tbuckley/cabot-search huggingface dataset:
AT-50 * ALA-BASED PHOTODYNAMIC THERAPY IN RECURRENT MALIGNANT GLIOMA - A PILOT STUDY
Authors: J. Schroeteler, S. Schipmann, E. S. Molina, O. Grauer, W. Stummer, C. Ewelt
Journal: Neuro-Oncology (2014)

OBJECTIVE: Recurrent malignant glioma (RMG) is an orphan disease without standard therapeutic recommendation. ALA-based photodynamic therapy (PDT) for malignant gliomas has been investigated in-vivo and in-vitro, suggesting potential efficacy. We report our experience with ALA-PDT in malignant recurrent glioma patients. METHODS: Data of seven patients with diagnosis of RMG, treated by PDT in a compassionate setting between 02/2011-05/2014 were analyzed. All seven patients received 20 mg/kg bodyweight ALA orally 4-6 hours prior to surgery. A stereotactic biopsy was taken followed by PDT administration with a constant tissue power of 200 mW/cm being applied by diode laser into the target area for one hour. RESULTS: Prior to PDT, patients underwent two brain surgeries (median). Six patients received radiotherapy with a minimum of 60 Gy, temozolamide (TMZ) was taken by four patients and two patients were TMZ naive prior to PDT. Histologically, five glioblastomas (GBM), one anaplastic oligodendroglioma (AO) and one anaplastic astrocytoma (AA) were detected. MGMT negative promotor methylation status (PMS) was observed in five cases and positive MGMT-PMS in one tumor. After PDT, three patients received TMZ, one Avastin, one Lomustine, one was given no further chemotherapy, and in one patient data was missing. A median PFS of two and OAS of 13 months after PDT treatment, as well as a median OAS from first diagnosis of 24 months was reached. Brain edema responding to steroids was detected in three patients during first 24 hours after PDT. One patient treated with Bevacizumab showed wound healing complication. No other severe effects occurred. CONCLUSION: PDT was well tolerated and a median OAS of 13 months and complete OAS of 24 months suggest a survival advantage by PDT as an additive surgical treatment option in RMG.
A8.20 A novel resveratrol prodrug: anti-proliferative and pro-apoptotic effects in human T-cells
Authors: K Goldhahn, K Schmetterer, G Steiner, M Hintersteininger, T Erker, B Kloesch
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Resveratrol is a naturally occuring polyphenol produced in many plants (red grapes, raspberries, blueberries, etc.). The positive health effects of resveratrol are due its potent anti-inflammatory, anti-oxidant and anti-proliferative activities in many types of cancer cells. Due to the fact that resveratrol is sensitive to oxygen and is almost insoluble in water, its therapeutic application is very limited. Therefore, work is going on designing resveratrol analogues to improve the solubility and bioavailability of the natural resveratrol. Recently, we designed and synthesised a resveratrol prodrug (FEHH4–1) which is only active within the cells. Through esterification of all three phenolic groups, stability as well as lipophilicity of the natural resveratrol could be improved. In the present study, we compared the effects of resveratrol with FEHH4–1 on Jurkat T- cells. <h3>Material and methods</h3> Jurkat T- cells were stimulated with PMA/PHA in the absence or presence of different concentrations of resveratrol or FEHH4–1. Modulation in IL-2 promoter activity was monitored by a IL-2 luciferase reporter assay. IL-2 release was quantified by enzyme-linked immunosorbent assay (ELISA). The effects of resveratrol and FEHH4–1 on cell proliferation and apoptosis were evaluated by XTT assay, Annexin-V/7-AAD staining and Western blot. <h3>Results</h3> Both resveratrol and FEHH4–1 effectively attenuated IL-2 promoter activity and IL-2 expression in stimulated Jurkat T- cells. At a concentration of 25 µM, resveratrol blocked IL-2 production at about 50%, FEHH4–1, however, at about 80%. Additionally, we observed that FEHH4–1 reduced cell proliferation and induced apoptotic cell death at significantly lower concentrations than resveratrol. <h3>Conclusion</h3> The resveratrol prodrug FEHH4–1 significantly amplified the beneficial effects of resveratrol in Jurkat T- cells. In comparison to resveratrol, FEHH4–1 enhanced downregulation of IL-2 production, and decreased proliferation rate in Jurkat T- cells. These data indicate that FEHH4–1 could be a substitute for the natural resveratrol in the future.
