tbuckley/cabot-search huggingface dataset:
Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study
Authors: A. Psyrri, C. Fortpied, G. Koutsodontis, M. Avgeris, C. Kroupis, N. Goutas, J. Menis, L. Herman, L. Giurgea, É. Remenár, M. Degardin, I.S. Pateras, J.A. Langendijk, C.M.L. van Herpen, A. Awada, J.R. Germà-Lluch, H.R. Kienzer, L. Licitra, J.B. Vermorken
Journal: Annals of Oncology (2017)

EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell carcinomas. We conducted a retrospective analysis of prospectively collected data aiming to evaluate whether only HPV(-) patients (pts) benefit from adding docetaxel to PF, in which case deintensifying induction treatment in HPV(+) pts could be considered.Pretherapy tumor biopsies (blocks or slides) were assessed for high-risk HPV by p16 immunohistochemistry, PCR and quantitative PCR. HPV-DNA+ and/or p16+ tumors were subjected to in situ hybridization (ISH) and HPV E6 oncogene expression qRT-PCR analysis. Primary and secondary objectives were to evaluate the value of HPV/p16 status as predictive factor of treatment benefit in terms of PFS and OS. The predictive effect was analyzed based on the model used in the primary analysis of the study with the addition of a treatment by marker interaction term and tested at two-sided 5% significance level.Of 358, 119 pts had available tumor samples and 58 of them had oropharyngeal cancer. Median follow-up was 8.7 years. Sixteen of 119 (14%) evaluable samples were p16+ and 20 of 79 (25%) evaluable tumors were HPV-DNA+. 13 of 40 pts (33%) assessed with HPV-DNA ISH and 12 of 28 pts (43%) assessed for HPV E6 mRNA were positive. The preplanned analysis showed no statistical evidence of predictive value of HPV/p16 status for PFS (P = 0.287) or OS (P = 0.118).The incidence of HPV positivity was low in the subset of EORTC 24971 pts analyzed. In this analysis only powered to detect a large treatment by marker interaction, there was no statistical evidence that treatment effect found overall was different in magnitude in HPV(+) or HPV(-) pts. These results do not justify selection of TPF versus PF according to HPV status.
Efficacité et complications de la technique d'infundibulotomie au cours du cathétérisme des voies biliaires
Authors: P Potier, DH Trinh, A Widerspach-Thor, X Causse
Journal: Endoscopy (2006)

L'échec de cathétérisme sélectif de la voie biliaire principale par l'orifice papillaire survient dans environ 10% des cas. Cet échec conduit parfois à la réalisation d'une technique de pré-coupe dont la morbidité atteint 6 à 30% selon les séries publiées. La technique d'infundibulotomie est habituellement réservée à des situations particulières telles qu'un calcul biliaire enclavé ou une tumeur ampullaire. Les données concernant l'efficacité et les complications spécifiques de cette technique sont rares. L'infundibulotomie est la technique de secours exclusive dans notre centre. Nous avons donc pu étudier spécifiquement son efficacité et sa morbidité.
History of consolidation is prognostic in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease‐negative first complete remission
Authors: Armin Rashidi, Michael A. Linden, Todd E. DeFor, Erica Warlick, Nelli Bejanyan, Sophia Yohe, Daniel J. Weisdorf, Celalettin Ustun
Journal: American Journal of Hematology (2017)

Abstract Background Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo‐HCT) in minimal residual disease (MRD)‐negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo‐HCT in MRD‐negative CR1, does a history of prior consolidation provide additional prognostic information? Methods The inclusion criteria were: ( i ) Age &gt; 18 years, ( ii ) AML in CR1 after 1‐2 cycles of intensive induction chemotherapy, with or without consolidation, ( iii ) Allo‐HCT between 1/2003 and 4/2016 at our institution, ( iv ) Available standard‐sensitivity 4‐color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, ( v ) Flow cytometry‐based MRD‐negative status at the time of HCT. Results A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35‐0.99], P = .046), relapse‐free survival (0.60 [0.37‐0.96], P = .036), and relapse (0.50 [0.27‐0.92], P = .025). Analysis of potential sources of bias was unrevealing. Conclusions In AML patients undergoing allo‐HCT in MRD‐negative CR1, a history of prior consolidation was associated with favorable outcomes. If the path to pre‐HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD‐negative state. These results warrant validation in larger cohorts.
RETRACTED ARTICLE: Linc00152 promotes malignant progression of glioma stem cells by regulating miR-103a-3p/FEZF1/CDC25A pathway
Authors: Mingjun Yu, Yixue Xue, Jian Zheng, Xiaobai Liu, Hai Yu, Libo Liu, Zhen Li, Yunhui Liu
Journal: Molecular Cancer (2017)

