tbuckley/cabot-search huggingface dataset:
Concordance study of <i>HER2</i> fluorescence in situ hybridization (FISH) assays in upper gastrointestinal (UGI) adenocarcinomas.
Authors: Michael F. Press, Tobias Grob, Andreas Marx, Ivonne Villalobos, Angela Santiago, Roberta Guzman, Robert C. Gagnon, Carmen Arenas-Elliott, Catherine Elizabeth Ellis
Journal: Journal of Clinical Oncology (2014)

4072^ Background: Patient inclusion to the primary efficacy population of TRIO-013/LOGiC trial of lapatinib in combination with chemotherapy in advanced HER2-positive UGI adenocarcinomas required evidence of HER2 gene amplification confirmed by central lab. As no HER2 tests were approved for use in UGI cancers at trial start, the HER2 FISH assay used in the 2 trial central labs was PathVysion. A study was conducted in a cohort of UGI adenocarcinomas to determine concordance of PathVysion HER2 FISH assay between the 2 central labs and concordance between PathVysion HER2 FISH and HER2 IQFISH pharmDx, an assay recently approved in UGI adenocarcinomas. Methods: 488 UGI adenocarcinoma cases, procured as formalin-fixed, paraffin-embedded blocks, were screened by HercepTest to ensure representation of 4 immunochemistry (IHC) staining intensities. All IHC3+ and 2+cases were included; IHC1+ and 0 cases were binned by primary tumor (gastric, gastro-esophageal junction [GEJ] and esophageal) then randomly selected. Selected cases were sent to 2 trial central labs for HER2 FISH testing, blinded to the IHC results. Overall acceptance criteria were predefined as positive percent agreement (PPA) and N (negative) PA of at least 90%. Results: 159 cases were selected: 31 IHC3+; 20 IHC2+; 55 IHC1+; 53 IHC0. Of the 159 cases, 105 were gastric, 35 GEJ and 19 esophageal adenocarcinomas. All 159 cases were tested by 1 central lab using both assays; the PPA (95% Confidence Interval [CI]) and NPA (95% CI) were 97.9% (89.1, 99.6) and 99.1% (94.8, 99.8), respectively. Preliminary analysis in 126 cases tested by both central labs resulted in PPA of 95.6% (85.2, 98.8) and NPA of 94.5% (86.7, 97.8). Majority of IHC1+/0 cases were HER2 non-amplified by both assays (89%) and in both central labs (89% versus 93%). Of the 31 IHC3+ cases, 2 were considered HER2 non-amplified; both exhibited heterogeneity in HER2 IHC staining: 1 case was HER2 non-amplified by 1 central lab for both assays, yet amplified by the other central lab; other case was HER2 non-amplified by PharmDx assay only. Conclusions: There was reasonably high level of concordance within laboratory for different HER2 FISH assays as well as between labs for the same HER2 FISH assay. Clinical trial information: NCT00680901.
Private sector should have same safety rigour as NHS, say surgeons after Paterson conviction
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The Royal College of Surgeons has called for a review of transparency and safety standards in the private sector after the conviction of Ian Paterson, a rogue breast surgeon.

Last month Paterson was found guilty of 17 counts of wounding with intent and three of unlawful wounding, after carrying out unnecessary operations.1 He is due to be sentenced at the end of May.

In an open letter published on Wednesday 17 May the president and vice presidents of the royal college sought to reassure the public …
WebArrayDB: A microarray database and analysis suite including cross-platform analysis
Authors: Xiao-Qin Xia, Michael McClelland, Xianling Cong, Yipeng Wang
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1650 

