bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5216: Exosome as a vehicle for delivery of membrane protein therapeutics, PH20 for enhanced tumor penetration and anti-tumor efficacy
Authors: yang yoosoo , Hong Yeonsun , Kim Gi Beom , Nam Gihoon , Kim In-san 
Published: August 2018

Abstract
As biochemical and functional studies of membrane protein remain a challenge, there is growing interest in the application of nanotechnology to solve the difficulties of developing membrane protein therapeutics. Exosome, composed of lipid bilayer enclosed nano-sized extracellular vesicles, is a successful platform for providing a native membrane composition. Here, we report an enzymatic exosome, which harbors native PH20 hyaluronidase (Exo-PH20), was able to penetrate deeply into tumor foci via hyaluronan degradation, allowing tumor growth inhibition and increased T cell infiltration into the tumor. This exosome-based strategy was developed to overcome the immunosuppressive and anti-cancer therapy-resistant tumor microenvironment, which is characterized by an overly accumulated extracellular matrix. Notably, our engineered exosome with the native GPI-anchored form of hyaluronidase had a higher enzymatic activity than a truncated form of the recombinant protein. In addition, the exosome-mediated co-delivery of PH20 hyaluronidase and a chemotherapeutic (doxorubicin) efficiently inhibited tumor growth. This exosome is designed to degrade hyaluronan along the path of its movement, thereby augmenting nanoparticle penetration and drug diffusion. Our results thus show that this is a promising exosome-based platform that harbors not only a membrane-associated enzyme with high activity but also therapeutic payloads.
Citation Format: yoosoo yang, Yeonsun Hong, Gi Beom Kim, Gihoon Nam, In-san Kim. Exosome as a vehicle for delivery of membrane protein therapeutics, PH20 for enhanced tumor penetration and anti-tumor efficacy [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 5216.
Abstract 5229: Expression and regulation of chondroitin sulfate in prostate cancer
Authors: Nakouzi Nader Al , Wang Chris Kedong , Nelepcu Irina , Crouzit Coralie , Nabavi Noushin , Almami Amal , Oo Htoo Zarni , Clausen Thomas Mandel , Gustavsson Tobias , Salanti Ali , Daugaard Mads 
Published: August 2018

Abstract
Increased levels of chondroitin sulfate (CS) glycosaminoglycans (GAGs) in prostate cancer (PC) have been observed for more than three decades. In 1984, De Klerk et al. noted that hyperplastic and cancerous prostate contained elevated levels of CS while other GAGs, like heparin sulfate (HS), were decreased. Chondroitin sulfate-modified proteoglycans (CSPGs), such as versican or tomoregulin (TENB2), have been promoted as PC progression markers. They have been associated with cell attachment to the matrix, the metastatic phenotype, disease progression, and androgen independence. Functionally, pericellular enrichment of CSPGs in the PC microenvironment promotes cell motility. Our team has discovered that human tumors display high levels of a specific highly sulfate type of CS normally restricted to placental and fetal tissue compartment. This "oncofetal" CS (ofCS) GAG can be conveniently detected and targeted using recombinant CS-binding VAR2CSA (rVAR2) lectins, derived from the malaria parasite Plasmodium falciparum. Recently, we identified chondroitin sulfate biosynthesis as being controlled by androgens in PC, modulating expression of the CHST11 and CHST13 carbon-4 GalNAc sulfotransferases. We established that these enzymes are under direct control of the androgen receptor (AR), regulating synthesis of the cancer-associated ofCS-modification on CSPGs. Glycosylation has a key role in many important biologic processes in cancer including cell differentiation. We identified CHST11 to be highly increased in high-risk neuroendocrine prostate cancer (NEPC) both in vitro, in vivo, and in situ. Moreover, cells that expressed neuroendocrine markers showed higher level of sulfation and ofCS. Our work reveals that alterations in GAG signatures regulated by AR might be responsible for progression neuroendocrine differentiation in prostate cancer. The prostate is an abundant secretor of PGs, and tumor-specific alterations in GAG signatures such as ofCS therefore constitute an untapped reservoir of potential biomarkers to be exploited as therapeutic targets.
Citation Format: Nader Al Nakouzi, Chris Kedong Wang, Irina Nelepcu, Coralie Crouzit, Noushin Nabavi, Amal Almami, Htoo Zarni Oo, Thomas Mandel Clausen, Tobias Gustavsson, Ali Salanti, Mads Daugaard. Expression and regulation of chondroitin sulfate 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 5229.
Abstract 5232: 1,25-Dihydroxyvitamin D3 mitigates lung cancer cell mediated mitochondrial dysfunction in human skeletal muscle
Authors: Ryan Zachary C. , Craig Theodore A. , Wang Xuewei , Delmotte Philippe , Salisbury Jeffrey L. , Lanza Ian R. , Sieck Gary C. , Kumar Rajiv 
Published: August 2018

