tbuckley/cabot-search huggingface dataset:
FRI0019 Efficacy of etanercept on tenosynovitis and rheumatoid nodules
Authors: MJ Kaiser, MC Bozonnat, C Jorgensen, JP Daures, J Sany
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Etanercept is an efficient treatment of Rheumatoid arthritis (RA), but the effect on extraarticular features remains unknown. <h3>Objectives</h3> To evaluate the efficacy of etanercept on extraarticular features of RA. <h3>Methods</h3> We looked for tenosynovitis, rheumatoid nodules in 87 patients (70 women,17 men) with RA or juvenile rheumatoid arthritis (JRA), at day 0, before beginning treatment with Etanercept (25 mg twice a week) and at day 180 of treatment. The population included 82 cases of RA and 5 cases of JRA, rheumatoid factor positive in 64 cases, median age 51 years (7‑76). The median duration of RA was 11 years (2‑32) and the median number of previous treatments was 5 (1‑10). <h3>Results</h3> The evolution of the median value of modified DAS 28 was highly significant, with a score of 4.0 at day 0 and 1.7 at day 180(p = 0.01). At day 180,72 patients could be assessed for the 3 parameters studied. At day 0,72 patients out of 87 had tenosynovitis. All tenosynovitis disappeared in 12 patients, some but not all tenosynovitis disappeared in 7 patients. New tenosynovitis appeared at day 180 in 8 patients, 45 patients remained unchanged. Moreover,22 nodules were counted in 10 patients out of 87 assessed at day 0. At day 180, the assessment remained unchanged. Nodules neither appeared nor disappeared. No other extraarticular features appeared during treatment. <h3>Conclusion</h3> Etanercept is an effective inhibitor of TNFa providing clinical and biological improvement in both RA and JRA. However, Etanercept had no efficacy on tenosynovitis and rheumatoid nodules.
Impact of local and systemic treatment on survival and on brain relapse of patients with localized or metastatic non-small cell lung cancer who develop brain metastasis.
Authors: Marie Florescu, Normand Blais, Mustapha Tehfe, Marie Josee Begin
Journal: Journal of Clinical Oncology (2012)

e18120 Background: Up to 20% of patients with localized NSCLC develop brain metastasis, and twice more with metastatic NSCLC. We analyze retrospectively 216 unselected consecutive patients diagnosed with stage I to IV NSCLC treated at Notre-Dame Hospital from 2006 to 2010. Methods: Patients who developed their brain metastasis within 6 months of the NSCLC diagnostic were considered to have synchronous brain metastasis although those who developed more than 6 months later were designated metachronous. We compared the survival Kaplan-Meyer plots with log-rank tests in between each group category: synchronous brain metastasis with localized NSCLC (Sync Loc), synchronous brain metastasis with metastatic NSCLC (Sync Meta), metachronous brain metastasis in patients with localized NSCLC (Mec Loc) and metachronous brain metastasis in patients with already metastatic extracranial NSCLC (Mec Meta). Results: Comparing the 38 patients of Sync Loc with the 95 patients of Sync Meta, we found a not statistical significant difference in median survival with 15.4 months (Sync Loc) vs 6.8 months (Sync Meta) (p=0.18), but a similar 2 years survival 20.4% (Sync Loc) vs 15.7% (Sync Meta). Despite, only 27% of patients of Sync Loc received systemic treatment compared with 43% of patients Sync Meta, the two groups had no statistically significant difference in the median brain-relapse free survival with 18.5 months vs 14.1 months (p=0.335). The metachronous brain metastasis group had a significant difference in the median overall survival with 32.1months for the 61 patients Mec Loc and 18.1months for the 24 patients Mec Meta. Interestingly, stage I NSCLC patients with metachronous metastasis have a 2 year overall survival of 81.6%, stage II of 64.2% and stage III of 49.2%, similar to patients with no brain metastasis. Conclusions: Patients with localized NSCLC diagnosed with synchronous brain metastasis have probably already a metastatic disseminated disease with the same outcome than patients with NSCLC with extracranial metastatic disease. However, patients with metachronous brain metastasis and treated localized NSCLC have a very good prognostic.
Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1
Authors: Suzanne Thomas, Linta Kuncheria, Victoria Roulstone, Joan N. Kyula, David Mansfield, Praveen K. Bommareddy, Henry Smith, Howard L. Kaufman, Kevin J. Harrington, Robert S. Coffin
Journal: Journal for ImmunoTherapy of Cancer (2019)

Oncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death and induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development as an oncolytic immunotherapy in this study as it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis and is a potent activator of both innate and adaptive immunity. HSV-1 also has a large capacity for the insertion of additional, potentially therapeutic, exogenous genes. Finally, HSV-1 has a proven safety and efficacy profile in patients with cancer, talimogene laherparepvec (T-VEC), an oncolytic HSV-1 which expresses GM-CSF, being the only oncolytic immunotherapy approach that has received FDA approval. As the clinical efficacy of oncolytic immunotherapy has been shown to be further enhanced by combination with immune checkpoint inhibitors, developing improved oncolytic platforms which can synergize with other existing immunotherapies is a high priority. In this study we sought to further optimize HSV-1 based oncolytic immunotherapy through multiple approaches to maximize: (i) the extent of tumor cell killing, augmenting the release of tumor antigens and danger-associated molecular pattern (DAMP) factors; (ii) the immunogenicity of tumor cell death; and (iii) the resulting systemic anti-tumor immune response.
Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors
Authors: Geoffroy Liegeon, Linda Harrison, Anouar Nechba, Guttiga Halue, Sukit Banchongkit, Ampaipith Nilmanat, Naruepon Yutthakasemsunt, Panita Pathipvanich, Suchart Thongpaen, Rittha Lertkoonalak, Thomas Althaus, Marc Lallemant, Jean-Yves Mary, Gonzague Jourdain
Journal: Journal of Infection (2019)
Differential microRNA expressions in human hepatocellular carcinoma cells
Authors: Queenie W L Wong, Raymond R.w Lung, Navy L Y Wong, Paul B S Lai, K F To, Nathalie Wong
Journal: Cancer Research (2006)

3037  MicroRNAs (miRNAs) are a class of small non-coding RNA, 21-24 nucleotides, with significant roles implicated in transcriptional silencing and translational suppression. Here, we investigated the differential miRNA expressions in 8 human hepatocellular carcinoma (HCC) cell lines using a microarray-based platform. Enriched low molecular weight RNA from HCC cell lines (HKCI-2, 3, 4, 8, 10, and Hep3B, HepG2, SNU475 from the ATCC collection) and a pool of normal livers were labelled by Cy3 and Cy5 respectively prior to screening against ∼200 human miRNA targets printed on the mirMAX array (Rutgers University, USA). Nineteen miRNAs that represented 8 up- and 11 down-regulated targets demonstrated median fold change at ≥10 in cell lines compared to normal liver controls. The 5 top ranked up-regulated miRNAs (at median fold change of >30) were hsa-mir-31, hsa-mir-182, hsa-mir-221, hsa-mir-222 and hsa-mir-301, while the 5 most repressed miRNAs (at median fold change of >30) were hsa-mir-122a, hsa-mir-126, hsa-mir-150, hsa-mir-155 and hsa-mir-223. Of interest was hsa-mir-221 and hsa-mir-222 being located at Xp11.3, a region that our group has previously shown to be associated with advanced stage HCC tumors. The increased hsa-mir-221 and hsa-mir-222 expression in the 8 HCC cell lines was further confirmed by Northern blotting with U6 RNA as the internal loading control. While negligible expressions of hsa-mir-221 and hsa-mir-222 were detected in normal livers, relative increments of hsa-mir-221 expression at 12- to 49-fold and hsa-mir-222 expression at 8- to 138-fold were suggested from densitometry analysis. Our current study presents novel findings on the differential expressions of miRNAs in HCC. The verified expression of hsa-mir-221 and hsa-mir-222 may be suggestive of these miRNAs as potential targets in the common Xp11.3 gains found in the progressive developments of HCC.
Bevacizumab as maintenance therapy (mBev) in metastatic breast cancer (MBC).
Authors: Loredana Militello, Paolo Carli, Vincenzo Di Lauro, Simon Spazzapan, Simona Scalone, Davide Lombardi, Alessandro Tuzi, Renato Talamini, Daniela Quitadamo, Elisa Turchet, Diana Crivellari
Journal: Journal of Clinical Oncology (2013)

