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Article ; Online: Developing Oncolytic Viruses for the Treatment of Cervical Cancer.

Kalafati, Eleni / Drakopoulou, Ekati / Anagnou, Nicholas P / Pappa, Kalliopi I

2023 Volume 12, Issue 14

Abstract: Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for ... ...

Abstract	Cervical cancer represents one of the most important malignancies among women worldwide. Current therapeutic approaches for cervical cancer are reported not only to be inadequate for metastatic cervical cancer, but are also considered as cytotoxic for several patients leading to serious side effects, which can have negative implications on the quality of life of women. Therefore, there is an urgent need for the development of innovative and effective treatment options. Oncolytic viruses can eventually become effective biological agents, since they preferentially infect and kill cancer cells, while leaving the normal tissue unaffected. Moreover, they are also able to leverage the host immune system response to limit tumor growth. This review aims to systematically describe and discuss the different types of oncolytic viruses generated for targeting cervical cancer cells, as well as the outcome of the combination of virotherapy with conventional therapies. Although many preclinical studies have evaluated the therapeutic efficacy of oncolytic viruses in cervical cancer, the number of clinical trials so far is limited, while their oncolytic properties are currently being tested in clinical trials for the treatment of other malignancies.
MeSH term(s)	Humans ; Female ; Oncolytic Viruses/physiology ; Uterine Cervical Neoplasms/therapy ; Oncolytic Virotherapy ; Quality of Life ; Immunotherapy
Language	English
Publishing date	2023-07-13
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12141838
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Article: Gene Therapy for Malignant and Benign Gynaecological Disorders: A Systematic Review of an Emerging Success Story.

Drakopoulou, Ekati / Anagnou, Nicholas P / Pappa, Kalliopi I

Cancers

2022 Volume 14, Issue 13

Abstract: Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular ... ...

Abstract	Despite the major advances in screening and therapeutic approaches, gynaecological malignancies still present as a leading cause of death among women of reproductive age. Cervical cancer, although largely preventable through vaccination and regular screening, remains the fourth most common and most lethal cancer type in women, while the available treatment schemes still pose a fertility threat. Ovarian cancer is associated with high morbidity rates, primarily due to lack of symptoms and high relapse rates following treatment, whereas endometrial cancer, although usually curable by surgery, it still represents a therapeutic problem. On the other hand, benign abnormalities, such as fibroids, endometriosis, placental, and embryo implantation disorders, although not life-threatening, significantly affect women's life and fertility and have high socio-economic impacts. In the last decade, targeted gene therapy approaches toward both malignant and benign gynaecological abnormalities have led to promising results, setting the ground for successful clinical trials. The above therapeutic strategies employ both viral and non-viral systems for mutation compensation, suicide gene therapy, oncolytic virotherapy, antiangiogenesis and immunopotentiation. This review discusses all the major advances in gene therapy of gynaecological disorders and highlights the novel and potentially therapeutic perspectives associated with such an approach.
Language	English
Publishing date	2022-06-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14133238
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Article ; Online: Metabolic rewiring is associated with HPV-specific profiles in cervical cancer cell lines.

Pappa, Kalliopi I / Daskalakis, George / Anagnou, Nicholas P

Scientific reports

2021 Volume 11, Issue 1, Page(s) 17718

Abstract: Both HPV-positive and HPV-negative cervical cancers are associated with aberrant metabolism, although the oncogenic drivers remain elusive. Here we show the assessment of the metabolomic profiles of four distinct cervical cell lines, a normal and three ... ...

