tbuckley/cabot-search huggingface dataset:
A multianalyte algorithm PCR-based gene blood test compared to single analyte ELISA-based blood tests for neuroendocrine tumor detection.
Authors: Irvin Mark Modlin, Daniele Alaimo, Stephen Callahan, Nancy S. Teixeira, Lisa Bodei, Ignat Drozdov, Mark S. Kidd
Journal: Journal of Clinical Oncology (2014)

e15168 Background: A critical requirement in NET management is a blood biomarker test that is sensitive, specific and reproducible. We evaluated a PCR-based 51 transcript signature, the NETest, to detect tumors, compared it to Chromogranin A (CgA), pancreastatin and neurokinin A. Methods: The multigene signature was evaluated in prospectively collected NETs (n=41, 61% small intestinal, 50% had metastastic disease, 44% under treatment). These were age (NETs: mean 56.9, range: 31-76; controls: mean 56.4, range: 33-75) and sex-matched (M:F = 10:31) with controls (1:1). All samples were analyzed by a 2-step PCR (51 marker genes) protocol and ELISAs: (DAKO-CgA), pancreastatin (MyBiosource-PST) and neurokinin A (RayBiotech-NKA). Sensitivity comparisons included chi-square, non-parametric measurements, ROC curves and predictive feature importance analyses. Results: PCR analysis was robust (inter/intra-assay variation <2%; inter/intra-assay reproducibility: <1.2). NETest performance metrics were: sensitivity 92.8%, specificity 92.8%, PPV 92.8% and NPV 92.8%. For the single analyte ELISA assays, metrics ranged from sensitivities: 75.6-80.5%, specificities: 31.7-87.8%, PPVs: 54.1-86.1% and NPVs: 61.9-78.3%. The AUCs from ROC analysis were: NETest: 0.96±0.025, CgA: 0.67±0.06, pancreastatin: 0.51±0.07 and neurokinin A: 0.73±0.05. The multigene transcript NETest was significantly better than any single analyte test (difference between areas: 0.13-0.45, Z-statistic = 2.6-6.58, p<0.01). Predictive Feature Importance analysis determined that NETest contributed the most value (61%) in arriving at the correct diagnosis compared to NKA (21%), CgA (9%), and PST (8%). Conclusions: A 51 panel multigene blood transcript analysis is significantly more sensitive than any single analyte assay (CgA, PST or NKA) for NET detection. The test is robust (<2% variation) and efficient (>93%). Our data indicate that a blood-based multigene analytic measurement will provide data that enables early detection of disease recurrence and predicts the efficacy of therapy.
Efficacy and safety of serelaxin when added to standard of care in patients with acute heart failure: results from a PROBE study, RELAX‐AHF‐EU
Authors: Aldo P. Maggioni, José López‐Sendón, Olav W. Nielsen, Jonas Hallén, Maryam Aalamian‐Mattheis, Yaqin Wang, Georg Ertl
Journal: European Journal of Heart Failure (2019)
Prospective Long-Term Follow-up after First-Line Subcutaneous Cladribine Treatment in Patients with Hairy Cell Leukemia. a Study of the SAKK (Swiss Group for Clinical Cancer Research)
Authors: Rudolf A. Benz, Kornelius Arn, Martin Andres, Thomas Pabst, Urban Novak, Felicitas Hitz, Reinhard Zenhäusern, Yves Chalandon, Ulrich Mey, Sabine Blum, Daniel Rauch, Willy Nettekoven, Nathan Cantoni, Mario Bargetzi, Alix O'Meara, Andreas Lohri, Simona Berardi, Qiyu Li, Georg Stussi
Journal: Blood (2018)
Survival time and differences between dementia with Lewy bodies and Alzheimer’s disease following diagnosis: A meta-analysis of longitudinal studies
Authors: Christoph Mueller, Pinar Soysal, Arvid Rongve, Ahmet Turan Isik, Trevor Thompson, Stefania Maggi, Lee Smith, Cristina Basso, Robert Stewart, Clive Ballard, John T. O’Brien, Dag Aarsland, Brendon Stubbs, Nicola Veronese
Journal: Ageing Research Reviews (2019)
Detection of <i>CDH1</i> gene variants in early-onset diffuse gastric cancer in Chinese patients.
Authors: Ying Jieer
Journal: Journal of Clinical Oncology (2014)

