tbuckley/cabot-search huggingface dataset:
NT-22 * PAV TREATMENT WITHOUT IMMEDIATE RADIOTHERAPY FOR ANAPLASTIC OLIGODENDROGLIAL TUMOR WITH 1p/19q CO-DELETION
Authors: T. Matsutani, S. Hirono, N. Shinozaki, Y. Iwadate, N. Saeki
Journal: Neuro-Oncology (2014)

OBJECTIVE: Recently, two randomized control trial, EORTC 26951 and RTOG 9402, has clarified that "PCV + Radiation Therapy (RT)" has survival benefit compared to "RT only" in anaplastic oligodendroglial tumor and 1p/19q co-deleted tumor is a good prognosis factor. However, it is still unclear that RT is always necessary in both 1p/19q status tumor. MATERIAL AND METHODS: We retrospectively analyzed PFS and OS in thirty-three consecutive patients with anaplastic oligodendroglial tumor, who had been treated according to our treatment strategy. Briefly, in 1p/19q co-deleted case, only PAV chemotherapy is administrated after initial surgery without immediate RT. For recurrence, PAV or TMZ chemotherapy is considered after re-evacuation of local recurrence and definition of LOH status. In non-co-deleted case, immediate RT with TMZ or PAV is considered as a first-line therapy. RESULTS: With a median follow-up of 35.1 months, PFS and OS were 32.4 and 52.9 months, respectively, in all of our patients. In 1p/19q co-deleted tumor, PFS and OS were 58.8 months and N.R., which were significantly longer than those in non-co-deleted tumor, 10.2 and 27.3 months, respectively. CONCLUSION: In co-deleted cases, our data showed shorter PFS than two of Phase III trials (58.8 vs. 157 or 100.8 months). However OS was N.R. and no remarkable differences were found in PFS and OS of all of our cases compared to RT/PCV arms. It may suggest that tumors without RT are still sensitive to adjuvant chemotherapy after recurrence and such shorter-time recurrence would not influence on survival time in co-deleted cases.
Abstract 2976: KSHV-initiated Notch activation leads to membrane-type-1 matrix metalloproteinase-dependent lymphatic endothelial-to-mesenchymal transition
Authors: Pirita Pekkonen, Fang Cheng, Nami Sugiyama, Stephen Henderson, Ville Rantanen, Mervi Aavikko, Sampsa Hautaniemi, Lauri Aaltonen, Chris Boshoff, Kari Alitalo, Kaisa Lehti, Päivi M. Ojala
Journal: Cancer Research (2012)

Abstract Kaposi sarcoma (KS), an angioproliferative disease associated with Kaposi sarcoma herpesvirus (KSHV) infection, harbors a diversity of cell types ranging from endothelial to mesenchymal cells of unclear origin. Using a novel three-dimensional (3D) cell model, we have demonstrated that KSHV induces transcriptional reprogramming of primary lymphatic endothelial cells (LEC) to mesenchymal cells via endothelial-to-mesenchymal transition (EndMT). As EndMT induction has been described in response to activation of the TGF-beta or Notch pathways, inhibitor studies were used to decipher their roles in our 3D system. Inhibition of the Notch pathway dramatically attenuated the EndMT in KSHV infected LECs (K-LECs) in 3D whereas inhibition or activation of the TGF-β pathway did not have any effect. Two viral gene products, vFLIP and vGPCR, were found to trigger Notch signaling and lead to the KSHV-induced EndMT. As Notch activation has been shown to inhibit angiogenic and lymphangiogenic sprouting, we assessed the effect of VEGFA or -C stimulation on the 3D K-LECs. Interestingly, VEGFA/C stimulation induced a dramatic outgrowth of (lymph)angiogenic sprouts and inhibited the KSHV-induced EndMT in the 3D K-LECs. This suggests that the KSHV-induced Notch signaling and mesenchymal reprogramming can override the lymphangiogenic properties of LECs in the absence of VEGF-A/C stimulation. These results further corroborate the central role of Notch signaling as a critical determinant for the lymphangiogenic vs. mesenchymal fate of LECs. The 3D K-LEC transcriptome showed