Abstract
To assess cellular mechanisms that could contribute to muscle weakness in the context of cancer cachexia, we evaluated the effect of conditioned medium (CM) from highly tumorigenic Lewis lung carcinoma (LLC1) cells, CM from less tumorigenic MLE12 cells and non-CM on human skeletal muscle mitochondrial morphology and function. We assessed mitochondrial oxygen consumption, morphology, enzyme activity and gene expression in human skeletal muscle cells in the presence of tumor conditioned medium or control medium. We examined the secretome of LLC1 cells for mediators of skeletal muscle changes. We demonstrate that LLC1 CM inhibits cellular O2 consumption rate (OCR) and increases the proton production rate in human skeletal muscle cells. Mitochondrial fragmentation and the expression of the fission mediator, FIS1, are increased, whereas the expression of fusion mediators, OPA1 and MFN2 are reduced by LLC1 CM. LLC1 CM reduces pyruvate dehydrogenase (PDH) activity thereby limiting the production of acetyl CoA. Reduced PDH activity is associated with reduced PDHA1 sub-unit expression. The amount inactive phospho-PDH is increased in association with reduced PDP2 expression and increased PDK4 and SIRT4 expression in human skeletal muscle cells treated with LLC1 CM. The expression of several signaling pathways is altered by LLC1 CM in human skeletal muscle cells. When compared to MLE12 cells, LLC1 cells show increased expression of mRNAs encoding several potential mediators of altered muscle function such as Gdf15, TGFβ-induced protein, IL11, Il27, Il33, Il34, and PTH-like protein. We show that the active vitamin D metabolite, 1α,25(OH)2D3, that we previously demonstrated increases myoblast mitochondrial oxygen consumption and PDH activity, mitigates LLC1 CM effects on hSkMC OCR, mitochondrial fragmentation and mediators thereof. Mitochondrial oxygen consumption, morphology and enzyme activity in human skeletal muscle cells are inhibited or altered by tumor cell conditioned medium, and are reversed by 1α,25(OH)2D3, the active metabolite of vitamin D.
Citation Format: Zachary C. Ryan, Theodore A. Craig, Xuewei Wang, Philippe Delmotte, Jeffrey L. Salisbury, Ian R. Lanza, Gary C. Sieck, Rajiv Kumar. 1,25-Dihydroxyvitamin D3 mitigates lung cancer cell mediated mitochondrial dysfunction in human skeletal muscle [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 5232.
Abstract 5239: Gli is a primary driver of prostate cancer cell growth
Authors: Li Na , Moore Jackson , Troung Sarah , Nouri Mannan , Foo Jane , Buttyan Ralph 
Published: August 2018

