tbuckley/cabot-search huggingface dataset:
Anti–mitotic function of a synthetic compound MMPT disrupting microtubule polymerization in human lung cancer cell lines
Authors: Fuminori Teraishi, Shuhong Wu, Ji-Ichiro Sasaki, Lidong Zhang, Hong-Bo Zhu, John J. Davis, Dietmar Jacob, Bingliang Fang
Journal: Cancer Research (2004)

5413   The microtubules is an important target in cancer chemotherapy. Various microtubule-interacting agents have been evaluated for their anticancer effects, and a few of them have been used as anticancer drugs clinically, including paclitaxel and the  Vinca  alkaloid vincristine. In searching for new anticancer agents, we identified the synthetic compound MMPT which can kill cancer cells more effectively than normal human fibroblasts. Subsequently, we investigated the antitumor property and mechanisms of action of MMPT in human lung cancer cell lines. MMPT inhibited cell growth with an IC 50  range of 4.9 to 6.7 μM in human non-small cell lung cancer (NSCLC) cell lines. This inhibitory effect is independent of p53 status. Moreover, MMPT had almost no toxic effects in normal human cells at the IC 50  level for NSCLC cells. Furthermore, MMPT showed similar antiproliferative effects against parental H460 and taxol-resistant H460 cells that have high a level of P-glycoprotein expression, suggesting that MMPT is not affected by P-glycoprotein status. Treatment of NSCLC cells with MMPT led to a time- and dose-dependent accumulation of cell-cycle arrest at mitosis; modulated levels of G 2 -M checkpoint proteins such as cyclin B1, cdc25C, Bcl-2, and histone H 3 , and induced apoptosis with caspase activation. Finally, MMPT induced abnormal spindle formation and prevented tubulin polymerization in mitotic cancer cells. Together, these results indicate that MMPT is a novel antimitotic compound with microtubule depolymerization activity and may have be potent against human NSCLC cells.
Establishment of chemo-resistant gastric cancer cell line and evaluation of their characteristics
Authors: Rieko Nakamura, Yoshiro Saikawa, Fumiki Asanuma, Yoshinori Yamada, Tetsuro Kubota, Yuko Kitagawa
Journal: Cancer Research (2008)

3220  Background: Recent development of novel anticancer drugs has shown possible roles of anticancer chemotherapy, improving patients’ quality of life (QOL) and prognosis. On the other hand, long-term treatment with an anticancer drug will result in progressive acquirement of drug-resistance in cancer cell itself. We previously reported No cross-resistance of taxanes to 5-FU and CDDP and cross-resistance between 5-fluoroutacil(5-FU) and cisplatin (CDDP) using wild types of human gastric cancer cell line (Maeda S, Saikawa Y, et al. Anticancer Res 23: 3147-3150, 2003).Methods: We have established CDDP-resistant and 5-FU-resistant gastric cancer cell lines using wild types of human gastric cancer cell lines; TMK-1, MKN-74, and MKN-45 with long-term exposure (several months) with low concentration of each drug (named as TMK-1/D, MKN-74/D, MKN-45/D, TMK-1/FU, MKN-74/FU, MKN-45/FU). IC50s were analyzed to demonstrate resistance to each drug, calculated with each concentration-survival curve with MTT method, and to evaluate cross-resistance or no cross-resistance to the other drugs including docetaxel (DOC) and paclitaxel (PAC). Results:1.The IC50s of CDDP were as follows: TMK-1 2.14±0.46μg/ml, TMK-1/D 10.43±2.20μg/ml, MKN-74 6.69±3.19μg/ml, MKN-74/D 28.53±9.80μg/ml, MKN-45 10.52±0.24μg/ml, MKN-45/D 13.16±4.62μg/ml, as the IC50 ratio of TMK-1/D to TMK-1 was 4.87 fold, and MKN-74/D to MKN-74 was 4.26 fold, while MKN-45/D to MKN-45 was only 1.25 fold. The IC50s of 5-FU were as follows: TMK-1 240.39±14.04μg/ml, TMK-1/FU 1236.84±54.90μg/ml, MKN-74 169.15±26.51μg/ml, MKN-74/FU 1859.23±52.3μg/ml, MKN-45 25.7±7.35μg/ml, MKN-45/FU 1574.50±105.30μg/ml, as the IC50 ratios of TMK-1/FU to TMK-1 , MKN-74/FU to MKN-74, and MKN-45/FU to MKN-45 were 5.03, 10.99, 61.26 fold, respectively. 2.Cross-resistance between 5-FU and CDDP in each resistant cell were confirmed, as the IC50 ratio of CDDP of TMK-1/FU to TMK-1, MKN-74/FU to MKN-74, and MKN-45/FU to MKN-45 was 4.72, 4.87, 2.77 fold, respectively. 3.The IC50s of DOC and PAC in each wild and resistant cell line were calculated. Interestingly, cross-resistance was not confirmed in PAC (0.38-0.48 fold) treatment, but DOC (5.04- 6.43 fold), in CDDP-resistant cell lines. On the other hand, in 5-FU-resistant cell lines, there is no cross-resistance between 5-FU and DOC (0.32-1.04 fold) or between 5-FU and PAC (0.78-2.00 fold).Conclusion: Acquired chemo-resistant cells established demonstrated various kinds of chemo-sensitivity to DOC/PAC, while 5-FU and CDDP have clearly shown cross-resistance even using the resistant cells to each drug.Appropriate drugs like DOC or PAC should be applied after acquired drug resistance to 5-FU or CDDP was suggested, in order to overcome 5-FU or CDDP chemo-resistance, while these results also suggested that even DOC might not be useful in CDDP chemo-resistance cells because of cross-resistance, in some occasion.
Radionuclide Imaging-Guided Chemo-Radioisotope Synergistic Therapy Using a 131I-Labeled Polydopamine Multifunctional Nanocarrier
Authors: Zhiqiang Li, Baikui Wang, Zheng Zhang, Bo Wang, Qiangqiang Xu, Wenjie Mao, Jie Tian, Kai Yang, Fu Wang
Journal: Molecular Therapy (2018)

