tbuckley/cabot-search huggingface dataset:
Cell Membrane‐Coated Magnetic Nanocubes with a Homotypic Targeting Ability Increase Intracellular Temperature due to ROS Scavenging and Act as a Versatile Theranostic System for Glioblastoma Multiforme
Authors: Christos Tapeinos, Francesca Tomatis, Matteo Battaglini, Aitor Larrañaga, Attilio Marino, Iker Aguirrezabal Telleria, Makis Angelakeris, Doriana Debellis, Filippo Drago, Francesca Brero, Paolo Arosio, Alessandro Lascialfari, Andrea Petretto, Edoardo Sinibaldi, Gianni Ciofani
Journal: Advanced Healthcare Materials (2019)

Abstract In this study, hybrid nanocubes composed of magnetite (Fe 3 O 4 ) and manganese dioxide (MnO 2 ), coated with U‐251 MG cell‐derived membranes (CM‐NCubes) are synthesized. The CM‐NCubes demonstrate a concentration‐dependent oxygen generation (up to 15%), and, for the first time in the literature, an intracellular increase of temperature (6 °C) due to the exothermic scavenging reaction of hydrogen peroxide (H 2 O 2 ) is showed. Internalization studies demonstrate that the CM‐NCubes are internalized much faster and at a higher extent by the homotypic U‐251 MG cell line compared to other cerebral cell lines. The ability of the CM‐NCubes to cross an in vitro model of the blood‐brain barrier is also assessed. The CM‐NCubes show the ability to respond to a static magnet and to accumulate in cells even under flowing conditions. Moreover, it is demonstrated that 500 µg mL −1 of sorafenib‐loaded or unloaded CM‐NCubes are able to induce cell death by apoptosis in U‐251 MG spheroids that are used as a tumor model, after their exposure to an alternating magnetic field (AMF). Finally, it is shown that the combination of sorafenib and AMF induces a higher enzymatic activity of caspase 3 and caspase 9, probably due to an increment in reactive oxygen species by means of hyperthermia.
Abstract LB-246: Apoptotic mechanisms of <i>Vernonia amydalina</i> delile in the prevention of prostate cancer
Authors: Clement G. Yedjou, Solange S. Tchounwou, William K. Johnson, Sylvianne Njiki, Paul B. Tchounwou
Journal: Cancer Research (2019)

Abstract Prostate cancer is one of the common cancers in males and its incidence keeps increasing globally. Approximately 81% of prostate cancer is diagnosed during the early stage of the disease. The treatment options for prostate care include surgery, radiotherapy, and chemotherapy, but these treatments often have side effects that may result in a poor quality of life such as impotence or decreased bowel function. Our central goal is to test the apoptotic mechanisms of Vernonia amydalina Delile (an edible medicinal plant that is relatively inexpensive, non-toxic, and virtually without side effects) for the prevention of prostate cancer using human adenocarcinoma (PC-3) cells as a test model. To address our specific goal, PC-3 cells were treated with Vernonia amydalina Delile (VAD). Cell viability was determined by the MTT assay and cell morphology was analyzed by acridine orange and propidium iodide (AO/PI) dye using the fluorescent microscope. Cell cycle arrest and cell apoptosis were evaluated by Flow Cytometry assessment. Nucleosomal DNA fragmentation was detected by DNA laddering. Data obtained from the AO/PI dye assessment indicated that VAD significantly reduced the number of live cells in a dose-dependent manner, showing a gradual increase in the loss of viability in VAD-treated cells. A similar result was obtained by the MTT assay. We observed a significant increase in DNA damage in VAD-treated cells compared to the control group. Flow cytometry data demonstrated that VAD induced apoptosis in treated cells compared to the control cells. These results suggest that induction of cell death, cell cycle arrest, and cell apoptosis are involved in the therapeutic efficacy of VAD as anticancer candidate towards the prevention and/or treatment of prostate cancer. Citation Format: Clement G. Yedjou, Solange S. Tchounwou, William K. Johnson, Sylvianne Njiki, Paul B. Tchounwou. Apoptotic mechanisms of Vernonia amydalina delile in the prevention of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-246.
Targeting low-expressing ERBB-2 and acquired resistant high-expressing ERBB-2 breast carcinomas.
Authors: Michalis Karamouzis, Geena Dalagiorgou, Sonia A. Perez, Urania Georgopoulou, Athanasios Papavassiliou
Journal: Journal of Clinical Oncology (2013)