e22149 Background: Preclinical models suggest that the anti-VEGF may improve the efficacy of anti-estrogen therapies in Hormonal Receptor positive (HR+) breast cancer, but there is lack of informations about the maintenance therapy with Bev (mBev) and Hormonal Therapy (HT). Methods: sixty-one pts with HER-2 negative MBC were treated, at our institution from 2007, with Bev+Taxanes (BT) as 1 st line chemotherapy and with HT in HR+ pts as maintenance therapy. Primary endpoints were the evaluation of Progression Free Survival (PFS) and Overall Survival (OS). Secondary endpoint was the safety with HT in HR+ pts. Results: Hormonal status was positive in 52/61 (85%). Antracyclines were administered as adjuvant therapy in 26 pts (42%), antra+tax in 26 (42%) pts, no adjuvant therapy in 9 pts (14%). At the time of first relapse, median age was 50 y/o (range 33-72). First line HT was given to 12 pts. Metastatic sites were only bone in 20 pts (32%), visceral in 15 pts (25%), bone + visceral in 19 pts (31%), lymph nodes in 7 pts (11%). ECOG PS was 0 in 56 pts and 1 in 5. Median number of cycles of BT was 7 (1-14). All pts were evaluated for PFS and OS and 45 pts were evaluated for objective response: complete response (CR) was achieved in 5/45 pts (11%) (duration 12 months), partial response (PR) in 34/45 pts (75%) (duration 6-7 months), stable disease (SD) in 6/45 pts (14%) (6 months). After the assessment of the response, 34/61 pts received maintenance Bev (mBev); among this group, 24/34 pts with HR+ were also treated with HT until disease progression. The median number of cycles of mBev was 8 (1-42). Median PFS was 13.5 months (95%CI: 10.2-18.2) and median OS was 36 months (95%CI: 22-51). The BT regimen was well tolerated: 2 pts experienced cardiotoxicity with a reduction in left ventricular ejection fraction (LVEF); the most common side effects were hypertension (grade 1 in 11 pts e grade 2 in 16 pts), bleeding in 8 pts, proteinuria in 7 pts (grade 1 in 5 pts and grade 2 in 2 pts). Conclusions: Hormonalmaintenance and Bev can extend the overall benefit of therapy and it is well tolerated and associated with long-term clinical outcome. Our results are encouraging for prolonging Bev in association with HT as maintenance therapy until disease progression.
Plasma deconvolution identifies broadly neutralizing antibodies associated with hepatitis C virus clearance
Authors: Valerie J. Kinchen, Guido Massaccesi, Andrew I. Flyak, Madeleine C. Mankowski, Michelle D. Colbert, William O. Osburn, Stuart C. Ray, Andrea L. Cox, James E. Crowe Jr, Justin R. Bailey
Journal: Journal of Clinical Investigation (2019)

A vaccine for hepatitis C virus (HCV) is urgently needed. Development of broadly neutralizing plasma antibodies during acute infection is associated with HCV clearance, but the viral epitopes of these plasma antibodies are unknown. Identifying these epitopes could define the specificity and function of neutralizing antibodies (NAbs) that should be induced by a vaccine. Here, we present the development and application of a high-throughput method that deconvolutes polyclonal anti-HCV NAbs in plasma, delineating the epitope specificities of anti-HCV NAbs in acute-infection plasma of 44 humans with subsequent clearance or persistence of HCV. Remarkably, we identified multiple broadly neutralizing antibody combinations that were associated with greater plasma neutralizing breadth and with HCV clearance. These studies have the potential to inform new strategies for vaccine development by identifying broadly neutralizing antibody combinations in plasma associated with the natural clearance of HCV, while also providing a high-throughput assay that could identify these responses after vaccination trials.
Sugary drinks and cancer risk: more to diet than just sugar
Authors: David Benton, Hayley A Young
Journal: BMJ (2019)

Chazelas and colleagues report that sugar intake, including fruit juice, is associated with a higher incidence of cancer.1 A fundamental question is whether examining a single nutritional villain in isolation is meaningful, rather than acknowledging the need for a wide ranging, varied, and balanced diet?

