tbuckley/cabot-search huggingface dataset:
RK-0202 for radiation-induced oral mucositis
Authors: M. S. Chambers, D. V. Welsh, R. A. Scrimger, W. Zehn, J. B. Epstein, J. Troha, S. T. Sonis
Journal: Journal of Clinical Oncology (2006)

5523 Background: This study evaluated the effect of RK-0202, administered as an oral rinse, on the incidence of severe oral mucositis in patients being treated with of radiation therapy (RT) for tumors of the head and neck. Methods: This was a prospective, randomized, placebo-controlled, double-blind study that compared the effect of 2 concentrations of RK-0202 with placebo on the incidence of severe oral mucositis at a cumulative RT dose of 60 Gy in 110 subjects. Twenty-seven subjects received RK-0202 5%, 38 received RK-0202 10%, 29 received placebo and 16 received standard of care. Subjects began dosing just prior to RT and continued dosing six times daily throughout RT. Oral mucositis was assessed twice weekly throughout RT by trained oral evaluators. Results: The higher dose of RK-0202 (10%) successfully attenuated severe oral mucositis as measured by WHO or NCI-CTC v.3 criteria. The incidence of WHO grade 3 or 4 oral mucositis by a cumulative RT dose of 60 Gy was 35% in the RK-0202 group vs. 54% in the placebo group (p = NS). By 50 Gy the incidences in the RK-0202 and placebo groups were 25% and 54%, respectively (p = 0.053). Similarly, the incidence of NCI grade 3 or 4 oral mucositis by 60 Gy was 64% in the RK-0202 cohort vs. 92% for subjects being treated with placebo (p = 0.005). Subjects treated with RK-0202 required less feeding tube placement compared to placebo recipients (3% vs. 22%, p = 0.037) and less opiate analgesia. The median percent of time on opiates was 6% on RK-0202 vs. 21% on placebo. The overall incidence of serious adverse events was significantly lower in subjects treated with RK-0202 (8% vs. 31%, p = 0.024). In general, there was no benefit noted among subjects who received RK-0202 as a 5% solution. Conclusions: RK-0202 significantly reduced the incidence of severe mucositis in subjects treated with radiotherapy for head and neck cancer and was not associated with significant adverse events. [Table: see text]
The Effect of Dietary Supplementation with n—3 Polyunsaturated Fatty Acids on the Synthesis of Interleukin-1 and Tumor Necrosis Factor by Mononuclear Cells
Authors: Stefan Endres, Reza Ghorbani, Vicki E. Kelley, Kostis Georgilis, Gerhard Lonnemann, Jos W. M. van der Meer, Joseph G. Cannon, Tina S. Rogers, Mark S. Klempner, Peter C. Weber, Ernst J. Schaefer, Sheldon M. Wolff, Charles A. Dinarello
Journal: New England Journal of Medicine (1989)

