tbuckley/cabot-search huggingface dataset:
Subsequent Neoplasms After a Primary Tumor in Individuals With Neurofibromatosis Type 1
Authors: Smita Bhatia, Yanjun Chen, F. Lennie Wong, Lindsey Hageman, Kandice Smith, Bruce Korf, Ashley Cannon, Daniel J. Leidy, Alejandro Paz, Joseph E. Andress, Gregory K. Friedman, Katie Metrock, Joseph P. Neglia, Michael Arnold, Lucie M. Turcotte, Peter de Blank, Wendy Leisenring, Gregory T. Armstrong, Leslie L. Robison, D. Wade Clapp, Kevin Shannon, Jean L. Nakamura, Michael J. Fisher
Journal: Journal of Clinical Oncology (2019)

PURPOSE Fundamental gaps in knowledge regarding the risk of subsequent neoplasms (SNs) in children with pathogenic neurofibromatosis type 1 (NF1) variants exposed to radiation and/or alkylator chemotherapy have limited the use of these agents. METHODS We addressed these gaps by determining the SN risk in 167 NF1-affected versus 1,541 non–NF1-affected 5-year childhood cancer survivors from the Childhood Cancer Survivor Study and 176 nonoverlapping NF1-affected individuals with primary tumors from University of Alabama at Birmingham and Children’s Hospital of Philadelphia exposed to radiation and/or chemotherapy. Proportional subdistribution hazards multivariable regression analysis was used to examine risk factors, adjusting for type and age at primary tumor diagnosis and therapeutic exposures. RESULTS In the Childhood Cancer Survivor Study cohort, the 20-year cumulative incidence of SNs in NF1 childhood cancer survivors was 7.3%, compared with 2.9% in the non-NF1 childhood cancer survivors ( P = .003), yielding a 2.4-fold higher risk of SN (95% CI, 1.3 to 4.3; P = .005) in the NF1-affected individuals. In the University of Alabama at Birmingham and Children’s Hospital of Philadelphia cohort, among NF1-affected individuals with a primary tumor, the risk of SNs was 2.8-fold higher in patients with irradiated NF1 (95% CI, 1.3 to 6.0; P = .009). In contrast, the risk of SNs was not significantly elevated after exposure to alkylating agents (hazard ratio, 1.27; 95% CI, 0.3 to 3.0; P = .9). CONCLUSION Children with NF1 who develop a primary tumor are at increased risk of SN when compared with non-NF1 childhood cancer survivors. Among NF1-affected children with a primary tumor, therapeutic radiation, but not alkylating agents, confer an increased risk of SNs. These findings can inform evidence-based clinical management of primary tumors in NF1-affected children.
Proteomic profiling in human tumor derived vascular endothelial cells (HTEC)
Authors: Thomas Mohr, Nina Gundacker, Verena Haudek, Editha Bayer, Christof Lenz, Reinhard Horvat, Christopher Gerner, Michael Micksche
Journal: Cancer Research (2007)

