tbuckley/cabot-search huggingface dataset:
Perception of cure among patients with metastatic genitourinary cancer initiating immunotherapy
Authors: Cristiane Decat Bergerot, Paulo Gustavo Bergerot, Errol J. Philip, Jo Ann Hsu, Nazli Dizman, Ulka Vaishampayan, Tanya Dorff, Sumanta Kumar Pal
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Despite the advent of checkpoint inhibitors (CPIs) for advanced genitourinary (GU) cancers, existing studies suggest that durable complete responses are observed in fewer than 10% of patients. This study sought to evaluate the association between expectations of cure reported by patients with advanced GU cancers initiating immunotherapy and quality of life (QOL), anxiety and depression. <h3>Patient and methods</h3> A single-institution, cross-sectional survey study was conducted with patients preparing to receive CPIs for treatment of metastatic renal cell carcinoma (RCC), urothelial cancer (UC) and prostate cancer (PC). Patients were assessed prior to initiation of immunotherapy for expectations of cure (divided into four quartiles), quality of life (QOL; Functional Assessment of Chronic Illness Therapy-General [FACT-G]), and symptoms of anxiety and depression (PROMIS). <h3>Results</h3> Sixty patients were enrolled, with metastatic RCC, UC and PC comprising 63, 28 and 8% of the study population, respectively. Median age of the cohort was 65 (range, 31–91), and 68% were male; 33% received CPI in the first-line setting. Despite extensive counseling from oncologists regarding potential clinical outcomes with immunotherapy, a substantial proportion of patients (23%) harbored inaccurate expectations regarding the potential benefit of immunotherapy. Importantly, patients with accurate expectations of cure reported lower anxiety scores using the PROMIS-Anxiety inventory. No significant differences were found between expectations of cure and quality of life or depression, using the FACT-G and PROMIS-Depression inventories, respectively. <h3>Conclusion</h3> The current study found that a considerable proportion of patients with advanced GU cancers harbor inaccurate expectations concerning the potential benefit of immunotherapy. These results suggest that more effective counselling may mitigate patient anxiety, and potentially promote treatment satisfaction and adherence.
Higher PD-L1 expression correlates with lymphocyte infiltration in early non-small cell lung cancer
Authors: P. Rocha, M. Rodrigo, L. Moliner, M. Hardy-Werbin, D. Casadevall Aguilar, X. Durán, O. Arpí, S. Clavé, M. Salido, X. Riera, S. Menendez, Á. Taus, L. Pijuan, L. Comerma, E. Arriola Aperribay
Journal: Annals of Oncology (2019)

Background: Patients with advanced NSCLC (Non-small cell lung cancer) benefit from ICIs (immune checkpoint inhibitors) as part of their treatment strategy. This benefit might also be observed in earlier stages. The aim of our work was to characterize the immune contexture of early NSCLC and assess the impact on outcome of immune biomarkers. Methods: Formalin-fixed paraffin embedded (FFPE) 1 mm cores from patients that underwent curative surgical treatment between 2006 and 2018 at Hospital del Mar (Barcelona, Spain), and did not received neoadjuvant therapy were included in a tissue microarray. PD-L1 expression as well as CD3, CD4, CD8, CD80 and CD103 were evaluated by immunohistochemistry. We report the percentage of positive cells for each marker from all nucleated cells. We evaluated the association between clinicopathological and molecular characteristics and immune biomarkers (Mann-Whitney, Kruskal-Wallis and Spearman correlation) and their impact on survival outcomes (Cox regression). Results: Samples from 195 patients were included (Adenocarcinomas n = 130, Squamous cell carcinoma n = 61, Other histology n = 4). In our cohort, 74.9% of the cases were males, predominantly smokers (87.2%). Tumor size was less or equal than 40mm in 72.3% of the cases. Stage I, II, III and IV tumors represent 44.6%, 25.1% and 26.7% of all cases included in our study, respectively. PD-L1 expression was <1%, 1 - <50% and ³50%, in 46.7%, 29.2% and 24.1% of the cases respectively. PD-L1 expression was positively correlated with higher percentage of CD4 (rho=0.195), CD8 (rho=0.3272), CD80 (rho=0.2152) and CD103 (rho=0.4237) (all p-values<0.05). CD103 expression was positively correlated with CD80 expression (rho=0.514; p < 0.001). A higher percentage of lymphocytes measured by CD3 expression in tumor tissue was correlated with better overall survival (p = 0.045; HR = 0.98 (0.96-0.99)) when adjusted by TNM 8thedition stage and adjuvant chemotherapy. No correlations with clinicopathological features were observed. Conclusions: Immune biomarker expression is highly heterogeneous in early NSCLC. Lymphocyte infiltration is associated with higher PD-L1 expression. Evaluation of immune biomarkers might better inform the choice of adjuvant treatment for NSCLC patients. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Inhibition of breast cancer cell proliferation by theaflavins from black tea through suppressing proteasomal activities
Authors: Jen-Kun Lin, Yu-Wen Chen, Shoei-Yn Lin-Shiau
Journal: Cancer Research (2006)

