tbuckley/cabot-search huggingface dataset:
Abstract P173: Community Engagement Makes for Recruitment Success into a Randomized Controlled Intervention Trial for Deaf Adults
Authors: Lisa M Lowenstein, Lori DeWindt, Erika Sutter, Steven Barnett, Thomas A Pearson
Journal: Circulation (2013)

The majority of Americans are either overweight or obese, including Deaf adults who use American Sign Language (ASL). Together, Deaf community members and researchers at the Rochester Prevention Research Center: National Center for Deaf Health Research (NCDHR) in Rochester, NY, identified obesity as a top health priority and chose to adapt a healthy lifestyle intervention for Deaf adults. Since this is one of the few healthy lifestyle interventions involving the Deaf community, we wanted to learn more about recruiting Deaf adults to participate in a healthy lifestyle intervention. Thus, we explored different recruitment strategies to learn what worked to recruit Deaf individuals into a 16-week healthy lifestyle intervention, Deaf Weight Wise (DWW), delivered by a Deaf counselor who uses ASL. Prior to DWW recruitment, we implemented an educational campaign to increase the Deaf community’s knowledge and awareness of NCDHR and how and why the research is conducted. Several different recruitment strategies were used including NCDHR-hosted events, outreach to other Deaf organizations/groups and local faith-based organizations, social media, existing research recruitment lists, word of mouth, and peer recruitment. At the initial study visit, NCDHR research staff asked all individuals who inquired about DWW how they learned about the study. All responses were documented and entered into our database. From August 2011 to June 2012, a total of 165 individuals inquired about DWW. Out of the 165, 132 attended a screening visit, and 104 fully enrolled into the study. Out of the 104 who enrolled into the study, many learned about DWW through one of the community organizations (28%, n=29), study participants (24%, n=25), or NCDHR hosted events (22%, n=23). None of the study participants reported that they learned about the study via a faith-based organization or social media. Participants were 68% (71/104) female, 91% (95/104) White, and 33% (34/104) had at least a 4-year college degree. On average, participants were 53.5 years old, weighed 92.9 kg, and had a Body Mass Index of 33.3 kg/m 2 . Retention and participation in the randomized trial has been excellent. In conclusion, recruitment was most successful with organizations and individuals with whom we had previously established relationships/networks with whom the NCDHR had long-term and positive engagement. Recruiting from faith-based organizations was challenging, which lacked this engagement. Future recruitment strategies include continued relationship-building with faith-based organizations and with individual community members and organizational leaders. Lessons learned from programs with the Deaf community likely also pertain to other linguistic and cultural groups.
Abstract 2558: Regulation of the expression of the DNA repair endonuclease 8-like 3 gene in hepatocellular carcinoma
Authors: Wenya Huang
Journal: Cancer Research (2019)

Abstract Hepatocellular carcinoma (HCC) is the fifth commonest malignancy in the world, but the molecular mechanism of HCC development is still unclear. Previous studies had showed that the endonuclease 8-like 3 (Neil3) gene, a DNA glycosylase for oxidative DNA repair, overexpressed in most of cancers including HCC. In our previous cDNA microarray analysis in HCC tissues, it was found that the Neil3 gene was highly expressed in mouse and human tumors. The results of real-time RT-PCR analysis in 113 HCC patients showed that the Neil3 gene mRNA was increased in most human tumors. The Neil3 gene expression levels were also highly correlated with HCC recurrence in the patients receiving the hepatectomy surgeries, suggesting that it can serve as a prognostic marker for HCC. In this study we characterized the molecular mechanisms of the Neil3 gene expression regulation in HCC. We analyzed the methylation status in the Neil3 gene promoter regions by DNA methylation array (Agilent) and found that the Neil3 gene promoter was hypo-methylated in HCC tumors. Also, by the promoter reporter assays it was found that the main regulatory region for its transcription activity was from -123 to +94 upstream to the transcription start site. Furthermore, the DNA affinity precipitation assay (DAPA) was performed to screen for the transcription factors that bind to the Neil3 promoter and identified that cell cycle regulator E2F1, Yin Yang 1 (YY1) and histone deacetylase 1 (HDAC1) bind to the Neil3 gene promoter. It suggested that E2F1, YY1 and HDAC1 play important roles in regulating Neil3 gene expression. These transcription factors have been known to enhance cell proliferation and potentially the NEIL3-mediated oncogenic properties. And treatments of the HDAC inhibitor SAHA increased the Neil3 mRNA and protein levels. The functional effects of these pro-oncogenic transcriptional factors to the NEIL3-relevant HCC progression are currently in investigation. The results of these studies will clarify the regulatory mechanisms for the Neil3 gene induction in HCC progression. Citation Format: Wenya Huang. Regulation of the expression of the DNA repair endonuclease 8-like 3 gene in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2558.
Endoscopic submucosal dissection for superficial esophageal cancer overlying a submucosal tumor originating from the muscularis propria
Authors: Rino Nankinzan, Takuto Suzuki, Yoshiyasu Kitagawa, Taketo Yamaguchi
Journal: Endoscopy (2019)

