tbuckley/cabot-search huggingface dataset:
Molecular analysis of solid tumors (MAST): A protocol for comprehensive preclinical evaluation of pediatric solid tumors.
Authors: Sara Michele Federico, Elizabeth Stewart, Cori Bradley, Justina McEvoy, Amos Loh, Anang Shelat, Jinghui Zhang, Xiang Chen, Alberto S. Pappo, Michael A. Dyer
Journal: Journal of Clinical Oncology (2014)

10036 Background: The genomic landscape of pediatric solid tumors is actively being investigated and to date, few recurrent actionable mutations have been identified. Using orthotopic xenografts, we developed MAST to better characterize the genetic lesions of these tumors as well as investigate the correlations between drug sensitivity, gene expression and genomic and epigenetic findings. Methods: We obtained tumor samples from 24 pediatric solid malignancies including neuroblastoma (n=5), rhabdomyosarcoma (n=7), osteosarcoma (n=9), Ewing sarcoma (n=1) and high grade sarcoma NOS (n=2). Fresh tumor samples were extensively analyzed including histology, electron microscopy, gene expression profiling, single nucleotide polymorphism (SNP) microarrays, whole genome sequencing, exome sequencing, RNA-seq and DNA methylation. Orthotopic xenografts were developed, characterized and compared to the original patient tumors. High-throughput screening of primary cultures derived from the xenografts was performed to test drug sensitivity. Clonal evolution, for tumors with banked tissue from diagnosis, was studied in tumor samples obtained at the time of disease recurrence. Results: Our analysis demonstrated that the xenografts closely recapitulate the molecular features of their primary tumors. Drug screening demonstrated that there was little, if any, correlation between the identified genetic lesions, molecular markers and drug hits. Clonal analysis of recurrent tumors identified variability of major and minor clones present at the time of diagnosis and recurrence and specific to the site(s) of disease. Conclusions: Through the MAST protocol we developed a diverse panel of pediatric solid tumors for preclinical testing.Our data suggests that up front genetic profiling of tumor tissue may not be predictive of response to targeted therapies for many patients with pediatric solid tumors. Further studies on clonal evolution are necessary as mutations present at diagnosis may differ from those present at recurrence. The MAST model sets a new standard for preclinical testing in which we will use cell biology studies combined with genomic analysis to identify new therapies.
Cegal Protocol : Evaluation of the Feasibility of a Chemogenomic Approach to Identify Personalized Therapy for Relapse or Refractory AML Patients
Authors: Norbert Vey, Marie Anne Hospital, Aude Collignon, Yves Collette, Daniel Birnbaum, Aude Charbonnier, Bilal Mohty, Evelyne D'Incan, Jerome Rey, Remy Castellano, Camille Montersino, Max Chaffanet, Nadine Carbuccia, Jose Adelaide, Benjamin Bouchacourt, Arnaud Guille
Journal: Blood (2018)
Abstract 17057: The Impact of Patient-Prosthesis Mismatch on Atrial and Ventricular Remodeling After Transcatheter Aortic Valve Replacement
Authors: Frédéric Poulin, Eric M Horlick, Anna Woo, Paaladinesh Thavendiranathan
Journal: Circulation (2013)

Background: In aortic valve surgery, patient-prosthesis mismatch (PPM) negatively affects left ventricular (LV) remodeling and clinical outcomes. The impact of PPM on LV and left atrial (LA) remode...
Oral Kaposi Sarcoma
Authors: Isabelle M. Sanchez, Lorelei E. DiTommaso, Maria M. Tsoukas
Journal: JAMA Dermatology (2019)

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 Dermatology 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 Dermatology journal
Efficacy of Lenalidomide Based Three Drug Versus Two Drug Regimen for Relapsed Multiple Myeloma: A Systematic Review and Meta-Analysis of Randomized Trials
Authors: Muhammad Usman, Warda Faridi, Muhammad Asad Fraz, Muhammad Junaid Tariq, Saad Ullah Malik, Fnu Sagar, Awais Ijaz, Abid Hussain, Malik Qistas Ahmad, Muhammad Jahanzeb Khalil, Amna Khalid, Midhat Lakhani, Ceren Durer, Seren Durer, Faiz Anwer
Journal: Blood (2018)
Association of activation of mTOR and MAPK signal pathway with prolonged survival in patients with malignant pleural mesothelioma.
Authors: Ayumi Kuroda, Seiji Matsumoto, Akifumi Nakamura, Masaki Hashimoto, Teruhisa Takuwa, Nobuyuki Kondo, Ikuko Torii, Tohru Tsujimura, Takashi Nakano, Seiki Hasegawa
Journal: Journal of Clinical Oncology (2014)

