tbuckley/cabot-search huggingface dataset:
Scoring system to predict under-evaluation in patients diagnosed with benign papilloma at ultrasound-guided core needle biopsy (CNB).
Authors: E Ko, W Han, J Lee, E Kim, H Moon, J Yu, D Noh
Journal: Cancer Research (2009)

Abstract Abstract #2001 Background: The aim of this study was to determine factors that predict under-evaluation of atypical lesion or malignancy in patients diagnosed with benign papilloma at ultrasound-guided core needle biopsy (CNB), and to develop a prediction algorithm for scoring the possibility of a diagnosis upgrade to atypical lesion or malignancy based on clinical, radiological and pathological factors. Methods: The study enrolled patients diagnosed with benign papilloma at ultrasound-guided CNB who subsequently underwent surgical excision of the lesion. Multivariate analysis was used to identify relevant clinical, radiological and pathological factors that may predict malignancy. Results: A total of 262 patients with benign papilloma at CNB were identified. Of the 110 patients who underwent subsequent surgical excision, 22 (20%) were diagnosed with atypical papilloma or malignancy. Multivariate analysis revealed that mass or calcification on mammography, size on imaging &amp;gt;15 mm, peripheral location, and a palpable lesion were independent predictors of malignancy. A scoring system was developed based on logistic regression models and beta coefficients for each variable. The area under the ROC curve was 0.868 (95% CI: 0.794-0.941), and the negative predictive value was 100% for a score of 0 or 1 (Of the 110 patients, 58 patients had the score of 0 or 1). Conclusions: A scoring system to predict malignancy in patients diagnosed with benign papilloma at CNB was developed based on four factors: peripheral location, palpable lesion, mass or calcification on mammography, size on imaging. This system was able to identify a subset of patients with lesions likely to be benign, indicating that imaging follow-up rather than surgical excision may be appropriate. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2001.
Abstract P4-03-01: Inhibition of Fatty Acid Synthase (FASN) Sensitizes Breast Cancer Cells to Chemotherapy and Disrupts the Lipid Rafts
Authors: I Espinoza, P Cheol Hong, R Busby, L. Ruth
Journal: Cancer Research (2010)

Abstract MN Background: Breast cancer is the second leading cause of cancer death of women worldwide. One of the major challenges for a better prognosis of breast cancer patients is the ineffectiveness of chemotherapy and drug resistance. To investigate the mechanisms of drug resistance, resistant cancer cell lines have been established with various anticancer agents. We found that FASN, an important metabolic enzyme overexpressed in aggressive carcinomas, is t responsible in part for the drug resistance phenotype of breast cancer cells. Our findings show that blockage of FASN augments the cytotoxicity of the anti-mitotic drug Taxol in breast cancer cells. Moreover, C75 and Taxol have a synergistic effect both drugs are combined. The in vivo effect of C75 and Taxol and the mechanism by which blockage of FASN sensitizes the cells to chemotherapy are unknown. Material and Methods: In this study first we show the effect of C75 plus Taxol in breast tumor growth. BT474 cells were injected into the mammary fat pad of nude mice to generate the tumors. When the tumors were measurable we treated the mice with C75, Taxol or with a combination of both drugs. Second we studied the lipid rafts disruption after treatments by sucrose gradient and immunofluorescence. Results: We found that C75 plus Taxol extensively inhibited the tumor growth 9 fold and reduced the tumor size in 4 fold comparedn to the control mice (no treatement). In comparison C75 alone reduced the tumor growth in 1.5 fold only; and Taxol 2.5 fold compared to the control mice. These results show for first time that blockage of FASN (with C75) sensitizes breast cancer tumors to Taxol treatment in vivo. In addition, we studied the possible mechanism involved in the sensitization of breast cancer cells to Taxol by FASN blockage. Previous studies reported that blockage of FASN or Taxol treatment decrease the sphingolipids synthesis. Sphingolipids and cholesterol are the most abundant fatty acid in the lipid rafts in the plasma membrane. Disruption of lipid rafts has been shown to induce apoptosis in different carcinoma cell lines. Based in these findings, we studied lipid rafts in BT474 cells treated with C75, Taxol or combination of both with sucrose gradient and immunofluorescence microscopy. Discussion: Our results show that C75 and Taxol disrupt the lipid rafts. Thesefindings show that FASN is a new mechanism of drug resistance and may be an ideal target for chemosensitization in breast cancer chemotherapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-03-01.
