tbuckley/cabot-search huggingface dataset:
Quantitative Assessment of the p53-Mdm2 Feedback Loop Using Protein Lysate Microarrays
Authors: Sundhar Ramalingam, Peter Honkanen, Lynn Young, Tsutomu Shimura, John Austin, Patricia S. Steeg, Satoshi Nishizuka
Journal: Cancer Research (2007)

Mathematical simulations of the p53-Mdm2 feedback loop suggest that both proteins will exhibit impulsive expression characteristics in response to high cellular stress levels. However, little quantitative experimental evaluation has been done, particularly of the phosphorylated forms. To evaluate the mathematical models experimentally, we used lysate microarrays from an isogenic pair of gamma-ray-irradiated cell lysates from HCT116 (p53(+/+) and p53(-/-)). Both p53 and Mdm2 proteins showed expected pulses in the wild type, whereas no pulses were seen in the knockout. Based on experimental observations, we determined model parameters and generated an in silico "knockout," reflecting the experimental data, including phosphorylated proteins.
The Gastric Cancer Treatment Controversy
Authors: Cornelis J.H. van de Velde, Koen C.M.J. Peeters
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.91.138 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12805321 The Gastric Cancer Treatment Controversy Cornelis J.H. van de VeldexCornelis J.H. van de VeldeSearch for articles by this author , Koen C.M.J. PeetersxKoen C.M.J. PeetersSearch for articles by this author Show More Department of Surgery Leiden University Medical Center Leiden, the Netherlands https://doi.org/10.1200/JCO.2003.91.138 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Risk of Recurrence in Women With Bipolar Disorder During Pregnancy: Prospective Study of Mood Stabilizer Discontinuation
Authors: Adele C Viguera, Theodore Whitfield, Ross J Baldessarini, D Jeffrey Newport, Zachary Stowe, Alison Reminick, Amanda Zurick, Lee S Cohen
Journal: American Journal of Psychiatry (2007)

Objective: This study estimated the risk of recurrence of mood episodes among women with a history of bipolar disorder who continued or discontinued treatment with mood stabilizers during pregnancy. Method: In a prospective observational clinical cohort study, the authors determined recurrence risk and survival-analysis-based time to recurrence of a new episode in 89 pregnant women with DSM-IV bipolar disorder. Eligible subjects were euthymic at conception and continued mood stabilizer treatment or discontinued treatment proximate to conception. Results: The overall risk of at least one recurrence in pregnancy was 71%. Among women who discontinued versus continued mood stabilizer treatment, recurrence risk was twofold greater, median time to first recurrence was more than fourfold shorter, and the proportion of weeks ill during pregnancy was five times greater. Median recurrence latency was 11 times shorter after abrupt/rapid versus gradual discontinuation of mood stabilizer. Most recurrences were depressive or mixed (74%), and 47% occurred during the first trimester. Predictors of recurrence included bipolar II disorder diagnosis, earlier onset, more recurrences/year, recent illness, use of antidepressants, and use of anticonvulsants versus lithium. Conclusions: Discontinuation of mood stabilizer, particularly abruptly, during pregnancy carries a high risk for new morbidity in women with bipolar disorder, especially for early depressive and dysphoric states. However, this risk is reduced markedly by continued mood stabilizer treatment. Treatment planning for pregnant women with bipolar disorder should consider not only the relative risks of fetal exposure to mood stabilizers but also the high risk of recurrence and morbidity associated with stopping maintenance mood stabilizer treatment.
Cytokine Receptor CXCR4 Mediates Estrogen-Independent Tumorigenesis, Metastasis, and Resistance to Endocrine Therapy in Human Breast Cancer
Authors: Lyndsay V. Rhodes, Sarah P. Short, Nicole F. Neel, Virgilio A. Salvo, Yun Zhu, Steven Elliott, Yongkun Wei, Dihua Yu, Menghong Sun, Shannon E. Muir, Juan P. Fonseca, Melyssa R. Bratton, Chris Segar, Syreeta L. Tilghman, Tammy Sobolik-Delmaire, Linda W. Horton, Snjezana Zaja-Milatovic, Bridgette M. Collins-Burow, Scott Wadsworth, Barbara S. Beckman, Charles E. Wood, Suzanne A. Fuqua, Kenneth P. Nephew, Paul Dent, Rebecca A. Worthylake, Tyler J. Curiel, Mien-Chie Hung, Ann Richmond, Matthew E. Burow
Journal: Cancer Research (2010)

Estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer patients. Metastasis has been associated with chemokine signaling through the SDF-1-CXCR4 axis. Thus, the development of estrogen independence and endocrine therapy resistance in breast cancer patients may be driven by SDF-1-CXCR4 signaling. Here we report that CXCR4 overexpression is indeed correlated with worse prognosis and decreased patient survival irrespective of the status of the estrogen receptor (ER). Constitutive activation of CXCR4 in poorly metastatic MCF-7 cells led to enhanced tumor growth and metastases that could be reversed by CXCR4 inhibition. CXCR4 overexpression in MCF-7 cells promoted estrogen independence in vivo, whereas exogenous SDF-1 treatment negated the inhibitory effects of treatment with the anti-estrogen ICI 182,780 on CXCR4-mediated tumor growth. The effects of CXCR4 overexpression were correlated with SDF-1-mediated activation of downstream signaling via ERK1/2 and p38 MAPK (mitogen activated protein kinase) and with an enhancement of ER-mediated gene expression. Together, these results show that enhanced CXCR4 signaling is sufficient to drive ER-positive breast cancers to a metastatic and endocrine therapy-resistant phenotype via increased MAPK signaling. Our findings highlight CXCR4 signaling as a rational therapeutic target for the treatment of ER-positive, estrogen-independent breast carcinomas needing improved clinical management.
Modification of the Cutaneous Dermatomyositis Disease Area and Severity Index, an outcome instrument
Authors: M. Yassaee, D. Fiorentino, J. Okawa, L. Taylor, C. Coley, A.B. Troxel, V.P. Werth
Journal: British Journal of Dermatology (2009)

Background Validated outcome measures in dermatology help standardize and improve patient care. A scoring system of skin disease severity in dermatomyositis known as the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) has been developed. Objectives To simplify and improve the tool for clinical research and care, we modified the CDASI and validated the new version, v2. Methods The original CDASI has four activity and two damage measures. The modified CDASI has three activity and two damage measures. The skin disease of 20 patients with dermatomyositis was evaluated by the same dermatologist using both the original and the modified CDASI. Global validation measures were implemented to assess overall skin disease state, skin disease activity and skin damage. Spearman’s rho (rsp), adjusted for multiple observations on subjects, was used to determine the relationship between the two versions of the CDASI and their correlation with the physician global measures (PGMs). Results The total score and activity and damage subscores of the original and the modified CDASI correlated perfectly with each other (rsp = 0·99, 1·00, 1·00). The PGM-overall skin scale correlated with the total scores (rsp = 0·72, rsp = 0·76) and activity subscores (rsp = 0·68, rsp = 0·63) but not with the damage subscores (rsp = 0·14, rsp = 0·15) of the original and the modified CDASI, respectively. However, the PGM-activity and PGM-damage scales correlated with the activity (rsp = 0·76, rsp = 0·75) and damage subscores (rsp = 0·90, rsp = 0·90), respectively, of the original and the modified CDASI. Conclusions The modified CDASI is perfectly correlated with the original CDASI. It has equally good concurrent validity with the PGM-overall skin and PGM-activity scales. The CDASI subscores have equally good concurrent validity with the PGM-activity and PGM-damage scales. We suggest that PGMs of skin disease activity and damage should be assessed separately for greater specificity. The modified CDASI is a refined and equally as useful outcome measure.
HOXB13 promotes androgen independent growth of LNCaP prostate cancer cells by the activation of E2F signaling
Authors: Young-Rang Kim, Kyung-Jin Oh, Ra-Young Park, Nguyen Thi Xuan, Taek-Won Kang, Dong-Deuk Kwon, Chan Choi, Min Soo Kim, Kwang Il Nam, Kyu Youn Ahn, Chaeyong Jung
Journal: Molecular Cancer (2010)

