tbuckley/cabot-search huggingface dataset:
AB0206 Impaired expansion of myeloid derived supressor cells (MDSCS) in both murine and human lupus
Authors: K. Vlachou, A. Fanouriakis, M. Glymenaki, M. Ioannou, G. Bertsias, P. Verginis, D. Boumpas
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> MDSCs (characterized in mice as CD11b<sup>+</sup>Gr1<sup>+</sup> and in humans as CD14<sup>-</sup>HLA-DR<sup>low</sup>CD15<sup>+</sup>CD33<sup>+</sup>) represent a phenotypically heterogeneous population of myeloid precursors of macrophages, dendritic cells and granulocytes. In EAE we have previously shown that immunization in the presence of Complete Freund’s Adjuvant (CFA) leads to expansion of MDSCs with a potent regulatory role in suppressing T-cell responses. Moreover, in patients with multiple sclerosis (MS) disease activity correlates with expansion of these cells and remission<sup>1</sup>. <h3>Objectives</h3> To examine whether defective MDSCs may facilitate aberrant immune responses in murine and human systemic lupus erythematosus (SLE). <h3>Methods</h3> We used the lupus prone (NZB x NZW) F1 female mice [3 months old, pre-SLE (n=6) and 6-8 months old, SLE mice (n=6)]. C57BL/6 (B6) female mice [3 mo (n=2) or 6 mo (n=6)] were used as controls. B6 mice immunized with myelin peptide (MOG) in CFA (Experimental Autoimmune Encephalomyelitis) were used as a disease control (n=3). To phenotype MDSCs in F1 under different immune context we injected F1 mice (n=3, 2 mo) with CFA. Cells were isolated from the bone marrow and spleen of the indicated groups and were stained with fluorescent-conjugated antibodies for the aforementioned markers and for 7AAD. Analysis was performed in humans as well, using samples from SLE patients (n=29) and healthy controls (n=26). Phenotyping and enumeration of cell populations were performed by flow cytometry. <h3>Results</h3> Analysis of spleen as well as bone marrow of diseased (6-8 mo) and healthy (3 mo) F1 lupus-prone mice revealed no significant differences in the frequency of MDSCs. However, immunization of pre-diseased F1 mice with CFA resulted in significant expansion of MDSCs; the effect was comparable to the one observed in MOG/CFA-injected B6 mice, suggesting that the MDSC compartment does not respond in lupus inflammatory milieu. Furthermore, in human SLE, we observed no significant difference between active (median 6330±4097, N=13) and inactive patients (4835±2909, N=16), corroborating the murine data for a defective expansion of these cells in this disease. <h3>Conclusions</h3> Together these data indicate an impaired MDSC expansion in the lupus, which may contribute to the aberrant immune responses in this disease. Ongoing experiments explore whether this is also associated with a defective function of MDSCs and the mechanisms involved. <h3>References</h3> Ioannou M, T Alissafi, I Lazaridis, G Derao, J Matsoukas, A Gravanis, V Mastorodemos, A Plaitakis, A Sharpe, D Boumpas, P Verginis. 2012. Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol 188(3):1136-46. <h3>Disclosure of Interest</h3> None Declared
Abstract 4022: Inactivation of the tumor suppressor BRG1 in lung cancer: Influence on nuclear receptors and cell differentiation
Authors: Octavio A. Romero-Ferraro, Fernando Setién, Alberto Villanueva, Albert Coll, Montserrat Sanchez-Cespedes
Journal: Cancer Research (2011)

Abstract BRG1, encoding an ATPase of the SWI/SNF chromatin remodelling complex, is genetically inactivated in a variety of human solid tumors, especially non-small cell lung cancer, thus, constituting a bona fide tumor suppressor gene. However, the mechanisms that mediate the tumor suppressor function of BRG1 are not completely elucidated. We previously reported that lung tumors with amplification at any of the MYC family of genes lacked BRG1 mutations, suggesting a functional relationship between both proteins. Using isogenic lung cancer cell lines, that stably and conditionally express wild type or mutant BRG1, we found that wtBRG1 induced the up-regulation of MYC-target genes. This was accompanied by a reduction in MYC levels. Interestingly, we observed an overlap in the gene expression pattern after restoring wtBRG1 in lung cancer cells and gene expression in normal lung, indicating that BRG1 is promoting cell differentiation. In addition, the effects of BRG1 activity in lung cancer cells, i.e. changes in morphology and in gene expression depended on the presence of specific vitamins/hormones. Exposition to these compounds conferred lung cancer cells specific morphological features that were compatible with cell differentiation, only after restoring wtBRG1. Finally, using lung orthotopic mouse models we demonstrated that BRG1 was able to cause significant tumor shrinkage and delay tumor progression. Taken together our data support a tight functional relationship between BRG1 and MYC by which inactivation of BRG1 in cancer cells leads to de-regulation of MYC activity and allow refractoriness to nuclear receptor-mediated external signals impairing the control important cellular processes, such as cell differentiation, proliferation and response to inflammation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4022. doi:10.1158/1538-7445.AM2011-4022
Subtotal Gastrectomy or Vagotomy for Peptic Ulcerations
Authors: Richard Warren, Edmund C. Meadows
Journal: New England Journal of Medicine (1949)

