tbuckley/cabot-search huggingface dataset:
Abstract 5567: Development of a novel magnetic anti-cancer drug for hyperthermic therapy.
Authors: Masanari Umemura, Hidenobu Fukumura, Itaru Sato, Xianfeng Feng, Haruki Eguchi, Yoshihiro Ishikawa
Journal: Cancer Research (2013)

Abstract Background: Hyperthermic therapy is a type of cancer treatment in which body tissue is exposed to high temperature (up to 113°F). Despite of its effectiveness, it has not been widely used. One reason is that it is technically difficult to increase high temperature only in a target cancer site. To address this issue, we have developed a novel nano-magnetic particle, i.e., EI236. EI236 exhibits not only anti-cancer effect, but also ferromagnetic property. Because of its magnetism, this drug can generate heat by itself when it is exposed to an alternating current magnetic field (ACMF). Method: We established a rabbit model of VX2 cells (rabbit osteosarcoma) grafted on legs to examine the anti-cancer and hyperthermal effects of EI236 in vivo. Rabbits were divided into five groups; 1) no treatment group 2) intra-venous (iv.) EI236 injection group 3) intra-arterial (ia.) EI236 group 4) ia. Methotrexate (MTX) injection group, and 5) ia. EI236+ACMF group. The volume of tumor was measured daily, and then the samples were harvested and evaluated histologically by HE, Ki67, and TUNEL staining. Results: The effect of EI236 was similar to that of MTX when EI236 was injected via intra-arterial infusion. Via intra-arterial infusion was more effective than iva intra-venous infusion. When EI236 was injected and the tumor was exposed to ACMF for simultaneous chemotherapeutic and hyperthermal effects, it showed the greatest regression of tumor among all the groups examined. EI236 significantly increased necrosis as determined by HE staining, and further increased it by ACMF. Similarly, EI236 decreased cell proliferation as determined by Ki67, and further decreased it by ACMF. Moreover EI236 increased apoptosis as determined by TUNEL staining, and further increased it by ACMF. These results demonstrated that the exposure of ACMF greatly enhanced the anti-cancer effect of EI236. Taken together, EI236 exhibited simultaneous effects of anti-cancer and thyperthermia. Conclusion: These results demonstrate that EI236 can provide us in developing a new strategy of simultaneous hyperthermo-chemotherapy in the future. Citation Format: Masanari Umemura, Hidenobu Fukumura, Itaru Sato, Xianfeng Feng, Haruki Eguchi, Yoshihiro Ishikawa. Development of a novel magnetic anti-cancer drug for hyperthermic therapy. [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 5567. doi:10.1158/1538-7445.AM2013-5567
Abstract C38: Berberine/cisplatin-based radiotherapy for cervical cancer: The new and effective method to treat cervical cancer
Authors: Komal Komal, Akhtar Naseem, Vishal Kumar Deshwal, Alpana Sharma
Journal: Cancer Research (2011)

Abstract Background: Cervical cancer is the most common cancer in Indian females. The present treatment regime for cervical cancer is radiotherapy based on DNA crosslinking agent like cisplatin which is associated with various side effects. Berberine, a chemopreventive agent, is a natural compound extracted from Berberidaceae family that allows suppression and retardation of carcinogenesis and effectively inhibits inflammation. The objective of this study was to compare the cisplatin-based radiosensitization with a berberine/cisplatin-induced radiosensitization. Methods: HeLa, SiHa, and Ca Ski cells were cultured in DMEM medium supplemented in 10% FBS in a humidified atmosphere of 95% air and 5% CO2 at 37°C and were treated with 75 μM berberine/10 μg cisplatin and 10 μg cisplatin alone for 24 hrs followed by 2 Gy radiation dose from radiation source. Cells which were not sensitized with berberine/cisplatin were also treated with variable radiation doses. Apoptosis was measured by flow cytometery, protein expression was assessed using Western blotting, and caspase activity was measured using synthetic substrates. Results: Treatment of cervical cancer cells with berberine/cisplatin combination dose followed by radiation resulted in increased apoptosis in comparison to cisplatin sensitization and exposure to radiation. The combination of berberine/cisplatin resulted in increased expression of proapoptotic Bax, p73 and downregulation of antiapoptotic Bcl XI, inflammatory Cox 2, cyclin D1 and effective reduction in activity of telomerase in comparison to cisplatin-based radiotherapy. The combination dose also resulted in increased activation of caspase-9 and -3. Conclusion: The present study indicates that berberine has the potential to make cervical cancer therapies more effective and safer with minimization of side effects which are associated with generation of excessive reactive oxygen species in present cisplatin-based therapy regime. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C38.
