tbuckley/cabot-search huggingface dataset:
Endoscopic submucosal dissection for inflammatory bowel disease-related dysplasia: feasible, but be ready for a difficult procedure
Authors: Adolfo Parra-Blanco, Krish Ragunath
Journal: Endoscopy (2017)

See also:Endoscopic submucosal dissection of colitis-related dysplasia Endoscopy eFirstDOI: 10.1055/s-0043-114410
Phase 2 clinical study of metronomic oral cyclophosphamide (MOC) in advanced sarcomas
Authors: R. Quek, S.L. Lim, W.Y. Chay, L.T. Soh, S.H. Tan, W.L. Goh, M. Leong, R.C.L. Khoo, S. Selvarajan, K. Sittampalam, M. Tao, T. Tang, S.T. Lim, M. Farid
Journal: Annals of Oncology (2017)
Therapeutic Benefit and Gene Network Regulation by Combined Gene Transfer of Apelin, FGF2, and SERCA2a into Ischemic Heart
Authors: Edith Renaud-Gabardos, Florence Tatin, Fransky Hantelys, Benoît Lebas, Denis Calise, Oksana Kunduzova, Bernard Masri, Françoise Pujol, Pierre Sicard, Philippe Valet, Jérôme Roncalli, Xavier Chaufour, Barbara Garmy-Susini, Angelo Parini, Anne-Catherine Prats
Journal: Molecular Therapy (2017)

Despite considerable advances in cardiovascular disease treatment, heart failure remains a public health challenge. In this context, gene therapy appears as an attractive approach, but clinical trials using single therapeutic molecules result in moderate benefit. With the objective of improving ischemic heart failure therapy, we designed a combined treatment, aimed to simultaneously stimulate angiogenesis, prevent cardiac remodeling, and restore contractile function. We have previously validated IRES-based vectors as powerful tools to co-express genes of interest. Mono- and multicistronic lentivectors expressing fibroblast growth factor 2 (angiogenesis), apelin (cardioprotection), and/or SERCA2a (contractile function) were produced and administrated by intramyocardial injection into a mouse model of myocardial infarction. Data reveal that combined treatment simultaneously improves vessel number, heart function parameters, and fibrosis prevention, due to FGF2, SERCA2a, and apelin, respectively. Furthermore, addition of SERCA2a in the combination decreases cardiomyocyte hypertrophy. Large-scale transcriptome analysis reveals that the triple treatment is the most efficient in restoring angiogenic balance as well as expression of genes involved in cardiac function and remodeling. Our study validates the concept of combined treatment of ischemic heart disease with apelin, FGF2, and SERCA2a and shows that such therapeutic benefit is mediated by a more effective recovery of gene network regulation.
Abstract 19073: Is There a Need for Tools to Stratify Risk in Patients With Coronary Heart Disease
Authors: Kate Maguire, Rosemary Healy
Journal: Circulation (2016)

Introduction:  Despite the popularity of the terms “personalized,” “stratified” or “precision” medicine, it is unclear whether practicing physicians perceive the need for more precise risk stratification for patients with stable coronary heart disease (CHD). On the one hand, these “high risk” patients may be considered as already maximally treated by standard-of-care workflows and guidelines, and on the other there may be a perceived opportunity to improve compliance with known effective treatments and lifestyle changes, or to allocate more intensive (and expensive) interventions cost-effectively. Existing risk assessment tools in CVD secondary prevention are imprecise and may mischaracterize some patients, resulting in care gaps.   Hypothesis:  Physicians perceive a need for tools to improve risk stratification of patients who are treated for CVD secondary prevention to supplement clinical assessment and laboratory tests, and they have confidence that they could act upon the results.   Methods:  We conducted a 30 minute online survey with 153 physicians (59 cardiologists (CD), 91 primary care physicians (PCP) and 3 endocrinologists) to solicit opinions about need for improved risk stratification of patients managed for CVD secondary prevention.   Results:  Physicians ranked the following to be the most important areas for improvement: 1) Need for better predictive tests/risk assessment (32% of CDs, 31% of PCPs); 2) better lipid therapies (27% of CDs, 20% of PCPs); 3) patient compliance/motivation (16% of CDs, 31% of PCPs); 4) tests to guide management (10% of CDs, 8% of PCPs). They considered the following to be the key benefits of a risk assessment test: 1) Guide patient management (32% of CDs, 38% of PCPs); 2) reliable risk prediction (29% of CDs, 37% of PCPs); 3) patient compliance/motivation (20% of CDs, 14% of PCPs).   Conclusions:  Physicians identified care gaps in CVD secondary prevention and recognized potential benefits of an accurate tool for risk stratification. PCPs highlighted the need for a better tool for patient motivation. Both specialties ranked the benefit of the risk assessment test to guide patient management as most important.
Hedgehog signaling drives medulloblastoma growth via CDK6
Authors: David R. Raleigh, Pervinder K. Choksi, Alexis Leigh Krup, Wasima Mayer, Nicole Santos, Jeremy F. Reiter
Journal: Journal of Clinical Investigation (2017)

