tbuckley/cabot-search huggingface dataset:
Abstract 2588: Prediction of the 5-year risk of hepatocellular carcinoma during long-term antiviral therapy in the general Korean population
Authors: Jae-Jun Shim, In Hwan Oh, Jung Wook Kim, Chang Kyun Lee, Jae Young Jang, Ju-Seog Lee, Byung-Ho Kim
Journal: Cancer Research (2016)

Abstract Oral antiviral therapy using nucleos(t)ide analogues can decrease risk for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B. However, wide use of antiviral therapy is limited by stringent treatment indications in many countries. We compared preventive effect of antiviral therapy on HCC development between current and new extended indication for the treatment. We established Korean cohort with chronic hepatitis B virus (HBV) infection using the fifth National Health and Nutrition Examination Survey (KNHANES). The cohort represented 993,872 subjects with chronic HBV infection more than 40 years in Korea. We estimated five-year risk of HCC before and after antiviral therapy using a HCC prediction score (REACH-B). The National Health Insurance (NHI) in Korea, the European Association for the Study of the Liver (EASL) guideline, and a new extended indication were compared. During a 5-year period, predicted HCC cases were 2,725 per 100,000 individuals (0.55% / year). When the cohort was treated under the Korean NHI indication, EASL, and new extended indication, HCC risk decreased to 2,531 (-7.1%), 2,089 (-23.3%), and 1,122 (-58.8%) cases per 100,000 individuals, respectively (P &amp;lt; 0.0001). As participation rate in antiviral therapy among eligible patients increased every 10%, HCC risk decreased to -0.74%, -2.39%, and -5.87%, respectively. New extended indication could decrease HCC risk eight times more than the current Korean NHI indication. Prediction of HCC development among chronic HBV infection is feasible in the virtual population level. Considering the large preventive effect of antiviral therapy, the treatment indications should be revised to increase eligible patients. Indications for antiviral treatment used in this study and predicted reduction of HCC riskKorean NHIEASLNew extended indicationLiver enzymeAST or ALT ≥ 80 IU/LALT ≥ ULN x 1AnyHBV DNA level≥ 20,000 IU/mL≥ 2,000 IU/mL≥ 2,000 IU/mLHCC risk reduction, mean (SD) (%)-7.14 (0.14)-23.33 (0.26)-58.82 (0.07) Citation Format: Jae-Jun Shim, In Hwan Oh, Jung Wook Kim, Chang Kyun Lee, Jae Young Jang, Ju-Seog Lee, Byung-Ho Kim. Prediction of the 5-year risk of hepatocellular carcinoma during long-term antiviral therapy in the general Korean population. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2588.
Abstract 3202: Transgenic antigen-specific, HLA-A*02:01-allo-restricted cytotoxic T cells recognize tumor-associated target antigen STEAP1 with high specificity
Authors: David Schirmer, Richard Klar, Oxana Schmidt, Dirk Wohlleber, Wolfgang Uckert, Uwe Thiel, Felix Bohne, Dirk H. Busch, Angela M. Krackhardt, Stefan Burdach, Günther H. Richter
Journal: Cancer Research (2016)

