tbuckley/cabot-search huggingface dataset:
Clinical and preclinical activity of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk of hematologic malignancies, against blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Authors: Arthur E. Frankel, Jung Hee Woo, Jeremy Preston Mauldin, Hetty Eileen Carraway, Olga Frankfurt, Stephen J. Forman, Christopher Brooks, Ivan Bergstein, Thomas Cirrito, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2013)

TPS3105^ Background: Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN), a rare and aggressive dendritic cell-derived hematologic malignancy that typically involves the skin and invariably progresses to a leukemic phase, has a dismal prognosis with a median survival of approximately 14 months. Since BPDCN cells express high levels of the interleukin-3 receptor (IL-3R), SL-401, a novel targeted therapy directed to IL-3R, is being developed to treat BPDCN and other IL-3R-expressing hematologic malignancies. SL-401 is a recombinant biologic comprised of IL-3 conjugated to a truncated diphtheria toxin, a potent inhibitor of protein synthesis (Frankel et al, Prot Eng 13, 575, 2000). SL-401 is cytotoxic in vitro to IL-3R-expressing leukemia blasts (Frankel et al, Leukemia 14, 576, 2000) and inhibits tumor growth in vivo (Black et al, Leukemia 17, 155, 2003). Recently, SL-401 demonstrated ultra-high anti-tumor potency against BPDCN cells in the femtomolar (10 -15 M) range (Angelot-Delettre et al, Blood 118 Suppl 2588, 2011). Methods: In a Phase I/II trial of SL-401 in patients with IL-3R-expressing advanced hematologic malignancies, 4 patients with heavily pretreated BPDCN received a single cycle of SL-401 as a 15-minute infusion daily for 5 days. Results: All patients had CD4+/CD56+/CD123+ (IL-3Ralpha) expressing blasts and had failed previous combination chemotherapy regimens and allogeneic bone marrow transplantation. There were no serious adverse events. Three patients treated with SL-401 at 12.5 μg/kg/day (the planned pivotal Phase IIb trial dose) experienced complete responses (CRs). The CRs included disappearance of BPDCN in the skin, bone marrow, peripheral blood, spleen and lymph nodes. CR durations are 5, 3+, and 1+ months to date. Conclusions: Given these robust clinical responses, as well as the mechanistic rationale for SL-401 in BPDCN, additional BPDCN patients are being evaluated in the study and a pivotal Phase IIb multi-cycle trial in this ultra-orphan indication is being planned. Clinical trial information: NCT00397579.
Development of OAT-1746, a novel arginase 1 and 2 inhibitor for cancer immunotherapy
Authors: P.S. Stanczak, M.M. Grzybowski, P. Wolska, A.M. Zdziarska, M. Mazurkiewicz, R. Blaszczyk, J. Nowicka, A. Sosnowska, K. Ramji, D. Nowis, J. Golab, A. Golebiowski, P. Dobrzanski, K. Dzwonek
Journal: Annals of Oncology (2017)
PROSABI: Prospective multi-centre study of prognostic factors in castration resistant prostate cancer (CRPC) patients treated with abiraterone acetate (AA)
Authors: D. Lorente Estelles, J. Puente, A. Medina, R. Lozano Mejorada, L. Rivera, M.I. Pacheco, M.I. Sáez, J.M. Piulats Rodriguez, E.M. Fernandez Parra, P. Borrega García, B. Pérez Valderrama, E. Gallardo Diaz, R. Villatoro, R. Morales Barrera, S. Vazquez Estevez, A. Pinto Marin, J.A. Contreras Ibañez, N. Romero Laorden, E. Castro Marcos
Journal: Annals of Oncology (2017)
Planes contra las pandemias gripales en Europa: antecedentes y principios
Authors: C Hannoun
Journal: Eurosurveillance (1998)

