tbuckley/cabot-search huggingface dataset:
Clinical impact of 22C3 PD-L1 expression in non-small cell lung cancer.
Authors: Naoyuki Okabe, Hironori Takagi, Hiroyuki Suzuki
Journal: Journal of Clinical Oncology (2018)

149 Background: Immune checkpoint inhibitors has been widely applied in the field of non-small cell lung cancer (NSCLC). Immunostaining of PD-L1 using 22C3 was carried out as a companion diagnosis for Pembrolizumab. To date, only PD-L1 expression thought to be a predictive biomarker approved in USA and JAPAN. However, clinical impact or characteristic of PD-L1 expression in NSCLC is still controversial. In this report, we tried to analyze the relationship between PD-L1 expression and clinic-pathological parameter in NSCLC. Methods: A total 110 of NSCLC samples (Biopsy tissue and surgical resection specimen) were stained with PD-L1 IHC assays by using 22C3 antibody. The expression rate of PD-L1 was examined and relationship between the PD-L1 expression and clinicopathological factors was statistically analyzed. Results: The frequency of Tumor Proportion Score (TPS) less than 1% was 50%, TPS 1 to 49% was 32.7% and TPS 50% or more was 19%. Compared with the previous clinical trials such as KEYNOTE 001 and the KEYNOTE 010, our data of positivity tended to be low. In comparison between histological subtype, the expression in squamous cell carcinoma was higher than non-squamous histology. Furthermore, in relation to smoking history, higher smoking subgroup tended to be higher than the group with low smoking subset. In addition, the specimen preserved for 3 years or longer had a low positive rate, suggesting the possibility of false negatives due to long term formalin fixation of tissue specimens. Conclusions: We examined the relationship between the expression rate of PD-L1 and clinicopathological factors in 110 tissue samples subjected to PD-L1 staining by 22C3 at our hospital. Our results consistent with recent previous studies. In considering to analyze the archived tissue, we recommend that more fresh sample should be use for PD-L1 testing.
Detection rates of bone erosions and estimation of erosion volume by ultrasonography in rheumatoid arthritis: A comparison with computed tomography
Authors: Uffe Døhn, Lene Terslev, Marcin Szkudlarek, Merete Lund Hetland, Michael Sejer Hansen, Annette Hansen, Ole Rintek Madsen, Maria Hasselquist, Jakob Møllenbach Møller, Mikkel Østergaard
Journal: Annals of the Rheumatic Diseases (2010)
A Novel Method for Rapid Molecular Subgrouping of Medulloblastoma
Authors: Soledad Gómez, Alícia Garrido-Garcia, Laura Garcia-Gerique, Isadora Lemos, Mariona Suñol, Carmen de Torres, Marta Kulis, Sara Pérez-Jaume, Ángel M. Carcaboso, Betty Luu, Mark W. Kieran, Nada Jabado, Alexey Kozlenkov, Stella Dracheva, Vijay Ramaswamy, Volker Hovestadt, Pascal Johann, David T.W. Jones, Stefan M. Pfister, Andrés Morales La Madrid, Ofelia Cruz, Michael D. Taylor, Jose-Ignacio Martin-Subero, Jaume Mora, Cinzia Lavarino
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The classification of medulloblastoma into WNT, SHH, group 3, and group 4 subgroups has become of critical importance for patient risk stratification and subgroup-tailored clinical trials. Here, we aimed to develop a simplified, clinically applicable classification approach that can be implemented in the majority of centers treating patients with medulloblastoma. Experimental Design: We analyzed 1,577 samples comprising previously published DNA methylation microarray data (913 medulloblastomas, 457 non-medulloblastoma tumors, 85 normal tissues), and 122 frozen and formalin-fixed paraffin-embedded medulloblastoma samples. Biomarkers were identified applying stringent selection filters and Linear Discriminant Analysis (LDA) method, and validated using DNA methylation microarray data, bisulfite pyrosequencing, and direct-bisulfite sequencing. Results: Using a LDA-based approach, we developed and validated a prediction method (EpiWNT-SHH classifier) based on six epigenetic biomarkers that allowed for rapid classification of medulloblastoma into the clinically relevant subgroups WNT, SHH, and non-WNT/non-SHH with excellent concordance (&amp;gt;99%) with current gold-standard methods, DNA methylation microarray, and gene signature profiling analysis. The EpiWNT-SHH classifier showed high prediction capacity using both frozen and formalin-fixed material, as well as diverse DNA methylation detection methods. Similarly, we developed a classifier specific for group 3 and group 4 tumors, based on five biomarkers (EpiG3-G4) with good discriminatory capacity, allowing for correct assignment of more than 92% of tumors. EpiWNT-SHH and EpiG3-G4 methylation profiles remained stable across tumor primary, metastasis, and relapse samples. Conclusions: The EpiWNT-SHH and EpiG3-G4 classifiers represent a new simplified approach for accurate, rapid, and cost-effective molecular classification of single medulloblastoma DNA samples, using clinically applicable DNA methylation detection methods. Clin Cancer Res; 24(6); 1355–63. ©2018 AACR.
WORSENING TRICUSPID REGURGITATION ASSOCIATED WITH PERMANENT PACEMAKER AND IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IMPLANTATION: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Saed Alnaimat, Muhammad Khan, Muhammad Shariq Usman, Tariq Jamal Siddiqi, Sajjad Raza, Bilal Munir, Ankur Kalra
Journal: Journal of the American College of Cardiology (2018)
False Information About Breast Cancer Screening
Authors: Jay A. Baker
Journal: JAMA Internal Medicine (2018)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Prediction of Chemotherapeutic Efficacy in Non–Small Cell Lung Cancer by Serum Metabolomic Profiling
Authors: Yanhua Tian, Zhijie Wang, Xiaohui Liu, Jianchun Duan, Guoshuang Feng, Yuxin Yin, Jin Gu, Zhaoli Chen, Shugeng Gao, Hua Bai, Rui Wan, Jun Jiang, Jia Liu, Cong Zhang, Di Wang, Jiefei Han, Xue Zhang, Liangliang Cai, Jie He, Jie Wang
Journal: Clinical Cancer Research (2018)

