tbuckley/cabot-search huggingface dataset:
Abstract P5-01-11: Monitoring Primary Medical Therapy with Three-Dimensional Optical Mammography
Authors: LC Enfield, G Cantanhede, AP Gibson, JC Hebden, M Douek, A. Purushotham
Journal: Cancer Research (2010)

Abstract Background: Optical tomography is a functional imaging technique using near-infrared (NIR) light to produce three-dimensional (3D) breast images of tissue oxygen saturation and haemoglobin concentration. The advantages include the lack of ionising radiation and the quantative physiological information obtained. With increasing use of primary medical therapy, there is a need for a non-invasive functional imaging tool to evaluate response to treatment. Optical tomography was evaluated for monitoring early response to treatment. Materials and Methods: Women with newly diagnosed breast cancer, suitable for primary medical therapy, were recruited. Changes in physiological and optical properties within the tumour were evaluated during the course of neoadjuvant chemotherapy or endocrine therapy. For patient undergoing neoadjuvant chemotherapy, optical imaging wasperformed prior to treatment, at 2 week, halfway through and on completion of chemotherapy. Images of light absorption and scatter, haemoglobin concentration ([HbT]) and oxygenation (SO2) are produced. Results: To date, ten women have been recruited to the project, and are being scanned throughout the course of their treatment. Five women are undergoing neoadjuvant chemotherapy and five are undergoing endocrine treatment prior to surgery. Nine women have been scanned more than once with five women scanned three times, and one has completed the protocol. The contrast between the tumour and the background tissue was calculated and any changes in ROI contrast and physiological parameters tracked. Initial scans show an increase in [HbT] and a decrease in SO2 in the region of the tumour. Changes in contrast and [HbT] in the tumour ROI can be seen early in treatment. A 45 year old patient was being treated with neoadjuvant taxane chemotherapy for a 26x21x34 mm Grade 2 carcinoma. The tumour [HbT] was 43.95±4.20 μM prior to treatment, falling to 25.6±6.43 μM by Week 9 and 19.19±0.36 μM by Week 18 of treatment and 23.5871± 1.6616 at the final scan. Background tissue [HbT] remained constant at ∼21±4 μM. Biopsy results classified the patient as a good responder to treatment. Initial data from other patients show changes in [HbT] at the two week scan, some showing a decrease and others show an increase in measured [HbT]. Future work will include correlation of optical data with clinical MRI findings, biopsy results and clinical outcome. Discussion: Optical imaging of the breast is feasible during primary medical therapy and can be used to assess response to treatment. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-01-11.
Time of Onset of Non-Insulin-Dependent Diabetes Mellitus and Genetic Variation in the β<sub>3</sub>-Adrenergic–Receptor Gene
Authors: Jeremy Walston, Kristi Silver, Clifton Bogardus, William C. Knowler, Francesco S. Celi, Sharon Austin, Brian Manning, A. Donny Strosberg, Michael P. Stern, Nina Raben, John D. Sorkin, Jesse Roth, Alan R. Shuldiner
Journal: New England Journal of Medicine (1995)

The β3-adrenergic receptor is expressed in visceral adipose tissue and is thought to contribute to the regulation of the resting metabolic rate and lipolysis.
Reduced Incidence of Preterm Delivery with Metronidazole and Erythromycin in Women with Bacterial Vaginosis
Authors: John C. Hauth, Robert L. Goldenberg, William W. Andrews, Mary B. DuBard, Rachel L. Copper
Journal: New England Journal of Medicine (1995)

Pregnant women with bacterial vaginosis may be at increased risk for preterm delivery. We investigated whether treatment with metronidazole and erythromycin during the second trimester would lower the incidence of delivery before 37 weeks' gestation.
The Role of Tc-99m (V) DMSA Scintigraphy in the Evaluation of Superscan on Bone Scintigraphy
Authors: D Yüksel, S Ilgan, N Arslan, O Uğur, E Oztürk, H Bayhan
Journal: Clinical Nuclear Medicine (2000)

