tbuckley/cabot-search huggingface dataset:
Cellular factors of local immunity in primary and recurrent soft tissue sarcomas.
Authors: Timur Aliev, Oleg Ivanovich Kit, Elena Yurievna Zlatnik, Inna Arnoldovna Novikova, Evgeniya M. Nepomnyashchaya, Olesya N. Selyutina, Elena Bondarenko, Tatiana Valeryevna Ausheva Ausheva, Larisa Nikolaevna Vashchenko, Elena Andreiko, Elmira Velieva, Emma Kechedzhieva, Irina Dashkova
Journal: Journal of Clinical Oncology (2016)

e22545 Background: The purpose of the study was to analyze some cellular factors of local immunity in microenvironment of primary and recurrent soft tissue sarcomas. Methods: 24 patients (13 women and 11 men aged 35 years and older) with primary (12) and recurrent (12) soft tissue sarcomas G1-G4T2BN0M0 received tumor excision. Poorly differentiated tumors (G3) prevailed. Tissues of tumors and visually unchanged tissues 1-2 cm from the tumor (peritumoral zone) and along the resection line were homogenized. Populations and subpopulations of lymphocytes were determined using flow cytometer FACSCantoII (BD) with panel of antibodies T-, B-, NK (CD45+, CD3, CD4, CD8, CD19, CD16/56); level of T-regs (CD4+CD25+CD127dim) was assessed. Percentages of lymphocytes expressing CD3, CD4, CD8, CD19 and CD16/56 markers were calculated from the total number of CD45+ lymphocytes, T-regs – from the number of CD3+CD4+ cells. Results: A number of differences were found in lymphocyte content between the tumor, peritumoral zone and resection line, as well as in local immunity parameters in primary and recurrent tumors. Tissues of primary tumors showed higher levels of СD3+, СD3+СD8+ lymphocytes and T-regs in comparison with peritumoral zone and resection line, while CD19+ and CD16/56+ levels were lower. Recurrent sarcomas did not show such a difference compared to non-malignant tissue (resection line); however, decrease in levels of T-cell subpopulations and increase in B- and NK-cell content were observed in peritumoral zone. Recurrent tumors contained significantly higher T-regs levels in both tumor tissue and resection line compared to primary tumors (8.3±1.2 and 1.7±0.3% from CD3+CD4+ cells, number of which had the opposite differences: 28.1±1.8% in recurrent and 33.6±1.7% in primary tumors; statistically significant differences, p < 0.05). Gender discrepancies were revealed: levels of T-regs in men were 2-3 times higher than in women. Conclusions: Differences in local factors of cellular immunity were revealed in tumor and non-malignant tissues in soft tissue sarcomas varying in primary and recurrent tumors and depending on the patient’s gender.
A phase 2, multicenter study to assess the efficacy and safety of autologous tumor-infiltrating lymphocytes (LN-144) for the treatment of patients with metastatic melanoma.
Authors: Amod Sarnaik, Brendan D. Curti, Diwakar Davar, John M. Kirkwood, Omid Hamid, Jose Lutzky, Melissa Wilson, Harriet M. Kluger, Eric D. Whitman, Giao Q. Phan, Sajeve Samuel Thomas, Karl D. Lewis, Hendrik-Tobias Arkenau, Jason Alan Chesney, Bente Larsen, Igor Gorbatchevsky, Sam Suzuki, Nancy Louise Samberg, Maria Fardis
Journal: Journal of Clinical Oncology (2018)

