tbuckley/cabot-search huggingface dataset:
A phase II study of ramucirumab as first-line monotherapy in patients (pts) with advanced hepatocellular carcinoma (HCC).
Authors: A. X. Zhu, R. S. Finn, M. F. Mulcahy, J. S. Gurtler, W. Sun, J. D. Schwartz, P. Rojas, A. Dontabhaktuni, H. Youssoufian, K. E. Stuart
Journal: Journal of Clinical Oncology (2010)

4083 Background: Vascular endothelial growth factor (VEGF)-mediated angiogenesis contributes to HCC pathogenesis. Ramucirumab (IMC-1121B) is a recombinant human monoclonal antibody that binds to the extracellular domain of the VEGF receptor 2 (VEGFR-2). There is a compelling rationale for antiangiogenic (and specifically anti-VEGFR-2) therapy in HCC. Methods: Pts with advanced HCC received ramucirumab 8 mg/kg IV every (q) 2 weeks until disease progression or intolerable toxicity. Eligibility included no prior systemic therapy, Child-Pugh (C-P) A-B cirrhosis, ECOG PS 0-1, CLIP score 0-3, bilirubin ≤ 3 mg/dL, transaminases ≤ 5X ULN, Cr ≤ 2 mg/dL and platelets ≥ 75K. Tumor evaluations were q6 weeks. The primary endpoint was progression-free survival (PFS). Other endpoints were overall survival (OS), response rate, safety, pharmacokinetic (PK)/pharmacodynamic (PD) profiles, and immunogenicity of ramucirumab. Results: 43 pts were enrolled; 42 received therapy. Pts were predominantly male (81%), C-P A (74%), ECOG PS 0 (43%) or 1 (55%), and HCV-infected (49%). Most had extrahepatic disease (76%), BCLC stage C (83%), and 17% had macrovascular invasion. Median PFS was 4.3 months (m) and 4.0 m for pts with BCLC C (4.2 m for pts with C-P A, 2.8 m for pts with C-P B cirrhosis). 3 pts (7%) with extrahepatic disease and BCLC C had partial response, and 18 (43%) had stable disease (50% disease control rate). The most frequent adverse events (AEs) were fatigue (62%), headache (38%), and hypertension (HTN) (38%). Serious AEs included fatigue (10% grade [G] 3), gastrointestinal (GI) bleeding (7% G3; 2% G5), HTN (12% G3; 2% G4), infusion-related reactions (5% G3), and headache (2% G3). Cmin concentrations were above the target trough concentration (20 mg/mL) for the entire treatment period; evaluation through cycle 13 suggests no long-term accumulation of ramucirumab when administered q2 weeks. Conclusions: Ramucirumab confers moderate disease control in advanced, sorafenib-naive HCC. The treatment was well tolerated for most patients; serious AEs included GI bleeding, infusion- related reactions and HTN. Updated data on clinical efficacy and PD profiles will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ImClone Systems Bayer, Genentech, ImClone Systems Lilly
Enquiring About Tolerance (EAT) study: Feasibility of an early allergenic food introduction regimen
Authors: Michael R. Perkin, Kirsty Logan, Tom Marrs, Suzana Radulovic, Joanna Craven, Carsten Flohr, Gideon Lack, Louise Young, Victoria Offord, Mary DeSousa, Jason Cullen, Katherine Taylor, Anna Tseng, Bunmi Raji, Sarah Nesbeth, Gillian Regis, Charlie Bigwood, Charlotte Stedman, Sharon Tonner, Emily Banks, Yasmin Kahnum, Rachel Babic, Ben Stockwell, Erin Thompson, Lorna Wheatley, Devi Patkunam, Kerry Richards, Ewa Pietraszewicz, Alick Stephens, Asha Sudra, Victor Turcanu
Journal: Journal of Allergy and Clinical Immunology (2016)

