LIVIVO - Search results -

Search results

Result 1 - 9 of total 9

Search options

Article: The progression-free survival ratio as outcome measure in recurrent ovarian carcinoma patients: Current and future perspectives.

van de Kruis, Nienke / van der Ploeg, Phyllis / Wilting, Jody H C / Caroline Vos, M / Thijs, Anna M J / de Hullu, Joanne / Ottevanger, Petronella B / Lok, Christianne / Piek, Jurgen M J

Gynecologic oncology reports

2022 Volume 42, Page(s) 101035

Abstract: Objective: Clinical efficacy of cytostatic anticancer agents can be determined with the progression-free survival (PFS) ratio. This outcome measure compares PFS achieved by a new treatment (PFS2) to the PFS of the most recent treatment on which the ... ...

Abstract	Objective: Clinical efficacy of cytostatic anticancer agents can be determined with the progression-free survival (PFS) ratio. This outcome measure compares PFS achieved by a new treatment (PFS2) to the PFS of the most recent treatment on which the patient has experienced progression (PFS1). Clinical benefit has been defined as a PFS-ratio (PFS2/PFS1) > 1.3. However, in order to demonstrate significant benefit, trial designs require an assumption on the proportion of patients who reach this ratio during palliative options. For ovarian carcinoma, data is lacking to support this assumption. Therefore in this study, we assess the PFS-ratio in recurrent ovarian carcinoma patients treated with current palliative options. Methods: We included 67 patients with recurrent high-grade serous (HGSC, 73.1%) or low-grade (LGOC, 26.9%) ovarian carcinoma. We determined the median PFS-ratio and investigated the association with clinicopathological characteristics. Results: Overall, we observed a median PFS-ratio of 0.69. The proportion of patients with a PFS-ratio > 1.3 was 22.4%. For HGSC patients, the median PFS-ratio was significantly lower than for LGOC patients (respectively, 0.58 and 1.26, Conclusions: Although the PFS-ratio represents a meaningful outcome measure in studies investigating cytostatic anticancer agents, we conclude that it is influenced by tumor histology and biological behavior. In future research, these factors should be taken into account when determining thresholds for clinical benefit in trial designs.
Language	English
Publishing date	2022-06-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2818505-5
ISSN	2352-5789
ISSN	2352-5789
DOI	10.1016/j.gore.2022.101035
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Signal transduction pathway activity in high-grade serous carcinoma, its precursors and Fallopian tube epithelium.

van der Ploeg, Phyllis / Uittenboogaard, Aniek / Bosch, Steven L / van Diest, Paul J / Wesseling-Rozendaal, Yvonne J W / van de Stolpe, Anja / Lambrechts, Sandrina / Bekkers, Ruud L M / Piek, Jurgen M J

Gynecologic oncology

2022 Volume 165, Issue 1, Page(s) 114–120

Abstract: Objective: To determine the activity of key signal transduction pathways in serous tubal intraepithelial carcinoma (STIC) and concurrent high-grade serous carcinoma (HGSC) and compare this to pathway activity in normal Fallopian tube epithelium (FTE).!## ...

Abstract	Objective: To determine the activity of key signal transduction pathways in serous tubal intraepithelial carcinoma (STIC) and concurrent high-grade serous carcinoma (HGSC) and compare this to pathway activity in normal Fallopian tube epithelium (FTE). Methods: We assessed mRNA expression levels of pathway-specific target genes with RT-qPCR in STIC and concurrent HGSC (n = 8) and normal FTE (n = 8). Subsequently, signal transduction pathway assays were used to assess functional activity of the androgen (AR) and estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor beta (TGF-β) and canonical wingless-type MMTV integration site (Wnt) pathways. Results: There were no statistically significant differences in pathway activity between STIC and HGSC, but STIC and HGSC demonstrated significantly lower ER and higher PI3K and HH pathway activity in comparison to normal FTE, suggesting these pathways as putative early drivers. In addition, we determined FOXO3a protein expression by immunohistochemistry and found loss of FOXO3a protein expression in STIC and HGSC compared to normal FTE. This observation confirmed that activation of PI3K signaling by loss of FOXO is an early hallmark of serous carcinogenesis. Furthermore, HGSC demonstrated significant loss of AR and Wnt pathway activity in relation to FTE, suggesting these pathways contribute to disease progression. Conclusion: Our observations, together with the previously described associations between p53 signaling and both PI3K and HH pathway activity, provide evidence that increased PI3K and HH pathway activity and loss of ER pathway activity may be underlying events contributing to neoplastic transformation of FTE into STIC.
MeSH term(s)	Adenocarcinoma in Situ/pathology ; Carcinoma in Situ/pathology ; Cystadenocarcinoma, Serous/pathology ; Epithelium/metabolism ; Fallopian Tube Neoplasms/pathology ; Fallopian Tubes/pathology ; Female ; Hedgehog Proteins ; Humans ; Ovarian Neoplasms/pathology ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction
Chemical Substances	Hedgehog Proteins
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2022.01.027
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 885: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Signal Transduction Pathway Activity in High-Grade, Serous Ovarian Carcinoma Reveals a More Favorable Prognosis in Tumors with Low PI3K and High NF-κB Pathway Activity: A Novel Approach to a Long-Standing Enigma.

