Pleckstrin Homology Domain Leucine-rich Repeat Protein Phosphatase Acts as a Tumor Suppressor in Oral Squamous Cell Carcinoma.

The pleckstrin homology domain leucine-rich repeat protein phosphatase (PHLPP) family has been found to have both tumor-suppressor and oncogenic properties across various types and locations of cancer. Given that PHLPP has not been previously studied in oral squamous cell carcinoma (SCC), we conducted an assessment of the expression of both its isoforms in oral SCC tissues and cell lines and compared these findings to their corresponding normal counterparts. In addition, we assessed the relationship between PHLPP and clinicopathological factors and patient survival. Quantitative real-time polymerase chain reaction was used to detect the mRNA levels of PHLPP1 and PHLPP2 in cancerous and normal cell lines in addition to 124 oral SCC and noncancerous adjacent epithelia (N = 62, each). Correlations between their expression rate and clinicopathological parameters were further evaluated in 57 patients. Data were statistically analyzed with t test and paired t test, analysis of variance, Mann-Whitney U, and Cox Regression tests (P < 0.05). We found significantly lower levels of both PHLPP isoforms in oral SCC tissues compared with noncancerous epithelia (P < 0.001, for both). However, in the cell lines, this difference was significant only for PHLPP1 (P = 0.027). The correlation between the two isoforms was significant only in cancerous tissues (P < 0.001). None of the clinicopathologic factors showed significant associations with either of the isoforms and there was no correlation with survival. We showed for the first time that PHLPP1 and PHLPP2 act as tumor suppressors in oral SCC at the mRNA level. The regulation of their mRNA appears to be different between normal and cancerous tissues.

Exploring the impact of naltrexone on the THBS1/eNOS/NO pathway in osteoporotic bile duct-ligated rats.

Hepatic osteodystrophy, a prevalent manifestation of metabolic bone disease, can arise in the context of chronic liver disease. The THBS1-eNOS-NO signaling pathway plays a pivotal role in the maturation of osteoclast precursors. This study aimed to investigate the impact of Naltrexone (NTX) on bone loss by examining the THBS1-eNOS-NO signaling pathways in bile duct ligated (BDL) rats. Male Wistar rats were randomly divided into five groups (n = 10 per group): control, sham-operated + normal saline, BDL + normal saline, sham-operated + NTX (10 mg/kg), and BDL + NTX. Parameters related to liver injury were measured at the study's conclusion, and Masson-trichrome staining was employed to evaluate collagen deposition in liver tissue. Bone THBS-1 and endothelial nitric oxide synthase (eNOS) expression levels were measured using real-time PCR, while the level of bone nitric oxide (NO) was assessed through a colorimetric assay. NTX treatment significantly attenuated the BDL-induced increase in circulating levels of liver enzymes and bilirubin. THBS-1 expression levels, elevated after BDL, were significantly suppressed following NTX administration in the BDL + NTX group. Despite no alterations in eNOS expression between groups, the bone NO level, significantly decreased in the BDL group, was significantly reduced by NTX in the BDL + NTX group. This study partly provides insights into the possible molecular mechanisms in BDL-induced osteoporosis and highlights the modulating effect of NTX on these pathways. Further research is needed to establish the impact of NTX on histomorphometric indexes.