BackgroundThe influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain.ObjectiveWe sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance.MethodsWe performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age.ResultsOne thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age).ConclusionEarly introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies.
Heterogeneity of Met Assessed By Immunohistochemistry (Ihc) and Fluorescence-In-Situ Hybridization (Fish) in Nonsquamous Non-Small Cell Lung Cancer (Nsnsclc)
Authors: D. Casadevall, J. Gimeno, S. Clavé, A. Taus, L. Pijuan, A. Luque, M. Lorenzo, S. Menendez, B. Espinet, J. Albanell, E. Arriola
Journal: Annals of Oncology (2014)
Macrophage levels in large cell lymphoma are associated with survival
Authors: M. S. McGrath, L. Shagrun, A. Morris, C. Behler
Journal: Journal of Clinical Oncology (2007)

8097 Background: Recent studies of follicular lymphoma have suggested that the presence of high levels of tumor associated macrophages (MO) conferred a poor prognosis. The current study evaluated large cell lymphomas for the presence of MOs and “proliferative MOs” (promacs), in HIV+ and HIV- LCL. Methods: Formalin-fixed and paraffin-embedded tissues from patients with LCL (and controls) were obtained from the ACSR (URL: http://acsr.ucsf.edu ) and evaluated for expression of CD68 (MO), PCNA (proliferation) and HIVp24 via the use of 0.6mm section tissue microarrays (TMA). Survival data was also evaluated. Results: 64 cases of LCL were evaluated, 31 of which were HIV+ (33 cases were HIV-). HIV p24 staining was seen with 13 of the 31 HIV+ cases(42%) , with staining only in MOs. Promacs (CD68+/PCNA+MOs) were more frequent in cases of HIV+ LCL (median of 18) and HIV- LCL (median of 5), than normal lymph nodes and reactive tonsillar tissue (p&lt;.001). In both HIV+ and HIV- cases of LCL, there was a trend towards shorter survival (p&lt;0.07) with increased numbers of MOs and promacs; p24 reactivity was unrelated to survival. Conclusions: In this preliminary study of MOs in LCL, MO number per TMA core was significantly correlated with promac number in all cases of LCL (p&lt;.001). HIV p24 localized to MOs in 42% of HIV+ LCL cases and was unrelated to survival. Increased promac numbers in cases of LCL correlated with decreased survival in all cases of LCL, but cases of HIV+LCL tended to demonstrate shorter survival than in cases of HIV- LCL. Of the latter group, higher numbers of macrophages (for example, greater than 46 macrophages/core) portend a worse prognosis, but this finding was not statistically significant in this preliminary study. No significant financial relationships to disclose.
An ankylosing spondylitis-associated genetic variant in the<i>IL23R-IL12RB2</i>intergenic region modulates enhancer activity and is associated with increased Th1-cell differentiation
Authors: Amity R Roberts, Matteo Vecellio, Liye Chen, Anna Ridley, Adrian Cortes, Julian C Knight, Paul Bowness, Carla J Cohen, B Paul Wordsworth
Journal: Annals of the Rheumatic Diseases (2016)

