tbuckley/cabot-search huggingface dataset:
Young people in Asia carry high risk for non-communicable diseases, finds report
Authors: Sanjeet Bagcchi
Journal: BMJ (2016)

Tackling four major risk factors among young people—tobacco use, harmful use of alcohol, physical inactivity, and unhealthy diet—can substantially reduce the burden of non-communicable diseases (NCDs) in Asia, a report by the Population Reference Bureau, a public policy think tank based in Washington, DC, has found.1

The report noted that more than half (54%) of the global deaths due to NCDs occurred in Asia, stating, “This region includes 28 countries and territories across East, Southeast, and South Asia. In almost half of these countries, NCDs make up three-quarters of deaths, and in most other countries in the region, NCDs account for at least …
Abstract 19920: Long-term Change in Cardiorespiratory Fitness and All-cause Mortality: A Follow-up Study
Authors: Jari A Laukkanen, Francesco Zaccardi, Hassan Khan, Sudhir Kurl, Rainer Rauramaa
Journal: Circulation (2015)

Background: The few studies that have assessed the association between changes in cardiorespiratory fitness and all-cause mortality have relied on exercise scores and other indirect measures of cardiorespiratory fitness (CRF). The aim of the study was to investigate whether long-term changes CRF, as assessed by the gold-standard method of respiratory gas exchange during exercise, are associated with all-cause mortality. Methods: Prospective cohort study (Kuopio Ischaemic Heart Disease Risk Factor Study), with a baseline examination between 1984 and 1989 (V1), a re-examination at 11 years (V2), and up to 15 years of follow-up from V2. VO 2 max was measured at both visits using respiratory gas exchange during maximal exercise test. The difference (ΔVO 2 max) was estimated as VO 2 max (V2) - VO 2 max(V1). This study was based on a population-based sample of men 42 to 60 years of age without no missing data on baseline and 11-year exercise test were included (N=579). Results: The mean ΔVO 2 max was -5.2 ml/min*kg. During a median follow-up of 13.3 (interquartile range: 12.5-14.0) years from V2, 123 (21.2%) all-cause deaths were recorded. In a multivariate analysis adjusted for baseline age, VO 2 max, systolic blood pressure, smoking status, low- and high-density lipoprotein cholesterol and triglycerides, C-reactive protein, body mass index, alcohol consumption, physical activity, socioeconomic status, and history of type 2 diabetes mellitus and ischaemic heart disease, 1 ml/min*kg higher ΔVO 2 max was associated with a 9% relative risk reduction of all-cause mortality (HR 0.91; 95% CI: 0.87 to 0.95) (Figure). Conclusions: In this population, long-term CRF reduction was associated with an increased risk of mortality, suggesting the importance of maintaining good CRF over the decades.
Abstract 4564: Elucidating the mechanism of the STAT3/NF-κB/EP4 signaling axis in pancreatic cancer
Authors: Amanda R. Munoz, James W. Freeman, Addanki P. Kumar
Journal: Cancer Research (2016)

Abstract Despite recent advances to pancreatic cancer (PanCA) management, the 5 year survival rate remains only 7%. This poor survival rate highlights the importance of increasing our molecular understanding of PanCA pathogenesis to develop effective therapies to improve patient outcomes. We previously demonstrated that targeting the STAT3/NF-κB signaling axis with Nexrutine® (a Phellodendron amurense bark extract) was able to inhibit autophagy, ROS production, and proliferation in multiple PanCA cell lines. Our data also indicated the potential involvement of prostaglandin receptor EP4 in mediating these effects. To our surprise, we observed decreased levels of EP4 in human pancreatic tumors implicating a possible protective role. However, the mechanism behind STAT3/NF-κB signaling and its link to EP4 are still unknown. Using genetic and chemical inhibition of STAT3 and EP4, we have sought to define the STAT3/NF-κB/EP4 signaling axis. Our results indicate that inhibition of STAT3 via knockdown (STAT3 KD) using shRNA does not affect the proliferative ability or viability of PanCA cell lines when compared to non-transfected control (NTC) cells. Even though proliferation and viability were un-affected, STAT3 KD increased Cox-2 levels in a KRAS mutant cell line (Capan-2) and inhibited Cox-2 in a KRAS WT cell line (BxPC-3). Inhibition of EP4 increased STAT3 and NF-κB activity in KRAS mutant cell lines while decreasing activity in the KRAS WT cell line. Furthermore, EP4 inhibition increased protein levels of IL-6 and dual inhibition of STAT3 and EP4 yielded increased NF-κB activity and decreased Cox-2 levels. Converse experiments in cells treated with IL-6 revealed inhibited EP4 expression and decreased NF-κB activity. This may be the reason behind the increased STAT3 activity noted in EP4 inhibited KRAS mutant cells and supports the notion that EP4 may be protective against PanCA development. Taken together, these data suggests a feedback loop in regulating the STAT3/NF-κB/EP4 signaling cascade and that STAT3/NF-κB signaling axis members are differentially regulated upon STAT3 or EP4 inhibition possibly depending on KRAS status. Supported by Initiative for Maximizing Student Development (IMSD) Training Grant (R25 GM095480; NMJB), NCCIH (R01 AT007448; APK), and VA-MERIT Award (I01 BX 000766; APK) Citation Format: Amanda R. Munoz, James W. Freeman, Addanki P. Kumar. Elucidating the mechanism of the STAT3/NF-κB/EP4 signaling axis in pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4564.
Abstract 4516: Evaluating the chromatin state as a predictive biomarker for BET inhibitor sensitivity in hematological malignancies
Authors: Joseph Castillo, Ryan Raisner, Karen Gascoigne, Gary Dos Santos, Emer Clarke, Alex Huang, Mark Lackner, Zineb Mounir
Journal: Cancer Research (2016)

