tbuckley/cabot-search huggingface dataset:
Demystifying the Role of Tumor Mutational Burden for Immunotherapy Selection
Authors: David A. Fabrizio, Priti Hegde, Brian Alexander
Journal: JAMA Oncology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Abstract 1658: Anti-CEACAM binding protein for fluorescence visualization of primary colon cancer in patient-derived orthotopic xenograph mouse models
Authors: Hannah M. Hollandsworth, Siamak Amirfakhri, Filemoni Filemoni, Verena Schmitt, Gunther Wennemuth, Alexej Schmidt, Robert M. Hoffman, Bernhard B. Singer, Michael Bouvet
Journal: Cancer Research (2020)

Abstract Background The Helicobacter outer protein (HopQ) is a novel surface-located Helicobacter pylori adhesion protein that binds to various human carcinoembryonic antigen-related cell adhesion molecules (CEACAM1, 3, 5, 6). Our aim was to validate fluorescence targeting of colorectal tumors in patient derived orthotopic xenograft models with fluorescently labeled HopQ. Materials/Methods CEACAM binding protein HopQ was conjugated to near-infrared dye IR800CW (LI-COR). Western blotting was performed with various colon cancer cell lysates to determine CEACAM expression. Nude mice (n=4) received orthotopic implantation of patient-derived primary colon tumors and patient-derived colon cancer metastases. Mice were administered either 25 ug or 50 ug of HopQ-IR800CW via tail vein injection and imaged 48 hours later. Intravital images were analyzed using the Image Studio Software Small Animal Imaging Analysis to determine tumor-to-background ratio (TBR). Results Western blotting demonstrated varied expression of CEACAM binding in all 15 patient derived colon cancer lysates. Dose response intravital imaging demonstrated TBR of 1.41 when administered 25 ug of HopQ-IR800CW and TBR 3.78 when administered 50 ug of HopQ-IR800CW. Conclusion CEACAM binding protein HopQ shows promising use for fluorescence imaging of patient derived orthotopic colon cancer. HopQ may be useful for tumor detection for pre-surgical diagnosis and fluorescence-guided surgery. Citation Format: Hannah M. Hollandsworth, Siamak Amirfakhri, Filemoni Filemoni, Verena Schmitt, Gunther Wennemuth, Alexej Schmidt, Robert M. Hoffman, Bernhard B. Singer, Michael Bouvet. Anti-CEACAM binding protein for fluorescence visualization of primary colon cancer in patient-derived orthotopic xenograph mouse models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1658.
Abstract 4582: Tumor matrix-targeted polymeric glyco-adjuvant for <i>in situ</i> cancer vaccination
Authors: Laura T. Gray, D. Scott Wilson, Jun Ishihara, Koichi Sasaki, Michal Raczy, Melody Swartz, Jeffrey Hubbell
Journal: Cancer Research (2020)

Abstract Cancer vaccination is challenging due to a lack of strong, clinically approved adjuvants and difficulty in identifying cancer-specific antigens. Here, in order to address these challenges, we report the creation of a targeted therapeutic cancer vaccine with two components: (1) a mannosylated, toll-like receptor 7 (TLR7)-agonizing polymer, p(Man-TLR7), and (2) a fusion protein consisting of serum albumin (SA) fused to a collagen binding domain (CBD), namely the A3 domain of von Willebrand factor. p(Man-TLR7) has been shown to elicit strong CD8+ T cell responses, which are vital for the success of cancer vaccines. As such, we hypothesized that chemically linking p(Man-TLR7) to a tumor-targeting protein would localize our polymeric glyco-adjuvant to the tumor, promoting the immunogenic processing of endogenous tumor antigens and bypassing the need to pre-identify tumor-specific antigens. In the approach presented here, CBD-SA acts as our tumor-targeting protein by actively binding to collagen in the tumor microenvironment via the CBD, in addition to utilizing the passive targeting of SA. Upon successful and reproducible generation of CBD-SA-p(Man-TLR7) conjugates, we observed that the conjugates retained the ability to bind both collagen I and collagen III. We then assessed the in vivo anti-tumor efficacy of