tbuckley/cabot-search huggingface dataset:
P17.53 * THE COMBINATION OF CARMUSTINE WAFERS AND FOTEMUSTINE IN RECURRENT GLIOBLASTOMA PATIENTS: OUR EXPERIENCE
Authors: G. Lombardi, A. D. Puppa, F. Zustovich, A. Pambuku, P. Farina, V. Zagonel
Journal: Neuro-Oncology (2014)

BACKGROUND: In the last years, few advances have been made improving progression-free survival and overall survival in patients with glioblastoma multiforme. There is no standard treatment for recurrent disease. We analyzed the feasibility of a multimodal strategy with second surgery plus carmustine wafers in the surgical cavity followed by intravenous fotemustine administration. METHODS: Retrospectively, we analyzed patients with recurrent glioblastoma treated with this multimodal strategy: carmustine wafers positioned during second surgery and subsequently, fotemustine drug as second-line treatment performed between 14 and 21 days after the second surgery. Intravenous fotemustine was administrated at 100mg/m2 every week for 3 consecutive weeks followed by a 5-week rest period; subsequently, an infusion every 3 weeks until progression disease or unacceptable toxicity or until a maximum of 12 cycles. During fotemustine therapy tumor response was evaluated by clinician assessment and by brain magnetic resonance imaging according to Macdonald criteria every two months or when clinically indicated. RESULTS: Twenty-four patients were analyzed. The median age was 53.6 years; all patients had KPS between 90 and 100, 19 patients (79%) performed a gross total resection >98% and 5 (21%) a gross total resection >90%. Seventeen patients were available for MGMT gene analysis and 10 (59%) patients had methylated MGMT gene promoter. The median time from first and second surgery was 17 months. The median progression-free survival from second surgery was 6 months (95% CI 3.9-8.05) and the median OS was 14 months (95% CI 11.1 - 16.8 months). No significant association was found between the resection rate (GTR >98% vs GTR >90%) and PFS (p = 0.4) and OS (p = 0.9). All patients were evaluable for toxicity which was predominantly haematological: 5 patients (21%) experienced grade 3-4 thrombocytopenia and 3 patients (12%) grade 3-4 leukopenia . Among non-haematological toxicity: 5 patients (21%) had grade 1-2 asthenia, 2 patients (8%) had grade 1-2 nausea/vomiting and 2 patients (8%) reported hypertransaminasemia. CONCLUSION: This multimodal strategy may be feasible in patients with recurrent glioblastoma; in particular, for patients in good clinical conditions
EX VIVO SIMULATION OF THE IMMUNE RESPONSE AGAINST OXDIZED LOW-DENSITY LIPOPROTEIN AS A NEW RISK STRATIFICATION IN CORONARY ARTERY DISEASE
Authors: Tomoyuki Honjo, Ryuji Toh, Nobuaki Tanaka, Masato Mitsuhashi, Kenta Mori, Takeshige Mori, Manabu Nagao, Tatsuro Ishida, Ken-ichi Hirata
Journal: Journal of the American College of Cardiology (2015)
Abstract 2000: Investigation of the molecular events associated with gene resilencing following withdrawal of epigenetic therapies
Authors: Luke B. Hesson, Vibha Patil, Mathew Sloane, Robyn L. Ward
Journal: Cancer Research (2011)

Abstract Epigenetic therapies are a potential new class of anticancer medication for the treatment of solid tumors as well as haematological malignancies. These therapies reverse changes to DNA methylation and histone modifications allowing re-expression of epigenetically inactivated genes. However, upon drug withdrawal reactivated genes undergo re-silencing. This study investigates the mechanism of gene re-silencing following withdrawal of epigenetic therapies, in an effort to identify strategies which deliver a permanent re-expression of epigenetically inactivated genes. Using the mismatch repair gene MLH1 as a model we investigated the molecular events associated with the re-silencing process in the colorectal cancer