tbuckley/cabot-search huggingface dataset:
PTU-059 Comparison Of Bipolar Radiofrequency Cutting And Mono Polar Cutting For Endoscopic Submucosal Dissection (esd) In A Porcine Model
Authors: ZP Tsiamoulos, C Hancock, PD Sibbons, BP Saunders
Journal: Gut (2014)

<h3>Introduction</h3> Current endoscopic knives utilise mono-polar energy to incise the mucosa, dissect the submucosa and coagulate bleeding vessels. Monopolar devices have proven efficacy but remain technically challenging to use with the risk of major complications. <h3>Methods</h3> A new bipolar endoscopic device “Speedboat-RS2, (S-RS2) Creo Medical Ltd, UK” was compared to a standard mono-polar endoscopic device (Flush-knife-BT/F-BT/Fujifilm, Japan) for endoscopic submucosal dissection (ESD) in the porcine colon. The S-RS2 blade delivers bipolar radio frequency (RF-400 KHz) cutting and microwave coagulation (5.8 GHz) for hemostasis, and contains a retractable needle for submucosal injection/tissue irrigation. It also has an insulated hull to prevent thermal injury to the underlying muscle layer. ESD was performed in a random order and video recorded on 5 consecutive 60kg pigs. The following parameters were measured: time taken to complete resection, complications encountered and histological assessment. Two animals were recovered for one week and four animals for four weeks. <h3>Results</h3> Ten consecutive resections were performed in the colorectum (2 per animal), 5 with S-RS2 and 5 with F-BT. Median time for S-RS2 to complete a resection was 44 min using RF cutting 30W, and for F-BT was 52min using monopolar cutting for mucosal incision (80W) and for submucosal dissection, monopolar forced coagulation 30W. Median flap size for S-RS2 was 36.8mm and for F-BT was 43mm. Microwave coagulation was applied for either minor bleeding or visible vessels on 25 occasions with S-RS2. Monopolar coagulation was applied 14 times with F-BT, mean energy 30W. The Hemostatic Coagrasper was used 7 times to control arteriolar bleeding during S-RS2 dissection when microwave was not sufficient and only once during Flushknife-RS2 dissection. Endoclips were placed to treat deep muscle injury in the resection base on 10 occasions in the F-BT resections (15clips placed) and on 3 occasions (3 clips) for the S-RS2 resections. There was only one study perforation – F-BT group, where urgent peritoneal decompression was required and the resection was abandoned. Histology (S-RS2 resections) showed an intact muscle layer in four resection bases and in one there was slight muscle alteration but muscle cell viability was retained. The muscle layer was absent in two F-BT resection bases and moderately altered in one. <h3>Conclusion</h3> Compared to Flush knife-BT ESD colonic resections (monopolar) the Speedboat-RS2 was was associated with less muscle injury and need for endoscopic clipping. However Speedboat-RS2 resections produced more intraprocedural bleeding requiring the haemostatic forceps. <h3>Disclosure of Interest</h3> Z. Tsiamoulos Consultant for: Creo Medical Ltd, C. Hancock Shareholder of: Creo Medical Ltd, P. Sibbons Paid instructor for: Creo Medical Ltd, B. Saunders Consultant for: Creo Medical Ltd, Paid instructor for: Olympus KeyMed.
Fortnightly review: Hereditary ovarian carcinoma
Authors: L. Kasprzak, W. D Foulkes, A. N Shelling
Journal: BMJ (1999)

Ovarian carcinoma is the fourth most common cause of cancer death in women in Western countries. Because of inadequate screening methods and the vague nature of the symptoms, patients present late in the course of the disease and the survival rate is poor. There are no strong environmental risk factors, and after age is controlled for the most important risk factor is a family history of ovarian carcinoma. The effect of a positive family history on a woman's risk of ovarian carcinoma is illustrated in table 1. In this review we focus on the hereditary aspects of ovarian carcinoma.

#### Summary points

We reviewed original articles and expert reviews from journals cited in Medline between 1980 and 1998 and supplemented this information with unpublished data from our colleagues. We also included information from recently published books. In performing the Medline searches we used the following key words: hereditary ovarian carcinoma, breast and ovarian carcinoma syndrome, ovarian cancer screening, prophylactic oophorectomy.

