tbuckley/cabot-search huggingface dataset:
Understanding international genomic diversity for breast cancer: Comparison of molecular subtypes of breast cancer in very young women (age ≤ 35) between Izmir (Western Turkey) and Boston (Massachusetts, USA).
Authors: Burcak Karaca, Tracy Ann Battaglia, Naomi Ko, Moly McCoy, Hatice Yasdik, Bonnie Sherman, Raika Durusoy, Canfeza Sezgin, Bulent Karabulut, Ruchan Uslu
Journal: Journal of Clinical Oncology (2013)

e12509 Background: One in forty women is diagnosed with breast cancer at a very young age (≤35 years). Studies suggest breast cancer molecular subtypes are different in young women, with a higher prevalence of triple negative and HER-2+ disease. Objective: Explore the impact of genetic diversity on molecular subtyping of very young breast cancer patients in geographically and ethnically diverse populations: Turkey and the United States. Methods: A retrospective analysis of women ≤35 years of age diagnosed with breast cancer from 1999-2011 at Ege University Faculty of Medicine (EUFM) and Boston Medical Center (BMC). Data were collected and abstracted from hospital cancer registries and electronic medical records. Molecular subtyping was based on immunohistochemical evaluation of estrogen, progesterone receptors, Ki-67, and HER2/neu. Bivariate analysis was conducted using Chi-Square and Fisher’s Exact tests. Results: There were 206 and 45 patients from EUFM and BMC, respectively. Mean age at diagnosis was 31.4±3; most were white (87%), parous (70%), had breast fed (74%), and no1st degree relatives with breast cancer (92%). BMC patients were younger (31.7±3 v. 29.9±3 p=.0006) and more racially diverse (0% v. 60% black/hispanic p &lt;.0001). There were clinicopathological differences between EUFM and BMC, including: histological subtype (IDC 68% v. 93% p=.02), HER-2/neu positivity (60% v. 16% p &lt;.0001), and Ki67 ≥15% (54% v. 83% p=.008). Missing data precluded subtyping in 25% and 22% of women at EUFM and BMC. Of subtypes determined, prevalence was the same; however, EUFM had more Luminal B and less Triple negative patients then BMC. Conclusions: Population-level similarities and proportional distinctions exist in molecular subtypes of breast cancer for women ≤35 years. In both countries, Luminal B and triple negative sybtypes were most common suggesting younger age rather than genetic diversity is an important determinant of molecular subtyping. [Table: see text]
Abstract 610: A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study
Authors: Joe Shearer, Laura Beane Freeman, Danping Liu, Gabriella Andreotti, Jennifer Hamilton, Julie Happel, Charles Lynch, Michael Alavanja, Jonathan Hofmann
Journal: Cancer Research (2019)

Abstract Background: In the Agricultural Health Study, a large prospective cohort of pesticide applicators, high lifetime use of the insecticide permethrin was associated with an increased risk of multiple myeloma. However, the biological mechanisms through which this association occurs remain to be fully understood. Methods: Hematologic perturbations were assessed among 33 permethrin-exposed male pesticide applicators enrolled in the Biomarkers of Exposure and Effect in Agriculture study, a molecular substudy within the Agricultural Health Study. Serial blood samples were collected from each participant coinciding with permethrin use including visits during the offseason, an exposure visit the day after use, and for 27 participants a follow-up visit approximately three weeks after use. Complete blood count with white blood cell differential and lymphocyte subsets were collected at each visit. Linear mixed models were used to assess the relationship between permethrin exposure and hematologic parameters, controlling for potential confounders including season of blood draw, age, body mass index, recent cold/infection, and use of other pesticides. Results: A statistically significant increase in the adjusted mean immature granulocyte count (37%, 95% CI=6%, 76%) was observed the day after permethrin use compared to an offseason visit. Statistically significant (P&amp;lt;0.05) alterations in several red blood cell (RBC) parameters were also observed on the day after permethrin use, including decreased RBC count and hemoglobin and increased mean corpuscular volume and RBC distribution width-SD. Decreases in RBC count and hemoglobin, and increased levels of RBC distribution width-SD persisted approximately three weeks after permethrin use. Conclusions: Altered hematologic parameters could be indicative of disrupted hematopoiesis, providing insights into the potential biologic plausibility of the observed association between permethrin use and multiple myeloma risk among pesticide applicators. Impact/Significance: Given the widespread use of permethrin in both residential and commercial settings, our findings may have public health implications beyond occupationally exposed pesticide applicators. Citation Format: Joe Shearer, Laura Beane Freeman, Danping Liu, Gabriella Andreotti, Jennifer Hamilton, Julie Happel, Charles Lynch, Michael Alavanja, Jonathan Hofmann. A longitudinal investigation of hematologic perturbations among permethrin-exposed pesticide applicators in the Biomarkers of Exposure and Effect in Agriculture Study [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 610.
Real-world treatment patterns in adult patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP ALL) in first hematologic complete remission (CR1) with and without minimal residual disease (MRD).
Authors: Shweta Shah, Darya Rose, Ze Cong, Shruti Tibrewala, Anita Chawla, Faraz Zaman
Journal: Journal of Clinical Oncology (2019)

