tbuckley/cabot-search huggingface dataset:
CSF1 Overexpression Promotes High-Grade Glioma Formation without Impacting the Polarization Status of Glioma-Associated Microglia and Macrophages
Authors: Ishani De, Megan D. Steffen, Paul A. Clark, Clayton J. Patros, Emily Sokn, Stephanie M. Bishop, Suzanne Litscher, Vilena I. Maklakova, John S. Kuo, Fausto J. Rodriguez, Lara S. Collier
Journal: Cancer Research (2016)

Abstract Current therapies for high-grade gliomas extend survival only modestly. The glioma microenvironment, including glioma-associated microglia/macrophages (GAM), is a potential therapeutic target. The microglia/macrophage cytokine CSF1 and its receptor CSF1R are overexpressed in human high-grade gliomas. To determine whether the other known CSF1R ligand IL34 is expressed in gliomas, we examined expression array data of human high-grade gliomas and performed RT-PCR on glioblastoma sphere-forming cell lines (GSC). Expression microarray analyses indicated that CSF1, but not IL34, is frequently overexpressed in human tumors. We found that while GSCs did express CSF1, most GSC lines did not express detectable levels of IL34 mRNA. We therefore studied the impact of modulating CSF1 levels on gliomagenesis in the context of the GFAP-V12Ha-ras-IRESLacZ (Ras*) model. Csf1 deficiency deterred glioma formation in the Ras* model, whereas CSF1 transgenic overexpression decreased the survival of Ras* mice and promoted the formation of high-grade gliomas. Conversely, CSF1 overexpression increased GAM density, but did not impact GAM polarization state. Regardless of CSF1 expression status, most GAMs were negative for the M2 polarization markers ARG1 and CD206; when present, ARG1+ and CD206+ cells were found in regions of peripheral immune cell invasion. Therefore, our findings indicate that CSF1 signaling is oncogenic during gliomagenesis through a mechanism distinct from modulating GAM polarization status. Cancer Res; 76(9); 2552–60. ©2016 AACR.
Definition of First-Line Endocrine Therapy for Hormone Receptor–Positive Advanced Breast Cancer
Authors: Tomás Reinert, Carlos H. Barrios
Journal: Journal of Clinical Oncology (2016)

survival with fulvestrant 500 mg compared with anastrozole in the first-line setting for ER-positive ABC. For the first time to our knowledge, an endocrine monotherapy strategy demonstrated improved efficacy compared with aromatase inhibition. The phase II FIRST (Fulvestrant First-Line Study Comparing Endocrine Treatments) trial raises some issues common to most if not all published trials on ET for ABC. Although considered a first-line ABC trial, FIRST included two distinct popu lations of patients with presumably different responses to ET. The trial included a majority of patients never exposed to ET and a group of patients previously treated with adjuvant tamoxifen. Overall, first-line fulvestrant improved overall survival compared with anastrozole. Interestingly,
Survivorship: Immunizations and Prevention of Infections, Version 2.2014
Authors: Crystal S. Denlinger, Jennifer A. Ligibel, Madhuri Are, K. Scott Baker, Wendy Demark-Wahnefried, Don Dizon, Debra L. Friedman, Mindy Goldman, Lee Jones, Allison King, Grace H. Ku, Elizabeth Kvale, Terry S. Langbaum, Kristin Leonardi-Warren, Mary S. McCabe, Michelle Melisko, Jose G. Montoya, Kathi Mooney, Mary Ann Morgan, Javid J. Moslehi, Tracey O’Connor, Linda Overholser, Electra D. Paskett, Jeffrey Peppercorn, Muhammad Raza, M. Alma Rodriguez, Karen L. Syrjala, Susan G. Urba, Mark T. Wakabayashi, Phyllis Zee, Nicole R. McMillian, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2014)

