tbuckley/cabot-search huggingface dataset:
Abstract 2801: Fueling immunity: The role of Myc in metabolic reprogramming of activated T cells
Authors: Ruoning Wang, Christopher Dillon, Douglas Green
Journal: Cancer Research (2011)

Abstract One of the fundamental problems in animal cells is the coordination of the metabolic program with cell proliferation-associated bioenergetic demand. Primary T lymphocytes rapidly switch from a quiescent phase to a rapid-proliferation phase one day after antigen stimulation. To meet the bioenergetic and biosynthetic demand for this burst of proliferation, T cells rapidly reprogram their metabolic pathways from fatty acid beta-oxidation and glucose aerobic respiration to glycolysis (converting glucose to lactate) and glutaminolysis (converting glutamine to metabolites of the TCA cycle). This is reminiscent of tumor-associated metabolic reprogramming in many ways. Recent work has indicated that oncogenic signaling can reform tumor metabolic programs by targeting relatively few key metabolic genes. However, we found that global regulation of the metabolic gene transcriptome precedes the switch of T cell metabolic activities. In silico analysis of DNA-binding motifs associated with the metabolic gene expression profile revealed HIF1a, c-Myc and p53 as three of the top-ranked candidate transcription factors responsible for T cell metabolic reprogramming. Consistent with this, HIF1a, c-Myc and p53 are each highly induced in primary T cells upon antigen stimulation and have been implicated in the regulation of tumor metabolism. However, while germline deletion of p53 and acute deletion of HIF1a showed no defects in metabolic reprogramming upon antigen stimulation, acute deletion of c-Myc in mature T lymphocytes profoundly reduced antigen-stimulated glycolysis and glutamine oxidation in primary T cells. In addition, c-Myc deletion significantly compromised T cell growth and T cell proliferation after antigen stimulation. Finally, we found that many of the key metabolic genes involved in glycolysis and glutamine oxidation are regulated in a c-Myc-dependent manner. Our results further suggest a novel c-Myc dependent metabolic pathway linking glutamine oxidation to the biosynthesis of polyamines, which is a group of metabolites essential for cell proliferation. Our studies clearly demonstrate that primary T lymphocytes drive a c-Myc-dependent metabolic reprogramming upon antigen stimulation, which may represent a general mechanism of the metabolic reprogramming under both pathological and physiological conditions. 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 2801. doi:10.1158/1538-7445.AM2011-2801
Kinetics of Recovery of CD4+ T Cells in Peripheral Blood of Deoxycoformycin-Treated Patients
Authors: R. G. Steis, W. J. Urba, W. C. Kopp, W. G. Alvord, J. W. Smith, D. L. Longo
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Kinetics of Recovery of CD4 + T Cells in Peripheral Blood of Deoxycoformycin-Treated Patients Get access Ronald G. Steis, Ronald G. Steis 1Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, National Cancer Institute-Frederick Cancer Research and Development CenterFrederick, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Walter J. Urba, Walter J. Urba 2Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center. Search for other works by this author on: Oxford Academic PubMed Google Scholar William C. Kopp, William C. Kopp 2Program Resources, Inc./DynCorp, National Cancer Institute-Frederick Cancer Research and Development Center. Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Gregory Alvord, W. Gregory Alvord 3Data Management Services, Inc., National Cancer Institute-Frederick Cancer Research and Development Center. Search for other works by this author on: Oxford Academic PubMed Google Scholar John W. Smith, II, John W. Smith, II 1Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, National Cancer Institute-Frederick Cancer Research and Development CenterFrederick, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan L. Longo Dan L. Longo * 1Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, National Cancer Institute-Frederick Cancer Research and Development CenterFrederick, Md. * Correspondence to: Dan L. Longo, M.D., Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702-1201. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 22, 20 November 1991, Pages 1678–1679, https://doi.org/10.1093/jnci/83.22.1678 Published: 20 November 1991 Article history Received: 14 June 1991 Revision received: 16 August 1991 Accepted: 16 August 1991 Published: 20 November 1991
