Journal of Oral Pathology & Medicine最新文献_第7页

The PI3K Inhibitor HCD Promotes Caspase Activation in Head and Neck Squamous Cells by Upregulating the Extrinsic and Intrinsic Apoptosis Pathways PI3K抑制剂HCD通过上调外源性和内源性凋亡途径促进头颈部鳞状细胞中Caspase的激活。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-15 DOI: 10.1111/jop.70060

Leong-Perng Chan, Ya-Ping Tseng, Hui-Ching Wang, Chen-Yu Chien, Che-Wei Wu, Ling-Feng Wang, Tung-Wen Yen, Po-Chun Wang, Chih-Chuang Liaw, Chia-Hua Liang

Background

16-hydroxycleroda-3,13-dien-15,16-olide (HCD), a compound isolated from Polyalthia longifolia var. pendula, has been identified as a PI3K inhibitor. P. longifolia var. pendula is recognized for its diverse pharmacological properties, including antimicrobial, hypotensive, anti-inflammatory, and cytotoxic activities. Considering the pivotal role of PI3K in the regulation of apoptosis in cancer cells, this study aims to investigate the apoptotic effects induced by HCD in head and neck cancer cell models.

Methods

The study focused on investigating the mechanism through which HCD induces apoptosis in oral squamous cell carcinoma (OSCC) using SCC25 and SCC180 cells. These cells were treated with HCD at IC₂₀, IC₅₀, and IC₈₀ concentrations over periods of 24, 48, and 72 h. Assessments included cell viability, oxidative stress levels using MitoSOX and CellROX, and the analysis of gene and protein expressions related to apoptosis via immunofluorescence staining, flow cytometry, RT-PCR, and western blotting.

Results

The results demonstrated that HCD significantly increased the sub-G₁ phase cell population, suppressed clonogenic activity, and promoted mitochondrial ROS production, accompanied by a reduction in glutathione levels. HCD also activated cytochrome c (cyto. c) release and Bax expression while downregulating Bcl-2 expression. Notably, in SCC25 cells, HCD induced apoptosis through the TNF-α/TNF-R and FasL/Fas death domains, leading to caspase cascade activation. Moreover, HCD showed dose-dependent growth inhibition of SCC25 cells, both alone and combined with cisplatin, by enhancing caspase-3 expression.

Conclusion

This investigation into HCD's molecular mechanisms in OSCC cells offers insight into developing effective anticancer therapies, highlighting its role in apoptosis induction through oxidative stress, mitochondrial pathways, and death receptor signaling.

背景：16-hydroxycleroda-3,13-dien-15,16-olide （HCD）是从长叶蓼中分离得到的一种化合物，已被鉴定为PI3K抑制剂。长叶黄因其多种药理特性而被公认，包括抗菌、降压、抗炎和细胞毒活性。考虑到PI3K在肿瘤细胞凋亡调控中的关键作用，本研究旨在探讨HCD对头颈部肿瘤细胞模型的凋亡作用。方法：利用SCC25和SCC180细胞，研究HCD诱导口腔鳞状细胞癌（OSCC）细胞凋亡的机制。这些细胞分别用浓度为IC20、IC50和IC80的HCD处理24、48和72小时。评估包括使用MitoSOX和CellROX检测细胞活力、氧化应激水平，并通过免疫荧光染色、流式细胞术、RT-PCR和western blotting分析与凋亡相关的基因和蛋白表达。结果：结果表明，HCD显著增加亚g1期细胞群，抑制克隆生成活性，促进线粒体ROS产生，并伴有谷胱甘肽水平降低。HCD还能激活细胞色素c。c)释放和Bax表达，下调Bcl-2表达。值得注意的是，在SCC25细胞中，HCD通过TNF-α/TNF- r和FasL/Fas死亡结构域诱导细胞凋亡，导致caspase级联激活。此外，HCD通过提高caspase-3的表达，显示出剂量依赖性的SCC25细胞生长抑制作用，无论是单独使用还是与顺铂联合使用。结论：对HCD在OSCC细胞中的分子机制的研究为开发有效的抗癌疗法提供了见解，突出了其通过氧化应激、线粒体途径和死亡受体信号传导诱导细胞凋亡的作用。

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引用次数: 0

A Comparative Analysis of Clinical Aspects of Conventional Polymorphous Adenocarcinoma and Cribriform Adenocarcinoma of Salivary Glands: A Systematic Review 常规涎腺多形性腺癌与筛状腺癌临床比较分析：系统综述。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-15 DOI: 10.1111/jop.70067

Bruno Romano de Oliveira, Warley Oliveira Silva, Carolina Cavaliéri Gomes, Jean Nunes dos Santos, Fabrício Tinôco Alvim de Souza

Background

Polymorphous adenocarcinoma (PmA) is the second most common malignant neoplasm in minor salivary glands; a subtype of this lesion was described in 2005 with more aggressive behavior, Cribriform Adenocarcinoma of Salivary Glands (CASG).

