tbuckley/cabot-search huggingface dataset:
Screening, Assessment, and Care of Anxiety and Depressive Symptoms in Adults With Cancer: An American Society of Clinical Oncology Guideline Adaptation
Authors: Barbara L. Andersen, Robert J. DeRubeis, Barry S. Berman, Jessie Gruman, Victoria L. Champion, Mary Jane Massie, Jimmie C. Holland, Ann H. Partridge, Kate Bak, Mark R. Somerfield, Julia H. Rowland
Journal: Journal of Clinical Oncology (2014)

A Pan-Canadian Practice Guideline on Screening, Assessment, and Care of Psychosocial Distress (Depression, Anxiety) in Adults With Cancer was identified for adaptation.American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The guideline was reviewed for developmental rigor and content applicability.On the basis of content review of the pan-Canadian guideline, the ASCO panel agreed that, in general, the recommendations were clear, thorough, based on the most relevant scientific evidence, and presented options that will be acceptable to patients. However, for some topics addressed in the pan-Canadian guideline, the ASCO panel formulated a set of adapted recommendations based on local context and practice beliefs of the ad hoc panel members. It is recommended that all patients with cancer be evaluated for symptoms of depression and anxiety at periodic times across the trajectory of care. Assessment should be performed using validated, published measures and procedures. Depending on levels of symptoms and supplementary information, differing treatment pathways are recommended. Failure to identify and treat anxiety and depression increases the risk for poor quality of life and potential disease-related morbidity and mortality. This guideline adaptation is part of a larger survivorship guideline series.Although clinicians may not be able to prevent some of the chronic or late medical effects of cancer, they have a vital role in mitigating the negative emotional and behavioral sequelae. Recognizing and treating effectively those who manifest symptoms of anxiety or depression will reduce the human cost of cancer.
Development of colonic neoplasia in p53 deficient mice with experimental colitis induced by dextran sulphate sodium
Authors: Shigehiko Fujii, Kazuaki Kitajima, Jun Takeda, Fumie Omotehara, Yasuo Ohkura, Yuko Ono, Johji Imura, Hitoshi Kawamata, Tsutomu Chiba, Takahiro Fujimori
Journal: Gut (2004)

<b>Background:</b> Several animal models for human ulcerative colitis (UC) associated neoplasia have been reported. However, most neoplasias developed in these models have morphological and genetic characteristics different from UC associated neoplasia. <b>Aims:</b> To establish a new colitis associated neoplasia model in p53 deficient mice by treatment with dextran sulphate sodium (DSS). <b>Methods:</b> DSS colitis was induced in homozygous p53 deficient mice (p53<sup>−/−</sup>-DSS), heterozygous p53 deficient mice (p53<sup>+/−</sup>-DSS) and wild-type mice (p53<sup>+/+</sup>-DSS) by treatment with 4% DSS. Numbers of developed neoplasias were compared among the experimental groups, and macroscopic and microscopic features of the neoplasias were analysed. Furthermore, K-ras mutation and beta-catenin expression were assessed. <b>Results:</b> p53<sup>−/−</sup>-DSS mice showed 100% incidence of neoplasias whereas the incidences in p53<sup>+/−</sup>-DSS and p53<sup>+/+</sup>-DSS mice were 46.2% and 13.3%, respectively. No neoplasias were observed in the control groups. The mean numbers of total neoplasias per mouse were 5.0 (p53<sup>−/−</sup>-DSS), 0.62 (p53<sup>+/−</sup>-DSS), and 0.2 (p53<sup>+/+</sup>-DSS). The number of neoplasias per mouse in the p53<sup>−/−</sup>-DSS group was significantly higher than that in the other DSS groups. The incidences of superficial type neoplasias were 91.7% in p53<sup>−/−</sup>-DSS mice, 75.0% in p53<sup>+/−</sup>-DSS mice, and 33.3% in p53<sup>+/+</sup>-DSS mice. The K-ras mutation was not detected in any of the neoplasias tested. Translocation of beta-catenin from the cell membrane to the cytoplasm or nucleus was observed in 19 of 23 (82.6%) neoplasias. <b>Conclusions:</b> The p53<sup>−/−</sup>-DSS mice is an excellent animal model of UC associated neoplasia because the morphological features and molecular genetics are similar to those of UC associated neoplasia. Therefore, this model will contribute to the analysis of tumorigenesis related to human UC associated neoplasia and the development of chemopreventive agents.
The Androgen Receptor Is Significantly Associated with Vascular Endothelial Growth Factor and Hypoxia Sensing via Hypoxia-Inducible Factors HIF-1a, HIF-2a, and the Prolyl Hydroxylases in Human Prostate Cancer
Authors: Jane L. Boddy, Stephen B. Fox, Cheng Han, Leticia Campo, Helen Turley, Suresh Kanga, Peter R. Malone, Adrian L. Harris
Journal: Clinical Cancer Research (2005)

