tbuckley/cabot-search huggingface dataset:
Similarities and differences in aging and in malignant transformation of human hematopoietic stem cells
Authors: H. Lannert, T. Able, T. Franz, R. Hofmann, A. Lenze, K. Horsch, V. Eckstein, R. Saffrich, A. D. Ho
Journal: Journal of Clinical Oncology (2006)

6555 Background: The tracking of stem cell aging, differentiation and deterioration by gene expression profiling and proteome analysis allows the comparison of different stages. The overall aim of a proteomic study is characterization of the complex network of cell regulation. We focused our investigations on different subsets of highly enriched CD34+ stem cells from different human origins: fetal liver, cord blood, bone marrow (BM), and mobilized stem cells from peripheral blood (PBSC), as well as CD34+ leukemia cells, thus e.g. to identify pathways and new targets for leukemia therapy. Methods: Mononuclear cells were isolated by a standard Ficoll separation method from the different blood sources. An Auto-MACS (Miltenyi) and FACS Vantage SE cell sorter (Becton Dickinson) was used to highly enrich (&gt;99%) CD34+ cells fractions. Sample preparation: Total RNA was isolated from sorted 1 × 10e6 cells by standard methods using RNA isolation kit (Qiagen). For gene expression analysis topic-defined PIQOR stem cell microarrays (936 genes) were performed. Proteomics started with the determination of protein concentrations, 2D-gel-electrophoresis were described in Proteome Works System (BioRad). Sypro ruby and/or coomasie stained gels were used for protein identification by Q-TOF analyses. The subcellular localization of the identified proteins were performed by fluorescence and confocal microscopy of all cell fractions. Results: 1. The microarray gene expression correlation shows many similarities between human healthy stem cells of different sources and ages, otherwise many differences: 125 upregulated genes (kinases: PAK1, ATM1, CDKN2A) and 32 downregulated genes (EBCTF, RAMP1) in malignant cells compared to healthy stem cells. 2. Proteomics analyses of the different cell fractions show a large overlap of the most dominant protein spots, &gt;200 spots were identified by Q-TOF. For example stathmin (oncoprotein Op18) is expressed at very high levels in leukemia cells and in PBSCs but not in BM cells, additionally demonstrated by fluorescence microscopy. Conclusions: Combining genomics and proteomics assays, pathways e.g. Op18 for proliferation and migration of healthy (mobilized) CD34+ cells from bone marrow and malignant leukemia cells could be identified. No significant financial relationships to disclose.
Triple-negative breast cancer (TNBC) and residual disease (non-pCR): Does size matter?
Authors: Peter Kern, Mahyar Badiian, Gunter Minckwitz, Rainer Kimmig, Cornelia Liedtke, Mahdi Rezai
Journal: Journal of Clinical Oncology (2012)

106 Background: TNBC is associated with distinctly worse survival rates than non-TNBC unless a pCR is achieved (Liedtke C et al. J Clin Oncol. 2008;26:1275-1281) or almost achieved (Symmans WF. J Clin Oncol. 2007;25:4414-4422). Recent pooled analyses pointed out that pCR defined as "no invasive and no in situ residuals in breast and lymph nodes" can best discriminate between patients with favorable and unfavorable outcomes (Minckwitz von G. J Clin Oncol. 16 April 2012). However, no differentiation has been made with regard to the prognosis within the category of "gross disease" (non-pCR, &gt; 5 mm) after primary systemic therapy (PST). Methods: In this retrospective case series study, we analyzed 506 non-pCR patients out of a cohort of 16,196 patients with neoadjuvant or adjuvant chemotherapy from breast units of the West German Breast Center (WBC) at 24 months after surgery. Results: Overall survival (OS) differed significantly between the non-pCR groups ypT1 a (88%) and ypT1b,c (both 77%) likewise the disease-free survival (DFS) was 79% versus 63% (p&lt; 0.05) at 24 months after surgery. Beyond ypT1-stage, we found that ypT1+2 and ypT3+4 set up two significantly distinct groups in OS and DFS, with OS rates of 79% for ypT1+2 and 60% respectively 68% for ypT3 and ypT4. DFS rates were alike differing with 68 % and 62 % for ypT 1 and ypT2 from both ypT3 and ypT4 (20% and 28%). Distant disease free survival (DDFS) was markedly superior in ypT1a (93%) and ypT1b (88%) versus ypT1c (77%). Stage-dependent DDFS was 82% for ypT1 respectively 81% for ypT2 and thus significantly different from stages ypT3 and ypT4 (43% and 52%) (p&lt; 0.05). Conclusions: Risk stratification currently is made dichotomously: pCR and non-pCR. However it does not differentiate within the group of non-pCR. This case cohort trial investigates the prognosis of non-pCR according to the actual size of the residual disease. Overall survival at 24 months after surgery has to be differentiated between the groups ypT1a and ypTb,c and moreover between ypT1+2 and ypT3+4. This is to our knowledge the largest case cohort study analyzing the effect of gross residual disease on prognosis of patients with TNBC demonstrating: size does matter.
Impact of Tumour Ras/Braf Status on Efficacy of First-Line Panitumumab + Folfiri in Patients (Pts) with Metastatic Colorectal Cancer (Mcrc)
Authors: M. Karthaus, R. Hofheinz, L. Mineur, R. Greil, J. Thaler, E. Fernebro, F. Overkamp, H. Kröning, K.S. Oliner, C.H. Köhne, J. Terwey
Journal: Annals of Oncology (2014)
High-resolution profiling of the human glioma genome
Authors: M. Bredel, C. Bredel, D. Juric, G. R. Harsh, H. Vogel, L. D. Recht, B. I. Sikic
Journal: Journal of Clinical Oncology (2005)

