tbuckley/cabot-search huggingface dataset:
Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer
Authors: Feng-Ming Kong, Randall K. Ten Haken, Matthew Schipper, Kirk A. Frey, James Hayman, Milton Gross, Nithya Ramnath, Khaled A. Hassan, Martha Matuszak, Timothy Ritter, Nan Bi, Weili Wang, Mark Orringer, Kemp B. Cease, Theodore S. Lawrence, Gregory P. Kalemkerian
Journal: JAMA Oncology (2017)

Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival.To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non-small-cell lung cancer (NSCLC).A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT.Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation.The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population.The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively.Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion.clinicaltrials.gov Identifier: NCT01190527.
Trump’s decision to leave climate pact threatens public health, US doctors warn
Authors: Michael McCarthy
Journal: BMJ (2017)

President Donald Trump’s decision to pull the US out of the Paris climate agreement will put the health of millions of people at risk, US medical societies said on Thursday 1 June.

Under the 2015 accord, the US and more than 190 other nations agreed to reduce their greenhouse gas emissions to help cut the risk and impact of global warming.1 The agreement emphasizes the benefits of tackling health and climate change together and asserts that reducing fossil fuel burning will decrease illness.

But, in a speech from the White House Rose Garden, Trump said …
Gflip/ox in the treatment of advanced pancreatic cancer.
Authors: Yashar Hirshaut, Daniel Khalil, Rachel V. Kramer, Daniel Helfgott
Journal: Journal of Clinical Oncology (2013)

e15192 Background: GFLIP and GLIP/Ox (Bruckner et al. ASCO, 2008) are effective in the treatment of pancreatic cancer (Bruckner, et.al. ASCO, 2008). A similar regimen FOLFIRINOX proved successful in a Phase 3 trial (Conroy, T. et al. NEJM, 2011). However, these regimens are not widely used because of concerns about efficacy and/ or toxicity. Our experience suggests that with dose adjustment when necessary, GFLIP/Ox is both effective and well tolerated. Methods: This is a retrospective review of 24 patients (12 M, 12 F) with unresectable or recurrent pancreatic cancer. The drugs/doses used were leucovorin 300mg, gemcitabine 500mg/M2, irinotecan 80mg/M2, fluorouracil (FU) 400mg/M2 bolus, FU 600mg/M2 46 hr. infusion, oxaliplatin 35 mg/M2, bevacizumab 10mg/M2 +/- cetuximab 400mg/2 given q2 wks. Doses were reduced up to 50% for pts. &gt;70 yrs. Results: 24 pts treated, 11 with cetuximab. Age range 44-87 yrs, mean 68.8 yrs. Response (RR) 38%, Disease Control (DC) 79%. PFS (19 pts) median 264 days (d). Median OS 382 d. Overall survival &lt;70 yrs median 814 d. &gt;70 yrs 304 d. With cetuximab (CTX) DC 91%, OS 512 d, without CTX DC 69%, OS 249 days. Side effects were fatigue, sensory neuropathy, anemia, neutropenia, generally grade 1-2. There was one case of grade 4 thrombocytopenia. There were no deaths attributable to chemotherapy. Conclusions: The median OS of this regimen is 12.7 mo. vs. 6.8 mo. for gemcitabine and 11.1 mo. for FOLFIRINOX. The RR of 38% compares favorably to the 31% RR for FOLFIRINOX. Taken together with the 27 month median overall survival among those under 70 (11 pts) makes GFLIP/Ox a regimen worth further study for this disease.
Budd-Chiari Syndrome Demonstrated on PET/CT
Authors: Brianna Abadie, Manu Singh, Samson Lu, Kenneth Daughters
Journal: Clinical Nuclear Medicine (2017)

