tbuckley/cabot-search huggingface dataset:
Do We Need a New End Point in Clinical Trials Today?
Authors: P. A. GANZ
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Do We Need a New End Point in Clinical Trials Today? Get access PATRICIA A. GANZ PATRICIA A. GANZ University of California, Los Angeles San Fernando Valley Program, VAMC (IIIB) Department of Medicine(1118) 16111 Plummer St. Sepulveda, CA 91343 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 14, 19 July 1989, Pages 1105–1106, https://doi.org/10.1093/jnci/81.14.1105 Published: 19 July 1989
Multiple Pathologic Fractures Mimicking Bone Metastases In a Patient With Cushing's Syndrome
Authors: ELIZABETH BARON, MAXIM SHEINFELD, ERELLA ALTER MIGDAL, RUTH HARDOFF
Journal: Clinical Nuclear Medicine (1996)

The deteriorating effects of corticosteroids on bone structure and metabolism have been well documented since they were first reported by Harvey Cushing in 1932. The main effects of corticosteroids causing osteoporosis include: direct suppression of osteoblasts, indirect stimulation of osteoclasts mediated by cytokinins and prostaglandins, and secondary hyperparathyroidism due to both decreased gut absorption and increased urinary excretion of calcium. Corticosteroids also have a suppressive effect on both gonadal function, adrenal androgens in women, as well as catabolic effects on muscle and bone matrix proteins. Therefore, high corticosteroid levels result in pathologic bone fractures. The authors describe a 33-year-old woman with adrenal Cushing's syndrome who had multiple pathologic fractures, including bilateral pelvic fractures, which mimicked bone metastases on bone scintigraphy. These findings resolved completely after the resection of the adrenal tumor. When a patient presents with multiple pathologic bone fractures, demonstrated on both radiography and scintigraphy, one should consider a diagnosis of metabolic bone disease, as well as other diagnostic possibilities.
AB0864 Fatigue in Fibromyalgia Syndrome and Patients with Osteoarthritis
Authors: W.-K. Yeung, K. Morgan, F. Mckenna
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Compared to other clinical groups with chronic pain, people with fibromyalgia syndrome (FMS) report higher levels of fatigue. It is not known whether this is driven by pain, psychological mechanisms or sleep disturbance. This study compared fatigue outcomes in patients with FMS and osteoarthritis (OA). The patients were part of a larger clinical assessment of psychosocial and polysomnographic variables. <h3>Objectives</h3> To determine the factors causing fatigue in FMS <h3>Methods</h3> 20 recently diagnosed FMS patients (all females; M=40.45, SD=11.21 range 19-58yrs) and 15 patients with OA (all females; M=44.60, SD=11.01 range 19-60yrs) exhibiting localized joint pain and sleep disturbance and were recruited from a single rheumatology unit at Trafford General Hospital, UK. All patients with FM fulfilled the 2010 ACR criteria for the diagnosis, confirmed by an experienced rheumatologist. All patients with OA had radiographic abnormality requiring surgical intervention. All participants completed self-reported sleep scores (Pittsburgh Sleep Quality Index), pain (VAS), fatigue (Fatigue Severity Scale), depression and anxiety measures (Hospital Anxiety and Depression score). All patients had 2 weeks actigraphic assessment of sleep. Multiple regression analysis was conducted with fatigue as the dependent variable and sleep, pain, depression and anxiety measures as predictors. Correlation with fatigue was evaluated compared with actigraphic parameters. <h3>Results</h3> The mean fatigue score in FMS was 51±8.40 and 38.27±10.92 in OA. The regression model was significant overall, F(21,10)=4.63, p=0.002, r<sup>2</sup>=0.54. After controlling for sleep quality, pain severity, pain interference, depression and anxiety, group membership was the only significant predictor of fatigue, B=-7.55, t=-2.40, p=0.026. Fatigue in FMS was correlated with duration of waking after sleep onset and number of awakenings on actigraphy (p=0.034). <h3>Conclusions</h3> This data shows that differences in fatigue noted in these two clinical groups are not solely driven by psychological factors. Other factors related to sleep structure may play a larger role in driving these differences. The number and duration of awakenings during sleep contribute to fatigue in FMS but not in OA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6010
Abstract PD01-07: Transcriptome Analysis of Triple Negative Breast Cancers Identifies Six Distinct Biological Subgroups and Reveals Therapeutic Strategies
Authors: BD Lehmann, JA Bauer, X Chen, ME Sanders, Y Shyr, JA. Pietenpol
Journal: Cancer Research (2010)