9522 Background: Gliomas are among the most lethal of human tumors. A hallmark genomic feature of gliomas is the presence of complex chromosomal aberrations that result in altered gene copy numbers. For some of these aberrations, certain genes have been linked to gliomagenesis, whereas for others, the presumed relevant targets remain to be identified. High-resolution, genome-wide mapping of exact boundaries of chromosomal alterations should facilitate the localization and identification of genes involved in gliomagenesis and may characterize genetic subgroups of glial brain tumors. Methods: We have performed such mapping using cDNA microarray-based comparative genomic hybridization technology to profile copy number alterations across 42,000 mapped human cDNA clones, in a series of 54 gliomas of varying histogenesis and tumor grade. Results: This gene-by-gene analysis demonstrated the power of the created maps to precisely localize and size target regions and new recurrent regions of gene copy number alteration in these tumors. Our study has also identified novel, common, minimally altered regions in a subset of gliomas. The focal and informative nature of these recurrent regions can be best appreciated by consideration of the peak amplitude of recurrence of individual gene alterations within a region. We have discovered five minimally deleted regions, harboring deletions in putative tumor suppressor genes, not previously reported in gliomas. Finally, our study has revealed recurrent patterns of occurrence of distinct chromosomal aberrations as well as their interrelationships, and shows that gliomas can be clustered into distinct genetic subgroups. A subset of alterations was demonstrated to be associated with either the astrocytic or oligodendrocytic tumor phenotypes. Conclusions: High-resolution genetic profiling in human gliomas has permitted the precise characterization of target regions and new regions of gene copy number change, has revealed recurrent patterns of occurrence of distinct chromosomal aberrations as well as their interrelationships, and has identified five common minimally deleted regions involving putative tumor suppressor genes that could have a role in gliomagenesis. No significant financial relationships to disclose.
A Machine Without an Owner’s Manual
Authors: Joseph G Rogers, Adam D DeVore
Journal: JACC Heart Failure (2016)

Contemporary growth in the use of left ventricular assist devices (LVADs) to support patients with advanced heart failure is remarkable. In the United States alone, more than 2,400 LVADs were implanted in adults in 2014 compared with 459 in 2008 [(1)][1]. Although perioperative survival is
HER2 expression in disseminated tumor cells (DTC) and corresponding primary tumors of breast cancer patients
Authors: T. N. Fehm, G. Pergola, U. Vogel, R. Bachmann, S. Becker, D. Wallwiener, E. F. Solomayer
Journal: Journal of Clinical Oncology (2005)

