tbuckley/cabot-search huggingface dataset:
Clinical implementation of intensity modulated arc therapy (IMAT) for rectal cancer
Authors: W. Duthoy, W. De Gersem, T. Boterberg, P. Smeets, M. Peeters, W. De Neve
Journal: Journal of Clinical Oncology (2004)

3685 Background: In rectal cancer, radiotherapy decreases local recurrence rates and improves survival. Small bowel (SB) radiation toxicity is strongly influenced by the volume of irradiated SB. Intensity modulation (IM) could avoid the irradiation of large volumes of SB. A planning strategy for intensity modulated arc therapy (IMAT) was developed and clinically implemented. We report on the planning results of the first seven patients treated with IMAT. Methods: Seven patients consented to participate to the study. Delineation of target volumes was done on a fused CT and MRI, with the help of a radiologist. For the IMAT plan, machine states (MS) were generated every 8 degrees using an anatomy-based segmentation tool. Adjacent MSs of the same class were stratified in arcs. The optimization of the arcs was done by weight optimization and leaf position optimization. Arcs with a constant angular delivery rate were extracted semi-automatically. The IMRT plans, which were made for comparison, used seven incidences. Segmentation and optimization tools were identical as for IMAT. The 3D plans used three conventional - partially wedged - beams (one posterior and two lateral fields), of which the outlines were shaped to the planning target volume (PTV). All plans were normalized to a median dose of 45 Gy in the PTV. Results: The IMAT plan resulted in 3–6 arcs and a mean delivery time of 6.3 minutes. The minimal dose in the PTV was not significantly different in any comparison between 3D, IMRT and IMAT plans (42, 41 and 41 Gy, respectively). Dose inhomogeneity in the PTV was highest for the IMAT plans (14.1%) and lowest for the 3D plans (9.9%). The volume of SB receiving more than 90% of the prescribed dose was 19% for 3D, 10% for IMRT and 7% for IMAT. Mean dose to the SB was significantly lower for the IMRT (12.1 Gy) and IMAT plans (12.4 Gy) than for the 3D plans (17.0 Gy). The volume of SB receiving a specified dose was lower for the IM plans when compared to the 3D plans. IMAT resulted in the lowest SB volume irradiated to doses between 20 and 45 Gy. Conclusions: IMAT is deliverable within a standard clinical time slot, and results in a significantly lower dose to the SB, without compromising the dose to the PTV. No significant financial relationships to disclose.
AB0269 Joint Involvement and Pattern of Deformity and Its Relationship with Seropositivity in Rheumatoid Arthritis
Authors: M.M. Rahman, S.M. Samsuzzaman, S.M. Choudhury
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and affects approximately 0.5-1% of the global population. Early diagnosis and treatment have been advocated to prevent structural damage and eventual long term disability. Bangladesh is a densely populated developing country where majority of the patients, suffering from RA, are being treated by general practitioners, orthopedists and internists because the country has very small number of rheumatologists <h3>Objectives</h3> This study was conducted to see the joint involvement and the pattern of deformity and its relationship with seropositivity in patients with RA in Bangladesh. <h3>Methods</h3> The study was carried out in the Department of Medicine, Sir Salimullah Medical College and Mitford Hospital, Dhaka over a period of 9 months from October 2010 to June 2011. A total of 100 RA patients, fulfilling the 1987 American College of Rheumatology (ACR) classification criteria, were the study population. <h3>Results</h3> All patients had pain in bilateral metacarpophalengial joints. 93% patients had bilateral tarsal and metatarsophalengial joint pain. Bilateral wrist pain and ankle pain were present in 90% of cases. Over 40% complained of pain in both elbow joints while 65% had pain in both knee joints. Swelling of the joints was found in small joints of the hands (98%) and foot (86%), in wrist (85%) ankle (80%) and knee joints (65%) on both sides. Elbow joint swelling was not frequently seen (20%). Joint deformity was found in 63% of cases. Swan-neck deformity in index finger was present in 16% cases, in middle finger in 46% and in ring finger in 38.1% of cases. The boutonniere deformity of middle finger and the Z-deformity of thumb were detected in 7.9 and 4.8% respectively. The mean duration of swan neck, boutonniere and Z-deformity were 22.4±5.7, 15.6±5.8 and 6.0±2.1 months respectively. 9% patients exhibited claw deformity of foot where the mean duration was 3 months. 46% of the patients had deformity of both wrist joints. The mean durations of wrist and elbow deformities were 51.4±6.7 and 12.0±4.5 months respectively. Hand deformity was significantly higher in patients (79.2%) with positive anti-cyclic citrullinated peptide antibody (anti-CCP antibody) when compared to patients with negative anti-CCP antibody (p&lt;0.001). Similarly, wrist joint deformity tend to have higher affinity for positive anti-CCP antibody (p=0.036). Deformities involving hand and wrist joints were more associated with positive RA tests (p&lt;0.001 and p=0.048 respectively). <h3>Conclusions</h3> RA patients with hand and wrist joint deformities have significantly higher tendency to be seropositive (anti-CCP antibody and RA positive). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4472
P121 Speech And Language Therapy In Pulmonary Rehabilitation: The Implication Of Education Sessions On Dysphagia Management
Authors: S. Lillie, J. Haines, A. Vyas, S. Fowler
Journal: Thorax (2014)

