tbuckley/cabot-search huggingface dataset:
Shc proteins predict outcome in treatment-naïve breast cancer patients: Do they also predict chemotherapy benefit?
Authors: A. R. Frackelton, L. J. Hafer, D. Turbin, D. G. Huntsman
Journal: Clinical Cancer Research (2006)

PR-9   Background: Better predictors of adjuvant chemotherapy benefit would improve clinical management of breast cancer patients. The Shc proteins, implicated in many pathways associated with aggressive cancers, can be measured in tumors by the OncoPlanTM immunohistochemical test, which reports on phosphorylated (PY)-Shc and an inhibitory form of the protein, p66 Shc. Previous studies have shown that OncoPlan is a strong predictor of disease outcome. Here we report on the ability of p66 Shc to identify those patients most likely to benefit from chemotherapy.Methods: Population-based primary invasive tumors from 2380 women from BC were arrayed in TMA format (no adjuvant therapy=1663; chemotherapy=717; relapsed=854; died of disease=501; 13yrs median follow-up). Shc staining was scored on a continuous 0-5 scale by two pathologists, blinded to patient data.Results: In 1663 patients not receiving chemotherapy prior to first relapse, p66 Shc as a continuous variable had strong ability to predict relapse-free survival (RFS) (hazard ratio (HR) = 0.64, 95% CI 0.44-0.93, P = 0.018) and disease-specific survival (DSS) (HR = 0.47, 95% CI 0.30-0.75, P = 0.001) in multivariate Cox models adjusted for nodal status, Her2 and ER status, age, tumor size and grade. In contrast, p66 Shc did not predict outcome in chemotherapy-treated patients (RFS HR = 1.06, 95% CI 0.67-1.65, P = 0.81; DSS HR = 1.00 95% CI 0.61-1.67, P = 0.98). This suggested that p66 Shc levels predicted tumor responsiveness to chemotherapy. To test this hypothesis, we examined chemotherapy9s protective ability in patients subgrouped by p66 Shc levels, using fully adjusted Cox model.The 60% of patients classified as high risk by OncoPlan (low p66 Shc levels) were strongly protected by chemotherapy (RFS HR = 0.53, 95% CI 0.38-0.75, P = 0.0001; DSS HR = 0.51, 95% CI 0.34-0.74, P = 0.001), whereas for the 40% of patients classified as low risk by OncoPlan, chemotherapy appeared to be a hazard (RFS HR = 1.2, 95% CI 0.79-1.8, P = 0.41; DSS HR = 1.9, 95% CI 1.15-3.02, P = 0.01). For the total population of patients, chemotherapy appeared to be protective (RFS HR = 0.74, 95% CI 0.59-94, P = 0.01; DSS HR = 0.81, 95% CI 0.62-1.05, P = 0.12).By drug, high risk patients were protected by AC (DSS HR = 0.31, 95% CI 0.017-0.57, P  1.5, P > 0.10).Conclusions: These data suggest that p66 Shc levels in primary tumors identify patients with a low risk profile who will derive little benefit from chemotherapy and also patients with a high risk profile, who will derive the most benefit.Supported in part by a Susan G. Komen Breast Cancer Foundation grant
THE VALUE OF STERNAL MARROW ASPIRATION AS A METHOD OF BONE MARROW BIOPSY
Authors: Ernest H. Falconer, Maurice E. Leonard
Journal: Annals of Internal Medicine (1941)

