tbuckley/cabot-search huggingface dataset:
A Strategy for Searching Antigenic Regions in the SARS-CoV Spike Protein
Authors: Yan Ren, Zhengfeng Zhou, Jinxiu Liu, Liang Lin, Shuting Li, Hao Wang, Ji Xia, Zhe Zhao, Jie Wen, Cuiqi Zhou, Jingqiang Wang, Jianning Yin, Ningzhi Xu, Siqi Liu
Journal: Genomics Proteomics & Bioinformatics (2003)

Abstract In the face of the worldwide threat of severe acute respiratory syndrome (SARS) to human life, some of the most urgent challenges are to develop fast and accurate analytical methods for early diagnosis of this disease as well as to create a safe anti-viral vaccine for prevention. To these ends, we investigated the antigenicity of the spike protein (S protein), a major structural protein in the SARS-coronavirus (SARS-CoV). Based upon the theoretical analysis for hydrophobicity of the S protein, 18 peptides were synthesized. Using Enzyme-Linked Immunosorbent Assay (ELISA), these peptides were screened in the sera from SARS patients. According to these results, two fragments of the S gene were amplified by PCR and cloned into pET-32a. Both S fragments were expressed in the BL-21 strain and further purified with an affinity chromatography. These recombinant S fragments were confirmed to have positive cross-reactions with SARS sera, either by Western blot or by ELISA. Our results demonstrated that the potential epitope regions were located at Codons 469–882 in the S protein, and one epitope site was located at Codons 599–620. Identification of antigenic regions in the SARS-CoV S protein may be important for the functional studies of this virus or the development of clinical diagnosis.
A Shift in the Clinical Spectrum of Eosinophilic Gastroenteritis Toward the Mucosal Disease Type
Authors: Joseph Y. Chang, Rok Seon Choung, Ru Min Lee, G. Richard Locke, Cathy D. Schleck, Alan R. Zinsmeister, Thomas C. Smyrk, Nicholas J. Talley
Journal: Clinical Gastroenterology and Hepatology (2010)
Prognostic Value of Baseline [18F] Fluorodeoxyglucose Positron Emission Tomography and 99mTc-MDP Bone Scan in Progressing Metastatic Prostate Cancer
Authors: Gustavo S.P. Meirelles, Heiko Schöder, Gregory C. Ravizzini, Mithat Gönen, Josef J. Fox, John Humm, Michael J. Morris, Howard I. Scher, Steven M. Larson
Journal: Clinical Cancer Research (2010)

Abstract Purpose: To compare the diagnostic and prognostic value of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scans (BS) in the assessment of osseous lesions in patients with progressing prostate cancer. Experimental Design: In a prospective imaging trial, 43 patients underwent FDG-PET and BS prior to experimental therapies. Bone scan index (BSI) and standardized uptake value (SUV) on FDG-PET were recorded. Patients were followed until death (n = 36) or at least 5 years (n = 7). Imaging findings were correlated with survival. Results: Osseous lesions were detected in 39 patients on BS and 32 on FDG-PET (P = 0.01). Follow-up was available for 105 FDG-positive lesions, and 84 (80%) became positive on subsequent BS. Prognosis correlated inversely with SUV (median survival 14.4 versus 32.8 months if SUVmax &amp;gt; 6.10 versus ≤ 6.10; P = 0.002) and BSI (14.7 versus 28.2 months if BSI &amp;gt; 1.27 versus &amp;lt; 1.27; P = 0.004). Only SUV was an independent factor in multivariate analysis. Conclusion: This study of progressive prostate cancer confirms earlier work that BSI is a strong prognostic factor. Most FDG-only lesions at baseline become detectable on follow-up BS, suggesting their strong clinical relevance. FDG SUV is an independent prognostic factor and provides complementary prognostic information. Clin Cancer Res; 16(24); 6093–99. ©2010 AACR.
Inequalities in outcomes for non-small cell lung cancer: the influence of clinical characteristics and features of the local lung cancer service
Authors: A. L. Rich, L. J. Tata, C. M. Free, R. A. Stanley, M. D. Peake, D. R. Baldwin, R. B. Hubbard
Journal: Thorax (2011)

