tbuckley/cabot-search huggingface dataset:
Abstract P3-10-40: Expression and Prognostic Significance of Cancer Testis Antigens (CTA) in Primary Breast Cancer: Possible Diagnostic Markers and Therapeutical Targets
Authors: D Balafoutas, A zur Hausen, A Jungbluth, D Denschlag, M Jäger, G Gitsch, E. Stickeler
Journal: Cancer Research (2010)

Abstract Backround: Cancer Testis Antigens (CTA) are a family of proteins normally expressed in the human germ cells such as in the testis. They also have been found in various types of malignant tumors including breast cancer. Because of their restricted expression pattern they are frequently able to elicit T-cell immune responses, and therefore they are considered as ideal targets for cancer immunotherapy. Breast differentiation antigen NY-BR-1 has also immunogenic properties. The aim of this study was to explore the CTA expression in breast cancer and detect possible clinical correlations. Materials and Methods: The expression patterns of 6 CTAs (MAGE A1- MA454, MAGE A3-M3H67, MAGE A4-57B, NY-ESO-1-E978, GAGE, MAGE A-6C1) and NY-BR-1 were examined by immunohistochemistry in a series of 210 non-selected patients with primary invasive breast cancer using the tissue microarray technique. The intensity of the stain was scored semi-quantitatively in a scale 0 to+3. The expression of the antigens was correlated to established clinicopathological parameters as well as disease-free (DFS) and overall (OS) survival. Results: CTA expression exhibited a predominantly cytoplasmic and occasionally nuclear localization. At least one CTA was identified in 37.2% of cases with expression of each antigen varying from 4.5 to 15%. NY-BR-1 was positive in 46.6% of tumors, with the well differentiated tumors showing more frequent expression. MAGE A4-57B (p=0.028 and 0.015) and MAGE A3-M3H67 (p=0.001 and 0.004, respectively) positivestaining was significantly correlated to shorter OS and DFS. MAGE A1-MA454 correlated significantly only with OS (p=0.028). GAGE and MAGE A-6C1 displayed a clear trend, but not statistically significant prognostic value concerning shorter DFS and OS. In multivariate analysis only MAGE A3-M3H67 (p=0.007 OS) and MAGE A4-57B (p=0.017 DFS, 0.052 OS) showed and independent prognostic relevance. Additionally, the mortality rate increased substantially if co-expression of any 3 or more CTAs was observed. Discussion: Our findings suggest that CTAs could serve as potential prognostic markers in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define potential new targets for specific breast cancer therapies. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-10-40.
Abstract 3845: The normal breast microenvironment of premenopausal women differentially influences the behavior of breast cancer cells in vitro and in vivo
Authors: Jodie M. Fleming, Tyler C. Miller, Mariam Quinones, Zhen Xiao, Xia Xu, Matthew J. Meyer, Erika Ginsburg, Timmothy D. Veenstra, Barbara K. Vonderhaar
Journal: Cancer Research (2010)

Abstract Introduction: Breast cancer studies frequently focus on the role of the tumor microenvironment in the promotion of cancer; however, the influence of the normal breast microenvironment on cancer cells remains relatively unknown. To investigate the role of the normal breast microenvironment on breast cancer cell tumorigenicity, we examined whether extracellular matrix molecules (ECM) derived from pre-menopausal African-American (AA) or Caucasian-American (CA) breast tissue would affect the tumorigenicity of cancer cells in vitro and in vivo. We chose these two populations because of the well-documented predisposition of AA to develop aggressive, highly metastatic breast cancer compared to CA women. Methods: The effects of primary breast fibroblasts on tumorigenicity were analyzed via real-time PCR arrays and mouse xenograft models. Whole breast-ECM was isolated, analyzed via zymography, and its effects on breast cancer cell aggressiveness were tested in vitro via soft agar and invasion assays, and in vivo via xenograft models. Breast ECM and hormone metabolites were analyzed via mass spectrometry. Results: Mouse mammary glands humanized with pre-menopausal CA-fibroblasts and injected with primary breast cancer cells developed significantly larger tumors compared to AA-humanized glands. Examination of 164 extracellular matrix (ECM) molecules and cytokines from CA-derived fibroblasts demonstrated a differentially regulated set of ECM proteins and increased cytokine expression. Whole breast-ECM was isolated; invasion and soft agar assays demonstrated that ER-/PR- cells were significantly more aggressive when in contact with AA ECM, as were ER+/PR+ cells with CA ECM. Using zymography, protease activity was comparatively upregulated in CA ECM. In xenograft models, CA ECM significantly increased the tumorigenicity of ER+/PR+ cells and enhanced metastases. Mass spectrometry analysis of ECM proteins showed only 1,759 of ∼8,000 identified were in common. In the AA dataset, proteins associated with breast cancer were primarily related to tumorigenesis/neoplasia, while CA-unique proteins were involved with growth/metastasis. Using a novel mass spectrometry method, 17 biologically-active hormones were measured; estradiol, estriol and 2-methoxyestrone were significantly higher in CA breast tissue. Conclusions: This study details normal pre-menopausal breast tissue composition, delineates potential mechanisms for breast cancer development, and provides data for further investigation into the role of the microenvironment in cancer disparities. 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 3845.
Abstract 4307: The effect of ablating ADF/cofilin pathway during skin homeostasis and tumorigenesis
Authors: Jing Zhou, Hitesh Patel, Valerie G. Brunton, Margaret C. Frame
Journal: Cancer Research (2012)