Abstract Background: Currently, there are targeted therapies for estrogen receptor (ER) positive and HER2-amplified breast cancers. However, treatment options for patients with triple negative breast cancers (TNBCs), tumors that are hormone receptor negative (ER and progesterone, PR) and lack HER2 amplification, has been limited by the heterogeneity and lack of moleclular understanding of the subtypes of this disease. Use of genomic information (gene expression, copy number analysis, methylation arrays, and next-generation sequencing) will unravel the complexity of the disease and identify novel targeted therapies. Methods and Findings: In order to identify biologically distinct TNBC subgroups and associated molecular drivers, we compiled an extensive TNBC transcriptome dataset from 21 independent breast cancer studies. We performed reiterative k-means clustering analysis on a 386 TNBC gene expression profile training set and identified six stable clusters that display unique gene expression patterns and gene ontologies. An independent set of 201 TNBC gene expression profiles was used to validate the six TNBC subgroups. We identified two basal-like subgroups (BL1 and BL2) characterized by cell cycle and DNA damage response genes, two mesenchymal-like subgroups (M and MSL) enriched in cell differentiation, epithelial-mesenchymal transition and growth factor pathways, an immunomodulatory subgroup (IM) defined by immune cell surface antigens, receptors and signal transduction genes, and a luminal subgroup (LAR) driven by androgen receptor signaling. Using tumor gene expression signatures, we identified representative cell lines to model each of the TNBC subgroups and also pharmacologically targeted prominent signaling pathways. Conclusions: Through transciptome analysis we subclassified TNBC into six biological subgroups and identified potential therapeutic targets for future exploration. The data generated in this study have significant value for target selection in drug discovery, clinical trial design and selection of biomarkers that will enable the alignment of TNBC patients to the appropriate targeted therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD01-07.
Horner's Syndrome Occurring with Spontaneous Pneumothorax
Authors: Lee R. Sataline, Thomas Kraus
Journal: New England Journal of Medicine (1965)

INTERRUPTION of the sympathetic pathways anywhere in their course from the hypothalamus to the ocular orbit results in Homer's syndrome and is manifested by homolateral miosis, ptosis of the upper lid, minimal enophthalmos and facial flushing.1 Anhidrosis occurs if the lesion is distal to the superior cervical ganglion.2 The syndrome usually results from injury to the sympathetic tract by tumors, trauma, Central-nervous-system disease, lymphadenopathy and vascular lesions.2 We recently observed a patient with Homer's syndrome that apparently resulted from a spontaneous pneumothorax. The disappearance of the syndrome after re-expansion of the lung supports this conclusion. We were unable to learn . . .
Thrombocytopenia and Bleeding Tendency after Extracorporeal Circulation
Authors: Paul J. Schmidt, James C. Peden, George Brecher, Anne Baranovsky
Journal: New England Journal of Medicine (1961)

THE ideal perfusion fluid for use in an artificial cardiopulmonary system should approach the patient's own blood in composition. For this reason antigenically compatible donor blood with viable erythrocytes capable of gas exchange is used. Data on the need for other formed blood elements are lacking. It was not anticipated that leukocytes would have to be provided because of the patient's known large body reserves.1 It could not be predicted whether the limited platelet reserves2 could fill the needs of the postoperative period.The storage of donor blood by available technics adversely affects the yield of viable platelets.3 , 4 Theoretically, therefore, . . .
Abstract 4640: High expression of the stem cell marker LGR5 is associated with a poor clinical outcome in patients with Ewing's sarcoma
Authors: Christopher A. Scannell, Diana Abdueva, Lingyun Ji, Cornelia von Levetzow, Richard Sposto, Timothy J. Triche, Elizabeth R. Lawlor
Journal: Cancer Research (2010)

