tbuckley/cabot-search huggingface dataset:
OSU-2S, a Novel PKC Activator, Mediates PKC Dependent Cell Death, Differentiation and Cell Cycle Arrest in Acute Myeloid Leukemia
Authors: Swagata Goswami, Rajeswaran Mani, Xiaokui Mo, Pearlly S. Yan, Michael B Broe, Ralf Bundschuh, Larry State Beaver, Kevan Zapolnik, Zhiliang Xie, Donna Bucci, David M. Lucas, Allison R. Walker, Alice S. Mims, Rebecca B. Klisovic, Ching-Shih Chen, John C. Byrd, Mitch A. Phelps, Sumithira Vasu, Natarajan Muthusamy
Journal: Blood (2017)
Fluorescent Cholangiography During Laparoscopic Cholecystectomy
Authors: Seth D. Goldstein, Timothy B. Lautz
Journal: JAMA Surgery (2020)

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Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled By Functional Lipoprotein Nanoparticles and the B Cell Receptor Inhibitor Ibrutinib: A Therapeutic Strategy Dependent on Cell of Origin (COO)
Authors: Jonathan Rink, Osman Cen, Kaylin Marie McMahon, Sol Misener, Shuo Yang, Colby Shad Thaxton, Leo I. Gordon
Journal: Blood (2017)
Antirheumatic drugs, B cell depletion and critical COVID-19: correspondence on ‘Clinical course of coronavirus disease 2019 (COVID-19) in a series of 17 patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine’ by Mathian<i>et al</i>
Authors: Quirin Notz, Patrick Meybohm, Peter Kranke, Dirk Weismann, Christopher Lotz, Marc Schmalzing
Journal: Annals of the Rheumatic Diseases (2020)

<b>Objective:</b> Patients with chronic idiopathic vulvar vestibulitis have increased mast cells when biopsied, and cromolyn has been suggested as a treatment. The purpose of this study was to assess the efficacy of 4% cromolyn cream in women with vulvar vestibulitis. <b>Methods:</b> A prospective, double blind, randomised, placebo controlled study was initiated at two centres. Patients with vulvar vestibulitis were assigned to apply cromolyn or placebo cream to the vestibule. Symptoms (burning, irritation) and signs (erythema, extent of erythema, tenderness) were recorded on a 0–3 scale. In the sexually active patient subgroup, dyspareunia was also evaluated. <b>Results:</b> 13 of the 26 evaluable patients received cromolyn. Patients in the cromolyn arm were more likely to have failed therapy with amitriptyline (p = 0.05), but the two groups were otherwise similar upon study entry. Overall, scores decreased from a median of 9 to 5 (p = 0.001) during the study, but the level of improvement was similar between both groups. Improvement was unrelated to duration of symptoms, fluconazole use, or sexual activity. Five patients (38%) taking cromolyn and six (46%) taking placebo felt they had a 50% or greater reduction in symptoms. In the 21 sexually active patients, the total score decreased from a mean of 12 to 8 (p = 0.005), but there was no statistically significant difference between study arms. <b>Conclusions:</b> Cromolyn cream did not confer a significant benefit in patients with vulvar vestibulitis. The large placebo response suggests the need for large well controlled studies of other treatment modalities.
Abstract 5363: A direct amplicon-based targeted sequencing assay for mutation analysis of single circulating tumor cells and correlation with circulating tumor DNA
Authors: Nolan G. Ericson, Vidushi Kapoor, Guoying Liu, Alisa C. Clein, Daniel E. Sabath, Eric P. Kaldjian, Tad George
Journal: Cancer Research (2020)

