tbuckley/cabot-search huggingface dataset:
Tc-99m-Labeled Leukocyte and Skeletal Scintigraphy in a Case of Pelvic Osteomyelitis
Authors: GEOFFREY R. STOREY, WARWICK BRUCE, MATTHEW KINCHINGTON, JOHN S. MAGNUSSEN, KEVIN C. ALLMAN, HANS VAN DER WALL
Journal: Clinical Nuclear Medicine (1998)

Osteomyelitis in red marrow-containing regions of the axial skeleton may produce photopenic defects on radiolabeled leukocyte scintigraphy. A 47-year-old man underwent elective penile reconstructive surgery. The postoperative course was complicated by wound infection, and the patient reported progressive anterior pelvic pain despite antibiotic therapy. A Tc-99m MDP bone scan revealed focal hyperemia and increased tracer uptake in the body of the pubis and pubic crest bilaterally, suspicious for regional osteomyelitis. A Tc-99m stannous colloid-labeled leukocyte study performed subsequently showed absent white cell accumulation in the corresponding area, with a normal pattern of distribution elsewhere in the skeleton. Bone biopsy from the pubic symphysis demonstrated a neutrophilic cellular infiltrate and granulation tissue consistent with active bony infection.
Abstract 1865: Ciglitazone increases ovarian cancer cell death by inhibiting GLUT-1 expression.
Authors: Jin Young Kim, So Jin Shin, Keon Uk Park, Young June Jeon, Chi Heum Cho, Eunyoung Ha
Journal: Cancer Research (2013)

Abstract Ciglitazone is a kind of thiazolidinedione and a potent, selective peroxisome proliferator-activated receptor γ (PPAR γ) ligand and it is active in vivo as an anti-hyperglycemic agent in the murine model. Glucose metabolism plays a key role in the maintenance of energy homeostasis in organisms and changes in cellular glucose uptake rate are found in malignant diseases. Significant increase in glucose consumption can be found in many malignant conditions and research so far has focused on its apoptotic and inhibition of proliferation properties but their role in cell death is unclear. We show that ciglitazone inhibits glucose uptake in ovarian cancer cell through GLUT-1 expression. In this study, we investigated the effect of ciglitazone to GLUT-1 expression and cell proliferation. We further demonstrate that ciglitazone pretreated tumor cell was increased apoptosis dose dependent manner and siGLUT-1 treated tumor cell showed increased apoptosis. Interestingly, not only cancer cell line but also in vivo state, ciglitazone could decrease tumor mass. Specificity protein (Sp) is highly expressed in tissues of prostate cancer, breast carcinomas and lung cancer when compared to normal tissues or cells. Previous studies showed that Sp1 plays an important role in carcinogenesis and metastasis of several human tumor types by regulating growth-related signal transduction, cell cycle control molecules, apoptosis, oncogenes, tumor suppressor genes. In this study there was no relation with apoptosis and SP1 expression. We demonstreated that ciglitazone inhibit glucose uptake in ovarian cancer cell lines and the relationship between ciglitazone and GLUT-1 in ciglitazone induced cell death. Citation Format: Jin Young Kim, So Jin Shin, Keon Uk Park, Young June Jeon, Chi Heum Cho, Eunyoung Ha. Ciglitazone increases ovarian cancer cell death by inhibiting GLUT-1 expression. [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 1865. doi:10.1158/1538-7445.AM2013-1865
Abstract 2366: Impact of EWS-FLI induced changes in gene expression and cell behavior on metastatic potential
Authors: Aashi P. Chaturvedi, Alana Welm, Stephen Lessnick, Mary Beckerle
Journal: Cancer Research (2011)