Cancer survivors are at an elevated risk for infection because of immune suppression associated with prior cancer treatments, and they are at increased risk of complications from vaccine-preventable diseases. This section of the NCCN Guidelines for Survivorship provides recommendations for the prevention of infections in survivors through education, antimicrobial prophylaxis, and the judicious use of vaccines. These guidelines provide information about travel and gardening precautions and safe pet care/avoidance of zoonosis, and include detailed recommendations regarding vaccinations that should be considered and encouraged in cancer and transplant survivors.
Abstract 203: Protein Synthesis Inhibitors 4E-BPs Regulate Cardiac Function
Authors: Denghong Zhang, Riccardo Contu, Michael Latronico, Kirk Peterson, Ju Chen, Gianluigi Condorelli
Journal: Circulation Research (2012)

Rationale: mTOR regulates cardiac functionality and hypertrophy. We have shown that cardiac-specific deletion of mTOR induces fatal dilated cardiomyopathy. This model of heart failure is characterized biochemically by accumulation of the mTOR substrate 4E-BP1, which inhibits protein synthesis through the regulation of translation initiation. Deletion of the 4E-BP1 gene, Eif4ebp1, in mTOR-KO mice significantly, albeit partially, improved cardiac function and survival. Objective: To investigate the role of the 4E-BP family in the heart by determining whether absence of its members improves cardiac function in different models of heart failure. Methods and Results: In the absence of Eif4ebp1, cardiac expression of the 4E-BP2 homolog increases strikingly. Deletion of Eif4ebp2 along with Eif4ebp1 (4E-BP1/4E-BP2-dKO mice) abrogated the negative effects of the loss of mTOR on cardiac function, and led to a further significant improvement in survival rate. Moreover, when 4E-BP1/4E-BP2-dKO mice where subjected to pressure-overload stress, cardiac function and survival were significantly improved compared with similarly treated control mice. The hypertrophic response to pressure overload in these mice was not affected by the absence of 4E-BPs. Conclusions: Our data indicate that 4E-BPs are responsible for an important part of mTOR effects on cardiac function, further strengthening the concept that the regulation of mRNA translation profoundly affects cardiac inotropism under stress.
Correlations Between Cancer Incidence Rates From the Canadian National Cancer Incidence Reporting System, 1969–78
Authors: G R Howe, G J Sherman, A Malhotra
Journal: JNCI Journal of the National Cancer Institute (1984)

Incidence rates for 19 cancers in females and 16 cancers in males have been computed from data reported by 8 Canadian provinces to the National Cancer Incidence Reporting System between 1969 and 1978. The rates, very similar in absolute and relative magnitude to those reported by the U.S. Third National Cancer Survey, have been used to examine patterns of correlation between various cancers within the 8 provinces. There is strong evidence of positive associations between a number of cancers, including a number of associations that have been reported in other similar correlational studies. Correlations that may be of particular interest in suggesting etiologic factors in common include clusters of smoking-related cancers (buccal cavity with pharynx, larynx, lung, and bladder), female sexual cancers (breast, corpus uteri, and ovary), and a group of cancers that have shown correlation in other studies (i.e., cancers of the pancreas and kidney, leukemias, lymphomas, and cancer of the prostate gland). Organs in the gastrointestinal tract (esophagus, stomach, colon, and rectum) anatomically close to each other show a high positive correlation in both females and males, but the further apart the organs are the lower is the correlation; these observations are consistent with other evidence of varying dietary etiologies. Two individual correlations of particular interest are those between female brain tumors and female bladder cancer (two cancers for which little is known of the etiology for a large percentage of them) and those between female breast cancer and female lung cancer. This study, the largest correlational study of incidence data reported to date, demonstrates the utility of such simple correlational analyses.
Diet and Physical Activity in the Prevention of Colorectal Cancer
Authors: Mamta Mehta, Moshe Shike
Journal: Journal of the National Comprehensive Cancer Network (2014)

Diet has been linked to the prevention of colorectal cancer (CRC) and may explain some of the differences in incidence and mortality among various populations. Evidence suggests that a high intake of red and processed meats is associated with an increased risk of CRC. The protective benefits of fiber are unclear, although in some studies fiber is associated with reduced CRC risk. The role of supplements, such as calcium, vitamin D, and folic acid, remains uncertain, and these nutrients cannot be currently recommended for chemoprevention. Obesity and sedentary lifestyle have been associated with an increased risk for colon cancer. Because of the inherent difficulty in studying the effects of specific nutrients, dietary pattern analysis may be a preferable approach to the investigation of the relationship between diet and risk for human diseases. Lifestyle modifications, such as increasing physical activity and consumption of a diet rich in fiber, fruits, vegetables, fish, and poultry and low in red and processed meats, have been advocated for primary prevention of several chronic diseases, and may in fact be beneficial for cancer prevention, particularly CRC.
The corelation between serum VEGF levels and known prognostic risk factors in colorectal carcinoma
Authors: R. Bestas, A. Isikdogan, T. Cil, S. Batun, A. Altintas
Journal: Journal of Clinical Oncology (2008)

