Browsing by Subject "Ovarian cancer"

Now showing 1 - 17 of 17
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    AADAC promotes therapeutic activity of cisplatin and imatinib against ovarian cancer cells
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Wang, Haijing; Wang, Disong; Gu, Tingting; Zhu, Mengjiao; Cheng, Ling; Da, Wentao
    Objective. To explore how AADAC functions in the malignant progression of ovarian cancer, and the effect of AADAC on drug therapeutic activity against ovarian cancer cells. Methods. AADAC level in tumor and normal samples from TCGA-OV dataset and its survival significance were analyzed by bioinformatics methods. Signaling pathway enrichment analysis for the high- and low-AADAC patients was achieved by using GSEA software. AADAC expression in the cell lines with different treatments was evaluated via qRT-PCR. Cell proliferative ability was assessed via MTT assay Cell migratory and invasive abilities were evaluated via transwell assay. Angiogenesis assay was performed to examine the angiogenetic ability. Results. AADAC was upregulated in ovarian cancer tissues, and patients with high expression of AADAC had favorable survival conditions compared to the low AADAC expression ones. Overexpression of AADAC inhibited the malignant progression of ovarian cancer cells. Both cisplatin and imatinib suppressed cancer cell malignant progression, while overexpressed AADAC synergistically enhanced such inhibition. Conclusions. The study demonstrated that AADAC could somehow suppress the malignant progression of ovarian cancer, especially at the cellular level. In addition, synergic tumor-inhibitory effects between AADAC and the anti-cancer drugs were identified. All the above results proposed a novel idea and candidate biomarker for ovarian cancer therapy.
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    Cisplatin induced apoptosis of ovarian cancer A2780s cells by activation of ERK/p53/PUMA signals
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Song, Hao; Wei, Mei; Liu, Wenfen; Shen, Shulin; Li, Jiaqun; Wang, Liming
    Cisplatin (CDDP) is one of the most effective anticancer agents widely used in the treatment of solid tumors, including ovarian cancer. It is generally considered as a cytotoxic drug which kills cancer cells by causing DNA damage, and subsequently inducing apoptosis in cancer cells. However, the underlying mechanisms leading to cell apoptosis remain obscure. In this study, the signaling pathways involved in CDDPinduced apoptosis were examined using CDDP-sensitive ovarian cancer A2780s cells. A2780s cells were treated with CDDP (1.5-3 μg/ml) for 6h, 12h and 24h. Using siRNA targeting P53 and PUMA, and a selective MEK inhibitor, PD98059 to examine the relation between ERK1/2 activation, p53 and PUMA expression after exposure to CDDP, and the effect on CDDP-induced apoptosis. The results shown that treatment of A2780s cells with CDDP (3 μg/ml) for 6-24h induced apoptosis, resulting in the activation of extracellular signalregulated kinase 1/2 (ERK1/2) and accumulation of p53 and PUMA (p53 upregulated modulator of apoptosis) protein. Knockdown of P53 or PUMA by siRNA transfection blocked CDDP-induced apoptosis. Inhibition of ERK1/2 using PD98059, a selective MEK inhibitor, blocked the apoptotic cell death but prevented CDDP-induced accumulation of p53 and PUMA. Knockdown of P53 by siRNA transfection also blocked CDDP-induced accumulation of PUMA. We therefore concluded that CDDP activated ERK1/2 and inducedp53-dependent PUMA upregulation, resulting in triggering apoptosis in A2780s cells. Our study clearly demonstrates that the ERK1/2/p53/PUMA axis is related to CDDP-induced cell death in A2780s cells.
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    Claudins as diagnostic and prognostic markers in gynecological cancer
    (Murcia : F. Hernández, 2009) Szabó, István; Kiss, András; Schaff, Zsuzsa; Sobel, Gábor
    Claudins are the main protein components of tight junctions (TJs) which function as selective barriers by controlling paracellular diffusion, maintain cellular polarity and play a role in signal transduction. The expression pattern of the 24 known members of the claudin family proved to be organ and tissue specific. The up- or downregulation of individual claudins has been described, especially during carcinogenesis. A significant increase of claudins-1 and -7 was detected in premalignant cervical lesions and invasive cancer compared with normal cervical epithelia. Claudins-3 and -4 were elevated in endometrial cancer. Claudin-1 overexpression characterized type II (seropapillary) endometrial carcinoma, while claudin-2 was elevated in type I (endometrioid) carcinoma. Claudins-3 and -4 were highly expressed in serous ovarian carcinoma. The expression data on claudins in different premalignant and malignant alterations suggest that these proteins might serve as diagnostic and prognostic markers and might be targets for future therapy.
