tbuckley/cabot-search huggingface dataset:
EPIG-09GENETIC AND EPIGENETIC TUMOR EVOLUTION IN GLIOMATOSIS CEREBRI
Authors: Sheng Li, Scott Connors, David Pisapia, Yujie Huang, Raymond Xu, Jeffrey Greenfield
Journal: Neuro-Oncology (2015)

Gliomatosis cerebri (GC) is a rare and aggressive cancer (fewer than 100 cases diagnosed in the United States each year). GC is an extensively infiltrating high-grade glial tumor to at least three lobes in the brain (median length of survival is 9.5 months). Accumulating evidence suggests that epigenetic dysregulation may play an important role in tumor progression, and epigenetic modulators have begun to show promise as therapeutic options in other pediatric and adult malignancies. However, the evolution of GC tumor genetics and epigenetic dynamics have not been well studied. Here we describe the GC somatic mutation spectrum of 12 patients and an intra-tumor evolution pattern between lower and higher grade areas in three patients. We performed exome-capture sequencing, and reduced representation bisulfite sequencing to examine the genetic and epigenetic dynamics for the GC samples. Recurrent mutations were found in genes related to Cell cycle, p53 signaling, Wnt signaling, and MAPK signaling pathways. Furthermore, we found increased epigenetic heterogeneity in tumor samples with enhancement compared to the normal brain samples, which suggests that epigenetic dynamics permits a superior evolutionary trajectory leading to GC progression. These findings may help explain tumor evolution and target mechanism for therapeutic diversification. By understanding the driver events, one may eventually provide more accurate diagnosis of the disease and define clinical targets for improvement of the treatment and survival rate of GC patients.
The role of modification of CURB-65 score as prediction factor for one year survival in acute exacerbation of COPD
Authors: Wiwien Heru Wiyono, Widya Sri Hastuti, Ratnawati, Iwang Gumiwang, Joedo Prihartono
Journal: European Respiratory Journal (2012)

Introduction : Acute exacerbation of COPD (AECOPD) is associated with a high risk of mortality. A risk-prediction model using information easily obtained on admission could help to identify high-risk individuals. The CURB-65 score was developed to predict mortality risk in community acquired pneumonia. A retrospective study found that this score was also associated with mortality in AECOPD.   Methods : Consecutive patients with physician diagnosed AECOPD admitted to a public hospital during a 1-year period were studied prospectively. The modification of CURB-65 Score were calculated from information obtained at initial hospital presentation. The modification of CURB-65 Score are one point each for  C onfusion,  U rea > 7 mmol/L,  R espiratory rate ≥30/min, Sistolic  B lood pressure  65  years and present of  cardiovascular  disease. Remeasure will be done every three month and looking for the corelation between both using McNemar test. After complete one year of evaluation, the relation between modification of CURB-65 score and risk of mortality will analyze using Chi Square test.   Result:  Research is still proceeding and 92 patients have been collected. 30-day mortality data were available for 92 of 92 patients. The 30-day mortality by score groups were: low risk (scores 0–1) 4.16% (2/48) and high risk (scores 2–6) 11,36% (5/44). There was significant correlation between modification of CURB-65 score and mortality ( p
A screen of approved drugs and molecular probes identifies therapeutics with anti–Ebola virus activity
Authors: Lisa M. Johansen, Lisa Evans DeWald, Charles J. Shoemaker, Benjamin G. Hoffstrom, Calli M. Lear-Rooney, Andrea Stossel, Elizabeth Nelson, Sue E. Delos, James A. Simmons, Jill M. Grenier, Laura T. Pierce, Hassan Pajouhesh, Joseph Lehár, Lisa E. Hensley, Pamela J. Glass, Judith M. White, Gene G. Olinger
Journal: Science Translational Medicine (2015)

