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151. Comparatively low attendance during Human Papillomavirus catch-up vaccination among teenage girls in the Netherlands: Insights from a behavioral survey among parents

Author

Gefenaite Giedre, Smit Marieke, Nijman Hans W, Tami Adriana, Drijfhout Ingrid H, Pascal Astrid, Postma Maarten J, Wolters Bert A, van Delden Johannes J M, Wilschut Jan C, and Hak Eelko

Subjects
Public aspects of medicine, RA1-1270
Abstract

Abstract Background The Dutch Human Papillomavirus (HPV) catch-up vaccination program in 2009 appeared less successful than expected. We aimed to identify the most important determinants of refusing the vaccination. Methods Two thousand parents of girls born in 1996 targeted for HPV vaccination received an invitation letter to participate in a questionnaire study. Two study groups were defined: the first group consisted of parents of girls who had accepted the vaccine and already received the first dose of HPV vaccination. The second group consisted of parents whose daughters were not vaccinated. The questionnaire consisted of a broad spectrum of possible determinants that were revealed after literature search and discussions with the stakeholders. Results Four hundred sixty nine questionnaires (24%) were returned, 307 (31%) from those who accepted and 162 (16%) from those who declined the vaccine. The decision not to accept the vaccine was largely determined by: (i) perception that the information provided by the government about the vaccine was limited or biased (OR 13.27); (ii) limited trust, that the government would stop the vaccination program if there were serious side effects (OR 9.95); (iii) lack of knowledge about the effectiveness of the vaccine (OR 7.67); (iv) concerns about the side effects of the vaccine (OR 4.94); (v) lack of conviction that HPV can be extremely harmful (OR 3.78); (vi) perception that the government is strongly influenced by vaccine producers (OR 3.54); and (vii) religious convictions (OR 2.18). Conclusions This study revealed several determinants for HPV vaccination uptake after implementation of the HPV vaccine for adolescent girls. These determinants should be taken into consideration in order to successfully implement HPV vaccination into National Immunization Programs.

Published
2012
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152. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3) : final results of an international, open-label, multicentre, randomised, phase 3 trial

Author

de Boer, Stephanie M., Powell, Melanie E., Mileshkin, Linda, Katsaros, Dionyssios, Bessette, Paul, Haie-Meder, Christine, Ottevanger, Petronella B., Ledermann, Jonathan A., Khaw, Pearly, Colombo, Alessandro, Fyles, Anthony, Baron, Marie Helene, Jürgenliemk-Schulz, Ina M., Kitchener, Henry C., Nijman, Hans W., Wilson, Godfrey, Brooks, Susan, Carinelli, Silvestro, Provencher, Diane, Hanzen, Chantal, Lutgens, Ludy C.H.W., Smit, Vincent T.H.B.M., Singh, Naveena, Do, Viet, D'Amico, Romerai, Nout, Remi A., Feeney, Amanda, Verhoeven-Adema, Karen W., Putter, Hein, Creutzberg, Carien L., McCormack, Mary, Whitmarsh, Karen, Allerton, Rozenn, Gregory, Deborah, Symonds, Paul, Hoskin, Peter J., Adusumalli, Madhavi, Anand, Anjana, Wade, Robert, Stewart, Alexandra, Taylor, Wendy, Kruitwagen, Roy F.P.M., Hollema, Harry, Pras, Elizabeth, Snyers, An, Stalpers, Lukas, Jobsen, Jan J., Slot, Annerie, Mens, Jan Willem M., and Stam, Tanja C.

Subjects
Canada, Time Factors, Endometrial Neoplasms/mortality, Clinical Trial, Phase III, Risk Factors, Paclitaxel/administration & dosage, Journal Article, Humans, Comparative Study, Aged, Neoplasm Staging, Gynecologic Surgical Procedures/adverse effects, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Research Support, Non-U.S. Gov't, Australia, Carboplatin/administration & dosage, Chemoradiotherapy, Adjuvant/adverse effects, Middle Aged, Europe, Multicenter Study, Treatment Outcome, Oncology, Randomized Controlled Trial, Carcinoma, Endometrioid/mortality, Lymph Node Excision, Female, Radiotherapy, Adjuvant, Dose Fractionation, Radiation, Neoplasm Grading, Cisplatin/administration & dosage, New Zealand
Abstract

