tbuckley/cabot-search huggingface dataset:
Abstract 6583: Systems scale characterization of malignant pleural mesothelioma to discover novel therapies
Authors: Sierra F. Wilferd, Chuong D. Hoang, Christopher L. Plaisier
Journal: Cancer Research (2020)

Abstract We have built a platform integrating systems genetics and functional genomics for the discovery of therapies to eradicate residual microscopic tumor foci after surgical resection of the deadly cancer malignant pleural mesothelioma (MPM). Using our SYstems Genetics Network AnaLysis (SYGNAL) network inference pipeline we constructed a malignant pleural mesothelioma gene regulatory network to discover disease causing TFs and miRNAs regulatory interactions. We then overlaid the MPM gene regulatory network with significant hits from pooled CRISPR-Cas9 knock-out out growth functional genomics screens in low passage number MPM patient-derived cell lines. We then queried this integrated network to identify patient survival associated TFs and miRNAs that when knocked-down (siRNA) or over-expressed (miRNA mimic), respectively, are likely to have anti-proliferative effects in low passage number patient-derived cell lines. The perturbation of a majority of these TFs and miRNAs led to significantly lower proliferation in the patient-derived cell lines. Further, the expression of the regulator or its target genes should function as a biomarker(s) for whether therapy will be effective for a particular patient's tumor. We are currently working with our collaborator at the NCI to develop these siRNA and miRNAs into their existing miRNA mimic hydrogel delivery system and test them in orthotopic xenografts using the low passage number patient derived cell lines. Citation Format: Sierra F. Wilferd, Chuong D. Hoang, Christopher L. Plaisier. Systems scale characterization of malignant pleural mesothelioma to discover novel therapies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6583.
Phase II and fluorodeoxyglucose positron emission tomography (FDG-PET) study in patients with advanced biliary tract cancers (BTCs) receiving bevacizumab (B) in combination with gemcitabine (GEM) and oxaliplatin (OX)
Authors: A. X. Zhu, J. A. Meyerhardt, L. S. Blaszkowsky, A. Muzikansky, T. A. Abrams, J. A. Chan, P. C. Enzinger, P. Bhargava, E. L. Kwak, D. V. Sahani
Journal: Journal of Clinical Oncology (2009)

4578 Background: Vascular endothelial growth factor (VEGF) expression is present in BTCs and is associated with poor survival. We performed a phase II study to examine the efficacy and tolerability of GEM and OX in combination with B (GEMOX-B) in patients (pts) with advanced BTCs. We also assessed the use of FDG-PET as an early indicator of response following treatment. Methods: Eligibility criteria included unresectable or metastatic measurable BTCs, 0–1 prior chemotherapy regimens, performance status ≤ 2, and adequate organ functions. Pts were treated with all 3 drugs intravenously on days 1 and 15 every 28 days (one cycle): B was given first at 10 mg/kg, followed by GEM at 1000 mg/m 2 as a dose-rate infusion at 10 mg/m 2 /minute, and OX at 85 mg/m 2 . Whole body FDG-PET scan was obtained at baseline and at the end of cycle 2. The primary endpoint of the study was progression-free survival (PFS). Results: The planned 35 pts (25 cholangiocarcinoma and 10 gallbladder carcinoma) were enrolled: median age = 60 (25–82), M/F = 21/14, median ECOG 1. All pts were evaluable for toxicity and 29 were evaluable for response. Treatment related grade 3–4 toxicities included neutropenia (20%), ALT (17%), neuropathy (14%), hypertension (11%), AST (9%), anorexia (9%), and thrombocytopenia (9%). 