3008  Angiogenesis plays a critical role in tumor progression. Mounting evidence suggests a distinct difference between HTEC and normal endothelial cells (EC) on mRNA and protein expression level. To investigate differences in main biological pathways of HTEC we have undertaken a proteome analysis of quiescent and VEGF-activated HTEC with human umbilical vein endothelial cells (HUVEC) serving as control. HTEC from ovarian carcinoma were isolated using magnetic beads coated with antibodies against CD31. For proteome profiling, cells from passages 3-5 where starved in serum and growth factor deprived medium (24hrs), incubated with 5ng/ml VEGF (6hrs) and labeled with 35S methionine/cysteine (last 2 hrs). The cytosolic fraction of the cell homogenisate was subjected to high resolution 2D gel electrophoresis. Determination of protein amount by fluorimaging was combined with determination of incorporated 35S by autoradiography. Proteins where identified by mass fingerprint analysis preparation of tryptic protein hydrolysates and Matrix-Assisted Laser Desorption Ionization-Time-Of-Flight (MALDI-TOF) analysis. HTEC where morphologically similar to HUVEC, but showed a lower upregulation of CD62-E, CD54 and CD106 expression after treatment with Il-1β and TNF-α (RT-PCR and Fixed Cell ELISA). On 2D gels, over 630 spots where identified, encompassing cytoskeletal proteins, proteins involved in motility and plasticity, signal transduction, transcription, translation, regulation of apoptosis, coagulation, endocytosis, antigen presentation, detoxification and lipide, amino acid, carbohydrate and purine/pyrimidine metabolism. Whereas protein amount in quiescent and VEGF-activated EC did not differ significantly after 6 hours activation (fluorometry),synthesis profiles (incorporation of 35S) where markedly different in HTEC compared to HUVEC in quiescent as well as in VEGF activated cells. More than 250 proteins where differently expressed in quiescent state, whereas more than 150 proteins where differently expressed in VEGF activated state, respectively. Differences in synthesis rates encompassed a wide variety of proteins (e.g. Annexins, chloride and potassium channel proteins, Copine 1, α-Enolases, Ezrin, Heat Shock Proteins, S100 Calcium binding protein, Stress 70 Protein, Tubulins, Vinculin). These results show a distinct and permanent change in the protein expression pattern of tumor vascular endothelial cells. These changes are possibly responsible for abnormalities of the tumor vasculature and may lead to the development of new strategies for antiangiogenic therapies.
Capillary malformation with segmental distribution and central atrophy: A series of 7 cases
Authors: Marta Ivars, Jose Manuel Azaña, Lisa Weibel, Martin Theiler, Pablo Boixeda, Diana Islas Norris, Victor Martinez-Glez, Noelia Agra, Lara Rodríguez-Laguna, Isabel Colmenero, María José Beato-Merino, Juan Carlos López-Gutiérrez
Journal: Journal of the American Academy of Dermatology (2019)
A thermally responsive Tat-elastin-like polypeptide fusion protein induces membrane leakage, apoptosis, and cell death in human breast cancer cells
Authors: Iqbal Massodi, Drazen Raucher
Journal: Cancer Research (2007)

2273  One of the major limitations of conventional cancer chemotherapy treatments for solid tumors is lack of selective delivery of anti cancer agents to tumor cells. Therefore, in order to avoid treatment-related damage to normal tissues it is necessary to develop targeted therapies designed to increase the amount of the drug that reaches the cancer tissue and simultaneously reduce the nonselective cytotoxicity in normal tissues. In our studies we used thermally responsive elastin like polypeptide (ELP) as a macromolecular drug delivery vehicle, which offers an advantage of active targeting to solid tumors by application of focused hyperthermia.  Uptake of therapeutic macromolecules such as high molecular weight compounds into live eukaryotic cells is hindered by the lipophilic nature of the plasma membrane. One approach for delivering macromolecules or proteins into the target cells is to couple them to cell penetrating peptides (CPP). CPPs are known to translocate through cell membranes and phospholipids vesicles. In our previous study, we evaluated the efficiency, kinetics and mechanism of cellular uptake of the CPPs penetratin, Tat, and MTS fused to Elastin-like polypeptides (CPP-ELP). We have shown that Tat enhanced cellular uptake of ELP carrier and it is one of the best candidates for drug delivery vehicle.  Toxicity properties of new therapeutic delivery vehicles is crucial to their utility as effective delivery vehicles, and it is one of the keys to selecting the best candidates for further development. Therefore, in order to exploit Tat-ELP for improved thermally targeted delivery of therapeutic cargoes, in this study, we extend our previous work, and evaluate cytotoxicity of thermally responsive Tat-ELP in various cell lines in response to hyperthermia. We report that Tat-ELP is cytotoxic for some cell lines at 420C but not at 370C which include SKMEL-2, SKOV-3, MCF-7 and non-tumor cell line WI-38.  MCF-7 human breast cancer cell line showed greater toxicity as compared to other tumor cell lines at 420C and were chosen to study the mechanism behind this increased toxicity. We have found that Tat-ELP combined with hyperthermia causes membrane leakage, apoptosis, and cell death. However, it did not show any hemolytic effect on murine RBCs with or without hyperthermia. This finding is important and indicates that the selection and design of thermally sensitive ELPs and other macromolecular carriers for delivery of cancer therapeutics should be optimized for increased activities against tumor cells and low cytolytic activities to normal mammalian cells and erythrocytes.
Albuterol and Pediatric Perioperative Respiratory Complications—Reply
Authors: Britta S. von Ungern-Sternberg, David Sommerfield, Graham L. Hall
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Mitochondrial Reprogramming Underlies Resistance to BCL-2 Inhibition in Lymphoid Malignancies
Authors: Romain Guièze, Vivian M. Liu, Daniel Rosebrock, Alexis A. Jourdain, María Hernández-Sánchez, Aina Martinez Zurita, Jing Sun, Elisa Ten Hacken, Kaitlyn Baranowski, Philip A. Thompson, Jin-Mi Heo, Zachary Cartun, Ozan Aygün, J. Bryan Iorgulescu, Wandi Zhang, Giulia Notarangelo, Dimitri Livitz, Shuqiang Li, Matthew S. Davids, Anat Biran, Stacey M. Fernandes, Jennifer R. Brown, Ana Lako, Zoe B. Ciantra, Matthew A. Lawlor, Derin B. Keskin, Namrata D. Udeshi, William G. Wierda, Kenneth J. Livak, Anthony G. Letai, Donna Neuberg, J. Wade Harper, Steven A. Carr, Federica Piccioni, Christopher J. Ott, Ignaty Leshchiner, Cory M. Johannessen, John Doench, Vamsi K. Mootha, Gad Getz, Catherine J. Wu
Journal: Cancer Cell (2019)
Breast cancer mortality among users of cholesterol-lowering drugs.
Authors: Teemu Johannes Murtola, Kala Visvanathan, Miia Artama, Harri Vainio, Eero Pukkala
Journal: Journal of Clinical Oncology (2013)