This study evaluated the biodistribution of Tc-99m (V) DMSA in patients with superscans on bone imaging and defined its role in differentiating the underlying cause.Nine patients (five with metastatic and four with metabolic bone disease) with classical superscans were entered into the study. All patients had the necessary radiologic and biochemical studies and a final diagnosis was reached accordingly. Tc-99m (V) DMSA scintigraphy was performed 1 week after Tc-99m MDP whole-body bone imaging.In four of five patients with widespread skeletal metastases, Tc-99m (V) DMSA scan showed diffusely increased bone uptake. In the remaining patient, the Tc-99m (V) DMSA scan showed a normal distribution pattern. All patients with metabolic bone disease had increased bone uptake on Tc-99m (V) DMSA scans.Tc-99m (V) DMSA shows increased bone uptake in patients having a superscan appearance in metastatic or metabolic bone disease. Tc-99m (V) DMSA imaging may play a role in the evaluation of patients with equivocal bone scan findings for a superscan.
Endoscopic closure of an iatrogenic duodenal perforation: a novel technique using endoclips, endoloop, and fibrin glue
Authors: J. Samarasena, Y. Nakai, D. Park, T. Iwashita, K. Chang
Journal: Endoscopy (2012)

An 80-year-old woman with a flat duodenal tubulovillous adenoma presented for endoscopic mucosal resection (EMR). This lesion had received treatment with EMR and Nd:YAG laser in the past. The lesion was located in the proximal second portion of duodenum (D2), measured approximately 2 cm, and was half-circumferential from the 12-o'clock to the 6-o'clock position.
Abstract 4855: KLLN, which shares a bidirectional promoter with PTEN, is an AR-regulated tumor suppressor, and induces p53-dependent and -independent apoptosis in breast cancer
Authors: Yu Wang, Xin He, Charis Eng
Journal: Cancer Research (2012)

Abstract 70% of breast cancer patients are diagnosed after menopause where the ovaries cease androgen production. Maintaining functional androgen receptor (AR) has been reported to correlate with good prognosis and better survival among breast cancer patients. We and others have shown that AR inhibits proliferation and induces apoptosis in breast cancer cells. However, the mechanism of AR's anti-tumor effect in breast cancer is still not fully understood. KLLN is a newly identified gene whose function has never been studied in tumorigenesis. KLLN and tumor suppressor gene PTEN, both located in 10q23.31, share the same promoter region but are transcribed in opposite directions. To perform in silico comparisons of KLLN expression between normal breast and breast cancer tissues, we selected 56 normal breast and 1170 tumor tissues from patients without exposure to any treatment using publicly available whole genome transcriptome datasets. We found that KLLN is significantly downregulated in breast carcinomas and that loss of KLLN expression is associated with increasing histological grade in invasive carcinomas. By using MCF-7 and MDA-MB-453 breast cancer cell lines as our models, we show that AR activates this bi-directional promoter, resulting in the upregulation of both KLLN and PTEN expression. For the first time, we identified KLLN as an AR-activated tumor suppressor, inhibiting breast cancer cell proliferation and suppressing tumor cell invasiveness in both cell lines. In MCF-7 cells, overexpression of KLLN directly activates TP53 expression as a transcription activator, accompanied by significant increase of PARP cleavage and apoptosis. We also found that KLLN could promote TP73 expression in both MCF-7 (p53-wildtype) and MDA-MB-453 (p53-null) cells at the transcriptional level, resulting in p53-independnt apoptosis. Therefore, we discovered a new pathway, which mediates AR-induced growth inhibition and apoptosis in breast cancer cells. Our study also indicates KLLN as a potential prognostic marker and novel therapy target for breast carcinomas. 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 4855. doi:1538-7445.AM2012-4855
THU0232 Trends in the Use of Methotrexate in Patients with Rheumatoid Arthritis Over the Last Three Decades
Authors: A. M. Bertoli, V. Barbá, I. Strusberg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Weekly low-dose MTX is now considered the anchor drug for the treatment of rheumatoid arthritis (RA) as improves both, short-term (disease activity) and long-term (radiographical progression, function and mortality rates) outcomes. <h3>Objectives</h3> To compare the probability of MTX utilization in patients with RA over three consecutive decades (80´s, 90´s y first decade of the 21st century) and to describe the variables associated with its use. <h3>Methods</h3> This was a retrospective analysis that included 1258 patients with RA (as per the 1987 ACR criteria) who were diagnosed between January 1980 and December 2009. The relationship between demographic (gender, age at first symptom and at diagnosis), clinical (date of diagnosis, diagnosis delay, presence of rheumatoid factor, sedimentation rate and joint erosions at diagnosis, extra-articular manifestations and follow-up time) and therapeutic (time to first time MTX) domains was examined. The cumulative rate of MTX utilization was estimated using the Kaplan-Meier method and the variables associated with its use analyzed with a Cox regression conditional model. Variables with a p value ≤ 0.05 were considered statistically significant. <h3>Results</h3> 1134 (91%) patients were ever treated with MTX and 680 (60%) reached doses ≥15 mg per week. Among those patients diagnosed during the 80´ (N= 211), 197 (93%) used MTX, during the 90´ (N= 426), 401 (94%) used MTX and during the first decade of this century (N= 610), 536 (88%) used MTX. The table below shows the cumulative rate of MTX utilization during the three decades (log rank test= 316.64; p &lt;0.001). <h3>Conclusions</h3> In this study, the cumulative rate of MTX utilization has largely increased over the last three decades, placing in evidence an earlier indication of this drug when treating patients with RA. These findings are in accordance with local and international guidelines for the treatment of RA that denote the need of an early and effective treatment of patients with this disease, being this drug a standard and non-expensive therapeutic intervention. <h3>Disclosure of Interest</h3> None Declared
Campaigners start legal action to stop closure of Leeds children's heart surgery unit
Authors: C. Dyer
Journal: BMJ (2012)