13 pts (45%) had a partial response (PR) and an additional 10 pts (34%) had stable disease (SD). With a median follow up of 9.9 months, the median overall survival was 13.2 months (95% CI, 7.3 to 20.5 months), and the median PFS was 7.0 months (95% CI, 5.4 to 9.6 months). The mean baseline SUVmax was 5.72±2.01 and post-treatment SUVmax was 3.73±1.88 with a median 36.4% decrease (n=32). The difference in SUV changes between the groups with PR/SD and progressive disease was statistically significant (p=0.006). An increase in adjusted post- to pre-treatment SUV increased the risk for tumor progression (hazard ratio=3.054). Conclusions: GEMOX-B demonstrated significant antitumor activity with tolerable safety profiles in patients with advanced BTCs. FDG-PET showed significant early decreases in SUVmax following treatment, and these changes correlated with tumor response and time to tumor progression. [Table: see text]
Salivary gland epithelial cells from patients with Sjögren’s syndrome induce B-lymphocyte survival and activation
Authors: Elodie Rivière, Juliette Pascaud, Nicolas Tchitchek, Saida Boudaoud, Audrey Paoletti, Bineta Ly, Anastasia Dupré, Hua Chen, Alice Thai, Norm Allaire, Bernd Jagla, Michael Mingueneau, Gaetane Nocturne, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2020)

Objective Primary Sjögren's syndrome (pSS) is characterised by chronic hyperactivation of B lymphocytes. Salivary gland epithelial cells (SGECs) could play a role in promoting B-lymphocyte activation within the target tissue. We aimed to study the interactions between SGECs from patients with pSS or controls and B lymphocytes. Methods Patients had pSS according to 2016 European League Against Rheumatism/American College of Rheumatology criteria. Gene expression analysis of SGECs and B lymphocytes from pSS and controls isolated from salivary gland biopsies and blood was performed by RNA-seq. SGECs from pSS and controls were cocultured with B-lymphocytes sorted from healthy donor blood and were stimulated. Transwell and inhibition experiments were performed. Results Gene expression analysis of SGECs identified an upregulation of interferon signalling pathway and genes involved in immune responses ( HLA-DRA , IL-7 and B-cell activating factor receptor ) in pSS. Activation genes CD40 and CD48 were upregulated in salivary gland sorted B lymphocytes from patients with pSS. SGECs induced an increase in B-lymphocyte survival, which was higher for SGECs from patients with pSS than controls. Moreover, when stimulated with poly(I:C), SGECs from patients with pSS induced higher activation of B-lymphocytes than those from controls. This effect depended on soluble factors. Inhibition with anti-B-cell activating factor, anti-A proliferation-inducing ligand, anti-interleukin-6-R antibodies, JAK1/3 inhibitor or hydroxychloroquine had no effect, conversely to leflunomide, Bruton's tyrosine kinase (BTK) or phosphatidyl-inositol 3-kinase (PI3K) inhibitors. Conclusions SGECs from patients with pSS had better ability than those from controls to induce survival and activation of B lymphocytes. Targeting a single cytokine did not inhibit this effect, whereas leflunomide, BTK or PI3K inhibitors partially decreased B-lymphocyte viability in this model. This gives indications for future therapeutic options in pSS.
