tbuckley/cabot-search huggingface dataset:
Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: A presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials
Authors: Kristian Reich, Craig Leonardi, Richard G. Langley, Richard B. Warren, Hervé Bachelez, Ricardo Romiti, Mamitaro Ohtsuki, Wen Xu, Nayan Acharya, Kathleen Solotkin, Jean-Frederic Colombel, Dana S. Hardin
Journal: Journal of the American Academy of Dermatology (2016)

Inflammatory bowel disease (IBD) occurs more frequently in patients with psoriasis. The 2 diseases have significant genetic overlap, but the pathogenesis underlying their co-occurrence is unknown.We sought to report adjudicated IBD cases (Crohn's disease [CD] and ulcerative colitis [UC]) in patients exposed to ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A.Adverse events (AEs) integrated from 7 randomized controlled and uncontrolled trials were analyzed for the controlled induction period, controlled maintenance period, and all ixekizumab-treated patients. Suspected IBD cases were reviewed by blinded external experts using internationally recognized criteria (Registre Epidemiologique des Maladies de l'Appareil Digestif registry).In all, 4209 patients (6480 patient-exposure years) were exposed to ixekizumab. Suspected CD (N = 12) or UC (N = 17) AEs were reported; 19 were adjudicated as definite/probable IBD (CD, N = 7, incidence rate = 1.1/1000 patient-exposure years; UC, N = 12, incidence rate = 1.9/1000 patient-exposure years). Among these, 3 occurred during induction (CD, N = 1; UC, N = 2) and 7 during maintenance (CD, N = 4; UC, N = 3). Twelve of 16 patients with reported IBD history have not had an IBD treatment-emergent AE/serious AE to date.Clinical review (adjudication) was not prespecified. AE data collected post-hoc may have been limited by length of time from occurrence.From an integrated database of 7 ixekizumab psoriasis trials, CD and UC cases were uncommon (<1%).
Painful skin lesions and squamous cell carcinoma predict overall mortality risk in organ transplant recipients: a cohort study
Authors: C.C. Oh, G.F.L. Hofbauer, A.L. Serra, C.A. Harwood, L. Mitchell, C.M. Proby, E.B. Olasz, D.D. Mosel, S. Piaserico, A.B. Fortina, A. Geusau, K. Jahn-Bassler, M.J.P. Gerritsen, D. Seçkin, A.T. Güleç, P. Cetkovská, J. Ricar, B. Imko-Walczuk, A. Dębska-Ślizień, J.N. Bouwes Bavinck
Journal: British Journal of Dermatology (2016)

Organ transplant recipients (OTRs) have a highly increased risk of cutaneous squamous cell carcinomas (SCCs). Sensation of pain in cutaneous tumours is a powerful patient‐reported warning signal for invasive SCCs in OTRs. To investigate the impact of painful vs. painless skin lesions and SCC vs. other skin lesions on the overall mortality risk in OTRs. We followed 410 OTRs from 10 different centres across Europe and North America between 2008 and 2015. These patients had been enrolled in an earlier study to define clinically meaningful patient‐reported warning signals predicting the presence of SCC, and had been included if they had a lesion requiring histological diagnosis. Cumulative incidences of overall mortality were calculated using Kaplan–Meier survival analysis, and risk factors were analysed with Cox proportional hazard analysis. There was an increased overall mortality risk in OTRs who reported painful vs. painless skin lesions, with a hazard ratio (HR) of 1·6 [95% confidence interval (CI) 0·97–2·7], adjusted for age, sex and other relevant factors. There was also an increased overall mortality risk in OTRs diagnosed with SCC compared with other skin lesions, with an adjusted HR of 1·7 (95% CI 1·0–2·8). Mortality due to internal malignancies and systemic infections appeared to prevail in OTRs with SCC. We suggest that OTRs have an increased overall mortality risk if they develop painful skin lesions or are diagnosed with cutaneous SCC.
Abstract LB-260: A small molecule Myc inhibitor has therapeutic effects on mouse pancreatic and other cancers
Authors: Dimitris Stellas, Matthias Szabolcs, Sanjay Koul, Zhe Li, Alexander Polyzos, Constantinos Anagnostopoulos, Zoe Cournia, Constantin Tamvakopoulos, Apostolos Klinakis, Argiris Efstratiadis
Journal: Cancer Research (2015)

