scholarly journals Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients

2020 ◽  
Author(s):  
yu zhan ◽  
xueyuan wu ◽  
gang zheng ◽  
jingjing jin ◽  
chaofu li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Curative Surgery ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
Prognostic Assessment ◽  
Therapy Strategies ◽  
Proline Rich Protein

Abstract Background: The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. Methods: Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. Results: In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1).Conclusions: The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.

scholarly journals Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients

2020 ◽  
Author(s):  
yu zhan ◽  
xueyuan wu ◽  
gang zheng ◽  
jingjing jin ◽  
chaofu li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Curative Surgery ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
Prognostic Assessment ◽  
Therapy Strategies ◽  
Proline Rich Protein

Abstract Background: The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. Methods: Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. Results: In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1).Conclusions: The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.

scholarly journals Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Yu Zhan ◽  
Xueyuan Wu ◽  
Gang Zheng ◽  
Jingjing Jin ◽  
Chaofu Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Curative Surgery ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
Prognostic Assessment ◽  
Therapy Strategies ◽  
Proline Rich Protein

Abstract Background The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. Methods Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. Results In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, the survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1). Conclusions The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.

scholarly journals Proline-rich Protein 11 Overexpression is Associated With a More Aggressive Phenotype and Poor Overall Survival in Ovarian Cancer Patients

2020 ◽  
Author(s):  
yu zhan ◽  
xueyuan wu ◽  
gang zheng ◽  
jingjing jin ◽  
chaofu li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Protein Expression ◽  
Strong Association ◽  
Curative Surgery ◽  
Poor Overall Survival ◽  
Over Expression ◽  
Proline Rich Protein

Abstract Background: The proline-rich protein 11 (PRR11) is a newly identified oncogene that exerts a strong association with a poor prognosis in various kinds of human cancers, yet its role in ovarian cancer (OC) remains unknown. Thus, the study aims to evaluate the level of PRR11 protein expression and its function in human ovarian cancer.Methods: In the present study, we used immunohistochemistry analysis to evaluate the levels of PRR11 protein expression in human specimens from 49 OC patients who underwent curative surgery in the First Affiliated Hospital of Wenzhou Medical University2007 to 2015.Results: In our analysis, 57.1% of the primary OC tumor tissue evaluated, presented over expression of PRR11. Meanwhile, survival analysis showed that the overall survival (OS) of patients presenting PRR11 over expression was significantly lower than the OS of the PRR11 negative patient group. Furthermore, in subsequent experiments we found that silencing PRR11 expression inhibited tumor cell proliferation and cell migration in vitro. In addition, cells subjected to PRR11 knockdown exhibited a decrease in tumor grow in vivo. The down regulation of PRR11 was acompanied by a decrease in N-cadherin and early growth response protein 1 (EGR1) expression.Conclusions: our results suggest that PRR11 may be considered as a potential target for prognosis assessment and gene therapy modalities for patients with OC.

scholarly journals HGG-15. THE IMIPRIDONE ONC201 IN COMBINATION WITH THE ONCOLYTIC ADENOVIRUS DELTA-24-RGD HAS A SYNERGISTIC EFFECT IN PRECLINICAL MODELS OF PHGGS AND DMGS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i20-i20
Author(s):  
Daniel de la Nava ◽  
Iker Ausejo-Mauleon ◽  
Virginia Laspidea ◽  
Lucía Marrodán ◽  
Marta Zalacain ◽  
...  
Keyword(s):  
Overall Survival ◽  
Negative Impact ◽  
Pediatric Brain Tumors ◽  
Therapeutic Benefit ◽  
In Vitro Cytotoxicity ◽  
Preclinical Models ◽  
Poor Overall Survival ◽  
Significant Negative Impact

Abstract Pediatric High Grade Gliomas (pHGGs), including Diffuse Midline Gliomas (DMGs), are aggressive pediatric tumors with a poor overall survival. In the last years, ONC201 has emerged as a promising agent in the field of pediatric brain tumors. Another interesting approach is virotherapy; Delta-24-RGD, which is an oncolytic virus, has demonstrated safety and effectiveness in different preclinical models and in clinical trials. Therefore, in this work we set to evaluate whether the combination of ONC201 with Delta-24-RGD could result in an increased therapeutic benefit in pHGGs and DMGs. Given that ONC201 targets mitochondrial metabolism in a preclinical setting, we assessed potential negative interactions of the combination therapy. While ONC201 treatment resulted in decreased viral protein load (E1A and fiber), there was no significant negative impact on the viral replication (measured by hexon staining). ONC201 did not disrupt the activation of mTORC1 pathway by the adenovirus. Furthermore, Delta-24-RGD did not affect the decrease in basal oxygen consumption rate induced by ONC201. Our results suggested that ONC201 and Delta-24-RGD are not antagonistic. Evaluation of the in vitro cytotoxicity in different human pHGG (CHLA-03-AA and SF188) and DMG (TP-54 and SU-DIPG-IV) cell lines showed that the combination treatment was significantly better that either agent alone. In vivo, a single local injection of Delta-24-RGD followed by a weekly ONC201 of mice bearing CHLA-03-AA cell line orthotopically significantly increased the median overall survival (PBS: 48 days; ONC201: 54.5 days; Delta-24-RGD: 62 days; ONC201+Delta-24-RGD: 95 days (P=0.0008)) of these mice leading to 20% long-term survivors, free of disease. Currently, we are evaluating the effect of the combination in immunosuppressed and immunocompetent models of DMGs. In summary, our data indicate ONC201 in combination with Delta-24-RGD could be a potential therapeutic choice for patients affected by pHGGs and DMGs.

