tbuckley/cabot-search huggingface dataset:
Carers' views of topical corticosteroid use in childhood eczema: a qualitative study of online discussion forums
Authors: E.J. Teasdale, I. Muller, M. Santer
Journal: British Journal of Dermatology (2016)

Childhood eczema is very common and can have substantial impact on quality of life. One of the main treatments is topical corticosteroids, but these are often underused by parents and carers for reasons that include concerns about safety.To explore understandings and concerns about topical corticosteroids among parents and carers of children with eczema who had posted messages in online forums.A qualitative study of messages and their resultant discussions about topical corticosteroids for childhood eczema posted by parents and carers on two U.K.-based discussion forums.Ninety-five forum users involved in 27 discussions relating to topical corticosteroid use in childhood eczema were identified dating from 2003 to 2015. Analysis of discussions highlighted three themes: (i) diverse beliefs about the use of topical corticosteroids; (ii) uncertainty and confusion about using and applying topical corticosteroids; and (iii) seeking to resolve conflicting advice received offline and advice on navigating health services. People expressed a general sense of cautiousness about topical corticosteroids, wide-ranging concerns and considerable confusion, for instance about potency or safe duration of use. They sought advice from other forum users who they perceived as having experiential expertise. Some posts attempted to reassure that topical corticosteroids were safe if used correctly, but overall the discussions seemed likely to amplify existing concerns.Given the prevalence of concerns and uncertainties about topical corticosteroids, signposting parents and carers of children with eczema towards detailed, credible information about how to use topical corticosteroids safely would be beneficial. In the absence of such information, parents and carers are likely to turn to online discussion forums where, although much useful support and advice can be found, the credibility of advice cannot be assured.
Long term follow up data of a phase II study of concurrent radiotherapy (RT) and gemcitabine (Gem) for patients with stage III or IV squamous cell carcinoma of the head and neck (SCCHN)
Authors: P. M. Specenier, D. Van Den Weyngaert, C. Van Laer, J. Van Den Brande, M. Huizing, S. Altintas, J. Vermorken
Journal: Journal of Clinical Oncology (2006)

5574 Background: RT with concurrent chemotherapy is superior to RT alone as treatment for locally advanced SCCHN. Gem is a potent radiosensitizer in vitro and in vivo and in addition has a good activity in SCCHN. Exploitation of these properties was the rationale for a single institution phase II study which evaluates the efficacy and toxicities of standard RT + weekly low dose Gem. Methods: Eligible were patients with primary inoperable or locally advanced stage III and IV SCCHN. Treatment: Planned RT was 70 Gy over 7 weeks with weekly Gem 100 mg/m 2 within 2 hours prior to RT (Eisbrüch et al., ASCO, 1997, 1998). Presented endpoints are response rate (according to WHO), acute and late toxicity (according to NCICTC), disease free survival (DFS), local relapse free survival (LRFS) and overall survival (OS). Results: 26 patients (21 male, 5 female; performance status 0–2; no prior treatment) entered the study between November 1998 and September 2003. Median age was 56 years (range 48–78). Tumor sites were oropharynx (6), hypopharynx (17), glottis (1), paranasal sinus (1), unknown (1). Clinical stage was III (2) or IV (24). 7 Patients had T4N2 disease and 2 had T4N3 disease. Patients received a median of 7 Gem cycles (range 2–8) and a median of 70 Gy (66–84.75). 7 patients underwent radical neck dissection. Grade 3–4 acute toxicities included mucositis (22/26), dermatitis (18/26), pharyngitis and/or oesophagitis (21/26), pain (7/25), xerostomia (1/24), neutropenia (1/26) and anemia (1/26). 21/26 patients needed tube feeding and 21/26 needed to be hospitalized. After recovery from acute toxicity 6/23 could feed normally, 5/23 needed soft food, 5/23 were able to swallow liquid food and 2/23 required permanent tube feeding. Response was evaluable in 22 patients (11 CR, 11 PR). Intial relapse was at distant sites in 9/26 and local in 8/26. Median follow up of the patients still alive is 46 months. Median OS is 576 days, median DFS is 401 days, median LRFS is not reached. 7/26 remain free of disease more than 3 years after end of treatment. Conclusions: RT + Gem (100 mg/m 2 /week) is feasible but toxic. The combination is highly active in SCCHN and provides a good long term local control. [Table: see text]
Reduced Intensity Conditioning Allogeneic Haematopoietic Stem Cell Transplantation - a Treatment Option in Elderly or Comorbid Patients with Acute Lymphatic Leukemia
Authors: Vladan Vucinic, Theresa Tumewu, Georg-Nikolaus Franke, Sebastian Schwind, Nadja Jaekel, Simone Heyn, Wolfram Poenisch, Haifa Kathrin Al-Ali, Sabine Leiblein, Rainer Krahl, Madlen Jentzsch, Gerhard Behre, Dietger Niederwieser
Journal: Blood (2014)
TSC2 Deficiency Unmasks a Novel Necrosis Pathway That Is Suppressed by the RIP1/RIP3/MLKL Signaling Cascade
Authors: Piotr T. Filipczak, Cindy Thomas, Wenshu Chen, Andrew Salzman, Jacob D. McDonald, Yong Lin, Steven A. Belinsky
Journal: Cancer Research (2016)