Abstract Ewing's sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that are most commonly diagnosed in childhood and adolescence. Unfortunately, drug-resistant relapse is not uncommon and is associated with very poor outcomes. No clinical or pathologic features currently exist that reliably predict chemosensitivity or relapse in newly diagnosed patients. In this study we used whole genome expression microarray profiling to identify potential markers of drug resistance and relapse in ESFT. Affymetrix human exon (HuEx) arrays were used to profile a highly drug resistant case of primary, localized ESFT before and after induction therapy. Comparison of gene summarized data from pre- and post-therapy samples with 10 chemosensitive tumors identified 309 genes to be differentially expressed in the resistant case at diagnosis (fold change&amp;gt;2). Of the 309 differentially expressed genes at diagnosis, 130 demonstrated an even greater change in expression post-induction therapy suggesting that these genes might be markers of the most highly drug-resistant cells. Intriguingly, two stem cell associated genes, PROM1 (prominin 1) and LGR5 (leucine-rich-repeat containing G-protein-coupled receptor 5), were included in the list of putative chemoresistance markers. Expression of PROM1 and LGR5 were 18-fold and 17-fold higher, respectively, at diagnosis and 31-fold and 21-fold higher post-induction therapy in the drug resistant case. To determine if either gene is associated with chemoresistant disease or relapse in ESFT we next evaluated whether their expression correlated with outcome in a large cohort of institutional and Children's Oncology Group patients. Clinical correlates analysis of HuEx gene expression data obtained from 53 tumors revealed no correlation between PROM1 expression and outcome. In contrast, increased expression of LGR5 was associated with worse event-free (p=0.008) and overall survival (p=0.046). Variable but detectable expression of LGR5 in ESFT tumors and cell lines was validated using quantitative RT-PCR. Finally, LGR5 expression in ESFT cells was compared to human embryonic and somatic stem cells and fibroblasts. Significantly, LGR5 was found to be highly expressed by neural crest stem cells but not by bone-marrow derived mesenchymal stem cells, differentiated neural crest cells, or embryonic fibroblasts. These data suggest that LGR5 might be useful as a predictor of outcome in ESFT and implicate a primitive neural crest stem cell phenotype in the developmental origins of drug-resistant and relapsed disease. 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 4640.
Submandibular Ectopic Thyroid Gland
Authors: MARIA SIRONI, AGNESE ASSI, MILENA ANDRUCCIOLI, GIANLUIGI SPREAFICO
Journal: Clinical Nuclear Medicine (1996)

a 45-year-old euthyroid woman had symmetric submandibular masses. Radionuclide imaging with Tc-99m pertechnetate will hide the presence of ectopic thyroid tissue because of the physiologic radionuclide uptake by the salivary glands, whereas a study using radioactive iodine allows a correct diagnosis. In this case, thyroid rests were situated in the submandibular regions, with no thyroid gland in the neck, probably because of an arrest in the normal descent of thyroid tissue after the development of the two lobes.
Aluminum Intoxication from Aluminum-Containing Phosphate Binders in Children with Azotemia Not Undergoing Dialysis
Authors: Sharon P. Andreoli, Jerry M. Bergstein, Donald J. Sherrard
Journal: New England Journal of Medicine (1984)

Aluminum intoxication developed in three infants with azotemia who were not undergoing dialysis and who had been treated with aluminum hydroxide from the first month of life. Biopsies of the iliac crest demonstrated the presence of severe osteomalacia and massive deposition of aluminum in the bone. Serum aluminum levels were significantly (P<0.001) higher in these 3 infants and in 1 other, all of whom received more than 100 mg of elemental aluminum per kilogram of body weight per day (mean ±S.D., 371.0+178.9 ng per milliliter [13.75+6.6±6.6 μmol per liter]) than they were in 8 older children with azotemia who were not undergoing dialysis and who received less than 100 mg of elemental aluminum per kilogram per day (27.0±18.6 ng per milliliter [1.0±0.68 μmol per liter]), 7 such children who did not receive aluminum hydroxide (20.28±9.2 ng per milliliter [0.75±0.34 μmol per liter]), and 16 children with normal renal function (21.04±4.9 ng per milliliter [0.78±0.18 μmol per liter]). In all the children with azotemia who were treated with aluminum hydroxide, there was a positive correlation (r = 0.90; P<0.01) between the serum aluminum level and the daily dose of elemental aluminum. These studies indicate that gastrointestinal absorption of aluminum can lead to aluminum intoxication in children with azotemia, and that infants may be particularly susceptible to this complication of therapy. (N Engl J Med 1984; 310:1079–84.)
PTH-029 Lifestyle Screening And Brief Interventions In A Gastroenterology Clinic
Authors: E Davies, A Kings, M Cornford-Hill, C Southwell, S Prabhakaran, T Haldane, M Vardy, I Ahmad, Y Merali, D Aldulaimi
Journal: Gut (2014)