Objective

To compare the clinical aspects of conventional PmA and CASG originating in minor salivary glands of the oral cavity through the analysis of observational studies reported in the literature between 2005 and 2025.

Method

This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The review included searches of Pubmed, Lilacs, Scopus, and Web of Science databases. A total of 988 records were identified, and after the selection process, 47 articles were chosen for inclusion.

Results

Females were the most affected (61% in PmA and 73.3% in CASG). The average age variation was 60 in PmA and 57.3 in CASG. The most frequent anatomical location was the palate (42.4%) in PmA and the tongue (46.7%) in CASG. Lymph node metastasis was found in 15.2% in PmA and in 60% in CASG. The most commonly used treatment was surgical excision (72.72%) in PmA and surgical excision and neck dissection (46.67%) in CASG. Recurrence rates were 9.09% in PmA and 33.33% in CASG. The average follow-up period was 21.7 months in PmA and 43.9 in CASG.

Conclusion

Female predilection and average age of 60 years are common between the two tumors. The clinical variables with quantitative differences are anatomical location, lymph node metastasis, treatment modality, and recurrence.

背景：多形态腺癌（PmA）是小唾液腺第二常见的恶性肿瘤；这种病变的一个亚型在2005年被描述为更具侵略性的行为，即唾液腺筛状腺癌（CASG）。目的：通过对2005年至2025年文献报道的观察性研究进行分析，比较传统PmA和起源于口腔小涎腺的CASG的临床特点。方法：本系统评价遵循系统评价和荟萃分析（PRISMA）指南的首选报告项目。该综述包括Pubmed、Lilacs、Scopus和Web of Science数据库的搜索。共确定了988条记录，经过筛选过程，选择了47篇文章纳入。结果：女性受影响最大（PmA为61%，CASG为73.3%）。PmA的平均年龄变化为60，CASG的平均年龄变化为57.3。最常见的解剖位置为上颚（42.4%）和舌部（46.7%）。PmA和CASG的淋巴结转移率分别为15.2%和60%。PmA最常用的治疗方法是手术切除（72.72%），CASG最常用的治疗方法是手术切除加颈部清扫（46.67%）。PmA复发率为9.09%，CASG为33.33%。PmA组平均随访21.7个月，CASG组平均随访43.9个月。结论：两种肿瘤均以女性为主，平均年龄60岁。具有数量差异的临床变量为解剖位置、淋巴结转移、治疗方式和复发。

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引用次数: 0

Single Nucleotide Polymorphisms as Markers of Genetic Susceptibility for Oral Submucous Fibrosis Risk: A Systematic Review and Meta-Analysis 单核苷酸多态性作为口腔粘膜下纤维化风险遗传易感性的标记：一项系统综述和荟萃分析。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-12 DOI: 10.1111/jop.70054

Divya Gopinath, Cheng Yung On, Chathathayil Mohammedali Shafeeque, Sajesh K. Veettil, Wanninayake M. Tilakaratne

Background

Varied susceptibility to Oral submucous fibrosis (OSF) among individuals exposed to the same environmental variables indicates that genetic variation may contribute as a risk factor in its development. The objective was to comprehensively analyze the association between single gene polymorphisms (SNPs) and the risk of OSF.

Methods

This comprehensive systematic review encompassed all relevant published studies up until June 2024 that examined the influence of gene polymorphisms on the likelihood of OSF. The search was conducted across multiple databases, including Medline, Scopus, and EBSCOhost. Data were pooled in a random-effect meta-analysis where at least two studies on the same SNP tested the same genotyping model. The assessment of heterogeneity was conducted using the I ² statistic. The Q-Genie tool was used to evaluate the quality of the included studies.

Results

Out of the 4573 papers initially searched, only 37 articles met the criteria to be included in this review. A total of 63 SNPs from 27 genes were tested, and 38 SNPs had significant associations. The meta-analysis revealed that five SNPs, including GSTM1 null (OR = 1.90; 1.41–2.56), GSTT1 null (OR = 2.41; 1.64–3.53), MMP3 (−1171; promoter region) (OR = 3.33; 1.45–7.61), XXCR3 (T vs. C) (OR = 1.70 (1.23–2.36)) and CYP1A1 m2 at Ncol site (−) (OR = 4.32; 1.22–15.29), are associated with an increased risk of OSF.

