Search Results (82)

(1) Background: Oral cancer (OC) is one of the most frequently diagnosed human cancers and remains a challenge for biologists and clinicians. More than 90% of OC cases are squamous cell carcinomas (OSCCs). Despite the use of modern diagnostic and prognostic methods, the 5-year survival rate remains unsatisfactory due to the late diagnosis of the neoplastic process and its resistance to treatment. This comprehensive review aims to present the latest literature data on the use and effectiveness of saliva as a non-invasive biomarker in patients with oral cancer. (2) Methods: The article reviews the current literature on the use of salivary omics biomarkers as an effective method in diagnosing and modifying treatment in patients with OSCC; the research corpus was acquired from the PubMed/Google/Scopus/Cochrane Library/Web of Science databases in accordance with the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA 2020) guidelines. (3) Results: The identification of salivary omics biomarkers involved in carcinogenesis and neoplastic transformation may be a potential alternative to traditional invasive diagnostic methods. Saliva, being both an abundant reservoir of organic and inorganic components derived from epithelial cells as well as a cell-free environment, is becoming an interesting diagnostic material for studies in the field of proteomics, genomics, metagenomics, and metabolomics. (4) Conclusions: Saliva-based analysis is a modern and promising method for the early diagnosis and improvement of treatment outcomes in patients with OSCC and oral potentially malignant disorders (OPMDs), with high diagnostic, therapeutic, and prognostic potential. Full article

Background: The relationship between oral contraceptive (OC) use and pancreatic cancer (PC) risk remains controversial, with inconsistent findings reported in observational studies. To clarify this relationship and better identify potential risk factors for PC prevention, more unbiased and robust approaches are needed. Methods: We investigated the potential causal relationship between OC use and PC risk using a two-sample Mendelian randomization (MR) analysis, with blood protein quantitative trait loci (pQTLs) as instrumental variables. To ensure the robustness of our findings, we performed a series of sensitivity analyses, colocalization analyses, and reverse MR. The causal effects of protein-coding genes on PC risk, as well as their expression patterns across different single-cell types, were subsequently investigated. To elucidate the potential pathogenic pathways, we conducted pathway enrichment analysis, protein–protein interaction (PPI) network analysis, and causal inference. Results: Our MR analysis identified five drug-targeted proteins significantly associated with PC risk. Higher levels of COMT, AGT, FN1, and UGT1A1, as well as lower levels of SERPINC1, were associated with an increased risk of PC. Among these, AGT, FN1, and COMT demonstrated consistent associations across sensitivity analyses and downstream analyses, providing robust evidence supporting their involvement in PC risk. Conclusions: This study provides genetic evidence suggesting, in European groups, a potential causal link between OC use and increased PC risk, possibly mediated through drug-targeted proteins such as AGT and FN1. These results highlight the importance for further research to elucidate the underlying mechanisms and assess the implications of OC use on PC risk. Full article

Mitochondrial-associated granulocyte macrophage colony-stimulating factor (Magmas) is a unique protein located in the inner membrane of mitochondria, with an active role in scavenging reactive oxygen species (ROS) in cellular systems. Ovarian cancer (OC), one of the deadliest gynaecological cancers, is characterised by genomic instability, affected by ROS production in the tumour microenvironment. This manuscript discusses the role of Magmas and efficacy of its novel small molecule inhibitor BT#9 in OC progression, metastasis, and chemoresistance. Magmas expression levels were significantly elevated in high-grade human OC compared to benign tumours by immunohistochemistry. The inhibition of Magmas by BT#9 enhanced ROS production and reduced mitochondrial membrane permeability, basal respiration, mitochondrial ATP production, and cellular functions, such as the proliferation and migration of OC cell lines in vitro. Oral administration of BT#9 in vivo significantly reduced tumour growth and spread and enhanced the survival of mice without having any effect on the peritoneal organs. These data suggest that Magmas is functionally important for OC growth and spread by affecting ROS levels and that the inhibition of Magmas activity by BT#9 may provide novel clinical benefits for patients with this malignancy. Full article

Background/Objectives: The low-resource, minority and underserved populations (LRMU) that carry the highest risk of oral cancer (OC) experience many barriers to early detection and treatment, resulting in disproportionately poor outcomes. One major barrier to better outcomes is poor compliance with specialist referral for diagnosis and treatment. The goal of this prospective study was to compare specialist referral compliance for Telehealth vs. in-person visits in LRMU individuals screening positive for increased OC risk. Methods: Forty subjects who had screened positive for oral potentially malignant lesions (OPMLs) were recruited from community clinics. The subjects indicated whether they would prefer an in-person or Telehealth specialist visit. They were offered assistance with all aspects of the visit, and then tracked over 3 months for referral compliance. A novel, very low-cost, simple Telehealth platform located within the community clinic was used for the remote specialist visits. Results: In the Telehealth group, 16/24 subjects attended their first scheduled remote specialist visit; 4/24 attended rescheduled visits within 3 months, and 4/24 did not comply at all. All attendees and specialists were able to complete the remote visits in full. Of the 7/16 subjects who completed in-person visits, 3/16 attended their first scheduled visit, and 4/16 complied within 3 months; 9/16 subjects did not comply at all with specialist referral. Significantly more individuals complied with Telehealth specialist referral at 1 month (p = 0.0006) and after 3 months (p = 0.0154). Conclusions: This novel Telehealth platform may improve compliance with specialist referral in low-resource individuals with OPMLs. Full article

Oral cancer (OC) ranks among the most prevalent head and neck cancers, becoming the eleventh most common cancer worldwide with ~350,000 new cases and 177,000 fatalities annually. The rising trend in the occurrence of OC among young individuals and women who do not have tobacco habits is escalating rapidly. Surgical procedures, radiation therapy, and chemotherapy are among the most prevalent treatment options for oral cancer. To achieve better therapy and an early detection of the cancer, it is essential to understand the disease’s etiology at the molecular level. Saliva, the most prevalent body fluid obtained non-invasively, holds a collection of distinct non-coding RNA pools (ncRNAomes) that can be assessed as biomarkers for identifying oral cancer. Non-coding signatures, which are transcripts lacking a protein-coding function, have been identified as significant in the progression of various cancers, including oral cancer. This review aims to examine the role of various salivary ncRNAs (microRNA, circular RNA, and lncRNA) associated with disease progression and to explore their functions as potential biomarkers for early disease identification to ensure better survival outcomes for oral cancer patients. Full article

Background/Objective: Ovarian clear cell carcinomas (OCCCs) are a rare histological subtype of epithelial ovarian cancer characterized by resistance to platinum-based therapy. CDK8/19, a component of the regulatory CDK module associated with Mediator complex, has been implicated in transcriptional reprogramming and drug resistance in various solid tumors. Our study aimed to investigate the therapeutic potential of CDK8/19 kinase inhibition using selective inhibitors SNX631 and SNX631-6 in OCCC treatment, both as monotherapy and in combination with standard chemotherapeutics. Methods: CDK8 and Ki67 levels were evaluated via immunohistochemistry in benign, primary, and metastatic ovarian cancer tissues. The efficacy of SNX631 alone and in combination with cisplatin or paclitaxel was assessed in OCCC cell lines (ES-2, TOV-21-G, RMG-1). In vivo evaluation utilized xenograft models with subcutaneous and intraperitoneal delivery of the OCCC ES2 cells and oral delivery of SNX631-6, with the monitoring of tumor growth, metastatic spread, and survival. Results: CDK8 protein levels were elevated in OC tissues, particularly in OCCC primary and metastatic lesions compared to benign tissue. While CDK8/19 inhibition showed limited effects on in vitro cell proliferation, SNX631-6 demonstrated significant antitumor and anti-metastatic activity in vivo. Notably, SNX631-6 enhanced the efficacy of cisplatin, substantially inhibiting tumor growth and extending overall survival. Conclusions: Therapeutically achievable doses of CDK8/19 inhibitors may provide clinical benefit for OCCC patients by inhibiting tumor growth and reversing platinum resistance, potentially addressing a critical treatment challenge in this rare ovarian cancer subtype. Full article

Objective: Head and neck cancer (HNC) is a common cancer represented by nearly 80% oral cavity (OC) and oropharyngeal cancers (OPCs). Seventy percent of OPCs are associated with the Human Papilloma Virus (HPV). Immunotherapy holds the promise of future improvements in treating HNC patients. The study objective was to determine whether durvalumab immunotherapy alone, prior to curative surgery, would significantly impact the oral salivary microbiome in a pilot cohort of HPV negative and positive OC and OPC patients. Methods: Early stage OPC patients with squamous cell carcinoma were recruited: 5 HPV+ and 12 HPV−, and treated with two or three administrations of durvalumab given every two weeks, prior to surgery. Unstimulated saliva was collected and processed for bacterial DNA Isolation and V1–V3 16S rRNA gene next generation sequencing, taxa identification, and determination of relative abundance at four time points: baseline prior to surgery (A) and weekly durvalumab treatment timepoints (B, C, and D). Alpha- and beta-diversity differences for the time series were determined in Primer_v7. MaAsLin2 in R was used to identify potential associations with the time series and/or HPV status. Linear decomposition model (LDM) R-package was used to investigate the relationship of salivary microbiome with HPV status. ROC curves were plotted for significant species in common between MaAsLin2 analysis and FDR-corrected Mann-Whitney U-test using XLSTAT. Results: Longitudinal microbiome data across four timepoints (A, B, C, D) were obtained (HPV+: n = 18 samples; HPV−: n = 46 samples). A total of 416 taxa were detected across all time points, ranging from 336 to 373 per group. There were no differences in α- and β-diversities for all longitudinal comparisons (C vs. BCD, AB vs. CD, or A vs. B, C, or D). However, comparison A vs. D showed a significant increase in Prevotella melaninogenica relative abundance, a potentially pathogenic species able to evade the immune system, after three weeks treatment. Moreover, differences in beta-diversity based on HPV status were found. LDM analysis identified Veillonella atypica, overrepresented in HPV+ group, as the top species accounting for HPV status. Conclusions: The results are consistent with findings from previous studies investigating HNC patients treated with chemoradiotherapy. More research is needed to understand possible impact of immunotherapy on opportunistic bacterial species, although negligible impact from durvalumab treatment on salivary microbiome was observed. Full article

Background/Objectives: Colorectal cancer (CRC) is the third most common cancer in the US and the second leading cancer-associated mortality cause. Available CRC therapies achieve modest outcomes and fail to prevent its recurrence. Epidemiological studies indicated that the Mediterranean diet rich in olive oil reduced CRC incidence. This study aimed at the identification and assessment of active anti-CRC olive phenolics. Methods: The MTT, wound-healing and colony formation assays were used to discover and assess the in vitro anti-CRC activity of olive phenolics. A nude mouse xenografting model was used to assess the in vivo CRC progression and recurrence suppressive activity of OC in pure and crude forms. OC was isolated from olive oil using liquid–liquid extractions. Results: Screening of olive phenolics for in vitro antiproliferative activity against a diverse panel of CRC cell lines identified the extra-virgin olive oil (EVOO) S-(-)-oleocanthal (OC) as the most active hit. OC showed IC₅₀ values of 4.2, 9.8, 14.5, and 4.9 μM against HCT-116, COLO-320DM, WiDr, and SW48 CRC cells, respectively. The lysine methyltransferases SMYD2 and EZH2, along with the receptor tyrosine kinase c-MET proved aberrantly dysregulated in invasive and metastatic CRC. SMYD2 and c-MET were validated as OC molecular targets in multiple malignancies. Daily oral 10 mg/kg OC treatments over 15 days suppressed 72.5% of the KRAS mutant HCT-116-Luc cells tumors weight in male nude mice. Continued OC daily oral use after primary tumor surgical excision over an additional 40 days significantly suppressed the HCT-116-Luc locoregional tumor recurrence and totally prevented the distant tumor recurrence. The SMYD2-EZH2 expressions and c-MET activation were notably suppressed by OC treatments in vitro and in collected animal primary tumors. Conclusions: OC and olive phenolics are potential nutraceutical interventions useful for CRC control and the prevention of its relapse. Full article

Background/Objectives: Oral cancer (OC) is a disease with poor prognosis mainly due to late diagnosis. There is considerable interest in the use and development of rapid, point of care (POC) non-invasive methods that can accelerate the diagnostic process. Bioimpedance (BI) is resistance to the passage of electric currents through tissue that reflects structural changes in the tissue. The aim of this study was to determine the spectrum of BI values in patients with oral cancer, to compare them with other oral lesions and healthy controls, and to determine the diagnostic value of the BI-based method for diagnosis of OC. Methods: Ninety-three participants divided into three groups participated in this study. The first group (31 participants) consisted of patients with histologically confirmed OC, the second group (31 participants) consisted of patients with an active reticular form of oral lichen planus (positive controls; OLP) and the third group (31 participants) consisted of healthy controls. In OC and OLP patients, BI was measured at three points (non-ulcerated lesional mucosa, clinically unaffected perilesional mucosa and unaffected mucosa on the contralateral side). In healthy controls, BI was measured on a healthy mucosa in the corresponding anatomical region. Measurements were performed at nine frequencies (1, 2, 5, 7, 10, 20, 70 and 100 kHz). Results: In OC patients, BI values in the lesion were significantly lower than BI values in clinically intact perilesional mucosa and the unaffected contralateral side at all frequencies. Furthermore, BI values of the clinically intact perilesional mucosa were significantly lower than the BI values of the healthy contralateral mucosa at frequencies of 1 kHz, 2 kHz, 5 kHz, 7 kHz and 10 kHz. Patients with OC had significantly lower BI values compared to patients with OLP and individuals with healthy oral mucosa at all frequencies. Conclusions: This study demonstrated the very good to excellent ability of this method to detect OC lesions, which needs to be confirmed by further studies on a larger number of participants. Full article

Background: Incidence of breast cancer (BrCa) may be correlated with country development, with a rise in cases anticipated in regions of the world that are currently undergoing an economic transformation. Herein, differences with regard to the occurrence of breast cancer between individual countries may depend on the distribution of risk factors, the level of early detection, also ethnicity and race, as well as clinical characteristics. The aim of our study was to identify and then investigate observational studies in which the risk of breast cancer was associated with the use of oral hormonal contraceptives (OCs), with particular emphasis on geographic region, and to conduct a systematic review and meta-analysis of the obtained data. Methods: RR (relative risk) was calculated and displayed in forest plots for visual interpretation. Accordingly, 74 studies involving a total of 198,579 women were eligible for inclusion in the meta-analysis. This is the first meta-analysis to comprehensively summarize the evidence between OC use and BrCa risk in connection with geographical region. Results: The cumulative results of the meta-analysis for specific parts of the world are: Africa (RR = 1.16, p = 0.216) and the Americas (RR = 1.03, p = 0.597); Asia (RR = 1.29, p = 0.014); European countries (RR = 1.01, p = 0.904); and Middle East countries (RR = 1.29, p = 0.043). Subgroup analyses showed an increased risk of BrCa for the analyzed variables that depended upon the geographical region. Conclusions: Our meta-analysis suggests that OC use may be associated with a higher BrCa risk, although a statistically significant association was not found for all geographical regions of the world. Full article

Emerging evidence suggests that aberrant expression levels of Sigma1 (SIGMAR1, also known as sigma-1 receptor) have been implicated in the progression of various diseases, including cancer. However, its significance in oral cancer (OC) has not been thoroughly explored. To advance in this field, the present study aimed to investigate the impact of SIGMAR1 knockdown in oral cancer cells. To do so, we included in this study our cohort of human OC samples and OC cell lines, which were utilized for experimental verification through several in vitro assays. Our findings revealed that SIGMAR1 overexpression was associated with poor survival rates and positively correlated with PD-L1 overexpression in human oral cancer samples. Furthermore, SIGMAR1 inhibition led to a decrease in PD-L1 expression and sensitized oral cancer cells to cisplatin treatment by enhancing apoptosis. These results suggest that SIGMAR1 knockdown may present a promising strategy worthy of further exploration in the management of oral cancer. Full article

The oral microbiome is crucial for human health. Although oral dysbiosis may contribute to oral cancer (OC), the detailed relationships between the microbiome and OC remain unclear. In this case-control study, we aimed to elucidate the connection between the oral microbiome and mechanisms potentially involved in oral cancer. The study analyzed 1022 oral saliva samples, including 157 from oral cancer patients and 865 from healthy controls, using 16S ribosomal RNA (16S rRNA) sequencing and a Light Gradient Boosting Machine (LightGBM) model to identify four bacterial genera significantly associated with oral cancer. In patients with oral cancer, the relative abundance of Streptococcus and Parvimonas was higher; Corynebacterium and Prevotella showed decreased relative abundance; and levels of fatty acid oxidation enzymes, including Carnitine palmitoyltransferase 1A (CPT1A), long-chain acyl-CoA synthetase, acyl-CoA dehydrogenase, diacylglycerol choline phosphotransferase, and H+-transporting ATPase, were significantly higher compared to controls. Conversely, healthy controls exhibited increased levels of short-chain fatty acids (SCFAs) and CD4+T-helper cell counts. Survival analysis revealed that higher abundance of Streptococcus and Parvimonas, which correlated positively with interleukin-6, tumor necrosis factor-alpha, and CPT1A, were linked to poorer disease-free survival (DFS) and overall survival (OS) rates, while Prevotella and Corynebacterium were associated with better outcomes. These findings suggest that changes in these bacterial genera are associated with alterations in specific cytokines, CPT1A levels, SCFAs in oral cancer, with lower SCFA levels in patients reinforcing this link. Overall, these microbiome changes, along with cytokine and enzyme alterations, may serve as predictive markers, enhancing diagnostic accuracy for oral cancer. Full article

Oral cancer (OC) presents a significant global health burden with rising incidence rates. Despite advancements in diagnosis and treatments, the survival rate for OC patients, particularly those with advanced or recurrent disease, remains low at approximately 20%. This poor prognosis is often due to a small population of cancer stem cells (CSCs) that are capable of self-renewal and immune evasion, playing pivotal roles in proliferation, tumor initiation, progression, metastasis, and therapy resistance. Exosomes, which are nano-sized extracellular vesicles (EVs), have emerged as crucial mediators of cell-to-cell communication within the tumor microenvironment (TME). These vesicles carry diverse molecules such as DNA, RNA, proteins, lipids, and metabolites, influencing various cellular processes. Emerging evidence suggests that CSC-derived EVs significantly promote tumor progression and metastasis and maintain the balance between CSCs and non-CSCs, which is vital for intracellular communication within the TME of oral cancer. Recent reports indicate that oral cancer stem cell-derived EVs (OCSC-EVs) influence stemness, immune evasion, metastasis, angiogenesis, tumor reoccurrence, and drug resistance. Understanding OCSC-EVs could significantly improve oral cancer diagnosis, prognosis, and therapy. In this mini-review, we explore OCSC-derived exosomes in oral cancer, examining their potential as diagnostic and prognostic biomarkers that reflect CSC characteristics, and delve into their therapeutic implications, emphasizing their roles in tumor progression and therapy resistance. However, despite their promising potential, several challenges remain, including the need to standardize isolation and characterization methods and to elucidate exosome-mediated mechanisms. Thus, a comprehensive understanding of OCSC-EVs could pave the way for innovative therapeutic strategies that have the potential to improve clinical outcomes for OC patients. Full article

Oral cancer (OC) is among the most common malignancies in the world. Despite advances in therapy, the worst-case scenario for OC remains metastasis, with a 50% survival rate. Therefore, it is critical to comprehend the pathophysiology of the condition and to create diagnostic and treatment plans for OC. The development of high-throughput genome sequencing has revealed that over 90% of the human genome encodes non-coding transcripts, or transcripts that do not code for any proteins. This paper describes the function of these different kinds of non-coding RNAs (ncRNAs) in OC as well as their intriguing therapeutic potential. The onset and development of OC, as well as treatment resistance, are linked to dysregulated ncRNA expression. These ncRNAs’ potentially significant roles in diagnosis and prognosis have been suggested by their differing expression in blood or saliva. We have outlined every promising feature of ncRNAs in the treatment of OC in this study. Full article

The anti-oral cancer effects of santamarine (SAMA), a Michelia compressa var. compressa-derived natural product, remain unclear. This study investigates the anticancer effects and acting mechanism of SAMA against oral cancer (OC-2 and HSC-3) in parallel with normal (Smulow–Glickman; S-G) cells. SAMA selectively inhibits oral cancer cell viability more than normal cells, reverted by the oxidative stress remover N-acetylcysteine (NAC). The evidence of oxidative stress generation, such as the induction of reactive oxygen species (ROS) and mitochondrial superoxide and the depletion of mitochondrial membrane potential and glutathione, further supports this ROS-dependent selective antiproliferation. SAMA arrests oral cancer cells at the G2/M phase. SAMA triggers apoptosis (annexin V) in oral cancer cells and activates caspases 3, 8, and 9. SAMA enhances two types of DNA damage in oral cancer cells, such as γH2AX and 8-hydroxy-2-deoxyguanosine. Moreover, all of these anticancer mechanisms of SAMA are more highly expressed in oral cancer cells than in normal cells in concentration and time course experiments. These above changes are attenuated by NAC, suggesting that SAMA exerts mechanisms of selective antiproliferation that depend on oxidative stress while maintaining minimal cytotoxicity to normal cells. Full article