tbuckley/cabot-search huggingface dataset:
Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study
Authors: James C Yao, Nicola Fazio, Simron Singh, Roberto Buzzoni, Carlo Carnaghi, Edward Wolin, Jiri Tomasek, Markus Raderer, Harald Lahner, Maurizio Voi, Lida Bubuteishvili Pacaud, Nicolas Rouyrre, Carolin Sachs, Juan W Valle, Gianfranco Delle Fave, Eric Van Cutsem, Margot Tesselaar, Yasuhiro Shimada, Do-Youn Oh, Jonathan Strosberg, Matthew H Kulke, Marianne E Pavel
Journal: The Lancet (2015)
Corbyn appoints new shadow health secretary
Authors: Gareth Iacobucci
Journal: BMJ (2015)

The UK Labour Party’s new leader, Jeremy Corbyn, has appointed Heidi Alexander as shadow health secretary.

The Lewisham East MP replaces Corbyn’s fellow Labour leadership candidate Andy Burnham in the health role, with Burnham moving to a new post as shadow home secretary.

Corbyn, who was elected …
Correction: Corrigendum: The genomic landscape of juvenile myelomonocytic leukemia
Authors: Elliot Stieglitz, Amaro N Taylor-Weiner, Tiffany Y Chang, Laura C Gelston, Yong-Dong Wang, Tali Mazor, Emilio Esquivel, Ariel Yu, Sara Seepo, Scott R Olsen, Mara Rosenberg, Sophie L Archambeault, Ghada Abusin, Kyle Beckman, Patrick A Brown, Michael Briones, Benjamin Carcamo, Todd Cooper, Gary V Dahl, Peter D Emanuel, Mark N Fluchel, Rakesh K Goyal, Robert J Hayashi, Johann Hitzler, Christopher Hugge, Y Lucy Liu, Yoav H Messinger, Donald H Mahoney, Philip Monteleone, Eneida R Nemecek, Philip A Roehrs, Reuven J Schore, Kimo C Stine, Clifford M Takemoto, Jeffrey A Toretsky, Joseph F Costello, Adam B Olshen, Chip Stewart, Yongjin Li, Jing Ma, Robert B Gerbing, Todd A Alonzo, Gad Getz, Tanja A Gruber, Todd R Golub, Kimberly Stegmaier, Mignon L Loh
Journal: Nature Genetics (2015)
Abstract 243: Expression of T-cell checkpoint ligands on circulating tumor cells is modulated following treatment of patients with an anti-tumor DNA vaccine
Authors: Brian T. Rekoske, Brian M. Olson, Douglas G. McNeel
Journal: Cancer Research (2015)