We examined whether the synthesis of interleukin-1 or tumor necrosis factor, two cytokines with potent inflammatory activities, is influenced by dietary supplementation with n—3 fatty acids. Nine healthy volunteers added 18 g of fish-oil concentrate per day to their normal Western diet for six weeks. We used a radioimmunoassay to measure interleukin-1 (IL-1β and IL-1α) and tumor necrosis factor produced in vitro by stimulated peripheral-blood mononuclear cells. With endotoxin as a stimulus, the synthesis of IL-1β was suppressed from 7.4±0.9 ng per milliliter at base line to 4.2±0.5 ng per milliliter after six weeks of supplementation (43 percent decrease; P = 0.048). Ten weeks after the end of n-3 supplementation, we observed a further decrease to 2.9±0.5 ng per milliliter (61 percent decrease; P = 0.005). The production of IL-1α and tumor necrosis factor responded in a similar manner. Twenty weeks after the end of supplementation, the production of IL-1βIL-1α, and tumor necrosis factor had returned to the presupplement level. The decreased production of interleukin-1 and tumor necrosis factor was accompanied by a decreased ratio of arachidonic acid to eicosapentaenoic acid in the membrane phospholipids of mononuclear cells. We conclude that the synthesis of IL-1β, IL-1α, and tumor necrosis factor can be suppressed by dietary supplementation with long-chain n—3 fatty acids. The reported antiinflammatory effect of these n—3 fatty acids may be mediated in part by their inhibitory effect on the production of interleukin-1 and tumor necrosis factor. (N Engl J Med 1989;320:265–71.)
TCT-147 Patient radiation exposure with a novel X-ray imaging technology during coronary angiography and angioplasty
Authors: Fernando Cura, Bonvini Victor, Pablo Lamelas, Gustavo O. Pedernera, Pablo Spaletra, Gerardo Nau, Lucio T. Padilla, Alfonsina Candiello, Jorge Belardi
Journal: Journal of the American College of Cardiology (2014)
AB0232 Predictive Factors for Foot Disability in Rheumatoid Arthritis Patients
Authors: D. Matei, A. Bighea, S. Patru, R. Traistaru
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> More than 90% of people with rheumatoid arthritis (RA) develop symptoms in the foot and ankle over the course of the disease. While each individual deformity is common, it is the combination of deformities that compounds the problem.(1) <h3>Objectives</h3> The objective of our study is to evaluate the predictive factors for forefoot impairments in different stages of rheumatoid arthritis (RA) patients. <h3>Methods</h3> We followed for 3 years 34 patients with RA. The patients were assessed twice: to the beginning of study and after 1 year. We evaluated the morning stiffness (minutes), the PJN, SJN-number of painful and swollen of the metatarsophalangeal (MTP) joints and, the level of pain (with VAS 100mm), the Health Assessment Questionnaire-walking subscale. The results were analyzed with the statistics programme SPSS. <h3>Results</h3> Pain and swelling MTP joint was present in 68% of patients (the average pain on VAS-6.89). The walking disability was present in 47% of patients. We also found an important correlation between the level of pain, swelling and walking disability (HAQ) (R 0.698, R<sup>2</sup> 0.551). <h3>Conclusions</h3> The significant correlation between the parameters analyzed in our study enables the supporting of the necessity for paying a considerable attention to forefoot assessment in RA patients because of important influence of walking disabilities in active life and participation in work, social and self-care activities. <h3>References</h3> http://orthoinfo.aaos.org <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5106
Abstract 3691: The correlation analysis of postoperative anxiety scale of colorectal cancer patient and the postoperative complication
Authors: Xiaodong Wang, Chao Fang, Zongli Hu, Jiqiao Yang, Bingyan Shu, Li Li
Journal: Cancer Research (2012)

Abstract Objectives Aim at evaluating the influence of postoperative anxiety scales on postoperative complications of colorectal cancer by clinically using the Hamilton anxiety. Methods Prospectively enrolling 126 patients definitely diagnosed with colorectal cancer from February to May in 2010at the Center of Gastrointestinal Surgery, West China Hospital, Sichuan University. By dividing them into three groups according to the anxiety scales, postoperative complication rates were compared between groups, relating postoperative anxiety factors were evaluated and clinical rating value between postoperative anxiety scale and postoperative complication incidence rate of patients was explored. Results There was a significant different of post complication rates among the three groups(x2=17.904, P&amp;lt;0.001), and the potential anxiety group(anxiety score=7-13)'s postoperative complication rate is lower than non-anxiety group(anxiety score&amp;lt;7) (x2=11.027, p=0.002)and anxiety group(anxiety score&amp;gt;14)(x2=20.677, P&amp;lt;0.001).The difference between the anxiety group and the non-anxiety group had no statistical significance(x2=1.636, p=0.274). The risk factors for postoperative anxiety were type of expense(p=0.053), resides(p=0.018), medical complication(p=0.014), neoadjuvant chemotherapy(p=0.053), the DUKE'S stage(p=0.009), the ordinary diet day after operation(p=0.001).After analyzing, the critical value was 17 point for anxiety score and the postoperative complication morbidity of patients was higher when the post anxiety scale was over 17(X2=12.538, P=0.004). Conclusions the postoperative anxiety scale of the colorectal patients has some corelations with the postoperative complication morbidity, and the ones whose score are high in anxiety scale are more likely to suffer from postoperative complications. However, the postoperative complication morbidity is relatively low in moderate anxiety patients. 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 3691. doi:1538-7445.AM2012-3691
CT, MRI, and 18F-FDG PET/CT in a Patient With Nested Stromal Epithelial Tumor of the Liver
Authors: Amin Samarghandi, David W. Barker, Elizabeth A. Hingsbergen, Milton J. Finegold, Nathan C. Hall
Journal: Clinical Nuclear Medicine (2014)