our conjugates in B16F10 tumor-bearing mice, testing both murine CBD-SA-p(Man-TLR7) and human CBD-SA-p(Man-TLR7) conjugates to evaluate the translatability of our approach. We observed an 84% decrease in average B16F10 tumor size and improved overall survival compared to untreated controls when mice were treated with intravenously-delivered murine CBD-SA-p(Man-TLR7) in combination with anti-PD-1 and anti-CTLA-4 antibodies. In the case of intravenously-delivered human CBD-SA-p(Man-TLR7), a 60% decrease in average tumor size compared to untreated controls was observed when mice were treated with our vaccine as a monotherapy. Further improved anti-tumor efficacy (an 85% decrease in average tumor size compared to untreated controls) and improved overall survival were observed when we combined our human CBD-SA-p(Man-TLR7) vaccination with anti-PD-1 and anti-CTLA-4 antibodies. In conclusion, in situ vaccination with CBD-SA-p(Man-TLR7) is a translatable approach that synergizes with checkpoint antibody therapy to provide therapeutic benefit in treatment of a poorly immunogenic melanoma model. Citation Format: Laura T. Gray, D. Scott Wilson, Jun Ishihara, Koichi Sasaki, Michal Raczy, Melody Swartz, Jeffrey Hubbell. Tumor matrix-targeted polymeric glyco-adjuvant for in situ cancer vaccination [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4582.
Abstract 264: Long noncoding RNA LNC01534 regulates cancer stem cells in colorectal cancer
Authors: Masahisa Ohtsuka, Wu Xin, Momoko Ichihara, Haruka Hirose, Hidekazu Takahashi, Chu Matsuda, Hiroki Akamatsu, Tsunekazu Mizushima, Yuichiro Doki, Hirofumi Yamamoto
Journal: Cancer Research (2020)

Abstract Introduction The clinical importance of cancer stem cells (CSCs) has been widely reported, and clinical studies targeting CSCs are in progress. Additionally, accumulating evidence suggests that long noncoding RNAs (lncRNAs) have essential roles in cancer initiation and progression, while deregulated lncRNA expression is found in a variety of cancer types. In this study, we focused on lncRNAs regulating CSCs in colorectal cancer (CRC). Objectives To identify the lncRNAs associated with CSCs and to evaluate their clinical relevance and function. Materials and Methods We separated CSCs and other cells in CRC using the ornithine decarboxylase (ODC) degron system to visualize CSCs based on the correlation between low proteasome activity and CSC properties. We performed comprehensive gene analysis comparing CSCs and other cells to identify a candidate lncRNA that regulates the stemness of CRC cells. Finally, we analyzed the clinical relevance and function of the lncRNA. Results The lncRNA LNC01534 showed high expression in CSCs compared with the level in other CRC cells. Using gene expression and clinical data from the Cancer Genome Atlas Project for CRC patients, we showed that LNC01534 was associated with overall survival in CRC. LNC01534 was also associated with overall survival and disease-free survival in 187 separate CRC samples. Functional studies revealed that the loss of LNC01534 function reduced proliferation and arrested the cell cycle in CRC cells. Furthermore, genes that underwent expression changes upon the knockdown of LNC01534 were evaluated by RNA-seq. This showed that the knockdown of LNC01534 affected the expression of genes related to endoplasmic reticulum (ER) stress and autophagy. Specifically, the expression levels of HSPA5, LC3-I, p62, and Beclin-1–genes related to ER stress and autophagy–increased upon suppressing LNC01534. Conclusions We demonstrated the clinical and biological relevance of LNC01534 in association with CSCs, and discovered the effect of LNC01534 on ER stress and autophagy to maintain stemness in CRC. Citation Format: Masahisa Ohtsuka, Wu Xin, Momoko Ichihara, Haruka Hirose, Hidekazu Takahashi, Chu Matsuda, Hiroki Akamatsu, Tsunekazu Mizushima, Yuichiro Doki, Hirofumi Yamamoto. Long noncoding RNA LNC01534 regulates cancer stem cells in colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 264.