Abstract Background: We have previously demonstrated in a murine tumor model that treatment with a DNA vaccine could lead to increased PD-1 expression on antigen-specific CD8+ T cells, led to upregulated levels of PD-L1 on tumors, and that the anti-tumor efficacy of the vaccine was enhanced when combined with PD-1/L1 blockade. We therefore examined whether prostate cancer patients previously treated with a DNA vaccine similarly upregulated these immunosuppresive ligands on their tumor cells, or the corresponding receptors on tumor-specific CD8+ T cells, and if augmented Th1-type immune responses were detectable following in vitro stimulation with checkpoint blockade. Methods: Circulating tumor cells (CTCs, CD45-/EpCAM+) from 16 prostate cancer patients with castrate-resistant disease, and antigen-specific (tetramer+) CD8+ T cells from those patients that were HLA-A2+ (6/16), were analyzed for their expression of various checkpoint ligands (PD-L1, galectin-9, HVEM) or receptors (PD-1, TIM-3, LAG-3, BTLA, CD160) using flow cytometry before and after treatment with a DNA vaccine encoding prostatic acid phosphatase (PAP). Immune responses to the PAP target antigen were measured in vitro for cytokine secretion via ELISA, or by a trans-vivo DTH-footpad assay, in the presence or absence of PD-1/L1 blockade. Results: Patients that developed either long-term immune responses or changes in PSA doubling time following vaccination had significantly higher levels of PD-L1 and HVEM, and lower levels of galectin-9, on their post-treatment CTCs than patients who did not develop responses. No significant changes in PD-1 or other regulatory receptors were detectable on tetramer+ CD8+ T cells. However, at least 25% of patients following immunization had augmented PAP-specific cytokine secretion in vitro when combined with PD-L1 blockade. PD-1 regulated PAP-specific responses were also observed in patients using the trans vivo DTH assay. Conclusions: These results demonstrate that the development of an anti-tumor immune response via DNA vaccination can lead to changes in checkpoint ligand expression on tumor cells and checkpoint-regulated immune responses. This suggests that combining DNA vaccines with blockade of one or more of these checkpoint pathways could produce enhanced anti-tumor responses in patients with prostate cancer. Citation Format: Brian T. Rekoske, Brian M. Olson, Douglas G. McNeel. Expression of T-cell checkpoint ligands on circulating tumor cells is modulated following treatment of patients with an anti-tumor DNA vaccine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 243. doi:10.1158/1538-7445.AM2015-243
The Impact of Pre-Operative Malperfusion on Outcome in Acute Type A Aortic Dissection
Authors: Martin Czerny, Florian Schoenhoff, Christian Etz, Lars Englberger, Nawid Khaladj, Andreas Zierer, Ernst Weigang, Isabell Hoffmann, Maria Blettner, Thierry P. Carrel
Journal: Journal of the American College of Cardiology (2015)
Neem-seed oil inhibits the growth of breast cancer cells
Authors: Thomas H. Charpentier, Paul T. Wilder, Kristen M. Varney, Eric A. Toth, David J. Weber
Journal: Cancer Research (2006)

1934  The centuries old practice of Ayurvedic medicine in India and Southeast Asia has utilized various parts of the neem tree, azadirachta indica, to provide protection against various diseases including cancer. However, scientists in the Western countries have not yet ascribed disease prevention or management properties to this plant or its products. Given the historical importance of neem in human heath, we tested in vitro the effect of neem-seed oil on the growth of one mouse (RIII/Sa-MT) and one human (MCF-7) breast cancer cell line. Cells were grown in culture dishes to approximately 50% confluence and exposed to the oil at various dilutions; untreated cells were used as controls. The number of viable cells remaining in the culture dishes after 24, 48 and 72 hrs. were determined. Cell death was assessed by morphological analysis, staining of condensed nuclei with Hoechst dye, and TUNEL assays. The results obtained after various time points indicated that neem-seed oil induced a slow, non-apoptotic process of cell death. To asses the effect of neem oil on the in vivo growth of mammary tumor cells, four-to-six-weeks old RIII/Sa female mice were inoculated with 2 million RIII/Sa-MT cells into number four mammary glands. Most of the inoculated mice developed palpable tumors within 10 days. The animals were divided into 2 groups: one group of 15 mice was kept as control, and the other group of 15 mice was inoculated with 50 μl neem oil at a dilution of 1: 25 in the vicinity of the tumor once a week followed by recording the size of the tumors grown during a period of 50 days. It was found that neem-seed oil-treatment reduced the tumor load by more than 50%. Taken together, our results indicate for the first time that a neem product is quite effective in inhibiting the growth of breast cancer cells in culture as well as in vivo, and suggest that the product could well be applied in human breast cancer chemoprevention and/or to combat tumor burden.
Abstract 14050: The Gut Flora Promotes Endothelial Dysfunction Through Vascular MicroRNA-204-mediated Down-regulation of Endothelial Sirtuin1
Authors: Ajit Vikram, Young-Rae Kim, Santosh Kumar, Julia S Jacobs, Kaikobad Irani
Journal: Circulation (2014)