Abstract Background Glioma is one of the most frequent intracranial malignant tumors. LncRNAs have been identified as new modulators in the origination and progression of glioma. Methods Quantitative real-time PCR were conducted to evaluate the expression of linc00152 and miRNA-103a-3p in glioma tissues and cells. Western blot were used to determine the expression of FEZF1 and CDC25A in glioma tissues and cells. Stable knockdown of linc00152 or over-expression of miR-103a-3p in glioma stem cells (GSCs) were established to explore the function of linc00152 and miR-103a-3p in GSCs. Further, luciferase reports were used to investigate the correlation between linc00152 and miR-103a-3p. Cell Counting Kit-8, transwell assays, and flow cytometry were used to investigate the function of linc00152 and miR-103a-3p in GSC malignant biological behaviors. ChIP assays were employed to ascertain the correlations between FEZF1 and CDC25A. Results Linc00152 was up-regulated in glioma tissues as well as in GSCs. Knockdown of linc00152 inhibited cell proliferation, migration and invasion, while promoted GSC apoptosis. Linc00152 regulated the malignant behavior of GSCs by binding to miR-103a-3p, which functions as a tumor suppressor. In addition, knockdown of linc00152 down-regulated forebrain embryonic zinc finger protein 1 (FEZF1), a direct target of miR-103a-3p which played an oncogenic role in GSCs. FEZF1 elevated promoter activities and up-regulated expression of the oncogenic gene cell division cycle 25A (CDC25A). CDC25A over-expression activated the PI3K/AKT pathways, which regulated the malignant behavior of GSCs. Conclusions Linc00152/miR-103a-3p/FEZF1/CDC25A axis plays a novel role in regulating the malignant behavior of GSCs, which may be a new potential therapeutic strategy for glioma therapy.
Intensive Blood Pressure Reduction and Spot Sign in Intracerebral Hemorrhage
Authors: Andrea Morotti, H. Bart Brouwers, Javier M. Romero, Michael J. Jessel, Anastasia Vashkevich, Kristin Schwab, Mohammad Rauf Afzal, Christy Cassarly, Steven M. Greenberg, Renee Hebert Martin, Adnan I. Qureshi, Jonathan Rosand, Joshua N. Goldstein
Journal: JAMA Neurology (2017)