Budd-Chiari syndrome is a rare clinical condition that involves diminution or interruption of hepatic venous blood flow from the liver. We describe a case of Budd-Chiari syndrome visualized via 18F-FDG PET/CT in a 60-year-old woman with medical history of B-cell non-Hodgkin lymphoma who presented with abdominal pain. FDG PET/CT fusion images demonstrate increased FDG uptake with SUVmax of 2.2 along the course of the middle hepatic vein with decreased attenuation within both the middle and right hepatic veins, consistent with thrombus.
Deconstructing Clinical Trials—Help From Oncology Value Frameworks
Authors: Joseph C. Del Paggio
Journal: JAMA Oncology (2017)

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
CX3CR1 expression associated with cellular migration, metastasis, and prognosis in human clear cell renal cell carcinoma
Authors: Yao Xin, ChaoNan Qian, Baocun Sun, Wenlu Li, Bin Tean Teh
Journal: Cancer Research (2007)

4666  Recent papers suggest that tumor cells from different cancer types have different profiles of chemokine receptor expression, might respond to chemokine gradients and contribute to metastatic spread. Oligonucleotide microarray results showed a significantly increased expression of CX3CR1 in Clear cell renal cell carcinoma (CCRCC) relative to normal kidney tissue, and promoted us to investigate whether fractalkine-CX3CR1 axis was involved in cell migration and distant metastasis in human CCRCC.  The expression level and localization of CX3CR1 in human CCRCC cell lines 786-O, A-498, Caki-1, SN12C and human embryonic kidney cell line HEK293T was realized by western-blotting and immunofluorescence. Wound healing assay and chemotaxis assay were performed to assess cellular migratory ability induced by fractalkine. To assess the signaling pathways involved, cells were incubated with 50nM fractalkine for different time periods, and then, the phosphorylation of p44/p42 MAPK and Akt were tested by western-blotting method. Fractalkine induced cellular migration was done after the cells were treated with the neutralizing antibody to CX3CR1, GPCR (G-protein couple receptor) inhibitor pertussis toxin (PTX), and the blockade of MEK UO126, respectively. Finally, both the expression of CX3CR1 and fractalkine were evaluated using immunohistochemical analysis on tissue microarray (TMA) composed of 78 primary CCRCC individual samples, 16 nonmalignant kidney cortex tissue samples and 16 metastatic lesions of CCRCC.  Western blotting showed the expression of CX3CR1 protein in 4 tested cell lines was superior to that in 293T cells. Wound healing assay suggested that fractalkine enhanced the migratory activity in the cells present with membranous CX3CR1. The directed migration activity of cancer cells was induced by fractalkine in a dose-dependent manner. Extracellular signal-related kinases (ERK1 and ERK2) were activated under soluble fractalkine stimulation, whereas the neutralizing antibody of CX3CR1, PTX, and UO126 prevented fractalkine-mediated cellular migration. Statistical analysis of TMA results revealed a significant correlation of high level of CX3CR1 membranous expression with metastasis status (P  In this present study, for the first time, we show that CX3CR1 expressed on cellular membrane of human CCRCC is associated with cellular migration, metastasis and poor prognosis.
Characterization of Variability in Toxicokinetics and Toxicodynamics of Tetrachloroethylene Using the Collaborative Cross Mouse Population
Authors: Joseph A. Cichocki, Shinji Furuya, Abhishek Venkatratnam, Thomas J. McDonald, Anthony H. Knap, Terry Wade, Stephen Sweet, Weihsueh A. Chiu, David W. Threadgill, Ivan Rusyn
Journal: Environmental Health Perspectives (2017)