Abstract 4711: Epigenetic modulation restores expression of functional progesterone receptor in endometrial cancer cells
Authors: Shujie Yang, Xue Xiao, Yuping Zhang, Xiangbing Meng, Kimberly K. Leslie
Journal: Cancer Research (2012)

Abstract Endometrial cancer, the most common gynecologic malignancy, is a hormonally regulated tumor. Given progesterone is a tumor suppressor in the endometrium, response to progestin-based therapy correlates positively with progesterone receptor (PR) expression. Many endometrial tumors have lost of PR, which limits the clinical application of progestin-based therapy. PRB promoter methylation was reported in 74% of endometrial cancer patients, which correlate with loss of PR expression. These clinical data suggest that restoring PR expression by epigenetic modulation might sensitize tumors to progestin-based therapy. Therefore, we hypothesized that restoring PR expression in endometrial cancer cells will inhibit proliferation and induce cell death. Epigenetic modulators, such as DNA methyltransferase inhibitors (DNMTi) and histone deacetylase inhibitors (HDACi) were evaluated as effective agents to restore PR expression in a panel of endometrial cancer cells. Treatment with the DNMTi 5-aza-2′deoxycytidine (5-aza-dC) or the HDACi LBH589 alone or in combination upregulated PGR mRNA levels. At the protein level, LBH589 treatment upregulated PR by 24 hours and sustained expression for at least 72 hours, even in the presence of progestrone. The upregulated PR expression by LBH589 treatment was dose dependent; an obvious increase in PR was detected with 10 nM LBH589 when compared with control, and the expression reached the highest level at 50 nM to 100 nM. To investigate if the restored PR is functional, we examined PR nuclear localization and expression of target genes. First, after treatment with LBH589 in the absence or presence of progesterone, PR nuclear localization was confirmed by immunostaining and nuclear fractionation followed by Western blotting. Next, a progesterone response element (PRE)-luciferase reporter assay was used to directly examine PR transcriptional activity. LBH589 treatment increased PRE-luciferase activity by 8- to 10-fold in Ishikawa and ECC1 cells. Furthermore, expression of endogeneous PR target genes containing PRE (FoxO1 and cyclin D) or Sp1 element (p21 and p27) was studied in response to LBH589 treatment. Restored PR upregulated FoxO1, p21, p27 and downregulated cyclin D1, demonstrating that PR is functional as a transcription factor. Our findings reveal that epigenetic modulators can restore endogenous PR expression in endometrial cancer cell lines. This preclinical study provides strong support that strategy to re-establish PR expression will result in resensitization of endometrial tumors to progestin therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4711. doi:1538-7445.AM2012-4711
Adolphe Vorderman's 1897 study on beriberi: an example of scrupulous efforts to avoid bias
Authors: Jan P Vandenbroucke
Journal: Journal of the Royal Society of Medicine (2013)

This paper highlights Adolphe Vorderman's investigations of the causes of beriberi using epidemiological observations among prison inmates in the Dutch East Indies (today Indonesia) in the 1890s.1 His investigations are featured in the James Lind Library because of Vorderman's scrupulous efforts to avoid bias. He built a number of methodological safeguards into his investigations, both to avoid being deluded by others, and to reduce the likelihood that he would, when collecting and analysing the data, delude himself by potential prejudices about the hypothesis that he was investigating.