Purpose: No validated biomarkers that could identify the subset of patients with lung adenocarcinoma who might benefit from chemotherapy have yet been well established. This study aimed to explore potential biomarker model predictive of efficacy and survival outcomes after first-line pemetrexed plus platinum doublet based on metabolomics profiling.Experimental Design: In total, 354 consecutive eligible patients were assigned to receive first-line chemotherapy of pemetrexed in combination with either cisplatin or carboplatin. Prospectively collected serum samples before initial treatment were utilized to perform metabolomics profiling analyses under the application of LC/MS-MS. Binary logistic regression analysis was carried out to establish discrimination models.Results: There were 251 cases randomly sorted into discovery set, the rest of 103 cases into validation set. Seven metabolites including hypotaurine, uridine, dodecanoylcarnitine, choline, dimethylglycine, niacinamide, and l-palmitoylcarnitine were identified associated with chemo response. On the basis of the seven-metabolite panel, a discriminant model according to logistic regression values g(z) was established with the receiver operating characteristic curve (AUC) of 0.912 (Discovery set) and 0.909 (Validation set) in differentiating progressive disease (PD) groups from disease control (DC) groups. The median progression-free survival (PFS) after chemotherapy in patients with g(z) ≤0.155 was significantly longer than that in those with g(z) > 0.155 (10.3 vs.4.5 months, P < 0.001).Conclusions: This study developed an effective and convenient discriminant model that can accurately predict the efficacy and survival outcomes of pemetrexed plus platinum doublet chemotherapy prior to treatment delivery. Clin Cancer Res; 24(9); 2100-9. ©2018 AACR.
Alachlor Use and Cancer Incidence in the Agricultural Health Study: An Updated Analysis
Authors: Catherine C Lerro, Gabriella Andreotti, Stella Koutros, Won Jin Lee, Jonathan N Hofmann, Dale P Sandler, Christine G Parks, Aaron Blair, Jay H Lubin, Laura E Beane Freeman
Journal: JNCI Journal of the National Cancer Institute (2018)

