tbuckley/cabot-search huggingface dataset:
Preoperative chemoradiotherapy (QT-RT) with capecitabine and oxaliplatin (CAPOX) in patients with locally advanced rectal cancer.
Authors: Aintzane Sancho, Ines Marrodan, Begoña Calvo, Alberto Muñoz, Joan Manel Mane, Sergio Carrera, Natalia Fuente, Eider Azkona, Mikel Arruti, Eddy Isabel Gutierrez, Irene Ugalde, Guillermo Lopez-Vivanco
Journal: Journal of Clinical Oncology (2013)

e14628 Background: Locally advanced rectal carcinoma is associated with high rate of abdomino-perineal amputation. We analyzed a cohort of patients (pts) diagnosed of locally advanced rectal cancer, treated with neoadjuvant QT-RT with CAPOX followed by four cycles of adjuvant CAPOX after surgery. Methods: Pts with locally advanced rectal cancer (T3-T4 and/or N+) were treated with oxaliplatin (50mg/m2 day 1, 8, 22 and 29) and capecitabine (1650mg/m2 on days 1 to 14 and 22 to 35) combined with pelvic radiotherapy (180cGy/day; 45Gy in 25 fractions). Surgery was scheduled 4 to 6 weeks after completion QT-RT. Four cycles of adjuvant XELOX were administered (capecitabine 2000mg/m2 on days 1 to 14) and oxaliplatin (130mg/m2 day 1) every 3 weeks. The main end points assessed were: rate of sphincter preservation, pathological complete response (pCR) rate, toxicity and feasibility of postoperative chemotherapy. Local staging was done with pelvic MRI and/or EUS. Results: From Sept 2005 to Nov 2012, 201 pts with locally advanced rectal cancer were included. Pts characteristics: M/F 135/66; ECOG 0/1/2: 48/149/4; median age 65 (28-81); upper/mid/distal rectum 29/105/67; stage cT3/N- 21, cT2-T3/N+ 140, cT4/N- 6, cT4/N+ 34. Full dose preoperative QT-RT was administered in 192 (95%). The main toxicities were diarrhea grade 2/3: 42/24 and neurotoxicity grade 1/2: 94/7. After treatment 198 pts underwent surgery. Sphincter preservation and R0 resections were achieved in 125 and 184 respectively. pCR was achieved in 35 pts (17.4%). 145 pts (72%) received all 4 cycles of adjuvant XELOX. Grade 3/4 toxicities included vomiting 3/0, diarrhea 7/0, skin-foot syndrome 2/0, mucositis 1/0, neurotoxicity 6/0, neutropenia 10/1 and thromopenia 6/1. Downstaging in T/N was achieved in 108/144 pts (53.7/71.6%) respectively. 3-year progression-free and overall survival were 75% and 83% respectively. No toxic deaths were reported. Conclusions: Combination QT-RT based in capecitabine and oxaliplatin is a well tolerated regimen and achieved encouring rates of pCR, R0 resection, sphincter preservation and tumor downstaging in patients with locally advanced rectal cancer.