An 11-year-old girl presented with abnormal weight gain and was found to have hepatomegaly. MRI of the abdomen revealed a 20-cm hepatic mass. F-FDG PET/CT showed a large hypermetabolic calcified hepatic mass and couple of mildly hypermetabolic pulmonary nodules with associated intrathoracic lymphadenopathy. Liver biopsy was consistent with nested stromal epithelial tumor of the liver, a rare nonhepatocytic, nonbiliary primary neoplasm of the liver associated with variable calcification and ossification.
P2-07-03: Collective Evidence Suggests Neutrality for BRCA1 V1687I, a Novel Sequence Variant in the Conserved THV Motif of the First BRCT Repeat.
Authors: L Cortesi, Nicolo A De, V Medici, M Marino, D Turchetti, LM Pradella, G Rossi, E Parisini, M Federico
Journal: Cancer Research (2011)

Abstract Background: Unequivocal classification of BRCA1 and BRCA2 variants of uncertain significance (VUS) with respect to their effect on protein function is a challenge with consequent implications for clinical decision-making. Currently, integration of different types of evidence derived from independent sources appears to be the most reliable approach to help define disease relevance for each single VUS. During a routine screening for BRCA1 and BRCA2 mutations carried out by the Modena study group for familial breast and ovarian cancer we identified a novel BRCA1 sequence change (c.5178G&amp;gt;A) that causes a valine to isoleucine (V to I) substitution at position 1687. The sequence alteration was found in a patient diagnosed with early onset breast cancer and it was present neither in other breast/ovarian cancer families screened nor in unaffected control individuals. No co-occurrence of the variant with any known clinically relevant BRCA1 mutations was observed. The C-terminally located BRCA1 V1687I lies in the conserved THV motif of the first BRCT repeat. Disease-causality has previously been suggested for two neighbouring sequence alterations, BRCA1 V1688del, whose repercussions on protein stability and function were also reported (De Nicolo et al., 2009), and BRCA1 H1686Q (Giannini et al, 2008). We aimed at garnering evidence that, together with family and genetic data, could help assess the clinical significance of the V1687I variant. Methods: We employed a multimodal approach that included immunohistochemistry on tumor sections, in silico analyses, comparative structural modeling, and ascertainment of BRCT-mediated functional associations. Results: Whereas tumor histology, receptor and HER2/neu status were compatible with a BRCA1-deficient phenotype, most algorithms we used to assess sequence and structure variation based on evolutionary conservation predicted the BRCA1 V1687I variant to be benign. In line with this prediction, analysis of the modeled BRCA1 V1687I BRCT domain did not reveal any major structural changes relative to the wild type counterpart and suggested that BRCA1 V1687I leaves the local architecture and overall stability of the protein largely unaltered. Consistently, the BRCA1 V1687I protein was properly expressed and localized to the nucleus, and it was still capable of binding BRIP1/FANCJ, CtIP and Abraxas, three BRCT-interacting, DNA damage response and repair partner proteins. Conclusions: Based on our collected evidence, the BRCA1 V1687I amino acid change, although occurring in an evolutionary conserved region, does not seem to affect the function of the correspondingly encoded protein, and hence it is a likely benign sequence alteration. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-07-03.
[Tc99m]-Sestamibi scintimammography to compare the efficacy of different neo-adjuvant chemotherapy regimens.
Authors: L. K. Dunnwald, D. A. Mankoff, G K Ellis, J R Gralow, M J Drucker, R Livingston
Journal: Clinical Nuclear Medicine (1998)

s Presented At The 22Nd Annual Western Regional Meeting Of The Society Of Nuclear Medicine October 1997
Abstract 3710: Individual and combined effects of Tamoxifen and fish oil on mammary carcinogenesis in polyoma middle T transgenic mice
Authors: Andrea Manni, Haifang Xu, Sharlene Washington, Cesar Aliaga, Timothy K. Cooper, John P. Richie, Bogdan Prokopczyk, Ana Calcagnotto, Neil Trushin, Christopher Hamilton, Laurence M. Demers, Jason Liao, Michael F. Verderame, Karam El-Bayoumy
Journal: Cancer Research (2011)