2279  Inhibitors of proteasome are currently emerging as novel cancer preventing and therapeutic agents. To determine whether the black tea polyphenols, including theaflavin, theaflavin-3-gallate, theaflavin-3’-gallate, theaflavin-3,3’-digallate (TF3), and (-)-epigallocatechin-3-gallate (EGCG) were potential proteasome inhibitors, we treated purified 20S or 26S proteasome and 26S proteasome in leukemia and cancer cell lines with these compounds. TF3 displayed a potent inhibitory effect on the growth of U937 cells with an estimated IC50 value of 6μM. Furthermore, TF3 had more efficient inhibition on the proteasomal chymotrypsin-like activity of purified proteasome derived from different sources and 26S proteasome in four kinds of cancer cell extracts as compared to those of EGCG. In addition, the theaflavins, especially TF3, inhibited the proteasomal chymotrypsin-like and peptidyl glutamyl peptide hydrolase (PGPH) activities of 26S proteasome in a concentration-dependent manner in human breast cancer MCF7 cells which have been described to be resistant to apoptosis induced by proteasome inhibitors. These results illustrated that proteasome inhibition by theaflavins lead to anti-proliferation of MCF7 cells. Furthermore, comparing well-characterized polyphenols on proteasome inhibition, the ester bond-bearing compounds, with some exceptions, exhibited more potently inhibitory effects on the proteasomal chymotrypsin-like activity than those without ester bond(s). Interestingly, the gallic acid and n-propyl gallate also had slightly inhibition on proteasome activities. Therefore, we suggest that the galloyl moiety might be the other important structure of polyphenols that contributes to the proteasome inhibition.
Microbiological diagnostics of bloodstream infections in Europe—an ESGBIES survey
Authors: E.A. Idelevich, H. Seifert, M. Sundqvist, L. Scudeller, S. Amit, A. Balode, A. Bilozor, P. Drevinek, Z. Kocak Tufan, A. Koraqi, B. Lamy, I. Mareković, J. Miciuleviciene, M. Müller Premru, A. Pascual, S. Pournaras, V. Saegeman, H.C. Schønheyder, J. Schrenzel, T. Strateva, R. Tilley, W.J. Wiersinga, D. Zabicka, Y. Carmeli, K. Becker
Journal: Clinical Microbiology and Infection (2019)
Abstract 16685: Obstructive Fibrosis Related to Transverse Conduction Slowing in Chronic Atrial Fibrillation
Authors: Nathan A Angel, Li Li, Rob S MacLeod, Nassir Marrouche, Ravi Ranjan, Derek J Dosdall
Journal: Circulation (2015)