BACKGROUND: Although women with endometrial cancer generally have a favourable prognosis, those with high-risk disease features are at increased risk of recurrence. The PORTEC-3 trial was initiated to investigate the benefit of adjuvant chemotherapy during and after radiotherapy (chemoradiotherapy) versus pelvic radiotherapy alone for women with high-risk endometrial cancer. METHODS: PORTEC-3 was an open-label, international, randomised, phase 3 trial involving 103 centres in six clinical trials collaborating in the Gynaecological Cancer Intergroup. Eligible women had high-risk endometrial cancer with FIGO 2009 stage I, endometrioid-type grade 3 with deep myometrial invasion or lymph-vascular space invasion (or both), endometrioid-type stage II or III, or stage I to III with serous or clear cell histology. Women were randomly assigned (1:1) to receive radiotherapy alone (48·6 Gy in 1·8 Gy fractions given on 5 days per week) or radiotherapy and chemotherapy (consisting of two cycles of cisplatin 50 mg/m 2 given during radiotherapy, followed by four cycles of carboplatin AUC5 and paclitaxel 175 mg/m 2) using a biased-coin minimisation procedure with stratification for participating centre, lymphadenectomy, stage of cancer, and histological type. The co-primary endpoints were overall survival and failure-free survival. We used the Kaplan-Meier method, log-rank test, and Cox regression analysis for final analysis by intention to treat and adjusted for stratification factors. The study was closed on Dec 20, 2013, after achieving complete accrual; follow-up is ongoing. PORTEC-3 is registered with ISRCTN, number ISRCTN14387080, and ClinicalTrials.gov, number NCT00411138. RESULTS: 686 women were enrolled between Nov 23, 2006, and Dec 20, 2013. 660 eligible patients were included in the final analysis, of whom 330 were assigned to chemoradiotherapy and 330 were assigned to radiotherapy. Median follow-up was 60·2 months (IQR 48·1-73·1). 5-year overall survival was 81·8% (95% CI 77·5-86·2) with chemoradiotherapy versus 76·7% (72·1-81·6) with radiotherapy (adjusted hazard ratio [HR] 0·76, 95% CI 0·54-1·06; p=0·11); 5-year failure-free survival was 75·5% (95% CI 70·3-79·9) versus 68·6% (63·1-73·4; HR 0·71, 95% CI 0·53-0·95; p=0·022). Grade 3 or worse adverse events during treatment occurred in 198 (60%) of 330 who received chemoradiotherapy versus 41 (12%) of 330 patients who received radiotherapy (p

Published
2018

153. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial

Author

de Boer, Stephanie M, primary, Powell, Melanie E, additional, Mileshkin, Linda, additional, Katsaros, Dionyssios, additional, Bessette, Paul, additional, Haie-Meder, Christine, additional, Ottevanger, Petronella B, additional, Ledermann, Jonathan A, additional, Khaw, Pearly, additional, D'Amico, Romerai, additional, Fyles, Anthony, additional, Baron, Marie-Helene, additional, Jürgenliemk-Schulz, Ina M, additional, Kitchener, Henry C, additional, Nijman, Hans W, additional, Wilson, Godfrey, additional, Brooks, Susan, additional, Gribaudo, Sergio, additional, Provencher, Diane, additional, Hanzen, Chantal, additional, Kruitwagen, Roy F, additional, Smit, Vincent T H B M, additional, Singh, Naveena, additional, Do, Viet, additional, Lissoni, Andrea, additional, Nout, Remi A, additional, Feeney, Amanda, additional, Verhoeven-Adema, Karen W, additional, Putter, Hein, additional, Creutzberg, Carien L, additional, McCormack, M, additional, Whitmarsh, K, additional, Allerton, R, additional, Gregory, D, additional, Symonds, P, additional, Hoskin, PJ, additional, Adusumalli, M, additional, Anand, A, additional, Wade, R, additional, Stewart, A, additional, Taylor, W, additional, Lutgens, LCHW, additional, Hollema, H, additional, Pras, E, additional, Snyers, A, additional, Westerveld, GH, additional, Jobsen, JJ, additional, Slot, A, additional, Mens, JM, additional, Stam, TC, additional, Van Triest, B, additional, Van der Steen-Banasik, EM, additional, De Winter, KAJ, additional, Quinn, MA, additional, Kolodziej, I, additional, Pyman, J, additional, Johnson, C, additional, Capp, A, additional, Fossati, R, additional, Colombo, A, additional, Carinelli, S, additional, Ferrero, A, additional, Artioli, G, additional, Davidson, C, additional, McLachlin, CM, additional, Ghatage, P, additional, Rittenberg, PVC, additional, Souhami, L, additional, Thomas, G, additional, Duvillard, P, additional, Berton-Rigaud, D, additional, and Tubiana-Mathieu, N, additional

Published
2019
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154. Abstract CT002: A strong HPV-specific T-cell response after chemo-immunotherapy for advanced cervical cancer is associated with prolonged survival

Author

Melief, Cornelis J M, primary, Welters, Marij J., additional, Vergote, Ignace, additional, Kroep, Judith R., additional, Kenter, Gemma G., additional, Ottevanger, Nelleke, additional, Tjalma, Wiebren A., additional, Denys, Hannelore, additional, Poelgeest, Mariette van, additional, Nijman, Hans W., additional, Reyners, Anna K., additional, Velu, Thierry, additional, Goffin, Frederic, additional, Lalisang, Roy, additional, Krebber, Willem-Jan, additional, Hooftman, Leon, additional, Visscher, Sonja, additional, Blumenstein, Brent A., additional, Stead, Richard B., additional, Gerritsen, Winald, additional, and Burg, Sjoerd van der, additional

Published
2019
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155. A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer

Author

Workel, Hagma H., primary, Lubbers, Joyce M., additional, Arnold, Roland, additional, Prins, Thalina M., additional, van der Vlies, Pieter, additional, de Lange, Kim, additional, Bosse, Tjalling, additional, van Gool, Inge C., additional, Eggink, Florine A., additional, Wouters, Maartje C.A., additional, Komdeur, Fenne L., additional, van der Slikke, Elisabeth C., additional, Creutzberg, Carien L., additional, Kol, Arjan, additional, Plat, Annechien, additional, Glaire, Mark, additional, Church, David N., additional, Nijman, Hans W., additional, and de Bruyn, Marco, additional

Published
2019
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159. Changes in (risk) behavior and HPV knowledge among Dutch girls eligible for HPV vaccination: An observational cohort study

Author

Global Public Health & Bioethics, Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Donken, Robine, Tami, Adriana, Knol, Mirjam J., Lubbers, Karin, Van Der Sande, Marianne A.B., Nijman, Hans W., Daemen, Toos, Weijmar Schultz, Willibrord C.M., De Melker, Hester E., Global Public Health & Bioethics, Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Donken, Robine, Tami, Adriana, Knol, Mirjam J., Lubbers, Karin, Van Der Sande, Marianne A.B., Nijman, Hans W., Daemen, Toos, Weijmar Schultz, Willibrord C.M., and De Melker, Hester E.