Medulloblastoma, an aggressive cancer of the cerebellum, is among the most common pediatric brain tumors. Approximately one-third of medulloblastomas are associated with misactivation of the Hedgehog (Hh) pathway. GLI family zinc finger 2 (GLI2) coordinates the Hh transcriptional program; however, the GLI2 targets that promote cancer cell proliferation are unknown. Here, we incorporated a Gli2-EGFP allele into 2 different genetic mouse models of Hh-associated medulloblastoma. Hh signaling induced GLI2 binding to the Cdk6 promoter and activated Cdk6 expression, thereby promoting uncontrolled cell proliferation. Genetic or pharmacological inhibition of CDK6 in mice repressed the growth of Hh-associated medulloblastoma and prolonged survival through inhibition of cell proliferation. In human medulloblastoma, misactivation of Hh signaling was associated with high levels of CDK6, pointing to CDK6 as a direct transcriptional target of the Hh pathway. These results suggest that CDK6 antagonists may be a promising therapeutic approach for Hh-associated medulloblastoma in humans.
Reply to Gheorghe et al.
Authors: Makoto Naganuma, Naoki Hosoe, Yoshihiro Nakazato, Haruhiko Ogata, Takanori Kanai
Journal: Endoscopy (2017)

See also: The role of confocal laser endomicroscopy in assessing mucosal healing in patients with ulcerative proctitisEndoscopy 2017; 49(12): 1285-1285DOI: 10.1055/s-0043-119216
AVATAR therapy for auditory verbal hallucinations in people with psychosis: a single-blind, randomised controlled trial
Authors: Tom KJ Craig, Mar Rus-Calafell, Thomas Ward, Julian P Leff, Mark Huckvale, Elizabeth Howarth, Richard Emsley, Philippa A Garety
Journal: The Lancet Psychiatry (2017)

A quarter of people with psychotic conditions experience persistent auditory verbal hallucinations, despite treatment. AVATAR therapy (invented by Julian Leff in 2008) is a new approach in which people who hear voices have a dialogue with a digital representation (avatar) of their presumed persecutor, voiced by the therapist so that the avatar responds by becoming less hostile and concedes power over the course of therapy. We aimed to investigate the effect of AVATAR therapy on auditory verbal hallucinations, compared with a supportive counselling control condition.
Abstract 21164: New Pulmonary Vein Derived Theory of Atrial Fibrillation
Authors: Mu Qin, Xu Liu
Journal: Circulation (2017)