Several FDA-approved drugs, including bepridil and sertraline, may be therapeutics against filovirus infections.
A phase II study of capecitabine (CAP) plus PHY906 in patients (pts) with advanced pancreatic cancer (APC)
Authors: M. W. Saif, J. Li, L. Lamb, A. Rosenberg, K. Elligers, S. Ruta, M. Mezes, N. Grant, S. H. Liu, E. Chu, Y. Cheng
Journal: Journal of Clinical Oncology (2009)

e15508 Background: Gemcitabine (G) is regarded as the standard treatment for pts with APC. However, a standard second-line chemotherapy regimen has yet to be defined after G. PHY906, a 4-herb traditional Chinese medicine has a history of &gt; 1,800 yrs of human use to treat GI symptoms including diarrhea. Preclinical studies showed that PHY906 may potentiate antitumor activity of CAP in human PANC-1 xenograft (ASCO 2007). A phase I study showed that CAP can be escalated up to 1750 mg/m 2 PO BID on d1- 7 and PHY906 800mg PO BID on d1–4 q 2 wks with no DLTs (ASCO, 2008). Delivered dose-intensity of CAP was similar at 1750mg/m 2 dose level as 1500mg/m 2 . Therefore, 1500mg/m 2 of CAP and PHY906 was further tested in a phase II study as second-line treatment in pts with APC. Methods: Pts with G-refractory APC with ECOG PS &lt;2 were treated with CAP 1500mg/m 2 d1–7 with PHY906 800mg d1–4 q 2 wks. Response was assessed by CT scan according to RECIST q 6 wks and toxicity according to NCI-CTC v3.0. Primary objective is overall survival. Secondary objectives include overall RR, PFS and measurement of cytokines to assess inhibition of NF-kappa B, a possible mechanism responsible for PHY906's pharmacological activity. Results: As of January 5, 2009, 25 pts have been enrolled. Baseline characteristics include median age, 65 (range, 40–85); male/female,15/10; ECOG PS 0/1, 4/19; median cycles: 3 (r: 0.5–15). At this point 5 pts are still in active treatment. 4 pts have confirmed OS &gt; 6 ms (1 still on study) with 2 further pts approaching 6 ms. Among evaluable pts, 1 had PR (5.3%), 11 SD (57.9%) and 7 PD (36.8%) after initial restaging scan. 36 % pts had &gt;30% reduction in CA19–9 as biochemical response. There were 7 deaths on/within 30 days of study treatment, 6 related to PD and 1 had acute MI. G3/4 toxicities diarrhea 3/25 (12%), fatigue, 1/25 (4%), HFS 1/25 (4%) and mucositis 1/25 (4%). 1 pt was removed from study due to G3 HFS. Biomarker studies (IL4, GM-CSF, TNF-alpha, IL10, MCP-1, IL2, IL6) are ongoing. Conclusions: This is the first clinical study to evaluate a botanical formulation PHY906 with CAP in G-refractory APC pts. CAP + PHY906 regimen appears a safe and feasible salvage therapy in APC and warrants further investigation. In addition, PHY906 may have a cytoprotective antidiarrheal and anti-HFS effect, making treatment with CAP more tolerable. [Table: see text]
Tumor Antigen Induction by the Envelope-Defective Bryan Strain of Rous Sarcoma Viruses 2
Authors: Reinhard Kurth, Gay Kitchener
Journal: JNCI Journal of the National Cancer Institute (1978)

Chicken, quail, and turkey cells were infected and/or transformed by various avian leukosis or sarcoma oncovirus (ALSV) strains as well as by the envelope-defective Bryan high-titer strain of Rous sarcoma virus [BH-RSV(-)]. All fibroblast-transforming avian sarcoma viruses (ASV), including BH-RSV(-), were able to induce the expression of the previously described avian tumor-specific cell-surface antigen(s) (TSSA). Thus TSSA was group-specific for all tested transforming ASV. Since BH-RSV(-) is a stable deletion mutant lacking the capacity to code for the 85 000d major virus envelope glycoprotein (gp85), it seemed unlikely that the group-specific antigen determinants of gp85 that were recently detected on ALSV-infected cells could account for TSSA expression.
A Prospective Study of Re-Evaluation of the Her2 Status in Metastatic or Recurrent Lesions in Gastric Cancers with Her2-Negative Primary Tumors: Gasther-1
Authors: S.R. Park, M.H. Ryu, Y.S. Park, H. Jung, B. Ryoo, Y. Kang
Journal: Annals of Oncology (2014)
3-D tumor invasion pattern analysis of cervical carcinoma
Authors: U.-D. Braumann, J.-P. Kuska, J. Einenkel, L.-C. Horn, M. Höckel
Journal: Journal of Clinical Oncology (2005)

