tbuckley/cabot-search huggingface dataset:
Abstract 2421: Extracellular DNA in pancreatic cancer metastasis
Authors: Fushi Wen, Alex Shen, Andrew Choi, Jiaqi Shi
Journal: Cancer Research (2011)

Abstract Extracellular nucleic acids have received increasing attention for their potential application in the rapid, accurate, and non-invasive early detection of cancer and other diseases, but less attention is given to their potential roles in cancer biology. We initiated a study to examine the role of extracellular DNA in pancreatic cancer metastasis. Pancreatic cancer is one of the most lethal cancers with a prognosis of just six months to live, and a five-year survival rate less than 5%. This is mainly due to the fact that at the time of diagnosis, 80-90% of patients have metastatic cancer already. To better understand the metastasis mechanism of this cancer, we tested the hypothesis that pancreatic cancer cells produce extracellular DNA to promote their metastasis and cancer cell adhesion to a new micro-environment. We first examined the presence of extracellular DNA associated with pancreatic cancer cells by DAPI and CYTOX Green stains and by immunofluorescence assay (IFA) with the DNA-specific antibody. A large amount of extracellular DNA was observed on the surfaces and in the vicinity of the MiaPaCa-2 and BxPC3 pancreatic cancer cells but not the normal pancreas HPDE cells cultured on coverslips and in the 3D matrigel. A similarly larger amount of cell-free DNA was also found associated with the cancer cell line when the DNA from the cell culture media was extracted and analyzed. We subsequently stained tissue slides from human pancreatic cancer tissues, normal pancreas tissues, and the pancreatic cancer tissue microarrays using DNA-specific dyes and DNA -specific antibody in IHC and IFA. These experiments further confirmed the presence of extracellular DNA associated with the pancreatic cancer cells. To understand the role of extracellular DNA in cancer metastasis, we studied the effect of treatment with DNase I on cell migration, invasion, proliferation, and colonization in vitro. We measured cell adhesion to plates coated with adhesion proteins. We also investigated de-attachment of cells from coverslips by proteinase K in the presence or absence of DNase I. These functional studies showed DNase I inhibited cell migration, invasion, and adhesion without affecting cell viability. In the 3D matrigel, DNase I completely changed the pancreatic cancer cell growth pattern. We conclude that extracellular DNA associated with cancer cells play a novel role in cell migration, invasion, and cell adhesion in vitro. To our knowledge, this is the first report on the presence of a large amount of extracellular DNA on the surface and in the surrounding of pancreatic cancer cells and on the potential novel role of extracellular DNA in pancreatic cancer metastasis. 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 2421. doi:10.1158/1538-7445.AM2011-2421
Treatment of Gallstones with Chenodeoxycholic Acid and Phenobarbital
Authors: Martin J. Coyne, George G. Bonorris, Ane Chung, Leonard I. Goldstein, Daniel Lahana, Leslie J. Schoenfield
Journal: New England Journal of Medicine (1975)

In a controlled trial, 36 patients with asymptomatic radiolucent gallstones were treated with chenodeoxycholic acid, 750 mg per day, phenobarbital, 180 mg per day, combination of both drugs, and placebo. After one year, chenodeoxycholic acid, phenobarbital and the combination, but not placebo, significantly decreased biliary cholesterol saturation. This effect was significantly greater with chenodeoxycholic acid and the combination than with phenobarbital. Gallstone size decreased more than 50 per cent in nine of 20 patients receiving chenodeoxycholic acid, either alone or combined with phenobarbital, but in no patient receiving only phenobarbital or placebo. Gallstones disappeared completely in two patients receiving the combination. Abnormalities in liver-function tests in three of 36 patients, and in five of 16 liver biopsies, occurred with equal frequency in the four treatment groups. Thus, after one year, phenobarbital alone was ineffective in gallstone dissolution. Chenodeoxycholic acid alone or combined with phenobarbital, however, offered a partially effective and safe treatment for asymptomatic radiolucent gallstones. (N Engl J Med 292:604–607, 1975)
Lung Metastasis From Prostate Cancer Revealed by 18F-FDG PET/CT Without Osseous Metastasis on Bone Scan
Authors: Hung-Yi Su, Meng-Lin Chen, Ping-Ju Hsieh, Teh-Sheng Hsieh, Ing-Ming Chao
Journal: Clinical Nuclear Medicine (2016)

