tbuckley/cabot-search huggingface dataset:
Amplication of the estrogen receptor 1 (ESR1) gene in mastopathy predicts development of breast cancer.
Authors: E Kilic, A Rufle, F Holst, M Ihnen, R Simon, I Zlobec, LM Terracciano, G Sauter
Journal: Cancer Research (2009)

Abstract Abstract #5037 Background: Mastopathy is a disease with fibrocystic changes (FCC) of the breast tissue commonly seen between the ages 30-50, but rare in postmenopausal women, and therefore suggestive of an association with estrogen stimulation. Whether FCC bears an elevated breast cancer risk is unclear. The role of ESR1 amplification in FCC has not previously been investigated. Material and Methods: Paraffin embedded tissues from 59 women with invasive breast cancer (BrCa) were analyzed. For all women, tissues with FCC taken at least 1.5 years before first diagnosis of BrCa (termed here “FCC old”) were also available. Average latency between FCC and BrCa was 6years (range1.5-17y). Immunohistochemistry (IHC) with antibody against estrogen receptor alpha (ER) and FISH-analyses with a probe for ESR1 (Zytovision, Bremerhafen/Germany) were performed. As a control, tissues from 19 women with FCC without a diagnosis of in situ or invasive breast carcinoma in the observed time frame (12-18y) were taken. Clinical-pathological data, such as histological subtype, tumour stage, tumour diameter, BRE-grade, patient's age and others, were available for statistical analysis. Results: After FISH analyses, 9 of 59 (15%) BrCa were amplified for ESR1. All ESR1-amplified BrCa were strongly positive for ER with IHC (at least 80% of tumour cells labelled). Tumour type or stage and BRE-grade did not correlate with ESR1-status. In all cases of ESR1 amplification in BrCa areas of amplification in FCC adjacent to the tumour were identified. Interestingly, in women with ESR1 amplification in BrCa, an amplification detectable in tissues with FCC prior to the first diagnosis of BrCa (“FCC old”) was noted but was absent in tissues from women with FCC who did not develop BrCa in the observed time frame. Non-neoplastic ESR1 amplified cells within FCC were strongly positive for ER with IHC. In unaltered mammary glands ESR1 amplification was not observed. Discussion: In this pre-selected collective of women with BrCa and history of FCC we found amplification of the ESR1 gene in 15% of BrCa. In these women, ESR1 amplification was also detectable in tissue with FCC taken prior to the first diagnosis of BrCa. This investigation shows that ESR1 amplification is an early event in breast pathology and its occurrence in FCC predicts development of BrCa. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5037.
INSUFLACIÓN CON AIRE AMBIENTE O CON DIÓXIDO DE CARBONO (CO2) DURANTE LA COLONOSCOPIA. ESTUDIO COMPARATIVO RANDOMIZADO DOBLE-CIEGO
Authors: P Díez Redondo, P Gil Simón, N Alcaide Suárez, R Atienza, J Barrio, C De la Serna Higuera, M Pérez-Miranda
Journal: Endoscopy (2010)

Objetivos: Comparar la intensidad del dolor experimentado por nuestros pacientes tras someterse a una colonoscopia con aire ambiente o con CO2. Valorar la seguridad de CO2 en colonoscopias realizadas con sedación moderada-profunda y su posible repercusión en el desarrollo de la técnica.
Abstract PD08-07: The Impact of 1-Year Supervised Exercise Training on Physical Performance and Quality of Life of Breast Cancer Patients — A Randomise Prospective Phase III Trial
Authors: T Saarto, H Penttinen, H Sievänen, P-L Kellokumpu-Lehtinen, C Blomqvist, R Nikander, R Huovinen, L Hakamies-Blomqvist, M-L. Luoma
Journal: Cancer Research (2010)

