tbuckley/cabot-search huggingface dataset:
Abstract 3077: LARP7<i>:</i> Potential novel tumor suppressor gene in gastric cancer
Authors: Yulan Cheng, Zhe Jin, Elizabeth Montgomery, Rachana Agarwal, Jian Yang, James Hamilton, Florin Selaru, Alexandru Olaru, Stefan David, John M. Abraham, Meltzer J. Stephen, Yuriko Mori
Journal: Cancer Research (2010)

Abstract Gastric cancer is one of the most deadly of all human tumors. However, little is known about events leading to this deadly disease. We previously reported that the RNA binding protein gene, La ribonucleoprotein domain family, member 7 (LARP7) was frequently subjected to genetic aberration in gastric cancers. LARP7 stabilizes the noncoding 7sk small nuclear RNA (7sk), and both LARP7 and 7sk compose 7sk snRNP that negatively regulates the positive transcription elongation factor b (P-TEFb). Hyperactive P-TEFb has been associated with hyper-proliferation and de-differentiation in various tissues. Therefore, the functional loss of LARP7 may contribute to gastric tumorigenesis. In the current study, we evaluated the involvement of LARP7 in human gastric cancer by assessing the LARP7 expression in normal and cancerous gastric tissues as well as by LARP7 knockdown in normal gastric epithelial cells. Methods: LARP7 expression was assessed by real-time quantitative RT-PCR in 30 normal and 25 cancerous gastric tissues. LARP7 knockdown was performed by the specific siRNA transient transfection in an immortalized normal human gastric epithelial cell line, HFE-145. Results: LARP7 mRNA expression was significantly decreased in gastric cancers compare to normal tissues (34.5% reduction, p&amp;lt;0.01). LARP7-targeting siRNA transfection in HFE-145 cells resulted in increased cell proliferation by 23% relative to the control siRNA transfection (p&amp;lt;0.05; measured by WST assay). We also observed a 28% decrease in 7sk quantity in LARP7-targeting siRNA transfectant relative to control siRNA transfectant (p&amp;lt;0.01). Conclusions: LARP7 downregulation is present in primary human gastric cancers and promotes 7sk downregulation as well as cell proliferation of normal gastric epithelial cells in vitro. Taken together, genetic aberrations that downregulate LARP7 may promote gastric tumorigenesis via p-TEFb deregulation. Further studies are warranted to explore the precise anti-tumor mechanisms of LARP7 and its potential role in the clinical care of patients. 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 3077.
Duodenal perforation from a pen
Authors: Jana Hashash, Lia Kaufman, Victor Chedid, Kenneth Fasanella
Journal: Endoscopy (2015)

A 25-year-old woman, who was a long-term resident of a neighboring psychiatric hospital because of schizophrenia, presented to our institution following the ingestion of a foreign body. She had a history of multiple foreign body ingestions and had required 19 esophagogastroduodenoscopies (EGDs) over the previous 18 months. In compliance with the American Society for Gastrointestinal Endoscopy (ASGE) guidelines, not all foreign body ingestions necessitated endoscopic retrieval. Foreign bodies not requiring removal include AA batteries, coins, belt buckles, zippers, and door hinges, among others, while other sharp-pointed objects and those > 6 cm in length require endoscopic intervention [1].
O6.05 * ERBB2/HER2-SPECIFIC NATURAL KILLER CELLS FOR ADOPTIVE IMMUNOTHERAPY OF GLIOBLASTOMA
Authors: M. C. Burger, C. Zhang, L. Jennewein, K. Schonfeld, S. Genssler, M. Grez, T. Tonn, M. Mittelbronn, J. P. Steinbach, W. S. Wels
Journal: Neuro-Oncology (2014)