A 54-year-old man, a case of prostate cancer, underwent radical prostatectomy and hormone therapy. Elevated prostate-specific antigen level developed 7 years later, but pelvic MRI and bone scan revealed negative results. Radiotherapy was performed under the suspicion of local recurrence but in vain. F-FDG PET/CT performed 1 more year later showed 3 FDG-avid lesions in the right lung and mediastinum. Lung and lymph node metastases were proved with video-assisted thoracoscopic surgery. Bone scan remained negative at that time.
Pupillary Effects of Levodopa Therapy
Authors: Michael I. Weintraub, Douglas Gaasterland, Melvin H. Van Woert
Journal: New England Journal of Medicine (1970)

In a patient with Parkinson's disease and subclinical postganglionic Horner's syndrome anisocoria developed during chronic oral L-dopa therapy. This provided an opportunity to investigate the mechanism of action of L-dopa and dopamine on the sympathetic innervation of the eye. Five patients, one of whom had a postganglionic Horner's syndrome without Parkinson's disease, served as controls. Topical dopamine and chronic systemic L-dopa produced pupil dilatation only in eyes with intact sympathetic innervation. Single large doses of Ldopa had no effect on the pupil size. L-dopa and topical dopamine appear to produce pupillary dilatation indirectly, through a peripheral increase in activity of intact sympathetic pathways, and not through direct alpha-receptor stimulation.
The origins of vaccination: myths and reality
Authors: Arthur Boylston
Journal: Journal of the Royal Society of Medicine (2013)

In 1796, 75 years after Lady Mary Wortley Montague and Charles Maitland introduced inoculation into England, Edward Jenner performed an experiment that would eventually lead to the eradication of smallpox and the end of inoculation. (NB: in this article, inoculation refers to immunization with smallpox virus and vaccination refers to immunization with cowpox virus.) He inoculated a child with material from a cowpox pustule just as he would have done from a smallpox pustule. About six weeks later, he performed a conventional inoculation on the same child using smallpox material. When there was no reaction to the inoculation, Jenner believed that he had demonstrated that cowpox could produce immunity to smallpox just like the real smallpox virus. His experiment had worked. But how did Edward Jenner get to this point, where had the ideas come from, and what lay behind his seemingly audacious practice on a defenceless child? History texts and children’s stories all focus on the supposed role of milkmaids in guiding Jenner to cowpox. Even the most recent histories of smallpox eradication say that he learned of cowpox’s benefits from a milkmaid. In many cases, the milkmaid is beautiful because she cannot catch smallpox. In some versions of this story, the fabled beauty of the unscarred milkmaids is widely known and gives Jenner his first clue. Occasionally, other names pop up but are quickly dispatched as not really significant and home in on Jenner as the man who realized why the milkmaids were so beautiful. Sadly the milkmaid story is a lie invented by John Baron, Jenner’s friend and first biographer. Jenner himself never claimed to have discovered the value of cowpox, nor did he ever say, despite a huge volume of correspondence, how he first came across the idea. The myths of the milkmaids are just that, myths. To modern eyes, Jenner is revered for eradicating smallpox by using cowpox; in his lifetime, however, Edward Jenner faced severe criticism from jealous competitors and from many ordinary doctors who did not trust his method because, unlike inoculation, it did not give permanent immunity to smallpox. John Baron invented the milkmaid story to counteract these criticisms. What really happened is more prosaic although no less fascinating. The Suttons’ improved method of inoculating spread rapidly through England. By 1768, a country surgeon, John Fewster, and his colleague, Mr. Grove, had become partners with them. Years later, in response to the renowned chemist George Pearson’s inquiries, Fewster wrote:
P746 VITAMIN D RELATED PATHWAY GENE POLYMORPHISMS ENHANCED THE PREDICTION OF TREATMENT RESPONSE IN ASIAN CHRONIC HEPATITIS C-INFECTED PATIENTS WITH UNFAVORABLE IL-28B rs12979860 GENOTYPES
Authors: K. Thanapirom, S. Suksawatamnuay, W. Sukeepaisarnjaroen, P. Tangkijvanich, S. Treeprasertsuk, P. Thaimai, S. Akkarathamrongsin, Y. Poovorawan, P. Kullavanijaya, P. Komolmit
Journal: Journal of Hepatology (2014)
1263 HEPATIC STEATOSIS INDUCED BY WESTERN DIET MODULATES EXPRESSION OF HGF AND ERK SIGNALLING AND IMPROVES LIVER REGENERATION IN MICE AFTER 70% PARTIAL HEPATECTOMY
Authors: S. Sydor, Y. Gu, L.P. Bechmann, J.-P. Sowa, H.A. Baba, U. Rauen, G. Gerken, A. Canbay
Journal: Journal of Hepatology (2012)
Living in areas with good public transport links can increase physical activity by 90 minutes a week
Authors: Anne Gulland
Journal: BMJ (2016)

