tbuckley/cabot-search huggingface dataset:
Expression of WAVE 1, 2 and 3 (CCN family) in human prostate cells
Authors: Herman Fernando, Howard Kynaston, Malcolm Mason, Wen Jiang
Journal: Cancer Research (2007)

1362  Introduction:   Invasive carcinoma cells acquire a migratory phenotype associated with an increased expression of several genes involved in cell motility (1). WASP(Wiskott-Aldrich Syndrome Protein), (N)-WASP and WAVE(WASP family verprolin-homologous protein)proteins are thought to play a role in signal dependent regulation of actin dynamics, which in turn is essential for a variety of cellular processes including the formation of membrane protrusions- the first step in cell motility. Evidence suggests that some members of the CCN family (for e.g. Cyr61, CTGF and Nov) stimulate mitosis, adhesion, apoptosis, growth arrest and migration of multiple cell types including prostate cancer. Other CCN members, namely WISPs also play a role in the invasiveness of prostate cancer cells (2). Not much data exists in literature about the expression of WAVE’s - also members of the CCN family, in prostate cancers. Here we report findings from a pilot study done to investigate the expression of WAVEs in prostate cancers.  Materials and Methods:   LNCaP, DU-145, PC-3, CaHPV, PZHPV, PNT1A and PNT2C2 were used in the study. Conventional RT-PCR was used to detect expression of the WAVE1-3 transcripts and β-actin and GAPDH were used as house keeping genes. Using immunohistochemical methods, a panel of prostate tissues which were earlier frozen-sectioned were stained for WAVE-1, -2 and -3 and later analysed for their expression using conventional RT-PCR.  Results:   Human prostate cancer cell lines showed a diverse pattern of expression of the three CCN members. WAVE-1 transcripts were found in most of the prostate cancer cell lines in both highly invasive and non-invasive cells. While PC-3 and DU145 cells showed a low level of WAVE-2 transcripts, non-invasive LN-CaP and CA-HPV showed good levels. Similarly, LNCaP, PNT1A and CA-HPV showed a strong positive signal to WAVE-3 expression and moderate expression in others. All three WAVEs were seen to be stained in normal human prostate epithelial cells, with WAVE-1 being the strongest and WAVE-3 the weakest. Interestingly, there was a visible reduction of WAVE-2 staining in tumour cells of the prostate tissues.  Conclusions:   We conclude from this preliminary study that WAVE’s have a differential expression pattern in human prostate cancer cell lines, which may have some link to the pattern of cell invasion and motility. Further studies are currently being undertaken in order to identify the molecular impact of WAVEs on the biological behaviour of prostate cancer cell lines.  References:  1. Hawizy A, Davies G, Mason MD, Kynaston H, Jiang WG. The role of WISPs in human prostate cancer. Presented at Prostate Cancer Symposium, ASCO, Feb. 2005, Orlando, Florida, US  2. Yamaguchi H et al. Cell Migration in tumors. Current opinion in Cell Biology 2005, 17:559-564
SAT0640 SHEAR-WAVE ELASTOGRAPHY OF SKIN STIFFNESS IN SYSTEMIC SCLEROSIS: A FIVE-YEAR FOLLOW-UP STUDY
Authors: Tânia Santiago, Margarida Coutinho, Maria Joao Salvador, P José Antonio, Da Silva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Measurement of skin involvement is essential for diagnosis and assessment of prognosis in systemic sclerosis (SSc). The mRSS is the gold standard measure of skin thickness. The mRSS has been criticised for being associated with high inter-observer variability and being too insensitive to detect relevant changes in skin thickness over time. Previously, our group demonstrated that shear-wave elastography (SWE) offers a potential for objective and quantitative assessment of skin involvement in SSc patients.