tbuckley/cabot-search huggingface dataset:
Predictors of antiretroviral therapy failure in an urban HIV/AIDS clinic in Addis Ababa, Ethiopia
Authors: Katherine Niemeyer, Akilah King, Sophie Mengistu, Nils Hennig
Journal: The Lancet Global Health (2016)

Background With the federal scale-up of antiretroviral therapy (ART) in Ethiopia, survival and quality of life for people with HIV/AIDS has increased. However, some patients do not respond to ART. Failure to suppress viral replication leads to increased morbidity and mortality, making early diagnosis of treatment failure imperative for the reduction of negative outcomes for patients. In this quality improvement project, we aimed to find predictors of treatment failure that can be used, with clinical and immunological monitoring, to guide diagnosis of first-line ART failure.
Multiple lymphomatous polyposis due to blastoid variant of mantle cell lymphoma diagnosed by computed tomography colonography and colonoscopy
Authors: Eduardo Rodrigues-Pinto, Armando Ribeiro, Elsa Fonseca, Guilherme Macedo
Journal: Endoscopy (2014)

An 88-year-old man with a past medical history of atrial flutter and congestive heart failure presented with rectal bleeding. Owing to his reluctance to undergo colonoscopy, he instead underwent computed tomography colonography, which showed one lesion in the splenic flexure and one lesion in the distal sigmoid colon, suggestive of colonic neoplasms ([Fig. 1]). The patient later did undergo a colonoscopy, which showed multiple yellowish, polypoid lesions dispersed throughout the colon ([Fig. 2 a – c]), some with erosions ([Fig. 2 d]). Several biopsies were taken from different segments of the colon.
Abstract 125: The DNp73 isoform provides novel insights into the regulation of p53 by BRCA1 to favor cell survival over cell death
Authors: Kimberly A. Scata, Wafik S. El-Deiry
Journal: Cancer Research (2010)

