tbuckley/cabot-search huggingface dataset:
CX3CR1-Fractalkine Expression Regulates Cellular Mechanisms Involved in Adhesion, Migration, and Survival of Human Prostate Cancer Cells
Authors: Shannon A. Shulby, Nathan G. Dolloff, Mark E. Stearns, Olimpia Meucci, Alessandro Fatatis
Journal: Cancer Research (2004)

Chemokines and their receptors might be involved in the selection of specific organs by metastatic cancer cells. For instance, the CXCR4-SDF-1alpha pair regulates adhesion and migration of breast as well as prostate cancer cells to metastatic sites. In this study, we present the first evidence for the expression of CX3CR1--the specific receptor for the chemokine fractalkine--by human prostate cancer cells, whereas human bone marrow endothelial cells and differentiated osteoblasts express fractalkine. The adhesion of prostate cancer cells to human bone marrow endothelial cells in flow conditions is significantly reduced by a neutralizing antibody against fractalkine, and they migrate toward a medium conditioned by osteoblasts, which secrete the soluble form of the chemokine. Finally, fractalkine activates the PI3K/Akt survival pathway in human prostate cancer cells.
TACE/ADAM-17: A Component of the Epidermal Growth Factor Receptor Axis and a Promising Therapeutic Target in Colorectal Cancer
Authors: Nipun B. Merchant, Igor Voskresensky, Christopher M. Rogers, Bonnie LaFleur, Peter J. Dempsey, Ramona Graves-Deal, Frank Revetta, A. Coe Foutch, Mace L. Rothenberg, Mary K. Washington, Robert J. Coffey
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Activation of the epidermal growth factor receptor (EGFR) requires cell surface cleavage of EGFR ligands, uptake of soluble ligand by the receptor, and initiation of EGFR tyrosine kinase activity. We define these collective events as the EGFR axis. Transforming growth factor-α (TGF-α) and amphiregulin are two EGFR ligands that are delivered preferentially to the basolateral surface of polarized epithelial cells where the EGFR resides. TACE/ADAM-17 (tumor necrosis factor-α converting enzyme/a disintegrin and metalloprotease) has been implicated in ectodomain cleavage of TGF-α and amphiregulin. Experimental Design: Using a human polarizing colorectal cancer (CRC) cell line, HCA-7, and a tissue array of normal colonic mucosa and primary and metastatic CRC, we determined the intracellular localization of TACE and the effects of EGFR axis inhibition in CRC. Results: Herein, we show that TACE is localized to the basolateral plasma membrane of polarized HCA-7 cells. TACE is overexpressed in primary and metastatic CRC tumors compared with normal colonic mucosa; the intensity of its immunoreactivity is inversely correlated with that of TGF-α and amphiregulin. Pharmacologic blockade of HCA-7 cells with an EGFR monoclonal antibody, a selective EGFR tyrosine kinase inhibitor, and a selective TACE inhibitor results in concentration-dependent decreases in cell proliferation and active, phosphorylated mitogen-activated protein kinase. Combining suboptimal concentrations of these agents results in cooperative growth inhibition, increased apoptosis, and reduced mitogen-activated protein kinase pathway activation. Furthermore, an EGFR tyrosine kinase–resistant clone of HCA-7 cells is growth-inhibited by combined monoclonal antibody and TACE inhibition. Conclusion: These results implicate TACE as a promising target of EGFR axis inhibition in CRC.
Serum high-density lipoprotein particles of alcohol-fed rats are deficient in apolipoprotein E
Authors: Renee C. Lin, Lawrence Lumeng, Vickie L. Phelps
Journal: Hepatology (1989)

