tbuckley/cabot-search huggingface dataset:
The histone deacetylase complex as a drugable target in colorectal cancer.
Authors: Barbara Mayer, Christian Ilmberger, Kathrin Halfter, Mareile Joka, Volker Heinemann, Jens Werner
Journal: Journal of Clinical Oncology (2015)

e22200 Background: The histone deacetylase inhibitor Vorinostat represents a promising drug for the treatment of multiple tumor types, including colorectal cancer. Efficacy of Vorinostat was examined as single agent and in combination therapy using multicellular tumor spheroids (MCTS) derived from patient tumor material. Methods: Surgical tumor tissue samples of fifteen colorectal cancer patients were processed in vitro for the formation of MCTS and treated in vitro with 5FU or Vorinostat, both in Monotherapy; 5FU plus either Oxaliplatin (FO), Irinotecan (FI) or Vorinostat (FV); 5FU plus Vorinostat and either Oxaliplatin (FOV) or Irinotecan (FIV). To assess therapeutic efficacy, a standard ATP assay was performed. For statistical analysis, Kolmogorov-Smirnov tests and t-tests were performed. Results: The standard therapy for colorectal cancer FO showed a residual metabolic activity of 20,11% which could be improved further by the addition of Vorinostat (FOV; 11,99%; p = 0,047). The combination of 5FU plus Vorinostat was more effective than 5FU monotherapy in 33% of the samples (p = 0,009) and also as effective as FO in 100% of the time (p = 0,726). FV was also significantly more effective than FI in 26% of the samples (p = 0,009). The addition of Vorinostat to FI (FIV) had a significant benefit over the double combination in 25% of the cases (p < 0,000). Conclusions: The standard FO therapy alone is very effective in vitro, but can be improved further by the addition of Vorinostat. As many patients do not adhere to the FO regime because of side effects caused by Oxaliplatin, the combination of 5FU plus Vorinostat is a valuable alternative, especially for patients with a poor health status.
Glucagon-Like Peptide 1 Receptor Agonists and Risk of Diabetic Retinopathy Complications: Cohort Study in Nationwide Registers From Two Countries
Authors: Peter Ueda, Björn Pasternak, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Mads Melbye, Henrik Svanström
Journal: Diabetes Care (2019)

Post hoc analyses of the Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN-6) showed an increased risk of diabetic retinopathy complications associated with semaglutide versus placebo among patients with a history of retinopathy, especially among those with insulin use (1). Although concerns have been raised regarding the safety of glucagon-like peptide 1 (GLP-1) receptor agonists in patients with existing retinopathy, subgroup analyses by retinopathy status at baseline have not been presented for other trials of GLP-1 receptor agonists; the two observational studies on GLP-1 receptor agonists and diabetic retinopathy performed to date have excluded patients with a history of retinopathy (2) or treatment of retinopathy (3).

