tbuckley/cabot-search huggingface dataset:
Tooth Discoloration in Patients With Neonatal Diabetes After Transfer Onto Glibenclamide
Authors: Janani Kumaraguru, Sarah E. Flanagan, Siri Atma W. Greeley, Roos Nuboer, Julie Støy, Louis H. Philipson, Andrew T. Hattersley, Oscar Rubio-Cabezas
Journal: Diabetes Care (2009)

OBJECTIVE To assess if tooth discoloration is a novel side effect of sulfonylurea therapy in patients with permanent neonatal diabetes due to mutations in KCNJ11. RESEARCH DESIGN AND METHODS A total of 67 patients with a known KCNJ11 mutation who had been successfully transferred from insulin injections onto oral sulfonylureas were contacted and asked about the development of tooth discoloration after transfer. RESULTS Altered tooth appearance was identified in 5 of the 67 patients. This was variable in severity, ranging from mild discoloration/staining (n = 4) to loss of enamel (n = 1) and was only seen in patients taking glibenclamide (glyburide). CONCLUSIONS These previously unreported side effects may relate to the developing tooth and/or to the high local concentrations in the children who frequently chewed glibenclamide tablets or took it as a concentrated solution. Given the multiple benefits of sulfonylurea treatment for patients with activating KCNJ11 mutations, this association warrants further investigation but should not preclude such treatment.
Abstract 1778: Anticancer activities and regulatory effects on apoptotic gene expression of Bufalin in the orthotopic transplantation model of human colorectal cancer in nude mice
Authors: Jie Wang, Dian-Xu Feng, Chao Chen, Zhen-Hua Ni, Ronghua Zhao, Qing-Song Zuo, Ya-Feng Chen, Xu Wang, Yong Zhang, Alan G. Casson, Teng Chen
Journal: Cancer Research (2011)

Abstract Background: Bufalin, a natural small-molecule compound from the Traditional Chinese Medicine “Chansu”, shows inhibitory effects on many human cancer cells. However, whether or not Bufalin has anticancer activity in human colorectal cancer (CRC), and its possible underlying mechanism, remains unclear. Objectives: 1) To investigate anticancer activities of Bufalin in human CRC using an orthotopic transplantation model in nude mice and 2) to study possible underlying mechanisms related to apoptosis. Materials and methods: An orthotopic transplantation tumor model was established by implanting human CRC HCT-116 cells into the colon of nude mice. Sixty mice were randomly divided into five treatment groups (12 mice in each group): normal saline group, 5-FU group, and 3 Bufalin groups with low (BL), medium (BM), and high (BH) doses. After cell transplantation, 0.2 ml normal saline, 25 mg/kg 5-Fu, or 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg Bufalin was injected intraperitoneally in mice in each corresponding group, daily for 7 days (days 15 to 21). Six mice in each group were sacrificed on day 24. Tumor size, growth inhibition rate, and morphological changes of tumor cell under microscopy were recorded. Apoptosis was determined by TUNEL staining, mRNA and protein expressions of Bcl-xl and Bax were evaluated with real-time RT-PCR and immunohistochemical staining, respectively. The overall survival (OS) was determined in the remaining 6 mice in each group. Results: The tumor size in mice treated with 5-Fu, BL, BM, or BH was significantly smaller than that in mice treated with normal saline (p&amp;lt;0.05), with the tumor inhibitor rates of 64.3%, 51.4%, 48.7%, and 36.3%, respectively. Under microscopy, increased tumor necrosis was observed in the 5-Fu, BM and BH groups. The tumor apoptotic rate in each of 3 Bufalin treated groups was significantly higher than that in the normal saline group (p&amp;lt;0.05). Real time RT-PCR and immunohistochemical staining showed both mRNA and protein expressions of Bcl-xl were decreased, whereas the expression of Bax increased, in tumor treated with Bufalin. The OS was prolonged in groups of BL and BM (p&amp;lt;0.05). Conclusion: Bufalin has significant anticancer activity in a human CRC orthotopic transplantation model in nude mice, and induces tumor cell apoptosis, which may be associated with the down-regulation of Bcl-xl and up-regulation of Bax in tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1778. doi:10.1158/1538-7445.AM2011-1778
Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers
Authors: Scott M. Lippman, Eric A. Klein, Phyllis J. Goodman, M. Scott Lucia, Ian M. Thompson, Leslie G. Ford, Howard L. Parnes, Lori M. Minasian, J. Michael Gaziano, Jo Ann Hartline, J. Kellogg Parsons, James D. Bearden, E. David Crawford, Gary E. Goodman, Jaime Claudio, Eric Winquist, Elise D. Cook, Daniel D. Karp, Philip Walther, Michael M. Lieber, Alan R. Kristal, Amy K. Darke, Kathryn B. Arnold, Patricia A. Ganz, Regina M. Santella, Demetrius Albanes, Philip R. Taylor, Jeffrey L. Probstfield, T. J. Jagpal, John J. Crowley, Frank L. Meyskens, Laurence H. Baker, Charles A. Coltman
Journal: JAMA (2008)

