tbuckley/cabot-search huggingface dataset:
Abstract 1984: Activated BMP signalling modulates multicellular spheroid formation and reattachment of ascites-derived human epithelial ovarian cancer cells in an in vitro model of metastasis
Authors: Teresa M. Peart, Monique Bertrand, Michel Prefontaine, Akira Sugimoto, Gabriel DiMattia, Trevor Shepherd
Journal: Cancer Research (2011)

Abstract Epithelial ovarian cancer (EOC) comprises close to 90% of ovarian tumours, and over 75% of cases are not discovered until advanced metastatic stages. Therefore, there remains a critical need to identify the mechanisms controlling late-stage spread of disease and develop more effective treatment regimes. EOC cells have the ability to form multicellular aggregates in malignant ascites which dramatically alters cell signalling, survival, and metastatic potential. Primary human EOC cells derived from patient ascites secrete and are responsive to bone morphogenetic proteins (e.g. BMP2 and BMP4). BMPs can function in an autocrine fashion to enhance the malignant characteristics displayed by EOC cells in adherent monolayer culture. Herein, we demonstrate that EOC cells with enhanced BMP signalling form smaller, more loosely-aggregated spheroids than control cells when grown in suspension culture. Upon reattachment to standard tissue culture plastic, EOC spheroids readily attach and cells disperse from the attached spheroid; EOC spheroids with enhanced BMP signalling have an increased cell dispersion rate when compared with controls. Activated BMP signalling in EOC spheroids induces Smad1/5/8 phosphorylation, increases ID1 and ID3 proto-oncogene expression, and promotes epithelial-mesenchymal transition as evidenced by increased Snail and Slug and reduced E-cadherin markers. To identify additional target genes mediating the phenotypic changes in EOC spheroids due to activated BMP signalling, we performed genome-wide expression analyses using Affymetrix arrays. From this study, 102 genes were significantly upregulated and 52 downregulated in primary human EOC cells and spheroids with enhanced BMP signalling. A number of these genes have been previously identified as BMP targets or members of the BMP signalling pathway, several of which are involved in negative feedback regulation (e.g. noggin, Smad6 and Smad7), as well as several genes encoding proteins associated with cellular adhesion. In addition, using the online Connectivity Map resource (www.broadinstitute.org/cmap), we revealed that the PI3K-Akt-mTOR pathway may be impacted by an activated BMP pathway in EOC cells. Indeed, BMP signalling induces phosphorylation of Akt in both adherent primary human EOC cells and multicellular spheroids. Thus, we are currently investigating whether the PI3K-Akt pathway and the targets identified by microarray analysis are required for the BMP signalling effects on EOC spheroid formation and reattachment. 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 1984. doi:10.1158/1538-7445.AM2011-1984
A Comparison of Plasma Vasopressin Measurements with a Standard Indirect Test in the Differential Diagnosis of Polyuria
Authors: Robert L. Zerbe, Gary L. Robertson
Journal: New England Journal of Medicine (1981)

The diagnoses provided by a standard indirect test of vasopressin function were compared with those obtained by radioimmunoassay of plasma vasopressin in 24 patients with nonglucosuric polyuria. All seven cases of severe neurogenic diabetes insipidus diagnosed by the indirect tests were confirmed by the vasopressin assay. However, two of six patients with partial neurogenic diabetes insipidus by indirect criteria had normal vasopressin secretion by the direct assay; one was found to have primary polydipsia, and the other nephrogenic diabetes insipidus. Moreover, three of 10 patients diagnosed as having primary polydipsia by the indirect test had clear evidence of partial vasopressin deficiency by the direct assay. The inability of the indirect test to distinguish accurately between partial neurogenic diabetes insipidus and primary polydipsia may be explained by increased sensitivity to low concentrations of vasopressin in the former disorder and a reduction of maximal concentrating ability in both. We conclude that the incorporation of a vasopressin assay improves accuracy in the differential diagnosis of polyuria.
A White Hand and a Red Hand — Erythromelalgia
Authors: Dan Lipsker
Journal: New England Journal of Medicine (2010)

A 14-year-old girl presented for evaluation of 3 years of intermittent episodes of acute pain in the hands and feet. She had no other medical history. These episodes of pain were frequently triggered by physical exercise and bathing. During physical examination, movement of the patient's right hand triggered burning pain, and the hand became acutely erythematous. Immersion of the right hand in warm water triggered the same kind of pain and erythema. The patient's presentation was typical of erythromelalgia, in which an increase in temperature triggers attacks of acute pain and red, swollen hands and feet. In some patients, pain . . .
Abstract 5596: Linkage between the lipogenic pathway and the progression of breast carcinomas.
Authors: Anatilde M. Gonzalez-Guerrico, Cheol Park-Hong, Celina Kleer, Ingrid Espinoza, Ruth Lupu
Journal: Cancer Research (2013)