Abstract BRCA1, the first breast cancer susceptibility gene to be identified, remains an enigma. Many roles have been ascribed to BRCA1 including DNA repair, cell cycle checkpoint activation, transcriptional regulation and chromatin remodeling. We have previously established that BRCA1 overexpression induces the stabilization of p53 without activating pro-apoptotic targets of p53, and that BRCA1 can protect cells from DNA damage-induced p53-dependent cell death. This seems to be specific to pro-apoptotic targets because p53 is still able to activate target genes involved in cell cycle arrest or DNA repair. In our efforts to understand this phenomenon, we have found that BRCA1 induces many of the same post-translational modifications that DNA damage induces including key phosphorylations and the acetylation of lysine 120 of p53, known to be important for apoptosis. Moreover, BRCA1-stabilized p53 localizes to the promoter regions of pro-apoptotic target genes whose expression is not upregulated. We hypothesized that p53 family members p63 and/or p73 may regulate the selectivity of p53 action in response to BRCA1. Unexpectedly, we found that BRCA1 upregulates DNp73 expression, an isoform of the p53 family member p73 lacking the transactivation domain, that has been previously implicated in cell survival. This observation has important implications for understanding the selectivity of p53-dependent transcription as well as the tumor suppressive action of BRCA1 that favors DNA repair over cell death. Our ongoing studies are evaluating the effects of the BRCA1-induced DNp73 isoform on interactions between p53 and p53 family members that regulate the genes involved in cell fate. These findings unravel a novel mechanism by which the selectivity of p53-dependent gene expression is regulated BRCA1 and further unravels the complex nature of these p53 and BRCA1 tumor suppressor pathways. 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 125.
1171 MICRORNA EXPRESSION PROFILING IN PERIPHERAL BLOOD MONONUCLEAR CELLS IDENTIFIES TWO MIRNAS ASSOCIATED WITH TREATMENT RESPONSE TO PEGINTERFERON-RIBAVIRIN IN CHRONIC HEPATITIS C VIRUS PATIENTS
Authors: M.-L. Yu, E. Hsi, C.-F. Huang, C.-Y. Dai, S.-H.H. Juo, J.-F. Huang, W.-L. Chuang
Journal: Journal of Hepatology (2012)
SAT0119 Effect of Abatacept on Bone Homeostasis and Osteopontin in Rheumatoid Arthritis
Authors: M. Kitano, S. Kitano, M. Ishizu, T. Furukawa, T. Yoshikawa, K. Fujita, Y. Katashima, C. Sato, A. Saito, A. Nishioka, M. Sekiguchi, N. Azuma, N. Hashimoto, S. Tsunoda, K. Matsui, T. Iwasaki, H. Sano
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Abatacept (CTLA4-Ig) is a new therapeutic agent used for rheumatoid arthritis (RA). Recently, it is reported that CTLA-4 directly inhibits osteoclast formation. On the other hand, Osteopontin (OPN) is produced by activated T lymphocytes and has been recognized as one of the key molecules for osteoclastic bone-resorption in RA. However, the effect of abatacept on bone homeostasis and OPN production in RA is poorly understood. In this study, we investigated the effects of abatacept on biochemical markers of bone, serum soluble receptor activator of NF-kappa B ligand (sRANKL), osteoprotegerin (OPG), and plasma osteopontin (OPN) in patients with RA. <h3>Objectives</h3> To demonstrate the effect of abatacept on bone homeostasis in RA. <h3>Methods</h3> 24 patients with RA (19 females, 5 males; age 59.8±14.7 years; disease duration 6.1±8.0 years; stage 2.0±1.2; class 1.8±0.6; DAS28-CRP 4.6±1.4; SDAI 26.7±12.8; use of MTX 83%; average dose of MTX 5.9±3.3mg/week; use of PSL 71%; average dose of PSL 3.9±3.2mg/day) were started on treatment with abatacept for 24 weeks. All patients were biologics naïve. In addition, circulating levels of type I collagen cross-linked N-telopeptides (NTx), osteocalcin, sRANKL, OPG, and plasma OPNwere examined by ELISA at baseline and after 12 and 24 weeks. <h3>Results</h3> After 24 weeks of abatacepttreatment, DAS28-CRP and SDAI decreased significantly from the baseline (4.6±1.4 vs 2.5±0.9; p&lt;0.01, 26.7±12.8 vs 8.6±6.0; p&lt;0.01, respectively), so that 14 patients achieved DAS28-CRP remission. After 12 weeks, average of NTx levels decreased significantly from the baseline (16.27±5.81 vs 14.23±3.48 nmol BCE/l; p&lt;0.01). After 24 weeks, average of osteocalcin levels increased significantly (5.80±3.02vs 6.45±2.61 ng/ml; p&lt;0.05) and average of OPN levels decreased significantly from the baseline (101.57±57.40 vs 71.76±29.49 pg/ml; p&lt;0.01). Average of RANKL levels tended to decrease from the baseline ((0.22±0.39 vs 0.12±0.20 pmol/l; p=0.06), whereas average of OPG levels did not change significantly from the baseline (4.67±1.96 vs 4.90±2.44 pmol/L; p=0.17). <h3>Conclusions</h3> These findings suggest that abatacept improves systemic bone metabolism in patient with RA through the increase of bone formation markers and the decrease of bone degradation markers. We consider that these mechanism result from the regulation of OPN and RANKL expression in activated T lymphocytes. Consequently, abatacept may control osteoclastic-bone destruction in RA via the suppression of RANKL induced-osteoclastogenesis and OPN induced-osteoclast attachment of bone surface. <h3>Disclosure of Interest</h3> None Declared
P598 ANGIOTENSIN CONVERTING ENZYME 2 (ACE2) GENE THERAPY USING A HIGH EFFICIENCY AND LIVER-SPECIFIC ADENO-ASSOCIATED VIRAL VECTOR ATTENUATES EXPERIMENTAL LIVER FIBROSIS IN MICE
Authors: K.Y. Mak, R. Chin, J. Torresi, S.C. Cunningham, I.E. Alexander, P.W. Angus, C.B. Herath
Journal: Journal of Hepatology (2014)
Abstract 2961: Spatiotemporal regulation of the SCF ubiquitin ligase component, Fbxo7
Authors: David E. Nelson, Heike Laman
Journal: Cancer Research (2011)

