tbuckley/cabot-search huggingface dataset:
Abstract 1844: No evidence for genetic factor increasing renal cell cancer risk in Hereditary Leiomyomatosis and Renal Cell Cancer syndrome
Authors: Taru A. Koski, Pia Vahteristo, Laura Näätsaari, Maija Kiuru, Auli Karhu, Riitta Herva, Satu-Leena Sallinen, Outi Vierimaa, Erik Björck, Stéphane Richard, Betty Gardie, Didier Bessis, Emmanuel Van Glabeke, Ignacio Blanco, Richard Houlston, Leigha Senter, Marja Hietala, Kristiina Aittomäki, Lauri A. Aaltonen, Virpi Launonen, Rainer Lehtonen
Journal: Cancer Research (2010)

Abstract Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary tumor predisposition syndrome with fumarate hydratase (FH), which encodes a tricarboxylic acid cycle enzyme fumarase, as the predisposing gene. The HLRCC family members carry heterozygous germline mutations of the FH gene and the tumors often harbor a second hit making the growth fumarase deficient. The phenotype includes benign cutaneous and uterine leiomyomas as well as renal cell cancer (RCC). The HLRCC related RCCs usually belong to histological papillary type II subtype and are solitary, unilateral and aggressive. The benign leiomyomas are the most common manifestation of the syndrome affecting almost all FH mutation carriers whereas the renal cell cancer phenotype affects only about 20% of the HLRCC families. Interestingly, majority of the families with multiple renal cell cancer cases have concentrated in Finland and the U.S. Why the malignant phenotype affects only a part of the HLRCC patients is unknown. There is no genotype-phenotype correlation and type or site of the FH mutation does not affect the phenotype. The fumarase enzyme activity levels do not correlate with the phenotype either. Thus it is possible that the appearance of RCC requires, in addition to FH mutation, another genetic factor. To search for such a factor in four Finnish HLRCC families with multiple RCC cases we performed genome wide linkage and/or identical by descent (IBD) analyses. After finemapping procedures the only region compatible with linkage was the FH locus itself in 1q43. The genes of the region were screened but no pathognomonic mutations were found. Although these results do not exclude the existence of a genetic RCC risk modifier in HLRCC, the role of FH mutations behind RCC tumors is emphasized. Counseling and genetic testing should be available for HLRCC family members and the FH mutation carriers should be carefully followed up to enable early detection and treatment of the aggressive cancers. 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 1844.
Abstract 4584: Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1.
Authors: Raul Catena, Nandita Bhattacharya, Tina El Rayes, Hyejin Choi, Suming Wang, Dingcheng Gao, Natasha Joshi, Seongho Ryu, Diane Bielenberg, Sharrell Lee, Svein Haukaas, Karsten Gravdal, Ole Halvorsen, Lars Akslen, Randolph Watnick, Vivek Mittal
Journal: Cancer Research (2013)

Abstract Previous studies have shown that metastatic tumors establish premetastatic niches comprised of recruited bone marrow (BM)-derived cells in potential distant target metastatic organs. These premetatatic niches serve as permissive hubs for supporting future metastases. However, little is known about whether tumors that lack metastatic potential establish such niches, or generate niches that inhibit metastasis. Here, we show that metastasis-incompetent tumors are also capable of systemically generating BM-derived niches in the metastatic organs. However, by secreting the glycoprotein prosaposin these tumors systemically stimulate expression of antitumorigenic factor thrombospondin-1 (Tsp-1) in the Gr1+ myeloid cells converting them it into a metastasis-refractory niche. Genetic deletion of Tsp-1 abolished the inhibition of metastasis, which was restored by BM transplant from Tsp-1+ donors. We developed a 5-amino acid peptide from prosaposin as a pharmacological inducer of Tsp-1 in Gr1+ BM cells. Strikingly, the peptide suppresses metastasis. These results provide mechanistic insights into why certain tumors are deficient in metastatic potential and implicate recruited Gr1+ myeloid cells as the main source of Tsp-1, contrary to previous notion. These results also underscore the plasticity of Gr1+ cells, which, depending on the context and the nature of paracrine factor/s can either promote or inhibit metastasis. Clinically, examination of a tumor tissue microarray (TMA) compiled from 103 prostate cancer patients with long and complete follow up, revealed that prosaposin expression positively correlated with increased overall survival, suggesting that the prosaposin peptide may be a potential therapeutic agent against metastatic cancer. Citation Format: Raul Catena, Nandita Bhattacharya, Tina El Rayes, Hyejin Choi, Suming Wang, Dingcheng Gao, Natasha Joshi, Seongho Ryu, Diane Bielenberg, Sharrell Lee, Svein Haukaas, Karsten Gravdal, Ole Halvorsen, Lars Akslen, Randolph Watnick, Vivek Mittal. Bone marrow-derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. [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 4584. doi:10.1158/1538-7445.AM2013-4584
P23 The incidence of congenital thoracic malformations: an increasing trend from 1994 to 2011 in a defined population
Authors: EA Gorman, S Thavagnanam, J Houton, A Dick, A Patterson, MD Shields
Journal: Thorax (2013)