Bicuspid Aortic Valve Morphology and Outcomes After Transcatheter Aortic Valve Replacement
Authors: Sung-Han Yoon, Won-Keun Kim, Abhijeet Dhoble, Stephan Milhorini Pio, Vasilis Babaliaros, Hasan Jilaihawi, Thomas Pilgrim, Ole De Backer, Sabine Bleiziffer, Flavien Vincent, Tobias Shmidt, Christian Butter, Norihiko Kamioka, Lena Eschenbach, Matthias Renker, Masahiko Asami, Mohamad Lazkani, Buntaro Fujita, Antoinette Birs, Marco Barbanti, Ashish Pershad, Uri Landes, Brad Oldemeyer, Mitusnobu Kitamura, Luke Oakley, Tomoki Ochiai, Tarun Chakravarty, Mamoo Nakamura, Philip Ruile, Florian Deuschl, Daniel Berman, Thomas Modine, Stephan Ensminger, Ran Kornowski, Rudiger Lange, James M. McCabe, Mathew R. Williams, Brian Whisenant, Victoria Delgado, Stephan Windecker, Eric Van Belle, Lars Sondergaard, Bernard Chevalier, Michael Mack, Jeroen J. Bax, Martin B. Leon, Raj R. Makkar
Journal: Journal of the American College of Cardiology (2020)
Abdominal Metastases of Intracranial Germ Cell Tumor Via Ventriculoperitoneal Shunt Detected by 18F-FDG PET/CT
Authors: Qiao Yang, Wenjia Zhu, Li Huo
Journal: Clinical Nuclear Medicine (2020)

Abstract Extraneural metastases of primary brain tumors are rare. Here, we provided a case of a 19-year-old man presenting with 2 intra-abdominal masses, who had a history of intracranial germ cell tumors and a ventriculoperitoneal shunt implanted in order to alleviate obstructive hydrocephalus. The intra-abdominal lesions showed intense FDG uptake and were confirmed to be germ cell tumors by postoperative histopathology. 18 F-FDG PET scan could be useful in monitoring metastases of intracranial germ cell tumors via ventriculoperitoneal shunt.
AB0218 Amyopathic dermatomyositis associated with pneumonitis: is methotrexate a risk factor ?
Authors: I Tekeoglu, A Akyokus, T Tuncer, B Butun, C Kacar, E Gilgil, G Arslan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> We described a case of dermatomyositis which subsequently developed intersititial lung disease. 35 years old woman was admitted to our department complaining of dermal eruptions without weakness of muscles. Characteristic skin changes included Gottron?s papules on the dorsal aspect of interphalangial joints, elbows and patella, heliotrop discoloration of eyelids with associated periorbital oedema, macular erythema of anterior neck and chest (V sign), face and fore head and mechanic?s hands. Serum CK levels and EMG was normal and no histological abnormality by muscle biopsy was found. Since she had not claimed evidence of muscle disease she was diagnosed as having dermatomyositis sine myositis (Amyopathic dermatomyositis) and initially treated with prednisolone (40 mg/day) and methotrexate (10 mg. per weak). Since her condition didn't changed high dose intravenous immunoglobulin (IVIG) therapy (1 gr/kg in three devided doses) was administered each month for six months. Marked improvement in dermal eruptions was observed following the second administration of IVIG therapy. Now in the eighth month of follow up she has been complaining of dyspnea on exertion for twenty days. High resolution computerised tomography (HRCT) of lung revealed paranchimal changes suggesting that bronchiolitis obliterans organising pneumonia (BOOP). Could this be the result of methotrexate therapy or a result of amyopathic dermatomyositis ? Lung involvement in amyopathic dermatomyositis is rare. Pulmonary drug toxicity is increasingly being diagnosed as a cause of acute and chronic lung disease. BOOP, which is commonly caused by cyclophosphamide and bleomycin as well as methotrexate and gold salts, appears on HRCT scans as poorly defined nodular areas of consolidation, centrilobular nodules, and bronchial dilatation. Knowledge of the drugs most frequently involved can facilitate diagnosis and institution of appropriate treatment. The results of lung biopy will be discussed in poster session. If lung biopsy will reveal the pathology methotrexate will be discontinued. <h3>Objectives</h3> <h3>Methods</h3> <h3>Results</h3> <h3>Conclusion</h3>
The ageing kidney: Molecular mechanisms and clinical implications
Authors: Yudong Fang, Athena Y. Gong, Steven T. Haller, Lance D. Dworkin, Zhangsuo Liu, Rujun Gong
Journal: Ageing Research Reviews (2020)

As human life expectancy keeps increasing, ageing populations present a growing challenge for clinical practices. Human ageing is associated with molecular, structural, and functional changes in a variety of organ systems, including the kidney. During the ageing process, the kidney experiences progressive functional decline as well as macroscopic and microscopic histological alterations, which are accentuated by systemic comorbidities like hypertension and diabetes mellitus, or by preexisting or underlying kidney diseases. Although ageing per se does not cause kidney injury, physiologic changes associated with normal ageing processes are likely to impair the reparative capacity of the kidney and thus predispose older people to acute kidney disease, chronic kidney disease and other renal diseases. Mechanistically, cell senescence plays a key role in renal ageing, involving a number of cellular signaling mechanisms, many of which may be harnessed as international targets for slowing or even reversing kidney ageing. This review summarizes the clinical characteristics of renal ageing, highlights the latest progresses in deciphering the role of cell senescence in renal ageing, and envisages potential interventional strategies and novel therapeutic targets for preventing or improving renal ageing in the hope of maintaining long-term kidney health and function across the life course.