Abstract Mouse models faithfully simulating human cancer are valuable for genetic identification of potential drug-targets but, among them, the most advantageous for practical use in subsequent preclinical testing of candidate therapeutic regimes are those exhibiting rapid tumor development. Considering that pancreatic ductal adenocarcinoma (PDA) is the deadliest of the major malignancies and an unresolved clinical problem, and that a KRAS mutation (predominantly in codon 12, such as KRASG12D; KRAS*) occurs with high frequency (∼90%) in PDA cases, we sought to develop a mouse PDA model that would exhibit high tumor incidence and short latency by ectopic overexpression of Kras*. This transgenic modification caused by two weeks postpartum the appearance of pancreatic intraepithelial neoplasia (PanIN), which evolved into invasive PDA within a week later, and resulted in a moribund condition at one month of age. Interestingly, however, this aggressive form of pancreatic tumorigenesis was effectively prevented by genetic ablation of Myc specifically in the pancreas On the basis of this observation, causally demonstrating that Kras* oncogenicity fully depends on unperturbed Myc activity, we tested with positive results the effective treatment of our mouse PDA model by using orally-administered Mycro3, a small-molecule inhibitor of Myc-Max dimerization. PET/CT image analysis demonstrated marked shrinkage of PDA, while immunohistochemical analyses showed an increase in cancer cell apoptosis and reduction in cell proliferation. Tumor growth was also drastically attenuated in Mycro3-treated NOD/SCID mice carrying orthotopic or heterotopic xenografts of human pancreatic cancer cells. In addition, Mycro3 was efficacious in treating xenografts generated either heterotopically or orthotopically (by tail-injection) using a human lung carcinoma cell line (KRASG12D) and also in treating KRAS-driven mouse mammary tumors. These results provide strong justification for eventual clinical evaluation of anti-Myc drugs as potential chemotherapeutic agents for the treatment of PDA and other Myc-dependent cancers. Citation Format: Dimitris Stellas, Matthias Szabolcs, Sanjay Koul, Zhe Li, Alexander Polyzos, Constantinos Anagnostopoulos, Zoe Cournia, Constantin Tamvakopoulos, Apostolos Klinakis, Argiris Efstratiadis. A small molecule Myc inhibitor has therapeutic effects on mouse pancreatic and other cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-260. doi:10.1158/1538-7445.AM2015-LB-260
The Polymorphisms of Base Excision Repair Genes Influence the Prognosis of Multiple Myeloma
Authors: Chiaki Ushie, Takayuki Saitoh, Atsushi Iwasaki, Norihiko Moriyama, Hikaru Hattori, Morio Matsumoto, Morio Sawamura, Jun Isoda, Hiroshi Handa, Akihiko Yokohama, Norifumi Tsukamoto, Hatsue Ogawara, Hirokazu Murakami
Journal: Blood (2012)
Media coverage of lung cancer
Authors: D. Blum, W. Boerckel
Journal: Journal of Clinical Oncology (2009)

e20565 Background: In 2000, a survey was conducted to assess media coverage for the four major cancers (breast, prostate, lung, colorectal). A 2004 follow-up survey revealed there were more lung cancer articles conveying positive messages and greater celebrity involvement and coverage of new treatments. A 2008 follow up survey was commissioned to determine whether the trend of increased coverage and favorability of message had persisted. Methods: Research firm Carma International analyzed a systematic random sample of 600 stories from U.S. media, including print, broadcast and web based sources (August, 2007-July, 2008). Coverage was analyzed by volume, story type, topics, awareness events and celebrity outreach. Topics and messages from this period were matched to those used in previous periods (August 1999 - July 2000, August 2003 - July 2004). Project parameters were held consistent between time periods to enable an accurate comparison of each cancer over time. Results: Lung cancer coverage experienced an increase in volume, up 23% (116 to143 stories) from the previous period, while breast cancer coverage increased 21% (333 to 402 stories). Lung cancer coverage was less positive with a drop to a slightly favorable rating of 48; research references declined from 29 to 14 and lung cancer garnered the lowest percentage of stories discussing treatment (14%); while tobacco/smoking references were found in 44% of lung cancer stories, up 31% from the earlier period and was the leading negative message. Positive message penetration declined over time for lung cancer coverage with 36% of stories carrying at least one positive message in 1999–2000 but only 28% in 2007–2008. Conclusions: While the volume of lung cancer coverage has increased significantly from over time, the tone of coverage has become significantly less favorable and more negative. Such findings identify a clear need to encourage media to consider how they report on lung cancer, specifically the prominence of smoking as a risk factor in cancer related stories, and to encourage reporting more hopeful messages including survivor stories, and new developments in lung cancer research/treatment. No significant financial relationships to disclose.
Abstract 4909: Increased IR-A/IR-B ratio in non-small cell lung cancers associates with lower epithelial-mesenchymal transition signature and longer survival in squamous cell lung carcinoma
Authors: Jiaqi Huang, Wei Zhu, Liyan Jiang, Katie Streicher, Chris Morehouse, Philip Brohawn, XiaoXiao Ge, Zhengwei Dong, Xiaolu Yin, Guanshan Zhu, Yi Gu, Parthiv Mahadevia, Brandon W. Higgs, Yihong Yao
Journal: Cancer Research (2015)