Article1 September 1941THE VALUE OF STERNAL MARROW ASPIRATION AS A METHOD OF BONE MARROW BIOPSYERNEST H. FALCONER, M.D., C.M., F.A.C.P., MAURICE E. LEONARD, M.D., C.M.ERNEST H. FALCONER, M.D., C.M., F.A.C.P.Search for more papers by this author, MAURICE E. LEONARD, M.D., C.M.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-15-3-446 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe purpose of this paper is to attempt an evaluation of the method of aspirating portions of the sternal marrow through a needle or a small canula for study of the marrow cells. The assumption is that by this procedure a fair sample of the cellular components of the organ known as bone marrow can be obtained. Since Arinkin1first described this method in 1929, it has been widely used and has been the subject of a number of excellent papers. Some authors2, 3, 4, 5, 6found the procedure satisfactory for study of the marrow. Others7, 8apparently experienced...References1. ARINKIN ML: Die intravitale Untersuchungsmethodik des Knochenmarks, Folia Haemat., 1929, xxxviii, 159. Google Scholar2. SEGERDAHL E: Ueber Sternalpunktionen, Acta med. Scand., 1935, Suppl. LXIV. Google Scholar3. YOUNGOSGOOD RHEE: Sternal marrow aspirated during life, Arch. Int. Med., 1935, lv, 186. CrossrefGoogle Scholar4. VOGELERFROSENTHAL PLAN: Hematological observations on bone marrow obtained by sternal puncture, Am. Jr. Clin. Path., 1937, vii, 436. CrossrefGoogle Scholar5. REICH C: A study of the diagnostic value of sternal puncture in clinical hematology, Am. Jr. Med. Sci., 1935, clxxxix, 515. CrossrefGoogle Scholar6. HOLMESBROWN WFGO: Clinical study of bone marrow by the method of sternal puncture, Proc. Soc. Exper. Biol. and Med., 1933, xxx, 1306. CrossrefGoogle Scholar7. CUSTER RP: Studies on the structure and function of bone marrow. III. Bone marrow biopsy, Am. Jr. Med. Sci., 1933, clxxxv, 617. CrossrefGoogle Scholar8. DAMESHEKHENSTELLVALENTINE WHHEH: The comparative value and the limitations of the trephine and puncture methods for biopsy of the sternal bone marrow, ANN. INT. MED., 1937, xi, 801. LinkGoogle Scholar9. RHOADSMILLER CPDK: Histology of the bone marrow in aplastic anemia, Arch Path., 1938, xxvi, 648. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication May 2, 1941.From the Department of Medicine, University of California Medical School, San Francisco.Aided by a grant from the Christine Breon Fund for Medical Research. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1941Volume 15, Issue 3Page: 446-458KeywordsBiopsyBone marrowCellsResearch funding ePublished: 1 December 2008 Issue Published: 1 September 1941 PDF downloadLoading ...
Codon modification of T cell receptors allows enhanced functional expression in transgenic human T cells.
Authors: Kirsten Bj Scholten, Duco Kramer, Esther Wm Kueter, Marcus Graf, Thomas Schoedl, Chris Jlm Meijer, Marco Wj Schreurs, Erik Hooijberg
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5552 

Expression of native transgenic T cell receptors in recipient human T cells is often insufficient to achieve highly reactive T cell bulks. Here we show that codon modification of an HPV16E7 specific T cell receptor (TCR), together with omission of mRNA instability motifs and (cryptic) splice sites, leads to a dramatic increase in the expression levels of the transgenic TCRs in human CD8+ T cells. The codon-modified TCRs have been tested in three different configurations; 1) TCRα-IRES-GFP in combination with TCRβ-IRES-NGFR, 2) TCRα-IRES-TCRβ, and 3) TCRα-2A-TCRβ. T cells carrying the codon-modified TCRs are functionally active against target cells loaded with relevant peptide, model tumor cells expressing the specific epitope as well as cervical carcinoma cells. The significant improvements we report here in the functional expression of specific human TCRs will hopefully expedite clinical application of TCR transfer-based immunotherapy.
Abstract 19565: SAMeTT2R2 Scores Predict Stroke Risk After Initiation of Vitamin K Antagonist Therapy for Atrial Fibrillation: a Real-world Practice Study
Authors: Carlos Martinez, Anja Katholing, Stephan Reitbrock, Gregory Y Lip, Ben Freedman
Journal: Circulation (2014)