Conclusion

The limited SNPs identified in this review could be used as markers to identify patients at a higher risk of OSF. Further studies are warranted to validate the SNPs, which demonstrate contradictory results among the currently available studies.

背景：暴露于相同环境变量的个体对口腔黏膜下纤维化（OSF）的易感性不同，表明遗传变异可能是其发展的一个危险因素。目的是全面分析单基因多态性（snp）与OSF风险之间的关系。方法：这项全面的系统综述包含了截至2024年6月的所有相关已发表的研究，这些研究检查了基因多态性对OSF可能性的影响。检索是在多个数据库中进行的，包括Medline、Scopus和EBSCOhost。数据汇集在随机效应荟萃分析中，其中至少有两项关于相同SNP的研究测试了相同的基因分型模型。异质性评价采用I2统计量。使用Q-Genie工具评价纳入研究的质量。结果：在最初检索的4573篇论文中，只有37篇符合纳入本综述的标准。共检测了27个基因的63个snp，其中38个snp具有显著相关性。荟萃分析显示，GSTM1 null （OR = 1.90; 1.41-2.56）、GSTT1 null （OR = 2.41; 1.64-3.53）、MMP3（-1171；启动子区）（OR = 3.33; 1.45-7.61）、XXCR3 (T对C) （OR = 1.70(1.23-2.36)）和Ncol位点CYP1A1 m2 (-) （OR = 4.32; 1.22-15.29）等5个snp与OSF风险增加相关。结论：本综述中发现的有限snp可作为识别OSF高危患者的标志物。需要进一步的研究来验证这些snp，这些snp在目前的研究中显示出相互矛盾的结果。

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引用次数: 0

Use of Cannabis and Odds Ratio for Oropharyngeal and Oral Cancer—A Cohort Study 使用大麻与口咽癌和口腔癌的优势比——一项队列研究。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-11 DOI: 10.1111/jop.70055

J. Katz, H. Gao, S. Spritzer, I. A. Garcia

Background

Widespread legalizations of cannabis in many states also cause increased interest in the adverse effects of its use, including increased risk for head and neck cancer.

Methods and Results

To test the hypothesis that cannabis increases the risk for head and neck cancers, we have used the i2b2 platform and ICD 10 codes to access a large Hospital database and identify patients with head and neck cancer and patients who were cannabis users. Binary Logistic regression of factors such as demographics, smoking, alcohol consumption, and HPV vaccine history was used. The odds ratio for oropharyngeal cancer among cannabis users was 3.12. After logistic regressions, it remained significant after adjusting for gender, age, and race but became insignificant after adjusting for alcohol, cigarette smoking, and HPV vaccine (1.07, 0.87, 1.02), respectively. The odds ratio for oral cancer among cannabis users was 2.38 before adjustments. It remained significant after adjustment for gender, age, race, and HPV vaccine but became insignificant after adjustment for alcohol and cigarette smoking (0.7, 0.62). After adjusting for cannabis use, the odds ratio for oropharyngeal cancer in the alcohol users was 7.95 and 7.39 for smokers. The odds ratio for oral cancer after adjusting for cannabis in the alcohol users was 9.67 and 7.52 in the cigarette smokers. HPV vaccination had an inhibitory effect on both cancers.

Conclusions

Alcohol and cigarette smoking rather than the use of cannabis may play a major role in establishing an association between cannabis use and both types of head and neck cancers.

背景：在许多州，大麻的广泛合法化也引起人们对其使用的不良影响的关注，包括头颈癌风险的增加。方法和结果：为了验证大麻增加头颈癌风险的假设，我们使用i2b2平台和ICD 10代码访问了一个大型医院数据库，并识别头颈癌患者和大麻使用者。采用二元Logistic回归分析人口统计学、吸烟、饮酒和HPV疫苗接种史等因素。大麻使用者口咽癌的优势比为3.12。经logistic回归后，在调整性别、年龄和种族后，它仍然显著，但在调整酒精、吸烟和HPV疫苗后，它变得不显著（分别为1.07、0.87、1.02）。在调整前，大麻使用者口腔癌的优势比为2.38。在调整性别、年龄、种族和HPV疫苗后，它仍然显著，但在调整饮酒和吸烟后，它变得不显著（0.7,0.62）。在对大麻使用进行调整后，饮酒者口咽癌的优势比为7.95，吸烟者为7.39。经大麻因素调整后，饮酒者患口腔癌的比值比为9.67，吸烟者为7.52。HPV疫苗对两种癌症都有抑制作用。结论：在大麻使用与两种头颈癌之间建立联系方面，酒精和吸烟而不是使用大麻可能发挥主要作用。