Published
2018

160. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial

Author

MS Radiotherapie, Cancer, de Boer, Stephanie M., Powell, Melanie E., Mileshkin, Linda, Katsaros, Dionyssios, Bessette, Paul, Haie-Meder, Christine, Ottevanger, Petronella B., Ledermann, Jonathan A., Khaw, Pearly, Colombo, Alessandro, Fyles, Anthony, Baron, Marie Helene, Jürgenliemk-Schulz, Ina M., Kitchener, Henry C., Nijman, Hans W., Wilson, Godfrey, Brooks, Susan, Carinelli, Silvestro, Provencher, Diane, Hanzen, Chantal, Lutgens, Ludy C.H.W., Smit, Vincent T.H.B.M., Singh, Naveena, Do, Viet, D'Amico, Romerai, Nout, Remi A., Feeney, Amanda, Verhoeven-Adema, Karen W., Putter, Hein, Creutzberg, Carien L., McCormack, Mary, Whitmarsh, Karen, Allerton, Rozenn, Gregory, Deborah, Symonds, Paul, Hoskin, Peter J., Adusumalli, Madhavi, Anand, Anjana, Wade, Robert, Stewart, Alexandra, Taylor, Wendy, Kruitwagen, Roy F.P.M., Hollema, Harry, Pras, Elizabeth, Snyers, An, Stalpers, Lukas, Jobsen, Jan J., Slot, Annerie, Mens, Jan Willem M., Stam, Tanja C., PORTEC study group, MS Radiotherapie, Cancer, de Boer, Stephanie M., Powell, Melanie E., Mileshkin, Linda, Katsaros, Dionyssios, Bessette, Paul, Haie-Meder, Christine, Ottevanger, Petronella B., Ledermann, Jonathan A., Khaw, Pearly, Colombo, Alessandro, Fyles, Anthony, Baron, Marie Helene, Jürgenliemk-Schulz, Ina M., Kitchener, Henry C., Nijman, Hans W., Wilson, Godfrey, Brooks, Susan, Carinelli, Silvestro, Provencher, Diane, Hanzen, Chantal, Lutgens, Ludy C.H.W., Smit, Vincent T.H.B.M., Singh, Naveena, Do, Viet, D'Amico, Romerai, Nout, Remi A., Feeney, Amanda, Verhoeven-Adema, Karen W., Putter, Hein, Creutzberg, Carien L., McCormack, Mary, Whitmarsh, Karen, Allerton, Rozenn, Gregory, Deborah, Symonds, Paul, Hoskin, Peter J., Adusumalli, Madhavi, Anand, Anjana, Wade, Robert, Stewart, Alexandra, Taylor, Wendy, Kruitwagen, Roy F.P.M., Hollema, Harry, Pras, Elizabeth, Snyers, An, Stalpers, Lukas, Jobsen, Jan J., Slot, Annerie, Mens, Jan Willem M., Stam, Tanja C., and PORTEC study group

Published
2018

161. Association of homozygous variants of STING1 with outcome in human cervical cancer.

Author

Lubbers, Joyce M., Koopman, Bart, Klerk‐Sluis, Jessica M., Rooij, Nienke, Plat, Annechien, Pijper, Harry, Koopman, Timco, Hemel, Bettien M., Hollema, Harry, Wisman, Bea, Nijman, Hans W., and Bruyn, Marco

Abstract

DNA‐sensing receptor Cyclic GMP–AMP Synthase (cGAS) and its downstream signaling effector STimulator of INterferon Genes (STING) have gained significant interest in the field of tumor immunology, as a dysfunctional cGAS‐STING pathway is associated with poor prognosis and worse response to immunotherapy. However, studies so far have not taken into account the polymorphic nature of the STING‐encoding STING1 gene. We hypothesized that the presence of allelic variance in STING1 would cause variation between individuals as to their susceptibility to cancer development, cancer progression, and potential response to (immuno)therapy. To start to address this, we defined the genetic landscapes of STING1 in cervical scrapings and investigated their corresponding clinical characteristics across a unique cohort of cervical cancer patients and compared them with independent control cohorts. Although we did not observe an enrichment of particular STING1 allelic variants in cervical cancer patients, we did find that the occurrence of homozygous variants HAQ/HAQ and R232H/R232H of STING1 were associated with both younger age of diagnosis and higher recurrence rate. These findings were accompanied by worse survival, despite comparable mRNA and protein levels of STING and numbers of infiltrated CD8+ T cells. Our findings suggest that patients with HAQ/HAQ and R232H/R232H genotypes may have a dysfunctional cGAS‐STING pathway that fails to promote efficient anticancer immunity. Interestingly, the occurrence of these genotypes coincided with homozygous presence of the V48V variant, which was found to be individually associated with worse outcome. Therefore, we propose V48V to be further evaluated as a novel prognostic marker for cervical cancer. [ABSTRACT FROM AUTHOR]