La gripe espanola de 1918-1919 afecto practicamente a todas las familias. El alivio experimentado al finalizar una guerra mundial atroz se vio empanado por una plaga que se cobro mas de 20 millones de victimas. La gripe, cuyas formas epidemicas varian en gravedad (tabla 1), a veces da lugar a epidemias espantosas.
MYH9 E1841K Mutation Augments Proteinuria and Podocyte Injury and Migration
Authors: Sylvia Cechova, Fan Dong, Fang Chan, Michael J. Kelley, Phillip Ruiz, Thu H. Le
Journal: Journal of the American Society of Nephrology (2017)

Intronic variants of the MYH9 gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease–associated nephropathy. However, the causal functional variants of MYH9 have remained elusive. Rare missense mutations in MYH9 cause macrothrombocytopenia and are occasionally associated with development of nephropathy. The E1841K mutation is among the common MYH9 missense mutations and has been associated with nephropathy in some carriers. To determine the contribution of the E1841K mutation in kidney disease, we studied the effects of the E1841K mutation in mice subjected to high salt or angiotensin II (Ang II) as models of hypertension and in mice subjected to renal mass reduction as a model of CKD. Despite similar levels of BP among wild-type ( MYH9+/+ ) mice and mice heterozygous ( MYH9+/E1841K ) and homozygous ( MYH9E1841K/E1841K ) for the mutation in each model, MYH9E1841K/E1841K mice exhibited mildly increased albuminuria in response to high salt; severe albuminuria, nephrinuria, FSGS, and podocyte foot effacement in Ang II–induced hypertension; and early mortality in the renal mass reduction model. Treatment with candesartan during Ang II–induced hypertension attenuated kidney disease development in MYH9E1841K/E1841K mice. In vitro , isolated primary podocytes from MYH9E1841K/E1841K mice exhibited increased lamellipodia formation and reorganization of F-actin stress fibers. Wound healing assays revealed that MYH9+/+ podocytes had the lowest migration rate, followed by MYH9+/E1841K then MYH9E1841K/E1841K podocytes. In conclusion, the MYH9 E1841K variant alters podocyte cytoskeletal structure and renders podocytes more susceptible to injury after a damaging stimulus.
Brigatinib (BRG) in anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC): Long-term efficacy and safety results from a phase 1/2 trial
Authors: L.A. Bazhenova, S.N. Gettinger, C.J. Langer, R. Salgia, K.A. Gold, R. Rosell, A.T. Shaw, G.J. Weiss, J. Haney, V.M. Rivera, D. Kerstein, R. Camidge
Journal: Annals of Oncology (2017)
Cannabis in fat: high hopes to treat obesity
Authors: Melody N. Hawkins, Tamas L. Horvath
Journal: Journal of Clinical Investigation (2017)

Cannabinoid receptor type-1 (CB1) is known to have a substantial impact on the regulation of energy metabolism via central and peripheral mechanisms. In this issue of the JCI, Ruiz de Azua and colleagues provide important insights into the regulation of adipocyte physiology by CB1. Mice with adipocyte-specific deletion of the CB1-encoding gene had an overall improved metabolic profile in addition to reduced body weight and total adiposity. These changes were associated with an increase in sympathetic tone of the adipose tissue and expansion of activated macrophages, both of which occurred prior to changes in body weight, lending support to a causal relationship between loss of CB1 in adipocytes and systemic metabolic changes. This work identifies adipocyte CB1s as a potential novel peripheral target for affecting systemic metabolism with diminished CNS effects.
Real world data about clinical efficacy and safety of apatinib in the treatment of advanced gastric cancer
Authors: J. Feng, B. Shen, Z. He, L. Deng, A. Dai, X. Shen, L. Chen, H. Jiang, X. Li, G. Zhou, J. Yu, L. Yang, P. Chen, M. Zhuang
Journal: Annals of Oncology (2017)
Prevalence of breast cancer risk factors in two different cohorts in relation to health care access and preventive programs in southern Brazil
Authors: M. Caleffi, A. J. Bedin, J. M. Zignani, L. G. Artico, J. M. Viegas-Butzke, R. Rutta, A. Schmidt, J. Giacomazzi, P. Ashton-Prolla, B. Weber
Journal: Journal of Clinical Oncology (2007)

