tbuckley/cabot-search huggingface dataset:
Abstract 1505: GATA3 expression is associated with poor differentiation of osteosarcoma cells
Authors: Koji Hiraoka
Journal: Cancer Research (2018)

Abstract Objective: GATA3, a transcriptional factor promoting differentiation of Th2 cells, was expressed in breast cancer cells or bladder cancer cells. We reported that Gata3 expression in soft tissue sarcoma is an independent factor for poor prognosis. However, the role of GATA3 in osteosarcoma is unknown. We investigated whether GATA3 expression is associated with cell differentiation or clinical prognosis of osteosarcoma. Methods: We examined whether decreased GATA3 expression in MG63 osteosarcoma cells by induction of siRNA GATA3 using electroporation affects cell differentiation. We also evaluated GATA3 expression in biopsy samples of 31 osteosarcoma cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics of GATA3-positive and GATA3-negative cases. In particular, the correlation between osteoid formation and GATA3 expression was examined. Result: GATA3 expression was observed in MG63 cells by Western blotting and real-time PCR. Decreased GATA3 expression caused by induction of siRNA promoted the expression of the osteoblast differentiation markers; osteopontin, osteocalcin and RUNX2; in MG63 cells, while ALP and DMP-1, pre-osteocyte markers, had not increased. The expression of p21, one of the differentiation markers of osteosarcoma, is also elevated by decreased GATA3 expression. GATA3 significantly expressed in osteosarcoma cases with less osteoid formation (P&amp;lt;0.001), although no significant correlation between GATA3 expression and clinical prognosis was observed. Conclusion: These data indicated that GATA3 expression might be associated with poor differentiation of osteosarcoma cells. GATA3 may be a target to treat for osteosarcoma through promotion of cell differentiation. Citation Format: Koji Hiraoka. GATA3 expression is associated with poor differentiation of osteosarcoma cells [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 1505.
Incidence and implications of oligometastatic breast cancer.
Authors: Supriya K. Jain, Paige L. Dorn, Steven J. Chmura, Ralph R. Weichselbaum, Yasmin Hasan
Journal: Journal of Clinical Oncology (2012)

e11512 Background: There is increasing evidence that prolonged disease control is possible in patients with a limited number of metastatic sites compared to those with more diffuse disease, especially when aggressive local therapy (surgery and/or stereotactic radiation) is administered. The objective of this study is to describe the frequency of oligometastatic breast cancer in patients who develop distant disease and to characterize their disease course. Methods: A retrospective review was performed of a tri-institutional database of Stage I-III breast cancer patients treated from 1978 to 2005. Patients were categorized as "oligometastatic" (OM) if ≤ 5 sites of disease were identified at time of first failure or “polymetastatic” (PM) if failure occurred at &gt; 5 sites. Patients were followed for ≥ 3 y after first metastasis, until death, or until development of &gt; 5 sites of metastatic disease. T and N stage, hormone receptor status, presenting symptoms of metastasis, number and site of metastases, actuarial overall survival (OS), and overall survival after first failure (OSAF) were examined. Kaplan-Meier, chi-square, and log-rank tests were used for statistical analysis. Results: Of 2,249 patients reviewed, 114 (5.1%) failed at distant sites and met inclusion criteria. The OM phenotype was observed in 21.9% (25/114). Of patients presenting with symptoms of metastasis, 18.3% were OM, whereas patients with metastases identified incidentally or by screening were OM in 42.1% of cases (p = 0.02). Median OSAF was significantly longer in OM patients (44.7 mos) than PM patients (18.1 mos) with 5 y OS of 48.5% and 10.7% respectively (p &lt; 0.001). Outcome of OM patients compared favorably to that of patients with bone-only metastases in whom the median OSAF was 25 mos and 5 y OS was 12.5%. Baseline features of OM and PM patients did not differ according to initial tumor size (p = 0.94), nodal stage (p = 0.5), or ER+ (p = 0.28). Conclusions: A significant proportion of early stage breast cancer patients with distant failure will have OM disease, and this subset is expected to have prolonged overall survival. The relatively favorable prognosis of patients with OM disease warrants consideration of aggressive local therapy and may have implications in the design of future clinical trials.