7585 Background: Malignant Pleural Mesothelioma (MPM) is a rare disease with poor prognosis. The combination chemotherapy with cisplatin and pemetrexed is the first line of MPM. The AKT/mTOR (Mammalian Target of Rapamycin) pathways and Ras/Raf/MEK/ERK (MAPK) pathway are known to be activated in some kind of cancer. The purpose of this study is to evaluate the correlation between the activation of these pathways and prognosis of MPM patients. Methods: 46 patients with MPM underwent a multimodality therapy including extrapleural pneumonectomy (EPP) at Hyogo College of Medicine, Nishinomiya, Japan from April 2004 to October 2012. These 46 cases consisited of 35 males (76.0%) and 11 females (23.9%) with median ages of 59.8 years (ranged from 37 to 71 years). Histologic subtype was 43 epithelial type (93.4%), 2 biphasic type (4.3%), 1 desmoplastic type (2.1%). Paraffin embedded surgical sample was used for immunohistochemistry to evaluate the expression of phospho-AKT, phospho- mTOR (p-mTOR), phospho-S6 Ribosomal Protein (p-S6RP), phospho-4EBP-1, phospho-mitogen-activated protein kinase kinase(p-MEK) and phospho-extracellular signal-regulated kinase(p-ERK) . Overall survival (OS) from the time of surgery was determined by Kaplan-Meier method and results were compared by log-rank test. Results: OS was significantly better in phospho-S6RP positive patients (32/46) in comparison with phosphor-S6RP negative patients (14/46) (43.6 months vs. 14.4 months, P=0.03). OS was significantly better in phospho-mTOR positive patients (18/46) in comparative with phosphor-mTOR negative patients (28/46) (37.1 months vs. 14.4 months, P=0.08).OS was significantly better in phospho-MEK negative patients (6/46) in comparative with phosphor-MEK positive patients (40/46) (31.7 months vs. 17.4 months, P=0.08). Conclusions: In MPM patients, high phospho-S6RP expression was predictive of improved OS. And this study support that the AKT/mTOR and MAPK pathways is promising candidate of molecular target therapy for MPM.
Disparities in breast cancer surgery: The lingering effect of race.
Authors: Vanessa Sheppard, Bridget Oppong, Fikru Hirpa, Samuel Onyewu, Felicia E. Snead, Echo Brathwaite, Kepher Makambi
Journal: Journal of Clinical Oncology (2014)

6576 Background: Stage migration may be associated with delays in surgical breast cancer treatment >90 days. Although it is not recommended to have a 3-month span from diagnosis to definitive surgical management, there are no precise guidelines that establish a model time interval. This study investigates racial disparities in time to receiving first surgical treatment (i.e. surgical delay) in breast cancer patients. Methods: A cohort study of 290 insured Black (56%) and White (44%) women with primary breast cancer participated in telephone interviews that gathered data on psychosocial (e.g., self-efficacy) and healthcare factors (e.g., communication, barriers). Clinical data were abstracted from medical records. Time to surgical delay was defined as the time in days between diagnosis and definitive surgical treatment. We also considered 60-day and delay outcomes. We used unadjusted hazard ratios to examine univariate relationships between delay outcomes and covariates. Cox proportional hazard models were used for multivariate analyses. Results: Median time to surgery was 41 days and was higher in Blacks (m=47 days) compared to Whites (m=33 days) (p= .001). Considering the 90-day outcome, Black women had greater delay to surgery than White women after covariates adjustment (HR= 1.7; 95% CI: 1.2 to 2.3). Women reporting internet use (vs. not) and those with breast conserving surgery (vs. mastectomy) had greater delay to surgery (p<. 01) after adjustment. Conclusions: Prolonged delays to definitive breast cancer surgery persist among Black women. Most notably, racial differences persisted for the 90-day interval that has been associated with poorer outcomes. Interventions to address delay in Black patients are needed.
Development of nonhuman primate models for prostate specific antigen (PSA) biology studies
Authors: James Mubiru, Gene Hubbard, Edward Dick, Jeffrey Rogers
Journal: Cancer Research (2008)