1538 Background: Breast cancer (BC) represents a public issue of great impact also in developing countries as Brazil, where BC incidence and mortality rates are continuosly increasing, the latter probably due to late diagnosis and lack of health care programs.Studies are needed to identified BC risk factors in different groups of women in Porto Alegre (POA), where BC incidence is 3-fold higher than other Brazilian cities. Preliminary analysis are presented to enable specialists to design preventive strategies of breast health care models. Methods: The study included a survey of risk factors of two social economic distinct groups of women over 15 years old with different access to health care programs in POA: 1) Núcleo Mama Porto Alegre (NMPOA): underserved women derived from public health care units, and 2) Núcleo Mama Moinhos (NMHMV): women with private insurance. Results: Data of 785 from NMHMV and 8921 from NMPOA are summarized in the table . Obesity and smokers are more frequent in the underserved population whereas a positive familial history is more common in the NMHMV group. Conclusions: Preliminary results showed significant differences among the two studied population demanding distinct strategies of prevention and management. The total number of 15.000 women will be presented together with reproductive factors and the their Gail model access. [Table: see text] No significant financial relationships to disclose.
Erlotinib, dasatinib, erlotinib-dasatinib versus placebo: A randomized, double-blind window study in operable head and neck squamous cell carcinoma (HNSCC).
Authors: Julie E. Bauman, Umamaheswar Duvvuri, William E. Gooding, Neil D. Gross, John Song, Wendell Gray Yarbrough, Faye M. Johnson, Lin Wang, Antonio Jimeno, Malabika Sen, Jason I Kass, Jonas Talmadge Johnson, Robert L. Ferris, Seungwon Kim, Tanya J Rath, Fred R. Hirsch, Gordon B. Mills, Natanya I Pollock, John T Flaherty, Jennifer R. Grandis
Journal: Journal of Clinical Oncology (2014)

6033 Background: The epidermal growth factor receptor (EGFR) and Src family kinases are upregulated in HNSCC. EGFR interacts with cSrc to activate oncogenic STAT3 signaling; dual targeting is synergistic in HNSCC cell lines. In preclinical models, phosphorylated cSrc (pSrc) mediates resistance to erlotinib (E), a small molecule EGFR inhibitor. Baseline over-expression of pSrc was associated with E resistance in our prior window trial. Here, we conducted a four-arm phase 0 trial of E; dasatinib (D), an ATP-competitive inhibitor of cSrc; E+D; vs. placebo (P). Methods: Patients with operable Stage II-IVa HNSCC were randomized 1:1:1:1 to 7-21 days of neoadjuvant E 150 mg daily (n=11), D 100 mg daily (n=13), E+D (n=15), or P (for E; n=14). Paired tumor specimens were collected pre- and post-treatment. The primary endpoint, percent change in RECIST-measurable index lesions, was compared among groups by 2-way ANOVA. We analyzed the relationship between tumor percent change and pharmacodynamic expression of EGFR and cSrc pathway constituents. Pre-defined, hypothesis-driven analytes included pSTAT3, pSrc, pMet, and pMAPK. Results: From Apr 2009-Dec 2012, 58 patients were consented, 55 randomized, and 53 treated. Rash was observed on E arms; GI toxicities were observed in all active treatment groups. There was a significant decrease in tumor size in the E arms (p=0.0014), and no additive or independent effect from D (p=0.24). Among E-treated patients, high baseline pMAPK expression was associated with reduction in tumor size (p=0.03). An E-treated patient experiencing complete clinical response harbored a somatic MAPK1E322Kmutation. Among D-treated patients, high baseline pSTAT3 was associated with tumor progression (p=0.03). Conclusions: Brief neoadjuvant treatment with E significantly decreased tumor size in operable HNSCC, with no independent or added effect from D. Baseline pMAPK expression and genomic MAPK alterations warrant further study as response biomarkers for anti-EGFR therapy. High basal pSTAT3 in HNSCC patients may be independent of cSrc, explain therapeutic resistance, and preclude further development of D in biomarker-unselected cohorts. Clinical trial information: NCT00779389.
Epidemiological study of histologically proven advanced hepatocholangiocarcinoma: An AGEO multicenter retrospective study
Authors: Y. Touchefeu, C. Prieux-Klotz, D. Tougeron, T. Lecomte, M. Caulet, T. Matysiak Budnik, V. Hautefeuille, M. Tiako-Meyo, A. Zaanan, M. Salimon
Journal: Annals of Oncology (2017)
Gymnastics injury incidence during the 2008, 2012 and 2016 Olympic Games: analysis of prospectively collected surveillance data from 963 registered gymnasts during Olympic Games
Authors: Pascal Edouard, Kathrin Steffen, Astrid Junge, Michel Leglise, Torbjørn Soligard, Lars Engebretsen
Journal: British Journal of Sports Medicine (2017)

