tbuckley/cabot-search huggingface dataset:
Prenatal Special Supplemental Nutrition Program for Women, Infants, and Children Participation
Authors: Maureen M. Black, Angela C. B. Trude, Bridget Armstrong
Journal: JAMA Pediatrics (2019)

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 Pediatrics 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 Pediatrics journal
Abstract LB-048: WRN helicase is a synthetic lethal target in microsatellite unstable cancers
Authors: Edmond M. Chan, Tsukasa Shibue, James McFarland, Benjamin Gaeta, Francisca Vazquez, Adam J. Bass
Journal: Cancer Research (2019)

Abstract Microsatellite instability (MSI), a class of genetic hypermutability that arises from impaired DNA mismatch repair (MMR), contributes to the development of many malignancies including colon, endometrial, gastric, and ovarian cancers. While immune checkpoint blockade (ICB) has been an effective therapy for many patients with MSI cancers, numerous patients with MSI malignancies do not respond to ICB or the use of these agents are limited by their toxicity. Hence, there is still a pressing need to develop further therapies against MSI cancers. One approach to develop novel therapeutics is to leverage synthetic lethality, a phenomenon whereby the simultaneous occurrence of two or more genetic events lead to cell death but one event alone does not. DNA repair processes represent attractive synthetic lethal targets since many cancers exhibit an impaired DNA repair pathway, which can lead these cancers to become dependent on specific repair proteins. The success of poly (ADP ribose) polymerase (PARP) inhibitors in homologous recombination-deficient cancers highlights the potential of this approach. Hypothesizing that other DNA repair defects would give rise to alternative synthetic lethal relationships, we asked if there are specific dependencies in MSI cancers. Here, we analyzed data from large-scale CRISPR/Cas9 and RNA interference (RNAi) functional genomic screens and found that the RecQ DNA helicase WRN was selectively essential in MSI models in vitro and in vivo, but dispensable in microsatellite stable models. WRN silencing induced double-strand DNA breaks, activated a DNA-damage response, and promoted apoptosis and cell cycle arrest preferentially in MSI models. MSI cancer models specifically required WRN’s helicase activity, but not its exonuclease activity. These findings expose WRN as a synthetic lethal vulnerability and promising drug target for MSI cancers. Citation Format: Edmond M. Chan, Tsukasa Shibue, James McFarland, Benjamin Gaeta, Francisca Vazquez, Adam J. Bass. WRN helicase is a synthetic lethal target in microsatellite unstable cancers [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 LB-048.
Abstract 164: MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 and promotes colorectal cancer metastasis
Authors: Qing Ji, Guoxiang Cai, Xuan Liu, Yi Zhang, Yan Wang, Lihong Zhou, Hua Sui, Qi Li
Journal: Cancer Research (2019)

Abstract Ectopic expression of lncRNA-MALAT1 has been discovered in recurrent colorectal cancer (CRC) and metastatic sites in post-surgical patients, however, its biological mechanism remained un-elucidated. Our study firstly revealed the novel mechanisms of MALAT1 in promoting CRC metastasis through at least the following two mechanisms: First of all, MALAT1 binds miR-15 family members, to “de-inhibit” their effect on LRP6 expression, enhances beta-catenin signaling, leading to elevated transcriptional levels of downstream target genes RUNX2. Secondly, MALAT1 binds SFPQ, dissociate SFPQ/PTBP2 dimer to release free PTBP2, which elevates translational levels of RUNX2, through interacting with IRES domain in the 5’UTR of the corresponding RUNX2 mRNAs. Moreover, elevated RUNX2 expression levels were detected in recurrent CRC tumors, which were closely associated with TMN stages and CRC patients’ survival. Our data demonstrated that, MALAT1 and RUNX2 may serve as two biomarkers for predicting the recurrence of CRC patients. Note: This abstract was not presented at the meeting. Citation Format: Qing Ji, Guoxiang Cai, Xuan Liu, Yi Zhang, Yan Wang, Lihong Zhou, Hua Sui, Qi Li. MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 and promotes colorectal cancer metastasis [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 164.
Abstract LB-236: Genomic characterization of circulating tumor cells in de novo metastatic prostate cancer
Authors: Shoujie Chai, Paymaneh D. Malihi, Ana M. Apariciop, Brian F. Chapin, Matthew Lin, Ryan Storgard, Carmen Ruiz Velasco, Anand Kolatkar, James Hicks, Peter Kuhn
Journal: Cancer Research (2019)