e18517 Background: B-cell precursor acute lymphoblastic leukemia (BCP ALL) is a rare and debilitating hematologic cancer. Among patients (pts) in complete remission (CR), minimal residual disease (MRD) is a strong prognostic factor for worse survival outcomes. Limited real-world data is available from the United States to characterize treatment patterns in BCP ALL pts. Methods: A chart review was conducted to assess treatment patterns among adult BCP ALL pts with and without MRD in first hematologic CR (CR1) across National Cancer Institute designated cancer centers, academic and community hospitals, and integrated delivery systems. The study period was the date of CR1 until 12 months post-CR1, relapse, or death. Eligible pts were ≥18 years of age with BCP ALL in CR1 between 4/2015 and 3/2017, with no other cancer diagnoses. Results: Overall, 65 (52%) of the 125 pts included in the study received drug therapy for ALL. Of the 79 total unique treatment regimens, the most frequently administered were intensification/consolidation regimens (46.8%), followed by long-term maintenance (36.7%), and preparation for hematopoietic stem cell transplantation (16.5%). Common regimens among Philadelphia chromosome-negative pts included hyper-CVAD (50%), monthly vincristine/prednisone, weekly methotrexate, and daily 6-mercaptopurine (31%), and CALGB 8811 (16.7%). The proportion of pts receiving drug therapy among community hospitals and academic settings were considerably similar (52% vs 48.3%).The majority of physicians selected hyper-CVAD as the standard of care for pts with MRD+ in CR1 (70.3%), with 48.4% of physicians selecting CALGB 8811, 32.8% selecting multiagent chemotherapy, and 29.7% selecting Linker-4, and 23.4% selecting monthly vincristine/prednisone, weekly methotrexate, daily 6-mercaptopurin. Conclusions: Nearly 50% of pts included in this study did not receive drug therapy for ALL (mean age: 47.8 years). The real-world treatment regimens among treated pts observed in this study are consistent with the NCCN guidelines although there is substantial heterogeneity in the management of BCP ALL.
Abstract 4788: Novel hybrid benzothiazole screening in U87-MG glioblastoma cell line
Authors: Priscilla Kyi, Desmond H. Murray, Denise L. Smith
Journal: Cancer Research (2019)

Abstract Benzothiazole is a heteroaromatic compound known for its wide range of bioactivities including anticancer, antiviral, antimicrobial, anti-inflammatory, anticonvulsant, antidiabetic, antihelminthic, and antitubercular activities. Research has shown that derivatives of benzothiazole exhibit inhibition of proliferation via apoptosis in various human cancer cell lines, such as liver cancer (Wang, et. al., 2010). In this study, a series of novel hybrid benzothiazole α-cyanostilbene derivatives and styrylbenzothiazole derivatives containing boronic acid and non-boronic acid pharmacophores were synthesized and their anti-cancer properties on U87-MG glioblastoma cells were investigated in vitro. U87-MG cells were incubated with synthesized novel hybrid compounds at varying concentration to determine the inhibitory concentration 50 (IC50) of the compounds. Most hybrid compounds displayed inhibitory effects on cell growth and the IC50 of the compounds varied depending on the nature of the pharmacophores. Moreover, boronic acid-containing compounds exhibit lower IC50 than nonboronic acid-containing compounds. Cell mobility has been investigated and we have found that treated cells were less mobile than untreated cells. In the future, we will be further screening for mobility, invasiveness, and mode of death of these novel hybrid benzothiazole treated glioblastoma cells. Citation Format: Priscilla Kyi, Desmond H. Murray, Denise L. Smith. Novel hybrid benzothiazole screening in U87-MG glioblastoma cell line [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 4788.
Dancing Dorsal Quadrilaterals—Organic or Functional?—Reply
Authors: Karlo J. Lizarraga, Philip D. Thompson, Anthony E. Lang
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Abstract 1425: Chimeric antigen receptors based on T cell receptor-like antibodies
Authors: Ling Wu, Joanna Brzostek, Shvetha Sankaran, Triscilla Tan, Conrad Chan, Jiawei Yap, Junyun Lai, Paul MacAry, Nicholas Gascoigne
Journal: Cancer Research (2019)