2903  Prostate specific antigen (PSA) is released at increased levels into the blood early in the development of prostatic diseases and therefore is widely used for screening, diagnosing and monitoring of prostate cancer, although it is also elevated in other prostatic disorders. Serum PSA level is the most widely used clinical biomarker for any cancer. The PSA gene is only found in humans and other nonhuman primates. Currently there is a lack of a truly appropriate animal model for the study of PSA and causes of individual variation in serum PSA level. Previous studies have shown that the baboon prostate is anatomically and histologically similar to its human counterpart and therefore can be used as a model for prostatic diseases. The purpose of this study was to assay and compare serum PSA levels of three nonhuman primate species commonly used in research with the aim of establishing a nonhuman primate model to study PSA biology.  Methods: Serum was collected from baboons, rhesus macaques and cynomolgus monkeys of different ages maintained at the Southwest National Primate Research Center, Southwest Foundation for Biomedical Research, in San Antonio, Texas. Serum PSA assay was done using the ultrasensitive radioimmunoassay method (AniLytics, Inc., Gaithersburg, MD).  Results:  The results showed that serum PSA levels in baboons ranged from 0.06-0.78ng/ml while those of rhesus macaques and cynomolgus monkeys ranged from 0.07-2.35ng/ml and 0.1 to 5.23ng/ml respectively  Conclusions:  a) Serum PSA can be measured in nonhuman primates, b) PSA values in nonhuman primates are comparable to those reported in humans without prostate disease, c) cynomolgus monkeys have the highest serum PSA values and also their values increased with age, d) nonhuman primates especially cynomolgus monkeys may be used for studies of PSA biology.
Intravenous sustained-release nifedipine ameliorates nonalcoholic fatty liver disease by restoring autophagic clearance
Authors: Solji Lee, Daewon Han, Hyun-Goo Kang, Su Jin Jeong, Jae-Eun Jo, Jongdae Shin, Do Kyung Kim, Hwan-Woo Park
Journal: Biomaterials (2019)
TRUSTY: A randomized multicenter phase II/III study of trifluridine/tipiracil and bevacizumab versus irinotecan, fluoropyrimidine, and bevacizumab as second-line treatment in patients with metastatic colorectal cancer progressive during or following first-line oxaliplatin-based chemotherapy.
Authors: Takayuki Yoshino, Eiji Oki, Hiroaki Nozawa, Takako Eguchi Nakajima, Hiroya Taniguchi, Satoshi Morita, Naruhito Takenaka, Daisuke Ozawa, Kuniaki Shirao
Journal: Journal of Clinical Oncology (2018)

TPS881 Background: Trifluridine/tipiracil is an oral combination preparation approved for the treatment of patients with metastatic colorectal cancer (mCRC). Trifluridine is a thymidine analog, and tipiracil is a thymidine phosphorylase inhibitor that improves the bioavailability of trifluridine. Phase I/II C-TASK FORCE study of trifluridine/tipiracil plus bevacizumab (Bev) for patients with refractory mCRC demonstrated a promising efficacy results with mild toxicity profile (Kuboki Y, et al. Lancet Oncology, 2017). Methods: We are conducting a randomized multicenter phase II/III non-inferiority study (JapicCTI-173618) to compare trifluridine/tipiracil plus Bev versus FOLFIRI plus Bev (in the control arm, S-1 can replace 5-FU) in second-line mCRC patients who have failed first-line oxaliplatin-based chemotherapy. Key eligibility criteria are a histologically confirmed colorectal adenocarcinoma, refractory to first-line chemotherapy including a fluoropyrimidine, oxaliplatin, and either Bev or an anti-EGFR antibody (if RAS wild-type), an age of 20 years or older, ECOG performance status of 0-1, and adequate oral intake. Patients are randomized in a 1:1 ratio to receive trifluridine/tipiracil plus Bev or FOLFIRI plus Bev using the minimization method stratified by RAS status, prior therapy (Bev/anti-EGFR antibody), and primary tumor sidedness. The primary endpoint is overall survival. The non-inferiority hypothesis will be achieved if the upper limit of the two-sided 95% CI of the HR is below 1.33 (as HR scale, power 0.80). If achieved, the non-inferiority hypothesis with the margin of 1.25 (as HR) and the superiority will be consequently tested. Secondary endpoints include progression-free survival, time to treatment failure, response rate, disease control rate, subsequent treatment, time to post-study treatment failure, the quality of life, and adverse events. The target sample size is 524 patients. Patients will be enrolled from October 2017. Clinical trial information: 173618.
Functionalization of PLLA with Polymer Brushes to Trigger the Assembly of Fibronectin into Nanonetworks
Authors: Mark Robert Sprott, Gloria Gallego‐Ferrer, Matthew J. Dalby, Manuel Salmerón‐Sánchez, Marco Cantini
Journal: Advanced Healthcare Materials (2019)

