tbuckley/cabot-search huggingface dataset:
Bone Mineral Content of Amenorrheic and Eumenorrheic Athletes
Authors: Barbara L. Drinkwater, Karen Nilson, Charles H. Chesnut, William J. Bremner, Sydney Shainholtz, Molly B. Southworth
Journal: New England Journal of Medicine (1984)

This study was designed to determine whether the hypoestrogenic status of 14 amenorrheic athletes was associated with a decrease in regional bone mass relative to that of 14 of their eumenorrheic peers. The two groups of athletes were matched for age, height, weight, sport, and training regimens. Bone mass was measured by dual-photon and single-photon absorptiometry at the lumbar vertebrae (L1 to L4) and at two sites on the radius. Vertebral mineral density was significantly lower in the amenorrheic group (mean, 1.12 g per square centimeter) than in the eumenorrheic group (mean, 1.30 g per square centimeter). There was no significant difference at either radial site. Radioimmunoassay confirmed a lower mean estradiol concentration (amenorrheic group, 38.58 pg per milliliter; eumenorrheic group, 106.99 pg per milliliter) and progesterone peak (amenorrheic group, 1.25 ng per milliliter; eumenorrheic group, 12.75 ng per milliliter) in the amenorrheic women, in four venous samples drawn at seven-day intervals. A three-day dietary history showed no significant differences in nutritional intake, including calcium with and without supplements. The two groups were similar in percentage of body fat, age at menarche, years of athletic participation, and frequency and duration of training but differed in number of miles run per week (amenorrheic group, 41.8 miles [67.3 km]; eumenorrheic group, 24.9 miles [40.1 km]). We conclude that the amenorrhea that is observed in female athletes may be accompanied by a decrease in mineral density of the lumbar vertebrae. (N Engl J Med 1984; 311: 277–81.)
Abstract P3-06-05: Expression of SPARC in human breast cancer and its predictive value in the GeparTrio neoadjuvant trial.
Authors: M Untch, J Prinzler, P Fasching, BM Müller, S Gade, I Meinhold-Heerlein, J Huober, T Karn, C Liedtke, S Loibl, V Müller, B Rack, C Schem, S Darb-Esfahani, G von Minckwitz, C Denkert
Journal: Cancer Research (2012)

Abstract Background: Secreted protein acidic and rich in cysteine (SPARC) is an albumin-binding protein and associated with poor prognosis in multiple cancers. The aim of this analysis was to determine the frequency of SPARC expression among different molecular breast cancer subtypes and to evaluate its predictive value for therapy response after neoadjuvant anthracycline/taxane based chemotherapy (CTX) in participants of the GeparTrio trial. Methods: We evaluated tumoral SPARC expression by immunohistochemistry on tissue microarrays (TMAs) constructed from formalin-fixed paraffin-embedded (FFPE) pre-treatment core biopsies from 667 patients (pts) of the GeparTrio trial. The details of the GeparTrio study design are described elsewhere (von Minckwitz, JNCI 2008). Cutoffs for SPARC expression were determined using the web-based software Cutoff Finder (http://molpath.charite.de/cutoff/). Results: SPARC protein expression was measurable by IHC on the TMAs and 176 (26.4 %) of 667 tumors were SPARC positive. SPARC expression was increased in pts with triple-negative breast cancer (TNBC) compared to hormone receptor or HER2 positive subtypes (p = 0.039). SPARC positivity was associated with an increased pCR rate in the overall population (p &amp;lt; 0.001). SPARC negative tumors had a pCR rate of 15%, which increased to 27% in SPARC positive tumors. Similarly, in TNBC the pCR rate increased from 26% in SPARC negative tumors to 47% in SPARC positive tumors (p = 0.032). In multivariate logistic regression analysis adjusted for standard clinicopathological factors, SPARC was independently predictive in the overall population (p = 0.010) as well as the subgroups of pts with TNBC (p = 0.036). Conclusions: SPARC is expressed in all biological breast cancer subtypes with TNBC revealing the highest expression rate. Our data suggest that SPARC expression may provide predictive information for response to neoadjuvant CTX. As SPARC is an albumin-binding protein and might mediate intratumoral accumulation of nab-Paclitaxel, prospective analysis of SPARC expression is planned in the GeparSepto trial. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-06-05.
Liver Function in Diabetes Mellitus
Authors: Rafael Camerini-Davalos, Alexander Marble, Hugo Muench
Journal: New England Journal of Medicine (1962)