A 62-year-old man was referred to our hospital for treatment of an esophageal cancer overlying a submucosal tumor (SMT). The SMT was present in the middle thoracic esophagus, and endoscopic ultrasonography (EUS) demonstrated a hypoechoic tumor with calcification inside, originating from muscularis propria. We diagnosed it as a benign tumor, such as a leiomyoma, and it underwent no change in size or form after 8 years of follow-up. The cancer however was superficial, and magnifying endoscopy combined with narrow-band imaging (NBI) revealed tortuous B1 vessels with irregular diameters and shapes. The biopsy specimen revealed squamous cell carcinoma, and endoscopic submucosal dissection (ESD) was therefore performed ([Fig. 1]).
Abstract 5280: Branched chain amino acids represent indispensible metabolic substrates in glioblastoma
Authors: Antony H. Prabhu, Shiva Kant, Pravin Kesarwani, Prakash Chinnaiyan
Journal: Cancer Research (2019)

Abstract Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options. Considerable advances have been made in understanding the genetic alterations driving these tumors, however, the metabolic alterations and mechanisms underlying these aggressive phenotypes remain unclear. We performed global metabolomic profiling of patient derived low-grade astrocytoma (LGA, n= 28) and GBM (n=80). Hierarchical clustering (HC) identified amino acid (AA) metabolism as a dominant metabolic node in GBM compared to LGA. Considerable inter-tumoral heterogeneity of AA metabolism was observed in GBM, with HC identifying two clearly distinct metabolic subtypes consisting of increased and decreased concentrations of AA and their metabolic intermediates. VIP analysis identified the accumulation of branched chain amino acids (BCAA)- leucine, valine and isoleucine as the top ranked metabolites differentiating these subtypes. Based on this, GBMs were classified as BCAA-high and BCAA-low. BCAA-high GBM was enriched with mesenchymal and classical subtypes while BCAA-low GBM was enriched with proneural and neural subtypes. Integrative analysis coupling these metabolic signatures with gene expression profiling performed on matched tissue demonstrated upregulation of BCAA metabolism-associated genes in BCAA-high GBM, along with global transcriptional programs designed to activate cell cycle progression. When extended into molecular subtype specific preclinical models, we demonstrated that BCAA were indispensible for survival of mesenchymal GBM cells, which was independent of the presence or absence of other non-essential and essential amino acids. Further, these cells were able to maintain long-term survival in a dormant state when grown in media devoid of all essential and non-essential AA other than BCAA and glutamine. Knockdown of key enzymes in BCAA metabolism led to robust cytotoxicity in this model, underscoring the importance of BCAA in GBM survival. Ongoing studies are designed to determine the biologic consequence and intermediary metabolism of BCAA in GBM. Collectively these results identify BCAA metabolism as a therapeutic target in GBM. Citation Format: Antony H. Prabhu, Shiva Kant, Pravin Kesarwani, Prakash Chinnaiyan. Branched chain amino acids represent indispensible metabolic substrates in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5280.
Ten-Year Follow-up of Newly Diagnosed Follicular Lymphoma Patients Treated with Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) As First-Line Therapy in JCOG0203 Trial
Authors: Takashi Watanabe, Kensei Tobinai, Masashi Wakabayashi, Yasuo Morishima, Hirobumi Kobayashi, Tomohiro Kinoshita, Takayo Suzuki, Motoko Yamaguchi, Kiyoshi Ando, Michinori Ogura, Masafumi Taniwaki, Naokuni Uike, Tadashi Yoshino, Shigeru Nawano, Takashi Terauchi, Tomomitsu Hotta, Kunihiro Tsukasaki
Journal: Blood (2017)
Abstract 18848: Carotid Artery Remodeling is Segment Specific: An in Vivo Study by Cardiovascular Magnetic Resonance Imaging
Authors: Hiroko Watase, Jie Sun, Daniel S Hippe, Niranjan Balu, Feiyu Li, Xihai Zhao, Zhai Fayad, Valentine Fuster, Thomas S Hatsukami, Chun Yuan
Journal: Circulation (2015)