We conducted a cohort study (January 2010 to December 2016) of patients with existing retinopathy using nationwide data in Sweden and Denmark from the prescription registers, patient registers, population registers, the national bureaus of statistics, and the Swedish National Diabetes Register. Data sources and general methods used have been described in detail elsewhere (4,5). We included patients, aged 35–84 years, who filled their first prescription for either a GLP-1 receptor agonist or a dipeptidyl peptidase 4 (DPP-4) inhibitor (active comparator) during the study period and had a history of diabetic retinopathy (retinal photocoagulation, treatment with intravitreal agents, vitreous hemorrhage, vitrectomy, retinal detachment, retinal bleeding, and diabetic eye complications/retinopathy). We excluded patients who had previously filled prescriptions for any …
FRI-354-Novel Gubra Amylin NASH diet-induced obese mouse model of biopsy-confirmed non-alcoholic steatohepatitis
Authors: Sanne Veidal, Michael Feigh, Michelle Boland, Denise Oro, Kirstine Tølbøl, Jacob Jelsing, Niels Vrang, Henrik B. Hansen, James Trevaskis
Journal: Journal of Hepatology (2019)
FRI-094-Targeting NEDDylation protects liver from acute drug-induced damage
Authors: Jorge Simón, David Fernández Ramos, Virginia Gutiérrez de Juan, Marina Serrano-Macia, Naroa Goikoetxea, Diego Saenz de Urturi, Rubén Rodríguez Agudo, Fernando Lopitz Otsoa, Sergio López de Davalillo, Xabier Buque, Marta Varela-Rey, Pablo Fernández-Tussy, Patricia Aspichueta, Teresa Cardoso Delgado, María Luz Martínez-Chantar
Journal: Journal of Hepatology (2019)
Thyroid Incidentaloma on 18F-fluorocholine PET/CT and 68Ga-PSMA PET/CT Revealing a Medullary Thyroid Carcinoma
Authors: Renaud Ciappuccini, Agathe Edet-Sanson, Virginie Saguet-Rysanek, Mathieu Gauthé, Stéphane Bardet
Journal: Clinical Nuclear Medicine (2019)

Abstract A 66-year-old man with prostate cancer underwent 18 F-fluorocholine PET/CT and thereafter 68 Ga-labeled prostate-specific membrane antigen PET/CT to explore a rising prostate-specific antigen level. Both PET/CT studies showed a thyroid incidentaloma of the right lobe. Neck ultrasound confirmed the presence of a 16-mm right thyroid nodule. The serum calcitonin level was moderately increased at 25 ng/mL (&lt;10). Cytology was non-diagnostic (Bethesda I). A right lobectomy was performed and pathology revealed a 15-mm medullary thyroid cancer. Two months after surgery, the calcitonin level returned to normal at 3.3 ng/mL.
Corrigendum to “The BACE1 product sAPPβ induces ER stress and inflammation and impairs insulin signaling” [Metab Clin Exp 85 (2018) 59–75]
Authors: Gaia Botteri, Laia Salvadó, Anna Gumà, D. Lee Hamilton, Paul J. Meakin, Gemma Montagut, Michael L.J. Ashford, Victoria Ceperuelo-Mallafré, Sonia Fernández-Veledo, Joan Vendrell, María Calderón-Dominguez, Dolors Serra, Laura Herrero, Javier Pizarro, Emma Barroso, Xavier Palomer, Manuel Vázquez-Carrera
Journal: Metabolism (2019)
FRI-184-Function and drug combination studies in cell culture models for AB-729, a subcutaneously administered siRNA investigational agent for chronic hepatitis B infection
Authors: Amy C.H. Lee, Emily P. Thi, Andrea Cuconati, Andrzej Ardzinski, Richard Holland, Hui Huang, Andrew S. Kondratowicz, Rose Kowalski, Lorne Palmer, Chris Pasetka, Rene Rijnbrand, Holly M. Steuer, Xiaohe Wang, Xin Ye, Michael J. Sofia
Journal: Journal of Hepatology (2019)
SAT-283-Plasma acylcarnitines are biomarkers of magnetic resonance imaging-proton density fat fraction response in NASH patients treated with the ACC inhibitor GS-0976
Authors: Michael Charlton, Michelle Lai, Mazen Noureddin, Jacqueline M. Tarrant, Tao Hu, Guang Chen, Bryan Mccolgan, Chuhan Chung, Jay Chuang, Scott D. Patterson, Robert Myers, Parvez Mantry, Peter Ruane, Rohit Loomba
Journal: Journal of Hepatology (2019)
Radial incision and cutting for releasing severe stricture enables successful delivery of an over-the-scope clip
Authors: Shintaro Fujihara, Hideki Kobara, Noriko Nishiyama, Masahiko Kobayashi, Yasutaka Kokudo, Hirohito Mori, Tsutomu Masaki
Journal: Endoscopy (2019)

Nonhealing gastrocutaneous fistula (GCF), a rare refractory complication after percutaneous endoscopic gastrostomy, has traditionally required invasive surgery. Recently, the over-the-scope clip (OTSC) (Ovesco Endoscopy, Tübingen, Germany) has been reported to be a minimally invasive, effective device to achieve fistula closure [1]. However it is associated with one drawback: because the outer diameter of the OTSC application cap is large and the bear claws at the clip’s tip are sharp, the presence of a severe gastrointestinal stricture makes delivery of an OTSC difficult. The standard treatment for refractory benign strictures, balloon dilation, is sometimes limited and an endoscopic radial incision and cutting technique has been developed as an alternative [2] [3]. We describe the release, by means of radial incision and cutting, of a stenosis due to severe esophageal stricture; this allowed successful delivery of an OTSC and closure of the gastrointestinal fistula.