Abstract There is increasing interest in sequence analysis of circulating tumor cells (CTCs) to identify actionable mutations that may complement circulating tumor DNA (ctDNA) findings. Because the amount of DNA present in a single cell is miniscule (~6 pg), whole genome amplification (WGA) is typically performed prior to next generation sequencing (NGS) library preparation. Existing WGA methods have inherent amplification biases leading to non-uniform genome coverage that can cause dropout of desired targets, as well as replication errors that can lead to false positive results. Targeted sequencing is an alternative approach that does not require WGA. We modified the CleanPlex® OncoZoom® Cancer Hotspot Panel protocol to perform targeted sequencing of single CTCs isolated by the RareCyte platform using A549 cell line spike-in and patient samples. We also used the CleanPlex panel to evaluate ctDNA from plasma isolated by blood collection tubes from two manufacturers (RareCyte and Streck). In both cases we compared OncoZoom results with and without prior WGA. Increased uniformity of coverage with decreased target dropout was observed when CleanPlex NGS libraries were prepared directly from cell lysates without WGA. Median read depth increased 48-fold when compared to the WGA method. On average, 23 out of 29 (79%) variants present in bulk A549 genomic DNA were observed without WGA in single model CTCs, while 15 of 29 (52%) were observed after WGA. Additionally, the false positive error frequency of non-WGA samples was 8-fold lower than in the WGA samples. CTCs and cell-free DNA from two metastatic breast cancer patients were also sequenced using OncoZoom. In one patient, PIK3CA E542K, a well-documented oncogenic mutation, was observed in 3 of 5 CTCs. In the other, ERBB2 L755S, a known HER2-reactivating mutation associated with chemoresistance, was found in 3 of 5 CTCs. Both patients' variants were present at similar allelic frequencies in plasma isolated from RareCyte and Streck cell-free DNA BCT tubes. Single-cell CleanPlex amplicon-based sequencing without prior WGA resulted in libraries with more complete and consistent coverage and lower error frequencies, enabling efficient and accurate assessment of somatic mutations in CTCs. This approach shows promise for cell-based liquid biopsy diagnostic applications. Citation Format: Nolan G. Ericson, Vidushi Kapoor, Guoying Liu, Alisa C. Clein, Daniel E. Sabath, Eric P. Kaldjian, Tad George. A direct amplicon-based targeted sequencing assay for mutation analysis of single circulating tumor cells and correlation with circulating tumor DNA [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 5363.
Phase I study of combination treatment with PTK 787/ZK 222584 (PTK/ZK) and cetuximab for patients with advanced solid tumors: Safety, pharmacokinetics, pharmacodynamics, and toxicity analysis
Authors: M. H. Langenberg, P. O. Witteveen, N. Lankheet, J. M. Roodhart, H. Rosing, J. H. Beijnen, E. E. Voest
Journal: Journal of Clinical Oncology (2009)

2575 Background: Based on the current knowledge of tumor biology there is a rationale to combine targeted therapies that block different growth factor pathways. Here we combined PTK/ZK, a small molecule inhibitor of all three vascular endothelial growth factor receptors, PDGFR and c-kit, with cetuximab, a monoclonal antibody against the epidermal growth factor receptor. Methods: In this phase I study patients were treated with PTK/ZK daily (cohort 1; 750 mg od, cohort 2; 1250 mg od, cohort 3; 250 mg [morning] and 500 mg [evening], cohort 4; 500 mg [morning] and 750 mg [evening]) combined with cetuximab 250mg/m 2 weekly in cycles of 28 days in cohorts of 3 patients. Toxicity was evaluated conform CTCAE classification version 3.0. Pharmacokinetics and circulating endothelial (progenitor) (CE(P)) cell analysis by flow cytometry were performed. Response was assessed using RECIST criteria. Results: Safety and tolerability were evaluated in 16 out of 18 treated patients (median age 61, range 43–78) with advanced tumors of the colon (8), lung (1), chordoma (2), biliary tract (1), cervix (1), ovarian (1), breast (1) and pancreatic cancer (1). The most frequently reported adverse events (all CTCAE grades) were acne (87%), dry skin (81%), fatigue (69%), nausea (63%), ataxia/dizziness (50%), vomiting (50%), headache (38%) and diarrhea (31%). One dose limiting toxicity (DLT) occurred in cohort 3 (grade 3 transaminitis (AST)). The study was terminated after cohort 4 because the predefined maximum doses for vatalanib and cetuximab were attained. Preliminary PK analysis revealed no significant changes in PTK/ZK exposure upon coadministration with cetuximab. Biomarker analysis showed stabilized CE(P)Cs levels during treatment. 7 out of 14 patients evaluable for efficacy analysis (50%) showed SD for at least 2 months and 1 patient (colon cancer) a PR for 11.5 months. Conclusions: This study shows that the combination of PTK/ZK and cetuximab is well tolerated with only slightly overlapping toxicity profiles and has anti tumor activity. No MTD was defined; the recommended phase II dose is the predefined maximum combination dose: weekly cetuximab 250 mg/m2 combined with twice daily PTK/ZK 500/750 mg. No significant financial relationships to disclose.
A translational phase II trial of celecoxib plus interferon-alpha (IFN-α2b) in metastatic renal cell carcinoma (RCC) patients (pts) with 3+ COX-2 tumor immunostaining
Authors: A. Schwandt, J. A. Garcia, P. Elson, J. Wyckhouse, J. H. Finke, J. Ireland, P. Triozzi, M. Zhou, R. Dreicer, B. I. Rini
Journal: Journal of Clinical Oncology (2009)