THU0157 Cartilage oligomeric matrix protein (comp) and soluble cd44 variant isoform v5 (scd44v5) in patients with erosive, seropositive rheumatoid arthritis (ra+)
Authors: J Feyertag, G Haberhauer, M Skoumal, EM Kittl, K Bauer, A Dunky
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> "*" <h3>Objectives</h3> COMP is a pentameric protein of five identical disulfide-linked subunits and belongs to the thrombospondin family of proteins. It is proposed to be a marker of cartilage degradation and may be correlated to disease activity with respect to joint destruction in patients with RA+ and osteo-arthritis. The concentration of COMP in serum may decrease due to effective treatment of RA+. sCD44v5 has been described in patients with erosive RA+ and in patients with (longstanding) psoriatic arthtitis. It has been proposed to be a (slow acting) marker of disease activity and disease prognosis. The influence of different therapeutic procedures on sCD44v5 serum levels has been described. We were searching for correlations of sCD44v5 and COMP in the course of disease of patients with erosive RA. <h3>Methods</h3> Serum levels of COMP and sCD44v5 were measured in 53 patients with RA+ (Steinbrocker stages II-IV, duration of disease &gt;2 years). Follow up measurements were performed 8 times always after 3 months. Additionally routine laboratory monitoring and clinical assessment of the disease status were performed. ELISA-tests were used to detect COMP- and sCD44v5-serum levels. <h3>Results</h3> In our 53 patients with RA+ we could find significant correlations of COMP and sCD44v5 (p &lt; 0,0001), of COMP and rheumatoid factor measurements (RF) (p &lt; 0,006), of sCD44v5 and RF (p &lt; 0,0001), of sCD44v5 and erythrocyte sedimentation rate (ESR) (p &lt; 0,003), and of sCD44v5 and (a modified) Ritchie-Index (p = 0,05). <h3>Conclusion</h3> To interpret the implications of our preliminary results with reference to disease activity, cartilage destruction, disease progression and prognosis under different therapeutic procedures in patients with RA+, further studies are necessary. (Supported by " Vienna Bürgermeister-Fond" No.1452). <h3>References</h3> "*"
Final 10-year analysis of prospective multicenter Chemo N0 trial for validation of ASCO-recommended biomarkers uPA/PAI-1 for therapy decision making in node-negative breast cancer
Authors: N. Harbeck, M. Schmitt, C. Meisner, C. Friedel, M. Untch, M. Schmidt, B. Lisboa, C. Sweep, F. Jänicke, C. Thomssen
Journal: Journal of Clinical Oncology (2009)

511 Background: Based on interim results of the prospective, randomized, multicenter Chemo N0 trial and an EORTC pooled analysis (n = 8,377), ASCO and AGO guidelines recommend invasion markers uPA/PAI-1 for risk assessment in N0 breast cancer. Methods: We present final analysis of the Chemo N0 trial (recruitment 1993–1998; n = 647; 12 centers) with 113 (5–167) months median follow-up. Patients (pts) with low tumor levels of uPA and PAI-1 (n = 283) were observed. Of 364 patients with high uPA and/or PAI-1, 242 were randomized to CMF chemotherapy (n = 117) vs. observation (n =125); 122 pts decided for or against CMF on their own. External quality assurance provided good ELISA standardization in 5 participating laboratories. Results: The actuarial 10-year recurrence rate (without any adjuvant systemic therapy) for high uPA/PAI-1 pts in the combined (randomized and not randomized) observation group was 23.0%, in contrast to only 12.9% in those with low uPA/PAI-1 (p = 0.011, log rank). High-risk pts randomized for CMF had a 26.0% lower estimated probability of disease recurrence than high-risk pts randomized