Abstract Fatty acid synthase (FASN) is a lipogenic enzyme responsible for the novo synthesis of fatty acids (FAs) from acetyl-CoA and malonyl-CoA in a NADPH dependent manner in cells. FAs are essential constituents of all biological membranes lipids and are important substrates for energy metabolism. While normal cells (except liver and adiposities) express low levels of FASN and have low to undetectable levels of FASN enzymatic activity, FASN expression and activity is observed in a vast majority of human cancers. Whether the increase in FASN is merely a consequence of disease progression or it is a “metabolic oncogene” that drives disease progression remains unclear. Here, we undoubtedly demonstrated that knockdown FASN results in inhibition of tumor formation and angiogenesis in athymic nude mice. Moreover, the histopathological features of the FASN knockdown remaining tissue in vivo appear globular, well differentiated with low nuclear grade compared to the control tumors, which appear invasive, undifferentiated, and of high nuclear grade. When tissues where stained for Ki-67, Vimentin and E-Cadherin the classical mesenchymal to epithelial transition (MET) was observed in the tissue derived from FASN knockdown tumors. Our studies establish a possible role for FASN as a “metabolic oncogene” in breast cancer. Given the data presented here, we propose that FASN is a perfect marker to develop personalized targeted therapy. Citation Format: Anatilde M. Gonzalez-Guerrico, Cheol Park-Hong, Celina Kleer, Ingrid Espinoza, Ruth Lupu. Linkage between the lipogenic pathway and the progression of breast carcinomas. [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 5596. doi:10.1158/1538-7445.AM2013-5596
Risk factors and dynamics of household transmission of respiratory syncytial virus and other respiratory viruses in rural Nepal
Authors: Emily M Scott, Laveta Stewart, Joanne Katz, James Tielsch, Jane Kuypers, Subarna K Khatry, Steven C LeClerq, Laxman Shrestha, Mark Steinhoff, Janet A Englund, Helen Y Chu
Journal: The Lancet Global Health (2016)

Background Pneumonia is the leading cause of child mortality worldwide and respiratory viruses are an important cause of childhood pneumonia. However, household transmission of respiratory viruses is not well described in resource-limited settings and more information might guide preventative efforts by identifying individuals at risk of transmission. We aimed to characterise the transmission of respiratory viruses within households and identify risk factors for household transmission.
Epidemic Mycoplasma Pneumonia
Authors: Bruce L. Evatt, Walter R. Dowdle, McClaren Johnson, Clark W. Heath
Journal: New England Journal of Medicine (1971)

Abstract Twenty-six of 55 members and pledges of a college fraternity became infected with Mycoplasma pneumoniae over a three-week period in the fall of 1968. The epidemic curve suggested a common source of exposure. The only period in which members and pledges shared a common environment before the outbreak was on a single day when all were present at a catered banquet for pledge initiation ceremonies. The precise source and means of infection could not be identified.
Autogenous Humoral Immunity to Baboon Xenotropic Endogenous Type C Virus 2
Authors: O. S. Weislow, S. Schneider, R. L. Heberling, S. S. Kalter, A. Hellman
Journal: JNCI Journal of the National Cancer Institute (1976)

