tbuckley/cabot-search huggingface dataset:
Variations in serum P1NP, BAP and YKL-40 levels after start of treatment for advanced prostate cancer and the relation to prognosis
Authors: K. Brasso, I. J. Christensen, J. S. Johansen, B. Teisner, P. A. Price, P. Iversen
Journal: Journal of Clinical Oncology (2004)

4734 Background: The amino-terminal propeptide of type I procollagen (PINP) and bone alkaline phosphatase (BAP) are secreted by osteoblasts and are markers of bone formation. YKL-40 is a growth factor secreted by cancer cells and inflammatory cells. Increased serum PINP, BAP and YKL-40 levels are found in patients with advanced prostate cancer.The aim was to examine the variation of serum PINP, BAP and YKL-40 levels after start of treatment for advanced prostate carcinoma and the relation to prognosis. Methods: BAP, PINP and YKL-40 were determined by ELISA in serum samples obtained from 106 patients with advanced prostate carcinoma before and after start of treatment with total androgen ablation or parenteral estrogen. The median observation time was 5.0 years (range 3.6–6.2). 78 patients died. Results: At baseline all 3 biomarkers were significantly elevated (p<0.001) compared to controls. After 6 months of treatment the biomarkers were significantly (p<0.0001) decreased compared to baseline values (Serum P1NP: pre-treatment median (range) 156 μg/l (32–3112) vs. 6 months post-treatment 114 μg/l (31–1490); serum BAP: 51 U/l (9–2420) vs. 28 U/l (10–740); serum YKL-40: 133 μg/l (22–975) vs. 84 μg/l (20–484)). If serum PINP, BAP and YKL-40 levels at 6 months were log transformed and treated as continuous variables univariate Cox analysis showed that serum PINP (HR=1.9, 95% CI: 1.5–2.5, p<0.0001) and serum BAP (HR=1.8, 95% CI: 1.4–2.3, p<0.0001) but not serum YKL-40 (HR=1.3, 95% CI: 0.9–1.9, p=0.22) were significantly associated with survival. Multivariate Cox analysis including age, performance status, tumor stage, Soloway score, WHO tumor grade, and serum PINP, BAP and YKL-40 6 mths after start of treatment showed that Soloway score (HR=3.4, 95% CI: 1.8–6.6, p=0.0003), serum PINP (HR=1.6, 95% CI: 1.2–2.2, p=0.0017) and WHO tumor grade (HR=2.7, 95% CI: 1.3–5.6, p=0.0097) were independent prognostic variables of survival. Conclusions: High serum PINP or BAP levels 6 months after start of treatment with total androgen ablation or parenteral estrogen in patients with advanced prostate carcinoma are associated with poor prognosis. No significant financial relationships to disclose.
GW26-e2363 Uric Acid is Positively Associated with hypertension But Negatively Associated With Coronary Artery Disease in Postmenopausal Women: The Multi-Ethnic Study of Atherosclerosis
Authors: Qinghua Yuan, Ujit Karmacharya, Bangdang Chen, Fen Liu, Xiang Ma, Yi-Tong Ma
Journal: Journal of the American College of Cardiology (2015)
Targeting Multiple Active Kinase Pathways In 11q23 Translocated Pediatric Acute Myeloid Leukemia Using a VEGFR2 Antibody Together with a MEK Inhibitor.
Authors: Arja ter Elst, Kim R Kampen, Sander H Diks, Frank JG Scherpen, Válerie de Haas, Maikel P Peppelenbosch, Evelina S. De Bont
Journal: Blood (2010)
Agriculture increases individual fitness
Authors: Karen Kovaka, Carlos Santana, Raj Patel, Erol Akçay, Michael Weisberg
Journal: Behavioral and Brain Sciences (2016)

We question the need to explain the onset of agriculture by appealing to the second type of multilevel selection (MLS2). Unlike eusocial insect colonies, human societies do not exhibit key features of evolutionary individuals. If we avoid the mistake of equating Darwinian fitness with health and quality of life, the adoption of agriculture is almost certainly explicable in terms of individual-level selection and individual rationality.