<h3>Importance</h3> The computed tomographic angiography (CTA) spot sign is associated with intracerebral hemorrhage (ICH) expansion and may mark those patients most likely to benefit from intensive blood pressure (BP) reduction. <h3>Objective</h3> To investigate whether the spot sign is associated with ICH expansion across a wide range of centers and whether intensive BP reduction decreases hematoma expansion and improves outcome in patients with ICH and a spot sign. <h3>Design, Setting, and Participants</h3> SCORE-IT (Spot Sign Score in Restricting ICH Growth) is a preplanned prospective observational study nested in the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-II) randomized clinical trial. Participants included consecutive patients with primary ICH who underwent a CTA within 8 hours from onset at 59 sites from May 15, 2011, through December 19, 2015. Data were analyzed for the present study from July 1 to August 31, 2016. <h3>Main Outcomes and Measures</h3> Patients in ATACH-II were randomized to intensive (systolic BP target, &lt;140 mm Hg) vs standard (systolic BP target, &lt;180 mm Hg) BP reduction within 4.5 hours from onset. Expansion of ICH was defined as hematoma growth of greater than 33%, and an unfavorable outcome was defined as a 90-day modified Rankin Scale score of 4 or greater (range, 0-6). The association among BP reduction, ICH expansion, and outcome was investigated with multivariable logistic regression. <h3>Results</h3> A total of 133 patients (83 men [62.4%] and 50 women [37.6%]; mean [SD] age, 61.9 [13.1] years) were included. Of these, 53 (39.8%) had a spot sign, and 24 of 123 without missing data (19.5%) experienced ICH expansion. The spot sign was associated with expansion with sensitivity of 0.54 (95% CI, 0.34-0.74) and specificity of 0.63 (95% CI, 0.53-0.72). After adjustment for potential confounders, intensive BP treatment was not associated with a significant reduction of ICH expansion (relative risk, 0.83; 95% CI, 0.27-2.51;<i>P</i> = .74) or improved outcome (relative risk of 90-day modified Rankin Scale score ≥4, 1.24; 95% CI, 0.53-2.91;<i>P</i> = .62) in spot sign–positive patients. <h3>Conclusions and Relevance</h3> The predictive performance of the spot sign for ICH expansion was lower than in prior reports from single-center studies. No evidence suggested that patients with ICH and a spot sign specifically benefit from intensive BP reduction. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT01176565
Dual inhibition of the Notch and Hedgehog developmental pathways in colon cancers suppresses viability by combined downregulation of the PI3K/Akt pathway
Authors: Raymond Meng, Christopher Shelton, Yue-Ming Li, Gary Schwartz
Journal: Cancer Research (2008)

1528   An urgent need exists for novel therapies to treat metastatic colon cancers. Because aberrant activation of the Notch and Hh developmental pathways may contribute to colon cancer progression through the induction of PI3K/Akt signaling, we hypothesized that inhibition of Notch and Hh activity may suppress tumor growth. The viability of six colon cancer cell lines was decreased up to 30% by single-agent treatment with gamma-secretase inhibitors (GSIs), which suppress Notch, or with cyclopamine (CY), which inhibits Hh, but not with the inactive CY derivative tomatidine. However, combined treatment with GSIs and CY synergistically suppressed viability by more than 50% to 75% (p p
The impact of long-standing metformin use on survival in breast cancer patients.
Authors: Yun Rose Li, Laura Steel, Elena Carrigan, Vicky Ro, Jenny Nguyen, Julia C. Tchou
Journal: Journal of Clinical Oncology (2016)

1569 Background: The role of biguanide Metformin, a first-line oral hypoglycemic agent, as a cancer prevention agent has been controversial. In breast cancer (BC) patients, few cohort studies have carefully examine the long-term impact of metformin use both before and after cancer diagnosis on patient outcomes. Methods: We examined the association between the pattern of metformin use and clinical outcomes of 1215 patients (median f/u 66.3 months), who underwent primary breast cancer (BC) surgery at our institution between 1997 and 2013. In total, 97 patients had recorded metformin use before (B) and 97 recorded metformin use after (A) BC diagnosis, with a median exposure of 70.8 and 40.4 months, respectively. Results: Compared to non-users, metformin use was associated with being older than the age of 50 at diagnosis (79.8% vs 66.5%; Fisher’s Exact Test (P < 1.98x10-15) and being African American (29.6% vs 9.7%; P < 7.48x10-15). Tumor size and nodal status were similar except that Her2+ breast cancer subtype (35.1 vs. 5.9%, p < 2.97 x 10-10) is more common in metformin users. Univariate Kaplan-Meier analysis showed that overall survival (OS) in metformin users (A and B combined) was worse initially but improved late in follow-up, as compared to non-metformin users. This prompted us to evaluate if OS differs between the two metformin user subgroups, A and B. Indeed, OS of subgroup A was better than non-users (HR = 0.38, 95% CI = 0.16 to 0.92), while OS of subgroup B was worse (HR 2.32; 95%CI 1.40-3.84). On multivariate analysis, a history of metformin use before BC diagnosis was associated with significantly worse OS (HR 2.19; 95%CI 1.24-3.87) while metformin use after BC diagnosis was comparable to non-users (HR 0.47; 95%CI 0.18-1.23). Conclusions: This is the first cohort study to examine the effect of long-standing metformin use relative to BC diagnosis on OS. Efforts to examine disease-specific survival and local and distant recurrence risks are ongoing. Our findings illustrates the complex interaction between underlying metabolic risk and BC outcomes, as well as underscore the value for multi-system approaches and the value of “deep-phenotyping” to population-based clinical studies.
Effect of Injection of Rat Bone Marrow on Recticular Tissues of Mice Exposed to X Radiation in the Midlethal Dose Range&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: C. C. Congdon, T. Makinodan, N. Gengozian
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Effect of Injection of Rat Bone Marrow on Recticular Tissues of Mice Exposed to X Radiation in the Midlethal Dose Range Get access C. C. Congdon, C. C. Congdon Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Makinodan, T. Makinodan Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Gengozian N. Gengozian Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 5, May 1957, Pages 603–613, https://doi.org/10.1093/jnci/18.5.603 Published: 01 May 1957 Article history Received: 23 January 1957 Published: 01 May 1957
Real world experience with exemestane and everolimus for advanced HR-positive breast cancer.
Authors: Ying Wang, Dan Le, Pierre Camateros, Caroline A. Lohrisch
Journal: Journal of Clinical Oncology (2017)

