tbuckley/cabot-search huggingface dataset:
Abstract LB-137: Integrated genomics: drug screening and personalized xenograft development approach to identify precision treatments for aggressive pediatric brain tumors
Authors: Maria Tsoli, Carol Wadham, Mark Pinese, Tim Failes, Swapna Joshi, Emily Mould, Julia Yin, Velimir Gayevski, Amit Kumar, Warren Kaplan, Paul Ekert, Laura Franshaw, Andrew Gifford, Martin Weber, Michael Rodriguez, Chelsea Mayoh, Richard Cohn, Greg Arndt, Richard Lock, Vanessa Tyrrell, Murray Norris, Michelle Haber, Loretta Lau, Dong Anh Khuong Quang, Marie Wong, Toby Trahair, Glenn M. Marshall, Mark J. Cowley, David S. Ziegler
Journal: Cancer Research (2018)

Abstract Brain tumors represent the most common solid tumors in childhood and account for significant morbidity and mortality. The lack of advances in treatment of the brain tumors is hindered by our lack of knowledge about the molecular pathogenesis of these malignancies as well as the availability of brain-permeable therapies. Personalised medicine approaches have the potential to enhance diagnostic, prognostic and / or therapeutic information. The TARGET study is a feasibility pilot study which focused on the development of genomic platforms, high throughput drug screening (HTS), and PDX models in order to identify personalised therapies for patients with aggressive pediatric tumors. In the pilot phase 59 patients were enrolled of which 28 were brain tumor patients (47%). In 28 curated cases molecular analysis identified a reportable somatic anomaly (SNVs, gene fusions, CNVs) in 82% (23/28), of which 78% (18/23) had actionable molecular aberrations. Four cases had a reportable germline predisposition variant and in 1 case, the genomic findings changed the primary diagnosis. Fresh tissue collection permitted in vitro HTS (112 single agents) in 58% of cases to date. Four PDX models have been established with additional 8 currently still being evaluated. This feasibility study demonstrates that an integrated approach based on genomic, in vitro and in vivo drug efficacy testing may be useful to guide the management of aggressive pediatric brain tumors. Citation Format: Maria Tsoli, Carol Wadham, Mark Pinese, Tim Failes, Swapna Joshi, Emily Mould, Julia Yin, Velimir Gayevski, Amit Kumar, Warren Kaplan, Paul Ekert, Laura Franshaw, Andrew Gifford, Martin Weber, Michael Rodriguez, Chelsea Mayoh, Richard Cohn, Greg Arndt, Richard Lock, Vanessa Tyrrell, Murray Norris, Michelle Haber, Loretta Lau, Dong Anh Khuong Quang, Marie Wong, Toby Trahair, Glenn M. Marshall, Mark J. Cowley, David S. Ziegler. Integrated genomics: drug screening and personalized xenograft development approach to identify precision treatments for aggressive pediatric brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-137.
Abstract 2318: Palbociclib, a CDK4/6 inhibitor, suppresses proliferation of triple negative breast cancer
Authors: Ahrum Min, Yu Jin Kim, Hyemin Hang, Jee Min Lim, Seongyeong Kim, So Hyeon Kim, Koung Jin Suh, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im
Journal: Cancer Research (2018)

