tbuckley/cabot-search huggingface dataset:
Comparative analysis of MRI vs mammography in evaluation of size, number of lesions and nodal status of breast cancer
Authors: S. Saha, S. Chitneni, R. Sehgal, M. Arora, B. Desouza, S. David, T. Singh
Journal: Journal of Clinical Oncology (2006)

600 Background: Breast MRI is thought to be better in evaluating patients (pts) with BrCa. Our study was to compare MRI vs mam to predict leisons and LNS in BrCa. Methods: A retrospective study of 100 consecutive pts with pathologically proven BrCa was done. All had preoperative MRI and mam. Findings were compared to the final pathologic size, used as gold standard. MRI and was done at same center and single surgeon did all surgeries. Results: Of 100 pts,MRI reported 124 lesions. MRI reported size in 107 and mam reported size in 63 lesions. In MRI detected sizes 8% had same size as pathological size, 66% were overestimated by a mean of 0.64cm and 26% were underestimated by a mean of 0.48cm. For mam lesions, 10% had same size, 34% were overestimated by a mean of 1.10cm, 57% were underestimated by a mean of 0.78 cm. Total of 25 additional lesions were found in 23 pts in same and 6 leisons in 6 pts in contralateral breast by MRI. MRI also detected enlarged axillary and intramammary LN in 15% pts, 40% were true positives(+ve) and 60% were false +ve. One pt had metastatic LN in the contralateral axilla detected by MRI and confirmed by lymphoscintogram and pathology. 3% pts had neo-adjuvant chemotherapy Conclusion: In our study mam underestimated the breast lesion size in pts significantly more than MRI, but MRI overestimated BrCa lesion size in more number of pts. The mean difference in size on MRI when compared to the pathological size is less than 1 cm, while mam overestimated by a mean of greater than 1cm. This might be particularly important for T1 and T2 lesions, where size is the most important criterion for the T-stage classification. The identification of additional lesions and enlarged LN on MRI further validates the utility of MRI. [Table: see text] No significant financial relationships to disclose.
Abstract 15092: Human Epicardial Adipose Tissue is a Source of Inflammatory Mediators in Aortic Stenosis
Authors: Valentina Parisi, Pietro Formisano, Vittoria D’Esposito, Federica Passaretti, Maria Rosaria Ambrosio, Domenico Liguoro, Aurelio Caruso, Gabriella Grimaldi, Tommaso Lonobile, Francesco Baldascini, Agnese Bevilacqua, Gaetana Ferro, Giuseppe Rengo, Nicola Ferrara, Dario Leosco
Journal: Circulation (2014)

INTRODUCTION: It is widely established that epicardial adipose tissue (EAT) influences key pathogenic mechanisms of coronary atherogenesis through secretion of several inflammatory mediators. Recent studies have demonstrated that pathophysiology of aortic valve stenosis (AS) is characterized by early atherosclerosis and inflammation.

HYPOTHESIS: In the present study we aimed to evaluate the amount of EAT and its secretory profile in human AS.

METHODS: We measured EAT thickness by echocardiography in 70 pts with isolated, severe AS, 54 pts with isolated, severe coronary artery disease (CAD), 37 pts with both AS and CAD, and 23 controls matched for age, gender, BMI and cardiovascular risk factors. During cardiac surgery, EAT and subcutaneous adipose tissue (SC) were collected from pts with isolated AS and CAD. The secretome of EAT and SC was analyzed by human cytokine 27-plex immunoassay.

RESULTS: Compared to controls, EAT thickness was significantly and similarly increased in pts with isolated AS and isolated CAD (p<0.05). In pts with coexistent AS and CAD, EAT thickness was significantly greater than the other 3 groups (p<0.05). Overall, EAT of AS and CAD pts showed a more marked inflammatory profile than SC. In particular, in AS pts, of 27 measured factors (including cytokines, chemokines, growth factors, and angiogenic mediators), 17 showed significant greater levels in EAT with respect to SC (p<0,05) (Fig A). In CAD pts, EAT secreted significant greater levels of 7 inflammatory mediators with respect to SC (p<0,05). Of note, in AS pts, there was a close relationship between EAT thickness and levels of secreted inflammatory mediators (p<0,05) (Fig B).