MANY reports have been published regarding the outcome of liver-function tests both in healthy persons and in those with pathologic states. The data have shown considerable variation from one study to another, including those in persons with diabetes. Some have stated that liver function is impaired in this disease,1 2 3 and others have maintained that it is normal in the patient with uncomplicated, well controlled diabetes.4 , 5 This becomes a matter of great importance when one carries out studies in diabetic patients receiving new drugs such as the orally administered hypoglycemic agents. To estimate any liver damage possibly incurred, the values should . . .
Abstract 5453: Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression
Authors: Anne Le, Charles R. Cooper, Arvin Gouw, Anirban Maitra, Ramani Dinavahi, Lorraine Deck, Robert Royer, David Vander Jagt, Gregg Semenza, Chi Van Dang
Journal: Cancer Research (2010)

Abstract As the result of genetic alterations and tumor hypoxia, many cancer cells avidly take up glucose and generate lactate through lactate dehydrogenase A (LDHA), which is encoded by a target gene of c-Myc and HIF-1. Previous studies with reduction of LDHA expression indicate that LDHA is involved in tumor initiation, but its role in tumor maintenance and progression has not been established. Furthermore, how reduction of LDHA expression by interference or antisense RNA inhibits tumorigenesis is not well understood. Here, we report that reduction of LDHA by siRNA or its inhibition by a small molecule inhibitor (FX11) reduced ATP levels and induced significant oxidative stress and cell death that could be partially reversed by the antioxidant N-acetylcysteine. Furthermore, we document that FX11 inhibited the progression of sizable human lymphoma and pancreatic cancer xenografts. When used in combination with the NAD+ synthesis inhibitor FK866, FX11 induced lymphoma regression. Hence, inhibition of LDHA with FX11 is an achievable and tolerable treatment for LDHA-dependent tumors. Our studies document a therapeutic approach to the Warburg effect and demonstrate that oxidative stress and metabolic phenotyping of cancers are critical aspects of cancer biology to consider for the therapeutic targeting of cancer energy metabolism. 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 5453.
Abstract 3856: A highly selective Erk-inhibitor with antiproliferative efficacy and the potential for combination therapy with modulators of the PI3K pathway
Authors: Irene Seipelt, Lars Blumenstein, Silke Baasner, Gilbert Mueller, Babette Aicher, Michael Teifel, Eckhard Guenther, Matthias Gerlach
Journal: Cancer Research (2010)

Abstract The Ras/Raf/Mek/Erk signal transduction is a key oncogenic pathway in a variety of human cancers. The mitogen activated protein kinase Erk is an important regulator of cell proliferation and was shown to be over-activated by dysregulated or mutated tyrosine kinase associated cell-surface receptors, Ras or Raf in diverse human tumors. We have established a small molecular compound class that inhibits Erk in the low nanomolar range and shows an excellent selectivity profile. Other serine threonine, lipid or tyrosine kinases are not inhibited at concentrations up to 10µM. Further characterization experiments revealed an ATP competitive mode of action and the potent inhibition of the cellular downstream target Rsk1 in tumor cells. The lead structure AEZS-131 produces cell cycle arrest in G1 and results in growth inhibition of cancer cells. Furthermore, the potential of combination therapy of AEZS-131 with inhibitors of the PI3K pathway was addressed and the analysis of combination effects on tumor cell proliferation is presented. These results support the evaluation of selective Erk inhibitors as anti-proliferative agents either as monotherapy or in combination with inhibitors of the PI3K/Akt pathway. 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 3856.
Tc-99m DMSA Localization in Infantile Hemangioma
Authors: Aysegul Dirlik, Zehra Ozcan, S Sureyya Ozbek, Bulent Karapinar, Ozer Ozyurt, Alphan Cura
Journal: Clinical Nuclear Medicine (2002)

DIRLIK, AYSEGUL M.D.*; OZCAN, ZEHRA M.D.*; SUREYYA OZBEK, S. M.D.†; KARAPINAR, BULENT M.D.‡; OZYURT, OZER M.D.*; CURA, ALPHAN M.D.‡ Author Information
Nordic Countries See Rapid Increase In Melanoma
Authors: S. Jenks
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Nordic Countries See Rapid Increase In Melanoma Get access Susan Jenks Susan Jenks Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 16, 19 August 1992, Pages 1230–1232, https://doi.org/10.1093/jnci/84.16.1230 Published: 19 August 1992
S126 Interleukin-1 Alpha (IL-1α) Released from Injured Lung Epithelium is a Critical Alarmin Driving Activation of a Potent Inflammatory Phenotype in Lung Fibroblasts
Authors: MI Suwara, LA Borthwick, R Mahida, NJ Green, K Mayer-Barber, A Gardner, J Mann, TA Wynn, PA Corris, SN Farrow, DA Mann, AJ Fisher
Journal: Thorax (2012)