Effects of chronic ethanol consumption on serum lip-oproteins have been studied in the rat. The serum levels of triglycerides, cholesterol, phospholipids and apolipo-proteins AI and AIV increased significantly after 1 week of ethanol feeding, and they remained elevated up to 7 weeks of alcohol drinking. By contrast, serum total apolipoprotein E decreased or, sometimes, did not change. Very-low-density lipoprotein cholesterol, triglycerides and very-low-density lipoprotein apolipoprotein E of the alcohol-fed rats increased in parallel and were about 2-to 2.5-fold over the controls. Whereas high-density lipoprotein cholesterol, phospholipids, apolipoprotein AI and AIV increased 1.2-fold by chronic alcohol feeding, the level of high-density lipoprotein apolipoprotein E decreased to 70% of that of the control rats. The rates of secretion of apolipoprotein AI, E and AIV into the culture medium by hepatocytes isolated from ethanol-fed rats were 1.8-, 1.3-and 1.1-fold higher than those from control rats. These data indicate that (i) chronic ethanol feeding increases very-low-density lipoprotein and high-density lipoprotein in the rat; (ii) serum high-density lipoprotein particles of the ethanol-fed rats are deficient in apolipoprotein E, and (iii) chronic ethanol feeding increases hepatic secretion of apolipoprotein AI, E and AIV. Since the steady-state serum level of apolipoprotein E decreases or remains unchanged in the presence of increased hepatic apolipoprotein E secretion, this imbalance suggests that alcohol feeding either accelerates the rate of degradation of serum apolipoprotein E or suppresses apolipoprotein E synthesis by nonhepatic tissues.
Axial bone proliferation causing cervical myelopathy in the mutilans form of psoriatic arthritis despite peripheral bone erosion: Figure 1
Authors: J Ly, C Pinto, A Doyle, N Dalbeth, F M McQueen
Journal: Annals of the Rheumatic Diseases (2009)

The radiographic features of psoriatic arthritis (PsA) can be broadly grouped into destructive and proliferative changes.1 Arthritis mutilans, described by Moll and Wright2 as “digital telescoping resulting from severe osteolysis” is the most florid form of erosive disease and occurs in less than 5% of cases. Bony proliferation is also characteristic of PsA and may help differentiate this condition from rheumatoid arthritis. We report a patient with PsA who developed cervical myelopathy as a result of proliferative bony change within the cervical spine, despite extremely severe erosive change at the peripheral joints.

The patient, a 65-year-old man, developed psoriasis at …
RESPONSE Re: Markers of DNA Repair and Susceptibility to Cancer in Humans: an Epidemiologic Review
Authors: M. Berwick
Journal: JNCI Journal of the National Cancer Institute (2000)

DNA repair is a system of defenses designed to protect the integrity of the genome. Deficiencies in this system likely lead to the development of cancer. The epidemiology of DNA repair capacity and of its effect on cancer susceptibility in humans is, therefore, an important area of investigation. We have summarized all of the published epidemiologic studies on DNA repair in human cancer through 1998 (n = 64) that addressed the association of cancer susceptibility with a putative defect in DNA repair capacity. We have considered study design, subject characteristics, potential biases, confounding variables, and sources of technical variability. Assays of DNA repair capacity used, to date, can be broadly grouped into five categories: 1) tests based on DNA damage induced with chemicals or physical agents, such as the mutagen sensitivity assay, the G(2)-radiation assay, induced micronuclei, and the Comet assay; 2) indirect tests of DNA repair, such as unscheduled DNA synthesis; 3) tests based on more direct measures of repair kinetics, such as the host cell reactivation assay; 4) measures of genetic variation associated with DNA repair; and 5) combinations of more than one category of assay. The use of such tests in human populations yielded positive and consistent associations between DNA repair capacity and cancer occurrence (with odds ratios in the range of 1. 4-75.3, with the majority of values between 2 and 10). However, the studies that we have reviewed have limitations, including small sample size, convenience controls, the use of cells different from the target organ, and the use of mutagens that do not occur in the natural environment. The evolving ability to study polymorphisms in DNA repair genes may contribute to new understandings about the mechanisms of DNA repair and the way in which DNA repair capacity affects the development of cancer.
Intravenous administration of the conditionally replicative adenovirus Ad5-Δ24RGD induces regression of osteosarcoma lung metastases
Authors: Harm CA Graat, Victor W van Beusechem, Frederik HE Schagen, M Adhiambo Witlox, Eugenie S Kleinerman, Marco N Helder, Winald R Gerritsen, Gertjan JL Kaspers, Paul IJM Wuisman
Journal: Molecular Cancer (2008)