The gut flora contributes to development of atherosclerosis. Endothelial dysfunction, one manifestation of which is impaired endothelium-dependent vasorelaxation, accompanies and promotes atherosclerotic vascular disease. Here we show that gut flora impair endothelium-dependent vasorelaxation by remotely up-regulating microRNA-204 (miR-204) which downregulates SIRTUIN1 (SIRT1) in the vascular wall. Microarray analysis in aortas of germ-free mice revealed a set of down-regulated microRNAs, including miR-204, which target SIRT1. Suppression of gut flora in mice with antibiotics in drinking water decreased aortic miR-204, increased aortic SIRT1, and improved endothelium-dependent vasorelaxation, effects that were reversed with discontinuation of antibiotics. In addition, miR-204 mimic impaired endothelium-dependent aortic vasorelaxation ex vivo. Moreover, high-fat diet feeding stimulated aortic miR-204, suppressed SIRT1, and impaired endothelial function, all of which were mitigated by administration of antibiotics, and reversed with stoppage of antibiotics. In contrast, antibiotics did not improve high-fat diet-induced endothelial dysfunction in mice conditionally lacking endothelial SIRT1. In addition, anti-miR-204 delivered systemically prevented high-fat diet-induced endothelial dysfunction and vascular SIRT1 decrease. Finally, serum from mice on antibiotics suppressed miR-204, and increased SIRT1, in endothelial cells, effects that were not observed with serum from mice in which antibiotics were discontinued. Therefore, the gut flora remotely downregulates endothelial SIRT1 through miR-204, leading to impairment of endothelial function.
Combined modality therapy of Hodgkin's disease: 10-year results of National Cancer Institute of Canada Clinical Trials Group multicenter clinical trial.
Authors: L Yelle, D Bergsagel, V Basco, T Brown, R Bush, J Gillies, L Israels, A Miller, D Rideout, D Whitelaw
Journal: Journal of Clinical Oncology (1991)

The purpose of this study was to compare four methods of treatment for stage III-IV Hodgkin's disease. Between January 1972 and September 1976, 266 patients with stage IIIB, IVA, and IVB Hodgkin's disease from 21 cancer treatment centers across Canada were registered as eligible; 40 were found to be ineligible. Of the 226 remaining patients, only seven were followed for less than 10 years. All patients received three courses of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy, which induced a complete response (CR) in 36%; an additional 42% obtained adequate disease control. Patients were randomly assigned to (1) treatment with radiation to the abdomen and mantle (group AX3, 62 patients) or (2) continue their treatment with an additional three courses of MOPP (group A, 105 patients). For the A group, a second randomization took place 3 months later (regardless of status at that time) to (1) no further treatment (AC6, 23 patients), (2) radiotherapy to the abdomen and mantle (AX6, 48 patients), or (3) maintenance chemotherapy at 3-month intervals for 1 year (AC10, 26 patients). The survival of AX3 patients was somewhat better than for the A group, but the difference was not significant (P = .0565). However, there was a significant interaction (P = .0029) between age and treatment, so that among patients less than 30 years of age, the survival of the A group was better, whereas for older patients, treatment with AX3 resulted in improved survival. Age itself remained a significant prognostic factor for survival after controlling for the amount of radiotherapy delivered to the abdomen and the dose intensity of vincristine for the first three courses of chemotherapy. The addition of radiation therapy to MOPP significantly reduced the frequency of nodal relapses. These results suggest that combined modality therapy may be beneficial for some patients with Hodgkin's disease and that age must be carefully considered in interpreting the results of clinical trials in Hodgkin's disease.
Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials
Authors: Simone Mocellin, Pierluigi Pilati, Marta Briarava, Donato Nitti
Journal: JNCI Journal of the National Cancer Institute (2015)