The herbicide alachlor has been widely used in US agriculture since its introduction in 1969. Experimental animal studies show that alachlor causes tumors in vivo; however, few epidemiologic studies have examined associations with human cancer risk. We evaluated alachlor use and cancer incidence in the Agricultural Health Study, updating an earlier analysis that suggested associations with lymphohematopoietic cancers with an additional 540 142 person-years of follow-up and 5113 cancer cases.Pesticide applicators in Iowa and North Carolina reported lifetime alachlor use at enrollment (1993-1997) and follow-up (1999-2005). Exposure was characterized by cumulative intensity-weighted days. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using Poisson regression for incident cancers from enrollment through 2012(NC)/2013(IA). Models adjusted for age, tobacco, alcohol, and other pesticides. All statistical tests are two-sided.Among 49 685 applicators, 25 640 (51.6%) used alachlor, with 3534 alachlor-exposed cancers. The relative risks of laryngeal cancer (nexposed = 34) increased in the second (RR = 4.68, 95% CI = 1.95 to 11.23), third (RR = 6.04, 95% CI = 2.44 to 14.99), and fourth quartiles (RR = 7.10, 95% CI = 2.58 to 19.53) of intensity-weighted days of use compared with no use (Ptrend = .001). Risk of myeloid leukemia was elevated, though not statistically significantly so, in the fourth quartile of intensity-weighted days of use (RR = 1.82, 95% CI = 0.85 to 3.87, Ptrend = .17).We observed a strong positive association with use of alachlor and laryngeal cancer and a weaker association with myeloid leukemia. The strength and robustness of the association with laryngeal cancer suggests that long-term occupational exposure to alachlor may be a risk factor for laryngeal cancer. This first report requires confirmation.
Constitutively active follicle-stimulating hormone receptor enables androgen-independent spermatogenesis
Authors: Olayiwola O. Oduwole, Hellevi Peltoketo, Ariel Poliandri, Laura Vengadabady, Marcin Chrusciel, Milena Doroszko, Luna Samanta, Laura Owen, Brian Keevil, Nafis A. Rahman, Ilpo T. Huhtaniemi
Journal: Journal of Clinical Investigation (2018)

Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process is considered impossible without the absolute requirement of LH-stimulated testicular testosterone (T) production. The role of FSH remains unclear because men and mice with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the role of FSH in spermatogenesis using transgenic mice expressing a constitutively strongly active FSHR mutant in a LH receptor–null (LHR-null) background. The mutant FSHR reversed the azoospermia and partially restored fertility of Lhr–/– mice. The finding was initially ascribed to the residual Leydig cell T production. However, when T action was completely blocked with the potent antiandrogen flutamide, spermatogenesis persisted. Hence, completely T-independent spermatogenesis is possible through strong FSHR activation, and the dogma of T being a sine qua non for spermatogenesis may need modification. The mechanism for the finding appeared to be that FSHR activation maintained the expression of Sertoli cell genes considered androgen dependent. The translational message of our findings is the possibility of developing a new strategy of high-dose FSH treatment for spermatogenic failure. Our findings also provide an explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs; LH/T deficiency with persistent spermatogenesis) and explain how the hormonal regulation of spermatogenesis has shifted from FSH to T dominance during evolution.
Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT)
Authors: Richard D. Carvajal, Sophie Piperno-Neumann, Ellen Kapiteijn, Paul B. Chapman, Stephen Frank, Anthony M. Joshua, Josep M. Piulats, Pascal Wolter, Veronique Cocquyt, Bartosz Chmielowski, T.R. Jeffry Evans, Lauris Gastaud, Gerald Linette, Carola Berking, Jacob Schachter, Manuel J. Rodrigues, Alexander N. Shoushtari, Delyth Clemett, Dana Ghiorghiu, Gabriella Mariani, Shirley Spratt, Susan Lovick, Peter Barker, Elaine Kilgour, Zhongwu Lai, Gary K. Schwartz, Paul Nathan
Journal: Journal of Clinical Oncology (2018)

Purpose Uveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial. Methods The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial ( ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m
Abstract P2-05-03: Novel driver genetic alterations in <i>MYB-NFIB</i>-negative breast adenoid cystic carcinomas
Authors: J Kim, FC Geyer, LG Martelotto, CKY Ng, RS Lim, P Selenica, A Li, F Pareja, N Fusco, M Edelweiss, O Mariani, S Badve, A Vincent-Salomon, L Norton, JS Reis-Filho, B Weigelt
Journal: Cancer Research (2018)

