tbuckley/cabot-search huggingface dataset:
Biomarkers of treatment effect in a phase II trial of velimogene aliplasmid in patients with metastatic melanoma.
Authors: Mary K Wloch, Dmitri D. Kharkevitch, Alice Chu, John Schulte, Larry R Smith, Richard T. Kenney, Alain Rolland
Journal: Journal of Clinical Oncology (2012)

e19058 Background: Velimogene aliplasmid (Allovectin, A) is a plasmid-based immunotherapeutic that encodes human leukocyte antigen-B7 and β-2 microglobulin. A is designed to induce allogeneic and tumor-antigen-specific T-cell responses against tumor cells. In a phase II trial, 127 patients with stage III or IV recurrent metastatic melanoma were treated in cycles of 6 weekly intralesional injections of 2 mg/dose. Complete (CR) or partial responses (PR) were observed in 15 patients (11.9%, 95% CI: 6.2-17.4), stable disease (SD) in 32 (25.2%), and progressive disease (PD) in 80 (63.0%). Methods: Serum collected before treatment and 3 weeks after each cycle from 29 patients who showed clinical benefit (CB: 15 CR or PR patients and 14 patients with SD for &gt;4 months) and 62 with PD (progressed by the end of the first cycle) were evaluated for 45 inflammation biomarkers in a quantitative multiplex immunoassay. Changes in analyte concentrations relative to baseline were evaluated by paired t-test or Wilcoxon signed-rank test. Results: Overall, 52% of patients had decreases in serum IL-10 after treatment; however, decreases were more prevalent in CB patients (71.4% for CB, 44.4% for PD; p=0.036; Chi-square test). At week 8, mean serum IL-10 concentration within a group was reduced relative to baseline in CB (p=0.008) but not PD patients suggesting greater treatment effect in CB patients. In CB patients, IL-10 remained at lower levels relative to baseline through week 26. CCL-3 decreased in CB patients by week 26 (p=0.021) and von Willebrand factor (a biomarker of vascular endothelium dysfunction) was increased at week 26 (p=0.007). In PD patients, by week 8, several biomarkers associated with metastatic melanoma (TIMP-1, VCAM-1, and TNF-R2) or inflammation (haptoglobin) increased (p=0.001, 0.022, &lt;0.001, 0.004, respectively) consistent with tumor progression, whereas others (IL-8 and stem cell factor) decreased (p=0.007, 0.013, respectively). Conclusions: Consistent with A’s proposed mechanism of action, treatment was associated with a decrease in the production of the T-cell suppressive cytokine, IL-10. Furthermore, biomarker profiles in the two groups were markedly different and analogous with treatment outcomes.
Postoperative detection of circulating EGFR transcripts as a surrogate marker for circulating tumor cells to predict tumor recurrence after adjuvant radio(chemo)therapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN).
Authors: Inge Tinhofer, Robert Konschak, Carmen Stromberger, Ulrich Keilholz, Volker Budach
Journal: Journal of Clinical Oncology (2013)

