tbuckley/cabot-search huggingface dataset:
Abstract 4831: Breast cancer cells metastasize to bone through E-selectin+ vascular gateways
Authors: Trevor Price, Monika Burness, Ayelet Sivan, Renee Cheng, John L. Magnani, Dorothy A. Sipkins
Journal: Cancer Research (2014)

Abstract The bone marrow (BM) has been suggested to serve as a protective environment for disseminated breast cancer cells (BCCs). The precise molecular signals that circulating BCCs use to identify and adhere to BM vasculature are unknown, yet these interactions are essential for the development of bone metastases. To address this question, we used in vivo fluorescence microscopy to track the interactions of estrogen receptor (ER)+ and ER- BCC lines with bone in real time in an intracardiac injection xenograft mouse model. Our data show that circulating tumor cells enter the bone through unique vascular niches where endothelial cell expression of the adhesive molecule E-selectin and of the chemokine SDF-1 are both upregulated. These vascular niches are the same sinusoidal capillary beds that serve as the site of entry for peripherally circulating hematopoietic stem and progenitor cells (HSPCs) returning to the BM. Similar to HSPCs, BCCs aberrantly express the major cell surface molecules known to regulate hematopoietic cell entry and exit through the BM, including CXCR4 (SDF-1 receptor) and multiple E-selectin ligands. While neither CXCR4 blockade nor general chemokine signaling inhibition in BCCs prevented BM dissemination, E-selectin blockade by the specific glycomimetic antagonist GMI-1271 decreased BCC entry in the BM by approximately three fold at 2 and 24 hours after treatment. Moreover, in studies comparing FACS isolated stem and non-stem MCF-7 BCCs, GMI-1271 inhibition of E-selectin specifically targeted CD44+CD24- breast cancer stem cell homing. Non-stem CD44+CD24+ BCCs demonstrated significantly less BM homing compared to stem BCCs, and their BM trafficking was less E-selectin dependent. These data reveal for the first time a molecular mediator of bone metastases at the point-of-entry for BCCs in the BM. In addition, the ability of BCCs to hijack HSPC trafficking pathways to metastasize to bone correlates with E-selectin ligand expression and may be a specific characteristic of the BCC stem cell subpopulation. Citation Format: Trevor Price, Monika Burness, Ayelet Sivan, Renee Cheng, John L. Magnani, Dorothy A. Sipkins. Breast cancer cells metastasize to bone through E-selectin+ vascular gateways. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4831. doi:10.1158/1538-7445.AM2014-4831
Abstract 5049: Functional significance of <i>L1CAM</i> in non-small cell lung cancer
Authors: Josephine Hai, Nikolina Radulovich, Chang-Qi Zhu, Sandy D. Der, Igor Jurisica, Ming-Sound Tsao
Journal: Cancer Research (2010)

Abstract Background: Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancers. Early stage NSCLC patients are treated by complete surgical resection, but the 5-year survival rate remains relatively poor at 50%. Deaths are mainly due to metastatic recurrence. Post-surgery (adjuvant) chemotherapy may significantly improve survival, but improved selection methods for patients who are most likely to benefit from the adjuvant treatment are required. Our laboratory has recently identified a 15-gene expression signature capable of classifying patients based on risk of death and at the same time predicting benefits of adjuvant chemotherapy in high-risk patients (J Clin Oncol 26: 2008, May 20 suppl; abstr 7510). We hypothesize that genes whose expression are de-regulated significantly in patients with a poor prognosis may play important roles in tumorigenesis and metastasis. Our goal is to functionally characterize the roles of these prognostic genes in the growth and metastatic potential of NSCLC. One of these signature genes is L1CAM, a cell adhesion molecule. Although extensively characterized in the nervous system, the role of L1CAM in NSCLC has not been defined. Methods: We stably modified the expression of L1CAM at both the RNA and protein levels in NSCLC cell lines using the lentiviral cDNA/shRNA system. In vitro matrigel assays were used to assess invasion and cell migration by wound-healing assays. Results: Downregulation of L1CAM expression resulted in decreased invasiveness and motility of metastatic NSCLC cell lines. In contrast, loss of L1CAM did not alter the growth rate on plastic. Studies on anchorage-independent growth and in vivo tumorigenicity and metastatic potential are ongoing and the results will be presented. Conclusion: Considering the importance of migratory phenotype in the first steps of metastasis, the results suggest that L1CAM contributes to malignancy in NSCLC and may be a novel therapeutic gene for this disease. (Supported by Canadian Cancer Society Research Institute grant #020527) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5049.
Points from Letters: Kilopascals
Authors: A. Hollman
Journal: BMJ (1975)

