tbuckley/cabot-search huggingface dataset:
Finnish new variant of Chlamydia trachomatis escaping detection in the Aptima Combo 2 assay also present in Örebro County, Sweden, May 2019
Authors: Magnus Unemo, Marit Hansen, Ronza Hadad, Ylva Lindroth, Hans Fredlund, Mirja Puolakkainen, Martin Sundqvist
Journal: Eurosurveillance (2019)

We identified the first two cases of the Finnish new variant of Chlamydia trachomatis (F-nvCT) beyond Finland in two clinical urogenital specimens in Örebro County, Sweden. These Aptima Combo 2 assay-negative specimens were Aptima Chlamydia trachomatis (CT) assay positive and had the characteristic C1515T mutation in the 23S rRNA gene. From 22 March to 31 May 2019, 1.3% (2/158) of the CT-positive cases in Örebro County were missed because of the F-nvCT. International awareness, investigations and actions are essential.
Outcomes of patients with t(11;14) multiple myeloma: An International Myeloma Working Group (IMWG) multicenter study.
Authors: Brian G. Durie, Hartmut Goldschmidt, Maria-Victoria Mateos, Veronica Gonzalez, Juan Du, Kihyun Kim, Giampaolo Merlini, Silvia Mangiacavalli, Chang Ki Min, Meletios A. Dimopoulos, Efstathios Kastritis, Heinz Ludwig, Graca Esteves, Hiroshi Handa, Fernando Escalante, Carlos Fernández de Larrea Rodríguez, Michel Delforge, Chris Cameron, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2019)

8015 Background: Multiple myeloma (MM) is a heterogeneous disease with varying survival outcomes depending on the presence of certain genetic abnormalities. Common abnormalities include trisomies, translocations involving chromosome 14, and amplifications or deletions of chromosomes 1, 13, and 17. t(11;14), occurring in approx. 15% of patients (pts) with MM, is considered a standard risk abnormality, but recent data suggest that the prognosis may be inferior to what had been expected. This is of particular relevance as new therapeutic options such as the BCL-2 inhibitor venetoclax has been shown to be effective in t(11;14) pts. Methods: This was a multicenter study designed and conducted by the IMWG, to identify the outcomes of pts with t(11;14) using a retrospective cohort of pts. Pts with MM diagnosed between 2005 and 2015 with t(11;14) identified on FISH performed within six months (mos) of diagnosis, and with treatment details available and if alive, a minimum of 12 mos of follow up, were enrolled. Results: The current analysis includes 848 pts with a median age of 64.4 years; 60.0% are male. The median follow-up from diagnosis for the entire cohort was 45.7 mos; 84.7% of the pts were alive at the last follow up. ISS stage distribution included: Stage 1 (35.3%), Stage II (38.9%) and stage III (25.8%). The distribution of FISH abnormalities included: del 13q (14.5%), 1q amp (12.1%), del 17p or monosomy 17 (6.1%). Pts received initial therapy with different regimens: IMiD-24.3%, PI-41.0%, both-20.8% and 13.8% had no novel agent. The drug classes by line of therapy are shown in table. An early stem cell transplant (SCT) was used in 40.8% of pts. The median time to next treatment (TTNT) after initial treatment was 15.0 (95% CI: 12.2 to 17.7) mos. The median overall survival from diagnosis for the entire cohort was 82.5 (95% CI: 73.5 to 95.8) mos. Conclusions: This is the first study to examine the outcomes of a large group of myeloma pts with t(11;14) abnormality. Pts receiving a combination if a PI and an IMiD appear to have the best survival outcomes and thse receiving an early SCT appear to have excellent survival with median OS approaching 10 years. Additional pts are being accrued to this study and additional analysis examining the variables affecting response duration and survival will be presented. [Table: see text]
Abstract 12488: Analysis of the Usefulness of Esophageal Temperature Monitoring for the Prevention of Esophageal Injury After Catheter Ablation of Atrial Fibrillation: Its Relation to the Distance Between the Esophagus and Left Atrium
Authors: Miwa Ito, Hiroshige Yamabe, Hisanori Kanazawa, Shozo Kaneko, Yusuke Kanemaru, Takuya Kiyama, Kenichi Tsujita
Journal: Circulation (2018)

