tbuckley/cabot-search huggingface dataset:
Paclitaxel Balloon Coating, a Novel Method for Prevention and Therapy of Restenosis
Authors: BrunoScheller, UlrichSpeck, ClaudiaAbramjuk, UlrichBernhardt, MichaelBöhm, GeorgNickenig
Journal: Circulation (2004)

Background— Drug-eluting stents have shown promising antirestenotic effects in clinical trials. Non–stent-based local delivery of antiproliferative drugs may offer additional flexibility and also reach vessel areas beyond the immediate stent coverage. The aim of the present study was to evaluate a novel method of local drug delivery based on angioplasty balloons. Methods and Results— Stainless steel stents (n=40; diameter, 3.0 to 3.5 mm; length, 18 mm) were implanted in the left anterior descending and circumflex coronary arteries of domestic pigs. Both conventional uncoated and 3 different types of paclitaxel-coated, percutaneous transluminal coronary angioplasty balloons (contact with vessel wall for 1 minute) were used. No difference in short-term tolerance between coated and uncoated balloons and no signs of thrombotic events were observed. Quantitative angiography and histomorphometry of the stented arteries asserted the statistical equality of the baseline parameters between the control and the 3 tr...
68Ga-NOTA-RM26 PET/CT in the Evaluation of Breast Cancer
Authors: Jie Zang, Feng Mao, Hao Wang, Jingjing Zhang, Qingxing Liu, Li Peng, Fang Li, Lixin Lang, Xiaoyuan Chen, Zhaohui Zhu
Journal: Clinical Nuclear Medicine (2018)

This prospective pilot study investigated the value of Ga-NOTA-RM26, an antagonist targeting gastrin-releasing peptide receptor, in evaluation of breast cancer.Thirty-five women in suspicion of breast cancer based on mammography or ultrasonography were recruited with informed consent. They underwent PET/CT scans 30 minutes after intravenous injection of Ga-NOTA-RM26 in a dose of 1.85 MBq (0.05 mCi) per kilogram body weight within 1 week before surgery. The Ga-NOTA-RM26 uptake was correlated with the pathological and immunohistochemical findings.Ga-NOTA-RM26 positivity was found correlated with estrogen receptor (ER) expression (P = 0.006) and menstrual status (P = 0.019). In 34 patients diagnosed with breast cancer, the SUVmax was found significantly higher in the ER-positive breast cancer (4.97 ± 1.89) than in the ER-negative breast cancer (2.78 ± 0.65, P < 0.001). Ga-NOTA-RM26 was also found accumulated in normal breast tissue, with the SUVmax significantly higher in patients at the secretory phase of menstrual cycle (2.27 ± 0.71) than in those at the nonsecretory phase (1.59 ± 0.49, P = 0.017) and postmenopause (1.43 ± 0.44, P = 0.002). If the secretory phase patients were excluded, the sensitivity, specificity, and accuracy for differentiation of breast cancer from breast tissue increased from 85.3%, 86.8%, and 86.1% to 100%, 90.9%, and 95.5%, respectively.This pilot study indicates that the diagnostic accuracy of Ga-NOTA-RM26 PET/CT in breast cancer may correlate with ER expression and menstrual status of the patient. It may be better to avoid performing this examination during the menstrual secretory phase to reduce physiological uptake in normal breast tissue.
Advancing health research through research governance
Authors: Luis Alejandro Salicrup, Luis Gabriel Cuervo, Rodolfo Cano Jiménez, Nelly Salgado de Snyder, Francisco Becerra-Posada
Journal: BMJ (2018)