Effects of Kojic Acid-mediated Sonodynamic Therapy as a Matrix Metalloprotease-9 Inhibitor against Oral Squamous Cell Carcinoma: A Bioinformatics Screening and in vitro Analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a type of cancer that is responsible for a significant amount of morbidity and mortality worldwide. Researchers are searching for promising therapeutic methods to manage this cancer. In this study, an in silico approach was used to evaluate the activity of sonodynamic therapy (SDT) based on the use of Kojic acid as a sonosensitizer to inhibit matrix metalloprotease-9 (MMP-9) in OSCC. MATERIALS AND METHODS: The three-dimensional structure of MMP-9 was predicted and validated by computational approaches. The possible functional role of MMP-9 was determined in terms of Gene Ontology (GO) enrichment analysis. In silico, molecular docking was then performed to evaluate the binding energies of Kojic acid with MMP-9, and ADME parameters and toxicity risks were predicted. The pharmacokinetics and drug-likeness properties of Kojic acid were assessed. Moreover, after the determination of the cytotoxicity effect of Kojic acid-mediated SDT, the change of mmp-9 gene expression was assessed on OSCC cells. RESULTS: The results of the study showed that Kojic acid could efficiently interact with MMP-9 protein with a strong binding affinity. Kojic acid obeyed Lipinski's rule of five without violation and exhibited drug-likeness. The cytotoxic effects of Kojic acid and ultrasound waves on the OSCC cells were dose-dependent, and the lowest expression level of the mmp-9 gene was observed in SDT. CONCLUSIONS: Overall, Kojic acid-mediated SDT as an MMP-9 inhibitor can be a promising adjuvant treatment for OSCC. The study highlights the potential of in silico approaches to evaluate therapeutic methods for cancer treatment.

Oral manifestations of COVID-19 and its management in pediatric patients: A systematic review and practical guideline.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus causes coronavirus disease 2019 (COVID-19), a respiratory infection that has spread worldwide and is responsible for a high death toll. Although respiratory symptoms are the most common, there is growing evidence that oral signs of COVID-19 can also be seen in children. The purpose of this systematic review is to provide a comprehensive analysis of the available data on the oral manifestations of COVID-19 in children and to recommend appropriate methods of diagnosis and treatment. METHODS: A systematic search of the MEDLINE, EMBASE, Scopus, and Web of Science databases was done to discover relevant papers published between their establishment and January 2023. Articles detailing oral symptoms in pediatric patients with confirmed COVID-19 infection were included, and data on clinical characteristics, diagnosis, treatment, and outcomes were extracted and evaluated. RESULTS: A total of 24 studies involving 2112 pediatric patients with COVID-19 were included in the review. The most common presentations are oral lesions, taste and smell disorders, oral candidiasis, hemorrhagic crust, tongue discoloration, lip and tongue fissuring, gingivitis, and salivary gland inflammation. These manifestations were sometimes associated with multi-system inflammatory syndrome in children (MIS-C) or Kawasaki disease (KD). Management strategies varied depending on the severity of the oral manifestation and ranged from symptomatic relief with topical analgesics to systemic medications. CONCLUSION: Oral symptoms of COVID-19 are relatively prevalent in juvenile patients and can be accompanied by severe systemic diseases, such as MIS-C or Kawasaki illness. Early detection and adequate care of these oral symptoms are critical for the best patient results. Understanding the underlying pathophysiology and developing targeted treatments requires more investigation.

Erratum: Effect of amitriptyline on orthodontic tooth movement in rats: An experimental study.

[This corrects the article DOI: 10.34172/joddd.2020.033.].

Antimicrobial Effects of Postbiotic Mediators Derived from Lactobacillus rhamnosus GG and Lactobacillus reuteri on Streptococcus mutans.

BACKGROUND: Streptococcus mutans is a major component of dental plaque, contributing to cariogenic biofilm formation and inducing dental caries. Attempts have recently been made to use postbiotic mediators (PMs) to prevent dental caries. This research evaluated the antimicrobial/antibiofilm activity of PMs derived from Lactobacillus rhamnosus GG (LGG) and Lactobacillus reuteri (LR) against S. mutans in vitro. METHODS: PMs were obtained from the Lactobacilli supernatants. The minimum inhibitory concentration, minimum bactericidal concentration, antibiofilm potential, and metabolic activity of PMs against S. mutans were evaluated using CFU/mL, scanning electron microscopy, and XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reduction assay. The expression of gtfB gene as one of the most important genes involved in S. mutans biofilm formation was also measured using qRT-PCR. RESULTS: CFU score was reduced by both PMs, but the reduction was only significant in LGG (p = 0.02). Both PMs caused a significant decrease in the metabolic activity of S. mutans compared with the controls (p ≤ 0.002). S. mutans treated with LGG PMs exhibited more destructive effects than LR PMs (p > 0.05). S. mutans gtfB gene expression was significantly downregulated when treated with the PMs obtained from both LGG and LR (p = 0.01 for both). CONCLUSIONS: We showed that PMs isolated from two Lactobacillus strains inhibited S. mutans biofilm, metabolic activity, and gtfB gene expression. Therefore, these derivatives may be a suitable biofilm-destruction agent against S. mutants. However, the oral environment is a complex ecosystem that needs further investigation.

