tbuckley/cabot-search huggingface dataset:
A phase II cross-over study of docetaxel versus vinorelbine in anthracycline-resistant, advanced breast cancer.
Authors: C. C. Alifrangis, D. Shipway, O. Gojis, M. Emson, D. Mackie, R. C. Coombes, C. Palmieri
Journal: Journal of Clinical Oncology (2010)

1097 Background: Docetaxel and vinorelbine as single agents have both demonstrated efficacy in the treatment of metastatic breast cancer. This prospective study compared the efficacy of these two treatments in anthracycline refractory metastatic breast cancer, and assessed the disease response when used in cross over after disease progression on the initial regime. Methods: Patients with metastatic breast cancer who had progressed following anthracycline treatment were randomly assigned to either docetaxel 100mg/m2 on day 1 every 21 days or vinorelbine 25mg/m2 day 1 every 14 days. Patients were eligible to switch over to the other regime at progression. Results: 38 patients were randomized, 18 to docetaxel and 20 to vinorelbine, 4 patients became ineligible as a result of protocol violations or withdraw from study (1 in docetaxel, 3 in vinorelbine), and response data was not available on 1 patient randomized into docetaxel arms. The objective response was 12.5% (PR) in the docetaxel arm with 31% obtaining clinical benefit from stable disease (SD). In the vinorelbine arm there was a 6% PR with 6% SD. The median time to progression was 10.8 weeks (range 3-39 weeks) in the docetaxel arm and 9.5 weeks (range 4-37 weeks) in the vinorelbine arm. At progression 37.5% (6 patients) switched from docetaxel (T) to vinorelbine (V) and 53% (9 patients) from vinorelbine (V) to docetaxel (T). There was 1 objective response in V→T but none in T→V. The median time to progression was 9.5 weeks (2-16 weeks) in T→V and 15 weeks (range 7-43 weeks) in V→T. Grade 3 or 4 haematological toxicities were more common in the docetaxel arm (11) compared to the vinorelbine arm (1). Conclusions: Docetaxel and vinorelbine have similar efficacy as single agents in anthracycline refractory disease, however vinorelbine is better tolerated. Whilst an objective response was seen only in the crossover of V→T, clinical benefit was observed in both V→ T and T→V crossover. No significant financial relationships to disclose.
Abstract 13078: Model-based Reexpression of Vortex Formation Time Differentiates Between Pseudonormal vs. Normal Left Ventricular Echocardiographic Filling Patterns
Authors: Erina Ghosh, Sandor J Kovacs
Journal: Circulation (2013)

Introduction:  The column of blood aspirated into the LV during early, rapid filling (Doppler E-wave) forms an expanding toroidal vortex ring and facilitates leaflet tip coaptation during diastasis. Vortex formation time (VFT) is the standard dimensionless index used for quantification of vortex ring growth whose definition is  VFT standard   = (E-wave velocity time integral (EVTI) [cm])/(mitral orifice diameter [cm]). A previously validated expression, { VFT model-based   = (EVTI)/ (effective mitral orifice diameter)} incorporates left heart ‘constant-volume pump’ physiology and reveals VFT’s explicit E/E’ dependence. Previously,  VFT standard   has been shown to differentiate between normal vs. impaired filling based on E-wave differences. Here, we show that  VFT model-based   can differentiate between pseudonormal (PN) vs. normal (NL) E-wave patterns.   Method:  Thirteen age-matched NL and 12 PN subjects (defined as subjects with E/E’>8 and E’ peak   VFT standard   and 2)  VFT model-based   using the above stated definitions and previously validated methods.   Result:  VFT standard   did not differentiate between groups [NL (3.58±1.06) vs. PN (4.18±0.79), p = 0.13] whereas  VFT model-based   did [NL (3.15±1.28) vs. PN (4.75±1.35), p=0.006 (Fig. 1)].   Conclusion:  Compared to  VFT standard  ,  VFT model-based   is sensitive to the physiological changes associated with pseudonormalization. Since  VFT model-based   explicitly incorporates longitudinal chamber (E’) motion, VFT as a diastolic function index can now be used for analysis of pseudonormal filling patterns.
NIMG-67COMPUTER EXTRACTED TEXTURE DESCRIPTORS FROM DIFFERENT TISSUE COMPARTMENTS WITHIN THE TUMOR HABITAT ON TREATMENT-NAÏVE MRI PREDICT CLINICAL SURVIVAL IN GLIOBLASTOMA PATIENTS
Authors: Pallavi Tiwari, Jay Patel, Sasan Partovi, Prateek Prasanna, Anant Madabhushi
Journal: Neuro-Oncology (2015)