e11513 Background: Human epidermal growth factor receptors and their ligands are involved in carcinogenesis. Four ERBB receptors have been identified; ERBB1 (EB1), ERBB2 (EB2), ERBB3 (EB3) and ERBB4 (EB4). EB2 is over-expressed/amplified in 20-30% of BCa. Molecularly targeting agents, such as pertuzumab (P), in combination with standard therapy have shown important clinical results in EB2 (+) BCa patients. The aim of the project is to evaluate the expression/localization and dimerization pattern of EB1, EB2, EB3, EB4 in breast cancer cell lines (BCCLs) with or without heregulin-1 (He) and various EB2, EB3 and He inhibitors. The identification of a molecular phenotype of low-expressing and acquired resistant high-expressing EB2 BCa will enhance the targeted use of EB2 inhibitors in certain BCa patients Methods: Using confocal microscopy, localization/expression patterns were studied for EB1, EB2, EB3, EB4 in various human BCCs; here presented in MCF7 and SKBR3. Additionally, the dimerization pattern of EB2, EB3 and/or EB4 was studied with and without stimulation with He plus or minus P (kindly provided by Genentech, US). The dimers formation was studied using proximity ligation assay and immunofluorescence (DUOLINK; OLINK Biosciences, Sweden). Results: In MCF7-He stimulated cells EB2/EB3, EB2/EB4 and EB1/EB3 dimmers showed a 3-fold decrease formation compared to untreated cells. The EB1/EB4 dimmers were not significantly affected. After P addition in MCF7 cells a 3-fold decrease of dimmer formation was noticed compared to untreated cells for EB2/EB3, EB2/EB4 and EB1/EB3. The EB1/EB4 formation seemed only slightly affected by P. SKBR3-He stimulated cells resulted in a similar decrease of EB2/EB3, EB2/EB4 and EB1/EB3 dimmer formation compared to untreated cells. In the same BCLL, EB1/EB4 dimmer did not show any decrease after He treatment compared to untreated control cells. Further results quantified and analyzed for statistical significance will be shown Conclusions: The addition of P seems to block ligand-dependent heterodimerization of EB2 with other ERBB family members, such as EB3 and EB4.
Safety and efficacy of percutaneous endoscopic gastrostomy tube placement in patients with malignant peritoneal carcinomatosis induced bowel obstruction.
Authors: Pankaj G Vashi, Donald Peter Braun, Brenten Popiel, Digant Gupta
Journal: Journal of Clinical Oncology (2012)

e14012 Background: Percutaneous Endoscopic Gastrostomy (PEG) tube placement in advanced peritoneal carcinomatosis with bowel obstruction is a feasible palliative procedure to help patients with obstructive symptoms. We describe the safety and efficacy of using PEG tube for decompression in patients with large peritoneal masses. Methods: A consecutive case series of 62 patients (Apr-08 to Jun-11) with advanced abdominal carcinomatosis induced bowel obstruction. All patients were extensively treated for their cancer. None of them were surgical candidates due to extensive peritoneal involvement. All patients had symptoms of nausea, vomiting and pain at the time of PEG tube placement. All patients had a 28F (Bard) PEG tube placed for drainage. The primary outcomes of interest were complications and symptom resolution due to PEG tube placement. Frequency of nausea, vomiting and severity of pain was recorded daily in patient charts. Results: 16 were males and 46 females. The mean age was 50.5 years. Most common cancers were ovary, pancreas, colon and stomach. Of 62 patients, 57 patients had expired at the time of this analysis. Of those 57 expired, 49 had PEG tube at the time of death, while 8 had complete resolution of symptoms with PEG tube removed before death. The 5 out of 62 patients who are alive still have the PEG tube for drainage (average 70.4 days). The average duration of PEG tube placement for all patients combined was 70.9 days (range 6-312 days). Relief of nausea, vomiting and pain was observed in 53 (85.5%), 55 (88.7%) and 35 (56.5%) patients respectively. Of a total of 43 patients who had PEG tube placed for &gt;= 30 days, 24 (56%) could continue with their chemotherapy cycles because of symptom resolution. Non life threatening complications of PEG tube placement were observed in 9 (14.5%) patients. 3 had infection at the insertion site, 2 had bleeding and 3 had leaking at the PEG tube site while 1 had aspiration. 6 (9.7%) patients required replacement of the PEG tube due to occlusion. Conclusions: Placement of PEG tube in presence of advanced peritoneal carcinomatosis is safe and effective in relieving obstructive symptoms as well as extending the period of active cancer therapy.
Response to: ‘Bone health, an often forgotten comorbidity in systemic lupus erythematosus: a comment on the new recommendations’ by Orsolini <i>et al</i>
Authors: Antonis Fanouriakis, George Bertsias, Dimitrios T Boumpas
Journal: Annals of the Rheumatic Diseases (2019)