To determine the incidence and characteristics of injuries in female and male gymnastics disciplines (artistic, rhythmic and trampoline) during three Olympic Games with a view to ultimately improving injury prevention.The National Olympic Committee's head physicians and the medical teams of the Local Organising Committee of the Olympic Games reported daily the occurrence (or non-occurrence) of newly sustained injuries in artistic, rhythmic and trampoline gymnastics on a standardised report form during the 2008, 2012 and 2016 Summer Olympic Games.During the three Olympic Games, 81 injuries were reported in a total of 963 registered gymnasts, corresponding to an incidence of 84 injuries (95% CI 67 to 102) per 1000 registered gymnasts, with no difference in injury incidence between female and male gymnasts. Thirty-eight per cent of injuries led to time-loss from sport. The most frequent injury location and injury type were the ankle (22%) and sprain (35%), respectively. The most common diagnosis was ankle sprain (14% of all injuries and 23% of time-loss injuries). The injury incidence was highest in female (107±35) and male artistic gymnastics (83±32), followed by female rhythmic gymnastics (73±30), and lower in male (63±69) and female (43±43) trampoline gymnastics.Research should focus on preventing injuries in artistic gymnastics and of the condition of ankle sprain. Injury surveillance studies should be continued during major championships and throughout the entire competitive season as the Olympic Games provides only a snapshot (although an important one).
CORE-URO-01 study: comparison of safety and efficacy of pazopanib in first-line metastatic renal cell carcinoma (mRCC) with or without renal failure
Authors: C. Masini, M.G. Vitale, M. Maruzzo, G. Procopio, U. De Giorgi, S. Buti, S. Rossetti, R. Iacovelli, A. Guida, F. Atzori, C. Mucciarini, L. Cosmai, F. Vignani, G. Prati, S. Scagliarini, A. Berselli, C. Pinto
Journal: Annals of Oncology (2017)
Vigilancia centinela: una opción para la vigilancia de infecciones intestinales
Authors: C Gauci, T Melillo Fenech, H Gilles, S O'Brien, I Stabile, N Calleja, F Ruggeri, L Cuschieri, J Mamo
Journal: Eurosurveillance (2007)

