tbuckley/cabot-search huggingface dataset:
P2-11-09: EGFR Overexpression in Triple Negative Breast Cancer (TNBC) and Its Association with the Prognosis.
Authors: W Liu, L Zhang, K Ma, B Han, S Li, G Xu, Z Fan, N Liu, A Shi
Journal: Cancer Research (2011)

Abstract Objective: The aim of this study is to investigate EGFR expression in Triple Negative Breast Cancer (TNBC), and to find the relationship between EGFR overexpression and prognosis of TNBC, further to clarify the significance of EGFR in TNBC and provide valuable information for TNBC therapy. Methods: 42 triple ***negandection ***ssitive breast cancer patients(studying group) and 40 HER2(3+) breast cancer patients(controling group) who underwent surgery from January 2000 to December 2005 were analyzed. 82 cases of paraffin-embedded specimens were detected by Immunohistochemistry(IHC), fluorescence in situ hybridization(FISH) and polymerase chain reaction(PCR) to investigate the overexpression, amplification and mutation of EGFR gene. The distant-free survival(DFS) and overall survival(OS) of these patients were used to investigate the relationship between EGFR overexpression and the prognosis of TNBC. Results: 34(43.9%) EGFR overexpression was observed in all cases, while gene amplification was only 7(9.1%) cases. No EGFR gene mutation was found in all cases. Overexpression of EGFR occurring in 57.1% patients in TNBC group and 25.0% patients in HER2 group, and we didn't found any correlation between EGFR overexpression and clinicopathology. 50(61.0%) patients relapsed (TNBC 28,HER2 22) and 27(32.9%) patients died(TNBC 18,HER2 9) were observed during the more than 5 years follow-up. The 5-year DFS was 57.1% and 77.5% respectively, the 5-year OS was 71.4% and 87.5% in TNBC and HER2 groups. In TNBC group, the survival of the EGFR-overexpressing group patients was significantly lower than that of the non-EGFR-overexpressing group patients (p=0.018 for DFS, p=0.026 for OS); In HER2 group, no statistical difference was found (p=0.079 for DFS, p=0.055 for OS). Conclusions: This study showed that EGFR overexpression increased significantly in TNBC patients, which was no correlation with their clinico-pathological data. EGFR gene amplification was much less frequent than its overexpression. It suggested that EGFR gene amplification may not be the unique mechanism of EGFR overexpression in TNBC. There may be other possible mechanisms and pathways that cause EGFR overexpression. In addition, it may suggest that gefitinib therapy is useless in TNBC patients because we did not find any mutations in the tested exons of TNBC. EGFR overexpression may associate with a poor outcome of TNBC patients which suggest it could be a significant prognostic factor for TNBC patients. EGFR may play important role for molecular-targeting therapy of TNBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-11-09.
ASSESSING RIGHT VENTRICULAR FUNCTIONAL RESERVE DURING EXERCISE IN HEART FAILURE COMBINING CARDIOPULMONARY EXERCISE TESTING WITH EXERCISE-ECHOCARDIOGRAPHY
Authors: Greta Generati, Francesco Bandera, Marta Pellegrino, Valentina Labate, Valeria Donghi, Eleonora Alfonzetti, Marco Guazzi
Journal: Journal of the American College of Cardiology (2015)
AB0841 Tendon Involvement in Chronic Tophaceous Gout Detected by Dual-Anergy-Computertomography
Authors: M. Fiene, V. Karnebeck, C. Rosenberg, P.O. Behrndt
Journal: Annals of the Rheumatic Diseases (2014)