While cross-platform analysis is getting more popular, researchers still lack tools for storing, integrating and analyzing large numbers of microarray data sets with different platforms and from various sources. Building on WebArray (http://bioinformatics.skcc.org/webarray), an open source integrated microarray database and analysis suite (WebArrayDB) has been developed. In addition to allowing convenient uploading of data for storage in a MIAME (Minimal Information about a Microarray Experiment) compliant fashion, the suite allows projects to be mined with a large variety of R-based tools. In particular, differential analysis across multiple platforms and between experimental series are implemented. A variety of methods for probe alignment, normalization and statistical analysis can be applied to account for systematic bias. Probes (or probe sets for Affymetrix chips) from different platforms can be aligned based on either universal IDs, such as UniGene IDs, GenBank IDs, or user-defined IDs. For cross-platform normalization, in addition to the standard between-array normalization methods provided in the R/LIMMA package, we implemented the Median Rank Scores (MRS), Quantile Discretization (QD) and Gene Quantile (GQ). GQ is a method we developed, which is a quantile normalization of data from different platforms for each individual gene. Differential analysis can be performed using a t-test, non-parametric test, ANOVA or significance analysis of microarrays (SAM). The package was implemented on a LAMP system (a Linux server with Apache, MySQL and Python/Perl/PHP). The ability of WebArrayDB to maintain multiple databases and the flexibility of the database structure and software/hardware environment make it an ideal tool not only for individual researchers but also for research groups such as laboratories/cores or even bigger organizations. This software package can be obtained upon request from the authors. The tool has been applied to study the available public expression microarrays data sets of prostate cancer.
Impact of a risk model based on routine lab results on colorectal cancer screening in average risk population.
Authors: Shimon Ben Boursi, Ronac Mamtani, Kevin Haynes, Yu-Xiao Yang
Journal: Journal of Clinical Oncology (2015)

1567 Background: Risk scores for colorectal cancer (CRC) screening use limited variables and have low predictive values. We sought to develop and validate a novel CRC risk prediction model based on routinely available data from electronic medical records including laboratory results. Methods: We conducted a nested case-control study using a population-based database. The cohort was randomly divided into test and validation datasets. Cases were defined as those with a diagnostic code of CRC, aged 50-85. Subjects with CRC syndromes or IBD were excluded. For every case, 4 controls matched on practice site and duration of follow-up were selected using incidence-density sampling. Lifestyle parameters, medical history, medications, and lab results were examined as CRC risk factors using univariate conditional logistic regression. Variables with p-value < 0.25 were evaluated for the multivariate model, after correcting for linearity, using backward elimination. Discrimination ability was calculated using receiver operator curve (ROC). Goodness of fit was evaluated using the McFadden's R2. For the final model we calculated the net reclassification index (NRI) compared to a model including lifestyle parameters only. Results: Our study cohort included 45,498 subjects in the test set (n = 9,299 [20.44%] cases) and 22,490 subjects in the validation set (n = 4,580 [20.36%] cases). A multivariate model based on lifestyle parameters only (age, sex, height, obesity, ever smoking, alcohol dependence and previous screening colonoscopy) had an AUC of 0.58 (95%CI 0.57-0.59) with low goodness of fit. A model based on lab results only (hematocrit, MCV, lymphocytes and neutrophil to lymphocyte ratio [NLR]) had an AUC of 0.76 (95%CI 0.76-0.77) and a McFadden's R2 of 0.21 with a NRI of 47.6%. A combined model including sex, hemoglobin, MCV, white blood cells, platelets, NLR and medication prescriptions for oral hypoglycemics reached an AUC of 0.80 (95%CI 0.79-0.81) with a McFadden's R2 of 0.27 and a NRI of 60.7%. Similar results were shown in the validation set. Conclusions: A risk score based on sex, CBC, and medication use has good discriminating power for CRC risk in the average risk population.
Purified dry extract of <i>Paullinia cupana</i> (guaraná) (PC-18) for chemotherapy-related fatigue in patients with solid tumors: An early discontinuation study.
Authors: Adriana Braz del Giglio, Tatiana Goberstein Lerner, Henrique Soares Paiva, Renata Guise Soares Azevedo, Ricardo tuma Guariento, Cecilia Goldman, Bruno Carelli, Fernanda Schindler, Luiz Pianowski, Felipe Melo Cruz, Auro Del Giglio
Journal: Journal of Clinical Oncology (2013)