Her2/neu as a promising biomarker to stratify CRC patients with liver metastasis for trastuzumab treatment.
Authors: Mareile Joka, Melanie Zoller, Thomas Kirchner, Volker Heinemann, Jens Werner, Barbara Mayer
Journal: Journal of Clinical Oncology (2015)

e22217 Background: Hepatic metastasis is the most frequent metastatic lesion in colorectal cancer (CRC). Targeted therapy might overcome chemotherapeutic resistance in the metastatic situation. The present study analysed the prognostic and predictive impact of Her2/neu expression in liver metastasis compared to primary CRC. Methods: Cryosections obtained from 89 primary colorectal cancers and 58 liver metastases were characterized for Her2/neu expression using immunohistochemistry and FISH analysis. The impact of Her2/neu expression on survival was analyzed with Kaplan Meier analysis and Cox regression analysis. Results: Her2/neu Score3+ was found in 33.3% of the primary colorectal cancers. Her2/neu Score3+ cancer cells were preferentially found in female patients (women, Score3+: 25.64%; men, Score3+: 6.0%, p = 0.014). Moreover, Her2/neu Score3+ tumours were localized more frequently in the left-sided colon (left-sided, Score3+: 25.53%; right-sided, Score3+: 2.38%, p = 0.002). None of the primary tumor samples revealed Her2/neu amplification. In primary CRC, Her2/neu Score3+ expression had no impact on survival. Her2/neu Score3+ was found in 50% of the liver metastases. Comparison between untreated and pretreated liver metastases revealed no difference in Her2/neu expression pattern and scoring (p = 0.349). Similar as described in the primary tumors Her2/neu was not amplified in the metastatic lesions. Kaplan-Meier analysis showed that Her2/neu Score3+ expressing liver metastases correlated with short survival (p = 0.026). Cox regression analysis confirmed Her2/neu Score3+ status as an independent factor indicating short survival (p = 0.035). Conclusions: Her2/neu Score3 was identified a prognostic and predictive biomarker in metastatic CRC. Patients with a left-sided CRC and female patients will preferentially benefit from Trastuzumab therapy. Most interesting, CRC patients with liver metastasis might overcome chemotherapeutic resistance by targeted therapy using Trastuzumab.
Fructose Promotes Leaky Gut, Endotoxemia, and Liver Fibrosis Through Ethanol‐Inducible Cytochrome P450‐2E1–Mediated Oxidative and Nitrative Stress
Authors: Young‐Eun Cho, Do‐Kyun Kim, Wonhyo Seo, Bin Gao, Seong‐Ho Yoo, Byoung‐Joon Song
Journal: Hepatology (2019)

Fructose intake is known to induce obesity, insulin resistance, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the effects of fructose drinking on gut leakiness, endotoxemia, and NAFLD and study the underlying mechanisms in rats, mice, and T84 colon cells. Levels of ileum junctional proteins, oxidative stress markers, and apoptosis‐related proteins in rodents, T84 colonic cells, and human ileums were determined by immunoblotting, immunoprecipitation, and immunofluorescence analyses. Fructose drinking caused microbiome change, leaky gut, and hepatic inflammation/fibrosis with increased levels of nitroxidative stress marker proteins cytochrome P450‐2E1 (CYP2E1), inducible nitric oxide synthase, and nitrated proteins in small intestine and liver of rodents. Fructose drinking significantly elevated plasma bacterial endotoxin levels, likely resulting from decreased levels of intestinal tight junction (TJ) proteins (zonula occludens 1, occludin, claudin‐1, and claudin‐4), adherent junction (AJ) proteins (β‐catenin and E‐cadherin), and desmosome plakoglobin, along with α‐tubulin, in wild‐type rodents, but not in fructose‐exposed Cyp2e1 ‐null mice. Consistently, decreased intestinal TJ/AJ proteins and increased hepatic inflammation with fibrosis were observed in autopsied obese people compared to lean individuals. Furthermore, histological and biochemical analyses showed markedly elevated hepatic fibrosis marker proteins in fructose‐exposed rats compared to controls. Immunoprecipitation followed by immunoblot analyses revealed that intestinal TJ proteins were nitrated and ubiquitinated, leading to their decreased levels in fructose‐exposed rats. Conclusion: These results showed that fructose intake causes protein nitration of intestinal TJ and AJ proteins, resulting in increased gut leakiness, endotoxemia, and steatohepatitis with liver fibrosis, at least partly, through a CYP2E1‐dependent manner.
