tbuckley/cabot-search huggingface dataset:
Abstract 661: Efficiency of the multivalent pseudopeptide nucant 6L in castration- and chemo-resistant prostate cancers
Authors: Damien Destouches, Julie Gostoli, Stéphane Terry, Jean-Paul Briand, Robert Zimmer, José Courty, Alexandre de la Taille, Francis Vacherot
Journal: Cancer Research (2011)

Abstract Introduction: Targeted therapies on advanced prostate cancer, resistant to castration and chemotherapy, offer significant hope for future treatments. NucAnt 6L (N6L) is a ligand of surface nucleolin. This protein is overexpressed at the cell surface of tumoral and endothelial cells, and is involved in tumor growth and associated angiogenesis. It has been demonstrated that N6L displays, in vitro and in vivo, a double anti-tumoral activity. It inhibits growth of various human tumor cell lines derived from mammary and colorectal carcinoma, melanoma, glioblastoma and lymphoma. In addition, it can compromise associated angiogenesis. In this context, N6L might be of value for therapeutic intervention. Previous studies have demonstrated drug's efficacy of this agent in prostate cancer cell lines. However, its effect on therapeutic resistant lines has yet to be documented. Using in vivo and in vitro models, the aim of this work is to evaluate N6L activity on castration and chemo-resistant prostate cancers. Methods: When maintained in medium deprived of androgens, androgen-responsive LNCaP cells undergo a “transdifferentiation” process giving rise to neuroendocrine (NE) like LNCaP cells which are resistant to androgen deprivation and chemotherapeutic agents such as docetaxel. Here, the anti-tumoral activity of N6L has been evaluated, in vitro, on human LNCaP-NE cells. Cell viability, as assessed by MTT test, and soft agar assays were performed at 72 hours after treatment with N6L (range of 0.1 to 100 µM). In vivo, anti-tumoral activity was then confirmed using VCaP ectopic xenografts into athymic nude mice, a condition that mimics clinical evolution of advanced prostate cancers in human. Mice bearing tumors of about 600 mm3 were castrated. Mice were treated with either vehicle or N6L at 10 mg/kg by the intraperitoneal route at different times of tumor growth. Tumors volumes were monitored at different time points using the caliper method. Results: N6L induces death of LNCaP-NE cells with a IC50 of 16.2 µM. These findings were supported by soft agar assays in which LNCaP-NE cells were found to be sensitive to N6L treatment whereas they were resistant to docetaxel. In vivo, N6L inhibits VCaP tumor growth at different stages of tumor progression, the castration-sensitive state and also the castration resistant state. Conclusions: N6L, which is currently in I/IIb phase of clinical trials, might represent a new targeted approach to treat advanced prostate cancers resistant to castration and chemotherapy. 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 661. doi:10.1158/1538-7445.AM2011-661
PTU-170 A comparison of the early quality of life outcomes between open and laparoscopic oesophagogastric resectional surgery
Authors: A Menon, S Tolofari, B Knight, J Stockton, J Vickers, L Formela, K Akhtar, S Senapati
Journal: Gut (2012)

<h3>Introduction</h3> There is a paucity of data directly comparing health related quality of life (HRQL) between laparoscopic and open oesophagogastric resections. This study aims to evaluate differences between these groups in the early postoperative period. <h3>Methods</h3> The European Organisation for Research and Treatment Quality of Life Questionnaire Core 30 (EORTC QLQ-30) was administered to 34 patients preoperatively, and 1 month following laparoscopic gastrectomy (n=6), open gastrectomy (n=8), open two-phase oesophagectomy (n=7), and two-phase oesophagectomy with laparoscopic gastric mobilisation (n=13). Mann–Whitney U tests were used to compare HRQL between open and laparoscopic resections, and related sample Wilcoxon signed rank tests were used to compare 1 month and preoperative HRQL. <h3>Results</h3> There was no significant difference in median preoperative functional and global HRQL between both the open and laparoscopic gastrectomy groups (10 vs 11, p=0.41; 11 vs 11, p=1.00), and between the open and laparoscopic-assisted oesophagectomy groups (18 vs 11, p=0.18; 10 vs 11, p=0.70). Functional HRQL worsened significantly at 1 month with both open gastrectomy (18 vs 10, p=0.01) and open oesophagectomy (18 vs 11, p=0.02), but not with laparoscopic gastrectomy (15 vs 11, p=0.11) and laparoscopic assisted-oesophagectomy (15 vs 18, p=0.81). Global HRQL was significantly worse at 1 month with open gastrectomy (7 vs 11, p=0.04), but not in the other groups. Global HRQL was also found to be significantly higher at 1 month in the laparoscopic assisted oesophagectomy group compared with open oesophagectomy (10 vs 8, p=0.03). <h3>Conclusion</h3> These results demonstrate significant differences in HRQL between open and laparoscopic oesophagogastric resections even at 1 month, which may indicate that the laparoscopic approach is associated with faster postoperative recovery. <h3>Competing interests</h3> None declared.