TPS9595 Background: Adoptive cell therapy utilizing tumor-infiltrating lymphocytes (TIL) is recognized as an effective treatment in metastatic melanoma and other solid tumors elliciting durable and complete responses, even in heavily pretreated patients. Despite recent approvals of multiple checkpoint-directed therapies there remains an unmet need to improve therapeutic outcomes in patients with metastatic melanoma post checkpoint therapy. The C-144-01 study is evaluating TIL therapy with LN-144 in metastatic melanoma patients who have progressed on prior checkpoint-targeted therapy. C-144-01 is a phase 2 multicenter, open-label study enrolling patients in the US and Europe. LN-144 is manufactured at centralized GMP facilities providing either a non-cryopreserved (Gen 1), or a second generation cryopreserved (Gen 2) TIL infusion product. The Gen 2 process reduces manufacturing time for LN-144 to 22 days, allowing for dramatic efficiencies in scheduling, distribution and delivery needed for commercial use. Methods: Three treatment cohorts are being evaluated: Cohort 1 (N = 30) patients receive a single dose of Gen 1 LN-144; Cohort 2 (N = 30) patients receive a single dose of Gen 2 LN-144; and up to 10 eligible patients from either Cohort 1 or Cohort 2 may enroll in Cohort 3 for re-treatment with a second dose of LN-144. For patients in all cohorts, TIL for LN-144 manufacturing are extracted from surgically-resected tumors. LN-144 infusion is preceded by a non-myeloablative lymphodepletion regimen of Cy/Flu, and followed by up to 6 infusions of IV IL-2. Patients ≥ 18 years of age must have confirmed stage IIIc/IV met. melanoma and have progressed following ≥1 line of prior systemic therapy including an immune checkpoint inhibitor and BRAF-targeted therapy (if BRAF mutation-positive). Other major eligibility criteria include: minimum of 2 tumor lesions; adequate organ function; ECOG PS of 0 or 1. The primary endpoint is the evaluation of efficacy of LN-144 using ORR per RECIST 1.1; secondary endpoints are CR rate, DOR, DCR, PFS, OS, and safety. Key exploratory objectives include tumor response per irRECIST, immune correlates of response, and HRQoL. Clinical trial information: NCT02360579.
A phase II single arm multi-center trial evaluating the efficacy of pembrolizumab in the treatment of patients (pts) with incurable platinum refractory germ cell tumors (GCT).
Authors: Nabil Adra, Natraj Ammakkanavar, Milan Radovich, David J. Vaughn, Costantine Albany, Lawrence H. Einhorn, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2016)

TPS4579 Background: Initial cisplatin-based combination chemotherapy will cure 80% of pts with metastatic GCT. Pts who relapse after initial chemotherapy can still be cured with second and even third-line regimens. These regimens include high-dose chemotherapy (HDCT) or salvage standard-dose chemotherapy (SDCT). Despite remarkable results with salvage chemotherapy, about 15% of pts with metastatic GCT are currently incurable and have limited further treatment options. Tumors utilize the programmed death receptor 1 (PD-1) pathway to suppress immune control. Pembrolizumab is a potent highly selective IgG4 humanized monoclonal antibody designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Pembrolizumab has demonstrated activity in various malignancies. Investigating immune therapy with pembrolizumab is a novel approach for salvage therapy in pts with metastatic GCT. Methods: This is a multi-center, single arm, open label phase 2 trial of pembrolizumab 200mg IV Q3weeks as salvage therapy for pts with incurable GCT. Eligible pts are adult males or females with metastatic GCT (seminoma or non-seminoma) who progressed after first line cisplatin-based chemotherapy and after at least 1 salvage regimen (HDCT or SDCT). Pts with treated stable brain metastasis are eligible. Treatment with systemic corticosteroids/immunosuppressants within 7 days of first trial treatment is not permitted. All pts must provide a biopsy sample for PD-L1 expression evaluation and other exploratory analyses including tumor infiltrating lymphocyte and gene expression analysis. Pts are eligible irrespective of PD-L1 expression status. Pembrolizumab will be given for up to 52 weeks or until disease progression or unacceptable toxicity. Primary objective is overall response rate (ORR) using immune related response criteria (irRC) and secondary objectives are ORR using RECIST criteria, assess toxicity and tolerability of pembrolizumab, and duration of disease response. Using a Simon two-stage minimax design, we plan to enroll a total of 20 pts. This study is currently enrolling pts. Clinical trial information: NCT02499952.
Abstract 16123: Transcriptomic Profiling of Mitochondrial Dysfunction That Occurs in Arterial Calcification
Authors: Jen Xu, Lilun Ho, Kenneth Lim, Tzongshi Lu
Journal: Circulation (2017)

