tbuckley/cabot-search huggingface dataset:
Abstract 13497: Murc/Cavin-4 Regulates Cardiac Function Through Modulation of Caveolin-3 Function in β-adrenergic Receptor Signaling
Authors: Tetsuro Hamaoka, Takehiro Ogata, Daisuke Naito, Naohiko Nakanishi, Kotaro Miyagawa, Naoki Maruyama, Takeru Kasahara, Takeshi Shirayama, Tomomi Ueyama
Journal: Circulation (2014)

Background: Muscle-restricted coiled-coil protein (MURC)/Cavin-4 is a member of the cavin family which regulates caveolae function together with caveolins. In cardiomyocytes, caveolin-3, a critical...
Disulfonated tetraphenyl chlorin (TPCS2a)-induced photochemical internalisation of bleomycin in patients with solid malignancies: a phase 1, dose-escalation, first-in-man trial
Authors: Ahmed A Sultan, Waseem Jerjes, Kristian Berg, Anders Høgset, Charles A Mosse, Rifat Hamoudi, Zaid Hamdoon, Celia Simeon, Dawn Carnell, Martin Forster, Colin Hopper
Journal: The Lancet Oncology (2016)
Abstract 4223: Novel strategy for diagnosis of solid tumors by visualization of fusion transcripts
Authors: Fatu Badiane Markey, Mona Batish
Journal: Cancer Research (2016)

Abstract The discovery of chromosomal translocations as one major cause of cancers has led to the introduction of numerous diagnostic techniques to detect these chromosomal abnormalities. Chromosomal banding, DNA fluorescence in situ hybridization (DNA FISH), and RT PCR are all techniques used for the diagnosis of cancers. Despite the advancement these techniques have brought to the field, they are primarily optimized for the detection of blood cancers and are not very efficient for the detection of solid tumors which are very heterogeneous. One such cancer, Ewing's sarcoma (ES), is a prevalent pediatric, bone and soft tissue tumor that is caused by a chromosomal translocation between Ewing's sarcoma breakpoint region 1 (EWSR1) on chromosome 22 and various members of the ETS protein family. The most common fusion partner, in 85% of cases, is Friend leukemia integration 1 (FLI1) on chromosome 11 which leads to the formation of the fused EWS/FLI1 gene that codes for an aberrant transcription factor. However, even within this single translocation there are multiple breakpoint-fusion scenarios that can occur which results in heterogeneity and increases the chances of a faulty diagnosis with standard techniques. Considering the diversity that exists within the molecular abnormalities that result in Ewing's sarcoma and other solid tumors, there is a need for an alternative and more robust method of detection. The technique of single molecule fluorescence in situ hybridization (smFISH) has been modified by our group to target the EWS/FLI1 transcript that results from the chromosomal fusion; this new technique is referred to as “Fusion FISH”. In Fusion FISH, two differently labeled probe sets are designed to target each half of the EWS/FLI1 fusion transcript. A co-localization of the two probe sets indicates the presence of the EWS/FLI1 translocation and a positive test for Ewing's sarcoma. Preliminary data has established the success of Fusion FISH in detecting both type 1 and type 2 translocations in several Ewing's sarcoma cell lines. The fusion transcript is expressed at similar levels in all cell lines and clearly distinct from the signal of wild type EWS and FLI1 mRNA. Additional studies will examine this new technique in other solid cancers, patient tumor samples, and for validation of additional relevant mRNA biomarkers. Citation Format: Fatu Badiane Markey, Mona Batish. Novel strategy for diagnosis of solid tumors by visualization of fusion transcripts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4223.