Abstract The BET (bromodomain extra-terminal) family of proteins are a group of epigenetic regulators that control gene transcription by reading acetylated lysines on histone tails and recruiting transcription complexes. The various BET inhibitors developed show strong anti-tumor effects against a broad range of hematologic malignancies. The BET inhibitor JQ1 shows strong anti-proliferative activity in sub-sets of multiple myeloma (MM), acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and lymphoma cell line models. At present, however, predictive biomarkers of BET inhibitor sensitivity have not been identified. We hypothesize that the chromatin state characterized by various histone post-translational modifications (acetylation, methylation, etc.), can drive sensitivity to BET inhibition. By examining basal expression of epigenetic marks in panels of sensitive and resistant heme cell line models and further validating these histone modification trends in primary AML and multiple myeloma cultures, we may be able to identify predictive biomarkers of BET inhibitor sensitivity in hematological malignancies. Citation Format: Joseph Castillo, Ryan Raisner, Karen Gascoigne, Gary Dos Santos, Emer Clarke, Alex Huang, Mark Lackner, Zineb Mounir. Evaluating the chromatin state as a predictive biomarker for BET inhibitor sensitivity in hematological malignancies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4516.
A6.8 Biological Therapies in Juvenile Idiopathic Arthritis: Abstract A6.8 Table 1
Authors: ML Velloso Feijoo, R Martinez Perez, J Uceda Montañes, JL Marenco de la Fuente
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biological therapies have dramatically changed the prognosis for children with juvenile idiopathic arthritis (JIA). There are doubts about the possibility of discontinuing treatment once remission is achieved. We focus in this question in our series. <h3>Objective</h3> To assess the efficacy and safety of these drugs in our series of patients with JIA. <h3>Matherials and Methods</h3> We identified 9 children with JIA treated with biologic therapies, and we made a description of our experience. <h3>Results</h3> The mean age was 14.55 ± 5.85, with a female predominance (66.7%). At diagnosis, mean age was 4.94 ± 2.9, and at the beginning of biological treatment of 8.77 ± 2.63. The median time from diagnosis to initiation of biological therapy was 3.94 ± 2.83 years. The disease characteristics are detailed in the table. All the children had previously received DMARDs (66.6% methotrexate (MTX) and 33.3% MTX and sulfasalazine). Eight of the 9 patients (88.9%) were taking corticosteroids at baseline. Eight received etanercept (ETN) and one Adalimumab (ADA), with good outcomes in all the patients unless 1 that had to switch from ETN to ADA due to inefficacy, and improved after the change. The steroids were suspended in 75% of children (6). Differences between mean values of CRP, ESR, and platelets from baseline to actual moment were statistically significant. The median biologic time is 4 (1.11) years. Actually all the children are in remission, two of them (patients 1 and 4) without biological treatment or classic DMARDs (since 5 and 2 years respectively). None of the children have had significant adverse effects nor required hospitalisation from the beginning of therapy. <h3>Discussion</h3> ETN has proved its efficacy in JIA (regardless of the type of onset), as it has been reported in multiple efficacy and safety studies, including long term studies of up to eight years of continuous therapy. [1, 2] We present our experience in children treated with up to 11 years, with good outcomes in terms of efficacy and safety in all the patients, and also 2 patients still in remission after 2 and 5 years without treatment. <h3>References</h3> EH Giannini <i>et al</i>, Long-Term Safety and Effectiveness of Etanercept in Children with juvenile idiopathic selected categories of arthritis. <i>Arthritis Rheum</i>. 2009, 60(9):2794–2804. Pratsidou-Gertsi P, Trachana M, Pardalos G, Kanakoudi-Tsakalidou F. A follow-up study of juvenile idiopathic arthritis Patients with etanercept discontinued due to Who disease remission. <i>Clin Exp Rheumatol</i>. 2010 Nov–Dec, 28(6):919–22. Epub 2011 Jan 4.
Abstract 5062: Hypoxia-induced amoeboid cancer cell migration
Authors: Veronika te Boekhorst, Liying Jiang, Steffi Lehmann, Alba Zuidema, Peter Friedl
Journal: Cancer Research (2016)