CONCLUSIONS: This represents the first demonstration of increased EAT thickness in pts with severe AS. In AS pts, EAT inflammatory secretory profile is exalted with respect to SC and shows a close relationship with the amount of EAT. Overall, these preliminary data suggest a potential role for EAT in the pathogenesis of AS.

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Abstract 14724: Cardiometabolic Benefits of Exercise Training Among Fitness Non-responsive Patients with Type 2 Diabetes Mellitus: HART-D Study
Authors: Ambarish Pandey, Damon Swift, Darren McGuire, Colby Ayers, Ian Neeland, Neil M Johannsen, Steven N Blair, Conrad P Earnest, Timothy Church, Jarett Berry
Journal: Circulation (2014)

Introduction: Exercise training is associated with improved cardiorespiratory fitness (CRF) and metabolic profiles among patients with type 2 diabetes mellitus (T2DM). However, there is substantial heterogeneity in the magnitude of CRF response to exercise training, and it is uncertain if the metabolic effects of exercise training are limited to those patients who improve their CRF. Methods: The analysis sample included participants from the Health Bene[[Unable to Display Character: ﬁ]]ts of Aerobic and Resistance Training in Individuals with Type 2 Diabetes (HART-D) trial who were randomized to a control group or one of the 3 supervised exercise training groups (aerobic, resistance or combined) for 9 months. CRF response was defined as change in measured peak absolute oxygen consumption ([[Unable to Display Character: ∆]]VO2-peak, L O2/min) from baseline to end of study, using an exercise treadmill protocol. Participants were classified based on [[Unable to Display Character: ∆]]VO2-pe...
Management of Acute Myeloid Leukemia in Elderly Patients
Authors: Wolfgang Hiddemann, Wolfgang Kern, Claudia Schoch, Christa Fonatsch, Achim Heinecke, Bernhard Wörmann, Thomas Büchner
Journal: Journal of Clinical Oncology (1999)

ABSTRACT: Acute myeloid leukemia (AML) at older age is associated with several biologic and clinical characteristics. Hence, it may arise from an early level of hematopoietic stem cells and has a high frequency of blast cells with multidrug resistance glycoprotein MDR1 expression and particularly a high incidence of poor prognostic karyotypes. These factors, rather than age per se, underlie the poorer outcome as compared with younger cases. Prospective randomized studies clearly demonstrate, however, that elderly patients benefit from more intensive induction therapy and particularly from full-dose application of anthracyclines and possibly also cytarabine. Hematopoietic growth factors accelerate the recovery from treatment-induced neutropenia and may improve the remission rate, remission duration, and even overall survival. New treatment strategies need to be developed, however, for poor-prognosis AML subtypes in order to further improve the therapeutic perspectives for elderly patients with AML.
Phase I clinical and biomarker study of BIBF 1120, an oral multitarget tyrosine kinase inhibitor, in patients with advanced solid tumors (ST): Impact of CD133- and CD117-positive cells on a biomarker of an antiangiogenic inhibitor
Authors: I. Okamoto, H. Kaneda, T. Satoh, W. Okamoto, M. Terashima, T. Arao, K. Nishio, K. Nakagawa, K. Konishi, R. Kaiser
Journal: Journal of Clinical Oncology (2009)