Pretransplantation Anti-CCR4 Antibody Mogamulizumab Against Adult T-Cell Leukemia/Lymphoma Is Associated With Significantly Increased Risks of Severe and Corticosteroid-Refractory Graft-Versus-Host Disease, Nonrelapse Mortality, and Overall Mortality
Authors: Shigeo Fuji, Yoshitaka Inoue, Atae Utsunomiya, Yukiyoshi Moriuchi, Kaoru Uchimaru, Ilseung Choi, Eiichi Otsuka, Hideho Henzan, Koji Kato, Takeaki Tomoyose, Hisashi Yamamoto, Saiko Kurosawa, Ken-ichi Matsuoka, Takuhiro Yamaguchi, Takahiro Fukuda
Journal: Journal of Clinical Oncology (2016)

Purpose Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) is one important treatment option for patients with aggressive adult T-cell leukemia/lymphoma (ATLL). Mogamulizumab (anti-CCR4 monoclonal antibody; Mog) was recently approved as a treatment for ATLL in Japan. Major concerns exist about the possible adverse effects of pretransplantation Mog because Mog depletes regulatory T cells for several months. We assessed the impact of pretransplantation Mog on clinical outcomes after allo-HSCT. Patients and Methods We included 996 allo-HSCT recipients age 70 years or younger with aggressive ATLL who were given the diagnosis between 2000 and 2013 and who received intensive chemotherapy by multiple chemotherapeutic drugs as first-line therapy. Before allo-HSCT, 82 patients received Mog with a median interval of 45 days from the last Mog to allo-HSCT. Results Pretransplantation Mog was associated with an increased risk of grade 3 to 4 acute graft-versus-host disease (GVHD; relative risk, 1.80; P &lt; .01) and refractoriness to systemic corticosteroid for acute GVHD (relative risk, 2.09; P &lt; .01). One-year cumulative incidence of nonrelapse mortality was significantly higher in patients with pretransplantation Mog compared with those without (43.7% v 25.1%; P &lt; .01). The probability of 1-year overall survival was also significantly inferior in patients with pretransplantation Mog compared with those without (32.3% v 49.4%; P &lt; .01). In particular, use of Mog with intervals &lt; 50 days to allo-HSCT was associated with a dismal clinical outcome. Conclusion Pretransplantation Mog was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans. In clinical practice, Mog should be cautiously used for patients with ATLL who are eligible for allo-HSCT.
Sexual distress in early breast cancer (EBC) survivors.
Authors: L. Paquet, D. A. Frechette, S. F. Dent, X. Song, S. Verma
Journal: Journal of Clinical Oncology (2010)

e19595 Background: While research has identified sexual dysfunction in BC survivors, there is a paucity of data regarding sexual distress (SD). We are prospectively evaluating SD and its predictors in 200 women treated for EBC or colon cancers. Herein we report findings on SD in the BC cohort at baseline prior to any hormonal therapy (HT). Methods: Post-menopausal women completing adjuvant treatment for stage I-IIIa EBC prior to commencing HT were eligible. SD was assessed with the Female Sexual Distress Scale. Predictors selected were: 1) Quality of life and 2) endocrine symptoms measured with FACT-ES, 3) sexual problems related to desire, arousal, lubrication, satisfaction and pain during intercourse assessed with items selected from the Female Sexual Functioning Index, and 4) trait anxiety measured with the Spielberger's State-Trait anxiety inventory. Results: Since 2/2009, 70 patients have consented and half have completed the baseline questionnaires. A high (94%) proportion of women had at least 1 sexual problem, whereas 25% reported BOTH any sexual problem and SD. Thirty-three percent were sexually inactive and were more sexually distressed than sexually active women (p<0.1). Reported problems were: frequency (48%) and level (53%) of sexual desire, frequency (58%), level (40%) and satisfaction (32%) of arousal, vaginal dryness during sexual activity (29%). Only 16% were dissatisfied with their sexual life. Compared with published healthy control data, EBC patients had lower level of sexual functioning. Significantly greater SD was associated with lower sexual desire, arousal, and satisfaction, higher levels of endocrine symptoms and higher anxiety levels (p<0.05). Conclusions: The study confirms that sexual problems are common in women with EBC (>90%). Although less frequent, distressing sexual problems were observed in at least 25%. Clinicians should be encouraged to assess SD specifically in follow up visits in order to identify women who may benefit from psychosexual counselling. No significant financial relationships to disclose.
