tbuckley/cabot-search huggingface dataset:
Abstract 5134: The identification and characterization of genetic variations in lung adenocarcinomas in a Japanese population
Authors: Sachiyo Mimaki, Ayako Suzuki, Koutatsu Matsushima, Makito Suzuki, Naomi Ogasawara, Yutaka Suzuki, Katsuya Tsuchihara, Hiroyasu Esumi
Journal: Cancer Research (2012)

Abstract Lung adenocarcinoma is a major histological subtype of non-small cell lung cancer. Previous studies have revealed substantial clinical and molecular differences between the Asian and Caucasian populations. Kinase inhibitor-sensitive EGFR mutations are frequently detected in Asian, female and non-smoker population. These findings suggest unique genetic and/or environmental background of carcinogenesis of this tumor. In the present study, we generated and analyzed a dataset of single-nucleotide variants (SNVs) and small insertions and deletions (indels) in the entire exon regions (exomes) in Japanese lung adenocarcinomas. We chose consecutive 97 of surgically resected T2 cases registered to the database containing clinicopathological and lifestyle information established at National Cancer Center Hospital East. High integrity genomic DNA was extracted from archived methanol fixed paraffin embedded tissue samples. Whole exons were captured using Agilent SureSelect system and we generated 76-base paired-end sequences with an Illumina GAIIx platform. Approximately 30 million mapped sequences were obtained for each sample, providing 75x coverage of the target regions and 93% of the target regions also had 5x coverage. Using the sequence data, we identified SNVs and indels by BWA, SAMtools and GATK. EGFR mutations were observed among 55 cases and Sanger sequencing validated them. As well, known lung cancer-related gene mutations such as KRAS and TP53 were detected in exome data. Detailed profiling of somatic mutations provided wide variety of heterogeneity of known and novel gene mutations with both EGFR-mutant and -wildtype background. These heterogenity might define the unique signature of an individual tumor and be waited for further classification suitable for understanding genetic mechanism of carcinogenesis. 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 5134. doi:1538-7445.AM2012-5134
Clinical Observations Concerning Schizophrenic Patients Treated by Prefrontal Leukotomy
Authors: Jay L. Hoffman
Journal: New England Journal of Medicine (1949)

IT IS my purpose here to consider the clinical results of leukotomy in 42 patients treated by psychosurgery‡ at a Veterans Administration hospital during a two-year period — 1947 and 1948. To prepare for this I have reviewed the clinical records of these 42 patients and, within the past two weeks, have examined those who remained in the hospital. I have also gone over the social-service reports of the patients who have left the hospital and, in a few cases, have interviewed the relatives myself.I am less concerned in this report with statistics than I am with the qualitative . . .
Constipation Causing Elevated Iodine Activity in the Rectum Mimicking Thyroid Cancer Metastases
Authors: Bin Liu, Summer L Kaplan, Hua Yang, Ion Codreanu, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2014)

Iodine activity in the gastrointestinal tract on I or I imaging is usually diffuse and easy to recognize. Hereby we describe 2 cases of intense focal iodine activity in the rectum mimicking sacral metastases that were caused by constipation. Careful history taking and SPECT/CT imaging can be helpful in distinguishing rectal activity from metastatic lesions in such situations.
Outcomes and cost evaluation of the first two rounds of a colorectal cancer screening program based on immunochemical fecal occult blood test in northern Italy
Authors: F. Parente, C. Boemo, A. Ardizzoia, M. Costa, P. Carzaniga, A. Ilardo, R. Moretti, M. Cremaschini, E. Parente, M. Pirola
Journal: Endoscopy (2012)

