tbuckley/cabot-search huggingface dataset:
A exaustividade da notificação da malária nos Países Baixos entre 1995 e 2003 avaliada pelo método de captura-recaptura
Authors: S Klein, A Bosman
Journal: Eurosurveillance (2005)

Em 1999 nos Paises Baixos, devido a nova lei sobre doencas transmissiveis, a obrigacao de declarar a malaria foi transferida dos medicos aos laboratorios. Para estimar o impacto dessa mudanca, foi levado a cabo uma avialacao da exaustividade da notificacao da malaria nos Paises Baixos entre 1995 e 2003. Esta foi calculada em relacao aos dados dos laboratorios sentinela e das hospitalizacoes. O numero total de casos foi estimado com o metodo de captura-recaptura (CRM) para avaliar a exaustividade em relacao a esse valor. A exaustividade da notificacao para os dados sentinela foi de 18,2% (IC 95% de 15,7-20,7) em 1995-1998 e de 56,4 % (IC 95% de 47,0-65,8) para 2000-2003. Esta foi de 35,1% para o periodo 1995-2003 comparada com os dados de declaracao hospitalar. O numero estimado de casos de malaria entre 1995 e1998 foi de 3123 (IC 95% de 2796-3449) e de 5.043 (IC 95% de 4343-5742) entre 2000 e 2003. Em relacao a estes numeros a exaustividade da declaracao aumentou de 35,5% (IC 95% de 32,1-39,7) em 1995-1998 a 36,1 % (IC 95% de 31,7-41,9) para o periodo 2000-2003. Com o sistema de notificacao basado nos laboratorios, o numero absoluto de declaracoes de malaria aumentou de maneira significativa, embora a exaustividade tenha permanecido estavel em relacao aos dados de hospitalizacao. O aumento dos casos estimados de malaria pode ser artificial, pois os requisitos necessarios para o metodo de captura-recaptura nao foram respeitados durante todo o periodo do estudo.
Aumento en la incidencia de resistencia al trimetoprim y ciprofloxacino de la Salmonella typhimurium DT104 epidémica en Inglaterra y Gales
Authors: E J Threlfall, L. R. Ward, B Rowe
Journal: Eurosurveillance (1997)

Introduccion. Desde 1.990, cepas de Salmonella typhimurium lisotipo 104 (DT 104) con resistencia cromosomica a la ampicilina, cloranfenicol, estreptomicina, sulfonamidas y tetraciclinas (tipo R ACSSuT) (1) son cada vez mas frecuentes en la persona humana en Inglaterra y Gales (Figura 1). Desde 1.992, S. enteritidis fagotipo 4 representa la mayoria de los casos de salmonelosis humana (2). El 94% de los aislamientos enviados en 1.995 a los laboratorios de enteropatogenos 'Laboratory of Enteric Pathogens' (LEP, Laboratorio de Agentes Enteropatogenos) del 'Public Health Laboratory Service' (PHLS, Servicio de Laboratorios de Salud Publica), por los laboratorios de Inglaterra y Gales era multirresistente a cuatro o mas antibioticos.
Combination of nivolumab (nivo) + ipilimumab (ipi) in the treatment of patients (pts) with deficient DNA mismatch repair (dMMR)/high microsatellite instability (MSI-H) metastatic colorectal cancer (mCRC): CheckMate 142 Study
Authors: S. Lonardi, T. Andre, K.Y.M. Wong, M. Morse, R. McDermott, A. Hill, A. Hendlisz, H. Lenz, J. Leach, R.A. Moss, Z.A. Cao, J. Ledeine, S. Kopetz, M. Overman
Journal: Annals of Oncology (2017)
Safety and efficacy of early start of iron chelation therapy with deferiprone in young children newly diagnosed with transfusion‐dependent thalassemia: A randomized controlled trial
Authors: Mohsen Saleh Elalfy, Amira Adly, Hanem Awad, Mohamed Tarif Salam, Vasilios Berdoukas, Fernando Tricta
Journal: American Journal of Hematology (2017)