Efficacy of synthesized cubic spirulina platensis photosensitizer in anticancer photodynamic therapy: An in vitro study.

Photodynamic therapy (PDT) is an option in select cancer management. Photosensitizers derived from natural sources can offer additional health benefits and play a crucial role in enhancing the efficacy of PDT in cancer treatment. We herein synthesized a cubic form of spirulina platensis (SP) and compared its anticancer-PDT efficacy with the naturally-occurring microhelical SP (MSP) and phycocyanin (Pc) against a tongue cancer cell-line and fibroblast cells. Cubic SP (CSP) was synthesized and characterized using standard analyses. CAL-27 and HGF cell-lines were incubated at different concentrations with each photosensitizer and were irradiated with 635 nm diode-laser. The viability, cellular-uptake, apoptosis and oxidative stress potential were quantitatively analyzed and statistically compared at P<0.05. Our results demonstrated that all three photosensitizers were non-toxic to normal cells before laser irradiation. In CAL-27, viability significantly decreased after PDT in all photosensitizer groups (P<0.05). Whereas, in HGF, Pc exhibited phototoxicity after laser irradiation (P=0.032). Cell-death was mainly apoptotic in Pc and CSP, but necrotic in MSP. Cellular-uptake was significantly higher in Pc, but was similar in MSP and CSP. Increase in reactive oxygen species was significantly higher in the Pc group compared to both SPs (P<0.05). We concluded that both SPs were safe and efficient photosensitizers for anticancer-PDT. CSP exhibited predominant and significant apoptotic death in CAL-27 and HGF cell-lines, while MSP mainly induced necrotic cell death. Despite the good photosensitizing performance of Pc, its use in higher concentrations should be considered with caution, due to the reduced viability that occurred following its use in PDT.

Clinical prognostic value of the SMYD2/3 as new epigenetic biomarkers in solid cancer patients: a systematic review and meta-analysis.

BACKGROUND: SET and MYND domain-containing protein (SMYD) family with methyltransferase activity is involved in cancer progression. This novel meta-analysis aimed to evaluate the association of SMYD family with the clinical and survival outcomes in solid cancer patients. METHODS: We systematically searched Embase, PubMed, Scopus and Web of Science to select relevant articles. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals were extracted. Heterogeneity was evaluated by chi-square-based Q and I2 tests, while publication bias by funnel plots and Egger's test. RESULTS: Thirty-two articles (4,826 patients) met inclusion criteria. SMYD2/3 overexpression was statistically associated with poor overall survival (HR = 1.794, P < 0.001), disease/relapse/progression-free survival (HR = 2.114, P < 0.001), disease/cancer-specific survival (HR = 3.220, P = 0.003), larger tumor size (OR = 1.963, P < 0.001), advanced TNM stage (OR = 2.066, P < 0.001), lymph node metastasis (OR = 2.054, P < 0.001), and distant metastasis (OR = 1.978, P = 0.004). Subgroup analysis showed more significant association between SMYD2 overexpression and reduced survival outcomes than that in SMYD3. Conversely, the relationship between SMYD3 and various clinicopathologic factors was stronger compared to SMYD2. CONCLUSION: Enhanced SMYD2/3 expression may be an unfavorable clinical prognostic factor in different solid cancer types.

The effect of different combinations of fixatives and decalcifying agents on rat and rabbit hard tissues, a guide for histologic processing.