Introduction: Patients with paroxysmal atrial fibrillation (AF) often transition between sinus rhythm and AF. For AF to initiate there must be both a trigger and a substrate that facilitates reentrant activity. This trigger is often caused by a premature atrial contraction or focal activations within the atrium. Hypothesis: We hypothesize long strands of continuous fibrosis act as a substrate that slows conduction, but only after a premature contraction. Methods: A high density electrode plaque was placed on 13 controls and 6 chronic AF goats (an average of 6 months of rapid pacing induced AF). Conduction slowing following a premature contraction was quantified. Atrial fibrosis was quantified into two groups, non-obstructive and obstructive fibrosis. Obstructive fibrosis was considered fibrosis that was at least the length of a myocyte (100 μm), thus potentially disrupting transverse cell to cell conduction. Non-obstructive fibrosis had a length less than 100 μm. Results: Conduction velocity of the AF goats was significantly slowed compared to the control goats in the transverse direction (0.40±0.03 m/s vs. 0.53±0.15 m/s, p&lt;0.05) but not in the longitudinal direction (0.70±0.27 m/s vs. 0.76±0.18 m/s, p = N.S.) following a premature atrial contraction. The AF goats had more obstructive fibrosis than the controls (18±8 fibers/mm 2 vs. 9±3 fibers/mm 2 , p&lt;0.05). The control group trended towards more non-obstructive, diffuse fibrosis than the AF animals (1109±309 fibers/mm 2 vs. 718±380 fibers/mm 2 , p = 0.07, N.S). Conclusions: Structural and electrophysiological remodeling in chronic AF leads conduction velocity slowing transverse to fiber orientation. Histology from goats with a history of chronic AF had more obstructive fibrosis, which may lead to the conduction slowing and alteration in conduction pathways to make the tissue more susceptible to AF. The amount of obstructive fibrosis may be more important to AF outcomes than the total density of fibrosis.
Expression of connexin 43 in primary liver cancer associated or not with hepatitis C and its relationship with resistance of chemotherapy.
Authors: Alexandre Tavartkiladze, Teimuraz Sordia
Journal: Journal of Clinical Oncology (2015)

e22100 Background: The aims of our research will be to examine the expression of connexin 43 (Cx43) and mRNA and the genes of MDR1 (multi drug resistant 1), MRP and LRP using the technique of Northern Blot (resistance in drugs used in chemotherapies)in the primary liver cancer, and discuss the role of expression Cx43 and MDR1 gene in chemoresistance in primary liver cancer. Methods: We examined the expression of Cx43, and MDR1 genes in primary liver cancer tissue by immunohistochemistry and Northern Blot, and compared their expression in chemosensitivity and chemoresistance groups (total 18 patients with liver cancer associated Hepatitis C and 15 Patients with Liver Cancer without viral Hepatitis). Gemcitabine and 5-fluoruracil resistant primary liver cancer cell lines from the biopsy materials. Then testing the expression of Cx43, and MDR1. We tested chemosensitivity of liver cancer cells by ATP tumor chemosensitivity assay (ATP-TCA). Results: By Immunohistochemically, the rates of positive expression of Cx43 were 78% in the chemoresistance group, which were 94%, in the chemosensitivity group respectively (P < 0.05). The rate of positive expression of MDR1 in 11 chemoresistance liver cancer cases (70%) was higher than that in 7 chemosensitivity cases (30%, P < 0.05). In addition, the expression of MDR1 was negatively correlated with the expression of Cx43. By ATP-TCA, liver cancer cells were resistant to Gemcitabine and 5-fluoruracil. The tumor growth inhibition by Gemcitabine or 5-fluoruracil was higher in the group of in the cells lines from patients without Hepatitis C. Conclusions: Expression of Cx43 and MDR1 genes have significantly role in the Primary Liver Cancer Pathology and in the Treatment Protocoles. When the Expression the Cx43 is High in the Liver Cancer the sensitivity this cancer is higher on Gemcitabine and 5-fluoruracil and when Expression MDR1 is higher in the liver cancer the sensitivity this cancer is very low on Gemcitabine and 5-fluoruracil. Also is Significantly that in the liver cancer patient's with viral hepatitis are lesser sensitivity on chemotherapy in any expression Cx43 or MDR1 in comparison the patients without viral hepatitis
THU-231-Risk of hepatocellular carcinoma in patients with immune-tolerant chronic hepatitis B
Authors: Gyeol Seong, Dong Hyun Sinn, Wonseok Kang, Geum-Yon Gwak, Moon Seok Choi, Kwang Cheol Koh, Seoung Woon Paik, Yong Han Paik
Journal: Journal of Hepatology (2019)
Abstract #5219: Linear and circular vectors for cloning and mammalian expression of difficult DNAs.
Authors: Ronald Godiska, David Mead, Karen Usdin, Jacques Perrault
Journal: Cancer Research (2009)