Campaigners fighting to save the children’s heart surgery unit at Leeds General Infirmary have launched legal action in the High Court over the decision to close it.

Leeds is one of three units facing the axe as part of a review of children’s paediatric cardiac surgery services in England, which concluded that services should be concentrated in fewer, more specialised centres.1

The action group Save Our Surgery has applied to the High Court for permission to seek a judicial review of the decision last July by the Joint …
US president announces own tobacco deal
Authors: T. Rutter
Journal: BMJ (1997)

The United States president, Bill Clinton, has announced his own plan for reducing the consumption of cigarettes, thereby rejecting the settlement that had been written by state attorneys general, industry representatives, and some public health advocates (28 June, p 1849).

Declaring that the “health of our people and especially the health of our children must be paramount in our thinking,” President Clinton emphasised that the primary goal was to require the tobacco industry to reduce significantly the number of young people who smoke. He has proposed raising the price of a …
A tunable delivery platform to provide local chemotherapy for pancreatic ductal adenocarcinoma
Authors: Laura Indolfi, Matteo Ligorio, David T. Ting, Kristina Xega, Abraham R. Tzafriri, Francesca Bersani, Nicola Aceto, Vishal Thapar, Bryan C. Fuchs, Vikram Deshpande, Aaron B. Baker, Cristina R. Ferrone, Daniel A. Haber, Robert Langer, Jeffrey W. Clark, Elazer R. Edelman
Journal: Biomaterials (2016)
1256 PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORg IS INVOLVED IN THE BENEFITS OF RETINOL IN STEATOTIC AND NON-STEATOTIC LIVERS UNDERGOING PARTIAL HEPATECTOMY UNDER ISCHEMIA–REPERFUSION
Authors: M. Elias-Miró, M. Massip-Salcedo, J. Raila, F. Schweigert, M. Mendes-Braz, F. Ramalho, M.B. Jiménez-Castro, A. Casillas- Ramírez, R. Bermudo, A. Rimola, J. Rod'es, C. Peralta
Journal: Journal of Hepatology (2013)
Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy
Authors: Carlos A. Morillo, Jose Antonio Marin-Neto, Alvaro Avezum, Sergio Sosa-Estani, Anis Rassi, Fernando Rosas, Erick Villena, Roberto Quiroz, Rina Bonilla, Constança Britto, Felipe Guhl, Elsa Velazquez, Laura Bonilla, Brandi Meeks, Purnima Rao-Melacini, Janice Pogue, Antonio Mattos, Janis Lazdins, Anis Rassi, Stuart J. Connolly, Salim Yusuf
Journal: New England Journal of Medicine (2015)