Abstract Background Androgen signaling plays a critical role in the development of prostate cancer and its progression. However, androgen-independent prostate cancer cells emerge after hormone ablation therapy, resulting in significant clinical problems. We have previously demonstrated that the HOXB13 homeodomain protein functions as a prostate cancer cell growth suppressor by inhibiting androgen-mediated signals. However, the role of the HOXB13 in androgen-independent growth of prostate cancer cells remains unexplained. Results In this report, we first demonstrated that HOXB13 was highly overexpressed in hormone-refractory tumors compared to tumors without prostate-specific antigen after initial treatment. Functionally, in an androgen-free environment minimal induction of HOXB13 in LNCaP prostate cancer cells, to the level of the normal prostate, markedly promoted cell proliferation while suppression inhibited cell proliferation. The HOXB13-mediated cell growth promotion in the absence of androgen, appears to be mainly accomplished through the activation of RB-E2F signaling by inhibiting the expression of the p21 waf tumor suppressor. Indeed, forced expression of HOXB13 dramatically decreased expression of p21 waf ; this inhibition largely affected HOXB13-mediated promotion of E2F signaling. Conclusions Taken together, the results of this study demonstrated the presence of a novel pathway that helps understand androgen-independent survival of prostate cancer cells. These findings suggest that upregulation of HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling.
The influence of sex and age on appendicitis in children and young adults
Authors: J. A. H. Lee
Journal: Gut (1962)

A study has been made of the influence of age and sex on the incidence of cases of appendicitis and of fatal appendicitis in children and young adults. Appendicitis is uncommon in children under the age of 5, but the proportion of cases complicated by peritonitis is large, and the death rate in the population of this age is relatively high. Appendicitis is very common in adolescents, but here the proportion of cases complicated by peritonitis is small. However, because of the frequency of the condition, the death rate in the general population of this age is high, with a maximum at about the age of 15 years. These findings are compatible with the suggestion that the appendix during the 'teens is particularly liable to obstruct and hence to become inflamed because of the large proportion of lymphoid tissue which it contains. Inflammation of the appendix is more common in males than in females, and this male excess is greater in infants and pre-school children than it is in children of school age.
An Amino Acid Substitution-Selection Model Adjusts Residue Fitness to Improve Phylogenetic Estimation
Authors: H.-C. Wang, E. Susko, A. J. Roger
Journal: Molecular Biology and Evolution (2014)

Standard protein phylogenetic models use fixed rate matrices of amino acid interchange derived from analyses of large databases. Differences between the stationary amino acid frequencies of these rate matrices from those of a data set of interest are typically adjusted for by matrix multiplication that converts the empirical rate matrix to an exchangeability matrix which is then postmultiplied by the amino acid frequencies in the alignment. The result is a time-reversible rate matrix with stationary amino acid frequencies equal to the data set frequencies. On the basis of population genetics principles, we develop an amino acid substitution-selection model that parameterizes the fitness of an amino acid as the logarithm of the ratio of the frequency of the amino acid to the frequency of the same amino acid under no selection. The model gives rise to a different sequence of matrix multiplications to convert an empirical rate matrix to one that has stationary amino acid frequencies equal to the data set frequencies. We incorporated the substitution-selection model with an improved amino acid class frequency mixture (cF) model to partially take into account site-specific amino acid frequencies in the phylogenetic models. We show that 1) the selection models fit data significantly better than corresponding models without selection for most of the 21 test data sets; 2) both cF and cF selection models favored the phylogenetic trees that were inferred under current sophisticated models and methods for three difficult phylogenetic problems (the positions of microsporidia and breviates in eukaryote phylogeny and the position of the root of the angiosperm tree); and 3) for data simulated under site-specific residue frequencies, the cF selection models estimated trees closer to the generating trees than a standard Г model or cF without selection. We also explored several ways of estimating amino acid frequencies under neutral evolution that are required for these selection models. By better modeling the amino acid substitution process, the cF selection models will be valuable for phylogenetic inference and evolutionary studies.
P65. Minor-histocompatibility-antigen UTY as target for graft-versus-leukaemia and graft-versus-haematopoiesis in the canine-model
Authors: D Bund, FG Gökmen, J Zorn, R Buhmann, HJ Kolb, H Schmetzer
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts In haploidentical-SCT male-patients with female-donors have better prognosis compared to female-to-male-combinations due to Y-encoded minor-histocompatibility-antigens recognised by female-allo-immune effector-lymphocytes in the context of a graft-versus-leukaemia-(GvL)-effect. We
Sugar-sweetened beverage consumption: a risk factor for prevalent gout with<i>SLC2A9</i>genotype-specific effects on serum urate and risk of gout
Authors: Caitlin Batt, Amanda J Phipps-Green, Michael A Black, Murray Cadzow, Marilyn E Merriman, Ruth Topless, Peter Gow, Andrew Harrison, John Highton, Peter Jones, Lisa Stamp, Nicola Dalbeth, Tony R Merriman
Journal: Annals of the Rheumatic Diseases (2013)