Abstract Background: The absence of biomarkers that identify clinically meaningful biological subsets of prostate cancer results in the homogeneous application of systemic therapies to a heterogeneous disease and hampers therapy development. This heterogeneity may become more evident at the molecular level under the pressure of androgen withdrawal. Here, we longitudinally characterized peripheral blood circulating tumor cells (CTCs) from patients with de novo metastatic prostate cancer to examine the phenotypic and genomic changes induced by androgen suppression. Methods: Peripheral blood samples were collected at MD Anderson Cancer Center from a cohort of DNM1PCa patients under clinical trial NCT01751438. Timepoints of collection includes baseline (BSL, before treatment) and 6 months (6mo, after 6 months of systemic therapy). We used the High-Definition Single Cell Assay (HD-SCA) workflow for CTC enumeration, morphology (nuclear size, DAPI intensity, cytokeratin (CK), androgen receptor (AR) intensity and genomics (whole-genome copy number aberration analysis) evaluation. This workflow utilizes an enrichment-free fluorescence based (DAPI/ CK/ CD45/ AR) CTC identification system and single-cell genomic sequencing. Results: Twenty-nine of the 58 available blood samples contained CTCs: 15 of the 28 (53.6%) collected at BSL (median 2.00 CTCs/mL, range 0.84-74.15) and 14 of the 30 (46.7%) collected at 6mo (median 2.43 CTCs/mL, range 0.96-13.85). However, at the 6mo timepoint, the CTCs had undergone a significant morphological shift in nuclear area local ratio (BSL vs 6mo: 1.036 vs 1.165, p=0.039), DAPI intensity (0.199 vs 1.030, p=0.036), CK intensity (18.978 vs 15.651, p=0.006), AR intensity (0.681 vs -0.468, p=0.037) and AR+ percentage (36.25% vs 15.38%, p=0.020). Further, genomic analysis of two patients at BSL indicated copy number aberrations including PTEN, TP53, RB1 and BRCA2 loss and MYC gain. Discussion: This study aims at characterizing changes induced by systemic therapies in CTC potential biomarkers that identify distinct subsets of disease biology. The changes observed in patient subsets may serve as clinically relevant biomarkers to optimize treatment and improve prognosis. Citation Format: Shoujie Chai, Paymaneh D. Malihi, Ana M. Apariciop, Brian F. Chapin, Matthew Lin, Ryan Storgard, Carmen Ruiz Velasco, Anand Kolatkar, James Hicks, Peter Kuhn. Genomic characterization of circulating tumor cells in de novo metastatic prostate cancer [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 LB-236.
Abstract 3585: Amino acid transporter SLC6A14: A novel drug target for colorectal cancer
Authors: Mohd Omar Faruk Sikder, Sathish Sivaprakasam, Vadivel Ganapathy
Journal: Cancer Research (2019)