Response to: 'Bone health, an often forgotten comorbidity in systemic lupus erythematosus: a comment on the new recommendations' by Orsolini et alWe thank Drs Orsolini et al for their interest in the updated European League against Rheumatism (EULAR) recommendations for the treatment of systemic lupus erythematosus (SLE), 1 and we are grateful for bringing up a crucial aspect of the disease, namely osteoporosis and bone health in patients with this disease.Undoubtedly, prevention and treatment of osteoporosis represent a major challenge and a current unmet need in the holistic management of patients with lupus.The choice to omit the issue of bone health from the updated recommendations was only due to limited space in the manuscript; for this reason, a special focus was placed on infections and cardiovascular disease, as these currently represent two major causes of morbidity and mortality in lupus patients.Importantly, as the authors emphasise, the increased risk for osteoporosis and fractures in SLE seems to be only in part associated with the chronic use of glucocorticoids (GC).Ongoing disease activity, premature menopause caused by use of gonadotoxic drugs and vitamin D deficiency represent additional factors that contribute to a reduced bone mineral density in SLE. 2 The authors also correctly point out that an assessment tool for the evaluation of fracture risk customised for patients with SLE is lacking.The FRAX tool, which is recommended and widely used to calculate this risk, 3 may indeed underestimate the actual risk in the context of SLE.To this end, it relies on physicians caring after lupus patients to provide patients with practical instructions in order to minimise the risk for fractures.Lifestyle modifications, such as exercise uptake and maintenance of a normal body mass index, are important, as are smoking cessation and reduction of alcohol consumption.For patients receiving GC, the recent guidelines of the American College of Rheumatology for the prevention and treatment of GC-induced osteoporosis should be followed. 3We fully agree with Orsolini et al that a future update of the EULAR recommendations for the management of SLE should include specific guidance regarding bone health.
Has demand outpaced supply for clinical trial participants?
Authors: J. T. Tam, R. Hauser, D. Gura, A. Paraghamian, H. Thomas, S. Lichtman
Journal: Journal of Clinical Oncology (2006)

6016 Background: Current estimates are less than 5% of adult cancer patients participate in clinical trials. Initiatives to address barriers to accrual (such as age, physician bias, etc) are ongoing. However, with more drugs in the pipeline and more clinical trials being conducted, demand for trial participants may be outpacing the current “supply”. Methods: The ClinicalTrials.gov database, maintained by National Institutes of Health was selected for review on the basis that it is proposed to be the mandated repository for clinical trials information. Over a 2 month period, the database was mined for all active, US recruiting, phase I, I/II, II, and III trials in breast, lung, and prostate cancers. Results: There were 290 breast, 212 lung, and 177 prostate cancer trials with the prespecified criteria. The number of patients needed to complete these trials is 151,311 (breast), 33,498 (lung), and 53,181 (prostate). These represent 19.4% to 71.6% of the American Cancer Society incidence estimates of the studied tumors. NCI, industry, and academia sponsored, either solely or in collaborations, 42.1%, 26.5%, and 45.6% of trials, respectively. Majority of studies were phase II (51%), with 11.5% phase I, and 15.6% phase III. Remaining studies were either combined phase I/II studies or not specified. Significant percentage of trials involved pts with advanced/metastatic disease (54% breast, 51.4% lung, and 44.6% prostate). Conclusions: Although many studies have anticipated enrollment period over several years, the number of trial participants needed to complete these studies is quite daunting. Our results are likely under-estimates as not all studies currently enrolling patients may be included in this registry, and not all studies in the database specified the recruitment goal. Although not all trial participants are drawn from the incidence numbers, it is clear that given the current trial participation rate, demand has outpaced the supply. The medical community has the ethical responsibility to ensure sufficient patient enrollment for clinical trials. In addition to addressing accrual barriers, the authors encourage the establishment of a task force including academia, government, and industry to systematically evaluate and prioritize the types of trials being conducted. No significant financial relationships to disclose.
Human and mouse linked evaluation of tumors
Authors: Shunqiang Li, Austin Lin, Jeremy Hoog, Rebecca Aft, Yu Tao, Matthew Ellis
Journal: Cancer Research (2008)