Abstract 5075: An integrated <i>in silico</i> and proteomic approach towards the identification of novel cancer biomarkers based on tissue specificity
Authors: Ioannis Prassas, Shalini Makawita, Eleftherios Diamandis
Journal: Cancer Research (2011)

Abstract Serological biomarkers represent a non-invasive and cost-effective means to aid in clinical management of cancer patients, particularly in areas of disease detection, prognosis, monitoring and therapeutic stratification. Several notable biomarkers currently in clinical use are proteins that demonstrate high tissue specificity to a single tissue, such as prostate specific antigen (PSA) for prostate cancer and human chorionic gonadotropin (hCG) for testicular cancer, the former being highly expressed only in the prostate and the latter in the placenta. Recent advances in high-throughput technologies (e.g. high-content microarray chips, serial analysis of gene expression platforms, thorough expressed sequence tag annotation) has enabled creation of publicly available gene and/or protein databases which describe the expression of thousands of genes (and/or proteins) in multiple tissues. Furthermore, over the past five years, our laboratory has characterized the proteomes of over 35 cell lines from numerous cancer sites as well as relevant biological fluids using a 2D-LC-MS/MS approach, identifying between 1000-4000 proteins per cancer site. In this respect, the present study represents an integrative analysis of existing databases in combination with our in-house generated proteomic datasets, in pursuit of highly tissue specific proteins, which could be further explored as cancer biomarkers and/or therapeutic targets. Through stringent bioinformatic mining of the Human Protein Atlas, BioGPS, Unigene, TiGER, TiSGeD and other related databases, a list of proteins highly specific to normal lung, colon, prostate, testis and ovaries was generated. Interestingly, only a few proteins from each tissue were commonly reported as highly specific across all of these databases and these were selected for further analysis. Subsequent integration and comparison to our in-house generated proteomes: prostate cancer (PC3, LNCaP, 22Rv1 and seminal plasma from prostate cancer patients; 1958 proteins), lung cancer (H1688, H23, H460, and H520; 1856 proteins), ovarian cancer (HTB75, TOV-112D, TOV-21G and RMUG-S; 1123 proteins) and colon cancer (HCT116, LoVo, LS174T, LS180, SW1116, SW480 and SW620; 2124 proteins), helped to corroborate our candidate list. Three, 4, 5, 10 and 7 highly specific proteins based on the applied criteria were prioritized for colon, testis, ovaries, prostate and lung, respectively. The identification of known biomarkers within these lists (e.g. PSA, KLK2, MSMB) warrants the analysis of the remaining proteins in serum, as potential cancer biomarkers and/or therapeutic targets. 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 5075. doi:10.1158/1538-7445.AM2011-5075
Current Progress in Therapeutic Gene Editing for Monogenic Diseases
Authors: Versha Prakash, Marc Moore, Rafael J Yáñez-Muñoz
Journal: Molecular Therapy (2016)

Programmable nucleases allow defined alterations in the genome with ease-of-use, efficiency, and specificity. Their availability has led to accurate and widespread genome engineering, with multiple applications in basic research, biotechnology, and therapy. With regard to human gene therapy, nuclease-based gene editing has facilitated development of a broad range of therapeutic strategies based on both nonhomologous end joining and homology-dependent repair. This review discusses current progress in nuclease-based therapeutic applications for a subset of inherited monogenic diseases including cystic fibrosis, Duchenne muscular dystrophy, diseases of the bone marrow, and hemophilia and highlights associated challenges and future prospects.