A radioimmune precipitation assay was used to evaluate the humoral immune response of baboons (Papio cynocephalus) to their endogenous, xenotropic, type C (M7) virus. Using 125I or [3H]leucine-labeled intact virus preparation, we demonstrated that baboons possess naturally occurring virus-binding antibodies to this virus. Antibody appeared directed against envelope and not internal viral proteins. Immunoglobulins responsible for virus-binding were predominant in the IgG and IgA serum fractions, whereas IgM participated to a minor degree. The biologic activities of these immunoglobulins were investigated by means of a focus reduction assay for virus neutralization with a murine sarcoma virus (M7) pseudotype. We determined that, despite the presence of considerable virus binding, none of the normal baboon sera tested possessed neutralizing activity for M7 virus.
P1175 CEPEGINTERFERON-ALFA-2b IN COMBINATION WITH RIBAVIRIN IN TREATMENT-NAIVE PATIENTS WITH CHRONIC HEPATITIS C
Authors: O. Znoyko, E. Klimova, S. Maximov, S. Kizhlo, N. Petrochenkova, F. Nagimova, Y. Linkova, R. Ivanov, T. Chernovskaya
Journal: Journal of Hepatology (2014)
p16/MTS1/INK4A gene is frequently inactivated by hypermethylation in childhood acute lymphoblastic leukemia with 11q23 translocation
Authors: M Nakamura, K Sugita, T Inukai, K Goi, K Iijima, T Tezuka, S Kojika, K Shiraishi, N Miyamoto, N Karakida, K Kagami, T O-Koyama, T Mori, S Nakazawa
Journal: Leukemia (1999)
Urokinase Therapy in Clinical Pulmonary Embolism
Authors: Arthur A. Sasahara, Joel E. Cannilla, John S. Belko, Robert L. Morse, Allan J. Criss, Maureen Smith, Robert G. Simpson
Journal: New England Journal of Medicine (1967)

DESPITE significant advances in the early diagnosis of pulmonary embolic disease, little new has been added to therapy. Medical treatment, however, has improved through earlier and more frequent use of heparin or orally administered anticoagulants.1 Indications for use and route of administration of heparin, the extent of prophylaxis and the role of the anticoagulants in therapy of pulmonary embolic disease, however, still lack unanimous agreement.2 Although anticoagulant therapy has been effective in reducing thromboembolic episodes,3 no direct effect on the thromboembolus itself has been identified. In the immediate past several thrombolytic agents have yielded disappointing results. The reasons for failure . . .
Abstract 1472: MRP4 and PGT, members of the COX-2 pathway, may contribute to breast cancer progression
Authors: Tyler Kochel, Namita Kundu, Xinrong Ma, Jocelyn Reader, Angela Brodie, Amy M. Fulton
Journal: Cancer Research (2011)

Abstract Prostaglandin E2 (PGE2) is the major product of the cyclooxygenase 2 (COX-2) enzyme. PGE2 is a substrate of multiple drug resistance-associated protein 4 (MRP4) which exports it from the cell. PGE2 can then signal through any of its four GPCR-family receptors EP1-4. Each receptor is connected to a different cell function including adenylate cyclase activation, calcium flux, and inositol trisphosphate mobilization. Alternatively, extracellular PGE2 can be imported through prostaglandin transporter (PGT) and inactivated by 15-hydroxy prostaglandin dehydrogenase (15-PGDH). PGE2 plays a role in tumor progression as evidenced by the anti-tumor activity of COX-2 inhibitors. Adverse effects of these inhibitors have forced a search to identify other potential therapeutic targets in the COX-2 pathway (such as the receptors, transporters, and associated metabolic enzymes of PGE2). We hypothesize that disregulation of the COX-2 pathway can lead to increased metastatic potential in breast cancer. High extracellular PGE2 in the tumor microenvironment can stem from high COX-2 expression or elevated eicosanoid export activity. Continued prostaglandin signaling is thought to occur due to the interplay between increased expression of the exporting protein (MRP4) shuttling PGE2 into the pericellular space and decreased expression of the importing protein (PGT) removing PGE2 from the pericellular space. Higher concentrations of PGE2 in the pericellular space allow for increased signaling through PGE2 receptors EP1-4. Using a panel of breast cancer cell lines, we demonstrate that highly metastatic tumor cells can express low levels of COX-2, but still actively signal through PGE2 receptors. MRP4 mRNA and protein expression is increased in tumor cell lines with high metastatic potential while expression of PGT mRNA and protein is decreased in these cells when compared to cells with lower metastatic potential. This should lead to higher concentrations of extracellular PGE2 in the tumor microenvironment. Additionally, we have examined MCF7 cells stably transfected with aromatase and an anastrozole-resistant derivative of this cell line for expression of COX-2, EP4, EP1, MRP4 and PGT. At the mRNA level, COX-2, EP1, MRP4 and PGT decrease in the aromatase inhibitor-resistant cells. EP4 mRNA levels increase in the resistant cells. Examining the relative expression levels of all key members in the COX-2 pathway as they relate to tumor progression could highlight new therapeutic targets under this classification of breast 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 1472. doi:10.1158/1538-7445.AM2011-1472
Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer
Authors: Peter G. Rose, Brian N. Bundy, Edwin B. Watkins, J. Tate Thigpen, Gunther Deppe, Mitchell A. Maiman, Daniel L. Clarke-Pearson, Sam Insalaco
Journal: New England Journal of Medicine (1999)

