tbuckley/cabot-search huggingface dataset:
Radiofrequency ablation and endoscopic mucosal resection in Barrett's esophagus with early neoplasia. Can we avoid complications?
Authors: M. Conio, D. Fisher, L. Palazzo
Journal: Endoscopy (2013)

In the article by van Vilsteren et al. [1], the rationale behind simultaneous treatment of Barrett’s esophagus with radiofrequency ablation (RFA) and endoscopic mucosal resection (EMR) was to reduce the risk of perforation that could have been caused by the pressure of the HALO360° probe used for RFA (BÂRRX Medical, Sunnyvale, California, USA) on tissue scarred by previous extended EMR. However, the results did not support the idea that this is a safer or more effective strategy for management of Barrett’s esophagus.
Abstract 5042: <i>A-AS1</i>, a long non-protein coding RNA overexpressed in esophageal adenocarcinoma, influences cancer cell proliferation and apoptosis
Authors: Wenjing Wu, Jee Hoon Song, Yulan Cheng, Stephen J. Meltzer
Journal: Cancer Research (2012)

Abstract Esophageal adenocarcinoma (EAC) is one of the fastest-growing cancers in the Western world. 95% of EACs occur without any antecedent diagnosis of Barrett's esophagus (BE). In these 95% of EAC patients, 5-year survival is only 15%. The rising incidence and poor prognosis of EAC have intensified research efforts into earlier methods to detect this disease. The majority of the human genome is transcribed and generates mostly non-coding (nc)RNAs that do not encode protein information. Long non-coding RNAs (lncRNAs) are emerging as a novel class of ncRNAs, but knowledge about these ncRNAs is limited. Recently, dysregulation of lncRNAs has been shown in various types of cancer, suggesting that lncRNAs may be involved in tumorigenesis or tumor progression. In the present study, we report that a number of lncRNAs are differentially expressed in EAC tissues and cell lines relative to normal esophageal tissues and cell lines. One of these lncRNAs, A-AS1 is derived from the antisense strand of the A gene locus and is overexpressed in EACs relative to matched normal esophagus (NE). Cell proliferation and colony formation assays revealed that A-AS1 siRNA-mediated knockdown reduces cell proliferation and colony-forming ability. In vitro scratch assays, migration and invasion assays in vitro also demonstrated decreased migration and invasion induced by A-AS1 siRNA knockdown. Moreover, we found that inhibition of A-AS1 expression results in increased apoptosis in EAC cell lines. Taken together, these results suggest that the elevated expression of A-AS1 observed in EACs may have contributed to their development or progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5042. doi:1538-7445.AM2012-5042
Higher taxes on alcohol are the best way to reduce harm, analysis concludes
Authors: B. Christie
Journal: BMJ (2011)

Higher taxes on alcohol are the best way to raise prices and reduce the harm caused by overconsumption, says a new report from the Institute for Fiscal Studies. 

After it analysed recent policy changes across the United Kingdom, the institute concluded that neither the proposed ban in England and Wales on selling alcoholic drinks below their cost price nor minimum alcohol pricing in Scotland is the best way forward.

Its report says that banning below-cost sales would affect only 1% of off-licence sales. In contrast, proposals in Scotland …
NONINVASIVE ESTIMATION OF PULMONARY CAPILLARY WEDGE PRESSURE IN PATIENTS WITH MITRAL REGURGITATION BY SPECKLE TRACKING ECHOCARDIOGRAPHY
Authors: Nozomi Nomura, Yoshiaki Kawase, Yoshie Fujii, Keiko Ogawa, Ryuhei Tanaka, Hidemaro Sato, Hiroki Kondo, Jun Kikuchi, Tatsuya Saigusa, Takayoshi Kato, Taiji Miyake, Tomohiro Tsunekawa, Munenori Okubo, Kunihiko Tsuchiya, Shinji Tomita, Hitoshi Matsuo, Masanori Kawasaki, Shinya Minatoguchi
Journal: Journal of the American College of Cardiology (2015)
Abstract 4061: Depleting the cellular level of glutathione and subsequently <i>S</i>-glutathionylation of keap1 by electrophilic agents activates keap1-nrf2 pathway
Authors: Xiaoyu Zhang, Zhongjun Ma, Fang Sun, Liming Shen
Journal: Cancer Research (2010)