SAT-489-Efficacy and safety of thermal ablation in patients with hepatocellular carcinoma and high comorbidity
Authors: Maria Torner, Paola Rueda, Ana Gomez, Andrés Castano-Garcia, Carmen Álvarez-Navascués, Maria Luisa Gonzalez Dieguez, Valle Cadahía-Rodrigo, Amador Prieto, Alicia Mesa, Manuel Rodríguez, Maria Varela
Journal: Journal of Hepatology (2019)
Anti-tumor efficacy in SIOPEL 6: A multi-centre open label randomised phase III trial of the efficacy of sodium thiosulphate (STS) in reducing ototoxicity in patients receiving cisplatin (Cis) monotherapy for standard risk hepatoblastoma (SR-HB).
Authors: Penelope Rachel Brock, Rudolf Maibach, Margaret Childs, Kaukab Rajput, Edward A. Neuwelt, Derek Roebuck, Michael James Sullivan, Veronique Laithier, Milind Ronghe, Liane Lockwood, Patrizia dall'Igna, Eiso Hiyama, Benedicte Brichard, Jane Skeen, Maria Elena Mateos, Monique Fabre, Arun Atreiya Rangaswami, Michael Capra, Piotr Czauderna, Bruce Morland
Journal: Journal of Clinical Oncology (2015)

10039 Background: SR-HB is defined as tumor extension limited to PRETEXT I, II or III, no portal, hepatic veins, or intra-abdominal extra-hepatic disease, AFP > 100ng/ml and no metastases. Cis can cause permanent bilateral high-frequency hearing loss. STS may reduce this risk, but could also reduce Cis anti-tumor efficacy. Methods: Newly diagnosed patients with SR-HB were treated with 2-weekly cycles of Cis, 4 before primary tumor resection and 2 after. Patients were randomized to Cis alone or Cis and STS. Cis 80mg/m2 was administered i.v. over 6 hrs. STS was administered i.v. exactly 6 hrs after stop of Cis over 15 minutes at 20g/m2. Response was assessed after 2 and 4 cycles pre-operative with serum AFP and liver imaging. In case of progression after 2 cycles, STS was stopped and doxorubicin 60mg/m2 continuous infusion over 48 hrs added. The primary endpoint is centrally reviewed absolute hearing threshold, at the age of ≥ 3.5 years, by pure tone audiometry. With a sample size of 102, the trial has 80% power to detect a reduction in hearing loss defined as Brock grade ≥ 1 from 60% of patients with Cis to 35% with Cis+STS. Short term anti-tumor efficacy endpoint is disease status at end of treatment which was evaluated after every 20 patients and submitted to the IDMC. Throughout the trial, the IDMC recommended continuation after interim review of efficacy results. Results: From 2007 to end 2014, 45 sites from 12 countries randomized 53 patients to Cis and 60 to Cis+STS, median age at diagnosis was 12.8 months. Treatment was well tolerated and acute toxicity similar between arms. Efficacy results after 4 pre-op chemo cycles for the first 94 patients (47 Cis, 47 Cis+STS) were PR/SD/PD for Cis: 86%/8%/6% and for Cis+STS: 90%/5%/5%. Complete remission after resection and post-op chemo was 92% and 98%. In January 2015, 2 pts had died (Cis arm), and 2 (Cis) and 1 (Cis+STS) had progressed. Conclusions: End of treatment anti-tumor efficacy in SR-HB treated on the above protocol shows no adverse outcome related to STS. Final evaluation of hearing loss at ≥ 3.5 yrs of age, the primary endpoint, is expected in 2017. Clinical trial information: NCT00652132.