On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens — cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone — in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 μmol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3).
PMO-099 A comparative study of laparoscopic vs open distal pancreatectomy
Authors: D J Malde, Y Khaled, J Packer, N De Liguori, R Deshpande, D O'Reilly, D Sherlock, B J Ammori
Journal: Gut (2012)

<h3>Introduction</h3> The laparoscopic approach to distal pancreatectomy for benign and malignant diseases appears to offer advantages and is replacing open surgery in some centres. However, well-designed studies comparing laparoscopic distal pancreatectomy (LDP) to open distal pancreatectomy (ODP) are limited. We present a single-institution study comparing the outcomes of LDP to ODP. <h3>Methods</h3> The demographic details, clinical characteristics and outcomes of patients who underwent laparoscopic distal pancreatectomy were compared to those who had the surgery performed by open technique. The two approaches were compared on an intention-to-treat basis. Data shown represent medians. <h3>Results</h3> Between 2002 and 2009, 32 patients (20 female) underwent 16 LDP and 16 ODP respectively. The laparoscopic and open groups were comparable for age (57 vs 63 years, p<i>=</i>0.584), sex distribution and tumour size (3.9 vs 4 cm, p=0.939). Both groups had a comparable number of malignant cases (56% vs 50%, p=1.0). Although LDP took longer to complete (287.5 vs 240 min, p=0.061), it was associated with significantly lower blood loss (300 vs 500 ml, p=0.031) but comparable perioperative transfusion rate (p=0.471). The laparoscopic approach was associated with a significantly higher spleen-preservation rate (overall: 50% vs 12.5%, p=0.05; benign pathology: 85.7% vs 25%, p=1.0). LDP patients had a significantly lower HDU stay (1 vs 4.5 days, p&lt;0.001) and a significantly lower postoperative hospital stay (6.5 vs 13.5 days, p=0.001). There was no significant difference in the postoperative morbidity and the R0 resection margin status. <h3>Conclusion</h3> The laparoscopic approach to distal pancreatectomy results in significantly lower blood loss, and shorter HDU and hospital stay compared with open surgery. The postoperative morbidity and R0 resection margin rates were comparably similar. <h3>Competing interests</h3> None declared.
RIESGO DE RECIDIVA DE LAS COLECCIONES PANCREÁTICAS LÍQUIDAS (CPL) TRAS EL DRENAJE ENDOSCOPICO TRANSMURAL MEDIANTE STENTS METÁLICOS.
Authors: I Peñas Herrero, R Ruiz-Zorrilla, L Sancho del Val, N Alcaide Suárez, G Flores, A Vargas, P Gil-Simón, MH Núñez Rodríguez, C De la Serna Higuera, M Pérez-Miranda
Journal: Endoscopy (2012)

Introducción: La alta tasa de recidiva de las CPL (PSQ: pseudoquistes; NPO: necrosis pancreática organizada; y ABS: abscesos) tras el drenaje endoscópico transmural aconseja dejar in situ el stent quisto-gástrico (SQG) tras su resolución (Arvanitakis, GIE 2007). Se desconoce si ello puede obviarse con SQG metálicos. Objetivo: Evaluar la tasa de recidiva de las CPL resueltas mediante drenaje endoscópico transmural con SQG metálicos. Material y método: Revisión de pacientes con CPL por pancreatitis aguda resueltas tras drenaje endoscópico mediante SQG metálico (tubular o diábolo) identificados de base prospectiva durante 24 meses con un seguimiento mínimo de 30días desde la retirada del SQG hasta el último control. Resultados: 43 pacientes remitidos para drenaje de CPL, 16 analizados (10 varones; edad=64 [33–89] años, Tabla) y 27 excluidos: 3 CPL no drenables, 2 colecciones peripancreáticas de otro origen (biloma, ABS postquirúrgico), 5 PSQ por P. crónica y/o con drenaje solo transpapilar o transmural pig-tail plástico, 6 NPO drenadas pero con fracaso clínico (3 cirugía, 3 éxitus), 4 NPO drenadas todavía en resolución, 3 CPL resueltas pendientes retirada SQG (2 PSQ, 1 ABS), y 4 CPL drenadas pero sin datos evolutivos (3 PSQ, 1 NPO). Tras 68 (16–138) días, se retiraron sin complicaciones 14 SQG (7 diábolos, 7 tubulares), con migración espontánea asintomática de 2 diábolos. Tras 186 [50–433] días se produjo recidiva de un PSQ, dolor e hiperamilasemia sin colecciones en un caso, dos colecciones residuales. Conclusiones: La tasa de recidiva de las CPL resueltas mediante drenaje endoscópico con SQG metálicos tras un seguimiento medio de 6 meses es del 6.2%, muy inferior al 38% descrito con pig-tail plásticos. Estos datos merecerían validarse de forma prospectiva y controlada.
Abstract 1619: Combination of VEGFR inhibitor lenvatinib (E7080) and Met/EphB4 inhibitor golvatinib (E7050) overcomes VEGFR inhibitor-resistant tumor vascular.
Authors: Satoshi Kawano, Takayuki Nakagawa, Yuya Nakazawa, Yoshiaki Sato, Tomohiro Matsushima, Yasuhiro Funahashi
Journal: Cancer Research (2013)