Abstract	Both HPV-positive and HPV-negative cervical cancers are associated with aberrant metabolism, although the oncogenic drivers remain elusive. Here we show the assessment of the metabolomic profiles of four distinct cervical cell lines, a normal and three cancer cell lines, one HPV-negative (C33A) and two HPV-positive (SiHa HPV16+, HeLa HPV18+), employing an ultra performance liquid chromatography and a high resolution mass spectrometry. Out of the total 462 metabolites, 248 to 326 exhibited statistically significant differences, while Random Forests analysis identified unique molecules for each cell line. The two HPV+ cell lines exhibited features of Warburg metabolism, consistent with the role of the HPV E6 protein. SiHa and HeLa cells displayed purine salvage pathway activity, while C33A cells revealed synthesis of cytidine, via a novel mechanism. These data document a highly dynamic HPV-specific rewiring of metabolic pathways occurring in cervical cancer. Therefore, this approach can eventually provide novel mechanistic insights into cervical carcinogenesis.
MeSH term(s)	Cell Line, Tumor ; Cervix Uteri/metabolism ; Cervix Uteri/pathology ; Cervix Uteri/virology ; Female ; HeLa Cells ; Humans ; Niacin/metabolism ; Nucleic Acids/metabolism ; Papillomavirus Infections/metabolism ; Papillomavirus Infections/pathology ; Papillomavirus Infections/virology ; Proteomics ; Uterine Cervical Neoplasms/metabolism ; Uterine Cervical Neoplasms/pathology ; Uterine Cervical Neoplasms/virology
Chemical Substances	Nucleic Acids ; Niacin (2679MF687A)
Language	English
Publishing date	2021-09-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-96038-8
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Article ; Online: Mimiviruses: Giant viruses with novel and intriguing features (Review).

Kalafati, Eleni / Papanikolaou, Eleni / Marinos, Evangelos / Anagnou, Nicholas P / Pappa, Kalliopi I

Molecular medicine reports

2022 Volume 25, Issue 6

Abstract: The Mimivirus is a giant virus that infects amoebae and was long considered to be a bacterium due to its size. The viral particles are composed of a protein capsid of ~500 nm in diameter, which is enclosed in a polysaccharide layer in which ~120‑140 nm ... ...

Abstract	The Mimivirus is a giant virus that infects amoebae and was long considered to be a bacterium due to its size. The viral particles are composed of a protein capsid of ~500 nm in diameter, which is enclosed in a polysaccharide layer in which ~120‑140 nm long fibers are embedded, resulting in an overall diameter of 700 nm. The virus has a genome size of 1.2 Mb DNA, and surprisingly, replicates only in the cytoplasm of the infected cells without entering the nucleus, which is a unique characteristic among DNA viruses. Their existence is undeniable; however, as with any novel discovery, there is still uncertainty concerning their pathogenicity mechanisms in humans and the nature of the Mimivirus virophage resistance element system (MIMIVIRE), a term given to describe the immune network of the Mimivirus, which closely resembles the CRISPR‑Cas system. The scope of the present review is to discuss the recent developments derived from structural and functional studies performed on the distinctive characteristics of the Mimivirus, and from studies concerning their putative clinical relevance in humans.
MeSH term(s)	Amoeba ; CRISPR-Cas Systems ; Capsid ; Giant Viruses/genetics ; Humans ; Mimiviridae/genetics
Language	English
Publishing date	2022-05-04
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	2469505-1
ISSN	1791-3004 ; 1791-2997
ISSN (online)	1791-3004
ISSN	1791-2997
DOI	10.3892/mmr.2022.12723
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Article ; Online: The Optimized γ-Globin Lentiviral Vector GGHI-mB-3D Leads to Nearly Therapeutic HbF Levels In Vitro in CD34

Drakopoulou, Ekati / Georgomanoli, Maria / Lederer, Carsten W / Panetsos, Fottes / Kleanthous, Marina / Voskaridou, Ersi / Valakos, Dimitrios / Papanikolaou, Eleni / Anagnou, Nicholas P

Viruses

2022 Volume 14, Issue 12

Abstract: We have previously demonstrated that both the original γ-globin lentiviral vector (LV) GGHI and the optimized GGHI-mB-3D LV, carrying the novel regulatory elements of the 3D HPFH-1 enhancer and the 3' β-globin UTR, can significantly increase HbF ... ...