Abstract The BREX study is the largest randomised prospective study to investigate the effect of physical exercise in rehabilitation of breast cancer survivors shortly after adjuvant treatments.Patients: 537 Finnish breast cancer patients(aged 35-68 years) were enrolled into the 1-year aerobic exercise intervention study (BREX) between 2005 and 2007. Patients were randomly allocated into exercise or control group. Methods: The exercise intervention consisted of weekly supervised step aerobics and home training. The physical performance was tested by a 2-km walking test and figure-8 running. The intensity of physical activity was measured by a two-week diary (METs) and Quality of life (QoL)by the EORTC QLQ-C30 and BR-23, FACIT-F and BDI before the intervention and after 6 and 12 mo's. Results: 500/537 patients were included in the final analyses (263 exercise and 237 control group). Patients participated in the supervised weekly exercise training median 32/52 times, vigorous home training 1.6 and endurance 1.4 times per week. Results are shown in table 1 and 2. Conclusions: Supervised aerobic exercise training improved significantly physical performance, even though physical activity increased in both groups. Physical activity correlated positively to QoL during the intervention irrespectively of the study group. However, the intervention itself did not influence on QoL. Table 1. Table 2. Factors association to QoL change from baseline. Change versus change. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD08-07.
SP-04 * INTERNATIONAL PATTERNS OF PALLIATIVE CARE IN NEURO-ONCOLOGY: A PHYSICIAN SURVEY OF MEMBERS OF THE ASIAN SOCIETY OF NEURO-ONCOLOGY, THE EUROPEAN ASSOCIATION OF NEURO-ONCOLOGY AND THE SOCIETY FOR NEURO-ONCOLOGY
Authors: T. Walbert, V. Puduvalli, M. J. B. Taphoorn, A. R. Taylor, R. Jalali
Journal: Neuro-Oncology (2014)

INTRODUCTION: Brain tumor patients have limited survival and suffer from high morbidity requiring specific symptom management. Specialized palliative care (PC) services have been developed to address these symptoms and provide end of life management for patients with such malignancies. Global utilization patterns of PC in neuro-oncology are unknown. METHODS: In a collaborative effort of the Society for Neuro-Oncology (SNO), the European Association of Neuro-Oncology (EANO) and the Asian Society of Neuro-Oncology (ASNO), a 22 question survey was distributed to members. An additional paper copy was distributed at the SNO meeting quality of life session (2012) and the ASNO meeting (2013). Only physician responses are included in this report. Nonparametric methods including Wilcoxon two sample and Kruskal-Wallis tests were used to assess differences in responses. Demographic information included academic degree, specialty, formal training in neuro-oncology and PC, practice patterns and geographic locations. RESULTS: 487 evaluable responses were received (Asia-Oceania (AO) 234, Europe 74, US 179). AO providers received more formal training in PC than European physicians (p = 0.0377). Provider in all 3 regions agreed on referring patients at the onset of symptoms requiring palliation, but responders from AO refer a larger total proportion of patients to PC than provider in Europe (p <0.001). US respondents were less likely to utilize PC at the point of disease onset than providers in AO (p = 0065). US provider felt more comfortable dealing with end of life issues than AO physicians (p <0.001), but more patients were referred to formal hospice care in the US than in Europe or AO (p <0.001). CONCLUSION: This is the first report describing global differences of PC utilization in neuro-oncology. Significant differences in provider training, culture, access and utilization were mainly found between AO and the US or AO and Europe. PC patterns are more similar in Europe and the US.
AB0936 Renal Involvement in Sarcoidosis: A Study of 50 Cases
Authors: N. Boussetta, R. Dhahri, F. Jaziri, M. Mahfoudhi, S. Barbouchi, S. Turki, K. Ben Abdel Ghani, A. Khedhr
Journal: Annals of the Rheumatic Diseases (2014)

