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.

Novel osteoprotective nanocochleate formulation: A dual combination therapy-codelivery system against glucocorticoid induced osteoporosis.

Phosphatidylserine nanocochleates (Nanocochs) are novel delivery systems that may play a prominent osteoprotective role with their cargo, vitamin D3 (Vit-D3), against osteoporosis. Therefore, this study was conducted to characterize a Nanococh containing vitamin D3 (Nanococh-D3) and investigate its potential role in improving GIO in a rat model. Roll-shaped Nanococh-D3 particles were obtained in a size range of 320 nm with a sustained release performance. Oral Nanococh-D3 significantly increased the bioavailability of Vit-D3, enhanced bone mechanical strength, and improved osteogenic biomarkers including B-ALP, osteocalcin, Ca, and OPG in GIO rats. This formulation markedly suppressed gene expression of RANK and RANKL in treated rats. Histomorphometric analysis showed significant repairs in bone tissues and TRAP staining indicated a significant decrease in osteoclasts using Nanococh-D3 in osteoporotic rats. Nanococh alone similar to Nanococh-D3 acted better than AL as a standard anti-osteoporotic drug in the improvement of bone strength. In conclusion, our results established the potential role of Nanococh-D3 against osteoporosis in rats.

Is podoplanin expression associated with transforming growth factor-ß signaling in odontogenic cysts and tumors?

BACKGROUND: Induction of podoplanin by transforming growth factor-ß (TGF-ß) has been shown in a number of lesions but not in odontogenic tumors (OTs). We evaluated the association between these markers in OTs for the first time and compared their expression among the different neoplasms. METHODS: Immunohistochemistry using monoclonal antibody against podoplanin and TGF-ß was performed on 76 odontogenic cysts and tumors. Spearman's correlation coefficient, Kruskal-Wallis, and Mann-Whitney U tests followed by adjustment with Bonferroni were used for statistical analysis (P < .05). RESULTS: A significant difference in podoplanin expression was found among the lesions consisting of solid ameloblastomas, adenomatoid odontogenic tumors, ameloblastic fibromas, odontogenic myxomas (OMs), odontogenic keratocysts, and calcifying odontogenic cysts. Significant differences were observed only between OMs and each of the other neoplasms. Podoplanin immunostaining in the connective tissue was absent in most lesions. TGF-ß was significantly different among the study sample but not between the lesions in paired comparisons. None of the studied OTs showed significant correlations between podoplanin-TGF-ß, in either the epithelium or the stroma. These markers were also descriptively reported in calcifying epithelial odontogenic tumors. CONCLUSIONS: The inductive effect of TGF-ß on podoplanin seems to be limited, if any, in odontogenic lesions. Podoplanin appears to play a role in some aspects of OTs with epithelial or mixed origins. Despite the possible participation of podoplanin in tumorigenesis, it may not necessarily be involved in the aggressive behavior of OTs.

Expression of podoplanin and TGF-beta in glandular odontogenic cyst and its comparison with developmental and inflammatory odontogenic cystic lesions.

BACKGROUND: The number of studies investigating the immunohistochemical characteristics of glandular odontogenic cysts (GOCs) is limited, due to its rarity. TGF-beta has been suggested to induce podoplanin expression in some lesions. We aimed to evaluate and compare podoplanin and TGF-beta expression in GOC and other odontogenic cystic lesions. METHODS: A total of 43 samples including five GOCs, 10 dentigerous cysts (DCs), eight unicystic ameloblastoma (UAs), and 20 radicular cysts (RCs) were selected and subjected to immunohistochemical staining using monoclonal antibodies against podoplanin and TGF-beta. Kruskal-Wallis test and Mann-Whitney U-test were used for statistical analysis along with Bonferroni for adjusting P-values (P < 0.05). RESULTS: Podoplanin immunoreactivity was observed in 80%, 70%, and 100% of DCs, RCs, and UAs, respectively, while none of the GOCs were positive for this marker (P = 0.004). Significant differences were only found in the GOC specimens. TGF-beta positivity occurred in the capsule and epithelium of all GOCs and DCs, while RCs and UAs demonstrated different expression percentages in the capsular and epithelial tissues. Epithelial TGF-beta showed significant differences among the studied lesions (P = 0.007) with the main difference found between DCs with RCs and DCs with UAs. CONCLUSIONS: Lack of podoplanin expression might be involved in the characteristic histologic and behavioral features of GOC, which seems to be unrelated to TGF-beta expression.