Published
2021
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163. Ki-67 in endometrial cancer: scoring optimisation and prognostic relevance for window studies:scoring optimization and prognostic relevance for window studies

Author

Kitson, Sarah, Sivalingam, Vanitha N, Bolton, James, McVey, Rhona, Nickkho-Amiry, Mashid, Powell, Melanie E, Leary, Alexandra, Nijman, Hans W, Nout, Remi A, Bosse, Tjalling, Renehan, Andrew G, Kitchener, Henry C, Edmondson, Richard J, and Crosbie, Emma J

Subjects
Observer Variation, Endometrial Neoplasms/metabolism, Manchester Cancer Research Centre, Biomarkers, Tumor/metabolism, ResearchInstitutes_Networks_Beacons/mcrc, Humans, Female, Ki-67 Antigen/metabolism, Prognosis, Immunohistochemistry, Carcinoma, Endometrioid/metabolism
Abstract

Ki-67, a marker of cellular proliferation, is increasingly being used in pre-surgical window studies in endometrial cancer as a primary outcome measure. Unlike in breast cancer, however, there are no guidelines standardizing its measurement and its clinical relevance as a response biomarker is undetermined. It is, therefore, imperative that Ki-67 scoring protocols are optimized and its association with patient survival rigorously evaluated, in order to be able to clinically interpret the results of these studies. Using the International Ki-67 in Breast Cancer Working Group guidelines as a basis, whole slide, hot spot and invasive edge scoring protocols were evaluated using endometrial biopsies and hysterectomy specimens from 179 women. Whole sections and tissue microarrays, manual and semi-automated scoring using Definiens Developer software were additionally compared. Ki-67 scores were related to clinicopathological variables and cancer-specific survival in uni- and multivariate analysis. Against criteria of time efficiency, intra- and inter-observer variability and consistency, semi-automated hot spot scoring was the preferred method. Ki-67 scores positively correlated with grade, stage and depth of myometrial invasion (P-values all

Published
2017

165. Antigen-specific active immunotherapy for ovarian cancer

Author

Paijens, Sterre T, primary, Leffers, Ninke, additional, Daemen, Toos, additional, Helfrich, Wijnand, additional, Boezen, H Marike, additional, Cohlen, Ben J, additional, Melief, Cornelis JM, additional, de Bruyn, Marco, additional, and Nijman, Hans W, additional

Published
2018
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170. The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in the tumour microenvironment

Author

HAG Hart- Vaatziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Versluis, M A C, Marchal, S, Plat, A, Bock, G.H., Hall, T., de Bruyn, K.M.T., Hollema, H., Nijman, Hans W, HAG Hart- Vaatziekten, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Versluis, M A C, Marchal, S, Plat, A, Bock, G.H., Hall, T., de Bruyn, K.M.T., Hollema, H., and Nijman, Hans W

Published
2017

171. Moving forward with actionable therapeutic targets and opportunities in endometrial cancer: NCI clinical trials planning meeting report on identifying key genes and molecular pathways for targeted endometrial cancer trials

Author

MacKay, Helen J., primary, Levine, Douglas A., additional, Bae-Jump, Victoria L., additional, Bell, Daphne W., additional, McAlpine, Jessica N., additional, Santin, Alessandro, additional, Fleming, Gini F., additional, Mutch, David G., additional, Nephew, Kenneth P., additional, Wentzensen, Nicolas, additional, Goodfellow, Paul J., additional, Dorigo, Oliver, additional, Nijman, Hans W., additional, Broaddus, Russell, additional, and Kohn, Elise C., additional

Published
2017
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172. CD103+ tumor-infiltrating lymphocytes are tumor-reactive intraepithelial CD8+ T cells associated with prognostic benefit and therapy response in cervical cancer

Author

Komdeur, Fenne L., primary, Prins, Thalina M., additional, van de Wall, Stephanie, additional, Plat, Annechien, additional, Wisman, G. Bea A., additional, Hollema, Harry, additional, Daemen, Toos, additional, Church, David N., additional, de Bruyn, Marco, additional, and Nijman, Hans W., additional

Published
2017
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174. Immunological profiling of molecularly classified high-risk endometrial cancers identifies POLE-mutant and microsatellite unstable carcinomas as candidates for checkpoint inhibition

Author

Eggink, Florine A., primary, Van Gool, Inge C., additional, Leary, Alexandra, additional, Pollock, Pamela M., additional, Crosbie, Emma J., additional, Mileshkin, Linda, additional, Jordanova, Ekaterina S., additional, Adam, Julien, additional, Freeman-Mills, Luke, additional, Church, David N., additional, Creutzberg, Carien L., additional, De Bruyn, Marco, additional, Nijman, Hans W., additional, and Bosse, Tjalling, additional

Published
2017
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175. Somatic POLE proofreading domain mutation, immune response, and prognosis in colorectal cancer: a retrospective, pooled biomarker study