3572 Background: BIBF 1120 (Vargatef) is an orally bioavailable small molecule inhibitor of multiple receptor tyrosine kinases, including vascular endothelial growth factor receptors, fibroblast growth factor receptors and platelet-derived growth factor receptors. Methods: BIBF 1120 (150–250 mg) was administered orally twice-daily (bid) to heavily pre-treated solid tumor (ST) patients to determine safety, tolerability, maximum tolerated dose (MTD) and pharmacokinetics (PK). CD133- and/or CD117 (c-kit)-positive cells from CD34 + CD45 dim peripheral blood cells were evaluated using flow-cytometry on pre-treatment, Day 2, Day 8 and Day 29. Results: Twenty-one patients were treated at doses of 150 mg bid (n=3), 200 mg bid (n=12) and 250 mg bid (n=6). Dose-limiting toxicities (DLTs) of reversible Grade 3/4 elevated liver enzymes occurred in three of 12 patients at 200 mg bid and three of six patients at 250 mg bid; 200 mg bid was declared as the MTD. Best observed responses were stable disease in 16 (76.2%) patients and median progression-free survival was 113 days (95% CI: 77–119 days). PK analysis indicated that C max and AUC increased with increased dose within the dose range tested. Flow cytometry analysis revealed that BIBF 1120 treatment significantly increased the percentage of CD133 + CD117 - cells (p&lt;0.001) on Day 29 compared with pre-treatment, and conversely decreased that of CD133 - CD117 + cells (p&lt;0.01). In addition, CD133 + CD117 + cells tended to decrease in responders (stable disease) to a greater extent than in non- responders after treatment. Conclusions: BIBF 1120 dosed continuously at 200 mg bid was well tolerated and appeared to provide some clinical benefit. Our biomarker study provides a novel insight into CD133- and CD117-positive cells as a pharmacodynamic biomarker for an antiangiogenic inhibitor. [Table: see text]
Marfan syndrome, inherited aortopathies and exercise: What is the right answer?
Authors: Andrew Cheng, David Owens
Journal: British Journal of Sports Medicine (2016)

Exercise recommendations for those who have Marfan syndrome or other genetic predisposition for thoracic aortic disease remain controversial and at times ambiguous. There are no outcomes studies to help guide recommendations. In this review, we examine the guidelines regarding exercise and inherited aortic conditions, the theoretical reasoning and circumstantial evidence that support the guidelines, as well as the knowledge gaps that continue to exist.
Correlation between the presence of lectin binding sites of pulmonary adenocarcinoma cells and their metastatic cells
Authors: I. Thöm, O. Schult-Kronefeld, I. Burkholder, M. Görn, B. Andritzky, C. Kugler, L. Edler, U. Schumacher, E. Laack, C. Bokemeyer
Journal: Journal of Clinical Oncology (2006)

7212 Background: During tumor progression to metastasis, the aberrant glycosylation of tumor cell membrane glycoconjugates plays a key role. These changes can be detected histochemically by the use of lectins. The aim of the present investigation was to analyze a possible association between the presence of lectin binding sites of pulmonary adenocarcinoma cells and their lymph node and hematogenous metastatic cells. Methods: For this purpose, the expression of HPA-, PHA-L- and UEA-I binding sites were assessed in primary tumors, lymph node metastases and hematogenous metastases of 96 patients with metastatic adenocarcinomas of the lung who underwent surgery between 1999 and 2002. Results: We found a significant positive correlation between the binding of the lectins HPA (p = 0.002), PHA-L (p &lt; 0.00001) and UEA-I (p &lt; 0.00001) to the cells of the primary tumor and to its lymph node metastases. There was positive correlation between the binding of HPA to the cells of the primary tumor and the hematogenous metastases as well. Conclusion: We are the first to demonstrate a positive correlation between the binding of the lectins HPA, PHA-L and UEA-I to the cells of the primary tumor and to its lymph node metastases. Expression of HPA bindig sites is also preserved in the hematogenous metastases in metastatic disease. Our results support the hypothesis that the aberrant glycolsylation of tumor cell membrane glycoconjugates is involved in the metastatic spread of tumors. No significant financial relationships to disclose.
Phase III trial of cisplatin (P) plus etoposide (E) plus concurrent chest radiation (XRT) with or without consolidation docetaxel (D) in patients (pts) with inoperable stage III non-small cell lung cancer (NSCLC): HOG LUN 01–24/USO-023
Authors: N. H. Hanna, M. Neubauer, R. Ansari, R. Govindan, D. Bruetman, W. Fisher, N. Chowhan, S. Nattam, C. Yiannoutsos, L. Einhorn
Journal: Journal of Clinical Oncology (2007)