Poly-l-lactic acid (PLLA) has been used as a biodegradable polymer for many years; the key characteristics of this polymer make it a versatile and useful resource for regenerative medicine. However, it is not inherently bioactive. Thus, here, a novel process is presented to functionalize PLLA surfaces with poly(ethyl acrylate) (PEA) brushes to provide biological functionality through PEA's ability to induce spontaneous organization of the extracellular matrix component fibronectin (FN) into physiological-like nanofibrils. This process allows control of surface biofunctionality while maintaining PLLA bulk properties (i.e., degradation profile, mechanical strength). The new approach is based on surface-initiated atomic transfer radical polymerization, which achieves a molecularly thin coating of PEA on top of the underlying PLLA. Beside surface characterization via atomic force microscopy, X-ray photoelectron spectroscopy and water contact angle to measure PEA grafting, the biological activity of this surface modification is investigated. PEA brushes trigger FN organization into nanofibrils, which retain their ability to enhance adhesion and differentiation of C2C12 cells. The results demonstrate the potential of this technology to engineer controlled microenvironments to tune cell fate via biologically active surface modification of an otherwise bioinert biodegradable polymer, gaining wide use in tissue engineering applications.
Hippo Kinase Inactivation Contributes to Del(20q) Malignancies and Cooperates with JAK2-V617F to Promote Myelofibrosis in Mice
Authors: Samuel A Stoner, Ming Yan, Katherine Liu, Takahiro Shima, Huan-You Wang, Kei-Ichiro Arimoto, Rafael Bejar, Catriona Jamieson, Kun-Liang Guan, Dong-Er Zhang
Journal: Blood (2018)
Outcomes of radiofrequency ablation as first-line therapy for hepatocellular carcinoma less than 3 cm in potentially transplantable patients
Authors: Adam Doyle, Andre Gorgen, Hala Muaddi, Aloysious D. Aravinthan, Assaf Issachar, Oleg Mironov, Wei Zhang, John Kachura, Robert Beecroft, Sean P. Cleary, Anand Ghanekar, Paul D. Greig, Ian D. McGilvray, Markus Selzner, Mark S. Cattral, David R. Grant, Leslie B. Lilly, Nazia Selzner, Eberhard L. Renner, Morris Sherman, Gonzalo Sapisochin
Journal: Journal of Hepatology (2019)
Pharmacogenetic determinants of gefitinib trough concentration in patients with non-small cell lung cancer.
Authors: Shuang Xin, Yuxiang Ma, Xueding Wang, Yan Huang, Jiali Li, YuanYuan Zhao, Lingyan Chen, Rong Hu, Min Huang, Li Zhang
Journal: Journal of Clinical Oncology (2014)

e13533 Background: Some studies postulated that the plasma concentration of gefitinib may have great influence on its efficacy; meanwhile, it is well-known that polymorphisms in metabolic enzymes and transporters had great impact on drug exposure, which could partially account for interindividual variability of gefitinib clearance in the pharmacokinetic model. Therefore, this research investigated the association between genetic polymorphisms in CYP2D6, CYP3A4, CYP3A5, CYP1A1, POR, AHR, PXR, HNF4A and gefitinib trough concentration in patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 18 single nucleotide polymorphisms in CYP2D6 (rs1065852, rs5030656, rs1135840, rs28371725, rs16947), CYP3A4 (rs2242480), CYP3A5 (rs776746), CYP1A1 (rs762551, rs2606345, rs1048943), CYP1A2 (rs2069514), POR (rs2868177, rs121912974, rs17685), AHR (rs10249788, rs10248420, rs1169294), PXR (rs3814055) was selected and determined by Sequenom Massarray MALDI-TOF platform to analyze their association with the trough concentration of gefitinib in 81 NSCLC patients. Gefitinib trough concentration was detected on day 28 following first administration with HPLC-MS/MS. Mann-Whitney test and Kruskal-Wallis test were adopted to compare the distribution of gefitinib trough concentration between different genotype groups. Results: The trough concentration of gefitinib in CYP2D6 rs1135840 GG carriers was significantly higher than that in GC carriers plus CC carriers [223.31±74.76 vs 176.78±87.54 vs 164.36±131.27 (ng/mL), P<0.05]. CYP2D6 rs1065852 CT carriers had a higher gefitinib trough concentration than CC carriers [233.71±99.11 vs 149.28±74.02 (ng/mL), P<0.05]. Carriers of the CYP3A4 rs2242480 TT genotype had a significantly higher trough concentration than carriers of CT plus CC genotypes [314.77±66.72 vs 188.41±100.20 vs 186.72±91.18 (ng/mL), P<0.05]. Conclusions: This research demonstrated that the CYP2D6 rs1065852, CYP2D6 rs1135840 , CYP3A4 rs2242480 are associated with gefitinib concentration in NSCLC patients. A pharmacokinetic model incorporating the indicator of these polymorphisms may have potential for optimization of treatment with gefitinib.
Economic evaluation of everolimus plus exemestane versus bevacizumab plus paclitaxel and bevacizumab plus capecitabine for the management of postmenopausal women with ER+ breast cancer.
Authors: Georgia Kourlaba, Vasiliki Rapti, Athanasios Alexopoulos, John Relakis, Georgios Koumakis, Magdalini Chatzikou, Nikolaos Maniadakis, Vassilis Georgoulias
Journal: Journal of Clinical Oncology (2014)