Abstract 289: Probing the non-enhancing component of glioblastoma: Targeting what is left behind
Authors: Sen Peng, Rebecca Halperin, Harshil Dhruv, Sara Byron, Christophe Legendre, Joanna Phillips, Michael Prados, Michael Berens, Nhan Tran
Journal: Cancer Research (2018)

Abstract While genomic profiling and therapeutic selection support individualized GBM treatment, such therapeutic decision-making is usually made with reference to tumor obtained from the enhancing core region. GBM is known to be heterogeneous and exhibits a high resistance to standard therapies. To address whether non-enhancing tumor (representing the majority of tumor left behind after surgery) shows distinct genomic characteristics and therapeutic targets compared to the enhancing tumor core, we performed genome-wide exome-sequencing and RNA-sequencing for 12 patients with matched enhancing region and at least one non-enhancing region. Non-enhancing biopsies show a surprisingly high level of tumor content, with a median of 28% tumor cells and 6 of the 22 samples having greater than 50% tumor cells. Cognate non-enhancing and enhancing specimens demonstrated overall concordance in therapeutically actionable alterations (single nucleotide variants) and copy number alterations. However, non-enhancing regions were not genetically identical and did reveal additional and distinct variants compared to enhancing cores. For example, the non-enhancing region of patient 1 showed two nonsense NF1 mutations (R1534X; R2517X) while the enhancing region showed an NF1 frameshift mutation (F1247fs). Clonality analysis by LumosVar also indicated that 7 out of 12 patients harbored dissimilar cellular prevalence patterns between enhancing and non-enhancing regions. In addition, comparison of alternative polyadenylation between enhancing and non-enhancing regions uncovered distinct 3' UTR usage: e.g. SGMS2 and TOB1 tended to have longer 3' UTR in enhancing regions whereas longer 3' UTR of SYNPO and NOS1AP were prevalent in non-enhancing regions. We posit that the enhancing component of glioblastoma probably underrepresents the genomic alterations in patients' tumors. Given non-enhancing tumor is left behind after surgical debulking, genomic profiling of this region would potentially reveal more accurate tumor vulnerabilities and lead to more effective therapy. Supported by a grant from the Ben &amp; Catherine Ivy Foundation. Citation Format: Sen Peng, Rebecca Halperin, Harshil Dhruv, Sara Byron, Christophe Legendre, Joanna Phillips, Michael Prados, Michael Berens, Nhan Tran. Probing the non-enhancing component of glioblastoma: Targeting what is left behind [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 289.
Abstract 4882: Identification and optimization of chemical inhibitors that directly target KRAS G12D mutant
Authors: Xiaohong Tian, Guoyan Geng, Jian Hui Wu
Journal: Cancer Research (2018)

Abstract KRAS mutations are enriched in three lethal cancers, such as pancreatic ductal adenocarcinoma (PDAC) (&amp;gt; 90% of cases), colorectal cancer (CRC) (~50%) and lung cancer (~25%). Within these cancers, specific KRAS mutations dominate. KRAS G12D is the most common mutation in pancreatic and colorectal cancer. To date, accumulating studies have firmly established that constitutive activation of KRAS mutants is a driver of PDAC and CRC. Inhibitors of the downstream components of KRAS signaling only have limited success. Due to the high affinity of KRAS with GTP and no other obvious binding pocket on the KRAS surface for the design of inhibitors, KRAS has been considered ‘undruggable' for a long period of time. As a breakthrough, a novel direct inhibitor of the KRASG12C mutant was discovered in 2013, which forms a covalent bond with the cysteine at residue 12. However, such KRASG12C inhibitor is inactive against the G12D mutant as there is no Cysteine at residue 12. In this project, we have learnt from the excellent work of the G12C inhibitors and identified a novel compound as a direct inhibitor of the KRASG12D mutant. Importantly, this compound is active against the G12D mutant, but inactive against the KRAR wild-type. We demonstrated that our compound at 10 uM significantly inhibits the KRAS signaling in PANC10.05 pancreatic cancer cells and SNU-C2B colorectal cancer cells, both of which express endogenous KRASG12D mutant. Citation Format: Xiaohong Tian, Guoyan Geng, Jian Hui Wu. Identification and optimization of chemical inhibitors that directly target KRAS G12D mutant [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 4882.
Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates
Authors: Dawn M. Dudley, Koen K. Van Rompay, Lark L. Coffey, Amir Ardeshir, Rebekah I. Keesler, Eliza Bliss-Moreau, Peta L. Grigsby, Rosemary J. Steinbach, Alec J. Hirsch, Rhonda P. MacAllister, Heidi L. Pecoraro, Lois M. Colgin, Travis Hodge, Daniel N. Streblow, Suzette Tardif, Jean L. Patterson, Manasi Tamhankar, Maxim Seferovic, Kjersti M. Aagaard, Claudia Sánchez-San Martín, Charles Y. Chiu, Antonito T. Panganiban, Ronald S. Veazey, Xiaolei Wang, Nicholas J. Maness, Margaret H. Gilbert, Rudolf P. Bohm, Kristina M. Adams Waldorf, Michael Gale, Lakshmi Rajagopal, Charlotte E. Hotchkiss, Emma L. Mohr, Saverio V. Capuano, Heather A. Simmons, Andres Mejia, Thomas C. Friedrich, Thaddeus G. Golos, David H. O’Connor
Journal: Nature Medicine (2018)
Association of Out-of-Pocket Annual Health Expenditures With Financial Hardship in Low-Income Adults With Atherosclerotic Cardiovascular Disease in the United States
Authors: Rohan Khera, Javier Valero-Elizondo, Victor Okunrintemi, Anshul Saxena, Sandeep R. Das, James A. de Lemos, Harlan M. Krumholz, Khurram Nasir
Journal: JAMA Cardiology (2018)

<h3>Importance</h3> Health insurance is effective in preventing financial hardship from unexpected major health care events. However, it is also essential to assess whether vulnerable patients, particularly those from low-income families, are adequately protected from longitudinal health care costs for common chronic conditions such as atherosclerotic cardiovascular disease (ASCVD). <h3>Objective</h3> To examine the annual burden of total out-of-pocket health expenses among low-income families that included a member with ASCVD. <h3>Design, Setting, and Participants</h3> In this cross-sectional study of the Medical Expenditure Panel Survey from January 2006 through December 2015, all families with 1 or more members with ASCVD were identified. Families were classified as low income if they had an income under 200% of the federal poverty limit. Analyses began December 2017. <h3>Main Outcomes and Measures</h3> Total annual inflation-adjusted out-of-pocket expenses, inclusive of insurance premiums, for all patients with ASCVD. We compared these expenses against annual family incomes. Out-of-pocket expenses of more than 20% and more than 40% of family income defined high and catastrophic financial burden, respectively. <h3>Results</h3> We identified 22 521 adults with ASCVD, represented in 20 600 families in the Medical Expenditure Panel Survey. They correspond to an annual estimated 23 million or 9.9% of US adults with a mean (SE) age of 65 (0.2) years and included 10.9 million women (47.1%). They were represented in 21 million or 15% of US families. Of these, 8.2 million families (39%) were low income. The mean annual family income was $57 143 (95% CI, $55 377-$58 909), and the mean out-of-pocket expense was $4415 (95% CI, $3735-$3976). While financial burden from health expenses decreased throughout the study, even in 2014 and 2015, low-income families had 3-fold higher odds than mid/high–income families of high financial burden (21.4% vs 7.6%; OR, 3.31; 95% CI, 2.55-4.31) and 9-fold higher odds of catastrophic financial burden (9.8% vs 1.2%; OR, 9.35; 95% CI, 5.39-16.20), representing nearly 2 million low-income families nationally. Further, even among the insured, 1.6 million low-income families (21.8%) experienced high financial burden and 721 000 low-income families (9.8%) experienced catastrophic out-of-pocket health care expenses in 2014 and 2015. <h3>Conclusions and Relevance</h3> One in 4 low-income families with a member with ASCVD, including those with insurance coverage, experience a high financial burden, and 1 in 10 experience a catastrophic financial burden due to cumulative out-of-pocket health care expenses. To alleviate economic disparities, policy interventions must extend focus to improving not only access, but also quality of coverage, particularly for low-income families.