9580 Background: The presence of disseminated tumor cells (DTC) in bone marrow (BM) of breast cancer patients is associated with poor prognosis. Several studies have indicated that these patients may benefit from secondary adjuvant immunotherapy. HER2 protein is suggested as one of the promising targets. The phenotype of the primary tumor is the current gold standard to make antibody based treatment decisions. However, the antigenic profile of primary tumors and DTC may be different. The aims of this study were (1) to determine the HER2 status of DTC in BM of breast cancer patients (2) and to compare the HER2 status of DTC and corresponding primary tumors. Method: Cytospins from bone marrow aspirates of 124 primary breast cancer patients (stage I-III) were analyzed for this study. A double labeling procedure was used for the identification of cytokeratin-positive (CK+)/HER2 positive cells. Slides were incubated with the pan-anti-cytokeratin antibody C11 conjugated to FITC and the polyclonal rabbit antibody CB11 against the HER2 protein. CB11 was detected by a secondary antibody labeled with Texas Red. HER2 status of the primary tumor was immunohistochemically assessed by the HERCEP-test (Dako Co., CA). Results: Disseminated tumor cells (DTC) were detected in the bone marrow of 47 patients. The number of DTC ranged from 1 to 70 per slide. 24 of these patients had HER2 positive DTC. HER2 positivity (score: 2+/3+) could be demonstrated in 12 of 46 primary tumors. Concordance rate between primary tumor and DTC was 63%. In three patients with HER2 positive tumors HER2 negative DTC were detected. In contrast, 14 patients with HER2 negative tumors (score: 0/1+) had HER2 positive DTC. The HER2 expression in DTC was heterogeneous in 8 of 20 patients with more than one CK-positive cell. Conclusions: (1) HER2 positive DTC can be detected in patients with HER2 negative primary tumors. Therefore, the antigenic profile of DTC should be included in the treatment decision for antibody based strategies. (2) The DTC are heterogeneous with regard to HER2 positivity. The effect of heterogeneity on the patient’s response is yet to be determined. No significant financial relationships to disclose.
Healthy People 2010: objectives for the United States
Authors: R. M Davis
Journal: BMJ (2000)

In January the United States Department of Health and Human Services released Healthy People 2010 , the nation's health goals for this decade.1 The report contains 467 specific objectives grouped into 28 "focus areas" (see box). It is the third set of 10 year national goals put out by the department, following earlier versions for 1990 and 2000. Once again it prompts the questions raised by most target setting exercises—of manageability and accountability.2 The scope and depth of the report are impressive, reflecting four years' work and broad consultation with the public, health experts, and over 350 national organisations and 270 state agencies. It is grounded in scientific evidence and covers an array of health behaviours, environmental factors, and other important determinants of individual and community health. A toolkit has been developed to help build support for Healthy People 2010 activities at the state and local levels, 3 and the public is being asked to join the campaign (www.health.gov/healthypeople/youcando/default.htm) #### Healthy People 2010 focus areas
Noncommunicable Lung Disease in Sub-Saharan Africa. A Community-based Cross-Sectional Study of Adults in Urban Malawi
Authors: Jamilah Meghji, Gilbert Nadeau, Kourtney J. Davis, Duolao Wang, Moffat J. Nyirenda, Stephen B. Gordon, Kevin Mortimer
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Noncommunicable diseases are major causes of morbidity and mortality in sub-Saharan Africa (sSA). Valid burden of disease estimates are lacking for noncommunicable lung disease in sSA.Objectives: We performed a community-based survey to determine the prevalence of chronic lung disease among adults 18 years or older in Malawi, using American Thoracic Society standard spirometry, internationally validated respiratory symptom and exposure questionnaires, and an assessment of HIV status.Methods: An age- and sex-stratified random sample of 2,000 adults was taken from the population of the Chilomoni district of Blantyre, Malawi. Fieldworkers collected questionnaire data, conducted HIV testing, and performed pre- and post-bronchodilator spirometry on eligible participants. Survey-weighted population prevalence estimates of respiratory symptoms and spirometric abnormalities were computed, and bivariate and multivariable regression were used to identify associated variables.Measurements and Main Results: Questionnaire data, HIV status, and standard spirometry were obtained from 1,059, 933, and 749 participants, respectively. Current respiratory symptoms, exposure to biomass, and ever-smoking were reported by 11.8, 85.2, and 10.4% of participants, respectively. HIV prevalence was 24.2%. Moderate to severe airway obstruction was seen in 3.6%. The prevalence of spirometric restriction was 38.6% using National Health and Nutrition Examination Survey III reference ranges and 9.0% using local reference ranges. Age was positively associated with obstruction, whereas low body mass index was associated with restriction.Conclusions: More than 40% of the Malawian adults in our urban population sample had abnormal lung function (mostly restrictive) in the context of widespread exposure to biomass smoke and a high prevalence of HIV. These findings potentially have major public health implications for Malawi and the broader sSA region.
Effect of anastrozole on bone mineral density: 5-year results from the ’Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial
Authors: R. E. Coleman
Journal: Journal of Clinical Oncology (2006)

