Promising Role of Alkaloids in the Prevention and Treatment of Thyroid Cancer and Autoimmune Thyroid Disease: A Comprehensive Review of the Current Evidence.

Thyroid cancer (TC) and thyroid autoimmune disorders (AITD) are among the most common diseases in the general population, with higher incidence in women. Chronic inflammation and autoimmunity play a pivotal role in carcinogenesis. Some studies, indeed, have pointed out the presence of AITD as a risk factor for TC, although this issue remains controversial. Prevention of autoimmune disease and cancer is the ultimate goal for clinicians and scientists, but it is not always feasible. Thus, new treatments, that overcome the current barriers to prevention and treatment of TC and AITD are needed. Alkaloids are secondary plant metabolites endowed with several biological activities including anticancer and immunomodulatory properties. In this perspective, alkaloids may represent a promising source of prophylactic and therapeutic agents for TC and AITD. This review encompasses the current published literature on alkaloids effects on TC and AITD, with a specific focus on the pathways involved in TC and AITD development and progression.

Pathophysiology and Main Molecular Mechanisms of Urinary Stone Formation and Recurrence.

Kidney stone disease (KSD) is one of the most common urological diseases. The incidence of kidney stones has increased dramatically in the last few decades. Kidney stones are mineral deposits in the calyces or the pelvis, free or attached to the renal papillae. They contain crystals and organic components, and they are made when urine is supersaturated with minerals. Calcium-containing stones are the most common, with calcium oxalate as the main component of most stones. However, many of these form on a calcium phosphate matrix called Randall's plaque, which is found on the surface of the kidney papilla. The etiology is multifactorial, and the recurrence rate is as high as 50% within 5 years after the first stone onset. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more effective drugs. This review aims to understand the pathophysiology and the main molecular mechanisms known to date to prevent recurrences, which requires behavioral and nutritional interventions, as well as pharmacological treatments that are specific to the type of stone.

Pattern and localization of perineural invasion predict poor survival in oral tongue carcinoma.

BACKGROUND: Survival rate for oral tongue squamous cell carcinoma (OTSCC) is still poor and, despite Tumor-Node-Metastasis staging system has been recently updated, patients included under the same stage still show difference in prognosis. Perineural invasion (PNI) emerged to be an indicator of tumor aggressive behavior and unfortunate events. In this study, we investigate the clinic and prognostic value of PNI in a cohort of OTSCC patients. METHODS: About 200 patients with OTSCC were retrospectively evaluated the presence of PNI. PNI was furtherly descripted as uni-/multifocal and as intra-/peritumoral. Disease-Specific and Relapse-Free Survival (DSS; RFS) were estimated; moreover, we included PNI in the current AJCC 8th Staging System, improving the prognostication model. RESULTS: Perineural invasion was found in 40.5% of patients. Intratumoral PNI predicted patients at high risk of being diagnosed with lymph-node metastasis. Tumors with positive PNI reported a worse DSS (Hazard Ratio=1.878, p-value = 0.008). Moreover, patients exhibiting both multifocal intra- and peritumoral PNI reported poorest DSS (Hazard Ratio = 2.409, p-value = 0.010). Patients were reclassified in a new staging system in case of multifocal PNI, providing better stratification capacity. CONCLUSIONS: Perineural invasion might serve as an additional prognostic factor in OTSCC, and by integrating PNI in the staging system, further improvements in prognostication might be reached.

Prognostic significance of tumor budding thresholds in oral tongue squamous cell carcinoma.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) represents the most common malignancy of the oral cavity. Tumor budding (TB) is a reliable prognostic factor in OTSCC; however, a standardized scoring system is not still validated. AIMS: The study aims to evaluate the prognostic role of TB in 211 OTSCC patients treated between 1997 and 2018. MATERIALS & METHODS: TB was evaluated on hematoxylin and eosin-stained sections in the hotspot area of the infiltrative front (×200-magnification). It was scored using a two-tier system, a three-tier system, and according to BD-model and revised-Grading system. Univariate and multivariate Cox regression analyses of disease-specific survival (DSS) and disease-free survival (DFS) were performed. A p < 0.05 was considered as statistically significant. RESULTS: The two-tier and three-tier systems resulted an independent prognostic factor of DSS. High-risk patients had a 2.21 and 3.08 times increased probability of poor DSS compared with low-risk group. It is significantly increased even for intermediate-risk group. No significant differences emerged classifying patients according to BD-model and revised-Grading system. DISCUSSION: These data confirm the prognostic value of TB in predicting DSS in OTSCC. Classifying patients into two groups using the 5-bud cutoff significantly discriminates their outcomes. CONCLUSION: Since the established role of DOI and the poor prognostic value of grading, TB could be considered an independent prognostic marker.