Tuberous sclerosis complex (TSC) is a genetic multiorgan disorder characterized by the development of neoplastic lesions in kidney, lung, brain, heart, and skin. It is caused by an inactivating mutation in tumor suppressor genes coding the TSC1/TSC2 complex, resulting in the hyperactivation of mTOR- and Raf/MEK/MAPK-dependent signaling that stimulates tumor cell proliferation and metastasis. Despite its oncogenic effect, cells with TSC deficiency were more sensitive to oxidative stress and dependent on mitochondrial metabolism, providing a rationale for a new therapeutic approach. The current study shows that simultaneous inhibition of two major pathways regulating redox homeostasis using l-buthionine-sulfoximine (BSO, glutathione synthesis inhibitor) and auranofin (thioredoxin reductase inhibitor) induces oxidative burst, mitochondrial damage, and necrotic cell death in TSC-deficient cells in a highly synergistic and cell context-specific manner. Furthermore, blocking RIP1/RIP3/MLKL-dependent signaling using chemical inhibitors necrostatin-1 (Nec-1) and necrosulfonamide (NSA) synergizes with BSO and auranofin in killing TSC-deficient cells. Expression analysis demonstrated that RIP1, RIP3, and MLKL protein levels are elevated in cells with TSC2 deficiency, and their inactivation enhances mitochondrial dysfunction in a glutaminolysis-dependent and autophagy-independent manner. Finally, supplementation with the mitochondrial metabolite α-ketoglutarate, whose synthesis is regulated by RIP1/RIP3/MLKL, rescues cells from the sensitizing effect of Nec-1 and NSA. Together, this study identifies a previously unrecognized novel regulated necrotic death pathway that involves mitochondrial homeostasis, is suppressed by the RIP1/RIP3/MLKL signaling in TSC-deficient cells, and could be a promising therapeutic target for TSC-associated tumors. Cancer Res; 76(24); 7130-9. ©2016 AACR.
The Role of LIGHT in Multiple Myeloma-Bone Disease
Authors: Giacomina Brunetti, Rita Rizzi, Angela Oranger, Isabella Gigante, Giorgio Mori, Grazia Taurino, Teresa Mongelli, Graziana Colaianni, Adriana Di Benedetto, Roberto Tamma, Giuseppe Ingravallo, Anna Napoli, Anna Mestice, Paola Curci, Silvia Colucci, Giorgina Specchia, Maria Grano
Journal: Blood (2014)
“Muddled thinking” over cannabis leaves patients in limbo, warn campaigners
Authors: Nigel Hawkes
Journal: BMJ (2016)

Companies selling cannabis based products have been told to remove them from the market within 28 days, after a review by the Medicines and Healthcare Products Regulatory Agency (MHRA) determined that they were medicinal products.

Campaigners for cannabis law reform welcomed the recognition that cannabidiol (CBD) had medicinal properties but warned that the MHRA’s action would deprive thousands of users of a product they relied on. They said that it was impossible to obtain marketing authorisation in the timescale given and may never be possible given the high costs of clinical trials and lack of patent protection for a product that contained many components.

