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Ultraviolet light-related DNA damage mutation signature distinguishes cutaneous from mucosal or other origin for head and neck squamous cell carcinoma of unknown primary site
摘要： Background: Head and neck squamous cell carcinoma of unknown primary site (HNSCCUP) is a diagnostic challenge. Identification of an ultraviolet (UV) light-related DNA damage signature using next-generation sequencing (NGS) can classify the primary site of origin as cutaneous. Methods: A 62-year-old male was seen with 2 months of left neck swelling. He was a lifetime nonsmoker but had a history of cutaneous squamous cell carcinoma (SCC) of the left helix. He was also found to have left hilar adenopathy. He had a p16-negative HNSCCUP on fine needle aspiration (FNA) biopsy of the left neck. Results: NGS of the FNA specimen revealed a high number of somatic mutations that were mostly C to T transitions, indicating a UV mutation signature and confirming the diagnosis of cutaneous SCC. Conclusions: Identification of a UV DNA damage signature with NGS distinguishes HNSCCUP of cutaneous vs mucosal or other squamous cell carcinoma origin.
关键词： unknown primary squamous cell carcinoma of head and neck,cutaneous tumor mutation burden,next-generation sequencing,ultraviolet light-related DNA damage signature,skin cancer
更新于2025-09-23 15:23:52
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Hyperbaric oxygen combined with 5-aminolevulinic acid photodynamic therapy inhibited human squamous cell proliferation
摘要： The photodynamic therapy (PDT) depends on the presence of molecular oxygen. Thus, the efficiency of PDT is limited in anoxic regions of tumor tissue and vascular shutdown. It is reported the use of hyperbaric oxygen (HBO) may enhance the efficiency of PDT. However, there are rarely studies about utilizing HBO plus PDT for treatment with human squamous cell carcinoma (SCC). Therefore, this study aimed to investigate and compare the therapeutic effect of combined therapy and PDT alone treatment. Multiple cellular and molecular biology techniques were used in the current study such as CCK-8, western blotting, flow cytometry, MDC staining and immunofluorescence assay. The results of combination index indicated that HBO combination with PDT synergistically inhibited A431 cells proliferation in vitro. In addition, we found that HBO significantly enhanced PDT-induced cell apoptosis via increasing the active caspase-3, active caspase-9, Apaf-1 and Bax levels and down-regulating Bcl-2. Meanwhile, the result of MDC and immunofluorescence assay confirmed that HBO increased PDT-induced autophagosome formation in A431 cells. Interestingly, autophagy inhibitor 3-methyladenine (3-MA) further increased combination-induced cell apoptosis by increasing the levels of active-caspase 9 and Apaf-1. Our results showed that HBO combined with PDT markedly induced A431 cells apoptosis and autophagy. Nevertheless, autophagy play a pro-survival role against apoptosis. Thus, HBO combination with PDT may constitute a promising approach to treat human squamous cell carcinoma in the future.
关键词： human squamous cell carcinoma,5-aminolevulinic acid photodynamic therapy,apoptosis,autophagy,hyperbaric oxygen
更新于2025-09-23 15:23:52
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NIR Infrared imaging after peritumoral injection of indocyanine green to guide lymph node dissection in head and neck squamous cell carcinoma: A pilot feasibility study
摘要： In head and neck squamous cell carcinoma (HNSCC), neck dissection is part of the surgical therapy. Beyond to the fact that radicality is a critical prognostic factor, this dissection could lead to significant morbidity, potentially avoidable when resected lymph nodes (LN) are proven to be non-invaded at pathology. Therefore, the definition of a method able to reliably identify the specific LN drainage area in HNSCC would represent a relevant progress, to better guide the neck dissection, potentially improving the radicality and reducing the morbidity. As near-infrared fluorescence imaging (NIR-FI) after indocyanine green (ICG) peritumoral injection has been validated as a sentinel procedure, we hypothesized that this approach could represent a new technique to identify the tumor-drainage area in HNSCC. We prospectively evaluated this technique in 14 patients with oral or oropharyngeal carcinoma scheduled for primary tumor resection and LN dissection. The trial was approved by the ethics committee of the Institut Jules Bordet (CE-2178) (EudraCT 2014-000298-37) and all patients signed informed consent before inclusion.