Hypoxia regulates key biological processes including angiogenesis via the transcription factor, hypoxia-inducible factor (HIF). In prostate cancer, angiogenesis is also influenced by androgens, and recent cell line studies suggest that this effect is partly mediated by HIF. The study aimed to assess whether a relationship exists in human prostate cancer between expression of the androgen receptor, HIFs, and the key angiogenesis factor, vascular endothelial growth factor (VEGF).A tissue microarray comprised of 149 radical prostatectomy specimens was constructed. Semiquantitative immunohistochemical analysis was used to assess the expression of the androgen receptor, VEGF and HIF-1a and 2a, and their regulatory prolyl hydroxylase enzymes (PHD1, PHD2, and PHD3). Statistical analysis compared these factors with each other and with prostate-specific antigen relapse.There was a significant correlation between HIF-1a and HIF-2a expression (P = 0.02), and with androgen receptor (P = 0.04 and P < 0.001, respectively) and VEGF expression (P = 0.05 and P < 0.001, respectively). VEGF was also significantly related to the androgen receptor (P = 0.05), whereas PHD2 was inversely related to HIF-2a expression. No significant association was shown between HIF-1a or HIF-2a and time to prostate-specific antigen recurrence (P = 0.20 and P = 0.94, respectively).These findings confirm the relationship between hypoxia and the androgen receptor in prostate cancer, and show for the first time, the role of HIF-2a in this disease process. They provide clinical evidence to support the recent cell line findings that androgens may regulate VEGF levels through the activation of HIF in androgen-sensitive tumors. Inhibition of both the HIF pathways may provide new therapeutic options in the management of this disease.
Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study
Authors: Laurent Beaugerie, Nicole Brousse, Anne Marie Bouvier, Jean Frédéric Colombel, Marc Lémann, Jacques Cosnes, Xavier Hébuterne, Antoine Cortot, Yoram Bouhnik, Jean Pierre Gendre, Tabassome Simon, Marc Maynadié, Olivier Hermine, Jean Faivre, Fabrice Carrat
Journal: The Lancet (2009)
MUC4-Mediated Regulation of Acute Phase Protein Lipocalin 2 through HER2/AKT/NF-κB Signaling in Pancreatic Cancer
Authors: Sukhwinder Kaur, Neil Sharma, Shiv Ram Krishn, Imay Lakshmanan, Satyanarayana Rachagani, Michael J. Baine, Lynette M. Smith, Subodh M. Lele, Aaron R. Sasson, Sushovan Guha, Kavita Mallya, Judy M. Anderson, Michael A. Hollingsworth, Surinder K. Batra
Journal: Clinical Cancer Research (2013)

