Invasive Squamous Cell Carcinoma Research Articles

LncRNA FOXD2-AS1 promotes the growth, invasion and migration of OSCC cells by regulating the MiR-185–5p/PLOD1/Akt/mTOR pathway

Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185–5 p and that miR-185–5 p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185–5 p/PLOD1/Akt/mTOR pathway activity.

Invasive Oral Squamous Cell Carcinoma Mimicking a Dentoalveolar Abscess: Report of a Case in a 14-Year-Old Patient

IntroductionA diagnosis of oral squamous cell carcinoma in adolescent patients is extremely rare. When an oral squamous cell carcinoma lesion arises near the teeth and/or periodontium, it can be easily misdiagnosed as an inflammatory condition of endodontic or periodontal origin. MethodsThis is a case report of an otherwise healthy 14-year-old patient who was referred for endodontic evaluation and treatment of a soft-tissue swelling in the anterior maxilla. ResultsThe unexpected definitive diagnosis of invasive oral squamous cell carcinoma underscores the importance of proper diagnostic testing. ConclusionsAccurate interpretation of pulp testing results, periapical and cone beam computed tomography imaging, timely biopsy, and prompt definitive treatment are critical when a lesion of nonodontogenic origin is suspected.

Diagnose und Therapie aktinischer Keratosen

Actinic keratosis (AK) is considered a chronic and recurring in situ skin neoplasia, with a possible transformation into invasive squamous cell carcinoma (SCC). Among others, predominant risk factors for development of AK are UV-light exposure and immunosuppression. Basal epidermal keratinocyte atypia (AK I) and proliferation (PRO Score) seem to drive malignant turnover, rather than clinical appearance of AK (Olsen I-III). Due to the invasiveness of punch biopsy, those histological criteria are not regularly assessed. Non-invasive imaging techniques, such as optical coherence tomography (OCT), reflectance confocal microscopy (RCM) and line-field confocal OCT (LC-OCT) are helpful to distinguish complex cases of AK, Bowen's disease and SCC. Moreover, LC-OCT can visualize the epidermis and the papillary dermis at cellular resolution, allowing real-time PRO Score assessment. The decision-making for implementation of therapy is still based on clinical risk factors, ranging from lesion- to field-targeted and ablative to non-ablative regimes, but in approximately 85% of the cases a recurrence of AK can be observed after a 1-year follow-up. The possible beneficial use of imaging techniques for a non-invasive follow-up of AK to detect recurrence or invasive progression early on should be subject to critical evaluation in further studies.

Molecular Classification of Vulvar Squamous Cell Carcinoma and Precursor Lesions Using Immunohistochemistry

Abstract Introduction: Vulvar malignancies are very rare. Two pathogenic pathways have been described in the development of vulvar squamous cell carcinoma.One is related to HPV infection and the other is related to TP 53 mutation. HPV infection related squamous cell carcinomas have a good prognosis and squamous cell carcinomas related to TP 53 mutation have the worst prognosis. Recently a third pathway which is neither HPV dependent nor p53 mutant has been identified. This pathway is found to have intermediate prognosis with better clinical outcome. Aims: The aim of this study was to classify vulvar squamous cell carcinoma and its precursor lesions molecularly using two immunohistochemical stains p16 and p53 in a cohort of South Indian population. Subjects and Methods: A retrospective observational study was conducted between January 2011 and December 2020 in the department of histopathology at a tertiary care hospital in Hyderabad, India. A total of 22 cases including all the vulval biopsies with suspected squamous cell carcinoma or precursor lesions and excision specimens operated for squamous cell carcinoma were included in this study. Paraffin blocks of representative cases were stained with hematoxylin and eosin stain, p16 and p53 immunohistochemistry (IHC) stains. Results: Out of 22 cases, two cases (9.0%) were precursor lesions of the vulva and 20 cases (90.9%) were invasive squamous cell carcinoma. Eleven (50%) of these cases were p53 mutant (p53+/p16−), 10 (45.4%) of these cases were HPV positive (p16+/p53−), and one of these cases (4.5%) was neither HPV positive nor p53 mutant (p16−/p53−). Conclusions: Classification of vulvar squamous cell lesions molecularly using simple immunohistochemical stains in routine diagnostic workup will aid in risk stratification of patients and help in their management and prognostication.