An assessment of physical activity levels and cardiorespiratory fitness in individuals living with hepatitis C
Authors: A.M. Monaghan, C. Forde, M. Coghlan, O. El-Sherif, B. Hynes, H. Irish, M. McGrath, S.J. Miggin, S. Naimimohasses, C. Quinn, J. Gormley, S. Norris
Journal: Journal of Hepatology (2017)
Erratum: Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesis
Authors: Flora M. Vaccarino, Michael L. Schwartz, Rossana Raballo, Jon Nilsen, Julianne Rhee, Ming Zhou, Thomas Doetschman, J. Douglas Coffin, Jason J. Wyland, Yu-Ting Elizabeth Hung
Journal: Nature Neuroscience (1999)
A phase 2 randomized open-label study of ramucirumab (RAM) plus first-line platinum-based chemotherapy in patients (pts) with recurrent or advanced non-small cell lung cancer (NSCLC): Final results from squamous pts
Authors: S. Thomas, R.C. Doebele, D. Spigel, M. Tehfe, M. Reck, S. Verma, A. Zimmermann, E. Alexandris, P. Lee, P. Bonomi
Journal: Annals of Oncology (2017)
Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly
Authors: Florian Zink, Simon N. Stacey, Gudmundur L. Norddahl, Michael L. Frigge, Olafur T. Magnusson, Ingileif Jonsdottir, Thorgeir E. Thorgeirsson, Asgeir Sigurdsson, Sigurjon A. Gudjonsson, Julius Gudmundsson, Jon G. Jonasson, Laufey Tryggvadottir, Thorvaldur Jonsson, Agnar Helgason, Arnaldur Gylfason, Patrick Sulem, Thorunn Rafnar, Unnur Thorsteinsdottir, Daniel F. Gudbjartsson, Gisli Masson, Augustine Kong, Kari Stefansson
Journal: Blood (2017)
Sequential combination therapy with IFN, rhIL-2 and therapeutic vaccine enhanced HBsAg loss in entecavir-suppressed CHB patients (the Endeavor study): an interim analysis
Authors: D. Wu, M. Han, Y. Chen, X. Chen, Q. Xia, C. Zhu, Q. Xie, J. Jiang, L. Wei, D. Tan, X. Dou, Y. Yu, J. Hou, Q. Ning
Journal: Journal of Hepatology (2017)
High Rates of Prolonged Molecular Remissions After Tandem Autologous-Nonmyeloablative Allografting in Newly Diagnosed Myeloma
Authors: Marco Ladetto, Simone Ferrero, Daniela Drandi, Paola Omedè, Francesca Patriarca, Nicola Mordini, Silvia Cena, Daniela Barbero, Luigia Monitillo, Luisa Giaccone, Alberto Rocci, Sara Barbiero, Moreno Festuccia, Andrea Gallamini, Renato Fanin, Roberto Passera, Antonio Palumbo, Mario Boccadoro, Benedetto Bruno
Journal: Blood (2012)
A canine model for microsatellite instability in cancer
Authors: Elizabeth A. McNiel, Nicole J. Madrill, Kelly L. Griffin, James R. Mickelson
Journal: Cancer Research (2005)

6077  DNA microsatellite sequences (MS) are subject to replication errors, which for the most part, are detected and repaired by the mismatch repair (MMR) system. When MMR is defective, MS lesions accumulate, a phenomenon called microsatellite instability (MSI). Defects in MMR contribute to carcinogenesis and can confer inherited cancer susceptibility, as with hereditary nonpolyposis colon cancer (HNPCC) in humans. Therefore, defective MMR represents a potential target for preventative and therapeutic intervention. The lack of relevant animal models presents a major stumbling block, however. Mouse models demonstrate increased cancer susceptibility resulting from selective inactivation of MMR. Unfortunately, these models also highlight fundamental differences between mice and humans with respect to carcinogenesis. Cancers that occur spontaneously in pet dogs share etiology, morphology, and clinical characteristics with human cancers and have great potential to bridge the gap between mouse models and humans. To this end, we are working to better characterize the genetic events in canine carcinogenesis. Recently, we evaluated MSI in canine epithelial malignancies. We compared PCR-amplified MS sequences from normal DNA isolated from blood to tumor DNA obtained from paraffin embedded sections. Twenty-two MS loci were evaluated including both tetra- and di- nucleotide repeats. We identified aberrant MS alleles in 15 of 18 mammary carcinomas (MC) and 7 of 7 transitional cell carcinomas (TCC). Most tumors, 17 of 20, exhibited low level MSI, with 1 to 3, primarily tetranucleotide, loci affected. Five tumors, including 3 TCC and 2 MC, exhibited high-level MSI with 35-90% of microsatellites affected. Interestingly, these tumors exhibited instability primarily in dinucleotide repeat loci. Four of the five tumors exhibiting high-level MSI were from West Highland White Terriers, a breed that is predisposed to TCC. We conclude that MSI may be a useful tool to study mechanisms of canine carcinogenesis and hypothesize that cancer susceptibility in West Highland White Terriers may result from germline defects in MMR genes. We are continuing to investigate other canine tumors for MSI and are evaluating the canine MMR system as a possible cause for our observations. These investigations could establish a novel, large animal model of cancer causation.