Author

Domingo, Enric, primary, Freeman-Mills, Luke, additional, Rayner, Emily, additional, Glaire, Mark, additional, Briggs, Sarah, additional, Vermeulen, Louis, additional, Fessler, Evelyn, additional, Medema, Jan Paul, additional, Boot, Arnoud, additional, Morreau, Hans, additional, van Wezel, Tom, additional, Liefers, Gerrit-Jan, additional, Lothe, Ragnhild A, additional, Danielsen, Stine A, additional, Sveen, Anita, additional, Nesbakken, Arild, additional, Zlobec, Inti, additional, Lugli, Alessandro, additional, Koelzer, Viktor H, additional, Berger, Martin D, additional, Castellví-Bel, Sergi, additional, Muñoz, Jenifer, additional, de Bruyn, Marco, additional, Nijman, Hans W, additional, Novelli, Marco, additional, Lawson, Kay, additional, Oukrif, Dahmane, additional, Frangou, Eleni, additional, Dutton, Peter, additional, Tejpar, Sabine, additional, Delorenzi, Mauro, additional, Kerr, Rachel, additional, Kerr, David, additional, Tomlinson, Ian, additional, and Church, David N, additional

Published
2016
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176. Development of a next generation Semliki Forest virus-based DNA vaccine against cervical cancer

Author

Van De Wall, Stephanie, Ljungberg, Karl, Peng IP, Peng, Boerma, Annemarie, Nijman, Hans W., Liljeström, Peter, Daemen, Toos, Targeted Gynaecologic Oncology (TARGON), Translational Immunology Groningen (TRIGR), and Microbes in Health and Disease (MHD)

Subjects
DNA vaccine, electroporation, Semliki Forest virus, DNA immunization, viruses, virus vector, tumor model, memory, Wart virus, intramuscular drug administration, vaccine, human, mouse, risk, hybrid protein, therapy, DNA, vaccination, infection, female, shelf life, protein, epithelium cell, neoplasm, DNA A, uterine cervix cancer
Abstract

Cervical cancer is the second most prevalent cancer among women worldwide. The disease develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression of early proteins E6 and E7 with transforming capacities in cervical epithelial cells. Our group pioneered the application of a replication-defective recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. In preclinical studies, we demonstrated that recombinant SFV (rSFV) encoding HPV E6 and E7 (rSFVeE6,7), induces robust HPV-specific cellular immune and memory responses upon intramuscular (i.m.) administration in mice resulting in excellent therapeutic anti-tumour efficacy. Despite the clear potency of the SFV vector system, there are a number of inherent challenges. These include manufacturing costs, shelf-life and anti-vector responses. DNA vaccination is an alternative method with the potential to be inexpensive and safe. In this project, the drawbacks associated with both SFV-based vaccines and DNA vaccines are circumvented with the development of a DNA vaccine based on the SFV replicase (DREP). This next generation vaccine will exploit the advantages of both strategies for the development of an immunotherapeutic response against cervical neoplasia by encoding the fusion protein eE6,7 (DREPeE6,7). Our initial results show that upon intradermal delivery via electroporation of mice with DREP-eE6,7, similar E7-specific responses were elicited as compared to i.m. administration of rSFVeE6,7. These results will be further confirmed for assessment of therapeutic efficacy using a TC-1 tumor model.

Published
2014

177. Refinement of high-risk endometrial cancer classification using DNA damage response biomarkers: a TransPORTEC initiative.

Author

Auguste, Aurélie, Genestie, Catherine, De Bruyn, Marco, Adam, Julien, Le Formal, Audrey, Drusch, Françoise, Pautier, Patricia, Crosbie, Emma J., MacKay, Helen, Kitchener, Henry C., Powell, Melanie, Pollock, Pamela M., Mileshkin, Linda, Edmondson, Richard J., Nout, Remi, Nijman, Hans W., Creutzberg, Carien L., Bosse, Tjalling, and Leary, Alexandra

Published
2018
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178. Author Correction: Prediction of recurrence risk in endometrial cancer with multimodal deep learning

Author

Volinsky-Fremond, Sarah, Horeweg, Nanda, Andani, Sonali, Barkey Wolf, Jurriaan, Lafarge, Maxime W., de Kroon, Cor D., Ørtoft, Gitte, Høgdall, Estrid, Dijkstra, Jouke, Jobsen, Jan J., Lutgens, Ludy C. H. W., Powell, Melanie E., Mileshkin, Linda R., Mackay, Helen, Leary, Alexandra, Katsaros, Dionyssios, Nijman, Hans W., de Boer, Stephanie M., Nout, Remi A., de Bruyn, Marco, Church, David, Smit, Vincent T. H. B. M., Creutzberg, Carien L., Koelzer, Viktor H., and Bosse, Tjalling

Published
2024
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179. Markers of fibroblast-rich tumor stroma and perivascular cells in serous ovarian cancer: Inter- and intra-patient heterogeneity and impact on survival

Author

Corvigno, Sara, Wisman, G. Bea A., Mezheyeuski, Artur, van der Zee, Ate G. J., Nijman, Hans W., Åvall-Lundqvist, Elisabeth, Ostman, Arne, Dahlstrand, Hanna, Corvigno, Sara, Wisman, G. Bea A., Mezheyeuski, Artur, van der Zee, Ate G. J., Nijman, Hans W., Åvall-Lundqvist, Elisabeth, Ostman, Arne, and Dahlstrand, Hanna