N e a r ly 1 0 ye a r s s i n c e PA H O implemented its policy on research for health, countries in Latin America and the Caribbean have progressed, but improvements are still needed in health research governance.• Greater coordination among all government entities overseeing health research quality is needed in countries across the region.• The lack of adequate funding aligned with national research priorities remains a limiting factor for many national health research systems.• Substantial gaps in research skills and capacity remain across the region.
Fetal gene therapy for neurodegenerative disease of infants
Authors: Giulia Massaro, Citra N. Z. Mattar, Andrew M. S. Wong, Ernestas Sirka, Suzanne M. K. Buckley, Bronwen R. Herbert, Stefan Karlsson, Dany P. Perocheau, Derek Burke, Simon Heales, Angela Richard-Londt, Sebastian Brandner, Mylene Huebecker, David A. Priestman, Frances M. Platt, Kevin Mills, Arijit Biswas, Jonathan D. Cooper, Jerry K. Y. Chan, Seng H. Cheng, Simon N. Waddington, Ahad A. Rahim
Journal: Nature Medicine (2018)
Abstract 12757: Prevalence and Outcome of Thrombotic and Embolic Complications in Adults After Fontan Operation
Authors: Alexander Egbe, Heidi Connolly, Talha Niaz, David Driscoll
Journal: Circulation (2016)

Introduction: There are limited studies of thrombotic and embolic complications (TEC) in the adult Fontan population. Hypothesis/objectives: To determine the prevalence, risk factors, and outcomes of TECs in this population. Method: Review of adults with a previous Fontan operation, followed at Mayo Clinic, 1994-2014. Systemic TEC was defined as intracardiac thrombus, ischemic stroke, or systemic arterial embolus. Non-systemic TEC was defined as Fontan conduit/right atrial thrombus or pulmonary embolus. Results: We identified 387 patients; mean age 28 ±7 years and follow-up 8±2 years. An atriopulmonary connection (APC) was done for 286/387 patients. Atrial arrhythmias were present in 278/387 (72%). There were 121 TECs (systemic n=36, non-systemic n=85) in 98/387 patients (25%). Risk factors for systemic TEC were atrial arrhythmia (hazard ratio [HR], 2.28; P =.001) and APC (HR, 1.98; P =.02); non-systemic TEC also had similar risk factors. All 98 patients received warfarin but warfarin was discontinued in 10/98 because of bleeding; and 8 of these 10 had a second TEC after discontinuing warfarin. Thrombi resolution occurred in 16/82 (20%) that continued to receive warfarin 16 (20%) and had follow-up imaging; 8 with other comorbid conditions had Fontan conversion. In total, 24/98 patients had a second TEC, most of whom had inadequate anticoagulation. Conclusions: TEC was not uncommon; risk factors for TEC were APC and atrial arrhythmias. Most patients were treated successfully with warfarin alone. A second TEC occurred in most patients whose anticoagulation was discontinued because of bleeding events. Legends Kaplan-Meier Curves comparing freedom from TEC. (A). Freedom from TECs in all patients and in patients with vs without atrial arrhythmia (AA) ( P =.002). (B). Freedom from TECs in all patients and in patients with vs without atriopulmonary connection (APC) ( P =.001). “No APC” group comprise of patients with total cavopulmonary connections.
Correlation of extent of ALK FISH positivity and crizotinib efficacy in three prospective studies of ALK-positive patients with non-small-cell lung cancer
Authors: J.-C. Soria, S.N. Ho, M. Varella-Garcia, A.J. Iafrate, B.J. Solomon, A.T. Shaw, F. Blackhall, T.S. Mok, Y.-L. Wu, K. Pestova, K.D. Wilner, A. Polli, J. Paolini, S. Lanzalone, S. Green, D.R. Camidge
Journal: Annals of Oncology (2018)
Abstract 15765: A Meta-analysis of Catheter Ablation versus Medical Therapy in Ventricular Tachycardia
Authors: Mohit Turagam, Poonam Velagapudi, Madhav Lavu, Sandia Iskandar, Donita Atkins, Luigi Di Biase, Andrea Natale, Madhu Reddy, Dhanunjaya Lakkireddy
Journal: Circulation (2016)

