tbuckley/cabot-search huggingface dataset:
Abstract 578: Roles of mitochondrial protein kinases in targeted cancer therapy
Authors: Tiannan Guo, Oi Lian Kon, Siu Kwan Sze
Journal: Cancer Research (2011)

Abstract Targeted cancer therapy is based on the curious dependence that some cancer cells have on a single oncogenic molecule, typically a protein kinase (the phenomenon of “oncogene addiction”). However, the molecular mechanisms of such dependence are incompletely understood. We have adopted a quantitative proteomic approach to investigate the phenomenon that MET-overexpressing cancer cells are paradoxically more sensitive to MET inhibition than cells with basal MET expression. Unexpectedly, we found that mitochondria are a direct target of MET kinase inhibition, in addition to inhibition of plasma membrane MET. Effects on activated MET in the mitochondria of cancer cells that are sensitive to MET inhibition could reflect a novel and critical non-canonical mechanism that contributes to the efficacy of MET-targeted therapeutics. We hypothesize that protein kinases which aberrantly translocate to mitochondria modulate mitochondrial proteins and functions. Here we have employed advanced LC-MS/MS-based stable isotope labeling with amino acids in cell culture (SILAC) quantitative phosphoproteomic approaches to identify, quantify and functionally annotate phosphorylated mitochondrial proteins of various cancer cell lines, including those that are sensitive or resistant to targeted agents. We identified several phosphorylated protein kinases e.g. MET, EGFR, HER2 and HER3, that were translocated to mitochondria of cancer cells. In addition to documenting the first kinome and phosphoproteome of mitochondria in cancer cells, we present evidence showing that the aberrant presence of protein kinases in mitochondria predicts sensitivity to specific kinase inhibitors. In conclusion, our data reveal a novel mitochondrial mechanism of oncogene addiction, and suggest that mitochondrial protein kinases might play decisive roles in molecularly-directed therapies. 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 578. doi:10.1158/1538-7445.AM2011-578
Preliminary experimental study on carcinogenicity of arsenic trioxide in rat lung.
Authors: N Ishinishi, Y Kodama, K Nobutomo, A Hisanaga
Journal: Environmental Health Perspectives (1977)

To investigate carcinogenic or cocarcinogenic properties, copper ore (Kinkaseki) and flue dust collected from a metal refinery and arsenic trioxide (As2O3) were administered into the lung of male Wistar-King rats by an intratracheal instillation method. No squamous cell carcinoma of the lung was found among the rats given three arsenical substances, while adenoma or adenocarcinoma was observed. Squamous cell carcinoma of the lung was observed in rats, when copper ore, flue dust, and arsenic trioxide were instilled into the lung together with benzo[a]pyrene (B[a]P. The incidence of squamous cell carcinoma of the lung in rats exposed to Kinkaseki, flue dust, and As2O3 in addition to B[a]P was higher than that in rats given B[a]P alone. The results of this study indicate that solid arsenical substances, such as arsenic trioxide, metal ore and flue dust from a metal refinery, seemed to act on the carcinogenicity of B[a]P in a cocarcinogenic manner.
Getting a Handle on ASCUS: A New Clinical Trial Could Show How
Authors: C. McNeil
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Getting a Handle on ASCUS: A New Clinical Trial Could Show How Get access Caroline McNeil Caroline McNeil Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 11, 7 June 1995, Pages 787–789, https://doi.org/10.1093/jnci/87.11.787 Published: 07 June 1995
P3-11-06: A Pilot Study of RPFNA in Overweight and Obese Postmenopausal Women.
Authors: LA Korde, VS Grieco, I Imayama, C Kumai, C Mason, CR Duggan, C-Y Wang, A McTiernan
Journal: Cancer Research (2011)

