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1
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Cao C, Sun X, Chen X, Zhang Y, Yue C. Mendelian randomization analysis reveals genetic evidence for a causal link between inflammatory bowel disease and uterine cervical neoplasms. Front Genet 2025; 15:1436512. [PMID: 39935692 PMCID: PMC11810950 DOI: 10.3389/fgene.2024.1436512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 12/11/2024] [Indexed: 02/13/2025] Open
Abstract
Background Inflammatory bowel disease (IBD) has been reported to be associated with risk of uterine cervical neoplasm. We aimed to evaluate the causal relationship between IBD and uterine cervical neoplasm using a bidirectional Mendelian randomization analysis. Methods We derived instrumental variables for IBD, including Crohn's disease and ulcerative colitis, from the IEU Open genome-wide association study (GWAS) database, and for the histological subtypes of uterine cervical neoplasm from the FinnGen repository's GWAS data. The collected GWAS data predominantly represent individuals of European ancestry. The inverse-variance weighted (IVW) method was employed as primary analysis approach. Results IBD (IVW odds ratio = 1.127, 95% confidence interval = 1.016-1.251; p = 0.024) and CD (IVW odds ratio = 1.119, 95% confidence interval = 1.023-1.224; p = 0.014) exhibited a significant causal effect on malignant cervical carcinoma. Sensitivity analyses confirmed these findings. Conclusion Genetically predicted IBD and CD are risk factors for the development of malignant cervical carcinoma. Patients with IBD and CD require specific attention to prevent cervical squamous cell carcinoma. Further studies to elucidate the underlying mechanisms may reveal new therapeutic targets.
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Affiliation(s)
- Chunge Cao
- Department of Obstetrics and Gynecology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
| | | | - Xiaohu Chen
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Ying Zhang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Chaoyan Yue
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
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2
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Ghiani L, Chiocca S. The oncogenic role of the NSD histone methyltransferases in head and neck and cervical cancers. Tumour Virus Res 2024; 19:200301. [PMID: 39645166 DOI: 10.1016/j.tvr.2024.200301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/04/2024] [Accepted: 12/05/2024] [Indexed: 12/09/2024] Open
Abstract
Understanding the role of NSD proteins in virus-induced cancers could reveal new therapeutic strategies. Targeting NSD proteins may not only disrupt the epigenetic changes triggered by viruses but also help restore normal cellular function. For instance, developing NSD inhibitors could counteract abnormal histone modifications caused by viral infections and slow cancer progression. Our review on the NSD protein family emphasizes its critical role in epigenetic regulation and cancer progression, also in virus-induced cancers. As research on the molecular mechanisms of NSD proteins advances, these proteins are emerging as promising candidates for targeted cancer therapies, particularly in cancers driven by histone modifications and transcriptional dysregulation.
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Affiliation(s)
- Lavinia Ghiani
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy
| | - Susanna Chiocca
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Via Adamello 16, 20139 Milan, Italy.
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3
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Branda F, Pavia G, Ciccozzi A, Quirino A, Marascio N, Gigliotti S, Matera G, Romano C, Locci C, Azzena I, Pascale N, Sanna D, Casu M, Ceccarelli G, Ciccozzi M, Scarpa F. Human Papillomavirus (HPV) Vaccination: Progress, Challenges, and Future Directions in Global Immunization Strategies. Vaccines (Basel) 2024; 12:1293. [PMID: 39591195 PMCID: PMC11598998 DOI: 10.3390/vaccines12111293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/16/2024] [Accepted: 11/18/2024] [Indexed: 11/28/2024] Open
Abstract
Human papillomavirus (HPV) is a widespread viral pathogen, responsible for a significant burden of cervical and other cancers worldwide. Over the past decades, the development and widespread adoption of prophylactic HPV vaccines have dramatically reduced the incidence of HPV-related diseases. However, despite the efficacy of these vaccines, global immunization efforts still face several obstacles, including low vaccination coverage in low- and middle-income countries, vaccine hesitancy, and disparities in access to healthcare. This review aims to provide a comprehensive overview of the current state of HPV vaccines, including their mechanisms of action, safety profiles, and real-world efficacy. We will explore the impact of HPV vaccines on cancer prevention, examine the challenges related to vaccine distribution and uptake, and assess the role of public health policies in improving global vaccination rates. Additionally, the review will highlight the latest advancements in therapeutic HPV vaccines, ongoing research into next-generation vaccines, and the potential of HPV vaccination strategies in the context of personalized medicine. By examining these factors, we aim to provide insights into the future directions of HPV vaccination and its role in global public health.
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Affiliation(s)
- Francesco Branda
- Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (C.R.); (M.C.)
| | - Grazia Pavia
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro-“Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (G.P.); (A.Q.); (N.M.); (S.G.); (G.M.)
| | - Alessandra Ciccozzi
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.)
| | - Angela Quirino
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro-“Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (G.P.); (A.Q.); (N.M.); (S.G.); (G.M.)
| | - Nadia Marascio
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro-“Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (G.P.); (A.Q.); (N.M.); (S.G.); (G.M.)
| | - Simona Gigliotti
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro-“Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (G.P.); (A.Q.); (N.M.); (S.G.); (G.M.)
| | - Giovanni Matera
- Unit of Clinical Microbiology, Department of Health Sciences, “Magna Græcia” University of Catanzaro-“Renato Dulbecco” Teaching Hospital, 88100 Catanzaro, Italy; (G.P.); (A.Q.); (N.M.); (S.G.); (G.M.)
| | - Chiara Romano
- Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (C.R.); (M.C.)
| | - Chiara Locci
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.)
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
| | - Ilenia Azzena
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
| | - Noemi Pascale
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
- Department of Chemical Physical Mathematical and Natural Sciences, University of Sassari, 07100 Sassari, Italy
| | - Daria Sanna
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.)
| | - Marco Casu
- Department of Veterinary Medicine, University of Sassari, 07100 Sassari, Italy; (I.A.); (N.P.); (M.C.)
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, University Hospital Policlinico Umberto I, Sapienza University of Rome, 00161 Rome, Italy;
| | - Massimo Ciccozzi
- Unit of Medical Statistics and Molecular Epidemiology, Università Campus Bio-Medico di Roma, 00128 Rome, Italy; (C.R.); (M.C.)
| | - Fabio Scarpa
- Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; (A.C.); (C.L.); (D.S.)
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4
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Yue J, Yin Y, Feng X, Xu J, Li Y, Li T, Liang S, He X, Liu Z, Wang Y. Discovery of the Inhibitor Targeting the SLC7A11/xCT Axis through In Silico and In Vitro Experiments. Int J Mol Sci 2024; 25:8284. [PMID: 39125853 DOI: 10.3390/ijms25158284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 07/22/2024] [Accepted: 07/24/2024] [Indexed: 08/12/2024] Open
Abstract
In the development and progression of cervical cancer, oxidative stress plays an important role within the cells. Among them, Solute Carrier Family 7 Member 11 (SLC7A11/xCT) is crucial for maintaining the synthesis of glutathione and the antioxidant system in cervical cancer cells. In various tumor cells, studies have shown that SLC7A11 inhibits ferroptosis, a form of cell death, by mediating cystine uptake and maintaining glutathione synthesis. Additionally, SLC7A11 is also involved in promoting tumor metastasis and immune evasion. Therefore, inhibiting the SLC7A11/xCT axis has become a potential therapeutic strategy for cervical cancer. In this study, through structure-based high-throughput virtual screening, a compound targeting the SLC7A11/xCT axis named compound 1 (PubChem CID: 3492258) was discovered. In vitro experiments using HeLa cervical cancer cells as the experimental cell model showed that compound 1 could reduce intracellular glutathione levels, increase glutamate and reactive oxygen species (ROS) levels, disrupt the oxidative balance within HeLa cells, and induce cell death. Furthermore, molecular dynamics simulation results showed that compound 1 has a stronger binding affinity with SLC7A11 compared to the positive control erastin. Overall, all the results mentioned above indicate the potential of compound 1 in targeting the SLC7A11/xCT axis and treating cervical cancer both in vitro and in silico.
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Affiliation(s)
- Jianda Yue
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Yekui Yin
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Xujun Feng
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Jiawei Xu
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Yaqi Li
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Tingting Li
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Songping Liang
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Xiao He
- Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
- Shanghai Frontiers Science Center of Molecule Intelligent Syntheses, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China
- New York University-East China Normal University Center for Computational Chemistry, New York University Shanghai, Shanghai 200062, China
| | - Zhonghua Liu
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
| | - Ying Wang
- The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China
- Peptide and Small Molecule Drug R&D Plateform, Furong Laboratory, Hunan Normal University, Changsha 410081, China
- Institute of Interdisciplinary Studies, Hunan Normal University, Changsha 410081, China
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Mlynarczyk-Bonikowska B, Rudnicka L. HPV Infections-Classification, Pathogenesis, and Potential New Therapies. Int J Mol Sci 2024; 25:7616. [PMID: 39062859 PMCID: PMC11277246 DOI: 10.3390/ijms25147616] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/02/2024] [Accepted: 07/08/2024] [Indexed: 07/28/2024] Open
Abstract
To date, more than 400 types of human papillomavirus (HPV) have been identified. Despite the creation of effective prophylactic vaccines against the most common genital HPVs, the viruses remain among the most prevalent pathogens found in humans. According to WHO data, they are the cause of 5% of all cancers. Even more frequent are persistent and recurrent benign lesions such as genital and common warts. HPVs are resistant to many disinfectants and relatively unsusceptible to external conditions. There is still no drug available to inhibit viral replication, and treatment is based on removing lesions or stimulating the host immune system. This paper presents the systematics of HPV and the differences in HPV structure between different genetic types, lineages, and sublineages, based on the literature and GenBank data. We also present the pathogenesis of diseases caused by HPV, with a special focus on the role played by E6, E7, and other viral proteins in the development of benign and cancerous lesions. We discuss further prospects for the treatment of HPV infections, including, among others, substances that block the entry of HPV into cells, inhibitors of viral early proteins, and some substances of plant origin that inhibit viral replication, as well as new possibilities for therapeutic vaccines.
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Yadav R, Das PP, Sharma S, Sengupta S, Kumar D, Sagar R. Recent advancement of nanomedicine-based targeted delivery for cervical cancer treatment. Med Oncol 2023; 40:347. [PMID: 37930458 DOI: 10.1007/s12032-023-02195-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 09/11/2023] [Indexed: 11/07/2023]
Abstract
Cervical cancer is a huge worldwide health burden, impacting women in impoverished nations in particular. Traditional therapeutic approaches, such as surgery, radiation therapy, and chemotherapy, frequently result in systemic toxicity and ineffectiveness. Nanomedicine has emerged as a viable strategy for targeted delivery of therapeutic drugs to cancer cells while decreasing off-target effects and increasing treatment success in recent years. Nanomedicine for cervical cancer introduces several novel aspects that distinguish it from previous treatment options such as tailored delivery system, precision targeting, combination therapies, real-time monitoring and diverse nanocarriers to overcome the limitations of one another. This abstract presents recent advances in nanomedicine-based tailored delivery systems for the treatment of cervical cancer. Liposomes, polymeric nanoparticles, dendrimers, and carbon nanotubes have all been intensively studied for their ability to transport chemotherapeutic medicines, nucleic acids, and imaging agents to cervical cancer cells. Because of the way these nanocarriers are designed, they may cross biological barriers and preferentially aggregate at the tumor site, boosting medicine concentration and lowering negative effects on healthy tissues. Surface modification of nanocarriers with targeting ligands like antibodies, peptides, or aptamers improves specificity for cancer cells by identifying overexpressed receptors or antigens on the tumor surface. Furthermore, nanomedicine-based techniques have made it possible to co-deliver numerous therapeutic drugs, allowing for synergistic effects and overcoming drug resistance. In preclinical and clinical investigations, combination treatments comprising chemotherapeutic medicines, gene therapy, immunotherapy, and photodynamic therapy have showed encouraging results, opening up new avenues for individualized and multimodal treatment regimens. Furthermore, the inclusion of contrast agents and imaging probes into nanocarrier systems has enabled real-time monitoring and imaging of treatment response. This enables the assessment of therapy efficacy, the early diagnosis of recurrence, and the optimization of treatment regimens.