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    Clinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors
    (Murcia : F. Hernández, 2006) Zagorianakou, N.; Stefanou, D.; Makrydimas, G.; Zagorianakou, P.; Briasoulis, E.; Karavasilis, V.; Pavlidis, N.; Agnantis, N.J.
    Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which are expressed in normal cells during fetal and postnatal life but also in a variety of human neoplasms. MT expression in human tumors has been linked to resistance to anticancer drugs and differentiation and progression in some types of tumors. This study examined the immunohistochemical expression of MTs in benign, borderline and malignant tumors of ovarian surface epithelium and the possible correlations with clinicopathological parameters and survival. A total of 87 cases with diagnosis of ovarian surface epithelial tumors were included. Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14 borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off level >10% of tumor cells) was clearly associated with malignancy. A statistically significant correlation was found between the expression of MT in cancer cases and benign tumors (p<0.0001) and cancer cases and borderline tumors p= 0.003. In cancer cases a difference was observed between grade I and III (p=0.002). There was no correlation of MT overexpression with survival in the small number of ovarian carcinoma patients where it was analysed. MT constitutes a marker that characterizes aggressiveness and a high malignant potential in ovarian epithelial tumors. In diagnostic problems MT may help distinguish between benign, borderline and malignant tumors.
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    Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor
    (Murcia : F. Hernández, 2008) Surowiak, Pawel; Materna, Verena; Maciejczyk, Adam; Pudelko, Marek; Suchocki, Slawomir; Kedzia, Witold; Nowak-Markwitz, Ewa; Dumanska, Malgorzata; Spaczynski, Marek; Zabel, M.; Dietel, Manfred; Lage, Hermann
    Decreased expression of p16 may result from hypermethylation of the promoter or from deletion of the gene. It can lead to intensified proliferation of neoplastic cells and to cytostatic drug resistance. The study was aimed at the examination of prognostic value of p16 expression in relation to Ki67 and caspase-3 in ovarian cancers using immunohistochemistry. The immunohistochemical studies were performed on 73 paraffinembedded samples of ovarian cancers from 43 patients and samples from 6 healthy ovaries. We have used monoclonal antibodies against p16. ABC method and DAB were used for antigens visualisation. The intensity of the immunohistochemical reactions was appraised using the semi-quantitative IRS scale. In healthy ovaries we have shown strong reaction in the nuclei of surface epithelium. In the case of studied ovarian cancers, the reaction of a nuclear and cytoplasmic localization was obtained. The mean overall immunoreactivity score of nuclear p16 expression amounted to 5.30±3.44 SD in primary laparotomy material and 6.61±4.34 SD in secondary cytoreduction material. Statistical analysis demonstrated that lower p16 expression was typical of the younger patients and the patients who died. Kaplan- Meier’s analysis proved that lower expression of p16 was characteristic of cases with shorter overall survival. In the present study we have demonstrated that lowered p16 expression represented an unfavourable prognostic index in ovarian cancer. Lowered p16 expression was also typical for chemotherapy-resistant ceases (cases of lower caspase-3 and higher Ki67 at secondary cytoreduction expression).
