tbuckley/cabot-search huggingface dataset:
Repression of Vascular Endothelial Growth Factor Expression by the Zinc Finger Transcription Factor ZNF24
Authors: Jay Harper, Li Yan, Robyn M. Loureiro, Iinmin Wu, Jianmin Fang, Patricia A. D'Amore, Marsha A. Moses
Journal: Cancer Research (2007)

Abstract Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis. Although many positive regulators of VEGF have been identified, relatively little is known regarding the negative regulation of VEGF expression. We identified a zinc finger transcription factor, ZNF24, that may repress VEGF transcription. An inverse correlation between expression of VEGF and ZNF24 was observed in a series of independent studies. ZNF24 was up-regulated in angiogenic tumor nodules where VEGF expression is significantly decreased compared with preangiogenic nodules. In human breast carcinoma cells cultured under normoxic conditions, ZNF24 levels were significantly up-regulated whereas VEGF levels were low. In contrast, VEGF was significantly increased in hypoxic cells whereas ZNF24 was down-regulated. The same inverse correlation between ZNF24 and VEGF was also observed in 70% of matched cDNA pairs of normal and malignant tissues from human colon and breast biopsies. Overexpression of ZNF24 resulted in a significant down-regulation of VEGF, whereas silencing of ZNF24 with small interfering RNA led to increased VEGF expression. Cotransfection of ZNF24 and a VEGF promoter luciferase reporter construct in MDA-MB-231 cells resulted in a significant decrease in VEGF promoter activity. Taken together, these data suggest that ZNF24 is involved in negative regulation of VEGF and may represent a novel repressor of VEGF transcription. [Cancer Res 2007;67(18):8736–41]
Cytoplasmic transfer in oocytes: biochemical aspects
Authors: Rachel Levy, Kay Elder, Yves Ménézo
Journal: Human Reproduction Update (2004)

Cytoplasmic control of preimplantation development is not a 'new' concept; the first cytoplasmic transfer experiment was performed in the mouse during the early 1980s, as a means of overcoming cleavage arrest at the 2‐cell stage, the '2‐cell block'. Since the first human pregnancy following the transfer of cytoplasm from donor oocytes into the oocytes of a patient with a history of poor embryo development and recurrent implantation failure in 1997, >30 children have been born after direct injection of ooplasm from fresh, mature or immature, or cryopreserved–thawed donor oocytes into recipient oocytes via a modified ICSI technique. Transfer of ooplasm was thus applied with astonishing speed in humans, in the absence of extensive research to evaluate the efficacy and the possible risks of the method. This review focuses on biochemical mechanisms by which transfer of ooplasm might confer a benefit: by correcting a putative imbalance between anti‐ and pro‐apoptotic factors and/or correction of defective mitochondrial membrane potential. We also emphasize the 'empirical' state of this technique, and the related risks.
Cooperativity between MAPK and PI3K signaling activation is required for glioblastoma pathogenesis
Authors: M. Vitucci, N. O. Karpinich, R. E. Bash, A. M. Werneke, R. S. Schmid, K. K. White, R. S. McNeill, B. Huff, S. Wang, T. Van Dyke, C. R. Miller
Journal: Neuro-Oncology (2013)