5116 Background: Cyclooxygenase-2 (COX-2) has been correlated with RCC stage and grade, and overexpression can lead to dysregulation of dendritic cells (DC) and CD4+/CD25+/FOXP3+ regulatory T cells (Treg). A previous trial of celecoxib in combination with IFNα2b in RCC (Rini et al, Cancer. 2006) demonstrated an association between more intense COX-2 RCC tumor staining and clinical response. Methods: Pts with cytokine-naïve mRCC with at least 10% maximal COX-2 tumor staining received IFNα2b MU five times/week plus celecoxib 400 mg BID continuously. Baseline tumor tissue was stained for COX-2, CD4+ and CD8+ T cells, Treg and DC (s100 and CD208). Peripheral blood prostaglandin E2 (PGE2), DC and Treg number/function and intracellular T cell cytokine production were measured at baseline, at the end of cycles 2 and 4 and at end of treatment. Activation of DC was assessed by IL-12 and IL-10 mRNA and protein production by ELISA. The primary endpoint was objective response rate (ORR). Secondary endpoints were DC / Treg number and cytokine production changes with therapy. The trial tested a null hypothesis of ORR &lt;20% vs. alternative hypothesis of ORR &gt;40%; beta = 0.8 and alpha = 0.05 (n = 34). Immune parameters were analyzed using non-parametric methods. Results: Fourteen pts have been enrolled; 79% male, median age 62 (range, 43–74) and 64% ECOG performance status 0. All pts had prior nephrectomy and 36% had received prior tyrosine kinase inhibitors (TKI); MSKCC Risk Group was favorable 14%, intermediate 71%, and unfavorable 14%. The ORR was 21% and 69% of pts experienced tumor shrinkage. Median PFS is 4.4 months. Toxicity was as expected for IFN therapy. Baseline 3+ COX-2 staining was associated with elevated peripheral blood PGE2 levels (p = 0.02), reduced DC IL-12 expression (p = 0.04) and reduction in IFN gamma-producing CD3+CD4+ T-cells (p = 0.04) compared to a control group of RCC pts with &lt;10% 3+ COX-2 staining (n = 21). No significant changes in immunomodulatory cells were observed with therapy. Conclusions: COX-2 inhibition in combination with IFNα2b in maximal COX-2-expressing mRCC pts has clinical activity. COX-2 RCC tumor expression promotes an immunosuppressive phenotype. [Table: see text]
Sildenafil Potentiates the Therapeutic Efficacy of Docetaxel in Advanced Prostate Cancer by Stimulating NO-cGMP Signaling
Authors: Sakthivel Muniyan, Satyanarayana Rachagani, Seema Parte, Sushanta Halder, Parthasarathy Seshacharyulu, Prakash Kshirsagar, Jawed A. Siddiqui, Raghupathy Vengoji, Sanchita Rauth, Ridwan Islam, Kavita Mallya, Kaustubh Datta, Lei Xi, Anindita Das, Benjamin A. Teply, Rakesh C. Kukreja, Surinder K. Batra
Journal: Clinical Cancer Research (2020)

Docetaxel plays an indispensable role in the management of advanced prostate cancer. However, more than half of patients do not respond to docetaxel, and those good responders frequently experience significant cumulative toxicity, which limits its dose duration and intensity. Hence, a second agent that could increase the initial efficacy of docetaxel and maintain tolerability at biologically effective doses may improve outcomes for patients.We determined phosphodiesterase 5 (PDE5) expression levels in human and genetically engineered mouse (GEM) prostate tissues and tumor-derived cell lines. Furthermore, we investigated the therapeutic benefits and underlying mechanism of PDE5 inhibitor sildenafil in combination with docetaxel using in vitro, Pten conditional knockout (cKO), derived tumoroid and xenograft prostate cancer models.PDE5 expression was higher in both human and mouse prostate tumors and cancer cell lines compared with normal tissues/cells. In GEM prostate-derived cell lines, PDE5 expression increased from normal prostate (wild-type) epithelial cells to androgen-dependent and castrated prostate-derived cell lines. The addition of physiologically achievable concentrations of sildenafil enhanced docetaxel-induced prostate cancer cell growth inhibition and apoptosis in vitro, reduced murine 3D tumoroid growth, and in vivo tumorigenicity as compared with docetaxel alone. Furthermore, sildenafil enhanced docetaxel-induced NO and cGMP levels thereby augmenting antitumor activity.Our results demonstrate that sildenafil's addition could sensitize docetaxel chemotherapy in prostate cancer cells at much lesser concentration than needed for inducing cell death. Thus, the combinatorial treatment of sildenafil and docetaxel may improve anticancer efficacy and reduce chemotherapy-induced side-effects among patients with advanced prostate cancer.
Prevalence of SARS-CoV-2 Infection in Children Without Symptoms of Coronavirus Disease 2019
Authors: Ana Marija Sola, Abel P. David, Kristina W. Rosbe, Atsuko Baba, Lynn Ramirez-Avila, Dylan K. Chan
Journal: JAMA Pediatrics (2020)

