tbuckley/cabot-search huggingface dataset:
Molecular profiling of EGFR pathway according to location of colorectal cancer (CRC): Analysis of 1,001 patients in single institute.
Authors: Eiji Shinozaki, Yoshio Miki, Masashi Ueno, Masahiro Igarashi, Mitsukuni Suenaga, Keisho Chin, Masato Ozaka, Mariko Ogura, Toshiharu Yamaguchi, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2014)

3597 Background: Location of colon cancer (right-sided versus left-sided) was reported as a predictor of benefit from cetuximab in the subanalysis of NCIC CTG CO.17 trial. On the other hand, retrospective analyses have identified KRAS including codon61, codon146, BRAF, NRAS, or PIK3CA mutations as potentially negative predictive factors for anti EGFR treatments. This analysis aimed to reveal the prevalence of these mutations in the EGFR pathway according to location of CRC in a large cohort. Methods: Consecutive patients of 1,001 CRC from January 2012 to October 2013 were analyzed in this study. Multiplex genotyping of EGFR pathway was performed on archival samples using Luminex Assay (MABGEN and GENOSEARCH Mu-PACK, MBL) for KRAS including codons 61 and 146, BRAF, NRAS, and PIK3CA. We examined the correlation among mutation profile, clinical data and location of CRC. Statistical analysis was conducted by chi-square test. Results: The incidence of mutations; KRAS codon12 and 13, codon61 and 146, BRAF, NRAS and PIK3CA were 38%, 4.6%, 5.1%, 3.5% and 9.1%, respectively. So called all RAS mutations accounted for 47% in this cohort. The difference of prevalence according to the location of CRC was confirmed in KRAS codon 12 and 13, BRAF. The respective proportion of mutations were 55.9%, 14% for right sided(R), 30.6%, 5.5% for left sided(L), 37.2%, 1% for rectal(RC) CRC (KRAS: R vs L, RC P<0.01, BRAF: R vs L vs RC P<0.01). Conclusions: According to the location of CRC the incidence of KRAS codon 12 and 13, BRAF mutation were different. Increased BRAF mutation in R ,which was strong negative prognostic factor could affect unfavorable outcome of anti EGFR treatment.
Designing image segmentation studies: Statistical power, sample size and reference standard quality
Authors: Eli Gibson, Yipeng Hu, Henkjan J. Huisman, Dean C. Barratt
Journal: Medical Image Analysis (2017)

Segmentation algorithms are typically evaluated by comparison to an accepted reference standard. The cost of generating accurate reference standards for medical image segmentation can be substantial. Since the study cost and the likelihood of detecting a clinically meaningful difference in accuracy both depend on the size and on the quality of the study reference standard, balancing these trade-offs supports the efficient use of research resources. In this work, we derive a statistical power calculation that enables researchers to estimate the appropriate sample size to detect clinically meaningful differences in segmentation accuracy (i.e. the proportion of voxels matching the reference standard) between two algorithms. Furthermore, we derive a formula to relate reference standard errors to their effect on the sample sizes of studies using lower-quality (but potentially more affordable and practically available) reference standards. The accuracy of the derived sample size formula was estimated through Monte Carlo simulation, demonstrating, with 95% confidence, a predicted statistical power within 4% of simulated values across a range of model parameters. This corresponds to sample size errors of less than 4 subjects and errors in the detectable accuracy difference less than 0.6%. The applicability of the formula to real-world data was assessed using bootstrap resampling simulations for pairs of algorithms from the PROMISE12 prostate MR segmentation challenge data set. The model predicted the simulated power for the majority of algorithm pairs within 4% for simulated experiments using a high-quality reference standard and within 6% for simulated experiments using a low-quality reference standard. A case study, also based on the PROMISE12 data, illustrates using the formulae to evaluate whether to use a lower-quality reference standard in a prostate segmentation study.
Abstract 15652: Cholesterol Uptake Capacity, a Novel Measure of High Density Lipoprotein Functionality for Coronary Risk Stratification
Authors: Amane Harada, Ryuji Toh, Katsuhiro Murakami, Maria Kiriyama, Keiko Yoshikawa, Takuya Kubo, Keiko Miwa, Yasuhiro Irino, Kenta Mori, Nobuaki Tanaka, Tatsuro Ishida, Ken-ichi Hirata
Journal: Circulation (2016)