Abstract Background: Pediatric cancers, including Ewing sarcoma (ES), are only weakly immunogenic and the tumor-patients immune system often is devoid of effector T cells for tumor elimination. Based on expression profiling technology targetable tumor associated antigens (TAA) are identified and exploited for engineered T cell therapy. Here, the specific recognition and lytic potential of transgenic, allo-restricted CD8+ T cells directed against the ES-associated antigen STEAP1 was examined. Methods: Following repetitive STEAP1130 peptide-driven stimulations with HLA-A*02:01+ dendritic cells, allo-restricted HLA-A*02:01- CD8+ T cells were sorted with HLA-A*02:01/peptide multimers and expanded by limiting dilution. After functional analysis of suitable T cell clones via ELISpot, flow cytometry and xCELLigence assay, TCR α- and β-chains were identified. They were cloned into retroviral vectors, codon optimized, transfected into HLA-A*02:01- primary T cell populations and tested again for specificity and lytic capacity in vitro and in a Rag2-/-γc-/- mouse model. Results: Initially generated and transgenic T cells specifically recognized STEAP1130-pulsed or transfected cells in the context of HLA-A*02:01 with minimal cross-reactivity as determined by specific IFNγ release. They lysed cells and inhibited growth of HLA-A*02:01+ ES lines more effectively than HLA-A*02:01- ES lines. In vivo tumor growth was inhibited more effective with transgenic STEAP1130-specific T cells than with unspecific T cells. Conclusion: Our results identify TCRs capable of recognizing and inhibiting growth of STEAP1 expressing HLA-A*02:01+ ES cells in vitro and in vivo in a highly restricted manner. As STEAP1 is overexpressed in a wide variety of cancers, we anticipate these STEAP1-specific TCRs to be potentially useful for immunotherapy of other STEAP1 expressing tumors. Citation Format: David Schirmer, Richard Klar, Oxana Schmidt, Dirk Wohlleber, Wolfgang Uckert, Uwe Thiel, Felix Bohne, Dirk H. Busch, Angela M. Krackhardt, Stefan Burdach, Günther H. Richter. Transgenic antigen-specific, HLA-A*02:01-allo-restricted cytotoxic T cells recognize tumor-associated target antigen STEAP1 with high specificity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3202.
Mosquito Brigades and How to Organize Them.
Journal: JAMA (1902)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
P289 Isolated Mediastinal and/or Hilar Lymphadenopathy: what can EBUS-TBNA add?: Abstract P289 Table 1
Authors: V Connor, V Tippet, T Kennedy, B Challoner
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> In recent years, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been increasingly used to investigate patients with isolated mediastinal and/or hilar lymphadenopathy (IMHL). There is currently a lack of high quality research to confirm the diagnostic yield and accuracy for these patients. The aim of this review was to examine the diagnostic yield of EBUS-TBNA in patients with IMHL, to ensure accurate information is being given to patients considering undergoing the procedure. <h3>Methods</h3> A retrospective service review was carried out, including consecutive patients listed for EBUS-TBNA between June 2013–June 2014 in a single UK centre. <h3>Results</h3> 135 patients were evaluated who underwent EBUS-TBNA as a first diagnostic test (full results in Table 1). 35 patients with IMHL underwent EBUS-TBNA within the study period; IMHL was defined as the presence of enlarged mediastinal/hilar lymph nodes on computer tomography (CT) without suggestion of intrathoracic/extra-thoracic malignancy. 34 of these had a diagnostic test (97%); pathological cause was found in 9 patients (sarcoid n = 7, malignancy n = 2) with the remaining being diagnosed with reactive lymphadenopathy (n = 25 74%). This group of 35 patients was sub-classified into those with IMHL with a radiologically suggested diagnosis e.g. sarcoid (n = 22) and those with no suggested cause of IMHL (n = 13). EBUS-TBNA was diagnostic in 95% and 100% of patients respectively with the most common diagnosis in both groups remaining that of reactive lymphadenopathy. <h3>Conclusions</h3> A significant proportion of patients with IMHL were found to have a diagnosis of reactive lymphadenopathy. With a pathological cause only being found in a minority of cases the appropriateness of EBUS-TBNA to investigate these patients could be questioned. Our results found a significantly higher prevalence of reactive lymphadenopathy than previously published data; Evinson <i>et al</i>. reported this diagnosis 48% of patients and the REMEDY trial reported reactive lymphadenopathy in 5% of patients. The detection of IMHL and its burden on the health service is likely to increase with increasing use of CT. Due to this a large multi-centred prospective study of patients with IMHL would be advisable to further investigate what the most appropriate strategy to manage these patients should be.
Hypothalamic kappa opioid receptor mediates both diet‐induced and melanin concentrating hormone–induced liver damage through inflammation and endoplasmic reticulum stress
Authors: Monica Imbernon, Estrella Sanchez‐Rebordelo, Amparo Romero‐Picó, Imre Kalló, Melissa J. Chee, Begoña Porteiro, Omar Al‐Massadi, Cristina Contreras, Johan Fernø, Ana Senra, Rosalia Gallego, Cintia Folgueira, Luisa M. Seoane, Margriet van Gestel, Roger A. Adan, Zsolt Liposits, Carlos Dieguez, Miguel López, Ruben Nogueiras
Journal: Hepatology (2016)

The opioid system is widely known to modulate the brain reward system and thus affect the behavior of humans and other animals, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and adenoviral vectors overexpressing or silencing κOR were stereotaxically delivered in the lateral hypothalamic area (LHA) of rats. Vagal denervation was performed to assess its effect on liver metabolism. Endoplasmic reticulum (ER) stress was inhibited by pharmacological (tauroursodeoxycholic acid) and genetic (overexpression of the chaperone glucose‐regulated protein 78 kDa) approaches. The peripheral effects on lipid metabolism were assessed by histological techniques and western blot. We show that in the LHA κOR directly controls hepatic lipid metabolism through the parasympathetic nervous system, independent of changes in food intake and body weight. κOR colocalizes with melanin concentrating hormone receptor 1 (MCH‐R1) in the LHA, and genetic disruption of κOR reduced melanin concentrating hormone–induced liver steatosis. The functional relevance of these findings was given by the fact that silencing of κOR in the LHA attenuated both methionine choline–deficient, diet‐induced and choline‐deficient, high‐fat diet–induced ER stress, inflammation, steatohepatitis, and fibrosis, whereas overexpression of κOR in this area promoted liver steatosis. Overexpression of glucose‐regulated protein 78 kDa in the liver abolished hypothalamic κOR‐induced steatosis by reducing hepatic ER stress. Conclusions : This study reveals a novel hypothalamic–parasympathetic circuit modulating hepatic function through inflammation and ER stress independent of changes in food intake or body weight; these findings might have implications for the clinical use of opioid receptor antagonists. (H epatology 2016;64:1086‐1104)
Predictive value of MSI, 18qLOH, TS promoter, and MTHFR C677T variants on efficacy/toxicity of capecitabine adjuvant monotherapy: A mid-term report of a prospective observational study on 136 stage II/III colon cancer patients.
Authors: A. J. Dimovski, N. Angelovska-Petrusevska, B. Angelovska-Grozdanovska, A. Kapedanovska Nestorovska, N. Matevska, A. Eftimov, T. Josifovski
Journal: Journal of Clinical Oncology (2010)