EVER since the operation of vagotomy has been used in the treatment of peptic ulcer numerous reports have appeared analyzing the early postoperative results. The first of these that has made a direct comparison between the results of this operation and of those of subtotal gastrectomy has been that of Allen.1 He found good results in 85 per cent of the gastrectomy groups and 87 per cent of the vagotomy, fair results in 7 per cent and 6 per cent, and poor results in 8 per cent and 7 per cent of the two groups respectively. The postoperative mortality in . . .
Case 15-1995
Authors: D.B. Cines, M. Laposata
Journal: New England Journal of Medicine (1995)

Presentation of CaseA 70-year-old woman was admitted to the hospital because of obtundation, aphasia, and a right hemiparesis.She had a five-year history of treated hypertension. Four months before admission a lumpectomy was performed because of breast carcinoma, with normal findings on examination of axillary lymph nodes, and radiation therapy was begun. Forty-six days before admission the patient entered another hospital because of the onset of atrial fibrillation, and treatment with warfarin and quinidine was initiated. Four weeks before admission a complete blood count was normal except that the platelet count was 130,000 per cubic millimeter. The patient felt . . .
CORONARY ENDOTHELIAL FUNCTION MEASURED BY ACETYLCHOLINE CORRELATES WITH COLD PRESSOR TESTING IN WOMEN WITH SIGNS AND SYMPTOMS OF ISCHEMIA AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE
Authors: Ahmed AlBadri, Janet Wei, Puja K. Mehta, Sofy Landes, John W. Peterson, David Anderson, Bruce Samuels, Babak Azarbal, Eileen Handberg, Quanlin Li, Margo Minissian, Chrisandra Shufelt, Carl J. Pepine, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2016)
Serum P53 Antibody Does not Predict Chemoresistance in Metastatic Colorectal Cancer Treated with Folfox (XELOX) Plus Bevacizumab at 1st Line Chemotherapy
Authors: Hiroki Osumi, Eiji Shinozaki, Yosuke Kumekawa, Mariko Ogura, Masato Ozaka, Mitsukuni Suenaga, Satoshi Matsusaka, Keisho Chin, Nobuyuki Mizunuma
Journal: Annals of Oncology (2013)
Diffuse optical spectroscopic imaging measures tumor functional response to bevacizumab: initial studies.
Authors: W Tanamai, AE Cerussi, R Mehta, D Hsiang, BJ Tromberg
Journal: Cancer Research (2009)