<sup>1</sup> However, no studies have evaluated its sensitivity to change over-time. <h3>Objectives:</h3> To assess changes in skin stiffness in SSc patients using SWE over-time. <h3>Methods:</h3> This study included 19 SSc patients [89.5% females; age 57.5 years (10.3), 53% with limited form; disease duration 11.4 years (8.5)] at baseline and, 13 healthy controls [69.2% females; age 53.4 years (11.5). Skin stiffness was measured by SWE, using virtual touch image quantification, at the 17 sites corresponding to the mRSS, in each participant, at baseline and follow-up [a mean of 4.9 ((4.6-4.9) years later]. mRSS was performed at both time points. Differences between groups were analysed using the related-samples Wilcoxon Signed Rank test. Results are presented as median (interquartile range (IQR)). <h3>Results:</h3> In SSc patients, skin stiffness measured by SWE decreased in a strongly significantly way (p≤0.001), over time at all skin Rodnan sites, except the fingers (table 1). Interestingly, the same was observed in controls for all sites, except the leg. The effects of normal ageing correspond to 30 to 60% of the changes observed in SSc. Local Rodnan scores only decreased significantly at the forearms and fingers of SSc patients. The reduction of mRSS at the fingers did not correspond to improvements in SWV. Shear wave velocity (SWV) measurements correlated with mRSS both at baseline (rs:0.56; p=0.0001) and at follow-up (rs:0.74; p=0.0001). <h3>Conclusion:</h3> Although preliminary, this study provides the first evidence suggesting that 1. SWV of the skin is more sensitive to change over time than mRSS; 2. Skin stiffness reduces significantly over time in normal controls, and 3. Normal skin ageing may contribute to the overall decrease of SWV with time in SSc. Our results highlight the discriminant ability of SWV in detecting subtle skin changes not identified by mRSS. SWV may offer a significant improvement in the evaluation of skin stiffness and may provide relevant insights into the biology of healthy and scleroderma skin. Studies including a larger number of patients in different phases of skin involvement and data on normal reference values of these ultrasound measurements are needed to reach a definitive validation. <h3>References</h3> [1] - Santiago T, et al; Clin Exp Rheumatol. 2016;100:137-141. <h3>Disclosure of Interests:</h3> None declared
Epidermal growth factor receptor inhibitors as second-line treatment in advanced non-small cell lung cancer: A meta-analysis
Authors: M. C. Cruz, M. Tan
Journal: Journal of Clinical Oncology (2009)

7597 Background: Overall survival in lung cancer remains poor despite availability of chemotherapy, which is limited by its toxicity and drug resistance. Advancement in research resulted to the development of targeted therapies, specifically epidermal growth factor receptor (EGFR) inhibitors. Results of clinical studies on survival benefits of EGFR inhibitors were conflicting although beneficial improvements in the quality of life and adverse effects were consistently demonstrated. The aim of our study is to determine the overall survival benefit of EGFR inhibitors alone or in combination with chemotherapy in second-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: We did a meta-analysis of all randomized controlled trials involving patients with advanced NSCLC who failed at least one prior chemotherapy and were given EGFR inhibitor alone or in combination with chemotherapy compared to placebo or chemotherapy, with overall survival as an outcome. Pre-planned subgroup analysis was done on studies comparing EGFR to placebo and chemotherapy.Results: Five of the six trials included were analyzed for overall survival involving 4482 patients. Treatment with EGFR tyrosine kinase inhibitor (TKI) showed a trend towards significant survival benefit (RR=0.96, 95% CI 0.93–1.00, p=0.04) compared to placebo or chemotherapy. Preplanned subgroup analysis demonstrated significant survival benefit with EGFR-TKI versus placebo (RR=0.92, 95% CI 0.86–0.97, p=0.003) but comparable efficacy with chemotherapy (RR=1, 95% CI 0.96–1.06, p=0.84).Conclusions: Second-line treatment with EGFR-TKI demonstrated significant survival benefit versus placebo and comparable survival effect to chemotherapy. Further research should be done to identify patients’ characteristics associated with good treatment response. [Table: see text]