<h3>Introduction</h3> Pulmonary rehabilitation (PR) programs use multidisciplinary teams to optimise physical and social functioning of patients with chronic respiratory impairment. Such patients demonstrate an increased prevalence of oropharyngeal dysphagia as a consequence of impaired co-ordination between respiration and swallowing function. Often patients will not be aware of the warning signs of dysphagia and unfortunately will not be seen by a speech and language therapist until they are admitted to hospital. We report the outcomes of a pilot scheme whereby such patients underwent education, assessment and treatment for dysphagia as part of their PR programme.. <h3>Methods</h3> The pilot scheme ran between June 2013 and May 2014. Intervention consisted of: (1) a one hour group education session on the signs, symptoms and risks of dysphagia; (2) screening for oropharyngeal dysphagia; and (3) individual outpatient management in Airways Clinic. The majority of patients attending the education sessions had a diagnosis of Chronic Obstructive Pulmonary Disease (COPD). <h3>Results</h3> The education programme was delivered to 72 patients, and resulted in a significant improvement in dysphagia knowledge. The average score pre education was 3/11 and post education was 8/11. Fourteen patients (19%) exhibited or reported symptoms of dysphagia. Of these two patients were overtly aspirating and required food/fluid modification and seven patient’s required instrumental assessment in the form of fibre endoscopic evaluation of swallowing (FEES). During FEES, three patients showed penetration of food/ fluids and were at risk of silent aspiration. These patients attended for further SLT where diet/ fluids were modified, posture was assessed and dysphagia therapy was introduced. <h3>Conclusions</h3> Dysphagia education and management of patients in PR can contribute the early identification, patient awareness and self-management of dysphagia. We have confirmed that undiagnosed but clinically important dysphagia is present in patients undergoing PR. We are investigating whether improved dysphagia knowledge and early identification of dysphagia symptoms leads to reduced exacerbations and improved quality of life.
Adenoviruses as Gene-Delivery Vehicles
Authors: J M Wilson
Journal: New England Journal of Medicine (1996)

For gene therapy to realize its clinical potential, there must be efficient and safe strategies of delivering therapeutic genes to somatic cells in vivo. Perhaps this problem simply represents a special case of drug delivery in which the therapeutic gene constitutes the drug. But the relevance of traditional drug development to technological developments in gene therapy is questionable. Recombinant genes that can independently express a therapeutic RNA or protein are extraordinarily large and polar molecules — 10,000 times larger than traditional pharmaceutical agents. Moreover, the administration of genes as therapy requires vehicles —so-called vectors — that encapsulate the gene and . . .
A Clinical Trial of Immunosuppressive Therapy for Myocarditis
Authors: Jay W. Mason, John B. O'Connell, Ahvie Herskowitz, Noel R. Rose, Bruce M. McManus, Margaret E. Billingham, Thomas E. Moon
Journal: New England Journal of Medicine (1995)

Myocarditis is a serious disorder, and treatment options are limited. This trial was designed to determine whether immunosuppressive therapy improves left ventricular function in patients with myocarditis.
Case 6-2000
Authors: Richard L. Kradin, Eugene J. Mark
Journal: New England Journal of Medicine (2000)