scholarly journals SMPDL3B Predicts Poor Prognosis and Contributes to Development of Acute Myeloid Leukemia

2021 ◽  
Vol 8 ◽  
Author(s):  
Huiqing Qu ◽  
Ye Zhu
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Human Cancer ◽  
Negative Regulator ◽  
Poor Overall Survival ◽  
Clinicopathologic Characteristics ◽  
Acute Myeloid

Background: Acute myeloid leukemia (AML), characterized by the low cure rate and high relapse, urgently needs novel diagnostic or prognostic biomarkers and potential therapeutic targets. Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) is a negative regulator of Toll-like receptor signaling that plays important roles in the interface of membrane biology and innate immunity. However, the potential role of SMPDL3B in human cancer, especially in AML, is still unknown.Methods: The expression of SMPDL3B in AML samples was investigated through data collected from Gene Expression Omnibus (GEO). Association between SMPDL3B expression and clinicopathologic characteristics was analyzed with the chi-square test. Survival curves were calculated by the Kaplan–Meier method. Cox univariate and multivariate analyses were used to detect risk factors for overall survival. The biological functions of SMPDL3B in human AML were investigated both in vitro and in vivo.Results: Expression of SMPDL3B mRNA was significantly upregulated in human AML samples and closely correlated to cytogenetics risk and karyotypes. Elevated expression of SMPDL3B was associated with poor overall survival and emerged as an independent predictor for poor overall survival in human AML. Blocked SMPDL3B expression inhibited AML cells growth both in vitro and in vivo via promoting cell apoptosis.Conclusion: Taken together, our results demonstrate that SMPDL3B could be used as an efficient prognostic biomarker and represent a potential therapeutic target for human AML.

scholarly journals Evaluation of circulating microRNAs as non-invasive biomarkers in the diagnosis of ovarian cancer: a case–control study

2021 ◽  
Author(s):  
Kai Berner ◽  
Marc Hirschfeld ◽  
Daniela Weiß ◽  
Gerta Rücker ◽  
Jasmin Asberger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Microrna Expression ◽  
Urine Samples ◽  
Malignant Diseases ◽  
Liquid Biopsies ◽  
Expression Levels

Abstract Purpose Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide and over 150,000 women die from it every year. More than 70 percent of all ovarian cancer patients are diagnosed at a late-stage disease with poor prognosis necessitating the development of sufficient screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo. Methods Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a, miR-15a, miR-15b, miR-19b, miR-20a, miR-21, miR-100, miR-125b, miR-155, miR-222) were quantified performing quantitative real-time-PCR. Therefore, the three ovarian cancer cell lines SK-OV-3, OAW-42, EFO-27 as well as urine samples of ovarian cancer patients and healthy controls were analyzed. Results MiR-15a, miR-20a and miR-222 showed expression level alterations extracellularly, whereas miR-125b did intracellularly across the analyzed cell lines. MicroRNA expression alterations in single cell lines suggest subtype specificity in both compartments. Hypoxia and acidosis showed scarce effects on single miRNA expression levels only. Furthermore, we were able to demonstrate the feasibility to clearly detect the 12 miRNAs in urine samples. In urine, miR-15a was upregulated whereas let-7a was down-regulated in ovarian cancer patients. Conclusion Intracellular, extracellular and urinary microRNA expression alterations emphasize their great potential as biomarkers in liquid biopsies. Especially, miR-15a and let-7a qualify for possible circulating biomarkers in liquid biopsies of ovarian cancer patients.

scholarly journals Evaluation of Circulating microRNAs as Non-Invasive Biomarkers in the Diagnosis of Ovarian Cancer – A Case-Control Study

2020 ◽  
Author(s):  
Kai Berner ◽  
Marc Hirschfeld ◽  
Daniela Weiß ◽  
Gerta Rücker ◽  
Jasmin Asberger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Microrna Expression ◽  
Urine Samples ◽  
Malignant Diseases ◽  
Liquid Biopsies ◽  
Expression Levels