Several agents have been advocated for breast cancer primary prevention. However, few of them appear effective, the associated severe adverse effects limiting their uptake.We performed a comprehensive search for randomized controlled trials (RCTs) reporting on the ability of chemoprevention agents (CPAs) to reduce the incidence of primary breast carcinoma. Using network meta-analysis, we ranked CPAs based simultaneously on efficacy and acceptability (an inverse measure of toxicity). All statistical tests were two-sided.We found 48 eligible RCTs, enrolling 271 161 women randomly assigned to receive either placebo or one of 21 CPAs. Aromatase inhibitors (anastrozole and exemestane, considered a single CPA class because of the lack of between-study heterogeneity; relative risk [RR] = 0.468, 95% confidence interval [CI] = 0.346 to 0.634), arzoxifene (RR = 0.415, 95% CI = 0.253 to 0.682), lasofoxifene (RR = 0.208, 95% CI = 0.079 to 0.544), raloxifene (RR = 0.572, 95% CI = 0.372 to 0.881), tamoxifen (RR = 0.708, 95% CI = 0.595 to 0.842), and tibolone (RR = 0.317, 95% CI = 0.127 to 0.792) were statistically significantly associated with a therapeutic effect, which was restricted to estrogen receptor-positive tumors of postmenopausal women (except for tamoxifen, which is active also during premenopause). Network meta-analysis ranking showed that the new selective estrogen receptor modulators (SERMs) arzoxifene, lasofoxifene, and raloxifene have the best benefit-risk ratio. Aromatase inhibitors and tamoxifen ranked second and third, respectively.These results provide physicians and health care regulatory agencies with RCT-based evidence on efficacy and acceptability of currently available breast cancer CPAs; at the same time, we pinpoint how much work still remains to be done before pharmacological primary prevention becomes a routine option to reduce the burden of this disease.
Late-breaking abstract: Adaptive servo-ventilation in central sleep apnea. Ambulatory nocturnal pulse oximetry, a simplified method for monitoring outpatient?
Authors: Santiago Juarros Martínez, Enrique Macías Fernandez, María Villaverde de Lucas, Milagros del Olmo Chiches, Isabel Muñoz Diez, Mari Fe Muñoz Moreno, David Vielba Dueñas, Agueda Herrero Pérez, Vicente Roig Figueroa, Isabel Ramos Cancelo, Carlos Disdier Vicente
Journal: European Respiratory Journal (2014)

Background: Adaptive servo-ventilation (ASV) is an effective therapy for patients with hyperventilation-related central sleep apnea (CSA). Simplified method, such as ambulatory nocturnal pulse oximetry (NPO), can help in controlling outpatient therapy.

Methods: Patients who started ASV therapy in 2012 were analyzed. Basal oximetry parameters (Oxygen Desaturation Index (ODI), CT90) in the time of diagnosis, versus the same parameters by ambulatory NPO after 1 year of therapy were compared.

Results: 19 patients. Cardiac causes in 81% (fig 1).

![Figure][1] 



Cheyne-Stokes Breathing (CBS) in 52.6%. After 1 year of therapy: Patients with heart disease, ODI decreased from 35.9 ± 12 to 8.6 ± 6.7 (p 0.012). Patients without heart disease, ODI declined from 51.2 ± 34 to 8.6 ± 8.7 (p 0.043). Patients with CBS, ODI decreased from 36.7 ± 11 to 7.7 ± 6.5 (p 0.018). Patients without CBS, ODI reduced from 46.9 ± 31.5 to 9.6 ± 8.4 (p 0.018) and CT90 decreased from 18.4% ± 13.9% to 4.1 ± 5.2% (p 0.046). 36.8% of cases used ASV over 5 hours daily. In these, ODI decreased from 39.5 ± 12.7 to 7.1 ± 5.3 (p 0.028).

Conclusions: ASV to treat CSA, after 1 year, produces significant improvement in ODI in all patients, regardless of cause, with or without associated CBS. Good compliant patients show significant improvement in ODI. Ambulatory NPO can be useful for control, during ambulatory monitoring of these patients.