Identification of hepatitis B X protein regions responsible for the regulation of HBV transcription via histone modification
Authors: D.K.H. Wong, C.K. Chong, C.Y.S. Cheng, S.Y.J. Tsoi, F.-Y. Huang, F. Liu, W.-K. Seto, C.-L. Lai, M.-F. Yuen
Journal: Journal of Hepatology (2017)
Integrated analysis of controlled clinical trials evaluating efficacy and safety of sofosbuvir-based regimens in chronic hepatitis C genotype 6 (HCV GT 6)
Authors: M.H. Nguyen, W.-L. Chuang, T. Hassanein, K. Kowdley, C.-L. Lai, H.L.-Y. Chan, J.J. Feld, C. Letterio, T.A. Hahambis, J. Llewellyn, S. De-Oertel, D.M. Brainard, E.J. Lawitz, E.J. Gane
Journal: Journal of Hepatology (2017)
Mechanotransduction and Growth Factor Signalling to Engineer Cellular Microenvironments
Authors: Amaia Cipitria, Manuel Salmeron‐Sanchez
Journal: Advanced Healthcare Materials (2017)

Engineering cellular microenvironments involves biochemical factors, the extracellular matrix (ECM) and the interaction with neighbouring cells. This progress report provides a critical overview of key studies that incorporate growth factor (GF) signalling and mechanotransduction into the design of advanced microenvironments. Materials systems have been developed for surface‐bound presentation of GFs, either covalently tethered or sequestered through physico‐chemical affinity to the matrix, as an alternative to soluble GFs. Furthermore, some materials contain both GF and integrin binding regions and thereby enable synergistic signalling between the two. Mechanotransduction refers to the ability of the cells to sense physical properties of the ECM and to transduce them into biochemical signals. Various aspects of the physics of the ECM, i.e. stiffness, geometry and ligand spacing, as well as time‐dependent properties, such as matrix stiffening, degradability, viscoelasticity, surface mobility as well as spatial patterns and gradients of physical cues are discussed. To conclude, various examples illustrate the potential for cooperative signalling of growth factors and the physical properties of the microenvironment for potential applications in regenerative medicine, cancer research and drug testing.
Hand-foot-skin reaction of grade two or higher within sixty days as the best response criterion for survival prediction in hepatocellular carcinoma treated by sorafenib
Authors: E. Wang, D. Xia, W. Wang, W. Bai, Q. Wang, J. Yuan, X. Li, J. Niu, Z. Yin, J. Xia, D. Fan, G. Han
Journal: Journal of Hepatology (2017)
Abstract B03: Formation of lymph node metastases is not angiogenesis dependent
Authors: Dennis Jones, Han-Sin Jeong, Shan Liao, Daniel A. Wattson, Cheryl H. Cui, Dan G. Duda, Christopher G. Willett, Rakesh K. Jain, Timothy P. Padera
Journal: Cancer Research (2016)

Abstract Background: To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported. Methods: Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes. We further test our results in patient samples. Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW. Results: We reveal the surprising lack of sprouting angiogenesis during metastatic growth, despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases. We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab. Conclusion: We provide pre-clinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, and thus reveal a new mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The targets of clinically approved angiogenesis inhibitors are not active during early cancer progression in the lymph node, suggesting that inhibitors of sprouting angiogenesis as a class will not be effective in treating lymph node metastases. Citation Format: Dennis Jones, Han-Sin Jeong, Shan Liao, Daniel A. Wattson, Cheryl H. Cui, Dan G. Duda, Christopher G. Willett, Rakesh K. Jain, Timothy P. Padera. Formation of lymph node metastases is not angiogenesis dependent. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B03.
