tbuckley/cabot-search huggingface dataset:
Abstract 3103: Overexpression of homeoprotein six1 activates non-canonical TGF-beta signaling to induce epithelial-mesenchymal transition in human papillomavirus type 16-immortalized human keratinocytes.
Authors: Hanwen Xu, Lucia Pirisi, Kim E. Creek
Journal: Cancer Research (2013)

Abstract Inappropriate expression of embryonic genes, particularly homeodomain transcription factors, contributes to tumorigenesis and tumor progression. The overexpression of Six1, a member of the Six family of homeodomain transcription factors, has been found in various human cancers, and is associated with increased tumor progression and metastasis. Previous studies in our laboratory discovered that the expression of Six1 mRNA and protein increased during in vitro progression of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes (HKc/HPV16) toward a differentiation-resistant (HKc/DR) phenotype. However, the precise mechanisms of how Six1 promotes tumor onset at early and late stages of HPV16-mediated transformation remain unknown. In this study, we found that HKc/HPV16 and HKc/DR overexpressing Six1 exhibited a more mesenchymal phenotype compared to vector controls, as characterized by a fibroblastic morphology, and increased migration and invasion. We utilized Whole Human Genome Microarrays (4x44K from Agilent Technologies) to explore the gene expression changes associated with Six1 overexpression in HKc/HPV16 and HKc/DR. We found that overexpression of Six1 down-regulated epithelial-related genes (ex., E-cadherin and occludin) and up-regulated mesenchymal-related genes (ex., N-cadherin, vimentin, and snail), which strongly suggests that Six1 overexpression induces epithelial-mesenchymal transition (EMT). Gene expression changes determined by microarray analysis were confirmed by real time PCR and western blotting. Increased expression of TGF-beta receptors in response to overexpression of Six1 in HKc/DR did not lead to increased Smad-dependent signaling but did activate the Mitogen-activated protein kinase (MAPK) pathway, suggesting that MAPK non-Smad TGF-β signaling may be involved in Six1-mediated EMT. In conclusion, our study demonstrates that Six1 overexpression induces EMT, possibly by activation of the MAPK non-canonical (non-Smad) TGF-β pathway, during HPV16-mediated transformation of human keratinocytes. Citation Format: Hanwen Xu, Lucia Pirisi, Kim E. Creek. Overexpression of homeoprotein six1 activates non-canonical TGF-beta signaling to induce epithelial-mesenchymal transition in human papillomavirus type 16-immortalized human keratinocytes. [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 3103. doi:10.1158/1538-7445.AM2013-3103
Cytomegalic-Inclusion Disease in the Adult
Authors: Edwin R. Fisher, Earl Davis
Journal: New England Journal of Medicine (1958)

THE occurrence of cytomegaly with intranuclear inclusions is well recognized in newborn and older infants. This cellular alteration may be incidentally encountered at autopsy in salivary glands or less frequently disseminated in other viscera. On occasion it has been considered pathognomonic of a disease in infants characterized by jaundice, hemolytic anemia, thrombocytopenia, purpura, pneumonitis and cerebral calcification. Diagnosis during life may be facilitated by observation of the characteristic cells in the urinary sediment1 or gastric washings2 or in biopsies from the lung3 or liver.4 In patients with this disease the isolation of a virus producing identical cytologic changes in tissue . . .