 [1]: pending:yes
Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3)
Authors: B Bhatnagar, J S Blachly, J Kohlschmidt, A-K Eisfeld, S Volinia, D Nicolet, A J Carroll, A W Block, J E Kolitz, R M Stone, K Mrózek, J C Byrd, C D Bloomfield
Journal: Leukemia (2015)
Enhanced FcRn-dependent transepithelial delivery of IgG by Fc-engineering and polymerization
Authors: Stian Foss, Algirdas Grevys, Kine Marita Knudsen Sand, Malin Bern, Pat Blundell, Terje E. Michaelsen, Richard J. Pleass, Inger Sandlie, Jan Terje Andersen
Journal: Journal of Controlled Release (2015)
Incidence of Cancer and Mortality Following α-Tocopherol and β-Carotene Supplementation
Authors: Jarmo Virtamo, Pirjo Pietinen, Jussi K Huttunen, Pasi Korhonen, Nea Malila, Mikko J Virtanen, Demetrius Albanes, Phil R Taylor, Paul Albert
Journal: JAMA (2003)

In the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, alpha-tocopherol supplementation decreased prostate cancer incidence, whereas beta-carotene increased the risk of lung cancer and total mortality. Postintervention follow-up provides information regarding duration of the intervention effects and may reveal potential late effects of these antioxidants.To analyze postintervention effects of alpha-tocopherol and beta-carotene on cancer incidence and total and cause-specific mortality.Postintervention follow-up assessment of cancer incidence and cause-specific mortality (6 years [May 1, 1993-April 30, 1999]) and total mortality (8 years [May 1, 1993-April 30, 2001]) of 25 563 men. In the ATBC Study, 29 133 male smokers aged 50 to 69 years received alpha-tocopherol (50 mg), beta-carotene (20 mg), both agents, or placebo daily for 5 to 8 years. End point information was obtained from the Finnish Cancer Registry and the Register of Causes of Death. Cancer cases were confirmed through medical record review.Site-specific cancer incidence and total and cause-specific mortality and calendar time-specific risk for lung cancer incidence and total mortality.Overall posttrial relative risk (RR) for lung cancer incidence (n = 1037) was 1.06 (95% confidence interval [CI], 0.94-1.20) among recipients of beta-carotene compared with nonrecipients. For prostate cancer incidence (n = 672), the RR was 0.88 (95% CI, 0.76-1.03) for participants receiving alpha-tocopherol compared with nonrecipients. No late preventive effects on other cancers were observed for either supplement. There were 7261 individuals who died by April 30, 2001, during the posttrial follow-up period; the RR was 1.01 (95% CI, 0.96-1.05) for alpha-tocopherol recipients vs nonrecipients and 1.07 (95% CI, 1.02-1.12) for beta-carotene recipients vs nonrecipients. Regarding duration of intervention effects and potential late effects, the excess risk for beta-carotene recipients was no longer evident 4 to 6 years after ending the intervention and was primarily due to cardiovascular diseases.The beneficial and adverse effects of supplemental alpha-tocopherol and beta-carotene disappeared during postintervention follow-up. The preventive effects of alpha-tocopherol on prostate cancer require confirmation in other trials. Smokers should avoid beta-carotene supplementation.
Abstract 4203: Retinoic acid signal and annexins: A vicious circle of breast tumorigenesis
Authors: Stefano Rossetti, Wiam Bshara, Johanna Reiners, Francesca Corlazzoli, Austin Miller, Nicoletta Sacchi
Journal: Cancer Research (2015)