<h3>Background</h3> The treatment given to patients with lung cancer and survival vary between and within countries. The National Lung Cancer Audit (NLCA) linked to Hospital Episode Statistics was used to quantify the extent to which these outcomes are influenced by patient features and/or hospital facilities and performance indicators. <h3>Methods</h3> All patients with a histological diagnosis of non-small cell lung cancer (NSCLC) were included. Logistic regression was used to quantify the independent influence of features of both patients and hospitals on the likelihood of having surgery and Cox regression was used for survival analyses. <h3>Results</h3> There were 34 513 patients with NSCLC in our dataset. After adjusting for age, sex, performance status, stage and Charlson Index of comorbidity, patients with NSCLC first seen in thoracic surgical centres (27% of the cohort) were 51% more likely to have surgery than those seen in non-surgical centres (adjusted OR 1.51, 95% CI 1.16 to 1.97). Resection rates varied from 13% to 17% between non-surgical and thoracic surgical centres. Surgery was the most powerful determinant of overall survival (adjusted HR 0.41, 95% CI 0.39 to 0.44). <h3>Conclusion</h3> A minority of patients with NSCLC first seen in a thoracic surgical centre are more likely to have surgery and to benefit from the survival advantage this confers. This finding suggests that there is an opportunity to improve the outcome for patients with lung cancer in England by optimising access to thoracic surgeons in non-surgical centres.
Human Cytokines: Their Role in Disease and Therapy
Authors: A. P Greening
Journal: BMJ (1995)

Ed Bharat B Aggarwal, Raj K Puri Blackwell Science, £95, pp 736 ISBN 0 86542 352 0

Cytokines divide the medical profession into camps: the non-believers, the enthusiastic believers, and the “I would love to believe if only I could understand.” The first do not require a textbook, merely conversion. The second do not require a textbook but access to original papers. The third group wish to be lead gently through this enormous field with sympathy and understanding. Can one book hope to cover a …
Misregulated Wnt/β-Catenin Signaling Leads to Ovarian Granulosa Cell Tumor Development
Authors: Derek Boerboom, Marilene Paquet, Minnie Hsieh, Jinsong Liu, Soazik P. Jamin, Richard R. Behringer, Jean Sirois, Makoto M. Taketo, JoAnne S. Richards
Journal: Cancer Research (2005)

Misregulation of the Wnt/beta-catenin signaling pathway is a hallmark of several forms of cancer. Components of the Wnt/beta-catenin pathway are expressed in ovarian granulosa cells; nevertheless, its potential involvement in granulosa cell tumorigenesis has not been examined. To this end, human (n = 6) and equine (n = 18) granulosa cell tumors (GCT) were analyzed for beta-catenin expression by immunohistochemistry. Unlike granulosa cells of normal ovaries, most (15 of 24) GCT samples showed nuclear localization of beta-catenin, suggesting that activation of the Wnt/beta-catenin pathway plays a role in the etiology of GCT. To confirm this hypothesis, Catnb(flox(ex3)/+); Amhr2(cre/+) mice that express a dominant stable beta-catenin mutant in their granulosa cells were generated. These mice developed follicle-like structures containing disorganized, pleiomorphic granulosa by 6 weeks of age. Even in older mice, these follicle-like lesions grew no larger than the size of antral follicles and contained very few proliferating cells. Similar to corpora lutea, the lesions were highly vascularized, although they did not express the luteinization marker Cyp11a1. Catnb(flox(ex3)/+); Amhr2(cre/+) females were also found to be severely subfertile, and fewer corpora lutea were found to form in response to exogenous gonadotropin compared with control mice. In older mice, the ovarian lesions often evolved into GCT, indicating that they represent a pretumoral intermediate stage. The GCT in Catnb(flox(ex3)/+); Amhr2(cre/+) mice featured many histopathologic similarities to the human disease, and prevalence of tumor development attained 57% at 7.5 months of age. Together, these studies show a causal link between misregulated Wnt/beta-catenin signaling and GCT development and provide a novel model system for the study of GCT biology.
Advancing Treatment for Metastatic Bone Cancer: Consensus Recommendations from the Second Cambridge Conference
Authors: Robert E. Coleman, Theresa A. Guise, Allan Lipton, G. David Roodman, James R. Berenson, Jean-Jacques Body, Brendan F. Boyce, Laura M. Calvi, Peyman Hadji, Eugene V. McCloskey, Fred Saad, Matthew R. Smith, Larry J. Suva, Russell S. Taichman, Robert L. Vessella, Katherine N. Weilbaecher
Journal: Clinical Cancer Research (2008)