Abstract Ewing's sarcoma (ES) is frequently metastatic at presentation, a condition that is associated with poor prognosis. ES is caused by the oncogenic fusion of the EWSR1 and FLI1 genes to encode a chimeric EWS/FLI protein product that results in an altered transcriptional program. Because the metastatic potential of ES appears to develop at an early stage, we have explored whether the oncogene-driven misregulation of gene expression might contribute directly to promotion of metastasis. Metastasis is a complex process involving sequential and interrelated steps. In this study, we have examined the impact of EWS/FLI expression on cell migration, cell adhesion, and cytoarchitecture of ES cells by comparing the behavior of A673 ES cells with that of A673 cells in which we knocked down expression of EWS/FLI by RNA-interference. In contrast with what one might expect for a critical oncogene, we found that EWS/FLI expression reduced in vitro migration and Matrigel invasion. Consistent with these findings, expression of EWS/FLI abrogated cell adhesion and spreading. An in vivo mouse lung colonization assay revealed that ES cells treated with EWS/FLI RNAi adhere and colonize better in the lung tissue compared to ES cells, further supporting the in vitro adhesion results. At the cellular level, adhesion strength is correlated with the capacity of cells to form focal contacts and stress fibers. Knockdown of EWS/FLI expression in ES cells resulted in a striking remodeling of the actin cytoskeleton, with establishment of robust stress fibers and focal adhesions. Gene expression profiles, Western immunoblot analysis, and immunofluorescence staining confirmed that EWS/FLI expression is associated with reduced levels of focal adhesion proteins, including zyxin, a key regulator of actin assembly. Introduction of a zyxin cDNA expression construct into A673 ES cells was sufficient to restore the integrity of the actin cytoskeleton and focal adhesions, and to partially restore cell adhesion, both in vitro and in vivo, demonstrating a central role for zyxin in regulation of ES phenotype. Since release of cells from the primary tumor site is a critical initial step in metastasis, the profound impact of EWS/FLI expression on cytoarchitecture and cell adhesion may contribute to the metastatic phenotype in a unique, yet fundamental, way. Based on these data, we hypothesize that EWS/FLI-induced changes in gene expression simultaneously promotes both oncogenic transformation and tumor cell dissemination. 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 2366. doi:10.1158/1538-7445.AM2011-2366
Abstract 4296: Activated ALK accelerates the onset of neuroblastoma in MYCN-transgenic zebrafish
Authors: Shizhen Zhu, Jeong-Soo Lee, Jimann Shin, Antonio R. Perez-Atayde, Jeffery L. Kutok, Scott J. Rodig, Donna S. Neuberg, Feng Guo, Daniel Helman, Hui Feng, Rodney A. Stewart, Wenchao Wang, Rani E. George, John P. Kanki, A. Thomas Look
Journal: Cancer Research (2011)

Abstract Neuroblastoma is the most common extracranial solid tumor in children and originates during development of the peripheral sympathetic nervous system. Advanced-stage disease and a poor outcome are associated with amplification of the MYCN oncogene, often in combination with mutational activation or amplification of another oncogene ALK (anaplastic lymphoma kinase), suggesting that they cooperate in neuroblastoma pathogenesis. To investigate this possibility, we generated a transgenic zebrafish model of neuroblastoma in which human MYCN is expressed under the control of the dopamine-beta-hydroxylase promoter, and show that the resultant tumors recapitulate childhood neuroblastomas histologically, immunohistochemically, and ultrastructurally. Surprisingly, the tumors arise from a subpopulation of neuroblasts that migrate into the adrenal analogue (interrenal gland) in the zebrafish after organogenesis is complete. Coexpression of activated ALK with MYCN markedly increased the frequency of neuroblastoma and accelerated the time of onset, providing conclusive evidence for synergistic interplay between these two oncogenes in neuroblastoma pathogenesis. 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 4296. doi:10.1158/1538-7445.AM2011-4296
Abstract LB-194: The Wnt inhibitor VS-507 reduces cancer stem cell (CSC) function in vitro and tumorigenicity in mice
Authors: Jonathan A. Pachter, Jennifer Ring, Alissa Neill, Christian Vidal, Brian T. Sullivan, Kevin T. Sprott, Mahesh Padval, Qunli Xu
Journal: Cancer Research (2012)

