tbuckley/cabot-search huggingface dataset:
P10.19 Pure aqueductal tumors: A rare entity
Authors: T. Miwa, R. Tamura
Journal: Neuro-Oncology (2017)

Pure aqueductal tumors are completely different from tectal or tegmental tumors, and they indeed exist just within the aqueduct. We report our unique cases of pure aqueductal pilocytic astrocytoma (aPA) and rosette-forming glioneuronal tumor (aRGNT), and then we reviewed the pure aqueductal tumors by literatures. In our 18 years old aPA case, he had been followed by NF-1 in dermatology, and was pointed out mild enlargement of the lateral and third ventricle by MRI three years ago. There was no obvious cause of enlargement of ventricles at that time. A year ago, he showed transient mild headache and MRI showed progression of enlargement of the ventricles, and MRI showed small tumor located within the aqueduct. Because a tumor size showed enlargement gradually after that, endoscopic third ventriculostomy (ETV) and tumor biopsy was performed at the same time, and pathological diagnosis was typical type of pilocytic astrocytoma (Ki-67: 0.3%). After the operation, he was asymptomatic and showed a good course. Although the tumor size has increased, it is stable now and being carefully observed without any chemo-radio therapy. In our 28 years old aRGNT case, he had complained intermittent mild headache. MRI showed the tumor located within the aqueduct. ETV and tumor biopsy was performed at the same time, and pathological diagnosis was RGNT (Ki-67: 0.6%). After the operation, he was asymptomatic and showed a good course. Six months later, MRI showed the enlargement of tumor extended to the fourth ventricle. Tumor removal by craniotomy was performed by suboccipital approach. After the operation, he showed a good course. Pure aqueductal tumors are very rare. Because aqueductal tumors combine a hydrocephalus and also show several pathological diagnoses, perform the ETV plus biopsy at one time is effective. Pure aPA have been reported only 3 cases from the past papers. Among these 3 cases, 2 cases comorbid the NF-1 such as our case. Although typical tectal pilocytic astrocytomas are usually stable by normal observation, pure aqueductal tumors need careful observation because they sometimes show uncharacteristic growing in spite of low score of Ki-67 index.
Academic Performance, Motor Function, and Behavior 11 Years After Neonatal Caffeine Citrate Therapy for Apnea of Prematurity
Authors: Barbara Schmidt, Robin S. Roberts, Peter J. Anderson, Elizabeth V. Asztalos, Lorrie Costantini, Peter G. Davis, Deborah Dewey, Judy D’Ilario, Lex W. Doyle, Ruth E. Grunau, Diane Moddemann, Harvey Nelson, Arne Ohlsson, Alfonso Solimano, Win Tin
Journal: JAMA Pediatrics (2017)

