tbuckley/cabot-search huggingface dataset:
Association of Early Postresuscitation Hypotension With Survival to Discharge After Targeted Temperature Management for Pediatric Out-of-Hospital Cardiac Arrest
Authors: Alexis A. Topjian, Russell Telford, Richard Holubkov, Vinay M. Nadkarni, Robert A. Berg, J. Michael Dean, Frank W. Moler
Journal: JAMA Pediatrics (2017)

Out-of-hospital cardiac arrest (OHCA) occurs in more than 6000 children each year in the United States, with survival rates of less than 10% and severe neurologic morbidity in many survivors. Post-cardiac arrest hypotension can occur, but its frequency and association with survival have not been well described during targeted temperature management.To determine whether hypotension is associated with survival to discharge in children and adolescents after resuscitation from OHCA.This post hoc secondary analysis of the Therapeutic Hypothermia After Pediatric Cardiac Arrest (THAPCA) trial included 292 pediatric patients older than 48 hours and younger than 18 years treated in 36 pediatric intensive care units from September 1, 2009, through December 31, 2012. Participants underwent therapeutic hypothermia (33.0°C) vs therapeutic normothermia (36.8°C) for 48 hours. All participants had hourly systolic blood pressure measurements documented during the initial 6 hours of temperature intervention. Hourly blood pressures beginning at the time of temperature intervention (time 0) were normalized for age, sex, and height. Early hypotension was defined as a systolic blood pressure less than the fifth percentile during the first 6 hours after temperature intervention. With use of forward stepwise logistic regression, covariates of interest (age, sex, initial cardiac rhythm, any preexisting condition, estimated duration of cardiopulmonary resuscitation [CPR], primary cause of cardiac arrest, temperature intervention group, night or weekend cardiac arrest, witnessed status, and bystander CPR) were evaluated in the final model. Data were analyzed from February 5, 2016, through June 13, 2017.Hypotension.Survival to hospital discharge.Of 292 children (194 boys [66.4%] and 98 girls [33.6%]; median age, 23.0 months [interquartile range, 5.0-105.0 months]), 78 (26.7%) had at least 1 episode of early hypotension. No difference was observed between the therapeutic hypothermia and therapeutic normothermia groups in the prevalence of hypotension during induction and maintenance (73 of 153 [47.7%] vs 72 of 139 [51.8%]; P = .50) or rewarming (35 of 118 [29.7%] vs 19 of 95 [20.0%]; P = .10) during the first 72 hours. Participants who had early hypotension were less likely to survive to hospital discharge (20 of 78 [25.6%] vs 93 of 214 [43.5%]; adjusted odds ratio, 0.39; 95% CI, 0.20-0.74).In this post hoc secondary analysis of the THAPCA trial, 26.7% of participants had hypotension within 6 hours after temperature intervention. Early post-cardiac arrest hypotension was associated with lower odds of discharge survival, even after adjusting for covariates of interest.