Abstract	We have previously demonstrated that both the original γ-globin lentiviral vector (LV) GGHI and the optimized GGHI-mB-3D LV, carrying the novel regulatory elements of the 3D HPFH-1 enhancer and the 3' β-globin UTR, can significantly increase HbF production in thalassemic CD34
MeSH term(s)	Humans ; gamma-Globins/genetics ; Genetic Therapy ; Fetal Hemoglobin/genetics ; Genetic Vectors/genetics ; Lentivirus/genetics ; beta-Thalassemia/genetics ; beta-Thalassemia/therapy ; Anemia, Sickle Cell/genetics ; Anemia, Sickle Cell/therapy
Chemical Substances	gamma-Globins ; Fetal Hemoglobin (9034-63-3)
Language	English
Publishing date	2022-12-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14122716
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Article ; Online: p16/Ki-67 Dual Staining Is a Reliable Biomarker for Risk Stratification for Patients With Borderline/Mild Cytology in Cervical Cancer Screening.

Magkana, Maria / Mentzelopoulou, Panagiota / Magkana, Ekaterini / Pampanos, Andreas / Vrachnis, Nikolaos / Kalafati, Eleni / Daskalakis, Georgios / Domali, Ekaterini / Thomakos, Nikolaos / Rodolakis, Alexandros / Anagnou, Nicholas P / Pappa, Kalliopi I

Anticancer research

2022 Volume 42, Issue 5, Page(s) 2599–2606

Abstract: Background/aim: To evaluate p16/Ki-67 dual-staining performance for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the management of women with minor cervical abnormalities.: Patients and methods: All 759 enrolled ... ...

Abstract	Background/aim: To evaluate p16/Ki-67 dual-staining performance for detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in the management of women with minor cervical abnormalities. Patients and methods: All 759 enrolled patients were tested for cytology, high-risk human papillomavirus (HR-HPV) and dual p16/Ki-67 staining. Results: Positivity rates for HR-HPV and dual staining increased as dysplasia was worsened from non-CIN (37.6% and 0%) to CIN1 (62.5% and 1.6%) and CIN2+ (98.7% and 97.3%), respectively. HPV18 and HPV16 exhibited the highest odds ratios (53.16 and 11.31) in the CIN2+ group. Both p16/Ki-67 dual staining and HR-HPV presented similar sensitivities (97.3% and 98.7%, respectively) for CIN2+ detection. Dual staining specificity, however, was 99.3%, significantly higher compared to HR-HPV testing (52.2%). The utility of dual staining was evaluated in different screening strategies and appeared to reduce the number of colposcopies required for the detection of CIN2+ cases. Conclusion: p16/Ki-67 dual-staining cytology is a surrogate triage biomarker in cytology-based screening programs, with high performance for efficient risk stratification of women with mild cervical abnormalities.
MeSH term(s)	Cervical Intraepithelial Neoplasia/diagnosis ; Cyclin-Dependent Kinase Inhibitor p16 ; Early Detection of Cancer ; Female ; Humans ; Ki-67 Antigen ; Papillomavirus Infections/diagnosis ; Risk Assessment ; Staining and Labeling ; Uterine Cervical Neoplasms/diagnosis
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p16 ; Ki-67 Antigen
Language	English
Publishing date	2022-04-27
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.15738
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Article ; Online: Novel structural approaches concerning HPV proteins: Insight into targeted therapies for cervical cancer (Review).

Pappa, Kalliopi I / Kontostathi, Georgia / Lygirou, Vasiliki / Zoidakis, Jerome / Anagnou, Nicholas P

Oncology reports

2018 Volume 39, Issue 4, Page(s) 1547–1554

Abstract: Cervical cancer incidence is tightly linked to HPV infection, and particularly virus types 16 and 18 cause the majority of cases presenting with pre-cancerous stages of cervical intraepithelial neoplasia (CIN). Structural and functional information ... ...