Abstract Abstract #6056 Background: Diffuse Optical Spectroscopic Imaging (DOSI) is a non-invasive, bedside functional imaging technique that quantifies the concentrations and molecular states of tissue hemoglobin, water, and lipids. Pilot studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentrations before and after therapy. DOSI may offer a point-of-care measurement of tumor responses to therapeutic intervention. The majority of these DOSI studies have measured responses to Anthracyclines. However, the optical response to Bevacizumab has not been demonstrated in vivo in human subjects.&amp;#x2028; Materials and Methods: Twenty-one patients diagnosed with stage II/III cancers were followed with DOSI prior to and during their two-stage neoadjuvant chemotherapy regimen that featured (a) Anthracyclines (2-4 cycles) and (b) Trastuzumab/Bevacizumab (for HER2+/HER2- status, respectively). Changes between pre-treatment and pre-surgical DOSI-measured parameters were compared against final surgical pathology (complete, partial, or non-responder). A functional tissue optical index (TOI) was calculated that has been shown to discriminate between normal and malignant tissues.&amp;#x2028; Results: Both short-term and long-term changes in tumor physiology were observed. For both therapy strategies (N=21), statistically significant changes were measured in TOI from baseline to pre-surgery between complete (95+/-15%), partial (79+/-11%) and non-responders (38+/-42%). TOI changes after the initial therapy stage were strongest in patients with more favorable pathological responses (78%, 56%, and 12% for complete, partial, and non-responders respectively). For patients receiving Bevacizumab (N=9), more detailed serial image analysis of tumor deoxy-hemoglobin revealed short-term changes (7-14 days) where initial decreases in hemoglobin were soon followed by slow increases back to pre-treatment levels. Two of the patients who received Bevacizumab demonstrated detectible residual disease by DOSI after completion of all neoadjuvant therapy, despite that contrast-enhanced MRI signals had disappeared.&amp;#x2028; Discussion: We have provided evidence that DOSI may be well-suited to monitor the response of different cancer drugs, including anti-angiogenic compounds such as Bevacizumab, in breast cancer patients. While the usage of Bevacizumab in human subjects is still under investigation in breast cancer, we foresee that DOSI may be a useful tool in general for the development of drugs and dosing strategies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6056.
The Nicotine Content of Common Vegetables
Authors: Edward F. Domino, Erich Hornbach, Tsenge Demana
Journal: New England Journal of Medicine (1993)

To the Editor: The presence of nicotine and its metabolite cotinine in the body fluids of nonsmokers is usually taken as evidence of exposure to environmental tobacco smoke. Recently, the Centers for Disease Control and Prevention studied 800 people, both smokers and nonsmokers, all of whom tested positive for urinary cotinine1. There is considerable evidence that nicotine is present in certain human foods, especially plants from the family Solanaceae (such as potatoes, tomatoes, and eggplant). Castro and Monji,2 Sheen,3 and Davis et al.4 have reported on the nicotine content of foods and drinks. We have been able to confirm . . .
Effects of denosumab treatment in breast cancer patients with bone metastases and elevated bone resorption levels after therapy with intravenous bisphosphonates: results of a phase 2 randomized trial.
Authors: J Gralow, A Lipton, K Fizazi, G Gao, S Jun, H Yeh
Journal: Cancer Research (2009)

Abstract Abstract #1155 Background: Patients with breast cancer-induced bone disease and elevated urine-N-telopeptide (uNTx), a marker of bone resorption, are at increased risk for skeletal complications, disease progression, and death. Receptor activator of NF-kB ligand (RANKL) mediates osteoclastic bone resorption. Denosumab, a fully human monoclonal antibody, inhibits bone destruction by binding and neutralizing RANKL. Denosumab efficacy and safety were assessed in a phase 2, randomized, open-label, active-controlled trial in patients with bone metastases and elevated levels of uNTx after at least 8 weeks of intravenous (IV) bisphosphonate (BP) therapy. We report results in a subset of patients with breast cancer.&amp;#x2028; Methods: Cancer patients with bone metastases and uNTx &amp;gt;50 nM/mM creatinine [Cr] following at least 8 weeks of IV BP therapy were randomized to continue IV BP therapy every 4 weeks (Q4W) or switch to subcutaneous (SC) denosumab injection (180 mg) Q4W or every 12 weeks (Q12W). The primary endpoint was the proportion of patients who achieved uNTx &amp;lt;50 nM/mM at week 13. Safety was also assessed.&amp;#x2028; Results: The study population (N = 111) included 46 patients (41%) with breast cancer; the median time since diagnosis of bone metastases was approximately 1 year in both groups. At week 13, 76% of denosumab-treated patients and 33% of IV BP-treated patients had uNTx &amp;lt; 50 nM/mM. Denosumab-induced suppression of uNTx was rapid (as early as 2 weeks after initial treatment), sustained through week 25, and unaffected by baseline uNTx (Table). In the total study population, adverse events of grade 3, 4, or 5 were reported in 25 (71%) IV BP-treated patients and 40 (55%) denosumab-treated patients.&amp;#x2028; &amp;#x2028; Discussion: Denosumab reduced bone turnover in breast cancer patients with bone metastases and elevated uNTx despite prior IV BP therapy. Phase 3 trials of denosumab in cancer patients with bone metastases are in progress. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1155.
ET-06 * PRECLINICAL TESTING OF THE HISTONE DEACETYLASE INHIBITOR, PANOBINOSTAT, IN A GENETICALLY ENGINEERED DIFFUSE INTRINSIC PONTINE GLIOMA MOUSE MODEL
Authors: K. Barton, K. Misuraca, O. Becher
Journal: Neuro-Oncology (2014)

