tbuckley/cabot-search huggingface dataset:
Abstract 4787: Cyclin G2, a novel target of the SNF5/BAF47 tumor suppressor gene
Authors: Darmood Wei, Aubri Charboneau, Ho-yoon Chung, Donastas Sakellariou-Thompson, Brian Davies, Dennis A. Simpson, Yasumichi Kuwahara, William K. Kaufmann, Charles W. M. Roberts, Bernard E. Weissman
Journal: Cancer Research (2015)

Abstract Malignant Rhabdoid Tumor (MRT) is a rare and aggressive pediatric cancer that most frequently appears in the kidney (RTK) and brain (AT/RT). They are generally characterized by the lack of SNF5 (SMARCB1/INI1) expression, a subunit of the SWI/SNF chromatin remodeling complex. Previous studies have shown that reintroducing SNF5 into MRT cell lines reconstitutes the SWI/SNF complex and results in an inhibition of growth through induction of p21WAF1/CIP1, p16INK4A and p57KIP2 expression. However, the mechanisms behind this growth arrest remain incompletely characterized. In this current report, we used a RT-PCR Cell Cycle SuperArray to identify six candidate genes that showed increased expression after SNF5 reexpression but not after expression of a constitutively active RB gene. One of these genes, Cyclin G2 (CCNG2), a member of the non-canonical Cyclin G family, is thought to act as a negative regulator of the cell cycle. Using a panel of RTK and AT/RT cell lines, we confirmed that SNF5 reexpression leads to induction of CCGN2 in additional MRT cell lines. To determine if CCNG2 is a direct target of SNF5, we used chromatin immunoprecipitation analyses (ChIP) to verify that SNF5 binds to the CCNG2 promoter with peak binding at the transcription start site (TSS) after its reexpression in a MRT cell line. Importantly, primary MRT samples display reduced CCNG2 expression when compared to normal brain tissue or other types of pediatric brain cancers. Therefore, CCNG2 represents a new SNF5 target gene whose downregulation may play a role during MRT development. Citation Format: Darmood Wei, Aubri Charboneau, Ho-yoon Chung, Donastas Sakellariou-Thompson, Brian Davies, Dennis A. Simpson, Yasumichi Kuwahara, William K. Kaufmann, Charles W. M. Roberts, Bernard E. Weissman. Cyclin G2, a novel target of the SNF5/BAF47 tumor suppressor gene. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4787. doi:10.1158/1538-7445.AM2015-4787
A Histologic Basis for the Efficacy of SBRT to the lung
Authors: Neil M. Woody, Kevin L. Stephans, Martin Andrews, Tingliang Zhuang, Priyanka Gopal, Ping Xia, Carol F. Farver, Daniel P. Raymond, Craig D. Peacock, Joseph Cicenia, Chandana A. Reddy, Gregory M.M. Videtic, Mohamed E. Abazeed
Journal: Journal of Thoracic Oncology (2016)

Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early-stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established.We analyzed 740 patients with early-stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression.Overall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3-year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7-25.1), 8.7% (95% CI: 4.6-12.8), and 4.1% (95% CI: 0-9.6), respectively.Our results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.
Cell-Specific Computational Modeling of the PIM Pathway in Acute Myeloid Leukemia
Authors: Dana Silverbush, Shaun Grosskurth, Dennis Wang, Francoise Powell, Berthold Gottgens, Jonathan Dry, Jasmin Fisher
Journal: Cancer Research (2016)