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Affiliation(s)
- Rakhi Yadav
- Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Priyanku Pradip Das
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173229, India
| | - Sunil Sharma
- Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Sounok Sengupta
- Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173229, India
| | - Deepak Kumar
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173229, India.
| | - Ram Sagar
- Glycochemistry Laboratory, School of Physical Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
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Yang JY, Ke D, Li Y, Shi J, Wan SM, Wang AJ, Zhao MN, Gao H. CNIH4 governs cervical cancer progression through reducing ferroptosis. Chem Biol Interact 2023; 384:110712. [PMID: 37716418 DOI: 10.1016/j.cbi.2023.110712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 08/29/2023] [Accepted: 09/11/2023] [Indexed: 09/18/2023]
Abstract
Cervical cancer is one of the most leading causes of cancer death worldwide, and ferroptosis is implicated in the progression of cervical cancer. Cornichon family AMPA receptor auxiliary protein 4 (CNIH4) is involved in the progression of various human cancers; however, its function in cervical cancer remains unclear. The present study aims to investigate the role and mechanism of CNIH4 in cervical cancer using gain- and loss-of-function studies in vitro. SiHa and CaSki cells were infected with lentiviral vectors to manipulate the expression of CNIH4 in vitro, and cell viability, migration, invasion as well as ferroptosis were evaluated. Transcriptome sequencing analysis was performed to further validate the mechanism through which CNIH4 regulated the progression of cervical cancer. The expression of CNIH4 was upregulated in human cervical cancer tissues and cells, and strongly correlated with the decreases in overall survival and disease free survival rates of cervical cancer patients. CNIH4 silence inhibited, while CNIH4 overexpression facilitated the survival of human cervical cancer cells. Mechanistically, CNIH4 elevated solute carrier family 7 member 11 (SLC7A11)-mediated cystine import, and subsequently increased intracellular glutathione synthesis and glutathione peroxidase 4 activity, thereby inhibiting ferroptosis of human cervical cancer cells. SLC7A11 silence significantly abolished CNIH4-mediated inhibition of ferroptosis in cervical cancer cells in vitro. Our study for the first time reveals that CNIH4 inhibits ferroptosis of human cervical cancer cells through upregulating SLC7A11, defining CNIH4 as an attractive therapeutic and prognostic target for cervical cancer.
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Affiliation(s)
- Jun-Yuan Yang
- Department of Gynaecology II, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430071, Hubei, China.
| | - Dong Ke
- Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Yanli Li
- Department of Gynaecology II, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430071, Hubei, China
| | - Jie Shi
- Department of Gynaecology II, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430071, Hubei, China
| | - Shi-Meng Wan
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - An-Jin Wang
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Meng-Na Zhao
- Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
| | - Han Gao
- Department of Gynaecology II, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430071, Hubei, China.
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Brzeziński M, Stukan M. Anal Cancer and Anal Intraepithelial Neoplasia Risk among Patients Treated for HPV-Related Gynecological Diseases-A Systematic Review. J Clin Med 2023; 12:4216. [PMID: 37445251 DOI: 10.3390/jcm12134216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 06/15/2023] [Accepted: 06/17/2023] [Indexed: 07/15/2023] Open
Abstract
BACKGROUND The most important causative agent of neoplasms in the anogenital area is the human papillomavirus (HPV). Due to the anatomical proximity of the genital and anus area and the ease with which HPV infection is transmitted, it seems that patients after the treatment of HPV-related gynecological diseases may have an increased risk of developing a second HPV-related neoplasm anal cancer. The aim of this study was to determine the risk of anal intraepithelial neoplasia (AIN) and anal cancer (AC) among patients after the treatment of HPV-related gynecological diseases. METHODS We conducted a comprehensive review of the available literature from multiple databases. The study was performed following Cochrane Reviewers' Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. Moreover, we assessed the quality of each study using QUADAS-2. RESULTS Twenty-five studies were included in the final analysis. Patients after the treatment of HPV-related gynecological diseases have a significantly higher risk of AC (mean standardized incidence ratio (SIR) = 5.387, mean incidence risk (IR) = 0.096%, mean IR per 100,000 person-years = 10.37) and AIN (mean IR = 23.683%) compared to the population risk. CONCLUSIONS patients with HPV-related gynecological diseases should constitute a group for which an appropriate primary and secondary screening for AC should be introduced.
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Affiliation(s)
- Michał Brzeziński
- Department of Gynecological Oncology, Pomeranian Hospitals, 81-519 Gdynia, Poland
- Division of Oncological Propedeutics, Medical University of Gdańsk, 80-210 Gdańsk, Poland
| | - Maciej Stukan
- Department of Gynecological Oncology, Pomeranian Hospitals, 81-519 Gdynia, Poland
- Division of Oncological Propedeutics, Medical University of Gdańsk, 80-210 Gdańsk, Poland
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9
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Miśkiewicz J, Mielczarek-Palacz A, Gola JM. MicroRNAs as Potential Biomarkers in Gynecological Cancers. Biomedicines 2023; 11:1704. [PMID: 37371799 PMCID: PMC10296063 DOI: 10.3390/biomedicines11061704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/25/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
MicroRNAs are non-coding transcripts that, thanks to the ability to regulate the mRNA of target genes, can affect the expression of genes encoding tumor suppressors and oncogenes. They can control many important cellular processes, including apoptosis, differentiation, growth, division, and metabolism. Therefore, miRNAs play an important role in the development of many cancers, including gynecological cancers. Ovarian cancer, endometrial cancer, cervical cancer, and vulvar cancer are the most common cancers in women and are a frequent cause of death. The heterogeneity of the pathogenesis of these gynecological diseases makes the diagnostic process a significant obstacle for modern medicine. To date, many studies have been carried out, in which particular attention has been paid to the molecular pathomechanism of these diseases, with particular emphasis on miRNAs. To date, the changed profile of many miRNAs, which influenced the promotion of proliferation, migration, invasion processes and the simultaneous inhibition of programmed cell death, has been proven many times. Detailed understanding of the molecular effects of miRNAs in the above-mentioned gynecological cancers will enable the development of potential predictive and prognostic biomarkers, as well as the optimization of the diagnostic process.
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Affiliation(s)
- Joanna Miśkiewicz
- Department of Immunology and Serology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (J.M.); (A.M.-P.)
| | - Aleksandra Mielczarek-Palacz
- Department of Immunology and Serology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland; (J.M.); (A.M.-P.)
| | - Joanna Magdalena Gola
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 41-200 Sosnowiec, Poland
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Baban F, Auen T, Eschbacher KL, Swanson AA, Hartley CP. Invasive urothelial carcinoma with squamous differentiation and associated high-risk human papilloma virus infection: Clinical, cytologic, and histologic features of a rare entity. Ann Diagn Pathol 2023; 63:152103. [PMID: 36640642 DOI: 10.1016/j.anndiagpath.2022.152103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 12/30/2022] [Indexed: 01/07/2023]
Abstract
We correlate the fine needle aspiration (FNA) cytologic findings with the histologic features of an invasive high-grade urothelial carcinoma showing squamous differentiation in the setting of high-risk Human Papilloma Virus (hrHPV) infection. To our knowledge, only extensive urinary bladder catheterization has been associated with hrHPV-positive urothelial carcinoma with squamous differentiation, and rarely at that. Herein, we present a case arising in a patient with only sparse and intermittent catheterization. A 69-year-old woman presented with voiding difficulties, and after continued symptoms, a Foley catheter was placed, and a cystoscopy procedure revealed two 1-2 cm inflammatory masses. Excisional biopsies were interpreted as papillary urothelial carcinoma. One month follow-up pelvic imaging demonstrated a new mass involving the urinary bladder neck, with irregular wall thickening and perivesical fat stranding, as well as probable vaginal involvement. CT-guided FNA (CT-FNA) to collect smears and core biopsies revealed an invasive urothelial carcinoma with squamous differentiation. HPV-cytopathic changes amid squamous metaplasia and dysplasia were noted on FNA smears with HPV E6/E7 RNA in situ hybridization (ISH) showing on the FNA core biopsy specimen. Immunostains showed that the tumor cells were positive for P16 (strong, diffuse), CK7, p63, ER, and GATA3 (patchy). Subsequent radical cystectomy revealed the extent of the patient's carcinoma, with direct extension to the vaginal wall, and involvement of the radial soft tissue resection margins. Describing the cytomorphologic features of a hrHPV positive urothelial carcinoma with squamous differentiation, without an extensive history of urinary catheterization or prior known history of HPV infection, emphasizes the role of cytopathology as a powerful diagnostic tool for recognizing a unique and unexpected lesion.
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Affiliation(s)
- Farah Baban
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Thomas Auen
- Department of Pathology and Microbiology, University of Nebraska Medical Center, NE, USA
| | - Kathryn L Eschbacher
- Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
| | - Amy A Swanson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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Direct Comparison of HPV16 Viral Genomic Integration, Copy Loss, and Structural Variants in Oropharyngeal and Uterine Cervical Cancers Reveal Distinct Relationships to E2 Disruption and Somatic Alteration. Cancers (Basel) 2022; 14:cancers14184488. [PMID: 36139648 PMCID: PMC9496734 DOI: 10.3390/cancers14184488] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Revised: 09/05/2022] [Accepted: 09/13/2022] [Indexed: 11/17/2022] Open
Abstract
Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a loss of E2. Here, we compare patterns of HPV integration in UCSCC and OPSCC by analysis of affinity capture sequencing of the HPV16 genome in 104 OPSCC and 44 UCSCC tumors. These cohorts were contemporaneously sequenced using an identical strategy. Integration was identified using discordant read pair clustering and assembly-based approaches. Viral integration sites, structural variants, and copy losses were examined. While large-scale deep losses of HPV16 genes were common in UCSCC and were associated with E2 loss, deep copy losses of the HPV16 genome were infrequent in HPV16+ OPSCC. Similarly, structural variants within HPV16 favored E2 loss in UCSCC but not OPSCC. HPV16 integration sites were non-random, with recurrent integration hot-spots identified. OPSCC tumors had many more integration sites per tumor when compared to UCSCC and had more integration sites in genomic regions with high gene density. These data show that viral integration and E2 disruption are distinct in UCSCC and OPSCC. Our findings also add to growing literature suggesting that HPV tumorigenesis in OPSCC does not follow the model developed based on UCSCC.
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12
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Cervical Cancer Outcome and Tumor-Associated Macrophages: Research Evidence. IMMUNO 2022. [DOI: 10.3390/immuno2030028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Inflammation is a key factor in cancer promotion. Tumor-associated macrophages (TAMs), as part of the tumor microenvironment, are often associated with the progression of tumors and a worse prognosis in many cancers, namely on cervical cancer. This work exhaustively summarizes the conclusions of the different studies published concerning TAMs function in cervical cancer, from in vitro studies using cancer cell lines to the clinical perspective (histological samples-based studies). Most studies have led to the conclusion that TAMs increased density is directly related to increased severity of a malignant cervical lesion. Additionally, TAMs are normally polarized into an M2 phenotype, benefiting and promoting tumor progression, resulting in a worse disease outcome. The tumor microenvironment is also a highly critical contributor that not only influences tumor natural history but also modulates the specific immune response.
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13
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Leetanaporn K, Hanprasertpong J. Predictive Value of the Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) Index on the Oncological Outcomes of Locally Advanced Cervical Cancer Patients. Cancer Manag Res 2022; 14:1961-1972. [PMID: 35726336 PMCID: PMC9206525 DOI: 10.2147/cmar.s365612] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/04/2022] [Indexed: 12/16/2022] Open
Abstract
Purpose The oncological outcomes of locally advanced cervical cancer (LACC) patients after treatment are poor and heterogeneous. This study aimed to determine the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) inflammatory index in predicting oncological outcomes in LACC patients. Patients and Methods A total of 1588 LACC patients who received radiation therapy or concurrent chemoradiation were divided into training and test sets. Characteristics, survival, and a HALP cutoff determined by X-tile software were used to build predictive survival models on the training data. Validation of the model was performed on both sets. Results Patients with a HALP score ≤22.2 tended to have lower age (p < 0.001), lower comorbidity rate (p = 0.016), lower body mass index (p < 0.001), higher stage (p < 0.001), larger tumor size (p < 0.001), and higher likelihood to receive radiation alone than concurrent chemoradiation (p < 0.001). Survival analysis demonstrated that HALP >22.2 was independently associated with better progression-free survival (PFS; hazard ratio; HR 0.55) and overall survival (OS; HR 0.43). Validation of survival prediction by receiver-operating characteristics demonstrated a significantly improved area under the curve of survival prediction in both sets (p < 0.001) after the addition of the HALP index to the model. Conclusion A lower HALP score was an independent predictive factor for poorer oncological outcomes. The addition of the HALP index can improve the accuracy of predicting the oncological outcomes of LACC patients.
