tbuckley/cabot-search huggingface dataset:
Case 39-2005
Authors: Edward T. Ryan, Donna Felsenstein, Suzanne L. Aquino, John A. Branda, John G. Morgan
Journal: New England Journal of Medicine (2005)

A 63-year-old woman from Cameroon was referred to infectious-disease specialists because of a positive serologic test for syphilis and persistent peripheral-blood eosinophilia. In addition, a routine chest radiograph had shown a dilated aorta with calcification. Stool examination disclosed parasitic infections, which were treated, but eosinophilia persisted. A diagnostic test was performed.
Abstract 1249: Atrial Septal Defects Caused By Endocardial Specific Deficiency Of Transcription Factor Tbx5
Authors: Mona Nemer, Mathieu Nadeau, Romain Georges, Brigitte Laforest, Chantal Lefebvre, Gregor Andelfinger, Benoit Bruneau, Pierre Paradis
Journal: Circulation (2007)

In human, mutations in transcription factor Tbx5 cause the Holt Oram syndrome (HOS) characterized by forelimb and a large spectrum of cardiac malformations ranging from simple arrhythmia to complex...
Abstract 1724: Inhibition of the PI3K and mTOR pathways reverses gemcitabine resistance in pancreatic cancer
Authors: Vincent Chung, Shikha Gaur, David Ann, Yun Yen
Journal: Cancer Research (2011)

Abstract BACKGROUND: Despite chemotherapy, survival for most patients with pancreatic cancer is less than one year. These dismal statistics reflect the lack of effective therapy. Understanding the molecular pathways that drive cancer growth may help target our therapy. Over 90% of pancreatic cancers are K-ras mutant which activates the PI3K/AKT pathway and signals downstream to mTOR leading to cell growth, proliferation and survival. We explored the combination of gemcitabine and BEZ235, a novel dual PI3K/mTOR inhibitor, in pancreatic cancer cell lines. METHODS: Cytotoxicity assays were performed utilizing the CellTiter-96-Aqueous-One-Solution-Cell-Proliferation-Assay-(MTS) from Promega in K-ras mutant MIA PaCa-2 pancreatic cancer cell lines. We generated gemcitabine resistant cell lines by serial passage of cells with increasing concentrations of drug. We utilized the CalcuSyn program by Biosoft to quantify synergism or antagonism with drug combinations. We also collected cells 6 hours after drug treatment for analysis of phosphorylated proteins. RESULTS: MIA PaCa-2 wild-type and gemcitabine resistant cells were treated with 100, 50 and 25 nM of either gemcitabine, BEZ235 or the combination of both. At the 100 nM dose, cell viability of the wild-type cells was 66%, 55% and 39% respectively. In the gemcitabine resistant cells, cell viability was 84%, 63% and 44%. The combination index was 0.51 in the wild-type cells and 0.46 in the gemcitabine resistant cells indicating synergy in both cell lines. In both cell lines, p-S6K and p-AKT levels increased with gemcitabine treatment which was abrogated by treatment with BEZ-235. Interestingly, in the gemcitabine resistant cells, there appeared to be significantly increased levels of p-MEK1 compared to control. CONCLUSION: Because pancreatic cancer remains resistant to current therapies despite recent advances in the development of molecular targeted therapies, there is an urgency to understand these pathways. We showed that the combination of gemcitabine and BEZ235 is synergistic in both cell lines but cell viability still remains high at 39% and 44% respectively. Combination with a MEK inhibitor may help to increase cell apoptosis and studies are on-going. 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 1724. doi:10.1158/1538-7445.AM2011-1724
BENEFICIAL EFFECTS OF BLOOD PRESSURE REDUCTION ON AORTIC STIFFNESS AND CENTRAL HEMODYNAMICS IN PATIENTS WITH METABOLIC SYNDROME
Authors: Panagiota Pietri, Charalambos Vlachopoulos, Dimitris Terentes-Printzios, Nikolaos Ioakeimidis, Mahmoud Abdelrasoul, Ioanna Gourgouli, Panagiotis Xaplanteris, Christodoulos Stefanadis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2015)
DR-07 * TARGETING EGFR-VIII WITH DICHLOROACETATE IN TEMOZOLOMIDE RESISTANT GLIOBLASTOMA MODELS
Authors: K. K. Velpula, S. Asuthkar, J. D. Lathia, A. J. Tsung
Journal: Neuro-Oncology (2014)