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    La endometriosis atípica como lesión precursora del cáncer de ovario asociado a endometriosis un estudio prospectivo
    (Universidad de Murcia, 2018-11-22) Ñíguez Sevilla, Isabel; Sánchez Ferrer, María Luisa; Machado Linde, Francisco; Nieto Díaz, Aníbal; Escuela Internacional de Doctorado
    En la presente tesis hemos estudiado la probable transformación maligna de la endometriosis en cáncer de ovario asociado a endometriosis (COAE). Nuestra hipótesis de trabajo se basa en el potencial papel que juega la "endometriosis atípica" en la patogénesis del COAE, fundamentalmente en los histotipos, adenocarcinoma de células claras (AcCC) y el adenocarcinoma endometrioide (AcE). Exploramos la posibilidad de que represente una etapa evolutiva entre la endometriosis "típica" y el COAE. Además, nos planteamos si la atipia celular (EAC) y la hiperplasia o atipia arquitectural (EAA), los dos hallazgos histológicos globalmente referidos como endometriosis atípica (EA), tienen un significado diferente en la etiopatogenia del COAE. OBJETIVOS Objetivo Principal: Establecer la Prevalencia de EA y de sus subtipos histológicos: EAC y EAA en las pacientes con Endometriosis y COAE. Objetivos secundarios: Objetivo 1.- Establecer las diferencias en la prevalencia de los subtipos histológicos AcCC y AcE en las pacientes con COAE vs CO. Objetivo 2.- Comparar las características clínico-epidemiológicas y Factores de riesgo y pronósticos de los grupos de estudio: pacientes con diagnóstico postquirúrgico de Endometriosis, COAE y CO. MATERIAL Y MÉTODO: Estudio observacional prospectivo de serie de casos desde Enero 2014 hasta Abril de 2017 en pacientes asistidas en el Servicio de Ginecología y Obstetricia del Hospital Clínico Universitario Virgen de la Arrixaca, con el diagnóstico de endometriosis y/o cáncer de ovario sometidas a cirugía. Se realizó un análisis anatomopatológico e inmunohistoquímico de las piezas quirúrgicas de los diferentes grupos (EN, CO y COAE). RESULTADOS: Se incluyeron 266 pacientes. Se confirmó endometriosis en 185 pacientes, de las cuales, 159 casos tenían endometriosis aislada y 26 presentaban COAE. Del total de los 107 cánceres de ovario registrados (COT), 26 (24,3%) eran COAE y 81 (75,7%) cáncer de ovario sin endometriosis asociada (CO). El 53,1% de los CO el tipo histológico fue el seroso frente al 15,4% observado en los COAE. Así mismo, el 23,1% de los COAE fueron AcCC y el 42,3% eran AcE, versus el 6,2% y 14,8% respectivamente de los encontrados en CO (p<0,001). De las 185 pacientes con endometriosis, había 23 casos (12,43%) con características de EA. Estos 23 casos se distribuyen en 11 con EAC y 12 con EAA. Además 10 de los 11 casos de EAC se observan en endometriosis no asociada a CO mientras, que 8 de los 12 casos de EAA se objetivan en los COAE (p=0,009). De los estudios inmunohistoquímicos encontramos asociación (p=0,004) entre Ki-67 alto con EAA. No hayamos diferencias significativas ni para COX-2 ni BAF250a. En cuanto a la diferencias entre los tipos histológicos, se relacionan los carcinomas serosos con el grupo de CO, y los AcCC y AcE con COAE (p<0,001). En los estadios tumorales vimos asociación del estadio I con COAE (76,9% vs 44,45% en CO) (p<0,001). CONCLUSIONES: 1. Existe una asociación significativa entre Endometriosis Atípica y Cáncer de Ovario Asociado a Endometriosis. 
 2. Los tipos histológicos de Cáncer de Ovario asociados de forma significativa a Endometriosis fueron el Adenocarcinoma de Células Claras y el Adenocarcinoma Endometrioide, ambos incluidos en el tipo I del modelo de Kurman y Shild. 
 3. Nuestros datos sugieren que el Cáncer de Ovario Asociado a Endometriosis podría presentar un mejor pronóstico dentro del Cáncer de Ovario. 
 4. Existe una asociación significativa entre Endometriosis Atípica Arquitectural y Cáncer de Ovario Asociado a Endometriosis. 
 5. Nuestros datos apoyan la hipótesis de que la Endometriosis Atípica Arquitectural o Hiperplásica podría constituir una lesión precursora en la patogénesis del Cáncer de Ovario Asociado a Endometriosis. 