Glioblastoma (GBM) genomes feature recurrent genetic alterations that dysregulate core intracellular signaling pathways, including the G1/S cell cycle checkpoint and the MAPK and PI3K effector arms of receptor tyrosine kinase (RTK) signaling. Elucidation of the phenotypic consequences of activated RTK effectors is required for the design of effective therapeutic and diagnostic strategies. Genetically defined, G1/S checkpoint-defective cortical murine astrocytes with constitutively active Kras and/or Pten deletion mutations were used to systematically investigate the individual and combined roles of these 2 RTK signaling effectors in phenotypic hallmarks of glioblastoma pathogenesis, including growth, migration, and invasion in vitro. A novel syngeneic orthotopic allograft model system was used to examine in vivo tumorigenesis. Constitutively active Kras and/or Pten deletion mutations activated both MAPK and PI3K signaling. Their combination led to maximal growth, migration, and invasion of G1/S-defective astrocytes in vitro and produced progenitor-like transcriptomal profiles that mimic human proneural GBM. Activation of both RTK effector arms was required for in vivo tumorigenesis and produced highly invasive, proneural-like GBM. These results suggest that cortical astrocytes can be transformed into GBM and that combined dysregulation of MAPK and PI3K signaling revert G1/S-defective astrocytes to a primitive gene expression state. This genetically-defined, immunocompetent model of proneural GBM will be useful for preclinical development of MAPK/PI3K-targeted, subtype-specific therapies.
Hemostatic Regulators of Tumor Angiogenesis: A Source of Antiangiogenic Agents for Cancer Treatment?
Authors: Martina E Daly, Andreas Makris, Malcolm Reed, Claire E Lewis
Journal: JNCI Journal of the National Cancer Institute (2003)

The maintenance of vascular integrity and control of blood loss are regulated by a sophisticated system of circulating and cell-associated hemostatic factors. These factors control local platelet aggregation, the conversion of soluble fibrinogen to an insoluble fibrin polymer, and the dissolution of fibrin. However, hemostatic factors are also involved in a number of physiologic processes, including development, tissue remodeling, wound repair, reproduction, inflammation, and angiogenesis. In this review, we outline ways in which angiogenesis is coordinated with and regulated by hemostasis. We focus on inhibitors of angiogenesis contained within platelets or harbored as cryptic fragments of hemostatic proteins and assess the experimental and preclinical evidence for their ability to inhibit tumor angiogenesis and, thus, their potential to be anticancer agents. Finally, we review the results of recent clinical trials involving angiogenesis inhibitors and the evidence that antiangiogenic therapy may be associated with hemostatic complications.
Gestational Diabetes Mellitus in HIV-Infected and -Uninfected Pregnant Women in Cameroon
Authors: Jennifer Jao, Marcia Wong, Russell B. Van Dyke, Mitchell Geffner, Emmanuel Nshom, Dennis Palmer, Pius T. Muffih, Elaine J. Abrams, Rhoda S. Sperling, Derek LeRoith
Journal: Diabetes Care (2013)

Gestational diabetes mellitus (GDM) in both HIV-infected and -uninfected women has been poorly studied in Africa. We enrolled pregnant women ages 15–50 years at a large semiurban clinic in Cameroon. A 75-g oral glucose tolerance test (OGTT) was performed at 24–28 weeks' gestational age or at the earliest prenatal visit for those presenting after 28 weeks. Women were diagnosed with GDM according to American Diabetes Association criteria (1). Data on height, blood pressure, sociodemographics, obstetrical history, prepregnancy weight, HIV clinical status, combination antiretroviral therapy (cART) history, and pregnancy outcomes were collected. Exact logistic regression models were used to identify predictors of GDM.

Of 316 participants, 20 (63%) had GDM, and 3 had overt diabetes (DM). Women with GDM presented for OGTT later than those without (29 vs. 27 weeks, P = 0.04) (Table 1). After adjustment for age, gestational age at the time of OGTT, family history of DM, HIV, …
Polyclonal activation of human B lymphocytes by Fc fragments. I. Characterization of the cellular requirements for Fc fragment-mediated polyclonal antibody secretion by human peripheral blood B lymphocytes.
Authors: E L Morgan, W O Weigle
Journal: The Journal of Experimental Medicine (1981)

Fc fragments derived from human immunoglobulin were found to be capable of inducing both a proliferative and polyclonal antibody response in human peripheral blood lymphocyte cultures. The cell population proliferating in response to Fc fragments belongs to the B cell lineage. Expression of polyclonal antibody formation requires the presence of both adherent monocytes and T cells. The role of the monocyte is to enzymatically cleave the Fc fragment into 19,000 mol wt Fc subfragments that are then able to induce polyclonal antibody secretion. Stimulation of polyclonal antibody production by Fc subfragments occurs in the absence of adherent monocytes but still requires the presence of T cells.
The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children.
Authors: L J Bloem, A K Manatunga, D A Tewksbury, J H Pratt
Journal: Journal of Clinical Investigation (1995)