Background Gout is the most prevalent metabolic arthritis and affects about 8,3 million inhabitants in the USA. Epidemiologic data from Europe are comparable and indicate that gouty arthritis or chronic tophaceous gout evolves as a public health problem with raising prevalence. Patients with chronic tophaceous gout have a high cardiovascular risk. Additionally cardiovascular medication, such as acetylsalycilic acid, antihypertensive or diuretics have an influence of renal urate handling which might cause gout attacks. Therefore it is necessary to identify these patients to prevent them from new attacks. Serum measurement of urate levels might not be sufficient for this purpose. Objectives The dual-energy-computertomography (DECT) is a new method to detect monosodiumurate (MSU) deposits. Using two different x-ray voltages (80 and 140 kV) in combination with Hounsfield-units allows to separate calcium vom sodium and separate MSU from other adjacent structures. Using DECT for tophus detection reveals much more MSU deposits compared to clinical examination. We tried to determine the extent of the involvement of anatomical structures in tophus deposition. Methods In this study we used DECT to determine bone and tendon involvement of 14 patients with chronic tophaceous gout. There is no established gold standard for DECT evaluation. Therefore DECT-scans were independently assessed by a radiologist and a rheumatologist to determine the extent of bone and tendon involvement of the feet. Tophi were allocated to the involved bone and tendon. Tophussize was rated semiquantitatively (0-5). Results Our patients do not differ in their demographic data from other published results. There were more men than women affected and the average age is over 60 years old which is in line with other publications. Both examiners revealed more tophi on DECT scans than clinically apparent. Tendon involvement is much more common than clinically suspected. In contrast to the known bone manifestations (typically "Podagra") we found far more tendon involvement, mainly achilles tendon, than expected. Conclusions Radiologist and Rheumatologist differed in their results indicating that there might be a learning curve. Further validation is needed to compare the results with other groups to establish a gold standard for interpreting the results of this new technique. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5296
Abstract 684: Identification of biomarker genes associated with endocrine therapy responsiveness in patients with estrogen receptor positive IBC and nIBC
Authors: Steven J. Van Laere, Maurice PHM Jansen, Leen Sas, Anieta Sieuwerts, Peter B. Vermeulen, Els MJJ Berns, Luc Y. Dirix
Journal: Cancer Research (2012)

Abstract Introduction: Endocrine therapy is a cornerstone in the treatment of patients with Estrogen Receptor (ER) positive (+) breast cancer. Nevertheless, resistance to endocrine treatment, either de novo or acquired, irreversably develops. In this study, we build upon the endocrine therapy resistant phenotype of patients with ER+ Inflammatory Breast Cancer (IBC) to identify and validate predictive biomarkers of endocrine therapy responsiveness. Materials and methods: Expression profiles of 21 ER+ IBC and 42 non-stage matched ER+ nIBC samples were compared using Prediction Analysis of Microarrays. The resulting gene signature was applied onto expression datasets from ER+ nIBC patients with documented intervals of relapse-free survival (RFS) for adjuvant endocrine treatment (GSE17705; N=298) or of progression-free survival (PFS) for first-line endocrine treatment (Jansen dataset (JCO, 2005), N=101). The gene signature classified samples as “IBC-like” or “nIBC-like” and Kaplan Meier and Cox regression analyses were performed. Robust biomarkers for endocrine resistance were selected using permutation analysis and validated using qRT-PCR on a series of samples from 225 ER+ nIBC patients with metastatic disease receiving first-line tamoxifen. Results: We identified a gene signature of 139 unique genes able to discriminate ER+ IBC from ER+ nIBC samples (sensitivity: 100%; specificity: 87.5%). Application of this signature onto data sets of patients with ER+ nIBC revealed significant associations with RFS (HR=1.87, P=0.001) and PFS (HR=2.04, P&amp;lt;0.001) under endocrine therapy. Permutation analysis selected 6 genes robustly discriminating ER+ IBC from ER+ nIBC samples: ABAT, ADAMDEC1, CLEC7A, ETS1, ITK1 and STC2. Expression analysis with qRT-PCR confirmed the predictive value of ADAMDEC1 (HR=1.127, P=0.020), ABAT (HR=0.779, P&amp;lt;0.001) and STC2 (HR=0.866, P&amp;lt;0.001) in 225 patients with ER+ breast cancer treated with Tamoxifen. Ingenuity Pathway Analysis revealed an intricate network linking each of the core genes with ER-, NFkB- and TGFβ-signalling. Conclusion: In this study we identified and validated a gene signature predictive of response to endocrine therapy in patients with breast cancer by comparing ER+ IBC samples to ER+ nIBC samples. Within this gene signature, ADAMDEC1, ABAT and STC2 were identified as robust markers for endocrine therapy responsiveness. 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 684. doi:1538-7445.AM2012-684
Observation or standard axillary dissection after sentinel-node biopsy in breast cancer: Final results from the German KISS study.
Authors: C. Schem, W. Jonat, H. Ostertag
Journal: Journal of Clinical Oncology (2011)