Abstract 3714: Optimisation of quinazolinedione sulphonamides as novel inhibitors of poly(ADP Ribose) glycohydrolase (PARG)
Authors: Kate Smith, Ben Acton, Dominic James, Cliff Jones, Stuart Jones, Allan Jordan, Nicola Hamilton, Alison McGonagle, Daniel Mould, Helen Small, Alex Stowell, Julie Tucker, Ian Waddell, Bohdan Waszkowycz, Donald Ogilvie
Journal: Cancer Research (2016)

Abstract The macrodomain protein poly(ADP ribose) glycohydrolase (PARG) has been shown to be a critical component in the repair of single stand DNA breaks and counteracts the function of the ARTD family of poly(ADP ribose) polymerases, commonly known as the PARPs. As PARG exists as a single protein, it presents an attractive target for therapeutic intervention in cancer cells with enhanced dependence upon DNA repair. Inhibitors of this enzyme have proved difficult to discover and develop. Moreover, intact cell-active tool compounds which have the propensity to be used as robust chemical probes to understand PARG pharmacology, are absent from the literature. This poster will describe our work in this emerging area, optimising a series of drug-like quinazolinedione derivatives to deliver molecules with the correct physicochemical and biochemical properties to function as in vitro cell probe compounds. These unprecedented agents display potent on-target biochemical (5 nM) and cell (10 nM) activity with a significant window to acute 3-day cytotoxicity. Moreover, these agents are selective against PARP family members and the close glycohydrolase homologue ARH3. The medicinal chemistry optimisation of the scaffold will be described, alongside the outline pharmacology demonstrating on-target, selective inhibition of PARG in cells. Such tool compounds will be of value in revealing the detailed mechanisms of action of PARG in DNA repair and other PAR chain-mediated cellular processes, with the ultimate goal of delivering novel and clinically relevant therapeutic agents. Citation Format: Kate Smith, Ben Acton, Dominic James, Cliff Jones, Stuart Jones, Allan Jordan, Nicola Hamilton, Alison McGonagle, Daniel Mould, Helen Small, Alex Stowell, Julie Tucker, Ian Waddell, Bohdan Waszkowycz, Donald Ogilvie. Optimisation of quinazolinedione sulphonamides as novel inhibitors of poly(ADP Ribose) glycohydrolase (PARG). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3714.
Multicenter Total Therapy Gimema LAL 1509 Protocol for De Novo Adult Ph+ Acute Lymphoblastic Leukemia (ALL) Patients. Updated Results and Refined Genetic-Based Prognostic Stratification
Authors: Sabina Chiaretti, Antonella Vitale, Loredana Elia, Anna Lucia Fedullo, Silvana Albino, Alfonso Piciocchi, Paola Fazi, Francesco Di Raimondo, Antonella Fornaro, Francesco Fabbiano, Alfonso Maria D'Arco, Giovanni Martinelli, Francesca Ronco, Lidia Edwige Santoro, Nicola Cascavilla, Piero Galieni, Alessandra Tedeschi, Simona Sica, Nicola Di Renzo, Angela Melpignano, Angelo Michele Carella, Felicetto Ferrara, Marco Vignetti, Robin Foà
Journal: Blood (2015)
Abstract 986: Long noncoding RNA CCAT2 cooperates with miR-145 and miR-21 to regulate colon cancer stem cells
Authors: Yingjie Yu, Pratima Nangia-Makker, Lulu Farhana, Adhip P. N. Majumdar
Journal: Cancer Research (2016)