vogue in the future should Parliament as at present constituted beconme too unwieldy to function effectively.Moreover, the medical profession would be freer to set up and supervise what mtust surely come, and that is a body of aware persons to interview at regular intervals all persons in paid authority above a certain level of responsibility, in- cluding doctors, lawyers, M.P.s, teachers, etc., regairding their continuing suitability to hold such authority.Under the pro- fession's present subservience to politics this would be difficult to implement, if at all."What shall it profit a man if he shall gain the whole world and lose his own soul?"And as a profession we are in grave danger of doing just that.-I am, etc.,
The Identification of Pneumoconiosis From Hospital Discharge Data-Reply
Authors: David Valiante
Journal: JAMA (1990)

In Reply. —  Dr S. S. Winkler and Mr D. S. Winkler suggest that hospital discharge summaries only occasionally include the diagnosis of pneumoconiosis when the patient has roentgenographic evidence of pneumoconiosis but pneumoconiosis is not the primary cause of hospitalization. If this is true, then this would be an additional reason why hospital discharge data do not pick up all diagnosed cases of pneumoconiosis. Despite our reliance on hospital discharge data for the source of cases for our silicosis surveillance system, we are well aware that discharge data are not allinclusive. Our efforts to encourage reports by individual physicians, although continuing, have not been extremely successful. Hospital discharge data do capture more cases than the current legally mandated federal surveillance system for occupational disease. What is particularly useful about hospital discharge data are their ready availability at relatively low cost.  The underreporting on discharge summaries described in the Winklers'
Strategic priority setting for vaccines policy and global health education
Authors: C E Phelps, G Madhavan
Journal: The Lancet Global Health (2015)

BackgroundPriority setting for new and existing vaccines is a complex but important task. Health outcomes or cost-effectiveness are not the only criteria for priority ranking of vaccine candidates. Real life prioritisation and development of new vaccines invariably involves balancing many programmatic features, including dosage requirements and cost (and their consequences on coverage and efficacy), developmental risk, interface with existing programmes (for example, vaccination schedules and capabilities), focus on special populations, and even the strengthening of homeland security or public health aid. We aimed to develop a software tool to assist in the process of ranking candidate vaccines.MethodsSMART Vaccines (Strategic Multi-Attribute Ranking Tool for Vaccines) combines population-specific data about demographics, health burdens, costs of disease treatment, and design attributes of potential new vaccines to support a multi-attribute utility model. The software offers 28 total attributes (plus up to seven user-defined attributes) from which users can select and weight a subset (maximum of 10) to create SMART Scores to rank candidate vaccines. Sensitivity-analysis tools built into SMART Vaccines allow users to specify the most desirable target product profiles for a single disease, or the ranking of candidate vaccines across different diseases. The programme also allows users to add attributes to the model, and to specify the weights given to the seleted set of attributes used in evaluation of vaccine candidates.FindingsPreliminary testing with a range of public health organisations and vaccine developers has demonstrated that the concept underlying SMART Vaccines can be expanded for comparisons between public health interventions (treatment versus prevention of disease options), and even to quite different uses such as vaccines for animal health.InterpretationEarly uses of SMART Vaccines have demonstrated that the multi-criteria approach not only enhances transparency in public health decision making, but also allows incorporation of many influential factors that remain hidden or unrecognized in more traditional cost-effectiveness analysis. Furthermore, use of SMART Vaccines facilitates decision convergence when stakeholder interests have conflicting priorities. To bolster the further development of SMART Vaccines, we envision a user community with research universities, especially those with strengths in global public health, to act as the software host.FundingUS Department of Health and Human Services, National Vaccine Program Office and Fogarty International Center, National Institutes of Health.
Time to treatment with recombinant tissue plasminogen activator and outcome of stroke in clinical practice: retrospective analysis of hospital quality assurance data with comparison with results from randomised clinical trials
Authors: C. Gumbinger, B. Reuter, C. Stock, T. Sauer, H. Wietholter, I. Bruder, S. Rode, R. Kern, P. Ringleb, M. G. Hennerici, W. Hacke
Journal: BMJ (2014)