Enhanced Chemoresistance by Elevation of p185neu Levels in HER-2/neu-Transfected Human Lung Cancer Cells
Authors: C.-M. Tsai, D. Yu, K.-T. Chang, L.-H. Wu, R.-P. Perng, N. K. Ibrahim, M.-C. Hung
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Enhanced Chemoresistance by Elevation of p185 neu Levels in HER-2/neu-Transfected Human Lung Cancer Cells Get access Chun-Ming Tsai, Chun-Ming Tsai 1Chest Department, Veterans General Hospital-Taipei and Medical College, National Yang-Ming UniversityTaiwan Search for other works by this author on: Oxford Academic PubMed Google Scholar Dihua Yu, Dihua Yu 3Department of Tumor Biology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Kuo-Ting Chang, Kuo-Ting Chang 1Chest Department, Veterans General Hospital-Taipei and Medical College, National Yang-Ming UniversityTaiwan Search for other works by this author on: Oxford Academic PubMed Google Scholar Li-Hwa Wu, Li-Hwa Wu 2Section of General Surgery, Department of Surgery, Veterans General Hospital-Taipei and Medical College, National Yang-Ming UniversityTaiwan Search for other works by this author on: Oxford Academic PubMed Google Scholar Reury-Perng Perng, Reury-Perng Perng 1Chest Department, Veterans General Hospital-Taipei and Medical College, National Yang-Ming UniversityTaiwan Search for other works by this author on: Oxford Academic PubMed Google Scholar Nuhad K. Ibrahim, Nuhad K. Ibrahim 3Department of Tumor Biology, The University of Texas M. D. Anderson Cancer CenterHouston Search for other works by this author on: Oxford Academic PubMed Google Scholar Mien-Chie Hung Mien-Chie Hung 3Department of Tumor Biology, The University of Texas M. D. Anderson Cancer CenterHouston Correspondence to: C.-M. Tsai, M.D., Chest Department, Veterans General Hospital-Taipei, Shih-pai, Taipei, Taiwan 11217. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 9, 3 May 1995, Pages 682–684, https://doi.org/10.1093/jnci/87.9.682 Published: 03 May 1995 Article history Received: 24 August 1994 Revision received: 16 November 1994 Accepted: 25 January 1995 Published: 03 May 1995
A doctor's dilemma: Do you admit to working within the system?
Authors: B. Richard
Journal: BMJ (2000)

After 11 years as a reconstructive surgeon in Asia, I returned to practise in Britain. While visiting friends for the weekend my 9 year old daughter fell, and when I joined my family later that evening and bent down to give her a kiss I noticed the mild angulation of a Smith's fracture of her left wrist. We were off to visit my parents the following day so I simply told …
Abstract 249: A Sleeping Beauty screen in mice identifies Zmiz1 as a candidate cancer gene in human squamous cell carcinomas
Authors: Laura M. Rogers, Brian L. Swick, David K. Meyerholz, Adam J. Dupuy
Journal: Cancer Research (2010)

Abstract Cutaneous squamous cell carcinoma (SCC) is the second most frequent cancer in the United States, with over 250,000 new cases diagnosed annually. Current treatments rely upon surgical excision of the cancerous tissue. Often, however, surgical removal can be difficult for patients because tumors commonly develop on sun-exposed surfaces such as the face, ears, and hands. In addition, a low percentage of patients exhibit aggressive metastases that are not easily removed and often result in death. A deeper understanding of the underlying genes involved in disease initiation and progression will be essential for the development of nonsurgical treatments. A recent Sleeping Beauty (SB) transposon insertional mutagenesis screen identified Zmiz1 as a candidate cancer gene in cutaneous SCCs. Intriguingly, over 90% of SB-induced skin SCCs harbored mutations within the Zmiz1 gene, predicted to cause overexpression of an N-terminally truncated protein, which we named Zmiz1mut. Immunohistochemistry (IHC) analysis of SB-induced SCCs revealed aberrant nuclear Zmiz1 localization in tumor samples, while nuclear staining was absent in normal mouse skin. Importantly, nuclear Zmiz1 was also detected in ∼70% of human SCC tumors analyzed by IHC, indicating that aberrant Zmiz1 expression may also play a role in human disease. Furthermore, we have discovered that Zmiz1 nuclear staining is present in a significant percentage of breast, colon, and ovarian cancers. The purpose of this study is to determine