Nanomedicine, an emerging therapeutic strategy for oral cancer therapy

Oral cavity and oropharyngeal carcinomas (oral cancer) represents a significant cause of morbidity and mortality. Despite efforts in improving early diagnosis and treatment, the 5-year survival rate of advanced stage of the disease is less than 63%. The field of nanomedicine has offered promising diagnostic and therapeutic advances in cancer. Indeed, several platforms have been clinically approved for cancer therapy, while other promising systems are undergoing exploration in clinical trials. With its ability to deliver drugs, nucleic acids, and MRI contrast agents with high efficiency, nanomedicine platforms offer the potential to improve drug efficacy and tolerability. The aim of the present mini-review is to summarize the current preclinical status of nanotechnology systems for oral cancer therapy. The nanoplatforms for delivery of chemopreventive agents presented herein resulted in significantly higher anti-tumor activity than free forms of the drug, even against a chemo-resistant cell line. Impressive results have also been obtained using nanoparticles to deliver chemotherapeutics, resulting in reduced toxicity both in vitro and in vivo. Nanoparticles have also led to improvements in efficacy of photodynamic therapies through the development of targeted magnetic nanoparticles. Finally, gene therapy using nanoparticles demonstrated promising results specifically with regards to inhibition of gene expression. Of the few in vivo studies that have been reported, many of these used animal models with several limitations, which will be discussed herein. Lastly, we will discuss several future perspectives in oral cancer nanoparticle-based therapy and the development of appropriate animal models, distinguishing between oral cavity and oropharyngeal carcinoma

Is There any Relationship Between the Type of Alcoholic Beverage and Oral Cancer? : Focus on Red Wine in an European Perspective

Since decades, it has been suggested that regular, moderate consumption of red wine, a major component of Mediterranean diet, at main meals, may contribute to explain the healthy properties attributed to this traditional dietary style. Despite preclinical in vitro/in vivo data have shown many significant pharmacological activities of grape phytochemicals, mostly polyphenols, evidence in humans is still debated. This lack of consensus may be due to the equilibrium between the two main components of wine relevant for health: alcohol and phytochemicals. Because ethanol is a major risk factor in oral carcinogenesis, in this commentary, we briefly discuss the relationship between the type of alcoholic beverage and oral cancer in European countries

Antibacterial and antifungal activities of 2,3-pyrrolidinedione derivatives against oral pathogens

Among the novel approaches applied to antimicrobial drug development, natural product-inspired synthesis plays a major role, by providing biologically validated starting points. Tetramic acids, a class of natural products containing a 2,4-pyrrolidinedione ring system, have attracted considerable attention for their antibacterial, antiviral, antifungal and anticancer activities. On the contrary, compounds with a 2,3-pyrrolidinedione skeleton have been considerably less investigated. In this work, we established chemical routes to the substituted 2,3-pyrrolidinedione core, which enabled the introduction of a wide range of diversity. In the perspective of a potential application for oral healthcare, a number of analogues with various substituents on the 2,3-pyrrolidinedione core were investigated for their antimicrobial and antifungal activities. The most promising compound showed a significant antimicrobial activity on Streptococcus mutans and Candida albicans, comparable to that of chlorhexidine, the gold standard in oral healthcare

Dental treatment of a rare case of pyoderma gangrenosum with aggressive periodontal disease

Background and Overview: Pyoderma gangrenosum (PG) is a rare neutrophil-mediated autoinflammatory dermatosis that can involve the oral mucosa. Dental surgery is a potential triggering factor for the onset of PG lesions. The authors describe and discuss the dental management of a rare case of aggressive periodontitis in a patient with PG, from multiple tooth extractions to prosthetic rehabilitation, including administration of systemic steroid prophylaxis before surgery to prevent the potential onset of PG-related lesions. Case Description: A 22-year-old man who had a diagnosis of PG and who had aggressive periodontal disease underwent dental extractions, gingivoplastic surgery, and prosthetic rehabilitation. The patient received 8 milligrams of betamethasone intramuscularly 20 minutes before the oral surgery. The tissues healed perfectly, and no adverse effects were reported. Conclusions and Practical Implications: For minor oral surgery, prophylactic corticosteroids might help reduce the risk of developing PG-related lesions. The clinician should plan the prosthetic devices to be as atraumatic as possible