Summarize current knowledge, critical gaps in knowledge, and recommendations to advance the field of metastatic bone cancer.A multidisciplinary consensus conference was convened to review recent progress in basic and clinical research, assess critical gaps in current knowledge, and prioritize recommendations to advance research in the next 5 years. The program addressed three principal topics: biology of metastasis, preserving normal bone health, and optimizing bone-targeted therapies.A variety of specific recommendations were identified as important to advance research and clinical care over the next 5 years.Priorities for research in bone biology include characterizing components of the stem cell niche in bone, developing oncogenic immunocompetent animal models of bone metastasis, and investigating the unique contribution of the bone microenvironment to tumor growth and dormancy. Priorities for research in preserving normal bone health include developing methods to measure and characterize disseminating tumor cells, assessing outcomes from the major prevention trials currently in progress, and improving methodologies to assess risks and benefits of treatment. Priorities for optimizing bone-targeted therapies include advancing studies of serum proteomics and genomics to reliably identify patients who will develop bone metastases, enhancing imaging for early detection of bone metastases and early response evaluation, and developing new tests to evaluate response to bone-directed treatments.
Inherited and Acquired Risk Factors for Venous Thromboembolic Disease Among Women Taking Tamoxifen to Prevent Breast Cancer
Authors: Catherine Duggan, Kevin Marriott, Rob Edwards, Jack Cuzick
Journal: Journal of Clinical Oncology (2003)

Purpose: Venous thromboembolism (VTE) is of particular concern in women receiving tamoxifen in a chemopreventive setting. We investigate the association between acquired and inherited risk factors for VTE in the International Breast Cancer Intervention Study (IBIS-I) trial of tamoxifen prophylaxis for women at increased risk of breast cancer. Methods: We used a nested case-control study design to investigate the role of tamoxifen and acquired risk factors in the risk of developing a VTE. Results: Tamoxifen was associated with a significantly increased risk of developing a major VTE (odds ratio [OR], 2.1; 95% CI, 1.1 to 4.1). Women who had surgery, immobilization, or fracture in the previous month had a greatly increased risk of developing a major VTE (OR, 4.7; 95% CI, 2.2 to 10.1). Prothrombin and factor V Leiden mutations were found exclusively among control women: factor V Leiden in eight of 159 control women (5.0%) and the prothrombin mutation in three control women (1.9%). Thirty-five women with a VTE and a blood sample were negative for these mutations. The upper one-sided 97.5% CI for the OR of having either mutation was 1.87. Being overweight, smoking, or taking hormone replacement therapy was not associated with VTE in this study, but the CIs were wide. Conclusion: Tamoxifen and prior surgery, fracture, or immobilization were associated with a significantly increased risk of developing a VTE. Factor V Leiden and prothrombin mutations were not associated with thrombosis in this population.
Prostacyclin Analogues Differentially Inhibit Growth of Distal and Proximal Human Pulmonary Artery Smooth Muscle Cells
Authors: John Wharton, Neil Davie, Paul D. Upton, Magdi H. Yacoub, Julia M. Polak, Nicholas W. Morrell
Journal: Circulation (2000)

Background —Prostacyclin has proved to be a beneficial treatment for patients with severe pulmonary hypertension. We postulated that the response may reflect, at least in part, inhibition of pulmonary artery smooth muscle cell (PASMC) growth. Methods and Results —Human PASMCs were derived from distal (&lt;1-mm external diameter, n=8) and proximal (&gt;8-mm external diameter, n=12) pulmonary arteries obtained at transplant surgery and pneumonectomy. The effects of the stable prostacyclin analogues on [ methyl - 3 H]thymidine incorporation and cell proliferation were investigated by using immunohistochemically characterized cells. Distal cells proliferated faster than did proximal PASMCs and displayed a distinct sensitivity to cicaprost and iloprost. Both analogues inhibited thymidine uptake over 24 hours (20% to 60%, P &lt;0.001; n=8) and abolished stimulation of DNA synthesis by platelet-derived growth factor-BB (10 ng/mL) in distal but not proximal cells. The inhibitory effect of cicaprost was mimicked by isoproterenol (10 −5 mol/L), forskolin (10 −5 mol/L), and dibutyryl cAMP (5×10 −4 mol/L) and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (5×10 −5 mol/L). Cicaprost (10 −10 to 10 −6 mol/L) inhibited the proliferation of PASMCs, which had been stimulated with either platelet-derived growth factor-BB or serum, and increased cAMP production. These effects were potentiated by 3-isobutyl-1-methylxanthine and attenuated by the adenylyl cyclase inhibitor 2′,5′-dideoxyadenosine (10 −5 to 10 −4 mol/L). Conclusions —Cicaprost and iloprost inhibit DNA synthesis and proliferation to a greater extent in distal compared with proximal human PASMCs, acting at least in part via a cAMP-dependent mechanism. The results are consistent with the hypothesis that prostacyclin analogues inhibit vascular remodeling in pulmonary hypertension and demonstrate heterogeneity among human PASMCs.
Tryptophan-derived Catabolites Are Responsible for Inhibition of T and Natural Killer Cell Proliferation Induced by Indoleamine 2,3-Dioxygenase
Authors: Guido Frumento, Rita Rotondo, Michela Tonetti, Gianluca Damonte, Umberto Benatti, Giovanni Battista Ferrara
Journal: The Journal of Experimental Medicine (2002)

