INHIBITORY ACTIVITY OF NATURAL ACTIVE COMPOUNDS AGAINST HUMAN PAPILLOMA VIRUS PSEUDOVIRUS AND NOVEL DOSAGE FORM FOR USE THEREWITH

2013 ◽  
Vol 25 (03) ◽  
pp. 1350036
Author(s):  
Ming-Kuang Shih ◽  
Yu-Chou Chao ◽  
Ying-Chu Shih ◽  
Kuo-Kuei Huang

Cervical cancer is a common cancer amongst women, accounting for 9% of female cancer death. There are certain risk factors for the development of cervical cancer, in which human papilloma virus (HPV) infection is believed to be a significant cause. This study aimed at evaluating the inhibitory activity of active compounds derived from Chinese herbs against HPV and the underlying mechanism. First, conventional screening platform which uses HeLa cell line in conjunction with MTT assay was used to evaluate the cytotoxicity of these natural compounds. Then, a novel screening platform, in which the HeLa cells were infected by HPV 16 pseudoviruses expressing green fluorescent protein, was employed to screen for active compounds capable of inhibiting the HPV 16 pseudovirus infection. Two compounds, baicalein and gallic acid, was found to exhibit significant inhibitory activity against HPV 16 pseudovirus with IC50 values of 8.2 and 8.9 μg/ml, respectively. In addition, these two compounds showed insignificant cytotoxicity on HeLa cell line. Screening experiments using a novel dosage form consisting of a hydrophilic PU foam and aquagel indicated that the aquagel also inhibited the HPV 16 pseudovirus infection. In sum, the natural active compounds and novel dosage form proposed by the present study imply a potential treatment for vaginal administration to prevent HPV infection and the diseases it caused.

2019 ◽  
Vol 45 (2) ◽  
pp. 86-92
Author(s):  
Munira Jahan ◽  
Tania Islam ◽  
Sharmin Sultana ◽  
Monira Pervin ◽  
Prof. Ashrafunnessa ◽  
...  

Background: Cervical cancer is one of the most common types of cancer affecting women worldwide. Persistent HPV infection plays a major role in cervical cancer. The risk of cervical cancer has increased in parallel with the incidence of certain genotypes of human papilloma virus (HPV). Methods: The study was aimed to detect the distribution of HPV genotypes among cervical cancer patients from a specialized hospital in Dhaka, Bangladesh. HPV DNA testing was done by polymerase chain reaction (PCR) using SPF-10 broad-spectrum primers followed by genotyping by reverse hybridization using the INNO-LIPA genotyping system at the Department of Virology, Bangabandhu Sheikh Mujib Medical University, Dhaka. Results: HPV 16 was more prevalent (72.0%) in cervical cancer patients from Bangladesh followed by type 18 (6.0%) and 45 (2.0%). Genotype 16 and 18 alone and as co-infection were detected in 88.0% cases. Multiple HPV infection was found in 20% patients. Along with high risk (HR) HPV 16, 18 and 45 HR HPV 56, 39, 31 and 58 were also prevalent in multiple infections. Conclusion: Thus the study concluded that HR HPV 16 and HPV 18 were more prevalent genotypes among cervical cancer patients in a specialised hospital in Bangladesh. Along with HR HPV 16 and HPV 18, HR HPV 45, 56, 39, 31 and 58 were also prevalent Bangladesh Med Res Counc Bull 2019; 45: 86-92


2019 ◽  
Vol 7 (5) ◽  
pp. 338-344
Author(s):  
Miao Li ◽  
Qing-Fan Yang ◽  
Qian Cao ◽  
Jian Tang ◽  
Yu Gao ◽  
...  