People living in densely populated areas with a large number of public transport stops, public parks, and intersections are more likely to be physically active, a global study has found.1

The study, published in the Lancet , looked at 6822 adults aged 18-66 in 14 cities and towns around the world and found that those living in what it termed an activity-friendly neighbourhood took as much as 90 minutes more exercise a week than those who lived elsewhere. The researchers controlled for factors including age, sex, education, marital and employment status, and whether neighbourhoods were classed as high or low income.

The cities or …
Abstract B39: Human FANCA binds to nucleic acids and prefers single-stranded forms
Authors: Fenghua Yuan, Liangyue Qian, Jesse Y. Liu, Xinliang Zhao, Limin Song, Gennaro D'Urso, Chaitanya Jain, Yanbin Zhang
Journal: Cancer Research (2011)

Abstract Fanconi anemia (FA) is an autosomal recessive or X-linked disorder characterized by bone marrow failure, developmental defects, predisposition to cancer, and hypersensitivity of crosslinking agents. Fanconi anemia complementation group A (FANCA) gene is one of the 15 disease-causing genes and has been found to be mutated in ∼60% of all FA patients. Using the purified human WT-FANCA protein, we report that FANCA possesses intrinsic affinity to nucleic acids. FANCA binds to single-stranded DNA with affinity significantly higher than double-stranded DNA. FANCA also binds to single-stranded RNA with similar affinity to single-stranded DNA. FANCA requires a certain length of nucleic acids for optimal binding. Using DNA and RNA ladders, we determine the minimum numbers of nucleotides required for FANCA recognition are −30 and −40 for DNA and RNA respectively. A patient-derived FANCA truncation mutation, Q772X, has diminished affinity to both DNA and RNA. On the contrary, the complementing C-terminal fragment of Q772X, 772–1455, retains the differentiated DNA binding activity (ssDNA&amp;gt;dsDNA), indicating that the nucleic acids binding domain of FANCA is located at its C-terminus where most disease-causing mutations are found. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B39.
Spanning the levels in cerebellar function
Authors: Michael A. Arbib
Journal: Behavioral and Brain Sciences (1996)

We ask what cerebellum and basal ganglia "do," arguing that cerebellum tunes motor schemas and their coordination. We argue for a synthesis of models addressing the real-time role and error signaling roles of climbing fibers. "Synthetic PET" bridges between regional and neuro-physiological studies, while "synaptie eligibility" relates the neurochemis-try of learning to neural and behavioral levels. [CRÉPEL et al.; HOUK et al.; KANO; LINDEN; SIMPSON et al.; SMITH; THACH; VINCENT]
Late presentation of capsule endoscope aspiration with successful extraction by flexible bronchoscopy utilizing a snare wire loop
Authors: Mahmoud Amarna, Amanda Vanlandingham, Parag Brahmbhatt, Thomas Roy, Ryland Byrd
Journal: Endoscopy (2015)

Capsule endoscopy is a commonly employed technique to examine patients for gastrointestinal pathology. Pulmonary aspiration of a capsule endoscope is a rare complication of this procedure. There have been 15 well-described instances of bronchial aspiration of a capsule endoscope [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15].
Abstract 5094: Mutant specific mitochondrial localization of BRAFV600E: Clinically used BRAF kinase inhibitors are not able to block mitochondrial actions of BRAFV600E
Authors: Min Hee Lee, Koon Soon Kim, Seong Eun Lee, Min Jeong Ryu, Soung Joong Kim, Yong Kyoung Kim, Gi Ryang Kweon, Young Suk Jo, Minho Shong
Journal: Cancer Research (2010)

