tbuckley/cabot-search huggingface dataset:
Curcumin potentiates the growth-inhibitory effect of celecoxib in human colorectal cancer cells
Authors: Shahar Lev-Ari, Ludmila Strier, Dina Kazanov, Hadas Dvory-Sobol, Ilya Pinchuk, Brigette Marian, Dov Lichtenberg, Nadir Arber
Journal: Cancer Research (2005)

2475  Background: Colorectal Cancer (CRC) is one of the leading causes of cancer death in the western world. Multiple studies have indicated that specific COX-2 inhibitors may prevent CRC. However, the long-term use of COX-2 inhibitors is not toxic free and may be limited due to its gastrointestinal and cardiovascular side effects. The chemopreventive efficacy of the phytochemical, curcumin has been demonstrated in several in vitro and animal models. We have developed a unique in vitro model consisting of normal rat emterocytes (IEC18) and their ras transformed derivatives (IEC18-ras) (Arber et al. Oncogene 1996). Aim: Can curcumin potentiate the growth inhibition effect of a COX-2 inhibitor (celecoxib, Pfizer, NY, USA) in human colon cancer cells? Methods: HT-29 and IEC18-ras (expressing high levels of COX -2), Caco-2 (Expressing low levels of COX-2) and SW-480 (no expression of COX -2) cell lines were exposed to different concentrations of celecoxib (0-40μM), curcumin (0-20μM) and their combination. COX-2 activity was assessed by measuring PGE2 production by enzyme-linked immunoassay. COX-2 mRNA levels were assessed by RT-PCR. COX-1 and COX-2 expression was measured by western blotting analysis. Results:.Exposure to physiological doses of celecoxib (5 μM) and curcumin (10-15 μM) resulted in a synergistic inhibitory effect on cell growth. Growth inhibition was associated with inhibition of proliferation and induction of apoptosis. Curcumin augmented celecoxib inhibition of PGE2 synthesis. The drugs synergistically down-regulated COX-2 mRNA expression. Western blot analysis showed that the level of COX-1 was not altered by treatment with celecoxib, curcumin or their combination. Conclusions: Curcumin can potentiates the growth inhibitory effect of celecoxib by shifting the dose-response curve to the left. The synergistic growth inhibition effect was mediated through a mechanism that involves both COX-2 and non-COX-2 pathways. This synergistic effect is clinically important since it can be achieved in the serum of patients receiving standard anti-inflammatory or anti-neoplastic dosages of celecoxib.
Abstract 19820: Heterogeneity of Disease Progression Rates in Patients With Bicuspid Aortic Valve: Is There a Suitable Bio-marker?
Authors: Thanh H Nguyen, Ranjit Shah, Matthew Chapman, Onn A Ali, John D Horowitz
Journal: Circulation (2014)

Introduction: Bicuspid aortic valve (BAV) is associated with inflammatory activation and endothelial dysfunction. Worsening of aortic valve stenosis/regurgitation represents the most common complication of BAV, but clinical and biochemical markers of disease progression are not currently available. Objective: The objective of the current study was to (1) evaluate rates of progression of aortopathy and valve dysfunction, and (2) identify correlates of accelerated progression among BAV patients. Methods: 43 BAV patients aged 45 ± 16 (SD) years were evaluated clinically and with echo/MRI. Inflammatory activation was assessed via hs-CRP and myeloperoxidase (MPO) levels, endothelial function/NO responsiveness via flow-mediated dilatation (FMD), plasma asymmetric dimethylarginine (ADMA) levels, inhibition of platelet aggregation by SNP, and endothelial progenitor cell counts. Follow-up was undertaken after 47 ±16 months to determine rate of progression and of need for valve replacement; some patients did not undergo repeat echo (Figure). Biochemical/physiological correlates of valve dysfunction and aortic dimensions were sought via univariate and multiple linear regression analyses. Results: AV max increased from 2.1 ± 0.6 to 2.5 ± 1.1(m/s), p &lt; 0.05, while ascending aorta (Asc Ao) dimensions increased from 18.2 ± 6.1 to 21.2 ± 4.9 (mm/m 2 ), p &lt; 0.05 over the monitoring period. Although there was a direct correlation (p &lt; 0.01) between baseline AV max and MPO levels on multivariate analysis, this correlation did not extend to progression rates. Indeed neither clinical nor biochemical parameters predicted accelerated progression. Conclusions: (1) Progression of valve disease and aortopathy in BAV is often rapid, with annual mean rate of 0.1 m/s for AV max and 0.4 mm/m 2 for Asc Ao. (2) Despite physiological evidence linking BAV with inflammation and endothelial dysfunction, these biochemical factors did not appear to predict rapid disease progression.
Assessment of estrogen receptor expression by automated quantitative analysis in core biopsy and surgical specimens in ER negative, HER-2 positive breast cancer
Authors: R. M. Layman, D. G. Thomas, M. S. Sabel, K. A. Griffith, D. El-Ashry, A. F. Schott
Journal: Journal of Clinical Oncology (2008)