Introduction: Pulmonary veins (PV) is a major source of triggers for AF. However, the mechanism underlying the rapid firing of PV muscle sleeve is not fully understood. Hypothesis: AF is related to the compensatory increase in PV load in patients with pneumonectomy. Methods: A cohort of 128 patients were recruited and assigned to three groups, group 1: patients with left-sided pneumonectomy (N = 47), group 2: patients with right sided pneumonectomy (N = 21), and control group: patients with paroxysmal AF (N = 60). All patients underwent echocardiography and CT scan preoperatively; PVI was performed in three groups; 24-hour Holter monitoring was performed during 1-year of follow-up. Results: All patients in group 1 and 2 had paroxysmal AF, occurring decades after pneumonectomy. No inter-group differences in left atrial diameter were seen. The average diameter of LSPV (17.2±1.4 mm) and LIPV (14.7±1.2 mm) in group 1 was larger than those in control group (13.6±1.0 mm and 9.9±0.9 mm, P&lt;0.01). The diameter of RSPV and RIPV in group 2 (15.1±1.3 mm and 14.5±1.1 mm) and control group (13.2±1.3 mm and 10.2±1.2 mm) also showed significant differences (P&lt;0.01). Electrical activity in group 1 and 2 could be recorded in all the PV stumps. After isolation of contralateral PV, AF was terminated in 91.5% and 85.7% of patients in group 1 and group 2. During follow-up, the incidence of AF episodes was not significantly different among three groups. Conclusions: the PV-derived mechanism of AF depends on a compensative increase in contralateral PV load in patients that have undergone pneumonectomy, and partial PV mediated AF is hard to progress into persistent state.
Down-regulation of bcl-xl gene expression with histone deacetylase inhibitor
Authors: Xiaobo Cao, Philip Rasco, Jonathan Daniel, Charles Rodarte, Edward Childs, Roy W. Smythe
Journal: Cancer Research (2005)

5378   Introduction BCL-XL, an anti-apoptotic member of the bcl-2 gene family, is highly expressed in human mesothelioma. Over-expression of BCL-XL has been correlated with mesothelioma conventional clinical treatment resistance. Our research group demonstrated that down-regulation of BCL-XL expression by siRNA will induce apoptosis and sensitize mesothelioma cells to subsequent chemotherapy. Our lab also noticed that histone deacetylase inhibitors (HDACIs) could decrease bcl-xl expression. Here, we try to understand the mechanism how HDACI leads to decreased bcl-xl expression. Materials and Methods Human mesothelioma lines I45 and REN were used in the following experiments. Western blot and real-time RT-PCR were used quantiy the gene expression. EMSA and CHIP assay were performed to measure the activities of transcriptional factors. Epigenitic gene expression was detected by affimatrix gene chip analysis. Result Bcl-xl expression could be down-regulated with HDACI at transcriptional level. Our western blot and real-time RT-PCR data demonstrated that bcl-xl expression were decreased 70% after HDACI exposure. Our nucli run-on assay revealed that bcl-xl expression was regulated at transcriptional level. Deaminated Bcl-xl was not detected after HDACI exposure by western blot. Analysis of bcl-xl promoter demonstrated that bcl-xl could be regulated by ETS family, NF-KB and STATs. Eight promoter deletion constructs were created and tested in our Meso cell line I45 with and without HDACI exposure. Luceriferase was used as a reporter. Our data demonstrated that the distal 350 bp of promoter is critical for the transcription regulation of bcl-xl and response to the HDACI. Deletion of 350bp leaded to 60% reduction of promoter activity. HDACI could decrease 70% whole bcl-xl promoter activity and only 40% of xl p750  promoter activity deletion. This 350 bp contains several ETS binding sites and two NF-KB binding sites. EMSA was used to compare the activities of these transcriptional factors on bcl-xl promoter with and without HDACI. Only NF-KB activity showed reduced by HDACI. Reduction of NF-KB activity was confirmed by CHIP assay. CHIP assay revealed 80% reductuion. Ikk mutant adenovirus could lead to 80% of bcl-xl reduction on I45 cell lines. Inhibiting JACK-STATs pathway has no impact on bcl-xl expression. Our affimatrix gene array experiments showed that only limited (2-3%) genes expressions were increased or decreased. Transcription repressor NCOR was induced by HDACI. Increased N-COR expression was confirmed by western blot and real-time RT-PCR. mSin3a expression remained unchanged. Conclusion BCL-XL expression is regulated at transcriptional level. Inhibition of NF-KB activity by HDACI leads to reduced bcl-xl transcription. Induction of transcription repressor by HDACI might contribute to bcl-xl transcriptional reduction.
Prevalence of NTRK gene fusions in a large cohort of Japanese patients with lung cancer
Authors: A. Nakamura, H. Udagawa, S. Matsumoto, S. Sugawara, M. Shingyoji, A. Horiike, I. Okamoto, T. Hida, S. Saeki, Y. Ohe, D. Ogawara, Y. Kataoka, Y. Miyata, H. Mitsufuji, S. Kuyama, R. Kanemaru, T. Kato, A. Hirata, K. Yoh, K. Goto
Journal: Annals of Oncology (2017)
Evidence from 1970 on sugar’s effects on health never saw light of day
Authors: Bob Roehr
Journal: BMJ (2017)