BACKGROUND AND PURPOSE: In order to acquire the best method that can simultaneously maximize tissue morphology and staining quality, we compared the effect of different fixative and decalcifying solutions on the quality of rabbit and rat bone histology. METHOD: Fifty-four rat hemimaxillae and 54 rabbit quarter-parietal bones were allocated into 3 fixation groups (formalin, 10 %sodium-phosphate-buffered-formalin and 10 %calcium-phosphate-buffered-formalin). Each fixative was divided into 6 groups and decalcified with 5 % and 10 % nitric acid (NA), 5 % and 10 % formic acid (FA), Gooding-Stewart liquid (GSL) and EDTA. Slide quality was evaluated on hematoxylin/eosin slides by 3 observers and mean-scores for total-cell-characteristics (TCC) and total-tissue-characteristics (TTC) were statistically analyzed. RESULT: Significant differences in decalcification-time were observed in different combinations of decalcifiers and fixatives in both animals. In rats, TCC was better preserved when using 10 %NA/calcium-phosphate-buffered-formalin compared to 10 %NA/sodium-phosphate-buffered-formalin (P = 0.03). GSL/sodium-phosphate-buffered-formalin performed better than both other fixatives (P < 0.001). TCC differed among the decalcifiers in each of the fixatives. In rabbits, there were differences in TCC among the decalcifiers when formalin (P = 0.001) and sodium-phosphate-buffered-formalin (P = 0.01) were used. TTC only showed significant difference when 10 %FA was used in rats (P = 0.044), with formalin performing better than sodium-phosphate-buffered-formalin (P = 0.01). CONCLUSION: Based on our results, if time is an issue, 10 %NA/calcium-phosphate-buffered-formalin could provide good cellular quality and if time is not a consideration, FA (5 % or 10 %) with sodium-phosphate-buffered-formalin followed by EDTA with formalin, would have the best performance. In rabbits, GSL provides the fastest results, regardless of the fixative and FA/sodium-phosphate-buffered-formalin gives the best cellular quality.

Cell kinetic markers in cutaneous squamous and basal cell carcinoma of the head and neck / Marcadores cinéticos celulares em carcinomas espinocelulares e basocelulares cutâneos de cabeça e pescoço

Abstract Introduction: Proliferation markers play a significant role in the biologic behavior of tumors. Geminin is a known inhibitor of the cell cycle and DNA replication and has not been previously reported in cutaneous basal and squamous cell carcinomas of the head and neck. Objectives: We aimed to investigate proliferation markers ki67, MCM2, and geminin in head and neck cutaneous basal and squamous cell carcinomas. Methods: Forty cases of each tumor were immuostained with ki67, MCM2, and geminin followed by assessment of labeling indices (LIs). MCM2/ki67- and geminin/ki67-ratios were also determined; t-test was used for statistical analysis (p<0.05). Results: There was no significant difference in ki67 (p = 0.06) and MCM2 (p = 0.46) between cutaneous basal and squamous cell carcinomas; however, geminin LI was significantly higher in squamous cell carcinomas compared to cutaneous basal cell carcinomas (p < 0.001). Only geminin/ki67 showed a significant difference between the two tumors with the ratio showing significantly higher numbers in squamous cell carcinomas (p = 0.015). Conclusions: Geminin could be regarded as an effective factor in the pathogenesis of head and neck cutaneous cutaneous basal cell carcinomas and squamous cell carcinomas and may be one of the responsible elements in the difference between the biologic behavior of these tumors. © 2020 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (https://creativecommons.org/licenses/by/4.0/).

Resumo Introdução: Marcadores de proliferação têm um papel significativo no comportamento biológico dos tumores. A geminina é um inibidor conhecido do ciclo celular e da replicação do DNA e não foi relatada anteriormente em carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço. Objetivo: Investigar os marcadores de proliferação ki67, MCM2 e geminina em carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço. Método: Foram submetidos 40a casos de cada tumor à imunocoloração com ki67, MCM2 e geminina, seguida pela avaliação do índice de marcação.Também foram determinadas as razões MCM2/ki67 e geminina/ki67 e o teste t foi usado na análise estatística (p < 0,05). Resultados: Não houve diferença significativa no ki67 (p = 0,06) e no MCM2 (p = 0,46) entre carcinomas basocelulares e espinocelulares; no entanto, o índice de marcação da geminina foi significativamente maior no carcinomas espinocelulares em comparação ao carcinomas basocelulares (p < 0,001). Somente a razão geminina/ki67 mostrou diferença significativa entre os dois tumores, a razão mostrou números significativamente mais altos nos carcinomas espinocelulares (p = 0,015). Conclusões: A geminina pode ser considerada um fator efetivo na patogênese dos carcinomas basocelulares e espinocelulares cutâneos de cabeça e pescoço e pode ser um dos elementos responsáveis pela diferença entre o comportamento biológico desses tumores.