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    MiR-5195-3p functions as a tumor suppressor by targeting RHBDD1 in ovarian cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Wang, Zhanyu; Zhang, Xiaoping; Liu, Yongying; Shi, Xiaoyan; Li, Lijun; Jia, Yun; Wu, Fangfang; Cui, Haosen; Li, Liang
    Background. Recent studies have reported the tumor suppressive role of miR-5195-3p in the progression of several cancers, but the potential roles of miR-5195-3p in ovarian cancer (OC) remain largely unknown. Methods. We first analyzed the expression levels of miR-5195-3p in 83 pairs of human OC tissues and adjacent specimens by reverse transcription-quantitative PCR. The correlation of miR-5195-3p/rhomboid domain containing 1 (RHBDD1) and clinicopathological parameters was analyzed by chi-square test. The prognostic value of miR-5195-3p was evaluated by Kaplan-Meier method Cox proportional hazards models. The effects of miR-5195-3p on cell proliferation, cell cycle distribution, migration and invasion were examined by CCK-8 assay, colony formation assay, flow cytometry and transwell assay. Tumor forming was evaluated by nude mice model in vivo. The association between miR-5195-3p and RHBDD1 was verified by luciferase reporter assay. Results. We observed that miR-5195-3p level was remarkably reduced in OC tissues as compared to adjacent tissues. The expression of miR-5195-3p was associated with FIGO stage, depth of invasion and poor survival prognosis in OC patients. Overexpression of miR-5195-3p significantly suppressed cell proliferation, cell cycle G1/S transition, migration and invasion in OC cell lines (SKOV-3 and OVCAR3), while knockdown of miR-5195-3p obtained the opposite results. We further confirmed miR-5195-3p as a negative posttranscriptional modulator of RHBDD1. RHBDD1 expression was upregulated in OC tissues compared with adjacent tissues, which was inversely correlated with miR-5195-3p expression. The expression of RHBDD1 was associated with FIGO stage and distant metastasis. RHBDD1 overexpression reversed the suppressive role of miR-5195-3p on OC cell proliferation, migration and invasion. Consistent with the in vitro results, miR-51953p overexpression decreased the growth of subcutaneously inoculated tumors in nude mice. Conclusions. Taken together, the present results indicated that miR-5195-3p acts a tumor suppressor by targeting RHBDD1 in OC.
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    Ovarian cancer: insights into genetics and pathogeny
    (F. Hernandez y JuanF. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología., 2012) Liliac, Ludmila; Amălinei, Cornelia; Balan, Raluca; Grigoraş, Adriana; Căruntu, Irina-Draga
    Starting from the information on ovarian cancer provided by the mainstream publications, we construct a review focusing on the following issues: (i) the genetic profile, (ii) the role of the epithelial-mesenchymal transition in the acquirement of malignant features, (iii) the controversial hypothesis regarding the origin, and (iv) the involvement of the immune system in the tumoral microenvironment. Advances in the decipherment at the genetic level in the pathogenic mechanisms progressively lead to the idea of a genetic signature for the ovarian cancer. Moreover, the complementary approaches oriented towards the decryption of the intrinsic structure of the expressed molecules and, implicitly, the development of proteomics open new perspectives for an early diagnosis and an appropriate treatment. The research on the epithelial-mesenchymal transition (mainly those exploring the signaling pathways responsible for the switch between the loss of the epithelial characteristics and the gain of a mesenchymal cell phenotype, with results in the amplification of differentiation, motility and tumoral invasion) allow a deeper understanding of the complex pathogenic mechanism which governs ovarian carcinogenesis. The classic conception of ovarian cancer pathogeny, based on the role of the ovarian surface epithelium, is currently reconsidered, and a novel hypothesis is formulated, which supports direct involvement of the Fallopian tubes for the serous type. Although recent research suggests the implication of immune/inflammatory cells by specific mechanisms in ovarian cancer pathogenesis, there is yet reliable evidence concerning their modality of direct action and/or modulation of tumoral growth. Thus, ovarian carcinogenesis remains a research challenge, due to still numerous unknown factors involved in the malignant transformation sequences, originating from the genetic-molecular alterations and reflected by cellular and tissue expression patterns.