<b>Background and study aims: </b>Colorectal cancer (CRC) screening aims to reduce mortality by detecting cancers at an early stage and removing adenomatous polyps at an acceptable cost. The aim of the current study were to assess the outcomes and costs of the first two biennial rounds of a population-based CRC screening program using the immunochemical fecal occult blood test (i-FOBT) in a northern Italian province. <b>Methods:</b> All residents aged 50 – 69 years were invited to take part in a biennial screening program using a 1-day i-FOBT, followed by colonoscopy in positive individuals. The i-FOBT uptake, compliance to colonoscopy, detection rate for cancer or advanced adenomas according to age and sex, and direct cost analysis were carried out separately for the 1st and 2nd rounds of screening. <b>Results:</b> In 78 083 (1st round) and 81 619 (2nd round) individuals who were invited to screening, the participation rates were 49.7 % and 54.4 % and i-FOBT positivity rates were 6.2 % and 5.8 %, respectively. Detection rates for cancer and advanced adenomas were lower in the 2nd screening compared with the 1st one (1.6‰ vs. 2.5‰ for cancers and 15.8‰ vs. 17.9‰ for advanced adenomas, respectively), whereas positive predictive values for cancer and advanced adenoma were similar in both rounds. In 165 adenocarcinomas detected, 52 % were Dukes' stage A and 21 % were stage B. All cost indicators were slightly higher in the 1st round of screening compared with the 2nd. The direct cost per cancer or advanced adenoma detection was similar in the two rounds (€ 1252 and € 1260, respectively). <b>Conclusions: </b>Compliance and diagnostic yield of i-FOBT screening were satisfactory. Most detected cancers were at a very early stage. Program costs were reasonable and did not increase with repeat screening. Screening could contribute to decreasing the cost of CRC care by improving the stage at diagnosis.
Carmine as a Source of Nosocomial Salmonellosis
Authors: David J. Lang, Lawrence J. Kunz, Albert R. Martin, Steven A. Schroeder, L. Ariel Thomson
Journal: New England Journal of Medicine (1967)

INVESTIGATION of infections with Salmonella cubana that appeared to have been contracted by patients in the hospital called our attention to carmine dye as a source of the etiologic agent. Our experience is reported in order that future infections may be prevented.Carmine, a nonabsorbable bright-red dye that is manufactured from insects originally indigenous to Central America, has been widely used as a fecal dye marker. Contamination of carmine has further relevance to public health since this dye is used to color certain foods, drugs and cosmetics.Our findings suggest in addition that the contaminating bacterium, S. cubana, is not . . .
A phase I trial of the HSP90 inhibitor, alvespimycin (17-DMAG) administered weekly, intravenously, to patients with advanced, solid tumours
Authors: S. C. Pacey, R. Wilson, M. Walton, M. Eatock, A. Zetterlund, H. Arkenau, R. Beecham, F. Raynaud, P. Workman, I. Judson
Journal: Journal of Clinical Oncology (2009)

3534 Background: alvespimycin (17-dimethylaminoethylamino-17-demethoxygeldanamycin, 17-DMAG) inhibits N-terminal ATPase activity of Heat Shock Protein 90 (HSP90). Chaperone interactions are altered such that client proteins are targeted for degradation. The plethora of HSP90 client proteins offers the potential of simultaneous blockade across multiple, oncogenic signalling pathways. Methods: the maximum tolerated dose, at which ≤ 1/6 patients experienced dose limiting toxicity (DLT) was determined by dose-doubling (3+3) design. PK and PD biomarker data were used to define a biologically effective dose (BED). PK (LC/MS/MS) and PD (western blot) assays were validated and compliant with European clinical trial legislation. Cancer Research UK and the NCI were co-sponsors. Results: twenty five patients, median age 58 (range 38–78) years, received 475 infusions at doses between 2.5 and 106 mg/m 2 . Dose doubling was possible to 80mg/m 2 when grade 2 toxicity, including dry eye and blurred vision (2/5 patients) occurred. At 106mg/m 2 DLT were observed (grade 3 fatigue, diarrhoea, dehydration and grade 4 hypotension, AST rise) in 2/4 patients, one patient died from cardiac arrest. PK data were as follows; plasma t = 24.6 ± 8.6 hr, Vss 468 ± 383 L (mean ± SD) and clearance 27.7 L/hr (range 8.26 - 153). Maximum plasma concentration increased proportionally with alvespimycin dose, area under the curve was only linear ≤ 80 mg/m 2 . PD changes (HSP72 induction) in peripheral blood mononuclear cells were detected ≥ 20 mg/m 2 . HSP90 inhibition (client protein depletion and HSP72 induction) was not readily detected until 106 mg/m 2 . Tumour samples confirmed HSP90 inhibition 24 hours after 17-DMAG in 1/1 and 2/4 patients given 106 and 80 mg/m 2 , respectively. Two partial responses one, confirmed, in a patient with hormone refractory prostate cancer and one, investigator assessed, in a patient with melanoma occurred. Both remain on study after 27 and 18 months, respectively. Nine patients (36%) have been on trial ≥16 weeks. Conclusions: The recommended phase II dose of alvespimycin is 80 mg/m 2 weekly. PK and PD data support this as a BED. No significant financial relationships to disclose.
The<i>Forme Fruste</i>in Marfan's Syndrome
Authors: Richard L. Golden, Harold Lakin
Journal: New England Journal of Medicine (1959)