Recurrence of Thyroid Nodules after Surgical Removal in Patients Irradiated in Childhood for Benign Conditions
Authors: Leon Fogelfeld, Margaret B.T. Wiviott, Eileen Shore-Freedman, Michael Blend, Carlos Bekerman, Steven Pinsky, Arthur B. Schneider
Journal: New England Journal of Medicine (1989)

To determine the incidence of benign thyroid nodules and the risk factors for their recurrence after surgical removal, we followed 511 patients for 1 to 40.6 years (median, 11.2) after surgery for benign thyroid nodules arising after local irradiation for unrelated benign diseases in childhood. Recurrent thyroid nodules developed in 100 patients (19.5 percent). The risk of recurrence correlated inversely with the amount of thyroid tissue removed. Women had a higher recurrence rate than men (28.4 percent vs. 10.3 percent; P<0.05). Among the 299 patients who had been treated with thyroid hormone at the discretion of their physicians to suppress thyroid-stimulating hormone, 25 had recurrences (8.4 percent), as compared with 72 of 201 patients who did not receive thyroid hormone (35.8 percent) (hazard ratio taking into account the extent of surgery and the patient's sex, 2.5; 95 percent confidence interval, 1.5 to 4.1). Histologie analysis of the 73 tissue samples from patients with recurrences showed that 14 samples (19.2 percent) were malignant. Thyroid hormone treatment had no effect on the rate of thyroid cancer. We conclude that radiation-associated benign thyroid nodules have a high recurrence rate, similar to that reported among nonirradiated patients with benign thyroid nodules. We also conclude that treatment with thyroid hormone decreases the risk of benign recurrences, particularly in women, but not the risk of cancer. (N Engl J Med 1989; 320:835–40.)
AB1018 Clinical utility of bone turnover markers in a metabolic bone disease clinic:
Authors: G. Macdonald, A. Black
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Biochemical bone turnover markers (BTM) provide dynamic information on skeletal status and can complement information regarding bone mineral density (BMD) assessed by DEXA [1]. In the past, BTM were limited to use in research but their use in clinical practice is increasing. In our clinic, we measure the bone formation marker serum N-terminal of propeptide type 1 collagen (P1NP) and bone resorption marker serum c-terminal telopeptide (CTX). They can measure response to treatment with bisphosphonates showing suppression of bone turnover and also predict early response to anabolic agents which lead to increased bone turnover. They can allow earlier monitoring than DEXA where changes may not be seen for up to 2 years. Measurement of BTM may improve compliance with anti-osteoporotic medication although this has not been conclusively confirmed in clinical trials [2]. <h3>Objectives</h3> To assess whether measurement of BTM influences clinical decision making in a teaching hospital metabolic bone disease clinic. <h3>Methods</h3> We obtained the BTM results for 2 consecutive months from the metabolic bone disease clinic and obtained all available prior and subsequent results. The patients’ case records were reviewed to assess whether these results had any effect on clinical decision making <h3>Results</h3> Results were obtained for 57 patients. The majority had osteoporosis (n=55), other diagnoses were Paget’s disease and hypophosphataemic rickets. <h3>Conclusions</h3> Measurement of BTM provides valuable information in a metabolic bone disease clinic. In patients receiving IV zoledronate they ensured that further IV zoledronate was delayed if BTM were over suppressed. In patients receiving teriperatide they confirmed a metabolic response to this expensive therapy at an early stage. They led to a change in treatment in a further patient, no indication to change treatment in another patient and may also play a role in decisions regarding “drug holidays” from bisphosphonates. <h3>References</h3> Delmas, P.D., Eastell, R., Garnero, P., Seibel, M.J., and Stepan, J., The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation. Osteoporos Int, 2000; 11 Suppl 6: p. S2-17. Delmas, P.D., Vrijens, B., Eastell, R., Roux, C., Pols, H.A., Ringe, J.D., et al., Effect of monitoring bone turnover markers on persistence with risedronate treatment of postmenopausal osteoporosis. J Clin Endocrinol Metab, 2007; 92(4): p. 1296-304. <h3>Disclosure of Interest</h3> None Declared