Abstract SLC6A14 is a Na+/Cl− -dependent amino acid transporter capable of transporting 18 of the 20 proteinogenic amino acids, including arginine, leucine (mTOR activators) and glutamine (necessary for nucleotide biosynthesis). This transporter is expressed at basal levels in normal colon but significantly upregulated in colorectal cancer (CRC). However, the relevance of this upregulation to disease progression remains unknown. We postulated that deletion of SLC6A14 or pharmacological blockade of its function would suppress CRC by depleting amino acids and interfering with mTOR signaling selectively in tumor cells. To test this postulate, we first used Slc6a14-null mice. With two different models of spontaneous CRC (Apcmin/- and DSS/AOM), we found the tumor incidence and tumor growth were much lower in mice with Slc6a14-null background than in mice with Slc6a14. To evaluate the impact of pharmacologic blockade of the transporter on tumor growth we used a syngeneic tumor mouse model with MC-38 cells (a mouse CRC cell line); blockade of Slc6a14 with alpha-methyl tryptophan (α-MT) markedly reduced tumor growth. We then determined the transcriptome profiles of colonic epithelial cells and colonic non-epithelial cells from wild type mice and Slc6a14-null mice by RNAseq. There were hundreds of genes that were either upregulated or downregulated in the null mice. Ingenuity pathway analysis (IPA) of these data revealed predictive activation of canonical AMPK signaling pathway in colonic epithelial of Slc6a14-null mice. AMPK has anticancer activities by modulating multiple pathways including negatively regulating mTOR signaling. Moreover, upstream analysis showed predictive inactivation of two important tumor growth and survival signaling pathways ERK and EGF in the colon of the null mice. Likewise, significant upregulation of APC downregulated 1 (APCDD1) in epithelial cells in null mice implies predictive suppression of canonical Wnt signaling pathway. We also found marked differences in fecal microbiota as a result of Slc6a14 deletion. There was an increase in the relative abundance of beneficial microbiota including those capable of generating short chain fatty acids and lactic acid in null mice. We conclude that deletion of Slc6a14 or its pharmacological blockade protects against CRC by inducing amino acid starvation in tumor cells, thereby causing changes in multiple signaling pathways and in colonic microbiome. These studies identify SLC6A14 as a novel drug target for the treatment of colorectal cancer. Citation Format: Mohd Omar Faruk Sikder, Sathish Sivaprakasam, Vadivel Ganapathy. Amino acid transporter SLC6A14: A novel drug target for colorectal cancer [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 3585.
Acalabrutinib with obinutuzumab (Ob) in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Three-year follow-up.
Authors: Jennifer Ann Woyach, Kerry Anne Rogers, Seema Ali Bhat, James Stewart Blachly, Mojgan Jianfar, Melanie M. Frigault, Ahmed M. Hamdy, Raquel Izumi, Veerendra Munugalavadla, Cheng Seok Quah, Min Hui Wang, John C. Byrd
Journal: Journal of Clinical Oncology (2019)

7500 Background: Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor. This Phase 1b/2 trial evaluated acalabrutinib with the CD20 antibody Ob in TN and R/R CLL. Methods: Patient (pts) with TN and R/R (≥1 prior therapy) CLL were eligible. In 28-day cycles, acalabrutinib was given at 100 mg BID or 200 mg QD PO (n=15; all switched to 100 mg BID) until progressive disease (PD); Ob was given in standard fashion for 6 cycles starting with Cycle 2. The primary endpoints were overall response rate (ORR) and safety. Minimal residual disease (MRD) was assessed using flow cytometry (sensitivity 10 -4 ). Results: 19 TN and 26 R/R pts were treated; median age of all pts was 61 y (range 42-76). Pt characteristics, disposition, efficacy and MRD are in the Table. Common adverse events (AEs; any grade) were upper respiratory tract infection (71%), increased weight (71%), maculopapular rash (67%), cough (64%), diarrhea (62%), headache (56%), nausea (53%), arthralgia (51%) and dizziness (47%). Common Gr 3/4 AEs were decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight and cellulitis (9% each). There were 2 (4%) Gr 3 bleeding events (hematuria, muscle hemorrhage) and 1 (2%) Gr 3 atrial fibrillation event. Conclusions: Acalabrutinib plus Ob was well tolerated and yielded high response rates that were durable and deepened over time in TN and R/R CLL patients. Clinical trial information: NCT02296918. [Table: see text]
Abstract 2639: Insulin receptor alternative splicing during development and cancer
Authors: Safiya Khurshid
Journal: Cancer Research (2019)