e20680 Background: Paullinia cupana (guaraná) is an Amazonian plant that has been previously shown to be effective in treating chemotherapy-related fatigue (CRF) in patients with breast cancer. We aimed to evaluate the efficacy of a purified dry extract of P. cupana (PC-18) in patients with various solid tumors treated with chemotherapy. Methods: We included 40 patients with solid tumors who showed increases in their Brief Fatigue Inventory (BFI) questionnaire scores after one week of systemic chemotherapy. PC-18 was administered at 37.5 mg by mouth two times per day (PO bid), starting after one week of chemotherapy, for three weeks (induction phase). Patients who had an improvement in or stabilization of their BFI scores were randomized to receive either PC-18 at the same dose or placebo for the following three weeks (maintenance phase). Results: After PC-18 treatment, the BFI fatigue scores improved or stabilized in 36 out of the 40 patients (mean BFI score difference = 2.503; 95% CI: 1.716 – 3.375, P = 0.0002). Three weeks after randomization (16 patients on PC-18 and 17 on placebo), we observed no significant differences in the BFI, FACIT, HADS, and PSQI scores between patients randomized to PC-18 versus placebo. Conclusions: We conclude that the PC-18 extract is effective for the treatment of CRF in patients with a variety of solid tumors. A conditioning effect, which was observed in patients with early positive effects of PC-18 on CRF, may explain the better than expected fatigue scores of the placebo-treated patients.
A randomized, phase III study (FLAURA) of AZD9291, a novel EGFR-TKI, versus gefitinib or erlotinib in treatment-naïve patients with advanced non-small cell lung cancer and an EGFR-TKI-sensitizing mutation.
Authors: Suresh S. Ramalingam, Yuri Rukazenkov, Karen Thomas, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2015)

TPS8102 Background: EGFR-TKI is the recommended treatment for patients with advanced NSCLC who have an EGFR-TKI-sensitizing mutation (EGFRm). However, most patients develop resistance, and in ~60% of cases the EGFR T790M mutation is the cause. AZD9291 is an oral, potent, irreversible EGFR-TKI selective for EGFRm and T790M mutations. Preliminary data from a Phase I/II study demonstrated clinical activity and a manageable tolerability profile for AZD9291 as first-line treatment of patients with EGFRm advanced NSCLC. Methods: This Phase III, double-blind, randomized study (FLAURA, NCT02296125) is designed to assess the efficacy and safety of AZD9291 (80 mg qd, orally) versus standard of care (SoC) EGFR-TKI (gefitinib [250 mg qd, orally] or erlotinib [150 mg qd, orally]) in treatment-naïve patients with locally advanced or metastatic EGFRm NSCLC. Eligible patients must have pathologically confirmed adenocarcinoma harboring an EGFR Ex19del or L858R mutation, alone or in combination with another EGFRm, determined by local (accredited laboratory) or central testing. Patients ≥ 18 years of age ( ≥ 20 in Japan), WHO performance status 0–1, will be randomized 1:1 to receive either AZD9291 or SoC EGFR-TKI, stratified by mutation status (Ex19del or L858R) and race (Asian versus non-Asian), until RECIST v1.1 defined progression or a discontinuation criterion is met. Patients may continue randomized treatment beyond RECIST defined progression if they continue to show clinical benefit, as judged by the Investigator. The primary objective is to compare progression-free survival (PFS) for AZD9291 to SoC EGFR-TKI. PFS in patients with tumors harboring T790M is a key secondary objective. Additional secondary objectives include PFS by Ex19del or L858R detectable in circulating tumor DNA, objective response rate, duration of response, disease control rate, depth of response, overall survival, PK, health-related quality of life, patient satisfaction with treatment, and the safety and tolerability profile of AZD9291 compared with SoC EGFR-TKI. The study was opened to accrual in November 2014. Clinical trial information: NCT02296125.
New Approaches to Endocrine Therapy for Breast Cancer
Authors: William J. Gradishar
Journal: Journal of the National Comprehensive Cancer Network (2017)

The management of advanced hormone receptor–positive disease has evolved with the emergence of CDK4/6 inhibitors. Improvements in progression-free survival of approximately 10 months were noted in pivotal trials of palbociclib. Strong efficacy was also seen with ribociclib, which was recently approved by the FDA. In the adjuvant treatment setting of hormone receptor–positive disease, an important issue for consideration is the duration of endocrine therapy.
Correlation of high metabolic activity on 18F-FDG PET-CT at diagnosis with early relapse and mortality for patients with primary lung cancer.
Authors: Shahzad Raza, Belal Firwana, Zhen Wang, Ibraheem Yousef, James Riley Shortridge, Robert S Kikland, Gautam Kishore Kale, Uladzislau Naidzionak, Ravi Kiran Bobba, Donald C. Doll, Akm Mosharraf Hossain
Journal: Journal of Clinical Oncology (2014)