5130 Background: A high-resolutional (10μm) reconstruction of the 3-D tumor invasion of squamous cell carcinoma of the uterine cervix has become feasible for the first time using a newly developed dedicated image processing chain achieving the most detailed reconstruction (VOIs up to 150mm3) of a solid tumor’s invasion front so far. While routine analyses based on single histological sections have suggested the existence of detached tumor islets, despite suspected prognostic implications, precise analyses of the tumor-stromal interface were still missing. Methods: 13 serially sectioned specimen (pT1b1) have been 3-D reconstructed from digitised H&E stained serial sections (90–500 slices). The processing chain consisting of a coarse-to-fine sequence of three automatic image registration steps finally ends up with a 3-D tumor segmentation. For the morphological quantification of the tumoral invasion we use discrete compactness, an illustrative and robust measure providing the first algorithmic description of cervical tumor invasion. Results: While a single-section based verbal routine tumor invasion assessment has resulted in a typical three-tiered classification (closed, finger-like, diffuse), the new algorithmic invasion quantification has yielded a homogeneous spectrum of compactnesses. Lacking any subjectivity, those reproducible numbers turn out to be basically corresponding to the verbal assessments, but exhibit a much higher accuracy and in turn are considered both plausible and appropriate by the pathologist. Another very interesting outcome is that irrespective the invasion pattern, all tumors invade ’per continuitatem’ exhibiting a tumor massif but no detached tumor islets, a finding which is essentially facilitated by our 3-D reconstructions. Conclusions: Modern image processing techniques are of great importance for deepened insights into tumor-stromal interaction. Since 3-D reconstructions are not feasible for routine application, ongoing work investigates to what degree the essence of those algorithmic assessments can be obtained even on single 2-D sections available from a larger number of cases, by this enabling reliable conclusions on clinical questions like the prognostic relevance of the tumor invasion pattern. No significant financial relationships to disclose.
Circulating regulatory T cells in advanced breast cancer patients
Authors: M. V. Karamouzis, S. A. Perez, A. D. Gritzapis, A. Ardavanis, D. V. Skarlos, C. N. Baxevanis, G. Rigatos, M. Papamichail
Journal: Journal of Clinical Oncology (2006)

10567 Background: It has been recently shown that regulatory CD4+CD25 bright T cells (Tregs) are increased in patients with several malignancies and this increase correlates with advanced stage and dismal prognosis. Breast cancer (BC) patients represent a heterogeneous population with unpredictable natural history, even at advanced stages. We sought to monitor advanced stage (III and IV) BC patients, overexpressing HER-2/neu (HER) or not, for circulating Tregs before, during and after the administration of chemotherapy, either alone or in combination with Trastuzumab. Methods: Determination of circulating Tregs was performed in 50 μl whole peripheral blood by a Lyse NoWash FACS procedure and staining for CD45, CD4 and CD25. Tregs were determined as the lymphocytes expressing lower CD4 within the CD4+ T cell compartment and higher CD25 expression compared to the CD4 negative lymphocytes. Clinical evaluation of the patients was done according to RECIST criteria. Results: 24 HER+ and 19 HER- stage III / IV BC patients have been compared to 14 healthy donors, before therapy. The percentage of Tregs among the CD4+ T cell population of HER+ patients was significantly increased compared to both HER- patients and healthy donors (8,74 ± 2,68 vs 6,07 ± 1,85 and 6,55 ± 1,49, respectively). Trastuzumab combined with chemotherapy resulted in a progressive decrease in the percentage of circulating Tregs, reaching normal levels after the fourth cycle of treatment (6,95 ± 1,17). On a per patient basis, decrease in Tregs correlated either with documented partial response or stable disease, while increased Tregs during treatment coincided with progressive disease. No statistically significant change in the percentage of Tregs after chemotherapy was observed in HER- patients. Conclusions: 1) Increased Tregs do not directly correlate with clinical stage in BC, as stage III and IV HER (+) and (−) patients exhibit significantly different Tregs profiles. 2) HER+ advanced BC patients exhibit increased percentages of circulating Tregs and respond to the combination of Trastuzumab and chemotherapy by decreased Tregs. This decrease is either due to a reduction of the tumor burden or neutralization of circulating HER antigen by Trastuzumab, or a combination of both. No significant financial relationships to disclose.
PTH-220 Pregnancy in established home parenteral nutrition (HPN)
Authors: WJ Gashau, E Nixon, K Sutcliffe, S Lal
Journal: Gut (2015)