<b>Objective</b> To study the time dependent effectiveness of thrombolytic therapy for acute ischaemic stroke in daily clinical practice. <b>Design</b> A retrospective cohort study using data from a large scale, comprehensive population based state-wide stroke registry in Germany. <b>Setting</b> All 148 hospitals involved in acute stroke care in a large state in southwest Germany with 10.4 million inhabitants. <b>Participants</b> Data from 84 439 patients with acute ischaemic stroke were analysed, 10 263 (12%) were treated with thrombolytic therapy and 74 176 (88%) were not treated. <b>Main outcome measures</b> Primary endpoint was the dichotomised score on a modified Rankin scale at discharge ("favourable outcome" score 0 or 1 or "unfavourable outcome" score 2-6) analysed by binary logistic regression. Patients treated with recombinant tissue plasminogen activator (rtPA) were categorised according to time from onset of stroke to treatment. Analogous analyses were conducted for the association between rtPA treatment of stroke and in-hospital mortality. As a co-primary endpoint the chance of a lower modified Rankin scale score at discharge was analysed by ordinal logistic regression analysis (shift analysis). <b>Results</b> After adjustment for characteristics of patients, hospitals, and treatment, rtPA was associated with better outcome in a time dependent pattern. The number needed to treat ranged from 4.5 (within first 1.5 hours after onset; odds ratio 2.49) to 18.0 (up to 4.5 hours; odds ratio 1.26), while mortality did not vary up to 4.5 hours. Patients treated with rtPA beyond 4.5 hours (including mismatch based approaches) showed a significantly better outcome only in dichotomised analysis (odds ratio 1.25, 95% confidence interval 1.01 to 1.55) but the mortality risk was higher (1.45, 1.08 to 1.92). <b>Conclusion</b> The effectiveness of thrombolytic therapy in daily clinical practice might be comparable with the effectiveness shown in randomised clinical trials and pooled analysis. Early treatment was associated with favourable outcome in daily clinical practice, which underlines the importance of speeding up the process for thrombolytic therapy in hospital and before admission to achieve shorter time from door to needle and from onset to treatment for thrombolytic therapy.
INFLAMMATION INDUCES TRANSDIFFERENTIATION OF FIBROBLASTS TO MYOFIBROBLASTS WITH PATHOLOGICAL REMODELLING IN ENDOMYOCARDIAL BIOPSIES OF PATIENTS WITH HFNEF: ONE TRIGGER FOR DIASTOLIC DYSFUNCTION.
Authors: Dirk Westermann, Diana Lindner, Mario Kasner, Heinz-Peter Schultheiss, Carsten Tschope
Journal: Journal of the American College of Cardiology (2010)
Interest in interests in photodynamic therapy
Authors: D. de Berker
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, The article by Caekelbergh et al.1 in the October 2006 issue of this Journal raises a concern. The authors reinterpret and analyse old data to demonstrate that methyl aminolaevulinate‐based photodynamic therapy is cheaper than cryosurgery for actinic keratoses and a good treatment for nodular basal cell carcinomas. This is a contentious conclusion, reached through quite complex manipulation of data and not an analysis that would be commonly recognized in U.K. Dermatology. For this reason, it makes the independence of the authorship of paramount importance, where such an article may be used to justify expenditure of healthcare resources. The authors claim ‘no conflicts of interest’, but the details leave some scope for doubt and I would make an observation that requires explanation. The author for correspondence has an e‐mail address from IMS Health Incorporated. This is a global biotech and pharma intelligence company that, when writing this letter, has on its web site home page the boast (and I paste) ‘Learn how IMS helped a major pharma company generate an additional $300 million in incremental revenue’.
US health workers who give flu jabs to healthy people could face fines or imprisonment
Authors: Owen Dyer
Journal: BMJ (2004)