S78 Phenotypes of Induced Sputum in Difficult to Treat Asthma
Authors: R Herzallah
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> The clinical value of repeated induced sputum tests to monitor airway inflammation in children with severe asthma is contentious. In adult patients with severe asthma a management based on sputum eosinophil counts results in a reduction of exacerbations and fewer hospital admissions (Green R et al, Lancet 2002). This has not been shown in children. Several inflammatory phenotypes are described but clinical management strategies based on these have largely been unsuccessful. It has been suggested that the inflammatory phenotypes in the sputum are unstable over time (Fleming et al, Thorax 2012). We reviewed the results of induced sputum tests done as part of our severe asthma clinic to determine stability of inflammatory phenotypes in our patients. <h3>Methods</h3> We reviewed all sputum induction results for children with a diagnosis of asthma who underwent inductions between April 2008 and June 2012 at our centre. Samples were processes using our standard protocol (Pin et al, Thorax 1992). Samples were classified as eosinophilic (&gt;2.5% eosinophils and &lt;2.5% neutrophils), neutrophilic (&gt;54% neutrophils and &lt;2.5% Eos); mixed granulocytic (&gt;2.5% eosinophils, &gt;54% neutrophils); or paucigranulocytic (&lt;2.5% eosinophils, &lt;54% neutrophils) as previously suggested. <h3>Results</h3> 34 patients, 19 males and 15 females, with a BTS of 3 to 5 had a total of 86 inductions. 22 patients had 2 inductions and the rest had between 3 and 5 inductions. 18 of the 34 patients had a eosinophilic profile on their first induction and 24 of the 34 patients had a eosinophilic profile in at least one sample. 29 of the 34 patients had &gt;2.5% eosinophils (eosinophilc or mixed profile) in at least one sample. Of the remaining five who never had &gt;2.5% eosinophils, four had a neutrophic profile and the remaining child had a persistent paucigranulocytic profile. Using the above classification 25 out of the 34 patients switched phenotype at least once in the duration of the study. <h3>Conclusions</h3> There is no treatment based on the neutrophilic phenotype classification therefore the presence and percentage of eosinophils present appears to be the most useful information gained from sputum induction. Based on our data and that of others, classification into several inflammatory phenotypes does not appear clinically useful.
Ventilation-Perfusion Scintigraphic Correlation With Multimodality Imaging in a Proven Case of Swyer-James (Macleod's) Syndrome
Authors: AMIR SALMANZADEH, STEPHEN J. POMERANZ, PARSHAN S. RAMSINGH
Journal: Clinical Nuclear Medicine (1997)

The scintigraphic findings in a rare case of a unilateral matched ventilation perfusion defect, Swyer-James (Macleod's) syndrome, are presented. A 40-year-old man underwent ventilation/perfusion imaging for acute onset of dyspnea. The scan showed markedly diminished ventilation, vascular flow, and perfusion unilaterally on the left hemithorax. Chest radiography showed hyperlucency of the left lung. Pulmonary angiography showed left-sided hypovascularity, and the CT scan of the chest showed apical bullae and peribronchial thickening of the left lung. Ventilation/perfusion imaging and other radiologic assessment, along with the patient's medical history, confirmed the diagnosis of the Swyer-James syndrome. This condition should be considered as a differential diagnosis in a patient with unilaterally matched ventilation/perfusion deficits without an obvious etiology.