Many types of genetic regions, such as toxic cDNAs, repetitive DNAs, or AT-rich regions, are subject to rearrangement when cloned into bacterial cells. These fragments or their encoded proteins therefore cannot be studied directly nor transfected into mammalian cells for structure/function studies. The transcription-free \#8220;pSMART\#8221; vectors and the linear \#8220;pJAZZ\#8221; vectors have been developed to stably clone otherwise \#8220;unclonable\#8221; DNAs in E. coli. We describe here modifications of these vectors to facilitate transfection and expression of such difficult fragments in mammalian cells. The ends of the pJAZZ linear vector are free to rotate during transcription and replication, so the vector and cloned DNA fragments are not subject to torsional stress. In addition, transcriptional terminators flank the cloning site, preventing transcriptional interference between the vector and insert. Regions of potential secondary structure appear to be very stable in the linear, non-transcribed vectors. For example, up to 300 copies (~ 1 kb) of the GCC repeat of the Fragile X locus were stable in the pJAZZ vector, but not in any circular vectors. AT-rich fragments of up to 30 kb and other highly repetitive DNAs also have been accurately cloned and stably maintained in the pJAZZ vectors. We are now incorporating this technology into systems for either transient or stable transfection of mammalian cells. These new systems will enable cloning, expression, and genomic integration of a wide variety of previously recalcitrant cDNAs and genomic DNA fragm  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5219.
The significance of the serum leptin, ghrelin, tumor necrosis factor alpha and interleukine-1 levels in patients with non-small cell lung cancer.
Authors: Fatih Karatas, Bulent Yalcin, Hakan Akbulut, Gungor Utkan, Suleyman Sahin, Ahmet Demirkazik, Bekir Hacioglu, Fikri Icli
Journal: Journal of Clinical Oncology (2015)