11503 Background: In preparation for upcoming clinical trials to determine whether a pharmacologic agent used in the neoadjuvant setting will cause re-expression of estrogen receptor (ER) in ER negative, HER-2 positive breast cancer, we sought to evaluate the baseline variability in automated quantitative analysis (AQUA) scores in ER-negative breast cancers between core biopsies and surgical specimens. Methods: A tissue microarray (TMA) was constructed consisting of both ER positive and ER negative breast cancers to evaluate the reproducibility of our AQUA assay by performing the assay 4 times over 3 weeks. We then queried our databases to identify patients with ER- negative breast cancer who met the following criteria: core biopsy and breast surgery performed at our institution, no neoadjuvant therapy administered, invasive breast cancer with ER ≤10% by immunohistochemistry, and HER-2 positive by IHC 3+ or FISH. We then assessed AQUA scores on the core biopsy and final surgical specimens on the cohort of ER negative breast cancers. Results: The AQUA assay performed on the test TMA revealed good inter-assay reproducibility. ANOVA statistical analysis showed no significant difference between the 4 runs. Paired core biopsy and final surgical specimens were available for a cohort of 20 patients with ER-negative, HER-2 positive breast cancer. The range of averaged AQUA scores on the core biopsy samples was 4.77 –38.23 (mean 14.36, SD 9.84). The range of AQUA scores on the final surgical specimens was 6.89 –129.55 (mean 21.58, SD 28.61). There was no statistical difference in AQUA scores between the core biopsy and surgical specimens. Paired t-test analysis revealed p = 0.1894. Conclusions: The AQUA assay gives similar quantitative measurements of ER in untreated breast cancer patients at two different timepoints, and from core biopsy versus surgical specimen tissue. The AQUA assay will be used for evaluation of pharmacologic agents intended to cause ER re-expression in clinical neoadjuvant breast cancer specimens. No significant financial relationships to disclose.
Phylogenetic analysis of the alpha-globin pseudogene-4 (Hba-ps4) locus in the house mouse species complex reveals a stepwise evolution of t haplotypes.
Authors: M F Hammer, L M Silver
Journal: Molecular Biology and Evolution (1993)

A parsimony analysis was performed on restriction sites at the Hba-ps4 pseudogene locus within one of four inversions associated with mouse t haplotypes. The results suggest that all t haplotypes form a monophyletic group and that the in (17)4 inversion originated before the radiation of the Mus musculus species complex but after the divergence of the lineages leading to M. spretus, M. abbotti, and M. hortulanus. A time frame based on the evolutionary rate of mouse pseudogenes places the origin of this t haplotype inversion at 1.5 Mya, or approximately 1.5 Myr after the origin of the more proximal t complex inversion, in (17)2. The accumulated evidence indicates that complete t haplotypes have been assembled in a stepwise manner, with each of these inversions occurring on separate chromosomal lineages and at different evolutionary times. In addition, the evolutionary relationships of pseudogene sequences resulting from genetic exchange between wild-type and t haplotype alleles were examined. Analysis of sequences from the 5' and 3' sides of a putative site of recombination resulted in cladograms with different topologies. The implications for hypotheses concerning the evolutionary forces acting on t haplotypes and their rapid propagation throughout worldwide populations of mice are discussed.
Abstract 18354: Cardiac Magnetic Resonance Allows Noninvasive and Accurate Monitoring of Serial Changes in Pulmonary Vascular Resistance and the Acute Vasodilator Response in Chronic Pulmonary Hypertension
Authors: Ana GarcÍa-Álvarez, Leticia Fernández-Friera, Jose Manuel GarcÍa-Ruiz, Mario Nuño-Ayala, Daniel Pereda, Rodrigo Fernández-Jiménez, Gabriela Guzmán, David Sanz-Rosa, Jaime GarcÍa-Prieto, Jesus G Mirelis, Gonzalo Pizarro, ValentÍn Fuster, Borja Ibañez
Journal: Circulation (2012)