Background: It has been demonstrated that the short distance between the esophagus and the posterior left atrium (LA) is closely associated with the occurrence of esophageal injury (EI) after cathe...
Abstract 519: EVOEXS21546 is a novel non-brain penetrant A2AR inhibitor for cancer immunotherapy with accelerated drug development
Authors: Pierre Fons, Andy Bell, Michael Esquerre, Stephanie Versluys, Florie Bertrand, Iva Hopkins-Navratilova, Sean Robinson, Virgile Visentin, Adrian Schreyer, Richard Cox, Emilie Mirey, Emilie Pelissier, Celia bergeaud, Simone Culurgioni, Jeremy Besnard, Andrew Payne, Jerome Menegotto, Frederic Machet, Celine Poussereau-Pomie, Eric Cogo, Michael Paillasse, Federica Ferigo, Sabrina Pagliarusco, Joanna Lisztwan, Mark Whittaker, Craig Johnstone, Andrew Hopkins
Journal: Cancer Research (2019)

Abstract Evotec and Exscientia are collaborating to develop an innovative drug discovery platform for accelerating small molecule development in Immuno-Oncology. The primary focus is to target the immunosuppressive adenosine pathway. We have firstly sought to generate a novel and selective, non-brain penetrant A2AR antagonist. EVOEX21546 has been selected as our lead candidate with in vitro potency on primary human CD3+ T-lymphocytes for inducing the recovery of IL-2 production after CADO-mediated inhibition of T-cell activation. In addition, we have demonstrated the compound’s effect on other key biological features of T-cell activation including IFN-gamma production and T-cell proliferation. ADME/DMPK data show that EVOEX21546 has a favourable pharmacological profile consistent with its evaluation in syngeneic tumour models. Furthermore, we are pursuing efforts to understand the Mechanism-of-Action of EVOEXS21546 in order to identify the most relevant biomarker of activity for clinical translation. Finally, from the perspective to accelerate the IND submission, EVOEXS21546 entered an INDiGO campaign, an integrated and rapid process to reach IND complemented by high-end integrated CMC. These results, generated in the frame of the A2AR inhibitor pathway, have paved the way to an optimized process for identifying, improving and accelerating the path from drug discovery to the entering into the clinic for Immuno-Oncology drugs. Citation Format: Pierre Fons, Andy Bell, Michael Esquerre, Stephanie Versluys, Florie Bertrand, Iva Hopkins-Navratilova, Sean Robinson, Virgile Visentin, Adrian Schreyer, Richard Cox, Emilie Mirey, Emilie Pelissier, Celia bergeaud, Simone Culurgioni, Jeremy Besnard, Andrew Payne, Jerome Menegotto, Frederic Machet, Celine Poussereau-Pomie, Eric Cogo, Michael Paillasse, Federica Ferigo, Sabrina Pagliarusco, Joanna Lisztwan, Mark Whittaker, Craig Johnstone, Andrew Hopkins. EVOEXS21546 is a novel non-brain penetrant A2AR inhibitor for cancer immunotherapy with accelerated drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 519.
Abstract 2924: Evaluation of the pan-FGFR inhibitor AZD4547 with radiation in non-small cell lung cancer
Authors: Margot Miller, Michael Fisher, Gopika Senthilkumar, Saakshi Kaushik, Lindsey Able, Sean Brennan, Gopal Iyer, Randall Kimple, Andrew M. Baschnagel
Journal: Cancer Research (2019)