Caffeine citrate therapy for apnea of prematurity reduces the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability at 18 months and may improve motor function at 5 years.To evaluate whether neonatal caffeine therapy is associated with improved functional outcomes 11 years later.A follow-up study was conducted at 14 academic hospitals in Canada, Australia, and the United Kingdom from May 7, 2011, to May 27, 2016, of English- or French-speaking children who had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between October 11, 1999, and October 22, 2004. A total of 1202 children with birth weights of 500 to 1250 g were eligible for this study; 920 (76.5%) had adequate data for the main outcome.Caffeine citrate or placebo until drug therapy for apnea of prematurity was no longer needed.Functional impairment was a composite of poor academic performance (defined as at least 1 standard score greater than 2 SD below the mean on the Wide Range Achievement Test-4), motor impairment (defined as a percentile rank of ≤5 on the Movement Assessment Battery for Children-Second Edition), and behavior problems (defined as a Total Problem T score ≥2 SD above the mean on the Child Behavior Checklist).Among the 920 children (444 females and 476 males; median age, 11.4 years [interquartile range, 11.1-11.8 years]), the combined rates of functional impairment were not significantly different between the 457 children assigned to receive caffeine compared with the 463 children assigned to receive placebo (145 [31.7%] vs 174 [37.6%]; adjusted odds ratio, 0.78; 95% CI, 0.59-1.02; P = .07). With all available data, including those from up to 24 Swedish trial participants, the rates of poor academic performance on 1 or more of 4 subtests (66 of 458 [14.4%] vs 61 of 462 [13.2%]; adjusted odds ratio, 1.11; 95% CI, 0.77-1.61; P = .58) and behavior problems (52 of 476 [10.9%] vs 40 of 481 [8.3%]; adjusted odds ratio, 1.32; 95% CI, 0.85-2.07; P = .22) were broadly similar between the group that received caffeine and the group that received placebo. However, caffeine therapy was associated with a reduced risk of motor impairment compared with placebo (90 of 457 [19.7%] vs 130 of 473 [27.5%]; adjusted odds ratio, 0.66; 95% CI, 0.48-0.90; P = .009).Caffeine therapy for apnea of prematurity did not significantly reduce the combined rate of academic, motor, and behavioral impairments but was associated with a reduced risk of motor impairment in 11-year-old children with very low birth weight. At the doses used in this trial, neonatal caffeine therapy is effective and safe into middle school age.clinicaltrials.gov Identifier: NCT00182312; isrctn.org Identifier: ISRCTN44364365.
A case of ruptured hepatic angiomyolipoma in a young male
Authors: Sun Hwa Kim, Tae Wook Kang, Kyunghee Lim, Hyun Sung Joh, Jiseok Kang, Dong Hyun Sinn
Journal: Clinical and Molecular Hepatology (2017)

A 31-year-old male visited a local hospital due to sudden-onset severe abdominal pain. Abdominal computed tomography revealed a solid cystic mass with a size of approximately 12 cm and exhibiting both hemorrhage and fluid collection in the pelvic cavity. Emergency angiography and embolization were performed, and a large hepatic tumor was subsequently surgically resected. The tumor cells stained positive for human melanoma black-45 and smooth-muscle actin, and the pathologic diagnosis was hepatic angiomyolipoma. This case report also discusses the spontaneous rupture of a hepatic angiomyolipoma.
IMPACT OF LIPID PROFILES AND CLASSICAL RISK FACTORS ON CORONARY ARTERY SPASM AS ASSESSED BY ACETYLCHOLINE PROVOCATION TEST
Authors: Sang-Ho Park, Seung-Woon Rha, ARA CHO, Hyeok-gyu Lee, Wonyong Shin, Seung-Jin Lee, Dongkyu Jin, Amro Elnagar, Byoung Geol Choi, sung il Im, Sunwon Kim, Jin Oh Na, Seongwoo Han, Cheol Ung Choi, Hong Euy Lim, Jin Won Kim, Eung Ju Kim, Hong-Seog Seo, Chang Gyu Park, Dong Joo Oh
Journal: Journal of the American College of Cardiology (2012)
Response at Interim Evaluation Predicts Survival after Autologous Stem Cell Transplantation in Nodal Peripheral T-Cell Lymphoma; A Nordic Lymphoma Group Study
Authors: Fredrik Ellin, Knut Liestøl, Susanna Mannisto, Grete F Lauritzsen, Esa Jantunen, Peter A Meyer, Helle Toldbod, Thomas Relander, Francesco A d'Amore
Journal: Blood (2016)
Spironolactone Metabolites in TOPCAT — New Insights into Regional Variation
Authors: Simon de Denus, Eileen O'Meara, Akshay S Desai, Brian Claggett, Eldrin F Lewis, Grégoire Leclair, Martin Jutras, Joël Lavoie, Scott D Solomon, Bertram Pitt, Marc A Pfeffer, Jean L Rouleau
Journal: New England Journal of Medicine (2017)