Abstract Personalized therapy is a major goal of modern oncology, as patient responses vary greatly even within a histologically defined cancer subtype. This is especially true in acute myeloid leukemia (AML), which exhibits striking heterogeneity in molecular segmentation. When calibrated to cell-specific data, executable network models can reveal subtle differences in signaling that help explain differences in drug response. Furthermore, they can suggest drug combinations to increase efficacy and combat acquired resistance. Here, we experimentally tested dynamic proteomic changes and phenotypic responses in diverse AML cell lines treated with pan-PIM kinase inhibitor and fms-related tyrosine kinase 3 (FLT3) inhibitor as single agents and in combination. We constructed cell-specific executable models of the signaling axis, connecting genetic aberrations in FLT3, tyrosine kinase 2 (TYK2), platelet-derived growth factor receptor alpha (PDGFRA), and fibroblast growth factor receptor 1 (FGFR1) to cell proliferation and apoptosis via the PIM and PI3K kinases. The models capture key differences in signaling that later enabled them to accurately predict the unique proteomic changes and phenotypic responses of each cell line. Furthermore, using cell-specific models, we tailored combination therapies to individual cell lines and successfully validated their efficacy experimentally. Specifically, we showed that cells mildly responsive to PIM inhibition exhibited increased sensitivity in combination with PIK3CA inhibition. We also used the model to infer the origin of PIM resistance engineered through prolonged drug treatment of MOLM16 cell lines and successfully validated experimentally our prediction that this resistance can be overcome with AKT1/2 inhibition. Cancer Res; 77(4); 827–38. ©2016 AACR.
Novel Agent Perifosine Enhances Antitumor Activity of Bortezomib, Rituximab and Other Conventional Therapies in Waldenstrom’s Macroglobulinemia.
Authors: Xavier Leleu, Garrett O’Sullivan, Xiaoying Jia, Anne-Sophie Moreau, Hai Ngo, Evdoxia Hatjiharisi, Hiroshi Yasui, Zachary Hunter, Yu-Tsu Tai, Judith Runnels, Steven Treon, Teru Hideshima, Kenneth Anderson, Irene Ghobrial
Journal: Blood (2006)
Meta-Analysis Evaluating Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation As Front-Line Consolidation in Chronic Lymphocytic Leukemia: Results Do Not Justify This Treatment Approach
Authors: Tea Reljic, Ambuj Kumar, Benjamin Djulbegovic, Mohamed A Kharfan-Dabaja
Journal: Blood (2014)
Effects of an intensive lifestyle intervention program on portal hypertension in patients with cirrhosis and obesity: The SportDiet study
Authors: Annalisa Berzigotti, Agustín Albillos, Candid Villanueva, Joan Genescá, Alba Ardevol, Salvador Augustín, Jose Luis Calleja, Rafael Bañares, Juan Carlos García‐Pagán, Francisco Mesonero, Jaime Bosch
Journal: Hepatology (2016)

Obesity increases the risk of clinical decompensation in cirrhosis, possibly by increasing portal pressure. Whether weight reduction can be safely achieved through lifestyle (LS) changes (diet and exercise) in overweight/obese patients with cirrhosis, and if weight loss reduces portal pressure in this setting, is unknown. This prospective, multicentric, uncontrolled pilot study enrolled patients with compensated cirrhosis, portal hypertension (hepatic venous pressure gradient [HVPG] ≥6 mm Hg), and body mass index (BMI) ≥26 kg/m2 in an intensive 16-week LS intervention program (personalized hypocaloric normoproteic diet and 60 min/wk of supervised physical activity). We measured HVPG, body weight (BW) and composition, adipokines, health-related quality of life, and safety data before and after the intervention. Changes in HVPG and BW were predefined as clinically relevant if ≥10% and ≥5%, respectively. Safety and BW were reassessed after 6 months. 60 patients were included and 50 completed the study (56 ± 8 years old; 62% male; nonalcoholic steatohepatitis etiology 24%; BMI 33.3 ± 3.2 kg/m2 ; Child A 92%; HVPG ≥10 mm Hg, 72%). LS intervention significantly decreased BW (average, -5.0 ± 4.0 kg; P < 0.0001), by ≥5% in 52% and ≥10% in 16%. HVPG also significantly decreased (from 13.9 ± 5.6 to 12.3 ± 5.2 mm Hg; P < 0.0001), by ≥10% in 42% and ≥20% in 24%. A ≥10% BW loss was associated with a greater decrease in HVPG (-23.7 ± 19.9% vs. -8.2 ± 16.6%; P = 0.024). No episodes of clinical decompensation occurred. Weight loss achieved at 16 weeks was maintained at 6 months; Child and Model for End-Stage Liver Disease scores did not change.Sixteen weeks of diet and moderate exercise were safe and reduced BW and portal pressure in overweight/obese patients with cirrhosis and portal hypertension. (Hepatology 2017;65:1293-1305).
Roles of TET2 and C-CBL Mutations In the Progression of De Novo Myelodysplastic Syndrome to Acute Myeloid Leukemia
Authors: Hsiao-Wen Kao, Seishi Ogawa, Masashi Sanada, Der-Cherng Liang, Chang-Liang Lai, En-Hui Lee, Yu-Shu Shih, Tung-Liang Lin, Ming-Chung Kuo, Chein-Fuang Huang, Lee-Yung Shih
Journal: Blood (2010)
Abstract 4885: TOMA OS-Seq: A clinically oriented targeted resequencing method for detecting all mutation classes in DNA isolated from FFPE, FNAs and plasma
Authors: Yosr Bouhlal, Alexander McKenzie, Austin P. So
Journal: Cancer Research (2015)