Abstract Background: Abnormal cell cycle progression is a characteristic of cancer and targeting the cell cycle is a strategy for cancer treatment. TCGA reported that Cyclin D1 is overexpressed in 25% to 60% of invasive breast carcinomas, and CDK4/6 and CDKN2A/B aberrations are observed in 7.6% of breast cancer cases. Palbociclib is a specific inhibitor of CDK4/6, a key regulator of the G1 checkpoint. In hormone receptor positive breast cancer, the addition of palbociclib to endocrine treatment either aromatase inhibitor or fulvestrant significantly prolonged PFS in phase III trials. However, the effects of palbociclib have not been fully examined in triple negative breast cancer (TNBC) yet, although CCND amplification and CDKN2A loss are frequently observed in TNBC. Therefore, we investigated the effects of palbociclib on TNBC cells and attempted to identify the underlying mechanisms of palbociclib. Methods: The cytotoxicity assay, cell cycle analysis and western blotting were conducted to determine anti-tumor effect and action mechanisms of palbociclib on breast cancer cell lines. These in vitro data were validated in vivo model as well. Results: Human breast cancer cell lines showed heterogeneous response to palbociclib. Palbociclib induced G1 cell cycle arrest by blocking Rb phosphorylation, and inhibited cell proliferative signaling. In sensitive TNBC cells, palbociclib promoted senescence rather than apoptosis. In addition, palbociclib enhanced the antitumor effect of 5-FU by modulating thymidine synthase (TS) and E2F1 expression. The anti-tumor effects of palbociclib on TNBC cells were validated in TNBC-xenograft model as well. Conclusions: CDK4/6 inhibitor palbociclib showed anti-tumor effect in vitro and in vivo xenograft model of TNBC and acts synergistically with 5-FU by downregulating TS. Our results suggest that palbociclib has therapeutic potential for the treatment of TNBC, not limited in hormone positive breast cancer type. Our results provide a rationale for the future clinical trials of palbociclib in the treatment of breast cancers. Citation Format: Ahrum Min, Yu Jin Kim, Hyemin Hang, Jee Min Lim, Seongyeong Kim, So Hyeon Kim, Koung Jin Suh, Kyung-Hun Lee, Tae-Yong Kim, Seock-Ah Im. Palbociclib, a CDK4/6 inhibitor, suppresses proliferation of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2318.
<i>MUC16</i>Mutations and Prognosis in Gastric Cancer
Authors: Elizabeth C. Smyth, Rebecca C. Fitzgerald
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract 5677: Establishment and application of a panel of PBMC-humanized mouse tumor models in immune-oncology and targeted cancer immunotherapy
Authors: Lan Zhang, Haochen Wu, Fei Chen, Lianqi Zhao, Xiaoyu An, Weibin Tan, Xiaoyan Fu, Meng Qiao, Qian Shi, Wenqing Yang
Journal: Cancer Research (2018)

Abstract Background: Monoclonal antibodies and checkpoint blocking approaches have achieved remarkable success in cancer immunotherapy in clinical practices. Besides the success of anti-PD-1 and anti-PD-L1 antibodies (such as Keytrude and Tecentriq), two bispecific antibodies, Catumaxomab and Blinatumomab have been approved to treat cancer patients, and many more bispecific antibodies are currently in pre-clinical or clinical development. To meet the increasing market needs for fast, reliable and cost effective mouse tumor model systems, we developed a panel of humanized tumor models, designated as MiXenoTM platform. MiXenoTM could be used in a broad spectrum of applications in immuno-oncology drug discovery, including targeted cancer immune-therapy. Method: CrownBio has a collection of about 200 xenograft models, including subcutaneous, orthotropic and systemic models, which covers majority of cancer type. Gene expression and mutation status are often profiled in these models. To engage both host immune system and tumor antigens, we have developed some specific MixenoTM tumor models by inoculating tumor cells over-expressing specific anti-tumor antigens (e.g. EGFR, CD47, Braf or PD-L1) into PBMC-humanized immunocompromised mice. Reconstitution of human immune component with human PBMCs in these tumor-bearing mice provides a useful tool to evaluate the targeted immune-therapeutics including bispecific T cell engagers. Results: To validate the MiXenoTM models for targeted cancer immunotherapy, several xenograft models have been profiled and selected based on their tumor antigens or gene expression. Models with over-expression of a variety of tumor antigens (e.g. EGFR, CD47, Braf, PD-L1, etc.) were used to develop specific MixenoTM tumor models. The immune and tumor cells were engrafted either simultaneously or sequentially. Graft versus host disease (GvHD) can be managed by optimizing the immune cell constitution and tumor cell engraftment. Some models were also validated using stand of care I/O drugs and characterized by immune-phenotyping. Conclusions: MiXenoTM tumor models with specific tumor antigen targeting strategy are valid model systems to evaluate the human immuno-modulatory drugs including bispecific antibodies. Further studies are needed to expand model collections and to extend their applications in I/O space. Citation Format: Lan Zhang, Haochen Wu, Fei Chen, Lianqi Zhao, Xiaoyu An, Weibin Tan, Xiaoyan Fu, Meng Qiao, Qian Shi, Wenqing Yang. Establishment and application of a panel of PBMC-humanized mouse tumor models in immune-oncology and targeted cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5677.
Acne: a side‐effect of masculinizing hormonal therapy in transgender patients
Authors: C.C. Motosko, G.A. Zakhem, M.K. Pomeranz, A. Hazen
Journal: British Journal of Dermatology (2018)