SAT0302 Clinical and Laboratory Features of Late-Onset Psoriatic Arthritis in Comparison with Younger-Onset Disease: Data from an Early Arthritis Cohort
Authors: S. D’Angelo, M. Gilio, C. Palazzi, P. Leccese, A. Nigro, M. Lofrano, S. D. Bello, A. Padula, I. Olivieri
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Psoriatic arthritis (PsA) is generally observed in middle-aged patients but can also begin in the elderly. With the increasing life expectancy, it is highly likely that the number of patients with late-onset PsA will increase. <h3>Objectives</h3> The aim of the study was to establish in a cohort of patients with early PsA whether the age at the disease onset may influence the clinical and laboratory characteristics and the performance of CASPAR criteria. <h3>Methods</h3> Consecutive patients with a diagnosis of early (symptom duration &lt; 52 weeks) PsA, made by rheumatologists with long-standing expertise in PsA, were recruited in a prospective study. According to the age at the onset of musculoskeletal manifestations, patients were divided into younger-onset (YOPsA) (age &lt; 60 years) and late-onset (LOPsA) (onset age ≥ 60 years) PsA. Clinical features and sensitivity of the CASPAR criteria were studied in accordance to this age stratification. <h3>Results</h3> During a 3-year recruitment period, 76 PsA patients (34 M, 42 F; age 49±16, range 16-90 years) with a disease duration of 20±15 weeks (range 1-52) were enrolled. Compared to the 60 patients with YOPsA, the 16 patients with LOPsA had a significant shorter disease duration (15±17 <i>vs.</i> 21±15 weeks, p &lt; 0.05) and showed more frequently increased levels of ESR (75% <i>vs.</i> 43%, p &lt; 0.05) and CRP (87% <i>vs.</i> 52%, p &lt; 0.01) In addition, patients with LOPsA developed more frequently inflammatory extremity swelling with pitting edema (IESPE) over the dorsum of hands and/or of the feet (56% <i>vs.</i> 13%, p &lt; 0.01). There were no other significant differences between the 2 groups even though more males were observed in the LOPsA group (56% <i>vs.</i> 42%, p &gt; 0.05). The sensitivity of the CASPAR criteria was similar in YOPsA (78%) and LOPsA (75%). <h3>Conclusions</h3> Among patients with early PsA, some clinical and laboratory features may differ depending on the age at disease onset. However, in contrast with previous studies on patients with PsA of longer disease duration, early LOPsA is not more severe than early YOPsA. Finally, the CASPAR criteria seem to work similarly well in early LOPsA and YOPsA. <h3>Disclosure of Interest</h3> None Declared
Abstract 770: Association of YAP expression with colorectal cancer progression.