7512 Background: Concurrent chemoradiation is standard treatment for pts with inoperable stage III NSCLC. A previously reported single-arm, phase II study by SWOG (Gandara et al JCO 2003) suggested D following EP/XRT further improved survival. We report results from a randomized, prospective phase III trial comparing EP/XRT with or without consolidation D. Methods: Eligible pts had inoperable, stage IIIA/B NSCLC, PS 0–1, FEV-1 ≥ 1 L, and &lt; 5% wt loss. Pts (n=243) received P 50 mg/m 2 iv d 1,8,29,36 and E 50 mg/m 2 iv d1–5, 29–33 concurrently with chest XRT to 5940 cGy. Non-progressing pts were randomized to D 75 mg/m 2 iv every 21 d for 3 cycles vs observation (O). The primary endpoint was to compare OS (Kaplan-Meier analysis). Accrual of 259 pts to randomize180 was planned to demonstrate a difference in MST of 25 vs 15 mos (5% 2-sided alpha, 80% power). Based upon evidence of futility (predefined as p&gt;0.7271), a DSMB recommended early termination after an analysis of the initial 203 pts. Results: Median f/u 25.6 mos. Pt characteristics (n=203): 34%/66% F:M; median age 63; 39.4%/60.6% IIIA/B. G3/4 toxicities during EP/XRT included 9.8% febrile neutropenia (FN), 17.2% esophagitis. 147 of 203 pts (72.4%) were randomized to D (n=73) or O (n=74). G3/4 toxicities during D included: 10.9% FN, 8.2% pneumonitis. 28.8% of pts were hospitalized during D (vs 8.1% in O arm) and 5.5% died due to D. PFS for D was 12.3 vs 12.9 mos for O (p=0.9412). The MST for all pts was 21.15 mos; MST for D was 21.6 mos (95% C.I. 17.7–35) vs 24.2 mos for O (95% C.I. 18.1–34.4) (p=0.9402). Conclusions: The MST with EP/XRT was higher than historical controls; however, consolidation D does not further improve survival, is associated with significant toxicity including an increased rate of hospitalization and premature death, and should no longer be used for pts with unresectable stage III NSCLC. [Table: see text]
Tumor regression and pharmacodynamic (PD) biomarker validation in non-small cell lung cancer (NSCLC) patients treated with the ErbB/VEGFR inhibitor BMS-690514
Authors: R. Bahleda, J. Soria, C. Harbison, J. Park, E. Felip, N. Hanna, S. A. Laurie, J. Armand, F. A. Shepherd, R. Herbst
Journal: Journal of Clinical Oncology (2009)

