tbuckley/cabot-search huggingface dataset:
OP07. CYTOPLASMIC TACC3 REGULATES GENE EXPRESSION IN GLIOBLASTOMA MULTIFORME CELLS
Authors: Dr Euan Polson, Dr Heiko Wurdak
Journal: Neuro-Oncology (2017)

Human transforming acidic coiled-coil containing protein 3 (TACC3) is a non-motor mitotic spindle protein that plays a critical role during mitosis. However, TACC3 has also been implicated in the regulation of cell growth and differentiation in both normal and malignant cellular contexts. It has been recently shown that TACC3 can interact with various transcription factors/co-factors sequestering them in the cytoplasm and hence preventing their binding to, and activation of gene promoters in the nucleus. Consequently, deregulation of TACC3 is commonly linked to cancer development and increased expression of TACC3 is found in high-grade tumours such as glioblastoma multiforme (GBM), non-small cell lung cancer and invasive breast cancers. We are investigating the role of TACC3 in the initiation and progression of GBM and aim to identify TACC3-dependent gene expression networks and protein interaction partners. Analysis of protein expression in GBM tissue sections revealed a predominantly cytoplasmic localisation of TACC3. This staining pattern was also observed in other cancer tissues (breast, lung and lymphoma) and was in contrast to the low expression of TACC3 observed in non-cancerous tissues. Strikingly the cytoplasmic localisation of TACC3 was also apparent in vitro (patient derived GBM cells) and in vivo (xenograft tumours). We therefore utilised the cell cycle indicator FUCCI to determine the cell cycle phases of our GBM cells with regards to TACC3 expression. Our results indicated that the observed cytoplasmic TACC3 expression pattern arose predominantly during late S and early G2 phase. To gain insight into the role of cytoplasmic TACC3, we carried out gene expression analysis on isolated cell cycle populations from patient-derived GBM cells in the presence or absence of TACC3 targeting shRNAs. Initial principal components and gene set enrichment analysis unveiled key pathways altered in TACC3 knockdown populations relative to controls. Significant transcriptional changes were revealed for S phase and G2 cells in the absence of TACC3, including upregulation of the transcription factor SP1 and alterations in p53 regulated apoptotic pathways, PI3K/Akt and MAPK signalling pathways. Further analysis is ongoing and includes cross-referencing with proteomics data from TACC3 pull-downs and co-immunoprecipitation a studies. Overall, our data indicate a novel cell cycle-dependent regulatory role for cytoplasmic TACC3 in glioma, further supporting the notion of an oncogenic/tumour progression-promoting role of the TACC3 protein.
The Clonal Origins of Leukemic Progression of Myelodysplasia
Authors: Taehyung Kim, Marc Tyndel, Hyeoung Joon Kim, Jae-Sook Ahn, Seung Hyun Choi, Hee Jeong Park, Yeo-Kyeoung Kim, Deok-Hwan Yang, Je-Jung Lee, Sung-Hoon Jung, Soo Young Kim, Yoo-Hong Min, June-Won Cheong, Sang Kyun Sohn, Joon Ho Moon, Murim Choi, Moses Lee, Zhaolei Zhang, Dennis Dong Hwan Kim
Journal: Blood (2016)
A Comprehensive Progression Risk Score to Predict Treatment Free Survival for Early Stage Chronic Lymphocytic Leukemia Patients
Authors: Massimo Gentile, Tait D. Shanafelt, Giovanna Cutrona, Stefano Molica, Giovanni Tripepi, Isabel Alvarez, Francesca Romana Mauro, Nicola Di Renzo, Francesco Di Raimondo, Iolanda D. Vincelli, Katia Todoerti, Serena Matis, Caterina Musolino, Sonia Fabris, Ernesto Vigna, Luciano Levato, Simona Zupo, Francesco Angrilli, Ugo Consoli, Gianluca Festini, Giuseppe Longo, Agostino Cortelezzi, Annalisa Arcari, Massimo Federico, Donato Mannina, Anna Grazia Recchia, Neil E. Kay, Manlio Ferrarini, Antonino Neri, Fortunato Morabito
