tbuckley/cabot-search huggingface dataset:
Abstract 4766: Follicle stimulating hormone (FSH) inhibits apoptosis in ovarian cancer cell through regulating OCT4 stem cell signal pathway.
Authors: Zhenbo Zhang, Yaping Zhu, Xianming Xu, Xiaowei Xi, Robert C. Bast, Yinhua Yu, Youji Feng
Journal: Cancer Research (2013)

Abstract Ovarian cancer is the most lethal malignancy of the female reproductive system with an overall mortality rate of greater than 70%. Our group has demonstrated that Follicle stimulating hormone (FSH) stimulates the proliferation and invasion of ovarian cancer cells, inhibits apoptosis, and facilitates neovascularization by increasing expression of vascular endothelial growth factor (VEGF). OCT4, a stem cell marker, is overexpressed in several types of human cancer and can induce resistance to chemotherapy and inhibition of apoptosis. We have found that FSH stimulates the expression of OCT4 mRNA and protein in a time- and dose-dependent manner. Subcellular analysis by immunofluorescent staining confirmed that FSH stimulation increased OCT4 protein expression in both the cytoplasm and nucleus of ovarian cancer cells. Re-expression of OCT4 in ovarian cancer cells reversed the inhibition of apoptosis induced by FSH, whereas siRNA-mediated knockdown of OCT4 resulted in a significantly rate of apoptosis. Depletion of OCT4 resulted in reduction of p-AKT and survivin, and also blocked FSH-induced upregulation of p-AKT and survivin. Moreover, FSH stimulation induced the expansion of CD44+CD117+ cells with a stem cell-like phenotype. Interestingly, re-expression of OCT4 enhanced the expression of Notch, Sox2, and Nanog, molecules that play critical roles in cancer stem cell proliferation and differentiation. FSH upregulated the expression of Notch, Sox2 and Nanog and these effects were abolished by knocking down OCT4, suggesting that several cancer stem cell pathways are involved in FSH regulation. We have also examined OCT4 expression in surgical specimens of ovarian cancer. Immunohistostaining revealed that OCT4 expression was increased in ovarian carcinoma compared with benign cystadenomas and borderline tumors, and OCT4 expression was significantly correlated with histological grade. Staining for OCT4 was increased in serous cystadenocarcinoma, when compared with clear cell carcinoma. In summary, the OCT4 cancer stem cell signaling pathway may mediate FSH-induced inhibition of apoptosis and could provide a target for treatment of ovarian cancer. Citation Format: Zhenbo Zhang, Yaping Zhu, Xianming Xu, Xiaowei Xi, Robert C. Bast, Yinhua Yu, Youji Feng. Follicle stimulating hormone (FSH) inhibits apoptosis in ovarian cancer cell through regulating OCT4 stem cell signal pathway. [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 4766. doi:10.1158/1538-7445.AM2013-4766
P453The effect of transcutaneous carbon dioxide application on cutaneous microcirculation
Authors: K Cankar, M Finzgar, Z Melik
Journal: Cardiovascular Research (2014)

Purpose: The main reason for inefficient healing of chronic wounds is poor blood perfusion of a wound and tissue around it. The objective of the present study was to determine the effect of transcutaneous application of physiological vasodilator gaseous CO2 (hereinafter CO2 therapy) on cutaneous blood flow and to determine whether systemic effects occur during CO2 therapy. If artificially applied CO2 has the potential to improve perfusion and oxygenation of tissues can be useful for healing of chronic wounds. Methods: We measured laser Doppler (LD) flux in cutaneous microcirculation, skin temperature, electrocardiogram (ECG) and arterial blood pressure. The measurements were performed in healthy men, aged 21 to 28 years, who did not use any vasoactive substances at least 8 hours before the start of the experiments. Measurements have been carried out during 6-minute rest period and during 