Epidermal growth factor receptor (EGFR) gene amplification and its subsequent over-expression is the most frequent genetic alteration associated with glioblastoma (GBM) approximating 40%. EGFR amplification is accompanied by a gene rearrangement that overexpresses the receptor variant III (EGFRvIII) characterized by an in-frame deletion of 801 bp of coding sequence from exons 2-7. Our in vitro preliminary studies conducted using U373 cell lines stably expressing EGFRvIII (U373vIII) conferred increased proliferation and invasiveness when compared to control. Temozolomide (TMZ) resistance in this context is a well-known concept, where high initial response is met with eventual failure and tumor propagation. We thus generated an aggressive TMZ resistance model for U373vIII cells (U373vIII-TMZ-R) by continual exposure to 150uM TMZ for 6 months. After the initial phase of cell death in the majority and prolonged lag in replication, the eventual surviving U373vIII-TMZ-R colonies showed identical morphology and proliferation potential of the parent U373vIII. This resulted in a cell line mimicking the actual growth potential of recurrent GBM. We have previously shown that dichloroacetic acid (DCA) reduces EGFR expression in GBMs. Since EGFRvIII expression displays an aggressive phenotype yet remains tumor specific, we hypothesize studying DCA alone or in combination with dasatinib, an inhibitor of EGFR subcellular translocation, in U373vIII and U373vIII-TMZ-R cell lines. By more accurately depicting the status of GBM at the time of recurrence after standard of care chemotherapy treatment, the investigation of DCA will augment and possibly redefine our current understanding of resistance mechanisms and establish novel methods of circumventing this pervasive phenomena.
Abstract 1391: Simultaneous knockdown of MMP-9 and uPAR/cathepsin B retards α9β1 integrin-mediated cell migration via SSAT and potassium channel pathway in glioma xenografts
Authors: Krishna Kumar Veeravalli, Shivani Ponnala, Chandramu Chetty, Jasti S. Rao
Journal: Cancer Research (2011)

Abstract The α9β1 integrin accelerates cell migration through the binding of α9 cytoplasmic domain to spermidine/spermine-N1-acetyltransferase (SSAT), which catalyzes the catabolism of higher order polyamines, spermidine and spermine, to the lower order polyamine, putrescine. Our recent studies have clearly demonstrated the role of α9β1 integrin in MMP-9, uPAR and cathepsin B-mediated cell migration in glioma xenograft cells (4910 and 5310). In the present study, we aimed to investigate the underlying mechanisms through which MMP-9 and uPAR/cathepsin B knockdown inhibits α9β1 integrin-mediated migration in glioma xenograft cells. Western blot, RT-PCR and immunofluorescence analyses revealed downregulation of SSAT levels both at the mRNA and protein levels by siRNA-mediated simultaneous knockdown of MMP-9 and uPAR/cathepsin B. In addition, we noted a prominent reduction in the expression of SSAT with MMP-9 and uPAR/cathepsin B knockdown in the tumor regions of 5310 injected nude mice brains. Co-localization of α9 integrin with kir4.2, an inward rectifier potassium channel, was observed in both 4910 and 5310 xenograft cells. However, MMP-9 and uPAR/cathepsin B knockdown in these cells prominently reduced the co-localization of α9 with kir4.2. Interestingly, MMP-9, uPAR and cathepsin B overexpression in these xenograft cells significantly elevated SSAT mRNA and protein levels. Further, the migratory potential of MMP-9/uPAR/cathepsin B overexpressed 4910 and 5310 cells was not affected by either glybenclamide or tertiapin-Q but instead was significantly inhibited by either barium or kir4.2 siRNA treatments. Taken together, our results from the present and earlier studies clearly demonstrate that α9β1 integrin-mediated cell migration utilizes SSAT and kir4.2 potassium channel pathway, and inhibition of the migratory potential of these glioma xenograft cells by simultaneous knockdown of MMP-9 and uPAR/cathepsin B could be attributed to the reduced SSAT levels and co-localization of α9 integrin with kir4.2 potassium channels. Based on these findings, we conclude that the simultaneous knockdown of MMP-9 and uPAR/cathepsin B retards SSAT and potassium channel pathway-mediated cell migration through the α9β1 integrin. 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 1391. doi:10.1158/1538-7445.AM2011-1391
Doppler ultrasound-guided endoscopic needle-knife treatment of an anastomotic stricture following subtotal colectomy
Authors: Y. Li, B. Shen
Journal: Endoscopy (2011)

A 28-year-old woman presented to our clinic with a 2-month history of dyschezia after subtotal colectomy and ileorectal anastomosis (IRA). Sigmoidoscopy showed a 5-mm long, nonulcerated IRA stricture ([Fig. 1 a]), which was not traversable with a GIF-H180 gastroscope (Olympus, Tokyo, Japan).
Abstract B39: Nkx2-1 down-regulation underlies lung adenocarcinoma progression towards malignancy
Authors: Monte M. Winslow, Talya L. Dayton, Eric L. Snyder, Derek Y. Chiang, Caroline Kim, Roel Verhaak, Denise Crowley, Roderick T. Bronson, Matthew Meyerson, Tyler E. Jacks
Journal: Cancer Research (2009)