Between 5% and 10% of cases of ovarian carcinoma are the result of an inherited gene or genes. The percentage depends on the degree of relatives included in the calculation and the method of case ascertainment.2 Narod et al …
P13.09 * ADVANCES IN CLINICAL APPLICATION OF BORON NEUTRON CAPTURE THERAPY (BNCT) IN GLIOBLASTOMA
Authors: A. Detta, G. C. Cruickshank, S. Green, N. P. Lockyer, D. Ngoga, Z. Ghani, B. Phoenix
Journal: Neuro-Oncology (2014)

BNCT is a biologically targeted form of enhanced cellular radiotherapy where preferential accumulation of boron in the cancerous as opposed to adjacent normal cells is able to interact with incident neutrons to cause irreversible alpha particle DNA damage. The key to the implementation of this potentially powerful and selective therapy is the delivery of at least 30ppm 10B within the tumour tissue while minimising superfluous 10B in healthy tissue. It is thus an elegant technique for treating infiltrating tumours such as diffuse gliomas. In order to assess its clinical potential we carried out a pharmacokinetic study in glioblastoma patients where we sought to determine the optimal route of delivering a new formulation of the boronated drug (p-boronophenylalanine, BPA), its pharmacokinetic behaviour, toxicity profile, and cellular uptake. Using a number of analytical techniques, including inductively-coupled plasma mass spectrometry, secondary ion mass spectrometry (SIMS) and immunohistochemistry (IHC), boron was measured at various times in blood, urine, cerebrospinal fluid, extracellular fluid (ECF), and tumour-related solid tissue spanning 0.5 h pre- and up to 48 h post-BPA infusion in newly-diagnosed patients (n = 10). Blood was sampled through a central catheter whilst the ECF was sampled by parenchymal microdialysis catheters, placed remotely from the tumour site. Urine was collected over the same time period. Tumour and brain-around tumour (BAT) tissue was sampled stereotactically at 2.5 h and 3.5 h post-infusion. IHC expression levels of the BPA transporter molecule, L-amino acid transporter 1 (LAT-1), were recorded as % LAT-1 positive cells, and cellular boron levels were estimated as spatially resolved pixels in normalised-to-C+ isotopic SIMS images of the biopsies. There were no toxicity-related issues with this new formulation of BPA given at 375 mg/kg as a 2 h intravenous or intracarotid infusion with or without pre-infusion mannitol-induced BBB disruption. The pharmacokinetic profile indicates a high plasma-to-brain concentration gradient from intracarotid infusion and BBB manipulation and reliably places boron in high concentrations in the brain compartment. However, tumour and BAT uptake varied, but a continuing uptake in BAT over time to >30 ppm boron suggests a more favourable capacity to concentrate boron for BNCT after debulking surgery. At the cellular level, the ratio of boron uptake as measured by SIMS in tumour vs BAT was 0.96, 1.85 and 2.40 in the intravenous, intravenous plus mannitol BBB-D, and intracarotid cohorts respectively. Thus improved specific and targeted delivery of boron is possible. These observations conform to a three compartment model where tumoural uptake of boron is governed solely by the abundance and two-way kinetics of tumour LAT-1 activity rather than BBB penetration and may explain some of the variation in clinical results of others.
Abstract 3899: NOSH compounds: Nitric oxide- and hydrogen sulfide-releasing hybrids, a new class of anti-inflammatory pharmaceuticals
Authors: Federica Vannini, Han-Bee Kim, Mitali Chattopadhyay, Ravinder Kodela, Khosrow Kashfi
Journal: Cancer Research (2012)