1514 Background: Breast cancer is a common malignancy and cause of cancer death. Recent studies have suggested that statins, an established cholesterol-lowering drug group used in the prevention of cardiovascular mortality, could have beneficial effects against recurrence and progression of breast cancer. We evaluated breast cancer-specific mortality among users of statins and other cholesterol-lowering drugs (fibrates and bile-acid binding resins) in a cohort of breast cancer patients. Methods: Our study cohort included all newly diagnosed breast cancer patients in Finland during 1995-2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on cholesterol-lowering medication use was obtained from a national prescription database.We used Cox proportional hazards regression method to estimate mortality among medication users. Results: A total of 4,169 participants had used statins, while 313 had used fibrates or resins. Despite similar median age, tumor and treatment characteristics, only statin use was associated with decreased breast cancer mortality (participants with localized tumors: HR 0.33, 95% CI 0.24-0.42; metastatic tumors: HR 0.52, 95% CI 0.31-0.86). Fibrate and resin use were associated with increased overall mortality (HR 1.70, 95% CI 0.96-2.99 for participants with localized disease, HR 2.65, 95% CI 1.18-5.96 for participants with metastatic disease). Conclusions: Decreased breast cancer mortality among users of statins, but not other cholesterol-lowering drugs despite similar population characteristics suggests that this drug group may have benefit in prevention of cancer progression. Clinical trials testing statins’ efficacy in breast cancer patients are warranted.
Effect of photodynamic therapy on human prostate tumor microcirculation: potential mechanism of distant metastasis
Authors: Nicolas Solban, Alok Sinha, Sung Chang, William L. Rice, Pål K. Selbo, Tayyaba Hasan
Journal: Cancer Research (2005)

4636  Introduction: Photodynamic therapy (PDT) appears to hold promise for the treatment of localized recurrent prostate cancer. However, the long-term effects remain to be evaluated. We have observed that, in an animal model, subcurative PDT of prostate cancer increases distant metastasis, a side effect also reported after brachytherapy, hyperthermia and surgery. The objectives of this study are to evaluate the effect of PDT on the microcirculation of human prostate tumors as well as its potential role in vascular permeability and angiogenesis. Materials and Methods: This study was performed with the androgen responsive human LNCaP cells. 3x106 cells in 50% Matrigel was inoculated in SCID mice prostate, 3 weeks later experiments were performed. BPD was used at a concentration of 140 nM for in vitro assays and at concentration of 0.25 mg/kg body weight for in vivo treatment. PDT is performed 1 hr after incubation or injection of BPD. At various times following PDT treatment we have used, an ELISA to measured VEGF-A protein levels and RT-PCR to measure RNA levels. A modified Miles assay using FITC-Dextran was used to monitor in real time vascular leakage, and IHC was used to image VEGF. Results: PDT treatment of prostate tumors shows significant area of necrosis (H&E staining) as well as an increase in VEGF-A (IHC) 24 h post treatment. Quantification using an ELISA shows a 1,8 fold increase in VEGF-A levels 24 h following subcurative treatment. Using a modified Miles assay we were able to observe, in real time, an immediate increase in vascular permeability following PDT. Next we performed in vitro experiments to identify the mechanism of this increase. ELISA performed 24 h post PDT shows an increase in both intracellular and secreted VEGF-A levels (1,4x and 2,5x respectively). RT-PCR shows an increase in all 3 VEGF-A isoforms expressed in LNCaP cells 24 h following subcurative PDT (1,7x).Conclusion: Together the results presented in this study establishes that PDT alters tumor microcirculation, as well as transcription and synthesis of VEGF-A in vivo and in vitro at subcurative doses. Based on the current observations we conclude that the most effective application of PDT for long-term cure, may involve combined therapeutic regimens that counteract the potential metastatic effect of PDT, while retaining its impressive local tumor control.
Coeliac disease and HLA‐conferred susceptibility to autoimmunity are associated with IgE sensitization in young children
Authors: Neea Mustonen, Heli Siljander, Aleksandr Peet, Vallo Tillmann, Taina Härkönen, Onni Niemelä, Raivo Uibo, Jorma Ilonen, Mikael Knip
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Would You Refer This Patient With Cancer to a Palliative Care Specialist?
Authors: Phil Di Sorbo
Journal: Annals of Internal Medicine (2019)