DNA-aptamer-nanographene oxide as a targeted bio-theragnostic system in antimicrobial photodynamic therapy against Porphyromonas gingivalis.

The aim of this study was to design and evaluate the specificity of a targeted bio-theragnostic system based on DNA-aptamer-nanographene oxide (NGO) against Porphyromonas gingivalis during antimicrobial photodynamic therapy (aPDT). Following synthesis and confirmation of NGO, the binding of selected labeled DNA-aptamer to NGO was performed and its hemolytic activity, cytotoxic effect, and release times were evaluated. The specificity of DNA-aptamer-NGO to P. gingivalis was determined. The antimicrobial effect, anti-biofilm potency, and anti-metabolic activity of aPDT were then assessed after the determination of the bacteriostatic and bactericidal concentrations of DNA-aptamer-NGO against P. gingivalis. Eventually, the apoptotic effect and anti-virulence capacity of aPDT based on DNA-aptamer-NGO were investigated. The results showed that NGO with a flaky, scale-like, and layered structure in non-cytotoxic DNA-aptamer-NGO has a continuous release in the weak-acid environment within a period of 240 h. The binding specificity of DNA-aptamer-NGO to P. gingivalis was confirmed by flow cytometry. When irradiated, non-hemolytic DNA-aptamer-NGO were photoactivated, generated ROS, and led to a significant decrease in the cell viability of P. gingivalis (P < 0.05). Also, the data indicated that DNA-aptamer-NGO-mediated aPDT led to a remarkable reduction of biofilms and metabolic activity of P. gingivalis compared to the control group (P < 0.05). In addition, the number of apoptotic cells increased slightly (P > 0.05) and the expression level of genes involved in bacterial biofilm formation and response to oxidative stress changed significantly after exposure to aPDT. It is concluded that aPDT using DNA-aptamer-NGO as a targeted bio-theragnostic system is a promising approach to detect and eliminate P. gingivalis as one of the main bacteria involved in periodontitis in periopathogenic complex in real-time and in situ.

Quorum quenching of Streptococcus mutans via the nano-quercetin-based antimicrobial photodynamic therapy as a potential target for cariogenic biofilm.

BACKGROUND: Quorum sensing (QS) system can regulate the expression of virulence factors and biofilm formation in Streptococcus mutans. Antimicrobial photodynamic therapy (aPDT) inhibits quorum quenching (QQ), and can be used to prevent microbial biofilm. We thereby aimed to evaluate the anti-biofilm potency and anti-metabolic activity of nano-quercetin (N-QCT)-mediated aPDT against S. mutans. Also, in silico evaluation of the inhibitory effect of N-QCT on the competence-stimulating peptide (CSP) of S. mutans was performed to elucidate the impact of aPDT on various QS-regulated genes. METHODS: Cytotoxicity and intracellular reactive oxygen species (ROS) generation were assessed following synthesis and confirmation of N-QCT. Subsequently, the minimum biofilm inhibitory concentration (MBIC) of N-QCT against S. mutans and anti-biofilm effects of aPDT were assessed using colorimetric assay and plate counting. Molecular modeling and docking analysis were performed to confirm the connection of QCT to CSP. The metabolic activity of S. mutans and the expression level of various genes involved in QS were evaluated by flow cytometry and reverse transcription quantitative real-time PCR, respectively. RESULTS: Successful synthesis of non-toxic N-QCT was confirmed through several characterization tests. The MBIC value of N-QCT against S. mutans was 128 µg/mL. Similar to the crystal violet staining, the results log10 CFU/mL showed a significant degradation of preformed biofilms in the group treated with aPDT compared to the control group (P < 0.05). Following aPDT, metabolic activity of S. mutans also decreased by 85.7% (1/2 × MBIC of N-QCT) and 77.3% (1/4 × MBIC of N-QCT), as compared to the control values (P < 0.05). In silico analysis showed that the QCT molecule was located in the site formed by polypeptide helices of CSP. The relative expression levels of the virulence genes were significantly decreased in the presence of N-QCT-mediated aPDT (P < 0.05). CONCLUSIONS: The combination of N-QCT with blue laser as a QQ-strategy leads to maximum ROS generation, disrupts the microbial biofilm of S. mutans, reduces metabolic activity, and downregulates the expression of genes involved in the QS pathway by targeting genes of the QS signaling system of S. mutans.