e15079 Background: To study the correlation between the type and frequency of exon variants in E- cadherin (CDH1) gene and clinical characteristics of early-onset diffuse gastric cancer (EODGC) in Chinese patients. Methods: Peripheral blood samples were collected from 57 EODGC patients (age≤40 years) who underwent resection surgery for primary tumor. DNA was extracted from peripheral blood leucocytes and polymerase chain reaction amplification (PCR) was performed to amplify and sequence the CDH1 gene. Statistical analysis was performed using the SPSS 19 software package for Windows. Results: Missense variant in exon 5 was observed in 18 of the 57 EODGC patients with a variant frequency of 31.6%, while 2 patients (3.5% variant frequency) had variant in exon 12. Synonymous variant in exon 13 with a variant frequency 80.7% was observed in 46 patients. No significant correlation was observed between the missense variants in exon 5 and clinical pathological characteristics of the patients. Lymph node metastasis in patients with the exon 13 missense variant was significantly higher than those without variant (87% vs. 64%, P=0.07). The median overall survival (mOS) of 46 patients with synonymous variant in exon 13 was 34 months, while no death was observed in patients without variant (N=11, P=0.046). Conclusions: Missense variants in the exon 13 of CDH1 gene lead to lower survival rate in Chinese EODGC patients. Variants in other exons are not correlated with clinical or pathological characteristics.
Retrospective study of real world axitinib use in the United States.
Authors: Elizabeth A. MacLean, Kim Mehle, Daria Eremina, Jane M Quigley
Journal: Journal of Clinical Oncology (2014)

e15576 Background: Axitinib (Inlyta) was approved in January 2012 for treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy. The experience of patients and prescribers in routine clinical practice is often different than those in a controlled clinical trial setting. The purpose of this research was to understand axitinib use in routine clinical practice during its first year of availability in the U.S. Methods: Axitinib patients from 20 specialty pharmacies were matched to longitudinal claims from medical office/clinic and prescription databases. All data were de-identified. Included patients were diagnosed with RCC, had prior systemic therapy, and had received ≥ 1 dose of axitinib between February 2012 - January 2013. Results: 1,078 patients met criteria for inclusion with 67% of patients aged 55 and 74 years and equal proportions (15%) between 45 and 54 years or ≥75 years. The male to female ratio was 2.4:1. Medicare was the most common payer type (50%). Charlson co-morbidity index score, excluding metastatic carcinoma diagnoses, was 2-3 in 79%, 4-5 in 17% and 6-9 in 4% of patients with 34% of patients having no co-morbid diagnoses of interest. 38% of patients were indexed to axitinib as their 2nd line therapy, 27% as their 3rd line and 36% as fourth line or later. The most common prior therapy was sunitinib (33%). Of the 957 patients starting axitinib at 5mg BID, 79% experienced no change in dose, 9% subsequently had a decrease in dose, 8% increased and 4% increased then decreased in dose. Age was associated with decrease in dose (OR 1.049, 95% confidence limits 1.024-1.075). Conclusions: This retrospective claims based cohort study provides insight into routine clinical use of axitinib following approval in the U.S. These data further the understanding of the overall treatment, line of therapy, axitinib dosing patterns and demographics of RCC patients receiving systemic therapy. Axitinib real world dosing patterns differed from the Phase 3 clinical trial with 79% patients starting at 5mg BID remaining on that regimen. Patient demographics Patients (%) Age 0-54 193 (18%) 55-74 726 (67%) 75+ 159 (15%) Gender Female 315 (29%) Male 763 (71%) Axitinib Payer Type Commercial 468 (43%) Medicare 543 (50%) Medicaid 21 (2%) Other 46 (4%)
Salivary protease spectrum biomarkers of oral cancer
Authors: Yun Feng, Qian Li, Jiao Chen, Ping Yi, Xin Xu, Yaping Fan, Bomiao Cui, Yu Yu, Xiaoying Li, Yue Du, Qianming Chen, Lingling Zhang, Jingjing Jiang, Xuedong Zhou, Ping Zhang
Journal: International Journal of Oral Science (2019)