Abstract Fbxo7 is a member of the F-box family of proteins which direct the E3 ubiquitin ligase activity of the SCF holoenzyme. Apart from the SCF, Fbxo7 is also able to function as an assembly scaffold for Cyclin D/Cdk6 complexes, promoting cellular transformation. The expression of Fbxo7 in immortalised embryonic fibroblasts rendered them invasive and capable of anchorage independent growth and tumour formation in nude mice. Moreover, transformation was dependent on the presence of Cdk6. In recent experiments we showed that the over-expression of Fbxo7 in haematopoietic stem cells cooperated with p53 mutation to promote T cell lymphoma in adoptive transfer experiments conducted in mice, demonstrating it is a sensitive and causal agent in oncogenesis. In human cancers, Fbxo7 was found to be highly expressed in various tumours, including haematopoietic malignancies, as well as lung and colon carcinomas. Interestingly, in a number of these tumour samples, the subcellular distribution of Fbxo7 was altered, changed from predominantly cytoplasmic to nuclear, suggesting that the localization of Fbxo7 is critical to its function. We found that in proliferating cells, the localization of Fbxo7 was altered during the cell cycle phase: cytoplasmic during G1, and accumulating in the nucleus during S-G2. We have identified a functional NES motif embedded within the F-box domain of Fbxo7, the region which regulates its interaction with the SCF holoenzyme through binding to Skp1. Loss of the F-box domain it its entirety or targeted mutation of the NES renders the protein constitutively nuclear. We find also that binding of Fbxo7 to Skp1 prevents its interaction with Crm1, a component of the nuclear export machinery suggesting that association with the other SCF components directly promotes the nuclear accumulation of the protein. These findings suggest that during the latter part of the cell cycle SCF(Fbxo7) ubiquitin ligase activity is directed against a nuclear protein. A recent proteomics screen has now revealed new substrates for Fbxo7 within the nucleus which may help to decipher how the deregulation of the spatiotemporal regulation of Fbxo7 contributes to its role in cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2961. doi:10.1158/1538-7445.AM2011-2961
Intensified environmental surveillance supporting the response to wild poliovirus type 1 silent circulation in Israel, 2013
Authors: Y Manor, L M Shulman, E Kaliner, M Hindiyeh, D Ram, D Sofer, J Moran-Gilad, B Lev, I Grotto, R Gamzu, E Mendelson
Journal: Eurosurveillance (2014)

An emergency response was triggered by recovery of wild poliovirus type 1 (WPV1) of the South Asia (SOAS) lineage from sewage in southern Israel in April 2013 during routine environmental surveillance. Public health risk assessment necessitated intensification of environmental surveillance in order to facilitate countrywide monitoring of WPV1-SOAS circulation. This involved increasing sampling frequency and broadening the geographical area, for better coverage of the population at risk, as well as modifying sewage testing algorithms to accommodate a newly developed WPV1-SOAS-specific quantitative real-time RT-PCR assay for screening of RNA extracted directly from sewage concentrates, in addition to standard virus isolation. Intensified surveillance in 74 sites across Israel between 1 February and 31 August 2013 documented a sustained high viral load of WPV1-SOAS in sewage samples from six Bedouin settlements and two cities with Jewish and Arab populations in the South district. Lower viral loads and intermittent detection were documented in sampling sites representing 14 mixed communities in three of the five health districts in central and northern Israel. Environmental surveillance plays a fundamental role in routine monitoring of WPV circulation in polio-free countries. The rapid assay specific for the circulating strain facilitated implementation of intensified surveillance and informed the public health response and decision-making.
Endoscopic ultrasound-guided biliary drainage after failed ERCP: cumulative experience of 101 procedures at a single center
Authors: Laurent Poincloux, Olivier Rouquette, Emmanuel Buc, Jocelyn Privat, Denis Pezet, Michel Dapoigny, Gilles Bommelaer, Armando Abergel
Journal: Endoscopy (2015)

