scholarly journals The development of novel HPV Drugs by HDAC inhibitor based upon applied bioinformatics tool and their specialized algorithm

2019 ◽  
Vol 9 (5) ◽  
pp. 4428-4432

The HPV infection, which is the sole cause of cervical cancer, is a malicious threat for developing countries, for instance, Indonesia. Drug for coping HPV infection have been sold in the market namely SAHA or Vorinostat. Mainly, it works by inhibiting the Human Deacetylase Enzyme (HDAC) class II Homo sapiens. However, due to the contradicting report on its efficacy, a novel drug should be developed to remedy the resistance problem. Some groups have successfully developed novel HDAC inhibitors, based upon computational drug design.

2020 ◽  
Vol 14 (01) ◽  
pp. 97-103
Author(s):  
Fatimah S Alhamlan ◽  
Hadeel H Khayat ◽  
Dalia A Obeid ◽  
Asma M Tulba ◽  
Teejan S Baduwais ◽  
...  

Introduction: Human papillomavirus (HPV) infection is typically critical in the oncogenesis of cervical cancer. However, available HPV detection kits differ in their ability and sensitivity to detect various types of HPV, and this variability has led to inconsistencies in the reporting of the geographic prevalence of HPV types, especially in developing countries. Here, we compared results of the recently developed GenoFlow HPV array test, which detects 33 HPV genotypes, to those of the well-established reverse line blot (RLB) assay, which detects 23 HPV types. Methodology: In total, 608 cervical specimens with cytology results ranging from normal to cancer were collected using an endocervical brush from women attending outpatient clinics in Riyadh, Saudi Arabia. Results: Sixty-nine specimens (11%) were positive for HPV. HPV genotype detection using the GenoFlow test had a sensitivity of 62% and a specificity of 100%. Overall agreement between the two HPV genotyping methods was 97%, with a concordance rate of 95%. Among the GenoFlow test results, 2% indicated additional HPV types that were not detected in the RLB assay, whereas the GenoFlow test missed 0.3% of the HPV types that were detected by the RLB; however, both tests were in agreement in detecting all major HPV types. Conclusion: The GenoFlow test was reliable, with results comparable to the RLB test. However, because the GenoFlow test is less labor-intensive and takes less total time (3 hours), it is a promising, affordable alternative to the RLB for HPV diagnosis and screening programs.


2015 ◽  
Vol 4 (1) ◽  
pp. 21-25
Author(s):  
Meichang Ai

Abstract Cervical cancer is one of the most common malignant tumors that threaten women’s life and health in both developed and developing countries. Diet and smoking are independent etiological factors of cervical cancer. Among many independent etiological factors, human papillomavirus (HPV) infection is the most important one. HPV infection is universal among women of appropriate ages, and only persistent HPV infection is considered necessary to cause cervical cancer.


2018 ◽  
Vol 23 (1) ◽  
pp. 1 ◽  
Author(s):  
Arli Aditya Parikesit ◽  
Didik Huswo Utomo ◽  
Nihayatul Karimah

Cervical cancer is one of the primary causes of mortality in women due to human papilloma virus (HPV) infection. The fingerprint of an HPV infection could be detected using a long non-coding RNA (lncRNA) biomarker, enabling it to be utilized in molecular diagnostics. The primary structure or sequences of RNA should be annotated within conventional bioinformatics tools. Therefore, this study aimed to determine the fine-grained 2D and 3D structures of lncRNA PVT1 and its respective siRNA inhibitors. lncRNA PVT1 sequences from Homo sapiens, Mus musculus, and Rattus norvegicus were retrieved from Genbank (NCBI). Prediction of the 2D structure and analysis of the interactions of the lncRNA and siRNA were performed using the Vienna RNA package. The 3D structure of the RNA was computed using the SimRNA and ModeRNA software programs. The results showed that lncRNA PVT1 from H. sapiens and M. musculus had a conserved region. However, the lncRNA from both H. sapiens and M. musculus showed a low conserved region, and the 2D structure could not be determined; thus, the annotation and 2D model focused only on H. sapiens. Both of their lncRNA PVT1 also had a short half-life in the cell. Based on the 3D modeling pipeline, the 3D model of lncRNA PVT1 showed the stability and possible function as molecules, while the PVT1 siRNA-lncRNA interaction analysis revealed that the molecules could bind well. Based on these findings, the structures of both lncRNA PVT1 and its siRNA have the potential to be utilized as biomarkers.