van Lieshout, Laura / van de Stolpe, Anja / van der Ploeg, Phyllis / Bowtell, David / de Hullu, Joanne / Piek, Jurgen

Cancers

2020 Volume 12, Issue 9

Abstract: We investigated signal transduction pathway (STP) activity in high-grade serous ovarian carcinoma (HGSC) in relation to progression-free survival (PFS) and overall survival (OS). We made use of signal transduction pathway activity analysis (STA analysis), ...

Abstract	We investigated signal transduction pathway (STP) activity in high-grade serous ovarian carcinoma (HGSC) in relation to progression-free survival (PFS) and overall survival (OS). We made use of signal transduction pathway activity analysis (STA analysis), a novel method to quantify functional STP activity. Activity of the following pathways was measured: androgen receptor (AR), estrogen receptor (ER), phosphoinositide 3-kinase (PI3K), Hedgehog (Hh), Notch, nuclear factor-kappa B (NF-κB), transforming growth factor beta (TGF-β), and Wnt. We selected HGSC samples from publicly available datasets of ovarian cancer tissue, and used repeated
Language	English
Publishing date	2020-09-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12092660
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Phenotype-guided targeted therapy based on functional signal transduction pathway activity in recurrent ovarian cancer patients: The STAPOVER study protocol.

van der Ploeg, Phyllis / Hendrikse, Cynthia Se / Thijs, Anna Mj / Westgeest, Hans M / Smedts, Huberdina Pm / Vos, M Caroline / Jalving, Mathilde / Lok, Christianne Ar / Boere, Ingrid A / van Ham, Maaike Apc / Ottevanger, Petronella B / Westermann, Anneke M / Mom, Constantijne H / Lalisang, Roy I / Lambrechts, Sandrina / Bekkers, Ruud Lm / Piek, Jurgen Mj

Heliyon

2023 Volume 10, Issue 1, Page(s) e23170

Abstract: Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for ... ...

Abstract	Objective: Ovarian cancer is the fifth cause of cancer-related death among women. The benefit of targeted therapy for ovarian cancer patients is limited even if treatment is stratified by molecular signature. There remains a high unmet need for alternative diagnostics that better predict targeted therapy, as current diagnostics are generally inaccurate predictors. Quantitative assessment of functional signal transduction pathway (STP) activity from mRNA measurements of target genes is an alternative approach. Therefore, we aim to identify aberrantly activated STPs in tumour tissue of patients with recurrent ovarian cancer and start Study design: Patients with recurrent ovarian cancer and either 1) have platinum-resistant disease, 2) refrain from standard therapy or 3) are asymptomatic and not yet eligible for standard therapy will be included in this multi-centre prospective cohort study with multiple stepwise executed treatment arms. Targeted therapy will be available for patients with aberrantly high functional activity of the oestrogen receptor, androgen receptor, phosphoinositide 3-kinase or Hedgehog STP. The primary endpoint of this study is the progression-free survival (PFS) ratio (PFS2/PFS1 ratio) according to RECIST 1.1 determined by the PFS on matched targeted therapy (PFS2) compared to PFS on prior therapy (PFS1). Secondary endpoints include among others best overall response, overall survival, side effects, health-related quality of life and cost-effectiveness. Conclusion: The results of this study will show the clinical applicability of STP activity in selecting recurrent ovarian cancer patients for effective therapies.
Language	English
Publishing date	2023-12-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e23170
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Functional estrogen receptor signaling pathway activity in high-grade serous ovarian carcinoma as compared to estrogen receptor protein expression by immunohistochemistry.

van der Ploeg, Phyllis / van Lieshout, Laura A M / van de Stolpe, Anja / Bosch, Steven L / Lentjes-Beer, Marjolein H F M / Bekkers, Ruud L M / Piek, Jurgen M J

Cellular oncology (Dordrecht)

2021 Volume 44, Issue 4, Page(s) 951–957

Abstract: Purpose: Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry ... ...