Metastatic osteosarcoma (OS) has a very poor prognosis. New treatments are therefore wanted. The conditionally replicative adenovirus Ad5-Δ24RGD has shown promising anti-tumor effects on local cancers, including OS. The purpose of this study was to determine whether intravenous administration of Ad5-Δ24RGD could suppress growth of human OS lung metastases. Mice bearing SaOs-lm7 OS lung metastases were treated with Ad5-Δ24RGD at weeks 1, 2 and 3 or weeks 5, 6 and 7 after tumor cell injection. Virus treatment at weeks 1–3 did not cause a statistically significant effect on lung weight and total body weight. However, the number of macroscopic lung tumor nodules was reduced from a median of >158 in PBS-treated control mice to 58 in Ad5-Δ24RGD-treated mice (p = 0.15). Moreover, mice treated at weeks 5–7 showed a significantly reduced lung weight (decrease of tumor mass, p < 0.05), a significantly increased body weight gain (decrease of disease symptoms, p < 0.005) and a reduced number of macroscopic lung tumor nodules (median 60 versus > 149, p = 0.12) compared to PBS treated control animals. Adenovirus hexon expression was detected in lung tumor nodules at sacrifice three weeks after the last intravenous adenovirus administration, suggesting ongoing viral infection. These findings suggest that systemic administration of Ad5-Δ24RGD might be a promising new treatment strategy for metastatic osteosarcoma.
Work status and productivity costs due to ankylosing spondylitis: comparison of three European countries
Authors: A Boonen
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To compare work disability, sick leave, and productivity costs due to ankylosing spondylitis (AS) of three European countries. Methods: 216 patients with AS from the Netherlands, France, and Belgium participated in a two year observational study. Employment and work disability rates at baseline were adjusted for age and sex. Productivity costs were calculated by both the friction cost method and the human capital approach. The adjusted contributions of country to employment, work disability, and having an episode of sick leave were assessed by logistic regression and the contribution of the country to days of sick leave and costs by Cox proportional hazard analysis. Results: 209 patients completed the two years9 follow up with sufficient data for cost analysis. Adjusted employment was 55% in the Netherlands as compared with 72% in both other countries and only in the Netherlands was it lower than expected in the general population. Adjusted work disability was 41%, 23%, and 9% in the Netherlands, France, and Belgium and in all countries was higher than expected in the general population. In those with a paid job, the mean number of days of sick leave per patient per year because of AS was 19 (range 0–130), six (range 0–77), and nine (range 0–60 ) in the Netherlands, France, and Belgium respectively. Applying the friction cost method to those with a paid job resulted in mean costs per patient per year of 1257 euros (range 0–7356), 428 euros (range 0–5979), and 476 euros (range 0–2354) in the Netherlands, France, and Belgium. Applying the human capital approach to the whole group resulted in mean costs per patient per year of 8862 euros (range 0–46 818), 3188 euros (range 0–43 550), and 3609 euros (range 0–34 320) in the three countries, respectively. After adjusting for sociodemographic and disease characteristics, living in the Netherlands, as compared with both other countries, was associated with a higher chance of being work disabled (odds ratio (OR)=3.82; 95% confidence interval (CI) 1.33 to 11.01), but not with the risk of having an episode of sick leave. Similarly, living in the Netherlands contributed independently to the number of days sick leave (OR=0.65; 95% CI 0.43 to 0.97), a higher amount of friction costs (OR=0.63; 95% CI 0.42 to 0.96), and a higher amount of human capital costs (OR=0.46; 95% CI 0.32 to 0.68). Conclusion: There are remarkable differences in work status and productivity costs between the three European countries. This has implications for the generalisability of health economic studies.
Colorectal Carcinoma in Childhood and Adolescence: A Clinicopathologic Review
Authors: D. Ashley Hill, Wayne L. Furman, Catherine A. Billups, Shannon E. Riedley, Alvida M. Cain, Bhaskar N. Rao, Charles B. Pratt, Sheri L. Spunt
Journal: Journal of Clinical Oncology (2007)

Purpose Pediatric colorectal carcinoma (CRC) is rare, but the available data suggest that it is more likely than adult CRC to be advanced at presentation and to have a poor outcome. We sought to better characterize pediatric CRC. Patients and Methods We reviewed the clinical and pathologic features, prognostic factors, and outcome of CRC in 77 children and adolescents (ages 7 to 19 years) referred to St Jude Children's Research Hospital between 1964 and 2003. Results At presentation, 76 patients had one or more signs or symptoms of CRC (abdominal pain, altered bowel habits, weight loss, anemia). Tumors were evenly distributed between the right and left colon; 62% were mucinous adenocarcinoma. At presentation, 86% of patients had advanced-stage disease; more than half had distant metastases. Overall outcome was poor. Advanced stage and mucinous histology were significant predictors of adverse outcome. Stage-specific survival at 10 years was 67% ± 27% (stage 1), 38% ± 15% (stage 2), 28% ± 11% (stage III), and 7% ± 4% (stage 4). Although no patient had a diagnosis of polyposis syndrome before diagnosis of CRC, 17 (22%) had colon polyps and eight (including two who previously underwent pelvic radiotherapy) had multiple polyps. Conclusion Initial signs and symptoms of CRC are similar in pediatric and adult patients. The strikingly higher frequency of mucinous histology suggests that the biology of CRC differs in pediatric and adult patients and may contribute to poor outcomes. Children should be included in prospective clinical trials for CRC.
Infection with Trichophyton soudanense in a white Girl.
Authors: I. Sarkany
Journal: British Journal of Dermatology (1963)