CS1: A Potential New Therapeutic Target for the Treatment of Multiple Myeloma.
Authors: Eric D. Hsi, Roxanne Steinle, Balaji Balasa, Aparna Draksharapu, Benny Shum, Marukh Huseni, David Powers, Amulya Nanisetti, Marna Williams, Vladimir Vexler, Mohamad Hussein, Daniel Afar
Journal: Blood (2006)
Remote ischaemic conditioning reduces infarct size in animal<i>in vivo</i>models of ischaemia-reperfusion injury: a systematic review and meta-analysis
Authors: Daniel I. Bromage, Jack M.J. Pickard, Xavier Rossello, Oliver J. Ziff, Niall Burke, Derek M. Yellon, Sean M. Davidson
Journal: Cardiovascular Research (2016)

The potential of remote ischaemic conditioning (RIC) to ameliorate myocardial ischaemia-reperfusion injury (IRI) remains controversial. We aimed to analyse the pre-clinical evidence base to ascertain the overall effect and variability of RIC in animal in vivo models of myocardial IRI. Furthermore, we aimed to investigate the impact of different study protocols on the protective utility of RIC in animal models and identify gaps in our understanding of this promising therapeutic strategy.Our primary outcome measure was the difference in mean infarct size between RIC and control groups in in vivo models of myocardial IRI. A systematic review returned 31 reports, from which we made 22 controlled comparisons of remote ischaemic preconditioning (RIPreC) and 21 of remote ischaemic perconditioning and postconditioning (RIPerC/RIPostC) in a pooled random-effects meta-analysis. In total, our analysis includes data from 280 control animals and 373 animals subject to RIC. Overall, RIPreC reduced infarct size as a percentage of area at risk by 22.8% (95% CI 18.8-26.9%), when compared with untreated controls (P < 0.001). Similarly, RIPerC/RIPostC reduced infarct size by 22.2% (95% CI 17.1-25.3%; P < 0.001). Interestingly, we observed significant heterogeneity in effect size (T2 = 92.9% and I2 = 99.4%; P < 0.001) that could not be explained by any of the experimental variables analysed by meta-regression. However, few reports have systematically characterized RIC protocols, and few of the included in vivo studies satisfactorily met study quality requirements, particularly with respect to blinding and randomization.RIC significantly reduces infarct size in in vivo models of myocardial IRI. Heterogeneity between studies could not be explained by the experimental variables tested, but studies are limited in number and lack consistency in quality and study design. There is therefore a clear need for more well-performed in vivo studies with particular emphasis on detailed characterization of RIC protocols and investigating the potential impact of gender. Finally, more studies investigating the potential benefit of RIC in larger species are required before translation to humans.