Consumption of high fructose corn syrup (HFCS)-sweetened beverages increases serum urate and risk of incident gout. Genetic variants in SLC2A9, that exchanges uric acid for glucose and fructose, associate with gout. We tested association between sugar (sucrose)-sweetened beverage (SSB) consumption and prevalent gout. We also tested the hypothesis that SLC2A9 genotype and SSB consumption interact to determine gout risk.Participants were 1634 New Zealand (NZ) European Caucasian, Ma¯ori and Pacific Island people and 7075 European Caucasians from the Atherosclerosis Risk in Communities (ARIC) study. NZ samples were genotyped for rs11942223 and ARIC for rs6449173. Effect estimates were multivariate adjusted.SSB consumption increased gout risk. The OR for four drinks/day relative to zero was 6.89 (p=0.045), 5.19 (p=0.010) and 2.84 (p=0.043) for European Caucasian, Ma¯ori and Pacific Islanders, respectively. With each extra daily SSB serving, carriage of the gout-protective allele of SLC2A9 associated with a 15% increase in risk (p=0.078), compared with a 12% increase in non-carriers (p=0.002). The interaction term was significant in pooled (pInteraction=0.01) but not meta-analysed (pInteraction=0.99) data. In ARIC, with each extra daily serving, a greater increase in serum urate protective allele carriers (0.005 (p=8.7×10(-5)) compared with 0.002 (p=0.016) mmol/L) supported the gout data (pInteraction=0.062).Association of SSB consumption with prevalent gout supports reduction of SSB in management. The interaction data suggest that SLC2A9-mediated renal uric acid excretion is physiologically influenced by intake of simple sugars derived from SSB, with SSB exposure negating the gout risk discrimination of SLC2A9.
Phase II Study of R115777, a Farnesyl Transferase Inhibitor, in Myelodysplastic Syndrome
Authors: Razelle Kurzrock, Maher Albitar, Jorge E. Cortes, Elihu H. Estey, Stefan H. Faderl, Guillermo Garcia-Manero, Deborah A. Thomas, Francis J. Giles, Mary Ellen Ryback, Alain Thibault, P. De Porre, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2004)

To perform a phase II study of the farnesyl transferase inhibitor R115777 (Zarnestra; Johnson and Johnson Pharmaceutical Research and Development, Raritan, NJ) in patients with myelodysplastic syndrome (MDS), using doses recommended in a phase I study in relapsed/refractory leukemia.Patients with MDS were treated with R115777 at doses of 600 mg orally (PO) bid in cycles of 4 weeks of therapy followed by a 2-week rest period. Dose reduction rules for toxicity were applied.Twenty-seven of the 28 patients treated were assessable. Three patients responded (complete remission, n = 2; partial remission, n = 1). Responders included two patients with refractory anemia with excess blasts and one patient with refractory anemia with excess blasts in transformation. Two of the responders had a diploid karyotype and one had multiple cytogenetic abnormalities including monosomy 5 and 7. The starting dose of 600 mg PO bid resulted in side effects (myelosuppression, fatigue, neurotoxicity, rash, or leg pain) necessitating dose reduction (n = 4) or discontinuation of therapy (n = 7) in 11 (41%) of 27 patients during the induction period (12 weeks). Lower doses of 300 mg PO bid were well tolerated. All responses occurred in patients who had been reduced to this dose level during the initial two cycles.This study suggests that R115777 has modest activity in MDS patients, but that, in this patient population, 4 weeks of daily doses of 600 mg PO bid is not tolerated. Further exploration of the optimal dose/schedule and correlation with biologic end points are warranted.
Epitope-specific antibody response is controlled by immunoglobulin VH polymorphisms
Authors: Bruno Raposo, Doreen Dobritzsch, Changrong Ge, Diana Ekman, Bingze Xu, Ingrid Lindh, Michael Förster, Hüseyin Uysal, Kutty Selva Nandakumar, Gunter Schneider, Rikard Holmdahl
Journal: The Journal of Experimental Medicine (2014)