Abstract Background: Random periareolar fine-needle aspiration (RPFNA) is a research-based procedure used to obtain breast epithelial cells and fluid. Data suggest that atypia in epithelial cells from RPFNA specimens is associated with an increased risk of breast cancer, and changes in the degree of atypia may be a viable biomarker for response to chemopreventive interventions. Methods: We performed RPFNA on 37 overweight or obese (body mass index (BMI≥ 25.0 kg/m2) postmenopausal (50-75 y) women enrolled in a randomized clinical trial of Vitamin D vs placebo in combination with a lifestyle (diet + exercise)-based weight loss program. Eligibility criteria included serum vitamin D concentrations 10–32 ng/mL. The procedure was performed by two trained clinicians prior to randomization to assess baseline cell counts and degree of atypia. Two areas in the breast (10:00 and 2:00 positions) were infiltrated with lidocaine, and 8 to 10 aspirations of cellular material were performed using 1.5 inch, 21-gauge needles. The aspirated fluid was placed in 9 cc of Cytolyt Thinprep (Hologic Inc.) with 1 cc of 1% neutral buffered formalin and slides were prepared according to the University of Washington Department of Pathology non-gyn protocol. Results: Thirty-seven women were included in this analysis. The mean age and BMI of study participants was 59.3 years and 32.5 kg/m2, respectively. The mean 5-year Gail risk score for study participants was 1.96%; 52% of women had a 5-year Gail risk &amp;gt;1.66%. Eight participants (21.6%) had &amp;gt;50 cells present on cytology examination. One additional participant had 10–50 cells, and one had &amp;lt;10 cells. No specimens showed cellular atypia. The remainder of study participants had only blood or fibroadipose tissue on cytology specimens. Women with epithelial cells present were younger (mean age 55.0 vs. 60.2 years, p=0.05). There were no significant differences in BMI or Gail risk score between those with and without epithelial cells. Conclusions: RPFNA in our sample of overweight/obese postmenopausal women did not yield epithelial cells in a majority of participants. Younger age was associated with a greater cell count. We are planning further studies to determine whether other markers in RPFNA specimens can be used to assess breast tissue changes in response to chemopreventive interventions. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-11-06.
Early and Late Tc-99m Diphosphonate Uptake in a Giant Benign Breast Cystosarcoma Phyllodes Tumor
Authors: MARIANNE TONDEUR, MYRIAM VAN DER SCHUEREN, ROBERT DEVOS, BIRGIT CARLY
Journal: Clinical Nuclear Medicine (1999)

A 64-year-old woman with a large left breast mass had mammography and breast ultrasound that were suggestive of a giant fibroadenoma. Preoperative bone imaging as on the images showed intense uptake in the mass obtained 15 minutes after injection as well as on the late images. Pathologic examination revealed a large benign cystosarcoma phyllodes tumor.
DISECCIÓN SUBMUCOSA ENDOSCÓPICA DE LESIONES COLORRECTALES: EVOLUCIÓN Y COMPLICACIONES A CORTO PLAZO EN LA FASE INICIAL DE LA CURVA DE APRENDIZAJE
Authors: JC Marín-Gabriel, J Díaz Tasende, P Hernán-Ocaña, A González-Blanco, S Rodríguez Muñoz, AJ Del Pozo García, M Alonso-Riaño, F Colina-Ruizdelgado, M Pérez Carreras, A Domínguez-Rodríguez, G Castellano Tortajada
Journal: Endoscopy (2013)