8098 Background: BMS-690514 is an oral selective inhibitor of EGFR, HER2, and VEGFR1–3. Previous results from the phase I portion of this phase I/II study established 200 mg/day as safe and tolerable (ASCO 2008; abstr 2564). Methods: Erlotinib-naïve and erlotinib-resistant adult patients with advanced/metastatic, measurable NSCLC received BMS-690514 200 mg/d. Eligible patients had an ECOG PS ≤1 and adequate organ function. Objectives were to assess disease control rate (DCR; CR, PR, SD ≥4 months), safety, PK and potential predictive and PD biomarkers of BMS-690514. Response was assessed every 8 weeks (modified WHO criteria). Predictive biomarkers included EGFR copy number, and EGFR and KRAS mutations. PD biomarkers included immunohistochemistry of EGFR signaling proteins in skin biopsies, circulating sVEGFR2, blood pressure, skin rash and diarrhea. Results: For 60 patients treated, DCR were 11/28 (39%) and 7/32 (22%) for erlotinib-naive and -resistant patients, respectively. DCR was significantly higher among patients harboring an EGFR mutation (6/8) than those with WT EGFR (5/18). One erlotinib-naive patient had PR (57 wks) and subsequent surgical removal of remaining tumor. Regression (48%) was seen in one erlotinib-naive patient harboring a KRAS G13D mutation. One erlotinib-resistant patient had PR (66%, 31 wks). Two erlotinib-resistant patients with EGFR T790M mutations had SD with 6% and 31% decrease in tumor burden. Most frequent treatment-related AES were diarrhea (90%), skin rash (31%), asthenia (29%), anorexia (27%), hypertension (26%), and reversible acute renal insufficiency (11%). sVEGFR2 (14% decrease from baseline, n=14) and decreased pMAPK levels from skin biopsies (14 of 18 pts) were consistent with EGFR and VEGFR2 inhibition. Conclusions: BMS-690514 200 mg/d showed evidence of anti-tumor activity and disease control in patients with NSCLC, including erlotinib-resistant and those with WT EGFR, EGFR T790M or KRAS mutations. Predictive and PD clinical biomarkers confirmed inhibition of both EGFR and VEGFR signaling pathways by BMS-690514. A randomized phase II trial versus erlotinib in NSCLC is underway. [Table: see text]
Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression
Authors: Victoria da Silva-Diz, Pilar Simón-Extremera, Adrià Bernat-Peguera, Jana de Sostoa, Maria Urpí, Rosa M. Penín, Diana Pérez Sidelnikova, Oriol Bermejo, Joan Maria Viñals, Annie Rodolosse, Eva González-Suárez, Antonio Gómez Moruno, Miguel Ángel Pujana, Manel Esteller, Alberto Villanueva, Francesc Viñals, Purificación Muñoz
Journal: Cancer Research (2016)

Cancer stem-like cells (CSC) play key roles in long-term tumor propagation and metastasis, but their dynamics during disease progression are not understood. Tumor relapse in patients with initially excised skin squamous cell carcinomas (SCC) is characterized by increased metastatic potential, and SCC progression is associated with an expansion of CSC. Here, we used genetically and chemically-induced mouse models of skin SCC to investigate the signaling pathways contributing to CSC function during disease progression. We found that CSC regulatory mechanisms change in advanced SCC, correlating with aggressive tumor growth and enhanced metastasis. β-Catenin and EGFR signaling, induced in early SCC CSC, were downregulated in advanced SCC. Instead, autocrine FGFR1 and PDGFRα signaling, which have not been previously associated with skin SCC CSC, were upregulated in late CSC and promoted tumor growth and metastasis, respectively. Finally, high-grade and recurrent human skin SCC recapitulated the signaling changes observed in advanced mouse SCC. Collectively, our findings suggest a stage-specific switch in CSC regulation during disease progression that could be therapeutically exploited by targeting the PDGFR and FGFR1 pathways to block relapse and metastasis of advanced human skin SCC.
Interleukin-2 toxicity.
Authors: J P Siegel, R K Puri
Journal: Journal of Clinical Oncology (1991)

Because of the ability of interleukin-2 (IL-2) to support the proliferation and activation of numerous types of immunocompetent cells and to support the survival of adoptively transferred lymphocytes, there has been considerable interest in its use in the immunotherapy of malignancies. While studies to date have indicated that IL-2 has activity against some malignancies, considerable toxicity has also been observed. Careful prescreening and selection of patients and appropriate management of toxicity can minimize adverse outcomes. Studies of IL-2 effects have provided intriguing evidence of interactions of the immune/cytokine system with the neuroendocrine, cardiovascular, and other systems. Studies in animal models have demonstrated the central role of an intact immune system in mediating many toxicities of IL-2. Several adverse effects of IL-2 appear to be mediated by other cytokines whose production is induced by IL-2. Studies into the pathogenesis and manifestations of IL-2 toxicity have offered the hope of developing less toxic approaches to IL-2 therapy. Several lessons from the IL-2 experience are likely to be applicable in the clinical development of other cytokines.
Factors associated with perioperative systemic chemotherapy for bladder cancer: A population based study
Authors: J. M. McKiernan, G. J. Decastro, S. Gilbert, V. Grann, C. A. Olsson, D. Petrylak, M. Benson
Journal: Journal of Clinical Oncology (2005)

