tbuckley/cabot-search huggingface dataset:
IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
Authors: Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R. Kaufman, Andrew Albright, Jonathan D. Cheng, S. Peter Kang, Veena Shankaran, Sarina A. Piha-Paul, Jennifer Yearley, Tanguy Y. Seiwert, Antoni Ribas, Terrill K. McClanahan
Journal: Journal of Clinical Investigation (2017)

Programmed death-1–directed (PD-1–directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti–PD-1 therapies, including pembrolizumab. However, whether quantifying T cell–inflamed microenvironment is a useful pan-tumor determinant of PD-1–directed therapy response has not been rigorously evaluated. Here, we analyzed gene expression profiles (GEPs) using RNA from baseline tumor samples of pembrolizumab-treated patients. We identified immune-related signatures correlating with clinical benefit using a learn-and-confirm paradigm based on data from different clinical studies of pembrolizumab, starting with a small pilot of 19 melanoma patients and eventually defining a pan-tumor T cell–inflamed GEP in 220 patients with 9 cancers. Predictive value was independently confirmed and compared with that of PD-L1 immunohistochemistry in 96 patients with head and neck squamous cell carcinoma. The T cell–inflamed GEP contained IFN-γ–responsive genes related to antigen presentation, chemokine expression, cytotoxic activity, and adaptive immune resistance, and these features were necessary, but not always sufficient, for clinical benefit. The T cell–inflamed GEP has been developed into a clinical-grade assay that is currently being evaluated in ongoing pembrolizumab trials.
Hepatocyte-derived macrophage migration inhibitory factor mediates alcohol-induced liver injury in mice and patients
Authors: Veronica Marin, Kyle Poulsen, Gemma Odena, Megan R. McMullen, Jose Altamirano, Pau Sancho-Bru, Claudio Tiribelli, Juan Caballeria, Natalia Rosso, Ramon Bataller, Laura E. Nagy
Journal: Journal of Hepatology (2017)
Bladder Cancer and Water Disinfection By-product Exposures through Multiple Routes: A Population-Based Case–Control Study (New England, USA)
Authors: Laura E. Beane Freeman, Kenneth P. Cantor, Dalsu Baris, John R. Nuckols, Alison Johnson, Joanne S. Colt, Molly Schwenn, Mary H. Ward, Jay H. Lubin, Richard Waddell, G. Monawar Hosain, Chris Paulu, Richard McCoy, Lee E. Moore, An-Tsun Huang, Nat Rothman, Margaret R. Karagas, Debra T. Silverman
Journal: Environmental Health Perspectives (2017)

Ingestion of disinfection byproducts has been associated with bladder cancer in multiple studies. Although associations with other routes of exposure have been suggested, epidemiologic evidence is limited.
The association between neutrophil to lymphocyte ratio and overall survival in patients with triple-negative breast cancer.
Authors: Dilan Anil Patel, Bilal Hassan, Jingqin Luo, Cynthia X. Ma, Jian Li Campian
Journal: Journal of Clinical Oncology (2017)

e12591 Background: Recent reports have suggested that an elevated neutrophil to lymphocyte ratio (NLR) is associated with poor outcomes in various malignancies. Furthermore, radiation therapy (RT) alone or in combination with chemotherapy often results in reduced absolute lymphocyte counts (ALC), which has been postulated to impair host immune surveillance and anti-tumor responses. We sought to better understand whether an elevated NLR results in impaired OS in patients with triple-negative breast cancer. Methods: Our retrospective analysis was performed on a database of patients with biopsy proven triple-negative breast cancer treated at Washington University in St. Louis between 2002 and 2010. Patients who received radiation therapy and had adequate follow up in terms of clinical documentations and laboratory data were included. NLR and ALC were collected at baseline, post-adjuvant chemotherapy, prior to RT, end of RT, 2 months post RT, 1 year post RT, and completion of all planned treatments. Results: Total of 155 patients were included. We used a cutoff value of 3.0 to classify high NLR. Wilcoxon rank-sum test was used to compare NLR at each time point between deceased and alive patients. High NLR post chemotherapy is associated with worse OS (HR 1.127, 95% CI = 1.016-1.249; p&lt;0.05). In addition, NLRs from end of RT, 2 months post and 1 year post RT are associated with worse OS: (HR 1.109, 95% CI = 1.059–1.161; p &lt; 0.001); (HR 1.074, 95% CI = 1.041–1.109; p &lt; 0.001); (HR 1.069, 95% CI = 1.048–1.091; p &lt; 0.001) respectively. Conclusions: High NLR post-chemotherapy and RT are associated with worse OS in patients with triple-negative breast cancer.Further studies are warranted to establish NLR as a prognostic marker and an addition to risk prediction models. [Table: see text]
The Treatment of Tumoral Hydrocephalus in Adults by Means of a Variable Resistance Valve
Authors: R. Spaziante
Journal: Neuro-Oncology (1991)