“In the long term, it’s a good thing,” said Peter Reynolds of the pressure group CLEAR (Cannabis …
GW26-e0267 The Prevalence of Depression and Anxiety in Patients with Acute Coronary Syndrome
Authors: Feng Liang, Xiuhua Ma, Shuoqiang Hu, Chengwei Xing, Xin Li, Dongjing Zhao, Lantang Han, Shujun Cao, Dayi Hu
Journal: Journal of the American College of Cardiology (2015)
Phase I dose escalation trial of MVA-BN-PRO in men with nonmetastatic castration-resistant prostate cancer.
Authors: David G. McLeod, George W. Adams, Marc C. Gittleman, David L. Bihartz, Richard B. Reiling, Henry E. Ruiz, James S. Cochran, Julie Prettyman, Alain Delcayre, Wayne R. Godfrey, Fatema A. Legrand, Grace Mann, Olga Bandman
Journal: Journal of Clinical Oncology (2013)

193 Background: MVA-BN-PRO is an investigational prostate cancer immunotherapy comprising of a highly attenuated non-replicating vaccinia virus engineered to encode prostate specific antigen (PSA) and prostate acid phosphatase (PAP) proteins. Preclinical studies in mouse tumor models demonstrated vaccine-mediated induction of anti-PSA and PAP specific immune responses and anti-tumor activity. Results of the open-label multi-center evaluation in subjects with non-metastatic castration resistant prostate cancer are presented. Methods: Eligible subjects had documented prostate cancer with a rising PSA while on androgen suppression therapy and were chemotherapy naïve. Three cohorts of subjects were immunized subcutaneously receiving either 1, 2 or 4 injections of study drug (1 injection = 1×10 8 tissue culture infectious dose, TCID 50 ) at monthly intervals for three months (treatment). If the vaccinations were tolerated, re-treatment with an additional 3 monthly vaccinations was administered at the same dose. Responders, defined as subjects with stable or declining PSA at week 29 compared with baseline, were offered a 1-year extended treatment of up to 12 monthly vaccinations. Subjects were followed for one year after their last vaccination. The primary endpoint was safety. Immune responses (humoral and cellular) to MVA-BN-PRO including the transgenes PSA and PAP were assessed by the ELISA and ELISPOT assays, respectively. Exploratory analyses included anti-tumor activity as evaluated by serum PSA levels and progression by bone scan, per investigator determined, or death. Results: Twenty-four subjects were dosed. All subjects completed the initial 3 vaccinations (treatment) and 21 subjects received 6 vaccinations (re-treatment). Seven responders received additional vaccinations during the extended treatment. No dose-limiting toxicities were reported. There were no reported ≥ Grade 3 treatment-related adverse events (AE). The most common related AEs were Grade 1 or 2 general disorders and administration site reactions. Conclusions: MVA-BN-PRO was well tolerated. Results from immune analysis and clinical activity measured by PSA levels or radiological progression will be presented. Clinical trial information: NCT00629057.
Signaling pathways mediating spontaneous tumor promotion in BK5.IGF-1 transgenic mice skin
Authors: Okkyung Rho, Jerry Lu, Erik Wilker, John Digiovanni
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5721 