significant up-regulation of invasion related genes over the uninfected control. Intriguingly, comparison of the GEM profiles of the 3D K-LECs and KS biopsies, genes with similar co-regulation were found and included those involved both in EMT/EndMT and invasive processes. Using a panel of specific inhibitors we found a membrane associated matrix metalloproteinase MT1-MMP to be the major MMP involved in this process. Our data further identifies Notch as a previously unrecognized upstream regulator of MT1-MMP, and demonstrates that MT1-MMP as such is sufficient to induce EndMT in 3D cultured LECs. Mesenchymal markers and MT1-MMP were found co-distributed in the same cells with LANA in primary KS tumors suggesting that virus-induced EndMT may contribute to development of KS by giving rise to invasive cells, and providing the virus a permissive microenvironment for efficient spread of the viral genomes. 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 2976. doi:1538-7445.AM2012-2976
Abstract 1049: Akt1 and Akt2 are associated with poor outcome in glioblastoma multiforme
Authors: Anna M. Joy, Ivan Smirnov, Mitsutoshi Nakada, Burt G. Feuerstein
Journal: Cancer Research (2010)

Abstract The Akt pathway is implicated in progression of astrocytic tumors. To refine the Akt pathway as a therapeutic target in glioblastoma multiforme (GBM) we determined activated Akt isoform(s) that mediate cellular behavior, and are associated with clinical parameters. Akt1 and Akt2 message is associated with worse clinical outcome while Akt3v1 message is associated with better clinical outcome. Silencing individual isoforms with shRNA gives different phenotypes. Bioinformatic analysis indicates that PI3K/Akt pathway components cluster with individual Akt isoforms and with tumor subtype suggesting that different arms of the PI3K/Akt pathway are associated with individual isoforms. Taken together, the data indicate that Akt3 function differs from Akt1 and 2 function, and support a role for Akt1 and 2 in the malignant behavior of glioma cells. Selective inhibition of Akt1 and/or 2, or their downstream effectors may be more effective and less toxic than general inhibition of Akt or PI3K. Supported by the Barrow Neurological Foundation (AJ and BGF). 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 1049.
Abstract 185: Alteration of microRNA expression profiles in HPV-associated squamous cell carcinoma of the head and neck (SCCHN)
Authors: Ji-Eun Oh, Jeong-Oh Kim, Jung-Young Shin, Xiang-Hua Zhang, Sang-Hoon Chun, Hye-Sung Won, Chan-Kwon Jung, Sook-Hee Hong, Myoung-Ah Lee, Jin-Hyoung Kang
Journal: Cancer Research (2012)

Abstract Background High-risk type of human papillomavirus (HPV) has recently been found to be etiologically associated with 20 to 25% of SCCHN, particularly common in or pharyngeal tumors. We investigated the protein expression of PTEN/PI3K/AKT/mTOR signal pathway on HPV 16 +/− tonsillar squamous cell carcinomas. And, we analyzed microRNA expression profile in tongue cancer cell line transfected with HPV 16 E6/E7 oncogene. Method Tonsil cancer patients who had been treated at Seoul St. Mary's Hospital between 2000 and 2009 were reviewed. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded tumor tissues of 65 surgical specimens, and stained with antibodies against PTEN, PIK3CA, phosphorylated AktSer473, and phosphorylated mTORSer2448. High-risk HPV infection status was determined by in situ hybridization. The protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. MicroRNA expression was studied using microarrays (PANArray™ miRNA expression profiling kit) in two tongue cancer cell lines (YD8 and YD10B) transfected with HPV 16 E6/E7 oncogene. Results Of the 65 pts, 26 (40%) pts were HPV positive. Overall survival and relapse-free survival were significantly different