Endoscopic ultrasound (EUS)-guided biliary access is an alternative to percutaneous access after failed endoscopic retrograde cholangiopancreatography (ERCP). This report presents 7 years' cumulative experience of EUS-guided biliary drainage for obstructive jaundice in patients with failed ERCP.Between February 2006 and February 2013, 101 patients (malignant = 98, benign = 3) with previous failed ERCP underwent an EUS intra- or extrahepatic approach with transluminal stenting or an EUS-guided rendezvous procedure with transpapillary stent placement. A single endoscopist performed all procedures.A total of 71 patients underwent the intrahepatic approach (66 hepatogastrostomies and 5 EUS-guided rendezvous), and 30 underwent the extrahepatic approach (26 choledochoduodenostomies, 1 choledochojejunostomy, 1 choledochoantrostomy, and 2 EUS-guided cholangiographies). Technical and clinical success rates were 98.0 % and 92.1 %, respectively. There was no difference in efficacy between hepatogastrostomies and choledochoduodenostomies (94 % vs. 90 %; P = 0.69) or in major complications (10.6 % vs. 6.7 %; P = 1). Adverse events occurred in 12 patients (11.9 %): 10 in the hepatogastrostomy group (2 limited pneumoperitoneum, 1 hepatic hematoma, 5 bile leakage, 2 sepsis), and 2 in the choledochoduodenostomy group (1 arteriobiliary fistula and 1 sepsis). There were six procedure-related deaths, five among the first 50 patients and one among the last 51 patients. Hepatogastrostomy vs. choledochoduodenostomy, plastic vs. metal stenting, stent-in-stent vs. 1 stent, nasobiliary drain, or postoperative octreotide infusion were not prognostic of bile leakage.EUS-guided biliary drainage is an efficient technique, but is associated with significant morbidity that seems to decrease with the learning curve. It should be performed in tertiary care centers in selected patients. Prospective randomized studies are needed to compare EUS-guided biliary drainage with percutaneous transhepatic cholangiography drainage.
Abstract 2738: Early detection of colorectal cancer applying a combination of serum markers
Authors: Norbert Wild, Herbert Andres, Wolfgang Rollinger, Friedemann Krause, Peter Dilba, Michael Tacke, Johann Karl
Journal: Cancer Research (2010)

Abstract Background: Fecal occult blood testing (FOBT) is the recommended first line screening for the detection of colorectal cancer (CRC). To improve the detection of CRC we evaluated serum markers and combinations of serum markers as an alternative approach. Methods: Applying Lasso Regression, a specialized form of penalized logistic regression, we selected six markers for an evaluation in a collective of 857 patients including 301 CRC patients, 143 patients with adenoma, 266 healthy controls and 147 disease controls. For each marker and marker combination the performance was assessed. Results: We tested a total of 22 biomarkers for the detection of CRC from serum. Of these six markers were selected for a marker combination by Lasso Regression. Included were the well-known tumor markers CEA and CYFRA21-1 as well as novel markers or markers that are less routinely used for the detection of CRC: ferritin, osteopontin, anti-p53 and seprase. CEA showed the best sensitivity of all markers with 43.9 % at 95% specificity, followed by seprase (42.4%), CYFRA21-1 (35.5%), osteopontin (30.2%), ferritin (23.9%) and anti-p53 (20.0%). When these markers were combined a sensitivity of 72.3% was reached at a corresponding specificity of 95% and of 62.1% at 98% specificity. Focusing on more screening relevant stages, UICC stages 0-III, reduced the sensitivity slightly to 68.0% and 53.3%, respectively. In a sub-collective where matched stool samples were available (75 CRC cases and 234 controls) the sensitivity of the marker combination was comparable to fecal immunochemical testing (FIT) with 82.4% and 68.9% vs. 81.8% and 72.7% at 95% and 98% specificity, respectively. Conclusion: When six markers were combined to detect CRC from serum, the combination reached a performance that was comparable to FIT. This provides a novel tool for CRC screening to trigger a follow-up colonoscopy for a final diagnosis. 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 2738.
Abstract P5-02-02: Decreased Expression of Gremlin Correlates with Bone Metastasis and Poor Prognosis in Breast Cancer
Authors: L Ye, RE Mansel, WG. Jiang
Journal: Cancer Research (2010)