KLF5 induces apoptosis in colon cancer cells
Authors: Joseph M. Marinaro, Nicholas W. Bateman, Adrian R. Black
Journal: Cancer Research (2006)

4928  KLF5 is a transcription factor that has been linked to enhanced proliferation in multiple non-transformed cell types. In contrast to its growth promoting role in non-transformed cells, KLF5 has been implicated as a tumor suppressor in epithelial tissues including the intestine. An explanation for this paradox comes from the observation that, while KLF5 promotes colony formation in non-transformed intestinal epithelial cells, it inhibits this process in colon cancer cells. These opposing effects were further characterized by manipulating KLF5 expression in various intestinal epithelial cell lines. Retroviral mediated overexpression of KLF5 in HCT-116 and HCT-116b colon cancer cells, but not in non-transformed IEC-18 cells, led to cell death characterized by the appearance of blebbing and shrunken cells, that was not seen in control virus transduced cells. This cells death was due to apoptosis, as indicated by its inhibition by the pan-caspase inhibitor Z-VAD-FMK and by annexin V staining. A link between the observed apoptosis and KLF5 expression was further established by the finding that siRNA-mediated knockdown of KLF5 expression reduced the level of spontaneous apoptosis/annexin V staining in HCT-116b cells (colon carcinoma cells that express relatively high levels of KLF5). The differential ability of KLF5 to induce apoptosis cannot be attributed to genetic differences between the cell lines examined because, in contrast to parental IEC-18 cells, KLF5 induced apoptosis in IEC-18 cells which had been transformed with oncogenic H-Ras (IEC-Ras cells). Notably, the farnesyl-transferase inhibitor L-744,832 blocked the ability of KLF5 to induce apoptosis in Ras-transformed IEC-18 cells. By inhibiting signaling from oncogenic H-Ras but not endogenous K-Ras, this inhibitor reverses the transformed phenotype without appreciable affects on survival or proliferation of H-Ras transformed IEC-18 cells; thus, this finding links both the transformed phenotype and Ras signaling to the differential ability of KLF5 to induce apoptosis in non-transformed and transformed intestinal epithelial cells. Analysis of molecular mechanisms underlying KLF5-induced apoptosis point to the involvement of alterations in inhibitor of apoptosis proteins XIAP and survivin. This work was supported by NIH grant CA16056.
Improved Tumor Penetration and Single-Cell Targeting of Antibody–Drug Conjugates Increases Anticancer Efficacy and Host Survival
Authors: Cornelius Cilliers, Bruna Menezes, Ian Nessler, Jennifer Linderman, Greg M. Thurber
Journal: Cancer Research (2017)

Abstract Current antibody–drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo, yet improves the effectiveness of T-DM1 in vivo. Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758–68. ©2017 AACR.
Abstract 19798: The Nadph Oxidase Nox4 Promotes Endothelial Differentiation From Murine Induced-pluripotent Stem Cells
Authors: Fabian Hahner, Franziska Moll, Ralf P Brandes, Kathrin Schröder
Journal: Circulation (2017)

Out of the seven known isoforms of NADPH oxidase, Nox4 is the only constitutively active one, producing hydrogen peroxide. It is highly expressed in endothelial cells, where it plays an important r...
<sup>131</sup>I-Labeled Copper Sulfide-Loaded Microspheres to Treat Hepatic Tumors via Hepatic Artery Embolization
Authors: Qiufang Liu, Yuyi Qian, Panli Li, Sihang Zhang, Jianjun Liu, Xiaoguang Sun, Michael Fulham, Dagan Feng, Gang Huang, Wei Lu, Shaoli Song
Journal: Theranostics (2017)

Purpose: Transcatheter hepatic artery embolization therapy is a minimally invasive alternative for treating inoperable liver cancer but recurrence is frequent. Multifunctional agents, however, offer an opportunity for tumor eradication. In this study, we were aim to synthesized poly (lactic-co-glycolic acid) (PLGA) microspheres encapsulating hollow CuS nanoparticles (HCuSNPs) and paclitaxel (PTX) that were then labeled with radioiodine-131 (131I) to produce 131I-HCuSNPs-MS-PTX. This compound combines the multi-theranostic properties of chemotherapy, radiotherapy and photothermal therapy. In addition, it can also be imaged with single photon emission computed tomography (SPECT) imaging and photoacoustic imaging. Methods: We investigated the value of therapeutic and imaging of 131I-HCuSNPs-MS-PTX in rats bearing Walker-256 tumor transplanted in the liver. After the intra-arterial (IA) injection of 131I-HCuSNPs-MS-PTX, 18F-Fluorodeoxyglucose (18F-FDG) micro-positron emission tomography/computed tomography (micro-PET/CT) imaging was used to monitor the therapeutic effect. PET/CT findings were verified by immunohistochemical analysis. SPECT/CT and photoacoustic imaging were performed to demonstrate the distribution of 131I-HCuSNPs-MS-PTX in vivo. Results: We found that embolization therapy in combination with chemotherapy, radiotherapy and photothermal therapy offered by 131I-HCuSNPs-MS-PTX completely ablated the transplanted hepatic tumors at a relatively low dose. In comparison, embolization monotherapy or combination with one or two other therapies had less effective anti-tumor efficacy. The combination of SPECT/CT and photoacoustic imaging effectively confirmed microsphere delivery to the targeted tumors in vivo and guided the near-infrared laser irradiation. Conclusion: Our study suggests that there is a clinical theranostic potential for imaging-guided arterial embolization with 131I-HCuSNPs-MS-PTX for the treatment of liver tumors.