SC-16 * DIVERGENT CELL CYCLE REGULATION IN GBM CELLS PROVIDES A UNIQUE POINT OF INTERVENTION IN POLARIZED CD133+ CELLS
Authors: R. Lerner, M. Sidorov, R. Hashizume, Y. Yoshida, T. Ozawa, C. D. James, l. Petritsch
Journal: Neuro-Oncology (2014)

Recent studies in distinct glioma types have separately identified phenotypically distinct populations of tumor propagating cells (TPCs). Enrichment of TPCs by cell surface marker expression (CD133 [PMID:17051156], NG2 [PMID: 21907924]) has revealed the possibility of multiple TPC populations, within a single tumor, that have distinct properties and therapy sensitivities. Here we identify and compare the coexisting populations of glioblastoma multiforme (GBM) cells expressing the stem marker CD133 and the progenitor marker NG2. We compare the proliferative properties of CD133+ and NG2+ cells, and investigate how polarity and mode of division may determine other functional properties including cell cycle regulation and therapy sensitivity. Established and primary GBM cell cultures were analyzed by immunofluorescence and flow cytometry for expression of CD133 and NG2, alongside markers of polarity and proliferation. We showed that CD133+ and NG2+ GBM cells coexist as predominantly separate subpopulations. CD133+ cells are highly polarized and, compared to NG2+ or marker-negative subpopulations, are slower dividing. Cell cycle and gene expression analyses showed that the increase in cell cycle length in CD133+ cells is due to an extended G2-M period. As expected CD133+ cells have increased expression of DNA-damage response genes, however paradoxically we also detected increased activation of polo-like kinase 1 (PLK1). CD133+ cells were uniquely sensitive to the PLK1 inhibitor BI2536 in vivo, and treatment of intracranial GBM xenografts with the BRAF inhibitor PLX4720 and BI2536 showed greater anti-tumor activity than either alone. Our studies identified two putative TPC subpopulations in GBM with distinct cell cycle dynamics, DNA damage response and cell division mode. Ongoing work will investigate the role of Plk1 activity in linking these divergent phenotypes. Understanding this phenotypic heterogeneity in adjacent TPC types will allow the design of treatment strategies that eradicate multiple putative TPC populations.
Abstract 1392: CTGF inhibits cell motility in oral cancer cells through reducing COX-2 expression
Authors: Wan-Yu Yang, Chih-Hsin Tang, Jing-Yuan Chuang
Journal: Cancer Research (2011)

Abstract Oral squamous cell carcinoma (SCC) has a striking tendency to migrate and metastasize. Cyclooxygenase (COX)-2, the inducible isoform of prostaglandin synthase, has been implicated in tumor metastasis. Connective tissue growth factor (CTGF), a secreted protein that binds to integrins, modulates the invasive behavior of certain human cancer cells. However, the effect of CTGF on migration activity and COX-2 expression in human oral cells is mostly unknown. Here we found that CTGF reduced the migration and expression of COX-2 in human oral cancer cells. αvβ5 monoclonal antibody (mAb), phosphatidylinositol 3-kinase inhibitor (PI3K; Ly294002 and wortmannin) and Akt inhibitor reversed the CTGF-inhibited the migration and COX-2 down-regulation of oral cancer cells. CTGF stimulation decreased the phosphorylation of focal adhesion kinase (FAK), PI3K and Akt. In addition, c-Jun siRNA also antagonized the CTGF-inhibited migration and COX-2 expression. Moreover, CTGF decreased the binding of c-Jun to the AP-1 element on the COX-2 promoter. Taken together, our results indicated that CTGF inhibits the migration of oral cancer cells by decreasing COX-2 expression through the αvβ5 integrin receptor, FAK, PI3K, Akt, c-Jun and AP-1 signal transduction pathway. 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 1392. doi:10.1158/1538-7445.AM2011-1392
P2-02-04: Novel Functions of vps34 in Non-Transformed Epithelial Cells: Regulation of Cell Proliferation and Tumorigenesis.