In a subgroup of TOPCAT participants assigned to spironolactone, the spironolactone metabolite canrenone was measured to assess adherence. Canrenone levels were undetectable in 30% of participants from Russia, as compared with only 3% from the United States and Canada.
The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade
Authors: J.-P. Foy, C. Bertolus, M.-C. Michallet, S. Deneuve, R. Incitti, N. Bendriss-Vermare, M.-A. Albaret, S. Ortiz-Cuaran, E. Thomas, A. Colombe, C. Py, N. Gadot, J.-P. Michot, J. Fayette, A. Viari, B. Van den Eynde, P. Goudot, M. Devouassoux-Shisheboran, A. Puisieux, C. Caux, P. Zrounba, S. Lantuejoul, P. Saintigny
Journal: Annals of Oncology (2017)
Abstract A60: Loss of α3 integrin expression promotes α6 integrin internalization to Rab4 vesicles and migration of human prostate cancer cells
Authors: Lipsa Das, Todd A. Anderson, Jaime M. Gard, Isis C. Sroka, Stephanie R. Strautman, Raymond B. Nagle, Colm Morrissey, Beatrice S. Knudsen, Anne E. Cress
Journal: Cancer Research (2016)

Abstract Background: Metastatic prostate cancer express laminin binding integrins α6 and α3 while losing the expression of a variety of integrins present in normal prostate gland. Results: In human xenograft tissues, at least 70% of bone and soft tissue metastasis of prostate cancer (185 samples from 45 patients) had cytoplasmic expression of the α6 integrin that correlated to increased expression of intracellular trafficking proteins. Given the reported link between cytoplasmic integrin distribution and integrin endocytosis, surface labelled integrin α6 were quantified for internalization kinetics using flow cytometry. The integrin α6 was internalized 3-fold faster than α3 integrin (CD49c) (1.0 min-1), 1.5-fold faster than the vitronectin binding αv integrin (CD51) (2.2 min-1), and significantly slower than the unrelated transferrin receptor (TfR, CD71) (15 min-1). Silencing α3 expression increased α6 integrin internalization by 1.45 fold without affecting internalization of non-integrin control receptor, TfR. The internalized α6 integrin was targeted to early endosomes and Rab4 recycling vesicles and redistributed to a cell-cell staining pattern similar to human prostate cancer specimens. This was accompanied by a 1.8-fold increase in cancer cell migration that was dependent on α6 integrin. Silencing integrin α6 however, didn't affect the internalization rate or intracellular endocytic distribution of the α3 integrin. Conclusion and Significance: We conclude that internalization of the α6 and α3 integrins is coordinated in a unidirectional fashion and their relative expression can significantly modulate cancer cell migration. The observed loss of α3 integrin expression in high grade cancer is predicted to increase the internalization and pro-migratory features of α6 integrin in high grade cancer. Acknowledgements: Research was supported in part by NIH research grants R01 CA 159406, CA 23074 and CA09213. Patient tissue studies were supported by Biobank and Translational Research Core, Cedars Sinai Medical Center, CA, Pacific Northwest Prostate Cancer SPORE (P50CA97186), the PO1 NIH grants (PO1CA085859) and the Richard M. LUCAS Foundation. Citation Format: Lipsa Das, Todd A. Anderson, Jaime M. Gard, Isis C. Sroka, Stephanie R. Strautman, Raymond B. Nagle, Colm Morrissey, Beatrice S. Knudsen, Anne E. Cress. Loss of α3 integrin expression promotes α6 integrin internalization to Rab4 vesicles and migration of human prostate cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A60.
Abstract 304: Efficient Generation of Cardiac Purkinje Fiber-like Cells From ESCs by Activating cAMP Signaling
Authors: Su-Yi Tsai, Karen Maass, Jia Lu, Glenn I Fishman, Shuibing Chen, Todd Evans
Journal: Circulation Research (2015)

