tbuckley/cabot-search huggingface dataset:
Use of meta-analysis of gene expression profiling studies to identify biologically relevant pathways associated with aggressive breast cancer (BC) in young women.
Authors: P. Bedard, R. Salgado, S. K. Singhal, V. Durbecq, M. Ignatiadis, B. Haibe-Kains, M. Piccart, C. Sotiriou, S. Loi
Journal: Journal of Clinical Oncology (2010)

520 Background: BC diagnosed in women 35 years of age or younger is associated with aggressive clinical-pathological characteristics and poorer disease free survival. Our understanding of the biological processes associated with early onset BC is limited. Methods: We compiled clinical and gene expression profiling data from 4,831 early-stage BC patients across 31 datasets with a median follow-up of 6.6 years. Tumors were assigned to a molecular subtype and expression scores were computed for several published oncogenic pathway signatures. The chi-square and Mann-Whitney tests were used for between group comparisons. Distant metastasis free survival (DMFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Hazard ratios (HRs) were calculated using a Cox-proportional hazards model. Results: The pattern of molecular subtypes differed according to age at diagnosis (age ≤ 35: triple negative [TN] 39%, HER2 20%, LumA 16%, LumB 25%; age > 35: TN 19%, HER2 16%, LumA 30%, LumB 35%; p < 0.001). Young age was associated with an increased risk of distant metastasis (10-year DMFS 52.8% age ≤ 35 versus 69.1% age > 35, p = 0.002) that remained statistically significant after adjustment for known prognostic factors (HR 1.54, 95%CI 1.04-2.28, p = 0.031). This increased risk was most apparent in the TN (HR 2.05, 95%CI 1.10-3.90, p = 0.025) and LumB (HR 2.52, 95%CI 1.15-5.51, p = 0.021) subtypes. Compared with older patients (age>65), there was higher expression of proliferation, PTEN loss, and immune response and lower expression of stromal gene expression signatures (all p < 0.001) in young TN patients. In the LumB subset, young patients had increased expression of PI3K activated genes (p < 0.001). Histopathological validation of these genomic findings is ongoing. Conclusions: TN BC is more common in women ≤ 35 years of age. Young age is associated with a poor outcome from breast cancer, particularly for the TN and LumB subtypes. Increased expression of proliferation, immune response, and PTEN loss gene signatures in TN and PI3K activation in LumB suggests possible targets for biological investigation and future clinical trials in this high-risk population. No significant financial relationships to disclose.
Induction of anticancer immunity by MDA-7/IL-24
Authors: Ryo Miyahara, Sanjeev Banerjee, Kouichirou Kawano, Clay Efferson, Naotake Tsuda, Yasuko Miyahara, Constantine G. Ioannides, Sunil Chada, Rajagopal Ramesh
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5996 

We have previously demonstrated that ectopic expression of the melanoma differentiation associated gene-7 (mda-7)/interleukin-24 (IL-24 ) resulted in growth suppression and apoptosis not only in a wide variety of human cancer cells but also murine fiblosarcoma cell lines. In the present study we investigated whether MDA-7/IL-24 could induce systemic anti-cancer immunity. Treatment of murine fibrosarcoma (UV2237m) cells with an adenoviral vector carrying the mda-7/IL-24 gene (Ad-mda7; 10K vp/cell) resulted in intracellular expression and secretion of MDA-7/IL-24 protein. Implantation of Ad-mda7 treated tumor cells in syngenic C3H mice (1x106/animal) resulted in a significant ( P <0.001) inhibition of tumorigenicity. In contrast, implantation of untreated parental cells or Ad-luc treated tumor cells resulted in robust tumor growth. Challenge with parental tumor cells in mice that initially rejected Ad-mda7 treated tumor cells showed significant ( P < 0.01) inhibition of tumor growth compared to naive mice suggesting induction of systemic anti-tumor immunity in immunized mice. Studies investigating the mechanisms of anti-tumor immunity revealed that Ad-mda7 selectively enhanced H2Kk and not H2Kd MHC class I molecule expression in tumor cells in vitro . Analysis of splenocytes from mice that were implanted with Ad-mda7 treated tumor cells showed increased proliferative rate that were up to 30-fold higher than controls and produced Th1 type cytokines. Subset analysis of proliferating splenocytes demonstrated increases in CD3+CD4+ and CD3+CD8+ T-cells. Furthermore, a significant increase in CD3+CD8+ but not CD3+CD4+ cell population occurred when stimulated with irradiated tumor cells in vitro . Our results demonstrate for the first Ad-mda7 treatment of murine syngenic tumor cells induces cell death via apoptosis and immune activation leading to systemic anticancer immunity.
NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD
Authors: Zsofia Lazar, Nina Müllner, Monica Lucattelli, Cemil Korcan Ayata, Sanja Cicko, Gennady G. Yegutkin, Giovanna De Cunto, Tobias Müller, Anja Meyer, Madelon Hossfeld, Stephan Sorichter, Ildiko Horvath, Christian J. Virchow, Simon C. Robson, Giuseppe Lungarella, Marco Idzko
Journal: European Respiratory Journal (2015)

Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling. We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smoke-induced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39. Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema. Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage.
Red Cell Distribution Width and Other Red Blood Cell Parameters in Patients with Cancer: Association with Risk of Venous Thromboembolism and Mortality
Authors: Julia Riedl, Florian Posch, Eva-Maria Reitter, Ernst Eigenbauer, Christine Marosi, Ilse Schwarzinger, Christoph Zielinski, Ingrid Pabinger, Cihan Ay
Journal: Blood (2014)
Reply
Authors: Gilles Montalescot, Jean-Philippe Collet, Patrick Ecollan, Leonardo Bolognese, Jurrien ten Berg, Dariusz Dudek, Christian Hamm, Petr Widimsky, Jean-François Tanguay, Patrick Goldstein, Eileen Brown, Debra L. Miller, LeRoy LeNarz, Eric Vicaut
Journal: Journal of the American College of Cardiology (2015)
Nemo: a Phase 3 Trial of Binimetinib (Mek162) Versus Dacarbazine in Patients with Advanced Nras-Mutant Melanoma Who are Untreated or Have Progressed After Any Number of Immunotherapy Regimens
Authors: R. Dummer, P. Arenberger, P.A. Ascierto, J.W. De Groot, S. Hallmeyer, M. Lotem, G.V. Long, M. Marples, D. Schadendorf, A.N. Starodub, M. Taylor, P. Wolter, N. Yamazaki, E. Wasserman, J. Ford, M. Weill, K.T. Flaherty
Journal: Annals of Oncology (2014)
Abstract 17518: Good Attendance to Cardiac Rehabilitation is Associated with Achievement of Low C-Reactive Protein Levels in Patients after Acute Myocardial Infarction
Authors: Takahito Doi, Reon Kumasaka, Tetsuo Arakawa, Michio Nakanishi, Teruo Noguchi, Takahiro Ohara, Shigefumi Fukui, Kazuhiro Nakao, Masanobu Yanase, Hiroshi Takaki, Masaharu Ishihara, Satoshi Yasuda, Yoichi Goto
Journal: Circulation (2014)

Backgrounds: Cardiac rehabilitation with exercise training (CR/ET) has been reported to be associated with reduction in C-Reactive Protein (CRP). In patients with acute coronary syndrome receiving statin therapy, achievement of CRP levels below 2mg/L is known to be important for long-term event-free survival. However, the determinants of achieving low CRP after CR/ET are not fully understood. Methods: To address this issue, we studied 490 consecutive acute myocardial infarction (AMI) patients who participated in our CR/ET program and underwent measurements for serum CRP at the beginning and the end of the 3-month CR program. Patients with abnormally high CRP (&gt;= 20mg/L at baseline, &gt;=10mg/L at 3 months) or on hemodialysis were excluded. Patients were divided into 2 groups according to CRP levels at the end of the 3-month CR/ET: Low-CRP group (CRP&lt;=2.0mg/L, n=414), and High-CRP group (CRP&gt;2.0mg/dl, n=76). Results: At baseline, there were no significant differences between the two groups in age (Low-CRP group 64years vs High-CRP group 63years, NS), body mass index (BMI, 23 vs 23, NS), prevalences of diabetes, smoking habit and statin use, left ventricular ejection fraction (LVEF, 46 vs 44%, NS), or brain natriuretic peptide (BNP) levels (169 vs 164pg/ml, NS). Although the prevalence of dyslipidemia was significantly higher (76% vs 63%, p&lt;0.05), baseline CRP levels (4.5mg/L vs 5.9mg/L, p&lt;0.05) was significantly lower in Low-CRP group than High-CRP group. Notably, Low-CRP group had significantly greater number of attendance in CR/ET in 3 months than High-CRP group (18 vs 14times, p&lt;0.01). Multivariate logistic regression analysis (incorporating age, sex, BMI, history of dyslipidemia, baseline LVEF, peak CK, number of attendance in 3-month CR/ET, BNP, CRP, and statin use) demonstrated that history of dyslipidemia, lower baseline CRP levels, and greater number of 3-month CR/ET attendance were independent determinants (all p&lt;0.05) of achieving CRP levels below 2.0mg/L. Conclusion: Good attendance in CR/ET program is significantly associated with achievement of CRP levels below 2.0mg/L at 3 months, independent of baseline CRP levels, history of dyslipidemia, and statin use.
Postoperative leukopenia as an independent prognostic factor in gastric cancer patients.
Authors: Xiaofeng Chen, Dong Pei, Oluf D. Røe, Jing Qian, Fang Zhu, Shaohua He, Yingying Qian, Yiqian Liu, Yongmei Yin, Shu Yongqian
Journal: Journal of Clinical Oncology (2014)