Background Clinically important renal involvement occasionally occurs in sarcoidosis. Renal manifestations include abnormal calcium metabolism, nephrolithiasis and nephrocalcinosis, and acute interstitial nephritis with or without granuloma formation. Objectives To analyze the pattern of osteoarticular lesions in patients with sarcoidosis hospitalized in internal medicine departments. Methods We carried out a systematic retrospective analysis of cases with sarcoidosis admitted in the last 38 years, using hospital databases. Results 50 patients with sarcoidosis were included in the study (75% women) The mean age at the onset of symptoms of sarcoidosis was 42.47 years [18-70]. The average time between onset of symptoms and diagnosis was 17.74 months with a range of [3-84].Renal involvement was observed in 17 patients (34%) and was revealing in 9 patients (18%). There were 9 women and 8 men with a sex ratio of 0.88. The tubulointerstitial nephropathy was the most common manifestation, found in 12 cases. Glomerular nephropathy and renal lithiasis were present respectively in 2 (4%) and 3 cases (6%). The tubulointerstitial nephropathy found in 12 patients (24%) was biologically characterized by low proteinuria and aseptic pyuria. The kidneys were functionning normally in 3 patients. Renal failure was noted in 9 cases. Advanced renal failure (clearance <10 ml/min) was noted in 3 cases.We have not noted hypertension in our patients. The hypercalcemia was associated with renal failure in 7 cases (77%). Renal biopsy was performed in 7 cases showing interstitial tuberculoid granuloma in 5 cases and an aspect of chronic interstitial nephropathy with interstitial lymphocytic infiltrate and tubular atrophy in 2 cases. Glomerular nephropathy was present in 2 cases. Microscopic hematuria was present in one case. Renal failure and hypertension were absent. We did not notice any disorder of phosphate and calcium assesments. Biopsy was performed in 2 cases showing a tuberculoid granuloma associated with extra-membranous glomerulonephritis in one case and a remote in the other. - The kidney stones were found in 3 cases. They were bilateral and unobtrusive in all cases. Recurrent kidney stones were noted in one case. Hypercalciuria and hypercalcemia were found respectively in 3 cases and 2 cases. Conclusions Several small series have suggested that renal involvement (as defined by either histologic changes in the kidney or a decline in renal function in the absence of a biopsy) occurs in approximately 35 to 50 percent of patients, even if, in most cases, the disease may be silent and undetected for many years or forever. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5756
Complications of methylene blue dye infiltration for sentinel lymph node biopsy in breast cancer.
Authors: N Piscatelli, S Crawford, A Larkin, Q Robert, R Layeequr Rahman
Journal: Cancer Research (2009)

Abstract Abstract #4140 Background: Isosulfan blue has proven invaluable for sentinel lymph node identification in breast cancer. However, an intermittent supply shortage of this agent over the last few years has led to alternative usage of methylene blue. Worldwide, methylene blue is traditionally viewed as a less expensive and safer equivalent to isosulfan, with few reports of significant side effects. Its increased usage has led to anecdotal reports of local skin reactions. This study serves to review the rate of local complications observed following subareolar infiltration of methylene blue for sentinel lymph node identification in breast cancer staging.&amp;#x2028; Material Methods: This is a retrospective review of prospectively collected data in a university based surgical oncology practice. Records of all patients undergoing sentinel lymph node biopsy for breast cancer between August, 2007 and April, 2008 were reviewed (the switch from Isosulfan to Methylene blue was made in August of 2007). Local complication of fat necrosis was recorded. Tumor stage, neoadjuvant therapy, volume and dilution of dye used were analysed for association with fat necrosis.&amp;#x2028; Results: One hundred and three patients underwent sentinel node biopsy for breast cancer during the study period. Seven (7%) patients developed fat necrosis at the site of injection. The rate of injection site fat necrosis is associated with the volume of methylene blue [0% for &amp;lt;3cc and 7.2% for &amp;gt; 3cc (p = 0.0071)]; there was no association with tumor stage [3.2% for stage &amp;lt;1, 13.1% for stage 2 and 0% for stage 3 (p=0.343)] and tumor type [7.3% for invasive ductal cancer, 8.3% for invasive lobular and 0% for in situ cancer (p=1.000)].&amp;#x2028; Discussion: While methylene blue has typically been viewed as an inert agent for sentinel node biopsy, our study documents a 7% rate of fat necrosis. This is clinically significant in terms of painful symptoms and also the work-up that it may necessitate as a new mass in a breast cancer patient which has suspicious appearance on traditional imaging studies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4140.
Abstract 4251: Evaluating novel targeted therapeutic agents in T-cell acute lymphoblastic leukemia using a zebrafish xenotransplantation model
Authors: Dale Corkery, Tugce B. Balci, Jason N. Berman, Graham Dellairee
Journal: Cancer Research (2012)