The DNA Repair Pathway as a Target for Novel Drugs in Gynecologic Cancers
Authors: Stephanie Lheureux, Mansoor Mirza, Robert Coleman
Journal: Journal of Clinical Oncology (2019)

Article Tools REVIEW ARTICLES Gynecologic Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.19.00347 Journal of Clinical Oncology - published online before print August 12, 2019 PMID: 31403862 The DNA Repair Pathway as a Target for Novel Drugs in Gynecologic Cancers Stephanie Lheureux, MD, PhD1xStephanie LheureuxSearch for articles by this author; Mansoor Mirza, MD2xMansoor MirzaSearch for articles by this author; and Robert Coleman, MD3xRobert ColemanSearch for articles by this author Show More 1Princess Margaret Cancer Centre, Toronto, Ontario, Canada2Copenhagen University Hospital, Copenhagen, Denmark3The University of Texas MD Anderson Cancer Center, Houston, TX https://doi.org/10.1200/JCO.19.00347 First Page Full Text PDF Figures and Tables © 2019 by American Society of Clinical Oncology
Disordered Antigens and Epitope Overlap Between Anti–Citrullinated Protein Antibodies and Rheumatoid Factor in <scp>Rheumatoid Arthritis</scp>
Authors: Zihao Zheng, Aisha M. Mergaert, Lauren M. Fahmy, Mandar Bawadekar, Caitlyn L. Holmes, Irene M. Ong, Alan J. Bridges, Michael A. Newton, Miriam A. Shelef
Journal: Arthritis & Rheumatology (2019)

Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are commonly present in rheumatoid arthritis (RA) without a clear rationale for their coexistence. Moreover, autoantibodies develop against proteins with different posttranslational modifications and native proteins without obvious unifying characteristics of the antigens. We undertook this study to broadly evaluate autoantibody binding in seronegative and seropositive RA to identify novel features of reactivity.An array was created using a total of 172,828 native peptides, citrulline-containing peptides, and homocitrulline-containing peptides derived primarily from proteins citrullinated in the rheumatoid joint. IgG and IgM binding to peptides were compared between cyclic citrullinated peptide (CCP)-positive RF+, CCP+RF-, CCP-RF+, and CCP-RF- serum from RA patients (n = 48) and controls (n = 12). IgG-bound and endogenously citrullinated peptides were analyzed for amino acid patterns and predictors of intrinsic disorder, i.e., unstable 3-dimensional structure. Binding to IgG-derived peptides was specifically evaluated. Enzyme-linked immunosorbent assay confirmed key results.Broadly, CCP+RF+ patients had high citrulline-specific IgG binding to array peptides and CCP+RF- and CCP-RF+ patients had modest citrulline-specific IgG binding (median Z scores 3.02, 1.42, and 0.75, respectively; P < 0.0001). All RA groups had low homocitrulline-specific binding. CCP+RF+ patients had moderate IgG binding to native peptides (median Z score 2.38; P < 0.0001). The highest IgG binding was to citrulline-containing peptides, irrespective of protein identity, especially if citrulline was adjacent to glycine or serine, motifs also seen in endogenous citrullination in the rheumatoid joint. Highly bound peptides had multiple features predictive of disorder. IgG from CCP+RF+ patients targeted citrulline-containing IgG-derived peptides.Disordered antigens, which are frequently citrullinated, and common epitopes for ACPAs and RF are potentially unifying features for RA autoantibodies.