Sixteen adults with hydrocephalus caused by intracranial tumors were treated by ventriculo-atrial shunt using a one-piece variable resistance valve system. A complete recovery was achieved in all cases; no cases of malfunction, mechanical complications, over or underdrain-age, infections or side effects were recorded. Symptoms of increased intracranial pressure immediately regressed, while evolution of ventricular size on CT scan varied.
Anti-HER2 treatment in advanced metastatic HER2-negative breast cancer patients with elevated serum levels of the HER2 extracellular domain and/or HER2 overexpressing circulating tumor cells.
Authors: Christian M. Kurbacher, Christian A. Eichler, Annegret Barbara Quade, Gerhard Kunstmann, Susanne Herz, Jutta Anna Kurbacher, Mathias R. Warm
Journal: Journal of Clinical Oncology (2016)

597 Background: Patients (pts) with HER2-negative (HER2-) advanced metastatic breast cancer (MBC) may present with elevated serum levels of the HER2 extracellular domain (sHER2) or HER2 overexpressing circulating tumor cells (CTCs), potentially qualifying for anti-HER2 therapy. This retrospective study sought to clarify the value of HER2-directed Tx in ´occult´ HER2-positive (HER2+) MBC pts in the clinical routine. Methods: 31 pts with HER2- MBC (ER+, n = 27) exhibiting sHER2 values > 15 ng/mL (n = 8), HER2+ CTCs (n = 7), or both (n = 16) were included. Pts had failed 2-16 prior systemic treatments (median: 7). Pts received trastuzumab (T: n = 19), lapatinib (L: n = 4), T+L (n = 2), or T+pertuzumab (TP: n = 6). Anti-HER2 Tx was given alone (n = 5), or in combination with endocrine agents (n = 6), cytotoxics (n = 17), or other targeted drugs (n = 3). Responses were scored according to RECIST 1.1, OS was calculated from the start of Tx until death from any reason or loss to follow-up. Results: Anti-HER2 Tx was well tolerated. Median treatment duration was 17.0 wks. In 2 pts with L and 1 pt with T+L, Tx was discontinued due to toxicity (diarrhea, fatigue). 12 PR, 13 SD, and 6 PD accounted for an objective response rate of 35.4% and a clinical benefit rate of 80.6%. Median OS was 76.1 wks. In 25 pts, 9 with PR, 12 with SD, and 4 with PD, sHER2 measurements at baseline and after 3 wks were available. Most pts with PD showed increasing sHER2 levels. In the majority of pts with PR or SD, sHER2 dropped by more than 20% from baseline. However, 2 pts with PR to L, had increasing sHER2 valued. In 20 pts, 8 with PR, 7 with SD, and 5 with PD, serial CTC counts 6 wks from baseline were available. 4 pts with PD showed increasing CTCs. All pts with SD and PR presented with declining CTCs, mostly normalizing within 6 wks. Conclusions: Anti-HER2 Tx was effective in pts with pretreated occult HER2+ MBC. Thus, determination of both sHER2 and HER2 overexpressing CTCs is reasonable in tissue HER2-negative MBC pts in the clinical routine. Compared to sHER2, serial CTC measurements may be the more accurate predictor of response to anti-HER2 treatment, particularly in pts receiving L as part of their Tx.
Variations in Databases Used to Assess Academic Output and Citation Impact
Authors: Natalie M Plana, Jonathan P Massie, Jonathan M Bekisz, Stuart Spore, J Rodrigo Diaz-Siso, Roberto L Flores
Journal: New England Journal of Medicine (2017)

