Recent Insights into Mucinous Ovarian Carcinoma

Ricci, Francesca; Affatato, Roberta; Carrassa, Laura; Damia, Giovanna

doi:10.3390/ijms19061569

Cited by 54 publications

(55 citation statements)

References 68 publications

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“…mEOC is also different from other subtypes at the molecular level. In fact, only 16-52% of mEOCs have a TP53 mutation compared to 99% of HGSOCs [12,13]. mEOC is not associated with BRCA1/2 mutations, whereas approximately 25% of HGSOCs carry either germline or somatic mutations of these genes [12,14].…”

Section: Introductionmentioning

confidence: 99%

“…In fact, only 16-52% of mEOCs have a TP53 mutation compared to 99% of HGSOCs [12,13]. mEOC is not associated with BRCA1/2 mutations, whereas approximately 25% of HGSOCs carry either germline or somatic mutations of these genes [12,14]. KRAS mutations are observed in 40-50% of patients, and ERBB2 (human epidermal growth factor receptor 2, HER2) gene amplification has been observed in 20-30% of invasive mEOCs [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Affatato

Carrassa

Chilà

et al. 2020

Cancers

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Mucinous epithelial ovarian cancer (mEOC) is a rare subset of epithelial ovarian cancer. When diagnosed at a late stage, its prognosis is very poor, as it is quite chemo-resistant. To find new therapeutic options for mEOC, we performed high-throughput screening using a siRNA library directed against human protein kinases in a mEOC cell line, and polo-like kinase1 (PLK1) was identified as the kinase whose downregulation interfered with cell proliferation. Both PLK1 siRNA and two specific PLK1 inhibitors (onvansertib and volasertib) were able to inhibit cell growth, induce apoptosis and block cells in the G2/M phase of the cell cycle. We evaluated, in vitro, the combinations of PLK1 inhibitors and different chemotherapeutic drugs currently used in the treatment of mEOC, and we observed a synergistic effect of PLK1 inhibitors and antimitotic drugs. When translated into an in vivo xenograft model, the combination of onvansertib and paclitaxel resulted in stronger tumor regressions and in a longer mice survival than the single treatments. These effects were associated with a higher induction of mitotic block and induction of apoptosis, similarly to what was observed in vitro. These data suggest that the combination onvansertib/paclitaxel could represent a new active therapeutic option in mEOC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Affatato

Carrassa

Chilà

et al. 2020

Cancers

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“…Since mucinous OC shares several common pathological and molecular features with gastrointestinal tumours, it has long been hypothesized that standard gastrointestinal treatments could be more effective for this histotype than the current standard-of-care. In all the phase I/II cohorts of platinum-refractory OC patients treated with some of these approaches (e. g., capecitabine, oxaliplatin, FOLFOX, gemcitabine + oxaliplatin), only a very small number of mucinous OC patients were included, meaning it was difficult to draw clear conclusions [13].…”

Section: Influences On Platinum Sensitivity and Mechanisms Of Platinumentioning

confidence: 99%

Resistance to chemotherapy and anti-angiogenic therapy in ovarian cancer

Wieser

Marth

2019

memo

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Ovarian cancer (OC) is the foremost lethal gynaecologic malignancy and among the top five deadliest cancers in women. Current treatment comprises a combination therapy of surgery, platinumbased chemotherapy and anti-vascular endothelial growth factor (VEGF) antibodies. However, patients typically experience a disease relapse within two years. Recurrent OC is incurable and resistance to platins and anti-VEGF treatment is a major determinant of prognosis. Understanding the molecular mechanisms that contribute to tumour metastasis and chemoresistance are essential to improve patient outcome and especially survival. In a current OC model, tumour metastasis and chemoresistance critically depend on the biology of cancer stem cells (CSCs). Recent studies also suggest that intratumour heterogeneity is the main cause of treatment failure due to chemoresistance. Furthermore, the proinflammatory tumour microenvironment seems to contribute to metastasis and chemoresistance. Despite an improved understanding of the complex interplay between classical mechanisms of drug inactivation or efflux, clonal selection and the tumour microenvironment, mechanisms of resistance in human OC are poorly understood. This review summarises current concepts in the treatment of OC, mechanisms of resistance to chemotherapy and angiogenic inhibitors and approaches to overcome drug resistance.