AB124. SOH24AB_133. Diagnostic superiority of MRI in evaluating the presence of bone invasion in head and neck cutaneous squamous cell carcinoma

AB124. SOH24AB_133. Diagnostic superiority of MRI in evaluating the presence of bone invasion in head and neck cutaneous squamous cell carcinoma

TRIM Expression in HNSCC: Exploring the Link Between Ubiquitination, Immune Infiltration, and Signaling Pathways Through Bioinformatics.

Ubiquitination is an important post-translational modification. However, the significance of the TRIM family of E3 ubiquitin ligases in head and neck squamous cell carcinoma (HNSCC) has not been determined. In this study, the roles of TRIM E3 ubiquitin ligases in lymphovascular invasion in head and neck squamous cell carcinoma (HNSCC) were evaluated. TRIM expression and related parameters were obtained from UbiBrowser2.0, UALCAN, TIMER, TISIDB, LinkedOmics, STRING, and GeneMANIA databases. Immunohistochemistry was used to confirm their expression. TRIM2, TRIM11, TRIM28, and TRIM56 were upregulated in HNSCC with lymphovascular invasion. TRIM expression was strongly associated with immune infiltration, including key treatment targets, like PD-1 and CTL4. Co-expressed genes and possible ubiquitination substrates included tumor-related factors. The TRIMs had predicted roles in ubiquitination-related pathways and vital signaling pathways, eg, MAPK, PI3K-Akt, and JAK-STAT signaling pathways. Ubiquitination mediated by four TRIMs might be involved in the regulation of tumor immunity, laying the foundation for future studies of the roles of the TRIM family on the prediction and personalized medicine in HNSCC. The four TRIMs might exert oncogenic effects by promoting lymphovascular invasion in HNSCC.

LncRNA FOXD2-AS1 Promotes the Growth, Invasion and Migration of OSCC Cells by Regulating the MiR-185-5p/PLOD1/Akt/mTOR Pathway

Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185-5p and that miR-185-5p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185-5p/PLOD1/Akt/mTOR pathway activity.

An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium–silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

Therapeutic and fluorescence evaluation of 20% 5-aminolevulinic acid-mediated photodynamic therapy in actinic keratosis

BackgroundActinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20 % 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment. MethodsTwenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20 % ALA, and 3 h later, they were irradiated with LED red light (80–100 mW/cm2) for 20 min. A session of 20 % ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment. ResultsOne week after ALA-PDT, complete remission (CR) was reached in 53.6 % of patients. The CR of Grade I AK lesions was 100 %, that of Grade II lesions was 71.4 %, and that of Grade III lesions was 38.1 %. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1 % of the patients were satisfied with the treatment. ConclusionAK lesions can be safely and effectively treated with 20 % ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT.

Verbascoside inhibits oral squamous cell carcinoma cell proliferation, migration, and invasion by the methyltransferase 3-mediated microRNA-31-5p/homeodomain interacting protein kinase 2 axis

ObjectiveThe study aimed to investigate the effects of verbascoside on oral squamous cell carcinoma (OSCC) cellular behaviors and underlying molecular mechanisms. DesignFor this purpose, SCC9 and UM1 cell lines were treated with verbascoside, and their biological behaviors, including proliferation, migration, and invasion, were evaluated using cell counting kit-8, 5-Ethynyl-2′-deoxyuridine, and Transwell assays. The expression of methyltransferase-3 (METTL3), microRNA (miR)− 31–5p, and homeodomain interacting protein kinase-2 (HIPK2) were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between METTL3 and miR-31–5p was evaluated by RNA immunoprecipitation and methylated RNA immunoprecipitation, while the interaction between miR-31–5p and HIPK2 was evaluated by dual-luciferase reporter analysis. ResultsThe results indicated inhibition of OSCC cell proliferation, migration, and invasion post verbascoside treatment. Similarly, METTL3 was upregulated in OSCC cells and was inhibited post-verbascoside treatment. Overexpressing METTL3 promoted the cellular processes. Moreover, miR-31–5p was upregulated in OSCC cells, where METTL3 facilitated the processing of miR-31–5p in an N6-methyladenosine (m6A)-dependent manner. The HIPK2 served as miR-31–5p target, where overexpressing miR-31–5p or HIPK2 knockdown reversed the suppression of verbascoside-induced biological behaviors. ConclusionsVerbascoside inhibited the progression of OSCC by inhibiting the METTL3-regulated miR-31–5p/HIPK2 axis. These findings suggested that verbascoside might be an effective drug for OSCC therapy.