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Affiliation(s)
- Kittinun Leetanaporn
- Department of Biomedical Science and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Songkhla, 90110, Thailand
| | - Jitti Hanprasertpong
- Department of Obstetrics and Gynecology, Faculty of Medicine, Prince of Songkla University, Songkhla, 90110, Thailand
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14
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Ojha PS, Maste MM, Tubachi S, Patil VS. Human papillomavirus and cervical cancer: an insight highlighting pathogenesis and targeting strategies. Virusdisease 2022; 33:132-154. [DOI: 10.1007/s13337-022-00768-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 05/07/2022] [Indexed: 11/29/2022] Open
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15
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Computational and biological efficacy of stigmasterol against HeLa cells and Vero cells- first time isolated from the ethanolic extract of Annonamuricata Linn leaves. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2021.132186] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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16
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Li W, Li F, Zhang Y, Ren H, Bao X, Wang Z, Wang Y. X-Linked Inhibitor of Apoptosis Protein (XIAP)-Loaded Magnetic Mesoporous Silica Nanoparticles Incorporated with miR-233 to Improve Radio Sensitization of Cervical Cancer Cells and Promote Apoptosis. J Biomed Nanotechnol 2022; 18:747-753. [PMID: 35715921 DOI: 10.1166/jbn.2022.3281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
This study investigated the impact of magnetic mesoporous silica nanoparticles (MMSN)-encapsulated X-linked inhibitor of apoptosis protein (XIAP) and miR-233 on tumor microenvironment in cervical cancer, to provide targeted treatment and strategy, to improve radio sensitization of cancer cells. Cervical cancer cells were treated with normal saline (control group), XIAP-loaded metallic mesoporous silica nanoparticles (MMSNs), and miR-233-targeted material (XIAP group, XIAP+miR-233 group). Proliferation, apoptosis and colony forming ability of cancer cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, flow cytometry and colony formation experiments. In vivo experiments were established to observe the impact of XIAP-loaded MMSNs and miR-233 on tumor growth. Administration of XIAP-loaded MMSNs suppressed tumor growth of cervical cancer, and presence of miR-233 targeted material further decreased tumor volume, increasing radio sensitization of cancer cells. In vitro experiments confirmed that, combined treatment of XIAP and miR-233 suppressed cancer cell proliferation and invasion when inducing apoptosis. XIAP MMSNs characterized by large unit surface area, high dispersion and adhesion, and prolonged circulation time, improving drug delivery and treatment selectivity of chemotherapeutic drugs. This study suggests that XIAP MMSNs with miR-233 material suppress cervical cancer cell progression and tumor growth when augmenting radiosensitization of cancer cells, providing evidence for targeted therapy for the disease.
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Affiliation(s)
- Wen Li
- Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China
| | - Fang Li
- Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China
| | - Yang Zhang
- Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China
| | - Hongtao Ren
- Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China
| | - Xing Bao
- Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China
| | - Zhongwei Wang
- Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China
| | - Yali Wang
- Department of Radiation Oncology, The Second Affiliated Hospital of Xian Jiaotong University, Xi'an City, Shanxi Province, 710003, China
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17
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Zhang J, Fan J, Skwarczynski M, Stephenson RJ, Toth I, Hussein WM. Peptide-Based Nanovaccines in the Treatment of Cervical Cancer: A Review of Recent Advances. Int J Nanomedicine 2022; 17:869-900. [PMID: 35241913 PMCID: PMC8887913 DOI: 10.2147/ijn.s269986] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 02/09/2022] [Indexed: 12/24/2022] Open
Abstract
Persistent infection with high-risk human papillomaviruses (HPVs), such as HPV-16 and HPV-18, can induce cervical cancer in humans. The disease carries high morbidity and mortality among females worldwide. Inoculation with prophylactic HPV vaccines, such as Gardasil® or Cervarix®, is the predominant method of preventing cervical cancer in females 6 to 26 years of age. However, despite the availability of commercial prophylactic HPV vaccines, no therapeutic HPV vaccines to eliminate existing HPV infections have been approved. Peptide-based vaccines, which form one of the most potent vaccine platforms, have been broadly investigated to overcome this shortcoming. Peptide-based vaccines are especially effective in inducing cellular immune responses and eradicating tumor cells when combined with nanoscale adjuvant particles and delivery systems. This review summarizes progress in the development of peptide-based nanovaccines against HPV infection.
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Affiliation(s)
- Jiahui Zhang
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Jingyi Fan
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Mariusz Skwarczynski
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Rachel J Stephenson
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Istvan Toth
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
- School of Pharmacy, The University of Queensland, Woolloongabba, QLD, Australia
- Institute for Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
| | - Waleed M Hussein
- School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
- Correspondence: Waleed M Hussein, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, 4072, Australia, Tel +61 7 3365 2782, Email
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18
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Mitra S, Lami MS, Ghosh A, Das R, Tallei TE, Fatimawali, Islam F, Dhama K, Begum MY, Aldahish A, Chidambaram K, Emran TB. Hormonal Therapy for Gynecological Cancers: How Far Has Science Progressed toward Clinical Applications? Cancers (Basel) 2022; 14:759. [PMID: 35159024 PMCID: PMC8833573 DOI: 10.3390/cancers14030759] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 01/27/2022] [Accepted: 01/30/2022] [Indexed: 02/01/2023] Open
Abstract
In recent years, hormone therapy has been shown to be a remarkable treatment option for cancer. Hormone treatment for gynecological cancers involves the use of medications that reduce the level of hormones or inhibit their biological activity, thereby stopping or slowing cancer growth. Hormone treatment works by preventing hormones from causing cancer cells to multiply. Aromatase inhibitors, anti-estrogens, progestin, estrogen receptor (ER) antagonists, GnRH agonists, and progestogen are effectively used as therapeutics for vulvar cancer, cervical cancer, vaginal cancer, uterine cancer, and ovarian cancer. Hormone replacement therapy has a high success rate. In particular, progestogen and estrogen replacement are associated with a decreased incidence of gynecological cancers in women infected with human papillomavirus (HPV). The activation of estrogen via the transcriptional functionality of ERα may either be promoted or decreased by gene products of HPV. Hormonal treatment is frequently administered to patients with hormone-sensitive recurring or metastatic gynecologic malignancies, although response rates and therapeutic outcomes are inconsistent. Therefore, this review outlines the use of hormonal therapy for gynecological cancers and identifies the current knowledge gaps.
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Affiliation(s)
- Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (M.S.L.); (A.G.); (R.D.)
| | - Mashia Subha Lami
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (M.S.L.); (A.G.); (R.D.)
| | - Avoy Ghosh
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (M.S.L.); (A.G.); (R.D.)
| | - Rajib Das
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh; (S.M.); (M.S.L.); (A.G.); (R.D.)
| | - Trina Ekawati Tallei
- Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, Indonesia;
- The University Center of Excellence for Biotechnology and Conservation of Wallacea, Institute for Research and Community Services, Sam Ratulangi University, Manado 95115, Indonesia;
| | - Fatimawali
- The University Center of Excellence for Biotechnology and Conservation of Wallacea, Institute for Research and Community Services, Sam Ratulangi University, Manado 95115, Indonesia;
- Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado 95115, Indonesia
| | - Fahadul Islam
- Department of Pharmacy, Faculty of Allied Health of Sciences, Daffodil International University, Dhaka 1207, Bangladesh;
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India;
| | - M. Yasmin Begum
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 61441, Saudi Arabia;
| | - Afaf Aldahish
- Department of Pharmacology and Toxicology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (A.A.); (K.C.)
| | - Kumarappan Chidambaram
- Department of Pharmacology and Toxicology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia; (A.A.); (K.C.)
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh
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19
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The Efficacy of Therapeutic DNA Vaccines Expressing the Human Papillomavirus E6 and E7 Oncoproteins for Treatment of Cervical Cancer: Systematic Review. Vaccines (Basel) 2021; 10:vaccines10010053. [PMID: 35062714 PMCID: PMC8780177 DOI: 10.3390/vaccines10010053] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/24/2021] [Accepted: 12/27/2021] [Indexed: 12/15/2022] Open
Abstract
Cervical cancer is recognized as a serious public health problem since it remains one of the most common cancers with a high mortality rate among women despite existing preventative, screening, and treatment approaches. Since Human Papillomavirus (HPV) was recognized as the causative agent, the preventative HPV vaccines have made great progress over the last few years. However, people already infected with the virus require an effective treatment that would ensure long-term survival and a cure. Currently, clinical trials investigating HPV therapeutic vaccines show a promising vaccine-induced T-cell mediated immune response, resulting in cervical lesion regression and viral eradication. Among existing vaccine types (live vector, protein-based, nucleic acid-based, etc.), deoxyribonucleic acid (DNA) therapeutic vaccines are the focus of the study, since they are safe, cost-efficient, thermostable, easily produced in high purity and distributed. The aim of this study is to assess and compare existing DNA therapeutic vaccines in phase I and II trials, expressing HPV E6 and E7 oncoproteins for the prospective treatment of cervical cancer based on clinical efficacy, immunogenicity, viral clearance, and side effects. Five different DNA therapeutic vaccines (GX-188E, VGX-3100, pNGVL4a-CRT/E7(detox), pNGVL4a-Sig/E7(detox)/HSP70, MEDI0457) were well-tolerated and clinically effective. Clinical implementation of DNA therapeutic vaccines into treatment regimen as a sole approach or in combination with conservative treatment holds great potential for effective cancer treatment.
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20
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Basic V, Zhang B, Domert J, Pellas U, Tot T. Integrative meta-analysis of gene expression profiles identifies FEN1 and ENDOU as potential diagnostic biomarkers for cervical squamous cell carcinoma. Oncol Lett 2021; 22:840. [PMID: 34712364 PMCID: PMC8548783 DOI: 10.3892/ol.2021.13101] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Accepted: 09/16/2021] [Indexed: 12/23/2022] Open
Abstract
Cervical carcinoma is a global public health burden. Given that it is usually asymptomatic at potentially curative stages, the development of clinically accurate tests is critical for early detection and individual risk stratification. The present study performed an integrative meta-analysis of the transcriptomes from 10 cervical carcinoma cohorts, with the aim of identifying biomarkers that are associated with malignant transformation of cervical epithelium, and establish their clinical applicability. From among the top ranked differentially expressed genes, flap structure-specific endonuclease 1 (FEN1) and poly (U)-specific endoribonuclease (ENDOU) were selected for further validation, and their clinical applicability was assessed using immunohistochemically stained microarrays comprising 110 tissue cores, using p16 and Ki67 staining as the comparator tests. The results demonstrated that FEN1 expression was significantly upregulated in 65% of tumor specimens (P=0.0001), with no detectable expression in the non-tumor tissues. Furthermore, its expression was significantly associated with Ki67 staining in tumor samples (P<0.0001), but no association was observed with p16 expression or the presence of human papilloma virus types 16/18, patient age, tumor grade or stage. FEN1 staining demonstrated lower sensitivity than p16 (69.3 vs. 96.8%) and Ki67 (69.3 vs. 76.3%); however, the specificity was identical to p16 and higher than that of Ki67 (100 vs. 71.4%).ENDOU staining was consistent with the microarray results, demonstrating 1% positivity in tumors and 40% positivity in non-tumor tissues. Gene set enrichment analysis of cervical tumors overexpressing FEN1 revealed its association with enhanced growth factor signaling, immune response inhibition and extracellular matrix remodeling, whereas tumors with low ENDOU expression exhibited inhibition of epithelial development and differentiation processes. Taken together, the results of the present study demonstrate the feasibility of the integrative meta-analysis approach to identify relevant biomarkers associated with cervical carcinogenesis. Thus, FEN1 and ENDOU may be useful diagnostic biomarkers for squamous cervical carcinoma. However, further studies are required to determine their diagnostic performance in larger patient cohorts and validate the results presented here.