Abstract	Cervical cancer incidence is tightly linked to HPV infection, and particularly virus types 16 and 18 cause the majority of cases presenting with pre-cancerous stages of cervical intraepithelial neoplasia (CIN). Structural and functional information concerning HPV proteins can offer novel insight into the mechanism(s) of cancer progression in the cervical epithelium. Recently, novel structural determinants of the interactions of viral proteins with their targets in keratinocytes have been elucidated. These exciting findings open the way for the development of targeted anti-oncogenic therapies, and may eventually allow the introduction of novel approaches for a rational cervical cancer treatment.
MeSH term(s)	Epithelium/pathology ; Epithelium/virology ; Female ; Host-Pathogen Interactions/genetics ; Human papillomavirus 16/chemistry ; Human papillomavirus 16/genetics ; Human papillomavirus 16/pathogenicity ; Human papillomavirus 18/chemistry ; Human papillomavirus 18/genetics ; Human papillomavirus 18/pathogenicity ; Humans ; Keratinocytes/chemistry ; Keratinocytes/virology ; Precancerous Conditions/genetics ; Precancerous Conditions/pathology ; Precancerous Conditions/virology ; Structure-Activity Relationship ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/pathology ; Uterine Cervical Neoplasms/virology ; Viral Proteins/chemistry ; Viral Proteins/genetics
Chemical Substances	Viral Proteins
Language	English
Publishing date	2018-02-09
Publishing country	Greece
Document type	Journal Article ; Review
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2018.6257
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Article ; Online: Major challenges for gene therapy of thalassemia and sickle cell disease.

Papanikolaou, Eleni / Anagnou, Nicholas P

Current gene therapy

2010 Volume 10, Issue 5, Page(s) 404–412

Abstract: Gene therapy utilizing retroviral vectors is being postulated as a real therapeutic alternative for many hemopoietic inherited diseases, such as β-thalassemia or sickle cell disease. A major limitation of current vectors is their inability to achieve ... ...

Abstract	Gene therapy utilizing retroviral vectors is being postulated as a real therapeutic alternative for many hemopoietic inherited diseases, such as β-thalassemia or sickle cell disease. A major limitation of current vectors is their inability to achieve efficient gene transfer into quiescent cells, such as human CD34+ cells that reside in the Go phase of the cell cycle and are highly enriched in hemopoietic stem cells. For that reason, lentiviral vectors (LVs) were proven to be more efficient than oncoretroviral vectors. Additional problems of these vectors are a) the low titers observed due to regulatory elements of the β-globin locus, used for the improvement of the transgene's expression b) the eventual silencing of the transgene and c) the toxicity posed on CD34+ cells due to the usage of VSV-G as an envelope protein. These facts hamper their application for gene therapy of hematopoietic cells. Thus, the major current drawbacks of the field affecting therapeutic efficacy, include 1) insufficient transduction efficiency of the target hemopoietic stem cells, 2) inconsistent expression of the transgene, 3) putative aberrant expression near integration sites raising safety issues and 4) lack of long term expression of the transgene exhibiting eventual silencing. This review presents the current status of globin gene therapy for the hemoglobin disorders, reviews the recent results and discusses how the knowledge gained from these trials can be used to develop a safe and effective gene therapy approach for the treatment of β-thalassemia and SCD.
MeSH term(s)	Anemia, Sickle Cell/genetics ; Anemia, Sickle Cell/therapy ; Genetic Therapy/methods ; Genetic Therapy/trends ; Genetic Vectors ; Humans ; Thalassemia/genetics ; Thalassemia/therapy
Language	English
Publishing date	2010-08-09
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2146187-9
ISSN	1875-5631 ; 1566-5232
ISSN (online)	1875-5631
ISSN	1566-5232
DOI	10.2174/156652310793180724
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Zs.A 5883: Show issues

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Article ; Online: The Q192R polymorphism of the paraoxonase-1 (PON1) gene is associated with susceptibility to gestational diabetes mellitus in the Greek population.

Pappa, Kalliopi I / Gazouli, Maria / Anastasiou, Eleni / Loutradis, Dimitrios / Anagnou, Nicholas P

Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology

2017 Volume 33, Issue 8, Page(s) 617–620

Abstract: A key factor protecting from oxidative stress in gestational diabetes mellitus (GDM) and in type 2 diabetes (T2D) is paraoxonase-1 (PON1). Inconclusive and limited data exist regarding the effect of a coding polymorphism (Q192R) of the PON1 gene in ... ...