Presentation of CaseA 20-year-old man was admitted to the hospital because of back pain and hemoptysis.The patient had been in excellent health until about two and a half months earlier, when pleuritic, right-sided posterior chest pain developed. About two weeks before admission, a paroxysmal dry cough developed, and several days before admission, he began to cough up small amounts of bright red blood without obvious sputum.One day before admission, he coughed up several hundred milliliters of blood. He was admitted to another hospital, where a bronchoscopic examination was reported to show pearl-like nodules in the trachea that . . .
Microenvironmental changes in breast tumor progression: genetic or epigenetic?.
Authors: K Polyak, M Hu, M Shipitsin
Journal: Cancer Research (2009)

Abstract Abstract #PD-1 Increasing evidence suggests that changes in the cellular microenvironment contribute to tumorigenesis, but the molecular basis of these alterations is not well understood. We have characterized molecular alterations that occur during breast tumor progression in each cell type that compose normal breast tissue and in situ (DCIS-ductal Carcinoma In Situ) and invasive breast carcinomas using SAGE (Serial Analysis of Gene Expression) for gene expression profiling, SNP (Single Nucleotide Polymorphism) arrays and array CGH (Comprehensive Genomic Hybridization) for analyzing genetic changes, and MSDK (Methylation Specific Digital Karyotyping) for the characterization of DNA methylation profiles. Using these approaches we determined that gene expression and epigenetic changes occur in all cell types during breast tumor progression, whereas clonally selected genetic alterations are limited to tumor epithelial cells. We also determined that dramatic changes occur in the normal to DCIS transition, while we were not able to identify distinct in situ and invasive carcinoma molecular signatures. These findings suggest that the progression of in situ to invasive carcinoma may be influenced by non-epithelial cells composing the microenvironment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr PD-1.
FRI0239 Decreased prevalence of anxiety and depression in rheumatoid arthritis patients following b cell-targeted biologic therapy
Authors: I. R. Gaisin, L. V. Ivanova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Evidence suggests rheumatoid arthritis (RA) confers an increased risk of psychological morbidity, particularly anxiety and depression, which may affect the subsequent management and treatment adherence.<sup>1,2</sup> Few studies have studied psychological factors over time in RA patients.<sup>3</sup> <h3>Objectives</h3> We aimed to evaluate the prevalence of anxiety and depression in RA patients following rituximab treatment initiation and prolongation. <h3>Methods</h3> Biologics-naïve RA patients were followed up for 27 months after commencing and continuing rituximab therapy (1, 2, 3 standard courses). Anxiety and depression, and health-related quality of life (HRQoL) were assessed at baseline, 3, 15 and 27 months using the Hospital Anxiety and Depression Scale (HADS) and the Short Form (SF-36 v.1) Health Survey questionnaire, respectively. <h3>Results</h3> 86 patients [mean (SD) age 49.2 (9.3) years, 76 women; median (IQR) DAS28 5.64 (3.92–8.42); median (IQR) HAQ 1.85 (1.0–3.5)] were recruited. Median anxiety and depression scores decreased significantly between baseline and 3 months (p&lt;0.001) and remained decreased over the 27-month period. The prevalence of depression cases decreased twice from baseline to 27 months (66.3% to 30.0%), as did the prevalence of anxiety (79.1% to 40.0%). Patients reported poor baseline HRQoL. SF-36 v.1 domain scores substantially raised after 15 months. <h3>Conclusions</h3> Anxiety and depression levels decrease significantly following commencement and continuity of rituximab. B cell-directed therapy for patients with RA helps achieve remission of both anxiety and depression, and improves health-related quality of life. <h3>References</h3> McWilliams LA, Goodvin RD, Cox BJ. Depression and anxiety associated with three pain conditions: results from a nationally representative sample. <i>Pain</i> 2004;111:77–83. Garcia-Cebrian A, Gandhi P, Demyttenaere K et al. The association of depression and painful physical symptoms: a review of the European literature. <i>Eur Psychiatry</i> 2006;21:379–388. Overman CL, Bossema ER, van Middendorp H et al. The prospective association between psychological distress and disease activity in rheumatoid arthritis: a multilevel regression analysis. <i>Ann Rheum Dis</i> 2012;71:192–197. <b>Disclosure of Interest</b>: None Declared
Abstract LB-162: DNA-damage foci persistence and accelerated senescence as determinants of radiosensitization by glycolysis inhibitors
Authors: Elena V. Efimova, Edwardine Labay, Helena J. Mauceri, Thomas E. Darga, Olesya A. Ulanovskaya, Sergey A. Kozmin, Ralph R. Weichselbaum, Stephen J. Kron
Journal: Cancer Research (2012)