A sugar industry research group had evidence of an association between sucrose consumption and cardiovascular disease and bladder cancer nearly a half century ago, researchers have found, but the research was discontinued.

The charge comes from a team of researchers from the University of California, San Francisco, who analysed archived internal documents and other papers from the Sugar Research Foundation and groups that succeeded it.

Groups associated with the sugar industry have repeatedly claimed that sucrose does not have any metabolic effects related to chronic disease other than those associated with its energy content. The new analysis, published in PLoS Biology ,1 dismisses those claims and states that the industry knew of evidence to …
An open-label, randomized cross-over bioavailability study of oral paclitaxel and HM30181 compared with weekly intravenous (IV) paclitaxel in patients with advanced solid tumours
Authors: C G C A Jackson, S. Deva, K. Bayston, P. Barlow, K. Eden, N. Hung, G. Fetterly, D. Cutler, R. Kwan, D. Kramer, W-K Chan, T. Hung
Journal: Annals of Oncology (2017)
Incidence of Gastric-to-Pulmonary Aspiration in Patients Undergoing Elective Upper Gastrointestinal Endoscopy
Authors: J. Kyle Bohman, Adam K. Jacob, Kelsey A. Nelsen, Daniel A. Diedrich, Nathan Smischney, Oludare Olatoye, Rochelle Molitor, Nicholas R. Oblizajek, Andrew C. Hanson, Navtej S. Buttar
Journal: Clinical Gastroenterology and Hepatology (2017)
Impact of socioeconomic status on pretreatment cachexia and survival in non-small cell lung cancer.
Authors: Steven Lau, Bhavani S Gannavarapu, Kristen Carter, Ang Gao, Chul Ahn, Jeffrey John Meyer, David J Sher, Aminah Jatoi, Puneeth Iyengar
Journal: Journal of Clinical Oncology (2017)

101 Background: Socioeconomic status (SES) influences healthcare outcomes, but the influence of SES on cancer cachexia is unknown. We identify components of SES associated with pre-treatment cachexia in patients with non-small cell lung cancer (NSCLC) and assess their prognostic significance on survival. Methods: A prospectively maintained institutional tumor registry identified 1,365 patients with NSCLC consecutively treated at a tertiary care health system from 1/1/06 to 12/31/13. Insurance status was abstracted from the registry. Educational attainment and household income were estimated from census data using location of primary residence. Cancer cachexia was defined retrospectively using the international consensus definition. Multivariable regression analysis was used to identify prognostic factors of pre-treatment cancer cachexia and survival. Results: Cachexia was present at the time of NSCLC diagnosis in 30% of all patients including 17% of patients with stage I disease. Patients with Medicaid or no insurance were more likely to have pre-treatment cachexia compared to those with private insurance (Odds Ratio [OR] 1.9, 95% Confidence Interval [CI] 1.2-3.1; OR 2.1, 95% CI 1.2-3.4, respectively). Attainment of a high school diploma was inversely associated with pre-treatment cachexia (OR: 0.1, 95% CI 0.02-0.2). On multivariable analysis, comorbidity, histology, tumor grade, and disease stage were prognostic of survival among cachectic patients; however, insurance status, educational attainment, and household income were not. Conclusions: Lower SES is associated with pre-treatment cachexia in patients with NSCLC, but pre-treatment cachexia is detrimental to survival regardless of SES. Together, these findings suggest early intervention for patients with cancer cachexia may improve outcomes.
Abstract 20205: The Impact of Andexanet Alfa in a Porcine Polytrauma Model Under Apixaban Anticoagulation: Investigation of Hemostatic Safety and Efficacy
Authors: Oliver Grottke, Necib Akman, Pamela B Conley, Markus Honickel
Journal: Circulation (2017)