Abstract Iron overload is inevitable in patients who are transfusion dependent. In young children with transfusion‐dependent thalassemia (TDT), current practice is to delay the start of iron chelation therapy due to concerns over toxicities, which have been observed when deferoxamine was started too early. However, doing so may increase the risk of iron accumulation that will be manifested as toxicities later in life. This study investigated whether deferiprone, a chelator with a lower affinity for iron than deferoxamine, could postpone transfusional iron overload while maintaining a good safety profile. Recently diagnosed TDT infants ( N = 64 their age ranged from 10 to 18 (median 12) months, 54.7% males; receiving ≤6 transfusions; serum ferittin (SF) &gt;400 to &lt; 1000 ng/mL were randomized to “early start deferiprone” (.ES‐DFP) at a low dose (50 mg/kg/day) or to “delay chelation” (DC), and remained in the study until their serum ferritin (SF) level reached ≥1000 μg/L. 61 patients continued the study Levels of transferrin saturation (TSAT) and labile plasma iron (LPI) were measured as well. By approximately 6 months postrandomization, 100% of the subjects in DC group had achieved SF &gt; 1000 µg/L and TSAT &gt; 70% compared with none in the ES‐DFP group. LPI level &gt; 0.6 µM was observed in 97% vs. 40% of the DS and ES groups, respectively, ( P &lt; 0.001). The time to reach SF &gt; 1000 µg/L was delayed by 6 months in the ES‐DFP group ( P &lt; 0.001) without escalating DFP dose. No unexpected, serious, or severe adverse events were seen in the ES‐DFP group.
Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer
Authors: Hongzhe Li, Xinjing Wang, Chenlei Wen, Zhen Huo, Weishen Wang, Qian Zhan, Dongfeng Cheng, Hao Chen, Xiaxing Deng, Chenghong Peng, Baiyong Shen
Journal: Molecular Cancer (2017)

Pancreatic cancer, one of the top two most fatal cancers, is characterized by a desmoplastic reaction that creates a dense microenvironment, promoting hypoxia and inducing the epithelial-to-mesenchymal transition (EMT) to facilitate invasion and metastasis. Recent evidence indicates that the long noncoding RNA NORAD may be a potential oncogenic gene and that this lncRNA is significantly upregulated during hypoxia. However, the overall biological role and clinical significance of NORAD remains largely unknown. NORAD expression was measured in 33 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of NORAD on pancreatic cancer cells were studied by overexpression and knockdown in vitro. Insights into the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatics analyses and luciferase assays. In vivo, metastatic potential was identified using an orthotopic model of PDAC and quantified using bioluminescent signals. Alterations in RhoA expression and EMT levels were identified and verified by immunohistochemistry and Western blotting. NORAD is highly expressed in pancreatic cancer tissues and upregulated in hypoxic conditions. NORAD upregulation is correlated with shorter overall survival in pancreatic cancer patients. Furthermore, NORAD overexpression promoted the migration and invasion of pancreatic carcinoma cells, while NORAD depletion inhibited EMT and metastasis in vitro and in vivo. In particular, NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p, thereby promoting EMT. Elevated expression of NORAD in pancreatic cancer tissues is linked to poor prognosis and may confer a malignant phenotype upon tumor cells. NORAD may function as a ceRNA to regulate the expression of the small GTP binding protein RhoA through competition for hsa-miR-125a-3p. This finding may contribute to a better understanding of the role played by lncRNAs in hypoxia-induced EMT and provide a potential novel diagnostic and therapeutic target for pancreatic cancer.
Changements spectaculaires dans l'épidémiologie des lysotypes de Salmonella enterica sérotype Enteritidis en Europe occidentale de 1998 à 2003 - les résultats de la base de données internationale Enter-net sur les salmonelles
Authors: I. S.T. Fisher
Journal: Eurosurveillance (2004)