<h3>Introduction</h3> Congenital thoracic malformations (CTMs) are an uncommon heterogenous group of disorders including congenital cystic adenomatous malformation (CCAM), pulmonary sequestration (PS), congenital lobar overinflation (CLO), hybrid lesions and bronchogenic cysts. They are increasingly diagnosed antenatally with foetal ultrasonography and remain asymptomatic. In light of diagnostic advances, robust population based epidemiology is lacking. This study aimed to characterise the incidence of CTMs in a defined geographic area from 1994 to 2011. <h3>Methods</h3> Children with CTM in Northern Ireland are referred to a single tertiary centre. Patients with CTM born between 1994 and 2011 were identified from the paediatric respiratory and surgical clinics and from imaging reports on the regional radiology database. Medical records and imaging reports were reviewed retrospectively. Children diagnosed with CTM who were born outside of Northern Ireland were excluded. All births in Northern Ireland are registered with the Registrar General Office. Annual live birth rates were obtained from the Northern Ireland Statistics and Research Agency. Incidence was calculated per 10000 live births. <h3>Results</h3> In total there were 92 cases of CTM between 1994 and 2011, 53 cases (57%) had CCAM. An upward trend in the incidence of CTMs is demonstrated (Figure 1). The average incidence of CTMs from 1994 to 1999, 2000 to 2005 and 2006 to 2011 was 0.49 (range 0.41 to 0.82), 1.6 (range 0.89 to 1.85) 4.08 (range 2.34 to 7.73) respectively. A similar increase in the incidence of CCAM was demonstrated 0.14 (range 0to 0.42), 1.22 (range 0.93 to 1.40) and 2.19 (range 0.39 to 5.59) for the periods 1994 to 1999, 2000 to 2005 and 2006 to 2011 respectively. <h3>Conclusion</h3> This study provides incidence statistics for CTMs in a defined geographic location and demonstrates an increasing incidence between 1994 and 2011, likely due to advances in antenatal diagnosis. The retrospective nature of this study means that patients with CTM who were not followed up postnatally and not imaged postnatally would not be included. The incidence provided therefore represents the minimum incidence. The increasing incidence of CTMs has therapeutic implications as the complication rates may be lower than previously repoted.
ESTABLISHING A PRA THRESHOLD TO TREAT SENSITIZED PATIENTS AWAITING HEART TRANSPLANT IN THE ERA OF THE VIRTUAL CROSSMATCH
Authors: Rigved Tadwalkar, Michelle Kittleson, Jignesh Patel, Jaime Moriguchi, Matthew Rafiei, Ashley Osborne, David Chang, Lawrence Czer, Fardad Esmailian, Nancy Reinsmoen, Jon Kobashigawa
Journal: Journal of the American College of Cardiology (2013)
Abstract 4565: Whole exome sequencing links MAPK1 mutation to exquisite sensitivity to brief erlotinib monotherapy in head and neck cancer.
Authors: Vivian WY Lui, Eliezer Van Allen, Hua Li, Fan Zhang, Yan Zeng, Jonas T. Johnson, Levi A. Garraway, Gordon B. Mills, Jennifer Rubin Grandis
Journal: Cancer Research (2013)