35-minute CO2 therapy. One lower limb of each subject represented a studied extremity and was sealed in a plastic bag and exposed to CO2. The contralateral limb served as a control. It was also sealed in a bag and exposed to air. In this way we wanted to assess vasodilation due to elevated temperature and relative humidity alone in the sealed bag. For statistical analysis a paired t-test was used. A p-value of less than 0.05 was considered to be statistically significant. The study was approved by the National Medical Ethics Committee of Slovenia and written informed consent was obtained from each subject. Results: The studied population included 33 men, aged 23.8 ± 0.4 years, with body mass index of 24.2 ± 0.5 kg/m2. During CO2 therapy LD flux on the studied extremity increased (5.9 ± 0.7 PU vs. 26.1 PU ± 2.6 PU, p < 0.001) while on the control extremity it did not change significantly (5.2 ± 0.5 PU vs. 6.2 ± 0.7 PU). There were no statistically significant changes in systolic and diastolic pressure and skin temperature on both, studied and control extremity. Conclusions: The local vasodilation effect of applied CO2 therapy and absence of systemic cardiovascular effects, observed during the present study, argue for the clinical use of CO2 therapies. Additional studies are required for more detailed assessment of clinical usefulness of CO2 therapy. In order to achieve this we recommend independent analysis of each of the factors influencing the entry of CO2 in the circulatory system (skin hairiness, skin thickness, amount and composition of sweat, effect of positive pressure in the bag with CO2).
Abstract P3-11-13: Impact of Young Age on the Presentation, Management and Outcome of Breast Cancer in a Multi-Ethnic Asian Setting: Results from the Singapore-Malaysia Hospital-Based Breast Cancer Registry
Authors: N Bhoo Pathy, C-H Yip, NA Taib, N Saxena, P Iau, AM Bulgiba, S-C Lee, M Hartman, HM. Verkooijen
Journal: Cancer Research (2010)

Abstract Background: The proportion of very young women with breast cancer is high in Asia, ranging between 10% and 25%. Material and methods: Within the multi-institutional Singapore-Malaysia hospital-based breast cancer registry, we compared tumor characteristics, treatment and survival of very young (&amp;lt;35 years; n=210) and older (35-55 years; n=2,152) breast cancer patients diagnosed between 1990 and 2007. Overall survival (OS)was estimated by Kaplan-Meier analysis. Cox regression analysis was used to compute hazard ratios (HR) after splitting follow-up time along the age-axis and calendar-time axis. Results: Compared to older breast cancer patients, young patients presented with larger tumor (median diameter 25mm vs 30mm respectively: P&amp;lt;0.001), and less estrogen receptor positive (54% vs 46% respectively: P&amp;lt;0.01), and progesterone receptor positive tumors (57% vs 47%: P&amp;lt;0.01). Young women were more likely to receive chemotherapy (70% vs 61%: P&amp;lt;0.01), and less likely to be given hormone therapy (36% vs 57%: P&amp;lt;0.001). Among those with stage 0 to stage II disease, 5-year OS was 71.3% (95%CI: 61.7%-80.9%) in young patients and 85.6% (95%CI: 83.2%- 88.0%) in older women. After adjustment for stage, tumor profile and treatment, young patients had approximately 50% higher risk of death than their older counterparts (HR:1.46; 95% CI: 1.23-1.73). Ethnicity, tumor size, pathological lymph node staging, loco-regional therapy, and chemotherapy, were significant independent predictors of overall survival among young patients with breast cancer. Conclusion: Asian women diagnosed at a very young age, present with less favorable tumor characteristics and stage distribution. They have a 50% higher risk of death following their disease, which is independent of their stage at diagnosis, tumor characteristics and treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-11-13.
