tbuckley/cabot-search huggingface dataset:
Gastric hamartomatous inverted polyp mimicking ectopic pancreas on endoscopy and endosonography
Authors: Tsung-Chieh Yang, Ming-Chih Hou, Ping-Hsien Chen, Wei-Chih Liao, Anna Li
Journal: Endoscopy (2014)

Gastric hamartomatous inverted polyp (HIP) is difficult to diagnose preoperatively because of its rarity [1] [2]. It is pathologically benign, but has been reported as a paracancerous lesion [3] [4] [5], and therefore its diagnosis and treatment are clinically important. We report a case of gastric HIP and focus on its special characteristics on endoscopy and endosonography.
Imaging Prostatitis with Tc-99m Ciprofloxacin
Authors: Wonsick Choe, Moon-Hyun Chung, Won-Hong Kim, Sungeun Kim, Ji Kan Ryu, Kyung Jin Kang, Jun-Kyu Suh
Journal: Clinical Nuclear Medicine (2002)

CHOE, WONSICK M.D., M.P.H.; CHUNG, MOON-HYUN M.D.; KIM, WON-HONG M.D.; KIM, SUNGEUN M.D.; KAN RYU, JI M.D.; JIN KANG, KYUNG M.D.; SUH, JUN-KYU M.D. Author Information
AB0698 Sleep and its relationship to pain, dysfunction, and disease activity in juvenile rheumatoid arthritis.
Authors: S. Shyen, B. Amine, S. Rostom, D. El Badri, N. Mawani, M. Ezzahri, F. Moussa, S. Gueddari, M. Wabi, R. Abouqal, B. Chkirat, N. Hajjaj-Hassouni
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To determine what sleep abnormalities may exist in children with juvenile rheumatoid arthritis (JRA), and their relationship to pain, dysfunction, and disease activity <h3>Methods</h3> Case control study including 47 patients diagnosed with JIA. The diagnosis of JIA was made according to the criteria of the International League of Association of Rheumatology (ILAR), and 47 healthy children, age and sex matched. Sleep was assessed by questionnaire CSHQ (children's sleep habits questionnaire). All parents have filled the 45 items of the CSHQ, grouped into eight subscales: (1) bedtime resistance, (2) sleep onset delay, (3) sleep duration, (4) sleep anxiety, (5) sleep-disordered breathing, (6) night Wakings, (7) parasomnias, (8) morning wakening/daytime sleepiness. The disease activity was assessed by the number of painful joints, swelling, erythrocyte sedimentation rate, and c-protein reactive. Functional assessment was based on the value of CHAQ Arabic validated. Pain was assessed by visual analog scale pain (VAS). <h3>Results</h3> Forty-seven patients were included with 28 male (59.6%), mean age was 11.59 ± 3.35 years, with predominance of oligoarticular 12 (25.5%). Children with JIA had a total score of CSHQ significantly higher than the control cases (p = 0.001), significant differences were also found in the subscale sleep onset delay, night wakings, sleep disordered breathing and parasomnias, with a p-value respectively (0.024, 0.004, 0.004, 0.001). Significant association was found between the CSHQ total score and VAS activity physician (p = 0.016). Sleep onset delay was associated with VAS patient pain (p= 0,05), as nocturnal awakenings and VAS patient pain (p = 0.016). Finally, parasomnias and painful joints (p = 0.002); physician's VAS activity (p = 0.015) and patient pain VAS (p = 0.03) were also correlated. <h3>Conclusions</h3> This study suggests that sleep abnormalities are common in children with JIA. Strategies to improve sleep and reduce fatigue should be studied as a possible tool of improving the quality of life of children with rheumatic disease. <h3>Disclosure of Interest</h3> None Declared
The House and the ACA — A Lawsuit over Cost-Sharing Reductions
Authors: Timothy Stoltzfus Jost
Journal: New England Journal of Medicine (2015)

Interview with Prof. Timothy Jost on a lawsuit brought by the House of Representatives over the Affordable Care Act’s cost-sharing-reduction program. (09:16)Download The U.S. House of Representatives argues in a lawsuit that the Obama administration is illegally reimbursing insurers for reducing cost sharing for insurance enrollees under the Affordable Care Act, and a federal district court judge has agreed to consider the case.
Abstract 5214: Functional interaction between foxm1 and β-catenin
Authors: Aihua Gong, Guanzhen Yu, Nu Zhang, Ping Wei, Kenneth D. Aldape, Howard Colman, Jianfei Xue, Mingguang Liu, Raymond Sawaya, Keping Xie, W.K. Alfred Yung, René H. Medema, Xi He, Suyun Huang
Journal: Cancer Research (2012)