Introducción: La disección submucosa endoscópica es una técnica de reciente introducción en nuestro país. Objetivo: Recopilar la evolución y complicaciones, a corto plazo. Material y Métodos: Se recogieron de forma prospectiva 31 lesiones resecadas en el Hospital Universitario 12 de Octubre de Madrid (88,6%) y 4 realizadas en el Hospital Sanitas La Moraleja (11,4%). Resultados: Se llevaron a cabo 35 D.S.E.s entre septiembre de 2008 y junio de 2013. La mediana de edad fue de 67 años (44 – 89). La mediana de tamaño de las lesiones fue de 31 mm (13 – 90). Las lesiones estaban localizadas en recto (27; 77,1%), sigma (6; 17,1%), ángulo esplénico (1; 2,9%) y ángulo hepático (1; 2,9%). Se incluyeron 11 LST-G homogéneos (31,4%), 7 LST-G mixtos (20%), 7 LST-NG (20%) y 10 lesiones (28,6%) de diversa morfología. Se logró la exéresis en bloque en 14 casos (40%). De ellos, 7 R0 (20%). El estudio histológico mostró neoplasia mucosa de alto grado en 22 casos (62,8%). En 5 lesiones (14,3%) se identificó invasión s.m. En 3 (8,5%) de ellas la invasión superaba 1000µ por lo que se recomendó tratamiento quirúrgico complementario. Se detectaron 4 perforaciones (11,4%), de las cuales, 1 requirió cirugía (2,9%) y 5 casos de hemorragia digestiva (14,3%), resueltos con tratamiento endoscópico. Uno de los pacientes (2,9%) necesitó transfusión. El ingreso se prolongó una mediana de 5 días (rango: 4 – 14) debido a las complicaciones. Conclusión: La escasa posibilidad de entrenamiento con lesiones gástricas en nuestro medio, probablemente, da lugar a resultados iniciales en los que los porcentajes de resecciones en bloque y R0 son inferiores a lo esperado. La morbilidad asociada no dista de la descrita en otros países europeos.
DD-07 * A KINOME RNA INTERFERENCE SCREEN IDENTIFIES NOVEL THERAPEUTIC TARGETS FOR GLIOBLASTOMA
Authors: L. Pham, Y. Liang, S. Guo, S. Murphy, Z. Sheng
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM) is the most common primary central nervous system tumor. Despite aggressive therapies such as surgical resection, chemo- and radiotherapies, the life expectancy and survival rates for GBM patients are still low. There is an urgent need for more effective therapies. We here hypothesized that certain kinases that are essential for GBM cell survival and thereby the better therapeutic targets for GBM remain to be defined. To identify these kinases, we designed and performed a dropout RNA interference (RNAi) screen, in which we revealed a subset of kinases that may selectively control the survival of U87MG glioblastoma cells. We elected to focus on casein kinase 1 epsilon (CSNK1E) and maternal embryonic leucine zipper kinase (MELK), the latter of which has previously been demonstrated as an essential kinase for GBM in other reports. Expression levels of these kinases were also shown to be differentially elevated in GBM cells. Our further experiments confirmed that CSNK1E and MELK were essential for the viability of multiple GBM cell lines (U251, SNB75, LN18, SF268, and LN229) as well as primary GBM cells (VTC002). Intriguingly, our data indicate that depletion of CSNK1E using shRNAs is more effective than that of MELK in most GBM cell lines, making it a promising candidate for future targeted GBM therapy. Furthermore, we revealed that both kinases promote the GBM survival through inhibiting apoptosis. Collectively, our results demonstrate that CSNK1E is a novel therapeutic target for GBM. As such, our future work will involve evaluation of CSNK1E inhibitors in treating GBM in vivo using chemical inhibitors.
Molecular characteristics of matched brain metastasis (BM) versus the primary breast cancer (PBC).
Authors: R Duchnowska, J Jassem, C Shen, M Thorat, L Li, A Morimiya, Q Zhao, W Biernat, T Mandat, R Staszkiewicz, W Och, W Szostak, K Gugala, T Trojanowski, B Czartoryska-Arlukowicz, C Szczylik, H Nakshatri, P Steeg, G Sledge, S Badve
Journal: Cancer Research (2009)