1012 Background: Although widely applied, data from randomized trials on long-term results after a sentinel node biopsy (SNB) approach in early breast cancer (BC) are still limited. The KISS study is a large prospective randomized phase III trial performed in 33 German centers, which had completed a training program before recruiting patients (pts). Methods: 1182 pts with operable, clinically node negativ, invasive breast cancer were equally randomized to either a strategy of standard axillary dissection (SAD) independent of the SNB finding (SAD arm, n=594), or to a strategy of performing SAD only in case of a positive SNB finding or failure of SN detection (control arm, n=588), but observation only in pts with negative SNB. Patients were stratified according to center, age and tumor size. The trial was designed to exclude an absolute difference in relapse-free survival (RFS) of 5% after 5 years (y) with sufficient confidence. Logrank tests were used to compare RFS (primary endpoint) and overall survival (OS) between the two groups. Hazard ratio (HR) values > 1 indicate a more favorable outcome in the SAD group. The morbidity differences were scored and analyzed. Results: The proportions of pts with negative SNB was 68%/71%, with postive SNB 24%/21%, and with missing SN detection 7%/7% in the SAD and control arm, respectively. After a maximum follow-up time of 115 month, a total of 93 RFS events (40/53) and a total of 53 death events (23/30) were observed, leading to a total estimated RFS/OS rate at 3 y of 93%/97%. Comparisons of RFS yielded a HR of 1.44 (95% confidence interval: 0.95 − 2.18; p = 0.084), and of OS yielded a HR of 1.53 (0.88−2.66; p=0.13). Paraesthesia, lymphoedema and pain was significantly less common in the SNB negative group. Conclusions: As yet, no significant differences rather a trend in favour of the SAD group were observed, both for RFS and OS. This result basically confirms other large randomised trial results reported recently. But in respect to the published equivalence, the trend in favour of the SAD group was not expected.
FRI0535 Clinical Evaluation of R202Q Alteration of MEFV Genes in Turkish Children: is R202Q A Benign Polymorphism or A Disease-Causing Mutation?
Authors: E. Comak, S. Akman, C.S. Dogan, A. Uslu Gokceoglu, Y. Arikan, I. Keser
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is an inherited autosomal recessive disorder, caused by mutations in MEditerraneanFeVer gene (MEFV). To date over 200 alterations have been reported in MEFV genes. But, it is not clear whether all these alterations are disease-causing mutations. <h3>Objectives</h3> To evaluate the clinical and laboratory features of the children with R202Q alteration. <h3>Methods</h3> In our institution, molecular diagnosis of FMF was based on the automated DNA sequencing of the mutations in exon 2 and exon 10 of MEFV gene. Before December 2012, R202Q (605G&gt;A) mutations were not reported to the clinicians, because it was not considered as a disease causing mutation. As recently some authors suggest that R202Q may be a disease causing mutation for FMF, MEFV mutation analysis that was performed between February 2009 and December 2012 were re-evaluted for R202Q alterations. Patients with heterozygous R202Q, homozygous R202Q and compound heterozygous and complex cases were included in the study. Their medical records were screened retrospectively. <h3>Results</h3> A total of 225 children, 113 males, were included. The patients were classified according to the MEFV mutation types: heterozygous R202Q in 55, homozygous R202Q in 30 and compound heterozygous and complex cases in 140. Also, patients were re-classified according to FMF phenotypes as phenotype 1 in 113 (50.2%), phenotype 3 in 7 (3.1%) and "FMF-like" disease in 105 (46.6%). None of the patients were diagnosed as FMF phenotype 2. In FMF groups (phenotype 1), a total of 113 patients had R202Q alteration: 2 heterozygous and 7 homozygous R202Q, 46 homozygous R202Q and M694V, and 58 compound heterozygous. The main clinical characteristics of the patients were: abdominal pain in 71.5%, fever in 37.7%, arthralgia/myalgia in 30.2%, arthritis in 10.2%, chest pain in 14.6%, erysipelas-like erythema in 13.3%, headache in 6.2% and history of appendectomy in 6.2%. The frequency of abdominal pain was significantly lower in patients with homozygous R202Q alteration (p=0.021), whereas patients with heterozygous R202Q mutations, though not statistically significant, had a higher frequency of arthralgia/myalgia (40.0%). <h3>Conclusions</h3> R202Q alteration of MEFV gene leads to symptoms consistent with FMF in some cases. This alteration may be associated with a mild phenotype and show phenotypic differences other than the common MEFV mutations. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5247
Manifold Trails to Heritable Hypothyroidism
Authors: John B. Stanbury
Journal: New England Journal of Medicine (1971)