Abstract 13055: Ambulatory Pressure-Guided Heart Failure Management at an Advanced Heart Failure Program Shows Benefit Across Baseline Pressure Ranges
Authors: Jacob Abraham, Lian Wang, Rebecca Lewis, Katherine Callis, Josh Remick, Kateri Spinelli
Journal: Circulation (2018)

Introduction: Heart failure (HF) management guided by pulmonary artery pressure (PAP) monitoring using the CardioMEMS™ system has been shown to reduce PAP and HF hospitalization (HFH). Our aim was ...
AB0235 Relationship between the nottingham health profile and the health assessment questionnaire: evidence of validity in rheumatoid arthritis
Authors: P Emery, JM Woolley, WW Chan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To assess the validity of the Nottingham Health Profile (NHP) health-related quality of life measure in subjects with rheumatoid arthritis. It was hypothesised that improvements in the Health Assessment Questionnaire (HAQ) would be significantly related to the NHP. <h3>Methods</h3> Data on both the NHP and the HAQ were collected as part of a multicenter clinical trial conducted in Europe (n = 473). The NHP was administered at baseline and at weeks 12 and 24. The NHP consists of 38 items which assess physical mobility (MOB), pain (PAIN), energy (ENRG), sleep (SLP), emotional reactions (EMO), and social isolation (ISO). Both the NHP and the HAQ are scored so that lower scores indicate better HRQOL, and negative change scores indicate improvements. Validity was assessed by estimating the correlation between the scales of the NHP and the HAQ in cross-section and longitudinally (change score from baseline to week 24, Δ). It was hypothesised that both relationships would be positive, and that stronger relationships would be seen in the more physical HRQOL scales of the NHP (MOB and PAIN). <h3>Results</h3> In cross-section (first row of the Table 1), all six of the NHP scales were positively and statistically significantly correlated with the HAQ. Additionally, as shown in the second row, the changes in all six of the NHP scales were positively and statistically significantly correlated with the change in the HAQ (D HAQ). As predicted, the highest correlations were seen in the more physical HRQOL scales, MOB and PAIN. <h3>Conclusion</h3> These data support the validity of the Nottingham Health Profile as a measure of health-related quality of life in subjects with rheumatoid arthritis.
Abstract 15943: Phenotypes of Cardiogenic Shock Associated With Increasing In-Hospital Mortality: A Report From The National Cardiogenic Shock Working Group Registry
Authors: Katherine Thayer, Sarah Newman, Mohyee Ayouty, Lena Jorde, Reshad Garan, Jaime Hernandez Montfort, Claudius Mahr, Detlef Wencker, Shashank S Sinha, Esther Vorovich, Jacob Abraham, William O'Neill, Daniel Burkhoff, Navin K Kapur
Journal: Circulation (2019)

Introduction: Cardiogenic shock (CS) mortality remains prohibitively high. A major limitation in the field has been the lack of large registries that include hemodynamic data for analysis. The Nati...