Abstract The Wnt/β-catenin signaling pathway is aberrantly activated in human cancers and is critical for cancer formation, but its molecular mechanisms are not fully understood. In the current study, we found that FoxM1, which is also activated in most human tumors, is a novel downstream component of Wnt signaling and is critical for β-catenin transcriptional function in tumor cells. Wnt increases the level and nuclear translocation of FoxM1 through inhibition of FoxM1 protein degradation. FoxM1 binds directly to β-catenin and enhances β-catenin nuclear localization and transcriptional activity. Moreover, FoxM1, β-catenin and TCF-4 are mutually recruited to Wnt target-gene promoters, and FoxM1 promotes the assembly of the β-catenin-TCF transcription activation complex in the promoters hence the Wnt target gene expression. Furthermore, interaction of FoxM1 and β-catenin plays a critical role in glioma stem cell self-renewal and differentiation and is required for glioma formation. Finally, the expression levels of nuclear β-catenin in human GBM directly correlates with levels of nuclear FoxM1, supporting the critical role of FoxM1 in β-catenin activation in human GBM. Given the importance of FoxM1 and the Wnt/β-catenin signaling pathway in human cancers in general, our findings not only provide an improved understanding of the molecular mechanisms underlying Wnt/β-catenin activation and tumorigenesis but also suggest additional targets for therapeutic intervention. 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 5214. doi:1538-7445.AM2012-5214
IM-07 * NK CELL IMMUNOTHERAPY FOR PEDIATRIC BRAIN TUMORS: OVERCOMING RESISTANCE TO EXPAND THERAPEUTIC SUCCESS
Authors: W. Brugmann, A. Laureano, K. Michel, R.-H. Tao, B. Kennis, S. Somanchi, C. Denman, K. C. Ho, L. Silla, H. Singh, H. Huls, D. Sandberg, D. Lee, J. Bankson, A. Huang, L. Cooper, V. Gopalakrishnan
Journal: Neuro-Oncology (2015)

Pediatric brain tumors including medulloblastomas and ATRTs are associated with significant mortality and morbidity. Much of this morbidity is due to conventional treatments: radiation and chemotherapy. Therefore, there is an urgent need to develop new therapeutic options to combat these devastating diseases. Immunotherapy has gained traction as a potential alternative to current treatments. Because many immunotherapies rely on the presence of tumor-associated antigens (TAAs) and pediatric brain tumors have poorly defined antigen profiles, we pursued the development of natural killer (NK) cells, which don't require TAAs for their activity, to treat these malignancies. Our work shows that most medulloblastoma and ATRT cell lines are sensitive to NK cell lysis in vitro. Furthermore, both intratumoral NK cell injections as well as infusion at a distant site limit the medulloblastoma growth in mouse orthotopic xenograft models, indicating NK cell trafficking through the brain. These results have provided the foundation for a FDA-approved Phase I clinical trial to infuse NK cells directly into the fourth ventricle of patients who have undergone re-resection of infratentorial tumors. The trial is scheduled to enroll patients in February 2015. Interestingly, our pre-clinical data has also identified overexpression of a novel tumor-secreted immunosuppressive molecule, which was originally shown to confer cardio-protection following myocardial ischemia, in human ATRT samples, and its involvement in promoting resistance to NK cell-mediated lysis. In conclusion, our findings have paved the way for a first in pediatrics brain tumor immunotherapy trial that merges two cutting edge technologies: immunotherapy and loco-regional therapeutics delivery. Our study also offers a novel biomarker for predicting patient response to NK therapy.
Abstract 3262: Targeting PI3K-coupled MEK/ERK pathway for therapy in pediatric B-cell acute lymphocytic leukemia.
Authors: Xiang Wang, Ben-shang Li, Li-xia Ding, Chris Liang, Jian Ding, Ling-hua Meng
Journal: Cancer Research (2013)