Dual-Targeted Gold Nanoprism for Recognition of Early Apoptosis, Dual-Model Imaging and Precise Cancer Photothermal Therapy
Authors: Weiwei Zhang, Xiaoyuan Ding, Hao Cheng, Chenyang Yin, Jing Yan, Zhipeng Mou, Weiyun Wang, Danxi Cui, Cundong Fan, Dongdong Sun
Journal: Theranostics (2019)

Photothermal therapy as novel strategy to convert near-infrared (NIR) light into heat for treatment cancers has attracted great attention and been widely studied. However, side effects and low efficiency remain the main challenge of precise cancer photothermal therapy. Methods: In this study, we have successfully fabricated and characterized the dual-targeted gold nanoprisms, whereby bare gold nanoprisms (Au NPR) were conjugated to a phenanthroline derivatives-functionalized tetraphenylethene (TPE) and further stabilized with target peptide aptamers via Au-S bonds (Au-Apt-TPE). Then, the remaining nitrogen atoms of the Au-Apt-TPE could effectively chelate with Zn2+ ions (Au-Apt-TPE@Zn) for monitoring early stage apoptotic cells. Results: The as-synthesized Au-Apt-TPE@Zn exhibited good monodispersity, size stability and consistent spectral characteristics. TPE synthesized here showed aggregation-induced emission (AIE) characteristics, and zinc conjunction (TPE@Zn) endowed Au-Apt-TPE@Zn with the cell membrane-targeted ability to selectively recognize the membranes of early stage apoptotic cells but not respond to healthy cells, which provided valuable diagnosis information on therapeutic efficacy. Au-Apt-TPE@Zn achieved specifically nuclear-targeted ability by surface decoration of AS1411 DNA aptamer. Au-Apt-TPE@Zn under NIR irradiation showed effective photothermal therapy against SGC-7901 human gastric carcinoma cells growth in vitro by inducing apoptosis through triggering reactive oxygen species (ROS) overproduction and regulating multiple signal crosstalk. In vivo studies revealed that Au-Apt-TPE@Zn under NIR irradiation showed deep penetration and dual-model imaging application (cancer-targeted fluorescence imaging and light-up photoacoustic imaging). Au-Apt-TPE@Zn under NIR irradiation also displayed strong photothermal therapy against gastric carcinoma xenograft growth in vivo by induction of apoptosis. Importantly, analysis of histopathology, hematotoxicity and immunocytotoxicity indicated that Au-Apt-TPE@Zn had less side effect and high biocompatibility. Conclusions: Our findings validated the design of using Au nanoprism with AIE materials and dual-targeted decoration could be an effective strategy in recognition of early apoptosis, dual-model imaging and precise cancer photothermal therapy.
Maintenance therapy with biweekly cetuximab (C) in the first-line treatment of metastatic colorectal cancer (mCRC): The NORDIC 7.5 study (NCT00660582), by the Nordic Colorectal Cancer Biomodulation Group.
Authors: Per Pfeiffer, Halfdan Sorbye, Camilla Qvortrup, Mia Karlberg, Gisela Naucler, Christian Kersten, Kirsten Vistisen, Birgitta Lindh, Bengt Glimelius
Journal: Journal of Clinical Oncology (2012)

3538 Background: NORDIC 7.5 is a multi-center phase II trial of Nordic FLOX plus biweekly C followed by maintenance C in first-line treatment of mCRC, KRASwild-type (KRASwt). The aim was to complement the data of the NORDIC VII trial, arm C (Tveit et al, ASCO GI 2011). Specifically, the goal was to substantiate efficacy and safety of biweekly C as maintenance therapy and to assess time to failure of strategy (TFS) as an end-point in maintenance therapy studies. Methods: Patients had KRASwt, measurable, non-resectable mCRC; no prior chemotherapy for metastases; WHO PS 0-2 and good organ function. Patients received 8 courses of FLOX (bolus 5FU/folinic acid days 1 + 2 with oxaliplatin day 1 every 2 weeks) plus biweekly C (500 mg/m 2 every 2 weeks) for 16 weeks followed by biweekly C as maintenance therapy until progression (PD). After at least 2 months of maintenance therapy, patients restarted FLOX plus biweekly C at the time of RECIST PD, and continued until a second RECIST PD. The primary endpoint was response rate (RR). Eighty-six patients were planned to confirm a response rate of 60%. While awaiting the results of Nordic VII, we amended the protocol to include 150 patients. Secondary endpoints included PFS, OS, resection rate, and safety. TFS was an explorative endpoint. Results: From July 2008 to September 2010, 152 KRASwt patients were included in 11 Nordic centers. Results were updated December 2011. Median age 64 years; 94% PS 0-1. RR 62%, median PFS 8.0 months, median OS 23.2 months, median TFS 11.9 months. Ten patients (15%) had R0-resection of metastasis. FLOX + C was re-introduced in 47 of 85 patients (55%) who were candidates for re-treatment and was started median 18 days after PD. Median duration of re-introduction was 5 months (1-29), 9 patients (20%) had response. Elevated baseline platelets and neutrofiles were associated with poor OS. The most common grade 3/4 non-hematologic AEs in were diarrea (9%), skin rash (9%), infection without neutropenia (7%), and fatigue (7%) Conclusions: Maintenance therapy with biweekly cetuximab is an encouraging strategy with efficacy and toxicity comparable to weekly cetuximab.