Abstract P4-09-15: Preoperative TPS as Valuable Prognostic Marker for Breast Cancer
Authors: SK Ahn, HG Moon, HC Shin, HS Kim, CK Yom, W Han, D-Y. Noh
Journal: Cancer Research (2010)

Abstract BACKGROUND: Several serum markers are used in management of breast cancer patients. Among these, tissue polypeptide specific antigen (TPS) has been recently proposed as a potential new marker for breast cancer. METHODS: We reviewed the records of 2247 patents with breast cancer treated between November 2000 and December 2007. We evaluated the association between clinicopathologic features and recurrence free survival with preoperative TPS. RESULTS: Among 2271 breast cancer patients, elevated preoperative TPS level (TPS&amp;gt;80 U/L) were identified in 479 patients (21.1%). Age (&amp;gt;45), tumor size (&amp;gt;2cm), tumor stage, nodal metastasis, progesterone receptor, Ki-67, recurrence and visceral metastasis were associated with elevated TPS levels. 193 patients had evidence of relapse. Elevated TPS were associated with poor recurrence free survival. (P&amp;lt;0.001) On a multivariate analysis with using the Cox model, nodal metastasis, estrogen receptor, Ki-67, histologic grade and elevated TPS(p=0.053) were independent prognostic factors for recurrence free survival. CONCLUSION: Elevated preoperative TPS levels are associated with poor breast cancer outcome. Preoperative TPS can be a valuable prognostic marker for breast cancer. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-09-15.
Panendoscopic characterization of Peutz–Jeghers syndrome
Authors: H. Neumann, M. Vieth, J. Mudter, M. Raithel, M. Neurath
Journal: Endoscopy (2010)

A 57-year-old man presented with chronic fatigue, weakness, irritability, and lack of concentration. Physical examination revealed pale skin with grooved and brittle nails. In addition, hyperpigmented mucocutaneous lesions were noted in the mouth. Laboratory investigation was remarkable for iron deficiency anemia. Esophagogastroduodenoscopy (EGD) disclosed a large polypoid mass in the gastric cardia ([Fig. 1 a]). Chromoendoscopy with methylene blue (1 % dilution) revealed a Kudo pit pattern 3 L (large roundish and tubular pits; [Fig. 1 b]) which was confirmed by narrow-band imaging (Olympus, Tokyo, Japan; [Fig. 1 c]). Confocal laser endomicroscopy (EC-3870 CIFK, Pentax, Tokyo, Japan) showed disorganization of glands with suspicion of different cell types but there was a lack of atypia ([Fig. 1 d]). Endocytoscopy (XEC-120-U, Olympus, Tokyo, Japan) of the polyp revealed normal cells without nuclear or cytoplasmic changes ([Fig. 1 e]), and endoscopic ultrasound showed enlargement of the mucosa but no muscularis infiltration ([Fig. 1 f]). Subsequently, an oral double-balloon endoscopy (Fujinon, Omiya, Japan) disclosed multiple polyps in the jejunum, most of them smaller than 10 mm in diameter ([Fig. 1 g]). Endoscopic examination was completed with ileocolonoscopy, which revealed multiple polyps ranging in size from 2 mm to 25 mm ([Fig. 1 h]). Following genetic analysis, which disclosed mutation of the serine threonine kinase 11 (STK11)/LKB1 gene, a diagnosis of Peutz–Jeghers syndrome was made.