Abstract Acute lymphoblastic leukemia (ALL) is the most common hematological malignancy diagnosed in children and B cell type is prevalent among pediatric ALL. At present, cytotoxic agents are the major components for chemotherapy against ALL, which are limited by their severe side effects. PI3Kδ was found to be over activated in most B cell type leukemia, and one of its inhibitor CAL-101 (GS-1101) is in active clinical trials for B cell type acute or chronic leukemia with promising outcomes. However, the mechanism of action of PI3Kδ inhibitor against B-ALL needs to be further studied to optimize the therapeutic success. Herein, for the first time we found that blockade of PI3K-coupled MEK/ERK pathway by a novel PI3Kδ selective inhibitor X-370 is essential for its efficacy against B cell acute lymphocytic leukemia. X-370, which was obtained through rational design and screening displayed potent activity against PI3Kδ (IC50=7 nM), while sparing class II/III PI3Ks as well as a panel of protein kinases representative of the human kinome. X-370 selectively blocked constitutively activated and stimuli-induced PI3Kδ signaling among four isoforms of class I PI3Ks. X-370 abrogated both Akt and Erk signaling in human B cell leukemia cells, which is accompanied with induction of cell cycle arrest and apoptosis. Mechanism studies revealed that X-370 obstructed PDK1 from binding to and/ or phosphorylating MEK in a PI3Kδ-dependent manner. Accordingly, forced expression of constitutively activated MEK attenuated the antiproliferative activity of X-370. Furthermore, X-370 preferentially inhibited the survival of primary B-ALL cells containing PI3Kδ-coupled Erk phosphorylation, which were obtained from pediatric B-ALL patients. In summary, with a novel PI3Kδ selective inhibitor X-370, we found that inhibition of PI3Kδ led to abrogation of ERK signaling via an atypical PI3K/ PDK1/ MEK/ Erk signaling cascade. Inhibition of PI3Kδ-coupled Erk by a PI3Kδ inhibitor may predict its efficacy against B cell acute lymphocytic leukemia. These findings support the rationale for clinical testing of PI3Kδ inhibitor for the treatment of pediatric B-ALL and provide insight to optimize therapeutic strategy for such treatment. Citation Format: Xiang Wang, Ben-shang Li, Li-xia Ding, Chris Liang, Jian Ding, Ling-hua Meng. Targeting PI3K-coupled MEK/ERK pathway for therapy in pediatric B-cell acute lymphocytic leukemia. [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 3262. doi:10.1158/1538-7445.AM2013-3262
Surveillance of leishmaniases in France, 1999 to 2012
Authors: L Lachaud, J P Dedet, P Marty, F Faraut, P Buffet, J P Gangneux, C Ravel, P Bastien
Journal: Eurosurveillance (2013)

Leishmaniasis is endemic in the south of France, where autochthonous disease is caused by Leishmania infantum, and affects both humans and dogs. The prevalence of canine leishmaniasis is between 3 and 66% depending on the region and the methods used. Human leishmaniases are also imported into France, mainly from French Guiana and North Africa. The surveillance of autochthonous and imported human leishmaniases is based on passive notification to the National Reference Centre for Leishmaniases (NRCL) created in 1998. Between 1999 and 2012, 317 autochthonous and 1,154 imported cases were notified to the NRCL. The average number of autochthonous cases notified per year was 22.6, mainly cases of visceral leishmaniasis (84.5%). All cases were infected in the south of France. Leishmaniasis incidence is 0.22 per 100,000 inhabitants in the endemic area. Imported cases were more frequent (annual mean of 82.4 cases) and consisted predominantly in cutaneous leishmaniasis (CL) cases (91%), essentially L. major CL imported from Maghreb and Sub-Saharan Africa, and L. guyanensis CL from French Guiana. This national notification system allowed a better understanding of the incidence and distribution of the disease; it is also useful to assess the temporal-spatial evolution of the disease in France, which appears relatively stable.
Abstract 1465: Radiosensitization of NSCLC through modulation of autophagy and senescence
Authors: Rachel W. Goehe, Khushboo Sharma, Aparna Maiti, David A. Gewirtz
Journal: Cancer Research (2012)