A Conservative Tailoring of Ponatinib Dose in Chronic Myeloid Leukemia Patients Can Diminish Adverse Events While Maintaining Efficacy
Authors: Valentín García Gutiérrez, Andrés Novo, Antonio Jimenez-Velasco, Luis Felipe Casado Montero, Fermin Sanchez-Guijo, Raul Perez Lopez, Santiago Osorio-Prendes, Sunil Lakhwani Lakhwani, Angel Ramirez Payer, Guillermo Orti, Maria Teresa Gomez-Casares, Juan Manuel Alonso, Manuel Pérez-Encinas, Rolando Vallansot, Ernesto Pérez Persona, Maria Angeles Portero Frias, María José Ramírez Sánchez, Maria Alicia Senin, Gonzalo Caballero, Soledad Noya, Concepcion Boque, Maribel Mata, Mario Romo, Juan Luis Steegmann, Juan Carlos Hernandez-Boluda
Journal: Blood (2017)
Abstract 14298: The Normal Balance Between Antifibrotic Bmp-7 and Profibrotic Tgf-β Signaling is Lost on the Pressure Overload-induced LV Remodeling and Can Be Modified Favorably. A Translational Study
Authors: Francisco Nistal, David Merino, Ana V Villar, Raquel Garcia-Lopez, Mónica Tramullas, Luis Ruiz-Guerrero, Catalina Ribas, Maria A Hurle
Journal: Circulation (2015)

Introduction: Cytokynes of the Transforming Growth Factor-β(TGF-β) superfamily are involved in tissue fibrosis: TGF-β promotes fibrosis, whereas Bone Morphogenetic Protein-7 (BMP-7) is antifibrotic. Hypothesis: (i) LV remodeling in the pressure overload condition associates disequilibrium in the cellular signals mediated by these cytokynes; and (ii) BMP-7 exerts beneficial effects on LV remodeling and on reverse remodeling. Methods: We studied patients with aortic stenosis (AS; n=45) and surgical controls (n=30), and mice subjected to transverse aortic constriction (TAC; n=24). LV morphology and function were assessed by echocardiography; LV samples were analyzed by qPCR, immunoblotting and histology. Results: Pressure overload diminished the expression of BMP-7 and its effectors pSmad1/5/8 and increased the ratio TGF-β/BMP-7 in the LV from AS-patients and TAC-mice. BMP-7 expression correlated inversely with collagens, fibronectin and β-myosin heavy chain, with the degree of hypertrophy, and with the severity of diastolic dysfunction, and directly with systolic function. Multiple linear regression analysis disclosed BMP-7 and TGF-β as predictors, negative and positive, respectively, of hypertrophy. BMP-7 prevented the hypertrophic program elicited by TGF-β in cultured cardiomyocytes, and the transcriptional activation of Col1A1 promoter-luciferase reporter in NIH-3T3 fibroblasts. In TAC-mice, BMP-7 gain-of-function attenuated the development of structural damage and dysfunction, halted ongoing remodeling and facilitated reverse remodeling. BMP-7 loss-of-function exerted opposite effects. Luciferase reporter assays in NIH-3T3 fibroblasts suggested that BMP-7 promoted the transcription of the inhibitory Smad7, who in turn has a repressing effect on TGFβ signaling. Accordingly, in AS-patients and TAC-mice, the LV expressions of Smad7 and BMP-7 correlated directly. Conclusion: The disequilibrium between BMP-7 and TGF-β signals plays a relevant role in the pressure overload-induced myocardial remodeling in TAC-mice and AS-patients. We suggest that BMP-7 antagonizes the hypertrophic and profibrogenic effects of TGF-β through a mechanism involving Smad7. Funding: PI12/00999; RD12/0042/0018; RD12/0042/0012.