Letters17 September 2019Would You Refer This Patient With Cancer to a Palliative Care Specialist?Phil Di Sorbo, MSPhil Di Sorbo, MSEllis Medicine, Schenectady, New York (P.D.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0342 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I thank Reynolds and colleagues (1) for their thorough discussion on palliative care guidelines. I would like to offer several comments as part of the ongoing dialogue in this field.Their discussion of when to engage specialist-level palliative care services in relation to triggers or adverse events is helpful. However, as palliative care moves upstream (and specifically into primary care), I believe that this approach will only touch the surface and be applicable solely in emergency or episode-based situations. A more relevant population health management approach—one potentially closely tied to evidence-based primary care and value-based payment—would be ...Reference1. Reynolds EE, Buss MK, Schlechter BL, et al. Would you refer this patient with cancer to a palliative care specialist? Grand rounds discussion from Beth Israel Deaconess Medical Center. Ann Intern Med. 2019;170:488-96. [PMID: 30934082]. doi:10.7326/M19-0361 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Ellis Medicine, Schenectady, New York (P.D.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0342. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoWould You Refer This Patient With Cancer to a Palliative Care Specialist? Eileen E. Reynolds , Mary K. Buss , Benjamin L. Schlechter , and Anjala Tess Would You Refer This Patient With Cancer to a Palliative Care Specialist? Eileen E. Reynolds , Mary K. Buss , and Benjamin L. Schlechter Metrics 17 September 2019Volume 171, Issue 6Page: 447-448KeywordsConflicts of interestDisclosureHospitalizationsLength of stayMedicareMotivationPalliative carePrevention, policy, and public healthRisk assessmentsTouch ePublished: 17 September 2019 Issue Published: 17 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Results of a Phase 1/2 Trial of Chemoradiotherapy With Simultaneous Integrated Boost of Radiotherapy Dose in Unresectable Locally Advanced Esophageal Cancer
Authors: Dawei Chen, Hari Menon, Vivek Verma, Steven N. Seyedin, Jaffer A. Ajani, Wayne L. Hofstetter, Quynh-Nhu Nguyen, Joe Y. Chang, Daniel R. Gomez, Arya Amini, Stephen G. Swisher, Mariela A. Blum, Ahmed I. Younes, Hampartsoum B. Barsoumian, Jeremy J. Erasmus, Jeffrey H. Lee, Manoop S. Bhutani, Kenneth R. Hess, Bruce D. Minsky, James W. Welsh
Journal: JAMA Oncology (2019)