Abstract Background Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide and over 150.000 women die from it every year. More than 70 percent of all ovarian cancer patients are diagnosed at a late stage disease with poor prognosis necessitating the development of sufficient screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo.Methods Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a, miR-15a, miR-15b, miR-19b, miR-20a, miR-21, miR-100, miR-125b, miR-155, miR-222) were quantified performing quantitative real-time-PCR. Therefore, the three ovarian cancer cell lines SK-OV-3, OAW-42, EFO-27 as well as urine samples of ovarian cancer patients and healthy controls were analyzed.Results MiR-15a, miR-20a and miR-222 showed expression level alterations extracellularly, whereas miR-125b did intracellularly across the analyzed cell lines. MicroRNA expression alterations in single cell lines suggest subtype specificity in both compartments. Hypoxia and acidosis showed scarce effects on single miRNA expression levels only. Furthermore, we were able to demonstrate the feasibility to clearly detect the 12 miRNAs in urine samples. In urine, miR-15a was upregulated whereas let-7a was down-regulated in ovarian cancer patients.Conclusion Intracellular, extracellular and urinary micoRNA expression alterations emphasize their great potential as biomarkers in liquid biopsies. Especially miR-15a and let-7a qualify for possible circulating biomarkers in liquid biopsies of ovarian cancer patients.

scholarly journals BMP signaling is a therapeutic target in ovarian cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Tomohiko Fukuda ◽  
Risa Fukuda ◽  
Ryo Tanabe ◽  
Daizo Koinuma ◽  
Hiroo Koyama ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Kinase Inhibitors ◽  
Bmp Signaling ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Bmp Receptor ◽  
Tcga Dataset ◽  
Sphere Formation

AbstractBMP signaling has been found to have tumor-promoting as well as tumor-suppressing effects in different types of tumors. In this study, we investigated the effects of BMP signaling and of BMP inhibitors on ovarian cancer (OC) cells in vitro and in vivo. High expression of BMP receptor 2 (BMPR2) correlated with poor overall survival of OC patients in the TCGA dataset. Both BMP2 and BMPR2 enhanced OC cell proliferation, whereas BMP receptor kinase inhibitors inhibited OC cell growth in cell culture as well as in a mouse model. BMP2 also augmented sphere formation, migration, and invasion of OC cells, and induced EMT. High BMP2 expression was observed after chemotherapy of OC patients in the GSE109934 dataset. In accordance, carboplatin, used for the treatment of OC patients, increased BMP2 secretion from OC cells, and induced EMT partially via activation of BMP signaling. Our data suggest that BMP signaling has tumor-promoting effects in OC, and that BMP inhibitors might be useful therapeutic agents for OC patients. Considering that carboplatin treatment augmented BMP2 secretion, the possibility to use a combination of BMP inhibitors and carboplatin in the treatment of OC patients, would be worth exploring.

Common genes and pathways associated with in vitro/in vivo ovarian cancer chemo-response and overall survival

2013 ◽  
Vol 130 (1) ◽  
pp. e122
Author(s):  
N. Bou Zgheib ◽  
D. Marchion ◽  
P. Judson Lancaster ◽  
R. Wenham ◽  
S. Apte ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival

Translational Theragnosis of Ovarian Cancer: where do we stand?

2020 ◽  
Vol 27 (34) ◽  
pp. 5675-5715 ◽  
Author(s):  
Maria Grazia Perrone ◽  
Oreste Luisi ◽  
Anna De Grassi ◽  
Savina Ferorelli ◽  
Gennaro Cormio ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Imaging Techniques ◽  
Progression Free Survival ◽  
New Drugs ◽  
Specific Gene ◽  
Cancer Knowledge ◽  
Tumor Types

Background:: Ovarian cancer is the second most common gynecologic malignancy, accounting for approximately 220,000 deaths annually worldwide. Despite radical surgery and initial high response rates to platinum- and taxane-based chemotherapy, most patients experience a relapse, with a median progression-free survival of only 18 months. Overall survival is approximately 30% at 5 years from the diagnosis. In comparison, patients out from breast cancer are more than 80 % after ten years from the disease discovery. In spite of a large number of published fundamental and applied research, and clinical trials, novel therapies are urgently needed to improve outcomes of the ovarian cancer. The success of new drugs development in ovarian cancer will strongly depend on both fully genomic disease characterization and, then, availability of biomarkers able to identify women likely to benefit from a given new therapy. Methods:: In this review, the focus is given to describe how complex is the diseases under the simple name of ovarian cancer, in terms of cell tumor types, histotypes, subtypes, and specific gene mutation or differently expressed in the tumor with respect the healthy ovary. The first- and second-line pharmacological treatment clinically used over the last fifty years are also described. Noteworthy achievements in vitro and in vivo tested new drugs are also summarized. Recent literature related to up to date ovarian cancer knowledge, its detection by biomarkers and chemotherapy was searched from several articles on Pubmed, Google Scholar, MEDLINE and various Governmental Agencies till April 2019. Results:: The papers referenced by this review allow a deep analysis of status of the art in the classification of the several types of ovarian cancer, the present knowledge of diagnosis based on biomarkers and imaging techniques, and the therapies developed over the past five decades. Conclusion:: This review aims at stimulating more multi-disciplinary efforts to identify a panel of novel and more specific biomarkers to be used to screen patients for a very early diagnosis, to have prognosis and therapy efficacy indications. The desired final goal would be to have available tools allowing to reduce the recurrence rate, increase both the disease progression free interval and of course the overall survival at five years from the diagnosis that today is still very low.

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