Abstract Tumor hypoxia, by elevating hypoxia-inducible factors (HIFs), is an established inducer of epithelial-to-mesenchymal transition (EMT) and subsequent cancer cell invasion and metastasis. However, how hypoxia impacts on tumor cell invasion programs and translates into modes of dissemination of moving tumor cells remains unknown. Using breast cancer (BC) and head and neck cancer (HNC) cells which efficiently invade from multicellular spheroids into 3D fibrillar collagen, we addressed which signaling programs that control cell-cell adhesions, cell-matrix interactions and cytoskeletal dynamics and which modes of tumor cell migration are induced by hypoxia. While both cancer models primarily invaded collectively under normoxic conditions, severe hypoxia (0.2% oxygen) or pharmacological stabilization of HIF-1 using the prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG) induced EMT-like detachment and migration of single cells into collagen, exhibiting a 2- and 4-fold increase of single BC and HNC cells, respectively. Besides infrequent spindle-shaped movement, hypoxia or DMOG predominantly induced the transition from collective to amoeboid single-cell migration, with blebby amoeboid migration as the predominant migration mode (4- and 3-fold increase for BC and HNC, respectively) next to filopodial amoeboid migration. Hypoxia-induced amoeboid migration is characterized by variably fast and persistent migration, reaching up to several 100 μm/day, mediated by actin-rich filopodial or blebby protrusions at the leading edge. Criteria for amoeboid movement included (i) actin-containing blebs that interacted with collagen structures in a polarized fashion, (ii) weak dependence on matrix-metalloproteinase-mediated collagen remodeling, (iii) low dependence on focalized integrin-mediated matrix adhesions, and (iv) high dependence on RhoA-mediated actomyosin contraction for efficient bleb formation and migration speed. Interference with ROCK signaling using Y-27632 and myosin using blebbistatin significantly inhibited hypoxia-induced amoeboid dissemination and bleb formation. Thus, hypoxia induces plasticity of cancer invasion modes, with efficient blebby amoeboid dissemination as primary outcome. While blebby amoeboid motion is known as a rudimentary migration mode in embryonic stem cells, here we observe blebby amoeboid migration as a simple (low MMP- and integrin dependent) but efficient salvage migration mode of cancer cells under severe hypoxic stress. Citation Format: Veronika te Boekhorst, Liying Jiang, Steffi Lehmann, Alba Zuidema, Peter Friedl. Hypoxia-induced amoeboid cancer cell migration. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5062.
Abstract 755: ￼Antagonistic effect of M-MDSC and N-MDSC during astrocytoma progression
Authors: Chin-NIng Huang.
Journal: Cancer Research (2016)