Abstract Activating mutations of EGFR, primarily found in a subgroup of lung cancers, serve as predictive biomarkers for EGFR tyrosine kinase inhibitor (TKI) sensitivity. Clinical responses to EGFR TKIs in other cancers are only moderate and predictive biomarkers are lacking. Here, we report a head and neck cancer patient with no EGFR genetic alterations, who experienced a complete histologic clinical response after 14 days of erlotinib monotherapy on a window-of-opportunity presurgical trial. To determine the somatic genetic events underlying the extraordinary and unexpected response to erlotinib alone, whole exome sequencing was performed. A bi-allelic missense mutation of MAPK1(E322K) was detected in the tumor in the absence of other mutations reported to be correlated with EGFR TKI sensitivity in preclinical models or cancer patients. Combined bioinformatics analyses of genomics-drug databases revealed, for the first time, that loss-of-function of MAPK1 or MAPK1 mutation correlates with erlotinib sensitivity. Functional studies confirmed heightened sensitivity to erlotinib by loss-of-function of MAPK1 in HNSCC cells. Our preliminary findings suggest that this MAPK1 mutation, which is also found at low frequencies in HNSCC and cervical cancers, may identify a subgroup of cancer patients who may be cured with EGFR TKI monotherapy. Citation Format: Vivian WY Lui, Eliezer Van Allen, Hua Li, Fan Zhang, Yan Zeng, Jonas T. Johnson, Levi A. Garraway, Gordon B. Mills, Jennifer Rubin Grandis. Whole exome sequencing links MAPK1 mutation to exquisite sensitivity to brief erlotinib monotherapy in head and neck cancer. [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 4565. doi:10.1158/1538-7445.AM2013-4565
Collagen Disease of the Small Bowel
Authors: Irving Marshall
Journal: New England Journal of Medicine (1956)

IT is the purpose of this paper to discuss collagen disease of the small bowel and to report this condition in its early and late stages so that it can be readily recognized clinically in the operating room and possibly treated earlier. It is suggested that this lesion has not been reported by surgeons for lack of such a description and that it is more common than has been suspected. It was the primary lesion that necessitated operation in 3 cases reported below.The term collagen disease implies a systemic alteration of the connective tissue as seen in rheumatic fever, . . .
Abstract 809: High-resolution genomic profiling reveals gains of CCND1 and EGFR associated with disease progression in Taiwanese oral cavity squamous cell carcinomas.
Authors: Huei-Tzu Chien, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Sou-De Cheng, Ling-Ling Hsieh
Journal: Cancer Research (2013)