Introduction: Coronary atherosclerosis can be accompanied by coincident change in lumen and total vessel area, described as arterial remodeling. Early-stage atherosclerosis is believed to be associated with enlarged outer wall and preserved lumen (outward remodeling). However, direct in vivo evidence in the carotid artery is scarce. Magnetic resonance imaging provides a non-invasive means to characterize remodeling patterns in the carotid arterial wall. Hypothesis: We tested the hypothesis that carotid arteries exhibit expansive remodeling in a large cohort of asymptomatic subjects with multiple cardiovascular risk factors. We further examined whether remodeling is carotid segment specific. Methods: From the BioImage Study (NCT00738725), 525 subjects were evaluated with magnetic resonance imaging. Axial images of bilateral carotid arteries were acquired and categorized into common carotid artery (CCA), carotid bulb, and internal carotid artery (ICA) segments based on their distance to the flow divider. Lumen area (LA), total vessel area (TVA), and mean wall thickness (MWT) were measured on all slices and averaged for each CCA, carotid bulb, and ICA segments per subject. General linear models were used to examine cross-sectional associations of MWT with LA and TVA after adjustment for age, sex and body surface area. The regression slopes are presented as the cross-sectional area change per 1 mm MWT increase and were interpreted as indicators of the remodeling pattern. Results: A total of 489 subjects (mean age: 68 years; 49% female) with sufficient image quality were enrolled in this study. In the CCA, both TVA (Slope: 44.6 mm2, p&lt;0.001) and LA (Slope: 11.9 mm2, p=0.009) tended to be larger with increased MWT, suggesting outward remodeling. In the ICA, TVA also increased with MWT (Slope: 17.0 mm2, p&lt;0.001), while the LA tended to decrease (Slope: -6.8 mm2, p=0.07). In contrast, the TVA changed less in the carotid bulb with MWT (Slope: -8.2 mm2, p=0.29) while the LA distinctly decreased with increasing MWT (Slope: -35 mm2, p&lt;0.001), consistent with inward remodeling. Conclusions: In this asymptomatic cohort with multiple risk factors, carotid artery atherosclerosis is accompanied by arterial remodeling which appears to be segment specific.
Patient-Centered Outcomes in ARIEL3, a Phase III, Randomized, Placebo-Controlled Trial of Rucaparib Maintenance Treatment in Patients With Recurrent Ovarian Carcinoma
Authors: Amit M. Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I. Weberpals, Andrew R. Clamp, Giovanni Scambia, Alexandra Leary, Robert W. Holloway, Margarita Amenedo Gancedo, Peter C. Fong, Jeffrey C. Goh, David M. O’Malley, Deborah K. Armstrong, Susana Banerjee, Jesus García-Donas, Elizabeth M. Swisher, David Cella, Juliette Meunier, Sandra Goble, Terri Cameron, Lara Maloney, Ann-Christin Mörk, Josh Bedel, Jonathan A. Ledermann, Robert L. Coleman
Journal: Journal of Clinical Oncology (2020)

To investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo.Patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function × the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade ≥ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade ≥ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as μTOX × TOX + TWiST, with μTOX calculated using EQ-5D-3L data.The visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo; difference, 6.28 months [95% CI, 4.85 to 7.47 months]); BRCA-mutant cohort (130 rucaparib v 66 placebo; 9.37 months [95% CI, 6.65 to 11.85 months]); homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo; 7.93 months [95% CI, 5.93 to 9.53 months]); and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo; 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade ≥ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA-mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade ≥ 2 TEAEs also consistently favored rucaparib.The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.
Hospitalization due to community-acquired pneumonia in patients with chronic obstructive pulmonary disease: incidence, epidemiology and outcomes
Authors: J. Bordon, M. Slomka, R. Gupta, S. Furmanek, R. Cavallazzi, S. Sethi, M. Niederman, J.A. Ramirez
Journal: Clinical Microbiology and Infection (2019)
Abstract 3186: A novel combination therapy for treating advanced drug resistant acute lymphoblastic leukemia
Authors: Yorleny M. Vicioso, Rose Beck, Herman Gram, Abhishek Asthana, keman Zhang, Derek Wong, John Letterio, Reshmi Parameswaran
Journal: Cancer Research (2019)