Development of biocompatible nanomaterials with multiple functionalities for combination of radiotherapy and chemotherapy has attracted tremendous attention in cancer treatment. Herein, poly(ethylene glycol) (PEG) modified polydopamine (PDA) nanoparticles were successfully developed as a favorable biocompatible nanoplatform for co-loading antitumor drugs and radionuclides to achieve imaging-guided combined radio-chemotherapy. It is demonstrated that PEGylated PDA nanoparticles can effectively load two different drugs including sanguinarine (SAN) and metformin (MET), as well as radionuclides 131I in one system. The loaded SAN and MET could inhibit tumor growth via inducing cell apoptosis and relieving tumor hypoxia, while labeling PDA-PEG with 131I enables in vivo radionuclide imaging and radioisotope therapy. As revealed by the therapeutic efficacy both in cell and animal levels, the multifunctional PDA nanoparticles (131I-PDA-PEG-SAN-MET) can effectively repress the growth of cancer cells in a synergistic manner without significant toxic side effects, exhibiting superior treatment outcome than the respective monotherapy. Therefore, this study provides a promising polymer-based platform to realize imaging-guided radioisotope/chemotherapy combination cancer treatment in future clinical application.
Hémorragie digestive par rupture de varices oesophagiennes au cours de la cirrhose: quel est le score pronostique le plus fiable?
Authors: B Bouchabou, L Hamzaoui, A Ben Mohamed, M Medhioub, K Amal, MM Azouz
Journal: Endoscopy (2018)

La survenue d'une hémorragie digestive (HD) par rupture de varices oesophagiennes (RVO) compliquant un foie de cirrhose reste un événement grave représentant un tournent évolutif de la maladie sous-jacente. Une meilleure stratification du risque de survenue de cette complication permettrait d'optimiser la prise en charge et d'améliorer le devenir des patients. Plusieurs scores pronostiques ont été développés, afin d'identifier les patients à haut risque. Le but de ce travail est de trouver le score pronostique le complet et reproductible chez les patients cirrhotiques ayant une HD par RVO.
Assessing Metronomic Chemotherapy for Progressive Pediatric Solid Malignant Tumors
Authors: Xuemin Fang, Hajime Uno, Lee-Jen Wei
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis
Authors: Marcin Waligora, Malgorzata M. Bala, Magdalena Koperny, Mateusz T. Wasylewski, Karolina Strzebonska, Rafał R. Jaeschke, Agnieszka Wozniak, Jan Piasecki, Agnieszka Sliwka, Jerzy W. Mitus, Maciej Polak, Dominika Nowis, Dean Fergusson, Jonathan Kimmelman
Journal: PLoS Medicine (2018)

