tbuckley/cabot-search huggingface dataset:
Correlation between RECIST-criteria, morphologic response by CT and pathologic regression in hepatic metastasis secondary to colorectal cancer: The AVAMET study
Authors: R. Vera, M. Gómez, J.R. Ayuso, J. Figueras, P. Garcia-Alfonso, V. Martinez, A. Lacasta, A. Ruiz, M.J. Safont, J. Aparicio, J. Campos, J. Cámara, M. Martin, C. Montagut, C. Pericay, J.M. Viéitez, E. Falcó, M. Jorge, M. Marín Vera, M. Salgado Fernandez
Journal: Annals of Oncology (2017)

Background: The RECIST criteria may be limited in assessing response to biologic agents such as bevacizumab (BVZ). Computed tomography-based morphologic criteria (CTMC) might be an alternative to evaluate response in these cases. The aim of this trial was to evaluate the correlation of overall objective responses evaluated by RECIST with CTMC and the pathologic response (pR) after the resection of liver metastases from colorectal cancer. Methods: Patients with ≤ 4 resectable CLM, with no prior chemotherapy for metastatic disease, received 3 cycles of capecitabine/oxaliplatin (XELOX)+BVZ. Response was evaluated using RECIST criteria and CTMC. For CTMC, metastasis was assigned to 1 of 3 groups (Table): CTMC were defined as optimal (metastasis changed from a group 3 or 2 to a 1), incomplete (group changed from 3 to 2), and none (the group had not changed or increased). Those patients without progression, received another cycle of XELOX prior to surgery. After surgery, BVZ + XELOX was given for up to 4 additional cycles. pR was scored as minor (≥50% of residual tumor cells), major (1-49% residual tumor cells), and complete (no residual tumor cells detected).Table590PComputed Tomographic Morphologic GroupsComputed Tomographic Tumor CharacteristicsMorphology GroupOverall AttenuationTumor-Liver InterfacePeripheral Rim of enhancement3HeterogeneousIll definedMay be present2MixedVariableIf initially present, partially resolved1Homogeneous and hypoattenuatingSharpIf initially present, completely resolved Open table in a new tab Results: 83 patients were recruited. 68 were evaluated by RECIST and 67 of them by CTMC; 60 underwent surgery, 51 with metastases resection and histologically analysis. 33 of 68 pts reached partial response by RECIST (49%, 95%CI 37-60%) and 58 had optimal (26) or incomplete (32) response by CTMC (85%, 95%CI 75-92%). Complete (12) or major (30) pR was achieved in 42 of 51 pts (82%, 95%CI 70-90%). Although there was no correlation between the RECIST criteria, CTMC and pR, CTMC was more specific for predicting complete/major pR than RECIST (36 of 42, CTMC vs. 24 of 42, RECIST, p=.0038). In patients with liver resection overall survival at 48 months was 65.8%. Conclusions: CTMC was more specific for predicting complete/major pR than RECIST criteria. After liver metastases resection, 82% of patients had complete or major pR. CTMC seem to be a better surrogate marker of objective pR than RECIST. Clinical trial identification: 2011-000143-24 Legal entity responsible for the study: Grupo GEMCAD Funding: Roche Disclosure: All authors have declared no conflicts of interest.
Co-amplification of KIT/KDR/PDGRA in over 100,000 advanced cancer cases
Authors: U. Disel, R. Madison, J. Chung, M. Gounder, A. Oztan, A. Benson, J. Webster, S.J. Klempner, S.-H.I. Ou, S. Ganesan, K. Janeway, P.J. Stephens, J.S. Ross, A.B. Schrock, V.A. Miller, S. Ali
Journal: Annals of Oncology (2017)
International Union of Basic and Clinical Pharmacology. CII: Pharmacological Modulation of H<sub>2</sub>S Levels: H<sub>2</sub>S Donors and H<sub>2</sub>S Biosynthesis Inhibitors
Authors: Csaba Szabo, Andreas Papapetropoulos
Journal: Pharmacological Reviews (2017)