Masculinizing hormonal treatment in transgender men has the potential to increase the level of androgens at end organs, including the pilosebaceous unit. Androgen-induced sebocyte growth and differentiation, sebum production and infundibular keratinization may underlie the development of acne vulgaris among patients receiving this therapy.The aim of this article is to familiarize dermatologists with the sensitivities and challenges of treating acne in transgender male individuals.This review article discusses the pathogenesis and treatment of acne in transgender men on testosterone therapy and highlights the unique considerations in treating this underserved patient population.Despite the incidence of treatment-related acne and the unique considerations in treating transgender men, studies addressing this topic among this patient population are limited.Generally, the standard guidelines for the treatment of acne can be followed in treating these patients; however, several medical, social and psychological factors should be considered.
Sleep and Ventricular Premature Beats
Authors: Bernardlown, Marktykocinski, Andregarfein, Phillipbrooks
Journal: Circulation (1973)

Sixty-nine 24-hour electrocardiographic monitoring sessions were conducted in 54 ambulatory subjects. Thirty-one had coronary heart disease (CHD); 11 had miscellaneous heart ailments; and 12 were free of any heart disease. Monitoring was accomplished with a miniaturized cassette recorder and ventricular premature beats (VPBs) were analyzed as to incidence and grade. The occurrence of VPBs during sleep hours was compared to the awake state. In 22 patients, the incidence of VPBs was reduced by at least 50% during sleep. An additional 13 patients showed a reduction of 25 to 50%. If patients free of ectopic activity during 24-hour monitoring sessions are excluded from analysis, then in 35 of 45 patients, or in 78%, sleep was associated with a lowered occurrence of ventricular extrasystoles. During sleep the VPB grade was likewise lowered. Thus the mean grade for 45 patients changed from 2.75 while awake to 1.78 while asleep. It is of interest that in a number of these patients, trials of various antiarrhythmi...
Prostacyclin Receptor Desensitization Is a Reversible Phenomenon in Human Platelets
Authors: AndreasFisch, KarenTobusch, KerstinVeit, JürgenMeyer, HaraldDarius
Journal: Circulation (1997)

Background Long-term exposure of platelets to endogenous or exogenous prostacyclin or its analogues might result in desensitization of the platelet prostacyclin receptor in vitro and in vivo accompanied by a loss in receptor density on the platelet surface and a reduced sensitivity toward the inhibitory effects of prostacyclins. However, the reversibility of this process in platelets has not yet been investigated. Methods and Results Human platelets desensitized by the chemically stable prostacyclin analogue iloprost showed a significant reduction in [3H]-iloprost binding sites that was reversed by saponin permeabilization. This indicates functionally active internalized prostacyclin receptors. To assess whether the internalized prostacyclin receptors recycle to the cell surface after withdrawal of the agonist, iloprost sensitivity and prostacyclin receptor binding properties of iloprost (30 nmol/L, 2 hours) desensitized platelets incubated in iloprost-free autologous plasma were investigated. While desen...
Abstract 514: Lncrnauca1interacts directly with angiomotin to activate Hippo-YAP signaling in epithelial ovarian cancer
Authors: Xianzhi Lin, Tassja J. Spindler, Simon A. Gayther, Kate Lawrenson
Journal: Cancer Research (2018)