6014 Background: The prognostic role of circulating tumor cells (CTCs), occurring in up to 35% of LASCCHN patients, is still largely undetermined. In this prospective study we tested whether the detection of CTCs was associated with treatment outcome of adjuvant radio(chemo)therapy. Methods: Patients with LASCCHN (N=64) of the oropharynx (N=40), oral cavity (N=15), hypopharynx (N=3) or CUP (N=6) presenting after tumor surgery for adjuvant treatment were enrolled in this study. Peripheral blood samples were collected before start and at the end of adjuvant radio- (N=22) or radiochemotherapy (N=42). Transcripts of epidermal growth factor receptor (EGFR) were detected using RT-PCR. Samples positive in at least 2 of 3 PCR replicates were considered CTC-positive, according to previous studies. CTC detection was correlated with failure-free (FFS) and overall survival (OS). Results: CTCs were detected in blood samples from 21 of 64 patients (33%) whereas all 30 samples from healthy donors used as control were negative. The CTC+ and CTC- patient cohorts were comparable with relation to sex, age, smoking history, T and N stage, tumor localization, type of adjuvant treatment and the median follow-up for OS and FFS. Detection of CTCs before or after adjuvant treatment was not predictive for OS. However, the presence of CTCs at the start of adjuvant radio(chemo)therapy identified patients with reduced FFS (CTC- vs CTC+ [% of patients without relapse at 2 years]: 89% vs. 60%, HR: 0.30, 95% CI: .08-.92, p=.037). Multivariate Cox regression analysis revealed that the prognostic value of the CTC status was not influenced by the T and N stage and independent of whether the adjuvant treatment consisted of radio- or radiochemotherapy. Conclusions: Persistence of CTCs after tumor resection as detected by EGFR transcripts was established as an independent marker for tumor recurrence in LASCCHN. Postoperative detection of CTCs might prove useful for risk stratification in future clinical trials for optimization of adjuvant treatment, especially for the poor-prognosis group of CTC+ patients.
Re-Print- (r) Alpha Lipoic Acid Is a Safe, Effective Pharmacologic Therapy of Chronic Orthostatic Hypotension Associated with Low Sympathetic Tone
Authors: Gary L. Murray
Journal: Clinical Cardiology and Cardiovascular Interventions (2020)

Chronic orthostatic hypotension (OH), affecting 10 to 30% of the elderly, is associated with falls, and increased morbidity and mortality.Current pharmacologic therapy can cause or worsen hypertension and fluid retention.(r) α lipoic acid (ALA), a powerful natural antioxidant, avoids those complications and may assist management ofchronic neurogenic orthostatic hypotension (NOH).The purpose of this study is to demonstrate improvement in the symptoms of orthostatic dysfunction with r-ALA, including improved sympathetic (S) and blood pressure (BP) responses to head-up postural change (standing).A cohort of 109 patients with low S tone upon standing was detected using the ANX -3.0, Autonomic Monitor, ANSAR Medical Technologies, Inc., Philadelphia, PA.From the cohort, 29patients demonstrated NOH (change in (Δ) standing BP ≤ -20/-10 mm Hg) and 60 patients demonstrated orthostatic intolerance (OI, Δ standing systolic BP between -6 and -19 mm Hg).These 89 were given ALA orally: either 590 to 788 mg (r) ALA or 867 to 1,500 mg of the less expensive 50 to 50% mixture (r) ALA and inactive (s) ALA.Changes in their S-and P tone, and BPs, were compared with 20 control patients during mean follow-up of 2.28 years.Nineteen of 29 (66%) NOH patients responded with a Δ standing BP from -28/-6 mm Hg to 0/þ2 mm Hg.Forty of 60 (67%) of patients with OI responded with a Δ standing BP of -9/þ1 mm Hg to þ6/þ2 mm Hg.Although all patients treated with ALA increased S tone, the Δ BP depended upon the pretreatment of S tone.Those with the lowest S tone responded the least well.The only treatment side effects were nausea, intolerable in only 5%.Nausea improved with routine gastrointestinal medica-tions.Glucose levels improved in the 28% of patients who were diabetic.Also, resting hypertension improved.Control patients had no Δ BP and no increase in S tone.(r)ALA improves S-, and BP, responses to head-up postural change, and thereby NOH/OI, in a majority of patients without causing harmful side effects.
Abstract 16545: Gender Attitudes and the Use of Angiography Among Cardiologists
Authors: Stacie L Daugherty, Irene V Blair, Edward P Havranek, Anna Furniss, Miriam Dickinson, Debbi S Main, Elhum Karimkhani, Frederick A Masoudi
Journal: Circulation (2015)