An analysis of listings of 1469 clinical and research faculty in PubMed, Web of Science, Scopus, and Google Scholar showed major differences in numbers of publications and citations and in the h-index (a measure of productivity and citations) for each author.
Phase II study on radiofrequency ablation in early breast cancer.
Authors: Shigeru Imoto, Takayuki Ueno, Hirotsugu Isaka, Hiroki Ito, Kaisuke Miyamoto, Satoshi Morita
Journal: Journal of Clinical Oncology (2016)

e12536 Background: Recent advances of screening mammography and primary chemotherapy make it possible to identify small size of breast cancer (BC) and minimize surgical management. Previously we reported the result of radiofrequency ablation (RFA) immediately followed by breast-conserving surgery (BCS) in 30 patients with T1N0 BC (Breast, 18:130-4, 2009). Complete ablation was found in 26 patients (87%) from the pathological diagnosis of tumor specimens stained with hematoxylin–eosin and nicotinamide adenine dinucleotide diaphorase. Thus, we conducted a phase II study to evaluate the safety and reliability of RFA alone in BC (UMIN000020805). Methods: T1 and sentinel node-negative BC patients were eligible. BC with diffuse calcification or extensive intraductal component (EIC) was excluded. RFA was performed using a LeVeen needle electrode system (Boston Scientific Corporation, USA). Primary endpoint was breast deformity due to RFA, which was calculated from ratios of the length from nipple to several points measured in affected breast and unaffected breast before and after RFA. Secondary endpoints were adverse events, ipsilateral breast tumor recurrence (IBTR) and QOL assessment of FACT-B. Results: Although 29 patients were required for statistical significance, 20 patients agreed to undergo RFA between May in 2009 and February in 2013. Their mean age was 63 years old. It took from 4 to 24 minutes for ablation time. No severe adverse events were observed except pain control with NSAID administration. Most patients received breast irradiation and hormonal therapy. Breast deformity had been small between pretreatment and 12 months after RFA (n = 12). Total outcome index, FACT-G and FACT-B total index had been not changed at the time of pretreatment, 6 months and 12 months after RFA (n = 16). The median follow-up was 63 months. One patient had contralateral non-invasive BC, but IBTR and distant organ metastasis had not been observed in all patients. Conclusions: RFA is a promising alternative to BCS in stage I BC without EIC. Clinical trial information: UMIN000020805.
La tuberculose péritonéale: une pathologie trés fréquente à Fés-Maroc (200 cas en 5 ans)
Authors: M El Abkari, N Aqodad, D Benajah, A Ibrahimi
Journal: Endoscopy (2006)