Abstract Critical genetic errors, namely specific mutations, are required for the development and maintenance of cancer. Molecular diagnostics that leverage the breadth of next-generation sequencing (NGS) to identify this mutational landscape are therefore becoming an important clinical tool in the precision treatment of cancer. However, the widespread clinical adoption of NGS technologies is hampered not only by the challenges of assaying from various clinical matrices, but also by the complexity of the workflows utilized to create, analyze, and annotate an NGS library. To address these challenges, an adaptation of oligo-selective sequencing (OS-Seq) was developed with a workflow designed specifically for the requirements of the clinical laboratory. Termed TOMA OS-Seq)a panel of 96 genes - each with diagnostic or prognostic value - can be sequenced end-to-end from as little as 1 ng of input material, enabling targeted library construction from diverse sources such as fine-needle aspirates (FNAs), plasma as well as formalin-fixed paraffin embedded (FFPE) tissue. The minimized number of high-efficiency steps reduces the requirement for PCR, allowing the identification of copy number alterations (CNAs), re-arrangements, insertions and deletions (indels), as well as single nucleotide variants (SNVs) from these matrices. The performance of TOMA OS-Seq) was assessed using a panel of cell lines harboring known variants in all classes of mutations. Specifically, comparison with a 12-gene droplet digital PCR (ddPCR) based test (the Amplinome Test) demonstrated a high correlation (R2 &amp;gt; 0.95) of CNA measurements via TOMA OS-Seq) with ddPCR, when further challenged with FNAs. The application of TOMA OS-Seq) in assaying all mutation classes in circulating tumor DNA from plasma demonstrates the robustness and flexibility of this platform as clinically oriented targeted resequencing method. Citation Format: Yosr Bouhlal, Alexander McKenzie, Austin P. So. TOMA OS-Seq: A clinically oriented targeted resequencing method for detecting all mutation classes in DNA isolated from FFPE, FNAs and plasma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4885. doi:10.1158/1538-7445.AM2015-4885
Cellular Uptake: Assessing the Intracellular Integrity of Phosphine-Stabilized Ultrasmall Cytotoxic Gold Nanoparticles Enabled by Fluorescence Labeling (Adv. Healthcare Mater. 24/2016)
Authors: Janine Broda, Andrea Küster, Stefan Westhues, Dirk Fahrenkamp, Andreas T. J. Vogg, Julia Steitz, Felix M. Mottaghy, Gerhard Müller-Newen, Ulrich Simon
Journal: Advanced Healthcare Materials (2016)

On page 3118, a new hybrid structure consisting of a cytotoxic 1.4 nm sized gold core surrounded by a fluorophore-containing ligand shell is designed to monitor cellular uptake by Ulrich Simon and co-workers. The evolution of fluorescence upon cellular uptake discloses that the loss of the ligand shell or of parts of is the essential to unfold high AuNP cytotoxicity.
581. Exploring Potency of Small RNAs for HIV Latency Reactivation
Authors: Mayumi Takahashi, Jiehua Zhou, John C. Burnett, John J. Rossi
Journal: Molecular Therapy (2015)