Abstract The long noncoding RNA (lncRNA) urothelial cancer associated 1 (UCA1) is upregulated in multiple cancers, including epithelial ovarian cancer (EOC). Our present study aims to dissect the functional and mechanistic role of UCA1 in EOC. We first explored the effects of stable UCA1 knockout mediated by CRISPR/Cas9 genome editing. The effects of UCA1 loss were more profound in vivo, as UCA1 knockout significantly impaired tumor growth in a mouse xenograft model. Pathways downstream of UCA1 were catalogued using reverse phase protein arrays, which revealed that YAP signaling is activated in UCA1-overexpressing ovarian cancer cells. To characterize the UCA1 interactome, in vivo RNA antisense purification (UCA1-iRAP) experiments were performed using a modified ChIRP and RAP protocol to isolate in vivo RNA direct interactomes based on hybridization of short (20 base) biotinylated probes at a physiologically relevant temperature (37°C). UCA1-iRAP was performed using an EOC cell model, and proteins extracted were profiled by mass spectrometry (MS). Altogether, 19 unique proteins were reproducibly detected by UCA1-iRAP-MS. Interestingly 16 of these UCA1-associated proteins were not previously known RNA-binding proteins. Integration of UCA1-iRAP-MS data with multilayered functional characteristics of UCA1 knockout/knockdown identified angiomotin (AMOT), a known Hippo-YAP signaling modulator, as potential interacting partner for UCA1. The interaction between UCA1 and AMOT was confirmed using both Western blotting for AMOT using UCA1-iRAP proteins, and RT-qPCR for UCA1 RNA after AMOT immunoprecipitation in 3 independent EOC cell lines. Knockdown experiments showed that AMOT is required for UCA1 to activate the expression of YAP target genes, including CYR61 and AXL. Our results indicate that UCA1 interacts directly with AMOT to promote cell growth by activation of Hippo-YAP signaling in EOC, and for the first time identify UCA1 as a novel upstream regulator of YAP signaling. Moreover, the optimized iRAP method we developed in this study can be readily applied to characterizing the protein, DNA, and RNA interactomes of noncoding or coding transcripts implicated other complex traits. Citation Format: Xianzhi Lin, Tassja J. Spindler, Simon A. Gayther, Kate Lawrenson. Lncrna uca1 interacts directly with angiomotin to activate Hippo-YAP signaling in epithelial ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 514.
Analysis of Mural Cell Recruitment to Tumor Vessels
Authors: AlexandraAbramsson, ÖrjanBerlin, HaykPapayan, DenisePaulin, MosheShani, ChristerBetsholtz
Journal: Circulation (2002)

Background— Tumor blood vessels are both structurally and functionally abnormal compared with normal vessels. A limited support of mural cells may contribute to these abnormalities. Here, we characterized mural cell recruitment in 2 mouse tumor models and addressed the question of why tumor vessels fail to recruit a proper coat of mural cells. Methods and Results— We studied mural cell recruitment to the vasculature of 2 transplantable mouse tumor models, T241 fibrosarcoma and KRIB osteosarcoma. We found that both tumors formed a vessel network with heterogeneous and highly abnormal organization of mural cells. Transplantation of tumors to mice expressing lacZ in mural cells demonstrated that these cells were host-derived. Although tumor vessel endothelium expressed PDGF-B, an embryonic mitogen for mural cells, only very few PDGFRβ-positive cells were found to be associated with the developing tumor vasculature, suggesting a limited pool of recruitable mural cells. We tested whether exogenous mural cells ...
Abstract 20506: Use of Physiological Assessment With Prior Stress Testing and Fractional Flow Reserve in Elderly Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Timothy A Joseph, Jessica Lehrich, Paul S Chan, Jeptha P Curtis, Nihar R Desai, Venkatesh L Murthy, Nick Curzen, Brahmajee K Nallamothu
Journal: Circulation (2016)

Introduction: Current Appropriate Use Criteria (AUC) and guidelines for coronary revascularization emphasize the value of non-invasive stress testing and/or fractional flow reserve (FFR) prior to e...
Abstract LB-066: A high-throughput screen of an annotated small molecule library identifies substrates of P-glycoprotein
Authors: Tobie D. Lee, Olivia W. Lee, Kyle R. Brimacombe, Min Shen, Lu Chen, Rajarshi Guha, Bethelihem Tebase, Robert W. Robey, Suresh V. Ambudkar, Michael M. Gottesman, Matthew D. Hall
Journal: Cancer Research (2018)