511 Background: Since reporting the 1- and 2-year results from the ATAC trial bone sub-protocol, 68-month analysis results from the main ATAC trial have shown that, for postmenopausal women with invasive primary breast cancer, adjuvant treatment with anastrozole results in superior efficacy and tolerability compared with tamoxifen. Here we report 5-year bone mineral density (BMD) results from the monotherapy arms (anastrozole, n=81; tamoxifen, n=86) of the bone sub-protocol. Methods: Lumbar spine and total hip BMD were assessed by dual-energy X-ray absorptiometry at baseline and after 1, 2, and 5 years. Results: The median percentage changes in BMD at 1, 2, and 5 years, respectively, are shown in the table . Percentage changes in BMD from baseline to 5 years showed a statistically significant difference in favor of tamoxifen for both lumbar spine (treatment effect [percentage decrease of BMD on anastrozole relative to tamoxifen] −8.1; 95% confidence intervals [CI] −10.1, −6.1; p&lt;0.0001) and total hip (treatment effect −7.4; 95% CI −9.6, −5.3; p&lt;0.0001). For patients with data at baseline, 2, and 5 years, the rate of loss of lumbar spine BMD in the anastrozole group was significantly less from 2 to 5 years than from baseline to 2 years (mean difference in annual rate of change 0.0113, 95% CI 0.006, 0.017; p=0.0002), but there was no evidence of slowing down in the loss of total hip BMD. Five patients with osteopenia at baseline developed osteoporosis on treatment with anastrozole (4) or tamoxifen (1). No patients with normal BMD at baseline became osteoporotic at 5 years. Conclusions: Significant bone loss occurred throughout the 5 years in the anastrozole group, although there appeared to be a slowing down of the rate of bone loss in years 2–5. Although no patients with normal BMD at baseline had become osteoporotic at 5 years, regular monitoring of BMD and bone protection strategies are likely to be required in patients receiving anastrozole in the presence of pre-existing osteopenia. [Table: see text] [Table: see text]
HER2 amplification and overexpression between primary and liver metastatic breast cancer: Significance and implication.
Authors: Casey B. Williams, Pradip De, Jessica Klein, Kirstin Anne Williams, Brigitte Cyr, Misty Small, Michelle King, Jennifer Carlson, Yuliang Sun, Brandon Michael Young, Scooter Willis, Nandini Dey, Amy K. Krie, Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2014)

150 Background: The systemic management of metastatic breast cancer (MBC) is mostly based on the ER or HER2 status of the primary tumor. However, the hormonal status or the amplificaction/overexpression HER2 may change in every metastatic site because of the effects of the long-term treatment of metastatic cancer with endocrine therapy, chemotherapy, or targeted agents. The purpose of this study was to investigate the frequency of change in HER2 expression in primary and distant metastatic tumors (especially in liver) in HER2+ breast cancer patients. Methods: We retrospectively analyzed the results of 31 consecutive metastatic breast cancer patients that were seen in our center over 4 months from February 2014 through May 2014. All patients were rebiopsied after consultation and samples were sent for standard immunohistochemistry (IHC) for ER, PR, and HER2 and formalin-fixed, paraffin-embedded (FFPE) samples were sent for genomic (Foundation Medicine) and proteomic analysis (Theranostics). All results from the metastatic samples were compared to the baseline IHC and/or FISH results for HER2. Results: A change in HER2 status was observed in 26% of the cases. 16% of cases underwent a negative to positive conversion in HER2 status while 10% of cases underwent a positive to negative conversion. It is notable that all 5 patients that underwent a negative to positive conversion in HER2 status had biopsies taken from metastatic disease in the liver. Overall, 45% of patients with metastatic disease in the liver had a negative to positive conversion in HER2 status. Conclusions: The results of this study emphasize the significance of confirming HER2 expression in a recurrence lesion. This discordance may be due to the increasing level of genetic instability occurring throughout disease progression that can significantly influence the alterations of the HER2 gene. If feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from non-HER2 amplified breast cancer. Although HER2 status is usually appraised in primary tumor, knowledge of the HER2 status in metastases may be of potential value for therapeutic decision making.
Prognostic significance of staging in gastric lymphoma.
Authors: C R Thomas
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.6.1118 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2348228 Prognostic significance of staging in gastric lymphoma. C R Thomas JrxC R Thomas JrSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.6.1118 PDF "Prognostic significance of staging in gastric lymphoma.." Journal of Clinical Oncology, 8(6), pp. 1118–1119© 1990 by American Society of Clinical Oncology
BODE index as a predictor of survival in lung transplantation
Authors: Pilar Sanjuan, Isabel Otero, Pedro J. Marcos, Héctor Verea
Journal: European Respiratory Journal (2011)