Over the last decade, hydrogen sulfide (H<sub>2</sub>S) has emerged as an important endogenous gasotransmitter in mammalian cells and tissues. Similar to the previously characterized gasotransmitters nitric oxide and carbon monoxide, H<sub>2</sub>S is produced by various enzymatic reactions and regulates a host of physiologic and pathophysiological processes in various cells and tissues. H<sub>2</sub>S levels are decreased in a number of conditions (e.g., diabetes mellitus, ischemia, and aging) and are increased in other states (e.g., inflammation, critical illness, and cancer). Over the last decades, multiple approaches have been identified for the therapeutic exploitation of H<sub>2</sub>S, either based on H<sub>2</sub>S donation or inhibition of H<sub>2</sub>S biosynthesis. H<sub>2</sub>S donation can be achieved through the inhalation of H<sub>2</sub>S gas and/or the parenteral or enteral administration of so-called fast-releasing H<sub>2</sub>S donors (salts of H<sub>2</sub>S such as NaHS and Na<sub>2</sub>S) or slow-releasing H<sub>2</sub>S donors (GYY4137 being the prototypical compound used in hundreds of studies in vitro and in vivo). Recent work also identifies various donors with regulated H<sub>2</sub>S release profiles, including oxidant-triggered donors, pH-dependent donors, esterase-activated donors, and organelle-targeted (e.g., mitochondrial) compounds. There are also approaches where existing, clinically approved drugs of various classes (e.g., nonsteroidal anti-inflammatories) are coupled with H<sub>2</sub>S-donating groups (the most advanced compound in clinical trials is ATB-346, an H<sub>2</sub>S-donating derivative of the non-steroidal anti-inflammatory compound naproxen). For pharmacological inhibition of H<sub>2</sub>S synthesis, there are now several small molecule compounds targeting each of the three H<sub>2</sub>S-producing enzymes cystathionine-<i>β</i>-synthase (CBS), cystathionine-<i>γ</i>-lyase, and 3-mercaptopyruvate sulfurtransferase. Although many of these compounds have their limitations (potency, selectivity), these molecules, especially in combination with genetic approaches, can be instrumental for the delineation of the biologic processes involving endogenous H<sub>2</sub>S production. Moreover, some of these compounds (e.g., cell-permeable prodrugs of the CBS inhibitor aminooxyacetate, or benserazide, a potentially repurposable CBS inhibitor) may serve as starting points for future clinical translation. The present article overviews the currently known H<sub>2</sub>S donors and H<sub>2</sub>S biosynthesis inhibitors, delineates their mode of action, and offers examples for their biologic effects and potential therapeutic utility.
Efficacy of cabozantinib (C) after PD-1/PD-L1 checkpoint inhibitors in metastatic renal cell carcinoma (mRCC): The Gustave Roussy experience
Authors: L. Derosa, J.A. Rouche, E. Colomba, G. Baciarello, B. Routy, L. Albiges, B. Escudier
Journal: Annals of Oncology (2017)
How do Spanish medical oncologists manage breakthrough pain? A national study
Authors: E. Aranda, C. Camps Herrero, P. Khosravi, M. Feyjoo, A. Anton Torres, P. Gascon, J. Garcia Foncillas, E. Diaz Rubio, V. Guillem Porta, A. Carrato, M. Constenla Figueiras, J.J. Cruz Hernandez, R. López
Journal: Annals of Oncology (2017)
Abstract 20226: Meta-Analysis of Complications and Success of Catheter Ablation for Atrial Fibrillation in Octogenarians
Authors: Tatyana Aliyeva, Robert Chait
Journal: Circulation (2016)

Introduction: The population of the United States is aging and thus the prevalence and incidence of atrial fibrillation are increasing. Morbidity and mortality from this arrhythmia positively corre...
Broad immunomodulating effect of first-line pazopanib in metastatic renal cell carcinoma patients
Authors: E. Verzoni, L. De Cecco, M. Dugo, D. Rinchai, D. Bedognetti, P. Grassi, R. Ratta, A. Cova, P. Squarcina, V. Huber, R. Montone, M. Sorrentino, G. Procopio, L. Rivoltini
Journal: Annals of Oncology (2017)
A clinical trial of autologous formalin-fixed tumor vaccine (AFTV) for patients with glioblastoma multiforme
Authors: K. Tsuboi, E. Ishikawa, T. Yamamoto, S. Takano, A. Matsumura, T. Ohno
Journal: Journal of Clinical Oncology (2007)