The genetic apparatus of all forms of life is involved in an internal conflict: it seeks on the one hand to be conservative, to maintain its identity from generation to generation, and on the other, to allow enough variation among individuals for the evolutionary process to take place. This flexibility permits each person to be different from everyone else, but it includes the risk that the variant may be so far from the mode that adaptability is impaired. One then has inherited disease. Genetic variability has its source in the base sequences of the DNA, and is expressed in protein . . .
Child Abuse and Neglect
Authors: Lawrence S. Wissow
Journal: New England Journal of Medicine (1995)

Child abuse, long neglected by both society and medicine, is now a focus of public attention. Cases of suspected maltreatment are often featured in the news media and argued in the courts. Some cases raise profound questions about the relative rights of parents, children, and those charged with child abuse. Allegations of sexual abuse by celebrities have raised questions of privacy both for those charged with abuse and for their alleged victims, and cases of fatal physical abuse among middle-class families have challenged the stereotype that violence in the home occurs only among the poor or disadvantaged.Physicians and others . . .
Brief Report: Surface Active Agents as Tumor Promoters
Authors: E. Boyland
Journal: Environmental Health Perspectives (1983)

*TUC Centenary Institute of Occupational Health London School of Hygiene and Tropical Medicine, Keppel St., London WC1E-7HT, England. the types of promoter listed have not been demonstrated as such by animal experiments, but if a substance is a carcinogenic but not mutagenic, then it is most probably a tumor promoter. This assumes that mutagens are initiators and that promoters can induce cancer because initiators are present in the diet or environment. Until recently, the adventitious initiators were considered as contaminants such as aflatoxin or nitrosamines, but the mutagen and carcinogen, quercitin, is present as such or as glycosides in most vegetable matter and in animal foods. Substances which inhibit DNA repair or suppress immune response might also increase cancer incidence and so be considered as carcinogens without being promoters. Some neoplasia including liver tumors in mice, bladder, kidney and thyroid tumors in rats are easily induced by promoters so that their occurrence is almost indicative of tumor promotion. Tumor promoters are organotropic and can change the site of action of an initiator. Thus tryptophan can change the site of action of 2-acetylaminofluorene from the liver to the bladder and thiouracil from the liver to the thyroid. Some carcinogens, particularly aromatic amines, cause cancer in different organs in different species; this effect could be due to tumour promotion.
Abstract 1646: <i>In vivo</i> target validation in orthotopic hepatocellular carcinoma model using formulated siRNA
Authors: Baisong Liao, Debra Kellner, Chunrong Wang, Shilu Wu, Marion Molina, De-Min Zhu, Ashwin Gollerkeri, Catherine Pachuk
Journal: Cancer Research (2011)

Abstract Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and its incidence continues to increase. Although there are approved therapies for HCC, the prognosis remains poor. The 5-year survival rate is &amp;lt; 5%. Nucleic acid-based therapeutics such as RNAi may improve patient outcome. Nevertheless, target identification/validation for HCC and delivery of siRNA are major challenges facing the development of HCC-specific RNAi based therapeutics. To enable target validation in vivo using RNAi, we have developed nanolipid siRNA formulations for the in vivo delivery of siRNA to orthotopic tumors. PK/PD studies in model systems demonstrate that up to 80% knockdown of target protein is achievable within tumors and that significant knockdown persists for at least 10 days following a single dose of formulated siRNA. Efficacy studies using similar formulations of siRNAs against potential HCC tumor targets, including mTOR, will be presented. 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 1646. doi:10.1158/1538-7445.AM2011-1646
Immunohistochemical Localization of Growth Factors and Their Receptors in Uterine Leiomyomas and Matched Myometrium
Authors: D Dixon, H He, J K Haseman
Journal: Environmental Health Perspectives (2000)