Abstract Proteins of the cofilin pathway are key regulators of actin dynamics. There are three cofilin isoforms encoded by human and mice. Of these, ADF-cofilin(ADF) and cofilin1(COF) are expressed in most epithelial tissues while muscle-cofilin is not. Recent data has indicated that components of the cofilin pathway(ADF, COF) are frequently mis-regulated in cancer cells, but there are conflicting reports on how these cofilins and the upstream regulatory LIM kinases contribute to the malignant phenotype by their over-expression, or suppression. The data suggest that it is the balance of the cofilin pathway regulators, and the cofilin pathway “output” which determines the invasiveness of tumor cells. The cofilin pathway must therefore be considered as a whole. Therefore, we will address the role of the cofilin pathway in skin homeostasis and cancer by deletion of ADF and COF in the skin. We generated K14-Cre-ER/ADF(-/-)/COF(fl/fl) mice, which are nullizygous for ADF and have floxed COF under control of keratin14 Cre recombinase, as ubiquitous cofilin deletion is embryonic lethal. After 4-OHT-induced COF deletion, we examined the effects on skin homeostasis and skin tumorigenesis. However, the homozygous ADF and COF knockout mice died within a few days following induction of Cre. There was a thickening of the epidermis due to hyperplasia of the spinous layer of cells. A marked increase in apoptosis of epithelial cells was also evident, predominantly affecting cells of the basal layer, resulting in ulceration of the skin and oral mucosa. These animals become acutely sick due to the oral ulceration leading to reduced food and water intake. Immunohistochemical analysis showed that the “stress inducible” keratin6, which is usually observed in hyperproliferative conditions, was aberrantly expressed in the epidermis of the homozygous ADF and COF knock out mice. Both in vitro and in vivo experiments indicated that E-cadherin was lost from cell-cell contacts in double ADF/COF knockout keratinocytes. In addition, the double ADF/COF knockout keratinocytes migrated in a mesenchymal manner and their movement was 4 times faster than wild type keratinocytes, which retained cell-cell contacts and moved in collective manner. All these data indicate that the output of the cofilin pathway is likely to be involved in cancer cell processes, including migration, proliferation, differentiation and apoptosis. We are currently generating tumor-derived cell lines from invasive squamous cell carcinomas in which both ADF and COF have been deleted and analyzing cancer-associated behaviour both in vitro and in vivo. 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 4307. doi:1538-7445.AM2012-4307
Is Immunotherapy for Asthma Worthwhile?
Authors: Peter J. Barnes
Journal: New England Journal of Medicine (1996)

Although allergen immunotherapy has been used to treat allergic asthma for over 70 years, its role remains controversial. The consensus report on diagnosis and management of asthma of the National Institutes of Health recommends that allergen immunotherapy should be considered only when asthma is poorly controlled with drug therapy or when it is impossible to avoid allergens,1 whereas the British Thoracic Society Guidelines do not recommend immunotherapy under any circumstances.2 There have been many trials of immunotherapy, but the results are often difficult to interpret because of the use of allergen extracts that are not standardized, poor study design, and . . .
Relation of Massive Bowel Resection to Gastric Secretion
Authors: Paul L. Frederick, Jack S. Sizer, Melvin P. Osborne
Journal: New England Journal of Medicine (1965)