e14070 Background: There is a significant difference in survival and toxicity profiles among patients treated with 5-FU-based therapies. We evaluated the predictive value of TS promoter, MTHFR C677T, MSI and/or 18q LOH markers on efficacy/toxicity of adjuvant capecitabine monotherapy in 142 colon cancer patients. Here we report our interim analysis on the mid-term follow-up of 136 patients. Methods: Inclusion criteria were stage III (60 patients) or high-risk stage II (82 patients) disease and adjuvant treatment with capecitabine monotherapy (1,250 mg/m2 bid 12 hours apart for 14 days, repeated every 3 weeks for a total of 8 cycles). The follow-up data on efficacy (defined as relapse-free survival) or toxicity (adverse events and laboratory tests, graded according to the NCI-CTCAE v3.0) were available for a median of 24 months (range 6–48 months). DNA isolated from tumors and peripheral blood was genotyped for TS promoter and MTHFR C677T variants, mismatch repair and 18q LOH status of tumors using QF-PCRs and/or PCR-RFLP. Results: Treatment was generally well tolerated; 91 (64.1%) patients completed the treatment protocol. A 25% dose reduction was necessary in 39 (27.4%) patients mainly due to mild to moderate diarrhea, nausea and/or hand-foot syndrome. Twelve (8.5%) patients were excluded from the study due to incomplete follow-up data. The MTHFR 677 TT genotype was predictive of absence of side effects (OR 0.094, 95% CI 0.01-0.87, p = 0.014). Disease relapse was diagnosed in 18 patients. None of the 19 patients with MSI+ tumors and none of the six MTHFR677 TT homozygotes had disease relapse, but the numbers were too low to reach statistical significance. Tumor stage, age and gender of the patients were not predictive of disease recurrence. Conclusions: MSI+ and MTHFR 677TT genotype are predictive for mid-term relapse-free survival of colon cancer patients treated with capecitabine adjuvant monotherapy. MTHFR677TT genotype is also predictive for absence of severe side effects associated with capecitabine monotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Abstract 2826: Sustained melanoma regression is achieved with continuous palbociclib and PLX4720 treatment but not with intermittent or sequential dosing
Authors: Karen E. Sheppard, Carleen Cullinane, Claire Martin, Laura Kirby, Nicole Haynes, Kelly Waldeck, Richard Young, Todd VanArsdale, Grant McArthur
Journal: Cancer Research (2016)

Abstract In melanoma the development of resistance to BRAF inhibitors limits clinical responses. Thus the search for novel single agent and combination therapies as well as sequencing strategies that overcome or delay the emergence of resistance is needed. The p16-CDK4- cyclinD-RB1 pathway (CDK4 pathway) is deregulated in approximately 90% of melanomas and most melanoma cell lines are sensitive to palbociclib a specific CDK4/6 inhibitor. We hypothesized that dual targeting the MAPK/ERK and CDK4 pathways would lead to robust inhibition of the CDK4/Cyclin D complex and consequently induce greater tumor regression than single agent treatment. Proliferation and colony formation assays demonstrated that sequential and intermittent treatment with PLX4720 and palbociclib was not as effective as continuous combinational dosing. Only the combination of PLX4720 and palbociclib overcame the development of resistance leading to sustained inhibition of proliferation, cell death and induction of senescence. In A375 and HT144 human tumor xenograft models, palbociclib and PLX4720 initially induced tumor regression and tumor stasis, respectively, however resistance eventually developed to both agents. In contrast, the combination treatment induced rapid and sustained tumor regression. Biomarker studies indicate resistance to single agent PLX4720 was due to reactivation MAPK/ERK pathway and resistance to palbociclib to partial restoration of phosphorylated RB1. Tumor regression in the combination treatment was associated with the infiltration of leukocytes including activated natural killer cells indicating that these cells were involved in tumor clearance. These data demonstrate that dual targeting CDK4/6 and mutant BRAF evades resistance to single agents and leads to sustained tumor regression Citation Format: Karen E. Sheppard, Carleen Cullinane, Claire Martin, Laura Kirby, Nicole Haynes, Kelly Waldeck, Richard Young, Todd VanArsdale, Grant McArthur. Sustained melanoma regression is achieved with continuous palbociclib and PLX4720 treatment but not with intermittent or sequential dosing. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2826.
Abstract 1234: Galeterone-induced degradation of the androgen receptor involves inhibition of deubiquitinating enzymes
Authors: Daniel T. Dransfield, Nivedita Namdev, Douglas B. Jacoby, Karen Ferrante
Journal: Cancer Research (2016)