Abstract Introduction: Breast adenoid cystic carcinoma (AdCC) is a rare type of triple-negative breast cancer associated with an indolent clinical behavior. AdCCs provide a clear example of genotypic-phenotypic correlation with the majority harboring the MYB-NFIB fusion gene. In this study, we sought to identify alternative driver genetic alterations in breast AdCCs lacking the MYB-NFIB fusion gene. Methods: Nucleic acids obtained from four breast AdCCs lacking the MYB-NFIB fusion gene as defined by reverse transcription (RT)-PCR and/or fluorescence in situ hybridization (FISH) were subjected to RNA-sequencing (n=3), whole-genome (n=2) and/or targeted (n=1) massively parallel sequencing. Sequencing data were analyzed using state-of-the-art bioinformatics algorithms, and potential alternative driver genetic alterations were validated using orthogonal sequencing and molecular pathology methods. Results: RNA-sequencing revealed the presence of MYBL1-ACTN1 or MYBL1-NFIB fusion genes in two breast AdCCs, which were validated by whole-genome sequencing and/or MYBL1 FISH analysis. Both MYBL1 fusion gene-positive cases were found to overexpress MYBL1 as defined by quantitative RT-PCR analysis. In the third MYB-NFIB-negative breast AdCC studied, a high-level MYB gene amplification coupled with overexpression of MYB at the mRNA and protein levels was identified. In the fourth breast AdCC, which expressed high levels of MYB, whole-genome and RNA-sequencing revealed no definite alternative driver alteration, however, a MYBL2 intronic mutation was found in this case, which was associated with high levels of MYBL2 mRNA expression. In this case, single sample gene set enrichment analysis revealed activation of pathways similar to those activated in AdCCs harboring the MYB-NFIB or MYBL1 fusions genes. Conclusion: We demonstrate that in breast AdCCs lacking the MYB-NFIB fusion gene MYBL1 rearrangements and MYB amplification are likely alternative driver genetic events. Given that activation of MYB/MYBL1 and their downstream targets can be driven by the MYB-NFIB fusion gene, MYBL1 rearrangements, MYB amplification or other yet to be validated mechanisms (e.g. MYBL2 non-coding mutations), our findings further suggest that breast AdCCs constitute a convergent phenotype. Citation Format: Kim J, Geyer FC, Martelotto LG, Ng CKY, Lim RS, Selenica P, Li A, Pareja F, Fusco N, Edelweiss M, Mariani O, Badve S, Vincent-Salomon A, Norton L, Reis-Filho JS, Weigelt B. Novel driver genetic alterations in MYB-NFIB-negative breast adenoid cystic carcinomas [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-05-03.
New polymyxin derivatives that display improved efficacy in animal infection models as compared to polymyxin B and colistin
Authors: Martti Vaara
Journal: Medicinal Research Reviews (2018)

Abstract Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram‐negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. The discovery of both polymyxin B and colistin was published independently by three laboratories as early as in 1947. They were subsequently used in intravenous therapy. Unfortunately, they also exhibit significant and dose‐limiting nephrotoxicity. Therefore, polymyxins were reserved as agents of last‐line defense. The emergence of extremely multiresistant strains has now forced clinicians to reinstate polymyxins in the therapy of severe infections. However, the current dosage regimens lead to insufficient drug concentrations in serum and clinicians have been advised to use larger doses, which further increases the risk of nephrotoxicity. Very recently, the interest in developing better tolerated and more effective polymyxins has grown. This review focuses on describing four development programs that have yielded novel derivatives that are more effective than the old polymyxins in animal infection models. Compounds from three programs are superior to the old polymyxins in the rodent lung infection model with Acinetobacter baumannii and/or Pseudomonas aeruginosa . One of them is also more effective than polymyxin B in A. baumannii mouse thigh infection. The fourth program includes compounds that are approximately tenfold more effective in Escherichia coli murine pyelonephritis than polymyxin B.
Activity of third line (3L) therapy in patients with metastatic non-clear-cell renal cell carcinoma (mnccRCC).
Authors: Annalisa Guida, Gwénaël Le Teuff, Emeline Colomba, Carolina Alveosta Silva, Flore Salviat, Giulia Baciarello, Lisa Derosa, Yohann Loriot, Karim Fizazi, Mario Di Palma, Christophe Massard, Bernard Escudier, Laurence Albiges
Journal: Journal of Clinical Oncology (2018)