<h3>Context</h3>Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.<h3>Objective</h3>To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.<h3>Design, Setting, and Participants</h3>A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.<h3>Interventions</h3>Oral selenium (200 μg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac-α-tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.<h3>Main Outcome Measures</h3>Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.<h3>Results</h3>As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P&gt;.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.<h3>Conclusion</h3>Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.<h3>Trial Registration</h3>clinicaltrials.gov identifier: NCT00006392Published online December 9, 2008 (doi:10.1001/jama.2008.864).
Th2 cytokines exert a dominant influence on epithelial cell expression of the major group human rhinovirus receptor, ICAM-1
Authors: A Bianco, SK Sethi, JT Allen, RA Knight, MA Spiteri
Journal: European Respiratory Journal (1998)

Intercellular adhesion molecule (ICAM)-1 is a cell receptor important in both human rhinovirus (HRV) attachment and immune effector cell mobilization. The level of expression of ICAM-1 by epithelial cells (EC) therefore plays a crucial role in the intricate biological phenomena underlying viral binding, host infection and consequent inflammatory events. As T-helper (Th)2 lymphocytes predominate within the asthmatic airway, the influence was evaluated of Th2-associated mediators in the modulation of ICAM-1 expression on uninfected and HRV-infected EC. H292 EC were cultured in vitro, with varying concentrations of interleukin (IL)-4, IL-5, IL-10 and IL-13 for 24 h and then infected with live HRV-14. Surface ICAM-1 expression was assessed by immunocytochemistry. Infection with HRV-14 resulted in a twofold increase in ICAM-1 expression. IL-4, IL-5, IL-10 and IL-13 produced a 2.7-5.1-fold enhancement of ICAM-1 expression of uninfected cells and caused approximately a further twofold increase in infected cells over the expression induced by HRV infection itself. Interferon-gamma in combination with each Th2-associated cytokine only slightly reduced, but did not override, the Th2-induced level of ICAM-1 expression on both uninfected and virus-infected EC. These data suggest that the effects of Th2-associated cytokines on intercellular adhesion molecule-1 expression and recovery of infectious virus are dominant over the effects of the Th1-associated cytokines such as interferon-gamma. Since the airway mucosa in atopic asthma is predominantly infiltrated by Th2 lymphocytes, these results could explain both the increased susceptibility to human rhinovirus infection in asthmatic patients and the associated exacerbation of asthma symptoms.
A multi-institutional phase II trial of a novel inpatient schedule of continuous interleukin-2with interferon α-2b in advanced renal cell carcinoma: major durable responses in a less highly selected patient population
Authors: J.I. Clark, T.M. Kuzel, T.M. Lestingi, S.G. Fisher, P. Sorokin, B. Martone, M. Viola, J.A. Sosman
Journal: Annals of Oncology (2002)
FDG-PET oriented surgery for recurrent colorectal cancer
Authors: H. Ishikawa, A. Watanabe, T. Mukogawa, T. Inoue, S. Nishiwada, T. Kunishige, S. Ko
Journal: Gut (2011)

<h3>Introduction</h3> Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been accepted as an effective tool of diagnosis and staging for patients with known or suspected recurrent colorectal cancer. <h3>Methods</h3> This study is to analyze the clinical significance of FDG-PET on the diagnosis and indication of surgical intervention for recurrent colorectal cancer. Consecutive 48 patients, with known or suspected recurrence of colorectal cancer based on elevation of tumour markers or abnormal findings on the follow-up CT image, underwent FDG-PET for 70 times between December 2003 and August 2009. Patients were aged between 35 and 89 years (median 48); 27 were male, 16 were Duke9s A or B stage, and 26 had a history of colon cancer. The average of recurrence was two times (range 1–6). The average period between operation and first FDG-PET was 25 months (range 1–89). Of 48 cases 42 had elevated serum CEA or CA19-9 (91.3%). For each case the diagnosis of FDG-PET image was compared with that of CT image and the final diagnosis. <h3>Results</h3> 48 patients were divided into these three groups according to the purposes of FDG-PET; to identify recurrent colorectal cancer by FDG-PET (identification group, n=5), to determine malignancy and disease spread (disease spreading group, n=37), and to evaluate the possibility of surgical intervention in recurrence-confirmed cases (follow-up group, n=6). In the identification group, FDG-PET solely could identify recurrence and indicate operation for 4 cases (7 times). One of three cases shows disease-free survival for 33 months after common iliac replacement operation. In the disease spreading group, 23 cases with localised disease spread by FDG-PET findings were indicated operation, 14 cases with diffused disease spread were judged as contraindication of operation. The median survival period after recurrence of operation series was longer than that of contraindication series (36 months vs 22 months). In the follow-up group, FDG-PET could detect lesions of whole body at one study and one was indicated for salvage operation for liver metastasis. FDG-PET showed to be false-positive in one case and false-negative in three. Totally, the sensitivity of FDG-PET was 95.7% and its accuracy was 94.2%, whereas those of CT were 87.1% and 87.1%, respectively. <h3>Conclusion</h3> FDG-PET could visualise a malignant lesions at earlier stage, and was an effective modality to evaluate not only disease spread but distant metastasis for recurrence of colorectal cancer. In this study, we first demonstrated that FDG-PET oriented surgical indication has clinical importance for recurrent colorectal cancer.
A mouse model for Costello syndrome reveals an Ang II–mediated hypertensive condition
Authors: Alberto J. Schuhmacher, Carmen Guerra, Vincent Sauzeau, Marta Cañamero, Xosé R. Bustelo, Mariano Barbacid
Journal: Journal of Clinical Investigation (2008)