Proteases are important molecules that are involved in many physiological and pathological processes of the human body, such as growth, apoptosis and metastasis cancer cells. They are potential targets in cancer diagnosis and biotherapy. In this study, we analyzed the salivary protease spectrum of patients with oral squamous cell carcinoma (OSCC), oral benign masses and chronic periodontitis, as well as that of health, using human protease array kits, enzyme-linked immunosorbent assay, western blot and immunofluorescence. The salivary protease spectrum was found to be associated with oral diseases. For example, the saliva of patients with OSCC contained increased numbers of proteases than those of other oral diseases and health. The levels of matrix metalloproteinase (MMP)-1, MMP-2, MMP-10, MMP-12, A disintegrin and metalloprotease (ADAM)9, A disintegrin and metalloprotease with thrombospondin type 13 motifs (ADAMST13), cathepsin V and kallikrein 5 in the saliva of patients with OSCC were significantly increased compared with those of other groups. Taking MMP-1, cathepsin V, kallikrein 5 and ADAM9 as biomarkers of OSCC, cutoff values were199, 11.34, 9.29 and 202.55 pg·mL
CD38 Expression Levels on Myeloma Cells and the Frequency of Circulating CD38-Positive Treg Cells Are Associated with the Response to Daratumumab in Multiple Myeloma
Authors: Akihiro Kitadate, Hiroki Kobayashi, Yoshiaki Abe, Kentaro Narita, Daisuke Miura, Masami Takeuchi, Kosei Matsue
Journal: Blood (2018)
The immune status and apoptosis in lymphocytes in patients with refractory Hodgkin lymphoma.
Authors: Tatyana A. Snezhko, Irina B. Lysenko, Elena Yurievna Zlatnik, Natalya Dmitrievna Ushakova, Liubov Yu Vladimirova, Inna Arnoldovna Novikova, Andrey Vladimirovich Bakhtin, Olesya N. Selutina
Journal: Journal of Clinical Oncology (2014)

e14003 Background: Hodgkin's lymphoma refers to a potentially curable disease in oncology, but 5-10% of cases registered primary refractory to the standard care. The results of treatment of these patients are poor. The purpose of the study was to investigate the immune status of patients with refractory Hodgkin's lymphoma. Methods: 30 patients with primary resistant Hodgkin's lymphoma were treated during the 2011-2013 years. The inclusion criteria: histologically confirmed diagnosis of Hodgkin's lymphoma, age over 18 years, functional status 0-2 on the ECOG, compensated indexes of laboratory tests. Mean age was 37±8 years. The resistance to therapy is supposed to be in the absence of complete or partial response after 3 courses of induction chemotherapy, as well as in the development of disease recurrence within 3 months after its completion. 2 groups of the patients were analysed: 1st group standard polychemotherapy line 2, 2nd group- 2 line polychemotherapy in combination with extracorporeal immunotherapy. Extracorporeal immunotherapy: autologous leukocytes 103/ml by were incubated with recombinant interleukin-2 5 000 IU / ml and interferon-α2b at 10 000 IU / ml, for 180 minutes at 370 С with following by reinfusion to the patient before and after chemotherapy infusion. Immune status was assessed by flow cytometry, before and after treatment. Lymphocyte apoptosis was also studied. Used equipment: flow cytometer BD FACSCanto II. Results: After 1 course of treatment in the 2nd group patients the level of CD3 + CD4 + lymphocytes has increased from 36,25 ± 5,1 to 49,8 ± 3,15% (P <0,05). Standard chemotherapy induced increased apoptosis in lymphocytes up to 2 times. Apoptosis remained at the same level in the 2 group. Conclusions: Extracorporeal immunotherapy added to standard chemotherapy improves the immune status of patients with refractory Hodgkin's lymphoma.
Investigating the regulation of e-cadherin mRNA and protein expression by integrin α3β1 in breast cancer cells.
Authors: Anupam Batra
Journal: Journal of Clinical Oncology (2014)

1104 Background: E-cadherin is an adhesion glycoprotein in epithelial tissues and reduced expression is associated breast cancer metastasis. The cell surface integrin α3β1 is also associated with malignant progression of breast tumors. Our genome-wide microarrays identified that E-cadherin mRNA levels are modulated by α3β1 in MDA-MB-231 breast cancer cells. The current study investigates the association between these two important structural genes in breast cancer progression. Methods: MDA-MB-231 cells were stably transduced with lentivirus expressing short hairpin RNA (shRNA) targeting the α3 integrin subunit or with control shRNA. Total RNA was isolated for qPCR with primers specific for integrin α3, E-cadherin, and GAPDH. Immunoblot was performed using mouse anti-serum against E-cadherin or rabbit anti-serum against ERK, followed by secondary horse-radish peroxidase-congugated antibody. Immunohistochemistry (IHC) was then performed using rabbit anti-serum against either α3 or E-cadherin. Results: Our experimental model consisted of human breast cancer MDA-MB-231 cells with α3β1-expressing or α3β1-deficient populations. qPCR revealed a 24-fold (p < 0.05) increase in E-cadherin mRNA in α3β1-deficient cells relative to controls. These findings confirmed our earlier microarray data, which indicated that α3β1 suppresses the expression of E-cadherin mRNA. However, immunoblot of lysates from the same cells showed increased levels of E-cadherin protein in α3β1-expressing controls relative to α3β1-deficient cells. IHC showed increased staining in α3-expressing cells corroborating immunoblot results. Conclusions: E-cadherin mRNA levels were found to be increased in α3-deficient breast cancer cells whereas E-cadherin protein expression was down-regulated in the same cells as detected by immunoblot and IHC. We suggest that E-cadherin may be part of a group of genes up-regulated in the absence of α3β1, but that this regulation is counter-balanced by translational or post-translational down-regulation of E-cadherin protein. Further studies are needed to understand the complex regulatory networks that control E-cadherin expression in response to α3β1 in breast cancer progression.
Short time to ATRA administration and reduction of early mortality in patients with APL.
Authors: Namrata I. Peswani, Karen-Sue Carlson, Christopher R. Chitambar, Timothy S. Fenske, Parameswaran Hari, Laura Christian Michaelis, Linda S. Blust, Ehab L. Atallah
Journal: Journal of Clinical Oncology (2014)