We conducted a prospective, multicenter, randomized study involving 2854 patients with Chagas' cardiomyopathy who received benznidazole or placebo for up to 80 days and were followed for a mean of 5.4 years. The primary outcome in the time-to-event analysis was the first event of any of the components of the composite outcome of death, resuscitated cardiac arrest, sustained ventricular tachycardia, insertion of a pacemaker or implantable cardioverter–defibrillator, cardiac transplantation, new heart failure, stroke, or other thromboembolic event.
Radon Exposure, IL-6 Promoter Variants, and Lung Squamous Cell Carcinoma in Former Uranium Miners
Authors: Shuguang Leng, Cynthia L. Thomas, Amanda M. Snider, Maria A. Picchi, Wenshu Chen, Derall G. Willis, Teara G. Carr, Jacek Krzeminski, Dhimant Desai, Amin Shantu, Yong Lin, Marty R. Jacobson, Steven A. Belinsky
Journal: Environmental Health Perspectives (2015)

Background:High radon exposure is a risk factor for squamous cell carcinoma, a major lung cancer histology observed in former uranium miners. Radon exposure can cause oxidative stress, leading to pulmonary inflammation. Interleukin-6 (IL-6) is a pro-carcinogenic inflammatory cytokine that plays a pivotal role in lung cancer development.Objectives:We assessed whether single nucleotide polymorphisms (SNPs) in the IL6 promoter are associated with lung cancer in former uranium miners with high occupational exposure to radon gas.Methods:Genetic associations were assessed in a case–control study of former uranium miners (242 cases and 336 controls). A replication study was performed using data from the Gene Environment Association Studies (GENEVA) Genome Wide Association Study (GWAS) of Lung Cancer and Smoking. Functional relevance of the SNPs was characterized using in vitro approaches.Results:We found that rs1800797 was associated with squamous cell carcinoma in miners and with a shorter time between the midpoint of the period of substantial exposure and diagnosis among the cases. Furthermore, rs1800797 was also associated with lung cancer among never smokers in the GENEVA dataset. Functional studies identified that the risk allele was associated with increased basal IL-6 mRNA level and greater promoter activity. Furthermore, fibroblasts with the risk allele showed greater induction of IL-6 secretion by hydrogen peroxide or benzo[a]pyrene diolepoxide treatments.Conclusions:An IL6 promoter variant was associated with lung cancer in uranium miners and never smokers in two external study populations. The associations are strongly supported by the functional relevance that the IL6 promoter SNP affects basal expression and carcinogen-induced IL-6 secretion.Citation:Leng S, Thomas CL, Snider AM, Picchi MA, Chen W, Willis DG, Carr TG, Krzeminski J, Desai D, Shantu A, Lin Y, Jacobson MR, Belinsky SA. 2016. Radon exposure, IL-6 promoter variants, and lung squamous cell carcinoma in former uranium miners. Environ Health Perspect 124:445–451; http://dx.doi.org/10.1289/ehp.1409437
Abstract 1942: Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g.
Authors: Junius Salendo, Melanie Spitzner, Frank Kramer, Peter Jo, Tim Beissbarth, Hendrik A. Wolff, Heinz Becker, Mathias Dobbelstein, Michael Ghadimi, Marian Grade, Jochen Gaedcke
Journal: Cancer Research (2013)