Abstract S-glutathionylation is a reversible post-translational modification of protein cysteine with critical roles in oxidative stress and signal transduction. Keap1-Nrf2 pathway has emerged as a master regulator for the endogenous antioxidant response, which is critical in defending cells against carcinogenesis. Herein, we demonstrated that after depleting the cellular level of glutathione (GSH) by electrophilic agent (the GSH level decreased to 23 percent of control after the agent treatment for 4 h), Keap1 was modified by S-glutathionylation and Nrf2 expression increased both in nucleus and total cellular homogenates. The modification could be blocked by the addition of exogenous GSH, suggesting depleting the cellular level of GSH and alteration of intracellular GSH/GSSG ratio might be essential for S-glutathionylation of Keap1 and activating Keap1-Nrf2 pathway. Flexidock program was employed to elucidate the influence of Keap1 S-glutathionylation on Keap1-Nrf2 complex. After enforcing a disulfide bond between GSH and Cys434 residue in Keap1 and energy minimization, the two carboxylate oxygen atoms of GSH participate in hydrogen bond interaction with Arg483 and Arg380 residues in Keap1, which had been previously verified bound to DxETGE motif of Nrf2. The distance between GSH O1 and Arg483 NH1, GSH O2 and Arg380 NH1 were 2.587 Å and 2.569 Å, respectively, which could form potent hydrogen bonds and diminish the interaction between Keap1 and Nrf2, resulting in the accumulation of Nrf2 in the nucleus. We concluded from our findings that the activation of Keap1-Nrf2 pathway was triggered by Keap1 S-glutathionylation and conjugation with intracellular GSH might be a key event involved in the Nrf2 inducing activities of electrophilic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4061.
NOTES for the cardia: antireflux therapy via transluminal access
Authors: D. Wilhelm, A. Meining, A. Schneider, S. von Delius, A. Preissel, J. Sager, A. Fiolka, H. Friess, H. Feussner
Journal: Endoscopy (2010)

The current standard for surgical antireflux therapy is laparoscopic Nissen fundoplication, but natural orifice transluminal endoscopic surgery (NOTES) enables even less invasive access to the peritoneal cavity. We therefore aimed to evaluate a NOTES approach to antireflux therapy.An animal study including 24 pigs (16 nonsurvival and eight survival). After the peritoneal cavity had been accessed via the rectosigmoid, the gastroesophageal junction (GEJ) was laid open using conventional endoscopic instruments. Thereafter, a transcutaneously introduced hook was used for tunneling and lifting of the distal esophagus. Finally, an antireflux ring was placed around the cardia. Animals were observed over 10 days in the survival series. Correct application of the prosthesis, adverse events as a result of the procedure, and bacterial contamination were evaluated by autopsy.The esophagogastric junction was strengthened by applying the ring prosthesis in 22 of 24 animals. Four bleeding episodes were observed, three of which were handled endoscopically. Correct placement of the prosthesis was accomplished in 21 of 22 animals. In the survival series, 1 pig died after transhiatal herniation of the stomach, and 1 pig suffered from peritonitis due to intraoperative contamination. In 7 of the 8 survival animals, no bacterial growth was noted by smear culture. The intervention had to be performed as a hybrid NOTES procedure in all cases.Exposure of the GEJ and placement of an antireflux prosthesis via a hybrid NOTES procedure is feasible, despite some complications. This approach may be considered as a basis for optimization and further development of pure NOTES antireflux procedures.
NCI Projects Will Link Laboratory And Clinic
Authors: F. S. Antoine
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article NCI Projects Will Link Laboratory And Clinic Get access Florence S. Antoine Florence S. Antoine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 24, 20 December 1989, Pages 1865–1866, https://doi.org/10.1093/jnci/81.24.1865 Published: 20 December 1989
Paralysed man seeks legal clarity over doctors' role in assisting suicide
Authors: C. Dyer
Journal: BMJ (2011)

A man in England who is almost completely paralysed and who wants a doctor to be allowed to help him die is seeking a preliminary High Court declaration that lawyers and doctors will not be prosecuted or brought before professional regulators simply for their part in preparing his court application.

The Solicitors Regulation Authority and the General Medical Council have refused to give assurances that the lawyers and doctors involved in the case will not be accused of professional misconduct, and the director of public prosecutions for England and Wales will not guarantee not to prosecute them for assisting a suicide.

