Some studies confirmed that erythroblast transformation-specific-related gene (ERG) may be a pathogenic factor of oral squamous cell carcinoma (OSCC). However, the undergoing molecular mechanism has not been elucidated yet.
Objective
In this study, the investigation will focus on how the transcription factor ERG modulates the biological behaviors of OSCC.
Methods
In this study, cancer tissue specimens and corresponding paracancer tissues were collected from 54 patients. Real-time polymerase chain reaction analysis and Western blots were employed to detect the expression of multiple genes. Cell proliferation assays, Transwell, and flow cytometry assay were utilized to detect the proliferation, invasion, and apoptosis of OSCC cell, respectively. Dual luciferase reporter gene and chromatin immunoprecipitation assays were conducted to verify the regulation of ERG on PRDX1.
Results
ERG exhibits high expression levels in OSCC. Inhibition of ERG has been shown to effectively suppress the malignant growth of OSCC cells. Moreover, ERG has been found to transcriptionally upregulate the expression of PRDX1. The knockdown of PRDX1 has demonstrated its ability to inhibit the malignant growth of OSCC cells. Interestingly, when PRDX1 is overexpressed, it attenuates the inhibitory effect of si-ERG on the malignant growth of OSCC cells. This suggests that PRDX1 may play a crucial role in mediating the impact of ERG on malignancy in OSCC cells.
Conclusion
The transcription factor ERG promotes the expression of PRDX1, which could enhance the proliferation and invasion while inhibiting the apoptosis of OSCC cells.
{"title":"Erythroblast transformation-specific-related gene promotes metastasis of oral squamous cell carcinoma by transcriptionally upregulating peroxiredoxin 1","authors":"Yujia Gu, Xue Chen, Mei Tian, Ke Liu","doi":"10.1111/jop.13544","DOIUrl":"10.1111/jop.13544","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Some studies confirmed that erythroblast transformation-specific-related gene (<i>ERG</i>) may be a pathogenic factor of oral squamous cell carcinoma (OSCC). However, the undergoing molecular mechanism has not been elucidated yet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>In this study, the investigation will focus on how the transcription factor <i>ERG</i> modulates the biological behaviors of OSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, cancer tissue specimens and corresponding paracancer tissues were collected from 54 patients. Real-time polymerase chain reaction analysis and Western blots were employed to detect the expression of multiple genes. Cell proliferation assays, Transwell, and flow cytometry assay were utilized to detect the proliferation, invasion, and apoptosis of OSCC cell, respectively. Dual luciferase reporter gene and chromatin immunoprecipitation assays were conducted to verify the regulation of ERG on <i>PRDX1</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>ERG</i> exhibits high expression levels in OSCC. Inhibition of ERG has been shown to effectively suppress the malignant growth of OSCC cells. Moreover, ERG has been found to transcriptionally upregulate the expression of <i>PRDX1</i>. The knockdown of <i>PRDX1</i> has demonstrated its ability to inhibit the malignant growth of OSCC cells. Interestingly, when <i>PRDX1</i> is overexpressed, it attenuates the inhibitory effect of si-<i>ERG</i> on the malignant growth of OSCC cells. This suggests that <i>PRDX1</i> may play a crucial role in mediating the impact of <i>ERG</i> on malignancy in OSCC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The transcription factor ERG promotes the expression of <i>PRDX1</i>, which could enhance the proliferation and invasion while inhibiting the apoptosis of OSCC cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"404-413"},"PeriodicalIF":2.7,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155380","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}
Camila Alves Ferri, Vanessa Justo de Lima, Patrícia Koehler dos Santos, Pantelis Varvaki Rados, Fernanda Visioli
Background
Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response.
Methods
To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta-analysis using the Review Manager software.
Results
Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI).
Conclusion
Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer.