High-risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes. MATERIALS AND METHODS: Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes. RESULTS: Cases harbouring high-risk-of-death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild-type cases, while no significant difference in treatment outcomes was found between cases with low-risk-of-death mutations and wild-type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease. CONCLUSIONS: This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients.

LGALS3BP is a potential target of antibody-drug conjugates in oral squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody-drug conjugate (ADC) therapy. METHODS: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT-PCR, Western Blot analysis, and ELISA. RESULTS: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer-derived extracellular vesicles. Moreover, LGALS3BP high-expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC-payload DM4, with an IC50 around 0.3 nM. CONCLUSIONS: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC-based therapy.

Impact of periodontitis on circulating cell-free DNA levels as a measure of cardiovascular disease.

OBJECTIVES: The present study aims to assess the serum circulating cell-free (cfDNA) concentrations in patients with periodontitis and cardiovascular disease (CVD) and to evaluate the impact of periodontitis on circulating cfDNA levels and the confounding factors that might mediated the possible relationship. MATERIALS AND METHODS: Healthy controls (n=30) and patients with CVD (n=31), periodontitis (n=31), and periodontitis + CVD (n=30) were enrolled in the present study. All subjects underwent regular periodontal examination and blood sampling and cfDNA evaluation. The analysis of the plasma cfDNA concentrations was performed using a dsDNA Assay Kit. RESULTS: In comparison with healthy controls and CVD patients, periodontitis and periodontitis+CVD exhibited significantly higher expression of circulating cfDNA (p<0.05). There was a positive correlation among plasma cfDNA and clinical attachment loss (CAL) (p=0.019), high sensitivity C-reactive protein (hs-CRP) (p=0.027), and periodontal inflamed surface area (PISA) (p=0.003). Furthermore, the multivariate regression analysis evidenced that PISA (p<0.001), hs-CRP (p=0.014), and full-mouth bleeding score (FMBS) (p=0.004) were significant predictors of circulating cfDNA concentrations. CONCLUSIONS: The results of the study highlighted that the periodontitis and periodontitis + CVD group showed higher circulating cfDNA expression in comparison with healthy controls and CVD patients. Moreover, the extent of periodontitis was correlated with the increased cfDNA levels and represented a significant predictor of the increased circulating cfDNA concentrations. CLINICAL RELEVANCE: Unbalanced circulating cfDNA concentrations have been indicated to represent a possible risk of CVD and endothelial dysfunction. Periodontitis and periodontitis + CVD patients showed higher circulating cfDNA expression; moreover, the extent of periodontitis significantly predicted higher circulating cfDNA concentrations, suggesting the potential increased risk of developing CVD in periodontitis patients.

Cost/effectiveness analysis of treatment options for the rehabilitation of the total edentulous mandible.

BACKGROUND: Several solutions are available for the rehabilitation of edentulous jaws. Each treatment option is characterised by specific advantages and drawbacks. OBJECTIVE: The aim of this research was to perform a cost-effectiveness (CE) analysis of the main rehabilitative solutions of totally edentulous mandibles. METHODS: Decision tree models were built using TreeAge Pro Healthcare 2021 software to compare the following strategies: Conventional Denture (CD), Overdenture retained by two implants (OD-2), Overdenture retained by a bar on two implants (ODbar), Overdenture retained by 4 mini-implants (ODmini) and Fixed denture supported by 4 implants (FD). Costs were estimated using data from public rate tables. Effectiveness measures were obtained from a meta-analysis of literature data, normalising the different scales in 0-1 range. A value of 30 000€ per 1 normalised utility points was set as threshold of willingness to pay (WTP). Probabilistic sensitivity analysis (PSA) with 1000 Monte Carlo Simulations was performed to characterise uncertainty. RESULTS: Total costs ranged between 1804,40€ for CD and 10 008,80€ for FD rehabilitations, with an effectiveness of 0,69 and 0,95 normalised points (0-1 scale) for the two solutions. The ODbar resulted to be the most CE strategy at the established WTP value, with the highest Net Monetary Benefit (22 001,20€), followed by the OD-2 rehabilitation (21 866,80€). PSA analysis confirmed the dominance of OD-2 and ODbar strategies, confirming a net separation from the other alternatives. CONCLUSION: OD stabilised by 2 implants could represent a good rehabilitative solution for patients with edentulous mandible, being a good trade-off in terms of costs and effectiveness. Nevertheless, a standardised measure of oral health-related quality of life is needed to obtain more reliable results.