e19088 Background: Fluoro-deoxyglucose positron emission tomography-computed tomography 18F FDG PET-CT (PET) is a useful tool for diagnosis, staging, and confer prognostic information based on treatment response in primary lung cancer (LC). The aim of our study is to evaluate the pretreatment Standardized Uptake Value (SUV), a semi-quantitative measurement of FDG uptake in the tumor as an indicator of progression free-survival (PFS) and overall-survival (OS) in LC. Methods: We performed retrospective review of patients from 2011-2013 with pathologically confirmed LC who had pretreatment PET-CT.We compared maximum SUV at diagnosis between patients with disease-progression and OS using the Wilcoxon-Mann-Whitney test. Cox-proportional hazard models were used to estimate the association between outcomes of interest (disease-progression and mortality) and SUV after adjusting for age, gender, stage, performance status, and pathology. Results: There were 156 consecutive patients (median age:64 years, male:73,female:83) in the cohort with LC. Patients with tumor-progression had significantly higher SUV than those without progression (p<0.05). There was a significant (p<0.001) inverse linear correlation between SUV and both PFS and OS. After adjusting for demographics, stage, performance status, and pathology, higher SUV was associated with significantly higher risk of tumor progression (hazard ratio (HR):1.04,95% CI: 1.01-1.06) and higher risk of death (HR:1.04, 95% CI: 1.01-1.07). Stepwise regression showed that these associations were the most significant for lesions with maximum SUV 12 or above. In subset analysis, patients with stage IIIB/IV (n=97) with maximum SUV at diagnosis <12 versus (vs) SUV >12 had PFS 7 months vs 5 months (p<0.03) and OS was 24 months vs 10 months (p<0.01). Conclusions: We demonstrate that PET-CT at diagnosis is an independent tool for outcome prediction for both PFS and OS in LC. High metabolic activity on PET-CT tends to have more aggressive clinical course than those with low metabolic activity. Therefore, based on SUV at diagnosis, clinicians can stratify patients who are at increased risk of therapeutic failure.
Intratumoral delivery of inactivated modified vaccinia virus Ankara (iMVA) induces systemic antitumor immunity via STING and Batf3-dependent dendritic cells
Authors: Peihong Dai, Weiyi Wang, Ning Yang, Cristian Serna-Tamayo, Jacob M. Ricca, Dmitriy Zamarin, Stewart Shuman, Taha Merghoub, Jedd D. Wolchok, Liang Deng
Journal: Science Immunology (2017)

Advanced cancers remain a therapeutic challenge despite recent progress in targeted therapy and immunotherapy. Novel approaches are needed to alter the tumor immunosuppressive microenvironment and to facilitate the recognition of tumor antigens that leads to antitumor immunity. Poxviruses, such as modified vaccinia virus Ankara (MVA), have potential as immunotherapeutic agents. We show that infection of conventional dendritic cells (DCs) with heat- or ultraviolet-inactivated MVA leads to higher levels of interferon induction than MVA alone through the cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase)-STING cytosolic DNA-sensing pathway. Intratumoral injection of inactivated MVA (iMVA) was effective and generated adaptive antitumor immunity in murine melanoma and colon cancer models. iMVA-induced antitumor therapy was less effective in STING- or Batf3-deficient mice than in wild-type mice, indicating that both cytosolic DNA sensing and Batf3-dependent CD103+/CD8α+ DCs are essential for iMVA immunotherapy. The combination of intratumoral delivery of iMVA and systemic delivery of immune checkpoint blockade generated synergistic antitumor effects in bilateral tumor implantation models as well as in a unilateral large established tumor model. Our results suggest that inactivated vaccinia virus could be used as an immunotherapeutic agent for human cancers.
Sociocultural discourse in science: Flawed assumptions and bias in the CLASH model
Authors: Elizabeth E. Van Voorhees, Sarah M. Wilson, Patrick S. Calhoun, Eric B. Elbogen, Jean C. Beckham, Nathan A. Kimbrel
Journal: Behavioral and Brain Sciences (2017)

Abstract In this commentary, we contest Van Lange and colleagues' central claim that “countries closer to the equator are generally more violent.” We point to the lack of credible empirical evidence for this assertion and suggest that the CLASH model uses the language of science to lend false credibility to a problematic sociocultural discourse.
R0 resection of locally advanced pancreatic cancer encasing major visceral arteries using arterial reconstruction: Short- and long-term results.
Authors: Yuri Genyk, Lea Matsuoka, Anthony B. El-Khoueiry, Syma Iqbal, James Buxbaum, Rick Selby, Jacquez Vandam, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2012)