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy accounting for 25% of adult and 10-15% of pediatric ALL cases. The disease is characterized by infiltration of the bone marrow and peripheral blood with immature lymphoblasts bearing T-lineage markers. Although current multi-agent chemotherapy regimens have dramatically improved cancer outcomes, a significant proportion of T-ALL do not respond to therapy or relapse post therapy. Novel molecular-based treatment strategies are desperately needed to improve outcome and limit toxicity. Mutations that activate the NOTCH and PTEN/PI3K pathways are common in human T-ALL and may drive T-ALL cell proliferation. Gamma secretase inhibiting compounds that block NOTCH signaling have been effective against subtypes of T-ALL with NOTCH mutations but have had limited success in clinical trials due to severe gastrointestinal toxicity, and problems with drug resistance. Recently, inhibition of the PI3K pathway (including the downstream kinase AKT) have shown efficacy in vitro and in pre-clinical animal models. We have recently developed a novel human cancer xenotransplantation (XT) animal model using the zebrafish, which can be used for high throughput pre-clinical testing of human tumour-drug interactions for both leukemia and solid tumours (Corkery et al., 2011 Brit. J. Haemat.). Using the zebrafish XT model we are studying a number of compounds that specifically target the PI3K/AKT kinase pathway for ability to inhibit T-ALL cell proliferation in vivo. Preliminary proof-of-principal studies have shown that we can successfully engraft the PTEN-deficient T-ALL leukemia Jurkat cell line in zebrafish embryos. In agreement with published data, we have shown that treating Jurkat transplanted embryos with the mTOR inhibitor rapamycin inhibits in vivo proliferation of the human leukemia cells line by 60%, while, by contrast, the AKT inhibitor triciribine does not significantly inhibit proliferation. We have also successfully transplanted primary bone marrow from pediatric T-ALL patients which go on to engraft in the zebrafish embryos. The ability to screen novel compounds against a panel of primary patient samples could provide a more accurate means of predicting the efficacy of said compounds across heterogeneous patient populations. We are now employing the zebrafish XT model to study the effects of novel PI3K/AKT kinase inhibition on the proliferation of a panel of human T-ALL cell lines and primary patient samples as a means of rapidly selecting new drug candidates to move forward into the rodent model and Phase I clinical trials. 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 4251. doi:1538-7445.AM2012-4251
Abstract 1527: Hepatocyte growth factor modulates adhesion of ovarian cancer cells to the peritoneum mesothelium through p70 S6 kinase
Authors: Carman K.M Ip, Susan Yung, Tak-Mao Chan, Alice S.T. Wong
Journal: Cancer Research (2011)

Abstract Ovarian cancer has the highest mortality of all gynecological cancers. These deaths are mainly due to the highly metastatic characteristic with already widespread peritoneal dissemination and malignant ascites at the time of diagnosis. However the molecular mechanisms that regulate ovarian cancer progression are poorly understood. A key step in this process is the adhesion of ovarian cancer cells to the peritoneal mesothelium. Hepatocyte growth factor (HGF) is present at high concentrations in ovarian cancer ascitic fluid. We show here a role for HGF signaling in the regulation of the peritoneal adhesion of ovarian cancer cells. HGF increased binding of ovarian cancer cells to peritoneal extracellular matrix (ECM) proteins fibronectin and laminin and their receptors α5, α6, and β1 integrin expression. Blockade of HGF resulted in reduced attachment of ovarian cancer cells to these ECM proteins, with a concomitant reduction of α5, α6, and β1 integrin expression, confirming that the effect was HGF specific. Similarly, the peritoneal ECM adhesion could be reversed by neutralizing antibodies to α5, α6, and β1 integrin. The adhesive phenotype and integrin expression activated by HGF could be blocked by specific inhibition of p70 S6 kinase (p70S6K) using short hairpin RNA or small molecule inhibitor, suggesting that HGF transmits the signal through p70S6K. Importantly, it also inhibited adhesion to primary human peritoneal mesothelial cells. These results identify a potential novel mechanism for HGF-induced peritoneal adhesion, which is mediated through p70S6K through regulation of α5, α6, and β1 integrin (This work is supported by the Hong Kong Research Grants Council Grant HKU7599/05M to A.S.T.W.). 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 1527. doi:10.1158/1538-7445.AM2011-1527
Abstract 4809: Targeting integrin function in melanoma cells using vinculin activators results in enhances chemosensitivity
Authors: Elke S. Nelson, Andrew Folkmann, Kris DeMali
Journal: Cancer Research (2010)