Abstract Physiological retinoic acid (RA), the bioactive derivative of Vitamin A, is a signal necessary for epithelial cell morphogenesis. During acinar morphogenesis of normal breast epithelial cells in three dimensional (3D) culture, physiological RA activates in a spatiotemporal fashion both genomic and non-genomic RA receptor alpha (RARA) signalings, thus leading to growth-arrested acini with a lumen lined by a layer of polarized cells. In contrast, lack of activation of genomic RARA by physiological RA results in the formation of 3D amorphous acini without lumen and with uncontrolled proliferation of the luminal cells. This is similar to what is observed in early in situ breast cancer lesions, such as ductal carcinoma in situ (DCIS). Different factors that, directly or indirectly, affect genomic RARA in normal breast epithelial cells and, consequently, the morphogenetic action of RA signal, lead to deregulation of members of the Annexin family, including Annexin A8 (ANXA8). Interestingly, upregulation of ANXA8 is sufficient to affect the genomic RARA-mediated RA signaling with consequent development of 3D amorphous acini. Thus, ANXA8 upregulation consequent to functional inhibition of genomic RARA by different factors seems to reinforce through a feedback loop the extent of functional inhibition of genomic RARA itself. It is of significance that ANXA8 upregulation in DCIS does correlate with tumor grade and stage. Acknowledgements: Funding for this study was provided by the NCI R01 CA127614 grant, the Susan Komen Foundation, the Breast Cancer Coalition of Rochester, the Friends for an Earlier Breast Cancer Test, the Terri Brodeur Breast Cancer Foundation. Citation Format: Stefano Rossetti, Wiam Bshara, Johanna Reiners, Francesca Corlazzoli, Austin Miller, Nicoletta Sacchi. Retinoic acid signal and annexins: A vicious circle of breast tumorigenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4203. doi:10.1158/1538-7445.AM2015-4203
Electroanatomical Correlation of Repolarization Abnormalities in Brugada Syndrome
Authors: Satoshi Nagase, Shigeki Hiramatsu, Hiroshi Morita, Nobuhiro Nishii, Masato Murakami, Kazufumi Nakamura, Kengo F. Kusano, Hiroshi Ito, Tohru Ohe
Journal: Journal of the American College of Cardiology (2010)
Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial
Authors: Irwin Walker, Tony Panzarella, Stephen Couban, Felix Couture, Gerald Devins, Mohamed Elemary, Geneviève Gallagher, Holly Kerr, John Kuruvilla, Stephanie J Lee, John Moore, Thomas Nevill, Gizelle Popradi, Jean Roy, Kirk R Schultz, David Szwajcer, Cynthia Toze, Ronan Foley
Journal: The Lancet Oncology (2015)
Treatment of hyperactive children with D-phenylalanine
Authors: A J Zametkin, F Karoum, J L Rapoport
Journal: American Journal of Psychiatry (1987)

Eleven hyperactive boys were treated for 2 weeks with D-phenylalanine (20 mg/kg per day) and for 2 weeks with placebo in a double-blind crossover study. Tests included parent and teacher behavior ratings, cognitive measures, and blood and urine measures of norepinephrine, amino acids, and trace amines. No significant improvement or deterioration in behavior and no side effects were noted, and only serum phenylalanine was increased by the active treatment phase. This provides reassurance about the toxicity of aspartame, a food additive that contains phenylalanine, but argues against precursor loading treatment of hyperactivity.
IFN-λ resolves inflammation via suppression of neutrophil infiltration and IL-1β production
Authors: Katrina Blazek, Hayley L. Eames, Miriam Weiss, Adam J. Byrne, Dany Perocheau, James E. Pease, Sean Doyle, Fiona McCann, Richard O. Williams, Irina A. Udalova
Journal: The Journal of Experimental Medicine (2015)

The most studied biological role of type III interferons (IFNs) has so far been their antiviral activity, but their role in autoimmune and inflammatory diseases remains largely unexplored. Here, we show that treatment with IFN-λ2/IL-28A completely halts and reverses the development of collagen-induced arthritis (CIA) and discover cellular and molecular mechanisms of IL-28A antiinflammatory function. We demonstrate that treatment with IL-28A dramatically reduces numbers of proinflammatory IL-17–producing Th17 and γδ T cells in the joints and inguinal lymph nodes, without affecting T cell proliferative responses or levels of anticollagen antibodies. IL-28A exerts its antiinflammatory effect by restricting recruitment of IL-1b–expressing neutrophils, which are important for amplification of inflammation. We identify neutrophils as cells expressing high levels of IFN-λ receptor 1 (IFNLR1)–IL-28 receptor α (IL28RA) and targeted by IL-28A. Our data highlight neutrophils as contributors to the pathogenesis of autoimmune arthritis and present IFN-λs or agonists of IFNLR1–IL28RA as putative new therapeutics for neutrophil-driven inflammation.