{"title":"Use of Cannabis and Odds Ratio for Oropharyngeal and Oral Cancer—A Cohort Study","authors":"J. Katz, H. Gao, S. Spritzer, I. A. Garcia","doi":"10.1111/jop.70055","DOIUrl":"10.1111/jop.70055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Widespread legalizations of cannabis in many states also cause increased interest in the adverse effects of its use, including increased risk for head and neck cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>To test the hypothesis that cannabis increases the risk for head and neck cancers, we have used the i2b2 platform and ICD 10 codes to access a large Hospital database and identify patients with head and neck cancer and patients who were cannabis users. Binary Logistic regression of factors such as demographics, smoking, alcohol consumption, and HPV vaccine history was used. The odds ratio for oropharyngeal cancer among cannabis users was 3.12. After logistic regressions, it remained significant after adjusting for gender, age, and race but became insignificant after adjusting for alcohol, cigarette smoking, and HPV vaccine (1.07, 0.87, 1.02), respectively. The odds ratio for oral cancer among cannabis users was 2.38 before adjustments. It remained significant after adjustment for gender, age, race, and HPV vaccine but became insignificant after adjustment for alcohol and cigarette smoking (0.7, 0.62). After adjusting for cannabis use, the odds ratio for oropharyngeal cancer in the alcohol users was 7.95 and 7.39 for smokers. The odds ratio for oral cancer after adjusting for cannabis in the alcohol users was 9.67 and 7.52 in the cigarette smokers. HPV vaccination had an inhibitory effect on both cancers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Alcohol and cigarette smoking rather than the use of cannabis may play a major role in establishing an association between cannabis use and both types of head and neck cancers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"55 1","pages":"147-151"},"PeriodicalIF":2.3,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of the Telomere Length in PERI-Implant Oral Mucosa Cells 种植体周围口腔黏膜细胞端粒长度的研究。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-11 DOI: 10.1111/jop.70061

Fernando Costa Giffoni, Thaís Ellen Chaves Gomes, Priscila Nazaré de Souza, Paula Valente e Silva, Luiz Alexandre Viana Magno, Amanda Lage Cândido, Marcelo Faria Lasmar, Sebastião Guilherme de Oliveira Neto, Marcus Vinicius Lucas Ferreira, Thiago Moreira Gonçalves Araujo, Luara Isabela dos Santos, Bruno Ramos Chrcanovic, Ricardo Santiago Gomez, Roberta Rayra Martins-Chaves

Background

The biological effects of dental implants on peri-implant tissues have been widely investigated. Recent reports of oral squamous cell carcinoma (OSCC) cases adjacent to dental implants have raised concerns regarding the potential impact of implant materials on cellular aging and oncogenic transformation. Telomeres, which protect chromosome ends, undergo progressive shortening and play a critical role in cellular senescence and tumorigenesis. However, the impact of dental implants on telomere length in peri-implant mucosa remains unclear.

Objective

This study aimed to compare telomere length in mucosa adjacent to dental implants with that of gingival tissue associated with healthy teeth.

Methods

A paired cross-sectional study was conducted with 16 patients who had dental implants for at least 1 year. Swabs were collected from the peri-implant mucosa and healthy gingival mucosa of the same patient. Telomere length was assessed using quantitative PCR, with the relative telomere-to-single-copy-gene ratio (T/C) calculated using the 2^−∆∆Cq method.

Results

Telomere length in the peri-implant mucosa was not significantly different from that in the healthy gingival mucosa (p = 0.117).

Conclusion

These findings suggest that dental implants do not alter telomere length in adjacent mucosal cells.

背景：种植体对种植体周围组织的生物学效应已被广泛研究。最近报道的口腔鳞状细胞癌（OSCC）病例与牙种植体相邻，引起了人们对种植材料对细胞老化和致癌转化的潜在影响的关注。保护染色体末端的端粒逐渐缩短，在细胞衰老和肿瘤发生中起关键作用。然而，种植体对种植体周围粘膜端粒长度的影响尚不清楚。目的：本研究旨在比较种植体邻近黏膜与健康牙齿牙龈组织的端粒长度。方法：对16例种植牙至少1年的患者进行配对横断面研究。采集同一患者种植体周围粘膜和健康牙龈粘膜拭子。采用定量PCR评估端粒长度，采用2-∆∆Cq法计算端粒与单拷贝基因的相对比值（T/C）。结果：种植周黏膜端粒长度与健康牙龈粘膜端粒长度差异无统计学意义（p = 0.117）。结论：这些结果提示种植牙不会改变邻近粘膜细胞的端粒长度。