Abstract VS-507 was previously identified as a selective inhibitor of cancer stem cells (Gupta et al., Cell, 2009) using a high throughput screen that capitalized on the cancer stem cell (CSC) phenotype of cells pushed through EMT (epithelial-mesenchymal transition). We have now characterized the mechanism, CSC selectivity and anti-tumor activity of VS-507. In Wnt3A-stimulated MDA-MB-231 breast cancer cells, VS-507 was found to preferentially inhibit β-catenin signaling in a dose-dependent manner as indicated by a TOP-Flash reporter assay. Inhibition of β-catenin signaling in VS-507-treated cells correlated with decreased protein expression of LRP6, the common co-receptor of the Wnt signaling pathway. Since human mammary cells driven through EMT by stable overexpression of the transcription factor Twist have been shown to demonstrate the hallmarks of CSCs, we used HMLE-Twist cells to assess selectivity of VS-507 for CSC inhibition. In proliferation assays, VS-507 showed 10-fold greater potency against CSC-like mesenchymal HMLE-Twist cells as compared to non-CSC-like epithelial control HMLE cells. In addition, VS-507 induced dose-dependent inhibition of tumorsphere formation by MDA-MB-231 cells, further indicating inhibition of the CSC phenotype. The preferential effects of VS-507 on mesenchymal breast cancer cell lines relative to epithelial breast cancer cell lines was further probed among a panel of 13 adherent human breast cancer cell lines. In general, triple negative mesenchymal breast cancer cell lines such as MDA-MB-436 or HCC1395 were more potently inhibited by VS-507 than were epithelial breast cancer cell lines such as MCF7 or HCC1937. Finally, efficacy of VS-507 was characterized upon systemic administration of the compound to mice. Inhibition of both primary tumor growth and experimental metastasis were observed in triple negative breast cancer models. These observations suggest that VS-507 is a potent anti-tumor agent that attenuates Wnt/β-catenin signaling, cancer stem cell self-renewal, tumor growth and metastasis. These results support clinical development of VS-507 for the treatment of triple negative breast cancer. 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 LB-194. doi:1538-7445.AM2012-LB-194
MITRAL ANNULAR CALCIFICATION AND RISK OF STROKE IN SEVERE AORTIC STENOSIS: A PROPENSITY SCORE ANALYSIS
Authors: Alok Saurav, Pallavi Bellamkonda, Abhilash Akinapelli, Aiman Smer, Ratna Priya Gangi, Manu Kaushik, Venkata Alla, Claire Hunter, Aryan Mooss
Journal: Journal of the American College of Cardiology (2016)
Somatic activating mutations in <i>Pik3ca</i> cause sporadic venous malformations in mice and humans
Authors: Sandra D. Castillo, Elena Tzouanacou, May Zaw-Thin, Inma M. Berenjeno, Victoria E.R. Parker, Iñigo Chivite, Maria Milà-Guasch, Wayne Pearce, Isabelle Solomon, Ana Angulo-Urarte, Ana M. Figueiredo, Robert E. Dewhurst, Rachel G. Knox, Graeme R. Clark, Cheryl L. Scudamore, Adam Badar, Tammy L. Kalber, Julie Foster, Daniel J. Stuckey, Anna L. David, Wayne A. Phillips, Mark F. Lythgoe, Valerie Wilson, Robert K. Semple, Neil J. Sebire, Veronica A. Kinsler, Mariona Graupera, Bart Vanhaesebroeck
Journal: Science Translational Medicine (2016)

Mutant Pik3ca gives rise to venous malformations.
Peroral cholangioscopy for diagnosis and therapy of biliary tract disease using an ultra-slim gastroscope
Authors: J. Albert, M. Friedrich-Rust, M. Elhendawy, J. Trojan, S. Zeuzem, C. Sarrazin
Journal: Endoscopy (2011)

High-resolution video cholangioscopy is expected to improve diagnostic validity for diseases of the biliary tract. We report our experience in using an ultra-slim gastroscope for diagnosis and treatment of biliary tract disease. Cholangioscopy was attempted in 25 cases (22 patients) and succeeded in 22 cases (success rate 88%; 19 patients). Cholangiocellular carcinoma (CCC) was diagnosed by cholangioscopy in five of 10 cases (histopathologically confirmed in four), or ruled out in five. Cholangioscopy was used to detect stones in mega-choledochus (n=3), to clarify the postoperative condition of the bile ducts (n=2), to diagnose bile duct varices (n=1), and to release a dislodged self-expanding metal stent (n=1), and others. Argon plasma coagulation was successfully completed in a patient with mucin-producing adenomatosis of the bile ducts. One case of non-fatal air embolism occurred before replacing air with CO2 insufflation. In summary, peroral cholangioscopy with an ultra-slim gastroscope is feasible and helpful in selected patients, improving diagnostic validity, and offering new therapeutic interventions. This technique should only be performed using CO2 insufflation.
Nephrosis and Papillary Necrosis after Pyelonephritis
Authors: Gregorio V. Hernandez, Anthony S. King, Mark A. Needle
Journal: New England Journal of Medicine (1975)

We present a case of nephrotic syndrome complicating acute pyelonephritis in a 45-year-old man. His first attack of acute bacterial pyelonephritis had two unusual features: transient nephrotic syndrome and chronic recurrent episodes of papillary necrosis. The former, which lasted for two weeks, was characterized by edema, excretion of 7.7 g of urinary protein per 24 hours and hypoproteinemia (1.8 g per 100 ml). A percutaneous renal biopsy two weeks after the height of the nephrotic state showed normal glomeruli by light and electron microscopy and immunohistologic studies. Interstitial changes were noted. Over two years the patient has passed approximately 50 fragments, characterized as necrotic tissue containing tubular structures. He has no evidence of diabetes mellitus, urinary-tract obstruction or ureteral reflux, analgesic abuse or atypical vasculitis. He is afebrile but has recurrent bacteriuria despite antibiotics. This case demonstrates that acute pyelonephritis must be added to the list of diseases causing the nephrotic state.
Abstract 3633: eEF2 in acquired lapatinib resistance in HER2 positive breast cancer cells
Authors: Martina McDermott, Brigid Browne, John Crown, Neil O'Brien, Dennis Slamon, Michael Henry, Paula Meleady, Martin Clynes, Paul Dowling, Norma O'Donovan
Journal: Cancer Research (2010)