Abstract

Inter- and intra-patient variations in tumor microenvironment of serous ovarian cancer are largely unexplored. We aimed to explore potential co-regulation of tumor stroma characteristics, analyze their concordance in primary and metastatic lesions, and study their impact on survival. A tissue microarray (TMA) with 186 tumors and 91 matched metastases was subjected to immunohistochemistry double staining with endothelial cell marker CD34 and fibroblast and pericyte markers alpha-SMA, PDGF beta R and desmin. Images were digitally analyzed to yield "metrics" related to vasculature and stroma features. Intra-case analyses showed that PDGF beta R in perivascular cells and fibroblasts were strongly correlated. Similar findings were observed concerning `-SMA. Most stroma characteristics showed large variations in intra-case comparisons of primary tumors and metastasis. Large PDGF beta R-positive stroma fraction and high PDGF beta FR positive perivascular intensity were both significantly associated with shorter survival in uni- and multi-variate analyses (HR 1.7, 95% CI 1.1-2.5; HR 1.7, 95% CI 1.1-2.8). In conclusion, we found PDGF beta R- and alpha-SMA-expression to be largely independent of each other but concordantly activated in perivascular cells and in fibroblasts within the primary tumor. Stromal characteristics differed between primary tumors and metastases. PDGF beta R in perivascular cells and in fibroblasts may be novel prognostic markers in serous ovarian cancer., Funding Agencies|Cancer Research Foundations of Radiumhemmet; Swedish Research Council (STARGET Linne grant); Swedish Cancer Society; Stockholm City Council

Published
2016
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180. Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions : Lesion Clearance Is Related to the Strength of the T-Cell Response

Author

van Poelgeest, Mariëtte I E, Welters, Marij J P, Vermeij, Renee, Stynenbosch, Linda F M, Loof, Nikki M, Berends-van der Meer, Dorien M A, Löwik, Margriet J G, Hamming, Ineke L E, van Esch, Edith M G, Hellebrekers, Bart W J, van Beurden, Marc, Schreuder, Henk W, Kagie, Marjolein J, Trimbos, J Baptist M Z, Fathers, Lorraine M, Daemen, Toos, Hollema, Harry, Valentijn, A Rob P M, Oostendorp, Jaap, Oude Elberink, J Hanneke N G, Fleuren, Gertjan J, Bosse, Tjalling, Kenter, Gemma G, Stijnen, Theo, Nijman, Hans W, Melief, Cornelis J M, van der Burg, Sjoerd H, van Poelgeest, Mariëtte I E, Welters, Marij J P, Vermeij, Renee, Stynenbosch, Linda F M, Loof, Nikki M, Berends-van der Meer, Dorien M A, Löwik, Margriet J G, Hamming, Ineke L E, van Esch, Edith M G, Hellebrekers, Bart W J, van Beurden, Marc, Schreuder, Henk W, Kagie, Marjolein J, Trimbos, J Baptist M Z, Fathers, Lorraine M, Daemen, Toos, Hollema, Harry, Valentijn, A Rob P M, Oostendorp, Jaap, Oude Elberink, J Hanneke N G, Fleuren, Gertjan J, Bosse, Tjalling, Kenter, Gemma G, Stijnen, Theo, Nijman, Hans W, Melief, Cornelis J M, and van der Burg, Sjoerd H

Published
2016

181. Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response

Author

MS Gynaecologische Oncologie, Cancer, van Poelgeest, Mariëtte I E, Welters, Marij J P, Vermeij, Renee, Stynenbosch, Linda F M, Loof, Nikki M, Berends-van der Meer, Dorien M A, Löwik, Margriet J G, Hamming, Ineke L E, van Esch, Edith M G, Hellebrekers, Bart W J, van Beurden, Marc, Schreuder, Henk W, Kagie, Marjolein J, Trimbos, J Baptist M Z, Fathers, Lorraine M, Daemen, Toos, Hollema, Harry, Valentijn, A Rob P M, Oostendorp, Jaap, Oude Elberink, J Hanneke N G, Fleuren, Gertjan J, Bosse, Tjalling, Kenter, Gemma G, Stijnen, Theo, Nijman, Hans W, Melief, Cornelis J M, van der Burg, Sjoerd H, MS Gynaecologische Oncologie, Cancer, van Poelgeest, Mariëtte I E, Welters, Marij J P, Vermeij, Renee, Stynenbosch, Linda F M, Loof, Nikki M, Berends-van der Meer, Dorien M A, Löwik, Margriet J G, Hamming, Ineke L E, van Esch, Edith M G, Hellebrekers, Bart W J, van Beurden, Marc, Schreuder, Henk W, Kagie, Marjolein J, Trimbos, J Baptist M Z, Fathers, Lorraine M, Daemen, Toos, Hollema, Harry, Valentijn, A Rob P M, Oostendorp, Jaap, Oude Elberink, J Hanneke N G, Fleuren, Gertjan J, Bosse, Tjalling, Kenter, Gemma G, Stijnen, Theo, Nijman, Hans W, Melief, Cornelis J M, and van der Burg, Sjoerd H

Published
2016

182. CD103+ intraepithelial T cells in high-grade serous ovarian cancer are phenotypically diverse TCRαβ+ CD8αβ+ T cells that can be targeted for cancer immunotherapy

Author

Komdeur, Fenne L., primary, Wouters, Maartje C.A., additional, Workel, Hagma H., additional, Tijans, Aline M., additional, Terwindt, Anouk L.J., additional, Brunekreeft, Kim L., additional, Plat, Annechien, additional, Klip, Harry G., additional, Eggink, Florine A., additional, Leffers, Ninke, additional, Helfrich, Wijnand, additional, Samplonius, Douwe F., additional, Bremer, Edwin, additional, Wisman, G. Bea A., additional, Daemen, Toos, additional, Duiker, Evelien W., additional, Hollema, Harry, additional, Nijman, Hans W., additional, and de Bruyn, Marco, additional