3D Printing Nanoscale Bioactive Glass Scaffolds Enhance Osteoblast Migration and Extramembranous Osteogenesis through Stimulating Immunomodulation
Authors: Fujian Zhao, Weihan Xie, Wen Zhang, Xiaoling Fu, Wendong Gao, Bo Lei, Xiaofeng Chen
Journal: Advanced Healthcare Materials (2018)

Abstract Bioactive glass (BG) can repair bone defects, however, it is not clear whether BG has the ability for bone augmentation without making any bone defect. Unlike the intramembranous osteogenesis in bone defect repair, the extramembranous osteogenesis occurs outside the cortical bone and the osteoprogenitor cells show the reversed migration. Herein, nanoscale bioactive glass scaffolds (BGSs) are fabricated, and their role and immunomodulation‐related mechanism in the extramembranous osteogenesis are investigated. The in vitro migration and differentiation of calvaria preosteoblasts are studied by culturing with peripheral macrophage‐conditioned medium after stimulating with BGSs. The results indicate that the proinflammatory environment significantly promotes preosteoblast migration, but has limited effect on osteogenic differentiation. However, the anti‐inflammatory environment and BGSs significantly increase the osteogenic differentiation of preosteoblasts. The in vivo extramembranous osteogenesis evaluation shows that the active osteogenesis is observed near the skull. The osteoblasts derived from the reverse migration of cranial cells can be confirmed by comparing with the scaffolds implanted in back subcutaneous which is just colonized by fibrous tissue. This study may bring a fresh perspective for BG in bone regeneration and explore the osteogenic immunomodulation of peripheral macrophages in a nonosteogenic environment.
The impact of individual comorbidities on non-relapse mortality following allogeneic hematopoietic stem cell transplantation
Authors: Joshua A. Fein, Avichai Shimoni, Myriam Labopin, Noga Shem-Tov, Ronit Yerushalmi, Hila Magen, Nadav Furie, Eli Kopel, Ivetta Danylesko, Arnon Nagler, Roni Shouval
Journal: Leukemia (2018)
Skeletal Muscle Loss Is an Imaging Biomarker of Outcome after Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer
Authors: Jie Lee, Chih-Long Chang, Jhen-Bin Lin, Meng-Hao Wu, Fang-Ju Sun, Ya-Ting Jan, Shih-Ming Hsu, Yu-Jen Chen
Journal: Clinical Cancer Research (2018)

Purpose: This study investigates the association between body composition change during concurrent chemoradiotherapy (CCRT) and outcome in patients with locally advanced cervical cancer (LACC).Experimental Design: Pre- and posttreatment CT images of 245 patients with LACC who were treated between 2004 and 2015 were analyzed. Skeletal muscle index (SMI) and density (SMD), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) were measured from two sets of CT images at the level of the L3 vertebra. Sarcopenia and a low SMD were defined using published cut-off points. Predictors of overall survival (OS) and cancer-specific survival (CSS) were analyzed using Cox regression models.Results: The median follow-up was 62.7 (range, 7.3-152.3) months. Among the 245 patients, 127 (51.8%) had pretreatment sarcopenia, and 154 (62.9%) had a low SMD. SMI did not decrease significantly during CCRT, 0.6%/150 days [95% confidence interval (CI), -1.8-0.6; P = 0.35]. However, SMI loss during CCRT of >10.0%/150 days was independently associated with poorer OS (HR, 6.02; 95% CI, 3.04-11.93; P < 0.001) and CSS (HR, 3.49; 95% CI, 1.44-8.42; P = 0.006) when adjusted for FIGO stage, pathology, and treatment. Pretreatment sarcopenia and change of SMD, SATI, and VATI during CCRT were not associated with survival.Conclusions: Skeletal muscle measurements could be imaging biomarkers to predict outcomes for patients with LACC in clinical practice. Further studies are needed to determine whether multimodal interventions can preserve skeletal muscle mass and thereby improve survival. Clin Cancer Res; 24(20); 5028-36. ©2018 AACR.