A Reciprocal Link between Oral, Gut Microbiota during Periodontitis: The Potential Role of Probiotics in Reducing Dysbiosis-Induced Inflammation.

Human body is colonized by a florid microbial community of bacteria, archaea, fungi, protists, helminths, and viruses, known as microbiota, which co-evolves with the host and influences its health through all stages of its life. It is well known that oral microorganisms form highly structurally and functionally organized multi-species biofilms and establish a network of complex mutual inter-species interactions having a primary function in synergy, signaling, or antagonism. This ecological model allows the microorganisms to increase their resistance to antimicrobial agents and settle a balanced microbes-host symbiotic relationship that ensures oral and global health status in humans. The host-associated microbiome is an important factor in human health and disease. Therefore, to develop novel diagnostic, therapeutic, and preventive strategies, microbiome's functions and the reciprocal interactions every microbiome entertains with other microbial communities in the human body are being investigated. This review provides an analysis of the literature about the close connection between the two largest microbial communities in humans: the oral and the gut microbiomes. Furthermore, it focuses on how the alteration of their microbial and functional characteristics can lead to and reciprocally influence the onset of both oral and intestinal microbiome-associated illness, along with the potential role of probiotics in ameliorating inflammation and microbial dysbiosis.

Prognostic assessment of different methods for eosinophils detection in oral tongue cancer.

BACKGROUND: TATE has been proposed as a prognostic factor in oral cancer staging; however, the controversial literature data limit its application in the routine diagnosis. The aim of this study was to evaluate the prognostic value of TATE in patients with oral tongue cancer. The second aim was to identify any difference in the methods of eosinophil quantification or in the cutoff values reported in literature. METHODS: Clinic-pathological data of 204 patients treated at "Ospedali Riuniti" Hospital, Ancona, Italy, were collected. Evaluation of TATE was performed on hematoxylin-and-eosin-stained slides and correlation with survival outcomes was evaluated. The number of eosinophils per square millimeter was evaluated by using two methods, namely density (TATE-1) and classical (TATE-2) methods. For each of the 2 methods tested, patients were stratified into two or three groups, according to the most used cutoff values reported in literature. RESULTS: Regardless of the method of eosinophil quantification or the cutoff values used, patients with high TATE had a significantly better disease-specific survival. The density method (TATE-1) showed a better predictive performance, in particular when applying a single cutoff of 67 eosinophils/mm2 , two cutoffs of 10 and 100 eosinophils/mm2 , or two cutoffs of 50 and 120 eosinophils/mm2 . CONCLUSION: The evaluation of TATE is simple, cost-effective, and easy to implement in daily practice with the aim of improving risk stratification of patients affected by oral tongue cancer. Results of prognostic performance analysis suggest using density (TATE-1) method as the standard approach to evaluate TATE in future studies, enhancing replicability.

Role Played by Paraoxonase-2 Enzyme in Cell Viability, Proliferation and Sensitivity to Chemotherapy of Oral Squamous Cell Carcinoma Cell Lines.