for observation (intention-to-treat analysis: HR 0.74 (0.44–1.27); p = 0.28, log rank). In per-protocol analysis, the treatment benefit was significant: HR 0.48 (0.25–0.88), p = 0.019, adjusted for tumor stage and grading in Cox regression for DFS; for OS, HR was 0.64 (0.35–1.19); p = 0.162, adjusted for tumor stage and grading in Cox regression. Conclusions: Chemo N0 is the first prospective biomarker-based therapy trial in early breast cancer defining a patient group achieving good long-term DFS without any adjuvant therapy. This trial demonstrates that, using a standardized uPA/PAI-1 ELISA, about half of N0 pts, classified as low-risk, could be spared chemotherapy, while high-risk pts benefit from adjuvant chemotherapy. These 10-year results validate the long-term prognostic and predictive impact of uPA/PAI-1 at highest level of evidence (LOE I) and support their guideline-based routine use for risk-adapted individualized therapy decisions in N0 breast cancer. The ongoing NNBC-3 trial is evaluating optimal chemotherapy for uPA/PAI-1 high-risk patients. [Table: see text]
Drive-through testing for SARS-CoV-2 in symptomatic health and social care workers and household members: an observational cohort study
Authors: Benjamin J Parcell, Kathryn Brechin, Sarah Allstaff, Meg Park, Wendy Third, Susan Bean, Chris Hind, Rajiv Farmer, Daniel Chandler, James D Chalmers
Journal: Thorax (2020)

The requirement for health and social care workers to self-isolate when they or their household contacts develop symptoms consistent with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to critical staff shortages in the context of a pandemic. In this report, we describe the implementation of a drive-through testing service in a single National Health Service region in Scotland. From 17 March 2020 to 11 April 2020, 1890 SARS-CoV-2 reverse transcription PCR assay (RT-PCR) tests were performed. 22% of tests were positive. Allowing the remaining 78% of staff to return to work within 24 hours was estimated to save over 8000 working days during the peak pandemic period.
SARS-CoV-2 IgG and IgA antibody response is gender dependent; and IgG antibodies rapidly decline early on
Authors: Wolfgang Korte, Marija Buljan, Matthias Rösslein, Peter Wick, Valentina Golubov, Jana Jentsch, Michael Reut, Karen Peier, Brigitte Nohynek, Aldo Fischer, Raphael Stolz, Michele Cettuzzi, Oliver Nolte
Journal: Journal of Infection (2020)
Functional imaging of neoadjuvant chemotherapy response in women with locally advanced breast cancer using diffuse optical spectroscopy
Authors: H. Soliman, A. Gunasekara, M. Rycroft, J. Zubovits, R. Dent, J. Spayne, R. Jong, M. Yaffe, G. Czarnota
Journal: Journal of Clinical Oncology (2009)

3591 Background: Functional imaging with tomographic near infrared diffuse optical spectroscopy (DOS) can quantitatively measure tissue parameters such as the concentration of deoxy-hemoglobin (Hb), oxy-hemoglobin (HbO2), percent water (%water), and scattering power (SP). The purpose of this study was to evaluate the correlation between DOS functional parameters with pathologic outcomes. Methods: Patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy or chemoradiotherapy were recruited to this study (n=10). Five scans were conducted per patient: a baseline scan taken up to 3 days prior to treatment and at 1 week, 4 weeks, 8 weeks, and after neoadjuvant treatment prior to surgery. Pulsed near-infrared laser light was used to scan the suspended breast at four different wavelengths and data was used for tomographic reconstruction. Volume-of-interest (VOI) weighted tissue Hb, HbO2, %water, and SP corresponding