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Affiliation(s)
- Vladimir Basic
- Pathology and Cytology Dalarna, County Hospital Falun, Falun 791 82, Sweden
- Clinical Research Center Dalarna, Uppsala University, Falun 791 82, Sweden
| | - Boxi Zhang
- Department of Physiology and Pharmacology, Karolinska Institute, Stockholm 171 65, Sweden
| | - Jakob Domert
- Pathology and Cytology Dalarna, County Hospital Falun, Falun 791 82, Sweden
| | - Ulrika Pellas
- Clinical Research Center Dalarna, Uppsala University, Falun 791 82, Sweden
| | - Tibor Tot
- Pathology and Cytology Dalarna, County Hospital Falun, Falun 791 82, Sweden
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21
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Wang C, Zeng J, Li LJ, Xue M, He SL. Cdc25A inhibits autophagy-mediated ferroptosis by upregulating ErbB2 through PKM2 dephosphorylation in cervical cancer cells. Cell Death Dis 2021; 12:1055. [PMID: 34743185 PMCID: PMC8572225 DOI: 10.1038/s41419-021-04342-y] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 10/13/2021] [Accepted: 10/18/2021] [Indexed: 12/12/2022]
Abstract
Cervical cancer is the leading cause of cancer-related deaths in women, and treatment for cervical cancer is very limited. Emerging evidence suggests that targeting ferroptosis is a promising way to treat cancer. Here, we investigated the role of ferroptosis in cervical cancer, with a focus on the Cdc25A/PKM2/ErbB2 axis. Cervical cancer cells were treated with sorafenib to induce ferroptosis. Cellular MDA/ROS/GSH/iron detection assays were used to measure ferroptosis. MTT assays were performed to assess cell viability. qRT-PCR, western blot, and immunostaining assays were performed to measure the levels of proteins. Autophagy was monitored by fluorescence microscopy. Nuclear and cytosolic fractions were isolated to examine the location of PKM2 modifications. Co-IP experiments were conducted to determine the Cdc25A/PKM2 interaction. ChIP assays were performed to measure the binding affinity between H3K9Ac and the ErbB3 promoter, and a dual luciferase assay was performed to examine the transcriptional activity of ErbB2. A nude mouse xenograft model was used to examine the effects of the Cdc25A/ErbB2 axis on tumour growth in vivo. Cdc25A was elevated in human cervical cancer tissues but was reduced during sorafenib-induced ferroptosis of cervical cancer cells. Overexpression of Cdc25A inhibited sorafenib-induced ferroptosis by dephosphorylating nuclear PKM2 and suppressing autophagy. Cdc25A regulated autophagy-induced ferroptosis by increasing ErbB2 levels via the PKM2-pH3T11-H3K9Ac pathway. Cdc25A increased the resistance of cervical cancer to sorafenib, while knockdown of ErbB2 blocked these effects. Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer.
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Affiliation(s)
- Chen Wang
- Department of Gynecology and Obstetrics, the Third Xiangya Hospital of Central South University, 410013, Changsha, Hunan Province, P.R. China
| | - Jie Zeng
- Pharmacy Intravenous Admixture Services, the Third Xiangya Hospital of Central South University, 410013, Changsha, Hunan Province, P.R. China
| | - Li-Jie Li
- Department of Gynecology and Obstetrics, the Third Xiangya Hospital of Central South University, 410013, Changsha, Hunan Province, P.R. China
| | - Min Xue
- Department of Gynecology and Obstetrics, the Third Xiangya Hospital of Central South University, 410013, Changsha, Hunan Province, P.R. China
| | - Si-Li He
- Department of Gynecology and Obstetrics, the Third Xiangya Hospital of Central South University, 410013, Changsha, Hunan Province, P.R. China.
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22
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Li S, Han F, Qi N, Wen L, Li J, Feng C, Wang Q. Determination of a six-gene prognostic model for cervical cancer based on WGCNA combined with LASSO and Cox-PH analysis. World J Surg Oncol 2021; 19:277. [PMID: 34530829 PMCID: PMC8447612 DOI: 10.1186/s12957-021-02384-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 08/30/2021] [Indexed: 02/06/2023] Open
Abstract
AIM This study aimed to establish a risk model of hub genes to evaluate the prognosis of patients with cervical cancer. METHODS Based on TCGA and GTEx databases, the differentially expressed genes (DEGs) were screened and then analyzed using GO and KEGG analyses. The weighted gene co-expression network (WGCNA) was then used to perform modular analysis of DEGs. Univariate Cox regression analysis combined with LASSO and Cox-pH was used to select the prognostic genes. Then, multivariate Cox regression analysis was used to screen the hub genes. The risk model was established based on hub genes and evaluated by risk curve, survival state, Kaplan-Meier curve, and receiver operating characteristic (ROC) curve. RESULTS We screened 1265 DEGs between cervical cancer and normal samples, of which 620 were downregulated and 645 were upregulated. GO and KEGG analyses revealed that most of the upregulated genes were related to the metastasis of cancer cells, while the downregulated genes mostly acted on the cell cycle. Then, WGCNA mined six modules (red, blue, green, brown, yellow, and gray), and the brown module with the most DEGs and related to multiple cancers was selected for the follow-up study. Eight genes were identified by univariate Cox regression analysis combined with the LASSO Cox-pH model. Then, six hub genes (SLC25A5, ENO1, ANLN, RIBC2, PTTG1, and MCM5) were screened by multivariate Cox regression analysis, and SLC25A5, ANLN, RIBC2, and PTTG1 could be used as independent prognostic factors. Finally, we determined that the risk model established by the six hub genes was effective and stable. CONCLUSIONS This study supplies the prognostic value of the risk model and the new promising targets for the cervical cancer treatment, and their biological functions need to be further explored.
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Affiliation(s)
- Shiyan Li
- Department of Gynecology, Heilongjiang University of Traditional Chinese Medicine, Harbin, PR China
| | - Fengjuan Han
- Department of Gynecology, Heilongjiang University of Traditional Chinese Medicine, Harbin, PR China.
| | - Na Qi
- Department of Gynecology, Heilongjiang University of Traditional Chinese Medicine, Harbin, PR China
| | - Liyang Wen
- Department of Acupuncture and Moxibustion, Heilongjiang University of Traditional Chinese Medicine, Harbin, P.R. China
| | - Jia Li
- Department of Gynecology, Heilongjiang University of Traditional Chinese Medicine, Harbin, PR China
| | - Cong Feng
- Department of Gynecology, Heilongjiang University of Traditional Chinese Medicine, Harbin, PR China
| | - Qingling Wang
- Department of Gynecology, Shenzhen Nanshan Maternal and Child Health Care Hospital, Shenzhen, P.R. China.
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23
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Phosphorylation of RCC1 on Serine 11 Facilitates G1/S Transition in HPV E7-Expressing Cells. Biomolecules 2021; 11:biom11070995. [PMID: 34356619 PMCID: PMC8301946 DOI: 10.3390/biom11070995] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 07/01/2021] [Accepted: 07/01/2021] [Indexed: 11/25/2022] Open
Abstract
Persistent infection of high-risk human papillomavirus (HR-HPV) plays a causal role in cervical cancer. Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator, which undergoes a few post-translational modifications including phosphorylation. Here, we showed that serine 11 (S11) of RCC1 was phosphorylated in HPV E7-expressing cells. However, S11 phosphorylation was not up-regulated by CDK1 in E7-expressing cells; instead, the PI3K/AKT/mTOR pathway promoted S11 phosphorylation. Knockdown of AKT or inhibition of the PI3K/AKT/mTOR pathway down-regulated phosphorylation of RCC1 S11. Furthermore, S11 phosphorylation occurred throughout the cell cycle, and reached its peak during the mitosis phase. Our previous data proved that RCC1 was necessary for the G1/S cell cycle progression, and in the present study we showed that the RCC1 mutant, in which S11 was mutated to alanine (S11A) to mimic non-phosphorylation status, lost the ability to facilitate G1/S transition in E7-expressing cells. Moreover, RCC1 S11 was phosphorylated by the PI3K/AKT/mTOR pathway in HPV-positive cervical cancer SiHa and HeLa cells. We conclude that S11 of RCC1 is phosphorylated by the PI3K/AKT/mTOR pathway and phosphorylation of RCC1 S11 facilitates the abrogation of G1 checkpoint in HPV E7-expressing cells. In short, our study explores a new role of RCC1 S11 phosphorylation in cell cycle regulation.
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Ghebrendrias S, Pfeil S, Crouthamel B, Chalmiers M, Kully G, Mody S. An Examination of Misconceptions and Their Impact on Cervical Cancer Prevention Practices among Sub-Saharan African and Middle Eastern Refugees. Health Equity 2021; 5:382-389. [PMID: 34095709 PMCID: PMC8175255 DOI: 10.1089/heq.2020.0125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/29/2021] [Indexed: 11/12/2022] Open
Abstract
Objective: The purpose of the study was to understand cervical cancer screening and prevention practices of refugee women in San Diego, California and identify desired components of a cervical cancer screening toolkit. Methods: We conducted a qualitative study utilizing semi-structured focus groups and identified common themes via grounded theory analysis. Results: There were 53 female refugee participants from Sub-Saharan Africa and the Middle East. Over half of all women surveyed expressed a fear of pelvic exams and loss of modesty as barriers to seeking gynecologic care, with nearly 34% avoiding routine pap tests. Of the 18 participants who were asked if they were aware of the Human Papilloma Virus (HPV) vaccination, only one had heard of the vaccine and none had received it for themselves or their children. Over 60% of participants were interested in educational materials surrounding HPV and pap tests. Conclusion: There is a significant lack of knowledge regarding cervical cancer screening and HPV vaccination among refugee women in San Diego, California. Refugee women in this study were interested in multi-modal educational materials as part of a cervical cancer screening toolkit.
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Affiliation(s)
- Selemawit Ghebrendrias
- Division of Family Planning, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Diego, San Diego, California, USA
| | - Sarah Pfeil
- Department of Obstetrics and Gynecology, University of California, San Diego, San Diego, California, USA
| | - Bonnie Crouthamel
- Department of Obstetrics and Gynecology, University of California, Davis, Davis, California, USA
| | - Morgen Chalmiers
- Department of Obstetrics and Gynecology, University of California, San Diego, San Diego, California, USA
| | - Gennifer Kully
- Department of Obstetrics and Gynecology, University of California, San Diego, San Diego, California, USA
| | - Sheila Mody
- Department of Obstetrics and Gynecology, University of California, San Diego, San Diego, California, USA
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Man S, Li X, Zhu W. miR-4417 targets lncRNA PSMG3-AS1 to suppress cell invasion and migration in cervical squamous cell carcinoma. Oncol Lett 2021; 22:502. [PMID: 33986863 PMCID: PMC8114464 DOI: 10.3892/ol.2021.12763] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Accepted: 02/04/2021] [Indexed: 02/06/2023] Open
Abstract
Although long non-coding RNA (lncRNA) PSMG3-AS1 has been reported to participate in cancer biology, its role in cervical squamous cell carcinoma (CSCC) is unknown. The present study aimed to investigate the role of the lncRNA PSMG3-AS1 in CSCC. The expression levels of PSMG3-AS1 in both CSCC and non-tumor tissues from 64 patients with CSCC were measured by reverse transcription-quantitative PCR. The potential interaction between miR-4417 and PSMG3-AS1 was predicted using IntaRNA 2.0. Overexpression of miR-4417 and PSMG3-AS1 were achieved in CSCC cells to further explore the potential interaction between them. The effects of overexpression of miR-4417 and PSMG3-AS1 on CSCC cell invasion and migration were assessed by Transwell assay. The results revealed that PSMG3-AS1 expression was upregulated in CSCC tissues, and its high expression levels predicted a poor survival in patients with CSCC. miR-4417 expression was downregulated in CSCC tissues and was inversely correlated with PSMG3-AS1 expression. Moreover, miR-4417 was predicted to interact with PSMG3-AS1. In CSCC cells, overexpression of miR-4417 decreased the expression levels of PSMG3-AS1, while overexpression of PSMG3-AS1 did not affect miR-4417 expression. Transwell assay demonstrated that overexpression of PSMG3-AS1 increased CSCC cell invasion and migration. However, overexpression of miR-4417 inhibited CSCC cell invasion and migration, and attenuated the effects of PSMG3-AS1 overexpression in CSCC cells. In conclusion, the present study indicated that miR-4417 may target PSMG3-AS1 to suppress cancer cell invasion and migration in CSCC.