e18533 Background: Leptin, ghrelin, tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL1B) serum levels are known to be increased in patients with non-small cell lung cancer (NSCLC) compared to the healthy population. These hormones and cytokines have been shown to be associated with cachexia in many cancer types. This study examines the relations between serum leptin, ghrelin, TNFα and IL1B levels, and survival, cachexia and resectability. Methods: Seventy-one recently diagnosed NSCLC patients between 43 to 80 years old are enrolled the study. Leptin, ghrelin, TNFα and IL1B levels are measured by enzyme-linked immunosorbent assay. Decreases in body weight, histopathologic types, median survival and resectability of the patients are compared by the levels of serum leptin, ghrelin, TNFα, IL1B. Results: Mean age was 63.3 ± 8.22 year and 81% of them were male. Fifty-two percent of the patients were resectable. Squamous cell, adenocarcinoma and other histologies were found 60.5%, 32% and 7.2% respectively. Mean measured levels were as follows: Ghrelin 35.89 ± 16.7 pg/mL, leptin 12.90 ± 38.49 pmol/mL, TNFα 9.50 ± 2.43 pg/mL, IL1B 196 ± 147 pg/mL, CRP 14 ± 30.6 mg/dL and leukocyte number 8571 ± 3665 x106/mL. Unresectable patients have significantly lower serum ghreline levels (27.77 ± 2.4 pg/mL vs. 39.05 ± 1.21 pg/mL, p = 0,018). There was no significant relation between body weight loss or cachexia and serum levels of leptin, ghrelin, TNFα and IL1B. But, mean serum leptin levels were significantly higher in patients with adenocarcinoma, compared to squamous cell histology. (26.99 ± 6.2 pmol/mL vs. 5.10 ± 9.1 pmol/mL, p = 0,004). There was no significant relation between serum TNFα, leptin, IL1B and CRP levels and survival. Conclusions: Our findings supports that most significant prognostic factor in NSCLC is the respectability of the disease and patients with unresectable patients have the worst prognosis. We also found higher mean serum ghrelin levels in resectable patients and serum leptin levels in adenocarcinoma patients when compared to other histologies. Serum leptin levels may help in detecting adenocarcinoma subtype and/or follow-up of the patients.
SAT-187-Characterization of hepatitis e infection in israel: identification of HEV-7 in camels and high seroprevalence in specific human populations
Authors: Orna Mor, Rachel Shirazi, ravit bassal, Tamar Shohat, Marina Wax, Yael Gozlan, dan cohen, Dan David, Saif Abu-Mouch, ella mendelson, Ziv Ben Ari
Journal: Journal of Hepatology (2019)
FRI-023-Inadequate response to UDCA among PBC patients under routine care in the US: Rising serum bilirubin even in the normal range is a risk factor and subsequent clinical follow-up differs based on treatment response
Authors: Stuart C Gordon, Talan Zhang, Christopher L. Bowlus, Keith D. Lindor, Robert J Romanelli, Irina V. Haller, Heather Anderson, Jeffrey J. Vanwormer, Joseph A. Boscarino, Mark A Schmidt, Yihe G Daida, Amandeep Sahota, Jennifer Vincent, Kwan-Han Wu, Sheri Trudeau, Christina Melkonian, Loralee B Rupp, Mei Lu
Journal: Journal of Hepatology (2019)
TrichostatinA to stimulate expression of Bridge-1 and Smad2, 3 and 4 of the ActivinA signaling cascade: Bridge-1-siRNA to enhance antiproliferative response to ActivinA in human breast cancer cells MCF-7.
Authors: Constanze Banz-Jansen, Birte Muenchow, Achim Rody
Journal: Journal of Clinical Oncology (2015)

e12016 Background: Bridge-1, a PDZ domain containing co-activator, is known to be expressed in the human breast cancer cell line MCF-7. Expression of Bridge-1 is stimulated by Activin A, a growth inhibitor of MCF-7. To explore the influence of Bridge-1 on cell proliferation in MCF-7 cells we examined the expression of Bridge-1 and Smad2, 3 and 4 of the ActivinA signaling cascade after treatment with Trichostatin A, the histone deacetylase (HDAC) inhibitor, known for cell growth inhibition. Second we investigated the influence of Bridge-1-siRNA on proliferation of MCF-7 cells alone and after treatment with ActivinA. Methods: MCF-7 cells were treated with 10 ng/ml Trichostatin A and the expression of Bridge-1, Smad2, 3 and 4 investigated by real-time PCR (n = 7). Next immortalized, human breast cancer cells (MCF-7) were stimulated with ActivinA alone, ActivinA combined with Bridge-1-siRNA and Bridge-1-siRNA alone and proliferation measured with the colorimetric Cell Proliferation ELISA, BrdU (n = 6). Results: Stimulation of MCF-7 cells with Trichostatin A increases expression of Bridge-1 (p = 0.029), Smad2 (p = 0.0396), Smad3 (p < 0.0001) and Smad4 (p = 0.0019). ActivinA stimulation showed decreased proliferation (p = 0.0001) and combined ActivinA and Bridge-1-siRNA treatment inhibited proliferation even stronger (p = 0.0171). Treatment with Bridge-1-siRNA alone showed no significant inhibition of proliferation in MCF-7 cells. Conclusions: Treatment of breast cancer cells with the cell growth inhibitor Trichostatin A increases expression of Bridge-1 and Smad2, 3 and 4 of the ActivinA signaling cascade. The growth inhibitory effect of ActivinA was enhanced by Bridge-1-siRNA. Our findings underline the possible role of Bridge-1 in the regulation of cell growth in human breast cancer cells.
Percutaneous Coronary Intervention in Older Patients With ST-Segment Elevation Myocardial Infarction and Cardiogenic Shock
Authors: Abdulla A. Damluji, Karen Bandeen-Roche, Carol Berkower, Cynthia M. Boyd, Mohammed S. Al-Damluji, Mauricio G. Cohen, Daniel E. Forman, Rahul Chaudhary, Gary Gerstenblith, Jeremy D. Walston, Jon R. Resar, Mauro Moscucci
Journal: Journal of the American College of Cardiology (2019)
Sixty seconds on . . . housework
Authors: Abi Rimmer
Journal: BMJ (2019)