Abstract Background and aim This cross-sectional study investigated the prevalence and risk factors of high-risk human papilloma virus (HPV) infection, especially types 16 and 18, and cervical neoplasia in female Inflammatory bowel disease (IBD) patients. Methods From July 2014 to January 2017, sexually active, female, Chinese IBD patients (21–60 years) and age-matched controls underwent cervical ThinPrep cytology testing (TCT) and high-risk HPV-DNA detection, and completed questionnaires about awareness of cervical cancer and HPV. Cervical dysplasia was categorized as cervical intraepithelial neoplasia (CIN) 1, 2 and 3. Results Of 124 IBD patients (30 ulcerative colitis and 94 Crohn’s disease), 17 (13.7%) had high-risk HPV among whom 9 (7.3%) had HPV 16/18 infection and 4 (3.2%) had cervical CIN (3 CIN 3, 1 CIN 1) by pathology. Among 372 controls, 33 (8.9%) had high-risk HPV and only 1 (0.3%) had HPV 16 infection. Cervical TCT detected atypical squamous cells of unknown significance in one control; no control had CIN. The HPV 16/18 infection rate and CIN prevalence were significantly higher in IBD patients than controls (both P < 0.001). The HPV-infection rate was higher in patients administered methotrexate [P = 0.005, odds ratio (95% confidence interval) 4.76 (1.471–15.402)] or more than two immunosuppressants [P = 0.013, odds ratio (95% confidence interval) 3.64 (1.255–10.562)]. Thiopurine, steroid, infliximab and disease behavior/location were not associated with HPV infection. Only 29.3% of patients had undergone cervical-cancer screening. Awareness of HPV infection and HPV-related cervical cancer was poor (28.2%). Conclusions Female IBD patients are at increased risk of high-risk HPV infection and cervical neoplasia, which may be associated with immunosuppressants. Education and routine follow-up with HPV-DNA testing and TCT are recommended, especially in female Chinese IBD patients.


2020 ◽  
Vol 16 ◽  
Author(s):  
Jamshed Iqbal ◽  
Ayesha Basharat ◽  
Sehrish Bano ◽  
Syed Mobasher Ali Abid ◽  
Julie Pelletier ◽  
...  

Aims: The present study was conducted to examine the inhibitory effects of synthesized sulfonylhydrazones on the expression of CD73 (ecto-5′-NT). Background: CD73 (ecto-5′-NT) represents the most significant class of ecto-nucleotidases which are mainly responsible for dephosphorylation of adenosine monophosphate to adenosine. Inhibition of CD73 played an important role in the treatment of cancer, autoimmune disorders, precancerous syndromes, and some other diseases associated with CD73 activity. Objective: Keeping in view the significance of CD73 inhibitor in the treatment of cervical cancer, a series of sulfonylhydrazones (3a-3i) derivatives synthesized from 3-formylchromones were evaluated. Methods: All sulfonylhydrazones (3a-3i) were evaluated for their inhibitory activity towards CD73 (ecto-5′-NT) by the malachite green assay and their cytotoxic effect was investigated on HeLa cell line using MTT assay. Secondly, most potent compound was selected for cell apoptosis, immunofluorescence staining and cell cycle analysis. After that, CD73 mRNA and protein expression were analyzed by real-time PCR and Western blot. Results: Among all compounds, 3h, 3e, 3b, and 3c were found the most active against rat-ecto-5′-NT (CD73) enzyme with IC50 (µM) values of 0.70 ± 0.06 µM, 0.87 ± 0.05 µM, 0.39 ± 0.02 µM and 0.33 ± 0.03 µM, respectively. These derivatives were further evaluated for their cytotoxic potential against cancer cell line (HeLa). Compound 3h and 3c showed the cytotoxicity at IC50 value of 30.20 ± 3.11 µM and 86.02 ± 7.11 µM, respectively. Furthermore, compound 3h was selected for cell apoptosis, immunofluorescence staining and cell cycle analysis which showed promising apoptotic effect in HeLa cells. Additionally, compound 3h was further investigated for its effect on expression of CD73 using qRT-PCR and western blot. Conclusion: Among all synthesized compounds (3a-3i), Compound 3h (E)-N'-((6-ethyl-4-oxo-4H-chromen-3-yl) methylene)-4-methylbenzenesulfonohydrazide was identified as most potent compound. Additional expression studies conducted on HeLa cell line proved that this compound successfully decreased the expression level of CD73 and thus inhibiting the growth and proliferation of cancer cells.