Abstract To evaluate the insulin receptor isoform mRNA expression status in NSCLC patients RNA-seq data from 614 NSCLC [355 adenocarcinomas(LUAD) and 259 squamous cell carcinomas (LUSC)] and 92 normal lung specimens were obtained from The Cancer Genome Atlas (TCGA) to evaluate the mRNAexpression of insulin receptor isoform A (IR-A) and insulin receptor isoform B(IR-B). The differential expression status of the insulin receptor isoforms in NSCLC patients was confirmed using qRT-PCR assays with lung cancer cDNA arrays and primary tumor samples. The mRNA expression levels of IR-B were significantly lower in some NSCLC samples compared to normal lung specimens,including both LUAD and LUSC. Notably, no IR-B transcripts were detected - only the IR-A isoform was expressed in 11% of NSCLC patients. This decrease in IR-B expression contributed to an elevated IR-A/IR-B ratio, which was also associated with lower epithelial-mesenchymal transition gene signatures in NSCLC and longer patient survival under standard of care in LUSC. In addition to NSCLC, RNA-seq data from TCGA revealed a similar increase in IR-A/IR-B ratio in many other cancer types, with high prevalence in acute myeloid leukemia,glioblastoma multiforme, and brain lower grade glioma. Our results indicate a common reduction of the mRNA expression level of IR-B and an increased IR-A/IR-B mRNA ratio in NSCLC and other tumor types. The relationship of altered IR-A/IR-B ratios with cancer progression and patient survival should be prospectively explored in future studies. Citation Format: Jiaqi Huang, Wei Zhu, Liyan Jiang, Katie Streicher, Chris Morehouse, Philip Brohawn, XiaoXiao Ge, Zhengwei Dong, Xiaolu Yin, Guanshan Zhu, Yi Gu, Parthiv Mahadevia, Brandon W. Higgs, Yihong Yao. Increased IR-A/IR-B ratio in non-small cell lung cancers associates with lower epithelial-mesenchymal transition signature and longer survival in squamous cell lung carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4909. doi:10.1158/1538-7445.AM2015-4909
ERG, EVI1 and PRAME Are Relevant Markers of Treatment Response and Survival, and They Could Be Useful for Improving the Risk-Stratification in Citogenetically Normal Acute Myeloid Leukemia (CN-AML)
Authors: Carlos Santamaría, Carmen Chillón, Ramon García-Sanz, Cristina Pérez, Fernando Ramos, Alfonso García de Coca, Jose- Maria Alonso, Pilar Giraldo, Teresa Bernal, José-Antonio Queizán, José Nicolas Rodríguez, Pascual Fernández-Abellán, Abelardo Barez, María-José Peñarrubia, Mari Luz Amigo, Alejandro Martín García-Sancho, Miguel Angel Pozas, Ana Balanzategui, Joaquin Díaz-Mediavilla, Jesús F. San Miguel, Marcos González
Journal: Blood (2008)
A Pilot Study of Acupuncture in Treating Bortezomib-Induced Peripheral Neuropathy (BIPN) in Multiple Myeloma (MM) Patients.
Authors: Ting Bao, Neil Porter, James Primrose, Olga Goloubeva, Lisa Hester, Lulu Wang, Mariola Sadowska, Rena Lapidus, Michelle Medeiros, Lixing Lao, Susan Dorsey, Ashraf Z. Badros
Journal: Blood (2012)
Abstract 3023: Chromatin accessibility underlies the tumor suppressor role of BAF (mSWI/SNF) complexes in many human cancers
Authors: Courtney Hodges, Diana C. Hargreaves, Erik L. Miller, Gerald R. Crabtree
Journal: Cancer Research (2015)