Introduction: Despite the safety of factor Xa inhibitors the management of life-threatening bleeding is challenging. Andexanet alfa is an antidote under investigation for reversal of factor Xa inhi...
Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study
Authors: John P Campbell, Jennifer L J Heaney, Sankalp Pandya, Zaheer Afzal, Martin Kaiser, Roger Owen, J Anthony Child, David A Cairns, Walter Gregory, Gareth J Morgan, Graham H Jackson, Chris M Bunce, Mark T Drayson
Journal: The Lancet Haematology (2017)
Host resistance to endotoxic shock requires the neuroendocrine regulation of group 1 innate lymphoid cells
Authors: Linda Quatrini, Elisabeth Wieduwild, Sophie Guia, Claire Bernat, Nicolas Glaichenhaus, Eric Vivier, Sophie Ugolini
Journal: The Journal of Experimental Medicine (2017)

Upon infection, the immune system produces inflammatory mediators important for pathogen clearance. However, inflammation can also have deleterious effect on the host and is tightly regulated. Immune system-derived cytokines stimulate the hypothalamic-pituitary-adrenal (HPA) axis, triggering endogenous glucocorticoid production. Through interaction with ubiquitously expressed glucocorticoid receptors (GRs), this steroid hormone has pleiotropic effects on many cell types. Using a genetic mouse model in which the gene encoding the GR is selectively deleted in NKp46+ innate lymphoid cells (ILCs), we demonstrated a major role for the HPA pathway in host resistance to endotoxin-induced septic shock. GR expression in group 1 ILCs is required to limit their IFN-γ production, thereby allowing the development of IL-10-dependent tolerance to endotoxin. These findings suggest that neuroendocrine axes are crucial for tolerization of the innate immune system to microbial endotoxin exposure through direct corticosterone-mediated effects on NKp46-expressing innate cells, revealing a novel strategy of host protection from immunopathology.
Everolimus plus exemestane for hormone resistant metastatic breast cancer (MBC): A single institutional experience.
Authors: Luisa Foltran, Manuela Bertola, Alessandro Del Conte, Giovanni Lo Re, Alessandro Bestetti, Paolo Sandri, Silvana Saracchini
Journal: Journal of Clinical Oncology (2015)