The 46 year old man, named only as Martin, …
Tidal Volume and Frequency Dependence of Carbon Dioxide Elimination by High-Frequency Ventilation
Authors: Thomas H. Rossing, Arthur S. Slutsky, John L. Lehr, Philip A. Drinker, Roger Kamm, Jeffrey M. Drazen
Journal: New England Journal of Medicine (1981)

Six patients with chronic respiratory failure received mechanical ventilation with tidal volumes less than or equal to the dead-space volume, at frequencies of 30 to 900 breaths per minute. The rate of elimination of carbon dioxide from the ventilator system during a brief trial of high-frequency ventilation accurately predicted the long-term effectiveness of a given combination of frequency and tidal volume. Below frequencies of about 200 breaths per minute, the volume of carbon dioxide eliminated from these patients was most strongly related to the product of frequency and tidal volume; at higher frequencies, carbon dioxide elimination was determined by the tidal volume and was independent of frequency. These results suggest that although the effectiveness of high-frequency ventilation is primarily a function of the product of tidal volume and frequency, above a critical frequency the mechanical characteristics of the lung reduce gas transport by limiting the volume transmitted to the periphery of the lung. (N Engl J Med. 1981; 305:1375–9.)
Correlative Imaging With 18F-FDG PET/CT and MRI in Paraneoplastic Limbic Encephalitis
Authors: Anna Margherita Maffione, Sotirios Chondrogiannis, Alice Ferretti, Adil Al-Nahhas, Domenico Rubello
Journal: Clinical Nuclear Medicine (2013)

Limbic encephalitis is one of the most common paraneoplastic neurological syndromes, which is mostly associated with small cell lung cancer, testicular tumors, and breast cancer. F-FDG PET/CT can have an important role both in the identification of limbic encephalitis itself and in the detection of the unknown malignancy that might have caused it. We report a case of a 57-year-old female patient with paraneoplastic limbic encephalitis, confirmed both by MRI and F-FDG PET/CT, and the concurrent identification of an unknown lung malignancy by whole-body PET/CT.
Oncological Outcome and Patient's Satisfaction of Skin-Sparing Mastectomy and Immediate Breast Reconstruction: A Prospective Observational Study.
Authors: A. Anderson, G. Burgoyne, K. Mokbel
Journal: Cancer Research (2009)

Abstract INTRODUCTION: The management of early breast cancer with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) is not based on evidence from randomised controlled trials. The purpose of this study is to evaluate the oncological safety, post-operative morbidity and patients' satisfaction with SSM and IBR using the latissimus dorsi (LD) myocutaneous flap and/or breast prosthesis. METHODS: One hundred and twenty five consecutive women underwent 137 SSMs with IBR (12 bilateral), using the LD flap plus implant (n=85) or implant alone (n=42), indications included breast cancer (n=130)and prophylaxis (n=7). Most tumours (99.2%) were Tis, T1, or T2 and only one tumour was T3 stage. Nipple reconstruction was performed in 69 patients, using a small local flap technique (n=61), nipple sharing (n=6), free skin graft (n=1) or Monocryl mesh (n=1). Thirty patients underwent contra-lateral surgery in order to optimise symmetry, including 19 augmentations and 11 mastopexy/reduction mammoplasties. Patient satisfaction with the outcome of surgery was assessed on a linear visual analogue scale ranging from 0 (not satisfied) to 10 (most satisfied). RESULTS: There was no local recurrence (LR) after a mean follow-up of 33.2 months (range=3-98 months). Overall survival was 99.2%, seven patients developed distant disease and one patient died of metastatic breast cancer. No case of partial or total LD flap loss was observed. Morbidities included infection, requiring implant removal in two patients and one patient developed marginal ischaemia of the skin envelope. Significant capsule formation, requiring capsulotomy, was observed in 87% of patients who had either PMR or prior RT compared with 13% for those who did not have RT. Eighty two (65.6%) of 125 patients completed the questionnaire with a median satisfaction scores of 9 (range=5-10). CONCLUSION: SSM with IBR is associated with low morbidity, high levels of patient satisfaction and is oncologically safe for T(is), T1 and T2 tumours without extensive skin involvement. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3113.
Sudden Death from Cardiac Causes in Children and Young Adults
Authors: Richard R. Liberthson
Journal: New England Journal of Medicine (1996)