Introduction: Recent studies have shown that the capacity of high-density lipoprotein (HDL) to stimulate cholesterol efflux from lipid-laden macrophages is a better predictor of cardiovascular dise...
Selecting Patients With Thin Melanoma for Sentinel Lymph Node Biopsy—This Time It’s Personal
Authors: Vernon K. Sondak, Jane L. Messina, Jonathan S. Zager
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
Comment on “an endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of Kupffer cell polarization”
Authors: Shikun Yang, Jianhua Rao
Journal: Hepatology (2017)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. TO THE EDITOR: We read the article by Park et al.1, in which the authors suggest that Nogo‐B promotes M1 polarization of Kupffer cells (KCs), thereby increasing liver injury in alcoholic liver disease (ALD). The authors reported that Nogo‐B knockout ameliorated ethanol‐induced hepatic steatosis and injury by facilitating M2 polarization via accentuating endoplasmic reticulum (ER) stress. This study greatly enhanced our understanding of the association between Nogo‐B and ALD. However, we have some questions about expressions of cytokines in ER‐stressed macrophages treated with lipopolysaccharide (LPS) and effects of chop on M2 polarization of KCs. Park et al. reported that tunicamycin (TM) decreased expressions of proinflammatory cytokines (e.g., tumor necrosis factor α [TNF‐α], interleukin‐1β, and inducible nitric oxide synthase) in macrophages after LPS treatment compared with that just treated with LPS.1 Contrary to this result, we found that macrophages pretreated with TM, followed by LPS treatment, may produce higher levels of proinflammatory cytokines (e.g., TNF‐α and interleukin‐6) than those merely treated with LPS.2 Moreover, other studies have shown that TM enhances the inflammatory responses induced by LPS in macrophages.3 Consequently, we suggest that chemical‐induced ER stress may exhibit proinflammatory effects on macrophages; as such, the inflammatory responses induced with LPS in TM‐stimulated macrophages need to be confirmed further. The data reported by Park et al. showed that Nogo‐B knockdown significantly increased expression of C/EBP homologous protein (CHOP) in macrophages in response to TM; therefore, the authors suggest that Nogo‐B knockdown facilitates M2 polarization by ER stress/CHOP signaling. CHOP, a proapoptotic factor produced by unresolved ER stress, actually promoted cell apoptosis.4 Once cells were apoptotic, they released damage‐associated molecular patterns, which in turn initiated sterile inflammation and enhanced proinflammatory M1 polarization. In fact, previous studies have indicated that ER stress suppresses alternative activation of macrophages and M2 polarization in the adipose tissue.5 Thus, we question whether ER stress facilitates M2 polarization. We agree with the authors’ conclusion that Nogo‐B worsens ALD by promoting M1 polarization and inhibiting M2 polarization. However, further studies are required to confirm that Nogo‐B mediated ER stress facilitates M2 polarization and suppresses M1 polarization.
cIAP2 is a K63 ubiquitin ligase for RIP1 which is blocked by IAP BIR antagonists during death receptor-mediated apoptosis
Authors: Philip Barker, Mathieu Bertrand, Snezana Mulitinovic, Kathleen Dickson, Wai Chi Ho, Stephen Morris, James Jaquith, Alain Boudreault, Jon Durkin, John Gillard
Journal: Cancer Research (2008)