e15076 Background: Postoperative leukopenia is often seen in patients with gastric cancer in clinical practice. This retrospective study was carried out to define the incidence of leukopenia after gastrectomy and before chemotherapy, and to explore the relationship between postoperative leukopenia, clinicopathologic characteristics and survival of patients. Methods: A total of 614 consecutive gastric cancer patients subjected to potential curative gastrectomy were enrolled in this retrospective study. The relationship between changes of blood cells with clinicopathological features and survival were analyzed. Results: The mean white blood cell (WBC) count significantly decreased after surgery. According to our definition for postoperative leukopenia, (p-Leukopenia: WBC count before surgery ≥ 4.0 × 109 /L and postoperative WBC count < 4.0 × 109/L and an absolute decrease ≥ 0.5 × 109 /L), a total of 107 (17.4%) patients developed postoperative leukopenia. The decrease of neutrophils was more pronounced than lymphocytes. P-leukopenia was related to poor tumor differentiation. Both higher preoperative WBC (HR 1.624, 95%CI 1.261-2.091, p < 0.001) and p-leukopenia (HR 1.448, 95%CI 1.074-1.953, p = 0.015) were independent negative prognosis factors for survival. Patients with both higher pre-operative WBC count and p-leukopenia had the most dismal prognosis survival versus those with normal baseline WBC count and no p-leukopenia (25.8 months vs. 52.8months, p<0.001). Conclusions: Preoperative leukocytosis and postoperative leukopenia was evident in a subset of gastric cancer patients and were independent prognostic biomarkers for survival. The WBC count is a routine-test that is performed in all hospitals and we showed that this inexpensive low-tech analysis can aid in predicting outcome of gastric cancer patients. Prospective studies on WBC as cancer biomarkers are warranted.
Abstract #5488: IKK inhibitor Bay 11-7082 induces necrotic cell death in pre-B ALL cells
Authors: Xiangbing Meng, Stuart S. Winter, A. Marina Martinez, Bridget S. Wilson
Journal: Cancer Research (2009)

The IkappaB kinase (IKK) complex regulates the survival of cancer cells through activation of the NF\#954;B anti-apoptosis pathway and negative control of pro-apoptosis pathways such as Foxo3a. Here, the IKK inhibitor Bay 11-7082 was found to induce cell death within 4 to 6 hours in the pre-B ALL cell line, 697. Induction of reactive oxygen species (ROS) was observed within 30 min of Bay 11-7082 treatment. Bay 11-7082-induced cell death was blocked by the ROS scavenging agent, NAC, and by the necroptosis inhibitor necrostatin-1; caspase inhibitors failed to protect against Bay-11-7082. Direct involvement of IKK in pre-B ALL survival was confirmed by introducing the IKK inhibitory peptide, NBD, into 697 cells. Although NF\#954;B activity is down-regulated in Bay11-7082 treated 697 cells, the cell death pathway induced by this compound may be independent of NF\#954;B. This is suggested by observations that Bay 11-7082 effectively kills 697 cells expressing dominant negative I\#954;B\#945;. In support of IKK as a potential therapeutic target in pre-B ALL, primary leukemia blasts from 10 patients were also killed by short term incubation with Bay 11-7082 treatment.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5488.
Risk factors of radiation pneumonitis in lung cancer
Authors: H. J. Chang, K. E. Lee, M. Y. Choi, J. H. Lee, E. M. Nam, Y. C. Mun, C. M. Seong, K. J. Lee, H. S. Suh, S. N. Lee
Journal: Journal of Clinical Oncology (2008)