Macrophages exposed to macrophage colony-stimulating factor acquire the capacity to suppress T cell proliferation; this effect is associated with de novo expression of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO). We have purified IDO and tested its activity in in vitro models of T cell activation. IDO was able to inhibit proliferation of CD4+ T lymphocytes, CD8+ T lymphocytes, and natural killer (NK) cells; proliferation of B lymphocytes was not affected. The inhibitory role of tryptophan and of its catabolites was then tested. In the presence of tryptophan, only l-kynurenine and picolinic acid inhibit cell proliferation. In a tryptophan-free medium cell proliferation was not affected. In the absence of tryptophan inhibition induced by l-kynurenine and picolinic acid was observed at concentrations below the lowest concentration that was effective in the presence of tryptophan, and quinolinic acid acquired some inhibitory capacity. Inhibition of cell proliferation induced by the tryptophan catabolites resulting from IDO activity was selective, applying only to cells undergoing activation. Resting cells were not affected and could subsequently activate normally. We suggest that IDO exerts its effect on cell proliferation by (i) starting the cascade of biochemical reactions that produce the three catabolites and by (ii) enhancing their inhibitory potential by depriving the extracellular microenvironment of tryptophan.
The Expression of Fascin, an Actin-Bundling Motility Protein, Correlates with Hormone Receptor–Negative Breast Cancer and a More Aggressive Clinical Course
Authors: Brian J. Yoder, Elisa Tso, Marek Skacel, Jim Pettay, Shannon Tarr, Thomas Budd, Raymond R. Tubbs, Josephine C. Adams, David G. Hicks
Journal: Clinical Cancer Research (2005)

Abstract The invasion and metastasis of tumor cells is a major cause of mortality in cancer patients. In the current study, we investigated the expression of fascin, an actin-bundling motility-associated protein, in 210 invasive breast carcinomas with corresponding 5-year clinical follow-up. Fascin expression was compared with hormone receptor (ER/PR) status, HER2 status, cancer grade, cancer stage, metastasis pattern, disease-free survival, and overall survival. Fascin expression was seen in 16% (33/210) of the cases and correlated with ER negativity (22/33, P &amp;lt; 0.001), PR negativity (21/33, P &amp;lt; 0.001), Bloom-Richardson grade 3 (19/29, P &amp;lt; 0.001), and advanced stage (stage 3 or 4, P=0.04).There was no correlation between fascin expression and HER2 status or pattern of metastases. Patients whose tumors were positive for fascin showed both a decreased mean disease-free survival (74.44 versus 100.52 months, P = 0.002) and mean overall survival (77.58 versus 98.98 months, P = 0.002), independent of tumor stage and HER2 status, but not independent of ER/PR status or cancer grade. Given fascin's role in altering cell motility, overexpression may contribute to a more aggressive clinical course in ER/PR-negative breast cancers. If so, then fascin may represent a new molecular target for therapeutic intervention in patients with ER-negative breast cancer.
Comitogenic effects of estrogens on DNA synthesis induced by various growth factors in cultured female rat hepatocytes
Authors: Nan Ni, James D. Yager
Journal: Hepatology (1994)