15070 Background: Colorectal cancer is one of the most common forms of cancer in developed nations, and the incidence of this disease is continuing to increase. A clinician encountering patients with colorectal cancer needs to know the prognostic factor expected outcome to plan appropriate therapy. There are numerous variables being related to survival. Angiogenesis plays an important role in colorectal cancer progression. Evidence from preclinical and clinical studies indicates that vascular endothelial growth factor (VEGF) is the predominant angiogenic factor in human colorectal cancer and is associated with formation of metastases and poor prognosis. Methods: The aim of the presented study is to analyze serum VEGF levels and its correlation with the other clinicopathological characteristics of patients with colorectal carcinoma. 71 patient with colorectal adenocarcinoma were evaluated by estimation of VEGF and correlation with clinicopathological features. None of the patients received pre- and/or post-operative chemo- and/or radiotherapy. The results of serum VEGF were analysed with respect to stage, gender, age, CEA, metastases and topographical tumour localization. Results: Patients with stage 3–4 disease had significantly (P < 0.003) higher values of VEGF than patients with stage 1–2, who had comparable values. Patients with the primary tumour localized in the colon had no significantly (P=0.266.) higher levels of serum VEGF than patients with the primary tumour localized in the rectum. The VEGF expression significantly correlated with serum CEA level (p < 0.01) and clinical stages of CRC (p < 0.01). The VEGF expression was not correlated with patient ages (p = 0.955) and gender (p = 0.740). Conclusions: The VEGF expression was found significantly correlated with advanced stage, and metastases but not age, gender, and tumour localization. VEGF may play an important role in the invasion and metastasis of CRC. Therefore, VEGF could be applied as prognostic markers in CRC and measurement of VEGF in the serum may be a useful noninvasive clinical marker for evaluating the disease status. No significant financial relationships to disclose.
Side Effects of Chemotherapy
Authors: Eyal C. Attar, Thomas Ervin, Milos Janicek, Aaron Deykin, John Godleski
Journal: Journal of Clinical Oncology (2000)

Article Tools Side Effects of Chemotherapy Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.3.697 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10653887 Side Effects of Chemotherapy Eyal C. AttarxEyal C. AttarSearch for articles by this author , Thomas ErvinxThomas ErvinSearch for articles by this author , Milos JanicekxMilos JanicekSearch for articles by this author , Aaron DeykinxAaron DeykinSearch for articles by this author , John GodleskixJohn GodleskiSearch for articles by this author Show More Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA https://doi.org/10.1200/JCO.2000.18.3.697 First Page Full Text PDF Figures and Tables © 2000 by American Society of Clinical Oncology
Liaison psychiatry: referral patterns and their stability over time
Authors: Z J Lipowski, E J Wolston
Journal: American Journal of Psychiatry (1981)

The authors analyzed referral patterns for psychiatric consultation from medical and surgical wards on the basis of 2,000 referrals. They found that patients' demographic characteristics were stable over time. The diagnoses of depressive disorders and organic brain syndromes consistently predominated. Other studies have shown similar findings. The authors stress the importance of research on depressive disorders in the physically ill and of teaching the diagnosis of organic brain syndromes. They also underscore the value of the liaison nurse.
Reversible Abnormal Nonadherence to Glass and Responsiveness to Chemoattractants of Leukocytes From Patients With Advanced Cancer&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: D M Thomson
Journal: JNCI Journal of the National Cancer Institute (1984)