Abstract Metastasis leads to most cancer-related deaths, yet many of the molecular determinants and their mechanisms of action remain unknown. To uncover genetic programs that control the progression of lung adenocarcinoma towards malignancy, we developed and analyzed an autochthonous mouse model of this disease. Lentiviral-mediated somatic activation of oncogenic Kras and deletion of p53 in the lung epithelial cells of genetically-engineered mice induces the development of widely metastatic lung adenocarcinoma. Using cell lines derived from primary tumors and metastases, we determined the genome-wide expression changes that embody a metastatic profile. Here we show that the NK-2 related homeobox transcription factor, Nkx2-1 (Ttf-1/Titf1), controls cancer progression and malignant phenotypes. Lung adenocarcinoma progression in our model is associated with loss of Nkx2-1 expression, consistent with the poor prognosis for patients with NKX2-1 negative lung adenocarcinoma. In cells derived from non-metastatic tumors, shRNA-mediated reduction of Nkx2-1 results in increased metastatic potential in vivo and phenotypic alterations in vitro consistent with increased metastatic ability. Interrogation of Nkx2-1 regulated genes and analysis of tumors at defined stages of development indicate that Nkx2-1 may constrain tumors by repressing embryonically-restricted transcriptional regulators and components of the extracellular matrix. Citation Information: Cancer Res 2009;69(23 Suppl):B39.
Effect of Tracheostomy Tubes on the Resistance to Breathing and Pulmonary Resistance in Patients with Poliomyelitis
Authors: B. G. Ferris, David S. Pollard
Journal: New England Journal of Medicine (1960)

WHEN patients have severe airway obstruction or swallowing difficulties, as may occur with bulbar poliomyelitis, the insertion of a tracheostomy tube may be required to ensure a clear airway, to reduce respiratory resistance and to minimize aspiration. It has been recommended that as large a tube as possible be inserted,1 to maintain the internal diameter close to that of the trachea and not to increase the resistance to breathing unduly as the patient breathes through the tracheostomy tube.When patients are weaned from tracheostomy tubes, progressively smaller tubes are inserted over a period of days or weeks. To help the . . .
Multiple Complex Coronary Plaques in Patients with Acute Myocardial Infarction
Authors: James A. Goldstein, Demetris Demetriou, Cindy L. Grines, Mark Pica, Mazen Shoukfeh, William W. O'Neill
Journal: New England Journal of Medicine (2000)

Acute myocardial infarction is believed to be caused by rupture of an unstable coronary-artery plaque that appears as a single lesion on angiography. However, plaque instability might be caused by pathophysiologic processes, such as inflammation, that exert adverse effects throughout the coronary vasculature and that therefore result in multiple unstable lesions.To document the presence of multiple unstable plaques in patients with acute myocardial infarction and determine their influence on outcome, we analyzed angiograms from 253 patients for complex coronary plaques characterized by thrombus, ulceration, plaque irregularity, and impaired flow.Single complex coronary plaques were identified in 153 patients (60.5 percent) and multiple complex plaques in the other 100 patients (39.5 percent). As compared with patients with single complex plaques, those with multiple complex plaques were less likely to undergo primary angioplasty (86.0 percent vs. 94.8 percent, P = 0.03) and more commonly required urgent bypass surgery (27.0 percent vs. 5.2 percent, P < or = 0.001). During the year after myocardial infarction, the presence of multiple complex plaques was associated with an increased incidence of recurrent acute coronary syndromes (19.0 percent vs. 2.6 percent, P < or = 0.001); repeated angioplasty (32.0 percent vs. 12.4 percent, P < or = 0.001), particularly of non-infarct-related lesions (17.0 percent vs. 4.6 percent, P < or = 0.001); and coronary-artery bypass graft surgery (35.0 percent vs. 11.1 percent, P < or = 0.001).Patients with acute myocardial infarction may harbor multiple complex coronary plaques that are associated with adverse clinical outcomes. Plaque instability may be due to a widespread process throughout the coronary vessels, which may have implications for the management of acute ischemic heart disease.
P41 The Role of Obesity in Unexplained Breathlessness and Exercise Intolerance Evaluated by Cardio-Pulmonary Exercise Tests (CPET)
Authors: P James, Z Mangera, S Isse, B Ibrahim, R Gupta, K Wadsworth, D Mukherjee, B Yung, JT Samuel
Journal: Thorax (2012)