Background: Physician bias may contribute to gender disparities in the use of angiography. We performed the first study using the Implicit Association Test (IAT) to examine gender biases and their associations with angiography decisions. Methods: Cardiology physicians were emailed a web-based survey that included 2 gender-IATs and a two-part clinical vignette randomized by patient gender. The IATs measured attitudes about men versus women on strength and risk-taking. The vignette represented an intermediate likelihood of CAD regardless of gender; part-1 described a patient with symptoms of CAD and part-2 described an abnormal stress test. Physicians rated the likelihood of CAD and their agreement with the usefulness of angiography for that patient. We examined the association between gender attitudes and rated usefulness of angiography for the male and female patient, adjusting for the perceived likelihood of CAD. Results: Of the 503 cardiologists who responded, over half associated strength and willingness to take risks with males. For both parts of the case, cardiologists’ estimated the likelihood of CAD similarly by patient gender; yet, cardiologists’ more often rated the usefulness of angiography as “high” for the male versus female patient (Part-1: 19.7% vs. 9.8%; Part-2: 73.7% vs. 64.3%; p&lt;0.05 for both). These differences varied by gender attitudes; those with higher male-risk bias or male-strength bias rated angiography as more useful for men than for women. (Figure) After adjustment, only the relationship with male-risk bias and higher angiography rating for male patients persisted (p=0.01 for interaction). Conclusions: Despite similar estimates of CAD likelihood, cardiology physicians rated the usefulness of angiography higher for a standardized male than female patient. This difference significantly varied by gender-risk bias suggesting the concept of riskiness influenced decisions about angiography differently in women and male patients.
Abstract P3-02-15: Integrin a2 promotes stemness and lung metastasis in triple negative breast cancer
Authors: Valery Adorno-Cruz, Andrew Hoffmann, Xia Liu, Ruth Keri, Huiping Liu
Journal: Cancer Research (2020)

Abstract Accumulating evidence demonstrates that cancer plasticity and stem cell properties (stemness) drive both tumorigenesis and metastasis, and how to eliminate metastasis remains one of the biggest challenges in the clinic. Here we report that the integrin receptor CD49b-encoding ITGA2 is an oncogenic target of miR-206 regulating cancer stemness and metastasis through pathways linked to lipid metabolism and cell cycle regulation in metastatic triple negative breast cancer (TNBC). ITGA2 knockdown suppressed self-renewal related mammosphere formation and pluripotency marker expression, inhibited cell cycling, compromised migration and invasion, and therefore decreased lung metastasis of TNBC. RNA sequencing analyses revealed that ITGA2 knockdown inhibits newly identified pathways such as lipid metabolism and protein kinase activity. ACLY-encoded ATP citrate lyase is one of the top targets in CD49b promoting lipid biosynthesis and self-renewal of breast cancer cells. Overexpression of CCND1 rescues the phenotype of ITGA2 knockdown-induced cell cycle arrest. High expression levels of the ITGA2/ACLY/CCND1 axis are associated with an unfavorable relapse-free survival of patients with high grade breast cancer, in both basal-like and other subtypes. This study identifies ITGA2 as a potential therapeutic target of TNBC stemness, metabolism, and metastasis. Citation Format: Valery Adorno-Cruz, Andrew Hoffmann, Xia Liu, Ruth Keri, Huiping Liu. Integrin a2 promotes stemness and lung metastasis in triple negative breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-02-15.
MODIFIED BODY MASS INDEX IS ASSOCIATED WITH MORTALITY AFTER TREATMENT FOR SEVERE PULMONARY EMBOLISM
Authors: Elissa Driggin, Mahesh Madhavan, Shayan Nabavi Nouri, Sanjum S. Sethi, John Burton, Danial Saleem, Jianhua Li, Erika Rosenzweig, Ajay Kirtane, Koji Takeda, Daniel Brodie, Cara Agerstrand, Aakriti Gupta, Michelle Maier, Andrew Jeffrey Einstein, Sahil Parikh, Mathew Maurer, Philip Green
Journal: Journal of the American College of Cardiology (2020)
Holistic resource-rational analysis
Authors: Julia Haas, Colin Klein
Journal: Behavioral and Brain Sciences (2020)