PURPOSE: Glioblastoma Multiforme (GBM) is a highly aggressive and heterogeneous brain tumor. Currently all GBM patients are given “one-dose-fit-all” treatment. Identification of prognostic markers can allow for personalized therapy options for GBM. The underlying hypothesis of this study is that the heterogeneity in GBM (due to subtle variations in tumor enhancement, cellular density, necrosis that are not visually appreciable on volumetric analysis of MRI) is prognostic and can be captured using computerized texture descriptors extracted from within different tumor compartments (enhancing tumor, necrotic core, edema). These compartments together define tumor “habitat”, and computerized texture features from within the habitat can be predictive of short-term (STS) ( 24-months). METHODS: A total of 58 3Tesla MRI studies (27 STS, 35 LTS) with GdT1C, FLAIR, and T2w protocols were obtained from the TCIA repository. Enhancing tumor, and necrotic regions on Gd-T1 and edematous region jointly on T2w and FLAIR, were segmented by an expert using Slicer 3D. 135 2-D texture descriptors, and volumetric measurements were extracted on a per-voxel basis from each of the 3 sub-regions (tumor, necrosis, edema) on every MRI protocol. Feature selection was used to identify most discriminative features with a random forest classifier trained via 3-fold cross validation. Kaplan-Meier (KM) survival curves were used for analysis, with correction for multiple hypothesis testing to identify features that were significantly (p < 0.05) correlated with survival. RESULTS: Contributions from top 15 texture features within the tumor habitat, (edema, necrotic core, enhanced tumor), were together most significantly associated with survival, across Gd-T1-C (p = 0.003), FLAIR (p = 0.006), and T2w (p = 0.04) as compared to individual features, and volumetric measurements from the tumor habitat. CONCLUSION: Computerized texture features when jointly interrogated across compartments within the tumor habitat appear more prognostic of clinical survival in GBMs than features from enhancing tumor and tumor volume alone.
Epidemiology of Atherosclerosis and the Potential to Reduce the Global Burden of Atherothrombotic Disease
Authors: William Herrington, Ben Lacey, Paul Sherliker, Jane Armitage, Sarah Lewington
Journal: Circulation Research (2016)

Atherosclerosis is a leading cause of vascular disease worldwide. Its major clinical manifestations include ischemic heart disease, ischemic stroke, and peripheral arterial disease. In high-income countries, there have been dramatic declines in the incidence and mortality from ischemic heart disease and ischemic stroke since the middle of the 20th century. For example, in the United Kingdom, the probability of death from vascular disease in middle-aged men (35-69 years) has decreased from 22% in 1950 to 6% in 2010. Most low- and middle-income countries have also reported declines in mortality from stroke over the last few decades, but mortality trends from ischemic heart disease have been more varied, with some countries reporting declines and others reporting increases (particularly those in Eastern Europe and Asia). Many major modifiable risk factors for atherosclerosis have been identified, and the causal relevance of several risk factors is now well established (including, but not limited to, smoking, adiposity, blood pressure, blood cholesterol, and diabetes mellitus). Widespread changes in health behaviors and use of treatments for these risk factors are responsible for some of the dramatic declines in vascular mortality in high-income countries. In order that these declines continue and are mirrored in less wealthy nations, increased efforts are needed to tackle these major risk factors, particularly smoking and the emerging obesity epidemic.
Reduced <i>DICER1</i> Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli
Authors: Ghada Alsaleh, Ramzi Nehmar, Stephan Blüml, Cédric Schleiss, Eleonore Ostermann, Jean‐Philippe Dillenseger, Amira Sayeh, Philippe Choquet, Doulaye Dembele, Antoine Francois, Jean‐Hugues Salmon, Nicodème Paul, Gernot Schabbauer, Guillaume Bierry, Alain Meyer, Jacques‐Eric Gottenberg, Gabrielle Haas, Sebastien Pfeffer, Laurent Vallat, Jean Sibilia, Seiamak Bahram, Philippe Georgel
Journal: Arthritis & Rheumatology (2016)