Authors: H Su, T Xu, S Ganapathy, Z-M Yuan
Journal: Cancer Research (2011)

Abstract Autophagic and endocytic pathways are tightly regulated membrane rearrangement processes that are crucial for homeostasis, development and disease. A list of proteins regulating these cellular processes show altered expression in cancers, suggesting derailed autophagy or endocytosis as an emerging feature of cancer. Class III phosphatidylinositol 3-kinase (PI3kinase) Vps34 regulates both autophagic and endocytic systems by recruiting proteins containing PtdIns3P binding domains. Recently, many new insights into the biology of class III PI3Kinase have been reported. Most of these studies, however, used mainly transformed cells. It is unclear whether class III PI3Kinase works similarly in non-transformed cells. In the recent study, we explored this by depleting both transformed and non-transformed mammary epithelial cell lines of Vps34 using shRNA. In consistent with previous finding, vps34-depleted cells are defect in formation of FYVE-GFP puncta, and showed altered early and recycling endosome dynamics. In a shark contrast to transformed cells where knockdown of Vps34 was associated with decreased growth, Vps34 deficiency in non-transformed cells resulted in a marked increase in cell proliferation. The deregulated autophagy function found in Vps34-depleted cells appeared to be not involved in cell growth regulation as silence of either Atg7 or Beclin1 expression did not affect the growth rate. On the other hand, reporter luciferase-based ten-pathway screens suggested an altered activity of the MAPK pathway. Indeed, biochemical analysis indicated a sustained ERK activation resulting from the impediment of endosome-mediated EGFR turnover in Vps34 deficient cells. A contribution of the endosomal pathway to Vps34-mediated regulation of cell proliferation was further confirmed by using Rab5 and Rab11 mutants that deregulated early and recycling endosome, respectively. Importantly, inactivation of Vps34 compromised the cellular barrier against oncogene-mediated transformation, as demonstrated by the increased susceptibility of Vps34 depleted cells to Ras-induced colony formation in vitro and tumor development in mice. All together, our data uncover a novel role for the class III PI3Kinase-endosomal pathway in regulation of cell proliferation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-02-04.
Quantitation of Differential Sensitivity of Human-Tumor Stem Cells to Anticancer Drugs
Authors: Sydney E. Salmon, Anne W. Hamburger, Barbara Soehnlen, Brian G. M. Durie, David S. Alberts, Thomas E. Moon
Journal: New England Journal of Medicine (1978)

With a direct in vitro tumor-colony assay developed to measure sensitity of human-tumor stem cells to anticancer drugs, we performed 32 retrospective or prospective clinical studies in nine patients with myeloma and nine with ovarian cancer treated with standard agents that were tested in vitro. The results were clearly correlated (P is less than 0.00001). Unique patterns of sensitivity and resistance to the six drugs tested were observed for individual patients. In eight cases of myeloma and three of obarian carcinoma in vitro sensitivity corresponded with in vivo sensitivity whereas in one case of myeloma it did not. In vitro resistance correlated with clinical resistance in all five comparisons in myeloma and all 15 in ovarian cancer. We conclude that this assay shows sufficient promise to warrant larger-scale testing to determine its efficacy for selection of new agents and individualized cancer chemotherapy regimens.