1557  The inhibitor of apoptosis proteins (IAPs) are important regulators of cell death in cancer and overexpression of various IAPs predicts poor patient outcome in several types of malignancy. The best-studied IAP is X-linked IAP (XIAP), which directly inhibits caspase-3, caspase-7 and caspase-9. Interestingly, other IAPs do not appear to directly block caspase activity and therefore the precise pro-survival mechanisms used by these family remains uncertain. Smac is a mitochondrial protein that, once released into the cytosol, binds to a groove in the IAP BIR3 domain present in XIAP, cIAP1 and cIAP2. The interaction of Smac with XIAP releases inhibition of caspase-9 and the N-terminal stretch of four residues in Smac that binds the BIR3 domain, AVPI, has served as a structural template for the development of XIAP antagonists.  In this study, we demonstrate that AEG40730, a bridged AVPI mimetic, which binds IAP BIR3 domains with nM affinity, causes profound apoptotic sensitization to death ligands. In some cancer cell lines, treatment with AEG40730 alone results in caspase-8 dependent apoptosis and we show that this occurs through activation of a TNFα autocrine loop. RIP1 is a cytosolic adaptor protein that functions downstream of the TNF receptor which has emerged as a key element regulating apoptotic and survival signaling pathways. We show that RIP1 is constitutively ubiquinated in cancer cells and that AEG40730 treatment, by eliminating cIAP2, abolishes RIP1 ubiquination and thereby facilitates RIP1-dependent caspase-8 activation and cell death. We demonstrate that cIAP2 normally inhibits caspase-8 activation in cancer cells by functioning as an E3 ubiquitin ligase that directly mediates K63 polyubiquitin chain production on RIP1. Thus, RIP1 plays a crucial role in death receptor signaling and its switch from a pro-survival to a pro-apoptotic function is regulated via K63 ubiquitination that is induced by cIAP2. These findings provide new insights into the function of the IAPs and open new therapeutic opportunities in the treatment of cancer.   * These authors contributed equally to this project. This work was supported by a grant from the Canadian Institute of Health Research (CIHR) to PAB.
Prospective validation of a prognostic gene-ratio test for patients undergoing multimodality therapy for malignant pleural mesothelioma (MPM)
Authors: Lingsheng Dong, Gavin Gordon, Madhubalan Mani, Beow Yeap, William Richards, David Sugarbaker, Raphael Bueno
Journal: Clinical Cancer Research (2007)

B23  Rationale: MPM is a highly aggressive asbestos associated pleural malignancy recalcitrant to most therapies. Some MPM patients benefit from aggressive surgical resection followed by chemoradiation; yet, many others succumb within a few months of therapy. To better assign therapy, we developed a prognostic test based on the ratios of 4 gene expression levels to translate complex gene expression profiling data into simple tests for the prognosis of MPM (J Natl Cancer Inst, 95:598-605, 2003). We examined the efficacy of this test in a prospective clinical trial.  Methods: Tumors were collected from prospectively consented MPM patients (n=160) at the time of surgery (extrapleural pneumonectomy n=120, pleurectomy n=40) and linked to clinical data. Quantitative RT-PCR was used to measure relative expression levels of 4 genes (KIAA0977, GDIA1, L6, CTHBP) and calculate the geometric mean (GM) of 3 gene pair ratios (KIAA0977/GDIA1, L6/CTHBP, L6/GDIA1) to assign patients to a good (GM >1) or poor (GM
Predictors of mortality in Middle East respiratory syndrome (MERS)
Authors: Ki-Ho Hong, Jae-Phil Choi, Seon-Hui Hong, Jeewon Lee, Ji-Soo Kwon, Sun-Mi Kim, Se Yoon Park, Ji-Young Rhee, Baek-Nam Kim, Hee Jung Choi, Eui-Cheol Shin, Hyunjoo Pai, Su-Hyung Park, Sung-Han Kim
Journal: Thorax (2017)