Los sistemas de vigilancia centinela ofrecen ventajas frente a la vigilancia pasiva, que adolece de limitaciones conocidas a causa de la notificacion incompleta. Se ha efectuado un estudio piloto de la recogida de datos de vigilancia centinela de fuentes seleccionadas como opcion para la vigilancia de infecciones intestinales (II) en Malta.
Transcriptomic and epigenomic differences in human induced pluripotent stem cells generated from six reprogramming methods
Authors: Jared M. Churko, Jaecheol Lee, Mohamed Ameen, Mingxia Gu, Meenakshi Venkatasubramanian, Sebastian Diecke, Karim Sallam, Hogune Im, Gavin Wang, Joseph D. Gold, Nathan Salomonis, Michael P. Snyder, Joseph C. Wu
Journal: Nature Biomedical Engineering (2017)
A phase 1/2 study of ramucirumab plus nivolumab in patients with previously treated advanced gastric adenocarcinoma
Authors: H. Shoji, H. Miyamoto, H. Hara, D. Takahari, N. Machida, T. Esaki, K. Nagashima, K. Aoki, K. Honda, Y. Nagata, T. Miyamoto, N. Boku, K. Kato
Journal: Annals of Oncology (2017)
Resumen de infecciones ocupacionales por VIH descritas en informes publicados hasta diciembre de 1997
Authors: B G Evans, D Abiteboul
Journal: Eurosurveillance (1999)

Desde el primer caso documentado de seroconversion tras una exposicion ocupacional al VIH, declarado en 1984 (1), en muchos paises industrializados se han implantado sistemas nacionales o regionales de vigilancia de la infeccion por VIH adquirida en el trabajo. En 1992 (2), 1993 (3), 1995 (4) y, mas recientemente, en 1997 (5), se elaboraron diversos resumenes de casos de infeccion por VIH adquirida ocupacionalmente en el mundo, basados en informes publicados. Se desconoce la incidencia real de infeccion por VIH adquirida en el trabajo, aunque es probable que sea superior al total de casos declarados incluso en los propios paises industrializados donde se originaron los informes publicados. A nivel mundial, la incidencia es sin duda mucho mas elevada dado el bajo numero de infecciones ocupacionales notificado en zonas de alta prevalencia donde los sistemas de vigilancia no estan suficientemente desarrollados.
Polymorphisms in base excision repair genes and breast cancer susceptibility.
Authors: Robert C. Millikan, Temitope Keku, Jon Player, Allan Rene de Cotret, Tasha Smith, Jun Nakamura, William Kaufmann
Journal: Cancer Research (2004)