Abstract One of the most striking characteristics of cancer cells is their altered glucose metabolism. Many cancer cells display a dramatic elevation in glucose utilization, independent of the availability of oxygen or the activity of oxidative phosphorylation. Cancers often display the Warburg effect, wherein glycolysis drives fermentation of pyruvate to lactate even under aerobic conditions. Aerobic glycolysis has been widely investigated and it is now considered a metabolic hallmark of transformation and a key driver for cancer cell proliferation, malignancy, metastasis, and therapeutic resistance. En route to cancer, pre-malignant cancer cells have to overcome cellular senescence which is recognized as a barrier for tumorigenesis. Recent data link both replicative and accelerated senescence to persistent DNA damage signals that arise from domains of modified chromatin at sites of un-repairable double strand breaks. Our prior work has established the kinetics of resolution of these chromatin domains, dubbed ionizing radiation induced foci (IRIF), and resulting effects on accelerated senescence as determinants of radiation sensitivity and as a target that can sensitize cancer cells to genotoxic therapy. To obtain probes that impinge on the DNA damage response and senescence, we developed a cell based assay for high throughput, high content screening based on the detection of IRIF persistence. Screening over 2500 drugs, including natural products and drug-like compounds identified known DNA damaging agents as well as novel candidates. To gain mechanistic insight, we tested these “hits” in combination with the mitochondrial inhibitor antimycin A and discovered several that blocked ATP synthesis. Combining bona fide glycolytic pathway inhibitors with radiation enhanced IRIF persistence and accelerated senescence in vitro. The glucokinase inhibitor 2-DG increased IRIF persistence and senescence after irradiation of tumor xenografts. These data suggest a critical role for aerobic glycolysis in the proliferation and survival of cancer cells to prevent stress-induced premature senescence, specifically by blocking the formation of DNA damage foci and/or preventing their persistence. Rather than simply satisfying energy needs, aerobic glycolysis likely serves an important survival and immortalization function for cancer cells. As such, targeting the Warburg effect to promote cancer cell senescence appears to be an attractive strategy for therapeutic intervention, particularly in combination with genotoxic therapy. 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 LB-162. doi:1538-7445.AM2012-LB-162
Lactating Breast Producing a Mismatch on Ventilation Perfusion Lung Scan
Authors: ELIZABETH GALLEGOS, HELENA BALON
Journal: Clinical Nuclear Medicine (1996)

The authors present interesting pulmonary ventilation perfusion images in a postpartum lactating patient. The breasts are visualized due to Tc-99m DTPA uptake after inhalation for a ventilation study. It is known that iodide and pertechnetate concentrate in the breast tissue. Other radiopharmaceuticals, such as Se-75 methionine, Ga-67 citrate, In-111 leukocytes, Cr-51 EDTA, and P-32 phosphate also have been reported to concentrate in mammary tissue. Although usually higher in premenopausal women, the degree of concentration depends on the amount of fat and glandular tissue and is most pronounced during lactation.
IMPACT OF HEART FAILURE WITH PRESERVED EJECTION FRACTION ON THE OCCURENCE OF ISCHEMIC STROKE IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Sun-Joo Jang, Min-Seok Kim, Hee-Jung Park, Min Soo Cho, Duk-Hyun Kang, Jae-Kwan Song, Seong-Wook Park, Seung-Jung Park, Jae-Joong Kim
Journal: Journal of the American College of Cardiology (2012)
Abstract 1131: Differential induction of c-fms promoters by TGFβ in cervical cancer and macrophage cell lines
Authors: Nameer B. Kirma, Manonmani Ganapathy, Naveen K. Krishnegowda, Elizabeth M. De La Garza, Rajeshwar R. Tekmal
Journal: Cancer Research (2011)