Journal: Blood (2015)
A developmental approach to the prevention of hypertension and kidney disease: a report from the Low Birth Weight and Nephron Number Working Group
Authors: Valerie A Luyckx, Norberto Perico, Marco Somaschini, Dario Manfellotto, Herbert Valensise, Irene Cetin, Umberto Simeoni, Karel Allegaert, Bjorn Egil Vikse, Eric A Steegers, Dwomoa Adu, Giovanni Montini, Giuseppe Remuzzi, Barry M Brenner, Dwomoa Adu, Karel Allegaert, Chiara Benedetto, Barry M. Brenner, Irene Cetin, Jennifer Charlton, Robert Chevalier, Monica Cortinovis, Rosario D'Anna, Johannes Duvekot, Joaquin Escribano, Vassilios Fanos, Enrico Ferrazzi, Tiziana Frusca, Richard Glassock, Wilfried Gyselaers, Valerie Luyckx, Dario Manfellotto, Federico Mecacci, Giovanni Montini, Clive Osmond, Norberto Perico, Luca Ramenghi, Giuseppe Remuzzi, Paola Romagnani, Antonio Santoro, Umberto Simeoni, Marco Somaschini, Eric A. Steegers, Herbert Valensise, Bjorn Egil Vikse
Journal: The Lancet (2017)
Abstract 18963: Over-expression of Angiopoietin-2 in Human Patients With Continuous-flow Left Ventricular Assist Devices Induces Abnormal Angiogenesis and Predicts Gastrointestinal Bleeding Events
Authors: Corey E Tabit, Gene H Kim, Savitri E Fedson, Gabriel Sayer, Valluvan Jeevanandam, Nir Uriel, James K Liao
Journal: Circulation (2015)

Arteriovenous malformations are common in patients with Continuous-Flow Left Ventricular Assist Devices (LVAD) and may reflect deregulation of angiogenesis. Angiopoietin-2 (Ang-2) is a stimulator of angiogenesis produced by endothelial cells in response to thrombin. In this study, we evaluate Ang-2 expression in patients with LVAD compared with stable heart failure (HF) or orthotopic heart transplant (OHT) and test the hypothesis that elevated Ang-2 in patients with LVAD leads to increased angiogenesis. Blood samples were taken from 79 patients (n= 21 HF, 41 LVAD, 17 OHT) during routine heart catheterization. Ang-2 was measured by ELISA and thrombin was measured by Western Blot. Cultured human umbilical vein endothelial cells (HUVECs) were incubated with plasma from each patient and Ang-2 expression was measured by RT-PCR. HUVECs were then incubated on Matrigel with serum from each patient in the presence or absence of an Ang-2 blocking antibody and tube formation was measured by microscopy. Also, vena caval endothelial cells were isolated from discarded guide wires used during catheterization and Ang-2 expression was measured by quantitative immunofluorescence. In patients with LVAD vs. HF or OHT, Ang-2 was elevated in both serum (12.3±9.6, 4.5±2.1, and 4.9±2.0 ng/mL respectively, p&lt;0.01) and endothelial cells (56.3±14.1, 31.3±4.2, 35.0±11.2 AU respectively, p&lt;0.05). On Matrigel, serum from patients with LVAD vs. HF or OHT induced increased tube formation (57.1±3.2, 39.2±7.1, 34.7±5.1 tubes per low power field respectively, p&lt;0.05) and this elevation normalized with Ang-2 blocking antibody. Plasma from patients with LVAD vs. HF or OHT induced Ang-2 gene over-expression in HUVECs (1.6±0.4, 1.0±0.3, 0.6±0.2 RQ respectively, p&lt;0.01) and was associated with higher plasma thrombin. In patients with LVAD, serum Ang-2 &gt;10 ng/mL was associated with a higher 3 month risk of GI bleeding vs. Ang-2 &lt;10 ng/mL (30% vs. 0%, p&lt;0.01). Therefore, we conclude that over-expression of Ang-2 in patients with LVAD induces increased angiogenesis and predicts GI bleeding events. Thrombin is increased in patients with LVAD and their plasma induces Ang-2 over-expression in vitro . Therefore, Ang-2 overexpression may contribute to AVM formation in patients with LVAD.