Introduction: Arterial calcification(AC) is a significant contributor to cardiovascular mortality in patients with chronic kidney disease. We previously reported that heat shock protein 70 (HSP70) induction can inhibit vascular smooth muscle cell calcification. Mitochondrial complexes II, IV, NADH cytochrome c reductase, and cytochrome c oxidase activities were preserved by HSP70 induction leading to reduced apoptosis and RUNX2 expression. The molecular mechanisms of HSP70 vasculo-protective effects involving mitochondrial fusion regulation are currently unknown. Hypothesis: The goal of the present study was to investigate the transcriptomic profile of genes involved in mitochondrial function and vasculo-protective mechanisms of HSPs in AC. Methods: Human arteries were collected from healthy (n=15) and CKD (n=15) patients. AC was analyzed by Alizarin Red. Primary Human aortic endothelial cells (HAECs) was treated in calcification medium (CM: 5mM β-glycerolphosphate + 5mM CaCl2) in time-course experiments ...
TCT-573 Inter-hospital Transfer of TAVR Patients is Associated With Index Complications but Not Readmission Outcomes
Authors: Hanning Xing, Yas Sanaiha, Sarah Rudasill, Habib Khoury, Alexandra Mardock, Shervin Yazdani, Leela Gowland, Ramin Ebrahimi, Peyman Benharash
Journal: Journal of the American College of Cardiology (2018)
Quality of life among long-term ovarian cancer survivors.
Authors: Lari B. Wenzel, Kathryn Osann, Giulia Fulci, Aditi Wahi, Mary Scroggins, Michael J. Birrer
Journal: Journal of Clinical Oncology (2016)

e21570 Background: A consortium of multi-disciplinary investigators and patient advocates was assembled to address key questions related to outcomes of long-term (LT) survivors with ovarian cancer (OC). Given the relative dearth of information on LT OC survivors, this proof-of-concept study begins to characterize quality of life (QOL) variables associated with LT survivorship. Methods: A convenience sample of 32 long term (8+ years) OC survivors were identified through our Advocates Advisory Board, and were invited to participate in a LT survivor survey and qualitative interview. Descriptive statistics and univariate analyses were conducted to examine characteristics associated with survivor-specific distress. Results: Thirty-two LT ( ≥ 8 years) OC survivors completed quality of life questionnaires. They reported a current mean age of 63.9 (SD = 9.0, range: 44-82), and 14.0 (SD 5.7) years post diagnosis. Fifty-three percent reported at least one recurrence. Overall, patients reported good QOL with mean scores for FACT-O and FACT-TOI of 124.2 (SD 16.5) and 82.3 (SD 11.6), respectively. Although older age at diagnosis was significantly associated with more neurotoxicity (p = 0.031), those with a current age of 65+ reported significantly better QOL than those ≤ 65 (FACT-O: 130 vs. 118; p = 0.038), specifically with higher social (p = 0.007) and functional well-being (p = 0.017). There were no significant differences in QOL related to recurrence ( ≥ 1 vs none). Poor emotional well-being was the only QOL domain associated with survivor-specific distress (p < 0.0005). Sizeable proportions of survivors reported significant fear of future diagnostic tests (44%), fear of a second cancer (44%), fear of recurrence (50%), and fear of metastasis (47%), which did not appear to differ between those who had or had not experienced recurrent disease. Conclusions: In this national convenience sample of LT OC survivors, overall QOL is good, particularly for older survivors whose social and functional well-being is significantly better than the younger survivor population. However, the interplay between cancer-specific fears and compromised emotional well-being merits further investigation.
Implementation of individualized care plans in high risk oncology patients: A team based model to decrease unnecessary utilization.
Authors: Girish Chandra Kunapareddy, Benjamin Switzer, Pramod Pinnamaneni, Joseph Hooley, Leticia Varella, Christa Poole, Helen Tackitt, Carolyn Best, Christine Hallman, Amy Torres, Ruth Lagman, Alberto J. Montero
Journal: Journal of Clinical Oncology (2018)