FRI0145 The Role of Sctla-4 in Pathogenesis of Ankylosing Spondylitis and Evaluation of Its Relation with Clinical Manifestations
Authors: T. Senturk, P.S. Cetintepe, A. Neriman
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ankylosing Spondylitis (AS) is characterized by abnormal immune responses including T cell activation. Although Cytotoxic T lymphocyte associated molecule-4 (CTLA-4) is involved in down-regulating immune responses, a soluble form of CTLA-4 (sCTLA-4) has been identified and was found at high levels in several autoimmune diseases. We aimed to determine the relation between the serum levels of sCTLA-4 and AS disease activity. <h3>Objectives</h3> To evaluate the correlation between AS disease activity and sCTLA-4 level. <h3>Methods</h3> In this work, 38 AS patients, 28 rheumatoid arthritis (RA) patients and 27 healthy controls were studied. AS who had never been treated with TNF antagonist were studied. sCTLA-4 cytokine level for each patient was determined with the ELISA method. ESR, CRP, demographic characteristics (gender, age, symptom duration) and standardized assessment tool (BASDAI) were recorded for each patient group. Obtained experimental data were statistically compared. <h3>Results</h3> AS median age 39,37±12,11 years; %63,2 male, mean disease duration 19,00 (IQR:78). Compared to the RA group and healthy controls, high levels of sCTLA-4 were found in the AS group (p&lt;0,001). Soluble CTLA-4 serum levels were not correlated with the clinical index of disease activity (p=0,370). A correlation was noted between the serum levels of ESH and BASDAI for the AS group (p=0,012). <h3>Conclusions</h3> Our study investigates the role of sCTLA-4 levels in the pathogenesis of AS, and establishes a statistically meaningful difference between the serum levels of sCTLA-4 in AS patients, and those in RA patients and healthy controls (p&lt;0,001). Early diagnosis is important in AS patients, and disease-spesific diagnostic tests are required for this purpose. Therefore, sCTLA-4 levels can be useful for the early diagnosis in AS patients. Consequently, further research is needed to explore the relation between cytokine levels and clinical findings for the early-stage AS patients. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2449
Papillomatosis of the extrahepatic bile ducts and gallbladder diagnosed by endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP)
Authors: M. Kliment, O. Urban, M. Straka, L. Kudelka, P. Fojtik, P. Falt
Journal: Endoscopy (2011)

A 57-year-old man was referred for a diagnostic workup because of elevated serum liver enzyme levels (γ-glutamyltransferase 53.94 μkat/L, reference range 0.00 – 0.63). A transabdominal ultrasound revealed dilated extrahepatic bile ducts, and on endoscopic ultrasound (EUS) the common bile duct (CBD) was dilated with hyperechoic foci with no acoustic shadowing within, and a 20-mm hyperechoic frond-like mass was noted within the infundibulum of gallbladder ([Fig. 1]). The CBD and gallbladder walls were thin with smooth outer margins. Endoscopic retrograde cholangiography (ERC) revealed a 15-mm long filling defect within the dilated CBD ([Fig. 2]). A biopsy sample taken from the CBD showed evidence of tubulopapillary adenoma with foci of well-differentiated adenocarcinoma. An abdominal computed tomography (CT) scan showed atypical, but noncontrast-enhancing, hyperdense structures within the gallbladder infundibulum, which were not suggestive of tumor ([Fig. 3]). The patient underwent open laparotomy, cholecystectomy, and extensive resection of the extrahepatic bile ducts with Roux-en-Y hepaticojejunostomy. The histological examination confirmed the diagnosis of papillomatosis of the extrahepatic bile ducts, with foci of high-grade dysplasia ([Fig. 4]) and secondary growth extending into the gallbladder along the cystic duct.
Abstract 1370: Tumor endothelial cells acquire drug resistance by MDR1 upregulation via VEGF signaling in tumor microenvironment
Authors: Kosuke Akiyama, Noritaka Ohga, Yasuhiro Hida, Taisuke Kawamoto, Yoshihiro Sadamoto, Shuhei Ishikawa, Nako Maishi, Tomoshige Akino, Miyako Kondoh, Aya Matsuda, Nobuo Inoue, Masanobu Shindoh, Kyoko Hida
Journal: Cancer Research (2012)

Abstract Tumor endothelial cells (TECs) are therapeutic targets in antiangiogenic therapy. Contrary to the traditional assumption, it has been reported that TECs can be genetically abnormal and might acquire drug resistance. In this study, mouse TECs and normal ECs (NECs) were isolated to investigate drug resistance of TECs and the mechanism by which it is acquired. TECs were more resistant to paclitaxel with upregulation of multidrug resistance 1 (MDR1) mRNA, which encodes the P-glycoprotein, compared to NECs. Normal human microvascular ECs (HMVECs) were cultured in tumor-conditioned medium (tumor CM) and were found to become more resistant to paclitaxel through MDR1 mRNA upregulation and nuclear translocation of Y-box-binding protein 1 (YB-1), which is an MDR1 transcription factor. Vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) and Akt were activated in HMVECs by tumor CM. We observed that tumor CM contained a significantly high level of VEGF. A VEGF receptor kinase inhibitor, Ki8751, and a PI3K/Akt inhibitor, LY294002, blocked tumor CM-induced MDR1 upregulation. MDR1 upregulation via the VEGF/VEGFR pathway in the tumor microenvironment is one of the mechanisms of drug resistance acquired by TECs. We observed that VEGF secreted from tumors upregulated MDR1 through VEGFR2 and Akt activation. This is a novel mechanism of acquisition of drug resistance by TECs in a tumor microenvironment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1370. doi:1538-7445.AM2012-1370
Endoscopic ultrasonography using a miniprobe for staging of stenotic esophageal cancer
Authors: D Tuebergen, R Mennigen, N Senninger, M Bruewer
Journal: Endoscopy (2006)

Using miniprobes even highly stenotic tumors can be examined. The aim of the study was to assess the accuracy of miniprobe EUS (MEUS) in staging stenotic esophageal cancer.