La tuberculose sévit toujours à l'état endémique au Maroc avec 35000 nouveaux cas par an. La localisation péritonéale est la plus fréquente des formes abdominales représentant la 2éme étiologie des ascites. L'absence des nouveaux moyens diagnostiques non invasifs (ADA, Interféronγ, ….) offre à la laparoscopie une place capitale dans la prise en charge diagnostique.
Hypoxic Pulmonary Vasoconstriction Does Not Explain All Regional Perfusion Redistribution in Asthma
Authors: Vanessa J. Kelly, Kathryn A. Hibbert, Puja Kohli, Mamary Kone, Elliot E. Greenblatt, Jose G. Venegas, Tilo Winkler, R. Scott Harris
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Regional hypoventilation in bronchoconstricted patients with asthma is spatially associated with reduced perfusion, which is proposed to result from hypoxic pulmonary vasoconstriction (HPV).To determine the role of HPV in the regional perfusion redistribution in bronchoconstricted patients with asthma.Eight patients with asthma completed positron emission tomographic/computed tomographic lung imaging at baseline and after bronchoconstriction, breathing either room air or 80% oxygen (80% O2) on separate days. Relative perfusion, specific ventilation (sV), and gas fraction (Fgas) in the 25% of the lung with the lowest specific ventilation (sVlow) and the remaining lung (sVhigh) were quantified and compared.In the sVlow region, bronchoconstriction caused a significant decrease in sV under both room air and 80% O2 conditions (baseline vs. bronchoconstriction, mean ± SD, 1.02 ± 0.20 vs. 0.35 ± 0.19 and 1.03 ± 0.20 vs. 0.32 ± 0.16, respectively; P < 0.05). In the sVlow region, relative perfusion decreased after bronchoconstriction under room air conditions and also, to a lesser degree, under 80% O2 conditions (1.02 ± 0.19 vs. 0.72 ± 0.08 [P < 0.001] and 1.08 ± 0.19 vs. 0.91 ± 0.12 [P < 0.05], respectively). The Fgas increased after bronchoconstriction under room air conditions only (0.99 ± 0.04 vs. 1.00 ± 0.02; P < 0.05). The sVlow subregion analysis indicated that some of the reduction in relative perfusion after bronchoconstriction under 80% O2 conditions occurred as a result of the presence of regional hypoxia. However, relative perfusion was also significantly reduced in sVlow subregions that were hyperoxic under 80% O2 conditions.HPV is not the only mechanism that contributes to perfusion redistribution in bronchoconstricted patients with asthma, suggesting that another nonhypoxia mechanism also contributes. We propose that this nonhypoxia mechanism may be either direct mechanical interactions and/or unidentified intercellular signaling between constricted airways, the parenchyma, and the surrounding vasculature.
Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Daniel Sinnecker, Alexander Goedel, Karl-Ludwig Laugwitz, Alessandra Moretti
Journal: Circulation Research (2013)

Induced pluripotent stem cells offer the possibility to generate patient-specific stem cell lines from individuals affected by inherited disorders. Cardiomyocytes differentiated from such patient-specific induced pluripotent stem cells lines have been used to study the pathophysiology of arrhythmogenic heart diseases, such as the long-QT syndrome or catecholaminergic polymorphic ventricular tachycardia. Testing for unwanted drug side effects or tailoring medical treatment to the specific needs of individual patients with arrhythmogenic disorders may become future applications of this emerging technology.
Galectin-1 (Gal-1) expression as a prognostic factor in patients with newly diagnosed glioblastoma (GB) treated with Stupp regimen (GLIOCAT study).
Authors: Noelia Vilarino, Neus Martinez-Bosch, Carmen Balana, Francesc Alameda, Anna Estival, Estela Pineda, Sonia del Barco, Miguel J. Gil Gil, Carlos Mesia, Oscar Gallego, Cristina Carrato, Teresa Ribalta, Noemi Vidal Sarro, Natalia Balana, Jose Maria Velarde, Pilar Navarro, Maria Martinez-Garcia
Journal: Journal of Clinical Oncology (2017)