Immunohistochemical profile of oral mucosal and head and neck cutaneous melanoma.

BACKGROUND: In addition to ultraviolet radiation exposure, various molecular markers may differ between oral mucosal and cutaneous head and neck melanomas and lead to variations in their biologic behavior and prognosis. The aim of this study was to compare four such markers, namely microphthalmia transcription factor (MITF), P75, P53, and Ki-67 in malignant melanomas originating from the oral cavity and head and neck skin. METHODS: A total of 19 oral mucosal and 23 head and neck cutaneous melanomas were subjected to immunohistochemical analysis using antibodies against MITF, P75, P53, and Ki-67. Statistical comparison of data was performed by t-test and chi-square analysis (P < 0.05). RESULTS: Significant differences in MITF (P = 0.016) and Ki-67 (P = 0.002) were observed between oral mucosal and cutaneous melanomas. P75 (P = 0.80) and P53 (P = 0.76) did not differ significantly, between these locations. CONCLUSIONS: According to the results obtained in this study, the biological properties of cutaneous and mucosal melanoma differ, especially regarding MITF and Ki-67.

Odontogenic Myxoma: a study based on biopsy material over a 40-year period.

AIM: Odontogenic tumors, including odontogenic myxomas (OMs) are regarded as rare neoplasms in the human body. Nevertheless, they may be problematic for diagnosis and treatment planning due to possible variations between different races and countries. The aim of the current study was to present the clinicopathologic features of OM in an Iranian population over a 40-year period and compare them with those reported elsewhere. MATERIALS AND METHODS: Clinical/demographic data and histologic slides of OMs and all lesions that could be considered in their differential diagnosis, reported from 1967-2008 were analyzed. Statistical analysis was performed using χ(2) and t-test and p < 0.05 was regarded significant. RESULTS: Forty OMs were identified, of which 42.5% occurred in men (mean age, 27.4 years) and 57.5% in women (mean age, 28.2 years). Most tumors were observed in the posterior mandible. All cases possessed the classic World Health Organization histologic features; while 3, 15 and 6 cases showed epithelial rests, residual bone and conspicuous collagen bundles, respectively. Five patients were followed and none of their tumors recurred. CONCLUSION: The clinicopathologic characteristics of the current Iranian population are similar to most other reports with a predilection for the posterior mandible, 3rd decade and female subjects; however, there were variations in microscopic features of the studied cases. Clinical significance: Clinical and histologic information on OM in different populations may be useful in clinical settings and treatment planning. Reporting more detailed histologic data can help clarify the biology of this tumor and aid in its histopathologic diagnosis. i

An analysis of biopsy-proven tongue lesions among 8,105 dental outpatients.

AIM: The aim of the present study was to analyze data on the characteristics of tongue lesions in dental patients seeking care at the Oral Pathology Service of Tehran University of Medical Sciences, from 1985-2010. MATERIALS AND METHODS: Demographic data and histopathologic diagnoses were recorded for all lesions that were documented as occurring on the tongue according to the patient records in our department. Statistical analysis included chi-square, t-, and Fisher's exact tests. A 95% confidence interval (CI) was calculated, and p < 0.05 was considered significant. RESULTS: Tongue lesions constituted 6.3% of all received specimens which included 46 different defects. The most common lesions were lichen planus (LP), irritation fibroma (IF), squamous cell carcinoma (SCC) and pemphigus vulgaris (PV). Tongue lesions were significantly more common in women compared to men (CI = 0.65-0.94, p = 0.02). Mean age (47 years) did not differ between male and female subjects (CI = -2.49 - 3.93, p = 0.06). The dorsal surface followed by the lateral aspect was the most common site for tongue lesions. CONCLUSION: It seems that dental practitioners should be perceptive of LP, IF, SCC and PV, when examining the tongue. Histopathologic analysis is essential for achieving final diagnosis in a considerable number of lesions that commonly occur on this organ. Clinical significance: Access to demographic/prevalence data in different populations may be useful in clinical settings and could be complimented by histopathologic diagnosis in most instances. The present findings can be compared with those obtained from other epidemiologic studies in this field resulting in valuable data which may be used in several types of investigations. .