Abstract Introduction: The clinical usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) combined with their potentially life-threatening toxicity has prompted intensive efforts to identify safer alternatives, which will at least maintain their pharmacological properties. The search for a “better NSAID” has resulted in at least two modified hybrids, one that releases nitric oxide (NO-NSAIDs), and another that releases hydrogen sulfide (HS-NSAIDs). These agents although much safer and more potent than their traditional counterparts, have IC50s for cell growth inhibition that are in the micro-molar range. Therefore, we postulated that a new hybrid that incorporated the active parts of each compound may be more potent and effective than either one. Our hypothesis has proved to be correct. We have synthesized a number of NSAID based NOSH (nitric oxide-, hydrogen sulfide-releasing) compounds that release both H2S and NO, and have IC50s for cell growth inhibition in the low nano-molar range. Methods: Compounds: Aspirin based NOSH-1, NOSH-2, NOSH-3, and NOSH-4 were synthesized and purified by us with 1H-NMR verification. Human cancer cell lines: colon (HT-29, HCT 15, SW480), breast (MCF-7, MDA-MB-231, SKBR3), pancreas (BxPC-3, MIA PaCa-2), lung (A549), prostate (LNCap), leukemia (Jurkat). Cell growth: MTT. Anti-inflammatory: paw edema induced by intraplantar injection of 100 µL of 1% carrageenan, paw volumes measured up to the tibiotarsal joint immediately prior to carrageenan injection and thereafter at 1hr intervals up to 6hrs. Drugs were administered orally 1 hr before carrageenan; COX enzyme: immunoblotting, PGE2: ELISA Results: All NOSH compounds were more effective than aspirin in inhibiting the growth of colon, breast, pancreas, prostate, lung, and leukemia cancer cell lines. The IC50s at 24h were in the range 48 nM to 6.5 µM depending on the cell line and the compound. The corresponding IC50 for aspirin was &amp;gt;5000 µM in all cell lines. Our lead compound NOSH-1, had a enhanced potency of &amp;gt;100,000-fold. NOSH-1 dose-dependently decreased the carrageenan-induced edema 1h after administration and maintained this anti-inflammatory effect throughout the experiment (up to 6h). PGE2 levels within the inflamed rat paw were also reduced by NOSH-1. Carrageenan induced both COX-1 and COX-2 expression which were dose-dependently inhibited by NOSH-1. Conclusions: NOSH compounds are a new class of anti-inflammatory agents. NOSH-1, our lead compound is very potent in inhibiting a number of different cancer cell lines of different tissue origin suggesting a tissue independent effect. 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 3899. doi:1538-7445.AM2012-3899
Early Cardiovascular Death in Patients with Cancer
Authors: Mark Voskoboynik, Damien Urban, Linda Mileshkin
Journal: New England Journal of Medicine (2012)

Early Cardiovascular Death in Patients with CancerTo the Editor: The increased risk of cardiovascular death in the weeks after a diagnosis of cancer has been described in several recent articles. 1,2Each one cites the psychological stress of receiving a diagnosis of cancer as a potential explanation for this risk.We believe that a major and underreported confounder is the risk of cardiovascular death that accompanies surgical procedures that are therapeutic, diagnostic, or both in these patients.Surgery and general anesthesia are associated with a risk of cardiovascular illness and death in the initial postoperative period. 3Rates of cardiac death or nonfatal myocardial infarction range from less than 1% among patients who have undergone low-risk surgery to 5% or less among patients who have undergone intermediate-risk surgery to even higher rates among patients who have undergone high-risk surgery.To examine surgery as a major confounder (or maybe even cause) of cardiovascular death after a diagnosis of cancer, we conducted an analysis involving all 287,512 patients who received a diagnosis of cancer between 1998 and 2008 in the Surveillance, Epidemiology, and End Results (SEER) registry and who died within 1 month after diagnosis.We examined the proportion of cardiovascu-
Abstract 4887: Curcuminoid CLEFMA induces autophagy-associated apoptosis in lung cancer
Authors: Kaustuv K. Sahoo, Vivek R. Yadav, Vibhudutta Awasthi
Journal: Cancer Research (2012)