Abstract The traditional dogma holds that tumor size has a positive correlation with tumor progression. However, on murine orthotopical astrocytoma model ALTS1C1, we found that the tumor growth is not a linear function instead a shrinkage and regrowth wave was noticed. To examine the un-characteristic tumor growth behavior, the relative relationship among tumor cells, brain resident cells, such as astrocytes and microglia, and infiltrating cells, such as monocytic (CD45+CD11b+) or lymphocytic (CD45+CD11b-) lineage cells, was analyzed by flow cytometry and immunohistochemistry (IHC). Not only tumor area, peripheral organs, including spleen, blood, and lymph nodes were also examined. The preliminary data showed that in tumor shrinkage stage, CD3+ lymphocytes increased dramatically, while CD11b+CD45low microglia decreased. Furthermore, we found that the change of two subtypes of myeloid derived suppressor cells (MDSCs), Ly6G+ neutrophilic MDSC (N-MDSC) and Ly6G- monocytic MDSC (M-MDSC), was in opposite direction during tumor progression. The increase of M-MDSCs is associated with the increase of tumor size while the N-MDSC is decreased. More interestingly, the flow cytometry data shows that the total amount of CD11b+ macrophages was constant during tumor growth phase, but IHC shows the different distribution pattern of macrophage subsets within different tumor regions (invasion tumor front vs tumor core). Currently, we are examining the dynamic change of these cells following irradiation to identify the cells that are responsive for tumor shrinkage and re-growth following radiation therapy for brain tumor. These results will be presented in the meeting. Citation Format: Chin-NIng Huang. ￼Antagonistic effect of M-MDSC and N-MDSC during astrocytoma progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 755.
Total Therapy 1 (TT1): Status Report of the First Tandem Autotransplant (TAT) Trial for Multiple Myeloma (MM) - 15 Years Later.
Authors: Bart Barlogie, Guido Tricot, Athanasios Fassas, Raman Desikan, Elias Anaissie, Sundar Jagannath, John Crowley
Journal: Blood (2005)
CD47-Sirpα Interaction Modulates Homing and Engraftment of Human Acute Myeloid Leukemia Stem Cells in Mice.
Authors: Alexandre PA Theocharides, Liqing Jin, Armando G Poeppl, Tatiana K Prasolava, Olga I Gan, Mark D Minden, Jayne S Danska, John E Dick, Jean CY Wang
Journal: Blood (2009)
A phase I trial of docetaxel combined with synthetic lycopene in subjects with metastatic prostate cancer.
Authors: Michael B. Lilly, Chongze Ma, Ying Yuan, Wen-Pin Chen, Adam C. Soloff, Christine E. McLaren, Xiaolin Zi
Journal: Journal of Clinical Oncology (2015)

e16109 Background: Lycopene, the red pigment in tomatoes, has been show to inhibit the growth of prostate cancer cells in tissue culture and animal models. We have shown that lycopene acts synergistically with docetaxel to inhibit the growth of human prostate cancer cells in an IGF1-dependent manner (Tang Y, et al., Neoplasia 13:108). We have now conducted a phase I trial of synthetic lycopene (BASF) in combination with docetaxel in subjects with metastatic prostate cancer (NCT01949519). Methods: Eligible subjects had metastatic prostate cancer, ongoing medical or surgical castration, and no prior chemotherapy for at least 1 year. Androgen deprivation was maintained through the trial. Subjects were treated with docetaxel 75mg/m2 IV Q 21 days, plus lycopene at 30mg/d (cohort 1), 90mg/d (cohort 2), or 150mg/d (cohort 3). Bayesian model averaging continual reassessment method was used to guide dose escalation. Treatment was continued until disease progression, excessive toxicity, or withdrawal of consent. Multiple correlative studies were performed including IGF1R phosphorylation, circulating endothelial cell (CEC) levels, and plasma levels of IGF1, IGFBP3, IL6, VEGF, and lycopene. Results: Eighteen subjects have been enrolled, 3 in cohort 1, 3 in cohort 2, and 12 in cohort 3. One DLT has occurred in cohort 3 (pulm embolus), and this dose level is the MTD. No further dose escalation is planned due to incomplete absorption of lycopene and a plateau in the plasma level. Analysis of correlative studies is ongoing and will be presented. CECs are suppressed by lycopene 30mg/d, while higher doses increase the number of CECs, suggesting a hormesis effect. Conclusions: Synthetic lycopene can be given safely at doses up to 150mg/d, in combination with docetaxel. Lycopene produces dose-dependent biologic effects on CECs and cytokines. Optimum dose for further trials may be determined by biochemical assays rather than by toxicity. Clinical trial information: NCT01949519.
Abstract 770: Negative regulation of the CCL22/CCR4 axis by TNFR1 improves melanoma outcome
Authors: Caio Abner Leite, Paulo Henrique Melo, Jose Mauricio Mota, Douglas Silva Prado, Paula Ramos Viacava, Fernando Queiroz Cunha, Jose Carlos Alves Filho
Journal: Cancer Research (2016)