t(8;21) Acute Myeloid Leukemia (AML) Differs from inv(16) AML in Pretreatment Characteristics, Outcome and Prognostic Factors Predicting Outcome: A Cancer and Leukemia Group B (CALGB) Study.
Authors: Guido Marcucci, K. Mrózek, A. S. Ruppert, K. Maharry, J. E. Kolitz, R. J. Mayer, M. J. Pettenati, B. L. Powell, C. G. Edwards, L. J. Sterling, J. W. Vardiman, C. A. Schiffer, A. J. Carroll, R. A. Larson, C. D. Bloomfield
Journal: Blood (2004)
Clinical Risk Factors for Peripheral Neuropathy in Patients Treated with Subcutaneous or Intravenous Bortezomib for Newly Diagnosed Multiple Myeloma
Authors: Maximilian Merz, Hans-Juergen Salwender, Mathias Haenel, Uta Bertsch, Christina Kunz, Thomas Hielscher, Igor W. Blau, Christof Scheid, Elias Karl Mai, Dirk Hose, Bärbel Schurich, Markus Munder, Peter Brossart, Christian Gerecke, Hans Walter Lindemann, Matthias Zeis, Katja C. Weisel, Jan Duerig, Hartmut Goldschmidt
Journal: Blood (2015)
IL33 Promotes Colon Cancer Cell Stemness via JNK Activation and Macrophage Recruitment
Authors: Min Fang, Yongkui Li, Kai Huang, Shanshan Qi, Jian Zhang, Witold Zgodzinski, Marek Majewski, Grzegorz Wallner, Stanislaw Gozdz, Pawel Macek, Artur Kowalik, Marcin Pasiarski, Ewelina Grywalska, Linda Vatan, Nisha Nagarsheth, Wei Li, Lili Zhao, Ilona Kryczek, Guobin Wang, Zheng Wang, Weiping Zou, Lin Wang
Journal: Cancer Research (2017)

The expression and biological role of IL33 in colon cancer is poorly understood. In this study, we show that IL33 is expressed by vascular endothelial cells and tumor cells in the human colon cancer microenvironment. Administration of human IL33 and overexpression of murine IL33 enhanced human and murine colon cancer cell growth in vivo, respectively. IL33 stimulated cell sphere formation and prevented chemotherapy-induced tumor apoptosis. Mechanistically, IL33 activated core stem cell genes NANOG, NOTCH3, and OCT3/4 via the ST2 signaling pathway, and induced phosphorylation of c-Jun N terminal kinase (JNK) activation and enhanced binding of c-Jun to the promoters of the core stem cell genes. Moreover, IL33 recruited macrophages into the cancer microenvironment and stimulated them to produce prostaglandin E2, which supported colon cancer stemness and tumor growth. Clinically, tumor IL33 expression associated with poor survival in patients with metastatic colon cancer. Thus, IL33 dually targets tumor cells and macrophages and endows stem-like qualities to colon cancer cells to promote carcinogenesis. Collectively, our work reveals an immune-associated mechanism that extrinsically confers cancer cell stemness properties. Targeting the IL33 signaling pathway may offer an opportunity to treat patients with metastatic cancer. Cancer Res; 77(10); 2735-45. ©2017 AACR.