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.

The effect of different parameters of low-level laser used in the treatment of oral mucositis, on the viability and apoptosis of oral squamous cell carcinoma cells: In vitro study.

Oral mucositis is a complication of chemo/radiotherapy. To assess the impact of various power levels of diode-laser on the survival and expression of apoptosis-related genes in oral cancer cells, it is crucial to consider the potential existence of malignant cells within the treatment region and the reliance of laser effectiveness on its specific characteristics. Cal-27 cells were cultivated and exposed to a 660 nm-diode-laser at power levels of 20, 40, and 80 mW, alongside non-irradiated control cells. Viability and expression of Bax and Bcl-2 mRNA were assessed with Methyl Thiazolyl Tetrazolium (MTT) and Real-time Polymerase Chain Reaction (RT-PCR), respectively. The results were analyzed using one-way ANOVA and Tukey post-hoc test (p < 0.05). A significant reduction in viability was found only in the 20 mW group compared to controls (p = 0.001). Cell survival was significantly lower in cells receiving 20 mW laser than those treated with 40 and 80 mW (p < 0.05). None of the laser groups showed significant changes in BcL-2, but Bax was significantly lower in cells receiving 40 and 80 mW (p < 0.05), compared to controls. Laser irradiation at 660 nm (2 J/cm2, 30 s) significantly reduced the viability of oral cancer cells when using 20 mW power. These specifications align with the recommendation that the lowest possible laser dose should be applied for treating cancer patients. The exact mechanism of cell death following laser therapy with these specifications requires further investigation.

Exploring the concept of "inflammatory angiogenesis" in keratocystic odontogenic tumor.

OBJECTIVE: The aim of the present study was to investigate the role of inflammation in angiogenesis of keratocystic odontogenic tumor (KCOT). STUDY DESIGN: Twenty inflamed and 20 non-inflamed KCOTs were selected based on quantitative scoring of inflammation which was also applied on 20 radicular cysts. Microvessel density was assessed in all samples using CD34 antibody and angiogenesis was compared between the three groups. Statistical analysis was performed using one-way analysis of variance followed by post-hoc Scheffe test and P values less than 0.05 were considered significant. RESULTS: A statistically significant difference in angiogenesis was found between radicular cysts and both inflamed and non-inflamed KCOTs (P < 0.001), but not between inflamed and non-inflamed KCOTs (P =0.347). CONCLUSION: Based on the results obtained in the present study, it seems that the effect of inflammation on angiogenesis in KCOT is minimal. However further investigation using other methods of evaluation is suggested to fully clarify the role of "inflammatory angiogenesis" in this neoplasm.

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.

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

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

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.

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.

Anticancer Activity of Postbiotic Mediators Derived from Lactobacillus Rhamnosus GG and Lactobacillus Reuteri on Acute Lymphoblastic Leukemia Cells.

BACKGROUND: Leukemia remains a global health challenge, requiring the exploration of alternative therapies with reduced side effects. Probiotics, particularly Lactobacillus species, have gained attention because of their potential anticancer properties. This study investigated the anticancer and cytotoxic effects of postbiotic mediators (PMs) derived from Lactobacillus rhamnosus GG (LGG) and Lactobacillus reuteri (LR) on acute lymphoblastic leukemia (ALL) cells and peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: The PMs were prepared by culturing LGG and LR strains and isolating the supernatant. The MTT assay assessed cell viability on ALL Jurkat cells and PBMCs, and apoptosis analysis was conducted using flow cytometry. Quantitative real-time PCR was also performed to analyze BAX, BCL-2, BCLX, FAS, and p27 gene expression levels. RESULTS: The results showed that PMs derived from LGG and LR significantly reduced cell viability in Jurkat cells (P0.05) but not PBMCs (P0.05). Apoptosis analysis revealed an increase in apoptotic cells after PMs treatment. Nevertheless, gene expression analysis revealed no statistically significant difference between the treated and untreated groups in BAX, BCL-2, BCLX, FAS, and p27 gene expression levels (P0.05). CONCLUSION: Findings suggest that specific PMs derived from LGG and LR possess anticancer properties against ALL cells. This research highlighted the promise of PMs as a cutting-edge and less toxic adjuvant therapeutic strategy in cancer treatment.

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.

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.

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.