Abstract Objective: The fibroblast growth factor receptors (FGFR) are commonly altered in non-small cell lung cancer (NSCLC), including high level of amplification of FGFR1 in lung squamous cell carcinoma. FGFR signaling may play a role in the response to radiation. We investigated the radiosensitizing effects of the selective tyrosine kinase inhibitor AZD4547 in a NSCLC model using cell lines and tumor xenografts. Methods: A panel of six NSCLC cell lines were screened for FGFR1/2 DNA amplification, RNA expression, and protein expression. All cells were assessed for in vitro response to AZD4547. Immunoblots were used to examine the effect of AZD4547 on downstream signaling proteins. Apoptosis was measured by Annexin V staining and autophagy with acridine orange assay. Radiation clonogenic survival assays and xenograft growth delays experiments were performed to investigate radiosensitization. In vivo mechanistic studies were conducted using immunohistochemistry. Results: Cell lines demonstrated varying degree of FGFR1/2 RNA and protein expression. In sensitive cell lines, AZD4547 inhibited p-MAPK in a time dependent manner. In vitro clonogenic survival assays showed robust radiosensitivity with AZD4547 in three out of six NSCLC cell lines. All three cell lines overexpressed FGFR1 and two of the cells had high FGFR1 copy number. There was no radiosensitization seen in an immortalized normal human bronchial epithelial cell line. A significant increase in autophagy and apoptosis was observed with combined radiation and AZD4547. Significant tumor growth delay was observed with the administration of radiation and AZD4547 compared to radiation or drug alone in two NSCLC xenograft tumor models. IHC analysis revealed modulation of FGFR-downstream signaling (p-Erk and p-S6) and proliferative (Ki67) and apoptotic markers (Cleaved Caspace 3). Conclusion: These findings suggest that AZD4547 can augment the response of radiation in NSCLC model systems. FGFR1 and FGFR2 expression may be a potential targets for radiosensitization in NSCLC. Additional studies are underway to understand the mechanism of radiosensitization. Citation Format: Margot Miller, Michael Fisher, Gopika Senthilkumar, Saakshi Kaushik, Lindsey Able, Sean Brennan, Gopal Iyer, Randall Kimple, Andrew M. Baschnagel. Evaluation of the pan-FGFR inhibitor AZD4547 with radiation in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2924.
Abstract 15585: Disability-Free Survival After Coronary Artery Bypass Grafting in Patients With Heart Failure and Preserved versus Reduced Ejection Fraction
Authors: Louise Y Sun, Marc Ruel, Peter P Liu, Anan Bader Eddeen, Jack V Tu
Journal: Circulation (2017)

Introduction: We and others have previously demonstrated the importance of heart failure (HF) in the long-term survival of patients undergoing coronary artery bypass grafting (CABG). However, littl...
Abstract 2996: Systemic depletion of L-methionine with an engineered human enzyme for the treatment of melanoma
Authors: Carly S. Wilder, Achinto Saha, George Georgiou, Everett Stone, John DiGiovanni
Journal: Cancer Research (2019)

Abstract Metastatic melanoma is an aggressive form of cancer responsible for the majority of skin cancer related deaths. While treatment for metastatic melanoma has improved in recent years with the introduction of targeted therapies and immunotherapies, the five-year survival rate for stage IV melanoma remains only 15-20%. To address the need for alternative options for melanoma treatment, we have begun exploring use of an engineered human enzyme called methionine-gamma-lyase (hMGL). Many cancers, including melanoma, have a high requirement for methionine in comparison with non-cancerous cells. The hMGL enzyme works to exploit this difference by degrading extracellular L-methionine resulting in cancer cell starvation. The hypothesis tested in this research is that the systemic depletion of L-methionine using hMGL will provide significant benefits for melanoma treatment alone or in combination with other therapeutic agents. Treatment of several melanoma cell lines (A375, Hs294T, Skmel28, and B16F10) with various concentrations of hMGL demonstrated that L-methionine depletion reduced survival and led to a G2 cell cycle arrest. To investigate the mechanism of action, analyses of melanoma cells treated with hMGL have shown that signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation is significantly reduced. Additionally, hMGL treatment leads to activation of the uncharged tRNA amino acid sensing pathway as shown by an increase in p-eIF2α and Sestrin 2 and an increase in autophagy shown by a decrease in p-ULKSer757 and an increase in cleaved LC3B. Because L-methionine depletion affects levels of glutathione through reduction of cysteine synthesis, preliminary experiments were conducted to evaluate hMGL treatment combined with a thioredoxin reductase inhibitor. This combination, targeting two different intracellular antioxidant pathways, resulted in synergistic inhibition of survival in multiple melanoma cell lines. The current data support the hypothesis that L-methionine depletion using hMGL may have therapeutic efficacy either alone or in combinations for melanoma treatment. Research funded by CPRIT grant RP180590. Citation Format: Carly S. Wilder, Achinto Saha, George Georgiou, Everett Stone, John DiGiovanni. Systemic depletion of L-methionine with an engineered human enzyme for the treatment of melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2996.
Phase II trial of bevacizumab (B) and oral satraplatin (S) and prednisone in docetaxel pretreated metastatic castrate resistant prostate cancer (CRPC)
Authors: U. N. Vaishampayan, L. K. Heilbrun, E. I. Heath, D. W. Smith, B. Dickow, K. Baranowski, I. Powell, J. Fontana
Journal: Journal of Clinical Oncology (2009)