Abstract CLEFMA (4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid) is a novel curcuminoid discovered in our laboratory. Earlier we showed that CLEFMA induces oxidative stress-dependent cell death in lung adenocarcinoma H441 cells. Although apoptosis is the desired mechanism for chemotherapy-induced cell death, the associated pathways are often defective in lung cancers resulting in high levels of chemoresistance. Therefore, drugs that induce alternate modes of cell death, such as autophagy, may be beneficial. Drug-induced hyperinduction of autophagy is classified as type 2 programmed cell death. In most circumstances, autophagy parallels apoptosis, and such composite cell death is described as “autophagy-associated apoptosis”. Whether autophagy plays a synergistic or antagonistic role in overall cell death response to anticancer drugs is an important focus in cancer research. In this study, we have investigated the interaction between autophagy and apoptosis in CLEFMA mediated cell death. Methods: The human non-small cell lung carcinoma (H441) cell line was treated with CLEFMA (10 µM) and the molecular mechanisms of cell death were investigated. Growth inhibition was assessed by MTT or hexosaminidase assay. Apoptosis was measured by flow cytometry of annexin V-stained cells, RT-PCR and immunoblotting for apoptosis-related biomarkers. Induction of autophagy was established by electron microscopy and immunobloting for LC3B, ATG, beclin1, AKT and mTOR. Autophagy was inhibited by 3-methyladenine (3-MA 1 mM) as well as chloroquine and E64D+pepstatin combination. The tumor suppressive efficacy of CLEFMA was demonstrated in H441 xenograft mice intraperitoneally receiving 0, 5 and 10 µg/day of CLEFMA for 32 days. The mice were imaged for F-18-fluorodeoxyglucose uptake in tumor tissue. Results: CLEFMA suppressed the viability of H441 cell line in a dose-dependent manner (IC50 = 6.25 µM). It induced cell cycle arrest at G2/M phase with accompanying accumulation of p21 protein. Caspase 3/7 immunoblotting and annexin V flow cytometry confirmed the induction of apoptosis. At the same time, we observed induction of LC3BII and suppression of AKT/mTOR phosphorylation. The suppression of autophagy significantly increased CLEFMA-induced cell death and increased caspase cleavage. In the xenograft model, 5 and 10 µg CLEFMA significantly reduced the tumor volume by 72% and 96.2%, respectively; the tumor uptake of F-18-fluorodeoxyglucose was also reduced. Conclusions: We demonstrate the efficacy of CLEFMA as a potent tumor suppressive agent. The mechanistic results suggest that autophagy is a survival mechanism in CLEFMA-treated lung cancer cells and it antagonizes apoptosis. 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 4887. doi:1538-7445.AM2012-4887
AB0291 Association between Pentosidine, an Advanced Glycation End-Product, and Disease Activity in Patients with Untreated Rheumatoid Arthritis. A Preliminary Report
Authors: S. Mizuki, Y. Kashiwado, K. Yoshida, K. Oryoji, K. Kamada, E. Yokota
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Serum and urinary pentosidine, an advanced glycation end-product (AGE), levels were increased in patients with rheumatoid arthritis (RA) when compared with healthy controls. Antirheumatic medications including prednisolone, methotrexate and anti-tumor necrosis factor agents affect the serum and urinary pentosidine levels. In long-standing RA patients who were taking above medications, it might be difficult to evaluate whether disease activity or inflammation of arthritis affect pentosidine levels. To date no study to characterize pentosidine levels in untreated RA patients is currently available. Therefore, we studied urinary pentosidine levels in untreated RA patients and evaluated associations with RA disease-related variables. <h3>Objectives</h3> To evaluate the effects of RA disease activity on urinary pentosidine levels. <h3>Methods</h3> Consecutive nineteen patients, 63% women, with newly diagnosed RA according to 2010 American College of Rheumatology/European League Against Rheumatism classification criteria were included. Urinary levels of pentosidine were measured by HPLC after extraction of urine and normalised to the urinary creatinine. We calculated the correlations between pentosidine levels and the disease activity (DAS28, SDAI, CDAI), age, disease duration, mHAQ, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3 (MMP-3), rheumatoid factor (RF) and anti-CCP antibody, respectively. <h3>Results</h3> Two patients with diabetes mellitus and/or renal disorder were excluded. Backgrounds of the remaining seventeen patients were median age 60 years old, median disease duration 0.3 year, mean DAS28-ESR 4.56 and positive anti-CCP antibody 70.6%. Urinary pentosidine levels correlated significantly to swollen joint counts (68) (r=0.583, P=0.014). In patients of whom disease durations were less than one year, urinary pentosidine levels showed a tendency of correlation to DAS28-ESR (r=0.524, P=0.081), DAS28-CRP (r=0.499, P=0.099), SDAI (r=0.562, P=0.072). Moreover, pentosidine levels showed a tendency of correlation to MMP-3 (r=0.507, P=0.093) although the levels correlated neither to ESR, CRP nor RF, anti-CCP antibody. <h3>Conclusions</h3> Our study is the first to investigate associations of pentosidine levels with RA disease activity in newly diagnosed RA patients taking no antirheumatic medications. In untreated RA patients, we found positive correlations between urinary pentosidine levels and clinical disease activity and marker of inflammation. Inflammation and oxidative stress of RA may affect the accumulation of AGE. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4500
Abstract 892: Survey of human cancer tissues for the presence of bovine leukemia virus
Authors: Gertrude Case Buehring, Hanne M. Jensen, Henry Tesluk
Journal: Cancer Research (2011)