ALTHOUGH Marfan's syndrome is by this time well recognized in its classical form, it is still frequently unrecognized in its incomplete or atypical state, known as the forme fruste. It is the purpose of this paper to present another case of the familial occurrence of the syndrome and once again to call attention to the importance of recognition of the forme fruste of this disorder. It is hoped that the case histories reported below will serve as an aid in the more frequent recognition of this form of the syndrome.Since Marfan's1 original report in 1896, more than 350 . . .
Discordant Uptake of F-18 FDG and In-111 WBC in Systemic Vasculitis
Authors: Kottekkattu Balan, Dimitrius Voutnis, Ashley Groves
Journal: Clinical Nuclear Medicine (2003)

BALAN, KOTTEKKATTU M.B.B.S., M.D., F.R.C.P.I.; VOUTNIS, DIMITRIUS F.R.A.C.P.; GROVES, ASHLEY M.R.C.P., F.R.C.R. Author Information
Core needle versus standard needle for endoscopic ultrasound-guided biopsy of solid pancreatic masses: a randomized crossover study
Authors: Geoffroy Vanbiervliet, Bertrand Napoléon, Marie Saint Paul, Charlotte Sakarovitch, Marc Wangermez, Philippe Bichard, Clément Subtil, Stéphane Koch, Philippe Grandval, Rodica Gincul, David Karsenti, Laurent Heyries, Jean-Christophe Duchmann, Jean Bourgaux, Michaël Levy, Gilles Calament, Fabien Fumex, Bertrand Pujol, Christine Lefort, Laurent Poincloux, Maël Pagenault, Eduardo Bonin, Monique Fabre, Marc Barthet
Journal: Endoscopy (2014)

<b>Background and study aims:</b> A new core biopsy needle for endoscopic ultrasound (EUS)-guided sampling has recently been developed. The aim of this prospective multicenter study was to compare this needle with a standard needle in patients with solid pancreatic masses. <b>Patients and methods:</b> Consecutive patients with solid pancreatic masses referred to 17 centers for EUS-guided sampling were included. Each patient had two passes with a standard 22G needle and a single pass with a 22G core needle performed in a randomized order. Samples from both needles were separately processed for liquid-based cytology and cell-block preparation and were assessed independently by two blinded expert pathologists. The primary endpoint was the accuracy of the detection of malignancy. The reference standard was based on further cytohistological analysis obtained under ultrasound or computed tomography scanning, endoscopic or surgical guidance, and/or by clinical follow-up with repeated imaging examinations for at least 12 months. The secondary endpoints were the rate of technical failure and the quality of the cytohistological samples obtained. <b>Results:</b> Of the 80 patients included (49 men; mean age 67.1 ± 11.1), 87.5 % had final malignant diagnoses (adenocarcinoma n = 62, 77.5 %). There was no difference between the needles in diagnostic accuracy (standard needle 92.5 % vs. core needle 90 %; <i>P</i> = 0.68) or technical failure. Both pathologists found the overall sample quality significantly better for the standard needle (expert 1, <i>P</i> = 0.009; expert 2, <i>P</i> = 0.002). <b>Conclusions:</b> The diagnostic accuracy of EUS sampling for solid pancreatic masses using standard and core needles seems comparable but with a better overall histological sample quality for the former. <b>ClinicalTrial.gov identifier:</b> NCT01479803.
Abstract 616: Insulin-like growth factor binding protein-3 (IGFBP-3) facilitates the response to DNA-damaging chemotherapy in triple-negative breast cancer cells.
Authors: Mike Zhen Lin, Hasanthi C. de Silva, Janet Lee Martin, Robert Charles Baxter
Journal: Cancer Research (2013)

