scholarly journals Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Samira Sanami ◽  
Fatemeh Azadegan-Dehkordi ◽  
Mahmoud Rafieian-Kopaei ◽  
Majid Salehi ◽  
Maryam Ghasemi-Dehnoo ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Lymphocytes ◽  
Tertiary Structure ◽  
Therapeutic Vaccine ◽  
Epitope Prediction ◽  
Therapeutic Effects ◽  
Epitope Vaccine ◽  
In Vivo Experiments

AbstractCervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.

scholarly journals UBE2C Drives Human Cervical Cancer Progression and Is Positively Modulated by mTOR

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 37
Author(s):  
An-Jen Chiang ◽  
Chia-Jung Li ◽  
Kuan-Hao Tsui ◽  
Chung Chang ◽  
Yuan-chin Ivan Chang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Progression ◽  
Cancer Staging ◽  
Cervical Squamous Cell Carcinoma ◽  
Cancer Cell Proliferation ◽  
Gynecological Malignancy ◽  
In Vivo Experiments ◽  
Ubiquitin Conjugating Enzyme

Cervical cancer is a common gynecological malignancy, accounting for 10% of all gynecological cancers. Recently, targeted therapy for cervical cancer has shown unprecedented advantages. Several studies have shown that ubiquitin conjugating enzyme E2 (UBE2C) is highly expressed in a series of tumors, and participates in the progression of these tumors. However, the possible impact of UBE2C on the progression of cervical squamous cell carcinoma (CESC) remains unclear. Here, we carried out tissue microarray analysis of paraffin-embedded tissues from 294 cervical cancer patients with FIGO/TNM cancer staging records. The results indicated that UBE2C was highly expressed in human CESC tissues and its expression was related to the clinical characteristics of CESC patients. Overexpression and knockdown of UBE2C enhanced and reduced cervical cancer cell proliferation, respectively, in vitro. Furthermore, in vivo experiments showed that UBE2C regulated the expression and activity of the mTOR/PI3K/AKT pathway. In summary, we confirmed that UBE2C is involved in the process of CESC and that UBE2C may represent a molecular target for CESC treatment.

scholarly journals Synthesis and Characterization of Polyvinylpyrrolidone-Modified ZnO Quantum Dots and Their In Vitro Photodynamic Tumor Suppressive Action

2021 ◽  
Vol 22 (15) ◽  
pp. 8106
Author(s):  
Tianming Song ◽  
Yawei Qu ◽  
Zhe Ren ◽  
Shuang Yu ◽  
Mingjian Sun ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Photodynamic Therapy ◽  
Inhibitory Effect ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Potential Applications ◽  
Zno Quantum Dots ◽  
Zno Qds

Despite the numerous available treatments for cancer, many patients succumb to side effects and reoccurrence. Zinc oxide (ZnO) quantum dots (QDs) are inexpensive inorganic nanomaterials with potential applications in photodynamic therapy. To verify the photoluminescence of ZnO QDs and determine their inhibitory effect on tumors, we synthesized and characterized ZnO QDs modified with polyvinylpyrrolidone. The photoluminescent properties and reactive oxygen species levels of these ZnO/PVP QDs were also measured. Finally, in vitro and in vivo experiments were performed to test their photodynamic therapeutic effects in SW480 cancer cells and female nude mice. Our results indicate that the ZnO QDs had good photoluminescence and exerted an obvious inhibitory effect on SW480 tumor cells. These findings illustrate the potential applications of ZnO QDs in the fields of photoluminescence and photodynamic therapy.

Photodynamic effects of Radachlorin® on cervical cancer model

2005 ◽  
Vol 09 (12) ◽  
pp. 835-840 ◽  
Author(s):  
Sun-Young Kwak ◽  
Dae-Seog Lim ◽  
Su-Mi Bae ◽  
Yong-Wook Kim ◽  
Joon-Mo Lee ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Golgi Apparatus ◽  
Biological Significance ◽  
Annexin V ◽  
Light Irradiation ◽  
Control Group ◽  
Cancer Model ◽  
In Vivo Experiments