<h3>Background</h3> Activation of the innate immune system plays a key role in exacerbations of chronic lung disease. Myeloid cells are classically considered to drive innate immune responses yet the potential of fibroblasts to act as immune cells has been postulated. We hypothesized that alarmins released from lung epithelium during environmental insults such as oxidant injury and viral infection might induce innate immune responses in lung fibroblasts. <h3>Methods</h3> Human bronchial epithelial cells (BECs) and human lung fibroblasts (HLFs) were cultured from brushings taken from lung transplant recipients and resected lung tissue respectively. Cytokine concentrations were measured by ELISA or multiplex platform (MSD). Gene expression was assessed by qRT-PCR. Wild-type and <i>Il1a-/-</i> mice were infected with Influenza (PR8). Data were analysed using t-Student or Mann-Whitney U Test. Correlations were assessed using Spearman rank correlation coefficient. <h3>Results</h3> Conditioned media from PBECs subjected to oxidant injury contained elevated levels of alarmins. Treatment of HLFs with conditioned media significantly upregulated proinflammatory cytokine expression. Anti-IL-1α or IL-1Ra significantly reduced induction of IL-8 (93% and 95%), IL-6 (90% and 91%), MCP-1 (92% and 93%) and GM-CSF (95% and 94%). Anti-IL-1β had no effect. <i>Co-stimulation with Poly I:C significantly accentuated the IL-1</i>α<i> induced inflammatory phenotype in HLFs.</i> Bronchoalveolar lavage (BAL) form Influenza infected wild-type mice contains elevated levels of IL-1α and activates innate immune signalling in wild-type murine lung fibroblasts (MLFs) but not <i>Il1r1-/-</i> MLFs. BAL from <i>Il1a-/-</i> mice had no effect on MLFs and demonstrated a blunted neutrophilic response to Influenza. Clinically we show that IL-1α is increased in BAL of lung transplant recipients with infections and within 3 months of developing bronchiolitis obliterans syndrome (BOS) (p&lt;0.001) and that IL-1α levels positively correlated with elevated IL-8 (p&lt;0.001) and neutrophil counts (p&lt;0.001). <h3>Conclusions</h3> We propose a new paradigm of innate immune signalling in exacerbations of lung disease, where epithelial damage triggers a potent inflammatory phenotype in resident fibroblasts. The pivotal role of IL-1α in this process is accentuated in the presence of viral infection. This novel pathway warrants further evaluation of its therapeutic potential to limit the repeated cycles of injury and exacerbation in chronic lung diseases.
Breast Cancer Death Rates Decline for White Women
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Breast Cancer Death Rates Decline for White Women Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 3, February 1995, Page 173, https://doi.org/10.1093/jnci/87.3.173 Published: 01 February 1995
Split dosing with a low-volume preparation is not inferior to split dosing with a high-volume preparation for bowel cleansing in patients with a history of colorectal resection: a randomized trial
Authors: Alessandro Mussetto, Leonardo Frazzoni, Silvia Paggi, Silvia Dari, Liboria Laterza, Franco Radaelli, Cesare Hassan, Omero Triossi, Lorenzo Fuccio
Journal: Endoscopy (2015)