cell line RKO. These cells lack MLH1 expression due to biallelic promoter DNA hypermethylation. We treated RKO cells for 72hrs with a combination of 2.56µM 5-aza-2’deoxycytidine (a DNA methyltransferase (DNMT) inhibitor) and 19nM Trichostatin A (a histone deacetylase (HDAC) inhibitor). We observed MLH1 re-expression by quantitative RT-PCR, concomitant with de-methylation at the MLH1 promoter as determined by bisulphite sequencing. Methylation at the MLH1 promoter decreased from 90.9% in mock-treated cells to 74.7, 61.7, 62.4 and 65.9% at 0, 3, 5 and 7 days after drug withdrawal, respectively. We observed a reproducible re-silencing of MLH1 gene expression, which began three days after drug withdrawal and was complete by 120 days. We further demonstrate the recruitment of a nucleosome, located immediately upstream of the transcription start site, prior to the re-silencing of MLH1 expression that remained high whilst MLH1 transcript levels decreased. We propose that the recruitment of promoter nucleosomes precedes a reduction in transcriptional output and the re-methylation of promoter DNA. Ongoing work aims to dissect the re-silencing process further by investigating the dynamics of RNApolII occupancy and histone modifications at the MLH1 promoter. This study provides important information on the molecular events associated with gene re-silencing by addressing the temporal relationship between changes to gene expression, nucleosomal occupancy and DNA methylation. 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 2000. doi:10.1158/1538-7445.AM2011-2000
LIPOPROTEIN(A) IN FAMILIAL HYPERCHOLESTEROLEMIA WITH PROPROTEIN CONVERTASE SUBTILISIN KEXIN TYPE 9 GAIN-OF-FUNCTION MUTATIONS: IMPLICATION OF RESIDUAL RISK IN STATIN-ERA
Authors: Hayato Tada, Masa-aki Kawashiri, Atsushi Nohara, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi
Journal: Journal of the American College of Cardiology (2015)
Abstract 5514: Antitumor activity of (R,R’)-4′-methoxy-1-naphthylfenoterol in a rat C6 glioma xenograft model in the mouse.
Authors: Rajib K. Paul, Anuradha Ramamoorthy, Yongqing Zhang, Kevin G. Becker, Arnaud Paris, Jean-Francois Cloix, Michel Bernier, Irving W. Wainer
Journal: Cancer Research (2013)

Abstract (R,R’)-4’-methoxy-1-naphthylfenoterol (MNF) inhibits in vitro proliferation of several types of cancer cell lines. In this study, the in vivo antitumor effects of MNF were evaluated using rat C6 glioma cells implanted subcutaneously into the lower flank of 5 week-old NMRI/Nude female Swiss mice (0.5 x 10(6) cells, 100μl). Three days after the inoculation, the mice were subjected to intraperitoneal injections of saline or MNF (10μl/g, 2mg/kg of body weight) for 5 days per week for 2 weeks. Tumor volumes were measured everyday using slide calipers. Significant reductions in mean tumor volumes were observed in mice receiving MNF when compared with the saline-treated group (p &amp;lt; 0.001, n=17-19). At the end of the study, animals were sacrificed and tumors were collected for cDNA microarray, quantitative PCR and immunoblot analyses. Comparison of cDNA microarray analysis of tumors from mice treated with MNF vs. saline demonstrated a significant decrease in expression of genes involved in cellular proliferation, including mitotic checkpoint kinase MAD3L (BUB1B), cyclin-dependent kinase inhibitor 3 (CDKN3) and cyclin A2 (CCNA2), as well as molecular markers for glioblastoma, such as oligodendrocyte transcription factor 1 (OLIG1) and SRY-box 4 (SOX4). Target gene validation is currently in progress. Our results show that MNF reduces growth of flank xenografted C6 glioma tumors and expression of genes related to tumor proliferation and suggest that this compound may be useful in cancer treatment. This work was supported in part by the Intramural Research Program of the NIA/ NIH. Citation Format: Rajib K. Paul, Anuradha Ramamoorthy, Yongqing Zhang, Kevin G. Becker, Arnaud Paris, Jean-Francois Cloix, Michel Bernier, Irving W. Wainer. Antitumor activity of (R,R’)-4′-methoxy-1-naphthylfenoterol in a rat C6 glioma xenograft model in the mouse. [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 5514. doi:10.1158/1538-7445.AM2013-5514