Autografting for Acute Myeloid-Leukemia in 1St Remission - Evaluation of a Conditioning Regimen Containing Melphalan and Identification of Modifiable Treatment-Related Prognostic Factors
Authors: R Powles, J Mehta, S Singhal, J Treleaven, C Horton, D Tait, S Milan, S Meller, CR Pinkerton, D Catovsky
Journal: Blood (1994)
Enhancing efficacy of the multi-drug resistance-sensitive compound T138067 by advance treatment with negative modulators of the inhibitor of apoptosis protein survivin
Authors: Pasha Apontes, Xiang Ling, Youcef Rustum, Fengzhi Li
Journal: Cancer Research (2007)

5164   Previous studies demonstrated that the aberrant expression of survivin, a protein with a central role in the inhibition of apoptosis and promotion of cell division, is strongly implicated in the majority of human cancers. Survivin is obligatory/highly expressed during fetal development, but its expression in healthy adults is restricted to normal proliferative tissues and cells, e.g. thymus, testis and stem/progenitor cells. In contrast, survivin is highly expressed in cancer tissues, and has been widely recognized as an innovative target for cancer treatment.  2-fluoro-1-methoxy-4-pentafluorophenylsulfonamidobenzene  (T138067) is a synthetic compound, which inhibits mitosis via partial disruption of microtubule polymerization, resulting in G2/M cell cycle arrest and induction of apoptosis. Treatment of multi-drug resistant (MDR) human cancer cells lines and mouse xenograft tumors with T138067 elicits an apoptotic response and tumor regression, respectively. However, as a stand alone chemotherapeutic, it failed to extend overall survival in phase II clinical trials. We discovered that this compound increases survivin expression over time and speculated that this was part of the mechanistic basis for its poor clinical outcomes. Based on our initial observation, we hypothesized that if we could oppose the T138067-mediated induction of survivin, its potency might be dramatically enhanced. To test our hypothesis, we treated MCF-7 and ZR-75-1 human breast cancer cells first with agents that suppress survivin, SN-38 (the active form of CPT-11/irinotecan, which is currently used in the clinic), resveratrol (a natural component of red grapes), or using RNAi directed against survivin, followed by exposure to T138067, a sequential combination treatment that provoked massive cell death compared with T138067 alone. Mechanistically, while T138067 activates Akt and Erk1/2 which upregulate survivin, and inhibits p38 activation which is associated with inhibition of survivin expression, SN-38 and resveratrol neutralized these events, and downregulated the expression of survivin, a known drug-resistance factor. Together, our findings support the notion that T138067 may be effective against refractory human MDR tumors when used in combination with prior treatment with agents that abrogate the drug-induced survivin expression.
LB-ARHGDIB-1R As Novel Minor Histocompatibility Antigen For Therapeutic Application
Authors: Margot J Pont, Willemijn Hobo, M. Willy Honders, Simone A.P. van Luxemburg-Heijs, Michel G.D. Kester, Cornelis A.M. van Bergen, Harry Dolstra, J.H. Frederik Falkenburg, Marieke Griffioen
Journal: Blood (2013)
Dimensionality Reduction Reveals Distinct Shapes of Normal and Malignant Hematopoietic Cell Populations
Authors: Sean C Bendall, El-ad D. Amir, Michelle Tadmor, Kara L. Davis, Erin F. Simonds, Daniel Shenfeld, Jacob Levine, Garry P. Nolan, Dana Pe'er
Journal: Blood (2012)
GW26-e1433 Evaluation the Safety and Efficacy of the Corsair Microcatheter for Complex Coronary Lesion in Percutaneous Coronary Intervention
Authors: Aiqin Zhou, Yiming Zhong, Xiaoping Wang, Yiongling Liao, Fachuan Li, Kejun Tian
Journal: Journal of the American College of Cardiology (2015)
Tyrosine Kinase Inhibitor Imatinib Enhances Tumor Immunity By Depleting Functionally Mature Regulatory T Cells
Authors: Shinsuke Noguchi, Hiroyoshi Nishikawa, Hirobumi Saitoh, Atsushi Ohshima, Kenichi Sawada, Shimon Sakaguchi, Naoto Takahashi