R-CVP Chemoimmunotherapy for Limited-Stage Ocular Adnexal MALT Lymphoma with Adverse Factors: A Phase II Study
Authors: Sung-Yong Kim, Seok-Goo Cho, Won-Sik Lee, Suk-Woo Yang, Sung Yong Oh, Hee Bae Ahn, Deok-Hwan Yang, Seong Kyu Park, Jee Ho Chang, Hyo Jung Kim, Min Joung Lee, Jae Wook Yang
Journal: Blood (2016)
Abstract P5-11-06: BEAUTY and the breast: Is adjuvant chemotherapy the right time for a beauty boost? Results of a randomised controlled trial
Authors: M Saghatchian, B Lacas, J Deneuve, N Bouvet, M Mokdad-Adi, A Ghouadni, P Amiel, C Charles, D Boinon, S Delaloge, S Dauchy
Journal: Cancer Research (2017)

Abstract This abstract was not presented at the symposium.
Preferentially Expressed Antigen in Melanoma (PRAME) Expression in Normal and CML CD34+ Progenitor Cells Impairs Myeloid Differentiation.
Authors: Vivian Oehler, Carrie Cummings, Kathleen Sabo, Brent Wood, Katherine Guthrie, Ted Gooley, Era Pogosova-Agadjanyan, Paula Ladne, Derek Stirewalt, Janis L. Abkowitz, Jerald Radich
Journal: Blood (2008)
Abstract IA22: Clonal evolution and drug resistance in colorectal cancers: The EGFR-RAS signaling pathway
Authors: Alberto Bardelli
Journal: Cancer Research (2017)

Abstract When metastatic colorectal cancers are challenged with targeted agents almost invariably a subset of cells insensitive to the drug emerges. As a result, in most instances, targeted therapies are only transiently effective in patients. Strategies to prevent or overcome resistance are therefore essential to design the next generation of clinical trials. How can we overcome the near-certainty of disease recurrence following treatment with targeted agents? To address this question a deeper understanding of the evolutive nature of cancer cells is necessary. We used colorectal cancer (CRC) as a model system to test the hypothesis that by understanding tumor's evolution the emergence of drug resistance can be controlled. We find that clonal dynamics can be monitored in real time in the blood of patients, and liquid biopsies can be used to intercept the emergence of resistant clones before relapses are clinically manifest. We discovered that a multistep clonal evolution process driven by progressive increases in drug fitness underlies the development of resistance in cells and patient avatars. To have long-term efficacy, the use of targeted therapies must take into account the continuous evolution of cancer cells, that is to say, therapies must adapt to tumor evolution. One possibility is to anticipate the changes the tumors will make. For example, by knowing in advance how CRC cells overcome resistance to EGFR blockade, we devised further rounds of therapy. Another approach is to unleash the ability of cancer cells to be recognized by the immune system. We tested this possibility in syngeneic mouse models of colorectal tumors. Our findings indicate that inactivation of DNA repair triggers dynamic neoantigen evolution; impairs cancer growth and leads to prolonged therapeutic responses. Citation Format: Alberto Bardelli. Clonal evolution and drug resistance in colorectal cancers: The EGFR-RAS signaling pathway. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA22.
Abstract ES6-1: ES6-1 Assessment of residual disease and treatment implications post neoadjuvant therapy
Authors: JC Chang
Journal: Cancer Research (2017)

Abstract Breast cancer is a highly heterogeneous disease with various molecular subtypes that differ in regard to treatment approach as well as unresolved treatment issues. In women with HER2-amplified breast tumors, standard neoadjuvant therapy consisting of dual HER2 blockade with trastuzumab/pertuzumab plus chemotherapy can induce a high pathologic complete response (pCR) rate (60%), which translates into better overall survival (&amp;gt;90% at 3 years). A critical unresolved issue in the neoadjuvant treatment of HER2-amplified tumors is minimizing toxicity in select patients. Selection of non-cardiogenic regimens and chemotherapy-free or lighter chemotherapy regimens should be the focus for women whose disease is highly addicted to the HER2 pathway. New research directions are also exploring ways to minimize the extent of local surgery in the breast and axilla. Approximately 30% of patients with triple-negative breast cancer (TNBC) achieve pCR after neoadjuvant chemotherapy. While these patients tend to have a favorable prognosis, those with residual disease (RD) at the time of surgical resection may expect significantly worse outcomes and, at present, do not have targeted therapeutic options. Molecular analysis of tumor tissue from such patients may be used to identify the genetic alterations responsible for disease recurrence and to help individualize treatment with available agents. Transcriptome and sequencing analyses have identified important pathways and aberrations in the majority of residual tumors. Targeting these molecular abnormalities in conjunction with the tumor immune microenvironment may represent an effective therapeutic avenue to improve the outcomes of TNBC patients who have RD after standard neoadjuvant therapy. Adaptive clinical trials investigating neoadjuvant treatments directed against key pathways active in residual tumors are underway. Citation Format: Chang JC. ES6-1 Assessment of residual disease and treatment implications post neoadjuvant therapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr ES6-1.