<h3>Introduction</h3> There are few case reports of successful pregnancy in patients on Home Parenteral Nutrition (HPN). Most of the available literature focuses on acute, short-term PN use in hyperemesis gravidarum. We report five successful pregnancies on established HPN patients over a 30-year period in a national Intestinal Failure Unit. <h3>Method</h3> HPN macronutrient and fluid regimes during pregnancy were determined by resting energy requirements with additional alterations influenced by maternal stressors, underlying medical condition, maternal weight gain and foetal growth measurements. Micronutrient alterations were guided by recommended daily allowances (RDA) already precedent in obstetric care, adjusted according to biochemical and haematological indices checked regularly throughout gestation. <h3>Results</h3> The median time on HPN before pregnancy was 18 months (range 4–72). Two pregnancies presented late at 12 and 25 weeks gestation. Both were unplanned and one patient was on warfarin until 12 weeks gestation. No antenatal or postnatal anomalies were reported in this infant. Four out of five pregnancies reached full term, with one pre-term delivery at 30 weeks gestation. There were no documented cases of essential fatty acid or fat-soluble vitamin deficiency. In two cases, placentas were examined post-partum and showed no evidence of lipid deposition. Subsequent growth and development of all infants have been satisfactory. Median maternal weight gain was 5kg (range 1–5.5kg). Foetal measurements were deemed satisfactory in all pregnancies with birth-weights ranging between 10<sup>th</sup>and 75<sup>th</sup>centile for gestational age. All patients received a portion of their energy requirement from lipid emulsion. There were no documented catheter related infections during gestation or in the post-partum period. Two patients developed worsening liver enzymes on a background of Intestinal Failure Associated Liver Disease (IFALD). The first was attributed to increasing energy requirements during pregnancy and the second due to cholestasis of pregnancy. Both improved post-partum. <h3>Conclusion</h3> All women of child-bearing age on HPN should be counselled about pregnancy. Ideally, it should be planned to allow appropriate monitoring. With appropriate support, pregnancy and delivery can occur uneventfully with minor adjustments needed in established HPN regimes to ensure adequate foetal growth. <h3>Disclosure of interest</h3> None Declared.
Phase II genomics study in patients receiving ixabepilone as neoadjuvant treatment for breast cancer (BC): Preliminary efficacy and safety data
Authors: A. Llombart Cussac, J. Baselga, G. Manikhas, E. Kubista, G. Steger, S. M. Galbraith, M. A. Sullivan, K. Zerba, H. Lee, L. Gianni
Journal: Journal of Clinical Oncology (2005)

586 Background: Previous studies have confirmed the activity of ixabepilone (BMS-247550, a semi-synthetic analog of epothilone) in metastatic BC. The present study was designed to determine the pathological response obtained with ixabepilone as neoadjuvant therapy for BC and to obtain tumor samples for analysis of gene expression and identification of potential predictors of response to ixabepilone. Methods: Women with invasive stage IIA-IIIB breast cancer with tumors ≥3 cm diameter received 40 mg/m2 ixabepilone as a 3-hour infusion on Day 1 for up to four 21-day cycles, followed by surgery within 3–4 weeks of completion of chemotherapy. Biopsies for analysis of mRNA expression were obtained both pre- and post-therapy. Adjuvant chemotherapy with an anthracycline combination regimen followed by radiotherapy and tamoxifen were administered as indicated. Pathological response was assessed using the Sataloff criteria. Results: A total of 164 patients were enrolled. Data were available for 47 patients for this preliminary report. Median age was 57 years (range 27–77) and 100% were ECOG 0. Median tumor diameter was 4 cm (range 3–10), Grade 1/2/3/unk was 6%/47%/23%/23% and ER status of +/-/unk was 49%/47%/4%. A complete pathological response (pCR) in the breast was achieved in 10 patients (21%), of whom 8 (17%) also had pCR in the axillary lymph nodes. Grade 3/4 neutropenia occurred in 21%/13%. Common grade 2/3 toxicities on-treatment included arthralgia/myalgia (28%/6%), neuropathy (11%/2%), and mucositis (6%/2%). Conclusions: Based on this early analysis, ixabepilone has manageable toxicity and a pCR rate which compares favorably to that reported for studies of single agent taxanes (ranging from 3–20%). This analysis will be updated at the ASCO annual meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Expression of epidermal growth factor receptor (EGFR) in the bronchial epithelium of patients with chronic obstructive pulmonary disease (COPD)
Authors: Eman M. Saied, Adel S. Bediwy
Journal: European Respiratory Journal (2011)

COPD is a major health problem that is caused predominantly by smoking. In COPD, airway epithelium undergoes alterations which are partially attributed to activation of EGFR. Our aim was to study the expression of EGFR in bronchial epithelium of COPD patients and smokers in comparison to normal bronchial epithelium, to investigate its role in pathogenesis of COPD and in the epithelial alterations that characterize this disease.