The T235 allele of the angiotensinogen gene (AGT) has been associated with hypertension. Blood pressure increases faster over time in black children than in white children, and in adults hypertension is more prevalent in blacks. We sought evidence for a role for angiotensinogen to contribute to racial differences in blood pressure in a study of 148 white and 62 black normotensive children (mean age, 14.8 yr). The frequency of the T235 allele was 0.81 in blacks and 0.42 in whites (chi 2 = 77.3, P = 0.0001). The mean angiotensinogen level was 19% higher in blacks than in whites (P = 0.0001 for males, P = 0.004 for females). Genotype was positively related to serum angiotensinogen in white children (P = 0.0001 for males, P = 0.004 for females), but a similar relationship was absent in blacks where the frequency of M235 may have been too low to discern an association. Longitudinal blood pressure (measured twice yearly) adjusted for body mass index showed a marginally significant relationship to the angiotensinogen level (P = 0.07). An independent relationship of serum angiotensinogen with body mass index (P = 0.0001) and race (P = 0.0003) was also observed. In summary, T235 was more frequent, and the level of angiotensinogen was higher in blacks than in whites. Such a racial difference in the renin-angiotensin system may contribute to the disparity in blood pressure levels of white and black young people.
UCN-01-Induced Cell Cycle Arrest Requires the Transcriptional Induction of p21waf1/cip1 by Activation of Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase/Extracellular Signal-Regulated Kinase Pathway
Authors: Maria M. Facchinetti, Adriana De Siervi, Doreen Toskos, Adrian M. Senderowicz
Journal: Cancer Research (2004)

The small molecule UCN-01 is a cyclin-dependent kinase (CDK) modulator shown to have antiproliferative effects against several in vitro and in vivo cancer models currently being tested in human clinical trials. Although UCN-01 may inhibit several serine-threonine kinases, the exact mechanism by which it promotes cell cycle arrest is still unclear. We have reported previously that UCN-01 promotes G(1)-S cell cycle arrest in a battery of head and neck squamous cancer cell lines. The arrest is accompanied by an increase in both p21(waf1/cip1) and p27(kip1) CDK inhibitors leading to loss in G(1) CDK activity. In this report, we explore the role and the mechanism for the induction of these endogenous CDK inhibitors. We observed that p21 was required for the cell cycle effects of UCN-01, as HCT116 lacking p21 (HCT116 p21(-/-)) was refractory to the cell cycle effects of UCN-01. Moreover, UCN-01 promoted the accumulation of p21 at the mRNA level in the p53-deficient HaCaT cells without increase in the p21 mRNA half-life, suggesting that UCN-01 induced p21 at the transcriptional level. To study UCN-01 transcriptional activation of p21, we used several p21(waf1/cip1) promoter-driven luciferase reporter plasmids and observed that UCN-01 activated the full-length p21(waf1/cip1) promoter and a construct lacking p53 binding sites. The minimal promoter region required for UCN-01 (from -110 bp to the transcription start site) was the same minimal p21(waf1/cip1) promoter region required for Ras enhancement of p21(waf1/cip1) transcription. Neither protein kinase C nor PDK1/AKT pathways were relevant for the induction of p21 by UCN-01. In contrast, the activation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)/extracellular signal-regulated kinase mitogen-activated protein kinase pathways was required for p21 induction as UCN-01 activated this pathway, and genetic or chemical MEK inhibitors blunted p21 accumulation. These results demonstrated for the first time that p21 is required for UCN-01 cell cycle arrest. Moreover, we showed that the accumulation of p21 is transcriptional via activation of the MEK pathway. This novel mechanism, by which UCN-01 exerts its antiproliferative effect, represents a promising strategy to be exploited in future clinical trials.
EFFECTS OF EXCESS VITAMIN A ON CULTURES OF SKIN AND BUCCAL EPITHELIUM OF THE EMBRYONIC RAT AND MOUSE.
Authors: D. A. T. NEW
Journal: British Journal of Dermatology (1963)

