scholarly journals Phthalocyanine and Its Formulations: A Promising Photosensitizer for Cervical Cancer Phototherapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2057
Author(s):  
Lucimara R. Carobeli ◽  
Lyvia E. de F. Meirelles ◽  
Gabrielle M. Z. F. Damke ◽  
Edilson Damke ◽  
Maria V. F. de Souza ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Current Evidence ◽  
Lead Compounds ◽  
Common Causes ◽  
Oncological Diseases ◽  
Recent Developments ◽  
Current Therapies ◽  
Pharmaceutical Agents

Cervical cancer is one of the most common causes of cancer-related deaths in women worldwide. Despite advances in current therapies, women with advanced or recurrent disease present poor prognosis. Photodynamic therapy (PDT) has emerged as an effective therapeutic alternative to treat oncological diseases such as cervical cancer. Phthalocyanines (Pcs) are considered good photosensitizers (PS) for PDT, although most of them present high levels of aggregation and are lipophilic. Despite many investigations and encouraging results, Pcs have not been approved as PS for PDT of invasive cervical cancer yet. This review presents an overview on the pathophysiology of cervical cancer and summarizes the most recent developments on the physicochemical properties of Pcs and biological results obtained both in vitro in tumor-bearing mice and in clinical tests reported in the last five years. Current evidence indicates that Pcs have potential as pharmaceutical agents for anti-cervical cancer therapy. The authors firmly believe that Pc-based formulations could emerge as a privileged scaffold for the establishment of lead compounds for PDT against different types of cervical cancer.

scholarly journals High Levels of Within-Host Variations of Human Papillomavirus 16 E1/E2 Genes in Invasive Cervical Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yusuke Hirose ◽  
Mayuko Yamaguchi-Naka ◽  
Mamiko Onuki ◽  
Yuri Tenjimbayashi ◽  
Nobutaka Tasaka ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Viral Replication ◽  
Viral Genome ◽  
Invasive Cervical Cancer ◽  
Infected Woman ◽  
Human Papillomavirus 16 ◽  
Normal Cervix ◽  
High Level

Human papillomavirus type 16 (HPV16) is the most common HPV genotype found in invasive cervical cancer (ICC). Recent comprehensive genomics studies of HPV16 have revealed that a large number of minor nucleotide variations in the viral genome are present in each infected woman; however, it remains unclear whether such within-host variations of HPV16 are linked to cervical carcinogenesis. Here, by employing next-generation sequencing approaches, we explored the mutational profiles of the HPV16 genome within individual clinical specimens from ICC (n = 31) and normal cervix (n = 21) in greater detail. A total of 367 minor nucleotide variations (167 from ICC and 200 from the normal cervix) were detected throughout the viral genome in both groups, while nucleotide variations at high frequencies (>10% abundance in relative read counts in a single sample) were more prevalent in ICC (10 in ICC versus 1 in normal). Among the high-level variations found in ICC, six were located in the E1/E2 genes, and all of them were non-synonymous substitutions (Q142K, M207I, and L262V for E1; D153Y, R302T, and T357A for E2). In vitro functional analyses of these E1/E2 variants revealed that E1/M207I, E2/D153Y, and E2/R302T had reduced abilities to support viral replication, and that E2/D153Y and E2/R302T failed to suppress the viral early promoter. These results imply that some within-host variations of E1/E2 present at high levels in ICC may be positively selected for and contribute to cervical cancer development through dysfunction or de-stabilization of viral replication/transcription proteins.

scholarly journals Recent Developments in Targeting Eosinophil Accumulation as a Novel Therapeutic Approach for Asthma

2008 ◽  
Vol 1 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Garry M. Walsh ◽  
Alexander J. Robinson ◽  
Ping Wu
Keyword(s):  
Animal Studies ◽  
Large Body ◽  
Effector Cells ◽  
Asthmatic Patients ◽  
Cytokines And Chemokines ◽  
Recent Developments ◽  
Current Therapies ◽  
Inhibitory Molecules ◽  
Eosinophil Accumulation