<h3>Introduction</h3> Resting cardio-respiratory investigations may not indicate a cause for unexplained breathlessness and exercise intolerance (UB&amp;EI). CPET is an objective, non-invasive tool to measure cardio-respiratory function during exercise. Increased BMI can contribute to exercise intolerance. We present a review of CPET in evaluating patients referred to our centre with UB&amp;EI. <h3>Methods</h3> We did retrospective analysis of CPET results in patients referred to our centre over a two year period (2010 to 2012). All patients had resting cardio-respiratory function tests including coronary angiogram and stress echo cardiogram in some cases. CPET was performed by maximum symptom limited incremental protocol on a cycle ergometer starting with 3 minutes of rest followed by 3 minutes of unloaded cycling and subsequent increase in workload as per ATS recommendations. We defined obesity as BMI of ≥30 kg/m2. Tests were supervised by two qualified physiologists and reported by a consultant chest physician. <h3>Results</h3> Of 243 CPET tests performed during this period, 68 (28%) were done to evaluate UB&amp;EI. 38 patients(56%) were obese. Overall, obesity was the sole cause of UB&amp;EI in 22 patients (32%) and was a contributory factor in a further 15 patients (22%). In the obese subgroup, it was the sole cause in 21 patients (55%) and contributory in a further 16 patients (43%). Being overweight (BMI 29) was the sole cause of unexplained breathlessness in 1 non-obese patient. Obesity appeared to be the major contributing factor for UB&amp;EI even when present with other factors. In 23 patients (34%) more than one contributory factor was present (Cardiovascular/Respiratory/VQ mismatch/physical de-conditioning/functional). Physical de-conditioning was the sole cause in 5 patients (7%) and Hyperventilation in 2 patients (3%). <h3>Conclusion</h3> While the causes of UB&amp;EI are multi factorial, in our study obesity was a contributory and often key factor in over half the patients. In the obese subgroup, being overweight was the sole factor in over half and played a contributory role in almost all patients. CPET is a useful test to determine specific causes of UB&amp;EI when resting cardio-respiratory tests are non-contributory and can help with reassurance, dietary advice and exercise prescription.
Impacted gastroscope in the esophagus
Authors: Yoshitaka Imoto, Toshi Takaoka, Naoki Muguruma, Satoshi Teramae, Hirohiko Shinomiya, Satoshi Wada, Tetsuji Takayama
Journal: Endoscopy (2014)

An 81-year-old woman with hypertension was admitted to our hospital. Because she had been suffering from persistent nausea, esophagogastroduodenoscopy was performed. During the procedure, a large hiatal hernia was identified, and the scope was successfully introduced into the distal stomach. After several attempts to intubate the duodenum, the scope slipped back into the esophagus as it retroflexed and resisted straightening ([Fig. 1 a]), and a strong resistance was felt immediately. We attempted unsuccessfully to move the scope back and forth ([Fig. 1 b]). Under fluoroscopy, the tip of the scope was confirmed to be acutely angulated with distortion and impacted in the lower esophagus ([Fig. 2]). The retroflexed scope was withdrawn slowly under fluoroscopy and removed successfully in this position. Subsequent esophagoscopy showed a shallow trauma in the lower esophagus, but computed tomography of the chest and neck revealed no air density in the soft tissue.
Abstract 221: p21-activated kinase 1 (Pak1) phosphorylates BAD directly at serine 111 <i>in vitro</i> and indirectly through Raf-1 at serine 112
Authors: Jeffrey M. Field, Diana Z. Ye, Shenghao Jin, Ya Zhou
Journal: Cancer Research (2012)