Abstract Abstract #2028 Background: Brain is increasingly a site of relapse in breast cancer patients, however the molecular patho-physiology of this process is not well understood. Using a novel assay allowing high-throughput analysis of gene expression from formalin-fixed paraffin-embedded (FFPET) tumor samples, we compared molecular characteristics of BM with those of the PBC in a series of breast cancer patients who underwent excision of brain metastasis.&amp;#x2028; Methods: In each patient we performed molecular analysis of paired archived FFPET specimens from both the PBC and excised BM. Of the 37 pairs of PBC/BM samples, 24 pairs had sufficient pathology material for molecular analysis. Patient characteristics: mean age at PBC diagnosis was 46.7 years (range 27-67 years); 7 (29%) ER+, 17 (71%) ER-, 12 (50%) HER2-positive(3+). We performed cDNA-mediated annealing, selection, extension and ligation (DASL) assay (Illumina Corp) for expression of 502 known cancer genes, using 200 ng RNA. Statistical analysis for microarrays (SAM) accounting for the pairing of the primary and metastasized tumors was used to identify differentially expressed genes while controlling the false discovery rate (FDR &amp;lt;0.01). BeadStudio™ Absolute correlation clustering was used to cluster samples based on their expression profiles.&amp;#x2028; Results: In only 7 (29%) cases matched PBC and BM pair clustered together on unsupervised hierarchical clustering, the pairs in remaining cases clustered apart. Comparison of the two groups (PBC and BM) showed that 41 genes were up regulated in BM, including proliferation genes (CDC2, CDC25a, CCNA2 and E2F family), anti-apoptotic (BIRC5), DNA repair (RAD51, -54b, XRCC2, BRCA2, BARD1, TOP1), angiogenesis (VEGF), and development of drug resistance (ABCB1, -G2). In contrast, the 43 genes that were down regulated in BM included those associated with invasion (MMP2, -3, -14), cellular motility, and epithelial to mesenchymal transformation (CDH11). Additional analysis to validate these trends and to identify potential therapeutic targets is underway.&amp;#x2028; Conclusions: Although some BM retain remarkable similarity to the PBC, majority exhibit considerable deviation in their gene expression profile. These “adaptive” changes include greater resistance to drug therapy, increased DNA repair, a reversal back to the epithelial phenotype and decreased capacity for cell motility and invasion. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2028.
STATUS OF STEMI-PCI IN THE US TERRITORIES: THE PUERTO RICO INFARCTION NATIONAL COLLABORATIVE EXPERIENCE (PRINCE) INITIATIVE
Authors: Orlando Rodriguez-Vila, Miguel A. Campos, Fernando Lapetina, Jose Escabi, Carlos Nieves, Edgardo Bermudez, Juan C. Zevallos, Sameer Mehta
Journal: Journal of the American College of Cardiology (2016)
SP0193 Osteoarthritis Is A Disease Of Mechanics
Authors: D. Felson
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Mechanics means relating to or caused by movement or physical forces. I shall contend that OA is almost always caused by increased physical forces leading to damage to a joint. While examples of joint injury such as meniscal tears causing osteoarthritis are numerous, I shall contend that most or almost all osteoarthritis is caused in part by mechanically induced injury to joint tissues. Major traumatic injury induces OA in young joints with healthy tissues, but minor minimally traumatic injury is implicated as the cause of OA in older vulnerable joints. Further, once joint pathology has developed, like in clinical osteoarthritis, pathomechanics overwhelms all other factors in causing disease progression. Treatments which correct the pathomechanics have long lasting favorable effects on pain and joint function compared with treatments that suppress inflammation which have only temporary effects. Lastly, there is lots of evidence of inflammation in osteoarthritic joints, but I shall lastly contend that this inflammation is secondary— it is induced by mechanically induced joint injury and further that the role of this inflammation in worsening structural damage in the osteoarthritic joint has not yet been proven. <h3>Disclosure of Interest</h3> None Declared
P4-17-09: Comparative Performances of Prognostic Indexes for Breast Cancer Patients Presenting with Brain Metastases.
Authors: A-L Braccini, D Azria, S Thezenas, J-M Ferrero, G Romieu, W Jacot
Journal: Cancer Research (2011)