Current therapies for asthma are aimed at controlling disease symptoms and for the majority of patients inhaled glucocorticoid anti-inflammatory therapy is both effective and well-tolerated. However, concerns remain about the adverse effects of glucocorticoids while a subset of asthmatic patients remains symptomatic despite optimal treatment thereby creating a clear unmet medical need. There is considerable evidence that implicates eosinophils as important effector cells and immunomodulators in the inflammation characteristic of asthma. Numerous in vitro and animal studies have demonstrated essential roles for cell adhesion molecules in eosinophil adhesion and transendothelial migration including the selectins, ICAM-1, VCAM-1 together with many of the μ1 and μ2 integrins. A large body of evidence has also implicated several cytokines and chemokines in the selective recruitment of eosinophils to sites of asthmatic inflammation. Biopharmaceutical approaches have been used to identify inhibitory molecules that target key elements in the processes controlling eosinophil accumulation in asthma. This review will summarise the problems and successes regarding recent developments in therapeutic strategies aimed at reducing eosinophil-mediated inflammation in the asthmatic lung.

Effect of black seeds (Nigella sativa) volatile oil on the cervical cancer: In vitro study, on Hela cell lines

2019 ◽  
Vol 7 (4) ◽  
pp. 91-96
Author(s):  
Isra'a Al-sobhi ◽  
◽  
Rawan Al-Ghabban ◽  
Soad Shaker Ali ◽  
Jehan Al-Amri ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Hela Cell ◽  
Cell Lines ◽  
Nigella Sativa ◽  
In Vitro Study ◽  
Volatile Oil ◽  
Vitro Study ◽  
Hela Cell Lines ◽  
Black Seeds

Privileged Structures in the Design of Potential Drug Candidates for Neglected Diseases

2019 ◽  
Vol 26 (23) ◽  
pp. 4323-4354 ◽  
Author(s):  
Ana Cristina Lima Leite ◽  
José Wanderlan Pontes Espíndola ◽  
Marcos Veríssimo de Oliveira Cardoso ◽  
Gevanio Bezerra de Oliveira Filho
Keyword(s):  
Biologically Active ◽  
Neglected Diseases ◽  
Financial Return ◽  
Drug Candidates ◽  
Lead Compounds ◽  
Wide Range ◽  
Methods Of Synthesis ◽  
Current Therapies ◽  
Resistant Strains ◽  
Privileged Structures

Background: Privileged motifs are recurring in a wide range of biologically active compounds that reach different pharmaceutical targets and pathways and could represent a suitable start point to access potential candidates in the neglected diseases field. The current therapies to treat these diseases are based in drugs that lack of the desired effectiveness, affordable methods of synthesis and allow a way to emergence of resistant strains. Due the lack of financial return, only few pharmaceutical companies have been investing in research for new therapeutics for neglected diseases (ND). Methods: Based on the literature search from 2002 to 2016, we discuss how six privileged motifs, focusing phthalimide, isatin, indole, thiosemicarbazone, thiazole, and thiazolidinone are particularly recurrent in compounds active against some of neglected diseases. Results: It was observed that attention was paid particularly for Chagas disease, malaria, tuberculosis, schistosomiasis, leishmaniasis, dengue, African sleeping sickness (Human African Trypanosomiasis - HAT) and toxoplasmosis. It was possible to verify that, among the ND, antitrypanosomal and antiplasmodial activities were between the most searched. Besides, thiosemicarbazone moiety seems to be the most versatile and frequently explored scaffold. As well, phthalimide, isatin, thiazole, and thiazolidone nucleus have been also explored in the ND field. Conclusion: Some described compounds, appear to be promising drug candidates, while others could represent a valuable inspiration in the research for new lead compounds.

3D Culture Modelling: An Emerging Approach for Translational Cancer Research in Sarcomas

2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  
Keyword(s):  
High Throughput Screening ◽  
Cancer Biology ◽  
Soft Tissues ◽  
Three Dimensional ◽  
3D Culture ◽  
Resistance Mechanisms ◽  
In Vitro Models ◽  
Tumour Spheroids ◽  
Current Therapies

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.