Abstract Vascular endothelial growth factor receptor (VEGFR) inhibitors are approved for the treatment of several types of tumors, however, some tumor shows intrinsic resistance to VEGFR inhibitors. In addition, patients initially responding develop acquired resistance to VEGFR inhibitors after varying periods of time. Thus it is urgent to develop strategy to overcome anti-VEGF therapy resistance. Hepatocyte growth factor (HGF)/Met signaling is activated in various types of tumors. Recently, it is reported that HGF/Met signaling contributes to resistance to tyrosine kinase inhibitors such as EGFR, BRAF, ALK inhibitors. This suggests that Met inhibitors may be promising in treating HGF/Met activated anti-VEGF therapy-resistant tumors. We have identified lenvatinib (E7080) as a highly-potent VEGFR inhibitor and phase III trial is ongoing in thyroid cancer. Lenvatinib inhibited the growth of HUVEC induced by VEGF, however, addition of HGF to HUVEC conferred resistance to lenvatinib. This resistance was cancelled by the addition of golvatinib (E7050) which is identified as a potent Met/EphB4 inhibitor and phase I trial of the lenvatinib/golvatinib combination therapy is ongoing. In mouse models bearing various tumor cell lines expressing VEGF and HGF, treatment with lenvatinib alone demonstrated only moderate antitumor activity, however, combination with golvatinib demonstrated synergistic antitumor activity with decrease of tumor vessel density. Furthermore, it is reported that EphB4 has critical roles in tumor vessel development and maturation. Our unique in vitro assay systems, endothelial cells/pericyte 2D co-culture assay and endothelial cells/pericyte 3D co-culture sprouting assay, suggested that EphB4 inhibitory activity of golvatinib disrupted anti-VEGF therapy-resistant tumor vascular in the combination with lenvatinib. Together, these data demonstrated that combination therapy with golvatinib may be promising to overcome anti-VEGF therapy resistance. Citation Format: Satoshi Kawano, Takayuki Nakagawa, Yuya Nakazawa, Yoshiaki Sato, Tomohiro Matsushima, Yasuhiro Funahashi. Combination of VEGFR inhibitor lenvatinib (E7080) and Met/EphB4 inhibitor golvatinib (E7050) overcomes VEGFR inhibitor-resistant tumor vascular. [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 1619. doi:10.1158/1538-7445.AM2013-1619
¿SE EMPLEAN EN LOS HOSPITALES ESPAÑOLES PAUTAS ADECUADAS DE LIMPIEZA PARA LA COLONOSCOPIA, CONSIDERANDO EL MOMENTO DE LA ADMINISTRACIÓN?. RESULTADOS DE UNA ENCUESTA NACIONAL
Authors: A Parra-Blanco, P Zaballa, A Mancebo, M Ibáñez, R Fernández-Velázquez, M Rodríguez-Peláez, D Juzgado, O González-Bernardo, I Pérez, N González, G Pérez, J Ortiz Fernández-Sordo, MA Palacio, A Ono, C Alvarez, L Rodrigo
Journal: Endoscopy (2010)

Introducción: La calidad de la limpieza en la colonoscopia representa uno de los mayores problemas de esta exploración. Existe suficiente evidencia para recomendar que la preparación se administre, al menos en parte, pocas horas antes del inicio de la colonoscopia, con el objetivo de conseguir una limpieza adecuada (especialmente en el colon proximal) y una mayor detección de pólipos y lesiones planas. Estudios recientes sugieren que la colonoscopia puede no estar previniendo el cáncer de colon proximal, y una posible razón es que el agente de limpieza se esté administrando con una pauta inadecuada.