Integrative genomic analysis reveals cancer-associated mutations at diagnosis of CML in patients with high-risk disease
Authors: Susan Branford, Paul Wang, David T. Yeung, Daniel Thomson, Adrian Purins, Carol Wadham, Nur Hezrin Shahrin, Justine E. Marum, Nathalie Nataren, Wendy T. Parker, Joel Geoghegan, Jinghua Feng, Naranie Shanmuganathan, Martin C. Mueller, Christian Dietz, Doris Stangl, Zoe Donaldson, Haley Altamura, Jasmina Georgievski, Jodi Braley, Anna Brown, Christopher Hahn, Ieuan Walker, Soo-Hyun Kim, Soo-Young Choi, Sa-Hee Park, Dong-Wook Kim, Deborah L. White, Agnes S. M. Yong, David M. Ross, Hamish S. Scott, Andreas W. Schreiber, Timothy P. Hughes
Journal: Blood (2018)
Narrow-band imaging detects synchronous oropharyngeal squamous carcinoma during treatment of an early esophageal squamous cell carcinoma
Authors: Alexander Katzarov, Alexandru Lupu, Jérémie Jacques, Jérôme Rivory, Florian Rostain, Thomas Walter, Mathieu Pioche
Journal: Endoscopy (2018)

Squamous cell carcinoma (SCC) can appear synchronously in the upper aerodigestive tract and in the esophagus by the mechanism of field cancerization, as tobacco and alcohol are both major risk factors for these lesions [1] [2]. Narrow-band imaging (NBI) and Lugol chromoendoscopy are the standard techniques for assessment of superficial esophageal lesions, although Lugol staining can lead to adverse events, such as mucosal irritation, allergic reactions, and aspiration, especially in the oropharyngeal area. NBI has proven to be superior to white-light imaging (WLI), with significantly higher diagnostic sensitivity in the detection of superficial mucosal lesions of the esophagus and pharynx [3], by showing altered intrapapillary capillary loop (IPCL) pattern [4].