e18020 Background: APL represents a medical emergency with a high rate of early mortality, often due to hemorrhage. Delayed ATRA administration has been shown to increase the risk of early bleeding and death. To decrease the time to ATRA administration, we have implemented a hospital wide system at Froedtert Hospital (FH)/Medical College of Wisconsin (MCW) where a leukemia specialist is immediately notified by a hematopathologist if the diagnosis of APL is suspected. Here we report the outcomes of APL pts treated at our institution. Methods: We retrospectively reviewed charts of pts presenting to FH with newly diagnosed APL between July 2007 and July 2013. The study was approved by our institutional review board. We collected demographic data, response and survival. We also collected data on time to ATRA administration from onset of symptoms, from first contact with medical personnel as well as from admission to FH. Survival estimates and Kaplan-Meier analyses were performed using SAS version 9.3 (The SAS Institute, Cary, NC). Results: We identified 25 pts with newly diagnosed APL. The median age was 50 and 48 % of the pts were men. 6 pts were high risk, 12 were intermediate risk and 7 were low risk. The median follow-up time was 19 months (0.5 month to 67 months). All pts got at least one dose of ATRA. The median time for ATRA administration from FMLH admission was 4 hours (2-24), from first presentation to any medical facility was 2 days (0.3-28) and from onset of symptoms was 14 days (1-90). At our institution, ATRA was ordered and administered the day APL was suspected in 100% of the pts with or without confirmation of the diagnosis of APL. Three of the 25 (12%) pts died during induction. The causes of death were intracerebral bleed (Day 1 and 5) in 2 and respiratory failure (Day 5) in one pt. Of these pts, 2 were high risk and 2 were > 60 years of age. All of the 22 pts that survived the early phase of the disease have achieved hematologic complete remission. There have been no late deaths or relapses to date. Conclusions: A short time to ATRA administration is associated with reduced early mortality in pts with APL. We also demonstrate the feasibility of a short time to ATRA administration with implementation of an appropriate system.
Biology of Acute Myeloid Leukemia (AML) with Monosomy of Chromosome 7 or Loss of 7q. a Study on 487 Patients Analyzed By Gene Expression Profile (GEP), Single Nucleotide Polymorphism (SNP) Arrays and Metabolomics
Authors: Maria Chiara Fontana, Matteo Olivi, Giovanni Marconi, Mariachiara Abbenante, Eugenio Fonzi, Stefania Paolini, Chiara Sartor, Sarah Parisi, Samantha Bruno, Martina Pazzaglia, Stefano De Polo, Jacopo Nanni, Luca Bertamini, Simone Ragaini, Annalisa Talami, Maria Teresa Bochicchio, Emanuela Ottaviani, Anna Ferrari, Carmen Baldazzi, Nicoletta Testoni, Torsten Haferlach, Robert Kralovics, Jelena D. Milosevic Feenstra, Simona Soverini, Giovanni Martinelli, Antonio Curti, Michele Cavo, Cristina Papayannidis, Giorgia Simonetti
Journal: Blood (2018)
Abstract 20106: Prognostic Value of the Acute to Chronic Glycemic Ratio at Admission in Acute Myocardial Infarction
Authors: Jeness Campodonico, Nicola Cosentino, Valentina Milazzo, Monica De Metrio, Mara Rubino, Marco Moltrasio, Ivana Marana, Marco Grazi, Gianfranco Lauri, Giancarlo Marenzi
Journal: Circulation (2017)