Oral squamous cell carcinoma represents the most aggressive and frequent form of head and neck cancer. Due to drug resistance, the 5-year survival rate of patients with advanced disease is less than 50%. In order to identify molecular targets for effective oral cancer treatment, we focused on paraoxonase-2 enzyme. Indeed, based on data previously obtained from preliminary immunohistochemistry and Western blot analyses performed on tissue specimens, the enzyme was found to be upregulated in tumor compared with normal oral mucosa. Therefore, paraoxonase-2 gene silencing was achieved in HSC-3 and HOC621 oral cancer cell lines, and the effect on cell proliferation, viability, apoptosis induction and sensitivity to cisplatin and 5-fluorouracil treatment was evaluated. Fourier Transform InfraRed Microspectroscopy analyzed alterations of cellular macromolecules upon treatment. Enzyme level and cell proliferation were also determined in cisplatin-resistant clones obtained from HOC621 cell line, as well as in parental cells. Reported data showed that paraoxonase-2 knockdown led to a reduction of cell proliferation and viability, as well as to an enhancement of sensitivity to cisplatin, together with the activation of apoptosis pathway. Spectroscopical data demonstrated that, under treatment with cisplatin, oxidative damage exerted on lipids and proteins was markedly more evident in cells down-regulating paraoxonase-2 compared to controls. Interestingly, enzyme expression, as well as cell proliferation were significantly higher in cisplatin-resistant compared with control HOC621 cells. Taken together these results seem to candidate the enzyme as a promising target for molecular treatment of this neoplasm.

Bruxism in Children and Adolescents with Down Syndrome: A Comprehensive Review.

The role of bruxism in children and adolescents with Down syndrome, the most often diagnosed congenital syndrome, is still unclear. Therefore, this study aims to conduct a narrative review of the literature about bruxism in children and adolescents with Down syndrome to identify the prevalence, risk factors, and possible treatments of this disorder. Although an accurate estimate of its prevalence could not be inferred, it appears that bruxism is more prevalent in Down syndrome individuals rather than in the general pediatric population. No gender difference was observed, but a reduction in its prevalence was described with increasing age (around 12 years). The variability in the diagnostic techniques contributed to the heterogeneity of the literature data. Clinicopathological features of Down syndrome, such as muscle spasticity, oral breathing, and a predisposition to obstructive sleep apnea, may suggest a higher prevalence of bruxism in this patient group. Finally, given the paucity of studies on the management of bruxism in this population, it was not possible to outline a standard protocol for the non-invasive treatment of cases in which an observational approach is not sufficient.

Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer.

BACKGROUND: Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups. METHODS: A systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome-genome-transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients' overall survival. RESULTS: TP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner. CONCLUSIONS: The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks.

Addition of the tumour-stroma ratio to the 8th edition American Joint Committee on Cancer staging system improves survival prediction for patients with oral tongue squamous cell carcinoma.

AIMS: One of the objectives of current research is to customise the treatment of cancer patients. The achievement of this objective requires stratification of patients based on the most significant prognostic factors. The aims of this study were to evaluate the prognostic value of the tumour-stroma ratio (TSR), defined as the proportion of tumour cells relative to surrounding stroma, in patients with oral tongue squamous cell carcinoma (OTSCC), and to develop a prognostic nomogram based on the most significant clinicopathological features. METHODS AND RESULTS: Clinicopathological data of 211 patients treated at 'Ospedali Riuniti' General Hospital (Ancona, Italy) for OTSCC were collected. One hundred and thirty-nine patients were restaged according to the 8th edition American Joint Committee on Cancer (AJCC) staging system. Evaluation of the TSR was performed on haematoxylin and eosin-stained slides, and correlation with survival outcomes was evaluated. In addition, with the aim of integrating the independent value of the TSR with the 8th edition AJCC staging system, a prognostic nomogram for OTSCC has been developed. OTSCC with a low TSR (i.e. a high proportion of stroma and a low proportion of tumour cells) was shown to have negative prognostic value in terms of disease-specific survival, with a hazard ratio (HR) of 1.883 and a 95% confidence interval (CI) of 1.033-3.432 (P = 0.039), and overall survival (HR = 1.747, 95% CI 0.967-3.154; P = 0.044), independently of other histological and clinical parameters. For the cohort of 139 patients restaged according to the 8th edition AJCC staging system, variables correlating with a poor prognosis were: the TSR, perineural invasion, and sex. The nomogram built on these parameters showed good predictive capacity, outperforming the 8th edition AJCC staging system in stratifying disease-specific survival in OTSCC patients. CONCLUSIONS: Including the TSR in the predictive model could improve risk stratification of OTSCC patients and aid in making treatment decisions.

Differential expression of nicotinamide N-methyltransferase in primary and recurrent ameloblastomas and odontogenic keratocysts.

