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991.
Eijsink JJ Noordhuis MG ten Hoor KA Kok M Hollema H de Bock GH Nijman HW Schuuring E Wisman GB van der Zee AG 《Human pathology》2010,41(12):1735-1741
The objective of this study is to correlate the expression of epidermal growth factor receptor (EGFR) components with clinical behavior of early-stage cervical cancer. Tissue samples of 336 consecutive Federation of International Gynecologists and Obstetricians stage IB-IIA cervical cancer patients all treated primarily by radical surgery were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. As representatives for the EGFR pathway, expression of EGFR, pEGFR, PTEN, pAKT, and pERK was assessed by immunohistochemistry on tissue microarrays. Positive immunostaining was observed for EGFR in 32.1%, for pEGFR in 21.0%, for PTEN in 38.3%, for pAKT in 5.3%, and for pERK in 4.3% of tumor samples. Positive EGFR immunostaining was associated with squamous cell carcinoma of the cervix (odds ratio [OR], 7.41; 95% confidence interval [CI], 3.38-16.23, P < .001), negative pEGFR immunostaining with poor differentiation (OR, 0.39; 95% CI, 0.20-0.73, P = .004), and negative PTEN immunostaining with metastatic pelvic lymph nodes (OR, 0.51; 95% CI, 0.30-0.90, P = .019). In multivariate analysis, only pelvic lymph node metastasis (hazard ratio, 6.11; 95% CI, 3.46-10.77, P < .001) and poor differentiation (hazard ratio, 1.91; 95% CI, 1.12-3.26, P = .018) were related to disease-specific survival. In early-stage cervical cancer, loss of PTEN expression is associated with pelvic lymph node metastasis, suggesting PTEN to be one of the tumor suppressor genes affecting pelvic lymph node metastasis. However, expression of EGFR pathway components does not appear to have prognostic impact in surgically treated early-stage cervical cancer. 相似文献
992.
Liselotte van Asten Mariken van der Lubben Cees van den Wijngaard Wilfrid van Pelt Robert Verheij Andre Jacobi Pieter Overduin Adam Meijer Dirk Luijt Eric Claas Mirjam Hermans Willem Melchers John Rossen Rob Schuurman Charles Boucher Jurjen Schirm Louis Kroes Sander Leenders Joep Galama Marion Koopmans 《Journal of clinical virology》2010,47(2):204
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995.
Hartman EE Oort FJ Visser MR Sprangers MA Hanneman MJ de Langen ZJ va Heurn LW Rieu PN Madern GC van der Zee DC Looyard N van Silfhout-Bezemer M Aronson DC 《Diseases of the colon and rectum》2006,49(1):96-103
Purpose The aim of this study was to examine changes in the quality of life of adult patients with anorectal malformations or Hirschsprung's
disease over a three-year interval and to identify demographic, clinical, and psychosocial variables that explain possible
quality-of-life changes. Understanding the factors that affect changes in quality of life over time is particularly important
to provide adequate care.
Methods Questionnaires were administered to 261 patients (77 percent), with a three-year interval. Background characteristics, including
demographic and clinical variables, and psychosocial variables (i.e., self-esteem, mastery, social support, disease cognition) were measured on one occasion. Generic and disease-specific quality
of life were measured twice.
Results On average patients indicated no change in quality-of-life level after three years. However, variance in the change scores
revealed individual variation, indicating the presence of patients who improved and patients who deteriorated. Patients who
were female, older, have other congenital diseases, or a stoma reported poorer quality of life over time. The psychosocial
variable “disease cognition” most strongly affected the change in quality of life of patients with anorectal malformations
or Hirschsprung's disease.
Conclusions Our results could alert clinicians to patients who are at risk for quality-of-life deterioration and might therefore be in
need for extra care. Our findings illustrate the importance of psychosocial functioning for enhancing the quality of life
over time of these patients.
Supported by The Netherlands Digestive Diseases Foundation (MLDS) and Doctors for Children.