Whereas leukocytes from patients with early cancer usually show leukocyte adherence inhibition (LAI) to the sensitizing cancer extract, leukocytes from patients with advanced cancer seldom do. The chemoattractant-induced LAI response was studied to determine whether the abnormal response by leukocytes from patients with advanced cancer was related to changes in sensitivity to chemoattractants. Authentic chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine, chemotactic fragment of the fifth component of complement, and leukotriene B4 (LTB4) at optimum concentrations induced about 28-31% of adherent leukocytes to become nonadherent, these leukocytes being from either controls or patients with early breast cancer. However, chemoattractants induced no increased nonadherence of adherent leukocytes from patients with advanced breast cancer. In the control tubes, nonadherent cells for patients with advanced cancer were already increased by about 38% and were slightly greater than the chemoattractant-induced increased of nonadherent cells for control subjects or patients with early cancer. When the intracellular cyclic AMP of the cells were raised transiently, the nonadherent cells in the control tubes for patients with advanced cancer decreased by about 38% compared to 8% for control subjects and 13% for patients with early cancer. When nonadherence was returned to control levels, about 46% of adherent cells from patients with advanced cancer became nonadherent to chemoattractants or to the sensitizing cancer extract. Normal leukocytes, preexposed to chemoattractants, had increased nonadherence and did not respond to the same or other chemoattractants, imitating the state of leukocytes from patients with advanced cancer. However, if the cells were washed and intracellular cyclic AMP raised, nonadherent cells returned to normal levels in the control tubes and showed increased nonadherence with a repeat LTB4 exposure. The increased nonadherence of leukocytes from patients with advanced cancer as well as the refractoriness to chemoattractants was highly suggestive of in vivo activation of leukocytes possibly because of exposure to chemoattractant-like factors, generated by leukocyte-tumor antigen interactions.
Abstract 19546: Retinoblastoma Regulates Cardiac and Mesenchymal Stem Cell Niches during Adult Heart Regeneration
Authors: Konstantinos E Hatzistergos, Adam Williams, Wayne Balkan, Irene S Margitich, Joshua M Hare
Journal: Circulation (2012)

Introduction: Cardiac (CSCs) and mesenchymal stem cells (MSCs) stimulate cardiac repair, both primarily and secondarily by stimulating endogenous cardiac regeneration; however, the mechanisms underlying successful cardiac repair remain elusive and controversial. We addressed this issue in a porcine model of cell therapy by quantifying levels of Ser-608 hyperphosphorylated retinoblastoma (Rbser608+), which marks actively regenerating cardiomyocytes (CM) in adult newt hearts, and Ink4aARF (alternate reading frame of Ink4a), which inhibits cell cycle. Hypothesis: Interactions between CSCs and MSCs regulate Rbser608 and Ink4aARF expression in endogenous progenitors and CM to enhance cardiac regeneration. Methods: Twenty adult swine underwent myocardial infarction (MI), followed 2 weeks later by intramyocardial injection of 200M human (h)MSCs (n=5), 1M hCSCs (n=5), 200M hMSC plus 1M hCSC (MCC, n=5) or placebo (n=5). Tissue from immunosuppressed animals were analyzed 4 weeks later for exogenous cell engraftment (human Alu). Ink4aARF and Rbser608 were assessed in GATA4+ progenitors and mitotic CMs (phosphoH3+). Results: In situ hybridization demonstrated Alu+ cells in all groups. Engraftment was ∼7-fold greater in the MCC group compared to hCSCs or hMSCs (7.8±4.6, 0.2±0.2, 1.4±0.7 Alu+/cm3 respectively, p=0.0003) and infarct size was reduced 2-fold in MCC vs either cell type alone. Interestingly, Rbser608+ was expressed both in porcine GATA4+ progenitors as well as mature CM. There were 3 times as many Rbser608+/GATA4+ progenitors (150M/cm3) in the MCC hearts compared to the other 3 groups (p&lt;0.0001). In addition ∼20% of the CM were Rbser608+/Ink4a(-), suggesting that the MCC hearts contained CM capable of completing the cell-cycle (p&lt;0.0001). There was also a 46-fold increase in mitotic CMs in MCC hearts vs. either cell alone (P&lt;0.0001). Importantly, MCC recipients contained a subpopulation of Ink4aARF(−)/phosphoH3+ CM, supporting the existence of transient amplifying CM with the capacity to undergo multiple cell divisions. Conclusions: Together these findings demonstrate a novel mechanism of heart regeneration, where hMSC and hCSC interactions propagate Rbser608 in CM and CSCs to regulate cell-cycle and stem cell fate decisions.
Reply to N. Lowy et al and to J. Dhanda et al
Authors: Arti Hurria, Laura A. Levit, William Dale, Supriya G. Mohile, Hyman B. Muss, Louis Fehrenbacher, Allison Magnuson, Stuart M. Lichtman, Suanna S. Bruinooge, Enrique Soto-Perez-de-Celis, William P. Tew, Michael A. Postow, Harvey J. Cohen
Journal: Journal of Clinical Oncology (2016)
News
Authors: Tony Delamothe
Journal: BMJ (1989)