the functional significance of Zmiz1 mutation in cutaneous SCC. To this end, we engineered transgenic mice that express Zmiz1mut in a Cre-dependent manner. We crossed these mice to a K14-Cre strain to induce Zmiz1mut expression in the skin. Offspring inheriting both alleles proved to be tumor-prone, with over 80% of these animals developing SCC. These data confirm that Zmiz1 has oncogenic potential in the skin. Sequencing analysis of cDNA from tumors produced by our Zmiz1mut transgenic model uncovered no mutations in either p53 or H-Ras_mutations that are observed in other mouse models of skin cancer. IHC was also performed on tumor sections. As before, we observed a strong nuclear staining pattern in the tumors induced by Zmiz1mut expression, leading us to hypothesize that nuclear accumulation of Zmiz1 plays an active role in tumorigenesis. Current efforts are focused on further characterization of our unique skin cancer model and discovering the driving force behind nuclear accumulation of Zmiz1. 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 249.
AB1450-HPR The relationship between pain, physical activity and functional status in patients with knee osteoarthritis:
Authors: I. Yeldan, E. Tarakci, S. Baydogan, D. Tarakci
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA) is one of the most common causes of pain and disability in middle-aged and older people (1). OA of the knee is associated with significant losses in functional performance. Pain and functional status in knee OA deteriorated slowly (2). Although reductions in physical activity are reported, it has not been verified its relation with pain. <h3>Objectives</h3> To investigate the relationship between pain, physical activity level and functional status in patients with knee OA. <h3>Methods</h3> Sixty-one patients with knee OA (51 female, 10 male) with an age range of 46-85 were included in this study. Personal factors (age, sex) and pathophysiologic factors (radiologic score of knee OA, body mass index [BMI], comorbidities, duration of knee OA) were determined. Knee pain was measured using a Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)-pain. Physical activity level was assessed with theInternational Physical Activity Questionnaire (IPAQ). Functional status was evaluated by using WOMAC and Lequesne index. Pearson's correlation was used to examine relationships between the variables. <h3>Results</h3> The mean age and body mass index of patients were 61.60±9.07 years and 29.78±4.81 kg/m<sup>2</sup> respectively. The mean disease duration was 5.45±4.47 years. Significant correlations were observed between overall pain scores and physical activity level and functional measurements (Table 1). Pain was significantly related to decreased physical activity level and deteriorated functional status reported on the WOMAC or Lequesne index. <h3>Conclusions</h3> Our study revealed relationship between pain and physical activity level and functional status in knee OA. Our results emphasizes the importance of effective treatment in pain reduction to maintain functional status in patients with knee OA. <h3>References</h3> Thomas SG, Pagura SM, Kennedy D. Physical activity and its relationship to physical performance in patients with end stage knee osteoarthritis. J Orthop Sports Phys Ther. 2003 Dec;33(12):745-54. Van Dijk GM, Dekker J, Veenhof C, van den Ende CH; Course of functional status and pain in osteoarthritis of the hip or knee: a systematic review of the literature. Arthritis Rheum. 2006 Oct 15;55(5):779-85. <h3>Disclosure of Interest</h3> None Declared
THU0548 Interleukin-7 Accelerates Osteoclast Formation from Monocytes in Synovial Fluid from Patients from Rheumatoid Arthritis
Authors: S.-J. Yoo, S.-W. Kang, S.-C. Shim, J. Kim, I.-S. Yoo, S.-K. Lee, J.-H. Sim, H.-R. Kim