The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression

Dysbiosis of the oral microbiota is related to chronic inflammation and carcinogenesis. Fusobacterium nucleatum (Fn), a significant component of the oral microbiota, can perturb the immune system and form an inflammatory microenvironment for promoting the occurrence and progression of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms remain elusive. Here, we investigated the impacts of Fn on OSCC cells and the crosstalk between OSCC cells and macrophages. 16 s rDNA sequencing and fluorescence in situ hybridization verified that Fn was notably enriched in clinical OSCC tissues compared to paracancerous tissues. The conditioned medium co-culture model validated that Fn and macrophages exhibited tumor-promoting properties by facilitating OSCC cell proliferation, migration, and invasion. Besides, Fn and OSCC cells can recruit macrophages and facilitate their M2 polarization. This crosstalk between OSCC cells and macrophages was further enhanced by Fn, thereby amplifying this positive feedback loop between them. The production of CXCL2 in response to Fn stimulation was a significant mediator. Suppression of CXCL2 in OSCC cells weakened Fn’s promoting effects on OSCC cell proliferation, migration, macrophage recruitment, and M2 polarization. Conversely, knocking down CXCL2 in macrophages reversed the Fn-induced feedback effect of macrophages on the highly invasive phenotype of OSCC cells. Mechanistically, Fn activated the NF-κB pathway in both OSCC cells and macrophages, leading to the upregulation of CXCL2 expression. In addition, the SCC7 subcutaneous tumor-bearing model in C3H mice also substantiated Fn’s ability to enhance tumor progression by facilitating cell proliferation, activating NF-κB signaling, up-regulating CXCL2 expression, and inducing M2 macrophage infiltration. However, these effects were reversed by the CXCL2-CXCR2 inhibitor SB225002. In summary, this study suggests that Fn contributes to OSCC progression by promoting tumor cell proliferation, macrophage recruitment, and M2 polarization. Simultaneously, the enhanced CXCL2-mediated crosstalk between OSCC cells and macrophages plays a vital role in the pro-cancer effect of Fn.

HOXB9 promotes laryngeal squamous cell carcinoma progression by upregulating MMP12.

Transcriptional factor HOXB9, a part of the HOX gene family, plays a crucial role in the development of diverse cancer types. This study aimed to elucidate the regulatory mechanism of HOXB9 on the proliferation and invasion of laryngeal squamous cell carcinoma (LSCC) cells to provide guidance for the development and prognosis of LSCC. The CRISPR/Cas9 method was employed in LSCC cell lines to knock out the HOXB9 gene and validate its effects on the proliferation, migration, invasion, and regulation of LSCC cells. CCK-8 and flow cytometry were used to detect cell viability and proliferation; Tunnel was used to detect cell apoptosis, and transwell was used to detect cell migration and invasion. The effect of HOXB9 on tumor growth was tested in nude mice. The downstream target genes regulated by HOXB9 were screened by microarray analysis and verified by Western blotting, immunohistochemistry, chromatin immunoprecipitation, and double-luciferase reporter assays. The current research investigated molecular pathways governed by HOXB9 in the development of LSCC. Additionally, both laboratory- and living-organism-based investigations revealed that disrupting the HOXB9 gene through the CRISPR/CAS9 mechanism restrained cellular growth, movement, and infiltration, while enhancing cellular apoptosis. Detailed analyses of LSCC cell strains and human LSCC samples revealed that HOXB9 promoted LSCC progression by directly elevating the transcriptional activity of MMP12. HOXB9 could influence changes in LSCC cell functions, and the mechanism of action might be exerted through its downstream target gene, MMP12.

Fragile hands: targeting nonmelanoma skin cancer on older hands using 595nm pulsed dye laser.