AB0596 Retinal toxicity of antimalarials in rheumatology practice
Authors: D. Palma-Sánchez, S. Soro-Marín, A. Haro-Martinez, R. Gonzalez-Molina, M. Mayor-Gonzalez
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The antimalarial drugs are considered safe and well tolerated, with minimal risk of side effects. Hydroxychloroquine is considered safer but less effective than chloroquine, although the choice remains a matter of debate and is generally dependent on the experience. Both can cause ocular toxicity corneal and retinal deposition. The latter produces irreversible alterations of the vision and the patient may not perceive his presence at an early stage so regular eye tests are recommended <h3>Objectives</h3> To study the incidence of retinal toxicity in patients treated with antimalarials in a Rheumatology consultation. <h3>Methods</h3> We conducted a retrospective study of 39 patients treated with antimalarials in rheumatology consultation who were referred to ophthalmology to study retinal toxicity during 2011. Data collection included demographic data of patients, type of antimalarial prescribed, daily and cumulative doses, base rheumatic disease, corticosteroid use, associated morbidity and ophthalmological examination. <h3>Results</h3> Five out of 39 patients had alterations in the SD-OCT, and two out of these five were also observed in the funduscopy. Among the patients with retinopathy, three had been treated with chloroquine (CQ) and two with hydroxychloroquine (HCQ). The average duration of treatment in these patients was 2.37±1.37 years and the mean cumulative dose of CQ was 559 g and 172.5 g for HCQ. There is no statistically significant association between retinal toxicity and sex, age, rheumatic disease, duration or dose of treatment with p value greater than 0.05. <h3>Conclusions</h3> The incidence of retinal toxicity in our patients treated with antimalarial drugs was 12.8%. Chloroquine was the antimalarial that caused most of cases of retinopathy and the most sensitive test to detect it was the SD-OCT. <h3>References</h3> Peponis V, Kyttaris VC, Chalkiadakis SE, Bonovas S, Sitaras NM. Ocular side effects of antirheumatic medications: what a rheumatologist should know. Lupus. 2010;19(6): 675-682 Wolfe F, Marmor MF. Rates and predictors of hydroxochloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care Res (Hoboken). 2010;62(6): 775-84 Levy GD, Munz SJ, Pachal J, Cohen HB, Pince KJ, Peterson T. Incidence of hydroxychloroquine retinopathy in 1207 patients in a large multicenter outpatient practice. Arthritis Rheum 1997; 40: 1482-6. Kobak S, Deveci H. Retinopathy due to antimalarial drugs in patients with connective tissue diseases: are they so innocent? A single center retrospective study. Int J Rheum Dis. 2010 Aug;13(3):e11-5. Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011 Feb;118(2):415-22 <h3>Disclosure of Interest</h3> None Declared
Abstract P3-09-02: The HER2 –positive subtypes by stage and race/ethnicity
Authors: V Caggiano, C Parise
Journal: Cancer Research (2012)

Abstract HER2-positivity is often associated with poor survival. The purpose of this study is to determine if there are differences in mortality among the HER-positive subtypes when stratified by stage and race/ethnicity. Methods: Using the California Cancer Registry for years 2000–2010, we examined 99,897 cases of stages 1–3 ER+/PR+/HER2− and all HER2-positive first primary female invasive breast cancers. Race/ethnicity was defined as white, black, Hispanic, and Asian/Pacific Islander (API). Kaplan-Meier (KM) and the Log-Rank test were used to compute 6-year survival. Cox proportional hazards was used to assess the risk of mortality of each of the HER2-positive subtypes when compared with the ER+/PR+/HER2− subtype (the most common subtype). All analyses were adjusted for age, grade, year of diagnosis (&amp;lt;2007, 2007+), and socioeconomic status and run separately by race for stages 1, 2, and 3. Results: For all stages combined, of the subtypes comprising the luminal B-HER2 positive category, the ER+/PR+/HER2+ had the best survival (85%), only 2% less than the ER+/PR+/HER2−. When compared with the ER+/PR+/HER2− subtype, no difference in KM survival was noted for stage 1 luminal B (ER+/PR+/HER2+;ER+/PR−/HER2+; ER−/PR+/HER2+). Both had 90% 72-month survival. The ER−/PR−/HER2+ had 88% survival (p &amp;lt; 0.02). For stage 2, luminal B had 83% survival and ER−/PR−/HER2+ had 76% survival. Both were significantly different (p &amp;lt; 0.001) from the ER+/PR+/HER2− subtype (86%). The luminal B had 68% survival and the ER−/PR−/HER2+ had 55% survival for stage 3. Both were statistically significantly worse (p &amp;lt;.006) than the ER+/PR+/HER2− (72%). Adjusted mortality for the ER+/PR+/HER2+ was only increased for blacks in stage 1 (HR = 1.59; 95%CI=1.09–2.33). Mortality for the ER−/PR−/HER2+ was increased for whites in all stages; for blacks in stages 1 (HR = 1.82; 95%CI=1.11–3.00) and 3 (HR = 1.90; 95%CI=1.36–2.66); for Hispanics in stages 2 (HR = 1.58; 95%CI=1.28–1.95) and 3 (HR = 2.19; 95%CI=1.73–2.78); and APIs only in stage 2 (HR = 1.70; 95%CI=1.31–2.19) Year of diagnosis made no difference in risk of mortality in stage 1 for any race. For stage 2, blacks had slightly reduced mortality if diagnosed in 2007 or later, and for stage 3, all races except blacks had reduced risk of mortality when diagnosed in 2007 or later. Conclusions: 1. There is variation in survival among the luminal B-HER2 positive subtypes.2. The driving force behind the increased mortality of the HER2 positive subtype is the ER−/PR−/HER2+ subtype, the molecularly defined HER2 overexpressing subtype.3. Year of diagnosis does not influence survival in stage 1 for any race.4. There are differences in mortality among the HER2 positive subtypes when stratifying by stage and race and adjusting for age, grade, year of diagnosis, and SES. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-09-02.