Background: Catheter ablation (CA) is an effective treatment strategy when compared to medical therapy (MT) for ventricular tachycardia (VT) in ischemic cardiomyopathy. However, its effect on morta...
Retained Plasticity and Substantial Recovery of Rod-Mediated Visual Acuity at the Visual Cortex in Blind Adult Mice with Retinal Dystrophy
Authors: Koji M. Nishiguchi, Kosuke Fujita, Naoyuki Tokashiki, Hiroshi Komamura, Sayaka Takemoto-Kimura, Hiroyuki Okuno, Haruhiko Bito, Toru Nakazawa
Journal: Molecular Therapy (2018)

In patients born blind with retinal dystrophies, understanding the critical periods of cortical plasticity is important for successful visual restoration. In this study, we sought to model childhood blindness and investigate the plasticity of visual pathways. To this end, we generated double-mutant (Pde6ccpfl1/cpfl1Gnat1IRD2/IRD2) mice with absent rod and cone photoreceptor function, and we evaluated their response for restoring rod (GNAT1) function through gene therapy. Despite the limited effectiveness of gene therapy in restoring visual acuity in patients with retinal dystrophy, visual acuity was, unexpectedly, successfully restored in the mice at the level of the primary visual cortex in this study. This success in visual restoration, defined by changes in the quantified optokinetic response and pattern visually evoked potential, was achieved regardless of the age at treatment (up to 16 months). In the contralateral visual cortex, cortical plasticity, tagged with light-triggered transcription of Arc, was also restored after the treatment in blind mice carrying an Arc promoter-driven reporter gene, dVenus. Our results demonstrate the remarkable plasticity of visual circuits for one of the two photoreceptor mechanisms in older as well as younger mice with congenital blindness due to retinal dystrophies.
Update on Keratinocyte Carcinomas
Authors: Kishwer S. Nehal, Christopher K. Bichakjian
Journal: New England Journal of Medicine (2018)

Squamous-cell and basal-cell carcinomas of the skin are increasing in frequency. Basal-cell carcinomas are responsive to inhibition of the hedgehog pathway; squamous-cell cancers may be responsive to immune checkpoint inhibitors.
Transfer of miRNA in Macrophage-Derived Exosomes Induces Drug Resistance in Pancreatic Adenocarcinoma
Authors: Yoav Binenbaum, Eran Fridman, Zvi Yaari, Neta Milman, Avi Schroeder, Gil Ben David, Tomer Shlomi, Ziv Gil
Journal: Cancer Research (2018)

Pancreatic ductal adenocarcinoma (PDAC) is known for its resistance to gemcitabine, which acts to inhibit cell growth by termination of DNA replication. Tumor-associated macrophages (TAM) were recently shown to contribute to gemcitabine resistance; however, the exact mechanism of this process is still unclear. Using a genetic mouse model of PDAC and electron microscopy analysis, we show that TAM communicate with the tumor microenvironment via secretion of approximately 90 nm vesicles, which are selectively internalized by cancer cells. Transfection of artificial dsDNA (barcode fragment) to murine peritoneal macrophages and injection to mice bearing PDAC tumors revealed a 4-log higher concentration of the barcode fragment in primary tumors and in liver metastasis than in normal tissue. These macrophage-derived exosomes (MDE) significantly decreased the sensitivity of PDAC cells to gemcitabine, in vitro and in vivo This effect was mediated by the transfer of miR-365 in MDE. miR-365 impaired activation of gemcitabine by upregulation of the triphospho-nucleotide pool in cancer cells and the induction of the enzyme cytidine deaminase; the latter inactivates gemcitabine. Adoptive transfer of miR-365 in TAM induced gemcitabine resistance in PDAC-bearing mice, whereas immune transfer of the miR-365 antagonist recovered the sensitivity to gemcitabine. Mice deficient of Rab27 a/b genes, which lack exosomal secretion, responded significantly better to gemcitabine than did wildtype. These results identify MDE as key regulators of gemcitabine resistance in PDAC and demonstrate that blocking miR-365 can potentiate gemcitabine response.Significance: Harnessing macrophage-derived exosomes as conveyers of antagomiRs augments the effect of chemotherapy against cancer, opening new therapeutic options against malignancies where resistance to nucleotide analogs remains an obstacle to overcome. Cancer Res; 78(18); 5287-99. ©2018 AACR.
PRIMUS-001: An adaptive phase II study of FOLFOX-A (FOLFOX and <i>nab</i>-paclitaxel) versus AG (<i>nab</i>-paclitaxel and gemcitabine) in patients with metastatic pancreatic cancer, with integrated biomarker evaluation (ISRCTN75002153) – Part of Precision-Panc.
Authors: Janet Shirley Graham, Juan W. Valle, T.R. Jeffry Evans, Derek B Grose, James Paul, Jamie Stobo, Susie Cooke, Judith Dixon-Hughes, Hannah Weir, Sumitra Mohan, Andrew Biankin, David Kuang-Fu Chang
Journal: Journal of Clinical Oncology (2018)