Germline activation of H-RAS oncogenes is the primary cause of Costello syndrome (CS), a neuro-cardio-facio-cutaneous developmental syndrome. Here we describe the generation of a mouse model of CS by introduction of an oncogenic Gly12Val mutation in the mouse H-Ras locus using homologous recombination in ES cells. Germline expression of the endogenous H-RasG12V oncogene, even in homozygosis, resulted in hyperplasia of the mammary gland. However, development of tumors in these mice was rare. H-RasG12V mutant mice closely phenocopied some of the abnormalities observed in patients with CS, including facial dysmorphia and cardiomyopathies. These mice also displayed alterations in the homeostasis of the cardiovascular system, including development of systemic hypertension, extensive vascular remodeling, and fibrosis in both the heart and the kidneys. This phenotype was age dependent and was a consequence of the abnormal upregulation of the renin–Ang II system. Treatment with captopril, an inhibitor of Ang II biosynthesis, prevented development of the hypertension condition, vascular remodeling, and heart and kidney fibrosis. In addition, it partially alleviated the observed cardiomyopathies. These mice should help in elucidating the etiology of CS symptoms, identifying additional defects, and evaluating potential therapeutic strategies.
Long-term results in patients with onychomycosis treated with terbinafine or itraconazole
Authors: H. Heikkila, S. Stubb
Journal: British Journal of Dermatology (2002)

Previously, a double-blind, randomized, multicentre study (LION study) compared the efficacy of continuous terbinafine 250 mg daily for 3 or 4 months with itraconazole pulse therapy 400 mg daily for 3 or 4 months. At the end of the study at week 72 terbinafine proved to be more effective.To perform a 4-year follow-up of the Finnish participants in this study.Patients were re-examined clinically and mycologically.Complete clinical and mycological cure with terbinafine for 4 months was 78% compared with 35% with terbinafine for 3 months, 24% with itraconazole for 4 months and 28% with itraconazole for 3 months.These results suggest that the initial treatment for onychomycosis should be a 4-month continuous course of terbinafine.
WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells
Authors: Elin J Ekström, Caroline Bergenfelz, Verena von Bülow, Filiz Serifler, Eric Carlemalm, Göran Jönsson, Tommy Andersson, Karin Leandersson
Journal: Molecular Cancer (2014)

Abstract Background Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion. Methods Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data. Results We show that WNT5A signaling induces a Ca 2+ -dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro . Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM. Conclusions These data indicate that WNT5A has a broader function on tumor progression and metastatic spread than previously known; by inducing exosome-release of immunomodulatory and pro-angiogenic factors that enhance the immunosuppressive and angiogenic capacity of the tumors thus rendering them more aggressive and more prone to metastasize.
Survival in Daily Home Hemodialysis and Matched Thrice-Weekly In-Center Hemodialysis Patients
Authors: Eric D. Weinhandl, Jiannong Liu, David T. Gilbertson, Thomas J. Arneson, Allan J. Collins
Journal: Journal of the American Society of Nephrology (2012)