Introduction: Quality and duration of anticoagulation reflected by high proportion of Time in Therapeutic INR range (TTR) is associated with reduced thrombo-embolic and bleeding events in atrial fibrillation (AF). SAMeTT2R2, a novel score incorporating age, sex, ethnicity, smoking, co-morbidities, and interacting drugs, predicts inadequate anticoagulation control (TTR &lt;0.6) after commencing Vitamin K Antagonist (VKA) for AF, with scores ≥2 suggested as a cut-off to predict inadequate control. Aims: To determine whether SAMeTT2R2 score ≥2 at VKA inception is associated with an increased stroke risk in real-world practice. Methods: A cohort of VKA-naïve patients with incident non-valvular AF between 2001 - 2010 was formed from a large UK primary care database (Clinical Practice Research Datalink, CPRD) with linkage to hospital discharges, and death registry. SAMeTT2R2 score was calculated in a subset of 4468 in whom VKA treatment was initiated within 90 days of AF diagnosis, and scores 0-1, ≥2 were related to 3-year stroke incidence. Competing risk analysis accounting for death was performed to compare the risk of stroke between the two groups in an intention-to-treat analysis. Results: Of 4468 patients with incident AF commenced on VKA (mean age 70.7, 41.2% female), 3422 (76.6%) had a SAMeTT2R2 score of 0-1, and 1046 (23.4%) a score of ≥2. During 3-years 138 patients had a stroke and 58 of these occurred in the year following AF. Cumulative risk estimates for stroke in patients with scores ≥2 compared to 0-1 were significantly increased at 1, 2 and 3 years (log rank test, p&lt;0.01)(Figure). The proportion with TTR≥0.6 was 37.1% for scores ≥2 compared to 44.1% for scores 0-1 (p&lt;0.01). Conclusions: SAMeTT2R2 scores ≥2 predict increased stroke risk in the 3 years following incident AF in patients commenced on VKA treatment. These findings suggest that patients with high SAMeTT2R2 scores may require intensified anticoagulation control or use of oral non-VKA anticoagulants.
29th Annual meeting of the Society for Immunotherapy of Cancer (SITC)
Authors: Arthur A Hurwitz, Sylvia Lee, Susan Knox, Holbrook Kohrt, Gregory Verdeil, Emanuela Romano, Kim Margolin, Walter J Urba, Daniel E Speiser
Journal: Journal for ImmunoTherapy of Cancer (2015)

The 29<sup>th</sup> annual meeting of the Society for Immunotherapy of Cancer (SITC) was held November 7-9, 2014 in National Harbor, MD and was organized by Dr. Arthur A. Hurwitz (National Cancer Institute), Dr. Kim A. Margolin (Stanford University), Dr. Daniel E. Speiser (Ludwig Center for Cancer Research, University of Lausanne) and Dr. Walter J. Urba (Earle A. Chiles Research Institute, Providence Cancer Center). This meeting included over 1,600 registered participants from 28 separate countries, making it the largest SITC meeting held to date. It highlighted significant worldwide progress in the development and application of cancer immunology to the practice of clinical oncology, including advances in diagnosis, prognosis and therapy, utilizing several immunological pathways and mechanisms for a variety of oncologic conditions. Presentations and posters demonstrated that many concepts that had been pursued preclinically in the past are now being translated into clinical practice, with clear benefits for patients.
Abstract 18448: Laminar Flow and Klf2 Regulate the Paracrine Activity of Endothelial Cells by Modulating the Balance of Cxcr4 versus Cxcr7 Expression
Authors: Yosif Manavski, Anuradha Doddaballapur, Junhao Hu, Hellmut Augustin, Reinier Boon, Stefanie Dimmeler
Journal: Circulation (2014)

Recent studies suggest that endothelial cells are not only important for oxygen delivery but act as paracrine source for signals that determine tissue regeneration versus fibrosis. The paracrine regulation of liver regeneration by endothelial cells was shown to be critically controlled by the SDF-1 receptors CXCR4, which was shown to control the release of pro-fibrotic cytokines, whereas signaling via the CXCR7 receptor was shown to provide a pro-regenerative niche. The regulation of the endothelial CXCR4 versus CXCR7 expression and their role in heart regeneration is unclear. Here we show that laminar flow as well as the expression of the flow-induced transcription factor Krüppel-like factor 2 (KLF2) reduced mRNA expression of CXCR4 by (0.34±0.01 fold; p&lt;0.005) and (0.22±0.05 fold; p&lt;0.0005), respectively, whereas CXCR7 expression was significantly increased (flow: 6.59±0.52 fold; p&lt;0.005, KLF2: 36±12.3 fold; p&lt;0.05). Western blots confirmed that flow and KLF2 critically modulate the CXCR4 / CXCR7 protein expression. Interestingly, shear stress and KLF2 induce the expression of the CXCR7-downstream inhibitor of DNA binding 1 (Id1), a transcription factor known to induce pro-regenerative angiocrine factors. Cytokine arrays further demonstrate that flow and KLF2 overexpression change the paracrine release of important growth factors. For example, Activin A (1.7±0.69 fold) and IGF-binding proteins were increased (1.7±0.87 fold), whereas the release of pro-inflammatory cytokines IL-8 (0.16±0.02 fold) and MCP1 (0.43±0.01 fold) and growth factors VEGF-C (0.16±0.01 fold), PlGF (0.09±0.01 fold) and Endoglin (0.27±0.09 fold) were reduced. The changes in the release of these paracrine growth factors were partially reduced by siRNA-mediated silencing of CXCR7. In summary these data suggest that flow and KLF2 critically regulate the paracrine secretion of endothelial growth factors by modulating the balance of CXCR4 versus CXCR7 expression. Ongoing studies address the contribution of endothelial KLF2 in liver and heart regeneration in vivo.
Managing measles
Authors: G. Hussey
Journal: BMJ (1997)