Background. A growing body of evidence suggests that oxidative DNA damage represents an important pathway for breast carcinogenesis. Oxidative DNA damage is repaired in part by the base excision repair (BER) pathway. Polymorphisms in four BER genes (XRCC1, HOGG1, APE1 and MYH) were examined in relation to an index of oxidative DNA damage (apurinic sites in DNA) and risk of breast cancer. Methods. BER genotypes were examined in relation to levels of apurinic (AP) sites in DNA from participants in an on-going hospital-based case-control study conducted at UNC Memorial Hospital (LCCC 9830). An aldehyde reactive slot blot method was used to detect quantitate AP sites in freshly collected blood lymphocytes. Odds ratios for BER genotypes and breast cancer, and interactions with environmental exposures, were calculated using samples and information collected from the Carolina Breast Cancer Study (CBCS). The CBCS is a population-based case-control study of breast cancer in North Carolina that includes 2311 cases (894 African Americans, 1417 whites) and 2022 controls (788 African Americans, 1234 whites). Genotyping was conducted for both studies using the ABI 7700 Sequence Detection System (“Taqman”) with positive controls and 10% repeats. Results. In LCCC 9830, levels of AP sites were highest among participants with the following genotypes: XRCC1 codon 399 Arg/Arg; HOGG1 codon 326 Cys/Cys; APE1 codon 148 Asp/Asp; MYH codon 324 Gln/Gln. In the CBCS, odds ratios were close to the null for BER genotypes and breast cancer, and no statistically significant differences were observed in allele frequencies between cases and controls. A statistically significant dose-response relationship was observed between duration of smoking and breast cancer risk among women with the following genotypes: XRCC1 Arg/Arg (trend test P = 0.001) but not any Gln (P = 0.79); HOGG1 codon 326 any Cys (P = 0.01) but not Ser/Ser (P = 0.60); MYH 324 Gln/Gln (P = 0.008) but not any His (P = 0.95). There were no differences in odds ratios for smoking according to APE1 genotype. Odds ratios were elevated for duration of smoking among participants with combinations of two or more “at risk” BER genotypes (XRCC1 399 Arg/Arg, HOGG1326 any Cys, MYH 324 Gln/Gln): never smokers (referent), 20 years (OR = 2.2, 1.5–3.0) (trend test P
Overall survival (OS) in patients (pts) with EGFR T790M-positive advanced non-small cell lung cancer (NSCLC) treated with osimertinib: Results from two phase II studies
Authors: T. Mitsudomi, M.-J. Ahn, L. Bazhenova, F. Blackhall, T. Hida, M. Majem Tarruella, S.L. Vowler, G. Laus, P.A. Jänne, J.C.-H. Yang
Journal: Annals of Oncology (2017)
Correlation of altered expression of a long non-coding RNA, NEAT1, in peripheral blood mononuclear cells with dengue disease progression
Authors: Abhay Deep Pandey, Saptamita Goswami, Shweta Shukla, Shaoli Das, Suman Ghosal, Manisha Pal, Bhaswati Bandyopadhyay, Vishnampettai Ramachandran, Nandita Basu, Vikas Sood, Priyanka Pandey, Jayprokas Chakrabarti, Sudhanshu Vrati, Arup Banerjee
Journal: Journal of Infection (2017)
Prognostic significance of local immunity factors in esophageal cancer
Authors: E.N. Kolesnikov, O.I. Kit, E.Y. Zlatnik, A.L. Bazaev, A.Y. Maksimov, I.A. Novikova, O.N. Selyutina, E.S. Bondarenko, V.S. Trifanov, L.V. Kharin, P.N. Gabrichidze, M.A. Kozhushko, S.S. Mezentsev, L.Y. Vladimirova
Journal: Annals of Oncology (2017)
Application of Trusight Myeloid Panel on Whole Genome Amplified DNA in Myelodysplastic Syndrome Patients
Authors: Laura Palomo, Daniel Alvira, Francisco Fuster-Tormo, Vera Ademà, Maria Pilar Armengol, Paula Gomez-Marzo, Nuri de Haro, Mar Mallo, Blanca Xicoy, Lurdes Zamora, Francesc Sole
Journal: Blood (2016)
Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis
Authors: Caitlin R. Meeker, Yu-Ning Wong, Brian L. Egleston, Michael J. Hall, Elizabeth R. Plimack, Lainie P. Martin, Margaret von Mehren, Bianca R. Lewis, Daniel M. Geynisman
Journal: Journal of the National Comprehensive Cancer Network (2017)

Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50–64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.
Hypercoagulation Screening as Marker of Occult Cancer in a Population of Healthy Blood Donors: The Hypercan Prospective Study
Authors: Anna Falanga, Marina Marchetti, Sara Gamba, Laura Russo, Carmen Julia Tartari, Cinzia Giaccherini, Cristina Verzeroli, Francesca Piras, Viola Milesi, Alfonso Vignoli, Shenaz Brevi, Francesca Rio, Luca Barcella, Giuseppe Sampietro
Journal: Blood (2016)
PI3K/RICTOR-mTORC2 axis as a driver of prognosis and potential druggable target in squamous cell lung carcinoma (SqCLC)
Authors: S. Pilotto, M. Simbolo, A. Gkountakos, C. Vicentini, I. Sperduti, V. Ludovini, R. Chiari, S. Novello, M. Milella, A. Mafficini, L. Carbognin, E. Caregnato, A. Santo, M. Infante, M. Brunelli, V. Corbo, A. Scarpa, G. Tortora, E. Bria
Journal: Annals of Oncology (2017)