HIV-1 can establish a stably integrated, non-productive state of infection at the level of individual cells, known as HIV latency. The current drug based combinatorial anti-retroviral therapy (cART) against HIV infection can suppress the level of plasma virus in patient below detection limit. However, despite sufficient control of viremia in patients receiving cART, interruption of therapy could cause a rebound in viremia, suggesting the existence of a stable reservoir of latently infected cells. This demonstrates only minimal or no translation of viral proteins despite maintaining a low level of transcripts. Resting memory CD4+ T cells are the best characterized latent reservoir. These cells survive a long period of time with a half life of 44 months and are not susceptible to HAART. Eradication of the viral reservoir is estimated to take approximately 70 years. Therefore HIV latency is considered a primary barrier to HIV-1 eradication. HIV-1 gene expression is mostly dependent on host transcription factors. Drugs that target these factors have been explored to reactivate latent virus. The current focus on HIV latency activation strategy is focused on safe and effective combination of anti-latency drugs, especially since existing single agent treatments are not sufficient to reactivate latent cells from infected individuals. To understand the mechanisms of establishment and maintenance of HIV-1 latency and to explore reactivation strategies, in vitro systems to model the HIV latency have been developed in T-cell lines and primary CD4+ T-cells. We recently developed LTR-GFP-IRES-Tat (LGIT) latency models for unique U3 subtype isolates in Jurkat and primary CD4+ T cells, and demonstrated that variability of Sp1 and NF-kB binding sites in theU3 region among subtypes have a major impact on emergence of latency. In addition, these latent subtypes were efficiently reactivated by treatment with the combination of clinically promising anti-latency drugs, such as prostratin and SAHA. RNA based therapeutics such as antisense oligonucleotides, small interfering RNAs and aptamers hold a great potential for treatment of many diseases which include the diseases that lack treatments with current technologies. For example, RNA interference (RNAi) is an endogenous phenomenon where siRNAs specifically regulate gene expression. Unlike traditional small molecule and antibody-based drugs, siRNAs can specifically target virtually any gene. Today, siRNA is recognized as a potential novel therapeutic intervention and the study of RNAi based therapy has been accelerated. Using LGIT latency models, we recently found several siRNAs targeting factors in host transcriptional pathways were able to reactivate the latent provirus. The simultaneous treatment with IkB-α and BRD4 siRNAs showed efficient reactivation compared to individual siRNA treatments. Furthermore, we utilized an aptamer for targeted siRNA delivery and examined the potency of aptamer-siRNA chimeras for HIV-latency reactivation.
Human Herpes Virus-6 and Clinical Manifestations After Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Raffaella Greco, Francesca Lorentino, Daniela Clerici, Francesca Matteazzi, Alessandra Forcina, Luca Vago, Simona Malato, Maria Teresa Lupo Stanghellini, Matteo Carrabba, Andrea Assanelli, Magda Marcatti, Massimo Bernardi, Claudio Bordignon, Fabio Ciceri, Consuelo Corti
Journal: Blood (2011)
Analysis of Large Cohort Shows That Caribbean Adult T Cell Leukemia/Lymphoma Is a Chemotherapy Refractory Disease with Very Poor Prognosis That Behaves Distinctly from Japanese Subtypes
Authors: Monica I Zell, Amer Assal, Bhavana Konda, Ira Braunschweig, Olga Derman, Noah Kornblum, Ramakrishna Battini, Amit Verma, Murali Janakiram
Journal: Blood (2014)
Abstract 2223: C-terminal truncated hepatitis B virus X protein promotes hepatocarcinogenesis through enhanced stemness and resistance to therapy
Authors: Kai Yu Ng, Stella Chai, Man Tong, Xin-Yuan Guan, Alfred S. Cheng, Stephanie Ma
Journal: Cancer Research (2015)