Abstract Purpose: MUC4 shows aberrant expression in early pancreatic lesions and a high specificity for pancreatic cancer. It thus has a high potential to be a sensitive and specific biomarker. Unfortunately, its low serum level limits its diagnostic/prognostic potential. We here report that a multifaceted acute phase protein lipocalin 2, regulated by MUC4, could be a potential diagnostic/prognostic marker for pancreatic cancer. Experimental Designs and Results: Overexpression/knockdown, luciferase reporter and molecular inhibition studies revealed that MUC4 regulates lipocalin 2 by stabilizing HER2 and stimulating AKT, which results in the activation of NF-κB. Immunohistochemical analyses of lipocalin 2 and MUC4 showed a significant positive correlation between MUC4 and lipocalin 2 in primary, metastatic tissues (Spearman correlation coefficient 0.71, P = 0.002) from rapid autopsy tissue sample from patients with pancreatic cancer as well as in serum and tissue samples from spontaneous KRASG12D mouse pancreatic cancer model (Spearman correlation coefficient 0.98, P &amp;lt; 0.05). Lipocalin 2 levels increased progressively with disease advancement (344.2 ± 22.8 ng/mL for 10 weeks to 3067.2 ± 572.6 for 50 weeks; P &amp;lt; 0.0001). In human pancreatic cancer cases, significantly elevated levels of lipocalin 2 were observed in patients with pancreatic cancer (148 ± 13.18 ng/mL) in comparison with controls (73.27 ± 4.9 ng/mL, P = 0.014). Analyses of pre- and postchemotherapy patients showed higher lipocalin 2 levels in prechemotherapy patients [121.7 ng/mL; 95% confidence interval (CI), 98.1–150.9] in comparison with the postchemotherapy (92.6 ng/mL; 95% CI, 76.7–111.6; P = 0.06) group. Conclusions: This study delineates the association and the downstream mechanisms of MUC4-regulated elevation of lipocalin-2 (via HER2/AKT/NF-κB) and its clinical significance for prognosis of pancreatic cancer. Clin Cancer Res; 20(3); 688–700. ©2013 AACR.
Eliminating malignant contamination from therapeutic human spermatogonial stem cells
Authors: Serena L. Dovey, Hanna Valli, Brian P. Hermann, Meena Sukhwani, Julia Donohue, Carlos A. Castro, Tianjiao Chu, Joseph S. Sanfilippo, Kyle E. Orwig
Journal: Journal of Clinical Investigation (2013)

Spermatogonial stem cell (SSC) transplantation has been shown to restore fertility in several species and may have application for treating some cases of male infertility (e.g., secondary to gonadotoxic therapy for cancer). To ensure safety of this fertility preservation strategy, methods are needed to isolate and enrich SSCs from human testis cell suspensions and also remove malignant contamination. We used flow cytometry to characterize cell surface antigen expression on human testicular cells and leukemic cells (MOLT-4 and TF-1a). We demonstrated via FACS that EpCAM is expressed by human spermatogonia but not MOLT-4 cells. In contrast, HLA-ABC and CD49e marked >95% of MOLT-4 cells but were not expressed on human spermatogonia. A multiparameter sort of MOLT-4–contaminated human testicular cell suspensions was performed to isolate EpCAM+/HLA-ABC–/CD49e– (putative spermatogonia) and EpCAM–/HLA-ABC+/CD49e+ (putative MOLT-4) cell fractions. The EpCAM+/HLA-ABC–/CD49e– fraction was enriched for spermatogonial colonizing activity and did not form tumors following human-to–nude mouse xenotransplantation. The EpCAM–/HLA-ABC+/CD49e+ fraction produced tumors following xenotransplantation. This approach could be generalized with slight modification to also remove contaminating TF-1a leukemia cells. Thus, FACS provides a method to isolate and enrich human spermatogonia and remove malignant contamination by exploiting differences in cell surface antigen expression.
Viscosity and Clotting of Blood in Venous Thrombosis and Coronary Occlusions
Authors: LEOPOLD DINTENFASS
Journal: Circulation Research (1964)