Fruit juice is a valuable source of bioactive molecules with health …
Role of metabolic stress management in mammary tumorigenesis
Authors: Vassiliki Karantza-Wadsworth, Olga Kravchuk, Guanghua Chen, Eileen White
Journal: Cancer Research (2008)

1554  Autophagy is an evolutionarily conserved catabolic process whereby cellular organelles and bulk cytoplasm are targeted to lysosomes for degradation. Autophagy is a survival pathway required for cell viability during starvation; however, if it proceeds to completion, autophagy can lead to cell death. Autophagy also plays a role in tumorigenesis, as the essential autophagy regulator beclin1 is monoallelically deleted in many human ovarian, breast, and prostate cancers, and beclin1+/- mice are tumor-prone. Thus, autophagy likely suppresses tumorigenesis, but the mechanism has been unknown. We recently showed that allelic loss of beclin1 compromises the autophagy potential of immortalized mouse mammary epithelial cells (iMMECs) in vitro and in mammary tumors, sensitizes iMMECs to metabolic stress and accelerates lumen formation in mammary acini. Autophagy defects also activate the DNA damage response in vitro and in mammary tumors in vivo, promote gene amplification, and synergize with defective apoptosis to accelerate mammary tumorigenesis.  We are now investigating the mechanism by which autophagy mitigates metabolic stress and limits genome damage in mammary epithelial cells, so as to gain insight into how autophagy may suppress mammary tumorigenesis. A proteomic analysis was performed to determine how autophagy-competent mammary epithelial cells respond successfully to metabolic stress as compared to cells with autophagy defects. Protein extracts from apoptosis-defective beclin1+/+ and beclin1+/- iMMECs exposed to metabolic stress for 0 and 7 days were analyzed by two dimensional difference gel electrophoresis (2D-DIGE). More than a hundred proteins with differential expression under metabolic stress have been sequenced and mostly represent members of the GRP chaperone system, cellular metabolism, mitochondrial and cytoskeletal proteins. The 2D-DIGE results have been validated by Western Blotting and IF for a subset of the sequenced proteins. Expression of several proteins upregulated under metabolic stress has also been examined in 3D-morphogenesis assays. For most proteins examined to date, expression is higher in the central acinar cells, indicating that the acinar center is a physiologic area of increased metabolic stress. Finally, differential protein expression between wild-type and autophagy-defective iMMECs under conditions of metabolic stress is being validated on mammary tissues from beclin1+/+ and beclin1+/- female mice at different ages.  These studies may shed light into the mechanism by which failure to effectively manage metabolic stress by autophagy may promote genome damage and instability in mammary tumor cells, and thus breast cancer progression. Furthermore, new therapeutic targets may be identified and clues into how to best exploit the process of autophagy for therapeutic benefit may emerge.
The bio.tools registry of software tools and data resources for the life sciences
Authors: Jon Ison, Hans Ienasescu, Piotr Chmura, Emil Rydza, Hervé Ménager, Matúš Kalaš, Veit Schwämmle, Björn Grüning, Niall Beard, Rodrigo Lopez, Severine Duvaud, Heinz Stockinger, Bengt Persson, Radka Svobodová Vařeková, Tomáš Raček, Jiří Vondrášek, Hedi Peterson, Ahto Salumets, Inge Jonassen, Rob Hooft, Tommi Nyrönen, Alfonso Valencia, Salvador Capella, Josep Gelpí, Federico Zambelli, Babis Savakis, Brane Leskošek, Kristoffer Rapacki, Christophe Blanchet, Rafael Jimenez, Arlindo Oliveira, Gert Vriend, Olivier Collin, Jacques van Helden, Peter Løngreen, Søren Brunak
Journal: Genome biology (2019)

Bioinformaticians and biologists rely increasingly upon workflows for the flexible utilization of the many life science tools that are needed to optimally convert data into knowledge. We outline a pan-European enterprise to provide a catalogue ( https://bio.tools ) of tools and databases that can be used in these workflows. bio.tools not only lists where to find resources, but also provides a wide variety of practical information.
Abstract #5207: Label-free biosensor technology for monitoring oncogenic signaling pathways
Authors: Yuhong Du, Jing Zhao, Zhuo (Georgia) Chen, Dong M. Shin, Fadlo R. Khui, Haian Fu
Journal: Cancer Research (2009)

Cancer development and progression have been correlated with dysregulated intracellular signaling pathways that control cell proliferation, immortalization, apoptosis, invasion, and angiogenesis. Thus, innovative technologies are invaluable tools for effectively dissecting oncogenic signaling pathways and their targeting for drug discovery. In order to enhance detection sensitivity and selectivity, conventional methods often require artificially manipulated cell lines, for instance, with an introduced reporter. Here we report the application of a label-free biosensor technology for the detection of signaling pathways under physiological conditions. For this purpose, the Epic label-free biosensor utilizing the resonant waveguide grating technology was employed for monitoring growth factor induced signaling pathways that are often altered in tumors. Using the Epidermal Growth Factor Receptor (EGFR) signaling pathway as a model system, we have characterized the EGF-induced cellular dynamic mass redistribution (DMR) signals in various head and neck (HN 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5207.
Breast cancer risk is linked with ERCC2 genotypes and a corresponding haplotype in a German population
Authors: Christina Justenhoven, Ute Hamann, Beate Pesch, Volker Harth, Sylvia Rabstein, Christian Baisch, Yon-Dschun Ko, Thomas Brüning, Caren Vollmert, Thomas Illig, Hiltrud Brauch
Journal: Cancer Research (2005)