Abstract Purpose: Drug resistance and relapse are two major problems in Acute Lymphoblastic Leukemia (ALL) as these patients do not respond to chemotherapy. We observed BAFF-R expression on drug resistant and relapse B-ALL patient cells. We wanted to explore the in vivo therapeutic efficacy of a BAFF-R antibody, optimized for antibody dependent cellular cytotoxicity (ADCC), against drug resistant ALL cells. Experimental design: ADCC assay was performed using primary human natural killer (NK) cells isolated from normal donors or ALL patients. NK cell mediated cytotoxicity was measured using Calcein-AM assay. Immunocompromised NSG mice were used for in vivo xenograft model of ALL. Results: We found that anti-BAFF-R antibody enhanced NK cell mediated killing of drug resistant ALL cells in vitro. Early treatment with anti-BAFF-R antibody and NK cells significantly reduced disease burden in xenograft ALL models and increased overall mice survival. However, in advanced disease, the efficacy of NK cells to mediate ADCC is reduced. ALL cells are known to produce TGF beta, that causes NK cell dysfunction. We found that ALL cells produce TGF-β and co-culturing ALL cells with NK cells lead to a decrease in CD16 expression on NK cells, which is reversible by addition of EW-7197, a potent TGF-beta receptor I inhibitor. We found that EW-7197 treatment improved anti-BAFF-R antibody mediated ADCC of drug resistant ALL cells, in vivo, even if treatment is started late. Conclusion: Combination treatment using BAFF-R antibody, NK cells and EW-7197 is a potential strategy to treat advanced drug resistant ALL patients with BAFF-R expressing blasts. Citation Format: Yorleny M. Vicioso, Rose Beck, Herman Gram, Abhishek Asthana, keman Zhang, Derek Wong, John Letterio, Reshmi Parameswaran. A novel combination therapy for treating advanced drug resistant acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3186.
Abstract 12884: The WCT Formula: A Novel Algorithm Designed to Automatically Differentiate Wide-Complex Tachycardias
Authors: Adam May, Christopher DeSimone, David Hodge, Grace Lin, Suraj Kapa, Abhishek Deshmukh, Peter Noseworthy, Peter Brady
Journal: Circulation (2018)

Background: The successful differentiation of wide complex tachycardias (WCTs) into ventricular tachycardia (VT) or supraventricular wide complex tachycardia (SWCT) has undeniably important therape...
Abstract 881: A role for microsomal glutathione transferase 1 in melanin biosynthesis in melanoma
Authors: Jie Zhang, Zhi-wei Ye, Danyelle M. Townsend, Ralf Morgenstern, Kenneth D. Tew
Journal: Cancer Research (2019)