Abstract Introduction. Breast cancer cells frequently develop resistance to DNA-damaging therapy, and epidermal growth factor receptor (EGFR) may play an important role in this process. EGFR can modulate the repair of DNA double strand breaks (DSB) by non-homologous end-joining (NHEJ), by forming protein complexes that include the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). However many ER-negative breast tumors still respond poorly to DNA-damaging drugs even when combined with an EGFR inhibitor. IGFBP-3, an intracellular and secreted protein, is highly expressed in these tumors. Since we previously showed that IGFBP-3 can transactivate EGFR and translocate to the nucleus, the aim of this study was to determine whether IGFBP-3 forms part of the EGFR-DNA-PK complex that regulates the DNA damage response to DSB-inducing chemotherapeutic agents. Results. In the triple-negative breast cancer cell lines MDA-MB-468 and Hs578T, which express IGFBP-3 highly, protein complex formation and nuclear localization of EGFR, DNA-PKcs and IGFBP-3 were enhanced by exposure to cytotoxic drugs etoposide or doxorubicin and reduced by IGFBP-3 knockdown or the EGFR kinase inhibitor gefitinib. Concomitantly, the co-location of EGFR-IGFBP-3 complexes with lipid rafts, visualized by proximity ligation assay (PLA) and confocal microscopy, decreased in response to drug treatment, consistent with the loss of this complex from the plasma membrane. Furthermore, the phosphorylation of DNA-PKcs at Ser2056 and its substrate Artemis nuclease at S516, and DNA repair capacity as measured by a non-homologous end-joining assay, were all decreased by IGFBP-3 silencing, while H2AX phosphorylation was increased, suggesting that IGFBP-3 has an obligatory role in the DNA repair response to DNA-damaging therapy. Conclusion. The increased intranuclear interaction between EGFR and DNA-PKcs in response to DNA damage, and the subsequent stimulation of NHEJ activity, require the presence of IGFBP-3, which also forms part of the nuclear complex. This demonstrates a previously unrecognized “caretaker” role for IGFBP-3 in regulating DNA DSB repair by NHEJ. These novel findings suggests the possibility of a therapeutic approach for sensitizing ER-negative breast cancers to chemo- or radiotherapy by targeting the DNA repair function of IGFBP-3. (Supported by Australian Research Council grant DP0984232 to RCB). Citation Format: Mike Zhen Lin, Hasanthi C. de Silva, Janet Lee Martin, Robert Charles Baxter. Insulin-like growth factor binding protein-3 (IGFBP-3) facilitates the response to DNA-damaging chemotherapy in triple-negative breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 616. doi:10.1158/1538-7445.AM2013-616
SKIN NERVE ACTIVITIES AND CARDIAC ARRHYTHMIAS IN PATIENTS RECOVERING FROM OPEN HEART SURGERY
Authors: Mark J. Shen, Arthur Coffey, Susan Straka, David Adams, David B. Wagner, Richard Kovacs, Changyu Shen, Lan S. Chen, Shien-Fong Lin, Peng Sheng Chen
Journal: Journal of the American College of Cardiology (2016)
Abstract 2084: Reactive oxygen species activate the IRE1-XBP1 pro-apoptotic pathway by recruiting TRAF2 to IRE1 and activating an IRE1-TRAF2-JNK pathway in human glioma cells
Authors: Yeon Hyang Kim, Hyung-Kon Koh
Journal: Cancer Research (2011)