Diffuse Intrinsic Pontine Glioma (DIPG) is a type of incurable pediatric brain tumor with a dismal outcome. With overall survival of less than one year, and no therapeutic advancements over the last three decades, gaining a better understanding of how to treat these deadly tumors is crucial. Recent genomic analysis has revealed that nearly 80% of DIPGS harbor a K27M mutation in histone H3.3 (K27M H3.3) or histone H3.1 (K27M H3.1). In an effort to elucidate novel therapeutics to treat DIPG, we examined Panobinostat, a potent pan-histone deacetylase inhibitor (HDACi) currently in clinical trials for a variety of different cancers. HDACi are a promising new class of agents known to have multiple target effects. Panobinostat targets HDACs in Classes I, II and IV and can cause disruption of genes involved in cell cycle control, apoptosis, DNA damage repair, and differentiation. To determine the effect of Panobinostat on DIPG, we utilized cell lines derived from a genetically engineered DIPG mouse model driven by PDGF-B overexpression, p53 loss, and either K27M or WT H3.3. Our results indicate that Panobinostat is highly effective at low nanomolar concentrations (<50nM), decreasing proliferation and viability, and increasing apoptosis in a dose dependent manner. Furthermore, utilizing isogenic lines we found the sensitivity of DIPG cells to Panobinostat to be independent of their H3.3 mutational status and that both K27M H3.3 and WT H3.3 lines were equally susceptible to treatment. In conclusion, murine DIPG cell lines, both with and without the K27M H3.3 mutation, show high sensitivity to Panobinostat in vitro. We are currently investigating its efficacy in vivo with hopes of translation to the clinic as a new therapeutic avenue for DIPG.
Serologic Detection of a Y-Linked Gene in XX Males and XX True Hermaphrodites
Authors: Stephen S. Wachtel, Gloria C. Koo, W. Roy Breg, H. Tzvi Thaler, G. Morris Dillard, Ira M. Rosenthal, Harvey Dosik, Park S. Gerald, Paul Saenger, Maria New, Ernest Lieber, Orlando J. Miller
Journal: New England Journal of Medicine (1976)

To test the hypothesis that H-Y antigen (present on both somatic and germ cells in normal males but not normal females) is essential for testicular differentiation, we studied four XX males and three XX true hermaphrodites. Blood cells from six subjects and cultured gonadal fibroblasts from a seventh expressed H-Y antigen. Since expression of this antigen requires the presence of a gene normally carried by the Y chromosome, this gene, and perhaps additional Y chromosomal material, should have been present in the genome of these subjects. In one patient this presence is accounted for by a Y-to-X translocation, detectable by chromosome banding. In another a normal Y chromosome was present in a minor population of cells. In the remaining five, no karyotypic abnormality was detectable. Immunologic detection of H-Y antigen is a sensitive test for the presence of the Y chromosome or of its male-determining segment.
Case 5-2005
Authors: Paul D. Biddinger, Eric M. Isselbacher, Dali Fan, Jo-Anne O. Shepard
Journal: New England Journal of Medicine (2005)

A 53-year-old man had decreased energy and appetite after losing his job; he came to the emergency department for psychiatric evaluation. A diagnosis of major depressive disorder was made; on the medical-clearance evaluation, a pulmonary infiltrate and a high white-cell count were found. While awaiting admission, he became short of breath; pulmonary edema was observed.
Abstract 1129: Function of mutant EGFR in maintaining glioblastoma growth and heterogeneity
Authors: Maria Del Mar Inda, Rudy Bonavia, Scott Vandenberg, Webster Cavenee, Frank Furnari
Journal: Cancer Research (2011)