Human memory CD8 T cell effector potential is epigenetically preserved during in vivo homeostasis
Authors: Hossam A. Abdelsamed, Ardiana Moustaki, Yiping Fan, Pranay Dogra, Hazem E. Ghoneim, Caitlin C. Zebley, Brandon M. Triplett, Rafick-Pierre Sekaly, Ben Youngblood
Journal: The Journal of Experimental Medicine (2017)

Antigen-independent homeostasis of memory CD8 T cells is vital for sustaining long-lived T cell–mediated immunity. In this study, we report that maintenance of human memory CD8 T cell effector potential during in vitro and in vivo homeostatic proliferation is coupled to preservation of acquired DNA methylation programs. Whole-genome bisulfite sequencing of primary human naive, short-lived effector memory (TEM), and longer-lived central memory (TCM) and stem cell memory (TSCM) CD8 T cells identified effector molecules with demethylated promoters and poised for expression. Effector-loci demethylation was heritably preserved during IL-7– and IL-15–mediated in vitro cell proliferation. Conversely, cytokine-driven proliferation of TCM and TSCM memory cells resulted in phenotypic conversion into TEM cells and was coupled to increased methylation of the CCR7 and Tcf7 loci. Furthermore, haploidentical donor memory CD8 T cells undergoing in vivo proliferation in lymphodepleted recipients also maintained their effector-associated demethylated status but acquired TEM-associated programs. These data demonstrate that effector-associated epigenetic programs are preserved during cytokine-driven subset interconversion of human memory CD8 T cells.
Risk of suicide, deliberate self‐harm and psychiatric illness after the loss of a close relative: A nationwide cohort study
Authors: Mai‐Britt Guldin, Maiken Ina Siegismund Kjaersgaard, Morten Fenger‐Grøn, Erik Thorlund Parner, Jiong Li, Anders Prior, Mogens Vestergaard
Journal: World Psychiatry (2017)

The loss of a close relative is a common event, yet it is associated with increased risk of serious mental health conditions. No large-scale study has explored up to now the importance of the bereaved person's relation to the deceased while accounting for gender and age. We performed a nationwide Danish cohort study using register information from 1995 through 2013 on four sub-cohorts including all persons aged ≥18 years exposed to the loss of a child, spouse, sibling or parent. We identified 1,445,378 bereaved persons, and each was matched by gender, age and family composition to five non-bereaved persons. Cumulative incidence proportions were calculated to estimate absolute differences in suicide, deliberate self-harm and psychiatric illness. Cox proportional hazard regression was used to calculate hazard ratios while adjusting for potential confounders. Results revealed that the risk of suicide, deliberate self-harm and psychiatric illness was increased in the bereaved cohorts for at least 10 years after the loss, particularly during the first year. During that year, the risk difference was 18.9 events in 1,000 persons after loss of a child (95% CI: 17.6-20.1) and 16.0 events in 1,000 persons after loss of the spouse (95% CI: 15.4-16.6). Hazard ratios were generally highest after loss of a child, in younger persons, and after sudden loss by suicide, homicide or accident. One in three persons with a previous psychiatric diagnosis experienced suicide, deliberate self-harm or psychiatric illness within the first year of bereavement. In conclusion, this study shows that the risk of suicide, deliberate self-harm and psychiatric illness is high after the loss of a close relative, especially in susceptible subgroups. This suggests the need for early identification of high-risk persons displaying adjustment problems after loss of a close family member, in order to reduce the risk of serious mental health outcomes.