Abstract T cells are essential in adaptive immunity and play an indispensable role to eliminate abnormal or virus infected cells. By merging antibody technology and cell engineering, T cells equipped with a chimeric antigen receptor (CAR) can be redirected to the target in a non-MHC restricted fashion. Within the past few years, clinical trials using CAR T cells engineered to recognize B cell cancers have shown high rates of response (70%-90%) and durability of response that are unprecedented in acute and chronic leukaemia. However, severe toxicity has been observed due to massive, and to some extent nonspecific, T cell activation. Although CARs have been improved and investigated heavily, the extent to which a CAR is similar to its parental TCR extra- or intracellularly, and whether critical elements involved in normal TCR signalling are kept or rewired in CAR signalling, are unclear. A better understanding of these questions would greatly facilitate improvements in CAR technology and its usefulness in clinical practice. A CAR targeting a peptide-MHC complex (using an Fv from an antibody that recognizes MHC-peptide: in other words, a TCR-like Ab) mimics the process of TCR recognition and takes advantage of CAR technologies developed so far. It is thus an excellent study object to compare TCR and CAR signalling. Well-built research methods on TCR can be transferred immediately to TCR-like CAR, while the knowledge and findings generated through the studies of TCR-like CAR can in turn renew our perceptions on TCR. TCR-like antibodies targeting the EBV epitopes LMP1125-133, LMP2A426-434 or EBNA1562-570, were engineered as CARs. We find that conformation change, if any, upon ligand binding is not enough to activate downstream TCR signalling, but oligomerization is a crucial factor. Although CAR with a TCR-like specificity can recruit CD8 co-receptor to the immunological synapse, it is dispensable for activation of the T cell. Furthermore, the activation kinetics of CAR and TCR are distinctly different. TCR shows a pulse-like activation, whereas CAR shows an activation that gradually plateaus and remains steady. These unique properties of CAR identified in our study demonstrate that CAR signalling properties may be amenable to modifications leading to better specificity and activity in vivo. Our long-term goal is that the TCR-like CAR can be used to combat EBV induced Nasopharyngeal Carcinoma. Citation Format: Ling Wu, Joanna Brzostek, Shvetha Sankaran, Triscilla Tan, Conrad Chan, Jiawei Yap, Junyun Lai, Paul MacAry, Nicholas Gascoigne. Chimeric antigen receptors based on T cell receptor-like antibodies [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 1425.
Analysis of time to next treatment (TTNT) in melflufen and dexamethasone-treated patients (pts) with relapsed/refractory multiple myeloma (RRMM).
Authors: Sara Bringhen, Paul G. Richardson, Peter Michael Voorhees, Torben Plesner, Ulf-Henrik Mellqvist, Jeffrey A. Zonder, Brandi Nikcole Reeves, Stojan Zavisic, Johan Harmenberg, Jakob Obermüller, Pieter Sonneveld
Journal: Journal of Clinical Oncology (2019)