Abstract 1888: MM-111, a bispecific HER2 and HER3 antibody, inhibits trastuzumab-resistant tumor cell growth
Authors: Bo Zhang, Stephanie Nguyen, Alexandra Huhalov, Ulrik B. Nielsen, Clet Niyikiza, Charlotte F. McDonagh, Arthur J. Kudla, Matthew Onsum
Journal: Cancer Research (2012)

Abstract Amplification of human epidermal growth factor receptor 2 (HER2) occurs in approximately 25% of breast cancers and is associated with increased disease recurrence and poor prognosis. Trastuzumab, a monoclonal antibody targeting HER2, has demonstrated clinical benefit in HER2 over-expressing tumors. However, acquired resistance and disease progression is widely observed in patients treated with trastuzumab. In this experiment our objectives were to dissect the dynamic, molecular mechanisms involved in acquired resistance to trastuzumab and to determine whether MM-111, a novel bispecific antibody fusion protein that specifically targets the HER2/HER3 heterodimer and blocks heregulin binding to HER3, has activity in trastuzumab-resistant tumor cells. BT474 cells were cultured in the presence of trastuzumab and cells were periodically tested for response to trastuzumab and MM-111. Samples were also collected for protein and RNA analyses. Resistance to trastuzumab gradually increased in BT474 cells after four months of exposure to trastuzumab, as measured by a cell proliferation assay. Quantitative flow cytometry analysis showed EGFR, HER2, and HER3 levels on the cell surface of resistant cells were similar to the parental cells. Phospho-protein kinase antibody arrays revealed that signaling pathways associated with the ERK cascade were activated during the development of drug resistance. Western blotting further confirmed that phosphorylation of EGFR, ERK, CREB, c-Jun, and AFT-1 was increased in the resistant cells. Real-time polymerase chain reaction also showed transcript levels of HER ligands, including HRG1α, HRG1α, betacellulin, amphiregulin, epigen, TGFβ, and HB-EGF, dramatically increased in tumor cells that acquired resistance to trastuzumab. Compared to the BT474 parental cells, MM-111 showed a greater inhibition in trastuzumab-resistant cells in a spheroid growth assay. Furthermore, trastuzumab-resistant cells became more sensitive to gefitinib and erlotinib, both EGFR inhibitors. The combination of gefitinib or erlotinib with MM-111 showed greater inhibition than either drug alone. In conclusion, our data suggest that one mechanism by which HER2 overexpressing breast cancer cells develop resistance to trastuzumab is to up-regulate ligand-dependent EGFR and HER3 signaling pathways. The use of MM-111 and EGFR inhibitors may provide an effective therapeutic strategy for the treatment of trastuzumab-resistant cancer. 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 1888. doi:1538-7445.AM2012-1888
Abstract 5654: Novel tissue-targeted virogeneimaging system for squamous cell carcinoma therapy expressing cell cycle regulator cdk2ap1
Authors: Olga Zolochevska, Marxa L. Figueiredo
Journal: Cancer Research (2012)

Abstract Oral squamous cell carcinoma (OSCC) affects about 30,000 Americans each year, and although the overall prognosis has improved in recent years for localized carcinomas, metastases can decrease survival rates by half. For tongue and palate lesions, surgery is usually the initial treatment, but metastases aggressively develop at sites where conventional therapies are ineffective. Therefore, our goal has been to develop more effective therapeutic modalities for the disease utilizing expression of cell cycle arrest and apoptosis-modulating genes. Our