Management of Rare Ovarian Cancer Histologies
Authors: David M. Gershenson, Aikou Okamoto, Isabelle Ray-Coquard
Journal: Journal of Clinical Oncology (2019)

Article Tools REVIEW ARTICLES Gynecologic Cancer Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.18.02419 Journal of Clinical Oncology - published online before print August 12, 2019 PMID: 31403866 Management of Rare Ovarian Cancer Histologies David M. Gershenson, MD1xDavid M. GershensonSearch for articles by this author; Aikou Okamoto, MD, PhD2xAikou OkamotoSearch for articles by this author; and Isabelle Ray-Coquard, MD, PhD3xIsabelle Ray-CoquardSearch for articles by this author Show More 1The University of Texas MD Anderson Cancer Center, Houston, TX2The Jikei University School of Medicine, Tokyo, Japan3Centre Leon Bèrard, Université Claude Bernard Lyon, Groupe d'Investigateurs Nationaux pour l'Étude des Cancers de l'Ovaire (GINECO), Lyon, France https://doi.org/10.1200/JCO.18.02419 First Page Full Text PDF Figures and Tables © 2019 by American Society of Clinical Oncology
Author Correction: Neural computations of threat in the aftermath of combat trauma
Authors: Philipp Homan, Ifat Levy, Eric Feltham, Charles Gordon, Jingchu Hu, Jian Li, Robert H. Pietrzak, Steven Southwick, John H. Krystal, Ilan Harpaz-Rotem, Daniela Schiller
Journal: Nature Neuroscience (2019)
But how does it develop? Adopting a sociocultural lens to the development of intergroup bias among children
Authors: Niamh McLoughlin, Kathleen H. Corriveau
Journal: Behavioral and Brain Sciences (2019)

Abstract We argue that adopting a sociocultural lens to the origins of intergroup bias is important for understanding the nature of attacking and defending behavior at a group level. We specifically propose that the potential divergence in the development of in-group affiliation and out-group derogation supports De Dreu and Gross's framework but does indicate that more emphasis on early sociocultural input is required.
Immunogenicity of pembrolizumab in patients with advanced tumors
Authors: Marianne J. H. van Vugt, Julie A. Stone, “Rik” H. J. M. M. De Greef, Ellen S. Snyder, Leslie Lipka, David C. Turner, Anne Chain, Mallika Lala, Mengyao Li, Seth H. Robey, Anna G. Kondic, Dinesh De Alwis, Kapil Mayawala, Lokesh Jain, Tomoko Freshwater
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Pembrolizumab is a potent, humanized, monoclonal anti–programmed death 1 antibody that has demonstrated effective antitumor activity and acceptable safety in multiple tumor types. Therapeutic biologics can result in the development of antidrug antibodies (ADAs), which may alter drug clearance and neutralize target binding, potentially reducing drug efficacy; such immunogenicity may also result in infusion reactions, anaphylaxis, and immune complex disorders. Pembrolizumab immunogenicity and its impact on exposure, safety, and efficacy was assessed in this study. <h3>Patients and methods</h3> Pembrolizumab immunogenicity was assessed in 3655 patients with advanced or metastatic cancer treated in 12 clinical studies. Patients with melanoma, non–small cell lung cancer, head and neck squamous cell carcinoma, colorectal cancer, urothelial cancer, and Hodgkin lymphoma were treated with pembrolizumab at 2 mg/kg every 3 weeks, 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 200 mg every 3 weeks. An additional study involving 496 patients with stage III melanoma treated with 200 mg adjuvant pembrolizumab every 3 weeks after complete resection was analyzed