7573 Background: The clinical syndrome of radiation pneumonitis develops in 5–15% of patients receiving thoracic radiotherapy for lung cancer. In this study, we evaluated and identified the clinical characteristics, clinical courses of patients who developed radiation pneumonitis compared with patients who did not develop radiation pneumonitis. Methods: One hundred and five lung cancer patients who underwent thoracic radiotherapy between January 2001 and January 2006 were evaluated and clinical characteristics were reviewed retrospectively. Results: The median age of total patients was 60.9 years old and 86 cases (81.9%) of non-small cell lung cancer and 19 cases (18.1%) of small cell lung cancer patients were enrolled. Forty-one cases(39.0%) developed radiation pneumonitis. Among these patients, 23 cases (56.1%) of early radiation pneumonitis, 15 (36.7%) of intermediate and 3 (7.2%) of late were classified by development time. By severity, 10 cases (24.4%) of Grade 1, 23 (56.1%) of Grade 2, 7 (17.1%) of Grade 3 and 1 of Grade 4 radiation pneumonitis were observed. 21cases (51.2%) of patients who developed radiation pneumonitis were treated with corticosteroid for mean duration of 9.8 weeks. Non-smoking history (p=0.046), concomitant other lung disease (p=0.021), and NTCP (Normal Tissue Complication Probability)≥30% (p=0.012) significantly increased risk of radiation pneumonitis development in multivariate analysis. Development of radiation pneumonitis did not affect survival (p=0.456). Conclusions: Radiation pneumonitis was developed in 39% of patients who had received thoracic radiation due to primary lung cancer and 56.1% cases of these radiation pneumonitis patients developed within 2 months. In this study, non-smoking history, concomitant other lung disease and NTCP≥30% were identified as risk factors of radiation pneumonitis, thus, more attention will be needed to these patients group. No significant financial relationships to disclose.
Treatment patterns and costs associated with acute myeloid leukemia in the elderly: A population-based analysis
Authors: J. Menzin, K. Lang, C. Earle, T. Foster, D. Dixon, R. Van Gool
Journal: Journal of Clinical Oncology (2004)

6613 Background: Acute myeloid leukemia (AML) is the most common type of leukemia among adults in the U.S. However, data on treatment patterns and costs of AML are sparse. Methods: Using the linked SEER-Medicare database, we retrospectively evaluated mortality, patterns of treatment, healthcare resource use, and Medicare payments associated with AML and its relapse over 2 years among Medicare beneficiaries aged 65+ initially diagnosed with AML in a SEER registry between 1991 and 1999. The SEER-Medicare database includes SEER cancer registry data and Medicare claims for approximately 14% of cancer cases in 17 geographically diverse regions across the US. Chemotherapy was ascertained based on inpatient and outpatient bills. Relapse was identified using a validated algorithm. Costs of care were based on total Medicare payments. Results: A total of 3,439 elderly patients with AML were identified. Median survival was 2.4 months (mean±SD: 5.6±6.8), with less than 7% of patients alive at 2 years (medians of 3.9, 2.2, 1.4 months for ages 65–74, 75–84, and 85+). Mean total Medicare payments (±SD) (2001 US dollars) were $51,888±$54,825, and declined by age (due to poorer survival). In the 2 years following diagnosis, 34% of patients underwent chemotherapy treatment (ranging from 7% among those 85+ to 49% among those 65–74). Treatment rates increased by cohort diagnosis year (29% and 38% for patients diagnosed in 1991 and 1999), mostly among younger patients and those treated in teaching hospitals. Median survival among treated patients was 5 months longer than that for untreated, and costs were 3 times higher. Use of hospice care was low, but increased over time (12% and 29% for patients diagnosed in 1991 and 1999). Finally, 192 patients (16% of treated patients) relapsed and received retreatment with chemotherapy. These patients survived a median 18 months, with a median duration of remission of 7.3 months. Conclusions: AML among the elderly is associated with a poor prognosis, and substantial costs over the few remaining months of life. Treatment appears to be changing, with increasing use of chemotherapy and hospice care. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Johnson & Johnson Pharmaceutical Johnson & Johnson Pharmaceutical
Noninvasive Prediction of Atherosclerotic Progression: The PROSPECT-MSCT Study
Authors: Christos V. Bourantas, Stella-Lida Papadopoulou, Patrick W. Serruys, Antonis Sakellarios, Pieter H. Kitslaar, Paschalis Bizopoulos, Chrysafios Girasis, Yao-Jun Zhang, Ton de Vries, Eric Boersma, Michail I. Papafaklis, Katerina K. Naka, Dimitrios I. Fotiadis, Gregg W. Stone, Johan H.C. Reiber, Lampros K. Michalis, Pim J. de Feyter, Hector M. Garcia-Garcia
Journal: JACC. Cardiovascular imaging (2015)
Intracellular Immunization of Rhesus CD34+ Hematopoietic Progenitor Cells With a Hairpin Ribozyme Protects T Cells and Macrophages From Simian Immunodeficiency Virus Infection
Authors: Michael Rosenzweig, Douglas F. Marks, Donna Hempel, Marina Heusch, Günter Kraus, Flossie Wong-Staal, R. Paul Johnson
Journal: Blood (1997)
Plasma osteoprotegerin levels are inversely associated with nonalcoholic fatty liver disease in patients with type 2 diabetes: A case–control study in China
Authors: Yixin Niu, Weiwei Zhang, Zhen Yang, Xiaoyong Li, Wenjun Fang, Hongmei Zhang, Suijun Wang, Houguang Zhou, Jiangao Fan, Li Qin, Qing Su
Journal: Metabolism (2015)
Fate of new cancer drug is uncertain in Netherlands, as institute deems it too costly
Authors: Pieter van Eijsden
Journal: BMJ (2015)