2940  Attempts at understanding the molecular mechanisms underlying the anti-tumor effects of breast cancer treatments are frustrated in part by limited access to primary human tumors undergoing treatment and the lack of experimental models adequately recapitulating the biological features of the disease. Kuperwasser and colleagues reported successfully reconstructing functionally normal human breast tissues in mammary fat pads of NOD/SCID mice. In the present study, we seek to recapitulate human breast tumors using this technique. The procedure involves “humanization” of the stroma of the mammary fat pads of highly immunodeficient NOD/SCID mice by removing mouse mammary epithelia and implanting immortalized human breast fibroblasts, followed by a human breast tumor sample mixed with the same fibroblast line approximately two to four weeks later. We report successfully establishing multiple serially transplantable human breast tumors from core biopsy samples from both breast primary and metastatic sites using this technique. cDNA microarray analysis indicates high concordance in gene expression between the xenografts (passage 1-3) and the original human tumor with all probes present on the Agilent 44K array and a subset of 141 genes that distinguish between basal from luminal breast cancer. Furthermore, when the relative expression profiles of the original human tumor and xenograft passages 1 and 3 were compared with134 other breast cancers, the original human tumor and its engrafted counterpart clustered more closely with each other than with any other tumor. Passage 3 tumors in mice had similar histopathological features to the original human counterpart. In addition, in one case, a passage 3 tumor retained the aggressive metastatic features of its original human counterpart, confirmed by the presence of human centromeres in the disseminated disease in the mouse. To date, all 6 successfully engrafted tumors are from patients with triple negative tumors, indicating that this approach is a likely to form the basis for a new in vivo system for biological studies and preclinical testing of anticancer compounds for basal type breast cancer.  Supported by the Susan G Komen Foundation and the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine through a National Cancer Institute-funded Cancer Center Support Grant (P30 CA091842) and funding from the Fashion Footwear Association of New York (FFANY).
Ventricular Dysfunction Is a Critical Determinant of Mortality in Congenital Diaphragmatic Hernia
Authors: Neil Patel, Pamela A. Lally, Florian Kipfmueller, Anna Claudia Massolo, Matias Luco, Krisa P. Van Meurs, Kevin P. Lally, Matthew T. Harting
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Congenital diaphragmatic hernia (CDH) is an anomaly with a high morbidity and mortality. Cardiac dysfunction may be an important and underrecognized contributor to CDH pathophysiology and determinant of disease severity.Objectives: Our aim was to investigate the association between early, postnatal ventricular dysfunction and outcome among infants with CDH.Methods: Multicenter, prospectively collected data in the CDH Study Group (CDHSG) registry, abstracted between 2015 and 2018, were evaluated. Ventricular function on early echocardiograms, defined as obtained within the first 48 hours of life, was categorized into four hierarchical groups: normal function, right ventricular dysfunction only (RVdys), left ventricular dysfunction only (LVdys), and combined RV and LV dysfunction (RV&LVdys). Univariate, multivariate, and Cox proportional hazards regression analyses were performed.Measurements and Main Results: Cardiac function data from early echocardiograms were available for 1,173 (71%) cases and categorized as normal in 711 (61%), RVdys in 182 (15%), LVdys in 61 (5%), and combined RV&LVdys in 219 (19%) cases. Ventricular dysfunction was significantly associated with prenatal diagnosis, CDHSG stage, intrathoracic liver, and patch repair (all P < 0.001). Survival varied by category: normal function, 80%; RVdys, 74%; LVdys, 57%; and RV&LVdys, 51% (P < 0.001). The adjusted risk of death (hazard ratio) for cases with LVdys was 1.96 (95% confidence interval [CI], 1.29-2.98; P = 0.020) and for cases with RV&LVdys was 2.27 (95% CI, 1.77-2.92; P = 0.011). All cardiac dysfunction categories were associated with use of extracorporeal membrane oxygenation (P < 0.005).Conclusions: Early ventricular dysfunction occurs frequently in CDH and is an independent determinant of severity and clinical outcome.
The role of serum carcinoembryonic antigen in predicting objective responses to chemotherapy and overall survival in patients with non-small cell lung cancer.
Authors: Hongbing Liu
Journal: Journal of Clinical Oncology (2012)