Abstract	Purpose: Anti-estrogen therapy may be used as a palliative treatment option in high-grade serous ovarian carcinomas (HGSC). However, clinical implementation is limited as the use of estrogen receptor (ER) protein expression by immunohistochemistry remains insufficient in predicting therapy response. To determine the accuracy of ER protein expression as a marker for ER signaling pathway activity, we aimed to correlate ER protein expression to functional ER signaling pathway activity in HGSC. Methods: Immunohistochemical ER protein expression was visually scored using total percentages of stained tumor cells and histoscores. Subsequently, mRNA was extracted, and RT-qPCR analysis was performed. Functional ER pathway activity was assessed by a computational Bayesian model inferring ER signaling pathway activity from mRNA levels of ER-specific target genes. Results: Our analysis of 29 HGSCs shows that neither total percentage of ER protein expression, nor ER histoscores are significantly correlated to ER signaling pathway activity (respectively, p = 0.473 and p = 0.606). Classification of HGSC into three groups based on ER histoscores 0-100 (n = 6), 101-200 (n = 15) and 201-300 (n = 8) resulted in comparable mean ER signaling pathway activity among the groups (p = 0.356). Several samples in the higher ER histoscore groups had low ER signaling pathway activity, indicating that nuclear ER protein expression is not sufficient to describe transcriptional ER activation. Conclusion: Positive immunohistochemical ER staining is not always indicative of an active ER signaling pathway and is, therefore, a poor predictor of anti-estrogen response. Further research is needed to prove the predictive value of ER signaling pathway activity regarding anti-estrogen sensitivity in HGSC patients.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Cystadenocarcinoma, Serous/drug therapy ; Cystadenocarcinoma, Serous/genetics ; Cystadenocarcinoma, Serous/metabolism ; Estrogen Receptor alpha/biosynthesis ; Estrogen Receptor alpha/genetics ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Neoplasm Grading ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction/genetics
Chemical Substances	Biomarkers, Tumor ; Estrogen Receptor alpha ; RNA, Messenger
Language	English
Publishing date	2021-03-16
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	2595109-9
ISSN	2211-3436 ; 1875-8606 ; 2211-3428
ISSN (online)	2211-3436
ISSN	1875-8606 ; 2211-3428
DOI	10.1007/s13402-021-00600-5
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 6908: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: The effectiveness of monotherapy with PI3K/AKT/mTOR pathway inhibitors in ovarian cancer: A meta-analysis.

van der Ploeg, Phyllis / Uittenboogaard, Aniek / Thijs, Anna M J / Westgeest, Hans M / Boere, Ingrid A / Lambrechts, Sandrina / van de Stolpe, Anja / Bekkers, Ruud L M / Piek, Jurgen M J

Gynecologic oncology

2021 Volume 163, Issue 2, Page(s) 433–444

Abstract: Objective: To determine the clinical benefit of monotherapy with PI3K/AKT/mTOR inhibitors in patients diagnosed with advanced or recurrent ovarian cancer and to investigate the predictive value of current PI3K/AKT/mTOR biomarkers on therapy response.: ...