Ultrasonic Surgical Aspirator to Treat Deep Infrabony Defects: A New Flapless Minimally Invasive Approach

The primary outcome of the present study was to assess the percentage of pocket closure, and the secondary aim was to evaluate the clinical performance in terms of clinical attachment level (CAL) gain, probing pocket depth (PPD) reduction, and gingival recession (REC) after the use of cavitron ultrasonic surgical aspirator (CUSA) in deep infrabony defects. Fourteen deep infrabony defects in 11 patients who were previously treated with active periodontal therapy followed by one year of supportive periodontal therapy (at least three sessions) were additionally treated by the aid of CUSA. Eighty-six percent of the initial defects (12 out of 14) resulted in a PD\u2009<\u20095\u2009mm, showing complete resolution six months after CUSA treatment, without any adverse event and with negligible pain (VAS from 0 to 3). CUSA showed potential as a method to promote pocket healing, reduce PPD, and increase clinical attachment (P < 0.001) in deep infrabony defects. This trial is registered with ClinicalTrials.gov NCT03567161

World Workshop on Oral Medicine VII: Targeting the oral microbiome Part 2: Current knowledge on malignant and potentially malignant oral disorders.

Objective: The World Workshop on Oral Medicine VII chose the oral microbiome as a focus area. Part 1 presents the methodological state of the science for oral microbiome studies. Part 2 was guided by the question: What is currently known about the microbiome associated with oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa?. Materials and Methods: A scoping review methodology was followed to identify and analyse relevant studies on the composition and potential functions of the oral microbiota using high-throughput sequencing techniques. The authors performed searches in PubMed and EMBASE. After removal of duplicates, a total of 239 potentially studies were identified. Results: Twenty-three studies on oral squamous cell carcinoma, two on oral leukoplakia and four on oral lichen planus were included with substantial differences in diagnostic criteria, sample type, region sequenced and sequencing method utilised. The majority of studies focused on bacterial identification and recorded statistically significant differences in the oral microbiota associated with health and disease. However, even when comparing studies of similar methodology, the microbial differences between health and disease varied considerably. No consensus on the composition of the microbiomes associated with these conditions on genus and species level could be obtained. Six studies on oral squamous cell carcinoma had included in silico predicted microbial functions (genes and/or pathways) and found some similarities between the studies. Conclusions: Attempts to reveal the microbiome associated with oral mucosal diseases are still in its infancy, and the studies demonstrate significant clinical and methodological heterogeneity across disease categories. The immense richness and diversity of the microbiota clearly illustrate that there is a need for additional methodologically comparable studies utilising deep sequencing approaches in significant cohorts of subjects together with functional analyses. Our hope is that following the recipe as outlined in our preceding companion paper, that is Part 1, will enhance achieving this in the future and elucidate the role of the oral microbiome in oral squamous cell carcinoma and potentially malignant disorders of the oral mucosa