2085 Background: This clinical pilot study is to investigate the safety, feasibility, plus clinical response of autologous formalin- fixed tumor vaccine (ATFV) in primary glioblastoma multiforme (GBM) patients. Methods: Eleven (8 recurrent and 3 initially treated) primary GBM patients were evaluated. AFTV was prepared from formalin-fixed tumor tissue or paraffin-embedded tissue and premixed with original adjuvant materials. A delayed-type hypersensitivity test (DTH) was performed before and after each course of ATFV treatment that comprised 3 vaccinations at a 5-site intradermal inoculation. In addition, immunohistochemical analysis of MIB-1, p53, and MHC class-I complex was performed on the tumor tissue to analyze the difference in the response to the treatment. Results: The treatment was well tolerated with only local induration and low-grade fever. Among the 11 patients, the best responses were 1 complete remission, 2 partial response, 1 no change, and 7 progressive disease. In this series, the median survival period was 7 months from the initiation of the AFTV treatment, and 3 of the 4 responders survived for more than 20 months after AFTV inoculation. DTH reactions, immunohistological analysis of p53 and MHC class-I complex, and patient status may be useful to predict the efficacy of this therapy. Conclusion: This study demonstrated that AFTV treatment is safe, feasible, and potentially beneficial. Further clinical investigation is highly desirable in order to improve the outcome of GBM patients. No significant financial relationships to disclose.
Abstract #1513: Recruitment of histone acetyltransferase activity by the N-terminal homology domain of Pygopus augments TCF-dependent transcriptional activation
Authors: Phillip Andrews, Kenneth Kao, Catherine Popadiuk
Journal: Cancer Research (2009)

Pygopus is a core component of the beta-catenin/TCF transcriptional activation complex, hypothesized to augment target gene expression by interpreting and modifying the local histone code. Pygopus is essential for development of the early embryo for both Wnt-dependent and Wnt-independent activity and is also required for breast and epithelial ovarian cancer cell growth. The Pygopus protein consists of two conserved domains: a plant homeo domain (PHD), which interacts with the Legless (lgs) adapter protein linking it to the beta-catenin/TCF complex, and an N-terminal homology domain (NHD). The NHD is essential for transcriptional activity, but evidence is lacking on its interaction with other proteins. We now demonstrate that the interaction of Pygopus with histone acetyltransferase (HAT) family members via specific residues in its N-terminal homology domain (NHD) is required to enhance beta-catenin/TCF mediated transcription. The HAT family member CREB Binding Protein (CBP), a component of the beta-catenin/TCF complex, augmented Pygopus-mediated transcription from both TCF/LEF-specific reporter genes, as well as from DNA-tethered Pygopus. Furthermore, immunoprecipitated Pygopus protein complexes displayed CBP-dependent histone acetyltransferase activity. Our data support a model in which the chromatin relaxation requirement in TCF/beta-catenin-mediated transcriptional activation is fulfilled by recruitment of the histone acetyltransferase CBP by Pygopus.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1513.
GW28-e0380 The Accuracy of Ultrasound-Derived Three-Dimensional Printing Models for Atrial Septal Defect
Authors: Dan e Mei, Qing Deng, Hongning Song, Qing Zhou, Chuangli Feng, Dan Jia, Zhiyu Zhao, Ruiqiang Guo, Jinling Chen
Journal: Journal of the American College of Cardiology (2017)
Safety, efficacy and immune effects of venetoclax 400 mg daily in patients with relapsed chronic lymphocytic leukemia (CLL).
Authors: Matthew Steven Davids, Andrew Warwick Roberts, John Francis Seymour, John F. Gerecitano, Brad S. Kahl, Thomas J. Kipps, John M. Pagel, Soham D. Puvvada, Lori A. Gressick, Ming Zhu, Martin Dunbar, Brenda Chyla, Maria E. Verdugo, Su Young Kim, William G. Wierda
Journal: Journal of Clinical Oncology (2016)