SARS-Cov-2 infection in cancer patients, susceptibility, outcome and care.

The COVID-19 pandemic has led to many problems in cancer patients, which in part are due to insufficient knowledge of the exact implications of the virus on these individuals. Perceptions based on known facts about previous pandemics and coronaviruses might not agree with actual real-life experience and objective findings. We present a compilation of scientific facts and actual observations on different aspects of SARS-CoV-2 infection in cancer patients. These patients are at increased risk of viral contraction and have higher chances of severe disease/mortality. The latter is impacted by other factors and is still debated. In contrast to preliminary impressions, the benefits of anti-cancer treatments outweigh their risks and should be continued. Cancer patients generate antibodies in response to vaccination but in lower amounts than healthy people, especially those with hematologic cancers. Boosters, including third doses, have shown increased immune-responses in most patients. Vaccination should be prioritized in these individuals.

The anti-inflammatory effect of dapsone on ovalbumin-induced allergic rhinitis in balb/c mice.

AIMS: Allergic rhinitis (AR), a major chronic inflammatory disease of the respiratory system, is a public health issue because of its substantial negative impact on quality of life and work efficiency alongside its high prevalence and costs. Dapsone is a sulfone chemical with reported anti-inflammatory and antibacterial properties. Accordingly, we investigated the anti-inflammatory impact of dapsone on ovalbumin-induced allergic rhinitis in balb/c mice. MAIN METHODS: Intraperitoneal ovalbumin and hydroxide aluminum injection followed by intranasal ovalbumin administration sensitized female Balb/c mice. Mice received intraperitoneal dapsone either acute (5, 10, 20 mg/kg) 30 min before the last ovalbumin challenge, or chronic (20 mg/kg) on days 21 to 35. KEY FINDINGS: Both acute and chronic intraperitoneal usage of dapsone showed a considerable decrease in the nasal scratching behavior, the number of sneezing, serum IL-4 and IgE levels of ovalbumin-induced AR in balb/c mice, but there was a significant increase in serum IFNγ level. Histopathological analysis demonstrated a significant reduction of eosinophil numbers, following dapsone injection. Goblet cell hyperplasia and respiratory epithelial-thickness decreased significantly in the acute and chronic 20 mg/kg dapsone groups compared to the ovalbumin-induced controls. SIGNIFICANCE: This study shows that there is an association between acute and chronic dapsone treatment and some anti-allergic effects through an inflammation cascade.

Clinicopathologic significance of DNA replication licensing factors in head and neck diffuse large B-cell lymphoma.

OBJECTIVE: Diffuse large B-cell lymphoma (DLBCL) harbors defects in the proliferation pathway. We performed multiparameter analysis of proteins expressed during different cell cycle phases and correlated them with clinical parameters of head and neck DLBCLs. STUDY DESIGN: Thirty-nine DLBCLs were staged and immunohistochemically stained with MCM2, Ki67, and geminin. The receiver operating characteristic curve and its area under the curve were calculated, and sensitivity vs specificity curve analysis was performed. RESULTS: The highest labeling index was in MCM2, followed by Ki67 and geminin (P < .001). All pairs showed significant differences (P < .001). The best cutoff points to differentiate limited from advanced disease were 68% and 45% for MCM2 and Ki67, respectively. There was no acceptable cutoff for geminin (area under the curve = 0.667, P = .134). MCM2/Ki67 (P = .293) and geminin/Ki67 (P = .233) ratios did not differ between the stages. The median (interquartile range) of the geminin/Ki67 ratio was 0.57 (0.68), translating to a reduced G1. CONCLUSIONS: We suggest a role for cell cycle-related proteins in the biology and behavior of DLBCLs. MCM2 and Ki67 cutoffs can be a potential option to differentiate limited from advanced disease, where imaging and laboratory techniques are unavailable. The G1 decrease and the significantly higher MCM2 expression compared to Ki67 indicate replication disturbances, making factors involved in the G1 phase targets for treatment.