BACKGROUND: Odontogenic tumours are a group of rare heterogeneous diseases that range from hamartomatous tissue proliferations to benign and malignant neoplasms. Recurrences can occur after 10 years, so long-term clinical and radiological follow-up is required. The study of the molecular mechanisms involved in the development of these lesions is necessary to identify new prognostic markers. In this study, we evaluate the possible role of nicotinamide N-methyltransferase (NNMT) in ameloblastomas (AM) and odontogenic keratocysts (OKC). MATERIALS AND METHODS: A total of 105 surgical specimens of primary and recurrent lesions were obtained from 55 patients (25 AM, 30 OKC). In particular, 50 AMs (25 primary, 25 recurrences) and 55 OKCs (30 primary, 25 recurrences) were retrieved. We carried out immunohistochemical analyses to evaluate the cytoplasmic expression of NNMT, measuring the percentage of positive cells and the value of NNMT expression intensity. RESULTS: NNMT expression was significantly higher in recurrent than primary AMs (P = .0430). This result was confirmed by staining intensity, showing more cases with moderate/intense staining in recurrent AMs (P = .0470). NNMT expression was significantly lower in recurrent than primary OKC (P = .0014). Staining intensity showed more cases with moderate/intense staining in primary OKCs (P = .0276). CONCLUSIONS: This report is the first to evaluate NNMT expression in odontogenic lesions and to demonstrate a differential expression in recurrent AMs and OKCs, suggesting that there is potential for use of NNMT as prognostic marker.

Histological features and survival in young patients with HPV-negative oral squamous cell carcinoma.

OBJECTIVES: The frequency of oral squamous cell carcinoma in young adults has increased in the last decades, and there are conflicting results in literature about its prognosis in young subjects. The aim of this study was to analyse the clinical and pathological features of oral squamous cell carcinoma in a cohort of young adults in order to investigate the presence of new independent prognostic markers. MATERIALS AND METHODS: Only HPV-negative young patients (under 40-year-old) affected by oral squamous cell carcinoma were considered in this study. Clinical and pathological data were collected. Patients were re-staged according to the 8th edition of AJCC. RESULTS: Overall, 66 patients were considered in this study. Perineural invasion significant correlated with both 7th and 8th edition of AJCC, and lymphovascular invasion (p-value < .05). The multivariate survival analysis showed that patients with perineural invasion had a significant worse prognosis (HR = 6.384 95% C.I. 1.304-31.252; p-value = .022). CONCLUSIONS: Perineural invasion emerged as an independent prognostic factor for disease-specific survival in young patients with oral squamous cell carcinoma. Furthermore, the evaluation of this parameter is simple, inexpensive and can be used to augment the risk stratification of oral cancer based on the 8th edition of AJCC.

Odontogenic tumours: a 25-year epidemiological study in the Marche region of Italy.

PURPOSE: Epidemiological data of odontogenic tumours (OT) are conflicting, with significant differences among the countries. This study aims to evaluate incidence and prevalence of OTs in the Marche population in a period of 25 years, according to 4th Edition of WHO Classification. METHODS: In this study, only patients of Marche region treated for OTs were considered. Data were retrieved from Institute of Pathology, Marche Polytechnic University, Italy. Because this is the only tertiary referral centre for Head and Neck pathology within Marche region, the patient sample could be considered well representative of this area. From each case, age, sex, site, diagnosis and relapses were recorded. RESULTS: Overall, 100 patients were treated for OTs from 1994 to 2018 in Marche region. The annual incidence rate ranged from 0.13 to 0.39 per 100,000, while life prevalence was 6.50 per 100,000. Mean age of onset for primary OTs was 49.7 ± 20.1 years. Twenty-seven patients developed recurrences, showing a mean age of 54 ± 19.7 years and a mean recurrence time of 51.2 ± 34 months. CONCLUSION: This is the first epidemiological study on OTs in Italian population according to 4th Edition of WHO Classification. Although limited in their retrospective nature, these findings could accurately estimate epidemiology of OTs in Italy.

Impact of Elderly Masticatory Performance on Nutritional Status: An Observational Study.