Journal Article Infection with Trichophyton soudanense in a white Girl. Get access I. Sarkany I. Sarkany London, W.C.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 75, Issue 10, 1 October 1963, Pages 408–410, https://doi.org/10.1111/j.1365-2133.1963.tb13923.x Published: 01 October 1963
Predictive Biomarkers of Chemotherapy Efficacy in Colorectal Cancer: Results From the UK MRC FOCUS Trial
Authors: Michael S. Braun, Susan D. Richman, Philip Quirke, Catherine Daly, Julian W. Adlard, Faye Elliott, Jennifer H. Barrett, Peter Selby, Angela M. Meade, Richard J. Stephens, Mahesh K.B. Parmar, Matthew T. Seymour
Journal: Journal of Clinical Oncology (2008)

Purpose Candidate predictive biomarkers for irinotecan and oxaliplatin were assessed in 1,628 patients in Fluorouracil, Oxaliplatin, CPT-11: Use and Sequencing (FOCUS), a large randomized trial of fluorouracil alone compared with fluorouracil and irinotecan and compared with fluorouracil and oxaliplatin in advanced colorectal cancer. Methods The candidate biomarkers were: tumor immunohistochemistry for MLH1/MSH2, p53, topoisomerase-1 (Topo1), excision repair cross-complementing gene 1 (ERCC1), O-6-methylguanine-DNA-methyltranserase (MGMT), and cyclooxygenase 2 (COX2); germline DNA polymorphisms in GSTP1, ABCB1, XRCC1, ERCC2, and UGT1A1. These were screened in more than 750 patients for interaction with benefit from irinotecan or oxaliplatin; two markers (Topo1 and MLH1/MSH2) met criteria to be taken forward for analysis in the full population. Primary end points were progression-free survival (PFS) and overall survival. Results One thousand three hundred thirteen patients (81%) were assessable for Topo1 immunohistochemistry (low, &lt; 10%; moderate, 10% to 50%; or high, &gt; 50% tumor nuclei). In patients with low Topo1, PFS was not improved by the addition of either irinotecan (hazard ratio [HR], 0.98; 95% CI, 0.78 to 1.22) or oxaliplatin (HR, 0.85; 95% CI, 0.68 to 1.07); conversely, patients with moderate/high Topo1 benefited from the addition of either drug (HR, 0.48 to 0.70 in all categories; interaction P = .005; overall, P = .001 for irinotecan; P = .05 for oxaliplatin). High Topo1 was associated with a major overall survival benefit with first-line combination chemotherapy (HR, 0.60; median benefit, 5.3 months); patients with moderate or low Topo1 did not benefit (HR, 0.92 and 1.09, respectively; interaction P = .005). MLH1/MSH2 did not show significant interaction with treatment, although the low rate of loss (4.4%) limits the power of the study for this biomarker. Conclusion Topo1 immunohistochemistry identified subpopulations that did or did not benefit from irinotecan, and possibly also from oxaliplatin. If verified independently, this information will contribute to the individualization of treatment for colorectal cancer.
High resolution discovery and confirmation of copy number variants in 90 Yoruba Nigerians
Authors: Hajime Matsuzaki, Pei-Hua Wang, Jing Hu, Rich Rava, Glenn K Fu
Journal: Genome biology (2009)