The future of a newly licensed drug to treat lung cancer hangs in the balance in the Netherlands after the country’s National Health Care Institute (ZIN) found that its cost would be €134 000 (£97 000; $150 000) per quality adjusted life year (QALY) saved. This would be the first time in the Netherlands for a drug not to be reimbursed for financial reasons.

Nivolumab, which is used to treat squamous cell lung cancer, is made by Bristol-Myers Squibb and until now has been provided free by the company. It was approved by the European …
Multi-center, double-blind, randomized, placebo-controlled phase II study to assess the efficacy of recombinant MAGE-A3 vaccine as adjuvant therapy in stage IB/II MAGE-A3-positive, completely resected, non-small cell lung cancer (NSCLC)
Authors: J. Vansteenkiste, M. Zielinski, J. Dahabre, A. Linder, W. Malinowski, J. Jassem, M. Lopez-Brea, B. Passlick, F. Lehmann, V. Brichard
Journal: Journal of Clinical Oncology (2006)

7019 Background: About half of the patients with completely resected early-stage NSCLC will relapse. Adjuvant chemotherapy reduces the number of relapses at the expense of substantial toxicity. Activity of MAGE-A3 vaccination (i.e. recombinant MAGE-A3 protein and a potent GSK immunological adjuvant) has been proven in advanced melanoma. As about 35% of NSCLCs express the MAGE-A3 antigen, post-operative MAGE-A3 vaccination may be a targeted, well tolerated, and effective adjuvant therapy. Methods: Patients with completely resected, MAGE-A3 positive (assessed by quantitative RT-PCR), stage pIB or pII were 2:1, double-blind, randomly assigned to postoperative MAGE-A3 vaccination or placebo. Vaccination was started ≥6 weeks after surgery, with 5 vaccinations at 3-week intervals, followed by 8 vaccinations every 3 months. Randomization was stratified for stage (IB vs. II), histology (squamous vs. other), and lymph node procedure (sampling vs. dissection). Other anti-cancer adjuvant therapy was not allowed. Primary endpoint was time-to-recurrence, other endpoints were recurrence rates at different times, and survival. A sample size of 180 patients (120 active, 60 placebo) was chosen, to achieve 48% power (α=10%) to detect a 10% difference, assuming a 40% recurrence rate at month 30 in the placebo group (log rank test). A thorough interim efficacy analysis by an independent statistician (blinded to investigators and sponsor) is planned for 18 months after completion of recruitment. Results: 35% of 1,089 biopsies from 59 sites were MAGE-A3 positive. In two years, 182 patients were randomized (121 stage IB, 61 stage II). Overall, treatment was well tolerated, with high protocol compliance. Data collection for the interim efficacy analysis was initiated on December 19th, 2005. Median follow-up was 21 months, with 62 recurrences recorded. Conclusions: This study confirms expression of MAGE-A3 antigen in 35% of early NSCLC cases, and demonstrates good tolerability of postoperative MAGE-A3 vaccination. Efficacy results of the interim analysis will be available in February 2006. [Table: see text]