Abstract Recent exome sequencing studies of human cancer indicate that ∼20% of malignancies have mutations in the subunits of the BAF (mSWI/SNF) chromatin remodeling complex, implicating the complex as a major tumor suppressor. However, the mechanisms of tumor suppression remain uncertain. To understand how defective BAF subunits contribute to cancer, we analyzed the genomic states of 5,659 patient samples derived from 22 tumor types, and compared samples containing genetic defects of the BAF complex against samples containing no such defects. We show that in the majority of cancer types, tumors with BAF subunit defects have significantly higher mutation counts than cancers of the same tissue lacking BAF defects. By reconstructing the mutational processes active in each patient sample, we find that excess mutations in BAF-deficient cancers represent the signatures of defective mismatch repair, cytidine deamination, UV-damage response, DNA end joining, Pol epsilon function, and other enzymatic processes acting on DNA. In four cancer types where ChIP-seq tracks were available for the healthy cell type of origin, we tracked the locations of over 280,000 mutations, and find that excess mutations in BAF-deficient tumors are biased towards regions of elevated H3K36me3 and low H3K27me3 in their corresponding non-cancerous tissues. We hypothesized that these mutations resulted from inaccessibility for repair and maintenance factors when a BAF subunit is defective. We tested this hypothesis using topoisomerase IIa binding as model for processes that require enzymatic access to DNA, and found that rapid conditional deletion of the ATPase Brg led to an increase in genome-wide deposition of H3K27me3 at Brg-dependent topoisomerase IIa sites from an initial low state. Our data indicate that the tumor-suppressive functions of BAF complexes arise largely from the requirement for BAF complexes to maintain genomic stability by providing access to DNA for repair and maintenance mechanisms. Note: This abstract was not presented at the meeting. Citation Format: Courtney Hodges, Diana C. Hargreaves, Erik L. Miller, Gerald R. Crabtree. Chromatin accessibility underlies the tumor suppressor role of BAF (mSWI/SNF) complexes in many human cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3023. doi:10.1158/1538-7445.AM2015-3023
Informative rate and reproducibility of the investigational GeneSearch ProCaM assay in a multicenter laboratory setting
Authors: J. Baden, J. Markiewicz, J. Painter, J. Jones, K. Curtin, S. Canning, J. Quijano, W. Guinto, Y. Wang, G. Green
Journal: Journal of Clinical Oncology (2009)

e22038 Background: PSA tests have low specificity, which frequently results in unnecessary biopsy and typically limits screening to patients with PSA values &gt;4.0 ng/mL. The investigational ProCaM assay detects CpG island methylation within the promoter regions of three markers (GSTP1, RARß2, and APC) that are indicative of the presence of prostate cancer. The objective of this research study was to assess assay testing reproducibility and lot-to-lot variability. Methods: Assay reproducibility: 8 operators from 4 external clinical laboratories tested a panel comprised of a negative panel member (NM2C5 cells) for the internal control (ß-Actin), a high positive and low positive panel members (LNCaP cells) for all 3 markers and ß-Actin. Variability of assay results based on marker cycle threshold (Ct) values was determined. Lot variability: 3 unique lots of the ProCaM Test Kit were evaluated on DNA extracted from 169 post-DRE urine samples to show reproducibility across kit lots. Urine samples were collected from consenting subjects that were scheduled for prostate biopsy and tested by 3 operators at the same facility. Results: Assay reproducibility: The informative rate was 98% (766 valid results of 782 total tests). The overall intersite %CV and SD values for Cts were = 9.2% and 1.49%, respectively. The percent agreement with qualitative (positive/negative) outcome for High, Low, and Negative panel members was = 98% for GSTP1, RARß2, APC, and ß-Actin. Lot variability: Of the 169 biopsy results a histology positivity rate of 39% (66/169) was shown. Urine sample results for these samples showed that the areas under the curve for the 3 unique ProCaM Test Kit lots were equivalent (0.72, 0.74, 0.75, p &gt; 0.263). Using the result categories of negative and positive with identical cutoffs for GSTP1, RARß2, APC for samples with &gt;5 ssDNA copies 98% concordance was observed for all 3 lots evaluated. Conclusions: The investigational assay produces a qualitative result without the requirement for normalization or sample dilution and requires only one reaction per patient sample. Current results demonstrate that the assay has a high informative test rate and that results are reproducible across sites, operators runs, and kit lots. [Table: see text]
Abstract 19379: Red Blood Cell Washing Increases Kidney Injury in Cardiac Surgery Patients - The Role of Oxidised Lipids and Oxidative Stress
Authors: Marcin J Wozniak, Nikol Sullo, Saqib Qureshi, Nishith Patel, Dott Will, Pia Nielsen, Tracy Kumar, Lathishia Joel-David, Michael Wiltshire, Rebecca Cardigan, Gavin Murphy
Journal: Circulation (2015)