Abstract Purpose: Immunotherapy for melanoma skin cancer is mainly focused on preventing T cell deactivation through PD1 or CTLA4 inhibition. Another proposed mechanism to increase global T cell response is to prevent Treg immunossupressive function through TNFR1/TNF activation or CCR4/CCL22 inhibition. We aimed to evaluate the role of TNFR1 and CCR4 in an experimental model of melanoma. Experimental procedures: C57/Bl6 WT, TNFR1 -/- or CCR4 -/- mice were subcutaneously inoculated with 30,000 B16-F10 cells for tumor growth measurement and survival analysis. In a different set of experiments, mice were euthanized fourteen days after inoculation (D14) for spleen, lymph nodes and tumor harvesting for Treg (CD4+CD25+FoxP3+) and TAM (CD45+F4/80+CD206+) quantification by flow cytometry. CCL22 concentrations were quantified in conditioned media from bone marrow-derived macrophages (BMDM) from WT, or TNFR1 -/- mice. Furthermore, TNFR1 and CCR4 gene expression in human melanoma was determined by data mining in deposited datasets (GSE46517). Results: TNFR1-/- showed increased tumor volumes and reduced survival when compared to their WT counterparts. At D14, we detected increased Treg and TAM accumulation in TNFR1-/- tumor microenvironment. CCL22 concentrations were increased in conditioned media from M2-polarized BMDM from TNFR1-/- mice. CCR4 deficient mice presented reduced tumor volumes and increased survival, accompanied by a reduced Treg accumulation at D14. Data mining in GEO gene expression bank revealed that metastatic melanoma presented reduced TNFR1 and increased CCR4 expression. Conclusions: CCR4 inhibition is a potential strategy to reduce Treg accumulation and improve outcomes in cancer patients. Further assessments are required to demonstrate the role of TNFR1 pathway in CCR4 activation. Citation Format: Caio Abner Leite, Paulo Henrique Melo, Jose Mauricio Mota, Douglas Silva Prado, Paula Ramos Viacava, Fernando Queiroz Cunha, Jose Carlos Alves Filho. Negative regulation of the CCL22/CCR4 axis by TNFR1 improves melanoma outcome. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 770.
Characteristics of advanced NSCLC patients with at least 6 months erlotinib treatment duration in Czech Republic.
Authors: Helena Coupkova, Jana Skrickova, Karel Hejduk, Bortlicek Zbynek, Bohdan Kadlec, Frantisek Salajka, Milos Pesek, Vitezslav Kolek, Leona Koubkova, Dimka Sixtova, Petr Zatloukal, Jaromir Roubec, Milada Zemanova, Rostislav Vyzula, Stanislav Spelda
Journal: Journal of Clinical Oncology (2012)

e18062 Background: Erlotinib is approved for NSCLC treatment in Czech Rep since 2005. This analysis was performed to analyze the profile of pts treated with erlotinib longer than 6 months. Methods: This retrospective analysis evaluates data from Czech Tarceva Registry of pts treated outside clinical trials. Survival (mOS, mPFS) was evaluated by the Kaplan-Meier method, survival comparison was performed by Log Rank test. Results: Up to October 2011, 430 out of 2121 pts with completed data in registry were treated with erlotinib for 6 months and longer. Median age 65 years, 54.4% men; 29.8% smokers, 37.9% former smokers, 32.3 % non-smokers; 77% pts ECOG PS 0-1. 74.7% stage IV pts, 21.4% stage IIIB. 43.5% adenoca, 31.9% squamous ca,11% non-specific NSCLC, 6% bronchioloalveolar ca. Erlobinib administered as 1 st line treatment in 13% pts, 2L in 50.9%, 3L in 34.9%. Till October 2011, 322 pts (74.9%) finished the treatment, 108 pts (25.1%) still on erlotinib therapy. Treatment discontinued due to progression in 75% pts, death in 15%, toxicity in 3%. The entire group results (n=430): CR in 2.3%, PR in 17.7%, SD in 65.8%, PD in 2.6%. mPFS and mOS from erlotinib initiation 12.4 and 21.4 months respectively. mOS from diagnosis was 43.5 months. Statistical difference in mOS (from the erlotinib initiation) was observed between groups with PS ECOG 0-1 and PS 2-3, 22.0 vs 16.4 months (p=0.001), although there was no difference in both groups in mPFS (12.9 vs. 10.6 months). mPFS and mOS in pts with adenoca (n=187) from erlotinib initiation 14.4 and 23.7 months respectively. mOS from diagnosis was 45.6 months. mPFS and mOS in pts with squamous ca (n=137) from erlotinib initiation was 11.3 and 17.6 months respectively. mOS from diagnosis was 42.2 months. Conclusions: This analysis documented good activity of erlotinib in both adeno and squamous cell carcinoma. The difference in mOS and mPFS between both groups was statistically significant when measured from erlotinib initiation (mOS: p= 0.017, mPFS: p=0.022), however not statistically significant when measured from the date of diagnosis (p=0.361). Patients with PS 0-1 have statistically significantly greater mOS than patients with worse PS (p=0.001).