Photodynamic therapy (PDT) has been reported to be effective for treating various tumors and induce apoptosis in many tumor cells. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Radachlorin®, in a cervical cancer model, TC-1 cells. When TC-1 cells were exposed to varied doses of Radachlorin® with light irradiation (6.25 J/cm2), PDT induced a dose-dependent growth inhibition of TC-1 cells. All of these cells were significantly damaged after light irradiation and categorized to be early and late apoptosis, as determined by annexin V staining. Radachlorin® localized primarily into the Golgi apparatus of cells in 12 h of the treatment, and weak fluorescence intensity was also detected in mitochondria. On the other hand, in the in vivo experiments, following light irradiation (100 J/cm2), retarded tumor growth was significant in mice treated with Radachlorin®, as compared to the control group. Taken together, we propose that PDT after the application of Radachlorin® may induce the Golgi apparatus-mediated apoptosis of cervical cancer cells in vitro, and also be effective in the mice system.

scholarly journals Extracellular vesicular Wnt7b mediates HPV E6-induced cervical cancer angiogenesis by activating the β-catenin signaling pathway

2020 ◽  
Author(s):  
Jun-Jun Qiu ◽  
Shu-Gen Sun ◽  
Xiao-Yan Tang ◽  
Ying-Ying Lin ◽  
Keqin Hua
Keyword(s):  
Cervical Cancer ◽  
Umbilical Vein ◽  
Predictive Biomarker ◽  
Good Prediction ◽  
Hpv 16 ◽  
Hpv E6 ◽  
In Vivo Experiments ◽  
Cancer Tumor

Abstract Background: The E6 oncoproteins of human papillomavirus (HPV) 16/18 are the critical drivers of cervical cancer (CC) progression. Extracellular vesicles (EVs) are emerging as critical mediators of cancer-tumor microenvironment (TME) communication. However, whether EVs contribute to HPV 16/18 E6-mediated impacts on CC progression remains unclear. Methods: A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of EV-Wnt7b in HPV E6-induced CC angiogenesis. The prognostic value of serum EV-Wnt7b was determined and a predictive nomogram model was established. Results: HPV 16/18 E6 upregulated Wnt7b mRNA expression in four HPV 16/18-positive CC cell lines and their EVs. In vitro and in vivo experiments demonstrated that EV-Wnt7b mRNA was transferred to and modulated human umbilical vein endothelial cells (HUVECs) toward more proliferative and proangiogenic behaviors by impacting β-catenin signaling. Clinically, serum EV-Wnt7b levels were elevated in CC patients and significantly correlated with an aggressive phenotype. Serum EV-Wnt7b was determined to be an independent prognostic factor for CC overall survival (OS) and recurrence-free survival (RFS). Notably, we successfully established a novel predictive nomogram model using serum EV-Wnt7b, which showed good prediction of 1- and 3-year OS and RFS. Conclusions: Our results illustrate a potential crosstalk between HPV 16/18-positive CC cells and HUVECs via EVs in the TME and highlight the potential of circulating EV-Wnt7b as a novel predictive biomarker for CC prognosis.

Potential Anti-inflammatory Sesquiterpene Lactones from Eupatorium lindleyanum

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 123-128 ◽  
Author(s):  
Fang Wang ◽  
Huanhuan Zhong ◽  
Shiqi Fang ◽  
Yunfeng Zheng ◽  
Cunyu Li ◽  
...  
Keyword(s):  
Sesquiterpene Lactones ◽  
Folk Medicine ◽  
2D Nmr ◽  
In Vitro Assays ◽  
Raw 264.7 Cells ◽  
Therapeutic Effects ◽  
In Vivo Experiments ◽  
Anti Inflammatory

Abstract Eupatorium lindleyanum has traditionally been used as folk medicine in Asian countries for its therapeutic effects on tracheitis and tonsillitis. Investigation of the anti-inflammatory active constituents from E. lindleyanum led to the isolation of two novel sesquiterpene lactones, named eupalinolide L (1) and eupalinolide M (2), and seven known sesquiterpene lactones (3–9). The structures and configurations of the new compounds were determined on the basis of spectroscopic analysis, especially 2D NMR techniques. In vivo experiments showed that the sesquiterpenes fraction significantly reduced mouse ear edema induced by xylene (18.6%, p < 0.05). In in vitro assays, compounds 1–9 showed excellent anti-inflammatory activities, as they lowered TNF-α and IL-6 levels in lipopolysaccharide-stimulated murine macrophage RAW 264.7 cells (p < 0.001). The above results suggest that the sesquiterpene lactones from E. lindleyanum can be developed as novel potential natural anti-inflammatory agents.