Abstract It has been shown that alternative splicing of some genes changes during development from embryogenesis to adulthood. Intriguingly, transformation of cells is also often accompanied by a reversion to the embryonic spliced isoforms. Insulin receptor (IN-R) undergoes alternative splicing to produce two isoforms: the full-length IN-RB isoform and the exon 11-skipped IN-RA isoform. The IN-RB isoform encodes a receptor with high affinity for insulin, while the IN-RA isoform has high affinity for both insulin &amp; IGF2 growth hormones. IN-RAexploits the IGF pathway to accelerate growth, proliferation and angiogenesis. It is known that during embryogenesis the IN-R gets spliced to primarily express the INR-A form. Recently, the A isoform has has also been shown to be expressed in certain cancer types. Because the insulin receptor signaling converges on the mTOR/AKTpathway that is one of the most critical pathways for organismal development as well in cancer, it is important to understand the expression of these isoforms and their role in signaling and cellular fate. However, a tissue and a temporal description of the expression of these two isoforms is lacking. Towards this end we have shown that the mouse insulin receptor gene is spliced similarly to the human gene and have used the mouse model to study IR splicing during development. We harvested tissues from mice at different developmental stages (E10, E18, P1, P7, 3 months and 6 months) and performed RT-PCR for the insulin receptor gene. Our data confirmed that the whole embryos at embryonic day 10 (E10) express mostly IN-RA (90%). However, as the embryo develops and we can obtain discrete tissues we are able to detect tissue-specific profiles of IN-Rsplicing. For example, in bone at E18 as well as postnatal day P1 and 7, IN-RBis highly expressed (65%) and decreases to (40%) as the mouse reaches 6 months of age. Likewise, the liver and pancreas, which are primarily involved with metabolic functions, express mostly IN-RB(90%) from postnatal day P1 and into adult hood (6 months). In contrast, when we analyzed IR-splicing in human cancers, we find that in both liver cancer and cancers of the bone (osteosarcoma and Ewing’s sarcoma) there is a shift toward increased levels of the pro-proliferative isoform, IN-RA. We believe that understanding the molecular underpinnings of the splicing regulation during development will provide us with knowledge that will help us better understand the transformation process and how to control it, possibly through splicing corrective therapy. Citation Format: Safiya Khurshid. Insulin receptor alternative splicing during development and cancer [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 2639.
Abstract 15589: Protein-Protein Inhibitor Peptide of Drp1/Fis1 Interaction Protects the Heart Against Ischemia/Reperfusion Injury
Authors: Marie-Helene Disatnik, Julio C Ferreira, Juliane Cruz Campos, Katia Sampaio Gomes, Paulo M Dourado, Xin Qi, Daria Mochly-Rosen
Journal: Circulation (2013)

Background: The involvement of mitochondrial function and dynamics in cardiovascular health has been lately been demonstrated. Mitochondrial fission, governed by dynamin related protein 1 (Drp1) wa...
Challenges in the diagnosis of primary cutaneous <scp>CD</scp> 30 <sup>+</sup> anaplastic large‐cell lymphoma
Authors: G. Dobos, M. Battistella, F. Jouenne, S. Mourah, M.D. Vignon‐Pennamen, C. Ram‐Wolff, F. Herms, J.N. Dauendorffer, J. Rivet, J.M. Cayuela, D. Bouaziz, P. Brice, C Lebbé, M. Bagot, A. Masson
Journal: British Journal of Dermatology (2019)
Do we need adjuvant therapy in patients with rectal cancer and pathologic complete response, after conventional preoperative chemoradiation and laparoscopic (LapTME) or Transanal total mesorectal excision (TaTME)?
Authors: R. Reyes, J. Ayuso, M. Pagés, C. Conill, A. Darnell, E. Pineda, A. Gines, M. Fernández-Esparrach, M. Cuatrecasas, R. Moreno, A. Lacy, M. Pellisé, J. Maurel
Journal: Annals of Oncology (2019)
Diagnostic accuracy of dermatoscopic image retrieval
Authors: P. Tschandl, G. Argenziano, M. Razmara, J. Yap
Journal: British Journal of Dermatology (2019)