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Introduction</h3> Gingival recession is one of the most common mucogingival deformities requiring surgical correction. The American Academy of Periodontology Regeneration Workshop recommended connective tissue graft (CTG) combined with coronally advanced flap (CAF) for the treatment of Miller Class I and II single-tooth gingival recession. The disadvantages of harvesting autogenous tissue include postoperative bleeding, pain and discomfort at the donor site, restricted tissue supply, increased morbidity and prolonged operative times. Acellular dermal matrix (ADM) contains undamaged collagen and elastin matrices that can be used as a substitute for CTG during root coverage procedures. However, the use of ADM is still controversial. The objective of this split-mouth; randomised, controlled, clinical study is to evaluate the long-term effects of ADM graft (ADMG) combined with CAF on root coverage, aesthetics and patient satisfaction for the treatment of single gingival recession with thin gingival phenotype. <h3>Methods and analysis</h3> Forty participants with bilateral Miller Class I/II gingival recession will be randomised to receive an ADMG on one side and CTG on the contralateral side, combined with CAF. Gingival recession depth, gingival recession width and keratinised tissue width will be measured at baseline, 2 weeks and 1, 3, 6, 12 and 24 months. Mean root coverage, complete root coverage, root coverage aesthetic score, colour change (∆E) and patient satisfaction will be assessed during follow-up visits. <h3>Ethics and dissemination</h3> The present study has received approval from the Ethics Committee of Peking University School and Hospital of Stomatology (PKUSSIRB-202054029). Data of this study will be registered with the International Clinical Trials Registry Platform. Additionally, we will disseminate the results through scientific journal. <h3>Trial registration number</h3> ChiCTR2000033230.
PTU-066 A Model To Assess The Cost Of Flare In Ulcerative Colitis (uc) To The Nhs
Authors: A Bassi, K Tolley, G Wiseman, S Shaw
Journal: Gut (2014)

<h3>Introduction</h3> Disease flare in ulcerative colitis (UC) can result in substantial cost implications to the NHS. While the costs associated with treatment and management of UC are well-documented, estimates of the cost of flare are lacking. A cost analysis was performed to construct a model to estimate the costs associated with managing a flare across variable pathways. <h3>Methods</h3> A decision tree model was developed in Excel to estimate the direct medical costs of flares of various clinical severity. Within the model, the baseline UC patient cohort was maintained on Asacol<sup>®</sup> (mesalazine) at a maximum dose of 2.4 g/day. Simplified care pathways were mapped, assuming that patients would either be treated and managed in primary care, or as an outpatient, or admitted to hospital. Taking a conservative approach, costs for surgery and other procedures e.g., stoma care were excluded as these outcomes are rare and inclusion would significantly increase average flare cost estimates. Treatment and management strategies were based on best practice guidelines, published data sources and clinical expert opinion. Drug costs were calculated using the British National Formulary (BNF) and healthcare management costs were based on published unit costs. The relative proportions of patients likely to follow each route of the treatment pathway were estimated and weightings were applied to enable calculation of an average cost of flare. <h3>Results</h3> The estimated annual cost to manage a patient with UC in remission was £955. The estimated cost to control a flare in primary care was £175 and for secondary care outpatient management was £578. For secondary care inpatient management, the estimated cost was £3488. If a biologic/ciclosporin was needed, the estimated cost rose to £4272. All costs were inclusive of clinical investigations and treatment reviews. The proportions of patients managed via each pathway were applied to calculations resulting in an estimated average cost of flare of £984. <h3>Conclusion</h3> A model was developed, based on simplified decision tree pathways to enable estimation of the cost of flare in UC. Depending on the severity of the flare episode, costs ranged from £175 to £4272. In the future, this model can be used for economic evaluations of interventions to reduce the risk of flare in UC and to help understand the costly aspects of managing ulcerative colitis. <h3>Disclosure of Interest</h3> A. Bassi Speaker bureau with: Warner Chilcott (UK) Ltd, K. Tolley Consultant for: Warner Chilcott (UK) Ltd, G. Wiseman Employee of: Warner Chilcott (UK) Ltd, S. Shaw Consultant for: Warner Chilcott (UK) Ltd.