We evaluated the clinical characteristics, cytokine/chemokine concentrations, viral shedding and antibody kinetics in 30 patients with Middle East respiratory syndrome (MERS), including 6 non-survivors admitted to 3 MERS-designated hospitals. Old age, low albumin, altered mentality and high pneumonia severity index score at admission were risk factors for mortality. In addition, severe signs of inflammation at initial presentation (at hospital days 1-4), such as high inducible protein-10 (p=0.0013), monocyte chemoattractant protein-1 (p=0.0007) and interleukin 6 (p=0.0007) concentrations, and poor viral control (high viral load at hospital days 5–10, p&lt;0.001) without adequate antibody titres (low antibody titre at hospital days 11–16, p=0.07) during the course of disease, were associated with mortality.
Healthcare ratings among older cancer survivors.
Authors: Michael T. Halpern, Matthew Urato, Erin E. Kent
Journal: Journal of Clinical Oncology (2016)

10094 Background: Cancer survivors may experience unique challenges in receiving needed healthcare services. However, there is little information on individual-level factors influencing the experience of healthcare services among survivors. Methods: This study used healthcare ratings provided by cancer survivors in the Consumer Assessment of Healthcare Providers and Systems (CAHPS) Medicare Survey linked to data from NCI’s Surveillance, Epidemiology, and End Results (SEER) Program (SEER-CAHPS). CAHPS data on self-reported general and mental health status and five composite measures of experience with healthcare (customer service, doctor communications, getting care quickly, getting needed care, and getting prescription drugs) were linked to patient sociodemographic and cancer characteristics from SEER. Medicare beneficiaries diagnosed with cancer in SEER regions from 1997-2011 who participated in the CAHPS Medicare Survey at least one year after cancer diagnosis were included. The study included only individuals alive at least one year following CAHPS survey completion, at least age 66, and diagnosed with non-metastatic breast, colorectal, lung, or prostate cancer. Results: Among 23,969 cancer survivors with linked SEER-CAHPS data, higher self-rated general health was associated with higher ratings of care for all survivors except those diagnosed with lung cancer, while higher mental health predicted higher ratings among lung and prostate cancer survivors. Asian survivors generally provided lower ratings than did non-Hispanic White survivors. Among breast and prostate cancer survivors, fee-for-services Medicare (vs. Medicare advantage) was associated with lower customer service ratings but higher ratings for getting prescription drugs. Conclusions: Higher self-reported health status was frequently associated with improved experiences of care, but associations between other factors and healthcare rating varied. Interventions to improve general and mental health status of cancer survivors, such as increased access to palliative care services, may also improve their experience of care; however, efforts to enhance care for survivors need to be tailored to individual survivors’ characteristics.
Phase 1 dose-escalation study of BI 836909, an anti-BCMA bi-specific T-cell engager, in relapsed and/or refractory multiple myeloma (RRMM).
Authors: Max S. Topp, Michel Attal, Christian Langer, Philippe Moreau, Thierry Facon, Johannes Düll, Benjamin Hebraud, Carlos Gomez-Roca, Gerd Michael Munzert, Edith Gracien, Gerhard Zugmaier, Hermann Einsele
Journal: Journal of Clinical Oncology (2016)