While the regulatory role of individual microRNAs (miRNAs) in rheumatoid arthritis (RA) is well established, the role of DICER1 in the pathogenesis of the disease has not yet been investigated. The purpose of this study was to analyze the expression of factors involved in miRNA biogenesis in fibroblast-like synoviocytes (FLS) from RA patients and to monitor the arthritis triggered by K/BxN serum transfer in mice deficient in the Dicer gene (Dicer(d/d) ).The expression of genes and precursor miRNAs was quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). MicroRNA macroarray profiling was monitored by qRT-PCR. Cytokines were quantified by enzyme-linked immunosorbent assay. Experimental arthritis in mice was achieved by the transfer of serum from K/BxN donors. Apoptosis was quantified using an enzyme-linked immunosorbent assay.We found decreased DICER1 and mature miRNA expression in synovial fibroblasts from RA patients. These cells were hyperresponsive to lipopolysaccharide, as evidenced by their increased interleukin-6 secretion upon stimulation. Experimental serum-transfer arthritis in Dicer(d/d) mice confirmed that an unbalanced biogenesis of miRNAs correlated with an enhanced inflammatory response. Synoviocytes from both RA patients and Dicer(d/d) mice exhibited increased resistance to apoptotic stimuli.The findings of this study further substantiate the important role of DICER1 in the maintenance of homeostasis and the regulation of inflammatory responses.
Bioresorbable Coronary Scaffold Thrombosis
Authors: Serban Puricel, Florim Cuculi, Melissa Weissner, Axel Schmermund, Peiman Jamshidi, Tobias Nyffenegger, Harald Binder, Holger Eggebrecht, Thomas Münzel, Stephane Cook, Tommaso Gori
Journal: Journal of the American College of Cardiology (2016)
Glycosphingolipids as Tumor-Associated and Differentiation Markers&lt;xref ref-type="fn" rid="FN5"&gt;5&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN6"&gt;6&lt;/xref&gt;
Authors: S Hakomori, R Kannagi
Journal: JNCI Journal of the National Cancer Institute (1983)

Cette revue met l'accent sur quelques sujets d'evolution recente: 1) chimie des marqueurs glycolipidiques associes aux tumeurs et regis par le developpement; 2) facteurs affectant l'expression des glycolipides a la surface des cellules, et 3) application possible des marqueurs glycolipidiques au traitement et au diagnostic du cancer humain
The Trampoline and Serious Neurological Injuries
Authors: William G. Ellis
Journal: JAMA (1960)

Acrobatic tumbling on the trampoline, a canvas mat supported by springs within a steel frame, recently has become a popular sport for the general public. This report is based on the examination of 5 patients who suffered severe neurological injuries on the trampoline. The factors leading to their injuries were analyzed. All but one of the injuries resulted from backward somersaults imperfectly executed by persons unskilled in gymnastics. Acute cervical spine flexion led to quadriplegia in 3 patients, followed by death in one instance. One accident resulted in a fractured skull. Ten regulations for commercial trampoline centers are suggested, dealing especially with minimum instruction before attempting difficult gymnastic maneuvers such as somersaults. Public health officials and local medical authorities are asked to take the initiative in the enforcement of these regulations.
Biweekly neoadjuvant gemcitabine, epirubicin, and nano-particle albumin bound (nab) paclitaxel (GEA) with tumor SPARC analysis correlated with pathologic responses: Results of a multicenter phase II trial
Authors: B. R. Daniel, H. Doss, V. Gian, A. A. Meluch, P. B. Murphy, N. W. Peacock, E. Raefsky, D. A. Yardley, L. Simons, R. C. Inhorn
Journal: Journal of Clinical Oncology (2007)