macy.Stimulants were present in nearly all regimens, and antipsychotics became prominent in combinations after 2004.Discussion | Attention-deficit/hyperactivity disorder is the predominant diagnosis among youths who received psychotropic polypharmacy.The findings suggest an increase in concurrent use of antipsychotics with other psychotropics.Use of mood stabilizers decreased possibly as more youths received antipsychotics for mood disorders.Evidence of the efficacy and safety is needed to guide psychotropic polypharmacy practice.A study limitation is that the definition of psychotropic polypharmacy may have obscured medication switching.
Intra-articular saline injection is as effective as corticosteroids, platelet-rich plasma and hyaluronic acid for hip osteoarthritis pain: a systematic review and network meta-analysis of randomised controlled trials
Authors: Aaron Gazendam, Seper Ekhtiari, Anthony Bozzo, Mark Phillips, Mohit Bhandari
Journal: British Journal of Sports Medicine (2020)

Intra-articular (IA) injections represent a commonly used modality in the treatment of hip osteoarthritis (OA). Commonly used injections include corticosteroids (CCS), hyaluronic acid (HA) and platelet-rich plasma (PRP). A network meta-analysis allows for comparison among more than two treatment arms and uses both direct and indirect comparisons between interventions. The objective of this network meta-analysis is to compare the efficacy of the various IA injectable treatments in treating hip OA at up to 6 months of follow-up.This is a systematic review and network meta-analysis. Bayesian random-effects model was performed to assess the direct and indirect comparisons of all treatment options.PubMed, Embase, Cochrane Central Register of Controlled Trials, Scopus and Web of Science, from inception to October 2019.Randomised controlled trials assessing the efficacy of CCS, HA, PRP and placebo in the form of IA saline injection for patients with hip OA.Eleven randomised controlled trials comprising 1353 patients were included. For pain outcomes at both 2-4 and 6 months, no intervention significantly outperformed placebo IA injection. For functional outcomes at both 2-4 and 6 months, no intervention significantly outperformed placebo IA injection. Regarding change from baseline at 2-4 months and 6 months, pooled data demonstrated that all interventions (including placebo), with the exception of HA+PRP, led to a clinically important improvement in both pain, exceeding the minimal clinically important difference.Evidence suggests that IA hip saline injections performed as well as all other injectable options in the management of hip pain and functional outcomes.
Mass spectrometry profile as a predictor of overall survival benefit after treatment with epidermal growth factor receptor inhibitors in head and neck squamous cell carcinoma
Authors: C. H. Chung, E. H. Seeley, J. Grigorieva, W. G. Yarbrough, J. Gilbert, B. A. Murphy, A. Argiris, R. Caprioli, D. P. Carbone, E. E. Cohen
Journal: Journal of Clinical Oncology (2009)

6000 Background: Our previous study has shown that a matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) profile in serum or plasma can predict lung cancer patient survival after treatment with epidermal growth factor receptor inhibitors (EGFRI). We examined the ability of this same MALDI-MS profile in plasma or sera to predict for survival benefit of EGFRIs in patients with head and neck squamous cell carcinoma (HNSCC). Methods: Spectra were obtained in triplicate using MALDI-MS from 314 samples obtained from five HNSCC cohorts treated with 1) gefitinib (G, n = 100); 2) erlotinib and bevacizumab (E/B, n = 81); 3) cetuximab (C, n = 21); 4) surgery (S, n = 78); and 5) palliative chemotherapy (PC, n = 34). Each sample was classified into “good” or “poor” outcome groups and overall survival was examined using this MALDI-MS classifier (VeriStrat, Biodesix, Steamboat Springs, CO). Results: Successful classification could be achieved in 311/314 (98%) of the samples. In all EGFRI-treated cohorts, the classifier predicted survival benefit while the cohorts without EGFRI-treatment showed no survival difference by log-rank testing (G: p = 0.007, HR 0.41, 95%-CI 0.22–0.79; E/B: p = 0.02, HR 0.20, 95%-CI 0.05–0.78; C: p=0.06, HR 0.26, 95%-CI 0.06–1.06; and PC: p = 0.76, HR 0.88, 95%-CI 0.4–1.97), independent of performance status, age, gender and smoking history. Conclusions: This study suggests that the same predictive algorithm for MALDI-MS generated from patients with lung cancer treated with EGFRIs is also predictive of survival outcome in HNSCC patients treated with both TKIs and cetuximab, and may allow rational selection of patients most likely to benefit from an EGFRI monotherapy. [Table: see text]
Prevalence of Surface Contamination With SARS-CoV-2 in a Radiation Oncology Clinic
Authors: Imraan Jan, Kenneth Chen, Mutlay Sayan, Priyanka Uprety, Robert J. Laumbach, Ronald D. Ennis, Bruce G. Haffty
Journal: JAMA Oncology (2020)