To explore the functional basis for the association between ankylosing spondylitis (AS) and single-nucleotide polymorphisms (SNPs) in the IL23R-IL12RB2 intergenic region. We performed conditional analysis on genetic association data and used epigenetic data on chromatin remodelling and transcription factor (TF) binding to identify the primary AS-associated IL23R-IL12RB2 intergenic SNP. Functional effects were tested in luciferase reporter assays in HEK293T cells and allele-specific TF binding was investigated by electrophoretic mobility gel shift assays. IL23R and IL12RB2 mRNA levels in CD4+ T cells were compared between cases homozygous for the AS-risk 'A' allele and the protective 'G' allele. The proportions of interleukin (IL)-17A+ and interferon (IFN)-γ+ CD4+ T-cells were measured by fluorescence-activated cell sorting and compared between these AS-risk and protective genotypes. Conditional analysis identified rs11209032 as the probable causal SNP within a 1.14 kb putative enhancer between IL23R and IL12RB2. Reduced luciferase activity was seen for the risk allele (p<0.001) and reduced H3K4me1 methylation observed in CD4+ T-cells from 'A/A' homozygotes (p=0.02). The binding of nuclear extract to the risk allele was decreased ∼3.5-fold compared with the protective allele (p<0.001). The proportion of IFN-γ+ CD4+ T-cells was increased in 'A/A' homozygotes (p=0.004), but neither IL23R nor IL12RB2 mRNA was affected. The rs11209032 SNP downstream of IL23R forms part of an enhancer, allelic variation of which may influence Th1-cell numbers. Homozygosity for the risk 'A' allele is associated with more IFN-γ-secreting (Th1) cells. Further work is necessary to explain the mechanisms for these important observations.
A Panel of Gastrointestinal Stromal Tumours (Gist) Xenograft Models for in Vivo Preclinical Drug Testing
Authors: A. Wozniak, T. Van Looy, G. Floris, Y.K. Gebreyohannes, J. Wellens, H. Li, J. Cornillie, U. Vanleeuw, D. Hompes, M. Stas, R. Sciot, M. Debiec-Rychter, P. Schöffski
Journal: Annals of Oncology (2014)
R-CHOP compared with CHOP in patients with diffuse large B-cell lymphoma (DLCL): Russian experience
Authors: I. Poddubnaya, E. Osmanov, L. Babicheva, G. Tumyan, E. Sorokin, D. Stefanov
Journal: Journal of Clinical Oncology (2007)

18536 Background: R-CHOP is regarded as the best available treatment for untreated patients with aggressive and indolent B- NHL. Methods: 184 previously untreated patients with DLCL were included in retrospective study: 92 patients were treated by CHOP, 92 patients were treated by CHOP plus rituximab ( R-CHOP ). Age of patients ranged 16–87 years (median 50 years). The median follow- up was 18 months. Compared groups were balanced in all parameters. The advanced stage of disease (III-IV) at diagnosis had 66% patients treated with CHOP and 67,5 % patients treated with R-CHOP. =2 extranodal zones were initially revealed at 35% in CHOP group vs 47% in R- CHOP group. PS of 25 % patients in R-CHOP group and 30% patients in CHOP group was regarded as appropriate 3–4 degrees on ECOG. Increased LDH level was marked at 60% in CHOP-group vs 54% in R-CHOP. 29% patients in R-CHOP group and 21% patients in CHOP group had B-symptoms at diagnosis; bulky disease took place in 53% cases in R-CHOP group and 62% cases in CHOP. High IPI score had 47 % patients in CHOP-group vs 48 % in R-CHOP. Results: Complete response was achieved in 74% of the patients treated with R- CHOP, as compared to 56% of those treated with CHOP alone (p&lt;0,05). Disease progression during treatment was reported in 25% of patients in CHOP group and 18,5% in R-CHOP group. Median overall survival in patients treated with R-CHOP was NS, in patients treated with CHOP alone was 16 months. With a median follow-up of 18 months, 29 (31,5%) events (progression - 18,5%, relapse - 10%, death - 3% ) were observed in the R-CHOP group and 48 (52%) events ( progression - 25%, relapse - 20%, death - 7%) in the CHOP group (p&lt;0,05). Median event-free survival and relapse-free survival in the CHOP group was 12 months, in R-CHOP group NS. Toxicity was equivalent in both groups. Conclusions: We have established better direct efficiency and outcome of R-CHOP in any age of pts. No significant financial relationships to disclose.
P0779 : Ledipasvir/sofosbuvir with ribavirin for the treatment of fibrosing cholestatic hepatitis C after liver transplantation
Authors: X. Forns, D. Mutimer, M. Manns, K.R. Reddy, G.T. Everson, S.L. Flamm, J. Denning, S. Arterburn, T. Brandt-Sarif, P.S. Pang, J.G. McHutchison, N. Afdhal, M. Charlton, D. Samuel, E. Gane
Journal: Journal of Hepatology (2015)
Out, Out — Making Amyloid’s Candle Briefer
Authors: Raymond L. Comenzo
Journal: New England Journal of Medicine (2015)