Current Approaches to Drug Discovery for Chagas Disease: Methodological Advances

2019 ◽  
Vol 22 (8) ◽  
pp. 509-520
Author(s):  
Cauê B. Scarim ◽  
Chung M. Chin
Keyword(s):  
Drug Discovery ◽  
Chagas Disease ◽  
Drug Candidates ◽  
Lead Compounds ◽  
New Drug ◽  
Compound Libraries ◽  
Screening Assays ◽  
Cruzi Infection

Background: In recent years, there has been an improvement in the in vitro and in vivo methodology for the screening of anti-chagasic compounds. Millions of compounds can now have their activity evaluated (in large compound libraries) by means of high throughput in vitro screening assays. Objective: Current approaches to drug discovery for Chagas disease. Method: This review article examines the contribution of these methodological advances in medicinal chemistry in the last four years, focusing on Trypanosoma cruzi infection, obtained from the PubMed, Web of Science, and Scopus databases. Results: Here, we have shown that the promise is increasing each year for more lead compounds for the development of a new drug against Chagas disease. Conclusion: There is increased optimism among those working with the objective to find new drug candidates for optimal treatments against Chagas disease.

scholarly journals Frequent high-risk HPV co-infections excluding types 16 or 18 in cervical neoplasia in Guadeloupe

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stanie Gaete ◽  
Aviane Auguste ◽  
Bernard Bhakkan ◽  
Jessica Peruvien ◽  
Cecile Herrmann-Storck ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Population Based ◽  
Multiple Infections ◽  
French Caribbean ◽  
Papilloma Virus ◽  
Hpv Genotyping ◽  
Hpv Status ◽  
Hpv Genotypes ◽  
High Risk Hpv

Abstract Background Cervical cancer is the fourth cancer worldwide. The Human Papilloma Virus is responsible for 99% of the cases but the distribution of its genotypes varies among populations. We aimed to identify HPV genotypes distribution in women with grade 2/3 cervical intraepithelial dysplasia or invasive cervical cancer in Guadeloupe, a French Caribbean territory with a population mainly of African descent. Methods We used paraffin-embedded tumors for viral DNA extraction from women diagnosed between 2014 and 2016 and identified by the population-based cancer registry. The HPV Genotyping was performed with the InnoLIPA HPV Genotyping Extra kit®. Results Overall, 213 samples out of the 321 eligible records were analyzed. The HPV status was positive for 94% of the cases. The five most common oncogenic HPV genotypes were HPV31 (47%), HPV33 (38%), HPV16 (32%), HPV44 (31%) and HPV26 (28%). HPV18 was found in only in 5% of the cases. Among the studied cases, 94% had multiple infections. More than 60% of single infections were HPV16-related, accounting for 35% of HPV16 infections. Conclusions These results show a different distribution of oncogenic HPVs in Guadeloupe with “31 >  33 > 16” and a high frequency of multiple infections. Despite a lower coverage, the nine-valent vaccine is nevertheless adequate.

The Use of Biomarkers as Alternatives to Current Animal Tests on Food Chemicals

1998 ◽  
Vol 26 (4) ◽  
pp. 421-480
Author(s):  
Krys Bottrill
Keyword(s):  
Animal Studies ◽  
Developmental Toxicity ◽  
Reproductive Toxicity ◽  
In Vitro Test ◽  
Animal Testing ◽  
Dietary Biomarkers ◽  
Recent Developments ◽  
Mechanistic Basis ◽  
The Three Rs

Recent developments in biomarkers relating to the interrelationship of diet, disease and health were surveyed. Most emphasis was placed on biomarkers of deleterious effects, since these are of greatest relevance to the subject of this review. The area of greatest activity was found to be that relating to biomarkers of mutagenic, genotoxic and carcinogenic effects. This is also one of the major areas of concern in considerations of the beneficial and deleterious effects of dietary components, and also the area in which regulatory testing requires studies of the longest duration. A degree of progress has also been made in the identification and development of biomarkers relating to certain classes of target organ toxicity. Biomarkers for other types of toxicity, such as immunotoxicity, neurotoxicity, reproductive toxicity and developmental toxicity, are less developed, and further investigation in these areas is required before a comprehensive biomarker strategy can be established. A criticism that recurs constantly in the biomarker literature is the lack of standardisation in the methods used, and the lack of reference standards for the purposes of validation and quality control. It is encouraging to note the growing acknowledgement of the need for validation of biomarkers and biomarker assays. Some validation studies have already been initiated. This review puts forward proposals for criteria to be used in biomarker validation. More discussion on this subject is required. It is concluded that the use of biomarkers can, in some cases, facilitate the implementation of the Three Rs with respect to the testing of food chemicals and studies on the effects of diet on health. The greatest potential is seen to be in the refinement of animal testing, in which biomarkers could serve as early and sensitive endpoints, in order to reduce the duration of the studies and also reduce the number of animals required. Biomarkers could also contribute to establishing a mechanistic basis for in vitro test systems and to facilitating their validation and acceptance. Finally, the increased information that could result from the incorporation of biomarker determinations into population studies could reduce the need for supplementary animal studies. This review makes a number of recommendations concerning the prioritisation of future activities on dietary biomarkers in relation to the Three Rs. It is emphasised, however, that further discussions will be required among toxicologists, epidemiologists and others researching the relationship between diet and health.