8043 Background: Melflufen is a novel peptide-conjugated alkylator potentiated by intracellular aminopeptidases, which are markedly overexpressed in MM. Melflufen + dex had encouraging activity in pts with RRMM and ≥2 prior lines of therapy in the phase 1/2 O-12-M1 study (overall response rate 31%; median overall survival of 20.7 mo; Richardson et al. ASH 2017. Abs. 3150). TTNT is used in Real World Evidence (RWE) to assist treatment decisions and support economic reimbursement modeling. We report TTNT after melflufen + dex in O-12-M1. Methods: Pts with RRMM and ≥2 prior lines of therapy, including bortezomib and lenalidomide (len) received 40 mg IV melflufen on d 1 of each 28-d cycle + 40 mg weekly dex until progressive disease (PD)/unacceptable toxicity. Pts were followed up for 2 y after PD, and TTNT was retrospectively reviewed for subsequent therapy. Results: As of 9 Nov 2017, 45 pts were treated: median age, 66 y (47-78); ISS stage II/III, 60%; high-risk cytogenetics, 44%. Pts had 4 median prior lines of therapy; 87% were refractory to last line of therapy including alkylators (24%), proteasome inhibitors (PIs; 27%), IMiDs (56%), and monoclonal antibodies (mAbs, 9%); 11% were last-line double refractory. At data cutoff, 44 pts (98%) discontinued melflufen + dex, mainly due to adverse events (40%) and PD (29%). 26 pts received subsequent therapy. Median time from start of melflufen + dex to first subsequent therapy or death, whichever occurred first, (TTNT) was 7.9 mo (95% CI: 5.7-11.0); next therapy included alkylators (27%), PIs (38%), IMiDs (58%), and mAbs (8%). Conclusions: Types of subsequent salvage therapy used after melflufen + dex were similar to studies of approved agents in RRMM; TTNT was also similar (Table). Further trials are ongoing, including melflufen + dex vs pomalidomide (pom) + dex in pts with RRMM refractory to len (Phase 3 OCEAN study; NCT03151811). Clinical trial information: NCT01897714. [Table: see text]
Abstract 14654: Does Modern Excimer Laser Coronary Atherectomy Improve In-Hospital Mortality in Patients With Acute Myocardial Infarction ?
Authors: Takashi Shibui, Kiyotaka Yoshida, Sho Nagamine, Shinichiro Masuda, Takaaki Tsuchiyama, Takashi Ashikaga
Journal: Circulation (2018)

Introduction: Excimer Laser Coronary Atherectomy (ELCA) is an effective treatment to evaporate intra-coronary thrombi. We previously reported that ELCA improves Myocardial Brush Grade (MBG) in pati...
Artificial intelligence for pulmonary function test interpretation
Authors: Marko Topalovic, Nilakash Das, Wim Janssens
Journal: European Respiratory Journal (2019)

<b>The opportunities that may arise from using AI software for interpretation of PFTs and help in diagnosing lung diseases are evident. The idea of a complementary partnership between doctors and AI-supported systems sounds very promising.</b>http://bit.ly/2JE60gb
Abstract 4515: Utilizing nucleic-acid scavengers (NASs) to inhibit proinflammatory and proinvasive signaling in triple-negative breast cancer
Authors: Elias O. Eteshola, Ibtehaj A. Naqvi, Ruwan Gunaratne, Angelo Moreno, Smita K. Nair, Bruce A. Sullenger
Journal: Cancer Research (2019)