to the tumour was calculated and compared to pathological response as determined from full mount mastectomy specimens. Results: For all 10 patients the tumour-based VOI was significantly different than background tissue for all functional parameters (p&lt;0.001). Five patients had a good pathologic response. Four patients were considered non-responders. One patient initially had a poor clinical response to chemotherapy but after a change in chemotherapy had a good clinical response. Responders and non-responders were significantly different for all of the functional parameters (p&lt;0.05) at the 4 week scan. In the 5 patients with a good response the mean drop in Hb, HbO2, %water, and SP from baseline to the 4 week scan was 70.4% (SD=18.6), 66.5% (SD=24.5), 59.6% (SD=30.9), and 60.7% (SD=29.2), respectively. In contrast, the 4 non- responders had a mean drop of 17.7% (SD=9.8), 18.0% (SD=20.8), 15.4% (SD=11.7), and 12.6% (SD=10.2), for Hb, HbO2, %water and SP, respectively. Conclusions: Functional imaging using tomographic DOS parameters of Hb, HbO2, %water and SP could be used as an early detector of final pathologic tumour response. This could be evaluated in the future to assess response and potentially adjust chemotherapy regimens. No significant financial relationships to disclose.
Evaluation of Adjuvant! Online to predict the effect of optimal endocrine therapy (ovarian function suppression plus tamoxifen) for premenopausal breast cancer patients with estrogen-receptor-positive breast cancer
Authors: R. J. Paridaens, S. Gelber, B. F. Cole, R. D. Gelber, B. Thürlimann, K. Price, S. Holmberg, D. Crivellari, A. S. Coates, A. Goldhirsch
Journal: Journal of Clinical Oncology (2009)

585 Background: Adjuvant! Online (AOL) is a user-friendly, web-based tool that provides estimates of adjuvant therapy outcomes for individual patients. While reliable evidence underpins estimates for most patient cohorts, there is a paucity of data on the effect of adding chemotherapy to complete estrogen blockade for premenopausal women with estrogen-receptor positive breast cancer. Methods: International Breast Cancer Study Group (IBCSG) Trial 11–93 enrolled 174 premenopausal women with estrogen-receptor positive, node-positive breast cancer from 1993 to 1998. Fifty percent of patients had 1 positive axillary lymph node and 97% had between 1 and 3 positive nodes. Patients were randomized to receive ovarian function suppression plus five years of tamoxifen with or without chemotherapy. The estimated hazard rates and corresponding 10-year relapse-free survival percents obtained from Trial 11–93 data (Breast Cancer Res Treat. 2009;113:137–144) were compared with those predicted using AOL. Results: The 10-year relapse-free survival percents predicted from AOL were 64.4% (95% CI, 61.9% to 67.2%) for endocrine therapy alone and 74.9% (95% CI, 73.1% to 76.8%) for chemoendocrine therapy. By contrast, these estimates in Trial 11–93 were 76.4% (95% CI, 65.8% to 84.0%) for endocrine therapy alone and 74.9% (95% CI, 64.5% to 82.7%) for chemoendocrine therapy. The AOL estimate for the endocrine alone control group is lower than that observed in Trial 11–93 (p = 0.03), while the estimates for the two chemoendocrine therapy groups are similar. Conclusions: AOL appears to underestimate the effectiveness of adjuvant endocrine therapy alone for premenopausal women with endocrine responsive breast cancer, thus overestimating the added benefit - if any - from chemotherapy for this patient population. Prospective clinical trials addressing the question are warranted. No significant financial relationships to disclose.