Lifestyle, Glycosylated Hemoglobin A1c, and Survival Among Patients With Stable Ischemic Heart Disease and Diabetes
Authors: G B John Mancini, David J Maron, Pamela M Hartigan, John A Spertus, William J Kostuk, Daniel S Berman, Koon K Teo, William S Weintraub, William E Boden
Journal: Journal of the American College of Cardiology (2019)
SAT-460-Influence of sustained virological response in diagnostic performance of alpha-fetoprotein for hepatocellular carcinoma in patients with HCV-cirrhosis
Authors: Ana Gomez, Carmen Álvarez-Navascués, Valle Cadahía-Rodrigo, María Torner, Maria Luisa Gonzalez Dieguez, Maria Varela, Manuel Rodríguez
Journal: Journal of Hepatology (2019)
Investigating the beneficial experiences of online peer support for those affected by alopecia: an interpretative phenomenological analysis using online interviews
Authors: L.L. Iliffe, A.R. Thompson
Journal: British Journal of Dermatology (2019)

Those affected by alopecia are at risk of experiencing a range of psychosocial consequences. Alopecia UK provides online peer support via facilitated Facebook pages. Online peer support has been found to provide a variety of benefits in other long‐term conditions, such as providing information and emotional support. This study sought to gain an experiential account as to how online support provides benefit to people living with alopecia. A purposive sample of 12 participants was recruited directly from Alopecia UK's Facebook group. A total of 11 were diagnosed with alopecia and one participant was a family member of someone with alopecia. The qualitative approach of Interpretative Phenomenological Analysis was used to guide data collection and analysis. Participants took part in online synchronous interviews, which drew on review of participant‐selected screenshots of online activity. Four themes were identified, including 'gradual healing', 'image concern', 'belonging' and 'new identity and self‐acceptance'. The participants made use of the group through expressing emotion, finding practical advice, and also as a place to connect and share experiences. Participants also reported that the online support facilitated the return of social confidence. This study provides a detailed understanding as to how online peer support groups can be beneficial. Online groups have the potential to create a feeling of belonging, which can develop a sense of being accepted and understood and as such can be important in maintaining psychological well‐being. The findings indicate that online groups have the potential to be used as a platform for assisting people in developing both effective coping styles and feeling understood, and such platforms warrant further investment by healthcare professionals. What's already known about this topic? Alopecia may be associated with psychosocial distress due to both the individual impact and the reactions of others. Online peer support is known to be a beneficial method of providing psychosocial support for people living with a range of health conditions. What does this study add? An in‐depth view of the benefits experienced through belonging to an online peer support group for those diagnosed with alopecia, in addressing the psychosocial effects experienced with the condition. This research highlights the need for further investigation of the utility of supporting the development of online peer support for people living with skin conditions. Online peer support groups could be highly effective to use in combination with existing psychological therapies to connect others with shared experience. What are the clinical implications of this work? People living with alopecia can benefit from peer support, and healthcare professionals should ensure that patients know where they can gain access to both psychological support and peer support.