Abstract Oncogenic mutation in BRAF kinase (BRAFV600E) results active structural conformation characterized with greatly elevated ERK activities. However, other cellular effects which are specifically influenced by mutation in BRAF kinase remains to be identified. We investigated differences in subcellular localizations of wild type and mutant BRAFV600E and observed the effects of the BRAF inhibitors on subcellular compartment-specific effects of BRAFV600E. We found that significant portion of endogenous and exogenous BRAFV600E, but not wild type BRAF, was detected in mitochondrial fraction. The other BRAF mutants, BRAFV600D, BRAFV600K and BRAFV600R which shows higher kinase activities were able to localize in mitochondria. The localization of BRAFV600E onto mitochondria provides anti-apoptotic activities against staurosporine and TNFα/cycloheximide. In addition, inducible expression of BRAFV600E increases glucose uptake rate, decreased O2 consumption, suggesting reduced mitochondrial oxidative phosphorylation which are signature features found in cancer cells. Interestingly, suppression of MEK activities using U0126 did not affect both mitochondrial localization and anti-apoptotic activities of BRAFV600E. The BRAF inhibitor such as Sorafenib was effective to inhibit MEK/ERK activation, however, they did not block the mitochondrial localization of BRAFV600E. Therefore, these inhibitors did not block the antiapoptotic activities and not reduce high glucose uptake rate and glycolytic activities induced by BRAFV600E. We found oncogenic BRAF mutants are able to localize in mitochondria and these actions might be related to altered responses to apoptotic stimuli and to characteristic metabolic phenotypes. In addition, currently BRAFV600E inhibitors were not sufficient to block mitochondrial localization of BRAFV600E and it may explain the limited efficacy of these drugs in clinically advanced BRAFV600E-positive tumors. These observations provide new mutation- specific roles of BRAFV600E which is potentially important for the development of therapeutics. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5094.
Mega stents: a new option for management of leaks following laparoscopic sleeve gastrectomy
Authors: Jahangeer Basha, Sreekanth Appasani, Saroj Sinha, Pradeep Siddappa, Harpal Dhaliwal, Ganga Verma, Rakesh Kochhar
Journal: Endoscopy (2014)

Postoperative leaks occur after laparoscopic sleeve gastrectomy (LSG) in 1 % – 3 % of cases [1]. Placement of covered metallic stents is an effective treatment strategy [2] [3], but in about 16.9 % of cases stent migration occurs [4]. To avoid the complication of stent migration, we have used a large stent (Niti-S Mega esophageal stent; Taewoong Medical, Gyeonggi-do, South Korea) in two patients who developed leaks following LSG. The first patient was a 50-year-old woman with a body mass index (BMI) of 35, who developed abdominal pain and vomiting 2 days after LSG. Contrast-enhanced computed tomography (CECT) of her abdomen revealed two perigastric collections with contrast leak ([Fig. 1]). Endoscopy showed a fistulous opening at the gastroesophageal junction ([Fig. 2]). A fully covered Mega esophageal stent (length 23 cm; diameter: body 24 mm, flanges 32 mm) was placed under fluoroscopic guidance with the proximal end in the esophagus and the distal end in suprapapillary position in the descending duodenum using a fluoroscopic marker, thus covering the entire stomach sleeve ([Fig. 3]). Repeat abdominal CECT revealed no collection at 8 weeks and the stent ([Fig. 4]) was removed.
P691 KEY PATTERNS OF HBsAg MUTATIONS CORRELATE WITH MECHANISMS UNDERLYING LEVELS OF SERUM HBVDNA
Authors: M. Surdo, M.F. Cortese, C. Mirabelli, R. Salpini, J. Zhang, F. Van Hemert, V. Cento, M. Pollicita, G. Gubertini, G.M. De Sanctis, P. Trimoulet, H. Fleury, F. Mazzotta, R. Longo, G. Cappiello, A. Spanò, C. Sarrecchia, M. Andreoni, M. Angelico, J. Verheyen, C.F. Perno, V. Svicher
Journal: Journal of Hepatology (2014)
Forgiveness is institutionally mediated, not an isolable modular output
Authors: Don Ross
Journal: Behavioral and Brain Sciences (2012)