Presented at the Dutch Science Conference, Amsterdam, The Netherlands, January 27, 2005, initiated by Emma Children's Hospital
of the Academic Medical Center, University of Amsterdam.
Reprints are not available. 相似文献
996.
Warnatz K Bossaller L Salzer U Skrabl-Baumgartner A Schwinger W van der Burg M van Dongen JJ Orlowska-Volk M Knoth R Durandy A Draeger R Schlesier M Peter HH Grimbacher B 《Blood》2006,107(8):3045-3052
The homozygous deletion of the inducible costimulator (ICOS), an activation-induced member of the CD28 family on T cells, causes an antibody deficiency syndrome in affected humans. The identification of a total of 9 ICOS-deficient patients revealed that this monogenic disease comprises the full clinical phenotype described for common variable immunodeficiency (CVID), including recurrent bacterial infections, adult as well as childhood onset, splenomegaly, autoimmune phenomena (autoimmune neutropenia), intestinal lymphoid hyperplasia, and malignancy (carcinoma of the vulva). All patients exhibited a profound hypogammaglobulinemia and a disturbed B-cell homeostasis. The severe reduction of class-switched memory B cells resulted from poor germinal center formation in the absence of ICOS. The additional decrease of naive B cells was associated with a partial inhibition of the early B-cell development at the pre-B-I stage. T-cell homeostasis seemed not to be affected, but low IL-10 production by ICOS-deficient T cells may contribute to the disturbed germinal center reaction. Human ICOS deficiency is indistinguishable from CVID and thus serves as a monogenic model for this complex syndrome. 相似文献
997.
Mikolajczyk RT Horn J Damm O Kaufmann AM Kretzschmar ME 《Journal of the National Cancer Institute》2012,104(2):163; author reply 163-163; author reply 164
998.
Roossink F Wieringa HW Noordhuis MG Ten Hoor KA Kok M Slagter-Menkema L Hollema H de Bock GH Pras E de Vries EG de Jong S van der Zee AG Schuuring E Wisman GB van Vugt MA 《International journal of cancer. Journal international du cancer》2012,131(9):2056-2066
Treatment of advanced-stage cervical cancers with (chemo)radiation causes cytotoxicity through induction of high levels of DNA damage. Tumour cells respond to DNA damage by activation of the 'DNA damage response' (DDR), which induces DNA repair and may counteract chemoradiation efficacy. Here, we investigated DDR components as potential therapeutic targets and verified the predictive and prognostic value of DDR activation in patients with cervical cancer treated with (chemo)radiation. In a panel of cervical cancer cell lines, inactivation of ataxia telangiectasia mutated (ATM) or its substrate p53-binding protein-1 (53BP1) clearly gave rise to cell cycle defects in response to irradiation. Concordantly, clonogenic survival analysis revealed that ATM inhibition, but not 53BP1 depletion, strongly radiosensitised cervical cancer cells. In contrast, ATM inhibition did not radiosensitise non-transformed epithelial cells or non-transformed BJ fibroblasts. Interestingly, high levels of active ATM prior to irradiation were related with increased radioresistance. To test whether active ATM in tumours prior to treatment also resulted in resistance to therapy, immunohistochemistry was performed on tumour material of patients with advanced-stage cervical cancer (n = 375) treated with (chemo)radiation. High levels of phosphorylated (p-)ATM [p = 0.006, hazard ratio (HR) = 1.817] were related to poor locoregional disease-free survival. Furthermore, high levels of p-ATM predicted shorter disease-specific survival (p = 0.038, HR = 1.418). The presence of phosphorylated 53BP1 was associated with p-ATM (p = 0.001, odds ratio = 2.206) but was not related to any clinicopathological features or survival. In conclusion, both our in vitro and patient-related findings indicate a protective role for ATM in response to (chemo)radiation in cervical cancer and point at ATM inhibition as a possible means to improve the efficacy of (chemo)radiation. 相似文献
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1000.