Abstract Cell survival depends on the balance between protective and apoptotic signals. When the balance of signals tips towards apoptosis, cells undergo programmed cell death. This balance has profound implications in diseases including cancer. Oncogenes and tumor suppressors are mutated to promote cell survival during tumor development, and many chemotherapeutic drugs kill tumor cells by stimulating apoptosis. BAD is a pro-apoptotic member of the Bcl-2 family of proteins, which can be phosphorylated on numerous sites to modulate binding to Bcl-2 and 14-3-3 proteins and inhibit its pro-apoptotic activities. One of the critical phosphorylation sites is the serine 112 (S112), which can be phosphorylated by several kinases including Pak1. We mapped the Pak phosphorylation sites by making serine to alanine mutations in BAD and testing them as substrates in in vitro kinase assays. We found that the primary phosphorylation site is not S112 but serine 111 (S111), a site that is sometimes found phosphorylated in vivo. In transfection assays of HEK293T cells, we showed that Pak1 required Raf-1 to stimulate phosphorylation on S112. Mutating either S111 or S112 to alanine enhanced binding to Bcl-2, but the double mutant S111/112A bound better to Bcl-2. Moreover, BAD phosphorylation at S111 was observed in several other cell lines, and treating one of them with the Pak1 inhibitor 2,2α-Dihydroxy-1,1α-dinaphthyldisulfide (IPA-3) reduced phosphorylation primarily at S112 and to a smaller extent at S111, while Raf inhibitors only reduced phosphorylation at S112. Together, these findings demonstrate that Pak1 phosphorylates BAD directly at S111, but phosphorylated S112 through Raf-1. These two sites of BAD serve as redundant regulatory sites for Bcl-2 binding. 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 221. doi:1538-7445.AM2012-221
SC-34 * A NOVEL VEGF-RESPONSIVE lincRNA ORCHESTRATES GLIOMA STEM CELL-MEDIATED ANGIOGENESIS IN GLIOBLASTOMA
Authors: J. Wang, M. Wu, J. Karamchandani, P. Marsden, S. Das
Journal: Neuro-Oncology (2014)

Angiogenesis is a hallmark feature of glioblastoma. Recent data suggests that glioma stem cells (GSCs) contribute to pathologic angiogenesis through transdifferentiation into endothelial cells and vascluar pericytes. We have identified a VEGF-A-responsive lincRNA near the VEGFR1 gene, which we named LIVE1 (lincRNA-VEGFR1), that directs vascular network formation and regulates gene expression profiles in normal endothelial cells. Furthermore, LIVE1 is highly expressed in glioblastoma and enriched in CD133+ GSCs and CD133 + CD144+ neoplastic endothelial precursor cells. LIVE1 binds to the promoter of multiple VEGF targets and, through interactions with RNA helicase A and PARP1, facilitates their transciption in GSCs. LIVE1 expression directs GSCs toward a vascular pericyte fate choice. Depletion of LIVE1 in a xenograft model of glioblastoma results in a decrease in vascular denisty and perfusion, loss of pericyte coverage, and disruption of the vascular niche. Our findings demonstrate a novel role of lincRNAs in the orchestration of tumor angiogenesis, and reveal a new possible therepautic target.
Increased Fluorine-18 Fluorodeoxyglucose Uptake in the Right Atrial Wall in a Patient With Atrial Fibrillation
Authors: HIROFUMI FUJII, SEIEI YASUDA, MICHIRU IDE, WAKOH TAKAHASHI, AKIRA SHOHTSU, ATSUSHI KUBO
Journal: Clinical Nuclear Medicine (1999)

A 48-year-old woman was included in an oncology screening program using fluorine-18 fluorodeoxyglucose whole-body PET. The right atrial wall was imaged clearly on PET images. It was speculated that the metabolism of glucose in the right atrial wall was increased, because the patient had atrial fibrillation.
Mouse Mammary Tumor Expressing <i>MMTV-SmoM2</i> as a Tool To Study Lung Metastasis.
Authors: R. Moraes, J. Landua, M. Lewis
Journal: Cancer Research (2009)

Abstract Background: The hedgehog signaling network regulates pattern formation, proliferation, cell fate and stem/progenitor cell self-renewal in many organs. Altered hedgehog signaling is implicated in 20-25% of all cancers, including breast cancer. We demonstrated previously that expression of activated human SMO (SmoM2) under the mouse mammary tumor virus (MMTV) promoter in transgenic mice leads to increased proliferation, altered differentiation, ductal dysplasias, and increase the proportion of mammosphere-forming cells, with reduction of stem cell pool, in virgin mice.Material and Methods: We isolated and established a tumor line from this mouse line (named TU505). To investigate the role of hedgehog signaling in mammary tumorigenesis and metastasis we transplanted TU505 fragments (1-2mm3) to a cleared fat pad of 3 week-old mice. After 10 days we removed the primary tumors and let the mice recover for another 3 weeks, which at that time the animals were sacrificed and the lungs removed under stereomicroscope. The lung metastases visible at naked eyes were snap frozen for RNA isolation, and the remaining lungs fixed in 4%PFA.Results: The TU505 is a tumor expressing MMTV-SmoM2, triple-negative (ER-, PR-, and HEB2-), hormone independent, highly metastatic to the lung, and with a robust expression of Ptch1, Ptch2, Smo, Gli2, and Gli3. The gene expression of primary tumor and metastasis are compared.Discussion: The hedgehog signaling networks has been associated with metastasis. The TU505 is a strong tool to study mammary gland tumorigenesis and metastasis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2165.