Development of expression-based biomarkers of Dasatinib response in hematologic malignancies
Authors: Monica K. Akre, Amit Mitra, Wen Wang, Chad L. Myers, Brian Van Ness
Journal: Blood Cancer Journal (2017)

Numerous collections of cancer cell lines provide opportunities to characterize genetic signatures that distinguish response and resistance to a variety of drugs.The NCI-60, Cancer Cell Line Encylopedia (CCLE), and the Genomics of Drug Sensitivity in Cancer (GDSC) provide a wealth of information that includes genomic sequences, mutational status, gene expression, as well as response to panels of drugs used in cancer therapies 1-3 .This offers a unique opportunity to apply approaches that may provide genetic profiles that define response and resistance, with the potential to apply these as predictors in clinical decisions.The GDSC is a collection of 1047 cell lines from diverse tumor types that have been tested with 265 drugs 1 .The data collection includes DNA sequence, mutation status, and gene expression data that we have used to develop a pipeline of computational approaches that predict response and resistance.Drug response is determined by a 9 step twofold serial dilution of drug concentration and measuring cell viability.From these, two quantitative values are provided: the drug concentration required to reduce viability by 50% (IC50) and the area under the dose-response survival curve (AUSC).Gene expression data is available from the Affymetrix U219 gene array platform.Because expression patterns may vary widely simply based on tissue specificity, we chose to limit our initial analysis to B-cell malignancies, represented by 71 cell lines derived from leukemias, lymphomas, and myelomas.Our approach comprises a series of steps in which we classify response and resistance, develop a differential classification profile of gene expression patterns, identify features by pathway analysis, and validate on cell lines and
Efficacy and Safety of Frontline Bortezomib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR-CAP) Vs R-CHOP in a Subset of Newly Diagnosed Mantle Cell Lymphoma (MCL) Patients (Pts) Medically Eligible for Transplantation in the Randomized Phase 3 LYM-3002 Study (NCT00722137)
Authors: Johannes Drach, Huiqiang Huang, Olga S Samoilova, Andrew Belch, Charles M. Farber, André Bosly, Jan Novak, Jan Zaucha, Angela Dascalescu, Udomsak Bunworasate, Zvenyslava Masliak, Kateryna Vilchevskaya, Tadeusz Robak, Lixia Pei, Brendan Rooney, Helgi van de Velde, Franco Cavalli
Journal: Blood (2014)
구연 : 3cm 이하 소간세포암 치료에서 경피적 홀미움 키토산 복합체(밀리칸, Millican) 주입의 장기 치료 효과
Authors: 김자경, 한광협, 백용한, 전재윤, 문영명, 이종태
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 간암의 국소치료에 있어서 방사성 동위 원소인 홀미움-166(Ho166)은 연부 조직에 최대 8.4mm까지 침투 가능하여 피막 주위 병변까지 파괴할 수는 있으나, 주위의 정상 조직에로의 영향을 최소화 한다. 또한 홀미움 키토산 복합체(이하 밀리칸, Millican , 동화제약)는 간조직내에서의 안정적 효과를 위해 개발된 것으로 주위의 산성도 변화에 따라 인체 내에서는 겔(gel)상태로 변하여 안정적이고 지속적인 효과를 유지하는 장점이 있다. 본 연자 등은 이미 소간세포암의 치료에서 경피적 밀리칸 주입의 단기치료시 85%의 좋은 효과를 보고하였고 이들을 최소 1년이상 추적 관찰하여 장기 치료효과에 대해 알아보고자 하였다. 대상과 방법: 3cm이하 크기의 소간세포암 환자로 신약Ⅱ상 임상에 참여하여 경피적 밀리칸 주입술을 시행받은 40명을 대상으로 하였다. 투입 용량은 장경 1cm당 20 mci로 시행하였다. 간세포암의 진단은 영상 소견이 특징적이면서 혈청 태아단백(AFP)의 농도가 200 ng/mL이상인 경우나, 조직 검사상 확인된 경우(16명)로 하였다. 환자들은 수술에 적합하지 않거나 수술 받기를 거부한 경우로 밀리칸 2상 임상시험에 참여한 환자들이었다. 간내 위치상 복부 초음파 유도하 투여가 불가능한 경우는 제외되었다. 