e17638 Background: Estrogen receptor positive (ER+) metastatic breast cancer patients progressing on nonsteroidal aromatase inhibitors are candidates for treatment with everolimus (EVE) plus exemestane (EXE) or with chemotherapy. Methods: To conduct a cost-effectiveness (CE) analysis of EVE plus EXE versus bevacizumab (BEV) plus paclitaxel (PACL) and BEV plus capecitabine (CAPE) which are established treatments in the Greek healthcare setting. A Markov model, consisting of three health states, was used to describe disease progression and evaluate the CE of comparators. The model evaluated the comparators over a lifetime horizon in the course of a 1-month cycle from a third-party payer perspective. Efficacy, safety and utility data considered in the model were extracted from randomized Phase III clinical trials. Direct medical costs used reflecting the year 2013.Probabilistic sensitivity analysis was also conducted. Primary outcomes were quality-adjusted life years (QALYs) and total lifetime costs. Results: Discounted survival and quality adjusted survival of EVE plus EXE treated patients was higher compared to BEV plus PACL by 0.28 life-years and 0.19 QALYs, respectively, and by 0.21 life-years and 0.16 QALYs when compared to BEV plus CAPE.EVE plus EXE was the less costly treatment in terms of drug acquisition, administration and concomitant medications. The total lifetime cost per patient for EVE plus EXE was estimated at €46,251, for BEV plus PACL at €53,422 and for BEV plus CAPE at 50,619 €. The higher drug acquisition and administration cost of BEV plus PACL (EVE plus EXE: 16,956 € vs. BEV plus PACL: 22,379 €) partially explained the higher total lifetime cost over EVE plus EXE. Moreover, the higher pre-progressed costs of the BEV plus CAPE arm accounted for the largest part of the difference in the total lifetime cost between BEV plus CAPE and EVE plus EXE. Probabilistic analysis confirmed the results. Conclusions: Results suggest that EVE plus EXE may be a dominant (more effective and less costly) alternative relative to BEV plus PACL and BEV plus CAPE in the treatment of ER+ mBC patients failing initial therapy with NSAIs.
Pan-Asian adapted Clinical Practice Guidelines for the management of patients with metastatic non-small-cell lung cancer: a CSCO–ESMO initiative endorsed by JSMO, KSMO, MOS, SSO and TOS
Authors: Y.-L. Wu, D. Planchard, S. Lu, H. Sun, N. Yamamoto, D.-W. Kim, D.S.W. Tan, J.C.-H. Yang, M. Azrif, T. Mitsudomi, K. Park, R.A. Soo, J.W.C. Chang, A. Alip, S. Peters, J.-Y. Douillard
Journal: Annals of Oncology (2018)

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of metastatic non-small-cell lung cancer (NSCLC) was published in 2016. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Chinese Society of Clinical Oncology (CSCO) to convene a special guidelines meeting immediately after the Chinese Thoracic Oncology Group Annual Meeting 2018, in Guangzhou, China. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic NSCLC cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic NSCLC representing the oncological societies of China (CSCO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the six participating Asian countries. During the review process, the updated ESMO 2018 Clinical Practice Guidelines for metastatic NSCLC were released and were also considered, during the final stages of the development of the Pan-Asian adapted Clinical Practice Guidelines.