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Affiliation(s)
- Shuhong Man
- Department of Gynaecology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
| | - Xiaohan Li
- School of Public Health, Shandong University, Jinan, Shandong 250012, P.R. China
| | - Wei Zhu
- Nursing Department, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
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Ferrall L, Lin KY, Roden RBS, Hung CF, Wu TC. Cervical Cancer Immunotherapy: Facts and Hopes. Clin Cancer Res 2021; 27:4953-4973. [PMID: 33888488 DOI: 10.1158/1078-0432.ccr-20-2833] [Citation(s) in RCA: 166] [Impact Index Per Article: 41.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 03/12/2021] [Accepted: 04/08/2021] [Indexed: 11/16/2022]
Abstract
It is a sad fact that despite being almost completely preventable through human papillomavirus (HPV) vaccination and screening, cervical cancer remains the fourth most common cancer to affect women worldwide. Persistent high-risk HPV (hrHPV) infection is the primary etiologic factor for cervical cancer. Upward of 70% of cases are driven by HPV types 16 and 18, with a dozen other hrHPVs associated with the remainder of cases. Current standard-of-care treatments include radiotherapy, chemotherapy, and/or surgical resection. However, they have significant side effects and limited efficacy against advanced disease. There are a few treatment options for recurrent or metastatic cases. Immunotherapy offers new hope, as demonstrated by the recent approval of programmed cell death protein 1-blocking antibody for recurrent or metastatic disease. This might be augmented by combination with antigen-specific immunotherapy approaches, such as vaccines or adoptive cell transfer, to enhance the host cellular immune response targeting HPV-positive cancer cells. As cervical cancer progresses, it can foster an immunosuppressive microenvironment and counteract host anticancer immunity. Thus, approaches to reverse suppressive immune environments and bolster effector T-cell functioning are likely to enhance the success of such cervical cancer immunotherapy. The success of nonspecific immunostimulants like imiquimod against genital warts also suggest the possibility of utilizing these immunotherapeutic strategies in cervical cancer prevention to treat precursor lesions (cervical intraepithelial neoplasia) and persistent hrHPV infections against which the licensed prophylactic HPV vaccines have no efficacy. Here, we review the progress and challenges in the development of immunotherapeutic approaches for the prevention and treatment of cervical cancer.
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Affiliation(s)
- Louise Ferrall
- Department of Pathology, The Johns Hopkins University, Baltimore, Maryland
| | - Ken Y Lin
- Department of Obstetrics and Gynecology and Women's Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Richard B S Roden
- Department of Pathology, The Johns Hopkins University, Baltimore, Maryland.,Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.,Department of Obstetrics and Gynecology, The Johns Hopkins University, Baltimore, Maryland
| | - Chien-Fu Hung
- Department of Pathology, The Johns Hopkins University, Baltimore, Maryland.,Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.,Department of Obstetrics and Gynecology, The Johns Hopkins University, Baltimore, Maryland
| | - T-C Wu
- Department of Pathology, The Johns Hopkins University, Baltimore, Maryland. .,Department of Oncology, The Johns Hopkins University, Baltimore, Maryland.,Department of Obstetrics and Gynecology, The Johns Hopkins University, Baltimore, Maryland.,Department of Molecular Microbiology and Immunology, The Johns Hopkins University, Baltimore, Maryland
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27
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Chen Y, Chen D, Wang J, Zhang Y, Zhang J, Chen B, Chen Y, Zhang Y, Ma C. Dysregulated LncRNAs Act as Competitive Endogenous RNAs and Are Associated With Cervical Cancer Development in UYGHUR Women. Technol Cancer Res Treat 2021; 20:1533033821989711. [PMID: 33596784 PMCID: PMC7897819 DOI: 10.1177/1533033821989711] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Cervical cancer is one of the most malignant tumors in women, particularly those in rural and remote areas. Its underlying molecular mechanisms, including the functions of non-coding RNA (ncRNAs), require more extensive investigation. In this study, high throughput transcriptome sequencing (RNA-seq) was used to identify differentially expressed lncRNAs and mRNAs in normal, cervical intraepithelial neoplasia and cervical cancer tissues from Uyghur women in western China. Dysregulated lncRNAs were found to extensively participate in cervical cancer development, including viral carcinogenesis, cell cycle and cytokine-cytokine receptor signaling. Two miRNA-host lncRNAs, LINC00925 and MIR155HG, showed elevated expression in cervical cancer samples, but prolonged the survival time of cervical cancer patients. The 2 mature miRNAs of the above 2 lncRNAs, miR-9 and miR-155, also showed similar features in cervical cancer. In addition, we identified 545 lncRNAs with potential functions in regulating these 2 miRNAs as competing endogenous RNAs (ceRNAs). In summary, our study demonstrated the dysregulated lncRNAs/miRNAs, particularly LINC00925/miR-9 and MIR155HG/miR-155, regulate the development of cervical cancer by forming a interaction network with mRNAs, highlighting the importance of elucidating the underlying mechanisms of ncRNAs in cervical cancer development.
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Affiliation(s)
- Yanxia Chen
- Department of Gynaecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Dong Chen
- Center for Genome Analysis, ABLife Inc., Wuhan, Hubei, China.,ABLife BioBigData Institute, Wuhan, Hubei, China
| | - Jing Wang
- Department of Gynaecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Yu Zhang
- Center for Genome Analysis, ABLife Inc., Wuhan, Hubei, China
| | - Ji Zhang
- Shanghai Ruijin Hospital, Shanghai, China
| | - Bing Chen
- Department of Gynaecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Yaru Chen
- Department of Gynaecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Yi Zhang
- Center for Genome Analysis, ABLife Inc., Wuhan, Hubei, China.,ABLife BioBigData Institute, Wuhan, Hubei, China
| | - Cailing Ma
- Department of Gynaecology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China.,State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
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28
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Zhang H, Jin S, Ji A, Ma Y, Zhang C, Wang A, Wang R. LncRNA SLC16A1-AS1 Suppresses Cell Proliferation in Cervical Squamous Cell Carcinoma (CSCC) Through the miR-194/SOCS2 Axis. Cancer Manag Res 2021; 13:1299-1306. [PMID: 33603475 PMCID: PMC7884948 DOI: 10.2147/cmar.s276629] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 01/07/2021] [Indexed: 01/08/2023] Open
Abstract
Background SLC16A1-AS1 has been characterized as an oncogenic long non-coding (lncRNA) in breast cancer and bladder cancer, while its role in cervical squamous cell carcinoma (CSCC) is unknown. Methods CSCC and non-tumor tissue samples were collected from 60 female patients, and qPCR was performed to detect the expression of SLC16A1-AS1, miR-194 and SOCS2. Luciferase reporter assay was performed to detect the interaction between SLC16A1-AS1 and miR-194. Colony formation assay was used to detect cell proliferation. Results SLC16A1-AS1 was down-regulated in CSCC and correlated with poor survival. Overexpression of SLC16A1-AS1 could inhibit the proliferation of cervical cancer cells. In addition, SLC16A1-AS1 could sponge miR-194 and increase the expression levels of SOCS2, ultimately inhibiting the proliferation of cervical cancer cells. Conclusion SLC16A1-AS1 was downregulated in CSCC and suppressed cell proliferation in cervical squamous cell carcinoma (CSCC) through the miR-194/SOCS2 axis.
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Affiliation(s)
- Huizhen Zhang
- Department of Gynecology, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People's Republic of China
| | - Shuangling Jin
- Department of Gynecology, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People's Republic of China
| | - Aifang Ji
- Department of Clinical Laboratory, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People's Republic of China
| | - Ying Ma
- Department of Obstetrics, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People's Republic of China
| | - Chunyan Zhang
- Department of Gynecology, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People's Republic of China
| | - Ailan Wang
- Department of Gynecology, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People's Republic of China
| | - Rui Wang
- Department of Gynecology, Heping Hospital Affiliated to Changzhi Medical College, Changzi, Shanxi Province, 046000, People's Republic of China
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Xu Z, Shu H, Zhang F, Luo W, Li Y, Chu J, Zhao Q, Lv Y. Nimotuzumab Combined With Irradiation Enhances the Inhibition to the HPV16 E6-Promoted Growth of Cervical Squamous Cell Carcinoma. Front Oncol 2020; 10:1327. [PMID: 32850421 PMCID: PMC7419688 DOI: 10.3389/fonc.2020.01327] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2020] [Accepted: 06/25/2020] [Indexed: 12/24/2022] Open
Abstract
Human papillomavirus (HPV) 16 E6 has been proved to increase the radiosensitivity and lead to the EGFR overexpression in cervical cancer cells. In this study, to investigate the inhibition of nimotuzumab-mediated EGFR blockade combined with radiotherapy, we established a C33A cervical squamous cell line overexpressed HPV16-E6 and a nude mouse model bearing these cell lines. The CCK-8 assay was used to detect the effects of various treatments on the proliferation of C33A cells. Flow cytometry was used to detect the rates of apoptosis and cell cycle arrest. Gene transcription and protein expression were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. Immunohistochemical staining was used to evaluate protein expression in tumor tissue. We revealed that E6-overexpressing C33A cells grew faster and were more sensitive to radiotherapy than control cells in vitro and in vivo. The expression levels of EGFR, as well as those of downstream signaling molecules AKT and ERK 1/2, were significantly upregulated in C33A cells that overexpressed E6. We observed that nimotuzumab combined with radiotherapy could enhance the inhibition of C33A cell growth induced by E6, both in vitro and in vivo. We also observed enhanced effect after combination on G2/M cell cycle arrest and apoptosis in E6-overexpressing C33A cells. Furthermore, the combined therapy of nimotuzumab and radiation remarkably reduced the protein expression levels of EGFR, AKT, ERK 1/2 in vitro, and in vivo. In conclusion, HPV16 E6 expression is positively correlated with levels of EGFR, AKT, and ERK 1/2 protein expression. The combined treatment with nimotuzumab and radiotherapy to enhance radiosensitivity in E6-positive cervical squamous cell carcinoma was related to enhanced G2/M cell cycle arrest and caspase-related apoptosis.
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Affiliation(s)
- Zhonghua Xu
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hang Shu
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Fan Zhang
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Weiwei Luo
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Yan Li
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jinjin Chu
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qihong Zhao
- Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, China
| | - Yin Lv
- Department of Radiotherapy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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Comparative transcriptomic profiling in HPV-associated cervical carcinogenesis: Implication of MHC class II and immunoglobulin heavy chain genes. Life Sci 2020; 256:118026. [PMID: 32615187 DOI: 10.1016/j.lfs.2020.118026] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 06/26/2020] [Accepted: 06/26/2020] [Indexed: 12/24/2022]
Abstract
AIM We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection. MATERIALS AND METHODS Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated. CONCLUSION Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.