Background: Monitoring pulmonary vascular resistance (PVR) during the follow-up of patients with pulmonary hypertension (PH) and the acute vasodilator response require invasive right heart catheterization. A noninvasive method would be valuable. Hypothesis: Cardiac magnetic resonance (CMR) allows noninvasive monitoring of PVR and the acute vasodilator response. Methods: Two experimental models of chronic PH were developed in pigs. A precapillary PH model was induced by repeated pulmonary embolization with microspheres (n=8). A postcapillary PH model was generated with surgical banding of the main pulmonary vein (n=10). At baseline and every month, animals were evaluated by CMR (pulmonary artery mean flow velocity [PAvel] from phase-contrast images) with simultaneous invasive quantification of PVR using a CMR-compatible Swan-Ganz catheter (N=60 pairs of measurements). Generalized estimating equations analysis was used to correlate repeated measurements of PVR and PAvel. Additionally, correlation between acute changes in PAvel and PVR induced by pulmonary embolization (n=10) or vasodilator administration (n=10) inside the magnet was assessed using Spearman correlation. Results: Both models generated chronic PH (mPAP=30.8±4.8 and 54.5±12.8, pre and postcapillary respectively) with typical changes on pathology. CMR-model based on PAvel strongly correlated with serial measurements of PVR in both precapillary (r=0.86, p&lt;0.01) and postcapillary (r=0.97, p&lt;0.01, examples in figure A) models. Additionally, acute changes in PAvel were strongly correlated with the increase in PVR induced by acute embolization (r=-0.98, p&lt;0.001, figure B) or the fall in PVR produced by vasodilator testing (r=-0.89, p&lt;0.001, figure C). Conclusions: CMR allows noninvasive and accurate monitoring of acute and chronic changes in PVR and the acute vasodilator response in a broad spectrum of PH. This may be very valuable for the evaluation and follow-up of patients with PH.
A phase II clinical trial of neoadjuvant trabectedin in patients with nonmetastatic advanced myxoid/round cell liposarcoma (MRCL)
Authors: A. Gronchi, A. Le Cesne, N. B. Bui, E. Palmerini, G. Demetri, P. Hohenberger, R. J. Hohl, S. Pilotti, I. Perez, P. Lardelli
Journal: Journal of Clinical Oncology (2009)

10525 Background: Trabectedin (ET-743, Yondelis), a marine-derived alkaloid has demonstrated significant activity in the treatment of soft tissue sarcomas (STS) in phase III trials, and has recently received EMEA approval in this indication. A subtype that accounts for 10% of STS, MRCL, displays the fusion FUS-CHOP in 95% of all cases. Preliminary results of neoadjuvant trabectedin (T) in advanced MRCL show reduction in the radiological density of the tumor, clinical improvement, and a pathological complete response (pCR) in the resected tumor mass. A phase II study to further determine the response to T in the MRCL population is presented. Methods: In this multicenter Phase II trial, patients (pts) with locally advanced (stage III) or locally recurrent MRCL were treated for 3 - 6 cycles with T (1.5 mg/m 2 q3wk) in the neoadjuvant setting. Main endpoints were: pCR rate, objective response rate by RECIST, and correlation of molecular parameters from tissue samples with clinical outcomes. Results: Twenty-five pts with locally advanced MRCL have been recruited, of whom 20 are evaluable. All had the translocation (t12q13, 16p11) which causes the chimeric FUS-CHOP. Median age was 53 (23–75) and male:female ratio was 1. Thirteen pts completed therapy and underwent curative surgery. Pathological assessment was performed in 10 pts: 2 achieved pCR, 1 as per central pathology review and 1 by local pathology assessment. In addition, 1 pt had a very good pathological response. Ten patients remain to be histologically evaluated. Response rate by RECIST from pts who completed therapy was: 6 partial responses (46%) and 7 disease stabilizations. Remarkably, pathological response does not entirely correlate with response by RECIST since the pts with pCR still had radiological disease but no malignant component was found in the excised tumor mass (only connective and reactive tissue). Two serious adverse reactions of severe rhabdomyolysis, and asthenia, nausea and transaminase elevation were reported. Most common toxicities were liver enzyme elevation, neutropenia and thrombocytopenia. Conclusions: These preliminary results in terms of objective and complete pathologic responses, strongly suggest that T may have a role in the neoadjuvant setting in pts with MRCL. [Table: see text]
Rituximab compared to observation after high-dose consolidative first-line chemotherapy (HDC) with autologous stem cell transplantation in poor-risk diffuse large B-cell lymphoma: Updated results of the LNH98-B3 GELA study
Authors: C. Haioun, N. Mounier, J. F. Emile, S. Bologna, B. Coiffier, H. Tilly, C. Recher, C. Fermé, F. Morschhauser, C. Gisselbrecht
Journal: Journal of Clinical Oncology (2007)