Abstract	Objective: To determine the clinical benefit of monotherapy with PI3K/AKT/mTOR inhibitors in patients diagnosed with advanced or recurrent ovarian cancer and to investigate the predictive value of current PI3K/AKT/mTOR biomarkers on therapy response. Methods: A systematic search was conducted in PubMed, Embase and the Cochrane Library for articles reporting on treatment with PI3K/AKT/mTOR inhibitors in ovarian cancer. The primary endpoint was defined as the clinical benefit rate (CBR), including the proportion of patients with complete (CR) and partial response (PR) and stable disease (SD). Secondary endpoints included the overall response rate (ORR, including CR and PR) and drug-related grade 3 and 4 adverse events. Results: We included 233 patients from 19 studies and observed a pooled CBR of 32% (95% CI 20-44%) and ORR of 3% (95% CI 0-6%) in advanced or recurrent ovarian cancer patients treated with PI3K/AKT/mTOR inhibitors. Subgroup analysis tended to favor the studies who selected patients based on current PI3K/AKT/mTOR biomarker criteria (e.g. genomic alterations or loss of PTEN protein expression), but the difference in CBR was not statistically significant from studies with unselected populations (respectively, CBR of 42% (95% CI 23-62%) and 27% (95% CI 14-42%), P = 0.217). To better reflect true patient benefit, we excluded SD <6 months as a beneficial outcome which resulted in a pooled CBR of 7% (95% CI 2-13%). The overall proportion of patients with drug-related grade 3 and 4 adverse events was 36%. Conclusions: The efficacy of monotherapy with PI3K/AKT/mTOR inhibitors in advanced recurrent ovarian cancer patients is limited to a small subgroup and selection of patients with the use of current biomarkers did not improved the CBR significantly. Given the toxicity profile, we suggest that current treatment with PI3K/AKT/mTOR inhibitors should not be initiated unless in clinical trials. Furthermore, improved biomarkers to measure functional PI3K/AKT/mTOR pathway activity are needed to optimize patient selection.
MeSH term(s)	Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/adverse effects ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/antagonists & inhibitors ; Biomarkers, Tumor/metabolism ; Clinical Decision-Making ; Female ; Humans ; MTOR Inhibitors/administration & dosage ; MTOR Inhibitors/adverse effects ; Neoplasm Staging ; Ovarian Neoplasms/diagnosis ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/mortality ; Patient Selection ; Phosphatidylinositol 3-Kinases/analysis ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors/administration & dosage ; Phosphoinositide-3 Kinase Inhibitors/adverse effects ; Predictive Value of Tests ; Proto-Oncogene Proteins c-akt/analysis ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; TOR Serine-Threonine Kinases/analysis ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/metabolism ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor ; MTOR Inhibitors ; Phosphoinositide-3 Kinase Inhibitors ; MTOR protein, human (EC 2.7.1.1) ; AKT1 protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2021-07-10
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	801461-9
ISSN	1095-6859 ; 0090-8258
ISSN (online)	1095-6859
ISSN	0090-8258
DOI	10.1016/j.ygyno.2021.07.008
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 885: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Survival Is Related to Estrogen Signal Transduction Pathway Activity in Postmenopausal Women Diagnosed with High-Grade Serous Ovarian Carcinoma.

van Lieshout, Laura / van der Ploeg, Phyllis / Wesseling-Rozendaal, Yvonne / van de Stolpe, Anja / Bosch, Steven / Lentjes-Beer, Marjolein / Ottenheijm, Meggy / Meriaan, Annelen / Vos, Caroline / de Hullu, Joanne / Massuger, Leon / Bekkers, Ruud / Piek, Jurgen

Cancers

2021 Volume 13, Issue 20

Abstract: High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, has a high mortality rate. Although there are some factors associated with survival, such as stage of disease, there are remarkable differences in survival among women ...

Abstract	High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, has a high mortality rate. Although there are some factors associated with survival, such as stage of disease, there are remarkable differences in survival among women diagnosed with advanced stage disease. In this study, we investigate possible relations between survival and signal transduction pathway (STP) activity. We assessed the functional activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor beta (TGF-β) and canonical wingless-type MMTV integration site (Wnt) pathway in 85 primary tumor samples of patients with FIGO stage IIIC to IVB HGSC and disease-free survival (DFS) below 12 (
Language	English
Publishing date	2021-10-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13205101
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Cyclic activity of signal transduction pathways in fimbrial epithelium of the human fallopian tube.

van der Ploeg, Phyllis / Uittenboogaard, Aniek / Bucks, Karlijn M M / Lentjes-Beer, Marjolein H F M / Bosch, Steven L / van Rumste, Minouche M E / Vos, M Caroline / van Diest, Paul J / Lambrechts, Sandrina / van de Stolpe, Anja / Bekkers, Ruud L M / Piek, Jurgen M J

Acta obstetricia et gynecologica Scandinavica

2021 Volume 101, Issue 2, Page(s) 256–264

Abstract: Introduction: The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of ... ...