Dysfunction of the cardiac conduction system (CCS) significantly impacts pathogenesis of arrhythmia, a major cause of morbidity and mortality. Strategies to derive cardiac conduction cells including Purkinje fiber cells (PC) would facilitate models for mechanistic studies and drug discovery, and also provide new cellular materials for regenerative therapies. A high-throughput chemical screen using CCS:lacZ and Contactin2:eGFP (Cntn2:eGFP) reporter embryonic stem cell (ESC) lines was used to discover a small molecule, sodium nitroprusside (SN), that efficiently promotes the generation of cardiac cells that express gene profiles and generate action potentials of PC-like cells. Imaging and mechanistic studies suggest that SN promotes the generation of PC from cardiac progenitors initially expressing cardiac myosin heavy chain, and that it does so by activating cAMP signaling. These findings provide a novel strategy to derive scalable PC, along with insight into the ontogeny of CCS development.
Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey
Authors: S. Banerjee, R. Califano, J. Corral, E. de Azambuja, L. De Mattos-Arruda, V. Guarneri, M. Hutka, K. Jordan, E. Martinelli, G. Mountzios, M.A. Ozturk, M. Petrova, S. Postel-Vinay, M. Preusser, C. Qvortrup, M.N.M. Volkov, J. Tabernero, D. Olmos, M.H. Strijbos
Journal: Annals of Oncology (2017)
P08.10 Efficacy of Temozolomide and Aldoxorubicin combination in U87-luc glioblastoma xenograft mice model
Authors: M. Da Ros, A. Iorio, O. Fantappiè, V. De Gregorio, L. Bonaccorsi, G. Laffi, L. Genitori, I. Sardi
Journal: Neuro-Oncology (2017)

Introduction: Despite that Temozolomide (TMZ) is the standard of care recognized for its effectiveness in the treatment of glioblastoma (GBM), its prognosis remains poor. Therefore, combination chemotherapy using TMZ with other antitumor agents is now under investigation. We evaluated antitumor efficacy, tolerability and long-term response of the combination of TMZ with Aldoxorubicin (Aldoxo), a novel drug-conjugate of Doxorubicin, in a growing GBM xenograft mouse model. Materials and Methods: A human GBM cell line that expresses a luciferase reporter (U87-luc) was injected in the right lobe of the brain of Foxn1 mice. Following initial tumor growth for 7 days, mice were treated with Aldoxo (16 mg/kg, weekly intravenous administrations), TMZ (0.9 mg/kg, daily oral administrations) or their combination up to 5 weeks. Bioluminescence IVIS acquisitions have been performed at day 0, +3, +7 and then weekly until the end of experiment in order to quantify tumor growth and long-term response to therapy (until day +90). Results: In the first 28 days, all animals had developed tumors of varying size without significant difference between treated and untreated mice. At day +42, (end of treatment), there was a significant decrease in the tumors with TMZ and Aldoxo-TMZ therapy (P<0.05). At day +56, tumor volume in Aldoxo-treated mice was 4-fold smaller than in vehicle with no statistical significant difference among these groups; on the contrary, a significant tumor volume inhibition (TVI) was observed in Aldoxo-TMZ treated mice (TVI 90%, P=0,0190 vs vehicle), as well as in TMZ treated mice (TVI 92% P=0,0317 vs vehicle). Survival data showed that, although no different survival rate was in tumor-bearing mice treated with TMZ or Aldoxo-TMZ (37,5% at day +90), the combined treatment delayed the mortality compared to TMZ alone throughout the experimental period. Furthermore, by the 69-day time point all untreated mice were deceased whereas Aldoxo-treated group showed an increased survival rate at day +90 (12,5%). Conclusion: Our preliminary data demonstrated that, although the combination therapy schedule of Aldoxo and TMZ failed to significantly improve TVI in GBM xenograft mice model, it achieved a survival benefit when compared to TMZ alone, delaying mortality during the overall experimental period without adverse effects.
Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities
Authors: Kole T. Roybal, Wendell A. Lim
Journal: Annual Review of Immunology (2017)