Abstract Approximately 25% of breast cancers overexpress HER2. Although HER2 targeted therapies, trastuzumab and more recently lapatinib, have improved prognosis for HER2 breast cancer patients not all HER2 positive tumors respond to HER2 targeted therapies. Using phosphoproteomic profiling, we examined mechanisms of resistance in an in vitro model of acquired lapatinib resistance. SKBR3 cells were conditioned in lapatinib containing media (200 nM) for six months, after which time the resulting SKBR3-L cells exhibited significantly reduced growth inhibition (27.7 ± 0.1 %) when treated with lapatinib (1 µM) treatment compared to parental SKBR3 (90.7 ± 0.2 %) (p&amp;lt;0.01). Using phosphoproteomic profiling, eukaryotic elongation factor 2 (eEF2) was identified as a phosphoprotein which was significantly altered in the SKBR3-L cells compared to the parental SKBR3 cells. One form of phospho-eEF2 was up-regulated and 6 forms were down-regulated in SKBR3-L compared to SKBR3. eEF2 is a phosphoprotein with an essential role in protein synthesis. Phosphorylation of eEF2 at Thr56 and Thr58 by eEF2 kinase inhibits eEF2 activity. eEF2 kinase activity is regulated by the mTOR pathway, via phosphorylation by p70S6 kinase. To examine the role of eEF2 in lapatinib resistance, levels of phospho-eEF2, eEF2, phospho-p70S6K and p70S6K, were examined in a panel of HER2 positive breast cancer cell lines following 24 hour treatment with lapatinib (1 µM). Treatment with lapatinib resulted in a decrease in phospho-p70S6K and an increase in phospho-eEF2, with no change in the levels of total protein, in lapatinib sensitive cell lines. In order to further examine the role the mTOR pathway and eEF2, plays in acquired resistance to lapatinib, the effect of rapamycin, alone and in combination with lapatinib, was investigated in SKBR3 par and SKBR3-L cells. Combined treatment with lapatinib (200 nM) and rapamycin (2 nM) results in similar inhibition of growth (64.5 ± 3.3 %) in SKBR3-L cells as lapatinib alone in SKBR3 parental cells (62.5 ± 0.6 %). In conclusion, response to lapatinib is associated with decreased eEF2 activity in HER2 positive cell lines. Furthermore, inhibition of mTOR signaling, which causes inhibition of eEF2 activity, appears to restore sensitivity to lapatinib in our model of acquired lapatinib resistance. 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 3633.
GE-28 * INTEGRATED GENOMICS DEMONSTRATE RELATIVE SPATIAL HOMOGENEITY IN PEDIATRIC BRAIN TUMORS
Authors: M. Remke, F. M. G. Jorgensen, A. S. Morrissy, V. Ramaswamy, D. T. W. Jones, M. Marra, R. Packer, E. Bouffet, S. M. Pfister, N. Jabado, M. D. Taylor
Journal: Neuro-Oncology (2014)