Abstract 646: Soy food intake and risk of lung cancer: Evidence from the Shanghai Women's Health Study and a meta-analysis
Authors: Gong Yang, Xiao-Ou Shu, Wong-Ho Chow, Xianglan Zhang, Hong-Lan Li, Bu-Tian Ji, Hui Cai, Sheng-Hui Wu, Yu-Tang Gao, Wei Zheng
Journal: Cancer Research (2012)

Abstract Background: Recent large-scale clinical trials raised concerns regarding increased risk of aggressive lung cancer and lung cancer mortality among users of postmenopausal estrogen therapy. Soy and its phytoestrogens have been shown to act as a natural estrogen antagonist and have cancer-inhibitory activities in experimental studies. Objective: We prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and perform a meta-analysis of published data. Methods: Included in this analysis were 71,550 women recruited in the Shanghai Women's Health Study, a population-based cohort study. Usual soy food intake was assessed at baseline and re-assessed during follow-up through in-person interviews. Previous studies were identified through a MEDLINE search. Results: During a mean follow-up of 9.1 years, 370 incident lung cancer cases were identified; 340 were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer; the hazard ratio (HR) for the highest compared with lowest quintile of intake was 0.63 (95% CI: 0.44 - 0.90; P trend = 0.004). This inverse association appeared predominately among women with a later age at menopause (P interaction = 0.01) and varied by tumor aggressiveness as defined by length of survival (&amp;lt;12 versus β12 months), with corresponding HR of 0.49 for more aggressive lung cancer versus 0.76 for less aggressive lung cancer (P heterogeneity = 0.057). Similar inverse associations were observed for isoflavone intake. A meta-analysis of seven studies conducted among never smokers found a summary odds ratio of 0.59 (95% CI: 0.49 - 0.71) for the highest versus lowest categories of soy or isoflavone intake. Conclusion: This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive lung cancer, and its effect may be modified by endogenous estrogens. 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 646. doi:1538-7445.AM2012-646
Abstract P5-05-10: EIA-Induced PP2A Expression Prevents β-Trcp Mediated FOXO3a Degradation and Enhances Chemosensitization by Inhibiting TAK1/IKK Signaling
Authors: Y-W Chang, J-L Su, M-C. Hung
Journal: Cancer Research (2010)

Abstract Background: E1A gene therapy was tested in multiple clinical trials in breast, ovarian, and head and neck cancers. E1A can sensitize paclitaxel-induced cell death and combined paclitaxel chemotherapy and E1A gene therapy is currently tested in a clinical trial for ovarian cancer patients. It has been shown that resistance to paclitaxel occurs in cells expressing low level of FOXO3a. We found that Forkhead box O-class (FOXO) transcription factor FOXO3a is critical for E1A-mediated chemosensitization to paclitaxel. Knocked down FOXO3a expression dramatically abolished E1A-induced chemosensitization of paclitaxel. E1A stabilized FOXO3a by preventing ubiquitin-dependent proteolysis. The E3 ligase involved in stabilizing FOXO3a is β-transducin repeat-containing proteins (ßTrCP); ßTrCP binding to FOXO3a requires phosphorylation of FOXO3a at Ser644 by IKKβ. E1A reduces βTrCP-mediated ubiquitination of FOXO3a by inhibiting IKKβ activity. Further, inhibited IKKß activity is due to E1A-induced expression of PP2A, which binds to transforming growth factor β-activated kinase 1 (TAK1), thus inhibiting TAK1's activation of IKKβ. In this study, we found that E1A stabilizes FOXO3a which is required to sensitize paclitaxel-induced apoptosis. The stabilization is achieved by E1A-induced expression of PP2A/C, which inhibits the binding of TAK1 to IKKβ, therefore abolishing IKKß's function in phosphorylating FOXO3a and FOXO3a degradation. This result provides a rationale for the combination of E1A gene therapy and paclitaxel chemotherapy and may also shed light on design of targeted therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-05-10.