4701 Background: There has recently been increased attention in the use of perioperative chemotherapy for bladder cancer. The patterns of treatment with perioperative chemotherapy for this disease outside the setting of clinical trials have not, to our knowledge, been well-examined. We used the SEER-Medicare database to evaluate the frequency of administration of perioperative chemotherapy for patients undergoing radical cystectomy. We further analyzed the demographic, cancer-specific, and diagnostic information available in the SEER and Medicare claims databases for factors that may be associated with chemotherapy administration. Methods: Using the SEER-Medicare database, we identified eligible patients 65 years of age or older who underwent radical cystectomy for bladder cancer between 1992 and 1999. We used logistic regression analysis to examine the associations between perioperative chemotherapy administration and several demographic and tumor-specific variables. These variables included: age at cystectomy; sex; marital status; ethnicity; SEER registry site; year of cystectomy; tumor histology; grade; stage at diagnosis; nodal status; and presence of synchronous upper urinary tract cancer. Results: A total of 1,353 patients were identified who met the criteria for inclusion in our analysis, of which 247 (18.3%) received perioperative chemotherapy. There were no correlations between the odds of receiving perioperative chemotherapy and most demographic variables, including age at the time of cystectomy, sex, race, socioeconomic and educational background. Stage IV and node-positive disease were associated with a significant increase in the odds of receiving perioperative chemotherapy. No differences in chemotherapy administration were found based on ratio of positive nodes, cancer histology, cancer grade, or synchronous upper urinary tract disease. Conclusion: Odds of receiving perioperative chemotherapy for bladder cancer are not associated with most demographic factors. However, tumor-specific factors, namely node positivity and stage IV tumors, are associated with odds of receiving such therapy. No significant financial relationships to disclose.
466 INTERLEUKIN-28B rs12979860 C ALLELE IS PROTECTIVE AGAINST ADVANCED FIBROSIS IN CHRONIC HEPATITIS C GENOTYPE 1 INFECTION: ANALYSIS OF THE AUSTRALASIAN CHARIOT STUDY COHORT
Authors: M.T. Kitson, G.J. Dore, J. George, P. Button, G.W. McCaughan, D.H. Crawford, W. Sievert, M.D. Weltman, W.S. Cheng, S.K. Roberts
Journal: Journal of Hepatology (2013)
Abstract 14559: Association of the Frontal QRS-T Angle with Adverse Cardiac Remodeling, Impaired Biventricular Function, and Worse Outcomes in Heart Failure with Preserved Ejection Fraction
Authors: Senthil Selvaraj, Leonard Ilkhanoff, Michael A Burke, Benjamin H Freed, Roberto M Lang, Eva E Martinez, Sanjiv J Shah
Journal: Circulation (2012)

Background: No prior studies have investigated the association of QRS-T angle with cardiac structure/function and outcomes in heart failure with preserved ejection fraction (HFpEF). We hypothesized...
Abstract 11891: Chronic Allograft Vasculopathy is Promoted by Increased Mitochondrial Activity
Authors: Tobias Deuse, Xiaoqin Hua, Mandy Stubbendorff, Thomas Streichert, Joachim Velden, Hermann Reichenspurner, Evangelos Michelakis, Robert C Robbins, Sonja Schrepfer
Journal: Circulation (2012)

Background: This study aimed at investigating the efficacy of dichloracetate (DCA) to prevent the development and progression of chronic allograft vasculopathy (CAV) by regulating the mitochondrial...