4070  The polygenic concept of breast cancer susceptibility calls for the identification of genetic variants contributing to breast cancer risk. Suspect molecular risks may include enzymes involved in hormone metabolism/catabolism and DNA repair. Reduced DNA repair proficiencies in women with breast cancer pointed to a possible role of DNA repair enzymes in the risk to develop the disease. The nucleotide excision repair (NER) enzyme encoded by the excision repair cross-complementing group 2 gene ERCC2 (formerly XPD) known to cause skin cancer by germline mutations has multiple regulatory cellular functions including NER, basal transcription, cell cycle control and apoptosis. ERCC2 polymorphisms ERCC2_6540_G>A (Asp312Asn) and ERCC2_18880_A>C (Lys751Gln) within the coding region of this evolutionarily highly conserved gene have shown to be of functional relevance, and therefore be potential candidates to confer breast cancer susceptibility. Using MALDI-TOF MS methodology we analyzed genotype frequencies in constitutional DNA of study participants of a German case-control study including 688 incident breast cancer cases and 724 population-based, age-matched controls. We identified ERCC2_6540_GG (Asp312Asp) as an at-risk genotype (OR 2.06; 95% CI: 1.39-3.07). The ERCC2_6540_GG associated breast cancer risk was even higher in women who were also carriers of the ERCC2_18880_CC (Gln751Gln) (OR 3.69, 95% CI: 1.76-7.74) or ERCC2_18880_AC (Lys751Gln) genotype (OR 2.61, 95% CI: 1.77-3.85). We identified ERCC2_6540_G/ERCC2_18880_C (312Asp751Gln) as the most potent risk conferring haplotype (OR 3.49, 95% CI 2.30-5.28). To our knowledge this is the first study assigning breast cancer risk to both the ERCC2 genotype encoding Asp312Asp and the haplotype encoding 312Asp/751Gln. We are currently exploring the role of other polymorphisms of DNA repair and hormone metabolism and will present how these integrate with the ERCC2 associated breast cancer risk in our population.
Comparison of dietary intakes of Canadian Armed Forces personnel consuming field rations in acute hot, cold, and temperate conditions with standardized infantry activities
Authors: Mavra Ahmed, Iva Mandic, Wendy Lou, Len Goodman, Ira Jacobs, Mary R. L’Abbé
Journal: Military Medical Research (2019)

Dietary Reference Intakes are used to guide the energy intake of the Canadian Armed Forces (CAF) field rations provided to military personnel deployed for training or operations. However, the high energy expenditures likely to occur under harsh environmental/metabolically challenging deployment conditions may not be adequately considered. This study examined the Ad libitum energy and nutrient intakes of CAF personnel (n = 18) consuming field rations in a resting thermoneutral environment and during a day of standardized strenuous infantry activities at varying environmental temperatures. Dietary intake was assessed using a measured food intake/food waste method during the experimental treatment and for 6 h after treatment. Four treatments were administered in a randomized counterbalanced design: exercise (as standardized infantry activities) in the heat (30 °C), exercise in the cold (− 10 °C), exercise in temperate thermoneutral (21 °C) air temperatures and a resting (sedentary) trial (21 °C). The average Ad libitum consumption of field rations was 70% of the provided total energy (2776 ± 99 kcal/8 h) during all treatments. Even with an acute challenge of increased energy expenditure and temperature stress in the simulated field conditions, participants’ energy intakes (1985 ± 747 kcal/8 h) under hot, cold and temperate treatments did not differ from energy intake during the sedentary condition (1920 ± 640 kcal/8 h). Participants’ energy intakes (1009 ± 527 kcal/6 h) did not increase during the 6 h posttreatment period when the stresses of the strenuous physical activities and the harsh environmental temperatures had subsided. These results should be considered when planning the provision of field rations for CAF personnel expected to be engaged in strenuous physical activities with prolonged exposure to temperature extremes.