Immunolocalization of transforming growth factor alpha (TGF-Alpha), epidermal growth factor (EGF), insulinlike growth factor (IGF)-I, vascular endothelial growth factor (VEGF(165,189,121)), basic fibroblast growth factor (FGF)-2, EGF receptor (R), IGF-IRbeta, and FGFR-1 was studied in uterine leiomyomas and matched myometrial samples taken from seven women (42-47 years of age) in the proliferative phase of the menstrual cycle. Immunolocalization of growth factor peptides was accomplished with either monoclonal or polyclonal antibodies to the amino or carboxy terminus of growth factor peptides or their respective receptors, or against full-length recombinant growth factor. All reactions were conducted using the avidin-biotin complex method. Immunolocalization of TGF-alpha, EGF, EGF-R, IGF-I, IGF-IRbeta, FGF-2, FGFR-1, and VEGF was observed in the cytoplasm of smooth-muscle cells of leiomyomas and matched myometrium. The cytoplasm of vascular smooth-muscle cells expressed TGF-alpha, EGF, EGF-R, IGF-I, IGF-IRbeta, FGF-2, FGFR-1, and VEGF, whereas the vascular endothelium was positive for TGF-alpha, EGF, EGF-R, FGF-2, and FGFR-1 in both leiomyomas and matched myometria. Fibroblasts within the fibrous component of some leiomyomas were positive for IGF-I and FGF-2 and minimally positive for FGFR-1. In addition, the extracellular matrix of leiomyomas showed focal localization of FGF-2 and IGF-I in some tumors. When scores of intensity and percent positive staining were compared, IGF-IRbeta was significantly increased in the leiomyomas compared to matched myometria, whereas EGF was significantly decreased in the uterine leiomyomas compared to matched myometria. In summary, these data revealed growth factors to be expressed differentially in smooth muscle, vascular and fibroblastic cell types of leiomyomas and matched myometria. Specifically, IGF-IRbeta was significantly increased in leiomyomas; although a similar increase was seen with IGF-I peptide, statistical significance was not achieved. The EGF peptide was significantly decreased in the leiomyomas compared to matched myometrium. These data suggest that IGF-IRbeta and IGF-I peptide may be one of several growth factor/receptor pathways important in uterine leiomyoma growth during the proliferative phase of the menstrual cycle. In addition, decreased EGF may be secondary to the predominant estrogenic milieu present at time of sampling, as it has been proposed that progesterone, and not estrogen, may regulate EGF.
Abstract 1287: High mobility of triple-negative breast cancer cells is due to repression of plakoglobin gene by SLUG
Authors: Charvann K. Bailey, Mukul K. Mittal, Smita Misra, Gautam Chaudhuri
Journal: Cancer Research (2012)

Abstract One of highly pathogenic breast cancer cell types are the SLUG-high claudin-low triple negative (negative in the expression of estrogen, progesterone and ERBB2 receptors) breast cancer (TNBC) cells. These cells are highly metastatic and have low levels of the motility regulatory catenin plakoglobin. In order to link high levels of the transcriptional repressor SLUG in the TNBC cells with low levels of plakoglobin we found that SLUG inhibits the expression of plakoglobin gene directly in these cells and thus, among other downstream effects, help disseminating these tumor cells. Overexpression of SLUG in the SLUG-deficient cancer cells significantly decreased the levels of mRNA and protein of plakoglobin. On the contrary, knockdown of SLUG in SLUG-high cancer cells elevated the levels of plakoglobin. Overexpression of SLUG in the SLUG-deficient cells elevated the invasiveness and motility of these cells. On the other hand, knockdown of plakoglobin in these low motility non-invasive breast cancer cells did not affect the ability of the cancer cells to penetrate Matrigel matrix but increase the growth and migration rates of these cells. This study thus implicates high levels of SLUG and low levels of plakoglobin as determinants in the progression of highly disseminating breast cancer. Supported in parts by the DOD-CDMRP grants BC050641, BC086542 and BC103645 to GC. 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 1287. doi:1538-7445.AM2012-1287
Fatal case of biliary cast syndrome in nontransplant patient
Authors: A. Dziurkowska-Marek, M. Hartleb, T. Marek, E. Nowakowska-Duława, R. Kaczor, M. Ciupińska-Kajor, M. Kajor
Journal: Endoscopy (2009)

A 69-year-old male, with no history of liver disease, was admitted after several days of low-grade fever, weakness, and jaundice, preceded by dyspepsia and diarrhea that occurred during recent holidays in North Africa. Laboratory tests revealed anemia (hemoglobin 7.7 g/dL), inflammation (C-reactive protein 148 mg/L, white blood cells 16.6 g/L), and liver injury (alkaline phosphatase [ALP] 426 U/L, gamma glutamyl transpeptidase [GGT] 160 U/L, alanine aminotransferase [ALT] 90 U/L, aspartate aminotransferase [AST] 114 U/L, bilirubin rapidly rising to 22 mg/dL). All possible etiologies of liver injury were excluded. Abdominal ultrasound and computed tomography revealed an enlarged liver with multiple focal lesions requiring differentiation between abscesses, metastases, or hamartomas ([Fig. 1] and [2]).