8012 Background: Rituximab has been evaluated as a single agent and also in combination with chemotherapy in aggressive and indolent lymphomas with evidence of efficacy. More recently, rituximab maintenance therapy has been successfully used to keep responding patients in remission. We have shown that consolidative HDC improves outcome of poor risk responder-patients (pts) with aggressive lymphoma. Methods: The aim of the present study was to evaluate the potential benefit, as randomly compared to observation, rituximab - 375 mg/m 2 /week for 4 weeks - 2 months after HDC, in decreasing the relapse rate (second randomization: R2). A secondary objective was to improve the response rate before HDC using the intensified ACE chemotherapy regimen (doxorubicin 75mg/m 2 d1, cyclophosphamide 1g/m 2 d1-d2, etoposide 150mg/m 2 d1-d3) as compared to the standard ACVBP induction regimen (R1). Four cycles were delivered every 15 days. In responding pts, HDC (mitoxantrone 45 mg/m 2 , cyclophosphamide 1500 mg/m 2 × 4d, etoposide 250 mg/m 2 × 4d and carmustine 300 mg/m 2 ) was started between d80 and d90. Results: From 10/99 to 05/03 (closing date), 476 pts younger than 60 years with diffuse large B-cell lymphoma and aa-IPI 2 or 3 (aa-IPI 3: 29%). were enrolled. 237 pts were assigned to ACE and 239 to ACVBP. Complete response (CR+CRu) rates to induction treatment did not significantly differ between the 2 regimens (65% and 63%, respectively). Death rate during induction phase was 4% in both arms. Among the 331 pts who received HDC, 269 were randomized (R2) to receive either rituximab (n=139) or observation (n=130). 545 infusions of rituximab were administered with no clinically relevant infectious toxicity except two severe VZV infections. With a median follow-up of 4 years after R2, a trend toward a better 4y-EFS was observed in the rituximab group (80% vs 71%, p=0.098). In addition, a two-sided log-rank test stratified by aa-IPI, induction treatment and response after HDC was performed and confirmed the results of the unstratified analysis. Conclusions: We conclude that early and brief rituximab maintenance is feasible after HDC and may prolong remission status. [Table: see text]
Cutting science budget would be “Neanderthal” behaviour, expert says
Authors: Nigel Hawkes
Journal: BMJ (2015)

The UK government would be behaving “like Neanderthals” if it cut the science budget sharply in the spending review due in November, the president of the Royal Society, Paul Nurse, told a briefing at the Science Media Centre in London on Tuesday 29 September.

Rumours of a 25-40% cut in spending by the Department of Business, Innovation and Skills, which holds the purse strings, have alarmed the science lobby. Nurse said that he did not believe that such deep cuts were contemplated for spending on research and development but that if they happened “they would destroy the scientific endeavour” in the United …
Long-term results of high-dose chemotherapy with autologous peripheral stem cells support on the outcome of progression free and overall survival in metastatic breast cancer patients classified according to a risk group scor
Authors: M. Martino, F. Morabito, M. C. Zavettieri, M. Nardi, S. Palazzo, G. Filippelli, B. Lazzaro, S. Molica, G. Longo, P. Iacopino
Journal: Journal of Clinical Oncology (2004)

711 Background: : MBC is an incurable disease with standard chemotherapy. HDC with autologous peripheral stem cells support is a controversial strategy to overcome drug resistance. Factors predicting survival are more important than treatment outcome in patients with MBC who receive standard endocrine or chemotherapy Methods: 74 patients with MBC, enrolled in 3 HDC protocols, were stratified according to three risk categories based on the disease-free time interval from primary diagnosis to metastasis, the hormone-receptor status of the tumor and the dominant site of metastasis (Possinger K et al. Cancer Treat Rev. 1987; 14:263–274). After stratification, 61.3%, 24% and 14.7% of the patients fit into the low, intermediate and high groups, respectively. All patients received at least one ASCT with HDC after standard chemotherapy, 53.8% received a double and 6.4% a triple course of HDC, so that altogether 125 ASCT were performed. The objectives of the study were to determine whether the risk categories, which are important for predicting outcome after standard chemotherapy, are also valid after HDC. Results: After the HDC program, the conversion rate to more favourable response was 27.4%. At a median follow-up of 28 mo. (range 0,3–99), PFS and OS were 19 + 4 % and 31 + 6 %. With regard to risk category, patients with low and intermediate risk score had a statistically longer median survival while there was no difference between low and intermediate risk groups. The risk groups correlated significantly with the median of progression free survival (7.1, 12.3, 31.6 mo. for the high, intermediate and low risk, respectively). Patients with CR did significantly better than patients with PR or SD disease in univariate analysis. In multivariate analysis, the attainment of a CR was the predominant predictor for both prolonged PFS and OS. Conclusions: Possinger prognostic risk categories do predict both overall and progression free survival, but it seems to be less relevant than response to HDC program. No significant financial relationships to disclose.
Wearable sensor-based balance training in older adult cancer patients with chemotherapy-induced neuropathy: A randomized controlled trial.
Authors: Michael Schwenk, Linda L. Garland, Gurtej Singh Grewal, Dustin Holloway, Amy Muchna, Jane Mohler, Bijan Najafi
Journal: Journal of Clinical Oncology (2015)