Overexpression of human IGF-1, using the bovine keratin 5 (BK5) promoter induces a persistent epidermal hyperplasia and leads to spontaneous skin tumor promotion. In previous work, MAPK, PI3K, and Akt activities were found to be elevated in the epidermis of BK5.IGF-1 transgenic mice compared to non-transgenic littermates. In the present study, we have examined the importance of PI3K/Akt signaling pathway in mediating the skin phenotype and the skin tumor promoting action of IGF-1 in these mice. Western blot analyses using epidermal lysates showed that signaling components downstream of PI3K/Akt were altered in BK5.IGF-1 mice. In this regard, increased serine 9 phosphorylation of GSK-3beta and hypophosphorylation and increased protein levels of beta-catenin were observed in the epidermis of BK5.IGF-1 transgenic mice. These data suggested that components of downstream of Akt might be affected including cell cycle machinery. Expression of cell cycle related proteins, particularly cyclin D1, E, and A, E2F and E2F4 protein levels were all elevated as well as higher cdk4/cyclin D1 and cdk2/cyclin E complex formation in the epidermis of BK5.IGF-1 transgenic mice. In addition, levels of Mdm-2, a major regulator of p53, were also elevated in epidermis of BK5.IGF-1 mice. Transgenic mice that overexpress a wild-type form of Akt using the BK5 promoter displayed strikingly similar biochemical changes in the epidermis. These mice also showed spontaneous skin tumor promotion and heightened sensitivity to skin tumor promotion by TPA similar to BK5.IGF-1 transgenic mice. In further studies, the PI3K inhibitor, LY294002, significantly blocked IGF-1-mediated epidermal hyperplasia and skin tumor promotion in DMBA initiated BK5.IGF-1 mice. Furthermore, inhibition of PI3K/Akt with LY294002 reversed many of cell cycle related changes. Collectively, the current results support the hypothesis that elevated PI3K/Akt activity and subsequent activation of one or more downstream effector pathways contribute significantly to the tumor promoting action of IGF-1 in the epidermis of BK5.IGF-1 mice. Supported by NIH Grant CA37111, UTMDACC Core Grant CA16672, and NIEHS Center Grant ES07784.
GW26-e4369 The effectiveness of ibutilide and the factors that affect the successful cardioversion and ibutilide-induced malignant arrhythmia
Authors: Xiaoying Chen, Yanzong Yang, Lianjun Gao, Dong Chang, Xiaomeng Yin, Yingxue Dong, Xiaohong Yu, Xianjie Xiao, Shulong Zhang
Journal: Journal of the American College of Cardiology (2015)
Cord Blood Transplantation after Non Myeloablative Conditioning (Minneapolis Protocol): Impact on Transplant Outcomes in 112 Adults with Hematologic Malignancy. A French Multicentric Study of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and Eurocord.
Authors: B. Rio, D. Blaise, M. Renaud, M. Uzunov, J.H. Bourhis, P. Ceballos, S. Maury, C.E. Bulabois, L. Fouillard, E. Deconinck, N. Dhedin, A. Sirvent, M. Michallet, N. Contentin, A. Huynh, A. Buzyn, S. Francois, R. Tabrizi, I. Yakoub-Agha, P. Chevalier, T. de Revel, S. Lapusan, F. Garnier, K. Boudjedir, Eliane Gluckman, V. Rocha
Journal: Blood (2007)
Patient-reported outcomes (PROs) in the double-blind phase 3 trial (NGR015) with NGR-hTNF plus best investigator choice (BIC) versus placebo plus BIC for previously treated patients with malignant pleural mesothelioma (MPM).
Authors: Vanesa Gregorc, Alessandra Bulotta, Maria G Viganò, Giovanni Citterio, Giovanna Petrella, Elena Brioschi, Monika Ducceschi, Luca Gianni, Scialini Colombi, Gloria Rossoni, Giulia Salini, Veronica Savia, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2016)

e20077 Background: In the NGR015 trial, patients failing a pemetrexed-based regimen were randomly assigned to weekly NGR-hTNF (N; n = 200) or placebo (P; n = 200), both given with BIC that included single-agent gemcitabine, vinorelbine or doxorubicin (95% of patients) or supportive care (5%). By predefined OS analyses, there was an interaction only between treatment and treatment-free interval (TFI) after end of first-line therapy (p = 0.008). In the short TFI subset ( < median; n = 198), N compared with P significantly improved OS (HR = 0.69; p = 0.02) and PFS (HR = 0.69; p = 0.01) Methods: PROs were collected by means of MPM-adapted Lung Cancer Symptom Scale (LCSS) questionnaires, which consisted of 100-mm visual analog scales (with 0 being the best rating) for 8 items: 5 major symptoms (appetite loss, fatigue, cough, dyspnea and pain) plus 3 summary items (total symptom distress, activity status and overall quality of life). Outcomes were measured by time to symptomatic deterioration (TSD; ≥ 25% increase) and responder analysis (patients with ≥ 10% decrease) Results: At baseline, completion rate (90%) and scores (median, 36%) were identical in the two groups. Median TSD did not differ between N and P (3.0 and 3.1 months, respectively; HR for symptomatic worsening = 1.01; p = 0.97). In the short TFI subset, there were no significant differences between N and P in completion rate (89% and 76%) and baseline score (median, 36% and 38%). Baseline scores were inversely related to OS (p < 0.0001). Median TSD was slightly longer for N than for P (HR = 0.78; p = 0.29). Among patients with short TFI, decreased scores (with negative changes denoting improvement) were reported over all time points from baseline to 2nd, 4th and 6th cycle (median, -1.5% vs 5%, -4% vs 6% and -3% vs 2% for N vs P, respectively). The proportion of patients with ≥ 10% decrease was 49% vs 37% and median OS among these patients was 15.6 vs 8.4 months for N vs P, respectively Conclusions: Clinical benefits observed by adding NGR-hTNF to chemotherapy in pretreated MPM patients with short TFI were not associated with detrimental effects on patient self-reported outcomes Clinical trial information: NCT01098266.
An Open-Label Phase II Study to Investigate the Safety and Efficacy of Rituximab Plus Chlorambucil in Previously Untreated Patients with CD20-Positive B-Cell Chronic Lymphocytic Leukaemia (CLL).
Authors: Peter Hillmen, John G. Gribben, George A Follows, Donald W. Milligan, Hazem A. Sayala, Paul Moreton, David Oscier, Claire E. Dearden, Daniel B. Kennedy, Andrew R. Pettitt, Amit Nathwani, Dena Cohen, Walter M Gregory, Andy C. Rawstron, Colin R.W. Hayward, Christopher Pocock
Journal: Blood (2009)
Long Term Survival of Patients with Chronic Myelocytic Leukemia after Allogeneic Stem Cell Transplant Using a Reduced Intensity Regimen of Melphanlan, Lomustine and Cyclophosphamide.
Authors: Yongqian Jia, Ting Liu, Ting Niu, Caigang Xu, Wentong Meng, Jianchun Lu, Hui Wang
Journal: Blood (2005)
METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N 6‐methyladenosine‐dependent primary MicroRNA processing
Authors: Jin‐zhao Ma, Fu Yang, Chuan‐chuan Zhou, Feng Liu, Ji‐hang Yuan, Fang Wang, Tian‐tian Wang, Qing‐guo Xu, Wei‐ping Zhou, Shu‐han Sun
Journal: Hepatology (2016)