Abstract Colon cancer-associated transcript-2 (CCAT2), a long noncoding RNA (lncRNA), has been reported to be over-expressed in colorectal cancer to promote tumor growth and metastasis and also reduces sensitivity to chemotherapy, a property related to cancer stem cells (CSCs). MicroRNAs, small endogenous noncoding RNAs, negatively control the expression of target genes by cleaving mRNA or through translation repression. We have recently reported cooperation of miR-21 and miR-145 to regulate colon CSCs proliferation and differentiation. Down-regulation of miR-21 enhances CSC enriched chemo-resistant colon cancer cells’ susceptibility to chemo- therapeutic regimens. Although both CCAT2 and miR-21 increase WNT signaling activity and reduce chemosensitivity to 5-FU, a critical evidence on how CCAT2 regulates stemness leading to chemo-resistance is lacking. The primary goal of this investigation was to examine whether CCAT2 associates with miR-145 and miR-21 and whether this association plays a role in regulating stemness of colon cancer cells. We have observed that CCAT2 transcript level is dependent on p53 expression and activity, as evidenced by a marked increase in CCAT2 expression in p53 wild type harboring HCT-116 colon cancer cells compared with p53 null HCT-116 and p53 mutant HT-29 cells. We further revealed that knockdown of CCAT2 increased the expression of miR-145 and negatively regulates miR-21 in HCT-116 cells and impairs proliferation and differentiation of these cells. On the other hand, upregulation of CCAT2 induces proliferation of HCT-116 cells and also increases the expression of CSC markers CD44 and CD166. We have also observed that miR-145 and miR-21 cooperation plays a role in regulating colon cancer stem cells by down-regulating Sox2 and increased activity of Wnt/β-catenin pathway. Our current results suggest that lncRNA CCAT2 cooperates with miR-145 and miR-21 to regulate colon cancer stem cells, which provides a potential therapeutic target for chemoresistance in colorectal cancer. Citation Format: Yingjie Yu, Pratima Nangia-Makker, Lulu Farhana, Adhip P. N. Majumdar. Long noncoding RNA CCAT2 cooperates with miR-145 and miR-21 to regulate colon cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 986.
Histamine-secreting microbes are increased in the gut of adult asthma patients
Authors: Weronika Barcik, Benoit Pugin, Patrick Westermann, Noelia Rodriguez Perez, Ruth Ferstl, Marcin Wawrzyniak, Sylwia Smolinska, Marek Jutel, Edith M. Hessel, David Michalovich, Cezmi A. Akdis, Remo Frei, Liam O'Mahony
Journal: Journal of Allergy and Clinical Immunology (2016)
Bortezomib Plus Melphalan and Prednisone (VMP) Followed By Lenalidomide and Dexamethasone (Rd) in Newly Diagnosed Elderly Myeloma Patients Overcome the Poor Prognosis of High-Risk Cytogenetic Abnormalities (CA) Detected By Fluorescence in Situ Hibridization (FISH)
Authors: Maria-Victoria Mateos, Norma C Gutierrez, María-Luisa Martín, Joaquín Martínez-López, Miguel T Hernandez, Rafael Martinez, Laura Rosiñol, Enrique M. Ocio, Ana Isabel Teruel, Albert Oriol, Juan Jose Bargay, Enrique Bengoechea, Yolanda Gonzalez, Jaime Perez De Oteyza, Mercedes Gironella, Cristina Encinas, Jesus Martin, Carmen Cabrera, Bruno Paiva, Noemi Puig, Joan Blade, Juan José Lahuerta, Jesus San Miguel
Journal: Blood (2015)
Long-term evaluation of vascular toxicity in patients with Ph+ leukemias treated with bosutinib.