Abstract Introduction: Incidence of brain metastases (BM) from breast cancer has increased over the past decade, especially for HER2(+) tumours. Several scores and prognosis systems have been developed in the brain metastases (BM) setting in order to help physicians tailor treatment options depending on patient prognosis and to stratify patients enrolled in clinical studies. The aim of our study was to compare the clinical relevance of the major classifications and existing prognostic scores in a population of breast cancer patients affected by BM. Methods and Materials: In this retrospective study conducted in Montpellier and Nice Cancer Centres, we retrospectively reviewed the clinical and biological data of 250 patients diagnosed with breast cancer BM between 1995 and 2010. Prognostic value and accuracy of recursive partitioning analysis (RPA), graded prognostic assessment (GPA), basic score for brain metastases (BS-BM) and a clinico-biological score (BS) developed in phase I study and validated in the BM setting were compared. Results: Median age at BM diagnosis was 55 years-old. Most patients (74%) had good performance status (0-1). Brain was the first metastatic site in one third of patients (33.6%). In 12.4% of cases, no extracerebral metastases were detected at BM diagnosis. Among the 250 patients’ tumors, 43.6% overexpressed HER2 receptor and 25.6% were triple negative (negative estrogen receptor, progesterone receptor and HER2 status). After a median follow up of 4.5 years, median overall survival from BM diagnosis was 8.9 months (CI 95%, 6.9−10.3 months). The four scores were able to discriminate patients according to their survival. Chi2 tests showed a correlation between the different scoring systems. In multivariate analysis, the elimination model identified RPA (p = 0.031; hazard ratio, 0.77; 95% confidence interval, 0.64−0.91) and BS (p = 0.043; hazard ratio, 0.5; 95% confidence interval, 0.31−0.80) as the only two independent predictors of survival. RPA was the most accurate score in order to identify patients with high life expectancy, while RPA and BS were the most accurate scores to classify patients with short life expectancy. Conclusions: In a general unselected population of breast cancer affected by BM, RPA seems to be the most useful score. Integration of biological parameters in addition of existing clinico-radiological scores is promising in order to improve the prognostic determination accuracy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-17-09.
Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Predicts Future Risk of Cardiovascular Events Independently of Established Risk Factors
Authors: Karin Leander, Anders Mälarstig, Ferdinand M. van’t Hooft, Craig Hyde, Mai-Lis Hellénius, Jason S. Troutt, Robert J. Konrad, John Öhrvik, Anders Hamsten, Ulf de Faire
Journal: Circulation (2016)

Background— The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease (CVD). The relationship between circulating PCSK9 and incident CVD in the general population is unknown. We investigated whether serum PCSK9 concentration is associated with incident CVD in a prospective cohort study of 4232 men and women 60 years of age at the time of recruitment. Methods and Results— Incident CVD was recorded by matching to national registries. After 15 years of follow-up, a total of 491 incident events (fatal and nonfatal myocardial infarctions, unstable angina, deaths from coronary heart disease, fatal and nonfatal ischemic strokes) were recorded. Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. Baseline serum PCSK9 concentration predicted incident CVD; concentration in quartile 4 compared with quartile 1 was associated with a hazard ratio of 1.69 (95% confidence interval, 1.30–2.19) after adjustment for sex. Further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), triglycerides, hypertension, diabetes mellitus, smoking, overweight, obesity, physical inactivity, and statin use resulted in a decrease in the hazard ratio to 1.48 (95% confidence interval, 1.12–1.95). Conclusions— Serum PCSK9 concentration is associated with future risk of CVD even after adjustments for established CVD risk factors. Further studies are needed to confirm this observation.
SEX DIFFERENCES IN DEMOGRAPHICS, RISK FACTORS AND PRESENTATION IN STABLE CONTEMPORARY OUTPATIENTS WITH SUSPECTED CORONARY ARTERY DISEASE: INSIGHTS FROM THE PROMISE TRIAL
Authors: Kshipra Hemal, Neha Pagidipati, Adrian Coles, Rowena Dolor, Daniel Mark, Patricia Pellikka, Udo Hoffmann, Sheldon Litwin, Melissa Daubert, Svati Shah, Kevin Ariani, Renee Bullock-Palmer, Kerry Lee, Pamela Douglas
Journal: Journal of the American College of Cardiology (2016)
The<i>Journal</i>'s App for the iPad
Authors: Edward W. Campion, Cynthia L. Bowab, Jacqueline M. Prince, John E. Muenning, Thomas J. Easley, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2012)

Thanks to a newly built software application (or “app”), the Journal can now be downloaded and read in an issue format on the iPad. The NEJM iPad Edition is now available in the iTunes App Store at no charge. The issue of February 23, 2012, is free, so that readers can see how an issue looks, works, and reads on their iPads. The app is designed as an issue-based reader, meaning that it allows downloads of the full text of single issues, including figures and tables, beginning with the first issue of 2012. Learning to navigate easily within and between . . .
Umbilical Cord Blood May Be Lifeline for Some Patients
Authors: J. Corliss
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Umbilical Cord Blood May Be Lifeline for Some Patients Get access Julie Corliss Julie Corliss Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 14, 21 July 1993, Pages 1107–1108, https://doi.org/10.1093/jnci/85.14.1107 Published: 21 July 1993