Abstract There are currently no known effective regiments able to prevent the development of estrogen-receptor (ER) negative breast cancer in humans. We hypothesize that ER, frequently upregulated in preneoplastic mammary lesions, may contribute to the development of hormone-independent tumors through crosstalk with multiple cellular oncogenic pathways. Therefore, a multi-targeted approach is likely to be necessary to prevent ER negative tumors. In our previous study, we tested this hypothesis in CD rats and we showed that omega-3 rich fish oil (FO) potentiated the suppressive effect of Tamoxifen (Tam) on mammary carcinogenesis (A. Manni, et al. Cancer Prev Res 3:322, 2010). In the present investigations, we tested this hypothesis in polyoma middle T transgenic mice, since in this experimental system the development of ER negative tumors is preceded by preneoplastic lesions overexpressing functional ER, as evidenced by the concomitant upregulation of progesterone receptors which are products of estrogen action. Administration of increasing concentrations of Tam (1 ppm, 10 ppm, and 100 ppm) admixed with 20% corn oil (CO) modified AIN-76A diet, starting at 3 weeks of age, significantly delayed mammary carcinogenesis, inhibited tumor multiplicity by ∼50%, tumor volume by ∼90%, and tumor weight by ∼70% in a dose dependent fashion. At termination (week 12), however, tumor incidence was nearly 100% in all experimental groups. When Tam treatment was started after tumors had developed, no inhibition of tumor growth was observed, a finding consistent with the absence of ER in invasive adenocarcinomas in this experimental model. Administration of increasing concentrations of FO in the diet (5% FO + 15% CO; 10% FO + 10% CO, 17% FO + 3% CO) started at 3 weeks of age did not affect any of the tumor parameters compared to the control 20% CO diet. Combined administration of suboptimal (1 ppm) and optimal (100 ppm) doses of Tam with 17% FO and 10% FO respectively, delayed carcinogenesis and suppressed tumor multiplicity and volume to the same extent as observed with Tam alone. Therefore, the results indicate that, under these experimental conditions, FO failed to potentiate the chemopreventive action of Tam. Our results, however, provide support for the role of ER expression by the preneoplastic lesions in the development of hormone independent tumors and, consequently, for the importance of including ER targeting in combined chemoprevention strategies. 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 3710. doi:10.1158/1538-7445.AM2011-3710
A3.09 Synovial fibroblasts as determinants for arthritis specific pattern of joint involvement
Authors: M Frank-Bertoncelj, K Klein, G Russo, A Bratus, E Karouzakis, C Kolling, A Filer, CD Buckley, RE Gay, S Gay, C Ospelt
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Most forms of arthritis occur with a distinctive pattern of joint involvement. To elucidate whether stromal differences between the joints might play a role in the susceptibility of joints to develop arthritis, we compared the transcriptome, epigenetic marks and functions of synovial fibroblasts (SF) isolated from different joints. <h3>Material and methods</h3> SF were isolated from hand, shoulders, and knees from RA and OA patients. Total RNA was isolated and sequenced on theIlluminaHiSeq 2000 (n = 21). Epigenetic regulation was studied by methyl-DNA -immunoprecipitation and treatment with bromodomain inhibitors. Adhesion to tissue culture plates (n = 20) and proliferation (n = 15) were measured with the xCELLigence-RTCA-DP Instrument. Transwell plates were used to measure migration of leukocytes from healthy donors towards supernatants of cultured SF (n = 14). <h3>Results</h3> Based on their transcriptome profile, SF clustered according to their joint of origin. Hand SF featured increased expression of transcripts in the HOX cluster that are also increased in distal limb buds during embryonic development, eg, HOXD13, HOXA13 and HOTTIP. Accordingly, genes upregulated in hand SF were clustered in biological processes such as 'limb development' (enrichment score (ES) 4.3) and 'tissue morphogenesis' (ES 3.4). The expression of these developmental transcripts in adult SF was maintained by histone acetylation and lack of DNA methylation. Other biological processes enriched in hand SF were 'cell-cell signalling' (ES 2.9), 'cell migration' (ES 1.9) and 'defense response' (ES 0.9). Genes that were lower expressed in hand SF were mainly enriched in 'cell adhesion' (enrichment score 2.3) and 'embryonic morphogenesis (enrichment score 2.3). Functionally adhesion was significantly lower in handcompared to shoulder SF (cell index 0.6 ± 0.2 vs. 0.9 ± 0.2, p = 0.01). Hand SF proliferated faster than shoulder SF (doubling time: 39 ± 3h vs. 67 ± 15h, p = 0.03) and significantly more leucocytes migrated towards the supernatants from cultured hand SF than shoulder SF. <h3>Conclusions</h3> SF from different anatomic locations exhibit significant differences in their transcriptome, particularly in the expression of embryonic transcription factors encoded in the HOX cluster. Hand SF display differences in their chemotactic, proliferative and adhesive properties, which may explain why chronic arthritidis tend to be more destructive in hands compared to other joints.
P01.09 * INHIBITION OF FGFR1 SENSITIZES HUMAN GLIOBLASTOMA TO RADIOTHERAPY
Authors: V. Gouaze-Andersson, S. Mazoyer, J. Martinez-Gala, C. Delmas, M. Taurand, E. Cohen-Jonathan-Moyal, C. Toulas
Journal: Neuro-Oncology (2014)