Abstract Introduction: Radiotherapy (IR) is a key treatment modality in the treatment of patients with non-small cell lung cancer (NSCLC), and is commonly combined with chemotherapy to prolong survival, although the gain is generally quite modest. An underlying cause for the relatively poor cure rate is the resistance to chemotherapy, which is partially associated with the dysregulation of cell death signaling, particularly apoptotic pathways. Thus, the current work was designed to exploit the capacity of 1,25D3 (the hormonally active form of vitamin D) to radiosensitize A549 cells. Experimental Procedure: In vitro studies assessed the effects of 100nM 1,25D3 alone, radiation alone (6 Gy) and the combination treatment of 100nM 1,25D3 concurrently with radiation in A549 NSCLC cells. Cell viability was assessed over a period of 7 days and sensitization to radiation was confirmed by clonogenic survival assays. Senescence was measured by β-galactosidase staining as well as C12FDG fluorescence measurement by flow cytometry. Levels of the senescence associated markers p21, pRb, and p53 were monitored by western immunoblotting. Autophagy was inhibited pharmacologically using 5mM 3-MA and 10µM chloroquine. Autophagy induction was monitored by acridine orange with quantification using flow cytometry, while autophagic flux was based on degradation of p62. Results: 1,25D3 sensitized A549 cells to radiation based on reduced clonogenic survival; viable cell counting indicated that the combination treatment resulted in apparently irreversible growth arrest with no significant recovery. β-galactosidase staining, C12FDG measurement by flow cytometry, and p21 expression levels were indicative of senescence by Days 3 and 5 while acridine orange staining and p62 degradation demonstrated the induction of autophagy. Pharmacological suppression of autophagy induced by 1,25D3 + IR resulted in a temporary delay of senescence. Conclusions: For many years, cancer therapy has relied on cytotoxic treatment strategies for the eradication of tumors and overall patient survival. These therapies are associated with severe and often harmful side effects. Recent studies have suggested that therapy-induced senescence could provide an alternative strategy for improving cancer therapy. Our studies demonstrate that treatment with 1,25D3 has the capacity to sensitize A549 cells to radiation treatment by the induction of senescence that is preceded by autophagy. This model could represent a novel, pro-senescence therapy treatment to promote disease intervention and therapeutic gain for NSCLC. 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 1465. doi:1538-7445.AM2012-1465
Abstract 3018A: A novel type of oncogene SWAP-70.
Authors: Chung-Li Shu, Jing-Yang Lai, LIang-Cheng Su, Chih-Pin Chuu, Yasuhisa Fukui
Journal: Cancer Research (2013)

Abstract SWAP-70 is a protein that has been suggested to be involved in regulation of actin rearrangement. Having found that an artificial mutant of SWAP-70 can transform mouse embryo fibroblasts, we searched for mutations of the SWAP-70 gene, finding listings for several on the Web at www.sanger.ac.uk/genetics/CGP/cosmic/, including three mutations in ovarian cancers. (The number of such mutations has now reached seven.) We made expression vectors for the mutant SWAP-70 proteins and introduced into NIH3T3 cells. The cells expressing the mutant SWAP-70 exhibited faster growth than the parental or wild type SWAP-70-expressing cells. That these cells grew in soft agar suggests they may be malignant tumor cell lines. They were sensitive to nutrient starvation, supporting the idea that they are transformed cells. However, they failed to pile up and showed contact inhibition, unlike usual transformed cells. Upon expression of human SWAP-70 genes, MEK was activated. This activation appeared to contribute to the saturation density of the cells. Because SWAP-70 has been shown to be the last protein to receive signals from cytokines, it is likely that there is a feedback signaling pathway and that disorder of this signaling pathway can transform the cells. Citation Format: Chung-Li Shu, Jing-Yang Lai, LIang-Cheng Su, Chih-Pin Chuu, Yasuhisa Fukui. A novel type of oncogene SWAP-70. [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 3018A. doi:10.1158/1538-7445.AM2013-3018A
Abstract 1129: FLCN-putative tumor suppressor
Authors: Laurence Seabra, Michael Nahorski, Anne Rienmann, Xiaohong Lu, Derek Lim, Eamonn Maher
Journal: Cancer Research (2010)

Abstract Birt-Hogg-Dubé (BHD) is an autosomal dominantly inherited genodermatosis associated with the development of renal neoplasia, spontaneous pneumothorax and benign fibrofolliculomas. The BHD gene has been maps to chromosome 17p11.2 and encodes a protein called folliculin (FLCN). Although familial forms of renal cell carcinoma account for only about 3% of all cases, the elucidation of the molecular mechanisms of familial RCC syndromes has provided seminal insights into the pathogenesis of sporadic RCC. This is exemplified by the role of VHL tumor suppressor gene (TSG) inactivation in sporadic clear cell RCC. The FLCN TSG product has been linked to the mTOR/AMPK signaling pathways but the function of folliculin is much less well characterised than for other renal TSGs such as VHL. Among the multiple functions that have been associated with the VHL TSG product is a role in the regulation of apoptotic cell death. We have investigated whether folliculin also has a role in apoptosis. Comparison of isogenic FLCN null and replete cell lines demonstrated increased cell death in the latter. Flow cytometry revealed a 30 % shift in apoptotic index as determined by Annexin V vs PI staining which was demonstrated by a shift in the cell population towards an early apoptotic state. Expression of apoptosis-related proteins was investigated in FLCN null and replete cell lines using proteome array profiler. This demonstrated increased expression of SMAC, claspin HTRA2 and XIAP in FLCN replete cells. Further investigations to determine the precise role of folliculin in the regulation of apoptosis and the relationship between FLCN-induced apoptosis and p53 status are in progress. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 1129.
Abstract 3123: The Notch pathway inhibits TGF-β signaling in breast cancer through HEYL-mediated crosstalk.
Authors: Han Liangfeng, Adam Diehl, Nguyen K. Nguyen, Preethi Korangath, Teo Weiwen, Zhe Zhang, Scott Kominsky, Pedram Argani, Goran Landberg, Saraswati V. Sukumar
Journal: Cancer Research (2013)