Abstract Cervical cancer is the second most common gynecological malignancy in the world. An expected 12,200 total new diagnosed cases were estimated by the American Cancer Society for 2010 (Cancer Facts and Figures, 2010). Human papillomavirus infection, a major cause for cervical cancer, results in a persistent and pathological inflammatory response, contributing to establishment of disease and malignant progression. Our previous studies have shown that inflammatory factors, like Cox2, tumor associated macrophages, and cytokines such as macrophage colony-stimulating factor (CSF-1) and transforming growth factor beta (TGFβ) are elevated in cervical carcinomas. The receptors for CSF-1 (encoded by the c-fms oncogene) and TGFβ were also elevated in cervical carcinomas compared to normal cervical tissue. Both CSF-1 and c-fms have been implicated in aggressive gynecological malignancies, including cervical cancer. CSF-1/c-fms signaling is involved in proliferation, differentiation and recruitment of macrophages as well as cancer cell growth. We have previously demonstrated that TGFβ induced the expression of c-fms mRNA in cervical cancer cell lines and macrophage cell line THP-1. Using flow cytometry in this study, we have confirmed induction of c-fms protein at the cell surface due to TGFβ treatment, suggesting that TGFβ may enhance CSF-1 signaling by inducing cell surface expression of its receptor. Our goal was to examine the mechanisms underlying the regulation of c-fms in macrophages, relevant leukocytes associated with inflammation and pro-malignant growth within the tumor microenvironment. Two promoters for the c-fms gene exist, promoter one driving expression in trophoblasts (trophoblast specific promoter) and promoter two driving expression in macrophages (macrophage specific promoter). Consistent with our previous findings, TGFβ induced c-fms expression via MAPK p38 mainly at the trophoblast specific promoter in cervical cancer cells, as shown by the use of the p38 inhibitor SB203580. Our data also suggest that Casein kinase 1 mediates c-fms expression via this promoter in cervical cancer cells. In the macrophage cell line THP-1, p38 mediated the expression of c-fms via both promoters, as demonstrated by using exon specific RT-PCR primer sets. The c-fms mRNA induced at the macrophage specific promoter is the major c-fms transcript in THP-1 cells and is likely to mainly contribute to c-fms expression in these cells. Understanding the regulation of c-fms in macrophages and cervical cancer cells may pave the way to targeting c-fms expression to interrupt aberrant CSF-1 signaling in cervical cancer. 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 1131. doi:10.1158/1538-7445.AM2011-1131
Abstract 3358: Acquired epithelial-mesenchymal transition synergizes with normal epithelial cells to induce hepatic metastases
Authors: Idoia G. Zubeldia, Anne-Marie Bleau, Carmen Gil-Puig, Fernando Vidal-Vanaclocha, Alfonso Calvo, Jon Lecanda
Journal: Cancer Research (2011)

Abstract Identification of the required hallmarks for the tumor cells to disseminate to the liver represents an important milestone to delay cancer progression, and consequently to avoid the harmful consequences for patients. Largely unknown, a myriad of cell properties seem to cooperate in a successful metastatic process and in the chemo-/radio- therapeutic resistance. Our aim is to define the intrinsic characteristics of tumor cells that may contribute to epithelial-mesenchymal transition (EMT) in early and late metastatic events. We previously observed that: i) metastatic cells reaching the liver microenvironment display cancer stem features associated with EMT and increased TGFβ1-signaling (Zubeldia et al. Proceedings AACR, 2010; 51, #2304); ii) hepatic secondary tumors are enriched with a subpopulation of cells with a distinctive Sca1+ phenotype and a concurrent increased expression of other cancer stem markers (Zubeldia et al. Proceedings MRS-AACR, 2010; #A105). First, we demonstrated the high tumorigenicity of these metastatic liver-derived cell lines after subcutaneous injection in nude mice, without obvious correlation with their origin regarding TGFβ1-signaling. However, as shown by bioluminescent imaging, some of the novel metastatic liver-derived cell sublines were unable to achieve metastases following intrasplenic injection in C57BL/6J mice. We also noted a differential efficiency of each clone in primary tumor formation in this experimental model. Importantly, we found that co-injection of these cells (isolated from liver metastases) with non transformed hepatocytes (AML12) resulted in a significant increase of metastasis formation. We show an important role of normal cells for metastatic spread in early steps of tumor formation, and suggest the protective activity that the untransformed epithelial cells may have throughout the metastatic progression. We will present the therapeutic implications of our findings for the clinical treatment of carcinomas. 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 3358. doi:10.1158/1538-7445.AM2011-3358