Abstract We argue that Lieder and Griffiths’ method for analyzing rational process models cannot capture an important constraint on resource allocation, which is competition between different processes for shared resources (Klein 2018, Biology and Philosophy 33 :36). We suggest that holistic interactions between processes on at least three different timescales – episodic, developmental, and evolutionary – must be taken into account by a complete resource-bounded explanation.
Management of chronic myeloid leukemia in chronic phase (CML-CP) by American Hematology-Oncology Physicians (AHOP's): Diagnostic and treatment preferences after first-line imatinib (2010-2012).
Authors: James M. Foran, Michael E. Williams, Joanne Willey, Mark R. Green
Journal: Journal of Clinical Oncology (2013)

7046 Background: In CML-CP there is perceived complexity in risk stratification at diagnosis, and in testing for BCR-ABL kinase domain mutation (KD mut, including T315I) at relapse. We sought to understand AHOP practices in the context of NCCN and European LeukemiaNet guidelines. Methods: Between 2010 and 2012, we studied time dependent practice preferences of n=1,335 AHOP’s using a proprietary, live, case-based market research tool. A core case scenario and variations based on available diagnostic &amp; treatment options were constructed. Preference data were acquired using blinded audience response technology. All responses for each scenario were obtained contemporaneously prior to any display of summary respondent selections. All sources of research support were double blinded. AHOP's were presented with a scenario of 59-year old CML-CP patient, then indicated preferred management from up to 9 relevant available/emerging diagnostic or therapeutic options following relapse after 1st-line imatinib. Results: The majority of AHOP’s in 2012 either did not calculate (52%), or were unfamiliar (21%) with Sokal or Hasford risk stratification score. Diagnostic preferences following relapse from 2010-12 are noted in Table (distribution over time, p&lt;0.0001). If T315I was then detected in scenario, we noted marked differences in subsequent treatment preference in 2012 vs. 2011, respectively: decreased AlloBMT (16% vs. 32%); &amp; increased 2 nd -line dasatinib (26% vs. 14%) or bosutinib (12% vs. 8%) vs. nilotinib (8% vs. 20%) despite lack of efficacy for each in T315I. Preference increased slightly for ponatinib (16% vs. 14%), but not for omacetaxine (2% vs. 6%). Conclusions: Most AHOP’s do not apply risk stratification. Increasing preference for KD mut panel testing at relapse conforms to guidelines, although not all AHOP’s test. Heterogeneity in T315I treatment suggests uncertainty or unfamiliarity with newer agents, and evidence-based efforts are needed to improve awareness. [Table: see text]
Preoperative serum CA125 as an independent predictor for recurrence and death in operable patients with non-small cell lung cancer.
Authors: Jianguo Feng, Haiyan Xu, Hanmo Wu, Min Luo, Weimin Mao, Dan Su
Journal: Journal of Clinical Oncology (2013)

e18520 Background: The role of serum CA125 in the prognosis of non-small cell lung cancer (NSCLC) remains controversial, especially in early stage patients. The aim of this study is to analyze the prognostic value of CA125 in operable NSCLC. Methods: We retrospectively analyzed 645 patients with non-small cell lung cancer (NSCLC) who underwent curative surgical resection for lung cancer at Zhejiang Cancer Hospital of China from 2006 to 2011. Micropartical enzyme immunoassay was used to measure preoperative serum CA125. Pearson’s chi test was used in univariate analyses and a multivariable proportional hazard Cox regression model was applied to assess the prognostic significance of the different covariates. Kaplan-Meier was used to analyze survival curve. Results: The positive rate of preoperative serum CA125 was 18.9% (126/667) in all patients, and elevated CA125 concentration was associated to poorly differentiated tumor and advanced clinical stage. Moreover, CA125 was closely related to patient outcomes. The Kaplan-Meier survival curves were shown patient with normal CA125 concentration had significantly longer DFS (median DFS, not reach vs 21 months, p=0.000) and OS (median OS, 61 vs 29 months, p=0.000) than those with positive CA125. Multivariate Cox analysis indicated patients with positive CA125 had an elevated risk of disease recurrence or death compared with those who had negative one. The adjusted hazard ratio (HR) was 1.74 for replase (95% confidence interval [CI], 1.25-2.41, p=0.001) and 1.79 for death (95% CI, 1.34-2.41, p=0.000) after adjusted by age, gender, grade, stage, histology and smoking status. Conclusions: CA125 seems to play an important role in disease progression and it may be an independent predictive marker for prognosis in patients with NSCLC. [Table: see text]
Effect of RTVP-1 on the mesenchymal transformation of glioma stem cells (GSCs) and their self-renewal and migration.
Authors: Chaya Brodie, Nissim Giladi, Amotz Ziv-Av, Hae Kyung Lee, Susan Finniss, Simona Cazacu, Cunli Xiang, Laila Poisson, Shimon Slavin, Tom Mikkelsen
Journal: Journal of Clinical Oncology (2013)