Clinical validation of a rapid point of need HCV molecular test
Authors: A. Llibre, Y. Shimakawa, E. Mottez, S. Ainsworth, T.-P. Buivan, R. Firth, A. Fontanet, P. Castan, A. Madejon-Seiz, M. Laverick, S. Pol, P. McClure, W. Irving, G. Miele, M.L. Albert, D. Duffy
Journal: Journal of Hepatology (2017)
Proteomic analysis identifies argininosuccinate synthase 1 as a useful biomarker for hepatocellular adenoma classification and patient management
Authors: A. Abouhammoud, E. Henriet, J.-W. Dupuy, B. Dartigues, Z. Ezzoukhry, N. Senant, J.-F. Blanc, B. Lebail, M. Nikolski, P. Bioulac-Sage, C. Balabaud, A.-A. Raymond, F. Saltel
Journal: Journal of Hepatology (2017)
Association of survival with chemotherapy intensity, myelosuppression, and supportive care in patients with advanced solid tumors.
Authors: Gary H. Lyman, Marek S. Poniewierski, Adane Fekadu Wogu, Eva Culakova, Nicole Maria Kuderer, Jeffrey Crawford, David C. Dale
Journal: Journal of Clinical Oncology (2013)

6534 Background: The value of chemotherapy and supportive care for advanced cancer has been questioned. Two systematic reviews were conducted to study the impact of chemotherapy-induced myelosuppression and supportive care on subsequent survival. Methods: Phase 1 identified trials evaluating the relationship of chemotherapy associated with myelosuppression and subsequent survival in patients with cancer. Phase 2 evaluated randomized controlled trials (RCTs) chemotherapy with or without G-CSF support for advanced cancer. Outcomes included hazard ratios (HR), relative risk (RR) and absolute risk (AR) ±95% CI. Results: In Phase 1, 11 of 25 identified studies were conducted in patients with advanced/metastatic disease with 10 in patients with solid tumors. Among the 7 studies in patients with solid tumors reporting survival outcomes, a consistent association between chemotherapy-associated myelosuppression and reduced mortality was observed (HR=0.69; 0.61-0.77; P&lt;.0001). A significant interaction between myelosuppression and cancer type for mortality was observed (P=.046) with significant effects observed for all tumor types. In Phase 2, 22 of 61 RCTs identified were in patients with stage IV solid tumors. Mortality was reduced with chemotherapy with G-CSF support overall (RR=0.95; 0.92-0.98; P=.003) and in patients with non-small cell lung cancer (RR=0.90; P=.037; AR=-6.6%; P=.014), sarcomas (RR=0.73; P=.007; AR=-22.1%; P=.004) or urothelial cancers (RR=0.87; P=.019; AR=-11.4%; P=.016). Reductions in mortality were seen with dose dense chemotherapy (RR=0.88; P=.021; AR=-10.0%; P=.019) and when survival was the primary outcome (n=11;RR=0.92; P=.022; AR=-5.2%; P=.001) with a trend toward greater benefit with longer duration of follow-up (P=.071). Conclusions: Studies of patients with advanced solid tumors demonstrate favorable effects of chemotherapy effect on survival. Chemotherapy treatment resulting in myelosuppression is associated with reduced mortality. RCTs of patients with advanced/metastatic solid tumors confirm that greater chemotherapy dose intensity with G-CSF support is associated with greater reductions in mortality.