BACKGROUND: While EGFRvIII appears a logical target for immunotherapy, only a subpopulation of tumor cells express EGFRvIII and immune escape has been demonstrated. ErbB2 is overexpressed in a substantial proportion of glioblastomas and has been successfully utilized in immunotherapies. Natural killer (NK) cells are the first line of defense against viral infections and malignant cells. The continuously growing cytotoxic cell line NK-92 holds promise for cancer immunotherapy. Safety of infusion of high doses of NK-92 was established in previous phase I clinical trials utilizing irradiated cells to prevent permanent engraftment. METHODS: To provide NK-92 cells with pre-determined tumor-cell specificity, we generated a lentiviral second generation chimeric antigen receptor (CAR) construct (5.28.z) employing the ErbB2 (HER2)-specific scFv(FRP5) antibody fragment for target cell recognition, and human CD28-CD3 ζ as a composite signaling moiety. An ErbB2-specific single cell clone (NK-92/5.28.z) was isolated, which showed high and selective cytotoxicity towards ErbB2-expressing tumor cells of various origins in vitro. We evaluated the cytotoxicity of NK-92/5.28.z cells against a panel of glioblastoma cell lines and primary glioblastoma cultures with different levels of Erb2 expression in vitro and in vivo. RESULTS: 13 out of a total of 15 established glioblastoma cell lines and 5 out of 5 primary glioblastoma cell lines were specifically lysed by NK-92/5.28.z cells, although to varying degrees. ErbB2 expression was necessary for cytotoxicity of NK-92/5.28.z cells towards glioblastoma cells, and ectopic overexpression of ErbB2 enhanced their cytotoxicity. In subcutaneous glioblastoma xenograft models, injections of NK-92/5.28.z induced prolonged regression in NOD-scid/gamma (NSG) mice with grafts of LN-319 cells and retarded the growth of LNT-229 grafts. In an orthotopic intracranial model utilizing LN-319 cells, tumor size in mice intratumorally injected with NK-92/5.28.z cells weekly was substantially smaller compared to controls as assessed by MR imaging. Injections of NK-92/5.28.z cells also conferred an impressive advantage in symptom free survival in two independent experiments (median 73 days in controls versus 140 days in NK-92/5.28.z treated animals in experiment A, p < 0,05, and median 77 days in controls versus 163 days in NK-92/5.28.z treated animals in experiment B, p < 0,01). In preparation of a phase I trial, GMP-compliant protocols for expansion of the NK-92/5.28.z line were established. CONCLUSIONS: Adoptive immunotherapy with application of ErbB2-specific NK-92/5.28.z cells may be a promising new immunotherapy approach for ErB2 positive glioblastoma. A phase I trial for glioblastoma patients with local injections of NK-92/5.28.z cells is in preparation.
Abstract P6-04-02: Profiling of BRCA1 Mutated Breast Tumours Using a Breast Cancer Specific Microarray To Identify a Profile of BRCAl-Deficiency
Authors: G Irwin, E Lamers, F McDyer, J Mulligan, F Couch, R Kennedy, P Harkin, J. Quinn
Journal: Cancer Research (2010)

Abstract Background The BRCA 1 tumour suppressor gene is mutated in a significant proportion of hereditary breast cancer cases. Additionally, downregulation of BRCA1 mRNA and protein expression is reported in approximately one third of sporadic breast cancers. BRCA1 is strongly implicated in the maintenance of genomic stability by its involvement in multiple cellular pathways including: DNA damage signalling, DNA repair, cell cycle regulation, protein ubiquitination, chromatin remodelling, transcriptional regulation and apoptosis. To date, gene expression profiling has identified: (1) at least five breast cancer subtypes and (2) that BRCA1 mutant tumours segregate with basal-like breast cancers. These studies also provide evidence that breast cancers with germline mutations in BRCA1 are different from non BRCA1-related tumours. The main aim of this study is to investigate the underlying biology of BRCA1-mutated breast cancer. Methods Extensive gene expression profiling and data analysis were performed on a cohort of 70 FFPE (Formalin Fixed Paraffin Embedded) derived BRCA 1 mutated breast tumours and matched sporadic controls using the Almac Breast Cancer DSATM research tool. Functional analysis was performed with DAVID and METACORE. Validation of gene targets was performed by qRT-PCR and Western blotting. Results A list of differentially expressed transcripts has been derived from the comparison of these BRCA1 mutant breast tumours and matched sporadic controls. Functional analysis of this gene list has identified the key genes and molecular pathways that are deregulated in these tumours. BRCA1 deficiency was associated with deregulation of pathways involved in: (1) immune response, (2) metastasis and invasion, (3) cytoskeletal remodelling, (4) spindle assembly and chromosome separation, (5) apoptosis and survival. Validation of the key genes underlying this BRCA1-deficient breast cancer profile has been performed. Conclusions This approach has revealed a set of transcripts that could potentially be used to identify both hereditary and sporadic breast cancer patients with BRCA1- deficiency. The ability to perform gene expression profiling from FFPE derived breast tissue could also have significant clinical application. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-04-02.
SP0103 Treatment of hemophagocytic lymphohistiocytosis
Authors: J.-I. Henter
Journal: Annals of the Rheumatic Diseases (2013)