Abstract 4313: A LIM protein ajuba suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.
Authors: Ichidai Tanaka, Hirotaka Osada, Makiko Fujii, Yoshitaka Sekido
Journal: Cancer Research (2013)

Abstract Malignant mesothelioma (MM) is a highly aggressive neoplasm which is associated with asbestos exposure and around 50% of MM tumors have a mutation of the NF2 tumor suppressor gene. NF2 encodes merlin, a member of the ezrin/radixin/moesin protein family, and merlin is an upstream regulator of the Hippo signaling cascade. Activation of the Hippo pathway induces the activation of serine/threonine kinases LATS1/2, which phosphorylate and inactivate a transcriptional coactivator, YAP. The Hippo pathway activation negatively regulates tissue growth and its inactivation is involved in carcinogenesis. We previously found that, besides NF2 mutation, a subset of MM tumors harbor LATS2 mutation or YAP oncogene amplification. However, there are yet other MM cases that don't have any of these gene mutations, leading us to hypothesize that other components of this pathway might be altered. Recently, the LIM protein Jub in Droshophila was shown to activate Yoki (ortholog of human YAP) through suppression of the Hippo pathway. To determine whether the human ortholog of Jub, Ajuba, is involved in the Hippo signaling downregulation in MM, we analyzed 20 MM cell lines for the alteration of Ajuba. We found that the expression of Ajuba was significantly downregulated in 6 of 20 MM cell lines compared to an immortalized normal mesothelial cell line, Met-5A. Interestingly, three of the 6 cell lines with low Ajuba expression showed YAP activation, whereas Met-5A cells showed high Ajuba expression and YAP inactivation, both of which suggested that Ajuba might act as a tumor suppressor instead of oncogenic protein in mesothelial cells. We infected Ajuba-expressing lentivirus into these MM cell lines and found that exogenous Ajuba induced YAP phosphorylation and inhibited MM cell proliferation. Since the CCND1 and connective tissue growth factor (CTGF) genes are well-known transcriptional targets of YAP, we conducted a dual-luciferase reporter assay using these promoter regions to see if Ajuba affects their transcriptional activities. The dual-luciferase assay demonstrated that Ajuba suppressed the promoter activity of these genes and that the suppression of them was attenuated by LATS2 knockdown. These results indicated that Ajuba negatively regulates YAP through activation of LATS2. Our results suggest that the inactivation of Ajuba is one of the mechanisms for constitutive activation of YAP, which results in deregulation of MM cell proliferation. Citation Format: Ichidai Tanaka, Hirotaka Osada, Makiko Fujii, Yoshitaka Sekido. A LIM protein ajuba suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade. [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 4313. doi:10.1158/1538-7445.AM2013-4313
LAB-IMMUNOLOGY RESEARCH
Authors: M. Fujita, R. Zhang, S. Nakata, K. Kuzushima, D. A. Wainwright, I. V. Balyasnikova, B. Auffinger, A. U. Ahmed, Y. Han, M. S. Lesniak, A. Knight, H. Arnouk, G. Y. Gillespie, W. Britt, Y. Su, M. W. Lowdell, L. S. Lamb, J. Wang, L. Leiss, B. D. Choi, C.-T. Kuan, M. Cai, D. D. Bigner, J. H. Sampson, I. Shibahara, R. Saito, R. Zhang, M. Kanamori, Y. Sonoda, T. Kumabe, T. Kikuchi, T. So, N. Ishii, T. Tominaga, L. Zhang, H. Wang, I. Zhang, X. Chen, A. Da Fonseca, H. Fan, B. Badie, E. J. Sayour, P. McLendon, R. Reynolds, D. D. Bigner, J. H. Sampson, R. McLendon, D. A. Mitchell, E. J. Sayour, L. Sanchez-Perez, C. Pham, D. Snyder, W. Xie, X. Cui, D. D. Bigner, J. H. Sampson, D. A. Mitchell, M. J. McConnell, K. W. Broadley, K. Farrand, A. Authier, J. H. Brown, M. Hunn, I. Hermans, G. Cantini, F. Pisati, S. Pessina, G. Finocchiaro, S. Pellegatta, J. T. Yeung, R. Hamilton, I. Pollack, R. Jakacki, H. Okada, L. Sanchez-Perez, B. Choi, D. Snyder, X. Cui, R. J. Schmittling, C. Flores, L. Johnson, G. A. Archer, D. D. Bigner, D. A. Mitchell, J. H. Sampson, B. Raychaudhuri, P. Rayman, P. Huang, J. Ireland, S. Donnola, D. Hamburdzumyan, J. Finke, M. A. Vogelbaum, K. Batich, D. Snyder, W. Xie, E. Reap, G. Archer, J. Sampson, D. Mitchell, A. M. Martin, C. Nirschl, M. Polanczyk, K. J. Cohen, D. M. Pardoll, C. G. Drake, M. Lim, W. C. Rutledge, J. Kong, J. Gao, D. A. Gutman, L. A. Cooper, C. Chisolm, L. Scarpace, T. Mikkelsen, J. H. Saltz, C. S. Moreno, D. J. Brat, R. G. Everson, D. N. Lisiero, H. Soto, L. M. Liau, R. M. Prins, L. Zhang, G. C. Gonzalez, M. Chae, T. E. Peterson, I. F. Parney, M. Chae, T. E. Peterson, A. J. Johnson, I. F. Parney