TPS4158 Background: Platinum-containing regimens (e.g. FOLFIRINOX) have shown survival benefit for pancreatic cancer (PC), with some "exceptional responders"; biomarkers (BM) of response are not well defined. Tumors with mutations in BRCA1/2 and other Fanconi Anemia genes, are preferentially sensitive to DNA-damaging agents (e.g. platinum) through synthetic lethality mechanisms, as they are defective in DNA damage response (DDR). We have shown that DDR deficiency may be present in 20% of PC. PRIMUS-001 aims to exploit defective DDR as a therapeutic vulnerability, with integrated study of BM of DNA-damaging agent response. Methods: PRIMUS-001 will enroll patients who are profiled molecularly using Precision-Panc NGS Diagnostic (BM via bespoke clinical grade assay). It is a multicentre, randomized (1:1), open-label, phase II trial comparing FOLFOX-A (nab-paclitaxel 150mg/m2 IV, oxaliplatin 85mg/m2, folinic acid 350mg flat dose, fluorouracil infusion 2400mg/m2 continuous IV infusion) vs AG (nab-paclitaxel 125mg/m2, gemcitabine 1000 mg/m2). Treatment is until progression or unacceptable toxicity. PFS is the primary endpoint alongside assessment of the predictive value of BM (enhanced benefit of FOLFOX-A in BM+ve). The study has 2 interim futility analyses at which recruitment may: stop, continue in all-comers or BM +ve only. The final analysis occurs at 416 PFS events (460 patients recruited). The study determines if a phase III should occur in all-comers (+/- BM testing), be restricted to BM +ve patients or should not occur. The study has 87% power (5% 1-sided level of statistical significance) to detect a an increase in median PFS from 5.5 to 7.3 mnths in all-comers. In BM +ve patients there is 89% power (10% 1-sided) to detect an increase in median PFS from 5.5 to 10 mnths. The main inclusion and exclusion criteria are similar to major efficacy trials. Patients must come from the Precision-Panc Master Protocol with tumor tissue suitable for molecular analysis. Current Enrolment: To date 4 patients have been randomized: 3 to receive FOLFOX-A and 1 to receive AG treatment Clinical trial information: 75002153.
First results of radiotherapy after hyperbaric oxygenation with temozolomide for high-grade gliomas.
Authors: David Hamid Khelif, Clement Kintzinger, Said Taha, Philippe Gauchez, Marc Bintner, Emmanuel Chirpaz, JAN-Dirk Harms, Valerie Florence Magnin
Journal: Journal of Clinical Oncology (2012)