P13.15 * USING IMAGE-GUIDED AND INTENSITY-MODULATED RADIOTHERAPY TO REDUCE SCALP DOSE AND RADIOTHERAPY-RELATED ALOPECIA FOR PATIENTS WITH INTRACRANIAL TUMOURS TREATED WITH TOMOTHERAPY
Authors: D. L. P. Holyoake, C. Powell, A. R. Geater, S. J. Jefferies
Journal: Neuro-Oncology (2014)

INTRODUCTION: Radiotherapy to intracranial tumours commonly results in permanent alopecia on the scalp, an important and distressing sideeffect that has a negative impact on patient quality-of-life.We demonstrated that the radiotherapy dose to the scalp can be examined during radiotherapy planning and can be reduced by the adoption of image-guided and intensitymodulated radiotherapy techniques.METHOD: Twelve patients were selected who had been treated using TomoTherapy at Cambridge University Hospitals and had suffered resulting alopecia.A method of producing a realistic 'hair-bearing scalp' structure in the radiotherapy planning software was Overall survival
Abstract 2448: Development of a red fluorescent labeled agent for assessing HER2 expression <i>in vitro</i> and <i>in vivo</i>
Authors: Nara Narayanan, Garry Cuneo, Jeff Morin, Kristine Vasquez, Milind Rajopadhye, Wael Yared, Jeffrey D. Peterson, Sylvie C. Kossodo
Journal: Cancer Research (2012)

Abstract Upregulation of tumor HER2 occurs in approximately 25% women with breast cancer and is often associated with poor prognosis. We developed a red fluorescent imaging agent to non-invasively image and quantify tumor-associated HER2 expression in vivo. A red fluorescent dye (VivoTag 645; α=210,000 μ/cm; abs/em max 643/660 nm) was used to label trastuzumab, which is currently used to treat breast and stomach cancer. The red-labeled trastuzumab (VM4003) preferentially labeled HER2+ SKOV-3 human ovarian adenocarcinoma cells over HER2− human colorectal adenocarcinoma Colo-205 cells (10 fold), and the specificity of binding was confirmed by control experiments using free dye, labeled non-specific IgG, and competitive blockade with unlabeled excess trastuzumab. Fluorescence microscopy confirmed the expected membrane localization of fluorescence. In vivo and ex vivo imaging by fluorescence molecular tomography (FMT), showed significantly higher signal within the tumors, peaking at 6-72 hours following intravenous injection of 2 mg/kg VM4003, decreasing thereafter with a tissue half-life of 3 days. In vivo quantification of tumor signal in nude mice showed significantly higher tumor signal in HER2+ than in HER2− tumors (14.36 + 4 versus 2.39+ 0.74 pmol, at 6h imaging time, p=0.007; 18.77 + 4.45 versus 3.50+ 0.98 pmol, at 24h, p=0.001). Specificity of targeting was confirmed by competition with excess intravenous unlabeled trastuzumab, which achieved 70% signal inhibition in the tumors (tumor signal 16.12 + 3.03 versus 4.72 + 1.96 pmol, p=0.022 at 24h). Tumor volumes, as determined by direct measurements of tumor size, were comparable between both groups of mice (p=0.193). Fluorescence microscopy of ex vivo frozen tissue sections confirmed tumor fluorescence and signal localization associated to cell membranes and cytoplasm. In summary, red fluorescent-labeled trastuzumab selectively targets αER2, allowing both imaging in vitro and the non-invasive real-time tomographic imaging and quantification in vivo of HER-2 expression. 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 2448. doi:1538-7445.AM2012-2448
DOSE-RESPONSE RELATIONSHIP BETWEEN HYPERMAGNESEMIA AND QTC PROLONGATION
Authors: Chayakrit Krittanawong, Charat Thongprayoon, Thoetchai Peeraphatdit, Malcolm Bell, Vitaly Herasevich, Peter Brady, Suraj Kapa, Samuel Asirvatham, Niyada Naksuk
Journal: Journal of the American College of Cardiology (2015)
AB0492 Sonographic changes of temporomandibular joint in systemic sclerosis
Authors: D. Melchiorre, M. Maresca, A. Del Rosso, F. Bandinelli, M. Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The inflammatory involvement of temporomandibular joint (TMJ) in rheumatic diseases may induce the damage of the TMJ provoking a severe impairment of mouth opening and affecting patient's quality of life. TMJ may be also involved in systemic sclerosis (SSc). <h3>Objectives</h3> The aim of the present investigation was to evaluate the usefulness of US imaging for the detection of disc displacement, condylar alterations and intrarticular effusion in SSc patients (pts) compared with magnetic resonance imaging (MRI). <h3>Methods</h3> 35 SSc patients (females with mean age 65.9 years) with TMJ involvement were consecutively examined. US examination was performed on both TMJ, in static and dynamic phases, by means of My Lab70 US 7-18 MHz (Esaote, Genoa, Italy). The probe was placed along the axis of the mandibular branch. The following