tbuckley/cabot-search huggingface dataset:
Abstract 1706: Evaluation of LGR5 protein expression in colon cancer stem cells
Authors: Wei Fu, Rachel Gonzalez, Kehu Yuan, Caiwei Chen, Haitao Wei, Hsiangmin Lu, Qi Ren, Evelin Logis, Sean Kelly, Wei-Wu He, Donghui Ma
Journal: Cancer Research (2016)

Abstract Cancer stem cells are a subpopulation of cancer cells responsible for cancer initiation, development and metastasis. A number of studies demonstrated that Leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5) can drive cancer development through triggering canonical Wnt signaling and its downstream gene expression. LGR5 is an important biomarker specifically expressed on colon cancer stem cells. In this study, we have successfully developed an LGR5 antibody with high specificity to detect endogenous LGR5 expression in different immunoassay application. By screening multiple anti-LGR5 hybridoma clones, antibody generated by clone UMAB212 was proven to be highly specific on our high density protein microarray chip assay. Here our experimental data demonstrated that clone UMAB212 recognizes not only human LGR5 protein but also mouse LGR5 protein in both western blot and flow cytometry applications. No cross-reactivity was observed with the other two LGR family members, LGR4 and LGR6. Furthermore, this antibody also works great on immunohistochemistry application on FFPE tissue blocks. In summary, UMAB212 is great tool for us to study LGR5 protein in different immunoassay setting and it could also be a potential cancer diagnostic reagent. Citation Format: Wei Fu, Rachel Gonzalez, Kehu Yuan, Caiwei Chen, Haitao Wei, Hsiangmin Lu, Qi Ren, Evelin Logis, Sean Kelly, Wei-Wu He, Donghui Ma. Evaluation of LGR5 protein expression in 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 1706.
Abstract 1365: Pseudo-cis and pseudo-trans amide conformations lead to potent targeted antifolates that are selectively transported by FR over RFC
Authors: Aleem Gangjee, Weiguo Xiang, Aamod Dehkne, Mike R. Wilson, Adrianne Wallace-Povrik, Carrie O’Connor, Zhanjun Hou, Larry H. Matherly
Journal: Cancer Research (2016)

Abstract Drugs usually bind to different targets in different conformations. As antitumor agents, antifolates first need to be selectively transported by tumor cells via the reduced folate carrier (RFC), the proton-coupled folate transporter (PCFT) or folate receptors (FRs). The second step is the binding of antifolates with the intracellular targets. We are systematically developing novel folate analogs with selective membrane transport for FRs and PCFT over the ubiquitously expressed RFC. These 6-substituted pyrrolo[2,3-d]pyrimidine antifolates are principally inhibitors of de novo purine biosynthesis at the steps catalyzed by glycinamide ribonucleotide formyl transferase (GARFTase) and 5-aminoimidazole-4-carboxamide (AICA) ribonucleotide formyltransferase (AICARFTase). We previously demonstrated that classical antifolates bind to FRα and GARFTase in different conformations. An amide in the bridge region of classical antifolates has two interchangeable lowest energy conformers, pseudo-cis and pseudo-trans. We reported that a novel antifolate (AGF238) with an amide in the bridge region binds to FRα in a pseudo-trans conformation and binds to GARFTase in a pseudo-cis conformation. As part of our continued efforts to pursue targeted antifolates as antitumor agents, we designed an expand series of amide-bridged classical antifolates with different energy barriers between the pseudo-cis and pseudo-trans conformers. Among these, AGF266 was exclusively transported by Chinese hamster ovary (CHO) cells engineered to express human FRα (IC50 = 0.42 nM) or FRβ (IC50 = 0.88 nM) over CHO expressing human RFC (IC50 &amp;gt; 1000 nM). AGF266 was also found to exhibit highly potent antitumor activity (IC50 = 0.79 nM in KB human tumor cells). AGF266 inhibited GARFTase as its principal cellular target, based on patterns of protection from growth inhibition by adenosine and AICA. Our in vitro findings of antitumor activity associated with FR selectivity suggest that further preclinical evaluation of AGF266 as a potential antitumor agent is warranted. Citation Format: Aleem Gangjee, Weiguo Xiang, Aamod Dehkne, Mike R. Wilson, Adrianne Wallace-Povrik, Carrie O’Connor, Zhanjun Hou, Larry H. Matherly. Pseudo-cis and pseudo-trans amide conformations lead to potent targeted antifolates that are selectively transported by FR over RFC. [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 1365.
Blockade of mTOR Signaling Potentiates the Ability of Histone Deacetylase Inhibitor to Induce Growth Arrest and Differentiation of Acute Myelogenous Leukemia Cells.
Authors: Chie Nishioka, Takayuki Ikezoe, Yang Jing, H. Phillip Koeffler, Akihito Yokoyama
Journal: Blood (2008)
IgD Amyloidosis: An Unrecognized Entity
Authors: Morie Abraham Gertz, Francis K Buadi, Suzanne R Hayman, David Dingli, Angela Dispenzieri, Philip R. Greipp, Shaji Kumar, Martha Q Lacy, John A Lust, Nelson Leung, S. Vincent Rajkumar, Stephen J. Russell, Steven R Zeldenrust, Joseph R. Mikhael, Vivek Roy, Robert A Kyle
Journal: Blood (2011)
Synthesis of Self‐Assembled Spermidine‐Carbon Quantum Dots Effective against Multidrug‐Resistant Bacteria
Authors: Yu‐Jia Li, Scott G. Harroun, Yu‐Chia Su, Chun‐Fang Huang, Binesh Unnikrishnan, Han‐Jia Lin, Chia‐Hua Lin, Chih‐Ching Huang
Journal: Advanced Healthcare Materials (2016)