Author(s):  
Kun Lee ◽  
Jingyi Si ◽  
Ricai Han ◽  
Wei Zhang ◽  
Bingbing Tan ◽  
...  

There are more supports for the view that human papillomavirus (HPV) infection might be an etiological factor in the development of cervical cancer when the association of persistent condylomata is considered. Biopsies from 318 cases with squamous cell carcinoma of uterine cervix, 48 with cervical and vulvar condylomata, 14 with cervical intraepithelial neoplasia (CIN), 34 with chronic cervicitis and 24 normal cervical epithelium were collected from 5 geographic regions of China with different cervical cancer mortalities. All specimens were prepared for Dot blot, Southern blot and in situ DNA-DNA hybridizations by using HPV-11, 16, 18 DNA labelled with 32P and 3H as probes to detect viral homologous sequences in samples. Among them, 32 cases with cervical cancer, 27 with condyloma and 10 normal cervical epitheliums were randomly chosen for comparative EM observation. The results showed that: 1), 192 out of 318 (60.4%) cases of cervical cancer were positive for HPV-16 DNA probe (Table I)


Author(s):  
Lifang Zhang ◽  
Yu Zhao ◽  
Quanmei Tu ◽  
Xiangyang Xue ◽  
Xueqiong Zhu ◽  
...  

Background: Cervical cancer induced by infection with human papillomavirus (HPV) remains a leading cause of mortality for women worldwide although preventive vaccines and early diagnosis have reduced morbidity and mortality. Advanced cervical cancer can only be treated with either chemotherapy or radiotherapy but outcomes are poor. The median survival for advanced cervical cancer patients is only 16.8 months. Methods: We undertook a structural search of peer-reviewed published studies based on 1). Characteristics of programmed cell death ligand-1/programmed cell death-1(PD-L1/PD-1) expression in cervical cancer and upstream regulatory signals of PD-L1/PD-1 expression, 2). The role of the PD-L1/PD-1 axis in cervical carcinogenesis induced by HPV infection and 3). Whether the PD-L1/PD-1 axis has emerged as a potential target for cervical cancer therapies. Results: One hundred and twenty-six published papers were included in the review, demonstrating that expression of PD-L1/PD-1 is associated with HPV-caused cancer, especially with HPV 16 and 18 which account for approximately 70% of cervical cancer cases. HPV E5/E6/E7 oncogenes activate multiple signaling pathways including PI3K/AKT, MAPK, hypoxia-inducible factor 1α, STAT3/NF-kB and MicroRNAs, which regulate PD-L1/PD-1 axis to promote HPV-induced cervical carcinogenesis. The PD-L1/PD-1 axis plays a crucial role in immune escape of cervical cancer through inhibition of host immune response. creating an "immune-privileged" site for initial viral infection and subsequent adaptive immune resistance, which provides a rationale for therapeutic blockade of this axis in HPV-positive cancers. Currently, Phase I/II clinical trials evaluating the effects of PD-L1/PD-1 targeted therapies are in progress for cervical carcinoma, which provide an important opportunity for the application of anti-PD-L1/anti-PD-1 antibodies in cervical cancer treatment. Conclusion: Recent research developments have led to an entirely new class of drugs using antibodies against the PD-L1/PD-1 thus promoting the body’s immune system to fight the cancer. The expression and roles of the PD-L1/ PD-1 axis in the progression of cervical cancer provide great potential for using PD-L1/PD-1 antibodies as a targeted cancer therapy.