Measles remains a leading cause of childhood morbidity and mortality in developing countries, with fatality rates in hospitalised children often exceeding 10%.1 Most deaths follow complications such as pneumonia, croup, and diarrhoea and are often associated with malnutrition. Reducing the severity of disease through appropriate management should thus be a priority. What is surprising and rather disturbing, however, is the lack of published scientific information on issues that are central to developing a sound basis for managing measles. A recent review of clinical problems associated with measles has highlighted the paucity of data on risk factors, aetiology, natural course, and management (except vitamin A) of the common complications of measles.2 The problems with prophylactic antibiotic trials are discussed by Shann in this week's BMJ .3 Nevertheless, on the basis of the available data, the World Health Organisation's Expanded Programme on Immunisation has developed a policy document on integrated management of measles to help health workers in developing countries to reduce the severity of measles.4 The basic principles are outlined in the box. #### Basic Principles of management
Partial dysfunction of Treg activation in sickle cell disease
Authors: Benoît Vingert, Marie Tamagne, Maxime Desmarets, Sadaf Pakdaman, Rahma Elayeb, Anoosha Habibi, Françoise Bernaudin, Frédéric Galacteros, Philippe Bierling, France Noizat‐Pirenne, José Cohen
Journal: American Journal of Hematology (2013)

Sickle cell disease (SCD) is a chronic inflammatory disease associated with multiple organ damage, chronic anemia, and infections. SCD patients have a high rate of alloimmunization against red blood cells (RBCs) following transfusion and may develop autoimmune diseases. Studies in mouse models have suggested that regulatory T cells (Treg) play a role in alloimmunization against RBC antigens. We characterized the phenotype and function of the Treg cell population in a homogeneous cohort of transfused SCD patients. We found that the distribution of Treg subpopulations differed significantly between SCD patients and healthy blood donors. SCD patients have a particular Treg phenotype, with strong CTLA-4 and CD39 expression and weak HLA-DR and CCR7 expression. Finally, we show that this particular phenotype is related to SCD rather than alloimmunization status. Indeed, we observed no difference in Treg phenotype or function in vitro using autologous feeder cells between strong and weak responders to alloimmunization.
SOME REASONS FOR FAILURES IN REFERRAL FOR PSYCHIATRIC CARE OF PATIENTS WITH PSYCHOSOMATIC ILLNESSES
Authors: I N BERLIN
Journal: Annals of Internal Medicine (1954)

Article1 June 1954SOME REASONS FOR FAILURES IN REFERRAL FOR PSYCHIATRIC CARE OF PATIENTS WITH PSYCHOSOMATIC ILLNESSESI. N. BERLIN, M.D.I. N. BERLIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-40-6-1165 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is estimated that more than 50 per cent of patients with psychosomatic disorders fail to follow through on referrals for psychiatric treatment.Experience over the past five years has aroused my interest in the problems of referral. These experiences were both in private psychiatric treatment of patients with psychosomatic disorders, and as psychiatric consultant to a university hospital psychosomatic seminar attended by the medical residents. Many colleagues, both internists and psychiatrists, agree that an overwhelming number of patients referred for psychiatric care because of psychosomatic illnesses do not make the initial contact with the psychiatrist. Further, they agree that...Bibliography1. Bartemeier LH: The attitude of the physician, J. A. M. A. 145: 1122 (Apr. 14) 1951. CrossrefMedlineGoogle Scholar2. Levine M: Psychotherapy in medical practice, 1943, Macmillan, New York. Google Scholar3. WattsWilbur MSDL: Clinical management of functional disorders: the diagnostic interview, J. A. M. A. 148: 704 (Mar. 1) 1952. CrossrefMedlineGoogle Scholar4. Whitehorn JC: Basic psychiatry in medical practice, J. A. M. A. 148: 329 (Feb. 2) 1952. CrossrefMedlineGoogle Scholar5. Ziskind E: Training in psychotherapy for all physicians, J. A. M. A. 147: 1223 (Nov. 24) 1951. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: San Francisco, California*Received for publication November 28, 1953.From The University of California School of Medicine, Department of Psychiatry, and The State of California, Department of Mental Hygiene, The Langley Porter Clinic, San Francisco, California. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1954Volume 40, Issue 6Page: 1165-1168KeywordsPatientsPsychiatry and mental health ePublished: 1 December 2008 Issue Published: 1 June 1954 PDF downloadLoading ...
δ-Aminolevulinic Acid Dehydrase Activity in Friend Virus-Infected Mice
Authors: Robert P. Tengerdy
Journal: Cancer Research (1966)