650 Background: Medical treatment of patients (pts) with mnccRCC remains uncertain, with no established standard treatment. In addition, no data on late line of treatment have been reported. The aim of this study was to investigate clinical outcome for patients receiving 3L therapy in mnccRCC Methods: Retrospective data analysis was performed using the IGRECC (Institut Gustave Roussy REnal Cell Carcinoma) database to describe clinical features and outcomes of 3L therapy in mnccRCC pts. Kaplan Meier estimation was applied for progression-free survival (PFS) and overall survival (OS) Results: Out of all pts with mRCC treated with a targeted therapy from 2005 to 2016, 202/1027 (20%) had mnccRCC. 117 (58%) received 2L therapy and 62 (30%) received 3L therapy. These pts had papillary RCC (61%), unclassified RCC (19), Xp11translocation renal cell carcinoma (13%) and chromophobe tumors (7%). The most common 3L therapies were: everolimus (29%), sorafenib (18%), other drugs in clinical trials (16%), sunitinib (11%), axitinib (10%) and cabozantinib (10%). Baseline characteristics are displayed in Table 1. With a median follow-up of 47 months (mo) (min: 0.7 max: 74), the median PFS is 5 mo (95%CI 2.7 - 5.8) and the median OS is 11.7 mo (95%CI 10 - 20). Pts with a favourable, intermediate and poor risk International Metastatic Renal Cell Cancer Database Consortium (IMDC) score had a median OS of 21 mo (95%CI 8 – NR), 11.9 mo (95%CI 10 – 25), and 6.2 mo (95%CI 2 – 8), respectively (p &lt; 0.0001). One patient (2%) obtained a partial response and 26 pts (51%) achieved a stable disease, among 51 evaluable pts Conclusions: This is the first report investigating the impact of 3L systemic therapy in a rare population. Selected pts could benefit of more lines of therapy and IMDC score appears to stratify well prognostic groups, especially poor risk patients. [Table: see text]
High-Sensitivity Troponins and Outcomes After Myocardial Infarction
Authors: Maria Odqvist, Per-Ola Andersson, Hans Tygesen, Kai M. Eggers, Martin J. Holzmann
Journal: Journal of the American College of Cardiology (2018)

It remains unknown how the introduction of high-sensitivity cardiac troponin T (hs-cTnT) has affected the incidence, prognosis, and use of coronary angiographies and revascularizations in patients with myocardial infarction (MI). The aim of this study was to investigate how the incidence of MI and prognosis after a first MI was affected by the introduction of hs-cTnT. In a cohort study, the authors included all patients with a first MI from the Swedish National Patient Registry from 2009 to 2013. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for risk of all-cause mortality, reinfarction, coronary angiographies, and revascularizations in patients with MI diagnosed using hs-cTnT compared with those diagnosed using conventional troponins (cTn). During the study period, 47,133 MIs were diagnosed using cTn and 40,746 using hs-cTnT. The rate of MI increased by 5% (95% CI: 0% to 10%) after the introduction of hs-cTnT. During 3.9 ± 2.8 years of follow-up, there were 33,492 deaths, with no difference in the risk of all-cause mortality (adjusted HR: 1.00; 95% CI: 0.97 to 1.02). There were, in total, 15,766 reinfarctions during 3.1 ± 2.3 years of follow-up, with the risk of reinfarction reduced by 11% in patients diagnosed using hs-cTnT (adjusted HR: 0.89; 95% CI: 0.86 to 0.91). The use of coronary angiographies (adjusted HR: 1.16; 95% CI: 1.14 to 1.18) and revascularizations (adjusted HR: 1.13; 95% CI: 1.11 to 1.15) increased in the hs-cTnT group. In a nationwide cohort study including 87,879 patients with a first MI, the introduction of hs-cTnT was associated with an increased incidence of MI, although with no impact on survival. We also found a reduced risk of reinfarction alongside increased use of coronary angiographies and revascularizations.