Abstract Bovine leukemia virus (BLV) is an oncogenic retrovirus that causes B cell leukemia/lymphoma in 5% of infected cattle. Infection is widespread in the USA: 24% of beef herds, 84% of dairy herds, and 100% of large dairy operations. BLV has been detected in T cells, B cells, endothelium, and mammary epithelium, and infected cells may be present in the blood and milk of cattle. Previously we found IgG antibodies to BLV in 39% of humans sampled, and BLV-related DNA in 60% (67/112) of malignant human breast tissues. Presence of BLV-related DNA in human mammary epithelium was significantly associated with breast cancer risk (odds ratio = 3.4, confidence interval = 1.77-6.44; P≪ .0002). The purpose of this study was to test other types of human cancers for BLV-related DNA as a first step in exploring whether BLV might be involved in malignancies of tissues other than breast. Specimens were surgical pathology archival material collected from 1992-2003. We performed PCR-in-situ hybridization (PCR-ISH) on formalin-fixed tissue sections, targeting the highly conserved tax region, which codes for the oncogenic protein of BLV. This method is not subject to molecular contamination, and can localize the signal to a particular cell type in the intact tissue. Our survey included the following malignancies: stomach, colon, pancreas, prostate, seminoma, ovary, endometrium, sarcoma (1 liposarcoma, 3 fibrosarcoma, 4 fibrohistiocytoma, 1 Ewing sarcoma), lymphoma (10 B cell, 2 T cell, 3 Hodgkin), squamous cell skin carcinoma, lung, thyroid, and brain (3 astrocytoma, 4 meningioma, 3 glioblastoma). BLV-related amplicons were detected in the following cancer types: stomach (5/10), colon (1/11), brain (2/10 [1 astrocytoma and 1 glioblastoma]), lymphoma (1/15 [T cell lymphoma]), sarcoma (1/9 [poorly differentiated high grade sarcoma]), and squamous cell skin carcinoma (2/10). No tissue type we tested showed a frequency of BLV-related DNA as great as we previously detected in breast cancer (60%). Sample sizes in this pilot survey were too small to provide an accurate estimate of overall frequency in the population or to make any conclusions about the association of BLV-related DNA with the malignancies studied. However, the data do provide some interesting leads for further research with an increased number of specimens and normal control tissue, especially for the cancer types exhibiting at least one positive specimen. This research was supported by a seed grant to HM Jensen from the Department of Pathology and Laboratory Medicine, School of Medicine, University of California, Davis. 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 892. doi:10.1158/1538-7445.AM2011-892
Migrating Thrombophlebitis Associated with Carcinoma
Authors: Edward A. Edwards
Journal: New England Journal of Medicine (1949)

AN apparently idiopathic thrombophlebitis may be associated with visceral carcinoma. In most cases the thrombosis is secondary to direct invasion by the tumor. There are other apparently rare cases in which multiple segments of vein are attacked at a distance from the tumor or its metastases. In these circumstances, the venous disorder takes on a particular form, unique for the great number of veins involved, the tendency for migration of the process from one segment to another, its persistence and its tendency to recrudescence. The affected veins show no invasion by tumor, and little reaction of any type. Some change . . .
Syphilitic Chancres of the Lips
Authors: Dong-Lai Ma, Sergio Vano-Galvan
Journal: New England Journal of Medicine (2013)

A 25-year-old man with no major medical conditions presented with two painless ulcerated lesions in the midline of the lips. The round ulcers measured 0.8 cm to 2.4 cm in diameter with clean, smooth bases and slightly elevated, indurated borders.
Primary-Effusion Lymphoma and Kaposi's Sarcoma in a Cardiac-Transplant Recipient
Authors: Dan Jones, Mary E. Ballestas, Kenneth M. Kaye, James M. Gulizia, Gayle L. Winters, Jonathan Fletcher, David T. Scadden, Jon C. Aster
Journal: New England Journal of Medicine (1998)

Human herpesvirus 8 (HHV-8) is a recently discovered virus that appears to have a pathogenic role in Kaposi's sarcoma, multicentric Castleman's disease, and primary-effusion lymphoma, a distinctive lymphoma that arises within body-cavity effusions.1–7 HHV-8 was originally detected in lesions of Kaposi's sarcoma in patients infected with the human immunodeficiency virus (HIV) but was subsequently found in forms of the tumor that occur in HIV-negative patients.8,9 Similarly, HHV-8–associated multicentric Castleman's disease occurs predominantly in patients with the acquired immunodeficiency syndrome (AIDS) but also in HIV-negative patients.5,10,11 These findings suggest a direct causal role of HHV-8 in the . . .