

20006 Background: Patients with high grade soft tissue sarcomas are treated with neoadjuvant chemotherapy. Sarcomas have biological features that may predict for poor outcome. Some of these features are tumor proliferation rate, level of tumor hypoxia, and upregulation of tumor drug resistance mechanisms. Methods: We have a group of specific PET imaging agents to quantify the level of activity of these tumor processes. Patients with soft tissue sarcomas receive [C-11]Thymidine (TdR) to assess cellular proliferation, [O-15] Water to quantify tumor blood flow and to serve as the input function for quantification of the other tracers, [C-11]Verapamil to assess drug resistance mechanism activity, and [F-18]Fluoromisonidazole) FMISO to quantify changes in tumor hypoxic volume in response to treatment. These studies are performed in a single PET imaging session prior to neoadjuvant chemotherapy, after the second of four cycles of therapy and in the week prior to resection. Results: An example of this complex study result, is demonstrated by a recent patient with a high grade soft tissue sarcoma. The tumor showed increased TdR uptake, a moderate hypoxic volume, and [C-11] verapamil uptake prior to initiation of neoadjuvant adriamycin based chemotherapy. After 2 cycles of therapy, there was a significant decrease in the maximum level and volume of TdR uptake and a large reduction in tumor hypoxic volume. Conclusions: These data would imply a high risk soft tissue sarcoma due the presence of increased cellular proliferation, a significant hypoxic volume and the absence of p-glycoprotein activity determined by the presence of [C-11]Verapamil uptake. However, early response is also suggested by the findings above. Patient outcome will be assessed and correlated with these tumor parameters to further understand what tumor biological risk factors can be quantified non-invasively and repeated throughout the clinical course in soft tissue sarcoma patients. Supported by NIH NCI PO1 42045–18 and S10 RR017229–01 [Table: see text] No significant financial relationships to disclose.
High-Resolution Analyses of Epigenetic Aberrations in Myelodysplastic Syndrome.
Authors: Go Yamamoto, Fumihiko Nakamura, Mitsuru Iio, Motohiro Kato, Yasuhito Nannya, Masashi Sanada14, Akira Hangaishi, Shigeru Chiba, Hiraku Mori, Mineo Kurokawa, Toshiki Watanabe, Mitsuhiro Omine, Seishi Ogawa
Journal: Blood (2007)
Co-Operativity between Antibody-Dependent Cellular Cytotoxicity (ADCC) and Immunotoxin-Mediated Killing of Human T-ALL Cells in a SCID Mouse Model: Simultaneous Delivery of Saporin Via CD7 and ADCC Via CD38 Is No Better Than the Simultaneous Delivery of Each Against Only CD7.
Authors: David J. Flavell, Sopsamorn U. Flavell
Journal: Blood (2006)
Pharmacokinetic analysis of nilotinib in Chinese chronic myelogenous leukemia (CML) patients (pts) with imatinib-resistant or-intolerant disease in blast crisis (BC), accelerated phase (AP) or chronic phase (CP)
Authors: L. Zhou, P. Hu, F. Meng, J. Wang, C. Wang, Z. Hu, Z. Shen
Journal: Journal of Clinical Oncology (2008)