e11576 Background: Everolimus (EVE) combined with exemestane (EXE) demonstrated synergistic effect to overcome endocrine resistance, thus improving progression-free survival (PFS) in postmenopausal MBC patients (pts) who progressed/recurred after non-steroidal aromatase inhibitors (NSAIs). This study aimed to evaluate the efficacy and safety of EVE + EXE in a clinical practice setting. Methods: Postmenopausal women with ER-positive, HER2-negative MBC, refractory to letrozole or anastrozole, received EVE (10 mg daily) plus EXE (25 mg daily) until disease progression or unacceptable toxicity. Socio-demographic and clinical data including previous hormone sensitivity were retrospectively reviewed. Median PFS, clinical benefit rate (CBR) and safety was reported. Results: A total of 23 consecutive pts were treated from September 2012 to January 2015. At the time of analysis 10 pts were still receiving EVE plus EXE with no tumour progression. Median age was 65 years (range: 49-78); 22% of pts had visceral metastasis and 65% bone metastasis. This study population was predominantly sensitive to previous endocrine therapy (87%). The majority of MBC women had: invasive ductal carcinoma (61%), progesterone-positive cancer (74%), ECOG performance status 0 (82%), one metastatic site (70%) and previous chemotherapy (74%). Nearly half of pts received EVE plus EXE as first-line therapy (52%), a quarter as second-line (26%) and a sixth as third line (17%). The median PFS was 9.9 months and CBR was 69%. The most frequent grade 3 adverse events were mucositis, fatigue and pneumonitis. Conclusions: EVE plus EXE is an effective and feasible treatment for hormone resistant MBC also in clinical practice. It represents an appropriate option in metastatic setting, since the benefit on PFS is at least comparable to chemotherapy. The toxicity profile needs a careful management.
Age-induced and photoinduced changes in gene expression profiles in facial skin of Caucasian females across 6 decades of age
Authors: Alexa B. Kimball, Maria B. Alora-Palli, Makio Tamura, Lisa A. Mullins, Chieko Soh, Robert L. Binder, Neil A. Houston, Emily D. Conley, Joyce Y. Tung, Nikki E. Annunziata, Charles C. Bascom, Robert J. Isfort, Bradley B. Jarrold, Raghu Kainkaryam, Heather L. Rocchetta, Dionne D. Swift, Jay P. Tiesman, Kazumi Toyama, Jun Xu, Xianghong Yan, Rosemarie Osborne
Journal: Journal of the American Academy of Dermatology (2017)
EGCG sensitizes human prostate carcinoma LNCaP cells to TRAIL-induced apoptosis
Authors: Imtiaz A. Siddiqui, Arshi Malik, Vaqar M. Adhami, Hasan Mukhtar
Journal: Cancer Research (2006)

2258  Epigallocatechin-3-gallate (EGCG), the major polyphenolic constituent present in green tea possesses anti-proliferative and anti-tumor promoting effects against several tumor types including prostate cancer. These effects of EGCG have been demonstrated to be triggered via disruption of cell cycle and induction of apoptosis of cancer cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an endogenous member of the tumor necrosis factor family of cell death-inducing ligands, induces apoptosis in a wide variety of cancer and transformed cells. However, some cells including the human prostate carcinoma LNCaP cells are only slightly susceptible to apoptosis induction by TRAIL. In this study, we determined if EGCG could sensitize LNCaP cells to limited apoptosis induction by TRAIL. LNCaP cells were treated with EGCG (20-80 μM) for 24 hours followed by the treatment with TRAIL (100 ng/ml) for another 24 hours. Control cells treated with the vehicle, EGCG alone and TRAIL alone were run in parallel. Cells were processed for studying cell-viability by an MTT assay and for investigating key death regulatory molecules by immuno-blot analysis. There was 20% cell death by TRAIL alone and 22%, 34% and 46% cell death by EGCG alone at 20, 40 and 80 μM respectively. Combination of EGCG and TRAIL resulted in 11 to 19% enhanced cell death as compared to additive effects of the each agent alone. Further, cells treated with EGCG and TRAIL exhibited increased induction of apoptosis when compared to each agent alone. The induction of apoptosis by the combination of TRAIL and EGCG was found to be accompanied by increased cleavage of procaspases-3, -6, -8, and -9 and cleavage of PARP. We also observed that combination of EGCG and TRAIL significantly up regulated DR4, a death receptor of TRAIL. In addition we found that EGCG and TRAIL mediated apoptosis occurs due to synergistic inhibition of survivin, an anti-apoptotic member of the inhibitor of apoptosis family of proteins, that is selectively expressed in most common human neoplasms and appears to be involved in tumor cell resistance to anticancer agents. We further observed enhanced induction of pro-apoptotic Bax and Bak and inhibition of anti-apoptotic Bcl2 in cells pre-treated with EGCG followed by TRAIL. Our results suggest that both the extrinsic (receptor-mediated) and intrinsic (chemical-induced) pathways of apoptosis are triggered in LNCaP cells treated with a combination of EGCG and TRAIL. These observations define a potential use of EGCG in sensitizing prostate cancer cells to TRAIL-induced apoptosis and offer a novel strategy for treating human prostate cancer.