CLINICAL experience with patients who have had massive bowel resection suggests that gastric hypersecretion may occur and can significantly affect the course. Summarized below are 2 cases in which an unusually favorable course followed massive bowel resection. Both patients had undergone previous surgery for duodenal ulcer. Two additional cases provided an opportunity to observe gastric hypersecretion after massive bowel resection. One of these patients suffered complications that were managed by surgical intervention to control gastric hypersecretion.Case 1. A 58-year-old man (U.H. [Columbus, Ohio] 343616x) required small-bowel and colon resection from a point 37.5 cm. (15 inches) distal to the . . .
P987 REPEATED LOCO-REGIONAL TREATMENTS IN CASE OF RECURRENCES FROM HEPATOCELLULAR CARCINOMA: 10 YEARS EXPERIENCE IN A LARGE SERIES
Authors: L. Tarantino, F. Sabbatino, P. Ambrosino, V. Iovino, G. Cuccorese, R. Giordano
Journal: Journal of Hepatology (2014)
Delayed Tc-99m Citrate Scintigraphy in the Evaluation of Palpable Breast Masses
Authors: A Mondal, R Sharma, K L Chakravarty, P Mishra, K Sahay, A Bhatnagar, A Gupta, K Sawroop
Journal: Clinical Nuclear Medicine (1999)

The aim of this study was to evaluate the potential of Tc-99m citrate as a new tumor-localizing agent in palpable breast masses. Scintimammography was performed in 43 female patients. Of these, 10 women (group A) were considered to be healthy with no palpable breast masses, and the remaining 33 patients (group B) had palpable breast masses. All patients with palpable breast masses underwent fine-needle aspiration cytology and subsequent biopsy within 2 weeks of the study. Nine patients had a primary malignant lesion of the breast, whereas 24 patients had benign disease. The patients with breast cancer underwent surgery, and subsequently a histopathologic diagnosis was made. Sensitivity, specificity, and accuracy values obtained in our study were 87%, 100%, and 90%, respectively. Scintimammograms were performed in these patients up to 24 hours. Initial uptake at 1 and 3 hours was noted in all the breast masses. However, benign masses did not show persistence of tracer uptake at 24 hours, whereas those that were malignant continued to show persistent radionuclide concentration. Thus, the uptake and outflow pattern seemed to differentiate benign breast disease from breast cancer. The study shows the potential of Tc-99m citrate for imaging and evaluating breast masses.
Abstract 1237: WT1, Wnt signaling and E-cadherin in prostate cancer
Authors: Adina Brett, Kurtis Eisermann, Gail Fraizer
Journal: Cancer Research (2010)

Abstract Prostate carcinoma is the most common malignancy and second leading cause of death among American men. The molecular mechanisms that control the progression of this type of cancer are still poorly understood. Among the genes proposed to play a role in prostate cancer is the zinc finger transcription factor, WT1. Previous studies in our lab have shown WT1 protein in a majority of high grade prostate tumor sections with little or no WT1 staining in non-neoplastic or benign prostatic hyperplasia (BPH) tissues. However, a mechanistic role for WT1 in prostate cancer has not been established. Recently, WT1 has been associated with the Wnt signaling pathway and Beta catenin, the central molecule in the pathway. The cytoplasmic levels of Beta catenin can be regulated through the canonical Wnt signaling or through the intracellular adhesion complex where it binds to E-cadherin. Importantly, E-cadherin has previously been identified as a WT1 target gene in NIH 3T3 cells. The objective of this study was to determine whether WT1 might regulate genes that, in turn, regulate the levels of Beta catenin in prostate cancer cells. First potential WT1 binding sites were identified in the promoters of two candidate genes, GSK3 Beta and E-cadherin, using a bioinformatics approach. Then the effect of transfection of LNCaP prostate cancer cells with GFP-tagged WT1 expression constructs was tested by quantitative real time PCR (QRT-PCR). In vivo evidence of direct binding of these gene promoters by WT1 protein was obtained by Chromatin immunoprecipitation (ChIP) of GFP/WT1 transfected LNCaP cells. Using evolutionary conservation analysis we identified two WT1 binding sites in the E-cadherin promoter conserved among primate species and one that was conserved among primates, rodents and dog. QRT- PCR results showed a decrease in E-cadherin transcripts in GFP/WT1 transfected LNCaP cells, compared with untransfected cells. ChIP was used to demonstrate that this effect on E-cadherin expression was direct and mediated by DNA binding to the E-cadherin promoter in vivo. Overall these results suggest that WT1 modulates E-cadherin and the Wnt signaling pathway in LNCaP cells. These findings suggest a novel mechanism for proliferation and migration of prostate cancer cells and ultimately may contribute towards an improved cancer therapy. This work was supported by NIHR15CA11360 (GF) and GSS KSU grant(AB) 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 1237.
Abstract 45: Dynamic biochemical tissue analysis of P-selectin ligands expressed on colon cancer.
Authors: Eric W. Martin, Venktesh S. Shirure, Ramiro Malgor, Vicente A. Resto, Douglas J. Goetz, Monica M. Burdick
Journal: Cancer Research (2013)