Journal Article EFFECTS OF EXCESS VITAMIN A ON CULTURES OF SKIN AND BUCCAL EPITHELIUM OF THE EMBRYONIC RAT AND MOUSE. Get access D. A. T. NEW, M.A.(Oxon.). Ph.D.(Lond.). D. A. T. NEW, M.A.(Oxon.). Ph.D.(Lond.). Strangeways Research Laboratory, Wort's Causeway, Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 8-9, 1 August 1963, Pages 320–325, https://doi.org/10.1111/j.1365-2133.1963.tb13568.x Published: 01 August 1963
First-line temozolomide combined with bevacizumab in metastatic melanoma: a multicentre phase II trial (SAKK 50/07)
Authors: R. von Moos, B. Seifert, M. Simcock, S.M. Goldinger, S. Gillessen, A. Ochsenbein, O. Michielin, R. Cathomas, M. Schläppi, H. Moch, P.H. Schraml, D. Mjhic-Probst, C. Mamot, N. Schönewolf, R. Dummer
Journal: Annals of Oncology (2011)
Effect of histamine receptor antagonists on bile damage to the gastric mucosa of canine Heidenhain pouches.
Authors: W D Rees, J Rhodes, M H Wheeler, E M Meek, B Williams, R G Newcombe
Journal: Gut (1977)

The net ionic fluxes of H+ and Na+ were examined in Heidenhain pouches during damage with sodium taurocholate solution. The increase in ionic flux which occurred with taurocholate could be prevented in animals given H1 and H2 histamine antagonists in combination. The results suggest that histamine mediates changes in the transmucosal ionic flux produced by bile acid.
<i>Reprimo</i> Methylation Is a Potential Biomarker of Barrett's-Associated Esophageal Neoplastic Progression
Authors: James P. Hamilton, Fumiaki Sato, Zhe Jin, Bruce D. Greenwald, Tetsuo Ito, Yuriko Mori, Bogdan C. Paun, Takatsugu Kan, Yulan Cheng, Suna Wang, Jian Yang, John M. Abraham, Stephen J. Meltzer
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Reprimo, a candidate tumor-suppressor gene, regulates p53-mediated cell cycle arrest at G2 phase, and tumor-suppressor gene methylation is involved in the pathogenesis and progression of esophageal cancer. Our aim was to determine whether and at what phase of neoplastic progression Reprimo methylation occurs in Barrett's adenocarcinogenesis, as well as its columnar or squamous cell-type specificity. We also sought to determine whether Reprimo expression could be restored in vitro by the demethylating agent 5-aza-deoxycytidine (5AzaC). Experimental Design: Quantitative methylation-specific PCR for Reprimo was done using an ABI7700 (Taqman) apparatus on 175 endoscopic biopsy specimens. In addition, reverse transcription-PCR and quantitative methylation-specific PCR were done on esophageal carcinoma cells before and after treatment with 5AzaC. Results: In Barrett's esophagus (BE; P = 0.001), high-grade dysplasia (HGD; P = 0.001), and esophageal adenocarcinoma (EAC; P = 0.00003), the level and frequency of Reprimo methylation were significantly higher than in normal esophagus (NE). There was no statistically significant difference between BE and EAC, HGD and EAC, or NE and esophageal squamous cell carcinoma (ESCC). Reprimo methylation occurred in 0 of 19 NE samples, 6 (13%) of 45 ESCC, 9 (36%) of 25 BE, 7 (64%) of 11 HGD, and 47 (63%) of 75 EAC. Analysis of Reprimo methylation in EAC versus NE revealed an area under the receiver-operator characteristic curve of 0.812 (P &amp;lt; 0.00001; 95% confidence interval, 0.73-0.90). In vitro 5AzaC treatment of OE33 EAC cells reduced Reprimo methylation and increased Reprimo expression. Conclusions: Reprimo methylation occurs significantly more frequently in BE, HGD, and EAC than in NE or ESCC, suggesting that this epigenetic alteration is a specialized columnar, cell-specific early event with potential as a biomarker for the early detection of esophageal neoplasia.
Mechanism of Lumen Enlargement During Intracoronary Stent Implantation
Authors: Javed M. Ahmed, Gary S. Mintz, Neil J. Weissman, Alexandra J. Lansky, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent
Journal: Circulation (2000)