This study reports a two‐step method to synthesize spermidine‐capped fluorescent carbon quantum dots (Spd–CQDs) and their potential application as an antibacterial agent. Fluorescent carbon quantum dots (CQDs) are synthesized by pyrolysis of ammonium citrate in the solid state and then modified with spermidine by a simple heating treatment without a coupling agent. Spermidine, a naturally occurring polyamine, binds with DNA, lipids, and proteins involved in many important processes within organisms such as DNA stability, and cell growth, proliferation, and death. The antimicrobial activity of the as‐synthesized Spd–CQDs (size ≈4.6 nm) has been tested against non‐multidrug‐resistant E. coli , S. aureus , B. subtilis , and P. aeruginosa bacteria and also multidrug‐resistant bacteria, methicillin‐resistant S. aureus (MRSA). The minimal inhibitory concentration value of Spd–CQDs is much lower (&gt;25 000‐fold) than that of spermidine, indicating their promising antibacterial characteristics. The mechanism of antibacterial activity is investigated, and the results indicate that Spd–CQDs cause significant damage to the bacterial membrane. In vitro cytotoxicity and hemolysis analyses reveal the high biocompatibility of Spd–CQDs. To demonstrate its practical application, in vitro MRSA‐infected wound healing studies in rats have been conducted, which show faster healing, better epithelialization, and formation of collagen fibers when Spd–CQDs are used as a dressing material.
Abstract 3102: Identify potential therapeutic drugs on head and neck cancer through systemic bioinformatics approach
Authors: Chen Yin-Ju, Jeng-Fong Chiou
Journal: Cancer Research (2016)

Abstract Head and neck cancer (HNC) is one of the ten most frequent cancers worldwide. In Taiwan, with the the rising incidence in the past decade, HNC has become the fourth male malignant disease since year 2009. The standard therapy methods of HNC are surgery, radiation, chemotherapy or the combination of these modalities. Overall 5-year survival rate in patients with HNC is one of the lowest among common malignant neoplasms treatment of this disease and has not significantly improved over the past decades. To improve the identification of potential therapeutic drug process, integrating the signature of diseases, genes, and drugs was analyzed through bioinformatics method to find therapeutic candidates through comparison of gene signatures between disease and drug treatment. Here, we integrated HNC gene signatures (including 202 oral squamous carcinomas and 69 normal control species) and connectivity map drug database, and after querying, the drug shown with negative correlation may serve as therapeutic candidates to reverse oral cancer signature. Four potential small molecules with antitumor properties including natural product extracts or clinical therapeutic drugs in other diseases were identified. One of the natural product extracts was found it inhibited cell migration ability, cell invasion capacity and cancer stem cell sphere formation capability. Furthermore, the compound was demonstrated that tit regulated the epithelial-mesenchymal transition markers, suppressed the expression of stemness-related transcription factors (SOX2, Oct-4, and NANOG), and increased the expression of cell differentiation marker (CK18). The compound can also increase cell sensitivity to chemodrug- and radiation treatment then then suppress tumor growth in vitro and in vivo. Taking together, our study demonstrates a novel approach in drug development, by a bioinformatics method to effectively identify potential compounds for head and neck cancer therapy. Citation Format: Chen Yin-Ju, Jeng-Fong Chiou. Identify potential therapeutic drugs on head and neck cancer through systemic bioinformatics approach. [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 3102.
MicroRNAs in idiopathic pulmonary fibrosis: involvement in pathogenesis and potential use in diagnosis and therapeutics
Authors: Huimin Li, Xiaoguang Zhao, Hongli Shan, Haihai Liang
Journal: Acta Pharmaceutica Sinica B (2016)