Two decades ago, a young British woman with systemic immunoglobulin-light-chain (AL) type amyloidosis, hepatomegaly, Howell–Jolly bodies on blood smear, 10% kappa-restricted marrow plasma cells, and a kappa band on urine immunofixation came to Boston for stem-cell transplantation. The kappa light-chain protein was encoded by the IGKV1-16 germline gene,1 as is the kappa light-chain protein in 17 of 131 AL amyloidosis kappa cases in the Amyloid Light Chain Database (ALBase) (http://albase.bumc.bu.edu); in contrast, kappa protein is encoded by IGKV1-16 in only 1 of 107 myeloma kappa cases in the ALBase (relative risk of amyloidosis, 13.9; 95% confidence interval, 1.9 to 102.7; . . .
Phosphatase PTP4A3 Promotes Triple-Negative Breast Cancer Growth and Predicts Poor Patient Survival
Authors: Petra den Hollander, Kathryn Rawls, Anna Tsimelzon, Jonathan Shepherd, Abhijit Mazumdar, Jamal Hill, Suzanne A.W. Fuqua, Jenny C. Chang, C. Kent Osborne, Susan G. Hilsenbeck, Gordon B. Mills, Powel H. Brown
Journal: Cancer Research (2016)

Abstract Triple-negative breast cancer (TNBC) has the worst prognosis of all breast cancers, and women diagnosed with TNBC currently lack targeted treatment options. To identify novel targets for TNBC, we evaluated phosphatase expression in breast tumors and characterized their contributions to in vitro and in vivo growth of TNBC. Using Affymetrix microarray analysis of 102 breast cancers, we identified 146 phosphatases that were significantly differentially expressed in TNBC compared with estrogen receptor (ER)-positive tumors. Of these, 19 phosphatases were upregulated (0.66-fold; FDR = 0.05) in TNBC compared with ER-positive breast cancers. We knocked down 17 overexpressed phosphatases in four triple-negative and four ER-positive breast cancer lines using specific siRNAs and found that depletion of six of these phosphatases significantly reduced growth and anchorage-independent growth of TNBC cells to a greater extent than ER-positive cell lines. Further analysis of the phosphatase PTP4A3 (also known as PRL-3) demonstrated its requirement for G1–S cell-cycle progression in all breast cancer cells, but PTP4A3 regulated apoptosis selectively in TNBC cells. In addition, PTP4A3 inhibition reduced the growth of TNBC tumors in vivo. Moreover, in silico analysis revealed the PTP4A3 gene to be amplified in 29% of basal-like breast cancers, and high expression of PTP4A3 could serve as an independent prognostic indicator for worse overall survival. Collectively, these studies define the importance of phosphatase overexpression in TNBC and lay the foundation for the development of new targeted therapies directed against phosphatases or their respective signaling pathways for TNBC patients. Cancer Res; 76(7); 1942–53. ©2016 AACR.
Synergistic tumoricidal effect between celecoxib and gabexate mesilate on the human breast cancer cells
Authors: Y. Suh, C. Chun, B. Song, S. Oh, S. Jung
Journal: Journal of Clinical Oncology (2007)