시술 후 추적검사는 1개월 후 복부 초음파검사와 2개월 후 컴퓨터 단층 촬영을 시행하였다. 결과: 총 40명 환자들의 평균나이는 57.4세(범위, 38-83세)였고 남자는 27명, 여자는 13명이었다. 평균 추적 관찰 기간은 24개월이었으며 평균 종양 장경은 2.3 cm(범위, 1.3-3.1)이었다. 평균 방사성 홀미움 투여량은 47.4 mCi(범위 30-60)였고, 치료 전후의 AFP 중간값은 각각 160 ng/mL와 15.8 ng/mL로 통계적으로 유의한 감소를 보였다. 치료 2개월 후 장경 3 cm이하의 환자 40명 중 31명(77.5%)에서 종양의 완전 괴사가 일어 났으며 장경 2 cm 이하의 12명 중에서는 11명(91.7%)에서 완전 괴사가 일어났다. 4명은 불충분한 위치 선정으로 잔류 종양이 있었다. 1년과 2년 국소 재발율은 각각 18.5%, 34.9%였으며 1,2,3년 생존율은 각각 87.2%, 71.8%, 65.3%였다. 40명 중 20명은 원래의 위치와 다른 간내 재발이 있었다. 치료 후 일시적인 발열(60%), 통증(57.5%), 오심 혹은 구토(32.5%), 백혈구 감소증(20%)이 있었으나 심각한 부작용은 없었다. 결론: 경피적 키토산 주입술은 새로운 국소 치료로 안전하고 유용한 치료로 생각되며 이후로도 지속적인 관찰과 연구가 요구된다.
Defining a global research and policy agenda for betel quid and areca nut
Authors: Hedieh Mehrtash, Kalina Duncan, Mark Parascandola, Annette David, Ellen R Gritz, Prakash C Gupta, Ravi Mehrotra, Amer Siddiq Amer Nordin, Paul C Pearlman, Saman Warnakulasuriya, Chi-Pang Wen, Rosnah Binti Zain, Edward L Trimble
Journal: The Lancet Oncology (2017)
Abstract A07: Hyperthermia plus radiotherapy in triple-negative breast cancer; before or after?
Authors: Zahra Joveini, Zhaleh Behrouzkia, Reza Zohdi Aghdam
Journal: Cancer Research (2017)

Abstract Introduction: Breast Cancer (BC) is the most common cancer among women. Hyperthermia is a new cancer treatment modality which is used in addition to other treatments to improve patient's survival. The clinical use of Hyperthermia in the combination of radiotherapy is debatable and shows important technical challenges. But the most challenge in this case is the order of this combination. We aimed to explore that in Triple-negative breast cancer applying hyperthermia before radiotherapy is better or after it. Methods and Material: The anti-proliferative activity of Hyperthermia alone and in combination with Radiotherapy in 4T1 balb/c triple negative breast cancer cell line was assessed by the standard 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyl-2H-tetrazolium bromide (MTT) method. We also used Acridine Orange/ Propidium Iodide fluorescent staining for approving the inhibitory effect. We exposed the cells to 43±0.2°C for 30 minutes in a regular incubator, as Hyperthermia treatment and also exposing into 4Gy Gamma irradiation as Radiotherapy. In two modality treatments the time interval was two hours. Then the viability rates of cells were determined after 24, 48 and 72 hours. Statistical analysis used: All data are expressed as the mean ± standard deviation. We used Kruskal-Wallis and Mann-Whitney for statistical analysis. P-values of less than 0/05 were considered to be statistically significant. Results: The findings indicated that adding hyperthermia before Radiotherapy showed 58 ± 4.06, 60.6±2.03 and 62.4±2.5 viability rate after 24,48 and 72 hours, respectively; while applying it after Radiotherapy showed 63.4 ± 1.81, 67.2±2.2 and 62.4±2.5 viability rate after 24,48 and 72 hours. Conclusions: It was concluded that in Triple negative breast cancer applying hyperthermia before radiotherapy is more efficient. Note: This abstract was not presented at the conference. Citation Format: Zahra Joveini, Zhaleh Behrouzkia, Reza Zohdi Aghdam. Hyperthermia plus radiotherapy in triple-negative breast cancer; before or after? [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr A07.