En Europe occidentale, Salmonella enterica serotype Enteritidis est le serotype de salmonelle le plus frequemment identifie par les laboratoires nationaux de reference d'Enter-net. Effectuer un lysotypage est donc primordial pour detecter et confirmer les epidemies et les tendances des infections. D'apres les donnees de la base de donnees Enter-net sur les salmonelles, un changement considerable est observe dans les lysotypes identifies en Europe entre 1998 et 2003. Alors qu'en 1998, le lysotype PT4 etait le lysotype le plus frequemment identifie chez l'homme (61,8%, 21 630 cas), en 2003, la proportion de PT4 est passee a 32,1% (8 794 cas), tandis que d'autres souches augmentaient en nombre absolu et en proportion. Cet article identifie les souches emergentes dont le role devient plus important en termes de sante publique.
Staphylococcus aureus Epicutaneous Exposure Drives Skin Inflammation via IL-36-Mediated T Cell Responses
Authors: Haiyun Liu, Nathan K. Archer, Carly A. Dillen, Yu Wang, Alyssa G. Ashbaugh, Roger V. Ortines, Tracy Kao, Steven K. Lee, Shuting S. Cai, Robert J. Miller, Mark C. Marchitto, Emily Zhang, Daniel P. Riggins, Roger D. Plaut, Scott Stibitz, Raif S. Geha, Lloyd S. Miller
Journal: Cell Host & Microbe (2017)
CMET-46. EXPRESSION OF HYDROGEN SULFIDE (H2S) PRODUCING ENZYMES IN METASTATIC BRAIN TUMORS
Authors: Mirna Lechpammer, Kiarash Shahlaie, Fady Girgis, Hilary Gonzales, John Bishop, Evgeny Nudler, David Zagzag
Journal: Neuro-Oncology (2017)

Cysteine metabolites, including hydrogen sulfide (H2S), are implicated in the growth and spread of invasive tumors. Previously our group reported increased cystathionine B-synthase (CBS, the brain’s main H2S producing enzyme) expression in astrocytomas with higher histopathological grade. In this study, we investigated the expression of CBS and other H2S producing enzymes [cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST)] in brain metastases of various solid tumor origins. We have retrospectively reviewed metastases from 62 patients, who underwent surgical resection or biopsy for newly diagnosed brain masses. Metastases originated from: lung (non-small cell lung cancer – NSCLC, n=21; neuroendocrine, n=5), breast (ductal invasive; n=10), kidney (n=14) and unknown primary tumors (n=12). Immunohistochemistry (IHC) for CBS, CSE and 3-MST expression performed on tissue microarrays was reviewed and semi-quantified in a blinded fashion. Moderate to high IHC expression was detected as follows: Lung = CBS: 62% (13/21) NSCLC, 80% (4/5) neuroendocrine; CSE: 33% (7/21) NSCLC, 40% (2/5) neuroendocrine; 3-MST: 19% (4/21) NSCLC, 0/5 neuroendocrine. Breast = CBS: 30% (3/10); CSE: 50% (5/10); 3-MST: 10% (1/10). Kidney = CBS: 57% (8/14), CSE: 14% (2/14), 3-MST: 43% (6/14). Unknown = CBS: 83% (10/12), CSE: 83% (10/12), 3-MST: 17% (2/12). Distinct expression patterns of the three H2S producing enzymes were observed in brain metastases depending on the primary tumor origin – with lung metastases having generally higher enzymes expressions than metastases originating from breast or kidney cancers. Especially intriguing observation is increased expression of CBS and CSE, along with presumptively higher H2S activity, in majority (83%) of poorly differentiated brain metastases of unknown primary tumor origin, supporting the importance of cysteine metabolites in cancer spread and aggressiveness. Our study suggests using cysteine metabolites for potential targeted treatment of brain metastases; a hypothesis that warrants investigation in larger, prospective, translational trials.
RTHP-18. LONG-TERM OUTCOME OF CRANIOSPINAL IRRADIATION FOR RECURRENT GERMINOMA
Authors: Masayuki Kanamori, Ryuta Saito, Yukihiko Sonoda, Toshihiro Kumabe, Teiji Tominaga
Journal: Neuro-Oncology (2017)