Background: Evaluation of interindividual variability is a challenging step in risk assessment. For most environmental pollutants, including perchloroethylene (PERC), experimental data are lacking, resulting in default assumptions being used to account for variability in toxicokinetics and toxicodynamics. Objective: We quantitatively examined the relationship between PERC toxicokinetics and toxicodynamics at the population level to test whether individuals with increased oxidative metabolism are be more sensitive to hepatotoxicity following PERC exposure. Methods: Male mice from 45 strains of the Collaborative Cross (CC) were orally administered a single dose of PERC (1,000mg/kg) or vehicle (Alkamuls-EL620) and euthanized at various time points (n=1/strain/time). Concentration–time profiles were generated for PERC and its primary oxidative metabolite trichloroacetate (TCA) in multiple tissues. Toxicodynamic phenotyping was also performed. Results: Significant variability among strains was observed in toxicokinetics of PERC and TCA in every tissue examined. Based on area under the curve (AUC), the range of liver TCA levels spanned nearly an order of magnitude (∼8-fold). Expression of liver cytochrome P4502E1 did not correlate with TCA levels. Toxicodynamic phenotyping revealed an effect of PERC on bodyweight loss, induction of peroxisome proliferator activated receptor-alpha (PPARα)-regulated genes, and dysregulation of hepatic lipid homeostasis. Clustering was observed among a) liver levels of PERC, TCA, and triglycerides; b) TCA levels in liver and kidney; and c) TCA levels in serum, brain, fat, and lung. Conclusions: Using the CC mouse population model, we have demonstrated a complex and highly variable relationship between PERC and TCA toxicokinetics and toxicodynamics at the population level. https://doi.org/10.1289/EHP788
What's hot that the other lot got
Authors: Janice Higginson
Journal: Thorax (2015)

It's 5 years since Ramsey et al 's landmark paper demonstrating Ivacaftors's ability to significantly change lung function in cystic fibrosis (CF) patients with the G551D mutation. The search is now on for a similar finding for the most common mutation—F508del. Although not as dramatic, Wainwright et al ( N Engl J Med 2015;373:220–31) have shown that combining a CF transmembrane conductance regulator (CFTR) corrector—Lumacafor—and a CFTR potentiator—Ivacaftor—does produce a significant improvement in FEV1.

The ban on smoking in a car carrying children will become UK law in October 2015; it is already law in some US states. Ahn et al ( J Paeds 2015; http://dx.doi.org/10.1016/j.jpeds.2015.06.049) add to the mounting evidence of the effect of secondhand smoke on children with their study of 2219 children admitted with pneumonia in Tennessee and Utah between 2010 and 2012. Children with ≥2 smokers in their household were more likely to go to an intensive …
In vitro-acquired resistance gene expression profile and in vivo response to oxaliplatin-based treatment
Authors: A. Martinez Cardús, E. Martinez-Balibrea, E. Musulén, A. Ginés, J. L. Manzano, L. Layos, V. Quiroga, E. Aranda, A. Abad
Journal: Journal of Clinical Oncology (2009)

e15041 Background: Resistance to oxaliplatin is one of the main problems of colorectal cancer (CRC) treatment success. It is not clear if intrinsic and acquired resistance processes are developed by related mechanisms. In a previous work (Martinez-Cardús et al. Mol Cancer Ther, January 2009), we determined a profile of oxaliplatin-acquired resistance related genes by using an in vitro model. In the present work, we analyzed this genetic profile in paraffin-embedded primary adenocarcinomas from CRC patients treated with oxaliplatin-fluoropyrimidine. mRNA expression data was correlated with response rate and time to progression (TTP) in order to determine the role of these genes as markers of resistance to oxaliplatin-based treatment. Material and Method: mRNA levels were analyzed by using Real Time PCR. β-actin and 18s were used as housekeeping genes and, as a reference sample, we used commercial pool of mRNA from different human tumours. Chi- square and Fisher test were used in order to value differences in response rate to treatment. TTP was studied by using Kaplan Meyer curves and Log rank test. Median and percentile 33 and 66 were used as threshold values to determine both high and low expression level groups for each gene analyzed. We considered statistically significant a two-sided p-value lower than 0.05. Results: Forty-four advanced CRC patients treated with fluoropyrimidine plus oxaliplatin were analyzed. 54.5% of them were males; primary tumour was localized in colon in a 65.9% of cases. According to qRT-PCR analysis, the in vitro oxaliplatin acquired resistance related genes could be detected in the tumours but the expression of any of them correlated significantly with in vivo resistance to oxaliplatin-based treatment by using the three different threshold values to define groups. Conclusions: According to our results, these genes could not be used as markers of resistance to oxaliplatin-based treatment in non-treated tumours. Thereby, oxaliplatin resistance acquisition genes seems not to be involved in intrinsic drug resistance probably due to the fact that acquired and intrinsic oxaliplatin resistance are not related mechanisms. Further studies to typify oxaliplatin intrinsic resistance potential markers are guaranteed. No significant financial relationships to disclose.
Olaparib for Metastatic Breast Cancer in Patients with a Germline <i>BRCA</i> Mutation
Authors: Mark Robson, Seock-Ah Im, Elżbieta Senkus, Binghe Xu, Susan M. Domchek, Norikazu Masuda, Suzette Delaloge, Wei Li, Nadine Tung, Anne Armstrong, Wenting Wu, Carsten Goessl, Sarah Runswick, Pierfranco Conte
Journal: New England Journal of Medicine (2017)