Abstract Selectin ligands are known to be upregulated in metastatic tumor cell lines, and growing evidence suggests selectin/selectin-ligand interactions mediate the adhesion of circulating tumor cells to distant sites. Thus, novel methods of characterizing selectin ligands expressed on human tissue may serve as valuable assays with significant diagnostic and prognostic potential. Because the kinetic and tensile properties of selectin/selectin-ligand bonds are influenced by local physiological conditions, i.e., wall shear stress due to hydrodynamic force, traditional immunohistochemical approaches cannot adequately detect selectin ligands. That is, though immunohistochemistry is very successful in identifying high affinity interactions, selectin/selectin-ligand interactions exhibit high affinity only when the external force applied on the bond is at an optimal value. This affinity is considerably weaker when applied force on the bond is significantly larger than this optimal value, or else is low or zero, as in traditional immunohistochemistry. Therefore, we have developed a method for detecting selectin ligands expressed on human tissue using a dynamic approach that allows for precise control of the force applied to the bonds between probe and target molecules. More specifically, we conjugated recombinant P-selectin to polystyrene microspheres and perfused this probe over tissue sections of colon cancer - which is known to express P-selectin ligands. Selectin/selectin-ligand adhesive interaction in the form of microsphere rolling on tissue was observed, and specific interaction was confirmed using 10 mM EDTA as a negative control. Increased probe surface coverage (i.e., higher density of P-selectin molecules coated on the surface of the microspheres) resulted in increased interaction with colon cancer tissue. In addition, rolling velocities measured between physiological wall shear stresses 0.25-2.0 dyne/cm2 indicated adhesive interaction of the selectin-conjugated probe with ligands in colon cancer tissues was stabilized at 0.75 dyne/cm2. Analysis of distinct regions within colon cancer tissue sections subjected to this dynamic biochemical tissue analysis revealed different levels of microsphere adhesion in discrete areas, evidence of heterogeneous cellular expression of P-selectin ligands. Taken together, these results demonstrate that functional P-selectin ligands are detectable using dynamic biochemical tissue analysis. Citation Format: Eric W. Martin, Venktesh S. Shirure, Ramiro Malgor, Vicente A. Resto, Douglas J. Goetz, Monica M. Burdick. Dynamic biochemical tissue analysis of P-selectin ligands expressed on colon 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 45. doi:10.1158/1538-7445.AM2013-45
Reinventing the wheel on structuring groups, with an inadequate psychology
Authors: Kevin MacDonald
Journal: Behavioral and Brain Sciences (2014)

Abstract The idea that structured organization of differentiated individuals influences group behavior is not new to evolutionary approaches. An adequate theory of groups needs to incorporate explicit processing, which is central to means-end reasoning involved in leadership and to the construction of ideologies that rationalize group structure. Explicit processing is also central to knowledge of others' reputations, thus enabling altruistic cooperation.
The Effect of the Angiotensin-Converting–Enzyme Inhibitor Zofenopril on Mortality and Morbidity after Anterior Myocardial Infarction
Authors: Ettore Ambrosioni, Claudio Borghi, Bruno Magnani
Journal: New England Journal of Medicine (1995)

