Research Topics
Genomes and Genes | Gemma G KenterSummaryAffiliation: Leiden University Medical Center Country: The Netherlands Publications
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Publications
Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasiaGemma G Kenter
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
N Engl J Med 361:1838-47. 2009..Spontaneous regression occurs in less than 1.5% of patients, and the rate of recurrence after treatment is high...
Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccineMarij J P Welters
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
Clin Cancer Res 14:178-87. 2008..The study aims to evaluate the effect of a human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides vaccine on the antigen-specific T-cell response in cervical cancer patients...
Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responsesMarij J P Welters
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Proc Natl Acad Sci U S A 107:11895-9. 2010..Foxp3(+) T cells have been associated previously with impaired immunity in malignancies. Here we demonstrate that the vaccine-prompted level of this population is associated with early treatment failure...
Circulating human papillomavirus type 16 specific T-cells are associated with HLA Class I expression on tumor cells, but not related to the amount of viral oncogene transcriptsMarjon A De Boer
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Int J Cancer 121:2711-5. 2007..We hypothesize that HLA Class I expression status on tumor cells might as well influence the response to HPV E6/E7 directed immunotherapy...
An unexpectedly large polyclonal repertoire of HPV-specific T cells is poised for action in patients with cervical cancerPeggy J De Vos Van Steenwijk
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Cancer Res 70:2707-17. 2010..This vast existing local T-cell population is awaiting proper stimulation and can be exploited for the immunotherapy of cancer...
Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicityGemma G Kenter
Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands
Clin Cancer Res 14:169-77. 2008..To determine the toxicity, safety, and immunogenicity of a human papillomavirus 16 (HPV16) E6 and E7 long peptide vaccine administered to end-stage cervical cancer patients...
A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesionsPeggy J De Vos Van Steenwijk
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
Cancer Immunol Immunother 61:1485-92. 2012..Thus, vaccination of HSIL patients results in increased HPV16-specific T-cell immunity. Further development of this type of treatment relies on the ability to motivate patients and in the reduction in the side effects...
High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancerSytse J Piersma
Department of Clinical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
Cancer Res 67:354-61. 2007..Our data indicate that, especially in a subgroup of LN- patients, a strong and effective interaction between immune system and tumor exists. This subgroup of cervical cancer patients may have the best prognosis...
Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction elementSytse J Piersma
Department of Clinical Oncology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands
Int J Cancer 122:486-94. 2008..This is crucial for the optimization of cancer immunotherapy in patients with pre-existing tumor-immunity...
Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasiaMuriel van den Hende
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
Int J Cancer 123:146-52. 2008....
Expression of Smad2 and Smad4 in cervical cancer: absent nuclear Smad4 expression correlates with poor survivalJudith N Kloth
Department of Pathology, The Leiden University Medical Center, Leiden, The Netherlands
Mod Pathol 21:866-75. 2008..003 and P=0.003, respectively) and overall 5-year survival (P=0.003 and P=0.010, respectively). Our findings support the hypothesis that Smad4 is a target molecule for functional inactivation in cervical cancer...
Distinct regulation and impact of type 1 T-cell immunity against HPV16 L1, E2 and E6 antigens during HPV16-induced cervical infection and neoplasiaMariette I E van Poelgeest
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
Int J Cancer 118:675-83. 2006..This argues that T-cell responses against early and late HPV16 antigens essentially differ in the manner in which they are induced and regulated, as well as in their impact on the subsequent stages of HPV16-induced cervical disease...
Surgery followed by persistence of high-grade squamous intraepithelial lesions is associated with the induction of a dysfunctional HPV16-specific T-cell responsePeggy J De Vos Van Steenwijk
Department of Gynaecology, Leiden University Medical Centre, Leiden, The Netherlands
Clin Cancer Res 14:7188-95. 2008..To characterize HPV16 E6- and E7-specific T-cell immunity in patients with high-grade squamous intraepithelial lesions (HSIL)...