Abstract
Canonical Hedgehog signaling is a Smoothened- (Smo-) driven process that activates transcription from Gli proteins. However, we have shown that Hedgehog is activated in prostate cancer (PCa) cells by a non-canonical, non-Smo-dependent process mediated by the binding of transcriptionally active androgen receptors (AR) to the protein processing domain on Gli2/3. This binding competes with β-TrCP, and protects Gli3 (the predominant Gli isoform in PCa cells) from cleavage to its truncated repressor form (Gli3R). Our observations are consistent with the idea that AR transcriptional activity (mediated by liganded full-length AR or by truncated ARs) is effectively coupled to Gli activity in PCa. Here we present our evidence that Gli is the primary driver of PCa cell growth and that suppression of Gli transcriptional activity or interference with AR binding to Gli (using a decoy peptide) is a strong growth suppressor of androgen-dependent (AD) and -independent (AI) PCa cell lines. Gli transcription was inhibited by GANT61 or HPI-1 or by exogenous overexpression of a Gli3R cDNA. Each of these conditions significantly suppressed the growth of LNCaP parental (AD) and LNCaP-AI cells. Knockdown of Gli3 with siRNA decreased growth of a wide variety of PCa cell lines up to 75%. Finally, a decoy peptide (270aa) containing the Gli2 AR binding site displaced Gli3 from AR complexes, increased the levels of Gli3R and significantly suppressed growth of AI cell lines. Collectively, our data supports the idea that androgen-driven growth of PCa is a result of non-canonical activation of Gli and that interference with Gli binding to DNA or with the Gli-AR interaction is a means for suppressing PCa cell growth.
Citation Format: Na Li, Jackson Moore, Sarah Troung, Mannan Nouri, Jane Foo, Ralph Buttyan. Gli is a primary driver of prostate cancer cell growth [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 5239.
Abstract 526: Mechanistic studies of TAp63 regulated oncogenic long noncoding RNAs in breast cancer metastasis
Authors: Li Xiaobo 
Published: August 2018

Abstract
Advanced breast cancer metastasis is the major cause of relapse. However, no effective treatment exists for the metastatic stage of breast cancer. Recently, regulatory long non-coding RNAs (lncRNAs) have been highlighted in p53 regulated genome protection in cancer metastasis; therefore approaches targeting lncRNAs is a promising strategy to treat breast cancer metastasis. Our laboratory aims to design such approaches through focusing on the p53 family member, TAp63 and its regulated lncRNAs. TAp63 has critical tumor suppressor function in breast cancer. Loss of function transforms mammary epithelial cells (MECs) into tumor initiating cells.
Our lab showed that loss of TAp63 in mouse MECs induces the expression of several lncRNAs. A locus conservation strategy was applied to identify the homologous lncRNAs relevant in human breast cancer progression. Targeting these lncRNAs with CRISPR/CAS9 system in human breast cancer cell line in mouse xenograft model demonstrated that they are required for the tumorigenic and metastatic potential of human breast cancer cells in vivo. The high-throughput protein microarray screening method was used to identify proteins that interact with these lncRNAs and facilitate their oncogenic functions. Importantly, the expression of both protein and lncRNA is negatively correlated with patient survival in breast cancer dataset, and positively correlated with breast cancer progression in human tissue microarrays.
We demonstrate the oncogenic effects of these lncRNAs in promoting breast cancer metastasis. Our data indicates that targeting lncRNAs directly or their effectors indirectly will provide innovative and effective therapeutics aiming the metastatic stage of breast cancer.
Citation Format: Xiaobo Li. Mechanistic studies of TAp63 regulated oncogenic long noncoding RNAs in breast cancer metastasis [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 526.
Abstract 5264: A prospective study of dietary inflammatory index scores and colorectal cancer risk: The Singapore Chinese Health Study
Authors: Luu Hung N. , Wang Renwei , Shivappa Nittin , Hébert James R. , Koh Woon-Puay , Yuan Jian-Min 
Published: August 2018