TMJ characteristics were evaluated in each joint: 1) joint space; 2) presence of joint effusion; 3) condylar profile; 4) position of the articular disc at open and closed mouth. In all pts was performed MRI on both TMJ. <h3>Results</h3> All SSc patients had reduced mouth opening with monolateral or bilateral TMJ pain. Not correlation with disease duration was found. <b>MRI</b>. In the patients joint effusion was depicted by a thin line or area of high signal intensity within the joint space. It was detected in 6/35 SSc pts (17.1%). Condilar alterations were detected by MRI in 19/35 SSc pts (54,2%). MRI revealed also disc displacement in 10/35 SSc pts (28,5%). In 7 SSc pts erosions were present. <b>US</b>. In 7/35 SSc pts (20%) US showed joint effusion. Condilar alterations were observed in 21/35 SSc pts (60 %). Disc displacement was evident in 12/35 SSc pts (34,2%). Erosions were detected in 9 SSc patients. <b>Concordance MRI-US</b>. The concordance between US and MRI was evaluated. For joint effusion, concordance was 83%. In US assessment of disc displacement, a concordance with MRI was 82.8%. A concordance for condilar alterations was detected 77%. <h3>Conclusions</h3> Our data show that the pathological changes of TMJ may be detected by US examination in SSc pts. It is important to note that pain in SSc pts is not usually related to the occurrence of joint effusion but more often to disc displacement or remodelling of the condyle and the presence of condylar alterations in SSc is an interesting finding observed by US. <h3>Disclosure of Interest</h3> None Declared
Misregulation of Suppressors of Cytokine Signaling in Eosinophilic Esophagitis
Authors: Maria Paz Zafra, Nataly Cancelliere, Pablo Rodriguez Del Rio, Monica Ruiz Garcia, Laura Estevez, Maria Victoria Andregnette, Silvia Sanchez-Garcia, Ana Fiandor, Joaquin Sastre, Santiago Quirce, Maria Dolores Ibañez, Victoria Del Pozo
Journal: Journal of Allergy and Clinical Immunology (2013)
AB1084 Bone oxalosis in a patient with chronic renal failure: About a new case
Authors: Y. Ben Ariba, I. Gharsallah, S. Sayeh, J. Laabidi, L. Metoui, F. Ajili, N. Ben Abdelhafidh, R. Battikh, B. Louzir, S. Othmani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Primary hyperoxaluria Type 1 is a congenital metabolic disease characterized by exaggerated production of oxalic acid. It is due to the deficiency of the hepatic enzyme, the alanine- glyoxylate aminotransferase. Calcium oxalate deposits may occur in several organs espacielly in kidneys, bones and soft tissus. Bone oxalosis is rare. <h3>Methods</h3> We report a new case of bone oxalosis collated in the internal medecine departement of the Military Hospital of Tunis. <h3>Results</h3> A twenty-one-year-old man was admitted for exploration of an end-stage renal failure. He had been on maintenance hemodialysis. He complained diffuse polyarthralgia and proximal bone pain. Physical examination revealed an average general state, an ascites, oedema of lower limbs and hepatomegaly. Joints were not painful. A liver biopsy was performed and closes in the diagnosis of primary oxalosis with deficiency of alanine- glyoxylate aminotransferase. The assay of oxalic acid was 8.4 mg/l (normal between 1.3 mg/l and 2.3 mg/l). Radiological examinations showed cortical erosions at metacarpophalangeal joints and phalanges, in addition to increased density area surrounded by areas of demineralization in carpal bones. In long bones, there were cortical defects associated to metaphyseal and epiphyseal mesangial sclerosis bands. Percutaneous iliac crest biopsy was performed and revealed large numbers of oxalate crystals within the medullary space with giant-cell granulomas, fibrosis and trabeculae rarefaction.The crystals were arranged in a radial rosettelike pattern and were birefringents under polarized light. These changes were associated with features of secondary hyperparathyroidism. <h3>Conclusions</h3> Bone oxalosis is rare, it was described since 1950. Radiological abnormalities are various. It also stresses that bone oxalosis may mimick secondary hyperparathyroidism, especially radiologically. Differential diagnosis is therefore mandatory and diagnosis should be anatomopathological. <h3>References</h3> Salyer WA, Keren D. Oxalosis as a complication of chronic renal failure. Kidney lnt 1973;4:61-66 Salyer WA, Keren D. Oxalosis as a complication of chronic renal failure. Kidney lnt 1973;4:61-66 Carsen GM, Radkowski MA. Calcium oxalosis. Radiology 1974 Gherardi G, Poggi A, Sisca 5, Calderaro V, Bonucci E. Bone oxalosis and renal osteodystrophy: a histopathological, histochemical and ultrastructural investigation. Arch Pathol <h3>Disclosure of Interest</h3> None Declared