Abstract Current therapies aimed at manipulating cell adhesion work by modulating interactions between integrins (the major adhesion receptors on the cell surface) and components of the extracellular matrix. However, a complete gain or loss of integrin function can lead to mechanism-based toxicities. An attractive alternative approach is to manipulate integrin-associated proteins. Vinculin, an actin binding protein that is recruited to the cytoplasmic tail of integrin β1, is a good candidate protein for such an approach, as it regulates the strength and lifetime of such complexes. Here we have investigated the effect that a vinculin activating peptide (VAP) has on integrin-mediated adhesion. In HeLa cells and mouse embryonic fibroblasts, VAP increased integrin-mediated signaling, as well as adhesion to fibronectin and collagen, in an integrin- and vinculin-dependent manner. These regulatory effects of VAP were dependent on the peptide's ability to bind to an amphipathic α-helix in the vinculin head; substitution of an isoleucine for alanine at position 50 within this region of vinculin abolished VAP's ability to enhance adhesion. In melanoma cells, VAP likewise increased integrin-mediated cell adhesion, and increased the cells’ sensitivity to cancer chemotherapeutics, suggesting that it might serve as an effective therapeutic agent. Overall, our findings demonstrate that integrin function can be manipulated by targeting the regulation of proteins that associate with the cytoplasmic domains of the integrins, and suggest that small molecules capable of such regulation may be employed as effective adjuvants to chemotherapy for melanoma. These findings lay the foundation for the development of a new class of therapeutics that act by regulating integrin-associated proteins. 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 4809.
Nerve Growth Factor and Pain
Authors: John N. Wood
Journal: New England Journal of Medicine (2010)

Osteoarthritis, a common, painful condition, occurs at a rate of 1% per year and affects the majority of people who are over 55 years of age. In a proof-of-concept, phase 2 study in this issue of the Journal, Lane and colleagues1 report that blocking the activity of nerve growth factor with a neutralizing humanized monoclonal antibody (tanezumab) can relieve pain from osteoarthritis. This finding raises the possibility of using neutralizing antibodies therapeutically, similar to the use of antibodies against tumor necrosis factor (TNF) in patients with rheumatoid arthritis. However, recent results of a phase 3 study, mentioned by Lane et . . .
Correlation Between Dna Copy Number and Clinicopathological Features: Biomarker Search Using Genome-Wide Analysis of Dna Copy Number Alterations in a Phase III Study of Postoperative Adjuvant Chemotherapy for Stage III Colon Cancer (Acts-Cc Trial)
Authors: T. Ishikawa, H. Uetake, K. Murotani, T. Kobunai, M. Ishiguro, S. Matsui, K. Sugihara
Journal: Annals of Oncology (2014)
GPs must continue to provide some non-core services NHS trusts could save (pounds sterling)150m by improving supplies management Level of provision for long term care must be defined GMC advises doctors on intimate examinations GMC wants to improve reporting of conduct cases Open information is a closed book
Authors: L. Beecham
Journal: BMJ (1996)

# GPs must continue to provide some non-core services {#article-title-2}

General practitioners must continue to provide some non-core services until there have been national negotiations to change their terms and conditions of service. Failure to do so would put doctors in breach of their terms of service.

The General Medical Services Committee's document, Core Services: Taking the Initiative, which was sent out to all general practitioners this week, identifies the services which should be provided by every doctor or practice (26 October, p1032). Among the non-core services there are some which general practitioners are still obliged to provide under their terms of service. The GMSC hopes to negotiate with the government to remove this obligation so that in the future these services may be contracted for separately and paid for outside intended average net remuneration.

They hope to make the following changes: removing the requirement to provide certificates for social security purposes; allowing a charge for all travel immunisations; abolishing the requirement to offer annual health checks to the over 75s; and removing the training of general practitioner registrars, intrapartum care, minor surgery, child health surveillance, and dispensing (other than of personally administered items) from core services and average intended net remuneration.

The medical care of highly dependent patients living in the community, often in nursing or residential homes, is another non-core service. The chairman of the GMSC, Dr Ian Bogle, said: “In the past these patients would have been in long stay hospital beds and so would have had resident doctors and specialised nursing care …
LOW DENSITY LIPOPROTEIN CHOLESTEROL (LDL-C) VALUES AMONG HIGH CARDIOVASCULAR RISK PATIENTS IN A REAL WORLD POPULATION
Authors: Rajeshwari S. Punekar, Kathleen Fox, Akshara Richhariya, Shravanthi Gandra, Mark Cziraky, Carly Paoli, Peter Toth
Journal: Journal of the American College of Cardiology (2016)