Authors: Jorge E. Cortes, Hagop M. Kantarjian, Hanna Jean Khoury, Tim H. Brümmendorf, Maureen G. Conlan, Kongming Wang, Kolette D. Fly, Mark Shapiro, Jeffrey Howard Lipton, Jean-Bernard Durand, Carlo Gambacorti-Passerini
Journal: Journal of Clinical Oncology (2014)

7060 Background: Vascular toxicities (eg, peripheral arterial occlusive disease [PAOD]) have been associated with BCR-ABL tyrosine kinase inhibitor (TKI) treatment (tx). Methods: We evaluated vascular (peripheral, cardiovascular, and cerebrovascular) toxicities based on tx-emergent adverse events (TEAEs) with bosutinib (BOS) in 2 ongoing studies: phase 1/2 study of BOS second/third/fourth-line tx (2L/3L/4L, up to 3 y) in Ph+ leukemia patients (pts) resistant/intolerant to prior TKIs; phase 3 study in chronic phase CML pts of BOS vs imatinib (IM) first-line tx (1L; up to 2 y). Results: 12.7% of BOS pts had vascular TEAEs (Table) with no significant differences for BOS vs IM (1L: P≥0.122). Individual cardiovascular TEAE incidences were low; only angina pectoris (1.2%) and coronary artery disease (CAD 1.2%) occurred in >1% of BOS pts. No individual cerebrovascular TEAE occurred in >3 BOS pts. Individual peripheral vascular TEAEs were rare; only hypertension (6.4%) occurred in >2 BOS pts (1L: 6.0% [BOS] vs 4.4% [IM], P=0.427). Only 1 pt had PAOD (BOS 3L; y 1). Newly occurring vascular TEAE rates decreased with longer BOS tx (2L/3L/4L: y1, 40/570 [7.0%]; y 2, 21/273 [7.7%]; y 3, 8/208 [3.8%]; 1L [BOS vs IM]: y 1, 16/248 [6.5%] vs 9/251 [3.6%]; y 2, 5/183 [2.7%] vs 5/209 [2.4%]). Risk factors for vascular TEAEs (P≤0.036) were age ≥65 y (both studies) and history of vascular disorders (2L/3L/4L). Vascular TEAEs were managed mostly by concomitant medication (61.5% of affected pts); few pts required dose delays (n=15) or reductions (n=1). Discontinuation due to vascular TEAEs occurred in 6 (0.7%) BOS pts (2L/3L/4L: CAD n=2, myocardial infarction n=2, cerebrovascular accident n=1; 1L: cerebral haemorrhage n=1 [vs 0 IM, P=0.497]). Conclusions: Vascular TEAE incidences with BOS in Ph+ leukemia pts were low individually and overall and not significantly different vs IM (1L). Peripheral vascular TEAEs, except hypertension, are rare with BOS. Clinical trial information: NCT00574873; NCT00261846. Pooled 2L/3L/4L 1L BOS* (n=818) BOS* (n=570) BOS* (n=248) IM† (n=251) Median (range) tx duration, mo – 11.1 (0.03–83.4) 33.1 (0.03–49.6) 33.3 (0.5–46.9) Vascular TEAEs, % 12.7 13.5 10.9 7.6 Cardiovascular 3.4 4.2 1.6 1.2 Cerebrovascular 1.8 2.3 0.8 0.4 Peripheral vascular 8.2 8.2 8.1 4.8 *500 or †400 mg/d starting dose.
Abstract 2771: Epigenetic regulation of the cocaine and amphetamine regulated transcript (CART) in cancer
Authors: Kate Connor, Sudipto Das, Bruce Moran, Laoighse Mulrane, William M. Gallagher, Darran O’Connor
Journal: Cancer Research (2016)

Abstract The cocaine and amphetamine regulated transcript (CART) is well documented in the central nervous system for its role in appetite regulation and reward pathways. In recent studies CART has been proven to be a poor prognostic marker in lymph node-negative, estrogen receptor (ER)-positive breast cancer patients, and has also been shown to be associated with worse survival in small bowel carcinoid tumours. The regulation of CART in these different cancer types however remains largely unknown. The presence of a large CpG island in the putative promoter region and the lack of expression of CART in many cancer cell lines suggest a possible epigenetic mechanism of suppression. A panel of various cancer cell lines (breast, colorectal, endometrial and ovarian) were assessed for endogenous CART expression via western blot and RT-PCR. Cells were then treated with forskolin and leptin; agents which have been previously shown to induce CART expression in the CNS. Cells were also treated with CART conditioned media, which has been previously shown to be the only factor capable of inducing CART expression. Treatment was carried out with varying doses of two DNA methyltransferase inhibitors, 5-Aza-2′-deoxycytidine and RG108, followed by examination of CART expression post treatment. Bisulfite sequencing of the promoter region of CART was performed in all cell lines and a small selection of formalin fixed paraffin embedded (FFPE) tissue samples. Whole methylome sequencing was carried out to confirm this promoter region of CART and study the global effects of treatment with epigenetic modifiers and CART peptide. Assessment of a collection of cell lines via western blot has shown CART expression to be negative across the panel. Moreover, treatment with forskolin and leptin did not result in re-expression of CART. Treatment with 5-Aza-2′-deoxycytidine has however resulted in increased CART mRNA levels, and subsequent bisulfite sequencing of the promoter region of CART has revealed dense methylation at the CpG island. Treatment with CART conditioned media may also induce promoter demethylation and subsequent re-expression of CART. Collectively, this data suggests the potential involvement of DNA methylation in the regulation of CART. Citation Format: Kate Connor, Sudipto Das, Bruce Moran, Laoighse Mulrane, William M. Gallagher, Darran O’Connor. Epigenetic regulation of the cocaine and amphetamine regulated transcript (CART) in cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2771.