Hemophagocytic lymphohistiocytosis (HLH) comes in two forms, a primary, genetic form and a secondary form. The primary form is caused by mutations in genes encoding proteins required for lymphocyte cytotoxicity and has a median survival of 1-2 months without adequate therapy. The secondary forms of HLH are often associated with infections, malignancies or systemic autoimmune diseases. In primary HLH, also called familial hemophagocytic lymphohistiocytosis (FHL), survival has increased from around 0% to around 55% in the international HLH studies run by the HLH Study Group of the Histiocyte Society. These treatments include chemo-immunotherapy with etoposide, corticosteroids, and cyclosporine A (CSA), and in primary HLH also hematopoietic stem cell transplant (HSCT). While milder forms of secondary HLH may respond to corticosteroids, CSA, and/or intravenous immunoglobulins (IVIG), severe secondary HLH will often require the addition of etoposide. Macrophage activation syndrome (MAS), also called rheuma-associated hemophagocytic lymphohistiocytosis (Rh-HLH), is a severe complication of systemic autoimmune disorders. MAS/Rh-HLH has several clinical and laboratory similarities to other forms of HLH, and is potentially life threatening. They may also be associated with potentially severe CNS affection. However, despite the success of using etoposide in other forms of HLH, the experience on the use etoposide in MAS/Rh-HLH is limited. We will report our experience at the Karolinska Children's Hospital on the care of patients with severe MAS/Rh-HLH, some of whom had severe CNS-involvement, where the clinical development prompted us to initiate chemo-immunotherapy including etoposide. All patients responded well and without severe side effects to weekly etoposide (75-100 mg/m<sup>2</sup>), as a complement to pulses with high-dose methylprednisolone. We conclude that chemo-immunotherapy including etoposide is worth considering in severe MAS/Rh-HLH and that initiation of this therapy should not be delayed in severely sick patients. <h3>Disclosure of Interest</h3> J.-I. Henter Consultant for: NovImmune SA
Vocal coordination and vocal imitation: A role for mirror neurons?
Authors: John D. Newman
Journal: Behavioral and Brain Sciences (2014)

Abstract Some birds and mammals have vocal communication systems in which coordination between individuals is important. Examples would include duetting or antiphonal calling in some birds and mammals, rapid exchanges of the same vocalization, and vocal exchanges between paired individuals and other nearby pairs. Mirror neurons may play a role in such systems but become functional only after experience.
Prolonged controlled mechanical ventilation in humans triggers myofibrillar contractile dysfunction and myofilament protein loss in the diaphragm
Authors: Sabah N A Hussain, Anabelle S Cornachione, Céline Guichon, Auday Al Khunaizi, Felipe de Souza Leite, Basil J Petrof, Mahroo Mofarrahi, Nikolay Moroz, Benoit de Varennes, Peter Goldberg, Dilson E Rassier
Journal: Thorax (2016)