between two groups (P = 0.05 and P = 0.036, respectively). PTEN expression was significantly higher in HPV-positive- than in HPV-negative patients (P = 0.02). PIK3CA, phosphorylated AktSer473, and phosphorylated mTORSer2448 expression was negatively correlated with HPV status, yet not significantly. HPV status (P = 0.03) and nodal stage (P = 0.05) were found to significantly affect overall survival, as determined by multivariate analysis. The expression profile of miRNAs was different in HPV 16 E6/E7 transformed cells compared with vector alone cells. In the final round, 8 of 158 miRNAs were selected to be most differently expressed miRNAs; let-7b, miR-1, miR-107, miR-122, miR-127-5p, miR-95, miR-23b and miR-370 (&amp;gt;1.2-fold). Conclusion We observed the higher expression of PTEN in HPV 16 positive tonsil tumor than HPV 16 negative tumor. Our data suggest that some microRNAs induced by E6/E7 oncogene might directly affect PTEN expression level independent of p53. We are underway on the experiments confirming that PTEN is regulated by which among these miRNAs. 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 185. doi:1538-7445.AM2012-185
1091 MULTI-COLOUR RGB MARKING TO ASSESS THE CLONALITY OF LIVER TUMOURS
Authors: M. Thomaschewski, K. Weber, K. Cornils, H. Ittrich, M. Lütgehetmann, T. Volz, D. Heim, M. Warlich, H. Wege, M. Dandri, B. Fehse, D. Benten
Journal: Journal of Hepatology (2013)
Abstract 2784: Association between polymorphisms in angiogenesis-related genes and risk of urothelial carcinoma in Taiwan
Authors: Yuan-Hung Wang, Chi-Tung Liu, Shauh-Der Yeh, Meei-Maan Wu, Kun-Hung Shen, Cheng-Hung Shen, Hung-Yi Chiou
Journal: Cancer Research (2011)

Abstract Introduction: Urothelial carcinoma (UC) including cancers of bladder, renal pelvis and ureter. Tumor staging and grading are considered to be useful indices for cancer prognosis. Recently, more and more studies indicated that angiogenesis is a necessary step in tumor growth and metastasis. This study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of four angiogenesis-related genes including FIH-1, VHL, HIF-1 and VEGF and clinico-pathological characteristics, recurrence, and survival rate of UC. Materials and Methods: In this case-control study, a total of 850 pathologically- confirmed UC cases and 850 cancer-free controls, frequency-matched on age, were recruited from those who admitted to the same hospitals for a health examination. Genotyping is determined using PCR-RFLP and Real-time PCR. Written informed consent was obtained from each of participants. This protocol was approved by the institutional review boards of the collaborated hospitals. Results: We found that study subjects with cigarette smoking, alcohol consumption, occupational exposure, arsenic exposure, and high-salt diet have a significantly higher UC risk of 2.0, 1.6, 1.8, 1.9 and 1.5. Study subjects carrying C/G and G/G genotypes of FIH-1 gene had a 1.3-fold risk of developing to stage II or worse status. Cigarette smokers with the C/C genotype of VHL gene had a higher UC risk of 2.4. In addition, cigarette smokers with the T/T genotype of VEGF-460 C/T polymorphism had 1.6- fold UC risk of developing to stage II or worse status. In the combined analysis, study subjects who carried 2 or more risk genotypes of angiogenesis-related genes had a significantly higher UC risk of 1.6 for developing to T2 and stage II or more serious. Conclusions: Our results suggested a significant association between polymorphisms in angiogenesis-related genes and morbidity and tumor stage of UC, however, without a significant association between these SNPs and tumor grade. 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 2784. doi:10.1158/1538-7445.AM2011-2784
AB0451 Polymyalgia rheumatica is more severe in female patients: a prospective study.