Introduction:  Chronic obstructive pulmonary disease (COPD) is one of the most frequent indications for lung transplantation (LTx), but survival benefit is still under debate. We analysed the survival impact of LTx in COPD using the BODE (body mass index, airway obstruction, dyspnoea, exercise capacity) index.   Aims:  The aim of our study was to analyse the survival impact of lung transplantation in COPD patients. We compared the post-transplant survival with the survival predicted by the BODE index as measured during pre-transplant clinical evaluation.   Methods:  Retrospective review of 59 consecutive lung transplants performed for COPD in our centre between June 1st 1999 and December 30th 2010. The pre-transplant BODE score was calculated for each patient. Predicted and observed post-transplant survival was then compared.   Results:  59 COPD patients were analyzed. Mean age was 57±6 years, 51 (86%) men. 52 (88%) patients had a BODE >7 and 7 (11.9%)   7 was 73.2±8.6. In the subgroups with a BODE score ≥7 and    Conclusions:  The results of this study showed a significant survival benefit of LTx in our cohort of COPD patients. Patients with BODE ≥7 will be the ones who benefit the most from the procedure.
A phase I/II trial of CD3/CD28 activated T cells (Xcellerated T Cells) in patients with hormone refractory prostate cancer
Authors: M. L. Glode, A. Pantuck, C. S. Higano, J. Meyer, L. Hami, S. Craig, R. J. Berenson, M. W. Frohlich
Journal: Journal of Clinical Oncology (2004)

2549 Background: T cells can be activated and expanded ex vivo from peripheral blood mononuclear cells using paramagnetic beads coated with antibodies to the CD3 and CD28 receptors (Xcellerate Process). Methods: Patients with androgen independent prostate cancer and no history of prior chemotherapy were enrolled. Patients received one infusion of 75–100 x 109 CD3/CD28 activated T cells (Xcellerated T Cells). Objectives of the study were to assess the safety of the therapy, changes in serum prostate specific antigen (PSA), and changes in markers of bone resorption. Results: 20 patients underwent leukapheresis, and 19 were treated (1 patient progressed prior to treatment). Baseline characteristics for the treated patients [median(range)] were: age 71.1 (55.1–84.4), PSA 28.2 ng/mL (6.2–348.0), and Gleason score 7 (4–9). Ten patients had documented bone metastases. Xcellerated T Cells were successfully manufactured in all patients. T cells expanded 125 ± 33 fold (mean ± S.D.). The final products were 99.1 ± 1.4% T cells with CD4:CD8 ratio of 5.2 ± 4.0. The mean number of viable cells infused was 84 ± 18 x 109. Toxicities possibly, probably or definitely related to the therapy of Grade 1, 2 or 3 severity were seen in 13, 3 and 1 patients respectively. The most common toxicities were rigors, pyrexia and nausea. The lymphocyte count per mm3 increased from 1218 ± 156 at Day 0, to 3455 ± 355 at Day 7 and 2756 ± 393 at Month 4 (mean ± SEM). Two patients had PSA declines of >50%, with PSA nadirs occuring 5 and 14 months following treatment. Serum markers of bone resorption (NTX, BAP, ICTP) measured in 5 patients with positive bone scans were not statistically different at Month 3 compared with baseline. Conclusions: Xcellerated T Cells can be delivered on an outpatient basis with few side effects, and result in sustained increases in lymphocyte counts, and significant PSA declines in some patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Xcyte Therapies, Inc. Xcyte Therapies, Inc. Xcyte Therapies, Inc.
Abstract 16784: Dynamic Change of Patent Foramen Ovale Area throughout Cardiac Cycle: A Real Time Three-Dimensional Transesophageal Echocardiographic Study
Authors: Jun Tanaka, Kenji Harada, Takeji Saito, Masaki Izumo, Swaminatha Gurudevan, Kirsten Tolstrup, James R Siegel, Takahiro Shiota
Journal: Circulation (2012)

Background: Patent foramen ovale (PFO) is a three-dimensional structure with dynamic change which makes it difficult to assess the morphology using two-dimensional (2D) methods. We aimed to assess ...