The mainstay of treatment for nonmelanoma skin cancer (NMSC) on thin skin remains surgical, but procedures on older hands may be complicated by skin fragility and dermal atrophy. Used without cooling, 595nm (nm) pulsed dye laser (PDL) has the capability of destroying NMSC through nonspecific thermal necrosis. The purpose of this study was to understand recurrence of NMSC on dorsal hands of older patients after one or two treatments using 595nm PDL. A retrospective chart review identified 147 cases of NMSC located on the dorsal hands treated with 595nm PDL. Cases of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) were included. All patients received one to two treatments with PDL. The primary outcome was the recurrence of carcinoma. Among NMSC cases treated with PDL, recurrence occurred in 12 patients (8.2%). No cases of BCC recurred during the study period. Recurrence of SCC was 4.7% for SCC in situ and 10.4% recurrence for invasive SCC (p = 0.34). Among 71 patients treated once, recurrence occurred in 10 patients (14.1%), and among 76 cases treated twice, recurrence occurred in 2 patients (2.6%, p = 0.01). Two treatments of PDL for NMSC on the dorsal hands of older patients was well tolerated, had low recurrence, and seemed more effective than one treatment.

Tirbanibulin 1% Ointment Effectiveness for Actinic Keratosis Treatment Evaluated by Dynamic Optical Coherence Tomography

Background. Actinic keratosis (AK) is a common premalignant skin condition. Its diagnosis is based on a clinical and sometimes dermoscopic examination, but, in some situations, a skin biopsy may be necessary. Dynamic optical coherence tomography (D-OCT) can often bypass this need, by noninvasive evaluation of skin morphology. Early and effective treatment of AKs is important to prevent the progression to invasive squamous cell carcinoma (iSCC). Tirbanibulin 1% ointment, a new topical field therapy for AKs, has recently been introduced. Objectives. The aim of this study was to evaluate the efficacy and safety of tirbanibulin 1% ointment for the field treatment of nonhyperkeratotic, nonhypertrophic AKs (Olsen grade 1) on the face and/or scalp in adults, using D-OCT technology. Methods. Patients, presenting multiple, mild to moderate AKs on the face and scalp, in treatment with tirbanibulin 1% ointment for five consecutive days of an area measuring 25 cm2, were evaluated with videodermoscopy (V-track Vidix 4.0) and D-OCT (VivoSight Dx, Michelson Diagnostics Ltd., Kent, England, United Kingdom), as normal clinical practice. The lesions were staged according to the Olsen classification, excluding the most aggressive lesions. Results. We retrospectively evaluated 50 patients (27 males and 23 females, mean age 76 ± 7.9 years). At 57 days posttreatment, the complete clearance rate was 68% (n = 34) and partial clearance rate was 76% (n = 38). D-OCT showed markedly improved morphology, including a better recognizable dermal-epidermal junction (DEJ), associated with reduced inflammation. The most common adverse events reported were erythema and scaling, which were mostly mild and self-limiting. Conclusions. This study demonstrated that tirbanibulin may be considered an effective and well-tolerated treatment option for nonhyperkeratotic, nonhypertrophic AKs. It showed a favorable safety profile, with mostly mild adverse events. D-OCT can be considered a useful tool for personalizing AK treatment and monitoring.

Dermoscopic Structure of Invasive Squamous Cell Carcinoma of the Nose: Considering the Search for Keratin Plugs

Dermoscopic Structure of Invasive Squamous Cell Carcinoma of the Nose: Considering the Search for Keratin Plugs

Lymphovascular Invasion in Cutaneous Squamous Cell Carcinoma.

Although there is a large body of literature regarding risk stratification and outcomes for perineural invasion (PNI) in cutaneous squamous cell carcinoma (cSCC), there is a relative paucity of studies exploring the role of lymphovascular invasion (LVI) in cSCC and a lack of clear evidence-based guidelines for how to manage patients with these tumors. This article is intended to review the available literature regarding LVI in cSCC and formulate evidence-based recommendations for clinical management. A literature review was conducted using PubMed to find relevant articles relating to outcomes and management of primary cSCC with LVI. The available literature suggests that LVI is a major risk factor for poor outcomes and increased morbidity and mortality in cSCC. Lymphovascular invasion is a very high-risk feature that should place these tumors in the highest-risk category, and management of these tumors should be similar to that of squamous cell carcinoma with PNI.