2048 Background: The outcome of patients with high-grade gliomas remains poor despite modern therapeutic arsenal. The objective of this study was to assess the feasibility and efficacy of radiotherapy (RT) given immediately after hyperbaric oxygenation (HBO) with Stupp protocol. Methods: All patients with histologically confirmed high-grade gliomas from 2008 till 2011 coveraged at GHSR hospital were enrolled. Patients underwent Stupp protocol consisting in 60 Gy RT with a daily dose of 2 Gy for 5 days per week administrated immediately after HBO. Temozolomide (TMZ) was administrated at the daily dose 75 mg/m², 7 days per week followed by 6 cycles of TMZ 150 to 200 mg/m² for 5 days each 28 day-cycle. HBO schedule was approximately 15 min of compression with air, 60 min of 100% oxygen inhalation and 10 min of decompression with oxygen. Results: A total of 21 patients were diagnosed and histologically confirmed high grade gliomas. Five were excluded because of HBO contraindications. Twelve patients (75%) had undergone debulking surgery. The time interval from completion of decompression to start of irradiation was less than 15 minutes (mean 14.25, range 8-18). Twelve patients (75%) received the complete dose of RT and TMZ. HBO was completed for 7 (43.75%). Five (31.25%) were temporarily stopped and 4 (25%) were definitively stopped. One patient (6.25%) suffered from pancytopenia with grade 4 thrombopenia and grade 3 neutropenia. The median follow up was 46.95 weeks (range 5.7-108.3). Nine patients (56.25%) are still alive. Four (25%) have a survival more than 16 months. Conclusions: HBO with Stupp protocol is feasible and promising but requiring a large multicentric study.
Influence of Mechanical, Cellular, and Molecular Factors on Collateral Artery Growth (Arteriogenesis)
Authors: MatthiasHeil, WolfgangSchaper
Journal: Circulation Research (2004)

Growth of collateral blood vessels (arteriogenesis) is potentially able to preserve structure and function of limbs and organs after occlusion of a major artery. The success of the remodeling process depends on the following conditions: (1) existence of an arteriolar network that connects the preocclusive with the postocclusive microcirculation; (2) activation of the arteriolar endothelium by elevated fluid shear stress; (3) invasion (but not incorporation) of bone marrow–derived cells; and (4) proliferation of endothelial and smooth muscle cells. Most organs of most mammals including man can rely on the existence of interconnecting arterioles in most organs and tissues with heart being the exception in rodents and pigs. Arterial occlusion lowers the pressure in the distal vasculature thereby creating a pressure gradient favoring increased flow through preexisting collaterals. This increases fluid shear stress leading to endothelial activation with cellular edema, upregulation of adhesion molecules, mitog...
Organophosphate and Pyrethroid Pesticide Exposures Measured before Conception and Associations with Time to Pregnancy in Chinese Couples Enrolled in the Shanghai Birth Cohort
Authors: Yi Hu, Lin Ji, Yan Zhang, Rong Shi, Wenchao Han, Lap Ah Tse, Rui Pan, Yiwen Wang, Guodong Ding, Jian Xu, Qingying Zhang, Yu Gao, Ying Tian
Journal: Environmental Health Perspectives (2018)

Background: Pesticides have been associated with reproductive disorders, but there is limited research on pesticide exposures and human fertility. Objective: We aimed to investigate the effects of preconception exposure to pesticides on time to pregnancy (TTP) and on infertility in a general population of couples planning to become pregnant in Shanghai, China. Methods: A total of 615 women who were planning a pregnancy were enrolled before conception and were prospectively followed for 1 y to observe their TTP. Preconception pesticide exposures were assessed by measuring urinary metabolites of organophosphates (OPs) and pyrethroids (PYRs). Fecundability odds ratios (FORs) and odds ratios (ORs) of infertility were estimated using Cox and logistic regression models, respectively. All analyses were repeated after restricting the sample to nulliparous women (n=569). Results: After adjusting for age, prepregnancy BMI, current smoking, education, annual household income, age at menarche, and two items from the Perceived Stress Scale (PSS-10), women in the highest quartile of diethylthiophosphate (DETP; an OP metabolite) had significantly longer TTP [adjusted FOR=0.68 (95% CI: 0.51, 0.92)] and increased infertility [adjusted OR=2.17 (95% CI: 1.19, 3.93)] compared with women in the lowest quartile. The highest versus lowest quartile of 3-phenoxybenzoic acid (3PBA; a PYR metabolite) was associated with longer TTP and infertility, with significant associations in nulliparous women [adjusted FOR=0.72 (95% CI: 0.53, 0.98); adjusted OR for infertility=2.03 (95% CI: 1.10, 3.74)]. Conclusion: Our study provides some of the first evidence that preconception OP and PYR exposures are associated with decreased fertility in Chinese couples. Given that OPs and PYRs are rapidly metabolized in humans, more studies are needed to confirm our findings. https://doi.org/10.1289/EHP2987
Scrutiny-Dependent Cancer and Self-fulfilling Risk Factors
Authors: Roberto Zanetti, Lidia Sacchetto, Stefano Rosso
Journal: Annals of Internal Medicine (2018)