It looks increasingly certain that the United States will enter the influenza season seriously short of vaccine, after a Food and Drug Administration team visiting Britain declared that 48 million potentially contaminated units of vaccine were 38unsafe for use.

The vaccines represented half of the United States's planned supply for this year. The manufacturer, the Chiron Corporation of California, had to close its Liverpool factory after its licence to produce Fluvirin vaccine was suspended by the United Kingdom's Medicines and Healthcare Products …
Another Selective Estrogen-Receptor Modulator for Osteoporosis
Authors: Carolyn Becker
Journal: New England Journal of Medicine (2010)

Selective estrogen-receptor modulators are nonsteroidal compounds that act as estrogen agonists in some tissues and as estrogen antagonists in others. Thus, they are uniquely suited for postmenopausal women. An ideal selective estrogen-receptor modulator would offer postmenopausal women the benefits of estrogen therapy (i.e., a reduced risk of fracture, urologic and vaginal atrophy, and hot flushes) without the risks (i.e., an increased risk of breast cancer, endometrial cancer, coronary heart disease, stroke, and venous thromboembolic events).Tamoxifen and raloxifene, the two selective estrogen-receptor modulators currently marketed for postmenopausal women in the United States, offer both benefits and drawbacks. Tamoxifen is associated . . .
Increased Uptake in Tc-99m MDP Scan of Sacral Chordoma:
Authors: Vivek Trikha, Vikas Gupta, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2004)

Chordoma is a malignant tumor arising from the remnants of the notochord. Approximately 50% of chordomas occur in the sacrococcygeal region. They are most common in the 50- to 60-year age group, and in men rather than in women. The earliest and most common symptom of sacral chordoma is sacral pain radiating to the legs. Other complaints include constipation and presence of a mass. The authors present a case of histologically proved sacral chordoma with bowel and bladder involvement. Most sacral tumors show increased uptake on radionuclide scintigraphy except chordomas, which usually have decreased uptake. This case is presented keeping in view its unusual bone scan features.
Pathogenesis of Campylobacter fetus infections. Failure of encapsulated Campylobacter fetus to bind C3b explains serum and phagocytosis resistance.
Authors: M J Blaser, P F Smith, J E Repine, K A Joiner
Journal: Journal of Clinical Investigation (1988)

Campylobacter fetus ssp. fetus strains causing systemic infections in humans are highly resistant to normal and immune serum, which is due to the presence of high molecular weight (100,000, 127,000, or 149,000) surface (S-layer) proteins. Using serum-resistant parental strains (82-40 LP and 23D) containing the 100,000-mol wt protein and serum-sensitive mutants (82-40 HP and 23B) differing only in that they lack the 100,000-mol wt protein capsule, we examined complement binding and activation, and opsono-phagocytosis by polymorphonuclear leukocytes. C3 consumption was similar for all four strains but C3 was not efficiently bound to 82-40 LP or 23D even in the presence of immune serum, and the small amount of C3 bound was predominently the hemolytically inactive iC3b fragment. Consumption and binding of C5 and C9 was significantly greater for the unencapsulated than the encapsulated strains. Opsonization of 82-40 HP with heat-inactivated normal human serum caused greater than 99% killing by human PMN. Similar opsonization of 82-40 LP showed no kill, but use of immune serum restored killing. Findings in a PMN chemiluminescence assay showed parallel results. Association of 32P-labeled 82-40 HP with PMN in the presence of HINHS was 19-fold that for the 82-40 LP, and electron microscopy illustrated that the difference was in uptake rather than in binding. These results indicate that presence of the 100,000-mol wt protein capsule on the surface of C. fetus leads to impaired C3b binding, thus explaining serum resistance and defective opsonization in NHS, mechanisms that explain the capacity of this enteric organism to cause systemic infections.
Cough medicines' effect is mainly placebo
Authors: Roger Dobson
Journal: BMJ (2006)