Abstract Higher organisms have multiple defenses against toxic chemical insult, ultraviolet light (UVR) and oxidative stress. These include thioredoxin and glutathione dependent enzymes, some of which are selenium (Se) dependent, including thioredoxin reductases, Se-dependent glutathione peroxidases, Se-independent glutathione transferases and peroxiredoxins. Microsomal glutathione transferase 1 (MGST1) shares an important and unique characteristic with Se-dependent glutathione peroxidase GPX4, namely the ability to reduce lipid hydroperoxides directly in membranes. In contrast to most other glutathione transferases and peroxidases, we previously found that deletion of MGST1 in mice was embryonic lethal, signifying some essential functional importance. We found that MGST1 was crucial for embryonic development through regulating early hematopoiesis in both zebrafish and mouse derived hematopoietic stem cells. Interestingly, after partial knock-down MGST1, the number of melanocytes located at the midline of zebrafish embryos was significantly reduced. Melanocytes are specialized cells that produce melanin, contributing to skin color, but also providing an antioxidant defense system that includes UVR - causative in the initiation of melanoma. Both mRNA and protein levels of MGST1 were markedly decreased in several amelanotic melanoma cell lines and melanogenesis was significantly decreased in B16 melanoma cells when MGST1 expression was knocked down by 60%. This was accompanied by increased UVB-induced cell death in these B16 cells. In contrast, in normal human melanocytes, recombinant adenovirus induced over-expression of MGST1 induced melanogenesis, concomitant with an increase of tyrosinase protein levels. UVB light was used to show that stimulus of melanin biosynthesis occurred in different melanoma cells in quantitative agreement with their levels of MGST1. We conclude that within the melanin synthetic pathway, MGST1 is critical in regulating conversion of dopaquinone to glutathionyl-DOPA, a precursor of pheomelanin. In the absence of MGST1, dopaquinone can cause toxicities and result in reduced or absent levels of melanin, leading to a deficiency in protection against UVR-induced DNA damage. Thus, absence of MGST1 produces embryonic lethality and influences the susceptibility of skin melanocytes to melanoma. Citation Format: Jie Zhang, Zhi-wei Ye, Danyelle M. Townsend, Ralf Morgenstern, Kenneth D. Tew. A role for microsomal glutathione transferase 1 in melanin biosynthesis in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 881.
Safety and preliminary efficacy in patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL) receiving lisocabtagene maraleucel (Liso-cel) in TRANSCEND NHL 001.
Authors: Michael Wang, Leo I. Gordon, Maria Lia Palomba, Jeremy S. Abramson, Charalambos Andreadis, Nilanjan Ghosh, Matthew Alexander Lunning, David G. Maloney, Thalia Andrea Farazi, Jacob Garcia, Benhuai Xie, Kathryn J. Newhall, Christine Dehner, Tanya Siddiqi
Journal: Journal of Clinical Oncology (2019)

7516 Background: Most pts with MCL relapse after first-line immunochemotherapy, with poor responses to salvage therapy. We report initial dose-finding results from pts with R/R MCL treated with liso-cel (JCAR017), an investigational, anti-CD19 CAR T cell product administered as a defined composition of CD4+/CD8+ CAR T cells, in the ongoing phase 1 TRANSCEND study. Methods: Eligible pts had confirmed MCL (cyclin D1 expression, t[11;14]) with R/R disease after ≥1 prior lines of therapy. After lymphodepleting chemotherapy, liso-cel was administered at 1 of 2 dose levels (DL): DL1 = 50 × 10 6 or DL2 = 100 × 10 6 total CAR+ T cells. Results: At data cutoff, 9 pts (DL1, n = 6; DL2, n = 3) had received liso-cel. The median (range) age was 66 (58‒78) years; 7 pts were male. Histologies included blastoid (n = 3) and pleiomorphic (n = 1) variants. 8 pts had documented Ki67 &gt; 30% (40%‒80%); 1 pt had TP53 mutation. Pts had received a median of 5 (3‒7) prior therapies; 3 pts had received prior hematopoietic stem cell transplant. All 9 pts had prior ibrutinib; 4 had a best response of progressive disease on ibrutinib. 6/9 pts (67%) received bridging chemotherapy. 4/9 pts (44%) had serious treatment-emergent adverse events (TEAEs). 5/9 pts (56%) had grade (G) 3/4 TEAEs, primarily anemia, neutropenia, and hypophosphatemia (22% each). 3/9 pts (33%) had cytokine release syndrome (CRS); all were G1. Median time to CRS onset was 6 (2‒7) days; median time to resolution was 6 (2‒6) days. 1 pt received tocilizumab and corticosteroids. There were no neurological events. 4 pts died, all in DL1 (3 from disease progression; 1 after receiving new anticancer therapy post liso-cel). Overall response rate was 78% (7/9 pts; 4/6 in DL1, median follow-up 12.4 [95% CI: 9.2–12.4] mo; 3/3 in DL2, median follow-up 1.4 [95% CI: 1.0–1.4] mo). 2 pts in DL1 maintained a durable CR until last follow-up (day 281 and 378, respectively). Median time to peak CAR+ T cell expansion: 9.5 (9–10) days at DL1 and 17.5 (10–27) days at DL2. Conclusions: In this phase 1 study in pts with R/R MCL, liso-cel treatment showed tolerable toxicity and had clinical activity. Updated DL2 data and longer follow-up will be presented. Clinical trial information: NCT02631044.