Introduction Worcestershire Acute Hospitals NHS Trust currently have an Alcohol Liaison Nurse (ALN) Service. In response to NICE and Making Every Contact Count we wanted to implement a lifestyle screening tool within the out patients clinic, and be able to offer signposting and an opportunistic Brief Intervention (BI) service. Methods Patients aged over 16 years attending a busy gastroenterology out-patients clinic were asked to complete a ‘lifestyle’ screening tool using the AUDIT-C (Babor 2001) to assess alcohol use and smoking status. Individuals identified as smokers, were advised of the health risk by the a specially trained health care assistant and signposted to a smoking cessation service. Individuals who were AUDIT-C positive (>5) were referred by the consultant to the Alcohol Liaison Nurse (ALN) for further assessment and Brief Intervention. Results 448 patients attended the clinic. 60% (n = 269) were asked to complete the tool (2 refused). 32 (12%) individuals were identified as smokers. 13 males with a median age of 56 and 19 females with a median age of 49. 18 accepted an advice card. 82 (31%) AUDIT-C >5. 46 males with a median age of 53 and 36 females with a median age of 51. 27 accepted referral to ALN (3 unable to contact). The highest reported motivating factors for change were improved physical and mental health, followed by better finances and weight loss. 75% of the sub-group receiving Brief Intervention could not identify any costs of change. The sub-group also scored high in relation to readiness to change and confidence to change following the BI. Extended BI reported reduced AUDIT-C scores and reduced drinking days/unit consumption. Conclusion The results suggests that lifestyle screening is a achievable and acceptable in a busy gastroenterology clinic. A significant proportion of patients attending a gastroenterology clinic are likely to be using alcohol at harmful levels or smoking and are therefore likely to benefit from opportunistic BI or signposting to smoking cessation services. References [http://www.alcohollearningcentre.org.uk/alcoholeLearning/learning/IBA/Module3\_v3/D/ALC\_Session/256/tab_642.html][1] Babor T, Higgins-Biddle J, Saunders J, Monteiro M. The Alcohol Use Disorders Identification Test. Guidelines for use in primary care. 2nd ed. Geneva, Switzerland: WHO 2001 The NHS’s role in the public’s health: A report from the NHS Future Forum. Accessed online [04/12/2013] [https://www.gov.uk/government/uploads/system/uploads/attachment\_data/file/216423/dh\_132114.pdf][2] Disclosure of Interest None Declared. [1]: http://www.alcohollearningcentre.org.uk/alcoholeLearning/learning/IBA/Module3_v3/D/ALC_Session/256/tab_642.html [2]: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/216423/dh_132114.pdf
SAT0144 The Causes of Discontinuation of Biologics(Bio)-Use in the Treatment of Rheumatoid Arthritis (RA) Under Practical Circumstances in Japan: from the “Ninja” Registry
Authors: Y. Saeki, S. Ohshima, M. Matsushita, E. Tanaka-Kudo, S. Tsuji, M. Yoshimura, A. Watanabe, M. Katayama, S. Teshigawara, Y. Katada, Y. Harada, A. Yura, K. Kagawa, J. Hashimoto, S. Tohma
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> With recent astonishing advances in drug therapy, “remission” has become a realistic therapeutic goal in RA. Among them the most powerful driving force might be the advent of “biologics (Bio)” targeting cytokines and lymphocytes. In fact, they have shown outstanding efficacy and become a master of drug. However, some issues remain to be addressed and resolved, including adverse effects such as serious infections, therapeutic failure and high cost. <h3>Objectives</h3> To examine the causes of discontinuation of Bio in 2,274 Japanese RA patients treated with Bio under practical circumstances. <h3>Methods</h3> The causes of discontinuation of Bio-use were analyzed by using the data from the “NinJa”, one of the largest Japanese RA patient registry established since 2002 and now consists of the clinical data of 10,368 patients from more than 30 hospitals. <h3>Results</h3> 2,274 (22.1%) of the total registered patients were treated with some Bio. Among them, 352 (15.5%), 940 (41.3%), 258 (11.3%), 63 (2.8%), 459 (20.2%), and 206 (9.1%) of the patients were treated with IFX, ETN, ADA, TCZ and ABT respectively. The cases (percentages) of discontinuation of Bio-use were 62 (17.6%), 71 (7.6%), 55 (21.3%), 39 (8.5%), and 20 (9.7%) in IFX, ETN, ADA, TCZ and ABT respectively. The causes of discontinuation were analyzed and shown in the following Table. Regarding “Failure”, the discontinuation rate was significantly higher ADA. In “Adverse effects”, there was no significant difference among all Bio, although a tendency of higher rate was observed in IFX and ADA. In contrast, it was relatively low in ABT. In addition, the discontinuation due to “Remission” was significantly higher in IFX compared to other Bio. <h3>Conclusions</h3> There were some characteristics in the causes of discontinuation among Bio. It seems to be feasible to achieve Bio-free remission in some Bio. With further investigations, these findings might provide us a clue to know how and which cases can be achieved Bio-free remission. <h3>Acknowledgements</h3> This study was supported by both the grants of NHO (National Hospital Organization) and the Ministry of Health, Welfare and Labor. <h3>Disclosure of Interest</h3> None Declared
Abstract 5365: Zeranol-containing serum (Z-Sera) harvested from 30-day Z-implanted heifers induce transformation of human normal breast epithelial cells through down-regulation of the protein tyrosine phosphatase γ (PTPγ) tumor suppressor gene
Authors: Young C. Lin, Weiping Ye, Ping-Ping Xu, Walter R. Threlfall, Hong Li, Shu-Hong Lin, Chieh-Ti Kuo
Journal: Cancer Research (2010)