<b>Background and study aim:</b> The study compared the efficacy of bowel cleansing using a low-volume mixed preparation (15 mg bisacodyl plus 2 L polyethylene glycol [PEG] solution) versus a standard high-volume preparation (4 L PEG) in patients with previous colorectal resection. <b>Patients and methods:</b> A total of 120 patients with prior colorectal resection for cancer undergoing surveillance colonoscopy were randomized to receive either a split-dose low-volume (n = 60) or high-volume (n = 60) preparation for bowel cleansing. The quality of bowel preparation, rated according to a modified Ottawa Bowel Preparation scale (mOBPS), represented the primary outcome measure. Tolerability, safety, and lesion detection rates were secondary outcomes. <b>Results: </b>No significant difference was observed between the low-volume and high-volume preparations in achievement of adequate cleansing (i. e. mOBPS ≤ 4; low-volume vs<i>.</i> high-volume group, 85.0 % vs<i>.</i> 81.7 %, <i>P</i> = 0.624). The low-volume preparation showed a higher success rate for cleansing of the right colon (<i>P</i> = 0.025); better tolerability in terms of intake of the whole amount of the preparation (<i>P</i> < 0.001) was also observed. According to the logistic regression analysis, the only predictors of unsuccessful cleansing were previous left colectomy (<i>P</i> = 0.012) and a longer elapsed time since the intervention (<i>P</i> = 0.034). Lesion detection rates were comparable between the groups. No serious adverse events were reported. <b>Conclusion: </b>A low-volume preparation is not inferior to a high-volume preparation for adequate bowel cleansing in patients with prior colorectal resection for cancer. If larger, multicenter, prospective studies confirm our findings, a low-volume preparation will represent a more tolerable option for such patients. Trial registration number: ClinicalTrial.gov identifier NCT01887158.
Colonic mucosal biopsies obtained during confocal endomicroscopy are pre-stained with fluorescein in vivo and are suitable for histologic evaluation
Authors: E. Coron, J. Mosnier, A. Ahluwalia, M. Rhun, J. Galmiche, A. Tarnawski, T. Matysiak-Budnik
Journal: Endoscopy (2012)

<b>Background and study aims:</b> Confocal laser endomicroscopy (CLE) with intravenous infusion of fluorescein allows noninvasive, real-time in vivo visualization of gastrointestinal mucosa at ~ × 1000 magnification (“virtual biopsy”). Conventional biopsies obtained during these procedures serve as the reference and established diagnostic standard. The aim of the present study was to assess whether the standard histologic biopsies that are obtained during CLE retain fluorescein in the tissues and allow the visualization of mucosal structures without any additional staining. <b>Patients and methods:</b> CLE optical imaging of the mucosa was performed in 16 patients who were undergoing CLE colonoscopy. Standard conventional biopsies were also obtained from both normal colonic mucosa and colonic polyps. De-paraffinized mucosal sections were examined under a fluorescence microscope for the presence and distribution of fluorescein, and then underwent immunostaining for expression of vascular endothelial growth factor (VEGF). <b>Results:</b> Standard mucosal biopsy sections from patients undergoing CLE displayed a strong fluorescence and showed well-delineated mucosal structures. In colonic adenomas, there was a 4.6-fold increased vascular permeability compared with normal mucosa (<i>P</i> < 0.001), indicated by fluorescein leakage to the extravascular space. Immunostaining demonstrated an aberrantly increased expression of VEGF in the epithelium of colonic adenomas but not in the epithelium of normal mucosa or hyperplastic polyps. <b>Conclusions:</b> This study shows for the first time that standard colonic biopsies obtained during CLE retain fluorescein, show excellent delineation of mucosal structures without additional staining, allow the evaluation of mucosal microvasculature and vascular permeability, and are suitable for immunostaining.
Abstract 3216: CREG1, an epigenetically regulated gene, cooperates with p16INK4a in cellular senescence
Authors: Benchamart Moolmuang, Michael A. Tainsky
Journal: Cancer Research (2010)

Abstract By passing cellular senescence, an irreversible growth arrest of cells that is activated in normal cells upon shortening of telomere and other cellular stress, to become immortal is one of the prerequisites for carcinogenesis. Using spontaneously immortal Li-Fraumeni Syndrome (LFS) fibroblasts, we found that CREG1 (Cellular Repressor of E1A-stimulated Genes1) is one of the genes whose expression fit the criteria of senescence-associated genes, decrease expression during immortalization and increase in senescence. Moreover, we found that epigenetic mechanism regulates CREG1 expression. CREG1 is a secreted glycoprotein that was shown to bind RB-family pocket proteins and inhibits E2F transactivation activity. Therefore, we hypothesize that CREG1 plays a role in cellular senescence involving p16INK4a/Rb pathway. Ectopic expression of CREG1 in the immortal LFS cell lines decreases cell proliferation but does not directly induce senescence. We confirmed this in osteosarcoma and fibrosarcoma cancer cell lines commonly seen in Li-Fraumeni Syndrome. Because CREG1 was shown to interact with RB pocket proteins in vitro, we tested that growth suppression by CREG1 may depend on the phosphorylation status of Rb. We found that p16INK4a is also downregulated in immortal cells and that coexpression of CREG1 and p16INK4a, and inhibitor of CDK and Rb phosphorylation, has a greater effect than CREG1 and p16INK4a alone to reduce cell growth, induce cell cycle arrest and cellular senescence in immortal LFS, osteosarcoma and fibrosarcoma cell lines. Moreover, cooperation of CREG1 and p16INK4a inhibits the expression of cyclin A and cyclin B by inhibiting promoter activity thereby decreasing mRNA and protein levels; these proteins are required for S-phase entry and G2/M transition. Whether CREG1 directly involved in transcriptional repression of cyclin A and B mediated by p16INK4a will be confirmed by ChIP assay. In conclusion, we are the first to find that CREG1 enhances p16INK4a-induced senescence by transcriptional repression of cell cycle mediated genes. Analysis of how CREG1 and its cooperation with p16INK4a regulate cell cycle and cellular senescence may provide better understanding of cellular immortalization, an early step in human tumorigenesis. 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 3216.
Asymmetric Thoracic Metaiodobenzylguanidine (MIBG) Activity Due to Prior Radiation Therapy
Authors: Xia Bai, Hua Yang, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2015)