McCullough et al. recognize that revenge and forgiveness jointly constitute a functional strategic complex. However, they model the halves of the complex as outputs of modules selected for regulating dyadic relationships. This is backwards. Forgiveness is a culturally evolved institution that can be exapted for use in dyadic contexts; it would be cheap talk among dyads were it not for the shadow of society.
Metastatic Wilm's Tumor to the Central Nervous System
Authors: JOHN R. STY, ROBERT G. WELLS, DAVID C. GREGG
Journal: Clinical Nuclear Medicine (1996)

A 6-year-old boy was examined for left leg and arm weakness. The patient had a left Wilm's tumor resected 6 years earlier. Treatment also consisted of chemotherapy and abdominal radiation. The child was asymptomatic until the present admission. A radionuclide bone scan was performed as part of the evaluation for metastatic bone disease. The examination demonstrated several regions in the skeleton with metastatic deposits. In addition, an area of abnormal extraosseous accumulation was identified in the right parietal region. A computed tomograph examination confirmed metastatic cerebral metastases. The case illustrates necessity to carefully evaluate the extraosseous components of the radionuclide bone images.
Enteroaggregative<i>Escherichia coli</i>As a Possible Cause of Diarrhea in an HIV-Infected Patient
Authors: Howard B. Mayer, Christine A. Wanke
Journal: New England Journal of Medicine (1995)

To the Editor: Chronic diarrhea is being recognized with increasing frequency in patients with human immunodeficiency virus (HIV) infection, and it contributes to morbidity in this population. Up t...
PL-03 * FEASIBILITY OF GENOMICS-ENABLED THERAPY FOR PEDIATRIC HIGH-GRADE GLIOMAS AND DIFFUSE PONTINE GLIOMAS
Authors: S. Mueller, W. Liang, S. Byron, K. Nazemi, S. Leary, L. Kilburn, M. Prados, N. Gupta, D. Craig, J. Carpten, M. Berens
Journal: Neuro-Oncology (2014)

Children with pediatric high-grade gliomas (pHGG) including diffuse intrinsic pontine gliomas (DIPG) continue to have a dismal prognosis and, as a result, novel therapeutic approaches are needed. We evaluated whether genomic profiling, defined as sequencing of tumor and germline exomes and tumor RNA, can be used to identify distinct, actionable events that may guide treatment of children with pHGG. Tumor from eight archival cases were assessed to confirm high tumor cellularity of samples (>60%) and were evaluated by genomic profiling. Successfully sequenced tumor specimens originated from DIPG (n = 2), astrocytoma grade II (n = 1), astrocytoma grade III (n = 1), glioblastoma (n = 4). We generated average mapped coverages of >145X across all exomes and generated >190M reads for each tumor RNA. Identified alterations were matched to potential therapeutic options using a custom drug-matching pipeline utilizing a pharmacopeia that includes FDA-approved drugs, potential repositioned agents, and investigational compounds. Alterations in genes previously implicated in pediatric glioma were identified, including mutations in histone H3 (H3F3A), PDGFRA, TP53, and ATRX and copy number loss of CDKN2A. Alterations associated with potential sensitivity to FDA-approved oncology agents included frameshift and splice-site mutations in TSC2 and extracellular mutations in PDGFRA (E229K, C235Y mutations; previously reported in pHGG), with predicted sensitivity to mTOR inhibitors and PDGFRA inhibitors, respectively. Inclusion of repositioned therapies and agents in clinical development expanded the actionable roster to include: CDKN2A deletion, BRD4 gain, PRKCI gain, ATM mutation, and overexpression of EZH2, KIF11, MELK, PLK4, and WEE1, several of which are direct targets of investigational agents currently in clinical trials. In conclusion, potentially actionable alterations were uncovered by applying integrative sequencing strategies to pHGG patients. Future efforts will apply this strategy in children with DIPG utilizing pre-treatment biopsies to inform treatment options following initial radiotherapy.