PM-12 * USING A ZEBRAFISH PEDIATRIC BRAIN TUMOR MODEL FOR PRE-CLINICAL DRUG SCREENING
Authors: K. Modzelewska, D. Picard, E. Boer, R. Miles, R. Jensen, T. Pysher, J. Schiffman, C. Jette, A. Huang, R. Stewart
Journal: Neuro-Oncology (2015)

Modeling cancer in zebrafish is a rapidly growing area of research due to unique imaging and drug screening attributes of the system, as well as cost. While over 20 different zebrafish cancer models have been established, no genetically engineered models of pediatric brain tumors exist. We are using genomic editing techniques with traditional transgenic approaches to model pediatric brain tumors in zebrafish for gene discovery and drug screening. As Primitive Neuroectodermal Tumors (PNETs) represent the largest group of malignant brain tumors in children, we used sequencing and genomics data to predict oncogenic drivers of different PNET subtypes and generated the first zebrafish PNET model. Specifically, we show that activation of NRAS signaling in embryonic oligodendrocyte precursor cells with p53-deficiency generate oligoneural PNETs along the entire CNS axis, with conserved histological and molecular features to human medulloblastoma and CNS-PNETs, including activated SHH signaling and loss of RB signaling. We have also developed new embryonic brain tumor transplantation assays for high-throughput drug screening on hundreds of animals/day and show MEK activity is essential for the oligoneural CNS-PNET tumor growth in vivo. Thus, MEK inhibitors may represent the first targeted therapy option for children with oligoneural CNS-PNETs. We will present these results and plans for expanding the zebrafish system to generate other classes of brain tumors and for growing human PDX's in zebrafish.
Perspektiven der Seelenheilkunde.
Journal: JAMA (1931)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 4480: Associations between phytanic acid and alpha-methylacyl-CoA racemase (AMACR) expression in the normal human prostate
Authors: Yachana Kataria, Peter Gann, Erika Enk, Ann Moser, Ryan Deaton, Yi Lu, Larisa Nonn, Roohollah Sharifi, Leslie Deane, Vijayalakshmi Ananthanarayanan, Margaret Wright-Geise
Journal: Cancer Research (2012)

Abstract Alpha-methylacyl-CoA racemase (AMACR) is an enzyme that is overexpressed in prostate cancer, with lower levels present in normal prostatic tissues. AMACR is involved in the metabolism of phytanic acid - a branched chain saturated fatty acid that has been linked with elevated risks of prostate cancer in several epidemiologic studies. Although considerable research has been done on AMACR as a clinical biomarker in prostate cancer, no study has evaluated the possible link between phytanic acid and AMACR gene expression in the normal human prostate, and thus the possibility that AMACR plays a causal role in prostate carcinogenesis. Fasting blood and histologcally benign prostate tissue samples were obtained from 31 men undergoing radical prostatectomy for the treatment of localized disease. Concentrations of phytanic acid in serum and tissues were determined by isotope dilution gas chromatography-mass spectrometry. RNA was extracted from epithelial cells isolated from fresh-frozen prostate tissues by laser capture microdissection, and AMACR mRNA levels were quantified using real time polymerase chain reaction. Tissue phytanic acid concentrations were not significantly correlated with serum levels nor with prostatic AMACR mRNA levels. Notably, AMACR was significantly inversely correlated