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“…Sebuah studi melaporkan bahwa stadium III/IV dari karsinoma ovarium subtipe musinosa memiliki prognosis yang lebih buruk, dimana median OS untuk subtipe musinosa adalah 14,6 bulan, sedangkan untuk subtipe serosa adalah 47,7 bulan. 13 Studi lain melaporkan nilai rentang median OS pada subtipe serosa dan subtipe clear cell dengan atau tanpa subtipe musinosa masingmasing adalah 18,2 -29,3 bulan dan 6 -14,2 bulan. 14 Karsinoma ovarium subtipe musinosa juga dilaporkan memiliki tingkat respon terhadap terapi berbasis platinum jauh lebih rendah daripada subtipe serosa.…”

Section: Pendahuluanunclassified

“…Begitu pula dengan penelitian yang dilakukan Marth et al 1 yang menunjukkan tidak terdapat perbedaan kadar IFN-γ yang sebesar 63%. 13 Sebuah konsensus general dari berbagai studi retrospektif mengungkapkan bahwa pada stadium lanjut (stadium III/IV), subtipe clear cell juga membawa prognosis yang buruk dengan ketidakpekaan terhadap kemoterapi berbasis platinum dibandingkan subtipe serosa dan lainnya. 15 Diantara pasien dengan stadium III/IV yang mendapatkan kemoterapi berbasis paclitaxel dan platinum, subtipe clear cell memiliki 5-year survival yang lebih rendah secara signifikan dibandingkan subtipe serosa (p=0,011).…”

Section: Pendahuluanunclassified

Perbedaan Kadar Interferon Gamma Cairan Asites Pada Subtipe Histopatologi Serosa dan Non-Serosa Kanker Ovarium Tipe Epitel

Kurniasari¹,

Fahmi²,

Anggorowati³

2019

Jurnal Kespro

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Background: Ovarian carcinoma serous subtype has a better prognosis than non-serous. Interferon gamma (IFN-γ) has a role in prognostic of ovarian carcinoma. IFN-γ may have both pro-tumor and anti-tumor activity. There is lack of evidence in determining IFN-γ level in ascites and its relationship with serous and non-serous.Objective: To determine the difference of IFN-γ level in ascites in serous and non-serous subtype of ovarian carcinoma. Methods:The study design was a cross-sectional. Ascites was taken intraoperatively from 11 samples of serous and 7 non-serous ovarian carcinoma patients underwent staging or debulking surgeries from September -December 2018. Ascites were evaluated using ELISA. Result:The mean of serous ascites IFN-γ level was lower (0.46±0.35 pg/ml (mean±SD)) than non-serous (0.97±0.88 pg/ml (mean±SD)), but there is no statistically significant (p = 0.104). Conclusion:There is no significant difference of IFN-γ level in ascites on serous and non-serous subtypes of ovarian carcinoma. ABSTRAKLatar Belakang: Karsinoma ovarium dapat dibedakan menjadi subtipe serosa dan non-serosa, dimana subtipe serosa memiliki prognosis yang lebih baik. IFN-γ dapat memiliki aktivitas pro-tumor maupun anti-tumor. Penelitian tentang kadar IFN-γ asites serta hubungannya dengan subtipe serosa dan non-serosa belum banyak dilakukan.Tujuan: Mengetahui perbedaan rata-rata kadar IFN-γ cairan asites pada subtipe serosa dan non-serosa karsinoma ovarium. Metode:Penelitian cross sectional selama periode September -Desember 2018. Pengambilan sampel asites dilakukan di kamar operasi RSUP Dr. Sardjito dan pengujian sitokin menggunakan Human IFN-γ ELISA Kit dilakukan di Laboratorium Biologi Molekuler FKKMK Universitas Gadjah Mada.Hasil dan Pembahasan: Pada 11 sampel subtipe serosa didapatkan rata-rata kadar IFN-γ sebesar 0,46 pg/ml, sedangkan pada 7 sampel non-serosa didapatkan rata-rata 0,97 pg/ml, namun perbedaan rata-rata tersebut tidak signifikan secara statistik (p=0,104). Simpulan: Tidak terdapat perbedaan rata-rata kadar IFN-γ dalam cairan asites pada subtipe serosa dan non-serosa karsinoma ovarium.Kata Kunci: interferon gamma (IFN-γ), karsinoma ovarium, asites, subtipe histopatologi ARTIKEL PENELITIAN

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Recent Insights into Mucinous Ovarian Carcinoma

Cited by 54 publications

References 68 publications

Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Identification of PLK1 as a New Therapeutic Target in Mucinous Ovarian Carcinoma

Resistance to chemotherapy and anti-angiogenic therapy in ovarian cancer

Perbedaan Kadar Interferon Gamma Cairan Asites Pada Subtipe Histopatologi Serosa dan Non-Serosa Kanker Ovarium Tipe Epitel

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