Abstract Glioblastoma Multiforme (GBM) exhibits intratumoral heterogeneity on the morphological and molecular levels, a hallmark feature which may contribute to its poor response to targeted therapy. A powerful oncogenic event in GBM is amplification and rearrangement of the epidermal growth factor receptor (EGFRvIII variant, deleted for exons 2-7, hereafter ΔEGFR), strikingly, despite its greater biological activity than wildtype EGFR (wtEGFR), only a minority of cancer cells in the primary tumor possess the hallmark ΔEGFR lesion, while the remainder of cancer cells express wtEGFR. We observed that the tumorigenicy of wtEGFR-expressing cells can be significantly enhanced by the presence of ΔEGFR-expressing cells within the tumor, suggesting that soluble factors produced by the latter cells might mediate this potent tumor enhancement. Using a combination of mixed tumor engraftments and biochemical analysis of paracrine factors and signaling pathways activation, we determined that human glioma tissues, glioma cell lines, glioma stem cells and primary mouse astrocytes, that express ΔEGFR each secrete IL-6 and/or LIF cytokines. This then prompts a novel interaction between the receptor that is common to these cytokines, gp130, and wtEGFR in neighboring cells that express amplified levels of EGFR, resulting in co-receptor activation and tumor growth enhancement. Ablating IL-6, LIF or gp130 uncouples this cellular cross-talk and potently attenuates tumor growth enhancement. In addition, over-expression of both receptors in the same cell potently enhances tumorigenicity in vivo and colony formation in vitro through the activation of wtEGFR, as well as Akt and STAT3 pathways, suggesting that the secretion of IL-6/LIF cytokines can act not only in a paracrine fashion, but also in an autrocrine fashion when the cell express both receptors. These findings demonstrate that the heterogeneity which characterizes GBM, and perhaps other tumors with this feature, does not occur stochastically, but instead can be an actively maintained feature and illuminates a heterotypic cancer cell interaction of potential therapeutic significance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1129. doi:10.1158/1538-7445.AM2011-1129
Abstract 5220: Early prediction of tumor response to APO866 treatment with 3′-deoxy-3′-[18F]fluorothymidine positron emission tomography in human ovary cancer xenografts in mice
Authors: Mette Munk Jensen, Kamille Dumong Erichsen, Fredrik Björkling, Jacob Madsen, Liselotte Højgaard, Maxwell Sehested, Andreas Kjær
Journal: Cancer Research (2010)

Abstract Introduction: APO866 is a new anti-tumor compound found to inhibit nicotinamide phosphoribosyltransferase (NAMPT), an enzyme involved in the biosynthesis of NAD. The compound has anti-tumor effect in several pre-clinical tumor models and is currently in several clinical phase II studies. 3′-deoxy-3′-[18F]fluorothymidine (FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to evaluate if FLT positron emission tomography (PET) may be used to monitor early anti-proliferative effects of APO866. Methods: In vivo uptake of FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after APO866 treatment (15 mg/kg ip twice daily for 7 days) was initiated. Baseline FLT scans were made before either APO866 (n=10 tumors) or vehicle (n=6 tumors) was injected and repeated after 24 hours (2 treatments), 48 hours (4 treatments) and 7 days (14 treatments). Tumor volume was followed with computed tomography (CT) during the experiment. FLT uptake was quantified using small animal PET/CT. One hour after iv injection of 10 MBq FLT, static PET scans were performed for 10 minutes and region of interests (ROIs) covering whole tumors were defined on PET/CT images for calculation of standard uptake values (SUV). Comparison within treatment groups was performed using paired t-tests and between control and APO866 groups with unpaired t-tests. All p-values were corrected for multiple comparisons using the Bonferroni algorithm. P&amp;lt;0.05 was considered significant. Results: Tumors treated with APO866 had volumes that were 122% (24h), 129 % (48h) and 88% (day 7) relative to baseline volumes day 0. In the control group tumor volumes were 123% (24h), 150% (48h) and 318% (day 7) relative to baseline volumes day 0. Tumor volume between groups were significantly different at day 7 (P=0.006). APO866 treatment caused significant decrease in uptake of FLT at 24 hours (−23%; P&amp;lt;0.001), 48 hours (−29%; P&amp;lt;0.001) and day 7 (−25%; P=0.0013) after treatment start compared to baseline uptake. In the control group uptake of FLT did not change. Conclusions: APO866 treatment caused a significant decrease in FLT uptake 24 and 48 hours after injection of first dose. The early reductions in tumor cell proliferation preceded decrease in tumor volume on day 7. Our data indicate that FLT PET is promising for early non-invasive assessment of APO866 anti-tumor effects. 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 5220.
Could Bertrand Russell's barber have bitten his own teeth? A problem of logic and definitions
Authors: Kenneth John Aitken
Journal: Behavioral and Brain Sciences (2014)

Abstract Guiding the positive evolution of behavior is an admirable goal. Wilson et al.'s arguments are based largely on studies of problem correction. The methodology is sound, but not the post hoc ergo procter hoc extrapolation. What is required is evidence that it can proactively generate positive change. The evolution of human behavior to date has been affected by many factors that include unmalleable and unpredicted environmental changes.