A 5-year-old patient suffered Horner syndrome, which was caused by a neuroblastoma in the left apex of the lung shown on the initial I-MIBG scan. After the surgical resection and external radiation to the left lung field, a follow-up I-MIBG scan revealed significantly less MIBG activity in the left upper chest compared to the contralateral right upper chest.
Abstract 283: Cancer MET at the metastatic lesion preserves the malignant features acquired via EMT.
Authors: Chie Kudo-Saito, Yutaka Kawakami
Journal: Cancer Research (2013)

Abstract Purpose: Cancer EMT is one of the mechanisms to acquire malignant features including invasiveness, drug resistance and stemness. However, the subsequent mechanism after EMT toward progression has not been fully understood yet. Based on the EMT-centered theory, it is simply thought that the reversal event of EMT, “MET," is caused in the tumor cells at the distant metastatic lesions. However, the molecular mechanism still remains unclear. In this study, we attempted to clarify the “post-EMT” mechanism in tumor cells. Results: Firstly, we prepared tumor cells harvested from metastatic lesions of mice after tumor implantation provisionally as “post-EMT” tumor cells. Murine metastatic melanoma B16-F10 cells were transduced with a neo resistant gene, and were subcutaneously (s.c.) implanted in many C57BL/6 mice to obtain spontaneous tumor metastasis. Three weeks later, various tissues including bone marrow were harvested from the mice, and the single-cell suspensions were cultured in G418-supplemented medium for tumor selection. To characterize the post-EMT tumor cells, RT-PCR, immunostaining and cellular functional assay were conducted. As compared to the primary tumor cells harvested from s.c. tumor tissues, these tumor cells proliferated extremely slowly, and were resistant to chemotherapeutics, but rapidly grew in vivo after implantation. However, these tumor cells were very adhesive accompanied by increase of epithelial markers such as E-cadherin, but not mesenchymal markers such as Snail, indicating epithelial features. In addition, its chemoresistance and in vivo tumorgenesis activity of these tumor cells were superior to those of even Snail-transduced B16-F10 tumor cells, which were harvested from the metastatic lesions in a similar way. DNA microarray analysis revealed the significant upregulation of epithelial markers and drug resistant genes such as c-kit and GDF15 in the post-EMT tumor cells, as compared to those of the Snail transfectant. These imply that “MET” may not be just a reversion of EMT. Conclusions: These results suggest that tumor cells revert into an epithelial state preserving malignant features acquired via EMT even after Snail lost at the metastatic lesions toward progression. We are now attempting to elucidate the molecular mechanism specific for the unique transition utilizing DNA microarray data. Citation Format: Chie Kudo-Saito, Yutaka Kawakami. Cancer MET at the metastatic lesion preserves the malignant features acquired via EMT. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 283. doi:10.1158/1538-7445.AM2013-283
Choledochal Cyst with Biliary Atresia
Authors: STEPHANIE E. SPOTTSWOOD, PAUL R. JOLLES, JEFFREY H. HAYNES, CHARLES E. BAGWELL
Journal: Clinical Nuclear Medicine (2001)

SPOTTSWOOD, STEPHANIE E. M.D., M.S.P.H.; JOLLES, PAUL R. M.D.; HAYNES, JEFFREY H. M.D.; BAGWELL, CHARLES E. M.D. Author Information