Whereas combined chemotherapy and radiation therapy to newly diagnosed germinoma achieve long-term tumor control, the optimal treatment recurrent germinoma remains unclear. To clarify long-term outcome of craniospinal irradiation (CSI) to recurrent germinoma. MATERIALS: Medical records of the cases with recurrent germinoma treated at Tohoku University Hospital after 1983 were reviewed for salvage therapy modalities, tumor control, and adverse effect. 26 of 145 cases with germinoma had 47 recurrent disease. Follow-up period was 12-287 months (median: 169 months) Initial recurrent sites were primary site in 4 and distant site in 22. 8 cases received salvage CSI, and 6 of 8 cases had no recurrence 5-151 months (median: 57 months) after salvage CSI. In contrast, 9 of 18 cases treated by salvage therapy other than CSI had recurrence within 36 months (median: 16 months), and 4 re-recurrent of 9 cases were controlled with CSI. 4 of 6 cases treated with salvage CSI at first recurrence had independent in daily life, whereas 4 cases treated with CSI after salvage therapy other than CSI was dependent in daily life due to psychic disorder or cognitive dysfunction. To avoid repeat salvage therapy, and subsequent decline in cognitive function and quality of life, CSI is recommended to recurrent germinoma, so far.
EXTH-34. COMBINED USE OF THE PAN-IDH MUTANT INHIBITOR AG-881 WITH RADIATION THERAPY SHOWS ADDED BENEFIT IN AN ORTHOTOPIC IDH1 MUTANT GLIOMA MODEL IN VIVO
Authors: Brandon Nicolay, Rohini Narayanaswamy, Michael D Amatangelo, Elia Aguado, Raj Nagaraja, Josh Murtie, Guowen Liu, Yuko Ishii
Journal: Neuro-Oncology (2017)

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 occur in >70% of diffuse low-grade gliomas (LGG). IDH1/2 mutations result in accumulation of the oncometabolite 2-hydroxyglutarate (2-HG), which facilitates tumorigenesis through DNA hypermethylation, increased repressive histone methylation, and inhibition of differentiation processes. Prior studies with an early tool compound, AGI-5198, which is active against mutant IDH1 (mIDH1) but not mutant IDH2 (mIDH2), suggest that inhibition of mIDH1 proteins can repress growth of mIDH1-driven gliomas. Furthermore, recent in vitro studies using AGI-5198 in mIDH1 glioma models have suggested that inhibition of mIDH1 proteins may be antagonistic to the LGG standard of care treatment of radiation + temozolomide (DNA alkylating agent). AG-881, a novel, potent, clinical stage inhibitor of both the mIDH1 and mIDH2 proteins was tested in subcutaneous and orthotopic mouse xenograft models of a human mIDH1-R132H grade III oligodendroglioma alone or in combination with either radiation or temozolomide. AG-881 treatment was well tolerated and the pharmacokinetic properties of AG-881 allowed for oral administration, which resulted in >98% inhibition of 2-HG production by mIDH1 tumors in the brain. We demonstrated that mIDH1 inhibition with AG-881 impedes glioma growth in vivo. The combination of AG-881 + radiation therapy produced a significantly greater effect on tumor growth inhibition when compared with each single-modality treatment alone. This combined-modality treatment benefit was observed both in mice given concomitant AG-881 + radiation therapy and mice treated sequentially with radiation therapy followed by AG-881 treatment. No antagonism with temozolomide or radiation therapy was observed in these in vivo models. Studies in preclinical models to further understand the distinct differences between results with AG-881 and AGI-5198 are ongoing. Taken together, these data support the further investigation of mIDH1 inhibition in combination with radiation in the clinic.
TMOD-14. ESTABLISHING A MOUSE MODEL OF FUNCTIONAL CONNECTIVITY DISRUPTION DUE TO GLIOMA GROWTH
Authors: Inema Orukari, Joshua Siegel, Adam Bauer, Joshua Shimony, Joshua Rubin, Joseph Culver
Journal: Neuro-Oncology (2017)