A prospective multi-center study to investigate the EGFR-TKI resistance profile, treatment algorithm and clinical outcome in Chinese patients with advanced EGFRm+ NSCLC who have received prior first generation EGFR TKI (PRECENT study, CCTC-1601, NCT02988141)
Authors: W. Liang, L. Wu, L. Wang, Y. Huang, R. Xu, L. Zhang, J. He
Journal: Annals of Oncology (2017)
Magnetic resonance elastography measured shear stiffness as a biomarker of fibrosis in pediatric nonalcoholic fatty liver disease
Authors: Jeffrey B. Schwimmer, Cynthia Behling, Jorge Eduardo Angeles, Melissa Paiz, Janis Durelle, Jonathan Africa, Kimberly P. Newton, Elizabeth M. Brunt, Joel E. Lavine, Stephanie H. Abrams, Prakash Masand, Rajesh Krishnamurthy, Kelvin Wong, Richard L. Ehman, Meng Yin, Kevin J. Glaser, Bogdan Dzyubak, Tanya Wolfson, Anthony C. Gamst, Jonathan Hooker, William Haufe, Alexandra Schlein, Gavin Hamilton, Michael S. Middleton, Claude B. Sirlin
Journal: Hepatology (2017)

Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two‐dimensional (2D) MRE in children with NAFLD. MR elastograms were analyzed manually at two reading centers, and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross‐validated. In 90 children with a mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r = 0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ = 0.53; center 2, ρ = 0.55; and automated analysis, ρ = 0.52; P &lt; 0.001). Overall cross‐validated accuracy for detecting any fibrosis was 72.2% for all methods (95% confidence interval [CI], 61.8%‐81.1%). Overall cross‐validated accuracy for assessing advanced fibrosis was 88.9% (95% CI, 80.5%‐94.5%) for center 1, 90.0% (95% CI, 81.9%‐95.3%) for center 2, and 86.7% (95% CI, 77.9%‐92.9%) for automated analysis. Conclusion : 2D MRE can estimate hepatic stiffness in children with NAFLD. Further refinement and validation of automated analysis techniques will be an important step in standardizing MRE. How to best integrate MRE into clinical protocols for the assessment of NAFLD in children will require prospective evaluation. (H epatology 2017;66:1474–1485)
DASIMAR: a novel prognostic biomarker for acute cirrhosis decompensation to guide early intervention - a prospective multicenter study
Authors: P. Holland-Fischer, N. Shah, R. Sawhney, G. Privitera, S. Spinella, S. Masson, G. Foster, G. Aithal, K. Nash, D. Forton, R. Aspinall, N. Davies, R. Jalan, R.P. Mookerjee
Journal: Journal of Hepatology (2017)
Antiviral efficacy of a novel hepatitis B virus expression inhibitor in combination with entecavir and wIFN-alpha in woodchucks model of chronic hepatitis B
Authors: S. Wildum, G. Steiner, S. Luangsay, M. Suresh, K. Korolowicz, M. Balarezo, C. Yon, M. Murreddu, X. Hong, B. Kallakury, R. Tucker, H. Mueller, S. Menne, J. Young, H. Javanbakht
Journal: Journal of Hepatology (2017)
Preventing decompensation of cirrhosis with clinically significant portal hypertension and without high-risk varices: a new indication for non-selective beta-blockers (NSBB)
Authors: C. Villanueva, A. Albillos, J. Genescà, J.C. Garcia-Pagan, J.L. Calleja, C. Aracil, R. Bañares, R. Morillas, M. Poca, B. Peñas, S. Augustin, J.G. Abraldes, E. Alvarado, F. Torres, J. Bosch
Journal: Journal of Hepatology (2017)
Unintentional recurrent laryngeal nerve injuries following thyroidectomy: Is it the surgeon who pays the bill?
Authors: C. Gambardella, A. Polistena, A. Sanguinetti, R. Patrone, S. Napolitano, D. Esposito, D. Testa, V. Marotta, A. Faggiano, P.G. Calò, N. Avenia, G. Conzo
Journal: International Journal of Surgery (2017)
Amino-functionalized nanoparticles as a platform for mTOR activity modulation in hepatocellular carcinoma Huh7 cell line
Authors: M. Lunova, V. Zablotskii, A. Prokhorov, M. Jirsa, M. Hof, A. Olżyńska, P. Jurkiewicz, Š. Kubinová, O. Lunov, A. Dejneka
Journal: Journal of Hepatology (2017)