efforts have focused on gaining understanding of the biology and therapeutic potential of p12cdk2ap1 (p12), an S-phase growth suppressor and proapoptotic gene commonly downregulated in OSCC. In vivo, we have showed that expressing p12 using a nonviral vector can result in effective reduction in tumor size and a dramatically altered tumor phenotype. Moreover, we have showed that p12 can have cell growth inhibitory effects in a cell-autonomous as well as non-cell autonomous manner, rendering expression of this cell cycle regulator a very promising new gene therapy strategy. Therefore, we hypothesized that this growth regulator molecule will comprise a highly efficient antiumor gene therapy for OSCC. We have developed a novel viral delivery vector system with high activity and high specificity expression in oral tumor cells. This Adenovirus (Ad) utilizes a two-step transcriptional amplification system driven by the SCCA2 promoter and a bidirectional target cassette containing the sequences for the p12 and ether firefly luciferase (Luc) or thymidine kinase (TK) imaging genes. We constructed and are characterizing novel configurations of these dE1dE3 Ad-SCCA2-p12/Luc or p12/TK bidirectional vectors for gene therapy and virogeneimaging (VGI) applications. We are currently testing the specificity of these vectors and their effectiveness in tumor growth inhibition at either floor of mouth, orthotopic, or distant sites following intratumoral or systemic administration. We propose VGI can be adapted to a nonviral system as well and may hold promise not only as a novel SCC-specific gene therapy but perhaps as a molecular imaging detection agent for tumor cells that have metastasized to distant and thus difficult to treat sites. 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 5654. doi:1538-7445.AM2012-5654
Abstract A34: Arf suppresses the growth and progression of Kras-driven lung tumors
Authors: Stephanie E. Busch, Kay E. Gurley, Russell D. Moser, Karen S. Kelly-Spratt, Christopher J. Kemp
Journal: Cancer Research (2011)

Abstract Non-small cell lung carcinoma (NSCLC) is among the deadliest of human cancers, with an overall five-year survival rate of 10–20%. Activating mutations in the Kras proto-oncogene occur in approximately one-third of NSCLC patients, but tumor suppression in the lung remains poorly elucidated. The Cdkn2a locus, which houses both the p16lnk4a and Arf tumor suppressor genes, is frequently altered in NSCLC; however, the specific role of Arf in lung tumorigenesis has not been well characterized. Several lines of evidence indicate that Kras and other oncogenes induce the expression of Art, which in turn stabilizes p53 activity and arrests the growth of transformed cells. To determine the extent to which Arf suppresses NSCLC development in vivo, we employed the urethane chemical carcinogenesis model of Kras-driven NSCLC. We treated both wild-type and Arf-deficient mice with urethane and found that early-stage lung adenomas in wild-type mice robustly expressed Arf, In contrast to adenomas, malignant lung adenocarcinomas exhibited little induction of Art. Moreover, Arf-deficient mice exposed to urethane displayed accelerated lung tumor-associated morbidity and significantly increased lung tumor size compared to Arf wild-type and heterozygous littermates. Malignant progression of adenomas to adenocarcinomas was also markedly elevated in Arf-deficient mice. These data demonstrate that Arf functions as a barrier to tumor promotion and progression in a carcinogen model of Kras-driven NSCLC. 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 A34.