Gliomas can cause significant changes in normal brain function that lead to cognitive deficits. Functional connectivity (fc) disruptions are thought to contribute to these deficits. However, investigating the effects of glioma growth on fc in humans is complicated by heterogeneity in lesion size, type, and location across subjects. In this study, we evaluated the effects of tumor growth on fc over time in a controlled mouse model of glioma. We also explored changes in hemodynamic parameters as a potential confound of fc measurements. Glioma cells (5x104 U87) were stereotactically injected into the forepaw somatosensory cortex of adult nude mice (n=14). Fc was evaluated weekly with functional connectivity optical intrinsic signal imaging (fcOIS), in conjunction with bioluminescence imaging (BLI) to monitor tumor growth. We calculated fc between homotopic brain regions and spatial similarity of fc maps. Additionally, cerebral blood flow (CBF) and hemodynamic lags were assessed. As a comparison, hemodynamic lags were assessed in human glioma patients using resting functional connectivity MRI. Fc disruptions initiate near the lesion; and over a period of several weeks, remote regions become disrupted. Decrements in fc were found to strongly correlate with the BLI signal in each mouse and across all time points investigated indicating increased tumor size is associated with disrupted fc. CBF and hemodynamic lags were both increased locally near the tumor in but not remotely. Human glioma patients similarly exhibited hemodynamic lags in tumor and in peritumoral tissues. We were able to detect fc disruptions due to brain tumor growth with fcOIS. Local hemodynamic changes may explain the local changes seen in fc, but not the remote changes in fc. A better understanding of how fc disruption contributes to the development of cognitive deficits in glioma patients may lead to better patient risk stratification and improved cognitive outcomes.
PDTM-17. IDENTIFICATION OF HUMAN PEDIATRIC BRAIN TUMORS CELLS IN PATIENT DERIVED ORTHOTOPIC XENOGRAFT MOUSE MODELS BY USING SPECIES-SPECIFIC PTGER2 GENE qPCR
Authors: Frank Braun, Mari Kogiso, Lin Qi, Huiyuan Zhang, Yuchen Du, Holly Lindsay, Sibo Zhao, Sarah Injac, Xiao-Nan Li
Journal: Neuro-Oncology (2017)

Pediatric brain tumors continue to be among the most difficult to cure and are the leading cause of cancer-related deaths in children. Research investigating pediatric brain cancer is still impaired by the lack of cancer models. We established a large panel of PDOX models as well as several paired permanent cell lines using in vivo and in vitro culture techniques. However, an inherent risk of xenograft models is the contamination of isolates of human tumors with host cells. Therefor strategies to identify the human/mouse ratio are essential. In this study we investigated Prostaglandin Receptor EP2 (PTGER2) as a useful target to identifying mouse cell contamination in PDOX models. Species specific primers based on Alcoster et al., 2011 were used to detect PTGER2 in xenograft and cultured cells. RT-qPCR was carried out using a StepOnePlus™ RT-PCR System. Reaction mix contained SYBR Green master mix, respective primers and 5ng of total gDNA in a total reaction volume of 10μL. The qPCR conditions were as follows: 50°C-2min, 95°C-10min, 40 cycles of (95°C-15sec, 61°C-1min). Primers were additionally controlled by analysis of amplified products on a 1.2% agarose gel. FACS was used to isolate human cells according to anti-Human HLA-ABC Ab and mouse-specific Ab cocktail surface staining and subjected to qPCR. Various models of pediatric brain cancer established in our group were investigated for mouse cell contamination. Xenograft as well as cultured cells were routinely analyzed. Our study confirms PTGER2 as a useful target for accurately estimate mouse cell in PDOX models. This enabled us to improve detection and characterization of HLA-ABC/mouse-cocktail double negative population as seen in FACS. In conclusion we have successfully implemented an reliable qRT-PCR approach to determine the human/mouse cell ration in any mixed PDOX cell population.
ACTR-67. PLASMA AND TUMOR PHARMACOKINETICS OF RIBOCICLIB IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: An-Chi Tien, Xun Bao, Alanna DeRogatis, Lindsay Higginbotham, Norissa Honea, Shwetal Mehta, Jing Li, Nader Sanai
Journal: Neuro-Oncology (2017)