scholarly journals Molecular and Cellular Mechanisms of Metformin in Cervical Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2545
Author(s):  
Ya-Hui Chen ◽  
Po-Hui Wang ◽  
Pei-Ni Chen ◽  
Shun-Fa Yang ◽  
Yi-Hsuan Hsiao
Keyword(s):  
Cervical Cancer ◽  
Potential Role ◽  
Treatment Options ◽  
Cellular Mechanisms ◽  
Anticancer Effects ◽  
Clinical Benefits ◽  
Underlying Mechanisms

Cervical cancer is one of the major gynecologic malignancies worldwide. Treatment options include chemotherapy, surgical resection, radiotherapy, or a combination of these treatments; however, relapse and recurrence may occur, and the outcome may not be favorable. Metformin is an established, safe, well-tolerated drug used in the treatment of type 2 diabetes; it can be safely combined with other antidiabetic agents. Diabetes, possibly associated with an increased site-specific cancer risk, may relate to the progression or initiation of specific types of cancer. The potential effects of metformin in terms of cancer prevention and therapy have been widely studied, and a number of studies have indicated its potential role in cancer treatment. The most frequently proposed mechanism underlying the diabetes–cancer association is insulin resistance, which leads to secondary hyperinsulinemia; furthermore, insulin may exert mitogenic effects through the insulin-like growth factor 1 (IGF-1) receptor, and hyperglycemia may worsen carcinogenesis through the induction of oxidative stress. Evidence has suggested clinical benefits of metformin in the treatment of gynecologic cancers. Combining current anticancer drugs with metformin may increase their efficacy and diminish adverse drug reactions. Accumulating evidence is indicating that metformin exerts anticancer effects alone or in combination with other agents in cervical cancer in vitro and in vivo. Metformin might thus serve as an adjunct therapeutic agent for cervical cancer. Here, we reviewed the potential anticancer effects of metformin against cervical cancer and discussed possible underlying mechanisms.

scholarly journals Amniotic Fluid Stem Cell-Derived Extracellular Vesicles Counteract Steroid-Induced Osteoporosis In Vitro

2020 ◽  
Vol 22 (1) ◽  
pp. 38
Author(s):  
Martina Gatti ◽  
Francesca Beretti ◽  
Manuela Zavatti ◽  
Emma Bertucci ◽  
Soraia Ribeiro Luz ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Extracellular Vesicles ◽  
Culture Medium ◽  
Cell Potential ◽  
Osteoblast Cell Line ◽  
Local Bone ◽  
Current Therapies ◽  
Amniotic Fluid Stem Cell ◽  
Related Proteins

Background—Osteoporosis is characterized by defects in both quality and quantity of bone tissue, which imply high susceptibility to fractures with limitations of autonomy. Current therapies for osteoporosis are mostly concentrated on how to inhibit bone resorption but give serious adverse effects. Therefore, more effective and safer therapies are needed that even encourage bone formation. Here we examined the effect of extracellular vesicles secreted by human amniotic fluid stem cells (AFSC) (AFSC-EV) on a model of osteoporosis in vitro. Methods—human AFSC-EV were added to the culture medium of a human pre-osteoblast cell line (HOB) induced to differentiate, and then treated with dexamethasone as osteoporosis inducer. Aspects of differentiation and viability were assessed by immunofluorescence, Western blot, mass spectrometry, and histological assays. Since steroids induce oxidative stress, the levels of reactive oxygen species and of redox related proteins were evaluated. Results—AFSC-EV were able to ameliorate the differentiation ability of HOB both in the case of pre-osteoblasts and when the differentiation process was affected by dexamethasone. Moreover, the viability was increased and parallelly apoptotic markers were reduced. The presence of EV positively modulated the redox unbalance due to dexamethasone. Conclusion—these findings demonstrated that EV from hAFSC have the ability to recover precursor cell potential and delay local bone loss in steroid-related osteoporosis.

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