scholarly journals Preclinical study of a novel therapeutic vaccine for recurrent respiratory papillomatosis

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Maxwell Y. Lee ◽  
Simon Metenou ◽  
Douglas E. Brough ◽  
Helen Sabzevari ◽  
Ke Bai ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
T Lymphocyte ◽  
Chronic Infection ◽  
Therapeutic Vaccine ◽  
Preclinical Study ◽  
Recurrent Respiratory Papillomatosis ◽  
Growth Delay ◽  
Lymphocyte Responses

AbstractActivation of antigen-specific T-lymphocyte responses may be needed to cure disorders caused by chronic infection with low-risk human papillomavirus (lrHPV). Safe and effective adjuvant therapies for such disorders are needed. The safety and efficacy of a novel gorilla adenovirus vaccine expressing a protein designed to elicit immune responses directed against HPV6 and HPV11, PRGN-2012, was studied using in vitro stimulation of T lymphocytes from patients with recurrent respiratory papillomatosis, in vivo vaccination studies, and therapeutic studies in mice bearing tumors expressing lrHPV antigen. PRGN-2012 treatment induces lrHPV antigen-specific responses in patient T lymphocytes. Vaccination of wild-type mice induces E6-specific T-lymphocyte responses without toxicity. In vivo therapeutic vaccination of mice bearing established HPV6 E6 expressing tumors results in HPV6 E6-specific CD8+ T-lymphocyte immunity of sufficient magnitude to induce tumor growth delay. The clinical study of PRGN-2012 in patients with disorders caused by chronic infection with lrHPV is warranted.

scholarly journals Therapeutic effects of topically-administered guar gum nanoparticles in oxazolone-induced atopic dermatitis in mice

2018 ◽  
Vol 5 (5) ◽  
pp. 2305-2325 ◽  
Author(s):  
Nandita Ghosh ◽  
Shinjini Mitra ◽  
Ena Ray Banerjee
Keyword(s):  
Atopic Dermatitis ◽  
Guar Gum ◽  
Fold Increase ◽  
Therapeutic Effects ◽  
Cyamopsis Tetragonoloba ◽  
Epidermal Thickness ◽  
In Vivo Experiments ◽  
Macrophage Populations

Introduction: Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish and scaly lesions. It mainly affects children and has a high prevalence in developing countries. AD may occur due to environmental or genetic factors. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by macrophages. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in AD. Methods: To assess the wound healing capacity of GN, we first treated adherent fibroblast cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiments, Balb/c mice ears were treated topically with oxazolone (Oxa) to induce AD, and then were topically treated with GN. The ear thickness increased significantly until day 28 upon treatment with Oxa. Results: Application of GN showed a significant decrease in ear thickness as assessed on day 28. The total cell count of skin cells that showed a fold increase, when treated with Oxa, was again decreased after topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining, was also increased when treated with Oxa, while GN application led to a significant decrease. Serum IgE levels were restored by GN. T helper cell and macrophage populations, when examined by flow cytometry, showed an increase in percentage when treated with Oxa; the percentage was reduced after application of GN. Hematoxylin & Eosin (H&E) staining of the ear tissue showed an increase in epidermal thickness in Oxa-treated mice, while GN application showed reduced cellular infiltration and epidermal thickness. Conclusion: Overall, our results showed that GN, when administered topically, was successful in alleviating dermatitis caused by Oxa.

scholarly journals Precision Nanomedicine Vol. 1, Issue 3, Table of Contents

2018 ◽  
Vol 1 (3) ◽  
Keyword(s):  
Pancreatic Cancer ◽  
Cervical Cancer ◽  
Tumor Cells ◽  
Delivery System ◽  
Complement Activation ◽  
Sol Gel ◽  
Therapeutic Vaccine ◽  
Basic Research