PARE0011 “The hidden side” – a project promoting the activity of young rheumatics
Authors: K. Mustkivi, I. Põldemaa, E. Adler
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In 2013, young rheumatics organised a two-stage project in Estonia – a 3-day seminar in September had 17 participants and a follow-up 1-day seminar in December 23 participants, including both patients and family members from all over the country. The project title "The Hidden Side" refers to rheumatic diseases as hidden disabilities as well as to the youth's abilities and will to do things that are hidden behind fear and lack of self-confidence. And as the youth association is coming to a turning point, which occasions a need for new leaders, this was the perfect timing to try and boost confidence! <h3>Objectives</h3> The main objective for the project was to involve and encourage young people with fewer opportunities to take action as youth leaders, project coordinators and organisational leaders. Another idea was to find out whether there is a need for such an association at all. In addition, the goal was to support the youth becoming more independent and decisive through new experiences in different fields as well as share their experiences and knowledge. <h3>Methods</h3> The 3-day seminar was organised in a small guesthouse in the middle of large forests and beautiful nature, the follow-up in a cosy hall where everyone could feel comfortable regardless of their disabilities. This all inspired a relaxed, safe and encouraging environment. The seminars were conducted by implementing methods of informal study (e.g. simulation games, group work, creative tasks, discussion groups and workshops). Team work and taking the lead was promoted for example by a canoe trip on a river. <h3>Results</h3> The project was very successful, which could already be seen during the follow-up seminar, where several young people already lead discussion groups on various subjects as well as workshops of different skills. The association acquired some new members and most importantly, 3 new board member candidates. The newly encouraged young people have already been active in several events. <h3>Image/graph</h3> <h3>Conclusions</h3> Young people with fewer opportunities have the abilities and will to take up different tasks and participate in social life. However, they are often discouraged and shy, much due to their disabilities and the fact that they are restricted in their ventures. The seminars showed that there is a need for support from someone who has similar experiences, a mentor, as well as from family members. <h3>Disclosure of Interest</h3> None Declared
648 VALIDATION OF 2010 AASLD GUIDELINE IN THE DIAGNOSIS OF HEPATOCELLULAR CARCINOMA FOR NON-CIRRHOTIC LIVER
Authors: T.-H. Hu, M.-T. Lin, K.-C. Chang, P.-L. Tseng, M.-C. Tsai, C.-C. Wang, Y.-H. Yen, Y.-F. Cheng, C.-L. Chen
Journal: Journal of Hepatology (2013)
S140 BMPR-II deficiency leads to an increase in egg deposition and cytokine release in the lungs of mice chronically infected with schistosomiasis
Authors: A Crosby, E Soon, F Jones, M Southwood, L Haghighat, M Toshner, T Raine, I Horan, P Yang, A Davenport, DW Dunne, NW Morrell
Journal: Thorax (2013)

<h3>Rationale and Objectives</h3> Schistosomiasis is the world-wide leading cause of pulmonary arterial hypertension (PAH) and is particularly prevalent in the third-world. More than 80% of patients with PAH in the western world have a mutation in bone morphogenetic protein type-II receptor (BMPR-II), which is a member of the transforming growth receptor-beta (TGF-b) superfamily and is important in cell proliferation and differentiation. The aim of the study was to determine if mice with a heterozygous null mutation in BMPR-II are more susceptible to schistosomiasis–induced PAH, compared to wild-type littermates. <h3>Methods</h3> Wild-type and mutant C56/BL6 mice were infected percutaneously with a low dose of <i>S.mansoni</i>. Non-infected WT and MUT mice were also studied. At 17 weeks post-infection right ventricular systolic pressure (RVSP) and right ventricular (RV) hypertrophy, liver and lung egg counts and body weight were measured. Pulmonary vascular remodelling and liver histology were assessed by morphometry, following immunohistochemistry. Micro-CT was performed to determine egg deposition. A macrophage phagocytosis assay was also performed. <h3>Measurements and Main results </h3> At 17 weeks post-infection there was no significant difference in RVSP, the degree of RV hypertrophy, mean area of liver vasculature, mean number of liver vessels or liver weight between infected BMPR-II + / + and BMPR-II +/- mice. However, there was a significant reduction in body weight, a significant increase in lung egg deposition and lung cytokine expression in the BMPR-II +/- mice compared to the wild-type mice 17 weeks post-infection. There was no significant difference in serum or liver cytokine levels. We saw a significant increase in pulmonary vessel wall thickness in both BMPR-II + / + and BMPR-II +/- mice infected mice, compared to their respective non-infected controls. There was no difference in the ability of macrophages from BMPR-II + / + and BMPR-II +/- mice to phagocytose fluorescently tagged beads. <h3>Conclusions</h3> This study has shown that BMPR-II mutations do not predispose to schistosomiasis-induced PAH, but that there is an increased ability of the eggs to gain access into the lungs and a subsequent heightened inflammatory response. This appears not to be due to an innate difference in the liver vasculature or a defect in egg clearance by macrophages.