Effects of polybrominated biphenyls on kidney function and activity of renal microsomal enzymes.
Authors: K M McCormack, W M Kluwe, V L Sanger, J B Hook
Journal: Environmental Health Perspectives (1978)

Polybrominated biphenyls (PBBs) cause hepatic microsomal enzyme stimulation and histopathological alterations in several organs, including kidney. Concern about effects of PBBs on the health of newborns has increased after the discovery of PBBs in milk of nursing mothers. Therefore, it was of interest to investigate the effects of PBBs on kidney function and the activity of renal microsomal enzymes in adult and immature animals. Seven and eleven day old pups were treated with a single IP injection of either peanut oil or 150 mg/kg PBBs (FireMaster BP-6) in peanut oil. Adult virgin rats were fed diet containing 0 or 100 ppm PBBs for 30 or 90 days. Treatment with PBBs only retarded weight gain after 90 days exposure. Kidney-to-body weight ratio was not altered by PBBs. Arylhydrocarbon hydroxylase activity was increased while epoxide hydratase activity was decreased (adults) or not affected (immature rats) in kidney following treatment with PBBs. Administration of PBBs had no effect on blood urea nitrogen, the clearance of inulin, p-aminohippurate (PAH), or fractional sodium excretion. Similarly, the in vitro accumulation of PAH and N-methylnicotinamide (NMN) by thin renal cortical slices and ammoniagenesis and gluconeogenesis in renal cortical slices were not affected by PBBs. In conclusion, treatment with PBBs resulted in modification of the activity of renal microsomal enzyme activities but had no detectable effect on renal function.
OP0230 Periostin, a novel matricellular protein, is required for cutaneous sclerosis in a mouse model of scleroderma
Authors: L. Yang, S. Serada, M. Fujimoto, H. Murota, Y. Kotobuki, S. Kitaba, T. Naka, I. Katayama
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Scleroderma impairs patients' quality of life and frequently threatens patients' lives. There is still no established treatment for the fibrosis in scleroderma.Elucidation of the underlying cause of this disease has been much awaited. Recently, the matricellular molecules and their associated molecules in skin were suggested to play key roles in scleroderma, and the studies on them are still on-going. <h3>Objectives</h3> Periostin, a novel matricellular protein, is recently reported to paly a crucial role in tissue remodeling, and highly expressed in fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma. <h3>Methods</h3> Using patients and healthy donors' skin tissues, expression of periostin was assessed by immunohistochemistry and immunoblotting analysis. Furthermore, we investigated periostin<sup>-/-</sup> (PN<sup>-/-</sup>) mice and wild-type (WT) mice to elucidate the role of periostin in scleroderma. To induce murine cutaneous sclerosis, mice were subcutaneously injected with bleomycin, while untreated control groups were injected with phosphate buffered saline. Bleomycin-induced fibrotic changes were compared between PN<sup>-/-</sup>and WT mice, by histologic analysis, as well as measuring profibrotic cytokines and extracellular matrix proteins (ECM) expression <i>in vivo</i> and <i>in vitro</i>. To determine the downstream signal transduction pathway for the effect of exogenous periostin, signal-transduction inhibitors were used <i>in vitro</i>. <h3>Results</h3> Elevated expression of periostin was observed in lesional skin of patients with scleroderma, compared with healthy donors. Regarding the animal experiments, although WT mice showed marked cutaneous sclerosis with increased expression of periostin and increased number of myofibroblasts by bleomycin treatment, PN<sup>-/-</sup> mice showed resistant to these changes. <i>In vitro</i>, PN<sup>-/-</sup> mice dermal fibroblasts showed reduced transcripts expression of transforming growth factor beta 1 (TGFβ1)-induced alpha smooth muscle actin (αSMA) and procollagen type I alpha 1 (Col1α1). Furthermore, recombinant mouse periostin directly induced Col1α1 expression <i>in vitro</i>, and this effect was inhibited by PI3K/Akt kinase inhibitor LY294002. <h3>Conclusions</h3> Periostin plays an essential role in the pathogenesis of scleroderma. <h3>Disclosure of Interest</h3> None Declared