The δ-aminolevulinic acid dehydrase (DALAD)[2][1] activity sharply increased in the spleen and liver of mice 1 week after inoculation with Friend virus (FV). FV causes leukemia and polycythemia in mice. The increase in DALAD activity corresponded to an increased 59Fe uptake in the spleen and liver, which indicates that DALAD activity is a useful parameter of erythropoietic activity. The data suggest that DALAD may be the key enzyme in hemoglobin biosynthesis.

 [1]: #fn-2
HIV-induced alteration in gut microbiota
Authors: Catherine A Lozupone, Matthew E Rhodes, Charles P Neff, Andrew P Fontenot, Thomas B Campbell, Brent E Palmer
Journal: Gut Microbes (2014)

Consistent with an important role for adaptive immunity in modulating interactions between intestinal bacteria and host, dramatic alteration in the composition of gut microbes during chronic HIV infection was recently reported by ourselves and independently by four other research groups. Here we evaluate our results in the context of these other studies and delve into the effects of antiretroviral therapy (ART). Although gut microbiota of HIV-positive individuals on ART usually does not resemble that of HIV-negative individuals, the degree to which ART restores health-associated prevalence varies across bacterial taxa. Finally, we discuss potential drivers and health consequences of gut microbiota alterations. We propose that understanding the mechanism of HIV-associated gut microbiota changes will elucidate the role of adaptive immunity in shaping gut microbiota composition, and lay the foundation for therapeutics targeting the microbiota to attenuate HIV disease progression and reduce the risk of gut-linked disease in people with HIV.
Abstract MP91: Self-Reported Sitting Time Using a Two-Question Method Is a Good Measure of Sedentary Behavior: Findings in the New York City Adult Population
Authors: Stella Yi, Katherine Bartley, Melanie Firestone, Donna Eisenhower
Journal: Circulation (2014)

Introduction: Sedentary behavior is defined as activities that require low energy expenditure (1.0 - 1.5 [METs]). Sitting time is a specific domain of sedentary behavior that is associated with metabolic disturbances, decreased life expectancy, and mortality - outcomes that occur independent of meeting physical activity guidelines. Population-level prevalence estimates of the ‘active couch potato’, or active adults who engage in at least 7+ hours of sitting time a day, are needed. Hypothesis: We tested that the two-question method of self-reported sitting time would have adequate construct validity for population surveillance. Methods: The New York City Health Department conducted the 2011 Physical Activity and Transit (PAT) Survey using random-digit dial (cell and landline telephones) methods (n=3811); an additional subset of participants wore accelerometers for a seven-day period (n=679). Sedentary time was defined as accelerometer minutes with &lt;100 counts on valid days (those with 10 hours of wear time). Self-reported sitting time was assessed from two questions on time spent sitting awake for daytime and evening. Construct validity was assessed using Spearman’s Rho and examination of a Bland-Altman plot. Multivariable regression models were used to assess demographic factors associated with sitting time and measured sedentary time. Prevalence of the ‘active couch potato’ was defined as those adults who were meeting the 2008 Physical Activity Guidelines for Americans of at least 150 min/week of physical activity, but who also self-reported sitting for 7+ hours per day, using both accelerometer and self-reported data. All data were weighted and analyzed in SUDAAN 10. Results: Self-reported mean daily sitting time was 444 min (7.4 hours); accelerometer-based mean daily sedentary time was 494 min (8.2 hours; correlation: r=0.32, p&lt;0.01). The mean difference was 49 min/d (Limits of Agreement: -441-343). In adjusted models, higher measured sedentary time was associated with older age and higher education. Sitting time was higher in women, Asians and those with a higher education, and lower in foreign-born persons and Hispanics, compared to referent groups. The prevalence of being an ‘active couch potato’ was 56.9% and was highest among high-income, highly educated New Yorkers. Conclusions: Sitting time can be accurately assessed by self-report for population surveillance, but may be limited in characterizing individual-level behavior. Differences in measurement characteristics suggest that accelerometer-based measurements may not be an appropriate way to validate self-reported sitting time. Sedentary behavior appears to be prevalent in two different groups: (1) older adults and; (2) working-age adults of higher socioeconomic status. Targeted interventions to minimize extended periods of sedentary activity among these groups are warranted. 1