Intravascular ultrasound analysis has assessed mechanisms of lumen enlargement after nonstent interventions, but not after stenting.Preintervention and postintervention intravascular ultrasound was used to study 25 de novo native coronary lesions treated with single MultiLink stents without preatheroablation. External elastic membrane, lumen, and plaque and media (P&M) areas were measured every 1 mm to include the lesion and reference segments that were 5 mm proximal and distal to it. Lesion mean lumen area increased from 4.0+/-1.0 mm(2) before the intervention to 8.8+/-2.0 mm(2) after the intervention (P<0.0001) as a result of an increase in mean external elastic membrane area (14. 2+/-2.7 to 16.1+/-3.0 mm(2), P<0.0001) and a decrease in mean P&M area (10.2+/-2.2 to 7.2+/-1.8 mm(2), P<0.0001). The decrease in lesion P&M was accompanied by an increase in both proximal reference mean P&M (7.0+/-1.9 to 8.4+/-2.0 mm(2), P<0.0001) and distal reference mean P&M (5.8+/-2.1 to 7.2+/-2.1 mm(2), P<0.0001). Volumetric analysis showed an axial redistribution of plaque away from the center of the lesion toward the reference segments to increase the plaque burden in both the proximal and distal reference segments. Total (lesion plus reference) mean P&M decreased from 8. 6+/-2.1 to 7.5+/-1.8 mm(2) (P<0.0001).The mechanisms of lumen enlargement after stenting involved (1) significant axial redistribution of plaque from the lesion into the reference segments, (2) vessel expansion, and (3) either plaque embolization or compression.
Frequency of p53 Mutations in Breast Carcinomas From Ashkenazi Jewish Carriers of BRCA1 Mutations
Authors: K A Phillips, K Nichol, H Ozcelik, J Knight, S J Done, P J Goodwin, I L Andrulis
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: Breast carcinomas occurring in carriers of BRCA1 gene mutations may have a distinctly different pathway of molecular pathogenesis from those occurring in noncarriers. Data from murine models implicate loss of p53 (also known as TP53) gene function as a critical early event in the malignant transformation of cells with a BRCA1 mutation. Therefore, breast tumors from BRCA1 mutation carriers might be expected to exhibit a high frequency of p53 mutations. This study examined the frequency of p53 mutations in the breast tumors of Ashkenazi Jewish carriers and noncarriers of BRCA1 mutations. METHODS: Tumor DNA from carriers and noncarriers of BRCA1 mutations was screened for mutations in exons 4 through 10 of the p53 gene by use of the polymerase chain reaction and single-strand conformation polymorphism (SSCP) analysis of the amplified DNA. Direct sequencing was performed on gene fragments that showed altered mobility in SSCP analysis. RESULTS: Mutations in the p53 gene were detected in 10 of 13 tumors from BRCA1 mutation carriers versus 10 of 33 tumors from noncarriers (two-sided P = .007). The p53 mutations were distributed throughout exons 4 through 10 and included both protein-truncating and missense mutations in both groups. CONCLUSIONS: A statistically significantly higher frequency of p53 mutations was found in breast tumors from carriers of BRCA1 mutations than from noncarriers, which adds to the accumulating evidence that loss of p53 function is an important step in the molecular pathogenesis of BRCA1 mutation-associated breast tumors. This finding may have implications for understanding phenotypic differences and potential prognostic differences between BRCA1 mutation-associated hereditary breast cancers and sporadic cancers.
Autoimmunity in Membranous Nephropathy Targets Aldose Reductase and SOD2
Authors: Marco Prunotto, Maria Luisa Carnevali, Giovanni Candiano, Corrado Murtas, Maurizio Bruschi, Emilia Corradini, Antonella Trivelli, Alberto Magnasco, Andrea Petretto, Laura Santucci, Silvia Mattei, Rita Gatti, Francesco Scolari, Peter Kador, Landino Allegri, Gian Marco Ghiggeri
Journal: Journal of the American Society of Nephrology (2010)