South Africa: "whites only" hospitals admit black patients Last week several hundred black South African patients pushed at the gates of"whites only" hospitals and found them open.Normally these hospitals admit black patients only as emergencies or if they need special care unavailable elsewhere.But on the day that the Mass Democratic Movement began its campaign against segregated health facilities administrators allowed black patients into their hospitals, where staff treated them as they would have treated white patients, admitting them if necessary or referring them back to outpatients.Doctors hailed it as a historic day.Professor Clive Rosendorff, dean of the faculty of medicine at the University of the Witwaters- rand, likened it to the civil rights victories won in the southern states of America."The eyes of the world are upon us today
A3.10 Serum calprotectinis elevated in patients with early rheumatoid arthritis but not in patients at risk of developing rheumatoid arthritis
Authors: K Prajzlerová, L Andrés Cerezo, P Hánová, H Mann, K Pavelka, J Vencovský, L Šenolt, M Filková
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Calprotectin (S100A8/S100A9 complex) is associated with disease activity, radiographic progression and may predict treatment response in patients with rheumatoid arthritis (RA). The aim of our study was to examine the serum levels of calprotectin in clinically suspect arthralgia patientswith positive antibodies to citrullinated peptide antigens (ACPA) who areat high risk of developing RA. <h3>Materials and methods</h3> This cross-sectional study included 20 ACPA+ arthralgiapatients, 55 patients with early RA (disease duration &lt;6 months who fulfilled 2010 ACR/EULAR classification criteria) and 68 healthy controls (HC). Disease activity was assessed using DAS28. Ultrasound of 28 small joints was performed in all patients with arthralgia to evaluate subclinical synovitis. Serum calprotectin levels were determined byELISA. Data were analysed using 1way ANOVA, Mann-Whitney test and Spearman's and Pearson's correlation coefficients. The data are expressed as mean±SD. <h3>Results</h3> Patients with clinically suspect arthralgia showed no clinical and ultrasound evidence of arthritis (grey scale and power Doppler for single joint ≤ 1). Of these, all were ACPA+, 70%females; age 41.92 ± 11.72 years, CRP 7.39 ± 19.19 mg/l. Treatment naïve patients with early RA had active disease (meanDAS28:5.54 ± 1.62), 65% were ACPA+, 71% were females; age 54.17 ± 16.77 years and CRP 20.46 ± 26.66 mg/l. Serum calprotectin in clinically suspect ACPA+ arthralgia patientswas not significantly different compared to HC (2980 ± 1610 vs. 3368 ± 1624 ng/ml, p = 0.35) but was significantly lower in both groups compared to early RA (5977 ± 5787 ng/ml, p = 0.01 and 0.02 respectively). There was no correlation between calprotectin and CRP in suspect arthralgia patients, however, in early RA, serum calprotectin significantly correlated with DAS28 (r = 0.432, p = 0.001) and CRP (r = 0.670, p &lt; 0.0001). <h3>Conclusions</h3> Calprotectin is not increased in ACPA positive patients who have normal ultrasound findings of small joints and thus may not help to predict RA development in this early stage of the disease. However, calprotectin is significantly elevated in patients with active early RA, where it serves as a reliable biomarker of disease activity. <h3>Acknowledgements</h3> IGA project no. NT 14498, project of MHCR 023728 and project SVV 260 155.