Autoantibody formation is essential for the development of certain autoimmune diseases like rheumatoid arthritis (RA). Anti-type II collagen (CII) antibodies are found in RA patients; they interact with cartilage in vivo and are often highly pathogenic in the mouse. Autoreactivity to CII is directed to multiple epitopes and conserved between mice and humans. We have previously mapped the antibody response to CII in a heterogeneous stock cohort of mice, with a strong association with the IgH locus. We positioned the genetic polymorphisms and determined the structural requirements controlling antibody recognition of one of the major CII epitopes. Polymorphisms at positions S31R and W33T of the associated variable heavy chain (VH) allele were identified and confirmed by gene sequencing. The Fab fragment binding the J1 epitope was crystallized, and site-directed mutagenesis confirmed the importance of those two variants for antigen recognition. Back mutation to germline sequence provided evidence for a preexisting recognition of the J1 epitope. These data demonstrate a genetic association of epitope-specific antibody responses with specific VH alleles, and it highlights the importance of germline-encoded antibodies in the pathogenesis of antibody-mediated autoimmune diseases.
The dexamethasone suppression test and mood following stroke
Authors: J R Lipsey, R G Robinson, G D Pearlson, K Rao, T R Price
Journal: American Journal of Psychiatry (1985)

Dexamethasone suppression tests (DSTs) were given to 65 acute and chronic stroke patients. For patients who had had a stroke less than 1 year earlier, nonsuppression on the DST was significantly associated with the presence of poststroke depression. The authors, who used the DSM-III symptom criteria for major depression, found that DST sensitivity was 67% but specificity was only 70%. False positive tests in the stroke patients seemed related to large lesion volume. The DST, although of limited clinical utility in this population because of false positive tests, may help define more homogeneous subtypes of poststroke depression for research.
Inducible costimulator–positive T cells are required for allergen-induced local B-cell infiltration and antigen-specific IgE production in lung tissue
Authors: Katja C. Beier, Andreas Hutloff, Max Löhning, Tilmann Kallinich, Richard A. Kroczek, Eckard Hamelmann
Journal: Journal of Allergy and Clinical Immunology (2004)
Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study
Authors: Eman Mosad, Hosny B Hamed, Rania M Bakry, Azza M Ezz-Eldin, Nesrine M Khalifa
Journal: Journal of Hematology & Oncology (2008)

We have analyzed t(12;21)(p13:q22) in an attempt to evaluate the frequency and prognostic significance of TEL-AML1 fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH). Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD).All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH) for t(12;21) in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD). We determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival.TEL-AML1 fusion gene was positive in (37.5%) in newly diagnosed patients. There was a significant correlation between TEL-AML1 fusion gene both at diagnosis (r = 0.5, P = 0.003) and as a MRD (r = 0.4, P = 0.01) with favorable course. Kaplan-Meier curve for the presence of TEL-AML1 fusion at the diagnosis was associated with a better probability of overall survival (OS); mean survival time was 47 +/- 1 month, in contrast to 28 +/- 5 month in its absence (P = 0.006). Also, the persistence at TEL-AML1 fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 +/- 2 months in the presence of MRD and it was 40 +/- 1 months in its absence. So, persistence of TEL-AML1 fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS.For most patients, the presence of TEL-AML1 fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of TEL-AML1 fusion as MRD has no additive prognostic value.