Abstract Background Copy number variants (CNVs) account for a large proportion of genetic variation in the genome. The initial discoveries of long (&gt; 100 kb) CNVs in normal healthy individuals were made on BAC arrays and low resolution oligonucleotide arrays. Subsequent studies that used higher resolution microarrays and SNP genotyping arrays detected the presence of large numbers of CNVs that are &lt; 100 kb, with median lengths of approximately 10 kb. More recently, whole genome sequencing of individuals has revealed an abundance of shorter CNVs with lengths &lt; 1 kb. Results We used custom high density oligonucleotide arrays in whole-genome scans at approximately 200-bp resolution, and followed up with a localized CNV typing array at resolutions as close as 10 bp, to confirm regions from the initial genome scans, and to detect the occurrence of sample-level events at shorter CNV regions identified in recent whole-genome sequencing studies. We surveyed 90 Yoruba Nigerians from the HapMap Project, and uncovered approximately 2,700 potentially novel CNVs not previously reported in the literature having a median length of approximately 3 kb. We generated sample-level event calls in the 90 Yoruba at nearly 9,000 regions, including approximately 2,500 regions having a median length of just approximately 200 bp that represent the union of CNVs independently discovered through whole-genome sequencing of two individuals of Western European descent. Event frequencies were noticeably higher at shorter regions &lt; 1 kb compared to longer CNVs (&gt; 1 kb). Conclusions As new shorter CNVs are discovered through whole-genome sequencing, high resolution microarrays offer a cost-effective means to detect the occurrence of events at these regions in large numbers of individuals in order to gain biological insights beyond the initial discovery.
Enhancement of Vasoreactivity and Cognition by Intranasal Insulin in Type 2 Diabetes
Authors: Vera Novak, William Milberg, Ying Hao, Medha Munshi, Peter Novak, Andrew Galica, Bradley Manor, Paula Roberson, Suzanne Craft, Amir Abduljalil
Journal: Diabetes Care (2013)

To determine acute effects of intranasal insulin on regional cerebral perfusion and cognition in older adults with type 2 diabetes mellitus (DM).
Prevention of Coronary Heart Disease and the National Cholesterol Education Program
Authors: Lewis H. Kuller
Journal: Circulation (2006)

he incubation period for the progression of atherosclerosis to clinical disease is long, which provides an opportunity for risk factor modification and prevention of coronary heart disease (CHD).The National Cholesterol Education Program (NCEP) utilized the Framingham risk score (FRS) to classify individuals by level of risk to receive drug therapy and/or dietary counseling to lower low-density lipoprotein cholesterol (LDL-C) and raise highdensity lipoprotein cholesterol (HDL-C).The rationale for choosing specific cutpoints for treatment was based on 3 key variables: (1) the efficacy of drug therapy to reduce the CHD incidence, (2) the safety of drug therapy, and (3) the cost of therapy.
Xenoestrogen-Induced Epigenetic Repression of <i>microRNA-9-3</i> in Breast Epithelial Cells
Authors: Pei-Yin Hsu, Daniel E. Deatherage, Benjamin A.T. Rodriguez, Sandya Liyanarachchi, Yu-I Weng, Tao Zuo, Joseph Liu, Alfred S.L. Cheng, Tim H-M. Huang
Journal: Cancer Research (2009)

Abstract Early exposure to xenoestrogens may predispose to breast cancer risk later in adult life. It is likely that long-lived, self-regenerating epithelial progenitor cells are more susceptible to these exposure injuries over time and transmit the injured memory through epigenetic mechanisms to their differentiated progeny. Here, we used progenitor-containing mammospheres as an in vitro exposure model to study this epigenetic effect. Expression profiling identified that, relative to control cells, 9.1% of microRNAs (82 of 898 loci) were altered in epithelial progeny derived from mammospheres exposed to a synthetic estrogen, diethylstilbestrol. Repressive chromatin marks, trimethyl Lys27 of histone H3 (H3K27me3) and dimethyl Lys9 of histone H3 (H3K9me2), were found at a down-regulated locus, miR-9-3, in epithelial cells preexposed to diethylstilbestrol. This was accompanied by recruitment of DNA methyltransferase 1 that caused an aberrant increase in DNA methylation of its promoter CpG island in mammosphere-derived epithelial cells on diethylstilbestrol preexposure. Functional analyses suggest that miR-9-3 plays a role in the p53-related apoptotic pathway. Epigenetic silencing of this gene, therefore, reduces this cellular function and promotes the proliferation of breast cancer cells. Promoter hypermethylation of this microRNA may be a hallmark for early breast cancer development, and restoration of its expression by epigenetic and microRNA-based therapies is another viable option for future treatment of this disease. [Cancer Res 2009;69(14):5936–45]
The association of keratosis pilaris atrophicans and woolly hair, with and without Noonan's syndrome
Authors: V.S. NEILD, J.S. PEGUM, R.S. WELLS
Journal: British Journal of Dermatology (1984)

We describe two cases in which keratosis pilaris atrophicans faciei (ulerythema oophryogenes) occurred in association with hereditary woolly hair. This association also occurred in the father of case I. In case 2, Noonan's syndrome was also present.