Background Pediatric Phase I cancer trials are critical for establishing the safety and dosing of anti-cancer treatments in children. Their implementation, however, must contend with the rarity of many pediatric cancers and limits on allowable risk in minors. The aim of this study is to describe the risk and benefit for pediatric cancer Phase I trials. Methods and findings Our protocol was prospectively registered in PROSPERO (CRD42015015961). We systematically searched Embase and PubMed for solid and hematological malignancy Phase I pediatric trials published between 1 January 2004 and 1 March 2015. We included pediatric cancer Phase I studies, defined as "small sample size, non‑randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested." We measured risk using grade 3, 4, and 5 (fatal) drug-related adverse events (AEs) and benefit using objective response rates. When possible, data were meta-analyzed. We identified 170 studies meeting our eligibility criteria, accounting for 4,604 patients. The pooled overall objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological malignancies, 27.90% (95% CI 20.53% to 35.27%); p < 0.001. The overall fatal (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade 3/4 AE rate per person equal to 1.32. Our study had the following limitations: trials included in our review were heterogeneous (to minimize heterogeneity, we separated types of therapy and cancer types), and we relied on published data only and encountered challenges with the quality of reporting. Conclusions Our meta-analysis suggests that, on the whole, AE and response rates in pediatric Phase I trials are similar to those in adult Phase I trials. Our findings provide an empirical basis for the refinement and review of pediatric Phase I trials, and for communication about their risk and benefit.
Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states
Authors: Pedro M Machado, Robert Landewé, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2018)

The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a measure of axial spondyloarthritis (axSpA) disease activity with validated cut-offs endorsed by the Assessment of SpondyloArthritis international Society (ASAS) and Outcome Measures in Rheumatology (OMERACT).1 2 In the 2016 update of the ASAS-European League Against Rheumatism (EULAR) management recommendations for axSpA, it is recommended that biological disease-modifying antirheumatic drugs should be considered in patients with persistently high disease activity despite conventional treatments, and that the preferred measure to define active disease should be the ASDAS (ASDAS of at least 2.1, ie, high disease activity).3 The 2017 update of treat-to-target recommendations in axial and peripheral SpA recommends that the treatment target should be inactive disease/clinical remission and that low/minimal disease activity may be an alternative treatment target. The same recommendations state that the preferred measure to define the target in axSpA is the ASDAS.4 

ASDAS cut-offs for disease activity states are 1.3, separating ‘inactive disease’ from ‘moderate disease activity’, 2.1, …
Maladie coeliaque: corrélation entre la clinique, l'aspect endoscopique, le profil sérologique et le degré d'atrophie villositaire
Authors: M Zeriouh, W Khannoussi, A El Mekkaoui, I Zahi, G Kharrasse
Journal: Endoscopy (2018)

La maladie coeliaque, entéropathie chronique auto-immune survenant chez des sujets génétiquement prédisposés et caractérisée sur le plan histologique par une atrophie villositaire. Plusieurs études récentes ont montré qu'il y avait une certaine corrélation entre la présentation clinique, le profil sérologique et le degré d'atteinte histologique au cours de la maladie coeliaque. Ce travail a pour objectif d'étudier cette corrélation dans une série de malades ayant une maladie coeliaque.
Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients
Authors: Yonathan Freund, Marine Cachanado, Adeline Aubry, Charlotte Orsini, Pierre-Alexis Raynal, Anne-Laure Féral-Pierssens, Sandrine Charpentier, Florence Dumas, Nacera Baarir, Jennifer Truchot, Thibaut Desmettre, Karim Tazarourte, Sebastien Beaune, Agathe Leleu, Mehdi Khellaf, Mathias Wargon, Ben Bloom, Alexandra Rousseau, Tabassome Simon, Bruno Riou
Journal: JAMA (2018)