Distinctive expression of DNA replication factors in squamous cell carcinomas of the lip, face and oral cavity.

OBJECTIVE: Uncontrolled proliferation and aberrations in cell-cycle progression are fundamental issues in cancer. In this study we aimed to determine and compare deoxyribonucleic acid (DNA) replication licensing factors at the mRNA and protein levels among squamous cell carcinomas (SCCs) of the lip, facial-skin and oral cavity. MATERIALS AND METHODS: A total of 103 lip, oral and face SCCs were immunohistochemically stained with MCM2 (mini-chromosome maintenance 2), geminin, and ki67, and their labeling-indices were calculated. Also, 57 SCCs from the same regions along with their adjacent normal tissues underwent quantitative reverse transcription-polymerase chain reaction analysis. RESULTS: All three proteins were overexpressed in the studied SCCs, but only geminin (P = 0.004) showed significant difference among the three regions, with higher levels in oral SCCs compared to lip (P = 0.005) and skin (P = 0.024) tumors. Geminin expression did not differ between skin- and lip-SCCs (P = 0.822). MCM2/ki67 ratio was higher in oral- compared to skin-neoplasms (P = 0.039), but no difference was found in geminin/ki67 among the SCC-subsites. There were significant differences in MCM2 and geminin mRNA between carcinomatous- and normal-tissues in all tumors, but not among the three locations. CONCLUSION: MCM2 and geminin are involved in the tumorigenesis of lip, face and oral SCC at both mRNA- and protein-levels. Geminin may have a role in the site-specific biologic behavior of SCC. Skin SCCs had the highest proportion of licensed non-proliferating cells, while actively proliferating cells were more prominent in oral tumors. Regarding DNA replication, lip SCCs seem to be closer to skin tumors compared to their oral counterparts.

In Vitro Anti-tumor Effects of Photodynamic Therapy on Oral Squamous Cell Carcinoma: A Review.

Introduction: Due to the increasing prevalence and high mortality rate of oral squamous cell carcinoma (OSCC) and problems with its routine treatments, more recent modalities like photodynamic therapy (PDT) have been developed. PDT effectively destroys tumor cells with minimum side effects. Research on in vitro effects of PDT may be helpful in determining the molecular mechanisms responsible for its effectiveness and can lead to the development of more efficient techniques. The aim of this study was to review the use of PDT in OSCC among in vitro studies. Methods: A literature search for English articles on PDT in OSCC was performed in PubMed, Scopus, Google Scholar, and Web of Science. Data were extracted based on the inclusion/exclusion criteria, which were detailed using the PICO framework: all eligible in vitro studies evaluating the effects of PDT on the viability of OSCC compared to controls without PDT were included. Results: Forty-one out of 567 studies were selected. The tongue was the most common OSCC site, 5-aminolevulinic acid was the most used photosensitizer (PS), cell viability/toxicity and apoptosis were the most evaluated outcomes, and lasers with wavelengths of 600-700 nm were the most common light sources and wavelengths respectively. Conclusion: PDT showed promising effects on reducing the viability of OSCC cells. Cell lines from various sources or even those originating from the same location sometimes responded differently to the same protocol. Considering the favorable results obtained from natural PSs and regarding their additional health-promoting properties, their use in future investigations with different cell lines and light specifications is recommended.

The effect of photodynamic therapy on head and neck squamous cell carcinoma cell lines using spirulina platensis with different laser energy densities.