e12538 Background: BOLERO-2 demonstrated a significant progression free survival (PFS) advantage for EvEx compared to Ex alone in the treatment of metastatic hormone receptor positive breast cancer (HP-MBC) following failure with aromatase inhibitor (AI) in menopausal patients. Benefits and harms reported in clinical trials do not always mirror real life, thus we examined the frequency of dose modifications for toxicity and PFS in a real-world population. Methods: Women with HP-MBC started on EvEx between Dec. 2, 2013 and Nov. 1, 2015 in any one of five cancer centres in British Columbia, Canada were identified via the provincial pharmacy database. Clinical and prior treatment details, adverse events, and outcomes were compared to those of the BOLERO-2 study participants. Results: We identified151 patients treated with EvEx: median age was 53 (range 25 – 85), and 60 (40%) were ≤49. ECOG performance status was 0-1 in 122 (81%) and 2-3 in 29 (19%). 135 (89%) received prior treatment for MBC, which included non-steroidal AI in 117 (87%) and chemotherapy in 74 (55%). 94 (62%) received EvEx as 3 rd line treatment and beyond. Median follow-up was 714 days (range 10 – 1127); 66 (44%) were alive at time of analysis. Dose reductions, interruptions and discontinuations of everolimus due to toxicity occurred in 32%, 31%, and 30%, respectively, higher than reported in BOLERO-2. Median PFS was 6.1 months (95% CI: 4.9 – 7.7) in our cohort, similar to that of the investigator assessed EvEx arm of BOLERO-2. Majority, 52%, of dose reductions/interruptions occurred within the first month of treatment initiation. Conclusions: We observed similar PFS forEvEx in a real world population compared with BOLERO-2. Dose interruptions and reductions were frequent, but may have enabled patients to tolerate therapy for longer. Discontinuation rates for toxicity were high and may limit the efficacy of the combination in the real world. Recent findings of primary prophylaxis against mucositis may help enhance continuation and dose maintenance (Beck et al. JCO 2016). Alternately, starting at a lower dose of Ev and increasing to tolerance may be worth exploring, as despite higher rates of dose modifications, our PFS rate was similar to that in BOLERO-2.
Characterizing the transmissibility of cancer.
Authors: Seth Blumberg
Journal: Journal of Clinical Oncology (2016)