Journal: Blood (2015)
New primary sarcomas in survivors of childhood cancer: A detailed analysis of the effects of treatment: a report from the Childhood Cancer Survivor Study
Authors: T. O. Henderson, P. Rajaraman, M. Stovall, S. Smith, A. Mertens, A. Meadows, J. P. Neglia, P. Inskip, J. Whitton, L. L. Robison, L. Diller
Journal: Journal of Clinical Oncology (2008)

10007 Background: Childhood cancer survivors are at increased risk for the development of subsequent primary sarcomas. Exposure to radiation therapy is a known risk factor for the development of these sarcomas. However, the details of the dose-response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined. Methods: Subsequent sarcomas occurring within a cohort of 14,372 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Radiation doses at the site of the subsequent sarcoma were estimated, and chemotherapy information was abstracted from detailed medical records. Conditional logistic regression was used to estimate odds ratios (ORs) and calculate 95% confidence intervals (CIs). Results: Subsequent sarcomas were identified in 128 individuals. Sarcomas occurred a median of 12.8 years (range = 5.3 - 32.5 years) from original diagnosis. Radiation exposure was associated with increased risk of subsequent sarcomas (OR = 4.4, 95% CI = 2.1 - 9.4). Increased risk was apparent at doses below 10 Gy (OR = 13.0, 95% CI = 4.8 - 35.0) and reached 36-fold for doses above 40 Gy (95% CI =11.5 -112.9). Controlling for radiation, prior exposure to anthracyclines (OR = 2.4, 95% CI = 1.1 - 5.2) and bleomycin (OR= 6.4, 95% CI 1.7 - 25.0) were associated with an increased risk of new sarcoma. Alkylator exposure was not significantly associated with risk for sarcoma (OR = 1.5, 95% CI = 0.7 - 3.1). Conclusions: Exposure to radiation therapy, even at low doses, is the most important risk factor for the development of new sarcomas in childhood cancer survivors. Exposure to certain chemotherapy agents is also associated with risk for subsequent sarcomas. No significant financial relationships to disclose.
TET2 Is a Novel Tumor Suppressor Gene Inactivated in Myeloproliferative Neoplasms: Identification of a Pre-JAK2 V617F Event
Authors: Francois Delhommeau, Sabrina Dupont, Chloe James, Aline Masse, Jean Pierre le Couedic, Veronique Della Valle, Antonio Alberdi, Philippe Dessen, Michaela Fontenay, Nicole Casadevall, Jean Soulier, Olivier Bernard, William Vainchenker
Journal: Blood (2008)
Gut dysbiosis impairs recovery after spinal cord injury
Authors: Kristina A. Kigerl, Jodie C.E. Hall, Lingling Wang, Xiaokui Mo, Zhongtang Yu, Phillip G. Popovich
Journal: The Journal of Experimental Medicine (2016)

The trillions of microbes that exist in the gastrointestinal tract have emerged as pivotal regulators of mammalian development and physiology. Disruption of this gut microbiome, a process known as dysbiosis, causes or exacerbates various diseases, but whether gut dysbiosis affects recovery of neurological function or lesion pathology after traumatic spinal cord injury (SCI) is unknown. Data in this study show that SCI increases intestinal permeability and bacterial translocation from the gut. These changes are associated with immune cell activation in gut-associated lymphoid tissues (GALTs) and significant changes in the composition of both major and minor gut bacterial taxa. Postinjury changes in gut microbiota persist for at least one month and predict the magnitude of locomotor impairment. Experimental induction of gut dysbiosis in naive mice before SCI (e.g., via oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment and spinal cord pathology after SCI. Conversely, feeding SCI mice commercial probiotics (VSL#3) enriched with lactic acid–producing bacteria triggers a protective immune response in GALTs and confers neuroprotection with improved locomotor recovery. Our data reveal a previously unknown role for the gut microbiota in influencing recovery of neurological function and neuropathology after SCI.