Abstract Acquired resistance to Transforming growth factor-β (TGF-β) is a key step in the early stages of tumorigenesis. Mutations of TGF-β signaling components, often found in other cancers, are rare in breast cancer, and little is known about the development of this resistance in breast cancer. On the other hand, activation of Notch pathway is known to play a substantial role in promoting breast cancer development. We hypothesized that crosstalk between these two pathways occurs through HEYL, a basic helix-loop-helix (bHLH) transcription factor, and a known direct target of Notch. We found that HEYL is overexpressed in 40% of breast cancers. Expression of Notch increased HEYL expression while knockdown of RBP-J, a critical mediator of Notch, reduced HEYL expression in HS578T and MDAMB-231 breast cancer cells. Taking into account the contradictory biological effects of Notch and TGF-β signaling, we sought to examine whether HEYL inhibits the TGF-β pathway. TGF-β treatment or Smad3 overexpression significantly increased the luciferase activity of the TGF-β responsive reporter vector, p3TP-Luc, and the P15 (CDKN2B) gene promoter, but this transactivation was strongly inhibited by HEYL. Bimolecular fluorescence complementation assays confirmed the interaction between Smad 3 and HEYL; immunoprecipitation assays with deletion constructs showed that the Basic domain of HEYL interacts with the MH2 domain of Smad3, and that their interaction is necessary for HEYL to inhibit TGF-β signaling. In addition, using a tet-off inducible breast cancer cell model, HEYL was shown to transcriptionally up-regulate many genes that drive metastasis and tumor angiogenesis. Supporting this concept, HEYL/HER2 double transgenic mice showed nearly 50% increase in lung metastasis (20% vs 46%) compared to HER2/neu mice. Similarly, lung colonization occurred in 100% of mice injected with MDAMB231 while HEYL-shRNAs reduced incidence to 50%. Therefore, HEYL promotes breast cancer growth and metastasis in Smad-dependent and Smad-independent mechanisms. Citation Format: Han Liangfeng, Adam Diehl, Nguyen K. Nguyen, Preethi Korangath, Teo Weiwen, Zhe Zhang, Scott Kominsky, Pedram Argani, Goran Landberg, Saraswati V. Sukumar. The Notch pathway inhibits TGF-β signaling in breast cancer through HEYL-mediated crosstalk. [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 3123. doi:10.1158/1538-7445.AM2013-3123
Abstract 264: ENC1, a BTB/Kelch protein, links DNA-damage signals to apoptosis by ubiquitination of retinoblastoma protein
Authors: Rong Yu, Quan Ma
Journal: Cancer Research (2012)

Abstract ENC1 (ectodermal neuronal cortex 1) is a BTB/Kelch domain-containing protein, whose gene was originally identified in a p53-overexpressing cell line, and was later found to show abnormal expression in various tumor tissues. Here, we report that ENC1 is a new regulator that links DNA-damage signals to apoptosis. ENC1 is induced in different cancer cells by DNA-damage signals. The induced ENC1 protein then interacted with cullin-3 and retinoblastoma protein (Rb), forming an E3 ubiquitin ligase complex and ubiquitinating Rb protein. Upon ubiquitination, Rb protein failed to interact with E2F, allowing for transcriptional activation of E2F-dependent genes. Inhibition of ENC1 by RNA interference or by a dominant-negative mutant attenuated Rb ubiquitination, E2F-depedent gene activation, as well as apoptosis induced by DNA-damage signals. However, epitopic overexpression of ENC1 gene activated E2F-dependent genes, but failed to trigger apoptosis. Deletion and mutation analysis shows that a conserved motif located within Kelch domain at the C-terminus is essential for regulation of Rb function and apoptosis in response to DNA-damage signals. 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 264. doi:1538-7445.AM2012-264