Abstract
Background. Colorectal cancer (CRC) has increased dramatically in Singapore during the past three decades and becomes the most common cancer when both sexes combined. Extensive evidence shown the specific component of diet may modulate inflammation and thus influence to disease endpoints, including CRC. We determine the association between diet inflammatory index (DII)TM, a literature-derived, population-based score, developed to assess the inflammatory potential of an individual's diet, and CRC risk in Singaporean Chinese, using data from the Singaporean Chinese Health Study (SCHS).
Methods. A total of 61,321 SCHS study participants was included in the current analysis. The DII scores were calculated using validated food frequency questionnaires (FFQs). Cox proportional hazards model was performed to assess the association between DII scores and CRC risk.
Results. There was a positive association between DII score and CRC risk in females (HRs and respective 95% CIs: 1.30 (1.02-1.64), 1.32 (1.03-1.67), and 1.20 (0.93-1.55) for Q2, Q3, Q4 vs. Q1). DII score was associated with increased risk of colon cancer (HRQ4vsQ1=1.35, 95% CI: 1.08-1.68; Ptrend=0.04) and this association appeared stronger in females. Among never-smokers, the highest quartile of DII was associated with statically significant 43% increased risk of developing CRC in women compared to those in the lowest quartile (HRQ4vsQ1=1.43, 95% CI: 1.01-2.02; Ptrend=0.03). There was also a dose-response association between DII scores with colon cancer in women among those with BMI less than 25 (HRQ4vsQ1=1.66, 95% CI: 1.03-2.68; Ptrend=0.04).
Conclusions. Consumption of anti-inflammatory foods will reduce the risk of colorectal cancer, particularly among females and non-smokers. This will have substantial public health impact as prevention program should focus on promoting healthy and anti-inflammatory foods to reduce the risk of colorectal cancer.
Citation Format: Hung N. Luu, Renwei Wang, Nittin Shivappa, James R. Hébert, Woon-Puay Koh, Jian-Min Yuan. A prospective study of dietary inflammatory index scores and colorectal cancer risk: The Singapore Chinese Health Study [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 5264.
Abstract 5288: MPNST treatment and diagnosis in NF1: A health economic model
Authors: Turkson Lydia , Mamuszka Hannah , Grimshaw Kyla , Marshall Erica Marie 
Published: August 2018

Abstract
Biomarkers have many applications along the care process in rare cancers and have potential to optimize treatment decisions. However, many diagnostic tests struggle to gain market access and appropriate value in terms of payer coverage because of a lack of evidence on their health economic benefit to patients. CMS reimbursement guidelines, of cost-plus pricing for diagnostics does not always work for niche small rare disease subpopulations. Nor does it reflect the lifelong value of effective patient care.
To address this, we have developed a cost benefit model for early diagnostic intervention, based on retrospective data to determine mutation status and monitor for disease progression in people diagnosed with neurofibromatosis type 1 (NF1) and soft tissue tumors. NF1 is an autosomal dominant hereditary cancer syndrome that affects around 1:2,500 people and is caused by mutations in the NF1 gene. 50% of patients can have few to many neurofibroma which vary in clinical behavior from benign to malignant. About 10% of people can develop malignant peripheral nerve sheath tumors (MPNSTs) thought to develop from pre-existing benign neurofibroma. Currently, there is no reliable way of knowing which individual and which tumors are malignant. MPNSTs are often difficult to diagnose in the early phases with current imaging methods like CT or MRI. Overall, these patients face a lifetime risk of cancer up to 16-26% higher than the normal population. Once metastasizes MPNSTs are associated with poor prognosis, less than 25% survival rate at 5 years.
We built a model used retrospective anonymized patient treatment records to demonstrate cost and risk based benefits to patients, payers and clinical practitioners, on the effect of early intervention versus late on treatment cost, and patient outcome in the long-term care process. For NF1 patients. In conclusion, our model proposes a new framework to engage healthcare insurers and managed care physician groups in the US to quantify the health economic benefits of prognostic biomarker tests in patient populations with a lifelong genetic predisposition to cancer.
Citation Format: Lydia Turkson, Hannah Mamuszka, Kyla Grimshaw, Erica Marie Marshall. MPNST treatment and diagnosis in NF1: A health economic model [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 5288.
Abstract 5290: My crown or my health: Black women's knowledge of breast cancer and hair product-related risk
Authors: Teteh Dede , Clark Phyllis , Dawkins-Moultin Lenna , Kittles Rick , Montgomery Susanne 
Published: August 2018