Cytotoxic activity of a plant extract on cancer cells

Chemoprevention by natural products may be considered a promising approach to cancer control and management [1]. Many studies have demonstrated antiproliferative, cytostatic and cytotoxic activities of phytochemicals against cancer cells [2]. In this study, a plant extract from Arctium lappa, Berberis vulgaris and Eschscholtia californica was tested as potential anticancer agent. The antitumoral activity of this plant extract was tested on four human cancer cell lines: MCF-7 (breast carcinoma cells), Huh-7 (hepatic carcinoma cells), HTB-43 (oropharyngeal carcinoma cells) and ECV- 304 (urinary bladder carcinoma cells). The efficacy of the extract was compared to the common chemotherapeutic agent cyclophosphamide. Three plant extract concentrations were tested: 800, 650 and 450 ng/ml; for cyclophosphamide, three concentrations were assayed, according to literature data: 1300, 1000 and 850 ng/ml [3]. In addition, plant extract and cyclophosphamide were tested on two primary cell lines as controls, human gingival fibroblasts and human mammary fibroblasts. Cell viability was evaluated by the MTT [(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Sigma] colorimetric assay and the new xCELLigence system (Roche) for real-time monitoring of cell viability. All concentrations of plant extract exhibited a high level of cytotoxicity on MCF-7, Huh-7, HTB-43 and ECV-304 cancer cells, similar to cyclophosphamide, though they slightly reduced viability of human gingival and mammary fibroblasts. Conversely, the conventional chemotherapeutic drug showed a marked cytotoxicity on control cells. The potential of the plant extract has been demonstrated in vitro on various types of cancers, suggesting a possible use of this natural product as a promising anticancer agent. Further studies are needed to ascertain its efficacy in vivo and to elucidate its mechanism(s) of action at molecular and biochemical levels

Oral dysbiosis in pancreatic cancer and liver cirrhosis: A review of the literature

The human body is naturally colonized by a huge number of different commensal microbial species, in a relatively stable equilibrium. When this microbial community undergoes dysbiosis at any part of the body, it interacts with the innate immune system and results in a poor health status, locally or systemically. Research studies show that bacteria are capable of significantly influencing specific cells of the immune system, resulting in many diseases, including a neoplastic response. Amongst the multiple different types of diseases, pancreatic cancer and liver cirrhosis were significantly considered in this paper, as they are major fatal diseases. Recently, these two diseases were shown to be associated with increased or decreased numbers of certain oral bacterial species. These findings open the way for a broader perception and more specific investigative studies, to better understand the possible future treatment and prevention. This review aims to describe the correlation between oral dysbiosis and both pancreatic cancer and liver cirrhotic diseases, as well as demonstrating the possible diagnostic and treatment modalities, relying on the oral microbiota, itself, as prospective, simple, applicable non-invasive approaches to patients, by focusing on the state of the art. PubMed was electronically searched, using the following key words: "oral microbiota" and "pancreatic cancer" (PC), "liver cirrhosis", "systemic involvement", and "inflammatory mediators". Oral dysbiosis is a common problem related to poor oral or systemic health conditions. Oral pathogens can disseminate to distant body organs via the local, oral blood circulation, or pass through the gastrointestinal tract and enter into the systemic circulation. Once oral pathogens reach an organ, they modify the immune response and stimulate the release of the inflammatory mediators, this results in a disease. Recent studies have reported a correlation between oral dysbiosis and the increased risk of pancreatic and liver diseases and provided evidence of the presence of oral pathogens in diseased organs. The profound impact that microbial communities have on human health, provides a wide domain towards precisely investigating and clearly understanding the mechanism of many diseases, including cancer. Oral microbiota is an essential contributor to health status and imbalance in this community was correlated to oral and systemic diseases. The presence of elevated numbers of certain oral bacteria, particularly P. gingivalis, as well as elevated levels of blood serum antibodies, against this bacterial species, was associated with a higher risk of pancreatic cancer and liver cirrhosis incidence. Attempts are increasingly directed towards investigating the composition of oral microbiome as a simple diagnostic approach in multiple diseases, including pancreatic and liver pathosis. Moreover, treatment efforts are concerned in the recruitment of microbiota, for remedial purposes of the aforementioned and other different diseases. Further investigation is required to confirm and clarify the role of oral microbiota in enhancing pancreatic and liver diseases. Improving the treatment modalities requires an exertion of more effort, especially, concerning the microbiome engineering and oral microbiota transplantation