Abstract The genetic mechanisms underlying Taiwanese oral cavity squamous cell carcinoma (OSCC) are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays (Affymetrix 500K) to detect copy number alterations (CNAs) in 26 OSCC tumor tissues. Genomic copy number was determined by calculating the intensity ratio between the OSCC and a set of 270 normal DNAs from HapMap project. Segmented copy numbers for each tumor were inferred with the hidden markov model (HMM) using the Partek GS software. Genomic Identification of Significant Targets in Cancer (GISTIC) analysis (version 2.0) was used to identify significant CNAs using a residual Q-value cutoff of 0.25. A total of 25 significant regions (2 focal amplifications and 23 deletions) were identified. The well known oncogene EGFR and CCND1 are resided in these two focal amplification regions (7p11.2 and 11q13.3), respectively. Several candidate cancer related genes such as FHIT (3p14.2), FAT (4q35.1), SH3GL2 (9p22.2) and ARHGAP21 (10p12.1) are known to locate in the identified 23 deletion regions. Furthermore, we found that 7p11.2 amplification and 4q35.2 deletion was mutually exclusive by ‘inter-target relationships’ (ITR) analysis using dimension reduction permutation (DRP) methods. Copy number gains of EGFR and CCND1 were also confirmed along with fluorescence in situ hybridization (FISH) and TaqMan CN assay (Hs01818912_cn and Hs00655630_cn), respectively. We found that the concordance rate was 70.59% for EGFR and 75.00% for CCND1. To further explore the clinical value of copy number gains of EGFR and CCND1 in OSCC, 182 OSCC cases were analyzed. Preliminary results indicated that gains of CCND1 were associated with tumor differentiation, lymph node metastasis and lymph node extracapsular spread (LNECS); while amplification of EGFR gene was significantly associated with tumor stage and lymph node metastasis but not LNECS. Furthermore, gains of CCND1 were significantly associated with poor disease-free and overall survival. On the other hand, amplification of EGFR was not associated with either disease-free or overall survival. Taken together, we have identified that gains of CCND1 and EGFR gene were significantly associated with disease progression in Taiwanese oral cavity squamous cell carcinomas. Citation Format: Huei-Tzu Chien, Shiang-Fu Huang, I-How Chen, Chun-Ta Liao, Hung-Ming Wang, Sou-De Cheng, Ling-Ling Hsieh. High-resolution genomic profiling reveals gains of CCND1 and EGFR associated with disease progression in Taiwanese oral cavity squamous cell carcinomas. [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 809. doi:10.1158/1538-7445.AM2013-809
AB0514 Primary Disease of the Respiratory System in Patients with Systemic Lupus Erythematosus
Authors: H. Borrell, J. Narváez, E. Armengol, A. Zacarías, S. Heredia, A. Iriarte, A. Roset, M. Molina, X. Juanola, O. Capdevila, J.M. Nolla
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To evaluate the frequency of the different types of primary diseases of the respiratory system in a group of patients with Sistemic Lupus Erytematosus (SLE). <h3>Methods</h3> The target of the research were 243 patients with SLE who were assisted between 1980 and 2013 in a third level university hospital and they were registered in a specific data basis (Register AQUILES). There were chosen those patients with some kind of respiratory disease. <h3>Results</h3> 49 (20%) patients were identified. The most frequent manifestation was the pleurisy, present in 39 patients (16%). Other manifestations were the interstitial lung disease (ILD) present in 5 patients (2.1%), acute lupus pneumonitis (ALP) in 4 (1.6%), pulmonary hypertension in 7 (3%), respiratory muscular illness (shrinking lung syndrome) in 2 (0.8%) and pulmonary thromboembolism in 2 (0.8%). In the cases of ILD, the average time of evolution from SLE diagnosis was of 9.4±6.7 years. In the 5 patients, all of them were women, ILD evolved with dry cough and insidious dyspnea. 3 of these patients were controlled with glucocorticoids; the other two also required cyclophosphamide, achieving to stop the evolution of the disease in 1 case, whereas the other patient died. The ALP cases appeared within the first two years of the SLE evolution. The average age of the 4 women suffering from ALP was 38±12 years. In them, the symptoms appeared intensely with fever, pleuritic pain in 50% of the cases, cough with occasional haemoptoic expectoration, dyspnea, diffuse pulmonary infiltrates in the chest X-ray and active alveolitis in the CT. All of them were treated with prednisone at doses of 1 mg/kg/day and one of them was also given bolus of metylprednisolona. In two of the patients an immunosuppressing treatment was added. The evolution was favourable in all the cases. In the comparative research with 194 controls with SLE without respiratory involvement significant differences were observed, being the patients with lung affection those who presented the highest frequency of pericarditis (p=0.0001) and the highest score in the harm index of SLICC/ACR (p=0.001). <h3>Conclusions</h3> The pleural disease is the only primary disease of the respiratory system which is frequent in the SLE. The prevalence of the vascular lung disease, respiratory muscular disease, and of the different types of parenchymatous involvement is very low (≤3%). ALP is an early complication which usually takes place in the first years of the SLE evolution whereas ILD is a late complication. Both complications usually react to the treatment being the mortality rate low (11%). Neither the anti-Ro anti-bodies nor the anti-U1RNP seem to indentify the group of patients with the highest risk to develop these two complications. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5065
P175 Cross-sectional and longitudinal relationships of self-management behaviours and other psychological factors with outcomes in patients with severe asthma
Authors: J. R. Smith, M. J. Noble, B. D. W. Harrison, M. Adams
Journal: Thorax (2010)