Effective treatment options for locally advanced esophageal cancer are limited, and rates of local recurrence after standard chemoradiotherapy remain high.To evaluate toxic effects, local control, and overall survival rates after chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose to the gross tumor and nodal disease for patients with unresectable locally advanced esophageal cancer.A phase 1/2, single-arm trial was conducted in 46 patients from April 28, 2010, to April 9, 2015 (median follow-up, 52 months [range, 2-86 months]), at a tertiary academic cancer center. Outcomes of the study patients were compared with those of 97 similar patients treated at the same institution from January 10, 2010, to December 5, 2014, as part of the interim analysis. Statistical analysis was performed from December 15, 2018, to February 12, 2019.Chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose (50.4 Gy to subclinical areas at risk and 63.0 Gy to the gross tumor and involved nodes, all given in 28 fractions) with concurrent docetaxel and capecitabine or fluorouracil.Toxic effects, local (in-field) control, and overall survival rates.All 46 patients (11 women and 35 men; median age, 65.5 years [range, 37.3-84.4 years]) received per-protocol therapy, as intensity-modulated photon therapy (39 [85%]) or intensity-modulated proton therapy (7 [15%]); 11 patients (24%) ultimately underwent resection. No patients experienced grade 4 or 5 toxic effects; the 10 acute grade 3 toxic events were esophagitis (4), dysphagia (3), and anorexia (3) and the 3 late grade 3 toxic events were all esophageal strictures. The actuarial local recurrence rates were 22% (95% CI, 11%-35%) at 6 months, 30% (95% CI, 18%-44%) at 1 year, and 33% (95% CI, 20%-46%) at 2 years. Overall, 15 patients (33%) experienced local failure, at a median interval of 5 months (range, 1-24 months). The median overall survival time was 21.5 months (range, 2.3-86.4 months). Exploratory comparison with a 97-patient contemporaneous institutional cohort receiving standard-dose (non-simultaneous integrated boost) chemoradiotherapy showed superior local control (hazard ratio, 0.49; 95% CI, 0.26-0.92; P = .03) and overall survival (hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .02) in the group that received chemoradiotherapy with a simultaneous integrated boost.These findings suggest that chemoradiotherapy with a simultaneous integrated boost of radiotherapy dose for locally advanced esophageal cancer is well tolerated, with encouraging local control, and thus warrants further study.ClinicalTrials.gov identifier: NCT01102088.
A Single Institutional Experience Comparing Cryoprecipitate to Plasma in Patients with Disseminated Intravascular Coagulopathy (DIC) from Acute Myeloid Leukemia (AML)
Authors: Ghaith Abu-Zeinah, Mustafa Al-Kawaaz, Valery J Li, Yen-Michael S. Hsu, Melissa M. Cushing, Joseph Scandura
Journal: Blood (2017)
A CCL1/CCR8-dependent feed-forward mechanism drives ILC2 functions in type 2–mediated inflammation
Authors: Lisa Knipfer, Anja Schulz-Kuhnt, Markus Kindermann, Vicky Greif, Cornelia Symowski, David Voehringer, Markus F. Neurath, Imke Atreya, Stefan Wirtz
Journal: The Journal of Experimental Medicine (2019)

Group 2 innate lymphoid cells (ILC2s) possess indispensable roles during type 2–mediated inflammatory diseases. Although their physiological and detrimental immune functions seem to depend on the anatomical compartment they reside, their tissue tropism and the molecular and immunological processes regulating the self-renewal of the local pool of ILC2s in the context of inflammation or infection are incompletely understood. Here, we analyzed the role of the CC-chemokine receptor CCR8 for the biological functions of ILC2s. In vitro and in vivo experiments indicated that CCR8 is in comparison to the related molecule CCR4 less important for migration of these cells. However, we found that activated mouse and human ILC2s produce the CCR8 ligand CCL1 and are a major source of CCL1 in vivo. CCL1 signaling to ILC2s regulates their proliferation and supports their capacity to protect against helminthic infections. In summary, we identify a novel chemokine receptor–dependent mechanism by which ILC2s are regulated during type 2 responses.
Chronic respiratory symptoms but normal lung function: substantial disease burden but little evidence to inform practice
Authors: Milo A. Puhan
Journal: European Respiratory Journal (2019)

The treatment of symptomatic patients with chronic airway obstruction (defined by a forced expiratory volume in 1 s to forced vital capacity ratio of <0.7) is widely established. It includes drug and non-drug treatments to slow down disease progression, reduce symptoms and reduce the risk of exacerbations [1–5]. Individuals with chronic airway obstruction but no respiratory symptoms are commonly advised to take preventive measures ( e.g. smoking cessation) to slow down the decline of lung function [6]. But there is a third group of individuals that is much more difficult to deal with: individuals who have chronic respiratory symptoms but normal lung function.
Population Pharmacokinetics of Cefotaxime and Dosage Recommendations in Children with Sickle Cell Disease
Authors: Bérengère Koehl, Elsa Maksoud, Phuong Ha, Wei Zhao, Florentia Kaguelidou, Malika Benkerrou, Patricia Mariani, Mathie Lorrot, Albert Faye, Evelyne Jacqz-Aigrain, Andre Baruchel
Journal: Blood (2017)