Abstract Galeterone is a highly selective oral small molecule drug candidate that disrupts androgen receptor (AR) signaling through degradation of the AR, is a potent CYP17 lyase inhibitor, and possesses AR antagonist activity. Galeterone-induced AR degradation was observed in models having either full-length AR or known constitutively active truncated forms of the AR receptor that lack the ligand binding domain (LBD), AR-V7 and AR567es, suggesting the LBD of the AR is not required for galeterone-dependent AR degradation. Further, galeterone-induced AR degradation activity is blocked by co-administration of the proteasome inhibitor MG132. Along these lines, galeterone-induced AR degradation can be blocked by selective knock-down of the E3 ligases, Mdm2 and CHIP. We utilized a series of biochemical and cell-based in vitro methodologies to further elucidate and characterize additional signaling molecules participating in the proteasomal-dependent mechanism of galeterone-induced AR degradation. We screened a panel of 22 deubiquitinating enzymes (DUBs) in vitro and demonstrated that galeterone selectively inhibited enzymatic activity of two of the DUBs, USP12 and USP46. Separately, we used surface plasmon resonance to demonstrate a dose-dependent direct binding of galeterone to each of USP12 and USP46, alone or when pre-complexed with UAF1. USP12 is a co-activator of the AR, and selective knock-down of this DUB has been shown to increase AR degradation. USP12/USP46 have also been linked to regulation of phosphatases (PHLPPs) through ubiquitination. PHLPPs dephosphorylate AKT, providing an important regulatory mechanism for controlling the PI3K/AKT pathway. It is known that galeterone induces an increase in pAKT and pMdm2, the latter being a substrate of activated AKT. This suggests that inhibition of USP12/USP46 may regulate pAKT levels through enhanced degradation of PHLPPs via increased ubiquitination. These data support a differentiating mechanism of galeterone from other AR targeting agents whereby inhibition of USP12/USP46 leads to enhanced AR degradation. Citation Format: Daniel T. Dransfield, Nivedita Namdev, Douglas B. Jacoby, Karen Ferrante. Galeterone-induced degradation of the androgen receptor involves inhibition of deubiquitinating enzymes. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1234.
Use of Online Communication by Patients With Newly Diagnosed Breast Cancer During the Treatment Decision Process
Authors: Lauren P. Wallner, Kathryn A. Martinez, Yun Li, Reshma Jagsi, Nancy K. Janz, Steven J. Katz, Sarah T. Hawley
Journal: JAMA Oncology (2016)

5 (IQR, 2-9) seconds (P = .02),and the number of words included increased from 7 (IQR, 7-12) to 13 (IQR, 7-25) (P < .001).The median number of words per second increased from 1.5 to 3.2 per second from 2014 to 2015 (P < .001).In 2014, no differences were found in the number of COI disclosures between education and oral sessions.In 2015, oral sessions had more conflicts (median, 5.5; IQR, 0.5-11.5)than educational sessions (median, 3; IQR, 0-6) (P = .004).The Figure shows a waterfall plot of words per second in 2015.The baseline is set as 4 words per second, an optimistic estimate of maximum reading ability.In 2014, a total of 37 of 248 presentations (14.9%) had information overload, whereas in 2015 this number increased to 83 of 221 (37.6%) (P < .001).As a sensitivity analysis, we compared 2015 and 2013 and reached similar conclusions.Discussion | We found that the change in policy from disclosure of relevant to all financial COIs increased disclosed COI and information overload at ASCO annual meetings.Of concern, 83 of 221 presentations (37.6%) at last year's ASCO meeting had COI disclosure slides that were displayed at a speed so fast that they exceeded the range of comprehension for most readers.For COI disclosure to be meaningful, it must be able to be read and processed.We also found that 124 of 242 speakers (51.2%) had at least 1 financial COI, and this number increased to 151 of 216 (69.9%) when all financial ties were disclosed as opposed to only those deemed relevant.Our findings raise concern about whether current disclosure protocols constitute meaningful disclosure.The solution would be to extend the time of the disclosure slide so that no slide exceeds established limits of reading speed.Further investigation is needed on audience ability to process COI slides at professional meetings if disclosure is the major objective.