Evaluation of immunological cross-reactivity between clade A9 high-risk human papillomavirus types on the basis of E6-Specific CD4+ memory T cell responsesMuriel van den Hende
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
J Infect Dis 202:1200-11. 2010..Our data indicate that natural and vaccine-induced HPV16 E6-specific CD4(+) T cell responses are unlikely to mediate efficient cross-protection against other clade A9 members...
Human leukocyte antigen class I, MHC class I chain-related molecule A, and CD8+/regulatory T-cell ratio: which variable determines survival of cervical cancer patients?Ekaterina S Jordanova
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Clin Cancer Res 14:2028-35. 2008..To investigate the effect of intraepithelial tumor-infiltrating lymphocytes (ieTIL) and their ligands expressed by cervical tumor cells on the outcome of cervical cancer patients...
Lack of TNFalpha mRNA expression in cervical cancer is not associated with loss of heterozygosity at 6p21.3, inactivating mutations or promoter methylationJudith N Kloth
Department of Pathology, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
Mol Immunol 45:152-9. 2008..In conclusion, TNFalpha mRNA expression is absent in nearly half of the cervical tumors analyzed. Neither promoter methylation nor genetic causes for lack of expression were evident...
The detection of circulating human papillomavirus-specific T cells is associated with improved survival of patients with deeply infiltrating tumorsMoniek Heusinkveld
Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Int J Cancer 128:379-89. 2011....
Endothelium specific matrilysin (MMP-7) expression in human cancersCornelis F M Sier
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Matrix Biol 27:267-71. 2008..12, P=0.02, n=30). Our data suggest that MMP-7 is involved in tumor angiogenesis, thereby contributing to malignant growth and hence associated with decreased survival...
Single nucleotide polymorphisms in antigen processing machinery component ERAP1 significantly associate with clinical outcome in cervical carcinomaAkash M Mehta
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Genes Chromosomes Cancer 48:410-8. 2009..The location of the ERAP1-127 SNP in the peptidase M1 domain of the ERAP1 aminopeptidase suggests the possibility of direct functional consequences of variation at this locus...
Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigensSjoerd H van der Burg
Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
Proc Natl Acad Sci U S A 104:12087-92. 2007..Our findings offer a plausible explanation for the observed failure of the tumor-specific immune response in patients with cervical carcinoma...
Prognostic relevance of TGF-beta1 and PAI-1 in cervical cancerSuzanne Hazelbag
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Int J Cancer 112:1020-8. 2004..Although simultaneous presence of the 2 factors was observed in all tumors, induction of PAI-1 by TGF-beta(1) could not be demonstrated in our group of cervical carcinomas...
Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinomaRezaul Karim
Departments of Center for Human and Clinical Genetics, Immunohematology and Blood Transfusion, Clinical Oncology, Pathology, and Gynecology, Leiden University Medical Center, Leiden, The Netherlands
Clin Cancer Res 15:6341-7. 2009..The aim of this study was to determine B7-H1, B7-DC, and PD-1 expression in cervical carcinoma...
Detection of human papillomavirus (HPV) 16-specific CD4+ T-cell immunity in patients with persistent HPV16-induced vulvar intraepithelial neoplasia in relation to clinical impact of imiquimod treatmentMariette I E van Poelgeest
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
Clin Cancer Res 11:5273-80. 2005..We have charted HPV16-specific immunity in 29 patients with high-grade VIN and examined its role in the clinical effect of imiquimod treatment...
Genetic variation of antigen processing machinery components and association with cervical carcinomaAkash M Mehta
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Genes Chromosomes Cancer 46:577-86. 2007..Our data indicate that combined genetic variation in the TAP2, LMP7, and ERAP1 genes is associated with increased cervical carcinoma risk...
Role of tumor-derived proinflammatory cytokines GM-CSF, TNF-alpha, and IL-12 in the migration and differentiation of antigen-presenting cells in cervical carcinomaHenry J M A A Zijlmans
Department of Pathology, Leiden University Medical Center, Leiden, Netherlands
Cancer 109:556-65. 2007..The study assessed whether GM-CSF, TNF-alpha, and IL-12, produced by cervical cancer cells, are important for the activity, differentiation, and migration of antigen-presenting cells...