Authors: F. Muratore, P. Macchioni, L. Boiardi, C. Salvarani
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Recent data showed a longer-course of corticosteroid (CS) therapy, higher cumulative CS dosage and increased number of relapses in female patients with polymyalgia rheumatica (PMR) than in male (1,2). <h3>Objectives</h3> To assess gender-related differences in PMR activity and disease course using clinical, PMR-DAS (3), quality of life (QoL) and ultrasonographic (US) evaluation. <h3>Methods</h3> All patients with suspected PMR seen at our centre are followed according to a standardized protocol that include clinical examination, determination of laboratory parameters (including ESR, CRP, RF, ACPA test), HAQ questionnaire and US examination of shoulders and hips. All patients are treated with a fixed prednisone start dosage (12.5 mg/day) for four weeks and then tapered according to a standardized protocol. Consecutive patients seen in our rheumatological centre with new onset PMR and followed for at least 6 months were included prospectively during a 5 years period. <h3>Results</h3> The study cohort included 85 patients (24 m/61 f). At baseline visit there were no significant differences between male and female in demographic, clinical and laboratory data: age (76.2 ± 6.7 vs 74.6 ± 6.9 years, p ns); disease duration at diagnosis (12.8 ± 19.7 vs 15.3 ± 28.8 weeks, p ns); ERS (55.4 ± 18.9 vs 56.6 ± 24.2 mm/1<sup>st</sup>h, p ns); CRP (4.55 ± 2.3 vs 4.1 ± 3.5 mg/dl, p ns); PMR-DAS (36.9 ± 13.3 vs 36.8 ± 15.4 p ns); HAQ (1.7 ± 0.5 vs 1.8 vs 0.5 p ns); systemic symptoms (33.3% vs 45.9% p ns). At diagnosis a greater proportion of female patients showed at least one inflamed structure at US shoulder examination compared to male (100% vs 87%, p=0.004). Table 1 shows the significant differences between male an female at 6 months evaluation. At the end of the follow-up period 21 (87.5%) male and 55 (90.2%) female patients were still on steroid treatment (p ns) at a mean dose of 5.1 ± 5.3 and 5.2 ± 3.7 mg/day (p ns) respectively. <h3>Conclusions</h3> At six month evaluation female patients had a more active disease compared to male. Number of relapses/recurrences are higher (but the difference was not significant) among female. At diagnosis only US shoulder examination showed a more severe disease in female compared to male patients. <h3>References</h3> Narvaez J, Nolla-Solé JM, Valverde-García J, Roig-Escofet D Sex differences in temporal arteritis and polymyalgia rheumatica. J Rheumatol. 2002 Feb;29(2):321-5 Cimmino MA, Parodi M, Caporali R, Montecucco C Is the course of steroid-treated polymyalgia rheumatica more severe in women? Ann N Y Acad Sci. 2006 Jun;1069:315-21 Leeb BF, Bird HA A disease activity score for polymyalgia rheumatica. Ann Rheum Dis. 2004 Oct;63(10):1279-83 <h3>Disclosure of Interest</h3> None Declared
GW25-e2290 Effect of Sini Decoction on the expression of SOD and MDA in EAhy926 cells injured by homocysteine
Authors: Liu Yong, Song Zhiming, Zhou Bin, Yu Shujie, Liu Dinghui, Hao Baoshun, Wu Lin, Wang Min, Chen Lin, Qian Xiaoxian
Journal: Journal of the American College of Cardiology (2014)
Appendiceal mucocele in a young patient – does size matter?