Abstract 12419: Prognostic Factors of Hemodialysis Patients Undergoing Endovascular Treatments for Critical Limb Ischemia due to Isolated Infra-Popliteal Disease
Authors: Nobuhiro Suematsu, Osamu Iida, Mitsuyoshi Takahara, Yasutaka Yamauchi, Yoshimitsu Soga, Keisuke Hirano, Masatsugu Nakano, Daizo Kawasaki, Terutoshi Yamaoka, Kenji Suzuki, Yoshiaki Shintani, Yusuke Miyashita, Junichi Tasaki
Journal: Circulation (2012)

Background:  There is avid debate in management of peripheral arterial disease (PAD) among hemodialysis patients due to poor rates of both limb and patient survival. Endovascular treatment (EVT) for PAD is performed more routinely, and has similar outcomes as compared to bypass surgery in terms of amputation-free survival rate among patients with critical limb ischemia (CLI) due to infra-inguinal disease. However, the long-term patency of EVT in infra-popliteal disease is still unfavorable. The purpose of this study is to clarify the effectiveness of EVT and to investigate prognostic factors in the management of hemodialysis patients with CLI due to isolated infra-popliteal disease.   Materials and Methods:  A total of 546 hemodialysis patients who underwent EVT for CLI with isolated infra-popliteal disease at 11 hospitals in Japan between March 2004 and June 2011 were retrospectively analyzed.   Results:  Average patient age was 69.1 years (range 38 to 97) and 420 (74.6%) were male. The number of patients classified to Rutherford stage 4, 5, and 6, was 103 (18.9%), 332 (60.8%), and 111 (20.3%), respectively. 223 (40.8%) had HbA1c level >6.5%, and 195 (35.7%) were active smokers. During the follow-up period (mean: 557.5 days), 191 (35.0%) died and 67 (12.3%) underwent a major amputation. Cox proportional hazard regression analyses revealed that non-ambulatory state (1.82 [1.31-2.52], p   Conclusions:  Although the prognosis of limb and patient survival among those on hemodialysis with CLI is still poor, this study will help guide treatment decisions regarding EVT, bypass surgery, or major amputation.
Abstract 94: DDX31 cooperates with mutant p53 and EGFR to promote the multistep progression of invasive bladder cancer
Authors: Toyomasa Katagiri, Kei Daizumoto, Tetsuro Yoshimaru, Yosuke Matsushita, Tomoya Fukawa, Masaya Ono, Hiro-omi Kanayama
Journal: Cancer Research (2018)

Abstract Bladder cancer is the most common malignancy of the urinary tract worldwide. Approximately 70% of cases are diagnosed as non-muscle-invasive bladder cancer (NMIBC), while the remaining 30% of cases are classified as muscle-invasive bladder cancer (MIBC). Evidence based on molecular biology has highlighted that the aggressiveness of MIBC advances through a multistep mechanism due to many genomic alterations. Notably, alterations of TP53 and EGFR pathways frequently occur in bladder cancers and are associated with poor prognosis, respectively. However, the connection between the overexpression of EGFR and the p53 mutation in multistep carcinogenesis and the progression of MIBC remains unknown. Here we report the distinct critical roles of DEAD box polypeptide 31 (DDX31) in the multistep progression of muscle invasive bladder cancer (MIBC) through its sequential interaction with mutant p53 (mutp53) and EGFR. In early MIBC cells, nuclear DDX31 acts as a transcriptional co-activator that binds to mutp53/SP1 and enhances mutp53 transcriptional activation, thereby upregulating the EPB41L4B gene, which plays a critical role in metastatic behavior and promotes the invasion and migration of MIBC. Notably, in advanced MIBC, cytoplasmic DDX31, which is transported from the nucleus, functions as an adaptor scaffold protein that forms a complex with EGFR via its interaction with phosho-nucleolin (NCL), leading to constitutive activation of EGFR-Akt signaling. Significantly, high expression of both cytoplasmic DDX31 and p53 proteins is correlated with a poor prognosis in MIBC patients. More importantly, blocking the DDX31-NCL interaction via a dominant-negative peptide led to downregulation of EGFR-Akt signaling, resulting in a significant anti-tumoral effect of bladder cancer in vivo. Our findings reveal that DDX31 cooperates with mutp53 and EGFR to promote the multistep progression of MIBC and that inhibition of DDX31-NCL formation may lead to potential treatment strategies for advanced MIBC. Citation Format: Toyomasa Katagiri, Kei Daizumoto, Tetsuro Yoshimaru, Yosuke Matsushita, Tomoya Fukawa, Masaya Ono, Hiro-omi Kanayama. DDX31 cooperates with mutant p53 and EGFR to promote the multistep progression of invasive bladder 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 94.