CAR-T Therapy Is Approved for Mantle Cell Lymphoma
Authors: Rebecca Voelker
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 2528: Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4
Authors: Sang Yong Jung, Dong Ha Kim, Yong-Hee Cho, Yun Jung Choi, Seon Ye Kim, Ki Jung Sung, Chae Won Lee, Hyeon Jeong Lee, Chang-Min Choi, Jae Cheol Lee, Jin Kyung Rho
Journal: Cancer Research (2020)

Abstract Tumor-derived exsosomes (TEXs) contain enriched miRNAs act as novel non-invasive biomarkers for cancer diagnosis, and they are involved in cancer progression. In this study, we aimed to investigate which and how exosomal miRNA affect cancer progression in non-small cell lung cancer (NSCLC). We found that the only of A549 cell-released exosomes promote an angiogenic phenotype in HUVEC cells compared to other lung cancer cell-released exosomes. Using a miRNA array and RNA sequencing approach, we identified that specific miRNAs can modulate angiogenesis in A549 cell-released exosomes. Among these miRNAs, miR-619-5p significantly induced angiogenesis in HUVEC cells. Subsequently, RCAN1.4 was identified as a target of miR-619-5p and the suppression of RCAN1.4 inhibited the angiogenesis of HUVEC cells. Furthermore, the suppression of RCAN1.4 by miR-619-5p promoted the cellular mobility and proliferation in in vitro, as well as in vivo, tumor growth and metastasis in non-small cell lung cancer (NSCLC) cells. In patients with non-small cell lung cancer (NSCLC), the level of RCAN1.4 expression was significantly lower in tumor tissues than normal lung tissues, whereas the level of miR-619-5p was a significant higher in tumor tissue than normal lung tissues. We also found that there was a significant inverse correlation between the expression of miR-619-5p and that of RCAN1.4. In addition, miR-619-5p expression was higher in exosomes isolated from plasma of patients with NSCLC than normal. Finally, hypoxia condition led to enhance the amount of miR-619-5p within NSCLC cells-derived exosomes. In conclusion, exosomal miR-619-5p promotes tumor growth and metastasis of NSCLC by regulating RCAN1.4 in endothelial and tumor cells, and it can serve as a diagnosis and prognostic indicator for NSCLC patients. Citation Format: Sang Yong Jung, Dong Ha Kim, Yong-Hee Cho, Yun Jung Choi, Seon Ye Kim, Ki Jung Sung, Chae Won Lee, Hyeon Jeong Lee, Chang-Min Choi, Jae Cheol Lee, Jin Kyung Rho. Tumor-derived exosomal miR-619-5p promotes tumor angiogenesis and metastasis through the inhibition of RCAN1.4 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2528.
Abstract IA04: Drug resistance in end-stage high-grade serous ovarian cancer
Authors: Elizabeth L. Christie, Kathryn Alsop, George Au-Yeung, Ahwan Pandey, David D.L. Bowtell
Journal: Clinical Cancer Research (2020)

Abstract Background: Acquired drug resistance is the major obstacle in controlling high-grade serous ovarian cancer (HGSC) and leads to poor overall survival. Comparatively little massively parallel sequencing data exist from HGSC patients with recurrent or end-stage disease who have been extensively treated with chemotherapy or newer targeted agents, such as antiangiogenics or PARP inhibitors (PARPi). We previously identified four mechanisms of acquired resistance from whole-genome sequencing (WGS) of 23 HGSC patients with recurrent disease; a resistance mechanism of any kind was only identified in half of the patients. Aim: To characterize genomic features and identify mechanisms of acquired drug resistance in end-stage HGSC patients. Methods: Since 2012, we have collected tumor samples from 19 HGSC patients through our rapid-autopsy program. On average, we collect 17 tumor sites per patient during the autopsy, which is performed a median 6 hours after death. SNP array, WGS, and RNA sequencing were performed to detect germline and somatic mutations, copy number alterations and gene expression patterns. Results: A total of 89 end-stage tumor samples from 15 patients with germline or somatic mutations in components of the homologous recombination (HR) DNA repair pathway have been analyzed by SNP array, and a subset of those have undergone WGS (n=44) and RNAseq (n=47). As expected, all samples had a somatic pathogenic TP53 mutation and have highly aberrant somatic copy number profiles. Prominent mutational signatures (single- and double-base substitutions) are associated with defective HR and prior treatment with platinum drugs. The total single-base substitution mutation burden is similar across tumor samples within patients; however, many mutations are unique to individual tumor samples. Currently, reversion mutations, which are secondary mutations in HR genes, are the most common resistance mechanism identified in our cohort of end-stage patients. Conclusion: Our data are allowing us to understand HGSC at end stage, by examining the catalogue of resistance mechanisms within an individual patient and reconstructing the natural history of HGSC. Citation Format: Elizabeth L. Christie, Kathryn Alsop, George Au-Yeung, Ahwan Pandey, Australian Ovarian Cancer Study, David D.L. Bowtell. Drug resistance in end-stage high-grade serous ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA04.