Blood samples obtained from 22 patients with retinitis pigmentosa, 6 unaffected family members, and 8 unrelated controls showed serum copper and zinc to be in the normal range, contrary to the results in earlier reports. Likewise no significant variation of erythrocyte superoxide dismutase (SOD) and catalase levels was found between the 3 groups or when the patients were grouped by sex, age, or genetic distribution. The SOD proteins from controls and retinitis pigmentosa patients had identical mobilities on gel electrophoresis, isoelectric points, and heat stabilities. Our studies do not support the use of copper, zinc, or SOD in the diagnosis or treatment of retinitis pigmentosa.
Comment re: Preclinical Model of Spontaneous Melanoma Metastasis
Authors: Robert M. Hoffman
Journal: Cancer Research (2009)

To the Editor: 

Cruz-Munoz and colleagues ( [1][1]) state that their findings represent the first report of spontaneous central nervous system metastases generated from primary tumors of any human cancer in mice, which heritably maintain this phenotype. It should be noted, however, that with the
Combination of Temsirolimus (CCI-779) with Chemoradiation in Newly Diagnosed Glioblastoma Multiforme (GBM) (NCCTG trial N027D) Is Associated with Increased Infectious Risks
Authors: Jann N. Sarkaria, Eva Galanis, Wenting Wu, Allan B. Dietz, Timothy J. Kaufmann, Michael P. Gustafson, Paul D. Brown, Joon H. Uhm, Ravi D. Rao, Laurence Doyle, Caterina Giannini, Kurt A. Jaeckle, Jan C. Buckner
Journal: Clinical Cancer Research (2010)

The mammalian target of rapamycin (mTOR) functions within the phosphoinositide 3-kinase/Akt signaling pathway as a critical modulator of cell survival.The mTOR inhibitor temsirolimus (CCI-779) was combined with chemoradiotherapy in glioblastoma multiforme (GBM) patients in a dose-escalation phase I trial. The first 12 patients were treated with CCI-779 combined with radiation/temozolomide and adjuvant temozolomide. A second cohort of 13 patients was treated with concurrent CCI-779/radiation/temozolomide followed by adjuvant temozolomide monotherapy.Concomitant and adjuvant CCI-779 was associated with a high rate (3 of 12 patients) of grade 4/5 infections. By limiting CCI-779 treatment to the radiation/temozolomide phase and using antibiotic prophylaxis, the rate of infections was reduced, although 2 of 13 patients developed exacerbation of pre-existing fungal or viral infections. Dose-limiting toxicities were observed in 2 of 13 patients with this modified schedule. Weekly CCI-779 (50 mg/week) combined with radiation/temozolomide is the recommended phase II dose and schedule. The immune profile of patients in the second cohort was assessed before, during, and after CCI-779 therapy. There was robust suppression of helper and cytotoxic T cells, B cells, natural killer, cells and elevation of regulatory T cells during CCI-779/radiation/temozolomide therapy with recovery to baseline levels during adjuvant temozolomide of cytotoxic T cells, natural killer cells, and regulatory T cells.The increased infection rate observed with CCI-779 combined with chemoradiotherapy in GBM was reduced with antibiotic prophylaxis and by limiting the duration of CCI-779 therapy. The combined suppressive effects of CCI-779 and temozolomide therapy on discrete immune compartments likely contributed to the increased infectious risks observed.
Complementary Therapies for Physical Therapy: A Clinical Decision-Making Approach
Authors: Demetra John
Journal: JAMA (2008)

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