Low expression of interleukin-1 receptor antagonist correlates with poor prognosis via promoting proliferation and migration and inhibiting apoptosis in oral squamous cell carcinoma

BackgroundBiomarkers are biochemical indicators that can identify changes in the structure or function of systems, organs, or cells and can be used to monitor a wide range of biological processes, including cancer. Interleukin-1 receptor antagonist (IL1RA) is an important inflammatory suppressor gene and tumor biomarker. The goal of this study was to investigate the expression of IL1RA, its probable carcinogenic activity, and its diagnostic targets in oral squamous cell carcinoma (OSCC). ResultsWe discovered that IL1RA was expressed at a low level in OSCC tumor tissues compared to normal epithelial tissues and that the expression declined gradually from epithelial hyperplasia through dysplasia to carcinoma in situ and invasive OSCC. Low IL1RA expression was associated not only with poor survival but also with various clinicopathological markers such as increased infiltration, recurrence, and fatalities. Following cellular phenotyping investigations in OSCC cells overexpressing IL1RA, we discovered that recovering IL1RA expression decreased OSCC cell proliferation, migration, and increased apoptosis. ConclusionsIn summary, our investigation highlighted the possible involvement of low-expression IL1RA in OSCC cells in promoting invasive as well as metastatic and inhibiting apoptosis, as well as the efficacy of IL1RA-focused monitoring in the early detection and treatment of OSCC.

Ultrasound diagnostics: assessment of tumor thickness and depth of invasion in squamous cell carcinoma of the oral cavity

Aim. To evaluate the capabilities of ultrasound using various approaches in determining the depth of invasion of squamous cell carcinoma of the oral cavity and to compare the results obtained with data obtained by the use of other diagnostic methods. Materials and methods. In our reserch, ultrasonography was performed on 193 patients with primary malignant tumors of the mobile part of the tongue, floor of the oral cavity and tumors of rare locations (mucous membranes of the lip, cheek, alveolar processes). The age of the patients ranged from 15 to 85 years. In all patients, tumors were squamous cell carcinoma. ultrasound was performed using submandibular, intraoral and transbuccal approaches. ultrasonic data were compared with the results of pathomorphological examination, as well as of X-ray computed tomography and of magnetic resonance imaging with contrast. Results. A statistically significantly high correlation was obtained for all ultrasound approaches (submandibular, intraoral and transbuccal) with the depth of invasion of the oral tumor determined pathomorphologically (r = 0.78; r = 0.89; r = 0.93; p <0.001). Ultrasound using all approaches shows statistically significantly better results in determining the thickness of tumorsof the tongue and mouth floor in comparison with X-ray computed tomography and magnetic resonance imaging (p <0.001). All diagnostic methods are characterized by an overestimation of the tumor invasion depth (overdiagnosis) as compared with pathomorphological examination. for exophytic tumors and oral cavity tumors of mixed growth with an exophytic component, the depth of invasion was less than the tumor thickness. Conclusion. Ultrasound is an accessible, easily reproducible, radiation-free method, the resolution of which makes it possible to accurately determine not only the depth of invasion of oral tumors, but also the distance from the tumor to the midline of the tongue, that represents an important information when choosing the extent of surgical intervention.

Abstract CT004: A single arm phase 2 study of TVEC in patients with invasive cutaneous SCC: A novel therapeutic approach for low risk tumors