Abstract 3043: Survivin-mediated radio-sensitization response in p53 mutant tumor cells
Authors: David J. Grdina, Jeffrey S. Murley, Richard C. Miller, Ralph R. Weichselbaum, Alfred W. Rademaker, Gayle E. Woloschak, Jian Jian Li
Journal: Cancer Research (2016)

Abstract Doses of ionizing radiation ≤100 mGy induce changes in radiation sensitivity expressed by cells exposed to subsequent higher doses. This is referred to as an adaptive effect. We describe a unique survivin-associated adaptive response in which increased radiation resistance or sensitization of cells can be induced by exposure to doses as low as 5 mGy. Experiments were performed using two murine sarcomas, SA-NH and FSa,grown either in culture or as tumors, and two human cancer cell lines, Panc-1 (pancreatic epithelioid carcinoma) and MDA-MB-231 (breast adenocarcinoma). Doses of 5 mGy were used to induce changes in the response of these tumor cells to higher therapy doses using a multi-dosing paradigm. Effects on radiation sensitivity were associated with changes in both survivin concentration and its translocation to the cytoplasm (SA-NH, p53 wild type) or nucleus (FSa, Panc-1 and MDA-MB-231, p53 mutant). In vitro survival assays (2 Gy per fraction, two once daily fractions) and tumor growth delay (TGD) (5 Gy per fraction, five once daily fractions) studies were performed on SA-NH and FSa cells. Intracellular localization of survivin was determined by ELISA and correlated to survival response. 2 Gy alone had no effect on intracellular translocation of survivin. When preceded 15 min earlier by a 5 mGy exposure, survivin increased in the cytoplasm of SA-NH as compared to the nuclei of FSa, Panc-1 and MDA-MB-231 cells. SA-NH tumors were protected by 5 mGy exposures (1.9 day decrease in TGD, P = 0.032) while FSa tumors were sensitized (4.5 day increase in TGD, P &amp;lt; 0.001). Panc-1 and MDA-MB-231 tumor cells were also sensitized to ionizing radiation following 5 mGy exposures. Exposure of SA-NH to 4 mM of the free radical scavenger N-acetylcysteine inhibited the effect of 5 mGy on inducing this adaptive response. We have identified a very low radiation dose-induced survivin-mediated radio-sensitization response that could enhance therapeutic outcomes associated with the increased usage of imaging procedures in radiation therapy. This work was supported by NIH/NCI grant R01 CA132998 and DOE Low Dose Program/Project Grant DE-SC0001271 (D.J.G.) Citation Format: David J. Grdina, Jeffrey S. Murley, Richard C. Miller, Ralph R. Weichselbaum, Alfred W. Rademaker, Gayle E. Woloschak, Jian Jian Li. Survivin-mediated radio-sensitization response in p53 mutant tumor cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3043.
P0995 : The use of the attenuation coefficient computed on the ultrasonic image could improve the specificity of the classical ultrasonographic examination for the assessment of steatosis grade in diffuse liver diseases patients
Authors: M. Lupsor-Platon, C. Vicas, S. Nedevschi, H. Stefanescu, C. Radu, D. Crisan, Z. Sparchez, A. Serban, M. Grigorescu, R. Badea
Journal: Journal of Hepatology (2015)