Olaparib is an oral poly(adenosine diphosphate–ribose) polymerase inhibitor that has promising antitumor activity in patients with metastatic breast cancer and a germline BRCA mutation.
Obstructive sleep apnoea and depression: is there an association?
Authors: Edward O. Bixler, Jordan Gaines, Alexandros N. Vgontzas
Journal: European Respiratory Journal (2017)

In the study by Kendzerska et al . [1] published in this issue of the European Respiratory Journal , it is reported that obstructive sleep apnoea (OSA) and severity measures, such as the apnoea/hypopnea index, are not related to the risk of hospitalisation for depression. The sample of the study was large with >10 000 subjects, and the follow-up period was long, ∼10 years. The investigators focused on the more severe phenotype of the disorder that requires inpatient treatment to avoid possible misdiagnosis, which is more likely in milder cases, due to overlapping symptoms between OSA and depression. Treatment strategies for OSA and depression need to be considered carefully as they share many common risk factors <http://ow.ly/48v330bsm3y>
Genetic subclone architecture of tumor clone-initiating cells in colorectal cancer
Authors: Klara M. Giessler, Kortine Kleinheinz, Daniel Huebschmann, Gnana Prakash Balasubramanian, Taronish D. Dubash, Sebastian M. Dieter, Christine Siegl, Friederike Herbst, Sarah Weber, Christopher M. Hoffmann, Raffaele Fronza, Ivo Buchhalter, Nagarajan Paramasivam, Roland Eils, Manfred Schmidt, Christof von Kalle, Martin Schneider, Alexis Ulrich, Claudia Scholl, Stefan Fröhling, Wilko Weichert, Benedikt Brors, Matthias Schlesner, Claudia R. Ball, Hanno Glimm
Journal: The Journal of Experimental Medicine (2017)

A hierarchically organized cell compartment drives colorectal cancer (CRC) progression. Genetic barcoding allows monitoring of the clonal output of tumorigenic cells without prospective isolation. In this study, we asked whether tumor clone-initiating cells (TcICs) were genetically heterogeneous and whether differences in self-renewal and activation reflected differential kinetics among individual subclones or functional hierarchies within subclones. Monitoring genomic subclone kinetics in three patient tumors and corresponding serial xenografts and spheroids by high-coverage whole-genome sequencing, clustering of genetic aberrations, subclone combinatorics, and mutational signature analysis revealed at least two to four genetic subclones per sample. Long-term growth in serial xenografts and spheroids was driven by multiple genomic subclones with profoundly differing growth dynamics and hence different quantitative contributions over time. Strikingly, genetic barcoding demonstrated stable functional heterogeneity of CRC TcICs during serial xenografting despite near-complete changes in genomic subclone contribution. This demonstrates that functional heterogeneity is, at least frequently, present within genomic subclones and independent of mutational subclone differences.
Abstract 17170: Long-Term Outcome in Elderly Patients (=75 years) versus Younger Patients (<75 years) Undergoing PCI for Chronic Total Occlusion
Authors: Stephen O’Connor, Thierry Lefevre, Francesca Sanguineti, Yusuke Watanabe, Thomas Hovasse, Thierry Unterseeh, Marie-Claude Morice, Hakim Benamer, Philippe Garot, Yves Louvard
Journal: Circulation (2013)