Abstract A major difficulty in treating cancer is the development of cellular resistance to chemotherapeutics, a phenomenon known as multidrug resistance (MDR). MDR is primarily conferred by an upregulation of ATP-binding cassette (ABC) transporters, most notably P-glycoprotein (P-gp, MDR1, ABCB1), which are responsible for the active transport of drugs out of the cells thereby minimizing drug-target interactions. While numerous strategies to overcome transporter-mediated MDR have been explored, none have proved successful. An alternative approach is to exploit resistance by identifying drugs that target MDR cells over the nonresistant parental cells from which they were selected. As such, the development of MDR1-selective agents represents a novel and relatively unexplored strategy for resolving multidrug resistance. To identify such agents, we developed a series of robust, high-throughput assays to examine differential toxicity between drug-naïve cancer cell lines and their drug-selected, multidrug-resistant sublines. We performed high-throughput screens against several libraries of annotated compounds including the NCATS Pharmaceutical Collection (NPC), a comprehensive collection of all clinically approved drugs - to identify P-gp substrates, and classes of small molecules that exhibit selective toxicity against MDR tumor lines. Further mechanistic evaluation of these compounds has provided valuable insight into targets or pathways that appear to have been rendered more sensitive to inhibition in the course of multidrug resistance development. Citation Format: Tobie D. Lee, Olivia W. Lee, Kyle R. Brimacombe, Min Shen, Lu Chen, Rajarshi Guha, Bethelihem Tebase, Robert W. Robey, Suresh V. Ambudkar, Michael M. Gottesman, Matthew D. Hall. A high-throughput screen of an annotated small molecule library identifies substrates of P-glycoprotein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-066.
Abstract 1404: Role of catechol-O-methyltransferase gene in prostate cancer
Authors: Shigekatsu Maekawa, Taku Kato, Yutaka Hashimoto, Marisa Shiina, Ryan K. Wong, Varahram Shahryari, Soichiro Yamamura, Sahana Majid, Sharanjot Saini, Laura Z. Tabatabai, Yukio Homma, Rajvir Dahiya, Yuichiro Tanaka
Journal: Cancer Research (2018)

Abstract Prostate cancer is one of the most common malignancies and ranks the second most common cause of cancer-related deaths in men in the United States. Catechol-O-methyltransferase (COMT) is a phase II enzyme that detoxifies various catechol compounds that are reactive toward DNA and damaging to the cell. Studies have shown COMT to play a protective role against cancers such as renal and breast, but their effect on prostate is not well understood. In this study, the biological properties and function of COMT in prostate cancer were studied. Expression of COMT was initially measured in normal/benign and cancerous prostate tissues by immunohistochemistry, and cell lines by real-time PCR and western blotting. Cancerous cells displaying the lowest levels was then transfected with COMT. Gene effect on various cellular properties such as cell proliferation, migration, invasion and apoptosis, as well as growth in athymic nude mice were determined. COMT protein expression was lower in cancer regions compared to benign and normal regions of prostate tissues. Cancerous DU145 and DuPro cells also had reduced mRNA levels of COMT but with undetectable protein levels. Interestingly, re-expressing COMT in DU145 and DuPro cells led to decreased cell proliferation, migration, wound healing ability and invasion, and increased apoptosis compared to vector control. COMT also inhibited cell tumor formation in animal models. As a possible target, the TNFRSF11B gene was upregulated due to COMT. These results demonstrate COMT to protect against prostate cancer progression and to have a functional role by affecting apoptosis. COMT may thus be a potential biomarker or therapeutic target for prostate cancer. Citation Format: Shigekatsu Maekawa, Taku Kato, Yutaka Hashimoto, Marisa Shiina, Ryan K. Wong, Varahram Shahryari, Soichiro Yamamura, Sahana Majid, Sharanjot Saini, Laura Z. Tabatabai, Yukio Homma, Rajvir Dahiya, Yuichiro Tanaka. Role of catechol-O-methyltransferase gene in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1404.