A neural network is a computer system modelled on the human brain. Neural networks can learn to detect visual elements such as colours, shapes and edges by themselves, and as such they have shown great improvements in automated classification and diagnosis of skin tumours. Unfortunately, in the most common format, they only provide final probability values as, for example “5% melanoma, 60% nevus, 25% seborrheic keratosis”. Although experimental results have shown networks to be fairly accurate, it is hard for a user to have insight into the prediction, and how to integrate it with their own decision process. One option to make a neural network “explainable” is to simply let it search for and present similar images on a database, much like looking up a similar case one has seen in a book – only faster and more comprehensive. This also has the upside that when images don't look anything close to the searched skin lesion, a user immediately knows not to trust the automated analysis in that case. The authors showed in this study, that if a network provides similar images, these images can convey the same accuracy as the conventional “5% melanoma, 60% nevus, 25% seborrheic keratosis” output. They further found that searching for up to only 16 similar images is enough to provide that information. This study suggests that simply searching for similar images can harness the prediction abilities of neural networks while being understandable for an end user.
Abstract 4049: Cellular phenotypes of spleen cells in cancer patients targeted for adoptive cellular therapy
Authors: Kathryn Cole, Quan Ly, Jesse L. Cox, Michael A. Hollingsworth, James C. Padussis, Jason M. Foster, Luciano M. Vargas, James E. Talmadge
Journal: Cancer Research (2019)

Abstract The spleen is a rich resource of large numbers of lymphocytes, with potential for use in adoptive cellular therapy (ACT). This is of particular relevance to patients with a distal pancreatic ductal adenocarcinoma (PDAC) who frequently undergo a pancreatectomy that required a splenectomy to clear the nodal basin. In this study we compared the phenotypes of eight paired sets of peripheral blood (PB) and spleen cell populations to assess the frequency of myeloid derived suppressor cells (MDSC) and lymphocyte subpopulations. Because a positive clinical response to ACT requires a low frequency of T-regs and MDSC’s, both systemically and in the tumor microenvironment these cells were one of the foci for our studies. A high frequency of these cells negatively correlate with survival and positively with tumor burden. Indeed, in this study we observed a significant decrease in the frequency of granulocytic, monocytic and immature MDSC’s in the spleen vs PB (4.8±1.6 vs. 54.4±6.1; 0.2±0.1 vs. 0.9±0.4; and 0.6±0.1 vs. 2.3±0.8 percent respectively) but not T-regulatory (T-reg) cells (0.8+0.5 vs. 0.1+0.04 percent) supporting the potential superiority of spleen cells relative to PB as a cellular source for ACT. In addition to a significantly higher number of spleen cells as compared to the PB for expansion/infusion, spleens have a higher frequency of T-cells as compared to the PB including CD3+ (35+5 vs. 16+4%), CD4+ (19+2 vs. 10+2%) and CD8+ (10+1 vs. 5+2%) T-cells. The frequency of transitional memory (Ttm) T-cells, which have a high proliferative potential were also significantly increased in the spleen vs. PB (37.5±6 vs. 26±3.0%) as was the frequency of PD1+CD8+ T-cells (8+2 vs 1+0.5%), which have been shown to have tumor specific cytotoxicity in cancer patients. In summary the increased frequency of PD-1+CD8+ cells, a Ttm memory phenotype and low levels of an exhaustion phenotype (TIM3 and Lag3 expression) in spleen cells vs the PB is supportive of the potential utility of these cells for expansion and therapeutic utility for these cells. Citation Format: Kathryn Cole, Quan Ly, Jesse L. Cox, Michael A. Hollingsworth, James C. Padussis, Jason M. Foster, Luciano M. Vargas, James E. Talmadge. Cellular phenotypes of spleen cells in cancer patients targeted for adoptive cellular therapy [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 4049.
Proposal of optimal cut-off of preoperative serum tumor marker levels to predict postoperative recurrences of gastric cancer
Authors: B. Sato, M. Kanda, S. Ito, H. Teramoto, Y. Mochizuki, K. Ishigure, T. Murai, T. Asada, A. Ishiyama, H. Matsushita, C. Tanaka, D. Kobayashi, M. Fujiwara, Y. Kodera
Journal: Annals of Oncology (2019)
Evaluating Open Payments
Authors: Genevieve P. Kanter, George Loewenstein
Journal: JAMA (2019)

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