Abstract
Introduction/Purpose: Black women now have higher breast cancer (BC) incidence and mortality than White women. They also use more hair products containing hormonally-active chemicals. Studies are beginning to link chemical ingredients in these products to BC risk. Little is known about community knowledge of BC and the potential association with hair product-related risk. The purpose of this study was to evaluate the hazard level of hair products used by Black women, and assess their knowledge about BC and hair product-related risks.
Methodology: We employed principles of community-based participatory research and conducted the study through partnership between community advocates and university scientists. We collected hair products from locations frequented by Black women and hair stylists and used the Environmental Working Group's Skindeep© database to evaluate ingredient toxicity. We then explored knowledge of BC and hair product-related risk using a 41-item survey. Survey data were analyzed using SPSS.
Results: All 54 products evaluated contained hazardous ingredients. Fourteen of the ingredients had an overall high hazard rating between 7-10, with 10 indicating very high levels of toxicity. The potential harmful effects of these chemicals include cancer, endocrine disruption and reproductive system toxicant. Survey data showed most women (62%) in the sample had a college or graduate degree. Participants (n=211) were more knowledgeable about the diagnosis and treatment of BC (46.3%), lifestyle-related risk factors (59.6%), and genetic risk factors (54.9%) than about hair product risk (40.8%).
Conclusion: Several hair products frequently used by black women contained ingredients that have potential links to BC. Though the women in this study were highly educated, they had limited knowledge about the association between BC and toxins found in hair products. Research should further clarify the link between hair products and BC risk. As knowledge is evolving, given our emerging risk understanding, health educators and community advocates can promote efforts for women to learn more about exposure reduction to help them make informed decisions about the risk beauty product chemicals may hold regarding cancer. There is also a need for policies on personal care products that aim to protect the health of our communities.
Citation Format: Dede Teteh, Phyllis Clark, Lenna Dawkins-Moultin, Rick Kittles, Susanne Montgomery. My crown or my health: Black women's knowledge of breast cancer and hair product-related risk [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 5290.
Abstract 5297: LCA: A robust and scalable algorithm to reveal subtle diversity in large-scale single-cell RNA-Seq data
Authors: Cheng Changde , Easton John , Rosencrance Celeste , Li Yan , Ju Bensheng , Chen Wenan , Chen Xiang 
Published: August 2018

Abstract
Single-cell RNA sequencing (scRNA-seq) emerges as a powerful tool to characterize cell-to-cell variation and dynamics in a seemingly homogenous population. Efficient and affordable, scRNA-seq is gaining in popularity in both basic and translational biological research areas. However, significant challenges arise in the analysis of scRNA-seq data, including low signal-to-noise ratio with high data sparsity, rising scalability hurdles with hundreds of thousands of cells, and more. Due to inherent complexities in scRNA-seq data, the performance of currently available algorithms may not always be optimal even for fundamental tasks such as identifying heterogeneous subpopulations in the data. In this study, we developed Latent Cellular Analysis (LCA), a machine learning based analytical pipeline that combines similarity measurement by latent cellular states with a graph-based clustering algorithm. LCA features a dual-space model search for both the optimal number of subpopulations and the informative cellular states distinguishing them. LCA provides heuristic solutions for population number inference, dimension reduction, feature selection and confounding factor removal without explicit gene filtering. LCA has proved to be robust, accurate and powerful by comparison to multiple state-of-the-art computational methods on large-scale real and simulated scRNA-seq data. Importantly, LCA's ability to learn from representative subsets of the data provides scalability, thereby addressing a significant challenge for growing sample size in scRNA-seq data analysis.
Citation Format: Changde Cheng, John Easton, Celeste Rosencrance, Yan Li, Bensheng Ju, Wenan Chen, Xiang Chen. LCA: A robust and scalable algorithm to reveal subtle diversity in large-scale single-cell RNA-Seq data [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 5297.