with body mass index (Spearman correlation coefficient (r)= –0.43, p=0.02) and directly correlated with Gleason score (r=0.35, p=0.05). Stratification by body mass index revealed an unexpected inverse correlation between wAMACR gene expression levels and phytanic acid concentrations in the prostate (r= –0.95, p= 0.001) in obese men. In conclusion, blood and tissue levels of phytanic acid were not correlated, which suggests that blood measures should not be utilized as a surrogate measure of this fatty acid in the target organ. Contrary to expectation, tissue phytanic acid levels were significantly inversely associated with AMACR gene expression levels in the prostate, but only among obese men.These findings require confirmation in other, larger studies. 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 4480. doi:1538-7445.AM2012-4480
Sarcoidosis - Diagnosis by Endoscopic Ultrasonography
Authors: P Lago, F Castro-Poças, J Areias
Journal: Endoscopy (2006)

A 67-year-old woman presented with intermittent solid food dysphagia, which had 3 months of evolution. There weren't any other symptoms. Was evaluated with an upper endoscopy that revealed a sub-epithelial lesion in the esophageal wall, at 27cm from the incisor teeth. Endoscopic ultrasonography disclosed, between 23 and 30cm from the incisor teeth, a heterogeneous lesion mostly hypoechoic, with calcifications and areas suggestive of necrosis. The lesion presented mostly extrinsic to the esophageal wall but with small areas where it wasn't possible to define a cleavage plane with both adventitia and muscularis propria; the lesion had an irregular border and a maximum transversal diameter of 37mm. There were periesophageal and peritracheal lymph nodes, the largest with 10mm of diameter. It was performed a fine needle aspiration cytology under endoscopic ultrasonography guidance of this lesion. The histological examination identified epithelioid granulomas with some multinucleated giant cells, without caseation necrosis, suggestive of sarcoidosis. The axial computed tomography showed the lesion and the enlarged mediastinal lymph nodes noted in the endoscopic ultrasonography and revealed few pericentimetric nodes in the right lung periphery. The patient reported a progressive improve of the dysphagia, being at the present free of any symptom. She wasn't submitted to any treatment. We concluded that the patient has sarcoidosis, with predominance of lymph node involvement, in spontaneous remission and in clinical surveillance at the moment. We emphasize the rare form of clinical presentation of sarcoidosis and the role of fine needle aspiration guided by endoscopic ultrasonography in the diagnosis of this particular case. We also emphasize the importance of endoscopic ultrasonography in the study of lesions that present with protrusion of the digestive tract wall.
Allergic Reactions to Milk-Contaminated “Nondairy” Products
Authors: James E. Gern, Evelyn Yang, Helen M. Evrard, Hugh A. Sampson
Journal: New England Journal of Medicine (1991)

ADVERSE reactions to cow's milk have been estimated to occur in 0.1 to 7.5 percent of children.1 , 2 A variety of manifestations have been reported, including urticaria, angioedema, atopic dermatitis, rhinitis, wheezing, anaphylactic reactions, various gastrointestinal syndromes, and failure to thrive.3 , 4 Some patients may be extremely sensitive to milk; the ingestion of as little as one drop has been reported to cause generalized reactions.5 In children, repeated exposures to small quantities of food allergens may lead to recurrence of symptoms and delay the resolution of food allergy.2 , 6 , 7 The management of sensitivity to cow's milk is based on the complete elimination of . . .
The role of receptor tyrosine kinase and activated PI3K signaling in response/resistance to HER-2 targeted therapy.