e13076 Background: Although cancer screening has a remarkable impact on worldwide morbidity and mortality, patients are often non-compliant with screening recommendations. Our ability to understand and manage the seeds of non-compliance can reap substantial public health benefits. The Twitter social network provides a unique perspective on public sentiment regarding cancer screening modalities. Methods: We utilized a Naive Bayes algorithm to analyze over 30,000 tweets related to cancer screening via colonoscopy, pap smear or mammography. Tweets were classified as having positive, negative, or neutral sentiment. For each screening modality, we correlated tweet sentiment with demographic information as well as markers of social network visibility (i.e. Klout score). We also identified the most commonly occurring words among positive, negative and neutral tweets. Finally we used re-tweet rate to study the contagion of sentiment. Results: For mammography and pap smear-related tweets, sentiment was more likely to be positive than negative. In contrast, more colonoscopy-related tweets carried negative sentiment than positive sentiment. Contagion of sentiment paralleled the spread of infectious diseases with a ‘re-tweet’ rate that was close to the critical value of R0 = 1. Sentiment toward colonoscopy, mammoraphy, and pap smear did not correlate with Klout score. However, there was significant heterogeneity in re-tweet rate, beyond what would be expected by chance. Positive and negative tweets among each screening modality tended to share lexical features. Positive tweets showed a strong resonance with the benefit of early detection. Fear and pain were the principal lexical features seen in negative tweets. Conclusions: Twitter data provides a quantitative framework for how to improve the dissemination of positive sentiment, both in terms of how cancer screening is discussed with patients and how public health messages can be disseminated via social media.
Residual disease after HER2-directed therapies in the neosphere study: Modulation of tumor lymphocyte infiltration (TIL) and prognosis.
Authors: Giampaolo Bianchini, Tadeusz Pienkowski, Young-Hyuck Im, Giulia Valeria Bianchi, Ling-Ming Tseng, Mei-Ching Liu, Ana Lluch, Vladimir Semiglazov, Juan de la Haba-Rodriguez, Do-Youn Oh, Brigitte Poirier, Jose Luiz Pedrini, Pinuccia Valagussa, Luca Gianni
Journal: Journal of Clinical Oncology (2016)

517 Background: We investigated the treatment modulation of TIL, and its association with distant event free survival (DEFS) in patients (pts) with residual disease (RD) in the NeoSphere study Methods: In the NeoSphere 417 HER2+ pts were randomized to neoadjuvant TD, TPD, TP or PD (T=trastuzumab, P=pertuzumab, D=docetaxel), and recived FAC/FEC and trastuzumab after surgery. Paired core biopsy (CBx) and surgical samples (Sx) were available for assessment of stromal TILs ( (sTIL) in 137 of 296 pts with RD (46.3%). ΔTIL was defined as the percentage change of sTILs. In addition we also assessed pre- to post-treatment changes of mRNA expression of selected immune markers (CD8A, ICOS, 4-1BB, CD40L, PDL1, CTLA4) Results: There was no difference between mean pre- and post- sTILs (p=0.46). However, high inter- and intra-patient variability was present. ΔTIL higher than 40% was observed in 31 of 137 (22.6%; 10.2% increase and 12.4% decrease, respectively). ΔTIL was directly and significantly (p≤0.001) correlated with changes of the selected immune biomarkers, indicating co-regulation of TILs with immune activation (ICOS, 4-1BB, CD40L) and immune inhibition (CTLA4, PDL1). All arms of therapy (including TP without chemotherapy) showed a similar immune modulation. While pre- and post-treatment sTILs were not significantly associated with DEFS, a 10% increase of ΔTIL was linked to better DEFS in univariate (HR 0.84 [0.73-0.98], p=0.025) and multivariate (HR 0.75 [0.62-0.91], p=0.004; adj for ER status, nodal status and T stage) analysis. The 5 yrs DEFS for high, intermediate and low ΔTILs tertiles was 92.7%, 81.8% and 69.1%, respectively (log-rank test p=0.02) Conclusions: Trastuzumab and/or pertuzumab regimens modulated the amount of TILs and the expression of markers of immune activation (ICOS, 4-1BB) and inhibition (CTLA4, PDL1). Such modulation is linked to DEFS of patients with RD, and carries more prognostic information than either pre or post treatment sTILS. We also confirmed that PDL1 expression is dynamic and can be modulated by treatments. Overall, the data lend additional weight to studying combinations of immune checkpoint inhibitors with HER2-directed monoclonal antibodies