Abstract Breast cancers (BC) remain the most lethal malignancies amongst women worldwide and the second leading cause of cancer-related mortalities in the US. Subtype heterogeneity and aggressive invasive potential are believed to be the major contributors of these outcomes. BC lacking canonical histological receptors (i.e. ER/PR/HER2), called triple-negative (TNBC), are notoriously aggressive, difficult-to-treat, and metastatic. It has been observed that the degree of inflammation-driven tumorigenesis tends to correlate with increased levels of cell-free DNA (cfDNA) in cancer patient sera. Our lab had previously shown that nucleic-acid scavengers (NASs) could be used to block the pro-inflammatory and pro-invasive/metastatic signals (e.g. DAMPs) elicited by these cfDNA/RNA likely through innate immune sensors such as of the toll-like receptors (TLRs). Recently, we showed that treatment with the cationic polymer NAS, PAMAM-G3, elicited a drastic reduction in metastatic tumor burden to the liver in an immune-competent murine model of pancreatic cancer (I. Naqvi &amp; R. Gunaratne et al., Molecular Therapy 26, 2018). Ongoing work has shown that both chemotherapy-derived TNBC conditioned media and a TLR9 agonist greatly increased TNBC in vitro invasion and was significantly inhibited upon treatment with PAMAM-G3. To elucidate the mechanism by which this NAS works in these tumor settings, our lab has developed several PAMAM-G3 derivatives, including biotin, IR-, and near-IR fluorophore labeled molecules. These molecules will allow us to conduct DAMP capture and characterization experiments, as well as perform in vitro and in vivo live imaging experiments to gain better insights into NAS PK/PD properties. Mechanistic insight into NAS anti-metastatic and anti-inflammatory capabilities will enhance our basic understanding of metastatic progression and its interplay with the immune system. Moreover, these principles will aid in the development of novel of anti-metastatic therapies to improve TNBC patient outcomes. Citation Format: Elias O. Eteshola, Ibtehaj A. Naqvi, Ruwan Gunaratne, Angelo Moreno, Smita K. Nair, Bruce A. Sullenger. Utilizing nucleic-acid scavengers (NASs) to inhibit proinflammatory and proinvasive signaling in triple-negative breast 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 4515.
Abstract 3603: Sphingomyelin synthase inhibition in sarcomas results in ceramide accumulation and apoptosis
Authors: Jared J. Barrott, Trevor Meldrum, Farjana Afrin, Srinath Pashikanti
Journal: Cancer Research (2019)

Abstract Sphingolipid metabolism is critical to cellular homeostasis especially as cells undergo mitosis. It is, therefore, unsurprising that the sphingolipid pathway is upregulated in a number of a cancers. Sphingoid bases such as sphingosine and ceramide are rapidly synthesized to provide the building blocks of other sphingolipids. Inhibition of downstream enzymes that convert sphingosine and ceramide into sphingolipids can lead to an increase of ceramide, which results in cellular toxicity and initiation of apoptosis. Using the marine natural product Jaspine B and chemically synthesized analogues, we investigated the potency of inhibiting sphingomyelin synthase in sarcoma cell lines. Sphingomyelin synthase is a downstream enzyme that converts ceramide into sphingomyelin by adding the polar head group phosphorylcholine to ceramide. Jaspine B and its analogues exhibited submicromolar potency against several human sarcoma cell lines. It was determined that the inhibition of sphingomyelin synthase resulted in an increase in ceramide and sphingosine levels and that sphingomyelinase enzymatic activity increased. While the mitochondria mass remained the same, the membrane potential of the mitochondria was significantly affected by the presence of the inhibitors. In conclusion, inhibitors of sphingolipid metabolism are viable therapeutic options with high untapped potential to treat cancer. Citation Format: Jared J. Barrott, Trevor Meldrum, Farjana Afrin, Srinath Pashikanti. Sphingomyelin synthase inhibition in sarcomas results in ceramide accumulation and apoptosis [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 3603.
Advances and Applications in the Quest for Orthologs
Authors: Natasha Glover, Christophe Dessimoz, Ingo Ebersberger, Sofia K Forslund, Toni Gabaldón, Jaime Huerta-Cepas, Maria-Jesus Martin, Matthieu Muffato, Mateus Patricio, Cécile Pereira, Alan Sousa da Silva, Yan Wang, Erik Sonnhammer, Paul D Thomas
Journal: Molecular Biology and Evolution (2019)

Abstract Gene families evolve by the processes of speciation (creating orthologs), gene duplication (paralogs), and horizontal gene transfer (xenologs), in addition to sequence divergence and gene loss. Orthologs in particular play an essential role in comparative genomics and phylogenomic analyses. With the continued sequencing of organisms across the tree of life, the data are available to reconstruct the unique evolutionary histories of tens of thousands of gene families. Accurate reconstruction of these histories, however, is a challenging computational problem, and the focus of the Quest for Orthologs Consortium. We review the recent advances and outstanding challenges in this field, as revealed at a symposium and meeting held at the University of Southern California in 2017. Key advances have been made both at the level of orthology algorithm development and with respect to coordination across the community of algorithm developers and orthology end-users. Applications spanned a broad range, including gene function prediction, phylostratigraphy, genome evolution, and phylogenomics. The meetings highlighted the increasing use of meta-analyses integrating results from multiple different algorithms, and discussed ongoing challenges in orthology inference as well as the next steps toward improvement and integration of orthology resources.