Published
2016
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183. Improved Risk Assessment by Integrating Molecular and Clinicopathological Factors in Early-stage Endometrial Cancer—Combined Analysis of the PORTEC Cohorts

Author

Stelloo, Ellen, primary, Nout, Remi A., additional, Osse, Elisabeth M., additional, Jürgenliemk-Schulz, Ina J., additional, Jobsen, Jan J., additional, Lutgens, Ludy C., additional, van der Steen-Banasik, Elzbieta M., additional, Nijman, Hans W., additional, Putter, Hein, additional, Bosse, Tjalling, additional, Creutzberg, Carien L., additional, and Smit, Vincent T.H.B.M., additional

Published
2016
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184. Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial

Author

de Boer, Stephanie M, primary, Powell, Melanie E, additional, Mileshkin, Linda, additional, Katsaros, Dionyssios, additional, Bessette, Paul, additional, Haie-Meder, Christine, additional, Ottevanger, Petronella B, additional, Ledermann, Jonathan A, additional, Khaw, Pearly, additional, Colombo, Alessandro, additional, Fyles, Anthony, additional, Baron, Marie-Helene, additional, Kitchener, Henry C, additional, Nijman, Hans W, additional, Kruitwagen, Roy F, additional, Nout, Remi A, additional, Verhoeven-Adema, Karen W, additional, Smit, Vincent T, additional, Putter, Hein, additional, and Creutzberg, Carien L, additional

Published
2016
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185. CD103 defines intraepithelial CD8+ PD1+ tumour-infiltrating lymphocytes of prognostic significance in endometrial adenocarcinoma

Author

Workel, Hagma H., primary, Komdeur, Fenne L., additional, Wouters, Maartje C.A., additional, Plat, Annechien, additional, Klip, Harry G., additional, Eggink, Florine A., additional, Wisman, G. Bea A., additional, Arts, Henriette J.G., additional, Oonk, Maaike H.M., additional, Mourits, Marian J.E., additional, Yigit, Refika, additional, Versluis, Marco, additional, Duiker, Evelien W., additional, Hollema, Harry, additional, de Bruyn, Marco, additional, and Nijman, Hans W., additional

Published
2016
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186. Microsatellite instability derived JAK1 frameshift mutations are associated with tumor immune evasion in endometrioid endometrial cancer

Author

Stelloo, Ellen, primary, Versluis, Marco A., additional, Nijman, Hans W., additional, de Bruyn, Marco, additional, Plat, Annechien, additional, Osse, Elisabeth M., additional, van Dijk, Reinhardt H., additional, Nout, Remi A., additional, Creutzberg, Carien L., additional, de Bock, Geertruida H., additional, Smit, Vincent T., additional, Bosse, Tjalling, additional, and Hollema, Harry, additional

Published
2016
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187. Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response

Author

van Poelgeest, Mariëtte I.E., primary, Welters, Marij J.P., additional, Vermeij, Renee, additional, Stynenbosch, Linda F.M., additional, Loof, Nikki M., additional, Berends-van der Meer, Dorien M.A., additional, Löwik, Margriet J.G., additional, Hamming, Ineke L.E., additional, van Esch, Edith M.G., additional, Hellebrekers, Bart W.J., additional, van Beurden, Marc, additional, Schreuder, Henk W., additional, Kagie, Marjolein J., additional, Trimbos, J. Baptist M.Z., additional, Fathers, Lorraine M., additional, Daemen, Toos, additional, Hollema, Harry, additional, Valentijn, A. Rob P.M., additional, Oostendorp, Jaap, additional, Oude Elberink, J. Hanneke N.G., additional, Fleuren, Gertjan J., additional, Bosse, Tjalling, additional, Kenter, Gemma G., additional, Stijnen, Theo, additional, Nijman, Hans W., additional, Melief, Cornelis J.M., additional, and van der Burg, Sjoerd H., additional

Published
2016
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188. Prognostic value and clinicopathologic characteristics of L1 cell adhesion molecule (L1CAM) in a large series of vulvar squamous cell carcinomas

Author

Trietsch, Marjolijn D., primary, Oonk, Maaike H.M., additional, Hawinkels, Lukas J.A.C., additional, Bor, Rosalie, additional, van Eendenburg, Jaap D.H., additional, Ivanova, Zina, additional, Peters, Alexander A.W., additional, Nijman, Hans W., additional, Gaarenstroom, Katja N., additional, and Bosse, Tjalling, additional

Published
2016
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190. Prognostic significance of L1CAM expression and its association with mutant p53 expression in high-risk endometrial cancer

Author

Van Gool, Inge C, primary, Stelloo, Ellen, additional, Nout, Remi A, additional, Nijman, Hans W, additional, Edmondson, Richard J, additional, Church, David N, additional, MacKay, Helen J, additional, Leary, Alexandra, additional, Powell, Melanie E, additional, Mileshkin, Linda, additional, Creutzberg, Carien L, additional, Smit, Vincent T H B M, additional, and Bosse, Tjalling, additional

Published
2016
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191. Treatment Regimen, Surgical Outcome, and T-cell Differentiation Influence Prognostic Benefit of Tumor-Infiltrating Lymphocytes in High-Grade Serous Ovarian Cancer