18020 Background: Nilotinib, a potent and highly selective inhibitor of BCR-ABL, has been approved in both the US and EU for the treatment of patients with CML-CP and -AP resistant or intolerant to prior therapy including imatinib. It has previously been suggested that Asian patients may require different dosing regimens for TKIs than that normally recommended in Caucasian patients. We report here a pharmacokinetic (PK) analysis of nilotinib in 21 Chinese imatinib resistant or intolerant CML pts. Methods: The Expanding Nilotinib Access in Clinical Trials (ENACT) is an ongoing global study initiated to provide expanded access to nilotinib and to obtain additional safety information in pts with imatinib-resistant or -intolerant CML-CP, -AP, or blast crisis (-BC). In this study, nilotinib was administered at 400 mg twice daily (BID). Pharmacokinetic parameters of nilotinib, including area under the concentration-time curve (AUC), maximum concentration (Cmax), time to reach Cmax (Tmax), trough concentration (Cmin), and ratio of accumulation (RA), were obtained on days 1 and 15. Results: 21 Chinese CML patients were included in this analysis. 76% were male; mean age was 40 y (range, 19–67 y); mean body weight was 68.3 kg (range, 48–90 kg). Cmax of nilotinib occurred between 1–12.05 h after drug administration. Mean Cmax of the first dose of nilotinib was 638 ng/mL and occurred a median of 3h after first administration. After repeat dose of 400mg BID for 15 days, mean Cmax was 2161 ng/mL and a Cmin of 1743 ng/mL was reached. Mean AUC was 5076.32 ng·hr/mL on day 1 and 17751.30 ng·hr/mL on day 15. Thus, the steady-state serum level of nilotinib was more than 3 times the level measured after the first dose. The steady-state mean Cmax and AUC values observed in this study were comparable to those observed in previous studies with CML patients from other ethnic groups (Cmax=2260 ng/mL and AUC=18000 ng·hr/mL). The adverse event profile in this cohort was similar to that reported for the pivotal phase I/II registration study. Conclusions: The recommended nilotinib dosing of 400 mg BID is appropriate and well tolerated for Chinese patients with CML. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
Oncoprotein 18 (Op18) : A Differentially Expressed Gene Is a Novel Therapeutic Target in Multiple Myeloma
Authors: Dheeraj Pelluru, Jingyi Wang, Rao Prabhala, Mariateresa Fulciniti, Masood A. Shammas, Samirkumar B Amin, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2008)
An effective chemotherapy regimen for patients with heavily pretreated metastatic breast cancer (MBC) using vinorelbine (V) administered with weekly epirubicin (E) and continuous infusion of 5- fluorouracil (CIFU
Authors: G. Sanna, A. Balduzzi, L. Franceschelli, L. Corsetto, M. G. Zampino, I. Minchella, C. Catania, K. Lorizzo, A. Rocca, F. Nolè
Journal: Journal of Clinical Oncology (2004)

718 Background: MBC is a chronic disease, and no treatment may be considered as the standard approach. Therapeutic options should take into account both the efficacy and the tolerability of drugs, with the aim of reducing side effects, while improving survival. Methods: We investigated therapeutic efficacy and tolerability of a combination of V plus ciFu and weekly low-dose E (VEFU regimen) in pts with MBC. Also the role of reintroduction of E was assessed in pts previously exposed to anthracyclines (As), in whom no resistance to these drugs was observed (neither in the adjuvant nor in advanced disease setting). Thirty-two pts were treated; 29 pts were evaluable for response, 32 for toxicity. Median age 56 yrs (range: 29–70); PS 0/1: 15/17; 8 pre-and 24 postmenopausal. Sixteen had chemotherapy for metastatic disease. Seven pts had previous As (1 as adjuvant therapy, 5 for metastatic disease, and 1 in both adjuvant and metastatic settings) and 11 had previous FU as bolus injection with V. Treatment consisted of ciFU (200 mg /m2/die), V (20 mg/dose, i.v., on day 1 and 3) and weekly E (20 mg/m2 in 6 pts and 30 mg/m2 in 26 pts). Courses were repeated every 21 days. Results: CR was observed in 4 pts (14%); PR in 10 (34%), for an overall response rate of 48%. In addition, 4 pts (14%) had a minor response, 7 had a SD (24%) and 4 progressed while on treatment (14%). Two of 7 pts pretreated with As had a CR, 2 a PR, 2 a MR and 1 SD. Grade 3–4 granulocytopenia was observed in 33% of pts with E 20 mg/m2 and in 62% of those who had E 30 mg/m2. No neutropenic feverwas observed. Treatment was subjectively well tolerated with grade 2 nausea and vomiting only in 23% of pts receiving E 30 mg/m2; grade 2 alopecia was observed in 17% of pts receiving E 20 mg/m2 and 58% in those receiving E 30 mg/m2. Conclusions: This combination chemotherapy is effective, well tolerated and warrants further studies. No significant financial relationships to disclose.
Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation
Authors: Daniel O. Kechele, R. Eric Blue, Bailey Zwarycz, Scott T. Espenschied, Amanda T. Mah, Marni B. Siegel, Charles M. Perou, Shengli Ding, Scott T. Magness, P. Kay Lund, Kathleen M. Caron
Journal: Journal of Clinical Investigation (2017)

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation.
Improved selection of patients for hepatic surgery of colorectal liver metastases with (18)F-FDG PET: A randomized study
Authors: T. Ruers, B. Wiering, K. Paul, J. van der Sijp, R. Roumen, Koert de Jong, E. Comans, J. Pruim, H. Dekker, W. Oijen
Journal: Annals of Oncology (2009)