Authors: NA O'Brien, BC Browne, L Chow, C Ginther, B Bensadigh, J Arboleda, MJ Duffy, J Crown, N O'Donovan, DJ Slamon
Journal: Cancer Research (2009)

Abstract Abstract #2013 Background: Trastuzumab and lapatinib therapy provide proven clinical benefits to women with HER-2 positive breast tumors. However, not all patients that have high HER-2 levels respond. Here we describe the development and characterization of models of both clinical forms of trastuzumab resistance, i.e., de novo and acquired resistance.&amp;#x2028; Materials and Methods: Models of acquired resistance were established by culturing BT-474 and SKBR3 cells in high dose trastuzumab (105 μg/ml) for nine months. De novo resistance was examined in a panel of 17 HER-2 amplified cell lines. Response to the dual EGFR-HER2 inhibitor, lapatinib, was also measured. For each agent, response was measured by two independent assays; cell count and colony formation assay. Levels of HER-2, p-HER-2, EGFR, p-EGFR, IGF-1R, p-IGF-1R, p95, PTEN, and p27, and the presence of PIK3CA activating mutations were assessed in each cell line.&amp;#x2028; Results: Both BT-474 and SKBR3 conditioned cell lines have a reduced response to trastuzumab but remain sensitive to lapatinib. Analysis of the panel of HER-2 amplified cell lines revealed that SUM-225, HCC-1419, HCC-1954, HCC-1569 and JIMT-1 are models of de novo resistance to trastuzumab. The SUM-225 and HCC-1419 cell lines, despite being trastuzumab resistant, were exquisitely sensitive to lapatinib. The UACC-893, UACC-732, HCC-1569, MDA-MB-361 and JIMT-1 cell lines were identified as being resistant to lapatinib (IC50 &amp;gt; 1 μM), whereas the HCC-1569 and JIMT-1 were resistant to both trastuzumab and lapatinib. Resistance to trastuzumab correlated significantly with active PI3K signaling (p = 0.003), as assessed by combined analysis of PTEN status and PIK3CA mutation status. Response to lapatinib correlated significantly with levels of HER-2 (p = 0.013), pHER-2 (p = 0.086), p95 (p = 0.033), p-EGFR (p = 0.019) and p-IGFR (p = 0.046).&amp;#x2028; Conclusion: We have identified reliable, HER-2 overexpressing, cell line models of response and resistance to trastuzumab and lapatinib. Our analysis of these models indicates that activated PI3K signaling plays a crucial role in de novo resistance to trastuzumab while high levels of RTK signaling appears to sensitize HER-2 positive cells to lapatinib treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2013.
AB1175 Severe form of juvenile dermatomyositis with vasculopathy and ocular complications
Authors: M. Frkovic, Z. Mustapic, N. Vukojevic, I. Malcic, M. Jelusic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Juvenile dermatomyozitis (JDM) with vasculopathy is rare but the most severe form of JDM. Vasculopathy so far signified a poor prognosis with relapsing and chronic course and high risk of developing calcinosis, in other cases rapidly led to death. <h3>Objectives</h3> To analyze characteristics of the presenting and cumulative clinical features, laboratory features, treatement modalities, disease activity and oucome of children with JDM with vasculopathy. <h3>Methods</h3> All JDM patients and among them JDM patients with vasulopathy hospitalized during the period of 1991 – 2011 in Departement of Paediatric Rheumatology and Immunology, Zagreb University, School of Medicine, University Hospital Centre Zagreb, Croatia, were enrolled into the study. <h3>Results</h3> There were 31 children with JDM hospitalised in our Departement: 15 boys (48.4%) and 16 girls (51.6%) with mean age at disease onset 12.1 years. Seven hospitalised children (26.9%) had severe form of JDM with vasculopathy: two with acute gastrointestinal perforation and bleeding, one with urinary tract involmenet and chronical hematuria and four with multysistem involvement – brain oedema with hallucinations, respiratory distress syndome, myocarditis, gastrointesinal bleeding, one of them also with retinal cotton-wool spots and papillar oedema. In all JDM cases therapy included corticosteroids, in most cases combined with methotrexate and IV imunoglobulines, in severe vasculopathy cases also combined with cyclophosphamide and plasmaphereis. In last case, 8 years old girl hospitalized in our Departement in september 2011. with rapid progression of respiratory insufficiency within severe acute multysistem involvement including retinal cotton-wool spots and papillar oedema, with poor response to multiple drug therapy combined with plasmaphereis, on 24th day of treatement we applyed first dose of anti-TNF therapy (infliximab). Among all JDM patients with vasculopathy two patients had rapid progression with gastrointestinal perforations, profuse bleeding and lethal outcome, four patients has chronic course with calcinosis. In patient with severe acute multysistem involvement including retinal cotton-wool spots and papillar oedema, applyed anti-TNF therapy resulted in rapid complete resolution of eye changes and excellent, fast general recovery. <h3>Conclusions</h3> In our opinion, an early apply of anti-TNF therapy in JDM patient with severe acute multysistem vasculopathy results in excellent outcome so further studies of anti-TNF therapy in these cases are reasonable. <h3>Disclosure of Interest</h3> None Declared