Viscosity of blood was measured in the absence of anticoagulants by means of an improved cone-in-cone viscometer. Data obtained in a study of a series of patients suffering from venous thrombosis and coronary occlusion were compared with data from a control group of healthy subjects. The probability that the large difference in viscosity observed between normal and abnormal blood is due to chance is approximately 1 in 1,000,000. The viscosity of blood remains constant, at any rate of shear, during the first two to four minutes after removal of blood. Clotting starts after various time periods, depending not only on the intrinsic properties of the particular blood sample, but also on the velocity gradient at which such clotting takes place. The following general trends were established : at 36°C the onset of clotting is much more rapid at high rates of shear than at low rates of shear. It appears, however, that at lowered temperatures this trend is reversed. The causes of aggregation of red cells, and the role of this aggregation in clotting, are discussed. It is emphasized that blood is thixotropic, i.e., that its viscosity is both time and rate-of-shear dependent. Thixotropy of blood is due, mainly, to a reversible aggregation of red cells. This suggests the existence of intermittent sedimentation of red cell aggregates during flow in blood vessels. Owing to the existence of a velocity profile, in which the axial region is under zero or near-zero rate of shear, such aggregates should be present especially in large veins and arteries. It appears that an increased thixotropy and viscosity are symptomatic of some thrombotic states.
Murder trials begin in US against two high opioid prescribers
Authors: Owen Dyer
Journal: BMJ (2015)

A new stage in the US authorities’ crackdown against high prescribers of opioids has opened with the murder trials in California and Florida of doctors who are directly accused of killing patients who died of overdoses after taking prescribed drugs.

Hsiu-Ying “Lisa” Tseng, a Los Angeles area physician, is charged with three counts of second degree murder over the deaths in 2009 of three male patients aged 21, 25, and 28, alongside several felony counts of prescribing drugs to people unnecessarily.

Gerald Klein, 81, is charged in Florida with first degree murder in the overdose related death of Joey Bartolucci, 24, who died in bed after taking Xanax and hydromorphone prescribed at Klein’s East Coast Pain Clinic in West Palm Beach. Klein is one of 13 doctors and 19 others charged with various offences after a 2010 federal operation against a “pill mill” empire run by twin brothers, Jeffrey and Christopher George, which prescribed over 20 million oxycodone …
Prostate Cancer Survivorship Care Guideline: American Society of Clinical Oncology Clinical Practice Guideline Endorsement
Authors: Matthew J. Resnick, Christina Lacchetti, Jonathan Bergman, Ralph J. Hauke, Karen E. Hoffman, Terrence M. Kungel, Alicia K. Morgans, David F. Penson
Journal: Journal of Clinical Oncology (2015)

Purpose The guideline aims to optimize health and quality of life for the post-treatment prostate cancer survivor by comprehensively addressing components of follow-up care, including health promotion, prostate cancer surveillance, screening for new cancers, long-term and late functional effects of the disease and its treatment, psychosocial issues, and coordination of care between the survivor's primary care physician and prostate cancer specialist. Methods The American Cancer Society (ACS) Prostate Cancer Survivorship Care Guidelines were reviewed for developmental rigor by methodologists. The American Society of Clinical Oncology (ASCO) Endorsement Panel reviewed the content and recommendations, offering modifications and/or qualifying statements when deemed necessary. Results The ASCO Endorsement Panel determined that the recommendations from the 2014 ACS Prostate Cancer Survivorship Care Guidelines are clear, thorough, and relevant, despite the limited availability of high-quality evidence to support many of the recommendations. ASCO endorses the ACS Prostate Cancer Survivorship Care Guidelines, with a number of qualifying statements and modifications. Recommendations Assess information needs related to prostate cancer, prostate cancer treatment, adverse effects, and other health concerns and provide or refer survivors to appropriate resources. Measure prostate-specific antigen (PSA) level every 6 to 12 months for the first 5 years and then annually, considering more frequent evaluation in men at high risk for recurrence and in candidates for salvage therapy. Refer survivors with elevated or increasing PSA levels back to their primary treating physician for evaluation and management. Adhere to ACS guidelines for the early detection of cancer. Assess and manage physical and psychosocial effects of prostate cancer and its treatment. Annually assess for the presence of long-term or late effects of prostate cancer and its treatment.
Clinical Trial Registration
Authors: Catherine De Angelis, Jeffrey M. Drazen, Frank A. Frizelle, Charlotte Haug, John Hoey, Richard Horton, Sheldon Kotzin, Christine Laine, Ana Marusic, A. John P.M. Overbeke, Torben V. Schroeder, Hal C. Sox, Martin B. Van Der Weyden
Journal: Circulation Research (2005)
Small Heat-Shock Protein Hsp20 Attenuates β-Agonist–Mediated Cardiac Remodeling Through Apoptosis Signal–Regulating Kinase 1
Authors: Guo-Chang Fan, Qunying Yuan, Guojie Song, Yigang Wang, Guoli Chen, Jiang Qian, Xiaoyang Zhou, Yong J. Lee, Muhammad Ashraf, Evangelia G. Kranias
Journal: Circulation Research (2006)