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引用次数: 0

Clinical, Radiographic and Histopathological Analysis of Cemento-Ossifying Fibromas and Fibro-Osseous Lesions of the Oral and Maxillofacial Region: A 53-Year Retrospective Study and Update of Current Concepts 口腔颌面部骨水泥骨化纤维瘤和纤维骨性病变的临床、影像学和组织病理学分析：53年的回顾性研究和当前概念的更新。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-10 DOI: 10.1111/jop.70059

Hannah Gil de Farias Morais, Débora Frota Colares, Maurília Raquel de Souto Medeiros, Caio César da Silva Barros, Everton Freitas de Morais, Márcia Cristina da Costa Miguel, Roseana de Almeida Freitas

Background

Fibro-osseous lesions (FOL) of the jawbones and cemento-ossifying fibroma (COF) represent a heterogeneous group of lesions with overlapping histopathological features and variability in biological behavior. Thus, this study aimed to evaluate the clinical, radiographic, and histopathological characteristics of FOLs (cemento-osseous dysplasia—COD, fibrous dysplasia—FD, ossifying fibroma—OF) as well as COF, diagnosed at a reference center in oral pathology over 53 years.

Methods

Sex, age, symptoms, clinical diagnosis, time of evolution, anatomical site, size of the lesion, and radiographic characteristics were collected from all cases of lesions previously diagnosed as FOLs.

Results

Among 19 600 cases of oral and maxillofacial lesions diagnosed at our center, 156 (0.8%) had a histological diagnosis of FOL, with COD being the most common (37.2%). Radiographically, most cases presented as unilocular lesions (64.3%) (p = 0.034) with mixed radiolucency (53.8%). COD and COF frequently exhibited well-defined borders. Additionally, 50% of COD cases displayed a cotton-wool appearance, while half of FDs appeared as ground-glass opacifications. Histopathologically, a significantly high frequency of lamellar bone was observed in all types of FOL (p = 0.0001). In contrast, peritrabecular clefting was significantly found in FDs, and cementum-like tissue in CODs and COFs (p < 0.05). Lesional bone fusing with the normal adjacent bone was more significantly observed in COD and FD (p = 0.001).

Conclusion

A definitive and accurate diagnosis of FOL is achievable when cases are individually investigated, and all clinical, radiographic, and histopathologic features are analyzed.

背景：颌骨纤维骨性病变（FOL）和骨水泥骨化纤维瘤（COF）是一组异质性病变，具有重叠的组织病理特征和生物行为的可变性。因此，本研究旨在评估53年来在口腔病理参考中心诊断的FOLs（骨质发育不良- cod、纤维性发育不良- fd、骨化性纤维瘤- of）和COF的临床、影像学和组织病理学特征。方法：收集既往诊断为FOLs的所有病例的性别、年龄、症状、临床诊断、演变时间、解剖部位、病变大小及影像学特征。结果：本中心诊断的19 600例口腔颌面部病变中，组织学诊断为FOL的156例（0.8%），其中COD最为常见（37.2%）。影像学上，大多数病例表现为单眼病变（64.3%）（p = 0.034），混合透光度（53.8%）。COD和COF经常表现出明确的边界。此外，50%的COD病例表现为棉絮样样，而一半的fd表现为磨玻璃样混浊。组织病理学上，所有类型的FOL中板层骨的发生率都很高（p = 0.0001）。相比之下，FDs明显可见骨梁周围裂，CODs和COFs明显可见骨骨质样组织(p结论：单独调查病例，分析所有临床、放射学和组织病理学特征，可以获得FOL的明确和准确诊断。

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引用次数: 0

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-10 DOI: 10.1111/jop.70062

Wender Rodrigues Nazário, Anaíra Ribeiro Guedes Fonseca Costa, Débora de Oliveira Santos, Nayara Rúbio Diniz Del Nero, Tamiris Sabrina Rodrigues, Luiza Diniz Ferreira Borges, Carlos Ueira-Vieira, Sérgio Vitorino Cardoso, Adriano Mota Loyola, Paulo Rogério de Faria

Background

Oral squamous cell carcinoma (OSCC) is one of the most frequent head and neck cancers. The 4-nitroquinoline 1-oxide (4NQO) mouse model of oral carcinogenesis is a well-established model to investigate the mechanism behind OSCC development, including epigenetic alterations. Studies have shown that histone acetylation is a key regulator of gene expression and may play a role in such a tumor. This study investigates the acetylation of H3K9, H3K14, and H3K27 and the KAT2A gene expression in a sex-based approach in a 4NQO/ethanol (EtOH)-induced OSCC mouse model.