背景：头颈癌包括影响口腔、咽、喉和甲状腺的肿瘤。确定影响致癌过程的因素有助于确定罹患该疾病风险较高的亚群体，从而实施预防计划。维生素 D 受体多态性可通过改变维生素 D 代谢和细胞反应影响各种肿瘤的癌变：为了阐明维生素 D 受体多态性在头颈癌中的作用，我们在 Embase、PubMed、Scopus 和 Lilacs 数据库中进行了系统性检索。共有 19 篇文章符合纳入标准。研究人员记录了维生素D受体多态性等位基因（FokI、ApaI、BsmI、TaqI、Cdx2、rs2107301、rs2238135）的频率，并利用Review Manager软件汇总计算了荟萃分析中的几率：亚组分析表明，在癌症的解剖部位（ApaI 和 BsmI 中为口腔癌，TaqI 中为未指定的头颈部癌症亚部位）、基因分型方法（FokI 和 BsmI）以及研究的大陆（ApaI、FokI 和 BsmI）方面存在显著关联：与文献中的其他证据一样，我们的研究结果也不尽相同。因此，需要进行更多样本量更大的临床研究，才能就维生素 D 受体多态性与头颈癌之间的关系得出更准确的结果。
{"title":"Is vitamin D receptor (VDR) polymorphism associated with head and neck cancer risk? A systematic review and meta-analysis","authors":"Camila Alves Ferri, Vanessa Justo de Lima, Patrícia Koehler dos Santos, Pantelis Varvaki Rados, Fernanda Visioli","doi":"10.1111/jop.13543","DOIUrl":"10.1111/jop.13543","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta-analysis using the Review Manager software.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"341-357"},"PeriodicalIF":2.7,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087786","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}
This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy.
Materials and Methods
Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation.
Results
A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2–4.5), mandible site (OR, 3.6; 95% CrI: 2.7–5.2), and unicystic (OR, 1.6; 95% CrI: 1.1–2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups.
Conclusions
The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.
目的：本贝叶斯网络荟萃分析旨在分析骨髓母细胞瘤（AM）患者的临床病理特征与BRAF突变之间的关联，并评估诊断的准确性：检索了2010年至2024年的四个电子数据库。所使用的检索词专门针对 BRAF 和 AM。观察性研究或随机对照试验均符合条件。对AM患者的BRAF突变发生率和相应的临床病理特征进行了贝叶斯网络分析和诊断准确性评估：结果：共纳入了 20 项研究中的 937 例 AM 患者。结果：20 项研究共纳入 937 例 AM 患者，BRAF 基因突变在 AM 患者中的总发生率为 72%。根据贝叶斯网络分析，BRAF突变更可能发生在年轻（比值比[OR]，2.3；可信区间[CrI]：1.2-4.5）、下颌骨部位（OR，3.6；95% CrI：2.7-5.2）和单囊性（OR，1.6；95% CrI：1.1-2.4）的AM患者中。同样，年轻、下颌骨和单囊AM组的诊断准确率也较高：结论：与具有其他临床病理特征的患者相比，年轻患者、下颌骨受累患者和单囊AM患者的BRAF突变发生率、风险和诊断准确率更高。此外，分子检测与免疫组化分析的诊断准确性也非常一致。
{"title":"Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis","authors":"Ao-Bo Zhang, Jian-Yun Zhang, Yu-Ping Liu, Shuo Wang, Jia-Ying Bai, Li-Sha Sun, Tie-Jun Li","doi":"10.1111/jop.13542","DOIUrl":"10.1111/jop.13542","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and <i>BRAF</i> mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Four electronic databases were searched from 2010 to 2024. The search terms used were specific to <i>BRAF</i> and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of <i>BRAF</i> mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 937 AM patients from 20 studies were included. The pooled prevalence of <i>BRAF</i> mutations in AM patients was 72%. According to the Bayesian network analysis, <i>BRAF</i> mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2–4.5), mandible site (OR, 3.6; 95% CrI: 2.7–5.2), and unicystic (OR, 1.6; 95% CrI: 1.1–2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The incidence, risk, and diagnostic accuracy of <i>BRAF</i> mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"393-403"},"PeriodicalIF":2.7,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081561","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}
Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions.
Methods
This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting Candida albicans, Streptococcus mutans, and Porphyromonas gingivalis.
Results
LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against C. albicans and S. mutans, but was ineffective against P. gingivalis.
Conclusion
This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.