BACKGROUND: Considering the anti-cancer properties of spirulina platensis (S. platensis), we aimed to investigate the effectiveness of this algae as a novel natural photosensitizer for photodynamic therapy (PDT) against oral and hypopharyngeal cancer cells. The appropriate laser energy density to apply during PDT was also determined. METHODS AND MATERIALS: CAL-27, FaDu and HGF cell lines were exposed to S. platensis with concentrations of 0.3 g/l and 0.6 g/l and were irradiated with 635 nm diode laser using 2, 4, 12, and 24 J/cm2 energy densities with constant power. MTT assay was performed to investigate cell viability and cytotoxicity after 24 h. The results were analyzed using two-way ANOVA and post hoc Tukey tests (P-value<0.05). RESULTS: survival rate in CAL-27 (P-Value<0.001) and FaDu (P-Value<0.001) cell lines were significantly different following irradiation with various laser energy densities. Different concentrations of S. platensis had no significant effect on the viability of CAL-27 cells (P-Value=0.158) and FaDu cells (P-Value=0.072) and showed no significant cytotoxicity against HGF cells, with or without laser. CONCLUSION: S. platensis could be considered as a novel safe and effective natural photosensitizer for cancer PDT with no cytotoxic effect on normal cells. When combined with laser using appropriate energy densities, it has the ability to induce death in oral and hypopharyngeal cancer cell lines.

Cell kinetic markers in cutaneous squamous and basal cell carcinoma of the head and neck.

INTRODUCTION: Proliferation markers play a significant role in the biologic behavior of tumors. Geminin is a known inhibitor of the cell cycle and DNA replication and has not been previously reported in cutaneous basal and squamous cell carcinomas of the head and neck. OBJECTIVES: We aimed to investigate proliferation markers ki67, MCM2, and geminin in head and neck cutaneous basal and squamous cell carcinomas. METHODS: Forty cases of each tumor were immuostained with ki67, MCM2, and geminin followed by assessment of labeling indices (LIs). MCM2/ki67- and geminin/ki67-ratios were also determined; t-test was used for statistical analysis (p<0.05). RESULTS: There was no significant difference in ki67 (p=0.06) and MCM2 (p=0.46) between cutaneous basal and squamous cell carcinomas; however, geminin LI was significantly higher in squamous cell carcinomas compared to cutaneous basal cell carcinomas (p<0.001). Only geminin/ki67 showed a significant difference between the two tumors with the ratio showing significantly higher numbers in squamous cell carcinomas (p=0.015). CONCLUSIONS: Geminin could be regarded as an effective factor in the pathogenesis of head and neck cutaneous cutaneous basal cell carcinomas and squamous cell carcinomas and may be one of the responsible elements in the difference between the biologic behavior of these tumors.

Comparison between the Effect of 810 nm and 940 nm Diode Laser Irradiation on Histopathological Changes in Iatrogenic Oral Ulcers: an Animal Study.

STATEMENT OF THE PROBLEM: Considering the relatively high prevalence of oral mucosal ulcers, their fast healing is of significance. PURPOSE: This study aimed to histopathologically compare the effects of 810 nm and 940 nm diode laser on the healing of iatrogenic oral ulcers in rabbits. MATERIALS AND METHOD: In this single-blind experimental study, mucosal ulcers measuring 3mm in diameter and 1mm in depth were bilaterally created in the buccal mucosa of 18 rabbits using a biopsy punch. The defects were irradiated with 810 nm diode laser on the right side and 940 nm diode laser on the left side. Biopsy samples of the same depth were obtained from the ulcers on days 3 and 7 followed by histopathological analysis. The intensity of inflammation was determined on hematoxylin-eosin-stained sections using a four-point scale. Data were analyzed employing the Wilcoxon signed rank test. RESULTS: The degree of inflammation was not significantly different between the 810nm and 940nm diode laser groups on day 3; but on day 7, animals receiving 810 nm experienced a significantly lower degree of inflammation compared to those treated with 940 nm laser (p= 0.028). CONCLUSION: When comparing 810- and 940-nm diode lasers, 810 nm irradiation significantly decreased the severity of inflammation in oral wounds created on the buccal mucosa of rabbits in a time-dependent manner.