TPS8067 Background: Myeloma is an incurable disease that typically follows a relapsing course, with many patients (pts) requiring multiple lines of therapy. Outcomes in RRMM remain poor, particularly after failure of proteasome inhibitor (PI)- and/or immunomodulatory drug (IMiD)-based treatment. There remains a need for novel, targeted therapies for RRMM. BI 836909, a bi-specific T-cell engager (BiTE) that binds CD3ε on T-cells and BCMA on plasma cells, has demonstrated anti-myeloma activity in preclinical models (Hipp et al. ASH 2015; abs 2999). Here we report the design and objectives of the first in-human trial of BI 836909 – a multicenter, open-label, two-part, Phase 1, dose-escalation study evaluating intravenous (IV) and subcutaneous (SC) formulations of BI 836909 in RRMM. Methods: Adult pts with RRMM after ≥ 2 prior lines of therapy (including a PI and IMiD) and ECOG PS ≤ 2 are eligible. In part A, pts will receive escalating doses (modified 3+3 design) of BI 836909 as a continuous IV infusion for 4 weeks in 6-week cycles. Dose escalation will proceed based on clinical findings observed during the first 2–4 weeks of cycle 1. Pts will receive up to 5 cycles of treatment (up to 10 cycles for ongoing clinical benefit, at the investigator’s discretion) in the absence of disease progression, unacceptable toxicity, or other reasons necessitating withdrawal. Initiation of part B to assess SC BI 836909 will be based on clinical data from part A with the IV formulation. In part B, pts will receive escalating doses (3+3 design) of BI 836909 as a daily SC injection for 4 weeks in 6-week cycles, with stopping criteria as in part A. The primary objective of parts A and B is to determine the maximum tolerated dose of BI 836909 IV/SC for subsequent expansion cohorts. Secondary objectives include evaluation of safety (adverse events; effect on QTcF; immunogenicity), pharmacokinetics, efficacy, pharmacodynamics, and determination of recommended Phase 2 doses. As of 25 January 2016, 9 pts have enrolled in part A. The first four dose cohorts were safe and well tolerated. The study is expected to recruit approximately 100–120 pts in total. Clinical trial information: EudraCT 2014-004896-22.
Comparative Toxicity and Effectiveness of Trastuzumab-Based Chemotherapy Regimens in Older Women With Early-Stage Breast Cancer
Authors: Katherine E. Reeder-Hayes, Anne Marie Meyer, Sharon Peacock Hinton, Ke Meng, Lisa A. Carey, Stacie B. Dusetzina
Journal: Journal of Clinical Oncology (2017)

Purpose The combination of chemotherapy and trastuzumab is the standard of care for adjuvant treatment of human epidermal growth factor receptor 2-positive breast cancer. Two regimens have been widely adopted in the United States: doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab (ACTH) and docetaxel, carboplatin, and trastuzumab (TCH). No head-to-head comparison of these regimens has been conducted in a clinical trial, and existing trial data have limited generalizability to older patients. Methods We used SEER-Medicare data from 2005 to 2013 to compare outcomes of ACTH versus TCH among patients age older than 65 years. Propensity score matching was used to balance cohort characteristics between treatment arms. Outcomes included toxicity-related hospitalization, survival, and trastuzumab completion. Data from 1,077 patients receiving ACTH or TCH were analyzed, and the propensity-matched subsample included 416 women. Results There was a significant shift toward TCH over time, with 88% of patients receiving ACTH in 2005 compared with 15% by 2011. Among propensity score-matched patients, we found no difference between regimens in health care use overall or for chemotherapy-related adverse events (ACTH, 34% v TCH, 36.5%; P = .46). Patients receiving TCH were significantly more likely to complete trastuzumab (89% v 77%; P = .001). There was no difference in 5-year breast cancer-specific survival (ACTH, 92% v TCH, 96%; hazard ratio, 2.08; 95% CI, 0.90 to 4.82) or overall survival. Conclusion Among a matched sample of older patients, ACTH compared with TCH was not associated with a higher rate of serious adverse events or hospitalizations, but it was associated with less completion of adjuvant trastuzumab. We did not detect a difference in 5-year survival outcomes for ACTH compared with TCH. In the context of limited evidence in older patients, selection between these two regimens on the basis of concerns about differential toxicity or efficacy may not be appropriate.
Prolonged renal survival in light chain amyloidosis: speed and magnitude of light chain reduction is the crucial factor
Authors: Tamer Rezk, Helen J. Lachmann, Marianna Fontana, Sajitha Sachchithanantham, Shameem Mahmood, Aviva Petrie, Carol J. Whelan, Jennifer H. Pinney, Darren Foard, Thirusha Lane, Taryn Youngstein, Ashutosh D. Wechalekar, Paul Bass, Philip N. Hawkins, Julian D. Gillmore
Journal: Kidney International (2017)
The Epidemiology and Etiology of Human Bladder Cancer
Authors: Gilbert H. Friedell, M.D.
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article The Epidemiology and Etiology of Human Bladder Cancer Gilbert H. Friedell, M.D. Gilbert H. Friedell, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 43, Issue 1, July 1969, Pages 215–216, https://doi.org/10.1093/jnci/43.1.215 Published: 01 July 1969