N 6 ‐Methyladenosine (m 6 A) modification has been implicated in many biological processes. However, its role in cancer has not been well studied. Here, we demonstrate that m 6 A modifications are decreased in hepatocellular carcinoma, especially in metastatic hepatocellular carcinoma, and that methyltransferase‐like 14 (METTL14) is the main factor involved in aberrant m 6 A modification. Moreover, METTL14 down‐regulation acts as an adverse prognosis factor for recurrence‐free survival of hepatocellular carcinoma and is significantly associated with tumor metastasis in vitro and in vivo . We confirm that METTL14 interacts with the microprocessor protein DGCR8 and positively modulates the primary microRNA 126 process in an m 6 A‐dependent manner. Further experiments show that microRNA 126 inhibits the repressing effect of METTL14 in tumor metastasis. Conclusion : These studies reveal an important role of METTL14 in tumor metastasis and provide a fresh view on m 6 A modification in tumor progression. (H epatology 2017;65:529‐543).
Phase I Study of the Combination of Carfilzomib and Panobinostat for Patients with Relapsed and Refractory Myeloma: A Multiple Myeloma Research Consortium (MMRC) Clinical Trial
Authors: Jonathan L. Kaufman, Todd Zimmerman, Cara A Rosenbaum, Ajay K. Nooka, Leonard T Heffner, R. Donald Harvey, Charise Gleason, Colleen Lewis, Cathy Sharp, Kenisha W Barron, Sagar Lonial
Journal: Blood (2014)
The Role of Proteinase Inhibitor 9 (PI-9) in Granzyme B/Perforin-Mediated Cytotoxicity Induced by Cytotoxic T Cells in Allogeneic Hematopoietic Stem Cell Transfusion.
Authors: Osamu Horie, Tohru Murayama, Katsuyasu Saigo, Yasushi Utsunomiya, Ryukichi Ryo, Mitsuhiro Ito
Journal: Blood (2006)
MicroRNA-29b mediates altered innate immune development in acute leukemia
Authors: Bethany L. Mundy-Bosse, Steven D. Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C. Mao, Elshafa H. Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M. Croce, Karilyn Larkin, John C. Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G. Freud, Michael A. Caligiuri
Journal: Journal of Clinical Investigation (2016)

Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell–depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients. This absence was not due to elimination by cell death or selective reduction in proliferation, but rather to the result of a block in NK cell differentiation. Indeed, NK cells from leukemic mice and humans with AML showed lower levels of TBET and EOMES, transcription factors that are critical for terminal NK cell differentiation. Further, the microRNA miR-29b, a regulator of T-bet and EOMES, was elevated in leukemic NK cells. Finally, deletion of miR-29b in NK cells reversed the depletion of this NK cell subset in leukemic mice. These results indicate that leukemic evasion of NK cell surveillance occurs through miR-mediated dysregulation of lymphocyte development, representing an additional mechanism of immune escape in cancer.
T Cell Activation By Plasmacytoid Dendritic Cells Is Augmented By Inhibition of Vasoactive Intestinal Polypeptide Signaling: Implications for Cellular Immunotherapy
Authors: Jingxia Li, Reema Panjwani, Jian-Ming Li, Cynthia R. Giver, Maryellen Malone, Edmund K Waller
Journal: Blood (2015)