11060 Background: The triplet combination of gemcitabine (G), anthracyclines and taxanes have demonstrated significant activity in the metastatic as well as neoadjuvant breast cancer setting with objective response rates of 90% and pathologic CRs of 20–25% with a variety of schedules. SPARC, a poor prognostic indicator, is a glycoprotein expressed in many solid tumors, including breast cancer, and is thought to mediate active tumor transport of nab paclitaxel resulting in high intratumoral concentrations. The present tumor analysis correlates SPARC expression with pathologic responses to neoadjuvant GEA. Methods: Patients with clinical T1c-T4d and/or N0–3, M0 (T1N0M0 excluded) breast cancer, chemo naive, ECOG PS 0–2, normal LVEF, adequate organ function were treated with neoadjuvant G 2000 mg/m 2 , epirubicin 50 mg/m 2 , nab paclitaxel (A)175 mg/m 2 IV q14 x 6 cycles followed by surgery. Postoperative therapy: G 2000 mg/m 2 and A 220 mg/m 2 q14 x 4 cycles. Neulasta 6 mg sc D2 was given with all cycles although alternative granulocyte stimulating factors was permitted. Enrollment planned for 120 pts. Results: 72 pts are enrolled, 48 patients evaluable for toxicityand pathologic responses available for 35 pts. Median age: 48 years (29–73), ECOG PS 0 - 45 pts (96%), 1 - 3 (6%), median tumor size 4.5 cm, 79% ductal, 4% lobular, 13% inflammatory. 54% ER-/PR-, 81% HER2 negative. 21 (60%) were triple negative, basal subtype. Heme toxicity was minimal: G3/4 neutropenia: 4 (8%) pts, thrombocytopenia: 3 (6%) pts. There were no episodes of febrile neutropenia. Nonheme toxicity significant for G3/4 arthraglias: 5 (10%) pts &amp; fatigue in 3 (6%) pts. 3 pts hospitalized (infection, PE, abd pain). 1 pt developed PD during neoadjuvant therapy; 5 pts did not complete post op chemo (pt compliance: 2, PD: 2, MD discretion: 1). pCR was noted in both breast and LNs in 7 pts (20%) and pPR in 26 (74%). Conclusions: Neoadjuvant dose dense GEA is feasible and extremely well tolerated. Significant activity with a pCR of 20% is evident with the basal subtype of breast cancer. SPARC tumor analysis correlations with observed pathologic responses will be presented and updated with the continuing accrual to this trial. No significant financial relationships to disclose.
Transcriptome adaptation caused by vorinostat/bexarotene combination therapy in advanced cutaneous T-cell lymphoma.
Authors: M. B. Karpova, D. Gunz, M. J. Okoniewski, A. Cozzio, K. Schad, K. Baumann Conzett, R. Dummer
Journal: Journal of Clinical Oncology (2010)