Methods

A total of 120 C57Bl/6J mice (60 males and 60 females) were divided into four groups (n = 15). In the first 10 weeks, they were treated with 5 mg/mL propylene glycol (PPG) or 100 μg/mL 4NQO in drinking water, followed by either sterilized water or 8% EtOH for 15 weeks. After euthanasia, tongues were analyzed histopathologically. Immunohistochemistry and qPCR were also employed to study the histones and gene expression.

Results

Female mice showed increased H3K9ac and H3K14ac expression from normal mucosa to dysplasia, followed by decreased expression in OSCC. H3K9ac and H3K14ac expression in males was lower in the 4NQO/EtOH group. H3K27ac was higher in dysplastic lesions compared to OSCC, particularly in females. Comparatively, females had higher H3K9ac and H3K14ac expression in the 4NQO/EtOH group than males. KAT2A expression was lower in females treated with PPG/EtOH and 4NQO/H₂O than in males.

Conclusion

Our results indicate that H3 acetylation and KAT2A gene expression may play a key role in oral carcinogenesis on a sex-related basis.

背景：口腔鳞状细胞癌（OSCC）是最常见的头颈部肿瘤之一。4-硝基喹啉- 1-氧化物（4NQO）小鼠口腔癌模型是一种成熟的模型，用于研究OSCC发展背后的机制，包括表观遗传改变。研究表明，组蛋白乙酰化是基因表达的关键调控因子，可能在此类肿瘤中发挥作用。本研究在4NQO/乙醇（EtOH）诱导的OSCC小鼠模型中，以性别为基础研究了H3K9、H3K14和H3K27的乙酰化和KAT2A基因的表达。方法：将120只C57Bl/6J小鼠（公、母各60只）分为4组（n = 15）。在前10周，他们分别用5 mg/mL的丙二醇（PPG）或100 μg/mL的4NQO处理饮用水，然后用灭菌水或8%的EtOH处理15周。安乐死后，对舌头进行组织病理学分析。免疫组化和qPCR检测各组蛋白及基因表达。结果：雌性小鼠从正常黏膜到异常增生，H3K9ac和H3K14ac表达升高，OSCC中表达降低。4NQO/EtOH组H3K9ac和H3K14ac在男性中的表达较低。与OSCC相比，H3K27ac在发育不良病变中较高，尤其是在女性中。相比之下，女性在4NQO/EtOH组中H3K9ac和H3K14ac的表达高于男性。在PPG/EtOH和4NQO/H2O处理下，KAT2A在雌性中的表达低于雄性。结论：我们的研究结果表明H3乙酰化和KAT2A基因表达可能在口腔癌发生中起关键作用，并与性别相关。

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引用次数: 0

Hedgehog Components Are Present in Polymorphous Adenocarcinoma of the Salivary Gland Regardless of PRKD1 Mutation and Tissue Invasion 不管PRKD1突变和组织侵袭，Hedgehog成分存在于唾液腺多形性腺癌中。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-10 DOI: 10.1111/jop.70057

Dandara Andrade De Santana, Cecília Vitória Lima De Oliveira, Flávia Caló De Aquino Xavier, Manoela Domingues Martins, Bruno Cunha Pires, Tercio Guimarães Reis, Patrícia Ramos Cury, Clarissa Araújo Gurgel, Maria Cristina Teixeira Cangussu, Daniel Araki Ribeiro, Victor Coutinho Bastos, Carolina Cavalieri Gomes, Jean Nunes Dos Santos

Purpose

Polymorphous adenocarcinoma of the salivary gland is characterized by cellular uniformity associated with a variety of morphological growth patterns, a fact that makes its diagnosis challenging. Therefore, the identification of genetic alterations and signaling pathways emerges as a tool for elucidation of the pathogenesis of this tumor and accurate differential diagnosis. The aim of this study was to assess mutations in the PRKD1 gene and in protein components of the HH pathway (SHH, IHH, SMO, and GLI-1) in cases of polymorphous adenocarcinoma of the salivary gland.

Methods

Sanger sequencing was used to interrogate hotspot mutations in PRKD1 exon 15 and immunohistochemistry to analyze the protein expression of PRKD1, SHH, IHH, SMO, and GLI-1.