No, I’m talking about all of those domestic chores that need doing around the house: cooking, cleaning, laundry . . .

You may think that you’re joking, but a study published in JAMA Surgery has found that doctors who are mothers still do most of the childcare and housework.1 A survey of 1712 members of the Physician …
Returning Individual Research Results Regarding Gadolinium Deposition in the Brain Is the Preferable Choice
Authors: Caroline J. Huang, W. Patricia Bandettini, Marion Danis
Journal: The American Journal of Bioethics (2019)

"Returning Individual Research Results Regarding Gadolinium Deposition in the Brain Is the Preferable Choice." The American Journal of Bioethics, 19(4), pp. 77–78
Sarcopenia as prognostic factor in lung cancer patients: A systematic review and meta-analysis
Authors: J. Büntzel, J. Heinz, C. Röver, A. Bleckmann, C. Bauer, A. Emmert
Journal: Annals of Oncology (2019)

Background: Sarcopenia describes the loss of skeletal muscle mass. While this condition is associated with a high mortality in cancer patients, its influence on survival is still underestimated. Here we investigate the impact of sarcopenia on the prognosis of lung cancer patients. Methods: A systematic research for articles was performed using the PubMed database, Cochrane Library, Biomed Central, Science Direct and by manual search. Articles published between January 2009 and May 2018 meeting the inclusion criteria were investigated. We used data of overall survival in sarcopenic patients from retrospective and prospective studies for assessing the death risk. Sarcopenia was assessed either by computer tomography, by dual-energy X-ray absorptiometry scan or by bioelectrical impedance analysis. We extracted hazard ratio estimates from univariate and multivariate Cox proportional hazards models for meta-analysis. This study was prospectively registered at PROSPERO (International prospective register of systematic reviews; ID: 105940). Results: Fifteen studies were eligible for meta-analysis including a total of 2521 lung cancer patients (UICC I-IV). Univariate analysis revealed a twofold increased death risk in sarcopenic -compared non-sarcopenic- patients; multivariate analysis even yielded a significant, threefold elevated risk of death. This higher mortality is independent of tumour stage (UICC I-IIIA vs. IIIB-IV). The death risk reduces if muscle mass is increased. Conclusions: Here we investigated sarcopenia as potential prognostic factor in lung cancer patients. Muscle loss is an independent risk factor for increased death risk in lung cancer patients independent of cancer stage. This argues for implementing screening for sarcopenia into cancer care. Legal entity responsible for the study: The authors. Funding: Ministery of Science and Culture of Lower Saxony (Niedersächsischen Ministerium für Wissenschaft und Kultur). Disclosure: J. Bünzel: Scholarship of the "Göttinger Kolleg für Translationale Medizin", funded by the Ministery of Science and Culture of Lower Saxony (Niedersächsischen Ministerium für Wissenschaft und Kultur). All other authors have declared no conflicts of interest.
THU-341-Liver steatosis is a strong predictor of mortality and cancer in chronic hepatitis B regardless of viral load
Authors: Noam Peleg, Assaf Issachar, Michal Cohen-Naftaly, Orly Sneh Arbib, Marius Braun, moshe leshno, alon barsheshet, Amir Shlomai
Journal: Journal of Hepatology (2019)