Abstract To investigate the function of the oxidative stress in the endoplasmic reticulum (ER) -related cell death of glioma, the human glioma cells were treated with hydrogen peroxide, TNF, and thapsigargin to raise intracellular levels of hydroxyl radical and ER stress, respectively. Hydrogen peroxide and thapsigargin increased cytosolic Ca2+, induced the activation of caspase 3, and caused apoptosis in a dose-dependent manner. In contrast, TNF affect neither cell viability nor the increase of cytosolic Ca2+. Both hydrogen peroxide and thapsigargin increased the expressions of ER-associated molecules including p-PERK, IRE1-α, p-eIF, ATF-1, p-CREB and Ero1-α in human glioma cells, whereas TNF did not increase the expressions of them. Hydrogen peroxide and thapsigargin increased IRE1-α nuclease activity generating transcriptionally active form of XBP-1 and induced IRE1-α-TRAF2 complex formation which initiates JNK activation and increase of expressions of p-JNK1 and p-JNK2. On the other hand, TNF-α did not increase p-JNK1and p-JNK 2 levels. IRE1-α induction coincided with those of p-JNK1, p-JNK and induced formation of IRE1-α-TRAF2 in hydrogen peroxide- and thapsigargin- treated cells. Therefore, we conclude that the increase of expression of IRE1-α is necessary for activating TRAF2-JNK pathway and causing oxidative stress- induced cell death of glioma. 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 2084. doi:10.1158/1538-7445.AM2011-2084
Rosai-Dorfman Disease Mimics Lymphoma on FDG PET/CT in a Pediatric Patient
Authors: Bin Liu, Nam Ju Lee, Hansel J. Otero, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2013)

A previously healthy 3-year-old girl developed rhinorrhea, painful right neck swelling, and fever. Contrast-enhanced CT of the neck revealed cervical lymphadenopathy, for which lymphoma was considered. FDG PET/CT images showed intense activity not only in the neck but also in the thorax, abdomen, and pelvis. Biopsy was performed, and the diagnosis of Rosai-Dorfman disease was made.
Abstract 1335: Involvement of canonical Wnt/β-catenin signaling pathway in pancreatic ductal adenocarcinoma
Authors: Makoto Sano, David Driscoll, David S. Klimstra, Wilfredo DeJesus-Monge, Brian C. Lewis
Journal: Cancer Research (2012)

Abstract Pancreatic ductal adenocarcinoma (PDAC), a poor prognostic cancer, develops through the progression of premalignant lesions called pancreatic intraductal neoplasms (PanINs). Acinar-to-ductal metaplasia (ADM) is postulated to contribute to PanIN development, and the canonical Wnt/β-catenin pathway has been implicated in this process. To ascertain the impact of postnatal activation of the Wnt/β-catenin pathway in PanIN-PDAC progression, we combined the elasatse-tva-based RCAS-TVA pancreatic cancer model with the established LSL-KrasG12D, Ptf1a-cre model. Delivery of RCAS viruses encoding β-cateninS37A, but not RCAS-GFP, stimulated a shift to higher-grade PanIN lesions in young adult mice. Moreover, mice injected with RCAS-β-cateninS37A had reduced survival relative to RCAS-GFP controls (log-rank test; p &amp;lt;0.05). In addition, overexpression of active β-catenin or its DNA-binding partner TCF4 in PDAC cell lines enhanced cell proliferation, soft-agar colony formation, as well as migration and invasion activity. In contrast, these phenotypes were significantly blocked by the introduction of Icat, an inhibitor of the β-catenin/TCF4 interaction. Together, these data suggest that activation of the Wnt/β-catenin signaling pathway is closely related to pancreatic tumorigenesis and progression of this malignancy. 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 1335. doi:1538-7445.AM2012-1335
Primary Osteosarcoma of the Rib Identified on Bone Scintigraphy
Authors: Peng Xie, Jianmin Huang
Journal: Clinical Nuclear Medicine (2015)