21179 Background: Selective cyclooxygenase 2 (COX2) inhibitors, including celecoxib, has shown its antitumor effects against various cancers including breast cancer. Gabexate mesilate (GM) can be found to have anti-cancer activities against tumors such as colon cancer. We tried to determine whether synergism can exist between GM and celecoxib against human breast cancer cells. Methods: MCF7/Her18 (estrogen receptor positive) and MDA-MB-436 (estrogen receptor negative) human breast cancer cells were used. Celecoxib and GM were added into the culture media at a dose of 30 and 50 μM for estrogen receptor (ER) (+) cells and 50 and 75 μM for ER (-) cells. Cellular proliferation assays wer performed and trypan blue exclusion method was adopted to count the viable cells after culture. Cell cycle analysis and fluorescein-assorted cell sortings were done to check the cell cycle changes after treatment. Immunoblotting using Akt, phosphorylated Akt (p- Akt), β-catenin, COX2 and VEGF was done to evaluate changes in expression of these proteins. Results: Combination treatment group showed significantly enhanced tumoricidal effect than either mono-treatment group on cellular proliferation study. Combined treatment yielded more G1 phase population and G2-M phase cells. (p&lt;0.05) The level of Akt, p-Akt, VEGF, COX2 expression were decreased more significantly than either mono-treatment group. (p&lt;0.05) Conclusions: We think that there could be synergistic effect between GM and celecoxib on the human breast cancer cells. Either drug has been used for many cases without significant problem, and can be tried for further ex vivo studies to determine synergistic effects between them. Possible antiangiogenentic actions after the combination should be evaluated thoroughly in other cell lines to get more preclinical data. No significant financial relationships to disclose.
Response to Comment on Leese et al. Progression of Diabetes Retinal Status Within Community Screening Programs and Potential Implications for Screening Intervals. Diabetes Care 2015;38:488–494
Authors: Graham P. Leese, Irene M. Stratton, Martin Land, Max O. Bachmann, Colin Jones, Peter Scanlon, Helen C. Looker, Brian Ferguson
Journal: Diabetes Care (2015)

We thank Ziemssen et al. (1) for their comments on our recent article (2). The underlying issue is how much evidence is required before screening intervals are changed. Screening is a population-based activity, designed for maximum benefit of the population and the safety of the individual. Using a variable screening interval depending on risk could enable resources to be directed toward patients at the highest risk of visual loss.

We agree with Ziemssen et al. that some patients with clinically significant maculopathy will require treatment on referral to the ophthalmology clinic and apologize if we gave the wrong impression. We were trying to indicate that the vast majority of …
Randomized phase II trial of preoperative combined modality chemoradiation for distal rectal cancer
Authors: E. P. Mitchell, K. Winter, M. Mohiuddin, N. Hanna, A. Yuen, C. Nichols, R. Share, C. Hayostek, C. Willett
Journal: Journal of Clinical Oncology (2004)

3535 Background: Potential advantages of preoperative radiotherapy (RT) include increased resectability, sphincter preservation, local control, and overall survival. This randomized phase II study was designed to evaluate, pathologic complete response(pCR) to preoperative combined-modality chemotherapy with 5-fluorouracil (5FU) and RT, or with 5FU, irinotecan (I) and RT in patients with adenocarcinoma of the rectum. Methods: Patients with T3/T4 tumors located 0–9 cm from the dentate line, without distant metastases or extension to the anal canal, were stratified according to clinical staging and were randomized to receive :Arm 1 [(5FU/RT)-CVI 5-FU (225 mg/m2/d, 7 d/wk) + pelvic RT 45.6 Gy (1.23 Gy/bid, ≥6-hour interval) + boost to tumor (9.6 Gy for T3 and 14.4 Gy for fixed T4)]; orArm 2 [(5FU/RT/I -CVI 5-FU (225 mg/m2/d, M-F,) +I(50 mg/m2 once weekly x 4)+ pelvic RT 45 Gy (1.8 Gy/d) + boost to tumor (5.4 Gy for T3 and 9 Gy for fixed T4)]. Surgery was performed 4–10 weeks following completion of therapy. Primary endpoint was pCR, with an expected rate of ≥20%. Secondary endpoints included acute and late normal tissue morbidity, patterns of failure, and complete resection rates. Results: 106 patients were enrolled (52 in Arm 1 and 54 in Arm 2); 3 were ineligible or never received protocol therapy, and 103 underwent surgery and were evaluable. Patient characteristics for Arm 1 and Arm 2, respectively, were: median age 56 and 59 years; 84% and 85% Caucasian; 70% and 83% Zubrod score 0; 68% and 75% stage T3; and 54% and 55% N0. Grades 3 and 4 acute hematologic and non hematologic toxicities occurred in 13% and 38%, respectively, in Arm 1 and 12% and 45% in Arm 2. Conclusions: Both regimens were well tolerated with acceptable grade 3/4 toxicities. The pathologic complete response rates of 30% with 5FU/RT and 26% with 5FU/RT/I were higher than in previous reports. Further study of these regimens should be considered. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Pfizer
Contribution of the Environment to Cancer Incidence: An Epidemiologic Exercise
Authors: Ernst L. Wynder, Gio B. Gori
Journal: JNCI Journal of the National Cancer Institute (1977)