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Almonte M, Murillo R, Sánchez GI, González P, Ferrera A, Picconi MA, Wiesner C, Cruz-Valdez A, Lazcano-Ponce E, Jerónimo J, Ferreccio C, Kasamatsu E, Mendoza L, Rodríguez G, Calderón A, Venegas G, Villagra V, Tatti S, Fleider L, Terán C, Baena A, Hernández MDLL, Rol ML, Lucas E, Barbier S, Ramírez AT, Arrossi S, Rodríguez MI, González E, Celis M, Martínez S, Salgado Y, Ortega M, Beracochea AV, Pérez N, Rodríguez de la Peña M, Ramón M, Hernández-Nevarez P, Arboleda-Naranjo M, Cabrera Y, Salgado B, García L, Retana MA, Colucci MC, Arias-Stella J, Bellido-Fuentes Y, Bobadilla ML, Olmedo G, Brito-García I, Méndez-Herrera A, Cardinal L, Flores B, Peñaranda J, Martínez-Better J, Soilán A, Figueroa J, Caserta B, Sosa C, Moreno A, Mural J, Doimi F, Giménez D, Rodríguez H, Lora O, Luciani S, Broutet N, Darragh T, Herrero R. Multicentric study of cervical cancer screening with human papillomavirus testing and assessment of triage methods in Latin America: the ESTAMPA screening study protocol. BMJ Open 2020; 10:e035796. [PMID: 32448795 PMCID: PMC7252979 DOI: 10.1136/bmjopen-2019-035796] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 03/18/2020] [Accepted: 04/03/2020] [Indexed: 12/20/2022] Open
Abstract
INTRODUCTION Human papillomavirus (HPV) testing is replacing cytology in primary screening. Its limited specificity demands using a second (triage) test to better identify women at high-risk of cervical disease. Cytology represents the immediate triage but its low sensitivity might hamper HPV testing sensitivity, particularly in low-income and middle-income countries (LMICs), where cytology performance has been suboptimal. The ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) study will: (1) evaluate the performance of different triage techniques to detect cervical precancer and (2) inform on how to implement HPV-based screening programmes in LMIC. METHODS AND ANALYSIS Women aged 30-64 years are screened with HPV testing and Pap across 12 study centres in Latin America. Screened positives have colposcopy with biopsy and treatment of lesions. Women with no evident disease are recalled 18 months later for another HPV test; those HPV-positive undergo colposcopy with biopsy and treatment as needed. Biological specimens are collected in different visits for triage testing, which is not used for clinical management. The study outcome is histological high-grade squamous intraepithelial or worse lesions (HSIL+) under the lower anogenital squamous terminology. About 50 000 women will be screened and 500 HSIL+ cases detected (at initial and 18 months screening). Performance measures (sensitivity, specificity and predictive values) of triage techniques to detect HSIL+ will be estimated and compared with adjustment by age and study centre. ETHICS AND DISSEMINATION The study protocol has been approved by the Ethics Committee of the International Agency for Research on Cancer (IARC), of the Pan American Health Organisation (PAHO) and by those in each participating centre. A Data and Safety Monitoring Board (DSMB) has been established to monitor progress of the study, assure participant safety, advice on scientific conduct and analysis and suggest protocol improvements. Study findings will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER NCT01881659.
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Affiliation(s)
- Maribel Almonte
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Raúl Murillo
- Pontificia Universidad Javeriana, Bogotá, Colombia
| | | | - Paula González
- Agencia Costarricense de Investigaciones Biomédicas (ACIB), Fundación Inciensa, Guanacaste, Costa Rica
| | - Annabelle Ferrera
- Instituto de Investigaciones en Microbiología, Universidad Nacional Autónoma de Honduras (UNAH), Tegucigalpa, Honduras
| | | | | | | | | | | | - Catterina Ferreccio
- Advanced Center for Chronic Diseases, ACCDiS, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Elena Kasamatsu
- Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay
| | - Laura Mendoza
- Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay
| | | | - Alejandro Calderón
- Caja Costarricense de Seguro Social (CCSS), Región Pacífico Central, San José, Costa Rica
| | - Gino Venegas
- Clínica Angloamericana, Lima, Perú
- Escuela de Medicina Humana, Universidad de Piura, Lima, Perú
| | | | - Silvio Tatti
- Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Laura Fleider
- Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Carolina Terán
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
| | - Armando Baena
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - María de la Luz Hernández
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
- SMS-Oncology, Amsterdam, The Netherlands
| | - Mary Luz Rol
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Eric Lucas
- Screening Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Sylvaine Barbier
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Arianis Tatiana Ramírez
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
| | - Silvina Arrossi
- Centro de Estudios de Estado y Sociedad/Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
| | - María Isabel Rodríguez
- Instituto de Investigaciones en Ciencias de la Salud, Universidad Nacional de Asunción, San Lorenzo, Paraguay
| | | | - Marcela Celis
- Instituto Nacional de Cancerología, Bogotá, Colombia
| | | | - Yuly Salgado
- Instituto Nacional de Cancerología, Bogotá, Colombia
| | - Marina Ortega
- Hospital Nacional, Ministerio de Salud Pública y Bienestar Social, Itauguá, Paraguay
- Instituto Nacional del Cáncer, Ministerio de Salud Pública y Bienestar Social, Capiatá, Paraguay
| | - Andrea Verónica Beracochea
- Centro de Salud Ciudad de la Costa, ASSE, Ciudad de la Costa, Uruguay
- Hospital Policial, DNASS, Montevideo, Uruguay
| | - Natalia Pérez
- Hospital de Clínicas, Facultad de Medicina, UDELAR, Montevideo, Uruguay
| | | | | | | | | | - Yessy Cabrera
- Instituto de Investigaciones en Microbiología, Universidad Nacional Autónoma de Honduras (UNAH), Tegucigalpa, Honduras
| | | | - Laura García
- Laboratorio de Biología Molecular, Departamento de Patología Clínica, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay
| | | | - María Celeste Colucci
- Instituto Nacional de Enfermedades Infecciosas - ANLIS Malbrán, Buenos Aires, Argentina
| | | | | | | | - Gladys Olmedo
- Laboratorio Central de Salud Pública, Asunción, Paraguay
| | | | | | - Lucía Cardinal
- Hospital de Clínicas José de San Martín, Buenos Aires, Argentina
| | - Betsy Flores
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
| | - Jhacquelin Peñaranda
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
| | | | - Ana Soilán
- Hospital Nacional, Ministerio de Salud Pública y Bienestar Social, Itauguá, Paraguay
- Hospital Materno Infantil de San Lorenzo, Ministerio de Salud Pública y Bienestar Social, San Lorenzo, Paraguay
| | | | - Benedicta Caserta
- Departamento de Anatomía Patológica y Citología, Hospital de la Mujer, Centro Hospitalario Pereira Rossell, Montevideo, Uruguay
| | - Carlos Sosa
- Hospital Monseñor Víctor Manuel Sanabria Martínez, CCSS, Puntarenas, Costa Rica
| | - Adrián Moreno
- Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
| | - Juan Mural
- Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
| | | | - Diana Giménez
- Hospital Materno Infantil de Trinidad, Ministerio de Salud Pública y Bienestar Social, Asunción, Paraguay
| | - Hernando Rodríguez
- Hospital Materno Infantil de Trinidad, Ministerio de Salud Pública y Bienestar Social, Asunción, Paraguay
| | - Oscar Lora
- Facultad de Medicina, Universidad Mayor, Real y Pontificia de San Francisco Xavier de Chuquisaca, Sucre, Bolivia
- Hospital Gineco-Obstétrico y Neonatal "Dr Jaime Sánchez Porcel", Sucre, Bolivia
| | - Silvana Luciani
- Pan American Health Organization (PAHO), Washington, District of Columbia, USA
| | - Nathalie Broutet
- Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
| | - Teresa Darragh
- Department of Pathology, University of California, San Francisco, California, USA
| | - Rolando Herrero
- Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, Rhône-Alpes, France
- Agencia Costarricense de Investigaciones Biomédicas (ACIB), Fundación Inciensa, Guanacaste, Costa Rica
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Zhang C, Hua Y, Qiu H, Liu T, Long Q, Liao W, Qiu J, Wang N, Chen M, Shi D, Yan Y, Xie C, Deng W, Li T, Li Y. KMT2A regulates cervical cancer cell growth through targeting VDAC1. Aging (Albany NY) 2020; 12:9604-9620. [PMID: 32436862 PMCID: PMC7288919 DOI: 10.18632/aging.103229] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Accepted: 04/14/2020] [Indexed: 12/14/2022]
Abstract
Cervical cancer is an aggressive cutaneous malignancy, illuminating the molecular mechanisms of tumorigenesis and discovering novel therapeutic targets are urgently needed. KMT2A is a transcriptional co-activator regulating gene expression during early development and hematopoiesis, but the role of KMT2A in cervical cancer remains unknown. Here, we demonstrated that KMT2A regulated cervical cancer growth via targeting VADC1. Knockdown of KMT2A significantly suppressed cell proliferation and migration and induced apoptosis in cervical cancer cells, accompanying with activation of PARP/caspase pathway and inhibition of VADC1. Overexpression of VDAC1 reversed the KMT2A knockdown-mediated regulation of cell proliferation, migration and apoptosis. The in vivo results from a cervical cancer xenograft mouse model also validated that KMT2A knockdown suppressed tumor growth by inhibiting VDAC1, whereas KMT2A overexpression promoted cervical cancer growth. Moreover, analyses of Biewenga cervix database and clinical samples showed that both KMT2A and VDAC1 were upregulated in cervix squamous cell carcinoma compared with cervix uteri tissues, and their expression was negatively correlated with the differentiation grade of cervical cancer. Our results therefore indicated that the KMT2A/VDAC1 signaling axis may be a potential new mechanism of cervical carcinogenesis.
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Affiliation(s)
- Changlin Zhang
- Department of Gynecology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Yijun Hua
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Huijuan Qiu
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Tianze Liu
- The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
| | - Qian Long
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Wei Liao
- Department of Gynecology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Jiehong Qiu
- Department of Gynecology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Nang Wang
- College of Life Sciences, Jiaying University, Meizhou, Guangdong, China
| | - Miao Chen
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Dingbo Shi
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Yue Yan
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Chuanbo Xie
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Wuguo Deng
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
| | - Tian Li
- Department of Gynecology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
| | - Yizhuo Li
- Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
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Wu Y, Zhao J, Dong S, Wang Y, Li A, Jiang Y, Chen Z, Li C, Wang W, Zhang Z. Whole-exome and RNA sequencing reveal novel insights into the pathogenesis of HPV associated cervical cancer. Cancer Biomark 2020; 25:341-350. [PMID: 31306105 DOI: 10.3233/cbm-190055] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Worldwide, cervical cancer is the fouth leading cause of deaths in gynecological oncology. Although the causes of cervical cancer have been extensively investigated, understanding of its exact pathogenesis remains incomplete. OBJECTIVE This study aimed to identify alterations of genome and transcriptome of HPV associated cervical cancer pathogenesis using multi-omics approaches. METHODS Cervical cancer and matched adjacent non-tumor specimens of one HPV16+ and two HPV- patients were sampled for whole-exome sequencing (WES) and RNA sequencing to characterize DNA mutations and gene expression profiles. WES and Affymetrix SNP 6.0 arrays data were analyzed from 6 HPV- and 93 HPV16+ cervical cancer patients in the cancer genome atlas (TCGA) database, as an independent validation group. RESULTS WES identified 64 somatic mutation genes in tumors of 3 patients. HPV16+ tumor got fewer somatic mutated genes than HPV- tumors, which was validated by TCGA results. In this study, somatic mutated profile, CNV and gene expression heat map presented that HPV16+ tumors was distinct with HPV- tumors. The most significant altered pathways and GO terms were both related with cell cycle. Integrated analysis of multi-omics showed positive correlation between gene expression level and copy numbers. CONCLUSIONS The results of this study provided novel insights into the pathogenesis of HPV associated cervical cancer.
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Affiliation(s)
- Yibo Wu
- Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China.,Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China
| | - Jiangman Zhao
- Biotecan Medical Diagnostics Co., Ltd, Shanghai 201204, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai 201204, China.,Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China
| | - Shu Dong
- Biotecan Medical Diagnostics Co., Ltd, Shanghai 201204, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai 201204, China
| | - Yu Wang
- Biotecan Medical Diagnostics Co., Ltd, Shanghai 201204, China.,Shanghai Zhangjiang Institute of Medical Innovation, Shanghai 201204, China
| | - Ailu Li
- Department of Gynecology and Obstetrics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China
| | - Yancheng Jiang
- Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China
| | - Zixuan Chen
- Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China
| | - Chunxiao Li
- Department of Gynecology and Obstetrics, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China
| | - Wei Wang
- School of Public Health, Fujian Medical University, Fuzhou, Fujian 350004, China.,Key Laboratory of National Health and Family Planning Commission on Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Public Health Research Center of Jiangnan University, Wuxi, Jiangsu 214064, China
| | - Zhishan Zhang
- Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian 362002, China
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Álvarez-Paredes L, Santibañez M, Galiana A, Rodríguez Díaz JC, Parás-Bravo P, Andrada-Becerra ME, Ruiz García MM, Rodríguez-Ingelmo JM, Portilla-Sogorb J, Paz-Zulueta M. Association of Human Papillomavirus Genotype 16 Viral Variant and Viral Load with Cervical High-grade Intraepithelial Lesions. Cancer Prev Res (Phila) 2019; 12:547-556. [PMID: 31208965 DOI: 10.1158/1940-6207.capr-18-0397] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2018] [Revised: 05/15/2019] [Accepted: 06/11/2019] [Indexed: 11/16/2022]
Abstract
Human papillomavirus genotype 16 (HPV16) is by far the genotype most strongly associated with cervical cancer; viral variant and/or viral load of HPV16 could modulate this association. The objective was to determine the association between the viral variant and viral load of HPV16 and the presence of cervical high-grade lesions. This cross-sectional study included all women in whom HPV infection was found by cervical smear during routine gynecologic health checks. Women with single or multiple HPV16 infections (n = 176) were selected for viral variant and viral load analysis. Smear results were classified using the Bethesda system. HPV types were classified according to the International Agency for Research on Cancer. Odds ratios (OR) with their 95% confidence intervals (CI) were estimated by logistic regression, adjusted for age, immigrant status, and coinfection with other high-risk genotypes. No statistically significant associations were found regarding the detected viral variants. A viral load above the median (>1,367.79 copies/cell) was associated with a significant risk of high-grade epithelial lesion or carcinoma, after adjusting for age, immigrant status, coinfections, and viral variant: (adjusted OR 7.89; 95% CI: 2.75-22.68). This relationship showed a statistically significant dose-response pattern after categorizing by viral load tertiles: adjusted OR for a viral load greater than the third tertile was 17.23 (95% CI: 4.20-70.65), with adjusted linear P trend = 0.001. In patients infected with HPV16, viral load is associated with high-grade intraepithelial lesions or cervical carcinoma. This could be useful as prognostic biomarker of neoplastic progression and as screening for cervical cancer.