Authors: P. Cordero-Ruiz, J. Romero-Vázquez, F. Pellicer-Bautista, J. Herrerías-Gutiérrez
Journal: Endoscopy (2011)

A 22-year-old man was admitted because of abdominal pain localized to the right iliac fossa. An abdominal ultrasound scan was performed, which revealed a 3.5 × 8-cm mass with heterogeneous content and calcified walls in close proximity to the ascending colon. A computed tomography (CT) scan of the abdomen showed a 10 × 3.5-cm mass in the region of the appendix with homogeneous density, thin walls, and some small areas of calcification ([Fig. 1]). A colonoscopy was subsequently performed, which revealed a 5-cm mass protruding from the appendiceal area with a central orifice and surrounding erythematous mucosa ([Fig. 2]). A laparotomy and appendectomy were performed, removing an 8 × 3.5-cm mass without damaging the integrity of its surface. An exploration of the cecum showed that it was not affected. Following histopathological analysis of the resected tissue, the patient was diagnosed as having a simple or retention appendiceal mucocele ([Fig. 3]).
THU0599 From Bad to Worse? The Impact of Switching Biologic Agents Multiple Times on Work Productivity and Health-Related Quality of Life for Patients with RA.
Authors: T. Harrison, L. Martin, C. Barnabe, K. Fyie
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> We are interested in assessing the influence on work productivity in patients with RA who switch their biologic therapy due to lack of efficacy. Investigating the extent of this impact on patients with Rheumatoid Arthritis as they “cycle” through biologic therapies to achieve a well-controlled disease state contributes greatly to outcome evaluation. <h3>Objectives</h3> To evaluate changes in employment and work productivity between patients who have not required a switch in therapy and those who have switched biologic agents. A secondary objective was to investigate the relationship of employment and work productivity and HAQ scores. <h3>Methods</h3> Since 2000, the Alberta Biologics Pharmacosurveillance Program has captured clinical efficacy, safety and socioeconomic data in patients treated with biologic therapies. Patients complete HAQ and work productivity questionnaires every 6 months. HAQ scores and work productivity were evaluated in longitudinal analysis over the course of therapy. <h3>Results</h3> Our cohort includes 2718 patients (male and female of all races, mean age 53 years) who have been treated with one or more biologic agent, including etanercept, infliximab, adalimumab, certolizumab pegol, golimumab, rituximab, abatacept and tocilizumab. Mean indices of disease activity at baseline were: DAS28 (ESR) 5.4, tender joint count 12.4 and swollen joint count 8.9 and HAQ 1.47. From this cohort, we compared employment status and HAQ scores between patients who switched biologic agents up to four times (self-reported employment status n=729, hours worked n=1766). Our results show that there is a reduced rate of employment and a reduction in hours worked in those patients who switched biologic therapies more than once. For patients showing a decrease of 0.2 in their HAQ over course of treatment, 76% remained employed if they did not switch compared to 54% who did. <h3>Conclusions</h3> Patients who do not respond to biologic therapy experience a decrease in work productivity. These observations suggest that there needs to be an improved process to select the most effective agent when prescribing biologic therapies in RA patients. <h3>Disclosure of Interest</h3> None Declared
Abstract 3673: Expression profile of phosphorylated proteins from the mTOR and Fyn/RSK2 signaling pathways in solar UV-induced skin carcinogenesis
Authors: Yira Bermudez, Steven P. Stratton, George T. Bowden, Zigang Dong, Ann M. Bode, Clara Curiel-Lewandrowski, James A. Warneke, Craig A. Hurst, Julie E. Lang, David S. Alberts, Janine G. Einspahr
Journal: Cancer Research (2011)