2020 ◽  
Vol 26 (18) ◽  
pp. 2073-2086
Author(s):  
Saule Balmagambetova ◽  
Andrea Tinelli ◽  
Ospan A. Mynbaev ◽  
Arip Koyshybaev ◽  
Olzhas Urazayev ◽  
...  

High-risk human papillomavirus strains are widely known to be the causative agents responsible for cervical cancer development. Aggregated damage caused by papillomaviruses solely is estimated in at least 5% of all malignancies of the human body and 16% in cancers that affect the female genital area. Enhanced understanding of the complex issue on how the high extent of carcinogenicity is eventually formed due to the infection by the Papoviridae family would contribute to enhancing current prevention strategies not only towards cervical cancer, but also other HPV associated cancers. This review article is aimed at presenting the key points in two directions: the current cervical cancer prevention and related aspects of HPV behavior. Virtually all applied technologies related to HPV diagnostics and screening programs, such as HPV tests, colposcopy-based tests (VIA/VILI), conventional and liquid-based cytology, currently available are presented. Issues of availability, advantages, and drawbacks of the screening programs, as well as vaccination strategies, are also reviewed in the article based on the analyzed sources. The current point of view regarding HPV is discussed with emphasis on the most problematic aspect of the HPV family concerning the observed increasing number of highly carcinogenic types. Present trends in HPV infection diagnostics throughout the human fluids and tissues are also reported, including the latest novelties in this field, such as HPV assay/self-sample device combinations. Besides, a brief outline of the related prevention issues in Kazakhstan, the leading country of Central Asia, is presented. Kazakhstan, as one of the post-soviet middle-income countries, may serve as an example of the current situation in those terrains, concerning the implementation of globally accepted cervical cancer prevention strategies. Along with positive achievements, such as the development of a nationwide screening program, a range of drawbacks is also analyzed and discussed.


2020 ◽  
Vol 26 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.


BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e050113
Author(s):  
Sneha Sethi ◽  
Brianna Poirier ◽  
Karen Canfell ◽  
Megan Smith ◽  
Gail Garvey ◽  
...  

RationaleIndigenous peoples carry a disproportionate burden of infectious diseases and cancers and are over-represented among the socially disadvantaged of most countries. Human papillomavirus (HPV) is a risk factor and causative agent of cervical, oropharyngeal and other cancers. Recent literature shows evidence of Indigenous populations being at increased risk of HPV infections and its associated cancers.ObjectiveThis is a qualitative systematic review. The objective of this study was to explore the experiences and barriers Indigenous women face in relation to HPV awareness, knowledge and cervical screening, in order to better understand factors that may mitigate against or facilitate prevention efforts for HPV infection and associated cancers.MethodsTwo investigators independently searched MEDLINE, PubMed, SCOPUS and Web of Science databases (for articles published from inception until 30 June 2020) using a prespecified search strategy to identify qualitative studies on narratives of Indigenous women regarding HPV infection awareness, knowledge and cervical screening, across all geographic and income-level settings. Using a ‘meta-study’ approach, a social ecological model of cervical screening, infection and associated cancer prevention among Indigenous populations was formulated.ResultsFive core themes were identified and formulated within the social ecological model; intrapersonal factors, interpersonal factors, institutional/organisational factors, sociocultural/community factors and public policy. These collectively formed the proposed social ecological model of HPV infection awareness and cervical cancer prevention among Indigenous women. This model has been synthesised by taking into account personal stories of Indigenous women and healthcare workers, thus offering a more nuanced, organised, structured and culturally sensitive approach to policy translation.ConclusionThe social ecological model of HPV infection awareness and cervical cancer prevention among Indigenous women offers a holistic and practical approach for Indigenous health policy makers. It clearly addresses the high risk of Indigenous populations at a global level in experience of both HPV infection and HPV-related cancers.PROSPERO registration numberCRD42020207643.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 714
Author(s):  
Matthias Läsche ◽  
Horst Urban ◽  
Julia Gallwas ◽  
Carsten Gründker

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.


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