Abstract 3502: Do obese patients present with worse breast cancer
Authors: Melinda Wang, Julian Huang, Anees Chagpar
Journal: Cancer Research (2020)

Abstract Background: Obesity is a known risk factor for breast cancer development; however, it is unclear whether obesity results in worse disease in terms of stage at presentation, receptor profile, and tumor grade. We sought to determine the relationship between obesity and disease status at presentation in patients undergoing mastectomy for breast cancer. Methods: Medical records of breast cancer patients undergoing mastectomy at our institution between January 2010 and April 2018 were retrospectively reviewed. Patients were separated into obese (BMI ≥ 30) and non-obese (BMI &amp;lt; 30) categories, and compared using non-parametric statistical analyses. Results: Of the 927 patients in this cohort, 292 (31.3%) were obese. Sociodemographic and clinicopathologic factors of the obese and non-obese patients are shown in the table below. In general, obese patients were more likely to present with node positive disease (27.1% vs. 19.2%, p = 0.008) and positive triple negative status (10.0% vs. 15.4%, p = 0.026). Controlling for the potential confounders of race and insurance status, obesity remained associated with triple negative status (95%CI: 1.04 - 2.46; p = 0.033) and node positive disease (95%CI:1.17 - 2.31; p = 0.004). Factors associated with obese vs. non-obese mastectomy patientsFactorNot Obese (n = 635)Obese (n = 292)p-valueAge (yrs); median52520.494Race: White: no. (%)506 (79.7%)220 (75.3%)&amp;lt;0.001Race: Black: no. (%)49 (7.7%)52 (17.8%)Race: Asian: no. (%)35 (5.5%)5 (1.7%)Race: Other: no. (%)45 (7.1%)15 (5.1%)Insurance: Uninsured: no. (%)4 (0.6%)1 (0.3%)0.003Insurance: Medicaid: no. (%)63 (9.9%)54 (18.5%)Insurance: Medicare: no. (%)92 (14.5%)40 (13.7%)Insurance: Military: no. (%)11 (1.7%)9 (3.1%)Insurance: Private: no. (%)465 (73.2%)188 (64.4%)Node positive: no. (%)122 (19.2%)79 (27.1%)0.008Multifocality/Multi centricity: no. (%)142 (22.7%)68 (23.4%)0.800Presence of DCIS: no. (%)490 (77.2%)213 (72.9%)0.186Median invasive tumor size (cm)0.500.700.094AJCC Stage: 0: no. (%)217 (34.3%)90 (30.9%)0.073AJCC Stage: I: no. (%)207 (32.8%)78 (26.8%)AJCC Stage: II: no. (%)139 (22.0%)82 (28.2%)AJCC Stage: III: no. (%)65 (10.3%)40 (13.7%)AJCC Stage: IV: no. (%)4 (0.6%)1 (0.3%)ER+: no. (%)505 (79.5%)222 (76.0%)0.425PR+: no. (%)424 (66.8%)194 (66.4%)0.943Her2+: no. (%)95 (15.3%)30 (10.5%)0.111Triple negative: no. (%)62 (10.0%)44 (15.4%)0.026 Conclusion: Obese patients tend to present with more aggressive breast cancer, independent of sociodemographic factors. Citation Format: Melinda Wang, Julian Huang, Anees Chagpar. Do obese patients present with worse breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3502.