e18084 Background: Previous studies indicated the carcinoembryonic antigen (CEA) could predict the therapeutic objective response (OR) and overall survival (OS) of patients with cancers, including non-small cell lung cancer (NSCLC). However, the role it could play in evaluating therapeutic responses and OS in patients with NSCLC requires further elucidation. Herein, we investigated the potential role of CEA in predicting OR and OS in patients with NSCLC. Methods: 689 patients with NSCLC were enrolled between January 2000 and August 2011. The correlations between the CEA levels and OR or OS were examined via statistical analyses including the chi-squared test, logistical regression, paired-samples t-test, receiver operator characteristic curve, Kaplan-Meier survival analysis, log-rank test and Cox regression model. Results: The calculated cut-off for predicting an OR to chemotherapy in patients with NSCLC was a reduction of 5.28% in serum CEA. This value demonstrated a sensitivity of 61.3% and a specificity of 62.4%. Serum CEA levels significantly decreased after two cycles of chemotherapy in NSCLC patients (t = 2.196, P = 0.031). The Kaplan-Meier survival analysis indicated no significant correlation between baseline CEA and OS (log rank test =0.079). However, according to the Cox regression analysis the number of distant metastatic organs (=1 and ≥2) was the independent risk factor of the OS (P = 0.026; P =0.003), and the cycle numbers of chemotherapy was the protective factor for OS in patients with NSCLC (P=0.011).More importantly, baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes (P = 0.014; P = 0.017, respectively). Conclusions: Our study shows that baseline serum CEA was significantly associated with lung adenocarcinoma and adenosquamous subtypes. While the baseline level of serum CEA was not a prognostic factor, the post-treatment reduction of serum CEA level can predict the OR in patients with NSCLC,. The number of chemotherapy cycles was the independent protective factor, while the numbers of distant metastatic organs was the independent risk factor for NSCLC patients’ OS.
An augmented reality microscope with real-time artificial intelligence integration for cancer diagnosis
Authors: Po-Hsuan Cameron Chen, Krishna Gadepalli, Robert MacDonald, Yun Liu, Shiro Kadowaki, Kunal Nagpal, Timo Kohlberger, Jeffrey Dean, Greg S. Corrado, Jason D. Hipp, Craig H. Mermel, Martin C. Stumpe
Journal: Nature Medicine (2019)
New ligation technique using a double loop clip without adhesive for ulceration following endoscopic submucosal dissection of the colon
Authors: Satoshi Abiko, Ayumu Yoshikawa, Kazuaki Harada, Naoki Kawagishi, Itsuki Sano, Hisashi Oda, Takuto Miyagishima
Journal: Endoscopy (2019)

Various ligation techniques for post-endoscopic submucosal dissection (ESD) ulceration have recently been reported [1] [2] [3] [4] [5]; however, no technique has been established owing to the complexity involved and the fact that an expensive device is required. We devised a new ligation technique using a double loop clip (D-L clip) without an adhesive agent for ulceration following ESD of the colon.
Time Horizons in Cost Analyses
Authors: Istvan M. Majer, Shaji K. Kumar, Stephen Palmer
Journal: JAMA (2019)

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The E3 ubiquitin ligase SPOP controls resolution of systemic inflammation by triggering MYD88 degradation
Authors: Maria Guillamot, Dahmane Ouazia, Igor Dolgalev, Stephen T. Yeung, Nikos Kourtis, Yuling Dai, Kate Corrigan, Luna Zea-Redondo, Anita Saraf, Laurence Florens, Michael P. Washburn, Anastasia N. Tikhonova, Marina Malumbres, Yixiao Gong, Aristotelis Tsirigos, Christopher Park, Christopher Barbieri, Kamal M. Khanna, Luca Busino, Iannis Aifantis
Journal: Nature Immunology (2019)