Abstract	A key factor protecting from oxidative stress in gestational diabetes mellitus (GDM) and in type 2 diabetes (T2D) is paraoxonase-1 (PON1). Inconclusive and limited data exist regarding the effect of a coding polymorphism (Q192R) of the PON1 gene in conferring susceptibility to both states. In the present study, we investigated the association between the PON1 gene and the risk for GDM in the Greek population and assessed for the first time its transcriptional efficiency. We studied 185 women with GDM and 104 non-diabetic controls for the PON1 polymorphism. For PON1 mRNA expression, peripheral leucocytes were harvested from 20 GDM and 20 control women, harboring different genotypes for the polymorphism, using real-time quantitative PCR. The RR genotype and the R allele of the PON1 Q192R polymorphism were significantly associated with an increased risk for GDM (p = 0.012 and p < 0.0001, respectively). Furthermore, there was no statistical correlation between the individual metabolic parameters tested and the three genotypes. Finally, the expression levels of PON1 mRNA in GDM patients did not exhibit any statistical difference compared with normal controls (p = 0.138). These data independently document that the Q192R polymorphism is closely associated with GDM susceptibility, while the PON1 gene expression is not impaired in GDM.
Language	English
Publishing date	2017-08
Publishing country	England
Document type	Journal Article
ZDB-ID	639237-4
ISSN	1473-0766 ; 0951-3590
ISSN (online)	1473-0766
ISSN	0951-3590
DOI	10.1080/09513590.2017.1302419
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Zs.A 2284: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 608: Show issues

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Article ; Online: High resolution analysis of the intracellular proteome of cervical cancer cell lines unveils novel regulators of cervical carcinogenesis.

Pappa, Kalliopi I / Lygirou, Vasiliki / Kontostathi, Georgia / Makridakis, Manousos / Vougas, Konstantinos / Sfakianakis, Antonios / Daskalakis, George / Zoidakis, Jerome / Anagnou, Nicholas P

Oncology reports

2019 Volume 42, Issue 4, Page(s) 1441–1450

Abstract: Cervical cancer remains the fourth most common and most lethal type of cancer in women, despite the applied regular screening and prevention strategies, while the available treatment schemes still pose a threat to fertility. Substantial understanding of ... ...

Abstract	Cervical cancer remains the fourth most common and most lethal type of cancer in women, despite the applied regular screening and prevention strategies, while the available treatment schemes still pose a threat to fertility. Substantial understanding of the underlying mechanisms and development of novel diagnostic, prognostic and therapeutic approaches are critical steps for improving cervical cancer management. Towards this goal, a comparative proteomic analysis was conducted between three cervical cancer cell lines (HeLa: HPV18+, SiHa: HPV16+, C33A: HPV‑) and normal cervical keratinocytes (HCK1T). The total cell extract of each cell line was analyzed by liquid chromatography coupled to tandem mass spectrometry (LC‑MS/MS). Differential expression analysis revealed 919, 826 and 1,370 deregulated proteins in the comparisons of HeLa, SiHa and C33A with HCK1T cell lines, respectively. Pathway enrichment analysis of the differentially expressed proteins highlighted common cancer characteristics such as high metabolic demands and increased cell turnover, confirming the validity of the proteomic results. Extensive literature mining of the consistently differentially expressed proteins that resulted from the three comparisons was performed leading to a shortlist of 21 proteins that are potentially involved in cervical malignancy. The criteria for this shortlisting were the association of the proteins with various types of cancer, while there is no study as yet associating their expression to cervical cancer. Moreover, the expression trend of two of the shortlisted proteins was validated using western blot analysis. The proteomic datasets generated in this study can be utilized to enrich the current knowledge on cervical cancer pathology and unveil key molecular mechanisms of carcinogenesis. In conclusion, the shortlist of consistently deregulated proteins between cervical cancer cell lines and normal cervical keratinocytes can be used for validation in clinical samples and in functional investigation experiments that could ultimately lead to the discovery of novel disease biomarkers and drug targets.
Language	English
Publishing date	2019-08-08
Publishing country	Greece
Document type	Journal Article
ZDB-ID	1222484-4
ISSN	1791-2431 ; 1021-335X
ISSN (online)	1791-2431
ISSN	1021-335X
DOI	10.3892/or.2019.7269
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