Results

The PRKD1 c.2130A>C/T hotspot mutation was detected in 50% of the sequenced samples. A previously unreported variant, c.2110C>T resulting in p.His704Tyr, was identified in one case, while 100% of the samples carried the intronic variation rs2273813, regardless of tissue invasion (perineural, lymphovascular, fat, bone, muscle, and mucous acini). Immunostaining revealed significant results for several associations between PRKD1, IHH, SMO, and GLI-1. In contrast, SHH immunoexpression did not correlate with the expression of the other proteins.

Conclusion

The PRKD1 E710D hotspot mutation and protein expression of PRKD1 and HH components (SHH, IHH, SMO, and GLI-1) were detected in PAC regardless of tissue invasion, although HH proteins contributed to the morphogenesis of this rare oral cancer. Additionally, the positive correlation between the expression of PRKD1 and HH pathway components (IHH, SMO, and GLI-1) suggests a possible interaction between these proteins, independent of the HH pathway ligand.

目的：涎腺多形腺癌的特征是细胞均匀性与多种形态生长模式相关，这一事实使其诊断具有挑战性。因此，基因改变和信号通路的识别成为阐明该肿瘤发病机制和准确鉴别诊断的工具。本研究的目的是评估涎腺多形性腺癌病例中PRKD1基因和HH通路蛋白组分（SHH、IHH、SMO和gli1）的突变。方法：采用Sanger测序法查询PRKD1外显子15的热点突变，免疫组化分析PRKD1、SHH、IHH、SMO和gli1的蛋白表达。结果：50%的测序样本检测到PRKD1 C . 2130a >C/T热点突变。在一个病例中发现了一种以前未报道的变异，c.2110C . >T导致p.h as704tyr，而100%的样本携带内含子变异rs2273813，而不考虑组织侵犯（神经周围、淋巴血管、脂肪、骨骼、肌肉和粘液腺泡）。免疫染色显示PRKD1、IHH、SMO和gli1之间存在显著的关联。相反，SHH的免疫表达与其他蛋白的表达无关。结论：尽管HH蛋白参与了这种罕见口腔癌的形态发生，但在PAC中PRKD1 E710D热点突变以及PRKD1和HH组分（SHH、IHH、SMO和gli1）的蛋白表达与组织侵袭无关。此外，PRKD1与HH通路组分（IHH、SMO和gli1）的表达呈正相关，表明这些蛋白之间可能存在相互作用，独立于HH通路配体。

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引用次数: 0

AARS1 Implicates Malignancy and Immune Infiltration in Head and Neck Squamous Cell Carcinoma, Serving as a Prognostic Predictor AARS1与头颈部鳞状细胞癌的恶性和免疫浸润有关，可作为预后预测因子。

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-08 DOI: 10.1111/jop.70058

Shengkai Chen, Yuanhe You, Fangxing Zhu, Zhiyuan Zhang, Jianbo Shi, Zhuowei Tian

Background

The aberrant expression of AARS1 has been linked to tumor progression in various cancers. However, its role and underlying mechanisms in head and neck squamous cell carcinoma (HNSCC) remain unclear.

Methods

We validated AARS1 expression using databases and cell lines. Prognostic significance was assessed via Kaplan–Meier and Cox analyses. CCK-8, colony formation, wound healing, and flow cytometry evaluated the effects of AARS1 on HNSCC malignancy. Immune cell infiltration and immune checkpoint associations with AARS1 were analyzed using TIMER, CIBERSORT, MCPCOUNTER, and QUANTISEQ. Subsequently, histological staining and western blotting were performed to verify the identified relationship between AARS1 and immune suppression in HNSCC.

Results

AARS1 was significantly upregulated in HNSCC tissues and cell lines. High AARS1 expression predicted poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). Silencing AARS1 inhibited cell proliferation, migration, and resistance to apoptosis. In the AARS1 high-expression group, decreased CD8⁺ T cell infiltration was observed, along with increased expression of Siglec-15 and ITPRIPL1. These findings suggest that AARS1 might contribute to immune evasion and tumor progression in HNSCC.

Conclusion

Elevated AARS1 expression correlates with poor prognosis, malignant behaviors, and immune infiltration in HNSCC, indicating that AARS1 may serve as a potential therapeutic target.