<h3>Background</h3> Prolonged controlled mechanical ventilation (CMV) in humans and experimental animals results in diaphragm fibre atrophy and injury. In animals, prolonged CMV also triggers significant declines in diaphragm myofibril contractility. In humans, the impact of prolonged CMV on myofibril contractility remains unknown. The objective of this study was to evaluate the effects of prolonged CMV on active and passive human diaphragm myofibrillar force generation and myofilament protein levels. <h3>Methods and results</h3> Diaphragm biopsies were obtained from 13 subjects undergoing cardiac surgery (control group) and 12 brain-dead organ donors (CMV group). Subjects in each group had been mechanically ventilated for 2–4 and 12–74 h, respectively. Specific force generation of diaphragm myofibrils was measured with atomic force cantilevers. Rates of force development (K<sub>act</sub>), force redevelopment after a shortening protocol (K<sub>tr</sub>) and relaxation (K<sub>rel</sub>) in fully activated myofibrils (pCa<sup>2+</sup>=4.5) were calculated to assess myosin cross-bridge kinetics. Myofilament protein levels were measured with immunoblotting and specific antibodies. Prolonged CMV significantly decreased active and passive diaphragm myofibrillar force generation, K<sub>act</sub>, K<sub>tr</sub> and K<sub>rel</sub>. Myosin heavy chain (slow), troponin-C, troponin-I, troponin-T, tropomyosin and titin protein levels significantly decreased in response to prolonged CMV, but no effects on α-actin, α-actinin or nebulin levels were observed. <h3>Conclusions</h3> Prolonged CMV in humans triggers significant decreases in active and passive diaphragm myofibrillar force generation. This response is mediated, in part, by impaired myosin cross-bridge kinetics and decreased myofibrillar protein levels.
Mutagens in Meat Under Fire
Authors: R. Sinha
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Mutagens in Meat Under Fire Get access Rashmi Sinha, Ph.d. Rashmi Sinha, Ph.d. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 5, 4 March 1992, Pages 290–292, https://doi.org/10.1093/jnci/84.5.290 Published: 04 March 1992
Changing Incidence of Breast Cancer
Authors: A. GEASS, R. N. HOOVER
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Changing Incidence of Breast Cancer Get access ANDREW GEASS, ANDREW GEASS 1Center for Health Research Kaiser Permanente3414 North Kaiser Center Dr., Portland, OR 97227 Search for other works by this author on: Oxford Academic PubMed Google Scholar ROBERT N. HOOVER ROBERT N. HOOVER 2Environmental Epidemiology Branch Division of Cancer Etiology National Cancer InstituteExecutive Plaza North, Rm. 443National Institutes of HealthBethesda, MD 20892 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 13, 7 September 1988, Pages 1076–1077, https://doi.org/10.1093/jnci/80.13.1076-a Published: 07 September 1988
Fracture risk in women with breast cancer: can baseline assessment of risk be used to guide treatment?.
Authors: P Hadji, M Kalder, M Ziller, V Ziller, U Albert
Journal: Cancer Research (2009)

Abstract Abstract #6130 Background: Breast cancer (BC) therapies have been associated with decreases in bone health. Recent studies have shown that BC survivors have a 31% increased fracture risk compared with their peers, elevating the importance of monitoring bone health in women diagnosed with BC. Bone mineral density (BMD) has been the standard used by clinical guidelines (WHO, ASCO) to direct therapeutic decisions. However, emerging guidelines place BMD in the context of several other clinical risk factors that have been correlated with overall fracture risk. This retrospective, case-controlled study uses current and emerging guidelines to estimate the percentage of patients with newly diagnosed breast cancer who may be at increased risk for fracture and who require preventive therapy. Methods: Baseline data from 88 pre- and 402 postmenopausal women (PMW) with BC were compared with data from an equal number of healthy age- and body mass index-matched women. BMD was assessed by 2 methods; dual-energy x-ray absorptiometry (DXA) at the lumbar spine (LS) and total hip, and quantitative ultrasonometry (QUS) at the os calcaneus and phalanges. Baseline BMD measurements were collected at a mean duration of 15 and 242 days after diagnosis of cancer in pre- and PMW, respectively. Results: Baseline LS and total hip BMD was similar between the healthy control groups and patients with BC. Among estrogen receptor-positive (ER+) BC patients, 18.8% of premenopausal women and 36.9% of PMW were osteopenic, and 8.9% of PMW were osteoporotic (according to LS BMD). Among ER+ PMW with BC, 15.9% of patients &amp;gt; 65 years of age, 8.3% of patients 55 to 65 years of age, and 1.4% of patients &amp;lt; 55 years of age had osteoporosis. Only 9% of ER+ PMW with BC would have received bone-protective therapy using the BMD limits (T-score ≤ –2.5) set by ASCO treatment guidelines. Based solely on clinical risk factors (eg, if DXA were not available), 6.5% of patients would have been identified for bone-protective therapy. When clinical risk factors and BMD were both used in the fracture-risk assessment, 28.6% of women would have been eligible for bone-protective therapy. Overall, therapy based on ASCO guidelines was estimated to prevent 18% of fractures, whereas combining risk factors and BMD would prevent more than 45% of fractures. Conclusions: Current treatment thresholds seem to inadequately identify patients who would benefit from bone-protective therapy. The results presented here support the use of overall fracture risk assessment in PMW with breast cancer. Using both BMD and clinical risk factors may more effectively identify patients at risk for fracture, although further studies are needed. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6130.
Abstract 796: Novel mechanisms of drug resistance in leukemia cells associated with changes in HoxA9 and microRNA expression
Authors: Tsui-Ting Ho, Xiaolong He, William T. Beck
Journal: Cancer Research (2012)