Left ventricular dilatation and neuroendocrine activation are common after acute anterior myocardial infarction. Long-term treatment with an angiotensin-converting–enzyme (ACE) inhibitor may improve outcome by attenuating these processes. We investigated whether the ACE inhibitor zofenopril, administered for six weeks after anterior myocardial infarction, could improve both short-term and long-term outcome.
Elevated Uptake of F-18 FDG in PET Scans in Nonmalignant Disease
Authors: KHALID TAALEB, KLAUS PETER KAISER, HELMUT WIELER
Journal: Clinical Nuclear Medicine (2000)

The authors describe two patients with unusual elevated uptake of fluorine-18 fluorodeoxyglucose (F-18 FDG) in the presence of nonmalignant diseases. Uptake of F-18 FDG as a result of granulomatous disease has been previously described. In one patient, we report a very high uptake F-18 FDG in the lungs, liver, and spleen in a 47-year-old woman as a result of sarcoidosis. The differential diagnosis included malignant lymphoma. F-18 FDG uptake has also been shown in inflammatory lesions. In the other case, high uptake of F-18 FDG in the epigastrium was evident in a 51-year-old man as a result of a foreign body (wooden toothpick), that had silently perforated the gastric wall.
Abstract P1-14-02: Different Outcomes in Breast Cancer (BC) Patients with CNS Metastases According to IHC Phenotype
Authors: HL Gómez, CE Vigil, WR Cruz, SP Neciosup, JA Pinto, JF Suazo, LA Mas, FF Doimi, MJ Falla, CS. Vallejos
Journal: Cancer Research (2010)

Abstract Background: Phenotype plays an important role in BC biology and outcome. We evaluated the characteristics and outcomes of clinical stages I-III BC patients with recurrence according to the IHC phenotype: ER or PR+/HER2-; HER2+ (regardless the ER and PR status) and triple negative (ER-/PR-/HER2-), to determine the influence of phenotype in the SNC recurrence. Methods: We reviewed 1,232 clinical stage I-III BC treated at INEN (2000-2002). Phenotypes were categorized by IHC into [ER+ and/or PR+, HER2-], [ER-, PR-, HER2-] and [HER2+ (regardless ER/PR status)]. Patients were classified in 3 risk groups (recursive partitioning analysis [RPA]; Gaspar et al. Int J Radiat Oncol Biol Phys 1997;37:745) according to 4 criteria: those with Karnofsky Performance Status (KPS) less than 70 (Class III), those with a KPS of or more, aged less than 65, with a controlled primary, no other systemic metastases (Class I), all other patients (Class II). We used Kaplan-Meier estimates for comparing CNS-free metastases survival and survival after CNS recurrence according to IHC phenotype or classes. Results: A median follow-up of 7.6 years; 416 (33.8%) patients had local, regional or distant disease dissemination, and 454 (36.9%) deaths were registered. In total, 62 (5.0%) patients developed CNS metastases (60 cases of cerebral and 2 of meningeal metastases), 36 (2.9%) of whom had developed CNS metastases as the site of first recurrence. 12 (2.1%), 31 (7.7%) and 19 (7.5%) were ER or PR+/HER2-, HER2+ and triple negative, respectively. CNS metastases free survival shown significant differences between ER or PR+/HER2-, HER2+ and Triple negative (97.3%, 89.6% y 90.5%, respectively; P&amp;lt;0.001). Main multivariate predictive factor was IHC phenotype (P&amp;lt;0.001), using [ER or PR+/HER2-] as reference, other phenotypes were expressed by hazard ratios (HR); [HER2+] (HR=3.8, 95%CI; 1.9 - 7.4), triple-negative (HR=4.0, 95%CI; 1.9-8.4). In regard to the RPA groups, 3 (4.9%) were class I, 28 (45.9%) class II and 30 (49.2%) class III. Median survival after CNS recurrence was 12.9, 6.1 and 2.8 for RPA Class I,II and III, respectively]; however there was not significant differences (p=0.085). In the multivariate analysis for OS after SNC metastases, only phenotype was significant and Triple Negative have the higher risk (HR=2.064; IC95% 0.94 — 4.531; P=0.023), Risk groups have not significant effect (P=0.088). Phenotype and outcome Conclusion: IHC phenotype is a strong risk factor for outcome; triple negative, and Class III breast cancer patients present a shorter time to CNS recurrence and survival after CNS recurrence than other IHC phenotypes and other risk groups. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-14-02.