e14679 Background: Locally advanced disease is found in about 40% of patients with pancreatic cancer at initial presentation. Tumors involving major visceral arteries are commonly deemed unresectable. In this study we analyzed the feasibility of R0 resection of locally advanced pancreatic cancer encasing major visceral arteries using arterial reconstruction. Methods: The following data were collected: age, gender, operative details, post-operative complications, chemotherapy and/or radiation therapy and overall and disease free survival. Patient survival was calculated utilizing Kaplan-Meier survival probability estimates. Results: From Dec., 2002 to Jan., 2012, 13 patients underwent pancreatic resection with concomitant resection and reconstruction of major visceral arteries for pancreatic cancer (9 males and 4 females, median age 63 yrs (range: 50–82 yrs)). The arterial involvement included celiac artery (n=6), superior mesenteric artery (n=4) and hepatic artery (n=3). Resections included pancreatico-duodenectomy (n=9), distal pancreatectomy (n=3), and total pancreatectomy (n=1). Management of the arterial involvement included: resection of celiac axis without reconstruction (n=2), reconstruction of one artery (n=6), two arteries (n=4) and three arteries (n=1). Nine of the 13 patients underwent simultaneous venous reconstruction. R0 resection was accomplished in 11, R1 in 1, and R2 in 1 patient. Ten of the 13 patients received neoadjuvant and/or adjuvant chemo- or chemo-radiation therapy outside protocols. To date, 4 patients are alive and disease free at 1, 4, 15 and 111 months, and 1 patient is alive with recurrence at 100 months. Six-month patient survival was 65% and median overall survival was 17 months. The probability of 5-year survival was 22%. Conclusions: Our study indicates that in select patients with locally advanced pancreatic cancer with involvement of major visceral arteries R0 resection is feasible by performing pancreatic resection with arterial reconstruction. The survival data in this group of patients are encouraging and provide the opportunity to reconsider the contraindications to surgical management of such patients.
Could Albumin Be a Biomarker to Monitor the Effect of Intravenous Immunoglobulin on Guillain-Barré Syndrome?
Authors: Ying Wang, Hong-Liang Zhang
Journal: JAMA Neurology (2017)

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PGBD5 promotes site-specific oncogenic mutations in human tumors
Authors: Anton G Henssen, Richard Koche, Jiali Zhuang, Eileen Jiang, Casie Reed, Amy Eisenberg, Eric Still, Ian C MacArthur, Elias Rodríguez-Fos, Santiago Gonzalez, Montserrat Puiggròs, Andrew N Blackford, Christopher E Mason, Elisa de Stanchina, Mithat Gönen, Anne-Katrin Emde, Minita Shah, Kanika Arora, Catherine Reeves, Nicholas D Socci, Elizabeth Perlman, Cristina R Antonescu, Charles W M Roberts, Hanno Steen, Elizabeth Mullen, Stephen P Jackson, David Torrents, Zhiping Weng, Scott A Armstrong, Alex Kentsis
Journal: Nature Genetics (2017)
Peptide‐Functionalized Fluorescent Particles for In Situ Detection of Nitric Oxide via Peroxynitrite‐Mediated Nitration
Authors: Jason Y. H. Chang, Lesley W. Chow, W. Michael Dismuke, C. Ross Ethier, Molly M. Stevens, W. Daniel Stamer, Darryl R. Overby
Journal: Advanced Healthcare Materials (2017)

Nitric oxide (NO) is a free radical signaling molecule that plays a crucial role in modulating physiological homeostasis across multiple biological systems. NO dysregulation is linked to the pathogenesis of multiple diseases; therefore, its quantification is important for understanding pathophysiological processes. The detection of NO is challenging, typically limited by its reactive nature and short half‐life. Additionally, the presence of interfering analytes and accessibility to biological fluids in the native tissues make the measurement technically challenging and often unreliable. Here, a bio‐inspired peptide‐based NO sensor is developed, which detects NO‐derived oxidants, predominately peroxynitrite‐mediated nitration of tyrosine residues. It is demonstrated that these peptide‐based NO sensors can detect peroxynitrite‐mediated nitration in response to physiological shear stress by endothelial cells in vitro. Using the peptide‐conjugated fluorescent particle immunoassay, peroxynitrite‐mediated nitration activity with a detection limit of ≈100 × 10 −9 m is detected. This study envisions that the NO detection platform can be applied to a multitude of applications including monitoring of NO activity in healthy and diseased tissues, localized detection of NO production of specific cells, and cell‐based/therapeutic screening of peroxynitrite levels to monitor pronitroxidative stress in biological samples.