Abstract Background: Immune recognition and cytotoxic responses play an important role in the pathogenesis and progression of cutaneous squamous cell carcinoma (cSCC). Talimogene laherparepvec (TVEC) is an HSV-1 oncolytic immunological agent FDA approved for the local treatment of unresectable recurrent melanoma. It is proposed that T-VEC directly destroys cancer cells, and induces production of GM-CSF to enhance systemic antitumor immune priming. This proposed mechanism of action supports the novel approach to implement TVEC in the management of cSCC, particularly, in patients with increased burden of primary tumors. Methods: Study subjects were Immunocompetent, ≥ 18 years of age, and diagnosed with at least one histologically confirmed primary low-risk cSCC according to the Brigham and Women staging system. Unresectable lesions or patients unable/unwilling to undergo standard of care treatment were eligible to participate. Study lesions included target lesions injected (TLIs) and target non-injected lesions (TNILs). TNILs were selected to evaluate for abscopal effect when feasible. The TLIs were treated according to TVEC FDA approved protocol and followed for 1yr after the 1st injection. The primary study endpoint was to evaluate the overall response rate, defined as the proportion of subjects who achieved complete response and partial response in the TLIs. Safety and adverse effect profile (AEs), duration of response, time to response, durable response rate, and time to progression, were the secondary endpoints. A Simon 2 stage design was used. Total sample size was calculated to be 20 subjects. A total of 11 subjects were recruited, due to the COVID-19 pandemic and 100% CR observed in the interim analysis. NCT 03714828. Results: The analysis was conducted after all 11 participants completed Visit 8 (230-271 days from study initiation). Conclusions: TVEC showed extremely impressive ORR for patients with cSCC with a 95.8% CR for TLIs. AE profile of TVEC was mild and was well tolerated. Further studies evaluating the role of intralesional immunotherapy should be considered in patients with increased burden of cSCC. Table 1. summarizes the study results. For the primary endpoint 100% of participants achieved an overall response. Primary outcomes for patients (n = 11) Secondary outcomes for TLIs (n = 24) Time to response - days Mean ± standard deviation Median/Range (min, max) 41.6 ± 24.9 Time to response - days Mean ± standard deviation Median/Range (min, max) 48.7 ± 29.2 35/(18 - 112) 35/(18 - 112) Final response to TVEC - % Overall response rate (ORR) Partial response (PR) Complete response (CR) 100% (11/11) 9.1% (1/11) Response to TVEC - Overall response rate (ORR) Partial response (PR) Complete response (CR) 100% (24/24) 90.9% (10/11) 4.2% (1/24) 95.8% (23/24) Duration of response - days Mean ± standard deviation Median - Range (min, max) 206.0 ± 26.0 Duration of response - days Mean ± standard deviation Median - Range (min, max) 201.4 ± 29.6 212 (140 - 236) 209 (136 - 250) Durable response rate - % 90.9% (10/11) Durable response rate - % 83.3% (20/24) Secondary outcomes for TNILs (n = 2) Final response to TVEC - % 100% (2/2) Adverse Events NCI CTCAE (v. 4.0) Event n (%) 95% CI Severity Mild (Grade 1) Moderate (Grade 2) Fatigue 5 (45.5%) (16.7%, 76.6%) 4 (80%) 1 (20%) Flu-like symptoms 4 (36.4%) (10.9%, 69.2%) 3 (75%) 1 (25%) Headache 2 (18.2%) (2.3%, 51.7% 2 (100%) Citation Format: Clara Curiel-Lewandrowski, Delaney B. Stratton, Anngela C. Adams, Haiyan Cui, Denise Roe, Srinath Sundararajan. A single arm phase 2 study of TVEC in patients with invasive cutaneous SCC: A novel therapeutic approach for low risk tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT004.

Early growth response 1 regulates dual‑specificity protein phosphatase 1 and inhibits cell migration and invasion of tongue squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors in the head and neck, and among the OSCCs, tongue squamous cell carcinoma (TSCC) is one of the most common types. Although therapy strategies have recently advanced, the prognosis of TSCC has not substantially improved. Metastasis is one of the main causes of patient mortality in TSCC; therefore, it is necessary to elucidate the mechanism by which TSCC metastasis is regulated. In the present study, the early growth response 1 (Egr-1) expression in TSCC was analyzed based on GEO datasets and the effect of Egr-1 in TSCC tumor cell migration and invasion was measured using Transwell assay. By overexpressing dual-specificity protein phosphatase 1 (DUSP1) in cells with Egr-1 knockdown using lentivirus infection, the role of DUSP1 in Egr-1-regulated TSCC cell migration and invasion was determined. By using luciferase and ChIP assays, the mechanism behind how DUSP1 is regulated by Egr-1 was detected. In the present study, it was demonstrated that Egr-1 was downregulated in TSCC and the knockdown of Egr-1 increased TSCC cell migration and invasion. The expression of Egr-1 was also correlated with DUSP1. The overexpression of DUSP1 in Egr-1 knockdown cells, reduced the level of cell migration and invasion. Furthermore, it was demonstrated that knockdown of Egr-1 inhibited the promoter activity of DUSP1 and the site through which Egr-1 regulates DUSP1 transcription was identified. In conclusion, the present study demonstrated that Egr-1 regulates TSCC cell migration and invasion through modulating DUSP1, suggesting the potential of Egr-1 and DUSP1 as therapy targets for TSCC.