Despite post-operative radio-chemotherapy, the prognosis of the patients with a glioblastoma (GBM) remains poor because of a local recurrence, mainly due to resistance of the GBM cells to radiotherapy. We have previously demonstrated that FGF-2 controls cell radioresistance and that expression of FGFR1 in the tumor of patients with GBM was an independent prognostic factor of overall survival and of time to progression after radio-chemotherapy. These results led to the hypothesis that FGFR1 could be involved in the radioresistance of GBM and that inhibiting FGFR1 in tumor cells may increase the efficiency of radiotherapy. To investigate this, we used in vitro and in vivo silencing strategies in GBM radioresistant U87 cells mainly expressing FGFR1. We first showed that the surviving fraction after a 5Gy irradiation (SF5) of U87 cells was significantly reduced when FGFR-1 has been silenced compared to U87 control cells (SF5=0.58%±0.06 to 0.33%±0.03; p < 0.001). Moreover, inhibition of FGFR1 led to a significant increase of the mitotic cell death after irradiation. We then showed that inhibiting FGFR1 led to an inhibition of PLCγ phosphorylation which radiosensitizes U87 cells in vitro. We then performed an in vivo approach by generating subcutaneous limb xenografts with two different FGFR-1 silenced U87 clones, locally or sham irradiated with two 3 Gy fractions when tumor size reached 300 mm3. We showed a significant growth delay in the two silenced FGFR1 xenografts compared to control cell xenografts. In addition, a dramatic decrease in expression of hypoxia inducible factor, HIF-1α has been found by immunohistochemistry in silenced FGFR-1 xenografts compared to control cell xenografts and confirmed in vitro by western blot. Our data establishes the proof-of-concept of FGFR1 inhibition as a new treatment for radiosensitizing these aggressive tumors. Considering that we showed that FGFR-1 expression in GBM patients is an independent prognostic factor of survival and time to progression after radio-chemotherapy, our present study highly suggests the interest to associating a FGFR1 inhibitor with radiotherapy in clinical trials for patients with glioblastoma.
MECHANISMS OF ADAPTIVE RADIOPROTECTION IN GLIOMA STEM CELLS
Authors: H. Saya
Journal: Neuro-Oncology (2014)

BACKGROUND: Cancer stem cells (CSCs) play an important role in disease recurrence. Intrinsic characteristics such as high DNA repair ability and quiescence allow CSCs to survive acute injury. It is unclear, however, how CSCs escape the toxicity of the long-term treatment regimens used in clinical practice. Here, we have exposed a population of murine glioma stem cells (GSCs) to fractionated radiation and investigated the associated adaptive changes and their molecular determinants. METHODS: Initial tumors were formed by implantation of Ink4a/Arf-null neural stem cells overexpressing H-RASV12 into the forebrain of wild-type mice. GSCs purified from these tumors were then grown as tumorspheres and subjected to 60Gy of fractionated radiation. Control and post-irradiation GSCs and their allografts were compared to identify differentially expressed factors that underlie acquired radioresistance. RESULTS: Analysis of the molecular changes induced in GSCs during fractionated radiation revealed an increase in IGF1 secretion and a gradual up-regulation of the IGF type 1 receptor (IGF1R). Interestingly, IGF1-IGF1R up-regulation exerted a dual radioprotective effect. In the resting state, continuous IGF1 stimulation ultimately induced down-regulation of Akt/ERK and FoxO3a activation, which resulted in slower proliferation and enhanced self-renewal. In contrast, after acute radiation, the abundance of IGF1R and increased secretion of IGF1 promoted a rapid shift from a latent state towards activation of Akt survival signaling, protecting GSCs from radiation toxicity. Moreover, the IGF1 secretion could also exert protective effects in a paracrine manner, further enhancing overall radioresistance. Treatment of tumors formed by the radioresistant GSCs with an IGF1R inhibitor resulted in a marked increase in radiosensitivity. CONCLUSIONS: Our results show that GSCs can evade the damage of repeated radiation not only through innate properties, but also by establishing an IGF1-IGF1R autocrine trophic loop. Elucidation of stem-cell-specific mechanisms of adaptive resistance and identification of targetable key factors are crucial to the refinement of current treatment strategies and prevention of tumor relapse. SECONDARY CATEGORY: n/a.