7527 Background: Venetoclax (VEN) is an orally bioavailable BCL2 selective inhibitor. Patients (pts) with relapsed or refractory CLL or small lymphocytic lymphoma were treated in a phase 1 trial (M12-175, NCT01328626) with doses ranging from 150-1200 mg/day (Roberts, et al., NEJM 2016). Here we report the updated safety and efficacy data in the subset of CLL pts treated at the recommended phase 2 dose (RP2D) of VEN (400 mg daily), with a focus on effects on the host immune system. Methods: 59 CLL pts were enrolled to receive VEN 400mg/day. This analysis is restricted to the 57 pts with complete baseline and re-staging evaluations. Immunophenotyping studies were performed by flow cytometry on the peripheral blood. Results: As of December 1, 2015, the median time on study was 19 months (range 0.5-44). Pts had a median of 3 prior therapies (range 1-11). The overall response rate was 81%; 16% achieved complete remission. The 24-month estimate for progression-free survival was 62% [95% CI = 45, 75] and that for duration of response was 77% [95% CI = 58, 98]. The most common treatment emergent adverse events (AEs) were upper respiratory tract infection (49%), diarrhea (47%), and neutropenia (44%). Grade ≥ 3 AEs occurred in 86% of pts, with neutropenia being the most common (40%). 19/25 pts with neutropenia were treated with GCSF; all of them responded, 2 were also dose-reduced. 8 deaths were reported [Richters transformation (n = 4), complications after allogenic stem cell transplant (n = 2), small bowel obstruction, viral pneumonia (n = 1 each)]. Significant reductions were seen in blood B-cell counts, however, no appreciable reductions were observed in the mean absolute counts for CD3+ T-cells, CD4+ or CD8+ T-cells, or NK cells. Similarly, no significant changes were observed in immunoglobulin levels. Only 11/57 pts experienced Grade ≥ 3 infection, at the rates of 14% in the first 6 months and 9% for the subsequent time on study. Conclusions: VEN at RP2D of 400 mg/day resulted in a high response rate and durable remissions. While VEN can induce neutropenia, host T-cell numbers and immunoglobulin levels remained unchanged, and the risk of Gr ≥ 3 infection in this relapsed CLL population was low. Clinical trial information: NCT01328626.
High dose loco-regional chemotherapy for locally advanced angiosarcoma: A multicenter study
Authors: E. Huis in 't Veld, D.J. Grunhagen, K. Verhoef, H.G. Smith, A. van Akkooi, R.L. Jones, F. Van Coevorden, A.J. Hayes, W.J. van Houdt
Journal: Annals of Oncology (2017)
Efficacy and safety of patients treated long-term with trabectedin (t) on the expanded access program: A retrospective analysis
Authors: E. Davis, S. Schuetze, S. Patel, R. Maki, R.L. Jones, C.R. Shin, R. Knoblauch, G. Wang, M. Smith, G.D.S. Demetri, P. Merriam
Journal: Annals of Oncology (2017)
Phase III randomized, double-blind, controlled studies of the PI3K inhibitor copanlisib in combination with rituximab or rituximab-based chemotherapy in subjects with relapsed indolent B-cell non-Hodgkin’s lymphoma (iNHL): CHRONOS-3 and CHRONOS-4
Authors: J. Gerecitano, H. Zheng, L. Mongay Soler, R. Ito, D. Reis, C. Lu, J. Shen, B.H. Childs, P.L. Zinzani
Journal: Annals of Oncology (2017)
Activity of anti-PD1 drugs in uveal melanoma patients.
Authors: Sophie Piperno-Neumann, Vincent Servois, Pascale Mariani, Nathalie Cassoux, Raymond Barnhill, Manuel Jorge Rodrigues
Journal: Journal of Clinical Oncology (2016)

9588 Background: Metastatic uveal melanomas (MUM) are BRAF-wild type tumors of poor prognosis for which no systemic therapy is active. Anti-Programmed cell Death 1(anti-PD1) drugs have shown activity in metastatic skin melanoma patients (pts) thus granting an approval for unresectable or metastatic melanoma. We report our experience with anti-PD1 in MUM pts. Methods: Ambispective cohort of MUM pts treated with either nivolumab or pembrolizumab at Institut Curie. Response rate, progression-free survival (PFS) and overall survival were retrieved. Results: 21 evaluable pts started anti-PD1 treatment between June 2015 and January 2016. The population consisted of 10 men and 11 women, median age was 64 (32-77). Nine patients have been enucleated, 12 received proton beam therapy. The median time to first extra-ocular metastasis was 32 months (7-150). Anti-PD1 was prescribed after a median of 2 prior lines of systemic treatment (0-5). Performance status was 0 in 9 and 1 in 11 pts. Metastatic sites at initiation of anti-PD1 were liver, skin, lung, pancreas and bone for 18, 5, 5, 3 and 2 pts respectively. Liver was the sole metastatic site in 10 pts. LDH were above normal levels in 7 pts. Patients received a median number of 4 injections of nivolumab (2-14+) or 4 injections of pembrolizumab (3-4+). No objective response was observed, 6/14 pts showed stable disease as best response. Treatment was not suspended in any patient because of side effects. Median actuarial PFS is 3 months (0-6+). Conclusions: To date, anti-PD1 have shown no activity in our series of MUM pts. A national ambispective study is currently underway to evaluate anti-PD1activity in a larger series associated with biomarkers analyses (i.e. PD-L1 immunohistochemistry, genomic status). Until more optimistic results are reported or reliable biomarkers are found, anti-PD1 should not be considered as a standard option in MUM.
Surveillance de l’encéphalite à tiques en Europe et définition de cas
Authors: G Günther, L Lindquist
Journal: Eurosurveillance (2005)