MicroRNAs (miRNAs) are a class of phylogenetically conserved, non-coding short RNAs, 19-22 nt in length which suppress protein expression through base-pairing with the 3'-untranslated region of target mRNAs. miRNAs have been found to participate in cell proliferation, differentiation and apoptosis. Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and high lethality fibrotic lung disease for which currently there is no effective treatment. Some miRNAs have been reported to be involved in the pathogenesis of pulmonary fibrosis. In this review, we discuss the role of miRNAs in the pathogenesis, diagnosis and treatment of IPF.
Longer Duration and Earlier Age of Onset of Paternal Betel Chewing and Smoking Increase Metabolic Syndrome Risk in Human Offspring, Independently, in a Community-Based Screening Program in Taiwan
Authors: Amy Ming-Fang Yen, Barbara J. Boucher, Sherry Yueh-Hsia Chiu, Jean Ching-Yuan Fann, Sam Li-Sheng Chen, Kuo-Chin Huang, Hsiu-Hsi Chen
Journal: Circulation (2016)

Transgenerational effects of paternal Areca catechu nut chewing on offspring metabolic syndrome (MetS) risk in humans, on obesity and diabetes mellitus experimentally, and of paternal smoking on offspring obesity, are reported, likely attributable to genetic and epigenetic effects previously reported in betel-associated disease. We aimed to determine the effects of paternal smoking, and betel chewing, on the risks of early MetS in human offspring.The 13 179 parent-child trios identified from 238 364 Taiwanese aged ≥20 years screened at 2 community-based integrated screening sessions were tested for the effects of paternal smoking, areca nut chewing, and their duration prefatherhood on age of detecting offspring MetS at screen by using a Cox proportional hazards regression model.Offspring MetS risks increased with prefatherhood paternal areca nutusage (adjusted hazard ratio, 1.77; 95% confidence interval [CI], 1.23-2.53) versus nonchewing fathers (adjusted hazard ratio, 3.28; 95% CI, 1.67-6.43) with >10 years paternal betel chewing, 1.62 (95% CI, 0.88-2.96) for 5 to 9 years, and 1.42 (95% CI, 0.80-2.54) for <5 years betel usage prefatherhood (Ptrend=0.0002), with increased risk (adjusted hazard ratio, 1.95; 95% CI, 1.26-3.04) for paternal areca nut usage from 20 to 29 years of age, versus from >30 years of age (adjusted hazard ratio,1.61; 95% CI, 0.22-11.69). MetS offspring risk for paternal smoking increased dosewise (Ptrend<0.0001) with earlier age of onset (Ptrend=0.0009), independently.Longer duration of paternal betel quid chewing and smoking, prefatherhood, independently predicted early occurrence of incident MetS in offspring, corroborating previously reported transgenerational effects of these habits, and supporting the need for habit-cessation program provision.
Abstract 1093: The melanoma-enriched microRNA miR-4731 regulates genes involved in cell cycle and the melanosome
Authors: Mitchell S. Stark, Lisa Tom, Glen M. Boyle, Vanessa F. Bonazzi, Adrian C. Herington, Pamela M. Pollock, Nicholas K. Hayward
Journal: Cancer Research (2016)