Frequent hemodialysis improves cardiovascular surrogates and quality-of-life indicators, but its effect on survival remains unclear. We used a matched-cohort design to assess relative mortality in daily home hemodialysis and thrice-weekly in-center hemodialysis patients between 2005 and 2008. We matched 1873 home hemodialysis patients with 9365 in-center patients (i.e., 1:5 ratio) selected from the prevalent population in the US Renal Data System database. Matching variables included first date of follow-up, demographic characteristics, and measures of disease severity. The cumulative incidence of death was 19.2% and 21.7% in the home hemodialysis and in-center patients, respectively. In the intention-to-treat analysis, home hemodialysis associated with a 13% lower risk for all-cause mortality than in-center hemodialysis (hazard ratio [HR], 0.87; 95% confidence interval [95% CI], 0.78–0.97). Cause-specific mortality HRs were 0.92 (95% CI, 0.78–1.09) for cardiovascular disease, 1.13 (95% CI, 0.84–1.53) for infection, 0.63 (95% CI, 0.41–0.95) for cachexia/dialysis withdrawal, 1.06 (95% CI, 0.81–1.37) for other specified cause, and 0.59 (95% CI, 0.44–0.79) for unknown cause. Findings were similar using as-treated analyses. We did not detect statistically significant evidence of heterogeneity of treatment effects in subgroup analyses. In summary, these data suggest that relative to thrice-weekly in-center hemodialysis, daily home hemodialysis associates with modest improvements in survival. Continued surveillance should strengthen inference about causes of mortality and determine whether treatment effects are homogeneous throughout the dialysis population.
Enhancement of the Efficacy of Chemotherapy for Lung Cancer by Simultaneous Suppression of Multidrug Resistance and Antiapoptotic Cellular Defense
Authors: Refika I. Pakunlu, Yang Wang, William Tsao, Vitaly Pozharov, Thomas J. Cook, Tamara Minko
Journal: Cancer Research (2004)

Abstract The efficacy of chemotherapy of lung cancer is limited by the development of resistance in cancer cells during treatment. In most lung cancers, this resistance is associated with the overexpression of (a) multidrug resistance-associated protein (MRP) responsible for drug efflux from the cancer cells (pump resistance) and (b) BCL2 protein that activates antiapoptotic cellular defense (nonpump resistance). A novel liposomal proapoptotic anticancer drug delivery system was developed to enhance anticancer efficacy of the well-established drug doxorubicin (DOX). This multicomponent drug delivery system was tested on multidrug-sensitive and -resistant human small-cell lung cancer cells. The drug delivery system includes four components: (a) liposome as a carrier, (b) DOX as an inductor of apoptosis, (c) antisense oligonucleotides (ASOs) targeted to MRP1 mRNA as a suppressor of pump resistance, and (d) ASOs targeted to BCL2 mRNA as a suppressor of nonpump resistance. Intracellular internalization of ASOs and DOX; the influence of the proposed system on the expression of genes and proteins involved in the multidrug resistance, cytotoxicity, and apoptosis induction and antiapoptotic defense; and the activity of caspases were studied. It was found that the proposed liposomal delivery system successfully delivered ASOs and DOX to cell nuclei, inhibited MRP1 and BCL2 protein synthesis, and substantially increased the anticancer action of DOX by stimulating the caspase-dependent pathway of apoptosis in multidrug-resistant human lung cancer cells.
HSF1 as a Mitotic Regulator: Phosphorylation of HSF1 by Plk1 Is Essential for Mitotic Progression
Authors: Yoon-Jin Lee, Eun-Ho Kim, Jae Seon Lee, Dooil Jeoung, Sangwoo Bae, Seung Hae Kwon, Yun-Sil Lee
Journal: Cancer Research (2008)

Previously, heat shock factor 1 (HSF1) had been reported to induce genomic instability and aneuploidy by interaction with Cdc20. Here, we have further examined the functions of HSF1 in the regulation of mitosis. A null mutant or knockdown of HSF1 caused defective mitotic progression. By monitoring chromosomes in living cells, we determined that HSF1 was localized to the centrosome in mitosis and especially to the spindle poles in metaphase. HSF1 was phosphorylated by Plk1 at Ser(216) of the DSGXXS motif during the timing of mitosis and a phospho-defective mutant form of HSF1 inhibited mitotic progression. Phosphorylated HSF1 during spindle pole localization underwent ubiquitin degradation through the SCF(beta-TrCP) pathway. However, binding of HSF1 with Cdc20 stabilized the phosphorylation of HSF1. Moreover, SCF(beta-TrCP)-mediated degradation only occurred when phosphorylated HSF1 was released from Cdc20. HSF1 phosphorylation at Ser(216) occurred in the early mitotic period with simultaneous binding of Cdc20. The interaction of HSF1 with SCF(beta-TrCP) was followed and then the interaction of APC/Cdc20 was subsequently observed. From these findings, it was shown that Plk1 phosphorylates HSF1 in early mitosis and that the binding of phosphorylated HSF1 with Cdc20 and ubiquitin degradation by SCF(beta-TrCP) regulates mitotic progression.