Abstract The acquisition of resistance to anticancer drugs is a key obstacle to successful cancer therapy. An increasing number of studies have investigated the roles of microRNAs in drug resistance. We previously reported that the upregulation of miR-135b and miR-196b correlated positively with acquired drug resistance in the human T-cell leukemia cell line, CCRF-CEM (CEM), and that the elevation of expression of these two microRNAs in response to the DNA damaging agent etoposide appears to be histiotype-specific (T-T Ho et al, Proceedings of the 102nd Annual Meeting of the AACR 2011). To develop a mechanistic understanding of why these microRNAs are differentially expressed, we have studied miR-196b, which maps between the HoxA9 and HoxA10 genes on chromosome 7p15.2, suggesting that miR-196b and HoxA genes might be co-activated. Indeed, we found upregulation of HoxA9 mRNA after short-term (48 h) exposure of CEM cells to the topoisomerase II inhibitors etoposide and doxorubicin. Of note, we also found that HoxA9 is constitutively overexpressed in multidrug-resistant CEM/VM-1-5 cells. Of interest, we found that HoxA9 is clearly associated with drug resistance, as knockdown of HoxA9 using esiRNA (a heterogeneous mixture of siRNAs that all target the same mRNA) partially sensitized multidrug-resistant CEM/VM-1-5 cells to etoposide. This indicates that the expression of miR-196b is linked to HoxA gene transcription and to drug responsiveness. We subsequently confirmed that the expression of HoxA9 mRNA follows the same pattern in other leukemia cells. For example, both miR-196b and HoxA9 are upregulated in response to short-term etoposide exposure in HL-60 (acute promyelocytic leukemia), but not in solid tumor-derived MCF7 (breast cancer cell line) and its etoposide-resistant subline MCF7/VP, or Rh30 (rhabdomyosarcoma cell line) and its etoposide-resistant subline, Rh30/V1. We are presently assessing the role of HoxA9 in drug resistance in other leukemia cell lines and investigating the mechanistic basis for this effect. In summary, we report here a novel mechanism of anticancer drug resistance in leukemia cells that is associated with HoxA9 and specific changes in microRNA expression. This is the first report that HoxA9 may impact on anticancer drug resistance. (Supported in part by R01 CA40570 from NCI to WTB, and in part by UIC.) 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 796. doi:1538-7445.AM2012-796
Occurrence and Characteristics of Keap1-Mutations in Patients with Non-Small Cell Lung Cancer (Nsclc)
Authors: R. Frank, M. Scheffler, S. Michels, K. König, S. Merkelbach-Bruse, M. Serke, Y. Ko, U. Gerigk, T. Geist, L.C. Heukamp, R. Büttner, J. Wolf
Journal: Annals of Oncology (2014)
Genome-Wide shRNA Screen Implicates Mitogen Activated Protein Kinase (MAPK) Pathway In Glucocorticoid Resistance In Acute Lymphoblastic Leukemia
Authors: Jones L. Courtney, Christy M. Gearheart, Fosmire Susan, Wang Jinhua, Danielle S. Bitterman, Teena Bhatla, Wallace Bourgeois, Christopher C. Porter, William L. Carroll
Journal: Blood (2013)
Mesenteric Lymphoid Hamartoma Associated with Chronic Hypoferremia, Anemia, Growth Failure and Hyperglobulinemia
Authors: R. C. Neerhout, W. Larson, P. Mansur
Journal: New England Journal of Medicine (1969)

A mesenteric lymphoid hamartoma was found in a 16-year-old boy associated with growth arrest, chronic hypochromic anemia and hypergammaglobulinemia. Radioisotope tracer scanning technics revealed the lesion. After removal of the tumor all three findings improved in a short time. No definitive immunologic or infectious cause was elucidated. The finding of a foreign-body granuloma in the tumor was noted, but the etiologic role could not be determined.