Author

Wouters, Maartje C.A., primary, Komdeur, Fenne L., additional, Workel, Hagma H., additional, Klip, Harry G., additional, Plat, Annechien, additional, Kooi, Neeltje M., additional, Wisman, G. Bea A., additional, Mourits, Marian J.E., additional, Arts, Henriette J.G., additional, Oonk, Maaike H.M., additional, Yigit, Refika, additional, de Jong, Steven, additional, Melief, Cornelis J.M., additional, Hollema, Harry, additional, Duiker, Evelien W., additional, Daemen, Toos, additional, de Bruyn, Marco, additional, and Nijman, Hans W., additional

Published
2016
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192. Long-term impact of endometrial cancer diagnosis and treatment on health-related quality of life and cancer survivorship: Results from the randomized PORTEC-2 trial

Author

MS Radiotherapie, Cancer, De Boer, Stephanie M., Nout, Remi A., Jurgenliemk-Schulz, Ina M., Jobsen, Jan J, Lutgens, Ludy C.H.W., Van Der Steen-Banasik, Elzbieta M., Mens, Jan Willem M., Slot, Annerie, Stenfert Kroese, Marika C., Oerlemans, Simone, Putter, Hein, Verhoeven-Adema, Karen W., Nijman, Hans W, Creutzberg, Carien L., MS Radiotherapie, Cancer, De Boer, Stephanie M., Nout, Remi A., Jurgenliemk-Schulz, Ina M., Jobsen, Jan J, Lutgens, Ludy C.H.W., Van Der Steen-Banasik, Elzbieta M., Mens, Jan Willem M., Slot, Annerie, Stenfert Kroese, Marika C., Oerlemans, Simone, Putter, Hein, Verhoeven-Adema, Karen W., Nijman, Hans W, and Creutzberg, Carien L.

Published
2015

193. From Tumor Immunosuppression to Eradication: Targeting Homing and Activity of Immune Effector Cells to Tumors

Author

Draghiciu, Oana, Nijman, Hans W., and Daemen, Toos

Subjects
Article Subject
Abstract

Unraveling the mechanisms used by the immune system to fight cancer development is one of the most ambitious undertakings in immunology. Detailed knowledge regarding the mechanisms of induction of tolerance and immunosuppression within the tumor microenvironment will contribute to the development of highly effective tumor eradication strategies. Research within the last few decades has shed more light on the matter. This paper aims to give an overview on the current knowledge of the main tolerance and immunosuppression mechanisms elicited within the tumor microenvironment, with the focus on development of effective immunotherapeutic strategies to improve homing and activity of immune effector cells to tumors.

Published
2011
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194. A phase 1/2 study combining gemcitabine, Pegintron and p53 SLP vaccine in patients with platinum-resistant ovarian cancer

Author

Dijkgraaf, Eveline M., primary, Santegoets, Saskia J.A.M., additional, Reyners, An K.L., additional, Goedemans, Renske, additional, Nijman, Hans W., additional, van Poelgeest, Mariëtte I.E., additional, van Erkel, Arien R., additional, Smit, Vincent T.H.B.M., additional, Daemen, Toos A.H.H., additional, van der Hoeven, Jacobus J.M., additional, Melief, Cornelis J.M., additional, Welters, Marij J.P., additional, Kroep, Judith R., additional, and van der Burg, Sjoerd H., additional

Published
2015
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195. The epithelial polarity regulator LGALS9/galectin-9 induces fatal frustrated autophagy in KRAS mutant colon carcinoma that depends on elevated basal autophagic flux

Author

Wiersma, Valerie R, primary, de Bruyn, Marco, additional, Wei, Yunwei, additional, van Ginkel, Robert J, additional, Hirashima, Mitsuomi, additional, Niki, Toshiro, additional, Nishi, Nozomu, additional, Zhou, Jin, additional, Pouwels, Simon D, additional, Samplonius, Douwe F, additional, Nijman, Hans W, additional, Eggleton, Paul, additional, Helfrich, Wijnand, additional, and Bremer, Edwin, additional

Published
2015
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198. POLE Proofreading Mutations Elicit an Antitumor Immune Response in Endometrial Cancer

Author

van Gool, Inge C., primary, Eggink, Florine A., additional, Freeman-Mills, Luke, additional, Stelloo, Ellen, additional, Marchi, Emanuele, additional, de Bruyn, Marco, additional, Palles, Claire, additional, Nout, Remi A., additional, de Kroon, Cor D., additional, Osse, Elisabeth M., additional, Klenerman, Paul, additional, Creutzberg, Carien L., additional, Tomlinson, Ian P.M., additional, Smit, Vincent T.H.B.M., additional, Nijman, Hans W., additional, Bosse, Tjalling, additional, and Church, David N., additional

Published
2015
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199. Adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer: Toxicity and quality-of-life results of the randomized PORTEC-3 trial.

Author

Creutzberg, Carien L., primary, de Boer, Stephanie M., additional, Putter, Hein, additional, Powell, Melanie, additional, Mileshkin, Linda R., additional, Katsaros, Dionyssios, additional, Bessette, Paul, additional, Haie-Meder, Christine, additional, Ledermann, Jonathan A., additional, Ottevanger, P. B., additional, Khaw, Pearly, additional, Colombo, Alessandro, additional, Fyles, Anthony W., additional, Baron, Marie-Helene, additional, Nijman, Hans W., additional, Nout, Remi A., additional, Smit, Vincent T.H.B.M., additional, Verhoeven-Adema, Karen, additional, Kruitwagen, Roy F.P.M., additional, and Kitchener, Henry C., additional

Published
2015
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