Although sudden death in a young person is rare, it can have a great impact on both the lay and the medical communities. Such unanticipated deaths sometimes occur in dramatic circumstances and often have medical and legal ramifications. Some of these deaths are not predictable or preventable by current practical means; however, in many cases there are premonitory symptoms, a family history of sudden death at a young age, clinical or electrocardiographic abnormalities, or high-risk behavior.Among older adults, sudden deaths are often due to atherosclerotic coronary artery disease and terminal ventricular fibrillation. Each year there are 300,000 such deaths . . .
Severe Tibial Stress Injury
Authors: JANE A. E. DUTTON
Journal: Clinical Nuclear Medicine (2001)

From the Department of Nuclear Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom Received for publication November 1, 2000. Accepted November 30, 2000. Reprint requests: Jane A. E. Dutton, Department of Nuclear Medicine, Addenbrooke’s Hospital, Hill’s Road, Cambridge CB2 2QQ, United Kingdom. E-mail: [email protected]
Abstract 484: Persistent activation of mesenchymal stromal cells (MSCs) and tissue repair in the etiology of desmoid tumors (DT)
Authors: Adelaide M. Carothers, Hira Rizvi, Yvonne Heit, Rian M. Hasson, Jennifer Davids, Monica M. Bertagnolli, Nancy L. Cho
Journal: Cancer Research (2011)

Abstract Mesenchymal stromal cells (MSCs) are multipotent cells that can be isolated from various adult tissues and are implicated in a growing list of sarcomas. Desmoid tumors (DTs) have a clonal origin, are linked with wound healing, and mostly arise in the abdomen of patients with familial adenomatous polyposis (FAP) or sporadically. MSCs home to sites of tissue damage and the persistent activation of these cells in a wound healing context combined with deregulated Wnt signaling may lead to neoplasia. To test this idea, we performed immunohistochemistry on 17 sporadic and FAP-associated DTs from different individuals for the expression of multiple MSC markers (CD73, CD90, and Bmi1). While present in differing numbers, all specimens showed positive cells for all markers, and immunofluorescence (IF) showed co-localization of these markers and CD105 in cells within tumors. Matching adjacent normal fascia from a subset was negative for these antigens. A FAP DT-derived cell line was then made that also co-expressed these MSC markers but not CD34, a negative marker. Fluorescence-activated cell sorting analysis of surface antigen profiles confirmed that &amp;gt;90% of the cell population bore MSC positive, but not negative, markers. Although not genotyped, IF for the C- vs. N-termini of APC confirmed that only truncated APC product was expressed in our DT-derived MSC line. Upon growth for 5-6 weeks in differentiation medium, we confirmed by co-expression of CTGF and Sox9 (obligate chondrocyte markers) plus Alcian blue staining, PPARγ and c/EBPα (obligate adipocyte markers) plus Oil Red staining, and OPN and Runx2 (obligate osteocyte markers) plus von Kossa staining that the DT-derived MSCs were tripotent. In conclusion, this study supports the view that DT etiology involves the persistence of MSCs with deregulated Wnt signaling. The differentiation potential of these cells combined with expression of Bmi1, a transcriptional repressor downstream of Hedgehog and Notch signaling, suggest that inhibitors targeting these pathways may provide a rational systemic therapy to prevent primary or recurrent DT in high-risk patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 484. doi:10.1158/1538-7445.AM2011-484
Abstract 4803: A novel mitochondrial isoform of mammalian DNA methyltransferase 1
Authors: Lisa M. Shock, Prashant V. Thakkar, Erica J. Peterson, Richard G. Moran, Shirley M. Taylor
Journal: Cancer Research (2010)