Introduction: Allogeneic red blood cell (RBC) transfusion in cardiac surgery patients increases the risk of pulmonary and renal morbidity. These associations are attributable to the ‘storage lesion’ - accumulation of metabolites in the RBC supernatant that includes pro-inflammatory lipids, cell-free hemoglobin and energy depletion. Hypothesis: Storage lesion components trigger different events that lead to organ injury. Reducing storage lesion by RBC washing or rejuvenation will reduce organ injury. Methods: Samples from 60 cardiac patients participating in a randomized controlled trial of RBC washing prior to transfusion versus standard care were analysed for inflammatory markers. In a complementary experiment, 4 groups of pigs received crystalloid infusion or 14-day old RBC that were left untreated, washed or rejuvenated (Rejuvesol, Citra Labs, IN). Inflammatory markers, free hemoglobin and iron were measured in blood. Leukocyte invasion was determined by immunohistochemistry. The results were verified and further analysed in an in vitro inflammatory model. Results: Transfusion of stored RBC (~22 days) into humans or pigs was associated with leukocyte activation, and attenuated by washing. That was attributed to oxidised lipids on transfused RBC derived microvesicles that activated monocytes and platelets, as revealed in depletion experiments. Unexpectedly, transfusion of washed RBC increased kidney injury, which correlated with higher free haemoglobin levels, oxidative stress (confirmed by HMOX-1 levels and protein carbonylation), and endothelial injury in washed RBC recipients. Oxidative stress triggered non-standard endothelial activation defined by expression of VLA5 and fibronectin retention. Either pathway was reduced when rejuvenated blood was transfused. Conclusion: Monocytes/platelets and endothelium are activated by oxidized lipids/MV and reactive free haem, respectively, and can be alleviated by RBC rejuvenation.
Allergic sensitization at school age is a systemic low‐grade inflammatory disorder
Authors: B. L. Chawes, J. Stokholm, A.‐M. M. Schoos, N. R. Fink, S. Brix, H. Bisgaard
Journal: Allergy (2016)

Systemic low-grade inflammation has been demonstrated in a range of the frequent noncommunicable diseases (NCDs) proposing a shared mechanism, but is largely unexplored in relation to allergic sensitization. We therefore aimed to investigate the possible association with childhood allergic sensitization.High-sensitivity C-reactive protein (hs-CRP), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and chemokine (C-X-C motif) ligand 8 (CXCL8) were measured in plasma at age 6 months (N = 214) and 7 years (N = 277) in children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000 ) birth cohort. Allergic sensitization against common inhalant and food allergens was determined longitudinally at ages ½, 1½, 4 and 6 years by specific IgE assessments and skin prick tests. Associations between inflammatory biomarkers and sensitization phenotypes were tested with logistic regression and principal component analyses (PCAs).Adjusted for gender, recent infections, and a CRP genetic risk score, hs-CRP at 7 years was associated with concurrent elevated specific IgE against any allergen [adjusted OR (aOR) = 1.40; 95% CI, 1.14-1.72; P = 0.001], aeroallergens (aOR, 1.43; 1.15-1.77; P = 0.001), food allergens (aOR, 1.31; 95% CI, 1.02-1.67; P = 0.04), sensitization without any clinical allergy symptoms (aOR = 1.40; 1.06-1.85; P = 0.02), and with similar findings for skin prick tests. The other inflammatory markers were not univariately associated with sensitization, but multiparametric PCA suggested a specific inflammatory response among sensitized children. Inflammatory markers at age 6 months were not associated with subsequent development of sensitization phenotypes.Elevated hs-CRP is associated with allergic sensitization in school-aged children suggesting systemic low-grade inflammation as a phenotypic characteristic of this early-onset NCD.
PEG-Interferon for Chronic Phase CML - Still an Option in the Era of Imatinib?.
Authors: Christof Scheid, Andreas Draube, Udo Holtick, Oliver Cornely, Ulrich Hacker, Michael Fuchs, Ute Berger, Andreas Hochhaus, Rüdiger Hehlmann, Michael Hallek
Journal: Blood (2004)