Abstract The morbidity of breast cancer ranks first in the U.S. it remains the second leading cause of maligancy-related death in women, regardless of advances in novel therapeutic strategies. Many risk factors have been associated with breast cancer initiation, promotion and progression. Recently, Zeranol (Z), one of six growth promoters approved by FDA for use in the beef industry may cause health concerns due to the consumption of beef products containing bio-active Z metabolites. Our laboratory previously demonstrated that Z down-regulates the expression of estrogen-regulated PTPγ in primary cultured human normal breast epithelial cells and transforms the normal human breast epithelial cell line, MCF-10A, to neoplastic breast cancer cells. In the current study, we investigated the biologically active Z metabolites present in Z-Sera harvested from 30-day post Z implanted heifers (72 mg pellet) on MCF-7 cell growth and PTPγ mRNA expression in MCF-10A cells using non radioactive cell proliferation and real time PCR. Our results showed that Z-Sera at 0.5, 2.5 and 12.5% significantly increased the growth of MCF-7 cells by 42, 71, and 108%, respectively. While the sera harvested from the control heifers did not increase MCF-7 cell growth. Treatment with 2.5% Z-sera harvested 30, 60, 90 days post Z-implantation significantly down-regulated the expression of PTP γ mRNA in MCF-7 cells to 18.2, 36.5 and 51%, respectively. Furthermore, neoplastic transformation of MCF-10A cells resulted after exposure of 2.5% Z-Sera in culture medium to MCF-10A for 21-day. The expression of PTPγ mRNA, in transformed MCF-10A cells, was significantly reduced by 83, 96 and 97%, as compared to the controls. We hypothesize that the transformation of MCF-10A cells by bio-active Z metabolites contained in 2.5% Z-sera may be mediated through the down-regulation of estrogen-regulated PTPγ in MCF-10A cells. We have reported that the growth rate of pre-adipocytes isolated from the beef cattle 30-day post Z-implantation was 12 fold faster than the pre-adipocytes isolated from of the control beef cattle. In summary, our in vitro data suggest that potential adverse health risk may result from consuming beef products containing bio-active Z metabolites. (Supported by NIH grant R01 ES 015212). 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 5365.