6547 Background: Due to complexity of disease and treatments, oncology patients (pts) have among the highest hospitalization rate. In our cancer institute, just 6% of all discharged pts accounted for > 40% of all unplanned readmissions (UR), and continue to be of highest risk of future admissions, ICU stay, ED visits, overuse of chemotherapy and underutilization of hospice resources. We hypothesized that developing individualized care plans (ICP) will better provide the complex care necessitated by this group Methods: An Interdisciplinary Care Team (ICT) was created consisting of palliative medicine and oncology physicians/social workers/care coordinators/nurse managers. Twice monthly, pts with the highest utilization over a 60-day period with at least two UR were identified. ICPs were created using the team-based approach with parallel input from primary outpatient providers. Communication plans were created to ED and outpatient teams Results: A total of 71 pts, 356 hospitalizations, and 260 ED visits were evaluated over a 6-month period, with an avg number of hospitalizations of 0.82 per pt month (ppm). After creation ICT, this decreased to 0.23 ppm. Average ED visits, UR, avg length of stay per admission also decreased (see Table 1). Nearly all solid tumor pts had metastatic disease at ICT review, while pts with hematological malignancies were early in their treatment course receiving myelosuppressive therapy. These results were compared to a historical cohort prior to ICT with the same inclusion criteria, which maintained to show a high relative impact Conclusions: Creation of individualized care plans for high-utilizing cancer patients decreased number of hospitalizations, ED visits, unplanned readmissions, and length of stay in all disease groups, but ST patients seemed to have a greater impact than in HM patients Effect of ICP. All Patients N = 71 Solid Tumor N = 40 Malignant Hematology N = 31 Hospitalizations Before ICP 0.82 0.79 0.89 After ICP 0.36 0.27 0.49 30-day Readmissions Before ICP 0.49 0.48 0.51 After ICP 0.13 0.05 0.29 ED Visits Before ICP 0.60 0.61 0.57 After ICP 0.24 0.18 0.42 Average LOS per Admission Before ICP 7.17 6.24 8.48 After ICP 4.06 2.55 6.17
Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development
Authors: Patrick G. Holt, Danny Mok, Debasis Panda, Lynnsey Renn, Giulia Fabozzi, Nick H. deKlerk, Merci M.H. Kusel, Michael Serralha, Elysia M. Hollams, Barbara J. Holt, Peter D. Sly, Ronald L. Rabin
Journal: Journal of Allergy and Clinical Immunology (2018)
3D printed biofunctionalized scaffolds for microfracture repair of cartilage defects
Authors: Ting Guo, Maeesha Noshin, Hannah B. Baker, Evin Taskoy, Sean J. Meredith, Qinggong Tang, Julia P. Ringel, Max J. Lerman, Yu Chen, Jonathan D. Packer, John P. Fisher
Journal: Biomaterials (2018)
Do high VEGFA and EGF levels in blood indicate liver metastases only?
Authors: Irina V. Kaplieva, Oleg I. Kit, Elena M. Frantsiyants, Lidia K. Trepitaki, Natalia D. Cheryarina, Yulia A. Pogorelova, Dmitry Sergeevich Petrov, Petr Gabrichidze, Maksim N. Duritskiy
Journal: Journal of Clinical Oncology (2018)

e24007 Background: Liver metastasis is a common sign of tumor progression. Growth factors are tissue malignancy markers, while their dynamics in the blood of cancer patients is poorly studied. The purpose of the study was to analyze the dynamics of growth factors in the blood serum of cancer patients of various ages and genders with liver metastases. Methods: Levels of VEGFA, VEGFR, IGF1, IGF2, EGF and EGFR were determined by ELISA in the blood serum of 130 patients (men and women over 35 years old) with liver metastases. Primary cancers included gastrointestinal tumors (stomach, pancreas, colon, sigmoid colon, and rectum), breast, prostate, uterine, ovary and lung tumors. Results: Levels of VEGFA and EGF increased in the blood serum of all patients with liver metastases, regardless the primary tumor site. Moreover, levels of these two growth factors exceeded the levels in healthy people and in cancer patients without liver metastases: VEGFA – by 4.7 and 2.9 times, and EGF – by 3.1 and 2.2 times, respectively. Levels of other growth factors in the blood serum of the patients were similar to normal ones. Conclusions: High levels of VEGFA and EGF could be metastasis markers. To clarify the specificity of these changes, specifically for metastatic processes in the liver, the results should be compared with the blood levels of growth factors in patients with other metastases.
Malignant mesothelioma in 91 danish women: The environmental asbestos exposure.
Authors: Vasiliki Panou, Mogens Vyberg, Christos Meristoudis, Øyvind Omland, Ulla Møller Weinreich, Johnni Hansen, Oluf D. RÃ¸e
Journal: Journal of Clinical Oncology (2017)