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    p27Kip1 and cytoplasmic pSer10p27 are promising biomarkers for predicting prognosis and chemotherapy response in ovarian cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Zhu, Mengna; Sun, Si; Huang, Lin; Gao, Lingling; Chen, Mengqing; Cai, Jing; Wang, Zehua; Peng, Minggang
    The biological function of p27Kip1 largely depends on its subcellular localization and phosphorylation status. Different subcellular localizations and phosphorylation statuses of p27Kip1 may represent distinct clinical values, which are unclear in ovarian cancer. This study aimed to elucidate different subcellular localizations of p27Kip1 and pSer10p27 in predicting prognosis and chemotherapy response in ovarian cancer. Methods. Meta-analyses were executed to evaluate the association of p27Kip1 and phosphorylated p27Kip1 with the prognosis of ovarian cancer patients. The expression levels and patterns of p27Kip1 and pSer10p27 were evaluated by immunohistochemistry. The correlations between different p27Kip1 states, clinicopathological features, and prognosis were analyzed. p27Kip1 and pSer10p27 expression levels in cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines were detected using WB. KEGG analysis and WB were performed to evaluate the pathways in which p27Kip1 was involved. Results Meta-analyses showed that p27Kip1 was associated with significantly better overall survival (OS) in ovarian cancer (HR=2.14; 95% CI [1.71 - 2.68]) and pSer10p27 was associated with significantly poor OS in mixed solid tumors (HR=2.56; 95% CI [1.76 - 3.73]). In our cohort of ovarian cancer patients, low total p27Kip1 remained independent risk factors of OS (HR=2.097; 95% CI [1.121 - 3.922], P=0.021) and PFS (HR=2.483; 95% CI [1.364 - 4.518], P=0.003), while low cytoplasmic pSer10p27 had independent protective effects in terms of OS (HR=0.472; 95% CI [0.248 - 0.898], P=0.022) and PFS (HR=0.488; 95% CI [0.261 - 0.910], P=0.024). Patients with low total p27Kip1/ pSer10p27 and low nuclear p27Kip1 had worse chemotherapy responses, while patients with low cytoplasmic pSer10p27 expression had better chemotherapy responses. The protein levels of p27Kip1 and pSer10p27 were significantly reduced in the cisplatin-resistant cell lines SKOV3-cDDP and A2780-cDDP, and the level of p27Kip1/pSer10p27 was subjective to Akt activation. Conclusions The present study demonstrates that p27Kip1 and cytoplasmic pSer10p27 are promising biomarkers for predicting prognosis and chemotherapy response in ovarian cancer.
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    Principales complicaciones asociadas a la administración de quimioterapia intraperitoneal y endovenosa en pacientes con cáncer de ovario
    (Universidad de Murcia, 2017) Palmés Ferrera, Mercedes; Andersson Vila, Cassandra Ixena; Barrera Reyes, María del Carmen; García Gigán, María del Carmen; Graells Piqué, María Alba; Gómez Rodríguez, Esther
    Antecedentes: El cáncer de ovario causa más muertes que cualquier otro tipo de cáncer ginecológico. La mayoría de casos se diagnostican en una etapa avanzada de la enfermedad y el tratamiento de elección es generalmente la terapia combinada de quimioterapia intraperitoneal (IP) y endovenosa (EV). A pesar de que esta opción farmacológica ha demostrado alargar la supervivencia, se han reportado múltiples efectos adversos asociados a dicho tratamiento. Objetivo: Identificar los efectos adversos y las complicaciones derivadas del tratamiento con quimioterapia IP+EV en pacientes con carcinoma de ovario avanzado a partir de estadio IIIC, durante el periodo 2007-2015. Metodología: Se realizó un estudio descriptivo, longitudinal y retrospectivo. Un grupo de 17 mujeres diagnosticadas con cáncer de ovario a partir de estadio III fueron tratadas con quimioterapia IP+EV en el Hospital Clínic de Barcelona durante el periodo 2007-2015. Resultados: De las 17 pacientes que recibieron tratamiento con quimioterapia IP+EV, sólo 5 (29,41%) finalizaron los 6 ciclos de tratamiento. De forma notable, 12 (70,58%) pacientes no completaron el tratamiento debido a una serie de complicaciones, que fueron frecuentemente asociadas al reservorio IP y a trastornos psicológicos. Los principales efectos adversos reportados fueron astenia, neurotoxicidad y dolor abdominal. Conclusiones: La mayoría de pacientes interrumpieron la terapia debido a complicaciones relacionadas con el reservorio IP y trastornos psicológicos. Creemos que la enfermera juega un papel importante, no sólo en el manejo de los aspectos técnicos de la terapia, sino también en el soporte emocional a dichas pacientes durante esta etapa
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    Prognostic significance of tumour vascularisation on survival of patients with advanced ovarian carcinoma