CDK4/6-dependent cell-cycle regulation is disrupted in 78% of glioblastoma (GBM) patients and novel CDK4/6 inhibitors have shown anti-tumor activity in animal models. To explore the utility of ribociclib, a selective CDK4/6-inhibitor, in treating recurrent GBM patients, we conducted a phase 0/II clinical trial (NCT02933736) to examine plasma and tumor pharmacokinetics (PK) and pharmacodynamics (PD). Recurrent GBM patients enrolled in the phase 0 component were treated with daily oral ribociclib (900 mg) for 5 days prior to planned resection of their tumor. Patient selection was based on intact Rb expression and CDKN2A deletion or CDK4/6 amplification. Plasma, tumor, and CSF samples were collected at predefined time points, and drug concentrations in these samples were determined by validated LC-MS/MS methods. PD effects, including RB phosphorylation and FoxM1 expression, were compared to matched archival tissue. Patients with positive PK and PD outcomes were enrolled into the phase II component to evaluate clinical efficacy with a primary endpoint of progression-free survival. To date, 10 recurrent GBM patients have been screened and 5 patients enrolled into the phase 0 component, each undergoing surgery 2–4 hours after their final dose. No drug-related adverse events have been observed. Ribociclib showed better penetration into contrast-enhancing tumor regions than non-enhancing regions, with median tumor concentrations of 48.4 vs. 12.7 nmol/g, respectively, and median tumor-to-plasma partition ratios of 10.2 and 3.5, respectively. Ribociclib CSF concentrations (potentially pharmacologically-active, unbound drug) ranged from 0.32 – 0.68 nmol/mL (median, 0.58 nmol/mL), exceeding the in vitro IC50 for inhibition of CDK4/6 (<0.04 nmol/mL). 60% of phase 0 patients exhibited PD effects and were enrolled into the phase II component. Preliminary PK data suggests ribociclib achieves pharmacologically-active, and potentially therapeutic, concentrations in human GBM. Further studies to validate drug tumor penetration, tumor pharmacodynamic effects, and clinical efficacy are underway.
Safety in treatment of hepatocellular carcinoma with immune checkpoint inhibitors as compared to melanoma and non-small cell lung cancer
Authors: Zachary J. Brown, Bernd Heinrich, Seth M. Steinberg, Su Jong Yu, Tim F. Greten
Journal: Journal for ImmunoTherapy of Cancer (2017)

Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity.A literature review was performed for clinical trials that have been completed with single agent immune checkpoint inhibitors for patients with HCC, melanoma, and NSCLC. Gastrointestinal related adverse events including elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea were analyzed as well as those patients who were taken off therapy secondary to drug related toxicity and patients who died as a result of therapy.We found that although patients with HCC treated with immune checkpoint inhibitors have a substantial increase in AST/ALT as compared to patients with melanoma and NSCLC, this does not cause the patients to come off therapy or cause death secondary to drug toxicity.We propose immune checkpoint inhibitors are safe to pursue in the treatment of HCC.