INTRODUCTION: Comprehensive, genome-wide profiling and next-generation sequencing based studies have dramatically improved our understanding of pediatric brain tumor biology in recent years. However, the vast majority of these studies rely on the assumption that single biopsies are representative of all areas within a tumor. Intratumor heterogeneity comprises a common phenomenon previously described in glioblastoma multiforme and other tumors. Highly disparate genetic profiles of spatially separated areas within the same tumor may preclude development of personalized, molecularly targeted therapies based on single tumor biopsies. MATERIAL AND METHODS: To assess the degree of intratumor heterogeneity, we conducted multiregion whole exome sequencing, high-resolution DNA copy number analysis (Cytoscan HD) and DNA methylation profiling (Infinium HumanMethylation450 BeadChip) on over 25 distinct pediatric and adult brain tumors with a median of six biopsies per tumor (range 4-9). Histological entities comprised ATRT (n = 2), DIPG (n = 2), ependymoma (n = 1), glioblastoma (n = 10), medulloblastoma (n = 10), and medulloepithelioma (n = 1). We elucidated the degree of intratumor heterogeneity and subgroup affiliation using integrated genomics and unsupervised hierarchical clustering algorithms. RESULTS: Epigenetic signatures were highly similar in multiregion biopsies from a single tumor. However, we identified up to 250,000 CpG dinucleotides that were differentially methylated when determining the intertumor heterogeneity of DNA methylation patterns even within disease subgroups. In addition, pediatric brain tumors displayed highly similar focal and broad DNA copy number alterations compared to their adult counterparts. Multiregion sequencing further reinforced the relatively higher degree of intratumor homogeneity in pediatric brain tumors. Lastly, we showed that subgroup affiliation was stable in all multiregion biopsies in medulloblastomas and glioblastomas. CONCLUSIONS: Our results reveal that single biopsies are representative of the tumor genomics landscape in pediatric brain tumors and that DNA methylation based subgrouping is geographically stable.
EFICACIA DE UN ALGORITMO TERAPÉUTICO COMBINADO CON CPRE Y ECOENDOSCOPIA EN EL TRATAMIENTO DE LAS TRANSECCIONES DUCTALES COMPLETAS DE LA VÍA BILIAR: RESULTADOS A MEDIO PLAZO
Authors: N Alemán Pérez, I Peñas Herrero, R Ruiz-Zorrilla, P Gil Simón, R Sánchez Ocaña, C Almohalla, F García Pajares, C De La Serna Higuera, G Sanchez Antolin, M Pérez-Miranda
Journal: Endoscopy (2013)

Introducción: Las transecciones ductales completas (TDC) de la vía biliar no se consideran susceptibles de tratamiento endoscópico. Objetivo: Describir y evaluar la viabilidad de diversos abordajes endoscópicos para tratamiento de TDC. Material y Método: Desde septiembre-2010 se registran prospectivamente 248 CPRE por complicaciones postquirúrgicas (estenosis/fugas) en 150 pacientes (69 trasplante hepático TH, 81 Otras). Se identifican TDC en 17 pacientes (Mujeres = 9; edad = 59.6 [43 – 79] años) con TDC (7 TH; 7 colecistectomía CCx; 3 Otras). Resultados: Se logró recanalización en 12/17 TDC (70%), por CPRE aislada en 5 (4 TH, 1 CCx), y por CPRE combinada con abordaje anterógrado por USE en 7 (2 TH, 4 CCx, 1 Otra), en 4 casos la ausencia de dilatación biliar impidió abordaje USE y en otro no se logró recanalización a pesar de hepaticogastrostomía USE-guiada. Hubo 5 fracasos, remitidos a hepatico-yeyunostomía quirúrgica. 10/12 casos recanalizados precisaron maniobras forzadas por vía anterógrada o retrógrada: manipulación con el cabo rígido de la guía, needle-knife, aguja de Artifon, retroperitoneoscopia transhepática o anastomosis magnética. Se requirieron 1.5 (1 – 5) CPREs hasta lograr la recanalización. Se drenaron endoscópicamente 2 bilomas asociados a TDC. Once pacientes han finalizado 12 ciclos de tratamiento con retirada definitiva de prótesis (plásticas, n = 2; metálicas cubiertas ± plásticas, n = 10) tras 323(180 – 503) días de tutorización. Tras un seguimiento medio de 353 (30 – 900) días, hubo 3 recidivas (hepaticoyeyunostomía quirúrgica, tratamiento endoscópico en curso, resuelta tras nuevo ciclo endoscópico, una cada uno). Como complicaciones se registraron 2 colangitis y 1 sangrado. Conclusiones: El 70% de las TDC postquirúrgicas pueden recanalizarse endoscópicamente con métodos mecánicos forzados (guía rígida o agujas), diatérmicos o magnéticos. La USE permite rescatar para reconexión el 60% de los fracasos de la CPRE y el drenaje de bilomas. Los resultados definitivos del tratamiento endoscópico con prótesis de las TDC parecen equiparables a los de las estenosis parciales.
Assistance from Family Members, Friends, Paid Care Givers, and Volunteers in the Care of Terminally Ill Patients
Authors: Ezekiel J. Emanuel, Diane L. Fairclough, Julia Slutsman, Hillel Alpert, DeWitt Baldwin, Linda L. Emanuel
Journal: New England Journal of Medicine (1999)

In addition to medical care, dying patients often need many types of assistance, including help with transportation, nursing care, homemaking services, and personal care. We interviewed terminally ill adults and their care givers in six randomly selected areas of the United States (five metropolitan areas and one rural county) to determine how their needs for assistance were met and the frequency with which they received such assistance from family members and paid and volunteer care givers.