SP0160 Regulatory Functions of Macrophages
Authors: K. Barczyk-Kahlert
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Active resolution of inflammation is a previously unrecognized process essential for tissue homeostasis. Monocytes and macrophages are central components of the immune system. During infection and inflammation they play a pivotal role not only in the generation of inflammatory mediators and regulation of innate and adaptive immune responses but they also actively contribute to resolution of inflammation by producing anti-inflammatory cytokines and removal of pro-inflammatory pathogens, cellular debris and apoptotic cells present at later stages of inflammation. Diversity and plasticity are hallmarks of monocytes and macrophages. Glucocorticoids (GC) are still the most widely used drugs in the treatment of a wide range of chronic and autoimmune diseases acting on cells of the immune system, including monocytes and macrophages. It was generally believed, that anti-inflammatory actions of GC on monocytes and macrophages are mainly due to the suppression of their function. Our studies have shown that treatment of naive monocytes with GC does not cause the global suppression of monocytic effector function, but rather induces differentiation of cells with anti-inflammatory and regulatory phenotype (regulatory monocytes, Mreg). However, the exact mechanism of GC action on monocytes and macrophages during inflammation is still not completely elucidated. Analysis of the effects of GC on lipopolysaccharide (LPS)-triggered proinflammatory monocytes demonstrated that, also in this case, GC do not simply suppress LPS-mediated activation of monocytes but rather induce their reprogramming toward a specific anti-inflammatory phenotype which actively promotes resolution of inflammation. Unravelling specific GC-actions on monocytes may thus define novel pathways allowing anti-inflammatory therapy without enhanced risk for severe infections. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6186
Abstract 3441: Cross-species expression profiling identifies Forkhead-Box Q1 as a promoter of epithelial-mesenchymal transition and breast cancer metastasis
Authors: Haijun Zhang, Fanyan Meng, Gang Liu, Bin Zhang, Jun Zhu, Feng Wu, Stephen P. Ethier, Fred Miller, Guojun Wu
Journal: Cancer Research (2011)

Abstract Utilizing a cross-species expression profiling strategy that combines microarray techniques and metastatic cell lines of human and mouse origins, 22 up-regulated and 12 down-regulated genes were identified as an essential genetic program in highly-metastatic cell lines. The correlation of all gene expression levels and metastasis potential was confirmed by RT-PCR in a set of human and mouse cancer cells. Among these genes, Forkhead-Box Q1 (Foxq1) is a transcription factor with a function in metastasis that has not yet been reported upon. We showed that ectopic expression of Foxq1 increased cell migration and invasion in vitro; significantly enhanced lung metastatic capabilities of mammary epithelial cells in vivo and resulted in a marked epithelial to mesenchymal transition (EMT). In contrast, knockdown of Foxq1 expression led to the opposite change in vitro and in vivo. Neither ectopic expression nor knockdown of Foxq1 had significant effects in cell proliferation and colony formation in vitro. Additionally, we showed that Foxq1 repressed E-cadherin expression by binding to the E-box in its promoter region. Finally, we found that the expression of Foxq1 is regulated by TGF-β1, and that knockdown of Foxq1 blocked EMT induced by TGF-β1 treatment at morphological and molecular levels. Our study highlights the feasibility of cross-species expression profiling as a strategy in identifying metastasis-related genes. It also reveals that the inducement of EMT is a potential mechanism for the novel metastasis-promoting function of Foxq1 in breast cancer. 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 3441. doi:10.1158/1538-7445.AM2011-3441