The safety of the pulmonary embolism rule-out criteria (PERC), an 8-item block of clinical criteria aimed at ruling out pulmonary embolism (PE), has not been assessed in a randomized clinical trial.To prospectively validate the safety of a PERC-based strategy to rule out PE.A crossover cluster-randomized clinical noninferiority trial in 14 emergency departments in France. Patients with a low gestalt clinical probability of PE were included from August 2015 to September 2016, and followed up until December 2016.Each center was randomized for the sequence of intervention periods. In the PERC period, the diagnosis of PE was excluded with no further testing if all 8 items of the PERC rule were negative.The primary end point was the occurrence of a thromboembolic event during the 3-month follow-up period that was not initially diagnosed. The noninferiority margin was set at 1.5%. Secondary end points included the rate of computed tomographic pulmonary angiography (CTPA), median length of stay in the emergency department, and rate of hospital admission.Among 1916 patients who were cluster-randomized (mean age 44 years, 980 [51%] women), 962 were assigned to the PERC group and 954 were assigned to the control group. A total of 1749 patients completed the trial. A PE was diagnosed at initial presentation in 26 patients in the control group (2.7%) vs 14 (1.5%) in the PERC group (difference, 1.3% [95% CI, -0.1% to 2.7%]; P = .052). One PE (0.1%) was diagnosed during follow-up in the PERC group vs none in the control group (difference, 0.1% [95% CI, -∞ to 0.8%]). The proportion of patients undergoing CTPA in the PERC group vs control group was 13% vs 23% (difference, -10% [95% CI, -13% to -6%]; P < .001). In the PERC group, rates were significantly reduced for the median length of emergency department stay (mean reduction, 36 minutes [95% CI, 4 to 68]) and hospital admission (difference, 3.3% [95% CI, 0.1% to 6.6%]).Among very low-risk patients with suspected PE, randomization to a PERC strategy vs conventional strategy did not result in an inferior rate of thromboembolic events over 3 months. These findings support the safety of PERC for very low-risk patients presenting to the emergency department.clinicaltrials.gov Identifier: NCT02375919.
<i>In vivo</i> dermoscopic and confocal microscopy multistep algorithm to detect <i>in situ</i> melanomas
Authors: S. Borsari, R. Pampena, E. Benati, C. Bombonato, A. Kyrgidis, E. Moscarella, A. Lallas, G. Argenziano, G. Pellacani, C. Longo
Journal: British Journal of Dermatology (2018)

Although several dermoscopic features of in situ melanoma have been identified, data on confocal features of in situ melanoma are still lacking.To identify reflectance confocal microscopy (RCM) features of in situ melanoma and to develop a diagnostic score combining dermoscopy and RCM.In total, 120 in situ melanoma and 213 nevi (test set) were retrospectively analysed to assess the presence of dermoscopic and RCM criteria. Facial and acral lesions were excluded. Spearman's correlation, univariate and multivariate regression models were used to identify features significantly correlated with in situ melanoma diagnosis. Multivariate results on the test set allowed the development of a multistep algorithm, that was tested on a validation set of 100 lesions.The dermoscopic findings of an atypical network and regression were independent predicting factors for in situ melanoma diagnosis [odds ratio (OR) 3·44, 95% CI (confidence interval) 1·70-6·97 and OR 4·17, 95% CI 1·93-9·00, respectively]. Significant confocal predictors for malignancy were epidermal pagetoid spread (OR 2·83, 95% CI 1·32-6·04) and junctional cytological atypia (OR 3·39, 95% CI 1·38-8·30 if focal, OR 8·44, 95% CI 3·21-22·16 if widespread). A multistep diagnostic algorithm able to predict in situ melanoma with a sensitivity of 92·5% and a specificity of 61% was developed. The validation set confirmed the high diagnostic value (sensitivity 92%, specificity 58%).An easy and reproducible multistep algorithm for in situ melanoma detection is suggested, that can be routinely used in tertiary centres.
miRNAs Targeting ICP4 and Delivered to Susceptible Cells in Exosomes Block HSV-1 Replication in a Dose-Dependent Manner
Authors: Lei Wang, Xiaoqing Chen, Xusha Zhou, Bernard Roizman, Grace Guoying Zhou
Journal: Molecular Therapy (2018)