    (Murcia : F. Hernández, 2009) Labiche, Alexandre; Elie, Nicolas; Herlin, Paulette; Denoux, Yves; Crouet, Hubert; Heutte, Natacha; Joly, Florence; Héron, Jean-François; Gauduchon, Pascal; Henry-Amar, Michel
    Objective. The prognostic significance of microvessel density in ovarian cancer is still a matter of debate. Classically, the degree of vascularisation is assessed in areas of high vascular density (hot spots), considered as regions of increased probability of metastasis. Since ovarian tumours have a particular progression and dissemination behaviour, vascularisation outside hot spots may also contribute to their evolution. Methods. In the present study, the degree of tumour vascularisation was estimated both in whole histogical sections and in hot spots, in 235 patients with ovarian carcinoma, using fully automatic image analysis methods. Six parameters were estimated: mean microvessel density (MVD) and mean microvessel surface fraction (MSP) on the whole section, mean and maximum values of MVD and MSP inside hot spots (MVDHS1, MSPHS1 and MVDHS2, MSPHS2). Relationships between vascular parameters and clinicopathologic features were analysed. Results. In stage III-IV patients multivariate analysis showed that stage IV disease (hazards ratio (HR)=1.72, p=0.001), post-surgical residual disease 1cm (HR=2.86, p<0.001), upper MVD tercile (HR=1.45, p<0.022) and medial MVDHS1 tercile (HR=1.36, p=0.060) retained an independent prognostic value upon overall survival. Conclusion. Our results suggest that quantification of blood vessels, both on the whole histological section and in hot spots might be helpful in evaluating prognosis in advanced ovarian carcinomas.
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    Rosmarinic acid inhibits the proliferation of ovarian carcinoma cells by activating the p53/BAX signaling pathway
    (Universidad de Murcia, Histología e Histopatología, 2025) Özdemır İlhan; Doğan Baş Dilek; Öztürk Şamil; Karaosmanoğlu Özge; Cudi Tuncer Mehmet; Biología Celular e Histología
    Objective. While chemotherapeutic agents stop the development of cancer cells, they also kill healthy cells. This study aimed to increase anticancer effects and reduce side effects by combining a phytotherapeutic compound with a chemotherapeutic drug. Methods. This study examined the effects of nine concentrations of rosmarinic acid (RA) and doxorubicin (DOX) on human ovarian adenocarcinoma (OVCAR3) and skin keratinocyte (HaCaT) cell lines. Their cytotoxic effects were assessed based on cell viability, evaluated using the MTT assay, and apoptotic activity, evaluated using NucBlue staining and the gene and protein expression of tumor protein p53 (TP53) and BCL2 associated X, apoptosis regulator (BAX) quantified by qRT-PCR and western blots, respectively. Results. The half-maximal inhibitory concentration after 48 hours was 880.4 μM for RA and 2.26 μM for DOX. The cytotoxicity analysis revealed that cell viability decreased with the RA concentration. RA increased apoptosis in OVCAR3 cells by activating the p53/BAX pathway. Western blots showed that RA and DOX upregulated p53 and BAX protein levels in OVCAR3 cells. Conclusions. The RA and DOX combination inhibited cell proliferation by inducing apoptosis in OVCAR3 cells. These results suggest that RA may reduce the side effects of DOX toxicit
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    Staining of MUC1 in ovarian cancer tissues with PankoMab-GEX™ detecting the tumour-associated epitope, TA-MUC1, as compared to antibodies HMFG-1 and 115D8
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2013) Dian, Darius; Lenhard, Miriam; Mayr, Doris; Heublein, Sabine; Karsten, Uwe; Goletz, Steffen; Kuhn, Christina; Wiest, Irmi; Friese, Klaus; Weissenbacher, Tobias; Jeschke, Udo
    y. PankoMab-GEX™ is a novel humanized and glycooptimized antibody, which recognizes a novel specific tumour epitope of MUC1 (TA-MUC1). The aim of this study was to evaluate PankoMab-GEX™ binding to a variety of ovarian cancer specimens (n=156) and to normal ovarian tissue. In addition, PankoMab-GEX™ staining was compared to that of the well-known antiMUC1 antibodies HMFG-1 and 115D8. PankoMabGEX™ showed positive reactivity in serous (100% of cases, mean IRS 8.23), endometrioid (95% of cases, mean IRS 6.40), mucinous (58% of cases, mean IRS 4.17), and clear cell (92% of cases, mean IRS 7.58) carcinomas. In contrast to HMFG-1, healthy ovarian tissue was not recognized by PankoMab-GEX™. Staining with antibody 115D8 was increased with staging. Cytoplasmic PankoMab-GEX™ staining increased with tumour grade, but no correlation was found with staging. Univariate Kaplan-Meier analysis revealed a tendency of reduced survival of patients with high expression of TA-MUC1. The findings are encouraging with respect to a potential use of PankoMab-GEX™ as a new therapeutic antibody for the treatment of ovarian cancer patients.