Autologous SCT In Patients (pts) with Chemotherapy-Resistant Diffuse Large B Cell Lymphoma (DLBCL) Followed by Maintenance with Rituximab.
Authors: Rodolfo Calixto, Mauricio Ostronoff, Fabiana Ostronoff, Alexandre Sucupira, Djenane Manso, ANA Patricia Souto Maior, Rodrigo Florencio, Monique Martins, Luis Fabio Botelho, Mariana Coutinho
Journal: Blood (2010)
A Prognostic Index for Acute and Lymphoma Type Adult T-Cell Leukemia/Lymphoma
Authors: Hiroo Katsuya, Takeharu Yamanaka, Kenji Ishitsuka, Atae Utsunomiya, Hidenori Sasaki, Shuichi Hanada, Tetsuya Eto, Yukiyoshi Moriuchi, Yoshio Saburi, Masaharu Miyahara, Eisaburo Sueoka, Naokuni Uike, Shinichiro Yoshida, Kiyoshi Yamashita, Kunihiro Tsukasaki, Hitoshi Suzushima, Yuju Ohno, Hitoshi Matsuoka, Tatsuro Jo, Junji Suzumiya, Kazuo Tamura
Journal: Blood (2011)
Abstract P3-13-16: 200 experiences of oncoplastic surgery with the omental flap reconstruction
Authors: N Abe, N Sagawa, M Unesoko, H Zaha
Journal: Cancer Research (2017)

Abstract Background:There are several small case series about the omental flap for breast reconstructions. However, the long-term oncological safety and the clinical benefits remain uncertain, especially the flap is used as a part of oncoplastic breast surgery. We retrospectively studied 200 patients who underwent oncoplastic breast surgery using the laparoscopically harvested omental flap. Methods:A retrospective chart review of 200 patients who underwent oncoplastic surgery using the omental flap at our institution from April 2002 to March 2016 was performed. All the omental flaps were laparoscopically harvested, and mainly used as a partial reconstruction immediate after breast-conserving surgery (BCS). Short- and long-term laparoscopy-associated complications, local recurrences and cosmetic outcomes were evaluated. Results:Although 46 cases of nipple-sparing mastectomy or skin-sparing mastectomy were included, most of patients underwent partial breast reconstruction after BCS. The successful rate of laparoscopically harvesting of the omental flap was 99.5% (199 out of 200). The rate of complications was 12.0%. Laparoscopy-associated complications occurred in 4 cases (2.0%). The rate of positive margin was 6.5%. Local recurrence occurred in two cases (1.0%) during medial follow-up period of 78 months. In 24 patients (12.0%), the volume of the flap was insufficient. When applied to nipple-sparing mastectomy or skin-sparing mastectomy, volume luck occurred in 32.6% of patients. Cosmetic outcome was mostly satisfactory. Approximately 80% of patients scored good or excellent evaluated with 4 point scale by 3 health professions. The size of the reconstructed breast basically did not change even after radiation therapy. Donor-site scars were almost negligible just like those of laparoscopic cholecystectomy. Conclusions:The laparoscopically harvested omental flap has minimal donor-site morbidity and deformity. The long-term oncological safety is also promising. Although there is a limit of adaptable volume, the omental flap is an attractive option in partial breast reconstruction after BCS. Citation Format: Abe N, Sagawa N, Unesoko M, Zaha H. 200 experiences of oncoplastic surgery with the omental flap reconstruction [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-13-16.
Killer Immunoglobulin Receptor (KIR) Negative NK Cells Exhibit Potent Alloreactivity Against Primary Leukemia Targets When Interrupting MHC Class I Interactions through NKG2A Blockade.
Authors: Robert Godal, Michelle Gleason, Valarie McCullar, Sarah Cooley, Michael Verneris, Philip McGlave, Jeffrey S. Miller
Journal: Blood (2007)
Abstract IA22: Studying drug resistance through PDX models
Authors: Maurizio Scaltriti
Journal: Clinical Cancer Research (2016)

Abstract Emergence of drug resistance is the main limitation for a durable response to therapy. The mechanisms of such resistance need to be uncovered in order to identify those patients that are more likely to respond and/or develop novel strategies to overcome tumor adaptation to therapy. Patient-derived xenografts can be established from patients at any stage of their treatment. However, samples collected before the exposure to the pharmacological pressure (therapy-naïve) and tumors from patients that progressed to therapy after an initial response (acquired resistance) are preferable. Of particular interest are the models derived from outliers; that are either patients unexpectedly refractory to a given therapy (e.g. BRCA-mut tumors not responding to PARP inhibitors or HER2-positive tumors not responding to anti-HER2 agents) or patients that exhibited an exceptional response (magnitude/durability) to specific targeted agents. There are at least two advantages in using patient-derived material for this kind of studies. The availability of virtually limitless tissue allows deep genomic and proteomic analysis of tumor cells that supposedly resemble the clinical scenario. Moreover, the possibility to perpetuate these tumors is crucial to confirm the resistance phenotype and test novel and more efficacious therapeutic options. In my presentation I will include several examples of how patient-derived models have helped demonstrating the genuineness of previously hypothesized mechanisms of resistance to targeted therapy and have been instrumental to test combinatorial strategies that resulted in remarkable antitumor activity. Furthermore, I will show that patient-derived models can also serve as tools to test novel “smart” drug delivery systems. Citation Format: Maurizio Scaltriti. Studying drug resistance through PDX models. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr IA22.
Multiple Myeloma Cancer Stem Cells: Immunophenotypic and Functional Characterization, Gene Expression Profiling and Therapeutic Targets
Authors: Mariana Bleker de Oliveira, Paola Marino Dantonio, Veruska Lia Fook Alves, Rodrigo Carlini Fernando, Daniela Teixeira, Alexandre Basso, Mihoko Yamamoto, Gisele W. B. Colleoni
Journal: Blood (2016)
Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice
Authors: Marcel Wüthrich, Benjamin Gern, Chiung Yu Hung, Karen Ersland, Nicole Rocco, John Pick-Jacobs, Kevin Galles, Hanna Filutowicz, Thomas Warner, Michael Evans, Garry Cole, Bruce Klein
Journal: Journal of Clinical Investigation (2016)

The authors recently became aware that the IL-1R mice used for the original Supplemental Figure 7, A and B, were incorrectly genotyped and were heterozygous rather than homozygous knockout animals.The experiment with IL1r -/-animals was repeated, and the correct Supplemental Figure 7 is now available online.The correct text describing the experiments in the Results and Discussion sections appears below. ResultsLung CFUs also were reduced to the same extent in vaccinated Il18r -/-and wild-type mice (Supplemental Figure 7B).In contrast, IL-17-producing T cells recruited to the lungs of IL1r -/-mice were reduced, and the mice failed to acquire resistance in comparison with vaccinated wild-type controls.Thus, IL-18R, but not IL-1R, is dispensable in the development of T17 cells and vaccine resistance.Moreover, failed T17 differentiation of 1807 cells in Myd88 -/-mice is not due to impaired IL-18R signaling, but is likely due to impaired signaling via TLRs and IL-1R.