8050 Background: Despite the broad spectrum of therapeutic interventions, curative treatment for CTCL is missing. Transcriptome analysis is a comprehensive tool to reveal patterns of deregulated gene expression and identify epigenetic hot spots. We evaluated transcriptome adaptation during the Phase I study of vorinostat/bexarotene combination therapy in patients with advanced CTCL. Methods: Transcriptional profiling was performed on samples from 15 patients (4 PR, 9 SD, 2 PD). Pre- and on-treatment (day 14 into 1st cycle) skin biopsies were collected and compared. In several cases both, tumor and plaque lesions were available for analysis. Human Exon 1.0 ST microarrays by Affymetrix were used and transcriptional modifications were identified by R-Bioconductor using exonmap, limma, stats and samr packages. Enrichment analysis (EA) was performed using Genego Metacore. Results: Analysis of transcriptional adaptation showed that the magnitude of changes was relatively small: expression levels changing within 2 to 6 fold. Interindividual patient's variability was identified as the major factor influencing the molecular response. Plaque and tumor biopsies did not show any differences, suggesting that systemic treatment equally affects both types of lesions. EA of differentially expressed genes revealed that PD patients upregulate NOTCH and JNK stress-responsive cascades and downregulate JAK-STAT signaling. In responsive patients apoptosis (c-FLIP, p58) and chemotaxis (IL-8, CCL18, SOX4) networks were upreguated and inflammatory responses through NF-kB and IL5/IL13 were downregulated. Evaluation of alternative splicing showed that responsive patients tend to modify genes involved in recombinant and double-strand break DNA repair (ROR-alpha, PIR), fatty acid biosynthesis (ALOX15, FADS2, SC4MOL) and other processes. Conclusions: Vorinostat/bexarotene treatment caused tumor transcriptome to adjust, and progressive patients seem to escape through NOTCH and Rac/JNK signaling. Responsive patients characterized by apoptosis induction upon treatment. Results may help to initiate the development of personalized therapeutic strategies targeting responsive CTCL patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Bayer
Phase I Study of a Five-Day Intermittent Schedule for 1,2:5,6-Dianhydrogalactitol (NSC-132313) 2
Authors: Robert T. Eagan, Charles G. Moertel, Richard G. Hahn, Allan J. Schutt
Journal: JNCI Journal of the National Cancer Institute (1976)

Because 1,2:5,6-dianhydrogalactitol (NSC-132313 (DAG; the main conversion reaction product of the treatment of dibromodulcitol by mild akali or human serum) showed considerable antitumor activity in various mouse and rat tumor systems, a phase I study in 50 patients was conducted with five daily iv treatments repeated every 6 weeks. Thrombocytopenia was the dose-limiting toxicity. At a dose of 40 mg/m2/day for 5 days, the median platelet nadir was 31,000/mm3 and occurred on day 20; the plate count returned to normal within 8 days. At the same dose, the median white blood cell (WBC) nadir was 2,300/mm3 also on day 20-, the WBC count returned to normal within 7 days. Anemia, nausea, and vomiting were usually mild to moderate. No renal, hepatic, central nervous system, cardiac, or pulmonary toxicity was identified. Antitumor effects of DAG were observed in patients with renal, bladder, and small-cell lung cancers. An iv dose of 20-30 mg/m2/day for 5 consecutive days, repeated every 5-6 weeks, was recommended for phase II studies.
Integrated Akt/PKB Signaling in Immunomodulation and Its Potential Role in Cancer Immunotherapy
Authors: G. Xue, A. Zippelius, A. Wicki, M. Mandala, F. Tang, D. Massi, B. A. Hemmings
Journal: JNCI Journal of the National Cancer Institute (2015)