Methods: We studied 50 subjects (3 groups): group I (10 non-smoking controls), group II (10 apparently healthy smokers), and group III (30 COPD patients) who was subdivided into subgroup IIIA (COPD current smokers) and IIIB (COPD ex-smokers). Bronchoscopic biopsies were subjected to immunohistochemical staining for EGFR.

Results: Histological epithelial alterations were significantly exaggerated in group III compared to group II with no differences between subgroups IIIA and IIIB. EGFR expression was significantly higher in group II and III than group I. Group III showed significantly higher EGFR expression than group II. Subgroup IIIB had significant higher EGFR expression than IIIA. EGFR had a significant positive correlations with goblet cell hyperplasia and a significant negative correlation with FEV1 in groups II and III and a significant positive correlation with smoking index in group II.

Conclusion: EGFR plays an important role in epithelial changes in bronchial epithelium in COPD through active smoking, and it has a significant role in regulating mucus production in airway epithelium. Disruption of its cascade may provide a mechanism of airway inflammation by its effect on goblet cells and mucus secretion.
Prostate-specific antigen following prostate radiotherapy: how low can you go?
Authors: P W McLaughlin, H M Sandler, M R Jiroutek
Journal: Journal of Clinical Oncology (1996)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1996.14.11.2889 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8918484 Prostate-specific antigen following prostate radiotherapy: how low can you go? P W McLaughlinxP W McLaughlinSearch for articles by this author , H M SandlerxH M SandlerSearch for articles by this author , M R JiroutekxM R JiroutekSearch for articles by this author https://doi.org/10.1200/JCO.1996.14.11.2889 First Page PDF © 1996 by American Society of Clinical Oncology
Interim Guidelines for Prevention of Sexual Transmission of Zika Virus — United States, 2016
Authors: Alexandra M. Oster, John T. Brooks, Jo Ellen Stryker, Rachel E. Kachur, Paul Mead, Nicki T. Pesik, Lyle R. Petersen
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Zika virus is a mosquito-borne flavivirus primarily transmitted by Aedes aegypti mosquitoes (1,2). Infection with Zika virus is asymptomatic in an estimated 80% of cases (2,3), and when Zika virus does cause illness, symptoms are generally mild and self-limited. Recent evidence suggests a possible association between maternal Zika virus infection and adverse fetal outcomes, such as congenital microcephaly (4,5), as well as a possible association with Guillain-Barré syndrome. Currently, no vaccine or medication exists to prevent or treat Zika virus infection. Persons residing in or traveling to areas of active Zika virus transmission should take steps to prevent Zika virus infection through prevention of mosquito bites (http://www.cdc.gov/zika/prevention/).
Two cases of overlap severe cutaneous adverse reactions to benznidazole treatment for asymptomatic Chagas disease in a nonendemic country
Authors: J. González-Ramos, L. Noguera-Morel, H.Y. Tong, E. Ramírez, E. Ruiz-Bravo, T. Bellón, R. Cabañas, L. Cachafeiro, P. Herranz-Pinto
Journal: British Journal of Dermatology (2016)

Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk.
Emerging Therapy for the Treatment of Mantle Cell Lymphoma
Authors: Saurabh Rajguru, Brad S Kahl
Journal: Journal of the National Comprehensive Cancer Network (2014)

Mantle cell lymphoma (MCL) is a heterogenous disease with historically relative poor outcomes. However, new treatment strategies seem to be improving the prognosis for patients. Although no universally accepted standard of care exists, options for patients with newly diagnosed MCL include intensive and nonintensive strategies. Generally, intensive strategies produce more durable remissions and are selected for younger patients, whereas nonintensive strategies are most appropriate for older patients or patients with comorbidities. However, new options are closing the treatment gap between intensive and nonintensive strategies. Treatment options are also increasing for patients with relapsed/refractory MCL and include agents targeting the microenvironment and the B-cell receptor signaling pathway.