Chronic stimulation of the beta-adrenergic neurohormonal axis contributes to the progression of heart failure and mortality in animal models and human patients. In cardiomyocytes, activation of the beta-adrenergic pathway has been shown to result in transiently increased expression of a cardiac small heat-shock protein Hsp20. The present study shows that cardiac overexpression (10-fold) of Hsp20 may protect the heart against beta-agonist-induced cardiac remodeling, associated with isoproterenol (50 mug/g per day) infusion for 14 days. Hsp20 attenuated the cardiac hypertrophic response, markedly reduced interstitial fibrosis, and decreased apoptosis. Contractility was also preserved in hearts with increased Hsp20 levels. These beneficial effects were associated with attenuation of the ASK1-JNK/p38 (apoptosis signal-regulating kinase 1/c-Jun NH(2)-terminal kinase/p38) signaling cascade triggered by isoproterenol, whereas there was no difference in either extracellular signal-related kinase 1/2 or Akt activation. Parallel in vitro experiments supported the inhibitory role of Hsp20 on enforced ASK1-JNK/p38 activation in both H9c2 cells and adult rat cardiomyocytes. Immunostaining studies also demonstrated that Hsp20 colocalizes with ASK1 in cardiomyocytes. Taken together, our findings indicate that (1) beta-agonist-induced cardiac injury is associated with activation of the ASK1-JNK/p38 cascade; (2) increased expression of Hsp20 attenuates the induction of remodeling, dysfunction, and apoptosis in response to sustained beta-adrenergic stimulation; and (3) the beneficial effects of Hsp20 are at least partially attributable to inhibition of the ASK1-signaling cascade.
Preschool asthma after bronchiolitis in infancy
Authors: P. Koponen, M. Helminen, M. Paassilta, T. Luukkaala, M. Korppi
Journal: European Respiratory Journal (2011)