Abstract We previously identified miR-4731-5p (miR-4731) as a melanoma-enriched microRNA following comparison of melanoma with other cell lines from solid malignancies. Additionally, miR-4731 has been found in serum from melanoma patients and expressed less abundantly in metastatic melanomas from stage IV patients relative to stage III patients. As miR-4731 has no known function, we used biotin-labelled miRNA duplex pull-down to identify binding targets of miR-4731 in three melanoma cell lines. Using the miRanda miRNA binding algorithm, all pulled-down transcripts common to the three cell lines (n = 1092) were predicted to be targets of miR-4731 and gene-set enrichment analysis of these (via STRING v9.1) highlighted significantly associated genes related to the ‘cell cycle’ and ‘melanosome’ pathways. Following miR-4731 overexpression, a selection (n = 81) of pull-down transcripts underwent validation using a custom qRT-PCR array. These data revealed that miR-4731 regulates multiple genes associated with the cell cycle (e.g. CCNA2, ORC5L, and PCNA) and melanosome (e.g. RAB7A, CTSD, and GNA13). Furthermore, members of the synovial sarcoma X breakpoint family (SSX) (melanoma growth promoters) were also down-regulated (e.g. SSX2, SSX4, and SSX4B) as result of miR-4731 overexpression. We therefore speculate that loss of miR-4731 expression supports melanoma growth by, in part; reducing its regulatory control of SSX expression levels together with members of the cell cycle pathway, which warrants further investigation. Citation Format: Mitchell S. Stark, Lisa Tom, Glen M. Boyle, Vanessa F. Bonazzi, Adrian C. Herington, Pamela M. Pollock, Nicholas K. Hayward. The melanoma-enriched microRNA miR-4731 regulates genes involved in cell cycle and the melanosome. [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 1093.
Efficacy of BGJ398, a fibroblast growth factor receptor (FGFR) 1-3 inhibitor, in patients (pts) with previously treated advanced/metastatic urothelial carcinoma (mUC) with <i>FGFR3</i> alterations.
Authors: Sumanta K. Pal, Jonathan E. Rosenberg, Bhumsuk Keam, Juergen Wolf, Raanan Berger, Christian Dittrich, Jean H. Hoffman-Censits, David Quinn, Ruud van der Noll, Howard A. Burris, Matt D. Galsky, Gwenaelle Gravis, Jae-Lyun Lee, Jacques Medioni, Amir Mortazavi, Pablo Maroto, Katie Parker, Xueying Chen, Randi Isaacs, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2016)

4517 Background: FGFR3 alterations are frequent in UC (≈ 21%) and have a putative role in pathogenesis and progression. Antitumor activity observed in pts with UC in a phase 1 trial of the FGFR inhibitor BGJ398 (NCT01004224) led to initiation of an extended cohort of genetically selected pts to further characterize BGJ398 activity in UC. Methods: Eligible pts had mUC with activating FGFR3 mutations/fusions and prior platinum-based chemotherapy unless contraindicated. Pts received BGJ398 at the recommended phase 2 dose (RP2D)/schedule (125 mg once daily, 3 weeks on/1 week off). Overall response rate (ORR) and safety were evaluated. Results: At data cutoff (Nov 2, 2015), 33 pts with FGFR3-altered mUC (mutation [n = 31], fusion [n = 2]; based on mUC tissue) were enrolled. Bone or liver metastases were present in 42% and 48% of pts, respectively. Most pts (76%) had ≥ 2 prior therapies. The Kaplan-Meier estimate of median duration of exposure was 13.3 weeks (95% CI, 7.0-22.3 weeks); 15 pts (45%) remained on treatment at data cutoff (max, 42+ weeks). The ORR in 25 evaluable pts was 36% and included 1 unconfirmed complete response (CR; pathologically confirmed in a pt with persistent bone metastases after 2 cytotoxic regimens) and 8 partial responses (4 confirmed). Most responses were observed after 2 treatment cycles. Of 7 pts with stable disease, 6 had tumor reductions ranging from 10%-26%. Safety was similar to prior reports of the RP2D/schedule, with most adverse events (AEs) being G1/2 and manageable. Frequent AEs (all G; G3/4) were hyperphosphatemia (42%; 6%), constipation (36%; 0%), fatigue (36%; 6%), and elevated serum creatinine (36%; 3%). Conclusions: BGJ398 monotherapy is well tolerated and has encouraging activity in heavily pretreated pts with mUC. Responses were observed in pts with multiple prior therapies and in pts with bone metastases. This trial validates the biological role of FGFR3 and clinical benefit conferred by its blockade in UC. The 36% ORR observed in these patients is notable given their poor prognosis and limited therapeutic options. The CR in the pt with osseous metastases is unique and warrants further exploration. Clinical trial information: NCT01004224.
Abstract LB-268: Androgen signaling in cancer-associated fibroblasts contributes to progression of prostate cancer
Authors: Chun-Peng Liao, Leng-Ying Chen, Andrea Luethy, Youngsoo Kim, Robert MacLeod, Mitchell Gross
Journal: Cancer Research (2016)