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Affiliation(s)
| | - Miguel Santibañez
- Department of Nursing, Nursing Research Group-IDIVAL, University of Cantabria, Cantabria, Spain
| | - Antonio Galiana
- Department of Microbiology, University General Hospital of Elche, Alicante, Spain
| | | | - Paula Parás-Bravo
- Department of Nursing, Nursing Research Group-IDIVAL, University of Cantabria, Cantabria, Spain
| | | | | | | | | | - María Paz-Zulueta
- Department of Nursing, University of Cantabria, Cantabria, Spain. IDIVAL, GI Derecho Sanitario y Bioetica, GRIDES, Cantabria, Spain.
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Liontos M, Kyriazoglou A, Dimitriadis I, Dimopoulos MA, Bamias A. Systemic therapy in cervical cancer: 30 years in review. Crit Rev Oncol Hematol 2019; 137:9-17. [DOI: 10.1016/j.critrevonc.2019.02.009] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 12/09/2018] [Accepted: 02/24/2019] [Indexed: 11/25/2022] Open
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Umukoro C, Makinde O. Perspectives of visual inspection of the cervix with acetic acid as an alternative to Pap smear test as a preventive measure of cervical cancer among female nurses in University College Hospital, Ibadan, Nigeria. JOURNAL OF CANCER RESEARCH AND PRACTICE 2019. [DOI: 10.4103/jcrp.jcrp_10_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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37
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Pańczyszyn A, Boniewska-Bernacka E, Głąb G. Telomeres and Telomerase During Human Papillomavirus-Induced Carcinogenesis. Mol Diagn Ther 2018; 22:421-430. [PMID: 29777397 PMCID: PMC6061425 DOI: 10.1007/s40291-018-0336-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Human papillomaviruses (HPVs) belong to a small spherical virus family and are transmitted through direct contact, most often through sexual behavior. More than 200 types of HPV are known, a dozen or so of which are classified as high-risk viruses (HR HPV) and may contribute to the development of cervical cancer. HPV is a small virus with a capsid composed of L1 and L2 proteins, which are crucial for entry to the cell. The infection begins at the basal cell layer and progresses to involve cells from higher layers of the cervical epithelium. E6 and E7 viral proteins are involved in the process of carcinogenesis. They interact with suppressors of oncogenesis, including p53 and Rb proteins. This leads to DNA replication and intensive cell divisions. The persistent HR HPV infection leads to the development of dysplasia and these changes may progress to invasive cancer. During the initial stage of carcinogenesis, telomeres shorten until telomerase activates. The activation of telomerase, the enzyme necessary to extend chromosome ends (telomeres) is the key step in cell immortalization. Analyzing the expression level of hTERT and hTERC genes encoding telomerase and telomere length measurement may constitute new markers of the early carcinogenesis.
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Affiliation(s)
- Anna Pańczyszyn
- Department of Biotechnology and Molecular Biology, University of Opole, ul. Kominka 6, 45-035, Opole, Poland.
| | - Ewa Boniewska-Bernacka
- Department of Biotechnology and Molecular Biology, University of Opole, ul. Kominka 6, 45-035, Opole, Poland
| | - Grzegorz Głąb
- Public Higher Medical Professional School in Opole, Opole, Poland
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38
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Cheng MA, Farmer E, Huang C, Lin J, Hung CF, Wu TC. Therapeutic DNA Vaccines for Human Papillomavirus and Associated Diseases. Hum Gene Ther 2018; 29:971-996. [PMID: 29316817 DOI: 10.1089/hum.2017.197] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Human papillomavirus (HPV) has long been recognized as the causative agent of cervical cancer. High-risk HPV types 16 and 18 alone are responsible for over 70% of all cases of cervical cancers. More recently, HPV has been identified as an etiological factor for several other forms of cancers, including oropharyngeal, anogenital, and skin. Thus, the association of HPV with these malignancies creates an opportunity to control these HPV lesions and HPV-associated malignancies through immunization. Strategies to prevent or to therapeutically treat HPV infections have been developed and are still pushing innovative boundaries. Currently, commercial prophylactic HPV vaccines are widely available, but they are not able to control established infections or lesions. As a result, there is an urgent need for the development of therapeutic HPV vaccines, to treat existing infections, and to prevent the development of HPV-associated cancers. In particular, DNA vaccination has emerged as a promising form of therapeutic HPV vaccine. DNA vaccines have great potential for the treatment of HPV infections and HPV-associated cancers due to their safety, stability, simplicity of manufacturability, and ability to induce antigen-specific immunity. This review focuses on the current state of therapeutic HPV DNA vaccines, including results from recent and ongoing clinical trials, and outlines different strategies that have been employed to improve their potencies. The continued progress and improvements made in therapeutic HPV DNA vaccine development holds great potential for innovative ways to effectively treat HPV infections and HPV-associated diseases.
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Affiliation(s)
- Max A Cheng
- 1 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland
| | - Emily Farmer
- 1 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland
| | - Claire Huang
- 1 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland
| | - John Lin
- 1 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland
| | - Chien-Fu Hung
- 1 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland.,2 Department of Oncology, Johns Hopkins Medical Institutions , Baltimore, Maryland
| | - T-C Wu
- 1 Department of Pathology, Johns Hopkins Medical Institutions , Baltimore, Maryland.,2 Department of Oncology, Johns Hopkins Medical Institutions , Baltimore, Maryland.,3 Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions , Baltimore, Maryland.,4 Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions , Baltimore, Maryland
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39
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Rosales C, Rosales R. Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections. Vaccines (Basel) 2017. [DOI: 10.5772/intechopen.69548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
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40
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Naseem A, Bhat ZI, Kalaiarasan P, Kumar B, Gandhi G, Rizvi MMA. Genetic and epigenetic alterations affecting PARK-2 expression in cervical neoplasm among North Indian patients. Tumour Biol 2017. [DOI: 10.1177/1010428317703635] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
- Afreen Naseem
- Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
| | - Zafar Iqbal Bhat
- Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
| | | | - Bhupender Kumar
- Department of Biochemistry, Institute of Home Economics, University of Delhi, New Delhi, India
| | - Gauri Gandhi
- Department of Obstetrics & Gynecology, Lok Nayak Jayaprakash Hospital (LNJP), Maulana Azad Medical College (MAMC), New Delhi, India
| | - M. Moshahid Alam Rizvi
- Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India
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41
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Bronowicka-Kłys DE, Roszak A, Pawlik P, Sajdak S, Sowińska A, Jagodziński PP. Transcript levels of ten-eleven translocation type 1-3 in cervical cancer and non-cancerous cervical tissues. Oncol Lett 2017; 13:3921-3927. [PMID: 28521490 DOI: 10.3892/ol.2017.5930] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Accepted: 01/26/2017] [Indexed: 11/06/2022] Open
Abstract
Decreased expression of ten-eleven translocation (TET1, TET2 and TET3) proteins has been reported in various types of cancer. However, the expression levels of TET proteins in cervical cancer (CC) remain to be elucidated. The present study determined the levels of TET1, TET2 and TET3 transcripts in cancerous (n=80) and non-cancerous cervical tissues (n=41). The results revealed a significant reduction in TET1 transcripts (P=0.0000001) in cervical tissue samples from patients with primary CC compared with samples from control patients. Significantly decreased TET1 transcript levels, as compared to non-cancerous cervical tissues, were also observed in tissue samples with the following characteristics: Stage I (P=0.016), II (P<0.0001), III (P=0.00007) and grade of differentiation G1 (P=0.026), G2 (P=0.00006), G3 (P=0.0007) and Gx (P=0.0004) and squamous histological type (P<0.00001). TET1 transcript levels were significantly lower in patients aged 45-60 years (P=0.0002) and patients age >60 years (P=0.003), as compared with non-cancerous cervical tissues. TET2 transcript levels were lower in cervical cancer tissues classified as stage II (P=0.043) and TET3 transcript levels were lower in stage III samples (P=0.010), tissue samples with a grade of differentiation of G3 (P=0.025) and tissue with squamous type histology (P=0.047), all compared with non-cancerous cervical tissues. The present study demonstrated a significantly reduced level of TET1 transcripts in cancerous cervical tissues, as compared with non-cancerous tissues. Furthermore, decreased TET1-3 transcript levels were identified when patients with CC were stratified by clinicopathological variables, as compared with non-cancerous cervical tissues.
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Affiliation(s)
- Dorota Ewa Bronowicka-Kłys
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland
| | - Andrzej Roszak
- Department of Radiotherapy and Gynecological Oncology, Greater Poland Cancer Center, Poznań 61-866, Poland.,Department of Electroradiology, Poznań University of Medical Sciences, Poznań 61-866, Poland
| | - Piotr Pawlik
- Division of Gynecological Surgery, Poznań University of Medical Sciences, Poznań 60-535, Poland
| | - Stefan Sajdak
- Division of Gynecological Surgery, Poznań University of Medical Sciences, Poznań 60-535, Poland
| | - Anna Sowińska
- Department of Computer Science and Statistics, Poznań University of Medical Sciences, Poznań 60-529, Poland
| | - Paweł Piotr Jagodziński
- Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań 60-781, Poland
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42
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Daniel M, Cătană A, Popp RA, Dumitraș DE, Stamatian F, Buzoianu AD, Rotar IC. Genetic polymorphisms of glutathione S transferase and cervical intraepithelial neoplasia. REV ROMANA MED LAB 2016. [DOI: 10.1515/rrlm-2016-0036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Aim: The present study aim to analyze the relationship between GST M/T genotypes of glutathione S-transferases and cervical intraepithelial neoplasia.
Materials and Methods: A prospective case-control study has been designed including 69 cases with different degrees of cervical dysplasia and 107 controls. All patients had been examined colposcopically. For every patient both cervical and blood specimen have been obtained. The peripheral blood was used for GST M/T genotyping. The statistical analysis was performed using OR and chi-square at a level of significance inferior to 0.05.
Results: No statistically significant differences had been found between cases and controls for GST T-/M- geno-type (T-/M-, χ2=0.03, p= 0.8610) and T+/M+ χ2=0.65, p = 0.4197. Patients with in situ carcinoma had significant GST genotype association for T-/M+ genotype (OR=4.66, CI 95% [0.6528,24.9725], χ2=4.6, p=0.0314) and for T+/M- genotype (OR=0.12, CI 95% [0.0027,0.9465], χ2=0.05, p=0.0219).
Conclusion: The combination of GST genotypes can be included in a predictive score for patients with cervical carcinoma.