miRNAs are potent tools that in principle can be used to control the replication of infectious agents. The objectives of the studies reported here were to design miRNAs that can block the replication of herpes simplex virus 1 and which could be delivered to infected cells via exosomes. We report the following: (1) We designed three miRNAs targeting the mRNA encoding ICP4, an essential viral regulatory protein. Of the three miRNAs, one miRNA401 effectively blocked ICP4 accumulation and viral replication on transfection into susceptible cells. (2) To facilitate packaging of the miRNA into exosomes, we incorporated into the sequence of miRNA401 an exosome-packaging motif. miRNA401 was shown to be packaged into exosomes and successfully delivered by exosomes to susceptible cells, where it remained stable for at least 72 hr. Finally, the results show that miRNA401 delivered to cells via exosomes effectively reduced virus yields in a miRNA401 dose-dependent fashion. The protocol described in this report can be applied to study viral gene functions without actually deleting or mutagenizing the gene. miRNAs are potent tools that in principle can be used to control the replication of infectious agents. The objectives of the studies reported here were to design miRNAs that can block the replication of herpes simplex virus 1 and which could be delivered to infected cells via exosomes. We report the following: (1) We designed three miRNAs targeting the mRNA encoding ICP4, an essential viral regulatory protein. Of the three miRNAs, one miRNA401 effectively blocked ICP4 accumulation and viral replication on transfection into susceptible cells. (2) To facilitate packaging of the miRNA into exosomes, we incorporated into the sequence of miRNA401 an exosome-packaging motif. miRNA401 was shown to be packaged into exosomes and successfully delivered by exosomes to susceptible cells, where it remained stable for at least 72 hr. Finally, the results show that miRNA401 delivered to cells via exosomes effectively reduced virus yields in a miRNA401 dose-dependent fashion. The protocol described in this report can be applied to study viral gene functions without actually deleting or mutagenizing the gene.
Role of extracellular signal-regulated kinase pathway in diepoxybutane-induced apoptosis of human lymphoblasts.
Authors: Perpetua M. Muganda, Angela Hurst, Sridevi Yadavilli
Journal: Cancer Research (2004)

3384  Diepoxybutane (DEB) is the most potent metabolite of the environmental chemical 1, 3-butadiene (BD), which is prevalent in petrochemical industrial areas. BD is a known mutagen and human carcinogen, and possesses multi-organ systems toxicity that includes bone marrow depletion, spleen and thymus atrophy. Although the toxic effects of BD are known to be mediated through its epoxy metabolites, the cellular and molecular mechanisms of BD toxicity are not well understood. In working towards the elucidation of the cellular and molecular mechanisms of BD toxicity, our laboratory has recently reported the occurrence of apoptosis, but not necrosis, in human lymphoblasts exposed to low micromolar concentrations of DEB. The objective of this study was to identify apoptotic signaling pathways responsible for mediating DEB-induced apoptosis in human lymphoblasts. The mitogen-activated protein kinase (MAPK) pathways provide a mechanism by which signals are transduced from the cell surface to the nucleus, leading to activation of genes involved in a wide variety of cellular processes, including cell survival. We thus investigated the role of MAPKs in mediating DEB-induced apoptosis in human lymphoblasts. We found that the extracellular signal regulated kinase (ERK) was activated (as deduced by western blot analysis utilizing activation-specific antibodies) in response to DEB in an exposure time and DEB-concentration dependent manner; under these conditions levels of total ERK protein remained unchanged. A specific pharmacological inhibitor (PD98059) of MAPK kinase inhibited 60% of the DEB-induced apoptosis in human lymphoblasts at 24h post-exposure; under these experimental conditions the activation of the extracellular-signal regulated kinase (ERK) was inhibited. This is the first report to implicate the ERK MAPK pathway in mediating DEB-induced apoptosis. Since this pathway is known to control cell growth in most cell types, its involvement in mediating apoptosis may select for mutations which enable cells to escape apoptosis, leading to butadiene-induced carcinogenesis.
Liver Stiffness Reflecting Right-Sided Filling Pressure Can Predict Adverse Outcomes in Patients With Heart Failure
Authors: Tatsunori Taniguchi, Tomohito Ohtani, Hidetaka Kioka, Yasumasa Tsukamoto, Toshinari Onishi, Kei Nakamoto, Themistoklis Katsimichas, Kaoruko Sengoku, Misato Chimura, Haruko Hashimoto, Osamu Yamaguchi, Yoshiki Sawa, Yasushi Sakata
Journal: JACC. Cardiovascular imaging (2018)
Lung Function Trajectories From Childhood To Young Adulthood; A Peek Into The Future Of Lung Health?
Authors: Syed H. Arshad, Claire Hodgekiss, John W. Holloway, Graham Roberts, Wilfried Karmaus, Hongmei Zhang, Susan Ewart, Linda S. Mansfield, Ramesh Jagath Kurukulaaratchy
Journal: Journal of Allergy and Clinical Immunology (2018)
Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study
Authors: Howard A Burris, Ian W Flinn, Manish R Patel, Timothy S Fenske, Changchun Deng, Danielle M Brander, Martin Gutierrez, James H Essell, John G Kuhn, Hari P Miskin, Peter Sportelli, Michael S Weiss, Swaroop Vakkalanka, Michael R Savona, Owen A O'Connor
Journal: The Lancet Oncology (2018)