L’etude menee par P Stefanoff et ses collegues [1] souleve deux questions importantes sur les encephalites a tiques : l’absence d’une definition de cas acceptee par tous, et la qualite de la surveillance nationale des encephalites a tiques. Idealement, les cas declares devraient etre confirmes et les cas cliniques avec atteinte du systeme nerveux central (SNC) devraient etre separes des cas febriles sans manifestation neurologique. En Europe, la surveillance encephalites a tiques varie d’un pays a l’autre et n’est pas toujours obligatoire. Les efforts pour aboutir a un diagnostic, en particulier dans les formes moins graves et chez les enfants, sont variables ; de meme que la prise de conscience de la maladie dans les pays de faible endemicite. La seule base stable et adaptee a une surveillance nationale repose sur les cas presentant une maladie du SNC confirmee, bien qu’a l’echelon individuel, l’immunite vis-a-vis du virus de l’encephalite a tiques apres une maladie febrile moins severe ne soit pas depourvue d’interet. Le ratio « sans atteinte neurologique » sur « atteinte du CNS » est de l’ordre de trois, mais il existe des differences regionales quant a la virulence. Les differences liees a l’âge ne sont pas connues.
When cost-effective interventions are unaffordable: Integrating cost-effectiveness and budget impact in priority setting for global health programs
Authors: Alyssa Bilinski, Peter Neumann, Joshua Cohen, Teja Thorat, Katherine McDaniel, Joshua A. Salomon
Journal: PLoS Medicine (2017)

Potential cost-effective barriers in cost-effectiveness studies mean that budgetary impact analyses should also be included in post-2015 Sustainable Development Goal projects says Joshua Salomon and colleagues.
Predictive value of primary tumor location: Results from randomized phase II study of panitumumab + irinotecan versus cetuximab + irinotecan in patients with KRAS exon2 wild-type metastatic colorectal cancer (WJOG6510G)
Authors: T. Tamura, D. Sakai, N. Sugimoto, S. Tokunaga, A. Tsuji, H. Ishida, S. Otsu, T. Moriwaki, H. Satake, K. Uchino, S. Matsumoto, E. Baba, M. Sato, H. Taniguchi, J. Kishimoto, N. Boku, I. Hyodo, K. Muro
Journal: Annals of Oncology (2017)
AG-120, a novel IDH1 targeted molecule, inhibits invasion and migration of chondrosarcoma cells in vitro
Authors: V. Heredia, M. Mendiola, E. Ortiz, D. Bernabéu, J.J. Pozo-Kreilinger, M. Miguel, R. Crespo, A. Berjón, V. Martínez-Marín, A. Redondo
Journal: Annals of Oncology (2017)
Death by Gun Violence—A Public Health Crisis
Authors: Howard Bauchner, Frederick P. Rivara, Robert O. Bonow, Neil M. Bressler, Mary L. (Nora) Disis, Stephan Heckers, S. Andrew Josephson, Melina R. Kibbe, Jay F. Piccirillo, Rita F. Redberg, John S. Rhee, June K. Robinson
Journal: JAMA Psychiatry (2017)

The shooting in Las Vegas, Nevada, that left 59 people dead, 10 times that number wounded, and thousands of people with the psychological distress from being present at the scene during and after the massacre has once again raised the issue of what we as a nation can and should do about guns.The solution lies in not just focusing on Las Vegas and the hundreds of other mass shootings that have occurred in the United States in the last 14 months, but rather to underscore that on average almost 100 people die each day in the United States from gun violence.The 36 252 deaths from firearms in the United States in 2015 1 exceeded the number of deaths from motor vehicle traffic crashes that year (36 161). 1 That same year, the US Centers for Disease Control and Prevention reported that 5 people died from terrorism.Since 1968, more individuals in the United States have died from gun violence than in battle during all the wars the country has fought since its inception. 2uns do not make individuals, their families, or homes safer and they result in far more deaths to loved ones than to an intruder intending to cause harm. 3Often forgotten is that 60.7% of the gun deaths in 2015 in the United States were suicides. 1Means used to attempt suicide matter; guns will result in suicidal deaths well over 90% of the time, whereas ingestion of pills or wrist cutting will be unsuccessful more than 90% of the time.The majority of people who try to commit suicide but survive the attempt will not go on to die from suicide 4 ; if the attempt is with a gun, there will be no second chance at life.The journals of the JAMA Network are dedicated to improving the health of people across the globe.We do so by addressing the most important public health problems harming people and publishing the best science that can be done.The journals have published important work on gun violence; in the past year this has included studies on differences in gun use during terrorist attacks in the United States compared with other countries, 5 the effect of exposure to gun violence in the media on children's interest in real guns,