8560 Background: Malignant Mesothelioma (MM) is an asbestos-related malignancy that presents mainly in the pleura (MPM) and peritoneum (MAM). In a densely populated area of Aalborg city in North Jutland, Denmark, a large Eternit asbestos factory that was active for 60 years until 1986 and two shipyards were situated. The Region of North Jutland, Denmark has a high mm incidence in women of 1.0/100,000. Methods: From 1974-2015, 101 histological and cytological samples of women diagnosed with mm in Aalborg University Hospital were identified re-evaluated by modern immunohistochemistry. Patient information regarding asbestos exposure was retrieved from medical records and selected Danish registries. Asbestos exposure was classified as primary for asbestos workers; domestic, for women living with an asbestos worker; environmental, when living or working within 10.000 meters from an asbestos emitting location; unknown, where no source of asbestos exposure could be identified. Results: Clinical and histopathological mm diagnosis was certain for 91 women. Potential asbestos exposure is summarized in Table 1. The employment of the women and their relatives include work at the asbestos cement factory, shipyard, construction, laboratory, pipe factory, electrician and insulator. The women with domestic and combined domestic and environmental (secondary) exposure to asbestos were most prone to develop MPM rather than MAM while women primary exposed to asbestos developed MAM rather than MPM (p=0.016). Conclusions: This study showed that the vast majority (64%) of the women diagnosed with mm had documented non-occupational asbestos exposure and almost 1/5 had a sole environmental exposure, by living in proximity to asbestos industry. Environmental asbestos exposure is a serious risk factor for mm in women. Primary asbestos exposure, inferring more intense exposure through occupation, may predispose to peritoneal mesothelioma in women. [Table: see text]
Method development for detection of PD-L1 in circulating tumor cells in small-cell lung cancer patients.
Authors: Ying Cheng, Hui Li, Dandan Zhao, Yan Liu, Ying Wang, Xianhong Liu, Hongxia Cui
Journal: Journal of Clinical Oncology (2017)

e20012 Background: Previous studies showed that circulating tumor cells (CTCs), as liquid biopsy, are the alternative for tumor tissue in small-cell lung cancer treatment and study. Programmed death- ligand 1(PD-L1) is the most commonly used biomarker in immune-targeted therapy. The aim of this study is to develop a method to detect PD-L1 in CTCs in small-cell lung cancer patients. Methods: The anti-PD-L1 antibodies were purchased from both BD (clone MOPC-21) and Cell Signaling (clone E1L3N) Technology. Control cell lines were selected by single clone culturing technique and confirmed by immunecytochemistry and flow cytometry. CellSearch system was used to select and optimize antibodies, and to test CTCs in small-cell lung cancer patients. Results: After single clone culturing selection, the purity of PD-L1 positive H446 cells (positive control) was increased to 95% from 70%, and the purity of PD-L1 negative PC3 cells (negative control) increased from 90% to 95%. The dilution of 1:200 is the optimal antibody titer for CellSearch System with 98% positive rate and 3% negative rate. In all patients (n = 4) with CTCs presenting (n = 2), PD-L1was detected and the ratios of PD-L1 positive cells to CTC counting were 1:1 and 2:5, respectively. Conclusions: We developed the method for PD-L1 detection in CTCs and validated it in small-cell lung cancer patients, which paved the way for automatic detection of PD-L1 in liquid biopsy in the future.
TCT-795 Prognostic Impact of Race in Patients Undergoing PCI: Analysis of 22,638 Patients from 10 Randomized Coronary Stent Trials
Authors: Mordechai Golomb, Bjorn Redfors, Aaron Crowley, Ori Ben-Yehuda, Pieter Smits, Patrick Serruys, Clemens von Birgelen, Mahesh Madhavan, Roxana Mehran, Martin Leon, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Treating anorexia in people with advanced cancer. a randomised, double blind, controlled trial of megestrol acetate, dexamethasone or placebo.
Authors: David Christopher Currow, Paul A. Glare, Gareth Watts, Sandra Louw, Peter Martin, Katherine Clark, Belinda Fazekas, Meera Agar
Journal: Journal of Clinical Oncology (2018)

10020 Background: This multi-site, double blind, parallel arm, fixed dose phase III study compared megestrol acetate 480 mg/day, dexamethasone 4 mg/day and placebo for their net short-term effect on appetite and quality of life (QoL) in people with advanced cancer Methods: Inpatients or outpatients seeing a palliative care team with anorexia for ≥2 weeks with a score ≤4 on a 0-10 numeric rating scale (NRS; 0 = no appetite, 10 = best possible appetite) were recruited. Participants were randomised to receive megestrol 480 mg, dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary response assessment occurred at day 7, and responders were defined as having more than a 25% improvement in NRS compared to baseline. Results: There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% of participants in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group (p = 0·067) were responders. No differences in weight, performance status or quality of life were reported. Treatment emergent adverse events occurred in the majority of participants (90·4%), and included altered mood and insomnia. Hyperglycemia was more frequent in people on dexamethasone. Conclusions: Although there was little difference between treatment groups for the primary or secondary effectiveness endpoints, there was a consistent trend in secondary end-points favouring megestrol acetate than dexamethasone or placebo. Sub-group analyses indicate megestrol acetate may be more effective in maintaining body weight for subjects whose appetite responded. Clinical trial information: ACTRN12608000405314.