背景：在多种癌症中，AARS1的异常表达与肿瘤进展有关。然而，其在头颈部鳞状细胞癌（HNSCC）中的作用和潜在机制尚不清楚。方法：利用数据库和细胞系验证AARS1的表达。通过Kaplan-Meier和Cox分析评估预后意义。CCK-8、菌落形成、伤口愈合和流式细胞术评估AARS1对HNSCC恶性肿瘤的影响。使用TIMER、CIBERSORT、MCPCOUNTER和QUANTISEQ分析免疫细胞浸润和免疫检查点与AARS1的关联。随后，进行组织学染色和western blotting来验证已确定的HNSCC中AARS1与免疫抑制之间的关系。结果：AARS1在HNSCC组织和细胞系中表达显著上调。高AARS1表达预示着较差的总生存期（OS）、疾病特异性生存期（DSS）和无进展间期（PFI）。沉默AARS1抑制细胞增殖、迁移和凋亡抵抗。在AARS1高表达组，CD8+ T细胞浸润减少，siglece -15和ITPRIPL1表达增加。这些发现表明，AARS1可能有助于HNSCC的免疫逃避和肿瘤进展。结论：AARS1表达升高与HNSCC预后不良、恶性行为及免疫浸润相关，提示AARS1可能是潜在的治疗靶点。

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引用次数: 0

The Function of Hsa_circ_0001862 Regulating miR-23a-IRF1/PPP2R5E Axis to Oral Squamous Cell Carcinoma Development Hsa_circ_0001862调控miR-23a-IRF1/PPP2R5E轴在口腔鳞状细胞癌发展中的作用

IF 2.3 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral Pathology & Medicine

Pub Date : 2025-09-08 DOI: 10.1111/jop.70013

Xue Liu, Hui Xiong, Xuefeng Wang, Lina Li, Chang Liu, Feng Huo, Yadong Tao

Backgrounds

Head and neck cancer is among the top ten cancers worldwide, with most lesions in the oral cavity. Oral squamous cell carcinoma accounts for more than 90% of all oral malignancies and is a significant public health concern. Circular RNA and micro RNA, as non-coding RNA, plays an important role in the development of tumor transmission.

Aims

This study attempted to explore the pathogenesis of oral squamous cell carcinoma from the perspective of non-coding RNA.

Materials & Methods

We found that miR-23a was abnormally elevated in oral squamous cell carcinoma tissues. Taking this as an entry point, we searched for the circRNA and downstream target genes of miR-23a's upstream function through bioinformatics prediction. We determined the direct targeting relationship between miR-23a and hsa_circ_0001862, as well as the downstream target genes IRF1 and PPP2R5E, by dual luciferase reporter experiments. We used a series of cell phenotype experiments, such as CCK8, colony formation, scratch and trans-well assays, to verify the influence of each of the above genes on the tongue squamous cell line Tca-8113.

Results

Hsa_circ_0001862 regulates the expression level of miR-23a through sponging. In the occurrence and development of tongue squamous cell carcinoma, the expression level of miR-23a is abnormally increased, which can promote the occurrence and development of tongue squamous cell carcinoma by down-regulating the expression level of its target genes IRF1 and PPP2R5E.

Discussion

The identification of this signaling pathway provides a practical basis for early detection, early diagnosis and early treatment of oral squamous cell carcinoma.

Conclusion

The regulatory mechanism of hsa_circ_0001862-miR-23a-IRF1/PPP2R5E axis on the OSCC and the function of downstream target genes that play specific roles.

背景：头颈癌是全球十大癌症之一，病变多发生在口腔。口腔鳞状细胞癌占所有口腔恶性肿瘤的90%以上，是一个重大的公共卫生问题。环状RNA和微RNA作为非编码RNA，在肿瘤传播的发展中起着重要作用。目的：本研究试图从非编码RNA的角度探讨口腔鳞状细胞癌的发病机制。材料与方法：我们发现miR-23a在口腔鳞状细胞癌组织中异常升高。以此为切入点，我们通过生物信息学预测寻找miR-23a上游功能的circRNA及下游靶基因。我们通过双荧光素酶报告基因实验确定了miR-23a与hsa_circ_0001862以及下游靶基因IRF1和PPP2R5E之间的直接靶向关系。我们通过CCK8、菌落形成、划痕和跨孔实验等一系列细胞表型实验，验证了上述基因对舌鳞状细胞系Tca-8113的影响。结果：Hsa_circ_0001862通过海绵作用调控miR-23a的表达水平。在舌鳞状细胞癌的发生发展过程中，miR-23a的表达水平异常升高，可通过下调其靶基因IRF1和PPP2R5E的表达水平，促进舌鳞状细胞癌的发生发展。讨论：该信号通路的发现为口腔鳞状细胞癌的早期发现、早期诊断和早期治疗提供了现实依据。结论：hsa_circ_0001862-miR-23a-IRF1/PPP2R5E轴对OSCC的调控机制及发挥特定作用的下游靶基因的功能。

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引用次数: 0