Abstract LB-128: Synthetic lethal RNAi screening identifies inhibition of Bcl-2 family members as sensitizers to 5-Azacytidine in myeloid cells
Authors: James Bogenberger, Chang-Xin Shi, Tanner Hagelstrom, Irma Gonzales, Ashish Choudhary, Roger Tiedemann, David Azorsa, Keith Stewart, Raoul Tibes
Journal: Cancer Research (2010)

Abstract In order to identify novel targets and clinically exploitable vulnerabilities, we performed high-throughput RNA-interference (RNAi) synthetic lethality screening using myeloid cell lines TF-1 and ML-2 in combination with the hypomethylating agent 5-Azacytidine. A custom small interfering RNA (siRNA) library targeting nearly 1000 cancer-associated genes, including the human kinome, was utilized. Bcl-XL emerged as the strongest 5-Azacytidine sensitizing target in the erythroid cell line TF-1 but not in ML-2 cells. Additional siRNA sequences targeting Bcl-XL were transfected into a panel of myeloid cell lines and tested in drug dose response experiments using a ten-point serial dilution of 5-Azacytidine. The erythroid differentiated myeloid cell lines TF-1 and HEL both exhibited a 3 to 4-fold reduction in the IC50 of 5-Azacytidine upon knockdown of Bcl-XL, whereas IC50 values for non-erythroid, myeloid cell lines ML-2, THP-1 and MDS-L were unchanged. Furthermore, we tested lentiviral delivery of short-hairpin RNA (shRNA) targeting Bcl-XL in additional cell lines. Lentiviral knockdown of Bcl-XL confirmed 2 to 3-fold 5-Azacytidine sensitization in TF-1 and HEL cells while U937, HL-60, ML-2, THP-1 and MDS-L were not sensitized by Bcl-XL knockdown. Interestingly, while Bcl-XL knockdown with shRNA potentiated the effects of 5-Azacytidine in TF-1 and HEL, Bcl-XL knockdown alone resulted in considerable reductions in cell viability in TF-1 and HEL cells. These results demonstrate erythroid lineage-specific responses to Bcl-XL knockdown and suggest that Bcl-XL may represent an erythroid lineage-specific therapeutic vulnerability. To begin to explore this possibility we examined the putative BH3 mimetics Gossypol, Obatoclax and ABT-737 with 5-Azacytidine drug dose response experiments in myeloid cell lines. Neither Gossypol nor Obatoclax potentiated the effects of 5-Azacytdine. In striking contrast, ABT-737 resulted in a 2 to 4-fold reduction in the IC50 of 5-Azacytidine in all cell lines tested to date (TF-1, HEL, ML-2 and THP-1). ABT-737 sensitization to 5-Azacytidine was dose dependent. Furthermore, Combination Index (CI) values calculated with Calcusyn software demonstrate synergy between ABT-737 and 5-Azacytidine at clinically relevant concentrations. These results suggest that inhibition of anti-apoptotic Bcl-2 family members with a BH3 mimetic may represent an effective strategy for 5-Azacytidine combination therapy that can be directly translated into design of combination clinical trials in patients with myeloid leukemias. 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 LB-128.
Treatment of stage I seminoma, with one course of adjuvant carboplatin or surveillance, risk-adapted recommendations implementing patient autonomy: a report from the Swedish and Norwegian Testicular Cancer Group (SWENOTECA)
Authors: T. Tandstad, O. Ståhl, O. Dahl, H.S. Haugnes, U. Håkansson, Å. Karlsdottir, A. Kjellman, C.W. Langberg, A. Laurell, J. Oldenburg, A. Solberg, K. Söderström, U. Stierner, E. Cavallin-Ståhl, R. Wahlqvist, N. Wall, G. Cohn-Cedermark
Journal: Annals of Oncology (2016)
1269 VASCULAR HYPORESPONSIVENESS IN NON-CIRRHOTIC NAFLD-INDUCED PORTAL HYPERTENSION: ROLE OF NITRIC OXIDE AND CYCLOOXYGENASE AND COMPARISON WITH OTHER MODELS OF PHT
Authors: S.M. Francque, W.J. Kwanten, F. Couturier, J. Govaerts, B.Y. De Winter, J.G. De Man, P.A. Pelckmans, P.P. Michielsen
Journal: Journal of Hepatology (2013)
AB0382 Assessing neuropathic pain components in patients with rheumatoid arthritis:
Authors: J. Detert, V. Höhne-Zimmer, S. Schönberger, E. Roehner, G.-R. Burmester, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> This is a prospective analysis of a sample frequency of neuropathic pain (NP) components in patients (pts) with rheumatoid arthritis (RA). The current drug regimen addresses only inadequately NP phenomena and other factors such as anxiety, depression, and coping behavior. <h3>Objectives</h3> RA-pts have a NP component in addition to the inflammatory pain due to joint destruction and the resulting nerve irritation. <h3>Methods</h3> In this investigation 204 pts (163 ♀, 41 ♂) with RA were included according to classification criteria of ACR 1987. The disease duration of pts was ≥12 months. The mean age was 58.8 (SD: 13.5). All pts provided demographic information, and answered questions on their disease course (e.g. start of disease, medication). Furthermore, multiple data on pain perception (e.g. temporal occurrence, quality, quantity, characteristics) were collected. NP was also identified specifically using the pain<i>DETECT</i> Questionnaire (PDQ) in an interview.A descriptive statistical analysis was performed with SPSS 19. <h3>Results</h3> All data were collected in our outpatient department from June 2008 to November 2010. The mean disease activity score (DAS28<sub>ESR</sub>) was 3.2. The following table shows a selection of key results for the characterization of pain in RA-patients. <h3>Conclusions</h3> Most pts reported typical nociceptive pain. In their own words, pts also described an inflammatory pain and selected the characteristics of this pain from a list. Pain attacks occur more frequently in fall and winter. More than a third of patients report pain attacks that occur throughout the day. Hence, pain therapy should be adjusted accordingly. <h3>Disclosure of Interest</h3> J. Detert Grant/Research support from: Pfizer GmbH &amp; Co, V. Höhne-Zimmer: None Declared, S. Schönberger: None Declared, E. Roehner: None Declared, G.-R. Burmester Grant/Research support from: Pfizer GmbH &amp; Co, Consultant for: Pfizer GmbH &amp; Co, Speakers Bureau: Pfizer GmbH &amp; Co, F. Buttgereit Grant/Research support from: Pfizer GmbH &amp; Co, Consultant for: Pfizer GmbH &amp; Co, Speakers Bureau: Pfizer GmbH &amp; Co
Abstract 1253: Fer is required for mammary tumorigenesis
Authors: Peter A. Greer, Changnian Chi, Yan Gao, David LeBrun, Brian Golbourn, Waheed Sangrar
Journal: Cancer Research (2012)

Abstract Fer is a ubiquitously expressed cytoplasmic protein-tyrosine kinase (PTK) which is inducibly activated upon engagement of the epidermal and platelet-derived growth factor receptors (EGFR/PDGFR). Fer - and its homologous family member Fps/Fes - are structurally distinguished from other PTKs by a membrane-binding F-BAR domain implicated in regulating membrane-cytoskeletal dynamics during receptor endocytosis. We are investigating the role of Fer in EGFR internalization using both non-transformed mammary epithelial cells (MCF10A) and mammary tumor epithelial cells (MTEC) isolated from an ErbB2 mouse model of breast cancer. MCF10A Fer-knockdown cells (MCF10A-F2) and MTECs harboring a kinase-inactivating knock-in mutation at the fer locus (ferDR/DR) displayed elevated rates of EGF-induced endocytosis suggesting that Fer inhibits EGFR internalization. Elevated endocytic rates correlated with enhanced short-term MAPK signaling in both cell culture models and elevated steady-state Erk activity in ferDR/DR ErbB2 mammary tumors. Systems-level analyses using a physiochemical model of EGFR-MAPK signaling suggested that up-regulation of receptor endocytic rates could potentiate MAPK signal strength and sensitize this pathway to pharmacological inhibition at the receptor level. Inhibition of MAPK signaling with the EGFR/ErbB2 inhibitor, Lapatinib, confirmed this prediction, showing increased Erk signal-sensitivity to this drug in endocytosis-enhanced ferDR/DR MTECs. This correlated with a 10-fold reduction in the EC50 for Lapatinib cytotoxicity on ferDR/DR MTECs. Both the signaling and cytotoxicity phenoytypes were reversible