Journal: Neuro-Oncology (2012)
Lack of Efficacy of Thermography as a Screening Tool for Minimal and Stage I Breast Cancer
Authors: Myron Moskowitz, John Milbrath, Peter Gartside, Alfonso Zermeno, David Mandel
Journal: New England Journal of Medicine (1976)

In a study of thermograms of 42 patients with Stage 1 or smaller carcinomas of the breast, 44 confounding cases and 64 randomly selected subjects being screened, we found that the ability of expert thermographers to identify the patients with carcinoma correctly (true positive = 0.238) varied little from the ability of untrained readers (true positive = 0.301). Furthermore, in the expert group, the indexes of suspicion were so high (0.436) and the true-positive levels were so relatively low (0.238, P = 0.0005) that thermography may well have a very limited role as a screening or pre-screening modality for the detection of minimal or Stage 1 breast cancers.
Use of maintenance rituximab (R) in the United States following R-based induction for follicular lymphoma (FL).
Authors: C. Flowers, M. Taylor, J. Hirata, H. Dillon, A. D. Zelenetz, J. D. Hainsworth, J. R. Cerhan, E. S. Rogers, J. W. Friedberg, B. K. Link
Journal: Journal of Clinical Oncology (2010)

8100 Background: The benefits of R maintenance after R-based induction as front line therapy, and the patterns of R maintenance use for FL in the US remain undefined. Methods: The National LymphoCare Study (NLCS) is a multicenter observational study collecting data on treatment and outcomes for patients (pts) with newly diagnosed FL in the US. From 2004-2007, 2,734 pts were prospectively enrolled from 226 community and 38 academic sites. Initial treatment and maintenance/observation decisions were made by the treating clinician. Pts without progression within 215 days of completing initial induction were classified as either R maintenance or observation. Demographic and baseline disease characteristics were summarized for each group. Univariate associations between baseline factors, treatment setting, initial treatment, and R maintenance vs. observation were tested by X2. Results: Among pts receiving R-based induction, 1,046 met inclusion criteria for this analysis with a median age of 61 (range 22-97); FLIPI 0-1, 31%; 2, 31%; ≥3, 38%. Pts received initial R (n=220), RCVP (n=195), RCHOP (n=467), R-fludarabine (n=122), or R-other (n=42). After initial treatment with R alone, 54% of pts had R maintenance and 46% were observed. Following R- chemo, 45% of pts had maintenance and 55% were observed. Pts on R maintenance were more likely to have FL grade 1/2 (73% v 59%; p<0.001), stage 3/4 (81% v 70%; p=0.003), normal LDH(64% v 56%; p=0.029), >4 lymph nodes (39% v 34%; p=0.019) and ≥2 extranodal sites (27% v 19%; p=0.012). Pts in the West were more often observed (p=0.003). Pts receiving R alone vs. R-chemo were more likely to get maintenance (p=0.02). There were no differences in maintenance use by age, gender, race, or FLIPI. With median follow-up of 45 months, 257 progression events and 75 deaths have occurred. Conclusions: Following R-based induction, US practices are evenly split between maintenance R and observation. Grade 1/2, stage 3/4, and initial R alone are associated with more R maintenance use, but regional variation influences maintenance as much as other clinical factors. Results from completed phase 3 trials on R maintenance after R-based induction are needed to provide clearer standards for use. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, GlaxoSmithKline, sanofi-aventis Roche Amgen, Biogen Idec, Genentech, GlaxoSmithKline, Roche