Osteosarcomas generally arise in appendicular skeletons, but rarely in the ribs. We described Tc-MDP bone scan findings from a 23-year-old man with right back pain. The images demonstrated elevated activity in the region overlapping the posterior 8th to 10th ribs and in the L9-10 vertebral bodies. CT showed an 8.8 × 8.3 cm mildly peripherally calcified mass arising from the right 10th rib involving the 9th and 10th thoracic vertebrae. Pathological examination confirmed primary osteosarcoma of the rib.
A7.11 Resveratrol and a resveratrol-salicylate hybrid molecule suppress cytokine production and proliferation of human CD4<sup>+</sup>T-cells
Authors: K Goldhahn, B Kloesch, F Aldawsari, C Velazquez-Martinez, K Schmetterer, G Steiner
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Introduction</h3> Aberrant T-cell responses are crucially involved in the pathogenesis of systemic autoimmune diseases such as rheumatoid arthritis (RA) leading to chronic inflammation and organ damage. Resveratrol is a natural occuring polyphenol mainly produced in plants. The beneficial effects of resveratrol are due to its anti-inflammatory, anti-carcinogenic and anti-oxidant activities. The aim of this study was to investigate the effects of resveratrol and a novel resveratrol-salicylate hybrid molecule (C10) on human CD4<sup>+</sup> T-cells. <h3>Methods</h3> CD4<sup>+</sup> T-cells from healthy donors were pre-incubated with different concentrations of resveratrol or C-10 before being stimulated with anti-CD3/anti-CD28 antibodies. After 24 h and 72 h, respectively, cell culture supernatants were harvested and IL-2, IFN-γ and TNF-α release were quantified by ELISA. Proliferation rate was measured by thymidine incorporation. In addition, the up-regulation of the early activation markers CD25, CD69, CD71 and CD98 was analysed and phosphorylation of the MAP-kinase ERK as well as AKT and SRP6 was determined by westernblot or flow cytometry. <h3>Results</h3> Inhibition of IL-2, IFN-γ and TNF-α release was significantly more effective when the cells were treated with C-10 (p &lt; 0.05). In comparison to the untreated control, C-10 inhibited cytokine production by 35% (6.25 µM), by 55% (12.5 µM) or by 80% (25 µM) whereas resveratrol inhibited cytokine production only at 25 µM or 50 µM significantly. Moreover, proliferation rate in CD4<sup>+</sup> T-cells was significantly more decreased in the presence of C-10 at concentrations of 25 µM or 50 µM (p &lt; 0.0001). The expression of the early activation markers CD25, CD69, CD71 and CD98 was reduced in a dose dependent manner when the cells were exposed to resveratrol or C-10. Furthermore, the phosphorylation of ERK, Akt and S6RP was attenuated by resveratrol or C-10 to a similar degree. <h3>Conclusion</h3> Resveratrol and C-10 both suppressed cytokine secretion and proliferation of CD4<sup>+</sup> T-cells. The suppressive effects appear to be based on partial suppression of phosphorylation of several important signalling molecules involved in cytokine expression and cell growth. Since C-10 significantly amplified the effects of resveratrol these data suggest C-10 as an interesting candidate drug for treatment of RA and other T cell driven autoimmune diseases.
The Right Angle
Authors: Michael C. Reed, Gurpreet Dhaliwal, Sanjay Saint, Brahmajee K. Nallamothu
Journal: New England Journal of Medicine (2011)

A 25-year-old man presented to an ER with abdominal distention and discomfort. He had noticed his increased girth a year earlier and attributed it to beer, but it progressed after he cut back. His distention was associated with early satiety, fatigue, and exertional dyspnea.