Letters17 July 2018Scrutiny-Dependent Cancer and Self-fulfilling Risk FactorsRoberto Zanetti, MD, PhD, Lidia Sacchetto, MSc, and Stefano Rosso, MDRoberto Zanetti, MD, PhDPiedmont Cancer Registry, Torino, Italy (R.Z., S.R.)Search for more papers by this author, Lidia Sacchetto, MScPolitecnico di Torino, Torino, Italy (L.S.)Search for more papers by this author, and Stefano Rosso, MDPiedmont Cancer Registry, Torino, Italy (R.Z., S.R.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L18-0145 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Welch and Brawley (1) provide examples and thoughtful reflections on the effects of increased scrutiny and lowering of threshold criteria in cancer diagnosis. Detecting indolent cases causes spurious trends in incidence and can bias the conclusions of causal investigations of risk factors and outcomes of prevention and treatment. The authors conclude by urging epidemiologists to use more caution in interpreting results from incidence-inflated studies and shift to “harder” outcomes, such as mortality (which Richard Doll always recommended [2]). That the mortality output for certain types of cancer—including prostate; breast; thyroid; melanoma; and, to some extent, colon—could be ...References1. Welch HG, Brawley OW. Scrutiny-dependent cancer and self-fulfilling risk factors. Ann Intern Med. 2018;168:143-4. [PMID: 29297002]. doi:10.7326/M17-2792 LinkGoogle Scholar2. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst. 1981;66:1191-308. [PMID: 7017215] CrossrefMedlineGoogle Scholar3. Sacchetto L, Zanetti R, Comber H, Bouchardy C, Brewster DH, Broganelli P, et al. Trends in incidence of thick, thin and in situ melanoma in Europe. Eur J Cancer. 2018;92:108-18. [PMID: 29395684] doi:10.1016/j.ejca.2017.12.024 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Piedmont Cancer Registry, Torino, Italy (R.Z., S.R.)Politecnico di Torino, Torino, Italy (L.S.)Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L18-0145. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoScrutiny-Dependent Cancer and Self-fulfilling Risk Factors H. Gilbert Welch and Otis W. Brawley Scrutiny-Dependent Cancer and Self-fulfilling Risk Factors H. Gilbert Welch and Otis W. Brawley Metrics 17 July 2018Volume 169, Issue 2Page: 134KeywordsDisclosureEpidemiologyHealth promotionLesionsMedical risk factorsMelanomaMortalityPopulation statisticsStatistical dataThyroid ePublished: 17 July 2018 Issue Published: 17 July 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Next-Generation Sequencing and Eating of the Tree of Knowledge
Authors: Daniel A. Pollyea
Journal: Clinical Cancer Research (2018)

Clonal hematopoiesis is common, and the large-scale sequencing of patients' tumors in the clinical setting is becoming very common. The incidence of falsely reporting clonal hematopoiesis as tumor associated in patients with solid tumors is a concern, as it may lead to unintended consequences.See related article by Coombs et al., p. 5918.