This quality improvement study assesses surface contamination with SARS-CoV-2 in the radiation oncology department of a large COVID-19 referral center and discusses implications for routine cleaning and disinfecting practices.
Simultaneous triple stent-by-stent deployment following endobiliary radiofrequency ablation for malignant hilar biliary obstruction
Authors: Tadahisa Inoue, Rena Kitano, Mayu Ibusuki, Yuji Kobayashi, Kiyoaki Ito, Masashi Yoneda
Journal: Endoscopy (2020)

The simultaneous triple stent-by-stent (SBS) technique can prevent failure of the third stent insertion for trisectoral metal stenting in patients with malignant hilar biliary obstruction (MHBO) [1] [2] However, simultaneous insertion of three stent delivery systems is often challenging, especially for tight strictures. Endobiliary radiofrequency ablation (RFA), which can prolong stent patency in MHBO [3], renders the stricture and tumor degenerative [4], resulting in decreased tightness of the stricture. Here, we describe an initial case of simultaneous triple SBS deployment following endobiliary RFA for unresectable MHBO.
Quantitative assessment of HER2 status and correlation with efficacy for patients (pts) with metastatic breast cancer (MBC) in a phase II study of trastuzumab-DM1 (T-DM1)
Authors: I. E. Krop, H. A. Burris, H. Rugo, J. O'Shaughnessy, C. L. Vogel, L. Amler, A. Strauss, E. K. Wong, B. Klencke, J. Pippen
Journal: Journal of Clinical Oncology (2009)

1003 Background: The antibody-drug conjugate T-DM1 combines the biological activity of trastuzumab with targeted delivery of an anti-microtubule agent (DM1) to HER-2-expressing cancer cells. This analysis examines correlation of response to T-DM1 with HER-2 status, as assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), mRNA quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA) (HER-2 extracellular domain [ECD]), for pts enrolled in TDM4258g, a phase II study of T-DM1 in pts with MBC. Methods: TDM4258g is an open-label, single-arm study of T-DM1 administered at 3.6 mg/kg IV q3w. Pts had progressed on HER-2-directed therapy and received chemotherapy in the metastatic setting and were HER-2 + based on local testing. Archival tissue (paraffin block or &gt;7 unstained tumor slides) was collected for retrospective central laboratory testing. HER-2 DNA amplification was determined by FISH, and protein levels by IHC. qRT-PCR for HER-2 was performed on extracted RNA; baseline HER-2 ECD ELISA was performed on pt sera. HER-2 data for each pt were compared with pt's best response. Results: As of August 29, 2008, 112 pts had enrolled; 107 were efficacy-evaluable pts with median 4.4 mos follow-up. There were 42/107 (39.3%) partial responses (PR) (investigator assessment). Of 86 pts centrally tested, 64 (74.4%) were confirmed HER-2+ (FISH+ and/or IHC 3+), with 32/64 (50%) PR. Of 76 pts tested by both FISH and IHC, 15/76 (19.7%) were confirmed HER-2- (FISH- and IHC 2+/1/0), with 2/15 (13.3%) PR. In HER-2+ pts, response rates did not correlate with high versus low FISH+ counts, nor with HER-2 ECD levels. Among 39 HER-2+ (FISH+ and/or IHC3+) efficacy-evaluable pts with qRT-PCR data, there were 13/19 (68.4%) PR for pts with qRT-PCR above median levels, and 7/20 (35.0%) PR for pts with qRT-PCR below median. Conclusions: HER-2+ pts (by central retesting) had better responses to T-DM1 than HER-2- pts, although a small number of PR were observed in HER-2- pts. Assessment of HER-2 expression by qRT-PCR may identify pts more likely to respond to T-DM1 therapy. Updated data, including additional diagnostic markers, will be presented at the meeting. [Table: see text]