2073 Background: Glioblastoma (GBM), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. GBM are categorized into proneural, neural, classical and mesenchymal subgroups, the latter being characterized by increased invasion and poor prognosis. We recently reported that RTVP-1 is highly expressed in GBM and its expression is correlated with astrocytic tumor grade. Methods: We employed promoter and Chip analyses, analysis of tumor specimens submitted to TCGA , GSC self-renewal and migration assays, mesenchymal and neural differentiation, gene array analysis and pull-down assay followed by FRET. Results: The RTVP-1 promoter binds STAT3 and C/EBPb, the transcription factors that regulate mesenchymal transformation of GBM. The expression of RTVP-1 is higher in mesenchymal GBM and is inversely correlated with patient survival in the proneural group. We examined the expression and functions of RTVP-1 in GSCs, a small population of cancer stem cells that are implicated in the increased migration, radio- and chemo-resistance of GSCs and tumor recurrence. RTVP-1 was expressed in the different GSCs but not in the normal human neural stem cells (NSCs). Overexpression of RTVP-1 in NSCs induced their mesenchymal transformation, whereas silencing of RTVP-1 in GSCs decreased their mesenchymal and increased their neural phenotypes. Moreover, RTVP-1 promoted the self-renewal and migration of GSCs. Using gene array analysis of RTVP-1 silenced cells we identified IL-6 and CXCR4 as major mediators of RTVP-1 effects on the mesenchymal transformation and self-renewal of GSCs. In addition, using a pull down assay with His-tagged RTVP-1 we identified N-WASP and hnRNPK as novel interacting proteins of RTVP-1 that mediate its effects on glioma cell migration. Conclusions: RTVP-1 expression is associated with mesenchymal transformation of GSCs. RTVP-1 promotes self-renewal and migration of GSCs and these effects are mediated by the increased expression of IL-6 and CXCR4 and via interaction with N-WASP and hnRNPK. Collectively, these results suggest that RTVP-1 may represent a novel diagnostic marker and a therapeutic target in GBM.
THE SINGLE ACCESS TECHNIQUE (SAT) FOR IMPELLA CP® PROTECTED PERCUTANEOUS CORONARY INTERVENTIONS (PCI): A SINGLE CENTER EXPERIENCE
Authors: Ganesh Gajanan, Majid Asawaeer, Yiannis S. Chatzizisis, Andrew Goldsweig, Poonam Velagapudi, Edward O'Leary, David Barton
Journal: Journal of the American College of Cardiology (2020)
HEMATOLOGICAL MALIGNANCIES WITH THROMBOCYTOPENIA UNDERGOING PRIMARY PERCUTANEOUS PERICARDIOCENTESIS: PERIPROCEDURAL (30-DAY) OVERALL SURVIVAL ANALYSIS
Authors: Astrid Serauto, Michelle Lee, Juan C. Lopez-Mattei, Clarence Gill, Teodora Donisan, Dinu Balanescu, Konstantinos Marmagkiolis, Nicolas Palaskas, Peter Y. Kim, Anita Deswal, Cezar Iliescu
Journal: Journal of the American College of Cardiology (2020)
A comparative study of the response and toxicities in locally advanced head and neck cancer patients treated with paclitaxel, cisplatinum, 5-FU versus docetaxel, cisplatinum, 5-FU as neoadjuvant chemotherapy followed by concurrent chemoradiation.
Authors: Diptirani Samanta, Surendra nath Senapati, Kirti Ranjan Mohanty, Saroj Das
Journal: Journal of Clinical Oncology (2013)