H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma
Authors: Jaya Julie Joshi, Heather Coffey, Erik Corcoran, Jennifer Tsai, Chia-Ling Huang, Kana Ichikawa, Sudeep Prajapati, Ming-Hong Hao, Suzanna Bailey, Jeremy Wu, Victoria Rimkunas, Craig Karr, Vanitha Subramanian, Pavan Kumar, Crystal MacKenzie, Raelene Hurley, Takashi Satoh, Kun Yu, Eunice Park, Nathalie Rioux, Amy Kim, Weidong G. Lai, Lihua Yu, Ping Zhu, Silvia Buonamici, Nicholas Larsen, Peter Fekkes, John Wang, Markus Warmuth, Dominic J. Reynolds, Peter G. Smith, Anand Selvaraj
Journal: Cancer Research (2017)

Activation of the fibroblast growth factor receptor FGFR4 by FGF19 drives hepatocellular carcinoma (HCC), a disease with few, if any, effective treatment options. While a number of pan-FGFR inhibitors are being clinically evaluated, their application to FGF19-driven HCC may be limited by dose-limiting toxicities mediated by FGFR1-3 receptors. To evade the potential limitations of pan-FGFR inhibitors, we generated H3B-6527, a highly selective covalent FGFR4 inhibitor, through structure-guided drug design. Studies in a panel of 40 HCC cell lines and 30 HCC PDX models showed that FGF19 expression is a predictive biomarker for H3B-6527 response. Moreover, coadministration of the CDK4/6 inhibitor palbociclib in combination with H3B-6527 could effectively trigger tumor regression in a xenograft model of HCC. Overall, our results offer preclinical proof of concept for H3B-6527 as a candidate therapeutic agent for HCC cases that exhibit increased expression of FGF19. Cancer Res; 77(24); 6999-7013. ©2017 AACR.
Glycosaminoglycan and Proteoglycan‐Based Biomaterials: Current Trends and Future Perspectives
Authors: Jelena Rnjak‐Kovacina, Fengying Tang, John M. Whitelock, Megan S. Lord
Journal: Advanced Healthcare Materials (2017)

Proteoglycans and their glycosaminoglycans (GAG) are essential for life as they are responsible for orchestrating many essential functions in development and tissue homeostasis, including biophysical properties and roles in cell signaling and extracellular matrix assembly. In an attempt to capture these biological functions, a range of biomaterials are designed to incorporate off-the-shelf GAGs, typically isolated from animal sources, for tissue engineering, drug delivery, and regenerative medicine applications. All GAGs, with the exception of hyaluronan, are present in the body covalently coupled to the protein core of proteoglycans, yet the incorporation of proteoglycans into biomaterials remains relatively unexplored. Proteoglycan-based biomaterials are more likely to recapitulate the unique, tissue-specific GAG profiles and native GAG presentation in human tissues. The protein core offers additional biological functionality, including cell, growth factor, and extracellular matrix binding domains, as well as sites for protein immobilization chemistries. Finally, proteoglycans can be recombinantly expressed in mammalian cells and thus offer genetic manipulation and metabolic engineering opportunities for control over the protein and GAG structures and functions. This Progress Report summarizes current developments in GAG-based biomaterials and presents emerging research and future opportunities for the development of biomaterials that incorporate GAGs presented in their native proteoglycan form.