Prevalence of Violence Victimization and Perpetration Among Persons Aged 13–24 Years — Four Sub-Saharan African Countries, 2013–2015
Authors: Elizabeth A. Swedo, Steven A. Sumner, Susan D. Hillis, George Aluzimbi, Rose Apondi, Victor O. Atuchukwu, Andrew F. Auld, Peter J. Chipimo, Martha Conkling, Okpewuru E. Egbe, McKnight S.H. Kalanda, Chabila C. Mapoma, Emma Phiri, Lydia N. Wasula, Greta M. Massetti
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Violence is a major public health and human rights concern, claiming over 1.3 million lives globally each year (1). Despite the scope of this problem, population-based data on physical and sexual violence perpetration are scarce, particularly in low-income and middle-income countries (2,3). To better understand factors driving both children becoming victims of physical or sexual violence and subsequently (as adults) becoming perpetrators, CDC collaborated with four countries in sub-Saharan Africa (Malawi, Nigeria, Uganda, and Zambia) to conduct national household surveys of persons aged 13-24 years to measure experiences of violence victimization in childhood and subsequent perpetration of physical or sexual violence. Perpetration of physical or sexual violence was prevalent among both males and females, ranging among males from 29.5% in Nigeria to 51.5% in Malawi and among females from 15.3% in Zambia to 28.4% in Uganda. Experiencing physical, sexual, or emotional violence in childhood was the strongest predictor for perpetrating violence; a graded dose-response relationship emerged between the number of types of childhood violence experienced (i.e., physical, sexual, and emotional) and perpetration of violence. Efforts to prevent violence victimization need to begin early, requiring investment in the prevention of childhood violence and interventions to mitigate the negative effects of violence experienced by children.
Efficacy of platinum rechallenge chemotherapy in sensitive relapsed small cell lung cancer after a long-term treatment-free interval.
Authors: Yasushi Murakami, Hideo Saka, Masahide Oki, Chiyoe Kitagawa, Yoshihito Kogure
Journal: Journal of Clinical Oncology (2015)

e18554 Background: Sensitive relapsed small cell lung cancer (SCLC) is generally defined by a treatment-free interval (TFI ≧ 90 days). Platinum rechallenge chemotherapy is a treatment option and its efficacy was reported a few previous studies. However, there is a heterogeneity in sensitive relapsed SCLC, and some patients showed high sensitivity with an extremely long-term TFI. The role of platinum rechallenge in these highly sensitive SCLC patients is unknown. Methods: We retrospectively analyzed the medical record of SCLC patients who responded to a platinum-doublet regimen and received second-line treatment after a long TFI (≧ 180 days) at Nagoya Medical Center between April 2004 and December 2012. These patients were divided into those with platinum rechallenge chemotherapy (rechallenge group) and those with a single-agent chemotherapy (monotherapy group) for the analysis of treatment efficacy. The endpoints were overall survival (OS) and progression-free survival (PFS). Results: Thirty-nine patients (34 males and 5 females, median 68 years) were included in this study. Thirteen patients were classified into the rechallenge group and 26 patients into another group. No significant differences in gender, age, disease extent at diagnosis, TFI and ECOG performance status at relapse were found between two groups. Twenty patients (77%) in the monotherapy group were treated with amrubicin. There were statistically significant differences in PFS (median, 8.2 months in the rechallenge group vs. 4.9 months in the monotherapy group, p = 0.044) and OS (median, 44.2 months in the rechallenge group vs. 20.9 months in the monotherapy group, p < 0.01). Similar results were also observed in OS when analyzed separately according to disease extent. Conclusions: This retrospective study demonstrated that platinum rechallenge chemotherapy provides a better outcome than other single-agent chemotherapies. Platinum rechallenge might be recommended for sensitive relapsed SCLC patients with a long-term TFI.
SAT-040-Is spleen stiffness the new frontier for non-invasive assessment of portal hypertension?
Authors: Mauro Giuffrè, Daniele Macor, Flora Masutti, Fabio Tinè, cristiana abazia, Riccardo Patti, Matteo Rossano Buonocore, Anna Colombo, Alessia Visintin, Michele Campigotto, Fabio Monica, Saveria Lory Croce
Journal: Journal of Hepatology (2019)