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Affiliation(s)
- Mureșan Daniel
- Department of Mother and the Baby, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj Napoca, Romania
| | - Andreea Cătană
- Department of Molecular Sciences, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj Napoca, Romania
| | - Radu Anghel Popp
- Department of Molecular Sciences, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj Napoca, Romania
| | - Diana Elena Dumitraș
- Department of Economic Sciences, University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca, Romania
| | - Florin Stamatian
- 1 st Clinic of Obstetrics and Gynecology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj Napoca, Romania
| | - Anca Dana Buzoianu
- Department of Pharmacology, Toxicology and Clinical Pharmacology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
| | - Ioana Cristina Rotar
- 1 st Clinic of Obstetrics and Gynecology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj Napoca, Romania
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Abstract
Cancer has been recognized for thousands of years. Egyptians believed that cancer occurred at the will of the gods. Hippocrates believed human disease resulted from an imbalance of the four humors: blood, phlegm, yellow bile, and black bile with cancer being caused by excess black bile. The lymph theory of cancer replaced the humoral theory and the blastema theory replaced the lymph theory. Rudolph Virchow was the first to recognize that cancer cells like all cells came from other cells and believed chronic irritation caused cancer. At the same time there was a belief that trauma caused cancer, though it never evolved after many experiments inducing trauma. The birth of virology occurred in 1892 when Dimitri Ivanofsky demonstrated that diseased tobacco plants remained infective after filtering their sap through a filter that trapped bacteria. Martinus Beijerinck would call the tiny infective agent a virus and both Dimitri Ivanofsky and Marinus Beijerinck would become the fathers of virology. Not to long thereafter, Payton Rous founded the field of tumor virology in 1911 with his discovery of a transmittable sarcoma of chickens by what would come to be called Rous sarcoma virus or RSV for short. The first identified human tumor virus was the Epstein-Barr virus (EBV), named after Tony Epstein and Yvonne Barr who visualized the virus particles in Burkitt's lymphoma cells by electron microscopy in 1965. Since that time, many viruses have been associated with carcinogenesis including the most studied, human papilloma virus associated with cervical carcinoma, many other anogenital carcinomas, and oropharyngeal carcinoma. The World Health Organization currently estimates that approximately 22% of worldwide cancers are attributable to infectious etiologies, of which viral etiologies is estimated at 15-20%. The field of tumor virology/viral carcinogenesis has not only identified viruses as etiologic agents of human cancers, but has also given molecular insights to all human cancers including the oncogene activation and tumor suppressor gene inactivation.
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Affiliation(s)
- A J Smith
- Texas Tech University Health Sciences Center, Lubbock, TX, United States
| | - L A Smith
- Texas Tech University Health Sciences Center, Lubbock, TX, United States.
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Metformin targeting autophagy overcomes progesterone resistance in endometrial carcinoma. Arch Gynecol Obstet 2016; 294:1055-1061. [PMID: 27402506 DOI: 10.1007/s00404-016-4148-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2015] [Accepted: 07/06/2016] [Indexed: 10/21/2022]
Abstract
PURPOSE Metformin is the most prescribed anti-diabetic medication worldwide because of its proven efficacy and limited side effects. In this study, the significant anticancer effect of metformin was investigated in both endometrial carcinoma and progesterone-resistant endometrial carcinoma cells. METHODS We tested the growth inhibition assay using MTT cell proliferation, cell cycle assay, apoptosis assessment with flow cytometry using propidium iodide and Annexin V, and autophagy protein expression with western blot analysis. RESULTS Metformin inhibited the growth of cancer cells with different concentrations in a dose- and time-dependent manner. Moreover, the inhibition properties observed as a function of increased concentrations of metformin were markedly augmented when the medication was administered in the progesterone-resistant Ishikawa cells, even with a dose as low as 10 mM. The early and late phases of apoptosis were enhanced in the metformin-treated tumour cells that were analyzed. For the Ishikawa cells, the expression of p-AMPK, LC-3, and beclin1 was upregulated after treatment, whereas the AMPK levels were not modulated. Furthermore, for the Ishikawa-PR cells, the protein levels were similarly upregulated. Finally, we observed that the three proteins showed much more variability in Ishikawa-PR cells than in Ishikawa cells. CONCLUSION The application of metformin to target autophagy in endometrial cancer cells provides a new potential treatment for progesterone-resistant endometrial carcinoma.
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Wang GQ, Zhao WH, Zhao XX, Zhang J, Nan KJ. Association between IL-27 2905T/G genotypes and the risk and survival of cervical cancer: a case-control study. Biomarkers 2016; 21:272-5. [PMID: 26848614 DOI: 10.3109/1354750x.2015.1134665] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
BACKGROUND Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. PATIENTS AND METHODS A case-control study was conducted to investigate the possible associations of IL-27 gene polymorphisms with susceptibility to cervical cancer and clinical outcome. RESULTS Our results suggested that the IL-27 2905T/G was significantly associated with a decreased risk of cervical cancer. Further analysis showed IL-27 2905T/G genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the IL-27 2905T/G genotypes were statistically significantly associated with the survival in cervical cancer patients. CONCLUSION Our results showed that the IL-27 2905T/G genotypes were associated with decreased the susceptibility and development of cervical cancer in Chinese Han population.
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Affiliation(s)
- Guo-Qing Wang
- a Department of Internal Medicine-Oncology , the First Affiliated Hospital of Xi 'an Jiaotong University , Shaanxi , China .,b Department of Gynecologic Tumor and
| | - Wen-Hui Zhao
- c Department of Anesthesiology , Shaanxi Province Tumor Hospital , Shaanxi , China
| | | | - Jun Zhang
- b Department of Gynecologic Tumor and
| | - Ke-Jun Nan
- a Department of Internal Medicine-Oncology , the First Affiliated Hospital of Xi 'an Jiaotong University , Shaanxi , China
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46
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Bava SV, Thulasidasan AKT, Sreekanth CN, Anto RJ. Cervical cancer: A comprehensive approach towards extermination. Ann Med 2016; 48:149-61. [PMID: 26911282 DOI: 10.3109/07853890.2016.1145796] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Human Papilloma Virus (HPV) is one of the most common sexually transmitted pathogen, globally. Oncogenic types of HPV are the causative agents of many neoplastic diseases, including cervical cancer, which ranks as the most common cancer affecting females in developing countries. HPV infection of the cervical epithelium and the subsequent integration of viral DNA into the host genome are the major risk factors for cervical cancer. The scientific discovery of HPV as the causal agent of cervical cancer has led to the development of HPV-based diagnostic tools. Prophylactic vaccines, based on the oncogenic HPV type virus-like particles have been introduced in several developed countries as a preliminary preventive approach. Nevertheless, it remains a continuous threat to women in developing countries, where the prophylactic vaccines are unaffordable and organized screening programmes are lacking. This warrants implementation of prevention strategies that will reduce cervical cancer-related mortality. In this review, we have discussed molecular pathogenesis of HPV infection and the risk factors associated with it. The diagnosis, treatment and prevention strategies of HPV-related cervical cancer have also been discussed.
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Affiliation(s)
- Smitha V Bava
- a Department of Biotechnology , University of Calicut , Malappuram , Kerala , India
| | - Arun Kumar T Thulasidasan
- b Cancer Research Program, Division of Cancer Research , Rajiv Gandhi Centre for Biotechnology , Thiruvananthapuram , Kerala , India
| | - Chanickal N Sreekanth
- b Cancer Research Program, Division of Cancer Research , Rajiv Gandhi Centre for Biotechnology , Thiruvananthapuram , Kerala , India
| | - Ruby John Anto
- b Cancer Research Program, Division of Cancer Research , Rajiv Gandhi Centre for Biotechnology , Thiruvananthapuram , Kerala , India
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Shi J, Yuan M, Liu S, Duan X, Chen J. Correlation of IL-27 genetic polymorphisms with the risk and survival of cervical cancer in a Chinese Han population. Tumour Biol 2015; 37:6875-9. [PMID: 26662568 DOI: 10.1007/s13277-015-4512-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 11/25/2015] [Indexed: 12/18/2022] Open
Abstract
Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. However, there are no data about the role of IL-27 polymorphism in the development of cervical cancer. A hospital-based case-control study was conducted in 380 patients with cervical cancer and 380 healthy controls to investigate the possible associations of IL-27 gene polymorphisms (-964A/G, 2905T/G, and 4730T/C), with susceptibility to cervical cancer and clinical outcome. Our results suggested that the IL-27 2905T/G was significantly associated with a decreased risk of cervical cancer (TG vs. TT, odds ratio (OR) = 0.77; 95 % confidence interval (CI) = 0.60-0.86; GG vs. TT, OR = 0.95; 95 % CI = 0.72-0.96; TG+GG vs. TT, OR = 0.87; 95 % CI = 0.65-0.94). However, the genotype and allele frequencies of IL-27 (-964A/G and 4730T/C) polymorphisms in cervical cancer patients were not significantly different from controls. Further analysis showed IL-27 2905T/G genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the IL-27 2905T/G genotypes were statistically significantly associated with the survival in cervical cancer patients. Our results showed that the IL-27 2905T/G genotypes were associated with decreased susceptibility and development of cervical cancer in Chinese Han population.
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Affiliation(s)
- Jian Shi
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China.
| | - Meng Yuan
- College of Science and Technology, Yichang, 443002, Hubei, China
| | - Shuang Liu
- Department of Pathology, Bethune International Peace Hospital, Shijiazhuang, 050000, Hebei, China
| | - Xiaoyang Duan
- Department of Medical Oncology, Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China
| | - Juan Chen
- Xingtai National Hospital, Xingtai, 054000, Hebei, China
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Catarino R, Petignat P, Dongui G, Vassilakos P. Cervical cancer screening in developing countries at a crossroad: Emerging technologies and policy choices. World J Clin Oncol 2015; 6:281-290. [PMID: 26677441 PMCID: PMC4675913 DOI: 10.5306/wjco.v6.i6.281] [Citation(s) in RCA: 155] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2015] [Revised: 09/03/2015] [Accepted: 10/27/2015] [Indexed: 02/06/2023] Open
Abstract
Cervical cancer (CC) represents the fourth most common malignancy affecting women all over the world and is the second most common in developing areas. In these areas, the burden from disease remains important because of the difficulty in implementing cytology-based screening programmes. The main obstacles inherent to these countries are poverty and a lack of healthcare infrastructures and trained practitioners. With the availability of new technologies, researchers have attempted to find new strategies that are adapted to low- and middle-income countries (LMIC) to promote early diagnosis of cervical pathology. Current evidence suggests that human papillomavirus (HPV) testing is more effective than cytology for CC screening. Therefore, highly sensitive tests have now been developed for primary screening. Rapid molecular methods for detecting HPV DNA have only recently been commercially available. This constitutes a milestone in CC screening in low-resource settings because it may help overcome the great majority of obstacles inherent to previous screening programmes. Despite several advantages, HPV-based screening has a low positive predictive value for CC, so that HPV-positive women need to be triaged with further testing to determine optimal management. Visual inspection tests, cytology and novel biomarkers are some options. In this review, we provide an overview of current and emerging screening approaches for CC. In particular, we discuss the challenge of implementing an efficient cervical screening adapted to LMIC and the opportunity to introduce primary HPV-based screening with the availability of point-of-care (POC) HPV testing. The most adapted screening strategy to LMIC is still a work in progress, but we have reasons to believe that POC HPV testing makes part of the future strategies in association with a triage test that still needs to be defined.
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Abstract
Multiple studies have demonstrated an increased risk for extra-intestinal cancers in inflammatory bowel disease (IBD) patients, mainly from treatment modalities. Prominent cancers that are related to IBD treatment include the following: lymphoproliferative disorders associated with thiopurine use, hepatosplenic T cell lymphoma primarily in younger male patients on thiopurines and anti-tumor necrosis factor (TNF) agents, non-melanoma skin cancers in patients treated with thiopurines and anti-TNF agents, and melanomas in patients who are on monotherapy with anti-TNF agents. In addition, women with IBD may have higher rates of cervical dysplasia and cervical cancer. The focus of this review is to provide a comprehensive overview on extra-intestinal cancers in IBD patients and how to monitor for these malignancies.
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Affiliation(s)
- H Sifuentes
- Department of Gastroenterology and Hepatology, Georgia Regents University, 1120 15th Street, AD 2226, Augusta, GA, 30912, USA.
| | - S Kane
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.
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Kurmyshkina OV, Kovchur PI, Volkova TO. 'Drawing' a Molecular Portrait of CIN and Cervical Cancer: a Review of Genome-Wide Molecular Profiling Data. Asian Pac J Cancer Prev 2015; 16:4477-87. [DOI: 10.7314/apjcp.2015.16.11.4477] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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