Abstract Interactions between epithelial and stromal cells are important in the development of prostate cancer (PCa). Cancer-associated fibroblasts (CAFs) have been to support tumor progression, metastasis, and differentiation. Androgen receptor (AR) and related pathways are known to support the growth and survival of prostate epithelial cancer cells, the roles of AR-dependent processes in cancerous stroma are less clear. We sought to investigate if AR-dependent pathways present in CAF cells influence the growth and tumorogencity of epithelial cancer cells in relation to androgen-deprivation therapy in prostate cancer. Murine CAFs were isolated from a well-described PTEN-dependent cancer mouse model. A co-culture system was developed based on multiple lines of murine CAFs grown along with human prostate cancer epithelial cells, and a murine-specific anti-sense oligonucleotide (ASO) against murine AR was used to specifically suppress AR expression in murine CAFs in this system. Using this co-culture system, we found that murine CAFs promoted cell proliferation and colony formation in several human prostate cancer cell lines. Further, these processes were decreased by suppression of AR-expression in CAFs. Expression of genes related to tumorogenicity in epithelial cells were investigated by real-time quantitative PCR. Markers associated with epithelial-mesenchymal transition (EMT) and stemness were increased in human prostate cancer cells grown with low-AR CAFs. Our data indicates that suppression of AR in CAFs results in down-regulation in the growth and tumorogenecity of prostate cancer cells through pathways related to EMT and “cell reprograming”. As such, development of therapies which inhibit the tumor-promoting pathways present in stromal cells may be one approach to improve the treatment of prostate cancer. Citation Format: Chun-Peng Liao, Leng-Ying Chen, Andrea Luethy, Youngsoo Kim, Robert MacLeod, Mitchell Gross. Androgen signaling in cancer-associated fibroblasts contributes to progression of prostate 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 LB-268.
Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with <i>O<sup>6</sup>-methylguanine-DNA methyltransferase</i> (<i>MGMT</i>) promoter methylation: Final results of the multicenter, randomized, open-label, controlled, phase III CENTRIC study.
Authors: Roger Stupp, Monika E. Hegi, Thierry Gorlia, Sara Erridge, Danica Grujicic, Joachim Peter Steinbach, Wolfgang Wick, Rafal Tarnawski, Do-Hyun Nam, Astrid Weyerbrock, Peter Hau, Martin JB Taphoorn, Louis B. Nabors, David A. Reardon, Martin J. Van Den Bent, James R. Perry, Yong Kil Hong, Christine Hicking, Martin Picard, Michael Weller
Journal: Journal of Clinical Oncology (2013)

LBA2009 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Frozen tissue service offers fertility hope to young people with cancer
Authors: Jacqui Wise
Journal: BMJ (2016)

Scientists at Edinburgh University have developed a service to store testicular tissue from boys as young as 1 who are at risk of infertility because of cancer treatment. In future boys as well as girls might be able to have their fertility restored subsequent to chemotherapy.

The announcement comes after the birth of the first UK baby to be born after his mother had a transplant of her own, previously frozen, ovary tissue. The 33 year old woman from Edinburgh had a section of her ovary removed 11 years ago, …
Abstract 2760: Does a short open reading frame (sORF)-encoded protein participate in DNA repair
Authors: Les Hanakahi, Matthew Summerlin, Yi-Chia Tang, Jinho Heo
Journal: Cancer Research (2016)

Abstract Non-homologous end joining (NHEJ) is one of the major mechanisms for rejoining of DNA double-strand breaks. Knowledge of the molecular mechanism of NHEJ will help us to understand how this process preserves genome integrity, and how NHEJ errors cause chromosomal rearrangements that lead to cancer. Several critical participants in the NHEJ pathway have been identified and some mechanistic steps have been characterized. At present, a significant gap in our understanding of NHEJ is how NHEJ factors assemble at DSBs. It is plausible that additional, as yet unidentified, factors contribute to NHEJ assembly. We have biochemical and biological data implicating a short open reading frame (sORF)-encoded protein in NHEJ. sORFs are found in all genomes. Ribosome profiling, mass spectroscopy and RNA sequencing have predicted the existence of numerous sORF-encoded proteins of &amp;lt;100 amino acids in size. While the functional significance of the majority of these small proteins is not clear, we recently discovered that a 69 amino acid protein encoded by chromosome 7 open-reading frame 49 (C7orf49) interacts with critical NHEJ factors in human cells, and stimulates NHEJ in cell-free extracts. Treatment of cells with the DSB-inducing agent etoposide increased C7orf49 expression and nuclear localization, and knockdown of C7orf49 sensitized cells to etoposide. C7orf49-deficient cells exhibited a mild proliferation defect and increased sensitivity to etoposide. Our data suggest that this small protein may play an important role in double-strand beak repair by NHEJ and highlights the potential biological relevance of sORF-encoded proteins in the DNA damage response and in DNA repair. Citation Format: Les Hanakahi, Matthew Summerlin, Yi-Chia Tang, Jinho Heo. Does a short open reading frame (sORF)-encoded protein participate in DNA repair. [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 2760.