OBJECTIVES: To assess the procedural success rate and the long-term clinical impact of percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) in elderly patients. METHODS: A to...
Preclinical efficacy of the combination of olaparib plus carboplatin with vandetanib in triple-negative breast cancer.
Authors: Nandini Dey, Hui Wu, Yuliang Sun, Pradip De, Brian Leyland-Jones
Journal: Journal of Clinical Oncology (2012)

e13579 Background: BRCA1-deficiency confers sensitivity to PARP1 inhibition (alone or in combination with platinum compounds) in triple-negative breast cancer (TNBC). Recent understanding of the biology of TNBC tumor cells has recognized molecular targets suitable for treatment with targeted therapeutics including cell surface RTK(s), such as EGFR. Methods: We studied the effect of combination of PARP inhibitor, (olaparib) plus carboplatin with a dual EGFR/VEGFR inhibitor, vandetanib in a TNBC model in both in vitro and in vivo settings. We tested the effects of drug combinations on (a) cell signaling marker(s) of survival/proliferation/apoptosis, (b) adhesion-dependent and clonogenic survival, and (c) different phenotypes (migration, invasion, vascular mimicry, and cord formation) using TNBC cell and HUVEC cells. The combination of PARP1 inhibition and EGFR/VEGFR inhibition was evaluated in tumor-bearing athymic mice treated with olaparib plus carboplatin and vandetanib. Results: Data showed that, (1) EC50s for vandetanib ranged from 5-15 µM, (2) vandetanib (10 µM) inhibited phosphorylation of AKT (S473 &amp; T308), S6RP, 4EBP1 and ERK, (3) effect of olaparib on TNBC cell survival can be effectively studied in vitro by clonogenic assay, (4) TNBC cell lines exhibited higher sensitivity to vandetanib in clonogenic assay when combined with 10 µM fixed dose of olaparib, and (5) a combination of vandetanib with olaparib plus carboplatin time dependently increased caspase-3 and PARP cleavage, inhibited vascular mimicry, blocked fibronectin-directed migration, and suppressed clonogenic growth in TNBC cells.Vandetanib blocked (a) cord formation, (b) vitronectin-directed migration, and (c) HIF-1alpha accumulation and phosphorylation of proliferation markers (AKT, 4EBP1, and ERK) in HUVEC cells. Conclusions: Anti-proliferative/pro-apoptotic, and anti-migratory/invasive effects of vandetanib (alone or in combination with carboplatin plus olaparib) were observed both in tumor cells and in endothelial cells. We are currently studying in vivo the effect of combining olaparib plus carboplatin with vandetanib, in xenograft model the results of which will be presented in the meeting.
Biomarker Driven Phase II Clinical Trial of Trametinib in Relapsed/Refractory Multiple Myeloma with Sequential Addition of the AKT Inhibitor, GSK2141795 at Time of Disease Progression to Overcome Treatment Failure: A Trial of the Princess Margaret Phase II Consortium
Authors: Suzanne Trudel, Nizar J. Bahlis, Christopher P. Venner, Annette E Hay, Olena Kis, Signy Chow, Zhi Hua Li, Ellen Nong Wei, Lisa Wang, Christine Tran, Smitha Udagani, Chantale Blattler, Trevor J. Pugh, Helen X Chen, Amit Oza
Journal: Blood (2016)