Abstract Tumor relapse after chemotherapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive initial treatment. Chronic infection with hepatitis B virus (HBV) has long been linked to the development of HCC. Upon chronic infection, random HBV genome integration can lead to truncation of hepatitis B virus X (HBx) protein at the C-terminus. The resulting C-terminal-truncated HBx (HBx-ΔC) was previously shown to confer enhanced invasiveness and diminished apoptotic response in HCC cells. In this study, we found HBx-ΔC to be more frequently detected in HCC clinical samples than their matched non-tumor counterparts. In addition, we also identified a strong positive correlation between HBx-ΔC and the liver cancer stem cell marker CD133, in a panel of liver cell line tested. Subsequently, we delineated the role of a naturally occurring HBx-ΔC (HBx-Δ14) in promoting stemness and aggressive behaviors in HCC cells. The stable overexpression of HBx-Δ14 in HCC cell line (Huh7) and immortalized normal liver cell line (MIHA) promoted expression of stemness markers, EpCAM and SOX2. In vitro functional studies with HBx-Δ14 stably overexpressed in Huh7 demonstrated an increased ability to self-renew, resist chemotherapy (5-fluorouracil) and targeted therapy (sorafenib), migrate and induce capillary tube formation in endothelial cells. Similar functional results were also obtained when HBx-Δ14 was stably overexpressed in MIHA cells. Taken together, in addition to its role in enhancing HCC metastasis, we find HBx-Δ14 to confer cancer and stem cell-like features in HCC, and to play an important role in driving tumor relapse in this deadly disease. Citation Format: Kai Yu Ng, Stella Chai, Man Tong, Xin-Yuan Guan, Alfred S. Cheng, Stephanie Ma. C-terminal truncated hepatitis B virus X protein promotes hepatocarcinogenesis through enhanced stemness and resistance to therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2223. doi:10.1158/1538-7445.AM2015-2223
Abstract 679: CF102 induces apoptosis of hepatocellular carcinoma
Authors: Shira Cohen, Faina Barer, Salomon M. Stemmer, Pnina Fishman
Journal: Cancer Research (2015)

Abstract Background: The A3 Gi protein adenosine receptor (A3AR) is highly expressed in tumor compared to normal cells. A3AR agonists were shown to inhibit the growth of various tumor cell types via down-regulation of the Wnt and NF-κB signaling pathways. CF102 is a highly selective agonist of the A3AR, shown to have an anti-tumor effect in liver cancer in in vivo models. CF102 induced apoptosis via up-regulation of caspase-3 and the mitochondrial proteins Bax and Bad, demonstrating cell death in the tumor cells. In this study we explored the molecular mechanism involved with the effect of CF102 on human hepatocellular carcinoma cells. Methods: CF102 was added to a medium culture of Hep3b for 48 hours. CF102 effect was observed using Lactate dehydrogenase (LDH), MTT and H3 Thymidine proliferation assays. Cell mRNA and protein were extracted and were analyzed for different signaling pathways. Results: CF102 inhibits the proliferation of Hep3b cells and showed an apoptotic activity in MTT assay. A cytotoxicity effect of CF102 was observed when high levels of LDH were measured in the culture medium of CF102 treated cells compared to the control. Moreover, cyclin D1 expression levels were down-regulated and caspase-3 levels were up-regulated upon CF102 treatment. Both mRNA and protein expression levels of A3AR were down-regulated by CF102 with a subsequent decrease in all members of the JAK-STAT signaling pathway including pSTAT-1, p-JAK-2 and p-AKT along with up-regulation of SOCS-1 and SOCS-3. Conclusions: CF102 showed an anti-cancer activity via down-regulation of the A3AR and the JAK-STAT signaling pathway. CF102 induces cytotoxicity effect resulting in apoptosis of Hep3b cells, indicating that this drug may be considered as an anti-cancer drug for the treatment of human hepatocellular carcinoma. Note: This abstract was not presented at the meeting. Citation Format: Shira Cohen, Faina Barer, Salomon M. Stemmer, Pnina Fishman. CF102 induces apoptosis of hepatocellular carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 679. doi:10.1158/1538-7445.AM2015-679
Hematogones Contained in CD34+ Apheresis Products for Hematopoietic Progenitor Cell Transplantation Have No Adverse Impact On Engraftment Outcomes.
Authors: Sarah L. Ondrejka, Eric D. Hsi, Lisa A. Rybicki, Deborah A. Katanik, Brian J. Bolwell, Hien K. Duong
Journal: Blood (2012)