Glomerular targets of autoimmunity in human membranous nephropathy are poorly understood. Here, we used a combined proteomic approach to identify specific antibodies against podocyte proteins in both serum and glomeruli of patients with membranous nephropathy (MN). We detected specific anti-aldose reductase (AR) and anti-manganese superoxide dismutase (SOD2) IgG(4) in sera of patients with MN. We also eluted high titers of anti-AR and anti-SOD2 IgG(4) from microdissected glomeruli of three biopsies of MN kidneys but not from biopsies of other glomerulonephritides characterized by IgG deposition (five lupus nephritis and two membranoproliferative glomerulonephritis). We identified both antigens in MN biopsies but not in other renal pathologies or normal kidney. Confocal and immunoelectron microscopy (IEM) showed co-localization of anti-AR and anti-SOD2 with IgG(4) and C5b-9 in electron-dense podocyte immune deposits. Preliminary in vitro experiments showed an increase of SOD2 expression on podocyte plasma membrane after treatment with hydrogen peroxide. In conclusion, our data support AR and SOD2 as renal antigens of human MN and suggest that oxidative stress may drive glomerular SOD2 expression.
Ectopic Expression of Interferon Regulatory Factor-1 Promotes Human Breast Cancer Cell Death and Results in Reduced Expression of Survivin
Authors: Eva Pizzoferrato, Ye Liu, Andrea Gambotto, Michaele J. Armstrong, Michael T. Stang, William E. Gooding, Sean M. Alber, Stuart H. Shand, Simon C. Watkins, Walter J. Storkus, John H. Yim
Journal: Cancer Research (2004)

Abstract The overexpression of the inhibitor of apoptosis protein, survivin, may provide tumor cells with a distinct survival advantage in situ; hence, therapeutic strategies have been designed to inhibit its expression. In this study, we ectopically expressed the interferon regulatory factor (IRF)-1 protein in the breast carcinoma cell lines MDA-MB-468 and SK-BR-3 using a recombinant adenovirus (Ad-IRF-1). By screening microarray analysis of cDNA from the human breast cancer cell line MDA-MB-468 infected with Ad-IRF-1, we observed a 15-fold down-regulation of the survivin gene when compared with uninfected cells. Consequently, we tested survivin expression in Ad-IRF-1-infected MDA-MB-468 and SK-BR-3 breast cancer cell lines. Immunoblotting analyses supported the contention that ectopic expression of the IRF-1 protein results in down-regulation of survivin protein expression that is independent of p53. In addition, Ad-IRF-1 infection of these human breast cancer cell lines induces the expression of p21. We also report that increased apoptosis is observed in tumor cells infected with Ad-IRF-1 compared with Ad-Ψ5 mock-infected cells and that cell death is further augmented when the IRF-1-infected cells are cultured with Adriamycin. Moreover, in a xenogeneic mouse model of breast carcinoma, in vivo treatment of tumor-bearing mice with intratumoral Ad-IRF-1 injections results in tumor growth inhibition. In resected tumors from mice that had been treated with Ad-IRF-1, tumor cells that express the IRF-1 transgene have a predominant IRF-1-positive, survivin-negative phenotype. Collectively, these observations suggest that therapies designed to enhance IRF-1 expression within tumor cells may represent novel treatment strategies for breast cancer.