T cell development and maturation involve a variety of defined and coordinated developmental stages under the control of a variety of signaling networks. They function as the major mediator in cell-based immunity that defends against pathogen infections and executes immune surveillance against tumor cells. Protein kinase B (PKB, also called Akt) is central to multiple signaling pathways and transduces extracellular signals to dictate cellular responses towards proliferation, migration, anti-apoptosis, and maintenance of metabolic homeostasis. Although the prosurvival function of PKB was thought to be responsible for most of the functions regulated by PKB, emerging evidence has started to dissect its role in immunomodulation. More importantly, hyperactivation of PKB in cancer stroma frequently occurs in patients treated clinically with targeted cancer therapies, where it acts as a key mediator involved in the trapping of host immune cells in the vicinity of tumors, which supports cancer cell invasion and the escape of cancer cells from host immune surveillance. Encouragingly, recent studies have shown that inhibition of PKB improves the recognition of cancer cells by the host immune system, indicating a potential clinical strategy to rekindle the suppressed host immune response through the specific targeting of PKB. In this review, we explore how PKB signaling contributes to T cell development and cellular immune responses and discuss the mechanistic roles that PKB plays in the creation of immunosuppressive conditions and the escaping of immune recognition in the microenvironment of cancer.
&lt;italic&gt;In Vivo&lt;/italic&gt; Replacement of the Helper Virus in Bryan's Strain of Rous Sarcoma Virus by AMV and RPL12 Viruses
Authors: H. Graham Purchase, William Okazaki
Journal: JNCI Journal of the National Cancer Institute (1966)

Viremic chicks were obtained by intravenous inoculation of large doses of the following helper viruses in 11-day embryonating eggs: avian leukosis virus (RPL12), avian myeloblastosis virus (AMV), and Rous-associated virus (RAV-1). Bryan's “high titer” strain of Rous sarcoma virus (RSV) was then passaged 3 times consecutively in the wing webs of chicks made viremic to each helper virus. The RSV was titrated in the viremic chicks for each passage, and donor material for the next passage was taken from chicks inoculated with a limiting dilution of sarcoma virus. A stock of virus, differing from the original RSV and antigenically related to AMV (the helper virus) was produced by this procedure. It is concluded that the natural helper virus in Bryan's strain of RSV, i.e., RAV, was replaced in vivo by AMV and probably also by RPL12.
Accuracy of the WHO Haemoglobin Colour Scale for the diagnosis of anaemia in primary health care settings in low-income countries: a systematic review and meta-analysis
Authors: Heiko Marn, Julia Alison Critchley
Journal: The Lancet Global Health (2016)

Anaemia is a major cause of morbidity and mortality in low-income countries. Primary health-care workers in resource-poor settings usually diagnose anaemia clinically, but this is inaccurate. The WHO Haemoglobin Colour Scale (HCS) is a simple, cheap quantitative method to assess haemoglobin concentration outside of the laboratory. We systematically reviewed the literature to assess the accuracy of the HCS in primary care to diagnose anaemia, and compared this with clinical assessment.We searched the electronic databases including MEDLINE, EMBASE, SCOPUS, Web of Science, Cochrane library, CINAHL plus, Popline, Reproductive Health Library, and Google Scholar and regional databases up to Nov 14, 2014, "haemoglobin colour scale" in alternative spellings published in any language. Two reviewers independently screened studies, extracted data, and assessed quality using the QUADAS-2 instrument. Statistical analyses were carried out in STATA using the bivariate model.Of 141 records and abstracts screened, 14 studies were included. The pooled sensitivity of the HCS to diagnose anaemia was 80% (95% CI 68-88) compared with 52% for clinical assessment ([95% CI 36-67]; p=0·008). Specificity was similar between the HCS (80% [95% CI 59-91]) and clinical assessment (75% [56-88]; p=0·8250). For severe anaemia, diagnostic accuracy was again higher overall for the HCS (p<0·0001); sensitivity was 57% (36-76) for the HCS and 45% (95% CI 12-83) for clinical assessment, but specificity was 99·6% (95% CI 95-99·9) versus 92% (62-99). Combining clinical assessment and the HCS could result in higher sensitivity (anaemia: 91% [95% CI 81-96]); severe anaemia 83% (33-98), but at the expense of specificity (anaemia: 59% [35-79]; severe anaemia 90% [40-99]). Individual studies were highly heterogeneous but pooled results did not differ substantially in a series of sensitivity analyses for indicators of study robustness.In so-called real-life primary health-care conditions, HCS can significantly reduce misdiagnosis of anaemia compared with clinical assessment alone. Future research is required to optimise training, and assess clinical outcomes and cost-effectiveness.None.