The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.
Tracking the Evolution of Non–Small-Cell Lung Cancer
Authors: Mariam Jamal-Hanjani, Gareth A. Wilson, Nicholas McGranahan, Nicolai J. Birkbak, Thomas B.K. Watkins, Selvaraju Veeriah, Seema Shafi, Diana H. Johnson, Richard Mitter, Rachel Rosenthal, Max Salm, Stuart Horswell, Mickael Escudero, Nik Matthews, Andrew Rowan, Tim Chambers, David A. Moore, Samra Turajlic, Hang Xu, Siow-Ming Lee, Martin D. Forster, Tanya Ahmad, Crispin T. Hiley, Christopher Abbosh, Mary Falzon, Elaine Borg, Teresa Marafioti, David Lawrence, Martin Hayward, Shyam Kolvekar, Nikolaos Panagiotopoulos, Sam M. Janes, Ricky Thakrar, Asia Ahmed, Fiona Blackhall, Yvonne Summers, Rajesh Shah, Leena Joseph, Anne M. Quinn, Phil A. Crosbie, Babu Naidu, Gary Middleton, Gerald Langman, Simon Trotter, Marianne Nicolson, Hardy Remmen, Keith Kerr, Mahendran Chetty, Lesley Gomersall, Dean A. Fennell, Apostolos Nakas, Sridhar Rathinam, Girija Anand, Sajid Khan, Peter Russell, Veni Ezhil, Babikir Ismail, Melanie Irvin-Sellers, Vineet Prakash, Jason F. Lester, Malgorzata Kornaszewska, Richard Attanoos, Haydn Adams, Helen Davies, Stefan Dentro, Philippe Taniere, Brendan O’Sullivan, Helen L. Lowe, John A. Hartley, Natasha Iles, Harriet Bell, Yenting Ngai, Jacqui A. Shaw, Javier Herrero, Zoltan Szallasi, Roland F. Schwarz, Aengus Stewart, Sergio A. Quezada, John Le Quesne, Peter Van Loo, Caroline Dive, Allan Hackshaw, Charles Swanton
Journal: New England Journal of Medicine (2017)

Among patients with non-small-cell lung cancer (NSCLC), data on intratumor heterogeneity and cancer genome evolution have been limited to small retrospective cohorts. We wanted to prospectively investigate intratumor heterogeneity in relation to clinical outcome and to determine the clonal nature of driver events and evolutionary processes in early-stage NSCLC.
Widespread Use of Misidentified Cell Line KB (HeLa): Incorrect Attribution and Its Impact Revealed through Mining the Scientific Literature
Authors: Liwen Vaughan, Wolfgang Glänzel, Christopher Korch, Amanda Capes-Davis
Journal: Cancer Research (2017)

Continuous cell lines are widely used, but can result in invalid, irreproducible research data. Cell line misidentification is a common problem that can be detected by authentication testing; however, misidentified cell lines continue to be used in publications. Here we explore the impact of one misidentified cell line, KB (HeLa), on the scientific literature. We identified 574 articles between 2000 and 2014 that provided an incorrect attribution for KB, in accordance with its false identity as oral epidermoid carcinoma, but only 57 articles that provided a correct attribution for KB, as HeLa or cervical adenocarcinoma. Statistical analysis of 57 correct and 171 incorrect articles showed that the number of citations to these articles increased over time. Content analysis of 200 citing articles showed there was a tendency to describe the cell line in accordance with the description in the cited paper. Analysis of journal impact factor showed no significant difference between correct and incorrect groups. Articles using KB or citing that usage were most frequently published in the subject areas of pharmacology, pharmacy, oncology, and medicinal chemistry. These findings are important for science policy and support the need for journals to require authentication testing as a condition of publication. Cancer Res; 77(11); 2784-8. ©2017 AACR.
OS09.5 Synergistic effect of reirradiation and PD-1 inhibitors in recurrent high-grade gliomas
Authors: F. M. Iwamoto, L. Donovan
Journal: Neuro-Oncology (2017)