Introduction: Acute hyperglycemia is a powerful predictor of poor prognosis in acute myocardial infarction (AMI), particularly in patients without diabetes mellitus (DM). This emphasizes the import...
TET2 Mutation Associated with Organ Infiltrations in ATLL
Authors: Takuro Kameda, Kotaro Shide, Ayako Kamiunten, Yuki Tahira, Keiichi Akizuki, Masaaki Sekine, Tomonori Hidaka, Yoko Kubuki, Michihiro Hidaka, Atae Utsunomiya, Takayuki Ohshima, Keisuke Kataoka, Seishi Ogawa, Kazuya Shimoda
Journal: Blood (2018)
Trends in Testosterone Prescribing for Age-related Hypogonadism in Men With and Without Heart Disease
Authors: Nancy E. Morden, Steven Woloshin, Corinne G. Brooks, Lisa M. Schwartz
Journal: JAMA Internal Medicine (2018)

This cohort study examines the trend in prescription testosterone use among male Medicare beneficiaries with and without coronary artery disease aged 50 years or older.
Abstract 20834: Comparative Effect of Candesartan and Cavedilol in Prevention of Doxorubicin Induced Subclinical Cardiotoxicity
Authors: Byungho Kim, Woo-Baek Chung, Ho-Joong Youn, Myunhee Lee, Byung Joo Chae, Byung-Joo Song
Journal: Circulation (2017)

Introduction: The purpose of this study is to investigate the preventive effect of candesartan or carvedilol in the anthracycline-induced subclinical cardiotoxicity (SC). Methods: Two hundred seventy four patients from prospective registry for prediction and prevention of chemotherapy induced cardiotoxicity in breast cancer of our institution were selected. All patients were administered candesartan or carvedilol concomitantly with doxorubicin contained chemotherapy. One hundred four patients were treated with candesartan (CDST group, n=104) and ninety three patients were treated with carvedilol (CVDL group, n=93). Seventy seven patients were treated with candesartan and cavedilol combination (CDST+CVDL, n=77). One hundred six patients who did not take candesartan nor cavedilol were selected for control (CONT, n=106). Cardiac function of patients were evaluated by transthoracic echocardiography (TTE) before chemotherapy for baseline and followed up at least twice during chemotherapeutic period. The incide...
Surrogate biomarkers interleukin-6 and interleukin-10 in a spontaneous feline model of head and neck squamous cell carcinoma (HNSCC).
Authors: Jackie M. Wypij, Holly Pondenis
Journal: Journal of Clinical Oncology (2014)

e17056 Background: One translational approach to improving relevancy of cancer drug preclinical work is capitalization on biologically relevant companion animal translational research which allows spontaneous disease modeling with similarities to human cancer that cannot be recreated in induced models. An example is spontaneous feline oral squamous cell carcinoma (FOSCC) which mimics HNSCC with similar etiopathogenesis and molecular markers as well as tumor biology, clinical outcome, treatment, and prognosis. Interleukin-6 (IL-6) and -10 (IL-10) are promising surrogate biomarkers implicated in outcome in human head and neck squamous cell carcinoma (HNSCC). A putative anti-tumor effect of metformin, a novel anti-cancer drug, is mediation of tumor-associated cytokine levels. The aims of this study were to (1) characterize serum levels of interleukins in naturally-occurring FOSCC, (2) investigate IL-6 and IL-10 receptor expression in FOSCC cells, and (3) evaluate the effects of metformin on IL6 and IL-10 secretion from FOSCC cells. Methods: Serum IL-6 and IL-10 levels were measured in fourteen cats with naturally occurring FOSCC and fifteen control cats (Feline IL-6 and IL-10 DuoSet ELISA, R&D Systems). Receptor protein expression was evaluated using Western Blot of SCCF1 cell lysates. Effects of increasing concentrations of metformin on SCCF1 cell proliferation was assessed with a commercial assay. Results: IL-6 and IL-10 levels in cats with FOSCC (IL-6 median 411.2 pg/mL and IL-10 median 340 pg/mL ) were not statistically different from control cats (IL-6 median 951.8 pg/mL and IL-10 median 670 pg/mL). SCCF1 cells express IL-6R and IL-10R and metformin has a modest effect on interleukin secretion. Conclusions: Serum levels of IL-6 and IL-10 do not appear to be useful serum biomarkers for FOSCC. SCCF1 cells express interleukin receptors and demonstrate IL-6 and IL-10 secretion, with modulation by metformin. Further investigation is needed to evaluate the prognostic implication of serum vs. salivary interleukin levels in cats with spontaneous oral squamous cell carcinoma as well as the roles of these interleukins in tumor progression.