Depletion of myeloid cells exacerbates hepatitis and induces an aberrant increase in histone H3 in mouse serum
Authors: Xuehua Piao, Soh Yamazaki, Sachiko Komazawa‐Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
Journal: Hepatology (2016)

Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (CflarHep-low) mice. Cellular FLICE-inhibitory protein expression was down-regulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor–induced apoptosis. CflarHep-low mice developed acute hepatitis and recovered with clearance of apoptotic hepatocytes at 24 hours after injection of low doses of tumor necrosis factor α (TNFα), which could not induce hepatitis in wild-type (WT) mice. Depletion of Kupffer cells (KCs) by clodronate liposomes did not impair clearance of dying hepatocytes or exacerbate hepatitis in CflarHep-low mice. To elucidate the roles of BM-derived monocytes and neutrophils in clearance of apoptotic hepatocytes, we examined the effect of depletion of these cells on TNFα-induced hepatitis in CflarHep-low mice. We reconstituted CflarHep-low mice with BM cells from transgenic mice in which human diphtheria toxin receptor (DTR) was expressed under control of the lysozyme M (LysM) promoter. TNFα-induced infiltration of myeloid cells, including monocytes and neutrophils, was completely ablated in LysM-DTR BM-reconstituted CflarHep-low mice pretreated with diphtheria toxin, whereas KCs remained present in the livers. Under these experimental conditions, LysM-DTR BM-reconstituted CflarHep-low mice rapidly developed severe hepatitis and succumbed within several hours of TNFα injection. We found that serum interleukin-6 (IL-6), TNFα, and histone H3 were aberrantly increased in LysM-DTR BM-reconstituted, but not in WT BM-reconstituted, CflarHep-low mice following TNFα injection. Conclusion: These findings indicate an unexpected role of myeloid cells in decreasing serum IL-6, TNFα, and histone H3 levels via the suppression of TNFα-induced hepatocyte apoptosis. (Hepatology 2017;65:237-252).
The JAK2V617F mutation is a target for specific T cells in the JAK2V617F-positive myeloproliferative neoplasms
Authors: M O Holmström, M D Hjortsø, S M Ahmad, Ö Met, E Martinenaite, C Riley, P Straten, I M Svane, H C Hasselbalch, M H Andersen
Journal: Leukemia (2016)
Evaluation of serum profiles changes after neoadjuvant chemotherapy for breast cancer using MALDI-TOF/MS procedure
Authors: D. Hawke, C. Mazouni, F. André, K. Baggerly, K. Baggerly, S. Tsavachidis, A. U. Buzdar, P. Martin, R. Kobayashi, L. Pusztai
Journal: Journal of Clinical Oncology (2009)

e22072 Evaluation of serum profiles changes after neoadjuvant chemotherapy for breast cancer using MALDI-TOF / MS procedure. Background: Response to primary chemotherapy (CT) for breast cancer is heterogeneous among patients and a more tailored treatment would be beneficial in term of reducing exposure to an unnecessary toxicity and optimization of response rates. Mass spectrometry analysis of serum might be helpful in detecting specific changes in response to primary CT. Methods: An applied Biosystems 4700 Proteomics Analyzer matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer was used. A breast cancer cohort of 78 sera samples from 39 HER2 positive patients consisting of matched pretreatment and (6 months) posttreatment samples was used. Blood samples were collected serially before each treatment cycle every 3 weeks of neoadjuvant CT. Samples were divided into those who achieved pathological complete response (pCR, n= 20) and those who had residual disease (RD, n=19). Low-mass differentially expressed peptides were identified using MALDI-TOF/TOF. Results: This procedure yielded a total of 2329 and 3152 peaks respectively, for the responders and non-responders. Biological variation analysis revealed a total of 32 peaks for responders and 643 peaks for non-responders to be differentially regulated with a false discovery rate less than 20%. A total of 8 differentially expressed proteins were identified from their peptides after digestion and LC-MALDI-TOF/TOF. Four in tumors with pCR (AFM, C3, hemopexin, SAP) and four proteins in the RD group were identified (AP1, hemopexin, Complement B, amyloid P component) Conclusions: Our study suggests that MALDI mass spectrometry may be used to predict the tumor response to neoadjuvant chemotherapy. Proteomic analysis may be useful in developing tailored chemotherapy for breast cancer. No significant financial relationships to disclose.