195 Background: Chemotherapy-induced peripheral neuropathy (CIPN) can affect lower extremity joint proprioception leading to balance deficits and increased fall risk. This study evaluated the effect of a sensor-based exercise program on improving postural control in cancer patients with CIPN. Methods: Twenty two cancer patients (Age 70.3±8.7 years) with objectively confirmed CIPN (vibration perception threshold test, VPT &gt; 25 Volt) were randomized to twice weekly x 4 weeks sensor-based training including weight shifting and virtual obstacle crossing with real-time visual feedback of lower-extremities through wearable wireless sensors (intervention group, IG, n = 11) or no intervention (control group, CG, n = 11). Outcome measures included changes in sway of ankle, hip, and center of mass (CoM) in both medio-lateral (ML) and anterior-posterior (AP) directions during 30 second standing in feet closed position (both feet next to each other) with eyes open (EO) and eyes closed (EC), and semi-tandem position (big toe by arch of other foot) with EO, at baseline and post-intervention. All assessments were made using validated wearable sensors. Results: VPT score averaged 49.6 ± 26.7 Post intervention, sway of hip, ankle and CoM (ML) were significantly reduced in the IG compared to the CG during FC position (p = .010-.022). During the more challenging position of semi-tandem, all sway parameters except ankle were significantly reduced (p = .008-.039). Effect sizes were moderate-large (eta squared = .255-.388). Conclusions: This randomized controlled study using a novel wireless sensor-based training demonstrated improvements in balance in CIPN patients by measures of balance that have been related to fall risk. We speculate that the sensor-based training with real-time visual joint position feedback provided participants with enhanced information about joint movements and motor error in order to compensate for deteriorated/lost lower extremity joint proprioception from CIPN. This balance training system can be easily translated to an in-home setting and may decrease fall risk and thus improve cancer patients’ quality of life. Clinical trial information: NCT02043834.
Perceptions of breast and cervix cancer prevention in two populations of women in Peru: Impact of knowledge and access to health service
Authors: A. E. Alarcon-Rozas, K. Villacres, R. Cardenas
Journal: Journal of Clinical Oncology (2005)

6120 Objective: To know the preventive attitudes of gynaecological cancer in women older than 20 years through breast self-examination practice, mammography and cervical PAP in Sullana-Piura (North of Peru) and Comas (a poverty district of Lima). Patients and Methods: We collect information through paper interview in 100 and 426 women older than 20 years from Sullana (an urban-rural area) and Comas (a poverty urban area) respectively between January and March 2003. In this paper interview we took into account age, parity, first sexual intercourse, number of children, knowledge, utility and prevention of breast self-examination, mammography, as well as cervical PAP. Our data was stored in Excel (Window XP) and analyzed by Epi Info v. 12.0 with basic statistic. Results: Breast and Cervical Cancer Practice Prevention. Conclusions: In Peru the breast and cervical cancer are the most frequent neoplasm in women but unfortunately our preventive labour is poor. As a developing country we do not have a mammography machine in Sullana where the population of women older than 20 years is 56,374, and only 7% of women older than 40y have an annual mammography (they have to travel to another town). In contrast, it is worrisome that in Comas where exist many accessible mammography machines only 6% have their regular control. These women need more information because the regular BSE practice is less than 15% and of course regular mammography is less than 8% in both populations and this is because they do not know the utility of these practices. On the other hand only 47% and 63% have their regular PAP in Sullana and Comas respectively., and again they do not know the utility of cervical PAP. We urge to have a gynaecological cancer preventive program as well as an available mammography machines in many more towns. We think this data reflect what happen in many developing countries about cancer prevention. No significant financial relationships to disclose.