e13526 Background: Gal-1 is a β-galactoside binding protein that plays an important role in cancer, promoting cell invasion, proliferation, migration, angiogenesis and evasion of the immune response. Gal-1 is involved in glioma progression and is related to tumor grade and poor clinical outcome. Gal-1 has been implicated in resistance to chemotherapy and as a potential mediator of resistance to anti-VEGF therapy. The aim of our study was to evaluate the prognostic significance of Gal-1 in a homogenous cohort of GB patients and to analyze its potential predictive value of response to bevacizumab at recurrence. Methods: A substudy of GLIOCAT, a multicenter study of newly diagnosed GB patients treated with standard Stupp regimen (previously reported). GLIOCAT enrolled 432 patients between 2005-2014. Tissue was available from 243 cases, from which a tissue microarray (TMA) was constructed. Gal-1 expression in tissue from initial surgery was analyzed by immunohistochemistry. Results were evaluated by three reviewers and quantified by H-score. Expression levels were correlated with clinical outcome, known GB prognostic factors and response to bevacizumab. Results: We defined a cut off for Gal-1 H-Score of &gt;60 (cytoplasm) and &gt;25 (nucleus). HighcytoplasmicGal-1 expression significantly correlated with worse OS and with a trend for shorter PFS. In the multivariate analysis KPS, age, MGMT methylation status and, extent of resection but not Gal-1 expression were independent prognostic factors for survival. Of 92 patients who received bevacizumab at recurrence, only 54 were included in the TMA, and only 1 had low Gal-1 expression. We couldn’t find any relationship with OS or PFS in this population. Conclusions: Gal-1 expression may represent a prognostic factor for GB patients treated with standard therapy. [Table: see text]
Abstract 191: Increase of Prevalence of Acute Myocardium Infarction and Sudden Death Due to the Environmental Tragedy in South of Brazil.
Authors: Sergio L Zimmermann, Siegmar Starke, Harry Correa Filho, Miguel A Moretti, Antonio C Chagas, Sergio Timerman
Journal: Circulation (2010)

Introduction: Some data have been demonstrating the relation between myocardium infarction, sudden death and catastrophes in USA, Europe and Asia. In November 2008, Blumenau — South of Brazil occur...
A measure of intratumor heterogeneity to predict metastasis and metastasis-free survival in patients with triple-negative breast cancer.
Authors: Yucai Wang, Fang Yang, Yanru Wang, Victor Tsu-Shih Chang, Xiaoxiang Guan
Journal: Journal of Clinical Oncology (2016)

1069 Background: It is recognized that cancers are heterogeneous, but how to apply this concept clinically remains undefined. We studied whether a quantitative genetic definition of intratumor heterogeneity (ITH) can predict clinical outcomes in patients with triple-negative breast cancer (TNBC). Methods: We used copy number variations (CNVs) of Myc, EGFR and CCND1 in different cancer cells within a tumor as a genetic measure of ITH. Copy numbers of Myc, EGFR/CEP7 and CCND1/CEP11 were measured in 100 cells at three different locations of each mastectomy specimen. The Shannon index, a measure of diversity in a population, was calculated based on CNVs in the 300 cells to represent the ITH. The association of Shannon indices of Myc, EGFR/CEP7 and CCND1/CEP11 CNVs with development of metastasis and metastasis-free survival (MFS) was analyzed. Results: Twenty-eight patients were included in this study. After a median follow-up of 50.5 months (range 10-72), 8 patients developed distant metastasis. Patients who developed metastasis had significantly higher ITH, ie, Shannon indices of Myc (1.61 ± 0.09 vs 1.33 ± 0.08, P = 0.048), EGFR/CEP7 (1.76 ± 0.07 vs 1.38 ± 0.07, P = 0.008) and CCND1/CEP11 (2.03 ± 0.09 vs 1.77 ± 0.06, P = 0.021) CNVs. Higher Shannon indices of EGFR/CEP7 ( ≥ 1.5) and CCND1/CEP11 ( ≥ 1.8) CNVs were significantly associated with development of metastasis (P < 0.001 and P = 0.023, respectively, Chi-square), and were predictive of significantly worse MFS (P < 0.001 and P = 0.019, respectively, Log-rank). Higher Shannon index of Myc ( ≥ 1.5) CNV also had a trend to predict development of metastasis (P = 0.070) and worse MFS (P = 0.093), although not statistically significant. In contrast, age, tumor size, lymph node status, grade and stage were not predictive of metastasis and MFS in univariate analyses. Interestingly, enrichment of CD44+/CD24-putative cancer stem cells was also not associated with metastasis or MFS. Conclusions: Higher ITH, measured by Shannon indices of EGFR/CEP7 and CCND1/CEP11 CNVs, is significantly predictive of development of metastasis in TNBC, and is associated with significantly worse MFS in TNBC patients. ITH is a very promising novel prognostic factor in TNBC.
Nomograms to predict the presence of EGFR mutations and ALK rearrangements in non-small-cell lung carcinoma.
Authors: Wenfeng Fang, Shaodong Hong, Yunpeng Yang, Yuxiang Ma, Yuangyuan Zhao, Hongyun Zhao, Yan Huang, Li Zhang
Journal: Journal of Clinical Oncology (2016)