Prec. Nanomed. 2018 Oct;1(3):183-193. BASIC RESEARCH From the Clinical Editor: The number of women affected by cervical cancer worldwide is very significant and the disease is associated with human papilloma virus (HPV) infection. Although the use of HPV vaccines has proven to be useful in disease protection, they only work in women who have never been infected by HPV previously. Thus, the development of a therapeutic vaccine that targets HPV-infected cells is needed for women who are already infected with the virus. In this study, the authors describe the use of a self-adjuvating polymer-based delivery system for the development of a therapeutic vaccine. Therefore, while efforts are progressing, vaccine candidates are still required against late stage cervical cancer via improving the vaccine delivery system. Authors demonstrate that the combination of polymer-based and liposome delivery systems may be effective without the use of additional adjuvant and with just a single dose immunization. This finding has potential importance for other cancer vaccines as well. Prec. Nanomed. 2018 Oct;1(3):173-182 POTENTIAL CLINICAL SIGNIFICANCE From the Clinical Editor: The treatment of triple-negative breast cancer is often difficult due to frequent resistance to doxorubicin. Using different nano-formulations based on sol-gel technology to encapsulate doxorubicin, the authors here showed enhanced dose-response metrics and tumor cell kill of these cancer cells due to an increased drug accumulation in the local tumor environment. This platform shows early promise in terms of eventual clinical translatability. Prec. Nanomed. 2018 Oct;1(3):194-207. BASIC RESEARCH From the Clinical Editor: Surgical resection remains the main treatment modality for pancreatic cancer. Thus, the ability to delineate the tumor accurately during operation is important to ensure all tumor cells are resected. Here, the authors describe the development of a multimodal imaging probe using nanospheres to target epithelial cells of pancreatic cancer. The specificity to target only tumor cells was clearly shown in both in-vitro and in-vivo experiments. This technology may provide a new fluorescence imaging technique to help the field of surgical oncology in the future. Prec. Nanomed. 2018 Oct;1(3):208-217. BASIC RESEARCH From the Clinical Editor: Preclinical characterization of nanotechnology-based products is essential for translating innovative applications into clinics. In addition to the innate immune system complement activation plays an important role in regulating the adaptive immune response. Undesirable activation of the complement system in response to new composites may lead to hypersensitivity reactions. The authors describe the importance of mouse strain selection for in vitro complement activation analysis addressing also the existence of inter- and intraspecies variability.

scholarly journals The Role of Thermal Effects in Plasma Medical Applications: Biological and Calorimetric Analysis

2019 ◽  
Vol 9 (24) ◽  
pp. 5560 ◽  
Author(s):  
Luigi Cordaro ◽  
Gianluca De Masi ◽  
Alessandro Fassina ◽  
Clarice Gareri ◽  
Antonio Pimazzoni ◽  
...  
Keyword(s):  
Thermal Effects ◽  
Plasma Source ◽  
Total Power ◽  
Therapeutic Effects ◽  
Calorimetric Analysis ◽  
Blood Samples ◽  
In Vivo Experiments ◽  
Male Wistar Rats

Plasma Medicine tools exploit the therapeutic effects of the exposure of living matter to plasma produced at atmospheric pressure. Since these plasmas are usually characterized by a non-thermal equilibrium (highly energetic electrons, low temperature ions), thermal effects on the substrate are usually considered negligible. Conversely, reactive oxygen and nitrogen species (RONS), UV radiation and metastables are thought to play a major role. In this contribution, we compare the presence of thermal effects in different operational regimes (corresponding to different power levels) of the Plasma Coagulation Controller (PCC), a plasma source specifically designed for accelerating blood coagulation. In particular, we analyze the application of PCC on human blood samples (in vitro) and male Wistar rats tissues (in vivo). Histological analysis points out, for the highest applied power regime, the onset of detrimental thermal effects such as red cell lysis in blood samples and tissues damages in in-vivo experiments. Calorimetric bench tests performed on metallic targets show that the current coupled by the plasma on the substrate induces most of measured thermal loads through a resistive coupling. Furthermore, the distance between the PCC nozzle and the target is found to strongly affect the total power.

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