Background: To date, studies of single agent PD-1 or PDL-1 inhibitors in recurrent high-grade gliomas (HGG) have shown infrequent responses (< 10%) and limited efficacy. Reirradiation is considered one of the standard salvage regimens for selected patients with recurrent gliomas but tumor responses are also infrequent (< 5%). Radiotherapy counteracts the immunosuppressive tumor microenvironment by increasing MHC class I expression and enhancing tumor neoantigen presentation and has a significant synergistic effect with PD-1 inhibition in preclinical models of glioma. Methods: From December 2014 to June 2016, 20 patients (14 men, 6 women) with recurrent HGG were treated with the combination of reirradiation and PD-1 inhibitors. 18 patients had a glioblastoma, 1 anaplastic astrocytoma and 1 anaplastic oligodendroglioma. The median KPS at the start of this regimen was 70 (50 to 80). The median number of prior treatments for recurrent tumor was 2 (1–4), 100% had prior radaition, 95% prior temozolomide and 55% prior bevacizumab. 8 patients received pembrolizumab (2 mg/Kg every 3 weeks) and 12 patients received nivolumab (3 mg/Kg or 240 mg flat dose every 2 weeks). Median reirradiation dose was 35 Gy (12 Gy to 35 Gy). Results: There were 7 confirmed partial responses (35% objective response rate, ORR), 5 stable disease and 8 progressive disease. The median duration of response was 5 months (2.2 to 10+ months). Median PFS was 4 months and median OS was 10 months. Most common side effects were increased ALT (3 patients) and fatigue (2 patients). There was no obvious case of cerebral edema related to treatment. 5 patients required a mild increase of dexamethasone (2–4 mg) and all other 15 patients had decreased or stable dexamethasone dosage after the reirradiation. Conclusions: PD-1 inhibitors in combination with re-irradiation can be administered safely to patients with recurrent HGG. The ORR of 35% is an early signal of the potential synergist effect of the combination of PD-1 inhibitors with re-irradiation in HGG. This retrospective analysis of a heavily pre-treated population of recurrent HGG showed significantly higher ORR than either PD-1 inhibitors or re-irradiation alone. A clinical trial under development to test this hypothesis.
Estimating the annual burden of tick-borne encephalitis to inform vaccination policy, Slovenia, 2009 to 2013
Authors: Mario Fafangel, Alessandro Cassini, Edoardo Colzani, Irena Klavs, Marta Grgič Vitek, Veronika Učakar, Marion Muehlen, Marko Vudrag, Alenka Kraigher
Journal: Eurosurveillance (2017)

With an annual incidence between 8 and 15 per 100,000 population in the period from 2009 to 2013, Slovenia has one of the highest notified incidences of tick-borne encephalitis (TBE) in Europe. TBE vaccination coverage remains at about 7.3%. To inform vaccination policy, we used surveillance data from 2009 to 2013 to calculate the overall and age- and sex-specific mean annual TBE incidence. We estimated disability-adjusted life years (DALYs) with 95% uncertainty intervals (UI), using the Burden of Communicable Diseases in Europe approach from the European Centre for Disease Prevention and Control. The mean annual incidence was 11.6 per 100,000 population, peaking in older age groups (50-74 years: 18.5/100,000) while relatively lower among children (5-14 years: 10.2/100,000). We estimated an overall 10.95 DALYs per 100,000 population per year (95% UI: 10.25-11.65). In contrast to the TBE incidence, the disease burden in children aged 5-14 years was higher than in adults aged 50-74 years: 17.31 (95% UI: 14.58-20.08) and 11.58 (95% UI: 10.25-12.91) DALYs per 100,000 stratum-specific population, respectively. In a limited resource setting where prioritisation of TBE vaccination strategies is required, vaccination programmes targeting children may have a higher impact on disease burden.