<h3>Background</h3> Psychosocial factors are associated with various manifestations of severe asthma. Wider research and theory highlight complex, bi-directional pathways by which interactions may occur. However, few studies have explored relationships between multiple psychosocial factors and outcomes in severe asthma with these pathways in mind. <h3>Objectives</h3> This study investigated combined and independent cross-sectional and longitudinal relationships of self-management behaviours, an index of self-management (ISM), anxiety, depression, perceived control (PC) and socio-demographic/economic characteristics with asthma control, quality of life (QoL) and severe attacks amongst asthma patients on high levels of treatment and/or with a history of admissions. <h3>Methods</h3> Cross-sectional data from 132 adults recruited to a previously reported trial of an intervention and accompanying comparative study were subjected to multiple regression analyses. These systematically examined relationships between psychosocial factors and asthma outcomes, and were used to build final hierarchical regression models in which key clinical variables were controlled for. More limited data from a maximum of 112 patients were used to explore longitudinal relationships, primarily with asthma control. <h3>Results</h3> Final hierarchical regression models accounted for up to 69% and 73% of the variability in asthma control and QoL respectively (p&lt;0.001) and significantly predicted experience of a severe attack (p&lt;0.001). Variables showing significant independent relationships to outcomes in these models are highlighted in the Abstract P175 Table 1. Some individual behaviours and the ISM showed independent and differing cross-sectional relationships to each outcome. Other psychological factors were related to subjective outcomes but not severe attacks. Relationships of some psychosocial factors (eg, depression, unemployment) to outcomes were not fully mediated by other variables, including self-management behaviours. In longitudinal analyses, there was some evidence for depression directly contributing to poorer subjective outcomes, whilst relationships of PC and anxiety with outcomes were more variable and inconsistent. <h3>Conclusions</h3> Emotional and cognitive factors appear at least as important as self-management behaviours in relation to subjective outcomes in severe asthma. Along with a growing body of other research, findings suggest a particular need to identify and address depression amongst patients with severe asthma in practice, as in other chronic diseases.
Cigarettes, Alcohol, Coffee and Peptic Ulcer
Authors: Gary D. Friedman, A. B. Siegelaub, Carl C. Seltzer
Journal: New England Journal of Medicine (1974)

Abstract The relation of cigarette smoking, alcohol and coffee consumption and educational attainment to a history of peptic ulcer was studied in 36,656 white male and female subjects of multiphasic examinations, 30 to 59 years of age. Among men, a 2.1-fold greater percentage of cigarette smokers than of nonsmokers reported a history of peptic ulcer; for women the prevalence was 1.6 times greater in cigarette smokers. Duration of smoking, quantity smoked and inhalation were each related to a history of peptic ulcer. Although alcohol and coffee consumption were correlated with cigarette smoking and the two beverages reportedly stimulate gastric acid secretion, they were not positively related to prevalence of peptic ulcer and did not explain the relation of cigarette smoking to peptic ulcer; nor did educational attainment or body build. (N Engl J Med 290:469–473, 1974)
Abstract 1174: ASPP2: Tumor suppression through the control of polarity and proliferation
Authors: Xin Lu
Journal: Cancer Research (2012)

Abstract Cell polarity and proliferation are processes that play key roles in development. Loss of cell polarity and increased cellular proliferation are hallmarks of human cancer. The identification of molecules that are involved in the control of these processes is, therefore, important for our better understanding of tumor development and progression. p53 was recently found to be important in controlling the mammary epithelial stem cell pool. We have recently shown that ASPP2, a regulator of p53 and binding partner of many other proteins including YAP, is an important player in the regulation of cell polarity due to its ability to bind and regulate Par-3. Interestingly, ASPP2 is also able to directly regulate cell proliferation by affecting the activity of cyclin D1, by inhibiting the nuclear localisation of SUMO-modified cyclin D1. As ASPP2 is a haploinsufficient tumor suppressor, these findings identify ASPP2 as a unique regulator of cell polarity: able to influence cell polarity on the one hand and the cell cycle machinery on the other. ASPP2's interactions with p53, YAP and others, along with its potential role in controlling cell migration and EMT will be discussed. References Samuels-Lev Y, O'Connor DJ, Bergamaschi et al. ASPP proteins specifically stimulate the apoptotic function of p53. Mol Cell. 2001 Oct;8(4):781-94. Vives V, Su J, Zhong S, Ratnayaka I, Slee E, Goldin R, Lu X. ASPP2 is a haploinsufficient tumor suppressor that cooperates with p53 to suppress tumor growth. Genes Dev. 2006 May 15;20(10):1262-7. Sottocornola R, Royer C, Vives V et al. ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev Cell. 2010 Jul 20;19(1):126-37. Epub 2010 Jul 8. Wang XD, Lapi E, Sullivan A, Ratnayaka I, Goldin R, Hay R, Lu X. SUMO-modified nuclear cyclin D1 bypasses Ras-induced senescence. Cell Death Differ. 2011 Feb;18(2):304-14. Epub 2010 Aug 27. 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 1174. doi:1538-7445.AM2012-1174