Nerve-sparing radical hysterectomy: local recurrence rate, feasibility, and safety in cervical cancer patients stage IA to IIASabrina A H M van den Tillaart
Department of Gynaecology, Leiden University Medical Center, The Netherlands
Int J Gynecol Cancer 19:39-45. 2009..The aim of his study was to analyze and compare local recurrence rate, feasibility, and safety of nerve-sparing and non-nerve-sparing radical hysterectomy...
High human papillomavirus oncogene mRNA expression and not viral DNA load is associated with poor prognosis in cervical cancer patientsMarjon A De Boer
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Clin Cancer Res 13:132-8. 2007..Here, we describe the quantitative relation between HPV DNA copy number and mRNA expression of the viral oncogenes (E6 and E7) and the prognostic value of both measures in cervical cancer patients...
Substantial changes in gene expression of Wnt, MAPK and TNFalpha pathways induced by TGF-beta1 in cervical cancer cell linesJudith N Kloth
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Carcinogenesis 26:1493-502. 2005..TGF-beta1 excretion by tumor cells more likely contributes to paracrine stimulation of tumor development...
Prediction of BRCA1/2 mutation status in patients with ovarian cancer from a hospital-based cohortCatharina E Jacobi
Departments of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands
Genet Med 9:173-9. 2007..To describe patient, tumor, and family histories of cancer in a hospital-based cohort of patients with ovarian cancer and to identify the predictive value of these characteristics for (non)carrying a BRCA1 or BRCA2 mutation...
Simultaneous mapping of human papillomavirus integration sites and molecular karyotyping in short-term cultures of cervical carcinomas by using 49-color combined binary ratio labeling fluorescence in situ hybridizationAntoinette A T P Brink
Laboratory for Cytochemistry and Cytometry, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands
Cancer Genet Cytogenet 134:145-50. 2002..Our data illustrate the efficacy of 49-color COBRA-FISH to resolve complex karyotypes and simultaneously map specific sequences in metaphases obtained from short-term solid tumor cultures...
Combined array-comparative genomic hybridization and single-nucleotide polymorphism-loss of heterozygosity analysis reveals complex genetic alterations in cervical cancerJudith N Kloth
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
BMC Genomics 8:53. 2007..Integration of these 3 platforms allows detection of genomic alterations at high resolution and investigation of an association between copy number changes and expression...
Rapid enrichment of human papillomavirus (HPV)-specific polyclonal T cell populations for adoptive immunotherapy of cervical cancerAnnemieke de Jong
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Building 1 E3-Q, 2300 RC Leiden, The Netherlands
Int J Cancer 114:274-82. 2005..These HPV16E6-specific CD4(+) T cells may turn out to be an essential component of future adoptive T cell therapy for advanced cervical cancer, by orchestrating CTL dependent and independent tumoricidal mechanisms...
EMMPRIN-induced MMP-2 activation cascade in human cervical squamous cell carcinomaCornelis F M Sier
Department of Pathology, Leiden University Medical Center, The Netherlands
Int J Cancer 118:2991-8. 2006....
Anatomical basis for nerve-sparing radical hysterectomy: immunohistochemical study of the pelvic autonomic nervesCornelis P Maas
Department of Gynecology, Leiden University Medical Center, PO Box 9602, 2300 RC Leiden, The Netherlands
Acta Obstet Gynecol Scand 84:868-74. 2005..The nerve-sparing modification leads to macroscopic reduction in nerve disruption which is substantiated by microscopical evaluation of surgical margins...
Transforming growth factor-beta1 induces tumor stroma and reduces tumor infiltrate in cervical cancerSuzanne Hazelbag
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
Hum Pathol 33:1193-9. 2002..Our results indicate that cervical cancer cells affect the amount and the composition of the intratumoral stroma and the tumor infiltrate by the production and secretion of TGF-beta(1)...