separately. <h3>Results</h3> Of 3655 patients, 2000 were evaluable for immunogenicity analysis, 36 (1.8%) were treatment-emergent (TE) ADA-positive; 9 (0.5%) of these TE-positive patients had antibodies with neutralizing capacity. The presence of pembrolizumab-specific ADAs did not impact pembrolizumab exposure, nor did pembrolizumab immunogenicity affect the incidence of drug-related adverse events (AEs) or infusion-related reactions. There was no clear relationship between the presence of pembrolizumab-specific ADAs and changes in tumor size across treatment regimens. Of the 496 patients treated with pembrolizumab as adjuvant therapy, 495 were evaluable, 17 (3.4%) were TE ADA–positive; none had neutralizing antibodies. <h3>Conclusions</h3> The incidence of TE (neutralizing positive) ADAs against pembrolizumab was low in patients with advanced tumors. Furthermore, immunogenicity did not appear to have any clinically relevant effects on the exposure, safety, or efficacy of pembrolizumab. <h3>Trial registration</h3> ClinicalTrials.gov, NCT01295827 (February 15, 2011), NCT01704287 (October 11, 2012), NCT01866319 (May 31, 2013), NCT01905657 (July 23, 2013), NCT02142738 (May 20, 2014), NCT01848834 (May 8, 2013), NCT02255097 (October 2, 2014), NCT02460198 (June 2, 2015), NCT01953692 (October 1, 2013), NCT02453594 (May 25, 2015), NCT02256436 (October 3, 2014), NCT02335424 (January 9, 2015), NCT02362594 (February 13, 2015).
Effect of berubicin, the 4'-o-benzylated doxorubicin analog, on growth inhibition and apoptosis in multiple myeloma.
Authors: Michael Wang, Luhong Sun, Izabela Fokt, Liang Zhang, Arumugam Jayakumar, Waldemar Priebe
Journal: Journal of Clinical Oncology (2012)

e18557 Background: Doxorubicin (DOX), an anthracycline, topoisomerase II inhibitor, is routinely used for hematologic malignancies including multiple myeloma (MM); however, its efficacy is limited by drug resistance and cardiotoxcity. To overcome these limitations, we designed, synthesized and tested Berubicin (BRN). BRN has been evaluated in clinical trials in neuroblastoma multiforme. It is a representative of a novel class of mechanistically altered anthracycline analogs. The data obtained from this study will serve as the basis for the rapid translation of BRN from the bench to the clinic in a phase I clinical trial for patients with MM at MD Anderson Cancer Center. Methods: We investigated the effects of BRN, DOX and Bortezomib (BTZ) in 3 human MM cell lines, MM1S, ARP-1, U266, and freshly isolated primary samples from patients with MM. MM cells were treated with BRN, DOX, and BTZ. The effects of these compounds on cell proliferation, apoptosis, and the cell cycle were analyzed using MTS assay and flow cytometry analysis. Results: BRN potently inhibited the growth of the established MM cell lines, as well as the freshly isolated primary MM cells in a dose-dependent manner. It showed growth inhibition at IC50 of 5.99 nM (U266), 5.21 nM (MM1S) and 3.99 nM (ARP-1), and was more potent than doxorubicin (IC50 14.63 nM, 7.24 nM and 11.06 nM) and bortezomib (IC50 304.9 nM, 15.47 nM and 53.19 nM). In contrast, BRN did not affect the proliferation of patient-derived normal bone marrow cells (CD138 - cells) at the concentrations that were lethal to MM cells. Conclusions: Berubicin not only induced apoptosis in 3 cell lines in dose-dependent manners but also induced G2/M cell cycle arrest in 3 cell lines. In conclusion, BRN was effective against MM cells in vitro and will be applied to our planned clinical trial.