e16028 Background: In metastatic CRPC, second line therapy after docetaxel, remains a currently unmet need. Based on the efficacy and tolerability of S and B in prostate cancer, and the clinical synergy noted between chemotherapy and B, a phase II trial of the combination was conducted. Methods: Metastatic CRPC patients, with prior docetaxel based chemotherapy were eligible to receive S 80 mg/m2 orally for days 1–5, and B 10 mg/kg on day 1, and 15mg/kg on day 15 of each 35 day cycle. Prednisone was administered at a dose of 5 mg twice daily. Response was assessed every 2 cycles. Toxicity was assessed weekly during cycle 1 and on days 1 and 15 of each subsequent cycle. Primary endpoint was time to progression defined as a skeletal event, new areas of metastases on bone scans or per RECIST criteria for measurable disease. Results: 19 of 28 patients have been enrolled to date; 7 African American and 12 Caucasian,, with median age of 68.5 years and median pretherapy PSA of 137.8 ng/mL (range 16.8–994 ng/mL). 7 (44%) had bone pain, Gleason score of 7 and ≥ 8 in 7 and 12 patients respectively. Measurable disease progression was noted in 5 patients, bone scan progression in 6 patients, progression of both in 3 patients, and PSA only progression in 5 patients. 76 cycles have been administered; 7 patients continued on therapy beyond 6 cycles. The only grade 4 toxicity noted was pulmonary embolism in 2 patients, after 2 and 6 cycles of therapy. Grade 3 neutropenia, gastrointestinal toxicity, and electrolyte abnormalities were noted in 1 patient each. There were no treatment related deaths. 16/19 patients are response evaluable. 7 patients had a PSA decline of which 4 patients had a ≥30% PSA decline. 3 of 6 patients had a measurable disease response. 11 of 16 patients have progressed to date after median of 6 cycles of therapy. Time to progression and survival data will be reported. Conclusions: The combination was well tolerated, and revealed preliminary evidence of clinical efficacy in docetaxel pretreated metastatic CRPC. [Table: see text]
Abstract 18237: Relationship of Biomarkers: Clinical Depression or Heart Failure?
Authors: Teresita Corvera-Tindel, Lynn Doering
Journal: Circulation (2016)

Introduction: While brain natriuretic peptide (BNP) is linked with heart failure (HF) diagnosis, its role and that of pro-inflammatory cytokines i.e. tumor necrosis factor-alpha (TNF-α) and interle...
Is there any affordable and reliable score in local gastric cancer?
Authors: A. Cousillas Castiñeiras, E. Gallardo Martin, A. Fernández Montes, M. Covela Rúa, M. Carmona Campos, M. Salgado Fernandez, M. Pellón Augusto, Y. Vidal Insua, P. Gonzalez Villarroel, N. Martínez-Lago, J. De la Cámara Gómez, S. Candamio Folgar, E. Brozos Vázquez, M. Jorge Fernandez, F. Vázquez Rivera, J. Méndez Méndez, G. Quintero Aldana, M. Constenla
Journal: Annals of Oncology (2019)
GPs attract disproportionately large number of complaints
Authors: Helen Jaques
Journal: BMJ (2011)

GPs were the subject of more than half the complaints to the General Medical Council in 2010, despite representing only a quarter of registered doctors in the United Kingdom, new data from the regulator show.

GPs were also most likely to have their complaint reach a fitness to practise panel: 37% of doctors who appeared before a panel in 2010 were GPs.

However, nearly half (45%) of complaints against GPs were closed immediately on the basis that the alleged concerns would never raise a question about fitness to practise, as were around 50% of complaints against all doctors. 

Patients are more likely to see their …
Abstract 1978: Sarcoma invasion associated with heparan sulfate degradation
Authors: Donghong Ju, Leonard Lipovich, Mary A. Kosir
Journal: Cancer Research (2019)