1587 Background: EGFR mutations and ALK rearrangements are two most important driver genes in non-small-cell lung carcinoma (NSCLC). However, the testing rate of these two driver mutations remains low, either because tumor tissue is limited and/or tests are not routinely offered. This study aims to establish nomograms to allow for predictions of these two genetic aberrations. Methods: A total of 4160 NSCLC patients from Sun Yat-sen University were enrolled. Direct sequencing and Fluorescent in situ Hybridization were adopted to detect EGFR mutations and ALK rearrangements. Patients' clinicopathological features were collected and their associations with the two genetic aberrations were examined by multivariate logistic regression analysis. Independent variables were entered into nomogram development and internal validation via Bootstrap self-sampling methods, as indicated by concordance index (c-index) and calibration curve. Results: The number of ALK rearrangements and EGFR mutations were 320 (7.8%) and 1386 (33.6%), respectively. Independent predictors for ALK rearrangements were age (OR per 10 years’ increase, 0.5; p < 0.001), gender (ORmale vs female , 1.8; p = 0.035) and smoking pack-years (OR per 10 smoking pack-years, 0.8; p = 0.007). For EGFR mutations, age (OR per 10 years’ increase, 1.2; p = 0.006), smoking pack-years (OR per 10 smoking pack-years, 0.8; p < 0.001), histology (ORadenocarcinoma vs. non-aden , 5.8; p < 0.001) and differentiation of tumor (ORpoor vs. high differentiation , 0.5; p < 0.001) were the independent predictors. The c-index of the two nomograms for predicting ALK rearrangements and EGFR mutations were 0.76 and 0.75 after internal validation, respectively. The calibration cures show that the predicted probabilities by the two nomograms were mostly consistent with actual probabilities. Conclusions: The two nomograms for predicting ALK rearrangements and EGFR mutations could be useful tools for clinicians to predict the likelihood of these two genetic aberrations by incorporating simple clinicopathological data.
AB0132 Four cases in which the initial illness was typical of reiter`s syndrome and later became typical psoriatic arthritis
Authors: K Imre, E Koo, M Sesztak
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> It is generally accepted that in some patients reactive arthritis may progress further to ankylosing spondylitis. A generally accepted estimate is that 20 percent of patients with Reiter`s syndrome develop peripheral arthritis or axial disease. <h3>Objectives</h3> The study group consisted of 500 unrelated consecutive patients with psoriatic arthritis at 15 year follow up at the PsA outpatient clinic. We found four cases in which the initial illness was typical of Reiter`s syndrome and later became typical psoriatic arthritis. <h3>Methods</h3> <h3>Results</h3> One patient had persistent joint symptoms, two patients have at every 5 years recurrent bouts of arthritis and one patient suffered from severe, aggressive and unremitting disease. Over 1 to 5 years the skin lesions progressively assume the characteristics of psoriasis. The diagnosis of PsA was set up among 1–10 years. <h3>Conclusion</h3> The possibility that psoriatic arthritis and Reiter`s syndrome may be similar or closely related is illustrated by our cases, too. Such cases have suggested a more than coincidental interrelationship between Reiter`s syndrome and psoriatic arthritis.
The Observed and Expected Incidence of Cardiovascular (CV) Ischemic Events in Dasatinib (DAS)-Treated Patients (pts) Across a Clinical Trial Program
Authors: Giuseppe Saglio, Philipp le Coutre, Jorge E. Cortes, Jiří Mayer, Philip A. Rowlings, Francois-Xavier Mahon, Glenn S. Kroog, Kyna Gooden, Milayna Subar, Jeanette A. Preston, Neil P. Shah
Journal: Blood (2014)