Abstract Background: Bone morphogenetic proteins belong to TGF-β superfamily, which are a group of pluripotent factors, widely involved in prenatal and postnatal development and homeostasis of various tissues and organs. BMPs and their signaling have been indicated in tumorigenesis and progression of certain solid tumors. Recent studies have demonstrated a profound role played by Noggin, a BMP antagonist in bone metastasis from breast cancer, and have indicated a sound therapeutic potential. The current study examined expression of Gremlin, a BMP antagonist which is poorly understood in breast cancer, t, and its relevance to pathological and clinical parameters. Methods: Breast cancer tissues (n=82) and normal background tissues (n=24) were collected immediately after surgery. The clinical follow-up was routinely performed after surgery. The median follow-up period was 120 months. The expression of Gremlin was examined in a breast cancer cohort using quantitative real time PCR and immunhistochemistry (IHC). Results: IHC revealed a pattern of cytoplamic staining of Gremlin in mammary epithelial cells in breast tissues. Gremlin staining tended to be decreased in breast cancer, but there was no significant difference in its transcripts levels compared with that of normal background tissues. Gremlin transcripts were lower in both moderately differentiated and poorly differentiated tumors compared with well differentiated tumors. The level of Gremlin transcripts in primary tumors was decreased in the patients with poor prognosis (13343±6001) including those patients had local recurrence, metastases and died of breast cancer, p=0.023 when compared with 146209±56574 of patients remained disease free. This decreasing expression was also seen in the patients with disease specific bone metastases, which was 18834±13159 and p=0.032 compared to that of patients being disease free. Conclusions: Taken together, decreasing level of Gremlin transcript in primary tumors of breast cancer correlates with bone metastasis and poor prognosis. Its implication in disease specific bone metastasis and therapeutic potential warrants further investigation. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-02-02.
Abstract 347: Inhibition of ERK1/2 can sensitize human malignant mesothelioma cells and tumors to doxorubicin
Authors: Arti Shukla, Jedd M. Hillegass, Maximilian B. MacPherson, Stacie L. Beuschel, Nicholas H. Heintz, Pamela M. Vacek, Harvey I. Pass, Michele Carbone, Joseph R. Testa, Brooke T. Mossman
Journal: Cancer Research (2010)

Abstract Malignant mesothelioma (MM) has a poor prognosis because of its resistance towards different drugs. Extracellular signal regulated kinase (ERK) family is known to have important roles in tumorigenesis and drug resistance. Here we show that Doxorubicin (Dox) treatment activates ERK1/2 in different MM lines. Activated ERK1/2 play a significant role in cell survival as inhibition of ERK1/2 by U0126 in the presence of Dox results in significantly enhanced cell killing. We show here using small molecule inhibitor and RNA silencing approaches that ERK1/2 inhibition sensitizes human MM cells to Dox treatment. ERK1/2 inhibition by U0126 significantly inhibited certain important drug resistance and proapoptotic genes in human MM cells as measured by PCR Array using human drug resistance and metabolism template. MM cell lines stably transfected with shERK1 or shERK2 exhibited significant increases in the accumulation of Dox and decreases in the cell viability when treated with Dox as compared to shCon line. Microarray analysis performed on stable shERK1 and shERK2 lines showed more than 2 fold inhibitions in selected ATP binding cassette genes, which may be responsible in part for increased Dox accumulation and sensitivity. Finally, subcutaneous injection of stable human MM lines inhibited for ERK1 or ERK2 into SCID mice showed that inhibition of ERK1/2 sensitizes in vivo tumors to Dox. These studies demonstrate a key role of ERK1/2 in MM tumor drug resistance. This work is supported by National Cancer Institute grant P01CA114047 and VCC/LCCRO grant. 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 347.
Abstract SY16-02: Embracing complexity: A drosophila approach to cancer therapeutics.
Authors: Ross L. Cagan
Journal: Cancer Research (2013)

Abstract Cancer's complexity is a key difficulty in identifying useful therapeutics. In place of simplifying the disease, I will describe our use of Drosophila to develop complex, multigenic cancer models that directly reflect current human tumor sequencing data. These include colorectal, pancreatic, and thyroid tumor models. Further, I will discuss our approach– in collaboration with Kevan Shokat's laboratory– that combines fly genetics with medicinal chemistry to develop novel drugs through "rational polypharmacology," emphasizing a balance of "targets" and "anti-targets" that are designed to optimize therapeutic index. Citation Format: Ross L. Cagan. Embracing complexity: A drosophila approach to cancer therapeutics. [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 SY16-02. doi:10.1158/1538-7445.AM2013-SY16-02