Abstract INTRODUCTION: Sarcomas are locally aggressive, angiogenic and spread hematogenously. The purpose of this study was to quantify the effect of heparan sulfate degrading activity on invasion of K-ras-transformed sarcoma cells. METHODS: Heparan degrading enzyme assays were performed in triplicate on lysate from Balb/c 3T3 (fibroblasts) and K234 cells (K-ras-transformed 3T3) cells (sarcoma) using an enzyme assay kit (cat# MK412;Takara). Invasion assays were performed using Corning Matrigel Invasion Chamber (cat#354480; ThermoFisher ). 7.5 x 104 cells were placed in serum-free DMEM in the upper chamber (insert), and DMEM with 10% FBS as attractant in the lower chamber. After incubation for 24 h at 37 °C, the insert was removed and cells on the undersurface of the insert were fixed with 5% glutaraldehyde for 10 min, then stained with 1% crystal violet in 2% ethanol for 20 min. After the insert was dry, the cells on the filter were counted by microscope over multiple fields. For experiments with inhibitors, 10 ug/ml λ-carageenan (cat# 22049; Sigma), anti-NAP-2 antibody (cat# sc-19224; Santa Cruz Biotech), or anti-HPA1 antibody were used. RESULTS: Heparan sulfate-degrading activity was 0.0625 U/ug for K234 cell lysate compared to 0.0125 U/ug for Balb/c3T3 cells. λ-carageenan inhibited the activity completely confirming glycanase inhibition. Anti-NAP2 and anti-HPA1 antibody inhibited heparan sulfate degrading activity in 3T3 lysate. Invasion was two-fold greater by K234 cells than for 3T3 cells. When anti-NAP2 antibody was added to the invasion assay, both K234 and 3T3 cell invasion was inhibited by 55% and 54%, respectively. Less than 1% inhibition of invasion occurred with anti-HPA1 antibody. CONCLUSION: The invasion of heparan sulfate-containing Matrigel by K234 cells is partly influenced by heparan sulfate-degrading activity. The inhibition of the degrading activity by an anti-chemokine antibody decreased invasion, and invokes other processes for the malignant sarcoma phenotype. Citation Format: Donghong Ju, Leonard Lipovich, Mary A. Kosir. Sarcoma invasion associated with heparan sulfate degradation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1978.
Abstract 4806: Development of a novel antitumor agent NCT compound for the treatment of non-small cell lung cancer
Authors: Seung Yeob Hyun, Huong Thuy Le, Young-Sik Yong, Hye-Young Min, Jeewoo Lee, Ho-Young Lee
Journal: Cancer Research (2019)

Abstract Despite the development of advanced therapeutic regimens such as molecular targeted therapy and immunotherapy, the 5-year survival of patients with lung cancer is still less than 20%, suggesting the need to develop additional treatment strategies. Here we show the efficacy and biological mechanism of a novel antitumor agent, NCT compound. NCT compound exhibited significant inhibitory effects on the viability and colony formation of non-small cell lung cancer (NSCLC) cells and those carrying resistance to chemotherapy by inducing apoptosis. NCT compound markedly suppressed the migration of NSCLC cells. Consistently, NCT compound significantly suppressed tumor growth in a xenograft model. NCT compound showed minimal effects on the viability of normal cells and no overt toxic effects in mice, suggesting minimal toxicity of NCT compound. Further mechanistic studies revealed that NCT compound downregulated the activation of signaling pathway associated with cell proliferation and survival and the expression of epithelial-mesenchymal transition (EMT)-related markers. These results suggest the potential of NCT compound as an antitumor agent. Citation Format: Seung Yeob Hyun, Huong Thuy Le, Young-Sik Yong, Hye-Young Min, Jeewoo Lee, Ho-Young Lee. Development of a novel antitumor agent NCT compound for the treatment of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4806.
Abstract 3584: Role of long noncoding RNA LINC00461 in EGFR-TKIs resistant non-small cell lung cancer
Authors: Ji Yun Lee, Thi-Thu-Trang Luu, Duc-Hiep Bach, Ruoci Hu, Donghwa Kim, Sang Kook Lee
Journal: Cancer Research (2019)

Abstract Chemo-resistance is one of the major factors limiting the therapeutic efficacy and prognosis of non-small cell lung cancer (NSCLC) patients, especially with patients who harbor epidermal growth factor receptor (EGFR)-activating mutations. Accumulating evidence suggests that aberrant expression of long noncoding RNAs (lncRNAs) is in part associated with carcinogenesis. Therefore, we tried to identify lncRNAs and their potential target genes in drug-resistant NSCLC. We evaluated lncRNAs with drug-resistant NSCLC using microarray data and in vitro assays. W found that lots of lncRNAs were differentially expressed between the drug-resistant NSCLC cells (HCC827-gef) and its parental (HCC827) cells. Among them, LINC00461 was found to be up-regulated lncRNAs, and highly correlated with the drug resistance. Taken together, the present study provides the expression profiles of chemo-resistant lncRNAs and identifies LINC00461 as a potential biomarker associated with EGFR-TKI resistance in non-small cell lung cancer cells. This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MEST) (NRF-2016M3A9B6903499). Citation Format: Ji Yun Lee, Thi-Thu-Trang Luu, Duc-Hiep Bach, Ruoci Hu, Donghwa Kim, Sang Kook Lee. Role of long noncoding RNA LINC00461 in EGFR-TKIs resistant non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3584.