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    Topoisomerase 1A, HER,2neu and Ki67 expression in paired primary and relapse ovarian cancer tissue samples
    (Murcia : F. Hernández, 2006) Surowiak, P.; Materna, V.; Kaplenko, I.; Spaczynski, M.; Dietel, Manfred; Lage, H.; Zabel, M.
    In the present study we examined prognostic value of immunohistochemical estimation of topoisomerase 1A (TOP 1A) and HER-2/neu expression in ovarian cancers treated with platinum-based drugs but not with topotecan and the relation between expression of these proteins on the one hand and intensity of proliferation (Ki67) on the other. The analyses were performed on 73 samples of ovarian carcinoma originating from 43 first-look laparotomies (FLL) and, in 30 cases, from secondary cytoreductions (SCR)(after chemotherapy) from the same patients. In paraffin sections immunohistochemical reactions were performed using antibodies directed to HER-2/neu, TOP 1A and Ki67. Kaplan-Meier’s analysis disclosed a shorter overall survival time in cases with augmented expression of TOP 1A at FLL and with higher expression of Ki67 at SCR. A shorter progression-free time was detected in cases with higher proportion of Ki67 positive cells at FLL. No relationship could be disclosed between HER- 2/neu expression and the studied clinicopathological parameters. The studies confirmed high value of Ki67 estimation. The augmented expression of TOP 1A was demonstrated to represent an unfavourable prognostic factor. Thus, in cases with elevated expression of TOP 1A application of topotecan-based therapeutic schemes should be considered.
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    TRIB1 facilitates the proliferation and migration of ovarian cancer cells by inducing EMT progression
    (Universidad de Murcia, Departamento de Histología e Histopatología, 2025) Shi Guangyan; Holgersson Kristian; Xin Zhen; Szekely Laszlo; Du Qiqiao; Jing Xu; Biología Celular e Histología
    Aim. Ovarian cancer (OC) is a fatal female malignant tumor that severely impacts the health of women worldwide. Due to the lack of diagnostic biomarkers, 70% of OC patients are considered in the advanced stage at the first diagnosis. Exploring novel biomarkers for OC diagnosis has become an urgent clinical need to address. TRIB1 is a newly discovered oncogene in several malignant tumors, including acute myeloid leukemia, prostate cancer, and breast cancer. However, the biological function of TRIB1 in OC remains uncertain and, therefore, was explored in the present study. Methods. Levels of TRIB1 in OC and normal tissues were evaluated in the GEPIA database. TRIB1-KD was constructed in ES-2 cells and TRIB1-OE was constructed in OVCAR3 cells using a siRNA and OE vector, respectively. The proliferation ability was determined using the CCK-8 and clone formation assays. The migration ability was detected using the wound healing and Transwell assays. The expression of epithelial-mesenchymal transition (EMT) biomarkers was determined using western blotting. Results. TRIB1 was markedly upregulated in OC tissues compared with normal ovarian tissues in the GEPIA database. The TRIB1 level was slightly altered among ES-2, CAOV3, and SKOV3 cells, with the highest expression in ES-2 cells, which was greatly reduced in OVCAR3 cells. In TRIB1-KD ES-2 cells, a remarkably reduced proliferation ability was observed with the CCK-8 and clone formation assays, accompanied by a reduction in migration distance in the Wound healing assay and the number of migrated cells in the Transwell assay. In contrast, in TRIB1-OE OVCAR3 cells, increased proliferation ability was observed, accompanied by increased migration distance and number of migrated cells. Furthermore, EMT progression was markedly repressed in TRIB1-KD ES-2 cells and remarkably enhanced in TRIB1-OE OVCAR3 cells. Conclusion. TRIB1 facilitated the proliferation and migration of OC cells by enhancing EMT progression