Abstract	Introduction: The local environment of the fallopian tube represents the optimal conditions for reproductive processes. To maintain tissue homeostasis, signal transduction pathways are thought to play a pivotal role. Enhancing our understanding of functional signal transduction pathway activity is important to be able to clarify the role of aberrant signal transduction pathway activity leading to female subfertility and other tubal diseases. Therefore, in this study we investigate the influence of the hormonal cycle on the activity of key signal transduction pathways in the fimbrial epithelium of morphologically normal fallopian tubes. Material and methods: We included healthy pre- (n = 17) and postmenopausal (n = 8) patients who had surgical interventions for benign gynecologic conditions. Histologic sections of the fallopian tubes were reviewed by two pathologists and, for the premenopausal patients, hormone serum levels and sections of the endometrium were examined to determine the hormonal phase (early follicular [n = 4], late follicular [n = 3], early luteal [n = 5], late luteal [n = 5]). After laser capture microdissection, total mRNA was extracted from the fimbrial epithelium and real-time quantitative reverse transcription-PCR was performed to determine functional signal transduction pathway activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor-beta (TGF-β) and canonical wingless-type MMTV integration site (Wnt) pathways. Results: The early luteal phase demonstrated high AR and ER pathway activity in comparison with the late luteal phase (p = 0.016 and p = 0.032, respectively) and low PI3K activity compared with the late follicular phase (p = 0.036), whereas the late luteal phase showed low activity of HH and Wnt compared with the early follicular phase (both p = 0.016). Signal transduction pathway activity in fimbrial epithelium from postmenopausal patients was most similar to the early follicular and/or late luteal phase with regard to the AR, ER and PI3K pathways. Wnt pathway activity in postmenopausal patients was comparable to the late follicular and early luteal phase. We observed no differences in HH and TGF-β pathway activity between pre- and postmenopausal samples. The cyclic changes in signal transduction pathway activity suggest a stage-specific function which may affect the morphology and physiology of the human fallopian tube. Conclusions: We demonstrated cyclic changes in activity of the AR, ER, PI3K, HH and Wnt pathways throughout the hormonal cycle.
MeSH term(s)	Aged ; Epithelium/physiology ; Fallopian Tubes/physiology ; Female ; Hedgehog Proteins/metabolism ; Humans ; Menopause ; Menstrual Cycle ; Middle Aged ; Receptors, Androgen/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Wnt/metabolism ; Reference Values ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction
Chemical Substances	Hedgehog Proteins ; Receptors, Androgen ; Receptors, Estrogen ; Receptors, Wnt
Language	English
Publishing date	2021-12-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	80019-3
ISSN	1600-0412 ; 0001-6349
ISSN (online)	1600-0412
ISSN	0001-6349
DOI	10.1111/aogs.14306
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Um I Zs.168: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MA 5: Show issues

Order via subito

Details ▾

Article ; Online: Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low-grade ovarian carcinoma.

Hendrikse, Cynthia S E / van der Ploeg, Phyllis / van de Kruis, Nienke M A / Wilting, Jody H C / Oosterkamp, Floor / Theelen, Pauline M M / Lok, Christianne A R / de Hullu, Joanne A / Smedts, Huberdina P M / Vos, M Caroline / Pijlman, Brenda M / Kooreman, Loes F S / Bulten, Johan / Lentjes-Beer, Marjolein H F M / Bosch, Steven L / van de Stolpe, Anja / Lambrechts, Sandrina / Bekkers, Ruud L M / Piek, Jurgen M J

Cancer

2023 Volume 129, Issue 9, Page(s) 1361–1371

Abstract: Background: Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. ... ...

Abstract	Background: Advanced low-grade ovarian carcinoma (LGOC) is difficult to treat. In several studies, high estrogen receptor (ER) protein expression was observed in patients with LGOC, which suggests that antihormonal therapy (AHT) is a treatment option. However, only a subgroup of patients respond to AHT, and this response cannot be adequately predicted by currently used immunohistochemistry (IHC). A possible explanation is that IHC only takes the ligand, but not the activity, of the whole signal transduction pathway (STP) into account. Therefore, in this study, the authors assessed whether functional STP activity can be an alternative tool to predict response to AHT in LGOC. Methods: Tumor tissue samples were obtained from patients with primary or recurrent LGOC who subsequently received AHT. Histoscores of ER and progesterone receptor (PR) were determined. In addition, STP activity of the ER STP and of six other STPs known to play a role in ovarian cancer was assessed and compared with the STP activity of healthy postmenopausal fallopian tube epithelium. Results: Patients who had normal ER STP activity had a progression-free survival (PFS) of 16.1 months. This was significantly shorter in patients who had low and very high ER STP activity, with a median PFS of 6.0 and 2.1 months, respectively (p < .001). Unlike ER histoscores, PR histoscores were strongly correlated to the ER STP activity and thus to PFS. Conclusions: Aberrant low and very high functional ER STP activity and low PR histoscores in patients with LGOC indicate decreased response to AHT. ER IHC is not representative of functional ER STP activity and is not related to PFS.
MeSH term(s)	Female ; Humans ; Receptors, Estrogen/metabolism ; Biomarkers, Tumor/metabolism ; Neoplasm Recurrence, Local/drug therapy ; Ovarian Neoplasms ; Carcinoma, Ovarian Epithelial/drug therapy ; Signal Transduction ; Receptors, Progesterone/metabolism
Chemical Substances	Receptors, Estrogen ; Biomarkers, Tumor ; Receptors, Progesterone
Language	English
Publishing date	2023-03-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.34661
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Uh III Zs.146: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito