Updates in the Management of Advanced Nonmelanoma Skin Cancer.

Basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC) comprise the majority of nonmelanoma skin cancers. Advances have been made in treatment. Sentinel node biopsy should be considered for locally advanced, clinically node-negative cSCCs and MCCs. BCC patients failing traditional surgery and/or radiation are candidates for systemic hedgehog inhibitor therapy. Immune checkpoint inhibitor treatment is available for patients who failed traditional treatment with surgery and/or radiation or who are not candidates for these modalities. Specifically, cemiplimab is approved for advanced BCC; cemiplimab and pembrolizumab for advanced cSCC; and avelumab, pembrolizumab, and retifanlimab-dlwr for recurrent/metastatic MCC.

Treatment De-escalation in Oropharyngeal Carcinoma and the Role of Robotic Surgery.

Oropharyngeal squamous cell carcinoma (OPSCC) related to human papillomavirus (HPV) infection has better survival outcomes compared to non-HPV-related OPSCC, leading to efforts to de-escalate the intensity of treatment to reduce associated morbidity. This article reviews recent clinical efforts to explore different de-escalation frameworks with a particular emphasis on the emergence of transoral robotic surgery and surgically driven de-escalation approaches. It discusses the current evidence for incorporating surgery into an evolving treatment paradigm for HPV-related OPSCC.

The m-TORC1 inhibitor Sirolimus increases the effectiveness of Photodynamic therapy in the treatment of cutaneous Squamous Cell Carcinoma, impairing NRF2 antioxidant signaling.

Squamous Cell Carcinoma (SCC) is a subtype of Non-Melanoma Skin Cancer, the most common group of malignancies worldwide. Photodynamic therapy (PDT) is a non-invasive treatment approved for specific subtypes of SCC. Some malignancies resist PDT, forming more aggressive tumors and multiple relapses. Thus, new approaches aimed at optimizing the response to PDT are needed. The mTORC1 inhibitor rapamycin, also known as Sirolimus (SRL), interferes with protein synthesis and cell metabolism. The use of SRL as an immunosuppressant is associated to lower rates of SCC in kidney-transplanted patients, which are frequently affected by this pathology. We have evaluated SRL pre-treatment efficacy to enhance the damage induced by PDT with Methyl 5-aminolevulinate in two different cutaneous SCC established cell lines (SCC13 and A431) in vitro and therapy sensitization in PDT-resistant cell lines. We tested for the first time the SRL + PDT combination in a SKH-1 mouse model of photocarcinogenesis, diminishing the frequency of lesions and restraining tumor growth. Molecular studies revealed that protoporphyrin IX and reactive oxygen species production induced by PDT were promoted by SRL pre-treatment. Lastly, SRL modifies the expression and intracellular location of NRF2, interfering with the downstream antioxidant response modulated by NQO1 and HO-1. In conclusion, we propose SRL as a potential adjuvant to enhance PDT efficacy for SCC treatment.

Corrigendum: Differential Immunoexpression of Inhibitory Immune Checkpoint Molecules and Clinicopathological Correlates in Keratoacanthoma, Primary Cutaneous Squamous Cell Carcinoma and Metastases.

This Corrigendum relates to the following article: https://doi.org/10.2340/actadv.v104.13381.

Interobserver agreement on line-field confocal optical coherence tomography image markers in keratinocyte carcinomas and precursor lesions.

Line-field confocal optical coherence tomography (LC-OCT) is a new technology for skin cancer diagnostics. However, the interobserver agreement (IOA) of known image markers of keratinocyte carcinomas (KC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), as well as precursors, SCC in situ (CIS) and actinic keratosis (AK), remains unexplored. This study determined IOA on the presence or absence of 10 key LC-OCT image markers of KC and precursors, among evaluators new to LC-OCT with different levels of dermatologic imaging experience. Secondly, the frequency and association between reported image markers and lesion types, was determined. Six evaluators blinded to histopathologic diagnoses, assessed 75 LC-OCT images of KC (21 SCC; 21 BCC), CIS (12), and AK (21). For each image, evaluators independently reported the presence or absence of 10 predefined key image markers of KCs and precursors described in an LC-OCT literature review. Evaluators were stratified by experience-level as experienced (3) or novices (3) based on previous OCT and reflectance confocal microscopy usage. IOA was tested for all groups, using Conger's kappa coefficient (κ). The frequency of reported image marker and their association with lesion-types, were calculated as proportions and odds ratios (OR), respectively. Overall IOA was highest for the image markers lobules (κ = 0.68, 95% confidence interval (CI) 0.57;0.78) and clefting (κ = 0.63, CI 0.52;0.74), typically seen in BCC (94%;OR 143.2 and 158.7, respectively, p < 0.001), followed by severe dysplasia (κ = 0.42, CI 0.31;0.53), observed primarily in CIS (79%;OR 7.1, p < 0.001). The remaining seven image-markers had lower IOA (κ = 0.06-0.32) and were more evenly observed across lesion types. The lowest IOA was noted for a well-defined (κ = 0.07, CI 0;0.15) and interrupted dermal-epidermal junction (DEJ) (κ = 0.06, CI -0.002;0.13). IOA was higher for all image markers among experienced evaluators versus novices. This study shows varying IOA for 10 key image markers of KC and precursors in LC-OCT images among evaluators new to the technology. IOA was highest for the assessments of lobules, clefting, and severe dysplasia while lowest for the assessment of the DEJ integrity.

Relationship between NLR and penile squamous cell carcinoma: a systematic review and meta-analysis.

OBJECTIVE: We conducted this study to summarize the results of studies reporting the role of NLR (neutrophil to lymphocyte ratio) in PSCC (penile squamous cell carcinoma). METHODS: This meta-analysis was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria. A systematic search was conducted on PubMed, Scopus, and web of science up to March 10, 2023. Fourteen studies were included in the review. The NOS (Newcastle-Ottawa Scale) was used to determine the quality of the included studies. This meta-analysis was conducted on the studies reporting the relationship between NLR and survival using HR (hazard ratio) and 95% CI (confidence interval). RESULTS: There was a significant association between NLR levels and the prognosis, nodal stage, and anatomical tumor stage of PSCC patients. In the meta-analysis of the association of NLR with survival, NLR level was significantly associated with lower cancer-specific survival (HR = 3.51, 95% CI = 2.07-5.98, p < 0.001) and lower disease-free survival (HR = 2.88, 95% CI = 1.60-5.20, p < 0.001). However, NLR was found to have no association with the stage, grade, location, and size of the tumor. CONCLUSION: NLR has a significant diagnostic and prognostic value in PSCC.

Multi-regional genomic and transcriptomic characterization of a melanoma-associated oral cavity cancer provide evidence for CASP8 alteration-mediated field cancerization.

BACKGROUND: Precancerous and malignant tumours arise within the oral cavity from a predisposed "field" of epithelial cells upon exposure to carcinogenic stimulus. This phenomenon is known as "Field Cancerization". The molecular genomic and transcriptomic alterations that lead to field cancerization and tumour progression is unknown in Indian Oral squamous cell carcinoma (OSCC) patients. METHODS: We have performed whole exome sequencing, copy-number variation array and whole transcriptome sequencing from five tumours and dysplastic lesions (sampled from distinct anatomical subsites - one each from buccal anterior and posterior alveolus, dorsum of tongue-mucosal melanoma, lip and left buccal mucosa) and blood from a rare OSCC patient with field cancerization. RESULTS: A missense CASP8 gene mutation (p.S375F) was observed to be the initiating event in oral tumour field development. APOBEC mutation signatures, arm-level copy number alterations, depletion of CD8 + T cells and activated NK cells and enrichment of pro-inflammatory mast cells were features of early-originating tumours. Pharmacological inhibition of CASP8 protein in a CASP8-wild type OSCC cell line showed enhanced levels of cellular migration and viability. CONCLUSION: CASP8 alterations are the earliest driving events in oral field carcinogenesis, whereas additional somatic mutational, copy number and transcriptomic alterations ultimately lead to OSCC tumour formation and progression.

Silencing ANLN hinders the proliferation, migration, invasion, and angiogenesis of oral squamous cell carcinoma.

BACKGROUND: The actin-binding protein anillin (ANLN) functions as an oncogene in various cancers but has not been fully studied in oral squamous cell carcinoma (OSCC). This study aimed to investigate the expression of ANLN in OSCC tissues and cell lines, to better understand its role in mediating proliferative, angiogenic, invasive, and metastatic capabilities in this type of cancer. METHODS: ANLN mRNA and protein levels were assessed using qPCR and western immunoblotting. The expression intensity of ANLN was evaluated using immunohistochemical (IHC) staining. Biological functional assays were employed to characterize the behavior of OSCC cells influenced by ANLN. Additionally, comprehensive bioinformatics analysis, including GO analysis and KEGG enrichment analysis, was performed on differentially expressed genes in ANLN-mediated pathways. RESULTS: OSCC tumors and cell lines exhibited higher ANLN expression. Silencing of ANLN significantly suppressed OSCC cell proliferation, as evidenced by a significant reduction in the Ki-67 index both in vitro and in vivo. The migration and invasive ability of OSCC cells were markedly diminished, coinciding with a decrease in epithelial-mesenchymal transition activity. ANLN was also found to promote angiogenic activity in OSCC cells, partly through synergistic effects mediated by vascular endothelial growth factor A (VEGFA). Downregulation of ANLN expression led to decreased VEGFA levels, resulting in reduced angiogenesis characterized by fewer vascular branches. CONCLUSIONS: Our findings highlight the promising role of ANLN as a biomarker for both diagnostic and prognostic in OSCC. Targeting ANLN with inhibitory strategies could impede the oncogenesis processes at the core of OSCC development, presenting significant opportunities for advancing therapeutic interventions.

The role of prehabilitation in HNSCC patients treated with chemoradiotherapy.

BACKGROUND: Radiotherapy (RT) is used in head and neck squamous cell carcinoma (HNSCC) with excellent effectiveness, but it is burdened by important side effects, which may negatively impact patients' quality of life (QoL). In particular when associated with chemotherapy (CT), that has a radiosensitising effect (and its own toxicities), it is responsible for several adverse events, causing social discomfort and lower QoL, in patients who are already experiencing several tumor-related discomforts. Prehabilitation is a healthcare intervention consisting of several specialist visits prior to the start of treatment, with the aim of improving the patient's health status, resolving symptoms that interfere with treatment and impact QoL, and finally to better avoid or overcome complications. Of all cancer patients, HNSCC patients are among those who could benefit most from prehabilitation, both because of the high number of symptoms and toxicities and their difficult management. Despite this and the emerging data, prehabilitation is not often considered for the majority of patients undergoing (C)RT. In this review, we tried to understand what are the main areas in which interventions can be made prior to the (C)RT start, the possible side effects of the treatment, the effectiveness in their prevention and management, and the impact that prehabilitation may have in adherence to therapy and on the principal survival outcomes, providing important guidance for the planning of future studies. EVIDENCES AND CONCLUSIONS: Although there is no strong data evaluating multidisciplinary prehabilitation strategies, evidence shows that optimizing the patient's health status and preventing possible complications improve the QoL, reduce the incidence and severity of adverse events, and improve treatment adherence. While cardiology prehabilitation is of paramount importance for all patients undergoing concomitant CRT in the prevention of possible side effects, the remaining interventions are useful independently of the type of treatment proposed. Geriatricians have a key role in both elderly patients and younger patients characterized by many comorbidities to comprehensively assess health status and indicate which treatment may be the best in terms of risk/benefit ratio. Collaboration between nutritionists and phoniatrics, on the other hand, ensures adequate nutritional intake for the patient, where possible orally. This is because optimizing both body weight and muscle mass and qualities has been shown to impact key survival outcomes. Finally, HNSCC patients have the second highest suicide rate, and the disease has side effects such as pain, dysfiguration, and sialorrhea that can reduce the patient's social life and create shame and embarrassment: A psychological intake, in addition to the usefulness to the patient, can also provide current support to caregivers and family members. Therefore clinicians must define a personalized pathway for patients, considering the characteristics of the disease and the type of treatment proposed, to optimize health status and prevent possible side effects while also improving QoL and treatment adherence.

SEPT9: From pan-cancer to lung squamous cell carcinoma.

BACKGROUND: SEPT9 is a pivotal cytoskeletal GTPase that regulates diverse biological processes encompassing mitosis and cytokinesis. While previous studies have implicated SEPT9 in tumorigenesis and development; comprehensive pan-cancer analyses have not been performed. This study aims to systematically explore its role in cancer screening, prognosis, and treatment, addressing this critical gap. METHODS: Gene and protein expression data containing clinical information were obtained from public databases for pan-cancer analyses. Additionally, clinical samples from 90 patients with lung squamous cell carcinoma (LUSC) were used to further experimentally validate the clinical significance of SEPT9. In addition, the molecular docking tool was used to analyze the affinities between SEPT9 protein and drugs. RESULTS: SEPT9 is highly expressed in various cancers, and its aberrant expression correlates with genetic alternations and epigenetic modifications, leading to adverse clinical outcomes. Take LUSC as an example, additional dataset analyses and immunohistochemical experiments further confirm the diagnostic and prognostic values as well as the clinical relevance of the SEPT9 gene and protein. Functional enrichment, single-cell expression, and immune infiltration analyses revealed that SEPT9 promotes malignant tumor progression and modulates the immune microenvironments, enabling patients to benefit from immunotherapy. Moreover, drug sensitivity and molecular docking analyses showed that SEPT9 is associated with the sensitivity and resistance of multiple drugs and has stable binding activity with them, including Vorinostat and OTS-964. To harness its prognostic and therapeutic potential in LUSC, a mitotic spindle-associated prognostic model including SEPT9, HSF1, ARAP3, KIF20B, FAM83D, TUBB8, and several clinical characteristics, was developed. This model not only improves clinical outcome predictions but also reshapes the immune microenvironment, making immunotherapy more effective for LUSC patients. CONCLUSION: This is the first study to systematically analyze the role of SEPT9 in cancers and innovatively apply the mitotic spindle-associated model to LUSC, fully demonstrating its potential as a valuable biomarker for cancer screening and prognosis, and highlighting its application value in promoting immunotherapy and chemotherapy, particularly for LUSC.

Epithelial­derived head and neck squamous tumourigenesis (Review).

Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, Epstein­Barr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5­year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.

Modern radiation therapy for keratinocyte cancer: What the general practitioner needs to know.

BACKGROUND: Keratinocyte cancer (KC) in Australia poses a unique healthcare challenge due to its high prevalence and the requirement for multidisciplinary management of many cases. Advances in radiation therapy (RT) have increased its use in treating different keratinocyte cancer presentations. Understanding the indications for RT and the role that general practitioners (GPs) play in the treatment pathway are imperative to ensure best patient outcomes. OBJECTIVE: This review examined the efficacy, advances and treatment considerations of RT for the management of keratinocyte cancer, and role of the GP in the treatment pathway. DISCUSSION: Radiation therapy offers effective alternatives to, or adjuvants for, surgery in existing keratinocyte cancer treatments in appropriate cases. The evolving RT landscape necessitates GPs to be well informed for effective case identification, referral and management. This includes understanding RT advances, protocols, treatment reactions and managing patient expectations. Continuing education in this space is important for GPs to understand the suitability of RT for their patients.

Establishment of an Animal Model of Oral Squamous Cell Carcinoma Invading the Mandible.

OBJECTIVE: To establish an animal model of oral squamous cell carcinoma invading the mandible through multi-sample experiments that verified the stability, repeatability, tumorigenicity and mandible destruction rate of the model. METHODS: Oral squamous cell carcinoma cell suspension was injected into the outer side of the mandible through the anterior edge of the masseter muscle of naked mice to observe the tumourforming process. Then, the anatomical, histological and imaging examinations were carried out to determine whether the tumour had invaded the mandible. By comparing the tumour growth of multiple groups of various squamous cell carcinoma cells (CAL27, HN6 and HN30 cells), the changes in body weight and characteristics of tumour formation were compared, and the experience was summarised to further verify the stability, repeatability, tumour formation rate and arch damage rate of the model. RESULTS: The subsequent specimens of tumour-bearing nude mice were validated once the model had been established. In vitro, tumour tissue wrapped around the mandible's tumour-bearing side, and the local texture was tough with no resistance to acupuncture. Haematoxylin and eosin staining revealed that squamous cells were infiltrating the mandible in both the horizontal and sagittal planes. Microcomputed tomography results showed that the mandible on the tumour-bearing side displayed obvious erosion damage. Cell lines with various passage rates clearly had diverse tumour-bearing life cycles. CONCLUSION: This study successfully established an animal model of oral squamous cell carcinoma invasion of the mandible. The model has excellent biological stability, repeatability, tumorigenesis rate and mandible destruction rate.

Role of Antioxidant Enzymes in Pathogenesis of Oral Squamous Cell Carcinoma: a Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the antioxidant enzyme status in biological samples of patients with oral squamous cell carcinoma (OSCC) and compare them with biological samples of healthy people through a systematic review and meta-analysis. METHODS: Antioxidant enzymes of catalase (CAT), sodium dismutase (SOD) and glutathione peroxide (GPx) were included in the analysis. A literature search was conducted of the PubMed, Science Direct, Scopus, Web of Science and Wiley Online Library databases for studies published between January 1999 and December 2022. A total of 831 articles were selected, of which 131 were found to be relevant. Finally, the full texts of 12 studies were screened and included. Studies that evaluated other antioxidant enzymes were excluded. Standardised mean difference (SMD) was derived to conduct a meta-analysis using comprehensive meta-analysis v3 (Biostat, Englewood, NJ, USA). A random effects model with 95% confidence interval (CI) was used to estimate the effect size. P < 0.05 was considered significant. RESULTS: CAT levels were measured in eight studies (n = 567) and the mean values for the OSCC and control groups were 4.81 ± 2.57 and 10.02 ± 1.81, respectively (SMD 3.18, 95% CI 1.01 to 1.42; P = 0.001). SOD level was evaluated in 11 studies (n = 762) and the values for the OSCC and control groups were 3.78 ± 1.45 and 7.34 ± 1.79, respectively (SMD 3.66, 95% CI 1.51 to 1.94; P = 0.001). GPx level was evaluated in 10 studies (n = 697) and the values for the OSCC and control groups were 13.33 ± 1.42 and 16.54 ± 2.9, respectively (SMD 1.91, 95% CI 1.34 to 1.77; P = 0.001). The heterogeneity between the studies was severe (I2 ≥ 90%). The risk of bias between studies was low to moderate. CONCLUSION: Analysis revealed that the levels of antioxidant enzymes decreased in biological samples of patients with OSSC as compared to healthy controls. Understanding the pathological progress of OSCC by analysing the level of antioxidant enzymes is beneficial in formulating a personalised, targeted pro-oxidant therapy for cancer treatment.

Preoperative thromboelastography parameters in predicting the tumour stage of oral squamous cell carcinoma.

BACKGROUND: A variety of solid tumours, including oral squamous cell carcinoma (OSCC), can cause coagulation abnormalities, and this phenomenon is known as tumour-associated hypercoagulation. We aimed to explore the preoperative thromboelastography (TEG) parameter profiles of OSCC patients, and to investigate their trends in relation to tumour stage progression, and to evaluate their value for predicting cervical lymph node metastasis. METHODS: Data on thromboelastographic parameters and conventional coagulation indices were retrospectively collected, and comparisons were performed among preoperative primary OSCC patients (n = 311), recurrent/metastatic OSCC patients (n = 44) and a control group (n = 71). Among primary OSCC patients, the correlation with tumour stage and the predictive role of cervical lymph node metastasis were analyzed. RESULTS: Hypercoagulability occurred in OSCC patients and tended to become more pronounced as the tumour progressed. The whole-time phase of coagulation increased with increasing T stage, while the early phase of coagulation increased with increasing N stage. CONCLUSIONS: Preoperative TEG parameters are closely related to tumour stage and progression, suggesting that TEG can be used as an important indicator for predicting tumour stage and as a potential biomarker.

Serum mRNA levels of cytokeratin-19 and vascular endothelial growth factor in oral squamous cell carcinoma and oral potentially malignant disorders using RT-PCR.

BACKGROUND: Oral cancers, which include tumors of the oral cavity, salivary glands, and pharynx, are becoming increasingly prevalent worldwide. Squamous cell carcinoma accounts for over 90% of malignant oral lesions, with oral squamous cell carcinoma (OSCC) being notably common in the Indian subcontinent and other regions of Asia. This is especially true in South-Central Asia, including Sri Lanka, where it is particularly prevalent among men. This study aims to evaluate the levels of Vascular Endothelial Growth Factor-A (VEGF-A) and Cytokeratin-19 (CK-19) mRNAs in whole blood as a potential method for the early detection of OSCC. METHODS: The study included 40 patients (each from OSCC, Oral Submucous Fibrosis (OSF), Oral Leukoplakia (OLK), Oral Lichen Planus (OLP), and 10 healthy controls. The expression levels of VEGF-A and CK-19 mRNAs were measured from extracellular RNA extracted from whole blood samples using real-time reverse transcription polymerase chain reaction (RT-PCR) with sequence-specific primers. Receiver operating characteristic (ROC) curve analysis was used to evaluate the effectiveness of these biomarkers in detecting OSCC. RESULTS: The results demonstrated a significant increase in blood transcripts of the candidate mRNAs CK-19 and VEGF-A in patients with OSCC, OSF, OLK, and OLP. The Wilcoxon signed-rank test revealed a p-value of 0.002 for each specific comparison between diseased patients and healthy controls (i.e., OSCC vs. HC, OSF vs. HC, OLP vs. HC, OLK vs. HC) for both CK-19 and VEGF-A. When these two biomarkers were used together, they provided a 60% predictive probability for patients with OSCC (p = 0.023). CONCLUSION: This study highlights the efficacy of blood mRNA transcriptome diagnostics in detecting OSCC. This innovative clinical approach has the potential to be a robust, efficient, and reliable tool for early cancer detection. Blood-based transcriptomes could be further explored for their effectiveness in various health contexts and for routine health monitoring.

Assessment of the quality of oral squamous cell carcinoma clinical records in oral surgery with Surgical Tool for Auditing Records (STAR) scoring.

BACKGROUND: The Surgical Tool for Auditing Records scoring system [STAR] focuses on surgical record auditing with promising outcomes. It offers a structured approach to evaluating the quality of surgical notes. AIMS AND OBJECTIVES: This study aimed to assess the effectiveness of the STAR in evaluating oral surgical records and identifying areas for improvement in documentation practices. MATERIALS AND METHODS: The data was obtained from the Dental Information Archival Software (DIAS) of our institution. The sample size was determined using G*Power 3.1.9.4 software. Fifty consecutive oral surgery clinical records of oral squamous cell carcinoma patients were evaluated using STAR. Each record was reviewed for adherence to documentation standards including Initial Assessment (10 points), Follow-up Entries (8 points), Consent Documentation (7 points), Anesthesia Report (7 points), Surgical Log (9 points), and Discharge Synopsis (9 points). compiling a total STAR score (50 points). The data was tabulated in Google Sheets. The descriptive statistics with inter-observer agreement and the mean score were recorded. RESULTS: We observed that each of the 50 records received a score of 49/50 points on the STAR. Deductions were necessary in the Operative record section due to the lack of information regarding the sutures used. CONCLUSION: To summarize, this study emphasizes the effectiveness of the STAR scoring system in evaluating the quality of oral surgical records. Identifying deficiencies, particularly in documenting operative details, can improve the completeness and accuracy of patient records. It can ultimately enhance patient care and facilitate better communication among healthcare professionals.

Combined miR-181a-5p and Ag Nanoparticles are Effective Against Oral Cancer in a Mouse Model.

Purpose: Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy. Methods: We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved. Results: The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the ß-catenin signaling pathway and other downstream genes without inducing acute toxicity. Conclusion: Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the ß-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.

Squamous cell carcinoma of the urinary bladder in patients with chronic spinal cord injury: A case series.

INTRODUCTION: Patients with spinal cord injury/disorder (SCI/D) and neurogenic lower urinary tract dysfunction (NLUTD) are on a 16-28 folder higher risk for bladder cancer [1]. Whereas in the general population 90% of bladder tumors are transitional cell carcinoma (TCC) patients with NLUTD have a shift to squamous cell carcinoma with 36,8% and only 46.3% TCC [2]. In addition, there is a significant increase in the bladder cancer-specific death rate in SCI patients (3rd most common) compared to the general population (10th most common) [2]. Chronic inflammation and mechanical irritation by permanent indwelling catheters are discussed as risk factors for developing bladder cancer. Typical symptoms of bladder cancer are often absent in patients with NLUTD and a reliable screening has not been established. CASE PRESENTATION: We present a case series of six patients with SCI and with squamous cell carcinoma diagnosed in the last 5 years in our institution. In five patients, bladder management was performed by indwelling suprapubic catheters, one patient used reflex voiding. Three patients were diagnosed during the regular, annual neuro-urological check-up, the remaining due to increasing spasticity and autonomic dysregulation. Subsequently, five patients underwent cystectomy with ileal conduit or uretercutaneostomy, one patient refused further surgical treatment. Four patients died within one year after diagnosis. DISCUSSION: Squamous cell carcinoma of the bladder is more common in patients with NLUTD. Chronic inflammation and mechanical irritation may be the reasons for carcinoma genesis. A regular check including cystoscopy is strongly recommended to detect tumor development early.