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    Tumor heterogeneity has important consequences for personalized medicine in ovarian cancer
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Gui, Ting; Cao, Dongyan; Yang, Jiaxin; Shen, Keng
    Most patients with ovarian cancers relapse, and treatment failure has often been attributed to chemoresistance in tumor cells. Emerging evidence indicates that tumor heterogeneity may play an equally important role. Although the idea of tumor heterogeneity is not new, little attention has been focused on applying it to understand and control ovarian cancer progression. Recent advances in understanding its generation model, original basis, consequent problems, and derived therapies provide great potential for tumor heterogeneity to be a new insight in treatment of ovarian cancers.
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    Up-regulation of oxidized low-density lipoprotein receptor 1 correlates with decreased miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465, higher recurrence rate, and poor prognosis in ovarian cancer J. Liu, Y. Zeng and L. Zheng
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2023) Liu, Jun; Zeng, Ya; Zheng, Lang
    . Background. MicroRNAs (miRNAs) are widely involved in cell metabolism, and their abnormal expression is involved in the regulation of ovarian cancer development, metastasis, and recurrence. The current study aimed to explore the potential mechanism and prognostic value of miRNAs related to the targeted regulation of oxidized low-density lipoprotein receptor 1 (OLR1) expression in ovarian cancer. Methods. A prospective study was conducted including 132 ovarian cancer patients. Patients were followed up for 36 months. The dual-luciferase reporter gene detection was used to verify the targeting relationship between miRNA and OLR1. Cell Counting Kit-8 assay, flow cytometric analysis, transwell migration, and invasion assays were performed to address the malignant biological behaviors of ovarian cancer cells. Results. OLR1 protein and gene expression levels were significantly higher in ovarian cancer tissues and cell lines than in adjacent tissues and normal ovarian epithelial cells. OLR1 depletion facilitated apoptosis and impeded cell proliferation, migration, and invasion in ovarian cancer. Predictive software and dual-luciferase reporter assays showed that miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465 targeted OLR1 expression. Functionally, the introduction of miR106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, and miR-4465 mimics abrogated the aggressive phenotype in ovarian cancer cells. Lastly, compared with adjacent tissues, the levels of miR-106b-5p, miR-93-5p, miR3129-5p, miR-199b-3p, and miR-4465 in cancer tissues were significantly lower (P<0.001). Compared with high miR-106b-5p, high miR-93-5p, high miR-3129-5p, high miR-199b-3p, high miR-4465 group and low OLR1 group, the low miR-106b-5p, low miR-93-5p, low miR3129-5p, low miR-199b-3p, low miR-4465 group and high OLR1 group have significantly higher recurrence (all P<0.05) and higher mortality (all P<0.05). The identification value of recurrence assessment model [Y = 4.267+0.336*(miR-106b-5p)+0.168*(miR-93- 5p)+1.847*(miR-3129-5p)+2.119*(miR-199b3p)+0.872*(miR-4465)-3.408*(OLR1)] was high with an AUC of 0.918. The prognosis assessment model [Y = 3.914+0.143*(miR-106b-5p)+0.102*(miR-93- 5p)+0.115*(miR-3129-5p)+1.369*(miR-199b3p)+0.186*(miR-4465)-0.334*(OLR1)] also had high identification value with an AUC of 0.934. Conclusion. The combined detection of miR-106b-5p, miR-93-5p, miR-3129-5p, miR-199b-3p, miR-4465, and OLR1 is expected to become a molecular biomarker for the long-term prognostic assessment of ovarian cancer.