Authors: Daxing Xie, Xiangyang Wang, Jiang Min, Xiaolan Li, Jubo Hu, Jianping Gong
Journal: Cancer Research (2013)

Abstract YAP, a crucial transcriptional coactivator in the Hippo signaling pathway, is upregulated in several human tumors and suggested to promote tumor progression. However, its expression level and role in colorectal cancer (CRC) remain unknown. In this study, YAP expression and the correlation between YAP expression and CRC clinical features were investigated. Quantitative real-time polymerase chain reaction and Western blotting were performed on 30 matched pairs of fresh CRC tissues and adjacent normal mucosae from 30 CRC patients. Immunohistochemical analysis was performed on 116 matched pairs of paraffin-embedded CRC tissues and adjacent normal mucosae, as well as in 73 cases of metastatic lymph nodes. Our results showed YAP expression level in CRC or lymphatic metastatic tissues was clearly higher than that in normal mucosae (P&amp;lt;0.01), whereas that in CRC tissues with lymphatic metastasis was higher than that in tissues without lymphatic metastasis (P&amp;lt;0.05). YAP expression is associated with serosal invasion, lymphatic metastasis, lymph node ratio, remote metastasis, Dukes stage, and the carcinoembryonic antigen level (P&amp;lt;0.05). It is also an independent predictor of the survival of CRC patients (P&amp;lt;0.05). Patients with high YAP expression level exhibited lower overall survival rates than those with low expression (P=0.001). Further analysis showed that YAP predicted CRC prognosis primarily for patients with late-clinical-stage CRC (P=0.002). These findings suggest that YAP is a potential marker for predicting CRC progression and prognosis. YAP upregulation is associated with poor overall survival time in CRC patients, particularly in those with late stage of the disease. Therefore, YAP may be an effective therapeutic target for late-stage tumors. Citation Format: Daxing Xie, Xiangyang Wang, Jiang Min, Xiaolan Li, Jubo Hu, Jianping Gong. Association of YAP expression with colorectal cancer progression. [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 770. doi:10.1158/1538-7445.AM2013-770 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Quinidine Elimination in Patients with Congestive Heart Failure or Poor Renal Function
Authors: Kenneth M. Kessler, David T. Lowenthal, Howard Warner, Thomas Gibson, William Briggs, Marcus M. Reidenberg
Journal: New England Journal of Medicine (1974)

Abstract Plasma quinidine half-life values, determined by a relatively specific double extraction method in eight patients with poor renal function, eight with congestive heart failure, and nine controls were similar for all groups. When quinidine was measured by a nonspecific fluorescent method, the half-life values calculated for the uremic patients were longer than those for the controls. The nonspecific method does not differentiate slow biotransformation of quinidine from normal biotransformation but slow excretion of metabolites. Steady-state plasma quinidine concentrations were measured in 14 patients treated for arrhythmias and 12 with congestive heart failure. Therapeutic effectiveness was associated with concentrations of 2.3 to 5.0 μg per milliliter and ineffectiveness with lower levels or complicating illnesses. The relation of dose to steady-state blood level was similar for the two groups. Quinidine elimination appears to be grossly normal in patients with congestive heart failure or poor re...
Breast Cancer Prevention Trial Takes Off
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Breast Cancer Prevention Trial Takes Off Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 9, 6 May 1992, Pages 669–670, https://doi.org/10.1093/jnci/84.9.669 Published: 06 May 1992
Abstract 2206: Distinct somatic mutation patterns in multiple human cancers and their subtypes
Authors: Zhengyan Kan, Jeremy Stinson, Deeplai Bhatt, Joshua Kaminker, Howard Stern, Malek Faham, Somasekar Seshagiri
Journal: Cancer Research (2010)

Abstract We have systematic analyzed 4.5Mb of DNA representing 1507 genes in 450 human fresh frozen tumors covering four major human cancers and their subtypes for somatic mutations. For this analysis we used E. coli mismatch repair detection (MRD) for our primary mutation scans. All the identified variations were validated as somatic using nucleic acid mass spec and confirmed to be present in the original tumor and absent in the matched adjacent normal DNA. Of the all tumor samples analyzed ∼80% show somatic mutations in one or more genes studies. Of the genes analyzed we identified mutation in 842 genes. Applying statistical techniques and other measures we have identified 221 genes to be significantly mutated across all cancers studied. Further analysis of mutated genes by tumor types and subtypes revealed distinct patterns of significantly mutated genes. Besides the previously known mutated genes, we have identified several novel mutated genes with previously unknown role in cancers across the various cancer types studied. To further ascertain the relevance we have performed integrated analysis of mutation and copy number variations data from the samples studied and identified putative tumor supressors and oncogenes. Also, we have performed mutational analysis at the level of biological pathways and identified several mutated pathways. 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 2206.