关键词： Head and neck squamous cell carcinoma,Indocyanine green,Near-infrared fluorescence imaging,Lymph node dissection,Surgical guidance
更新于2025-09-23 15:21:01
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Optoelectronic properties analysis of silicon light-emitting diode monolithically integrated in standard CMOS IC
摘要： Objectives: The function of miR‐611 has not yet been reported. We aimed to investigate the effects of miR‐611 on tongue squamous cell carcinoma (TSCC) and the underlying mechanism. Materials and Methods: The expression level of miR‐611 in TSCC tissues was measured using quantitative reverse transcriptase–polymerase chain reaction (RT‐qPCR). Cell proliferation, migration and invasion were examined by performing CCK‐8, IncuCyte and Transwell assays. Bioinformatics analyses and microarrays were used to screen for target genes, which were verified using a luciferase reporter assay, RT‐qPCR and Western blotting. The xenograft model was used to assess the effects of miR‐611 in vivo. Results: miR‐611 was upregulated in TSCC tissues, which was significantly correlated with TNM stage and negatively associated with the overall survival of patients. In addition, upregulation of miR‐611 not only potentiated the proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) of TSCC cells in vitro, but also promoted tumour growth in vivo. FOXN3 was identified as a candidate target gene of miR‐611 and subsequently verified. Finally, miR‐611 induced a malignant phenotype of TSCC, which was rescued by overexpression of FOXN3. Conclusions: Our findings suggest that miR‐611 is a novel therapeutic target for TSCC.
关键词： miR‐611,FOXN3,tongue squamous cell carcinoma,epithelial–mesenchymal transition,proliferation
更新于2025-09-23 15:19:57
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Present and future perspectives of photodynamic therapy for cutaneous squamous cell carcinoma
摘要： Cutaneous squamous cell carcinoma (SCC) is the second most common skin cancer. Surgery remains the main stay of treatment, but some patients are not eligible for surgery and, more importantly, lesions at critical sites need nonsurgical approaches for tissue preservation. In this context, photodynamic therapy (PDT) has been extensively studied as noninvasive or minimally invasive treatment, and studies have shown promising results in terms of safety, efficacy, and cosmetic outcome. Also, studies have proposed different mechanism for its efficacy. However, human studies demonstrating its efficacy are limited in terms of sample size and tumor depth of invasion. Good results are mainly seen in case reports of microinvasive SCC, which is defined as SCC limited to papillary dermis. This inadequacy is due to inadequate penetration of topically applied photosensitizers through keratinized tumor surfaces. To overcome these hurdles, pretreatment with lasers or microneedles and encapsulation of photosensitizers into nanoparticles have been tried. Hence, the present article will discuss studies that have demonstrated the efficacy and safety of PDT for cutaneous SCC, studies that have postulated the mechanism of action of PDT, agents that have been used as PDT enhancers, and finally, the recent use of adjuvant therapy in combination with PDT.
关键词： mechanism of action,surgery,photodynamic therapy,nanomedicine,cutaneous squamous cell carcinoma
更新于2025-09-19 17:15:36
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Rapid, non-invasive fluorescence margin assessment: Optical specimen mapping in oral squamous cell carcinoma
摘要： Objective: Surgical resection remains the primary treatment for the majority of solid tumors. Despite efforts to obtain wide margins, close or positive surgical margins (< 5 mm) are found in 15–30% of head and neck cancer patients. Obtaining negative margins requires immediate, intraoperative feedback of margin status. To this end, we propose optical specimen mapping of resected tumor specimens immediately after removal. Materials and methods: A first-in-human pilot study was performed in patients (n = 8) after infusion of fluorescently labeled antibody, panitumumab-IRDye800 to allow surgical mapping of the tumor specimen. Patients underwent standard of care surgical resection for head and neck squamous cell carcinoma (HNSCC). Optical specimen mapping was performed on the primary tumor specimen and correlated with pathological findings after tissue processing. Results: Optical mapping of the specimen had a 95% sensitivity and 89% specificity to detect cancer within 5 mm (n = 160) of the cut surface. To detect tumor within 2 mm of the specimen surface, the sensitivity of optical specimen mapping was 100%. The maximal observed penetration depth of panitumumab-IRDye800 through human tissue in our study was 6.3 mm. Conclusion: Optical specimen mapping is a highly sensitive and specific method for evaluation of margins within < 5 mm of the tumor mass in HNSCC specimens. This technology has potentially broad applications for ensuring adequate tumor resection and negative margins in head and neck cancers.
关键词： Near-infrared,Oral cancer,Fluorescence imaging,Squamous cell carcinoma,Molecular imaging,Optical specimen mapping
更新于2025-09-19 17:15:36
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2125. Staphylococcus Species Identification by Fourier Transform Infrared (FTIR) Spectroscopic Techniques: A Cross-Lab Study
摘要： Staphylococcus aureus is well known to be associated with atopic dermatitis. Recent studies also report S. aureus presence in lesional skin of squamous cell carcinoma (SCC) and its precursor lesion, actinic keratosis (AK). Therefore, it is of potential clinical interest to monitor skin S. aureus colonization on AK lesions. Fourier transform infrared (FTIR) spectroscopy is a cost-effective, nondestructive, and reagent-free technique for rapid microbial identification. It is based on the use of spectral databases developed with well-characterized strains in conjunction with the application of multivariate statistical analysis to elaborate classification models. In the present cross-lab study, spectral databases containing FTIR spectra of over 1000 staphylococcal isolates obtained from reference and clinical microbiology laboratories across Canada were employed in the FTIR spectroscopic identification of Staphylococcus spp. isolated from AK, SCC and perilesional skin of patients at the Princess Alexandra Hospital Dermatology Clinic in Brisbane, Australia.