by rescued expression of wild type Fer in ferDR/DR MTECs. These data reveal a novel mechanism by which potentiation of EGFR endocytosis enhances the sensitivity of downstream signaling to inhibition by ErbB inhibitors. In this respect, Fer is a unique kinase target because it provides a direct means of pharmacologically intervening with the mechanism of EGFR endocytosis. The therapeutic significance of potentiating receptor endocytosis by targeting Fer is highlighted by observations of: (1) delayed onset of ErbB2-mediated breast tumorigenesis in ferDR/DR genetic backgrounds in vivo; and; (2) impaired tumor growth of Fer-deficient MDA-MB-231 cells in mammary-fat pad transplantation models. We envisage that anti-Fer based treatments may sensitize breast - and potentially other carcinoma types - to anti-ErbB therapies. These observations provide biological proof-in-principle for developing small molecule inhibitor-based therapies against Fer in breast 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 1253. doi:1538-7445.AM2012-1253
FRI0147 Screening for cardiovascular risk according to the eular recommendations in outpatients with rheumatoid arthritis reveals significant risk factors
Authors: J. Primdahl, J. Clausen, K. Hørslev-Petersen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Persons with rheumatoid arthritis (RA) have an increased risk for development of cardio-vascular-disease (CVD) and screening is recommended (1). <h3>Objectives</h3> To investigate the spread of risk factors for development of CVD and estimate the risk for cardio-vascular death in a hospital population with RA according to the EULAR recommendations (1). <h3>Methods</h3> Outpatients with RA ≤ 85 years of age connected to King Christian X's Hospital for Rheumatic diseases in Graasten, Denmark, were invited for a 30 minute nursing consultation. Risk for cardiovascular death was calculated according to the SCORE system (2) based on total/HDL-cholesterol ratio, smoking habits, blood pressure, age and gender (Denmark high risk country). The SCORE was adjusted depending on the patients' disease duration, IgM-RF and/or anti-CCP positivity and the presence of certain extra articular manifestations (1). History of CVD and diabetes mellitus (DM), fasting glucose, Body Mass Index (BMI), waist circumference and exercise habits were explored. <h3>Results</h3> From September 2011-November 2012 a total of 836 patients completed the screening; 598 (71.5%) female; Mean age 64.3(12.0). In total 152(19.1%) were already diagnosed with CVD and 74(9%) with DM; 95(14.3%)of the patients without DM had a fasting glucose ≥6.0mM/l. Among the 644 patients with no known CVD or DM, 158(24.5%) were smokers; 229(35.8%) had a systolic blood pressure ≥140; 397(65.6%) had a total-cholesterol ≥5.0mM/l; 326(55.4%) a LDL-cholesterol≥3.0 mM/l; 18(4.0%) female and 19(12.1%) male patients had a HDL-cholesterol level below the recommended 1.2/1.0 mM/l respectively. BMI was &gt;25 in 409(63.8%); waist circumference (cm) were above 80 (female)/ 94 (male) in respectively 297(63.3%) and 111(63.8%) patients; 418(64.9%) exercised less than five times a week. The risk SCORE was ≥5 in 122 (20.2%) of the patients with no known DM or CVD and they were referred to follow-up by their General Practitioner and community advice services. This number will decrease to 99 (16.2%) as Denmark is considered to be a low-risk country from May 2012. <h3>Conclusions</h3> Systematic screening revealed several risks factors which needed medical follow-up or support to initiate life-style changes. More than 20% had an increased risk of 5% or more for cardiovascular death in 10 years. <h3>References</h3> Peters, M.J., et al., <i>EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis.</i> Ann Rheum Dis, 2010. <b>69</b>(2): p. 325-31. 2: Conroy, R.M., et al., <i>Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.</i> Eur Heart J, 2003. <b>24</b>(11): p. 987-1003. <h3>Disclosure of Interest</h3> None Declared