6089 Background: To evaluate the response and toxicity of docetaxel, cisplatinum, 5-FU vs paclitaxel, cisplatinum, 5-FU as neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiation (CTRT) with weekly cisplatinum in locally advanced head and neck cancer. Methods: 40 locally advanced head and neck cancer patients who satisfied the eligibility criteria were randomized.21 patients received three cycles of NACT i.e paclitaxel (175 mg/m 2 ) on d1, cisplatinum (30 mg/m 2 ) and 5-FU (600 mg/m 2 ) d2-d4 (TCF) and 19 patients received three cycles of NACT docetaxel (75 mg/m 2 ) on d1, cisplatinum (30 mg/m 2 ) and 5-FU (600 mg/m 2 ) d2-d4 at three week intervals, followed by concurrent weekly cisplatinum 30 mg/m 2 along with conventional external beam radiation of total tumor dose dose 66 Gy. Response was assessed after NACT and again after six weeks, three months and six months of completion of chemoradiation. Toxicities were assessed after each cycles of NACT and also weekly during CTRT and thereafter. Results: Two weeks after completion of NACT complete response (CR) in TCF was 4.76%, partial response (PR) 80.9% and no response 9.5%. However in DCF, CR was 15.78 % PR was 73.68%. 10.52% patientd died due to toxicity. With a median follow up of seven months, in TCF CR was 57.14%, PR 33.33% and no response was 4.76%, whereas in DCF CR was 78.94%, PR 10.52% and death 10.5%. On evaluation of toxicities during NACT, patients in DCF had more significant neutropenia and in TCF more incidence of neuropathy. During CTRT, in TCF grade II and III mucositis was 54%, grade II neutropenia 5.6%, and grade II anemia 5.3%. In DCF mucositis grade II and III was 49.0%, neutropenia grade II 18.7% and anemia grade II was 7.4%. Late toxicities included were comparable in both arms. Conclusions: With a median follow up of 7 months, the CR in DCF was 78.94%, superior than TCF i.e 57.14%. Neutropenia was significant in DCF and neuropathy was high in TCF. In CTRT mucositis was the commonest toxicity observed in both TCF and DCF which was not statistically significant.
TRANSCATHETER AORTIC VALVE REPLACEMENT IMPROVES MITRAL VALVE REGURGITATION AND PATIENT OUTCOMES
Authors: Seyed Hossein Aalaei Andabili, Adriana Della Porta, Anthony Bavry, Siddharth A. Wayangankar, George Arnaoutakis, John Petersen, Ashkan Karimi, Thomas Beaver, R. David Anderson
Journal: Journal of the American College of Cardiology (2020)
COMORBIDITY BURDEN IN PATIENTS UNDERGOING LEFT ATRIAL APPENDAGE CLOSURE
Authors: Rodrigo Bagur, Yun-Hee Choi, David R. Holmes, Howard Herrmann, Juan Terre, M. Chadi Alraies, Tomo Ando, Luciano A. Sposato, Nikolaos Tzemos, Mamas A. Mamas, Shubrandu S. Sanjoy
Journal: Journal of the American College of Cardiology (2020)
CLO20-031: Radiotherapy-Induced Malignancies in Breast Cancer Patients With Pathogenic Germline Variants TP53 in an R337H-Mutation Enriched Cohort
Authors: Vanessa Petry Helena Bragaia, Renata Colombo Bonadio, Luiz Antonio Sena, Daniela Bevilacqua Heinemann Cohn, Allyne Cagnacci, Roberta Campos, Maria Del Pilar de Estevez Diz, Maria Candida Barisson Villares Fragoso
Journal: Journal of the National Comprehensive Cancer Network (2020)

"CLO20-031: Radiotherapy-Induced Malignancies in Breast Cancer Patients With Pathogenic Germline Variants TP53 in an R337H-Mutation Enriched Cohort" published on 20 Mar 2020 by National Comprehensive Cancer Network.