Abstract Chronic sun exposure is considered the main etiologic agent of non-melanoma skin cancer (NMSC). Inactivation of tumor suppressor p53 and activation of key oncogenic signaling pathways important in cell proliferation and transformation are considered crucial steps in the development of NMSC. Therefore, our overall hypothesis is that topically administered small molecule drugs can modulate specific targets in ultraviolet (UV)-induced signaling cascades resulting in attenuation or reversal of carcinogenic events in human skin. In the study herein, we evaluate the modulation of solar light-activated mTOR and Fyn/RSK2 signaling pathways in normal human skin and solar simulated light (SSL)-irradiated human skin to determine the expression profiles of upstream and downstream phosphorylated proteins p38 (Thr180/Tyr182), p44/42 MAPK (Thr202/Tyr204), histone H3 (Ser10), p90RSK (Thr359/Ser363), Akt (Ser473), mTOR (Ser2448), S6 ribosomal protein (Ser235/236), and 4E-BP1 (Thr37/46). The study population consisted of individuals 18 years or older in general good health with skin types II-III. SSL irradiation at various doses ranging from two to four times the minimal erythema dose (MED) was applied to unexposed skin. Punch biopsies were taken at baseline, 5 minutes, 1 h, 5 h, and 24 h post-irradiation and immediately fixed in 10% formalin. Tissues were evaluated by immunohistochemistry for the expression of phospho-proteins. Proliferating cell nuclear antigen (PCNA) and cleaved caspase 3 (Asp175) were evaluated as markers for keratinocyte proliferation and apoptosis, respectively. Marked SSL-induced changes in human epidermis were seen in the expression of phosphorylated histone H3, S6 ribosomal protein, and 4E-BP1 at 1 h, 5 h, and 24 h post-SSL as compared to control. A linear increase in phosphorylated p44/42 MAPK expression was observed at 1 h, 5 h, and 24 h post-SSL as compared to control. Phosphorylated Akt expression increased post-SSL, and appears dependent on duration and intensity of SSL exposure. Ultimately, the expression profile patterns of phosphorylated proteins in the mTOR and Fyn/Rsk2 pathways will be used to determine activity of new and selective chemoprevention agents being developed to target these SSL-induced skin carcinogenesis pathways. 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 3673. doi:10.1158/1538-7445.AM2011-3673
CN-12 * PINEAL PARENCHYMAL TUMOUR OF INTERMEDIATE DIFFERENTIATION: CASE SERIES FROM A SINGLE INSTITUTE
Authors: N. Mahtab, S. Ramamurthy, N. Willis, J. Lewis, E. Lethbridge
Journal: Neuro-Oncology (2014)

INTRODUCTION: Pineal parenchymal tumours of intermediate differentiation (PPTID) are a group of rare tumours with intermediate malignant potential between pineocytoma and pineoblastoma, for which there is currently no standard treatment paradigm. METHODS: Between 2001 and 2014, five patients with PPTID were treated at our institute. We retrospectively evaluated clinical outcomes. Patient demographics, presentation, staging, surgery, radiotherapy (RT) technique, late toxicities and any chemotherapy administered were noted from the hospital electronic data base. RESULTS: Patient age range 20-74 years. Common presenting symptom was headache and visual disturbance and neurological sign was diplopia. All had ventriculostomy plus or minus ventriculo-peritoneal shunt to relieve hydrocephalus. Two patients had biopsy only and three patients had excision of pineal tumour. Three patients underwent whole brain RT with boost to pineal region [35.07Gy in 21 fractions - whole brain, average boost dose- 17.81Gy (16.7- 20.04 Gy) at 1.67Gy/fraction]. Two patients had limited field RT to the pineal region (54Gy and 39.6 Gy delivered in 1.8 Gy/fraction). Four patients had complete radiological response on MRI post-RT. One patient had partial radiological response. Two patients recurred after an average disease free survival period of 54.5 months from diagnosis: one recurred locally and was retreated with radiosurgery; the other developed disseminated leptomeningeal disease and received platinum based palliative chemotherapy. Four patients are alive to date. Average overall survival including relapsed patients is 102.5 months. Median DFS and OS are 41 and 100 months respectively. All patients developed mild cognitive impairment. The patient who received platinum chemotherapy developed severe neuropathy. CONCLUSION: Patients with PPTID in this case series survived medium term and four remain on follow up. A prospective multi institutional study is recommended due to the potential for late adverse effects. However, because this entity is rare, the difficulties in achieving this are recognised therefore cases should be collated at centres for review.