Endoscopic Hemostasis in Sphincterotomy-Induced Hemorrhage: Its Efficacy and Safety
Authors: H J Kim, M H Kim, D I Kim, H J Lee, S J Myung, K S Yoo, E T Park, B C Lim, D W Seo, S K Lee, Y I Min
Journal: Endoscopy (1999)

Hemorrhage is induced in approximately 0.5-12% of endoscopic biliary sphincterotomy (ES) procedures. We prospectively investigated the risk factors for ES-induced hemorrhage and evaluated the safety as well as the effectiveness of endoscopic hemostasis.The study included 1304 patients who underwent ES between July 1996 and June 1998. Epinephrine spray was used initially for hemostatic treatment. If bleeding persisted, an epinephrine injection was given consecutively. In patients with exposed vessels, epinephrine injection followed by alcohol injection was given.ES-induced hemorrhage occurred in 136 (10.4%) patients. The type of sphincterotome used (needle-knife sphincterotome, P=0.025) and the cutting speed (the so-called "zipper" cut, P = 0.049) were revealed as significant variables with regard to the occurrence of bleeding. Mild, moderate, and severe bleeding were noted in 108 (79.4%), 22 (16.2%), and six (4.4%) patients, respectively. Once bleeding occurred, patients with an associated ampullary lesion (impacted stone or cancer) or with coagulopathy were more likely to bleed profusely. Initial hemostasis was achieved in all patients. However, rebleeding occurred in eight patients who were initially classified as having moderate or severe bleeding. Finally, ES-induced hemorrhage was successfully controlled in all patients after 1-3 treatment sessions (mean 1.1 sessions). The difference in the incidence of complications between the groups treated or not treated by endoscopic hemostasis was not statistically significant.ES-induced hemorrhage occurred in 10% of the patients studied. The use of needle-knife sphincterotomy and the cutting speed were independent risk factors for the occurrence of bleeding. Once bleeding occurred, its severity was affected by an associated ampullary lesion (impacted stone or cancer) or coagulopathy. Endoscopic hemostasis with epinephrine and/or alcohol was effective and safe in ES-induced hemorrhage.
Abstract 2913: Autophagy resulting from specific ablation of the proapoptotic function of cytochromec
Authors: Hua Li, Peng Wang, Jian Yu, Lin Zhang
Journal: Cancer Research (2010)

Abstract Apoptosis and autophagy are two evolutionarily conserved and sometimes mutually exclusive cell death regulatory mechanisms. The balance and cross talk between these two processes determine cell fate and have an important role in therapeutic response to anticancer agents. It has been shown that apoptosis can cross talk with autophagy through the actions of the Bcl-2 family proteins. For example, Bcl-2 inhibits autophagy by interacting with Beclin-1, the master regulator of autophagy. However, the underlying mechanisms by which apoptosis and autophagy regulate each other remain unclear. In this study, we investigated whether cytochrome c (cyto c), a critical regulator of the mitochondrial apoptotic pathway, is involved in regulating autophagy. A cyto c mutant (K72A) that retains its normal electron transfer function but fails to bind to Apaf-1 was knocked into HCT116 colorectal cancer cells by homologous recombination. Although the mutant cyto c can still be released from the mitochondria into the cytosol in response to apoptosis induction, caspase activation and other execution steps of apoptosis were inhibited. Remarkably, a significant increase in autophagy was observed in the cyto c-knockin cells, as indicated by formation of GFP-LC3 puncta and increased conversion of LC3-I into LC3-II. Furthermore, knockdown of Beclin-1 by siRNA suppressed autophagy in the cyto c-knockin cells. These results indicate that the execution steps of apoptosis downstream of cytochrome c release, including formation of apoptosome and activation of caspases, can inhibit autophagy. Autophagy can be unleashed when apoptosis is initiated, but fails to be executed. 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 2913.