Ethinyl estradiol is a weak complete carcinogen and potent tumor promoter. In vivo, ethinyl estradiol causes a rapid but transient increase in liver growth, whereas in cultured female hepatocytes it enhances DNA synthesis induced by epidermal growth factor and is thus classified as a comitogen. The objectives of this study were to determine: (a) whether estradiol also has comitogenic activity; (b) whether the comitogenic effects of estrogen extend to complete hepatic mitogens other than epidermal growth factor and (c) whether inhibition of hepatocyte DNA synthesis by transforming growth factor-beta can be blocked by estradiol. Female rat hepatocytes in primary culture were exposed to estradiol with and without various growth factors, and we determined DNA synthesis by measuring [3H]thymidine incorporation into extracted DNA or by determining the nuclear labeling index by means of autoradiography. The results show that estradiol, like ethinyl estradiol, has comitogenic activity for epidermal growth factor, although it is somewhat less potent. Four complete hepatic mitogens showed different abilities to stimulate DNA synthesis, with hepatocyte growth factor > transforming growth factor-alpha > epidermal growth factor > acidic fibroblast growth factor. Estradiol enhanced DNA synthesis occurring in response to all four of these complete hepatic mitogens. This finding suggests that the mechanism of estrogen comitogenesis may involve effects at a point where the different signal-transduction pathways leading from the growth factors converge. The level of estrogen-mediated enhancement of DNA synthesis was similar for all four mitogens, ranging from 1.5 to 2.2-fold, depending on the experiment. Furthermore, determination of the nuclear labeling index showed that estrogen enhancement of DNA synthesis was associated with an increase in the percentage of hepatocytes that responded to the growth factors. Finally, estradiol did not specifically block the growth-inhibitory effects of transforming growth factor-beta.
Smoking, humoral immunity, and ulcerative colitis.
Authors: E D Srivastava, J R Barton, S O'Mahony, D I Phillips, G T Williams, N Matthews, A Ferguson, J Rhodes
Journal: Gut (1991)

Since ulcerative colitis predominantly affects non-smokers and ex-smokers we have examined the possibility that smoking modifies the humoral immune response to an antigenic challenge from the gut lumen. Gut lavage was used in healthy subjects and patients with ulcerative colitis, including both smokers and non-smokers. Antibodies in the intestinal fluid to Escherichia coli (five pooled serotypes), Candida albicans, gliadin, ovalbumin, and beta lactoglobulin were measured by ELISA to determine specific antibody concentrations of IgG, IgA, and IgM classes. Total IgG, IgA, and IgM were also measured in intestinal secretions and serum. In addition, circulating antibody concentrations of IgG, IgA, and IgM to three gut commensals - E coli (five pooled serotypes) C albicans, and Poroteus mirabilis were measured. There was a significant reduction in the IgA concentration in intestinal fluid of smokers with ulcerative colitis compared with healthy non-smoking controls. No other significant differences were found between the groups. Overall, these data are not consistent with the idea that smoking suppresses immune responses in the gut and suggest that the effect of smoking in colitis is mediated by another mechanism.
Phosphorylation Regulates c-Myc's Oncogenic Activity in the Mammary Gland
Authors: Xiaoyan Wang, Melissa Cunningham, Xiaoli Zhang, Sara Tokarz, Bryan Laraway, Megan Troxell, Rosalie C. Sears
Journal: Cancer Research (2011)

Expression of the c-Myc oncoprotein is affected by conserved threonine 58 (T58) and serine 62 (S62) phosphorylation sites that help to regulate c-Myc protein stability, and altered ratios of T58 and S62 phosphorylation have been observed in human cancer. Here, we report the development of 3 unique c-myc knock-in mice that conditionally express either c-Myc(WT) or the c-Myc(T58A) or c-Myc(S62A) phosphorylation mutant from the constitutively active ROSA26 locus in response to Cre recombinase to study the role of these phosphorylation sites in vivo. Using a mammary-specific Cre model, we found that expression of c-Myc(WT) resulted in increased mammary gland density, but normal morphology and no tumors at the level expressed from the ROSA promoter. In contrast, c-Myc(T58A) expression yielded enhanced mammary gland density, hyperplastic foci, cellular dysplasia, and mammary carcinoma, associated with increased genomic instability and suppressed apoptosis relative to c-Myc(WT). Alternatively, c-Myc(S62A) expression reduced mammary gland density relative to control glands, and this was associated with increased genomic instability and normal apoptotic function. Our results indicate that specific activities of c-Myc are differentially affected by T58 and S62 phosphorylation. This model provides a robust platform to interrogate the role that these phosphorylation sites play in c-Myc function during development and tumorigenesis.