2020 ◽  
pp. 4-7
Author(s):  
M. R. Kamala Priya ◽  
Priya R. Iyer

Doxorubicin is the most common chemotherapy drug used in cancer therapy. Its usage is associated with various side-effects. In order to overcome the challenges in Doxorubicin administration, the present study has focussed on synthesizing a drug conjugate with biosynthesized gold nanoparticles and doxorubicin. The gold nanoparticles were biosynthesized using green extracts of medicinal plants with potential anticancer activities. The nanoparticle that possesses anticancer activity was conjugated with the drug for a combinatorial effect of the nanoparticles and the drug. The in vitro cytotoxicity was checked in Vero cell line through MTT assay. The in vitro anti proliferative effects were screened against cervical cancer in HeLa cell line. Fluorescence activated cell sorting analysis was carried out to detect the difference between live and dead cell populations. The preliminary confirmation was carried out in UV-VIS spectrophotometer. The morphological characterization was carried out by SEM and stability by Zeta potential. The IC50 of the nanocompounds demonstrated anti-proliferative activity against cervical cancer similar to the chemotherapeutic drug, Doxorubicin; additionally in a much lesser concentration of the drug. The in vitro cytotoxicity exhibited high viability of cells in Vero cell line with minimum viability of 80% in all the tested concentrations. There was a synergistic effect of the nanoparticles along with the drug; thereby an enhanced therapeutic efficiency was achieved. FACS analysis showed 36% of cell death in Dox treated HeLa cells whereas 96% of cell death in Nano-Dox treated HeLa cells. Nano-Dox conjugate has demonstrated high anticancer effects than drug alone Doxorubicin. Further biosynthesized nanomaterials based drug formulation can be developed as a potential strategy in cancer therapy.


2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Reetu Hooda ◽  
Neeru Baghla ◽  
Nisha Malik ◽  
Samander Kaushik

Abstract Objectives i) To compare the placental human papilloma virus (HPV) deoxynucleic acid (DNA) status of preterm deliveries with full term deliveries and to identify high risk (HR) genotypes (HPV 16 and 18); and ii) To compare the perinatal outcomes of HPV positive with HPV negative pregnant women. Methods A case control study was carried out on 100 antenatal women with singleton live pregnancies admitted in labor ward of a tertiary care teaching hospital from April 2017 to March 2018. The two study groups were i) spontaneous preterm deliveries between 24 and 36 + 6 weeks (n=50) and ii) full term deliveries ≥37 weeks (n=50). The placental tissue was analysed for HPV DNA and HR HPV genotypes were detected by type specific primers. A comparative analysis of perinatal outcomes between HPV positive and negative women was done. Results An overall placental tissue HPV prevalence of 12% (12/100) was observed in study cohort which was not significantly different between preterm and full term deliveries (16 vs. 8%, p=0.218). HPV 16 was significantly associated with preterm births (p=0.04). Both HPV affected and non-affected women were comparable in terms of mode of delivery and neonatal outcomes. However, a statistically significant association of preterm neonatal intensive care admissions with HR HPV 16 genotype was observed (p=0.04). Conclusions Spontaneous preterm births can be attributed to placental HPV infection, specifically HR HPV 16 genotype. This association identifies a potentially preventable cause of prematurity and its associated complications, in wake of availability of an effective vaccine.


MicroRNA ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 110-115 ◽  
Author(s):  
Sara Zamani ◽  
Amir Sohrabi ◽  
Seyed Masoud Hosseini ◽  
Marjan Rahnamaye-Farzami ◽  
Abolfazl Akbari

Background:Early diagnosis is an important factor to improve the survival of Invasive Cervical Cancer (ICC) patients. Molecular biomarkers such as micro RNA (miRNA) can be used in the early detection of ICC. The expression of miR-21 and miR-29a are deregulated in many types of human cancers.Objective:The aim of this study was to investigate the differences in miR-21 and miR-29a expression patterns in the Human Papilloma Virus (HPV) infection and various grades of cervical cancer among Iranian women.Methods:Small RNAs were extracted from positive for HPV, cervical cancer and healthy samples from 43, 50 and 46 individuals, respectively. Expression levels of miR-21 and miR-29a were analyzed by SYBR Green real-time RT-PCR using specific primers, and 5s rRNA as the internal reference gene.Results:Results have shown a significant increase in miR-21 and decrease in miR-29 in cancerous samples in comparison with the control groups (P < 0.0001).Conclusion:This study illustrated that miR-21 and miR-29a could be operated as an oncogene and tumor-suppressor in cervical cancer progression. More studies are needed to demonstrate the role of miR-21 and miR-29a as potential biomarkers for the diagnosis of cervical cancer in future investigations.


Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 229 ◽  
Author(s):  
Agnė Vitkauskaitė ◽  
Joana Celiešiūtė ◽  
Saulius Paškauskas ◽  
Erika Skrodenienė ◽  
Rūta Jolanta Nadišauskienė ◽  
...  

Background and objective: Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. Materials and methods: A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. Results: The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group (P < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy (P = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM (P < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women (P = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC (P = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment.


2016 ◽  
Vol 19 (1) ◽  
pp. 160-166 ◽  
Author(s):  
Gustavo David García Muentes ◽  
Lindsay Karen García Rodríguez ◽  
Ramiro Israel Burgos Galarraga ◽  
Franklin Almeida Carpio ◽  
Juan Carlos Ruiz Cabezas

ABSTRACT: Introduction: Human papillomavirus (HPV) is considered a necessary causative agent for developing oropharyngeal, anal and cervical cancer. Among women in Ecuadorian population, cervical cancer ranks as the second most common gynecological cancer. Not many studies about HPV burden have been published in Ecuador, and genotypes distribution has not been established yet. The little data available suggest the presence of other genotypes different than 16 and 18. Objectives: In the present study, we attempt to estimate the prevalence of HPV 16, HPV 18 and other 35 genotypes among Ecuadorian women undergoing cervical cancer screening. The overall prevalence of HPV infection was also estimated. Methods: Routine cervical samples were analyzed using Linear Array(r) HPV Genotyping test (Roche). Results: A total of 1,581 cervical samples obtained from Ecuadorian women undergoing cervical cancer screening were included in this study. HPV DNA was detected in 689 cervical samples (43.58%). Of these samples, 604 (38.20%) were positive for a single HPV genotype, while another 85 (5.37%) samples were positive for multiple HPV types. Genotype 16 (5.50%) resulted in the most frequently detected type in both single and multiple infections. HPV 33 (4.55%) and HPV 11 (3.80%) occupied the second and the third place in frequency among all detected genotypes. Conclusions: Viral genotypes different from HPV 16 and HPV 18 are frequently detected among Ecuadorian women. The overall prevalence of HPV resulted higher than the one reported in other South American countries with a greater burden in the second and third decades of life.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Pablo Moreno-Acosta ◽  
Alfredo Romero-Rojas ◽  
Nicolas Vial ◽  
Antonio Huertas ◽  
Jinneth Acosta ◽  
...  

This article is a preliminary investigational study that is aimed at giving hints about the interesting biomarkers involved in the transition process from low-grade cervix lesion to invasive cervical cancer. Our study focuses on the risk factors and tumour molecular changes in one patient. First in 1986, she was diagnosed a preinvasive cervix lesion. Then, 16 years later, she was diagnosed an invasive cervical cancer. The 2002 diagnosis was a squamous cell carcinoma of the cervix, stage IIIB (FIGO), whereas in 1986, she had been diagnosed a high-grade squamous intraepithelial cervical lesion. Retrospectively, the analysis of samples of preneoplastic lesions and invasive cervical cancer confirmed the histopathological diagnoses and detected the presence of HPV type and HPV-16 variants, as well as the overexpression of proteins such as hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1. Finally, the Arg72Pro polymorphism was detected in TP53. The role of high-risk HPV and HPV-16 variants and of hTERT, IGF1Rα, IGF1Rβ, CAIX, and GLUT1 variations seemed confirmed in the development and progression of cervical cancer. As a result, analyzing the molecular changes in one and same tumour that progresses from a low-grade cervix lesion to invasive cervical cancer could provide valuable information in order to improve detection, diagnosis, and treatment in the future.


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