Molecular testing for <scp>JAK</scp>2, <scp>MPL</scp>, and <scp>CALR</scp> in myeloproliferative neoplasms
Authors: Daniel Xia, Robert P. Hasserjian
Journal: American Journal of Hematology (2016)

Polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are myeloproliferative neoplasms characterized by recurrent somatic mutations in JAK2, CALR, and MPL. This short review addresses (1) the spectrum of mutations seen in PV, ET, and PMF, (2) the emerging genotype-phenotype correlations, (3) the current role of molecular testing in disease classification and management, and (4) several important considerations for selecting an appropriate molecular test. In our view, sequential testing algorithms and simultaneous assessment of multiple mutations by next-generation sequencing are both valid approaches to testing. Am. J. Hematol. 91:1277-1280, 2016. © 2016 Wiley Periodicals, Inc.
GW26-e5422 Patients with residual ischemia on intracoronary electrocardiogram after stenting coronary bifurcation lesions have more angina at 12 month follow-up – insights form intracoronary electrocardiography based strategy for treatment of coronary bifurcation lesions
Authors: D.V. Vassilev, K. Karamfiloff, R.G. Gil, Nguyen Ngoc Tu Quynh, Hau Van Tran, Gianluca Rigatelli
Journal: Journal of the American College of Cardiology (2015)
Donor Engraftment Following α-Emitter Astatine-211 (211At) Labeled Anti-CD45 Monoclonal Antibody (mAb) Nonmyeloablative Conditioning for Dog Leukocyte Antigen (DLA)-Identical Marrow Transplantation
Authors: Yun Chen, Brian T Kornblit, Hirohisa Nakamae, Donald K Hamlin, Erlinda B Santos, Rainer Storb, D. Scott Wilbur, Brenda M. Sandmaier
Journal: Blood (2010)
Modulated Expression of BCL-xL and GATA-1 Genes Is a Common Feature in Myeloproliferative Disorders (MPD) Both in JAK2-V617F Positive and Negative Patients
Authors: Sarah Pozzi, Francesca Bertolotti, Silvio Parodi, Raffaella Ponassi, Barbara Biasotti, Silvia Bruno, Vittorio Rosti, Alessia Parodi, Barbara Bruno, Davide Imperiale, Giovanna Piaggio, Marina Podestà, Andrea Gallamini, Caterina Passalia, Giovanni Barosi, Francesco Frassoni
Journal: Blood (2007)
Enhanced paradoxical type 2 responses generated by interleukin-12 in patients with gastric and colorectal cancer
Authors: M. Shibata, M. Suzuki, H. Kanou, H. Abe, T. Kimura
Journal: Journal of Clinical Oncology (2004)

2599 Background: Interleukin-12 has been reported to induce type 1 helper T cells (Th1) that produce interleukin (IL)-2 and gamma-interferon (G-IFN), and recognized as one of the strongest immunotherapeutic agent. However, it was found that serum levels of type 2 cytokine such as IL-10 increased after systemic administration of IL-12. Methods: To study this paradoxical phenomenon, peripheral blood mononuclear cells (PBMC) were used collected from 7 healthy volunteer (HV) and 45 patients with gastric and colorectal cancer, and were used for this study. These PBMC were stimulated with IL-12 and the concentrations of É°-IFN, IL-6, IL-10 in the culture supernatant were measured as production of each cytokine after cultivation for 24 hours. Results: The production of IL-6 and IL-10 in patients were significantly higher than in HV. Those of IL-6 by patients with distant metastasis were higher than those by HV. Those of IL-10 were significantly increased in patients with nodal involvement and with distant metastasis than in HV and patients without any metastasis, and these findings were clearer in gastric cancer. Those of IL-6 and IL-10 were significantly correlated each other. Those of G-IFN was increased in patients with nodal involvement and with distant metastasis. Conclusions: Thus IL-12 appeared to induce type 2 responses in patients with cancer and this phenomena may interfere an activation of cell-mediated immunity and may cause an unsuccessful immunotherapy against cancer. A new approach to alter this phenomena is required in order to realize an effective immunotherapy for malignant diseases. No significant financial relationships to disclose.