Abstract Background: Preoperative 5-fluorouracil-based chemoradiotherapy is the standard treatment for locally advanced rectal carcinomas. However, the individual tumor response is very heterogeneous, ranging from complete resistance to regression. Therefore, ascertaining the role of microRNAs (miRNAs) in therapy response as well as identification certain miRNA as predictive markers for response remains very crucial. Materials/Methods: Using an in-vitro model of 12 colorectal cancer cell lines, we compare the pretherapeutic miRNA expression profiles of these cell lines with the previously assessed radiochemoresistance of each cell lines, respectively. Differences in treatment sensitivity of the cell lines and miRNAs expression were then correlated. Colony formation assays in two independent cell lines were used for the functional validation in-vitro. To asses the clinical applicability miRNA expressions of 64 pretherapeutic biopsies from patients with locally advanced cancer treated with 5-FU based RCT were analyzed. Results: We identified 36 miRNAs whose expression levels correlated significantly with the heterogeneous sensitivity of the cell lines to chemoradiotherapy (p &amp;lt; 0.05). Microarray measurements were independently validated using semi-quantitative real-time PCR. miR-320, miR-132, miR-429, miR-224 and let-7g were then functionally validated in-vitro by transfection of corresponding miRNA mimics. Analysis of miRNA expression in rectal cancer patients biopsies showed high correlation of miR-224 expression with poor prognosis (p=0.043). Conclusion: We identified 36 miRNAs that associated with response to chemoradiotherapy. Functional validations of miR-320, miR-132, miR-429, miR-224 and let-7g have been undertaken in-vitro underlining the regulatory effects of the specific miRNAs. Further miR-224 found out to be significantly correlated to Disease Free Survival (DFS). An independent prospective validation in a clinical trial will be performed. Citation Format: Junius Salendo, Melanie Spitzner, Frank Kramer, Peter Jo, Tim Beissbarth, Hendrik A. Wolff, Heinz Becker, Mathias Dobbelstein, Michael Ghadimi, Marian Grade, Jochen Gaedcke. Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g. [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 1942. doi:10.1158/1538-7445.AM2013-1942
P333HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy
Authors: A Milano, AMC Vermeer, ER Lodder, J Barc, AO Verkerk, IAC Van Der Bilt, Y Pinto, I Christiaans, AA Wilde, CR Bezzina
Journal: Cardiovascular Research (2014)

Objective: The aim of this study was to identify the genetic defect underlying the combined clinical presentation of bradycardia and left ventricular noncompaction cardiomyopathy (LVNC), hypothesizing that these two clinical abnormalities have a common genetic cause.
SP0191 How to Deal with Methodology in Orphan Diseases
Authors: N. Ruperto
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Orphan diseases are an heterogeneous group of 6000 disorders which span from rare cancers to genetic syndromes, to auto-immune diseases. The current definition identify as rare disease conditions with a prevalence less that 1:2000 (1999 Orphan Drug regulation); the definition of ultra rare refers to a prevalence of less than 1:1,000,000. More than 400 orphan diseases are currently treated with a drug which has a specific indication; 15 new orphan indication have been designated in 2012. In the Orphanet database (www.orphanet.org) there are 488 ongoing clinical trials registered for 304 rare diseases or group of rare diseases (most of whom are trials in cancers). The majority of the trials are driven by pharmaceutical companies with about 25% having a public sponsor. A recent methodology workshop by the European Clinical Research Infrastructure Network (ECRIN) was dedicated to issue recommendations for performing clinical trials in rare diseases. The recommendations state to apply standard statistical methodologies, with proper sample size calculations, for rare diseases in general. For ultra rare diseases there was a suggestion to move toward adaptive licensing with re-assessment of the findings every 3 to 5 years with a systemic data collections. To enlarge enrollment international networking should be the standard despite the several difficulties now encountered with multi-national ethics committee approval, insurances, funding etc especially with studies conducted by academia. Appropriate endpoints should be applied with surrogate markers to be used only when appropriately justified and possibly validated. Registries lead by patient's organization/academia/industries possibly, linked together, should be the ideal situation for data collection. This lecture will describe the current challenges for running clinical trials in rare diseases in rheumatology. <h3>Disclosure of Interest</h3> None Declared
Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency
Authors: Waleed Al-Herz, Julia I. Chu, Jet van der Spek, Raj Raghupathy, Michel J. Massaad, Sevgi Keles, Catherine M. Biggs, Lucinda Cockerton, Janet Chou, Ghassan Dbaibo, Scott A. Elisofon, Rima Hanna-Wakim, Heung Bae Kim, Leslie E. Lehmann, Douglas R. McDonald, Luigi D. Notarangelo, Paul Veys, Talal A. Chatila, Raif S. Geha, H. Bobby Gaspar, Sung-Yun Pai
Journal: Journal of Allergy and Clinical Immunology (2016)