Asthma risk is lower after wheezing associated with respiratory syncytial virus (RSV) than with non-RSV infection in infancy. RSV is the main wheezing-associated virus in infants aged <6 months. We evaluated the outcome of children hospitalised for bronchiolitis at <6 months of age, with special focus on viral aetiology and early risk factors. Out of 205 infants hospitalised for bronchiolitis at <6 months of age, 127 (62%) attended a control visit at a mean age of 6.5 yrs and the parents of an additional 39 children were interviewed by telephone. Thus, follow-up data collected by identical structured questionnaires were available from 166 (81%) children. Viral aetiology of bronchiolitis, studied on admission by antigen detection or PCR, was demonstrable in 97% of cases. Current asthma was present in 21 (12.7%) children: 8.2% in the 110 former RSV patients versus 24% in non-RSV patients (p=0.01). 45 (27%) children had ever had asthma. In adjusted analyses, atopic dermatitis, non-RSV bronchiolitis and maternal asthma were independently significant early-life risk factors for asthma. The risk of asthma was lower after RSV bronchiolitis than after bronchiolitis caused by other viruses in children hospitalised at <6 months of age.
Differential Effects of Vascular Endothelial Growth Factor Receptor-2 Inhibitor ZD6474 on Circulating Endothelial Progenitors and Mature Circulating Endothelial Cells: Implications for Use as a Surrogate Marker of Antiangiogenic Activity
Authors: Paul Beaudry, Jeremy Force, George N. Naumov, Andrew Wang, Cheryl H. Baker, Anderson Ryan, Shay Soker, Bruce E. Johnson, Judah Folkman, John V. Heymach
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Circulating endothelial cells (CEC) comprise at least two distinct populations: bone marrow–derived circulating endothelial progenitors (CEP) and mature CECs derived from existing vasculature. We hypothesized that antiangiogenic agents may have differential effects on CEPs and mature CECs and that these changes may serve as a marker of biological activity. Experimental Design: The effect of angiogenesis inhibitors on CECs was evaluated by flow cytometry after vascular endothelial growth factor (VEGF)–induced mobilization and in mice bearing Lewis lung carcinoma (LLC). Tumor angiogenesis was evaluated in parallel by immunohistochemistry. Results: In nontumor-bearing mice, VEGF administration increased both mature CECs and CEPs. This increase was inhibited by the VEGF receptor 2 inhibitor ZD6474 as well as the VEGF inhibitor–soluble Flt-1. ZD6474 had no significant effect on CECs in the absence of exogenous VEGF stimulation. In contrast, LLC-bearing mice had an increase in mature CECs but not CEPs after 3 days of treatment with ZD6474. The increase in mature CECs was dose-dependent, accompanied by a decrease in tumor microvessel density, and preceded reduction in tumor volume. Treatment of LLC-bearing mice with the vascular targeting agent ZD6126 also increased mature CECs. Conclusions: VEGF inhibitors can have differential effects on mature CECs and CEPs, and agents inhibiting tumor angiogenesis may cause a concomitant increase in mature CECs. This increase occurs in tumor-bearing but not in nontumor-bearing mice, suggesting that tumor endothelium is a potential source of mature CECs. Therefore, assessing both mature CECs and CEPs may provide insights into the mechanism of antiangiogenic agents and serve as an early surrogate marker of biological activity.
Magnetovaccination as a Novel Method to Assess and Quantify Dendritic Cell Tumor Antigen Capture and Delivery to Lymph Nodes
Authors: Christopher M. Long, Hanneke W.M. van Laarhoven, Jeff W.M. Bulte, Hyam I. Levitsky
Journal: Cancer Research (2009)

A major parameter limiting immune responses to vaccination is the number of activated antigen-presenting cells (APC) that capture antigen and migrate to draining lymph nodes (LN). Currently, a quantitative noninvasive technique for monitoring in vivo antigen capture and delivery is lacking. The use of cellular magnetic resonance (MR) imaging (MRI) is a promising approach for this purpose; however, cellular imaging currently requires ex vivo prelabeling of cells with contrast agents followed by reintroduction of cells into the subject being monitored. Here, we describe an in vivo labeling method, which relies upon cell-to-cell transfer of superparamagnetic iron oxide (SPIO) from tumor cells to endogenous APCs, in situ, to quantify APC delivery to LNs in a tumor vaccine model. Mice were immunized with a tumor cell-based vaccine that was irradiated and labeled with SPIO. APCs that had captured SPIO were imaged over time as they accumulated in LNs. We show here that MRI is capable of monitoring, in vivo, the trafficking of magnetically labeled APCs inducing a tumor-specific immune response, and that these cells can be magnetically recovered ex vivo. Excellent correlation was observed between in vivo and ex vivo quantification of APCs, with resolution sufficient to detect increased APC trafficking elicited by an adjuvant. This study shows the potential of magnetovaccination and MRI cell tracking to systematically evaluate a key parameter relevant to the optimization of vaccine therapies through noninvasive MRI-based quantification of APC numbers.