关键词： atopic dermatitis,actinic keratosis,squamous cell carcinoma,microbial identification,Staphylococcus aureus,Fourier transform infrared spectroscopy
更新于2025-09-16 10:30:52
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PS02.062: CONFOCAL LASER ENDOMICROSCOPY IN THE ASSESSMENT OF PERSISTENT/RECURRENT INTESTINAL METAPLASIA/NEOPLASIA AFTER ENDOSCOPIC TREATMENT OF BORN
摘要： Recent studies revealed that membrane proteins, such as ion transporters, are specifically activated in cancer stem cells (CSCs). Therefore, these molecules are receiving a great attention as new chemotherapeutic targets of malignant tumor. This study aimed to investigate the expression and activity of ion transport-related molecules in CSCs of esophageal squamous cell carcinoma (ESCC).
关键词： Esophageal squamous cell carcinoma,FDG-PET/CT,esophageal cancer,Esophageal cancer,stem cell,TRPV2,Tranilast,False positive,LncRNA
更新于2025-09-11 14:15:04
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Computer-assisted diagnosis of early esophageal squamous cell carcinoma using narrow-band imaging magnifying endoscopy
摘要： Background We developed a computer-assisted diagnosis model to evaluate the feasibility of automated classification of intrapapillary capillary loops (IPCLs) to improve the detection of esophageal squamous cell carcinoma (ESCC). Methods We recruited patients who underwent magnifying endoscopy with narrow-band imaging for evaluation of a suspicious esophageal condition. Case images were evaluated to establish a gold standard IPCL classification according to the endoscopic diagnosis and histological findings. A double-labeling fully convolutional network (FCN) was developed for image segmentation. Diagnostic performance of the model was compared with that of endoscopists grouped according to years of experience (senior > 15 years; mid level 10 – 15 years; junior 5 – 10 years). Results Of the 1383 lesions in the study, the mean accuracies of IPCL classification were 92.0 %, 82.0 %, and 73.3 %, for the senior, mid level, and junior groups, respectively. The mean diagnostic accuracy of the model was 89.2 % and 93.0 % at the lesion and pixel levels, respectively. The interobserver agreement between the model and the gold standard was substantial (kappa value, 0.719). The accuracy of the model for inflammatory lesions (92.5 %) was superior to that of the mid level (88.1 %) and junior (86.3 %) groups (P < 0.001). For malignant lesions, the accuracy of the model (B1, 87.6 %; B2, 93.9 %) was significantly higher than that of the mid level (B1, 79.1 %; B2, 90.0 %) and junior (B1, 69.2 %; B2, 79.3 %) groups (P < 0.001). Conclusions Double-labeling FCN automated IPCL recognition was feasible and could facilitate early detection of ESCC.
关键词： esophageal squamous cell carcinoma,intrapapillary capillary loops,computer-assisted diagnosis,narrow-band imaging,magnifying endoscopy
更新于2025-09-10 09:29:36
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Brahma deficiency in keratinocytes promotes UV carcinogenesis by accelerating the escape from cell cycle arrest and the formation of DNA photolesions
摘要： Background: Ultraviolet radiation (UVR) is the principal cause of keratinocyte skin cancers. Previous work found that levels of the chromatin remodelling protein, Brahma (Brm), are diminished during the progression from actinic keratoses to cutaneous squamous cell carcinomas in humans, and its loss in UV-irradiated mouse skin causes epidermal hyperplasia and increased tumour incidence. Methods: The skins of mice and mouse and human keratinocytes deficient in Brm were exposed to UVR and evaluated for cell cycle progression and DNA damage response. Objective: To identify the mechanisms by which loss of Brm contributes to UVR-induced skin carcinogenesis. Results: In both mouse keratinocytes and HaCaT cells, Brm deficiency led to an increased cell population growth following UVR exposure compared to cells with normal levels of Brm. Cell cycle analysis using a novel assay showed that Brm-deficient keratinocytes entered cell cycle arrest normally, but escaped from cell cycle arrest faster, enabling them to begin proliferating earlier. In mouse keratinocytes, Brm primarily affected accumulation in G0/G1-phase, whereas in HaCaT cells, which lack normal p53, accumulation in G2/M-phase was affected. Brm-deficient keratinocytes in mouse skin and human cell cultures also had higher levels of UVR-induced cyclobutane pyrimidine dimer photolesions. These effects occurred without any compensatory increase in DNA repair or cell death to remove photolesions or the cells that harbor them from the keratinocyte population. Conclusion: The loss of Brm in keratinocytes exposed to UVR enables them to resume proliferation while harboring DNA photolesions, leading to an increased fixation of mutations and, consequently, increased carcinogenesis.
关键词： SWI/SNF,Cutaneous squamous cell carcinoma,UV radiation,Cell cycle arrest,DNA damage
更新于2025-09-04 15:30:14