Periodically, the Journal publishes solicited guest editorials as a means of transmitting to investigators in cancer research the essence of current work in a special field of study.The Board of Editors welcomes suggestions for future editorials that succinctly summarize current work toward a
Post-Hospital Outcomes of Patients With Acute Myocardial Infarction With Cardiogenic Shock
Authors: Rashmee U. Shah, James A. de Lemos, Tracy Y. Wang, Anita Y. Chen, Laine Thomas, Nadia R. Sutton, James C. Fang, Benjamin M. Scirica, Timothy D. Henry, Christopher B. Granger
Journal: Journal of the American College of Cardiology (2016)
Abstract 15146: Distribution of Energy Intake throughout the day and Weight Change: A Population-based Cohort Study in Spain
Authors: Pilar Guallar-Castillon, Ygor Hermenegildo, Esther Lopez-Garcia, Luz M Leon-Muñoz, Esther Garcia-Esquinas, Raul F Perez-Tasigchana, Fernando Rodriguez-Artalejo
Journal: Circulation (2014)

Introduction:  Experimental research in animals suggests that the timing of feeding may be associated with weight regulation. Moreover, the timing of the main meal predicted weight loss during a 20-week dietary intervention in obese individuals, independently from total 24-h energy intake. However, the association between the distribution of energy intake throughout the day and weight change in the general population is still uncertain.   Methods:  Data were taken from a cohort of 4243 individuals aged 18 years and older, selected in 2008-2010 and followed through 2012 (median follow-up: 3.5 years). Food consumption was collected at baseline with a validated dietary history, and energy intake was estimated at 6 eating occasions: breakfast, mid-morning snack, lunch, afternoon snack, dinner, and snacking (at any other moment). For each eating occasion, sex-specific quartiles of energy intake were calculated. Weight changes between baseline and end of follow-up were estimated, and weight gain was defined as a difference of >3 kg. Analyses were performed with logistic regression, and adjusted for the main confounders including total (24h) energy intake, quality of diet, prevalent and incident chronic diseases.   Results:  The percentage of 24-h energy intake in each of the 6 eating occasions throughout the day was respectively: 15.9, 5.1, 40.4, 4.6, 28.0, and 6.0%. In total, 16.5% of study participants gained > 3 kg of weight during follow-up. Compared to those whose energy intake at lunch was in the lowest quartile, the odds ratio (95% confidence interval) of weight gain was 0.77 (0.61-0.98) for those in the second quartile, 0.80 (0.62 to 1.03) for those in the third quartile, and 0.56 (0.42-0.75) for those in the highest quartile (p for trend:    Conclusion:  A higher energy intake at lunch (the main meal of the day in Spain) was associated with a lower risk of weight gain in the general adult population. Funding: Instituto de Salud Carlos III FIS Grant No: PI11/01379 and PI12/1166. FRAILOMIC Initiative (FP7-HEALTH-2012-Proposal No:305483-2).