Background and Objectives: Masticatory limitations on the dietary habits of edentulous subjects restrict their access to adequate nutrition, exposing them to a greater risk of protein energy malnutrition. The aim of this study is to verify the existence of an association between Masticatory Performance (MP) and nutritional changes in the elderly. Materials and Methods: 76 participants were enrolled. MP testing was performed using the two-color chewing gum mixing test. The system used reveals the extent to which the two differently colored chewing gums mix, and allows discrimination between different MPs. The assessment of the participants' nutritional statuses was carried out through a food interview. Anthropometric parameters were collected, and bioimpedance analysis was performed. Results: Mean MP was 0.448 ± 0.188. No statistically significant differences were detected between male and female subjects (p > 0.05). According to the Body Mass Index (BMI), obese patients had a lower MP than overweight and normal weight subjects (0.408 ± 0.225, 0.453 ± 0.169 and 0.486 ± 0.181, respectively). MP values were lower both in male and female subjects with a waist circumference above the threshold than those below it (0.455 ± 0.205 vs. 0.476 ± 0.110, respectively, in males and 0.447 ± 0.171 vs. 0.501 ± 0.138, respectively, in females). No relationship was noticed between MP and bioimpedance parameters (p > 0.05). Conclusions: A statistically significant relation was observed between MP and the number of missing teeth. A reduced MP could worsen nutritional parameters. A reduced MP did not seem to negatively affect bioimpedance parameters.

Overexpression of nicotinamide N-methyltransferase in HSC-2 OSCC cell line: effect on apoptosis and cell proliferation.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common malignancy of oral cavity. Despite advances in therapeutic approaches, the 5-year survival rate for oral cancer has not improved in the last three decades. Therefore, new molecular targets for early diagnosis and treatment of OSCC are needed. In the present study, we focused on the enzyme nicotinamide N-methyltransferase (NNMT). We have previously shown that enzyme expression is upregulated in OSCC and NNMT knockdown in PE/CA PJ-15 cells significantly decreased cell growth in vitro and tumorigenicity in vivo. MATERIAL AND METHODS: To further explore the role of the enzyme in oral cancer cell metabolism, HSC-2 cells were transfected with the NNMT expression vector (pcDNA3-NNMT) and the effect of enzyme upregulation on cell proliferation was evaluated by MTT assay. Subsequently, we investigated at molecular level the role of NNMT on apoptosis and cell proliferation, by exploring the expression of ß-catenin, survivin, and Ki-67 by real-time PCR. Moreover, we performed immunohistochemistry on 20 OSCC tissue samples to explore the expression level of NNMT and survivin ΔEx3 isoform. RESULTS: Enzyme upregulation significantly increased cell growth in vitro. Moreover, a positive correlation between NNMT and survivin ΔEx3 isoform expression levels was found both in HSC-2 cells and in OSCC tissue samples. CONCLUSION: Taken together, our results indicate a possible involvement of NNMT in the proliferation and tumorigenic capacity of OSCC cells and seem to suggest that the enzyme could represent a potential target for the treatment of oral cancer. CLINICAL RELEVANCE: The involvement of NNMT in cell growth and anti-apoptotic mechanisms seems to suggest that this enzyme could be a new therapeutic target to improve the survival of OSCC patients.

Survivin-Based Treatment Strategies for Squamous Cell Carcinoma.

Survivin, an anti-apoptotic molecule abundantly expressed in most human neoplasms, has been reported to contribute to cancer initiation and drug resistance in a wide variety of human tumors. Efficient downregulation of survivin can sensitize tumor cells to various therapeutic interventions, generating considerable efforts in its validation as a new target in cancer therapy. This review thoroughly analyzes up-to-date information on the potential of survivin as a therapeutic target for new anticancer treatments. The literature dealing with the therapeutic targeting of survivin will be reviewed, discussing specifically squamous cell carcinomas (SCCs), and with emphasis on the last clinical trials. This review gives insight into the recent developments undertaken in validating various treatment strategies that target survivin in SCCs and analyze the translational possibility, identifying those strategies that seem to be the closest to being incorporated into clinical practice. The most recent developments, such as dominant-negative survivin mutants, RNA interference, anti-sense oligonucleotides, small-molecule inhibitors, and peptide-based immunotherapy, seem to be helpful for effectively downregulating survivin expression and reducing tumor growth potential, increasing the apoptotic rate, and sensitizing tumor cells to chemo- and radiotherapy. However, selective and efficient targeting of survivin in clinical trials still poses a major challenge.