Abstract Cancer cells, in contrast to normal cells and tissues, fulfill their energy requirements by increased glycolysis, with a distinct downregulation of oxidative phosphorylation in the mitochondria. Regulation of enzymes of the glycolytic pathway under the anoxic conditions prevalent in human solid tumors by stabilization of HIF1α have been intensely investigated; however, the mechanisms regulating transcription of the mitochondrial genome, and its coordinate regulation with the nuclear genome are less well understood. Eukaryotic mitochondrial DNA carries a low but significant level of cytosine methylation, but molecular mechanisms responsible for the generation of this modification and its role in mitochondrial function has not been studied. The mitochondrial genome encodes 13 polypeptides involved in oxidative phosphorylation, as well as the tRNAs and rRNAs required for mitochondrial translation. All other proteins required for mitochondrial function are encoded by the nuclear genome and translocated to the mitochondria using mitochondrial targeting sequences frequently located at the N-terminus. We have identified a novel isoform of mammalian DNA methyltransferase 1 (DNMT1) that translocates to the mitochondrion, using a conserved N-terminal mitochondrial targeting sequence; the mRNA encoding this isoform is expressed from an upstream transcription start site. De novo methyltransferases DNMT3a and DNMT3b are not found in mammalian mitochondria. Expression of the mitochondrial DNMT1 isoform (mtDNMT1) is regulated by nuclear respiratory factor 1 (NRF1) and coactivator PGC1α, which together upregulate several nuclear-encoded mitochondrial genes involved in the electron transport chain, following hypoxic stress. The mitochondrial isoform (mtDNMT1) is also preferentially upregulated following loss of p53 function, leading to specific effects on mitochondrial gene expression and potentially affecting mitochondrial function. We therefore suggest that mitochondrial DNA methylation, established and maintained by mtDNMT1, plays a role in coordination of mitochondrial gene expression and that the expression of the mtDNMT1 isoform is under the control of p53. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4803.
DS-03 * SONIC HEDGEHOG ANTAGONISTS POTENTLY INDUCE APOPTOSIS IN THE CEREBELLAR EXTERNAL GRANULE LAYER: IMPLICATIONS FOR MEDULLOBLASTOMA TREATMENT
Authors: K. Noguchi, O. Cabrera, B. Swiney, J. Smith, N. Farber
Journal: Neuro-Oncology (2014)

There is a great interest in Hedgehog signaling both for its role in cerebellar development and medulloblastoma (MB) treatment. The cerebellum maintains its own proliferative layer called the external granule layer (EGL) that produces over 90% of its neurons. During development, the established dogma views Hedgehog signaling as a robust mitogenic stimulator of EGL proliferation. However, in other regions of the body, Hedgehog stimulation acts as a survival signal by potently inducing NPC apoptosis when signaling is lost. In this manner, the sonic hedgehog ligand's concentration gradient determines NPC survival or death thereby morphologically sculpting the developing nervous system. Therefore, we tested whether Hedgehog signaling also acts as a survival signal in the EGL by administering several Hedgehog antagonists (vismodegib, cyclopamine, and jervine). Remarkably, we found all Hedgehog antagonists (HAs) potently induced EGL apoptosis within a few hours of administration. This suggests a large portion of the HAs' anti-proliferative effects are due to the apoptotic loss of a large number of EGL NPCs. This research may also have important implications for MB formation and treatment. There is convincing evidence that EGL neural progenitor cells (NPCs) can be the tumor initiating cells for MBs (the most common malignant brain tumor in children). Therefore, we examined if HAs can also produce apoptosis in Patched mice which exhibit constitutive Hedgehog stimulation and are prone to MB formation. We found HA administration also potently increased apoptosis in both EGL NPCs and preneoplasms. This may have important implications for the treatment of MBs with HAs. For example, apoptosis involves signaling mechanisms distinct from proliferation that may need to be disabled for malignant transformation. In addition, the requirement for Hedgehog signaling may prevent metastasis by killing tumor cells as they spread to regions where such signaling is absent.
Local convection-enhanced delivery of an anti-CD40 agonistic monoclonal antibody induces antitumor effects in mouse glioma models
Authors: Takuhiro Shoji, Ryuta Saito, Masashi Chonan, Ichiyo Shibahara, Aya Sato, Masayuki Kanamori, Yukihiko Sonoda, Toru Kondo, Naoto Ishii, Teiji Tominaga
Journal: Neuro-Oncology (2016)

BackgroundGlioblastoma is one of the most malignant brain tumors in adults and has a dismal prognosis. In a previous report, we reported that CD40, a TNF-R-related cell surface receptor, and its ligand CD40L were associated with glioma outcomes. Here we attempted to activate CD40 signaling in the tumor and determine if it exerted therapeutic efficacy.