{"title":"Curcumin is effective in managing oral inflammation: An in vitro study","authors":"Majdy Idrees, Omar Kujan","doi":"10.1111/jop.13547","DOIUrl":"10.1111/jop.13547","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oral inflammation is among the most prevalent oral pathologies with systemic health implications, necessitating safe and effective treatments. Given curcumin's documented anti-inflammatory and antioxidant properties, this study focuses on the potential of a curcumin-based oral gel in safely managing oral inflammatory conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This in vitro study utilized four human cell lines: oral keratinocytes (HOKs), immortalized oral keratinocytes (OKF6), periodontal ligament fibroblasts (HPdLF), and dysplastic oral keratinocytes (DOKs). The cells were treated with Lipopolysaccharides (LPS) and curcumin-based oral gel to simulate inflammatory conditions. A panel of cellular assays were performed along with antimicrobial efficacy tests targeting <i>Candida albicans</i>, <i>Streptococcus mutans</i>, and <i>Porphyromonas gingivalis</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LPS significantly reduced proliferation and wound healing capacities of HOKs, OKF6, and HPdLF, but not DOKs. Treatment with curcumin-based oral gel mitigated inflammatory responses in HOKs and HPdLF by enhancing proliferation, colony formation, and wound healing, along with reducing apoptosis. However, its impact on OKF6 and DOKs was limited in some assays. Curcumin treatment did not affect the invasive capabilities of any cell line but did modulate cell adhesion in a cell line-specific manner. The curcumin-based oral gel showed significant antimicrobial efficacy against <i>C. albicans</i> and <i>S. mutans</i>, but was ineffective against <i>P. gingivalis.</i></p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study demonstrates the potential of the curcumin-based oral gel as a safe and effective alternative to conventional antimicrobial treatments for managing cases of oral inflammation. This was achieved by modulating cellular responses under simulated inflammatory conditions. Future clinical-based studies are recommended to exploit curcumin's therapeutic benefits in oral healthcare.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"376-385"},"PeriodicalIF":2.7,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.13547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Buccal mucosa squamous cell carcinoma (BMSCC) is an aggressive disease. This study investigated the clinicopathological significance of tumor budding (TB), depth of invasion (DOI), and mode of invasion (MOI) on occult cervical metastasis (CM) of BMSCC.
Methods
Seventy-one cT1–2N0 BMSCC patients were included in this retrospective study. TB, DOI, MOI, and other clinicopathological features were reviewed. Risk factors for occult CM, locoregional recurrence-free survival (LRRFS), and overall survival (OS) were analyzed using logistic regression and Cox's proportional hazard models, respectively.
Results
Multivariate analysis with the logistic regression model revealed that MOI, DOI, and TB were significantly associated with occult CM in early-stage BMSCC after adjusting for variates. However, multivariate analysis with the Cox's proportional hazard model found only TB to be a prognostic factor for LRRFS (hazard ratio 15.03, 95% confidence interval [CI] 1.94–116.66; p = 0.01; trend test p = 0.03). No significant association was found between MOI, DOI, or TB and OS.
Conclusions
The optimal predictor of occult CM and prognosis of early-stage BMSCC is TB, which may assist clinicians in identifying patients at high risk of cervical metastasis.
{"title":"Tumor budding is an optimal indictor of occult cervical metastasis in clinical early-stage buccal mucosa squamous cell carcinoma","authors":"Zhi Zheng, Huan-Xing Yang, Yi-Hong Fang, Jin Wang, Shi-Wei Fu, Qi-Ming Ouyang","doi":"10.1111/jop.13533","DOIUrl":"10.1111/jop.13533","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Buccal mucosa squamous cell carcinoma (BMSCC) is an aggressive disease. This study investigated the clinicopathological significance of tumor budding (TB), depth of invasion (DOI), and mode of invasion (MOI) on occult cervical metastasis (CM) of BMSCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Seventy-one cT<sub>1–2</sub>N<sub>0</sub> BMSCC patients were included in this retrospective study. TB, DOI, MOI, and other clinicopathological features were reviewed. Risk factors for occult CM, locoregional recurrence-free survival (LRRFS), and overall survival (OS) were analyzed using logistic regression and Cox's proportional hazard models, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Multivariate analysis with the logistic regression model revealed that MOI, DOI, and TB were significantly associated with occult CM in early-stage BMSCC after adjusting for variates. However, multivariate analysis with the Cox's proportional hazard model found only TB to be a prognostic factor for LRRFS (hazard ratio 15.03, 95% confidence interval [CI] 1.94–116.66; <i>p</i> = 0.01; trend test <i>p</i> = 0.03). No significant association was found between MOI, DOI, or TB and OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The optimal predictor of occult CM and prognosis of early-stage BMSCC is TB, which may assist clinicians in identifying patients at high risk of cervical metastasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"386-392"},"PeriodicalIF":2.7,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076139","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}
Ajay Kumar, Emmanuel Asiedu, Eman Hefni, Cheryl Armstrong, Deepak Menon, Tao Ma, Lauren Sands, Eberechi Mbadugha, Akrit Sodhi, Abraham Schneider, Silvia Montaner
Background
Angiopoietin-like 4 is a molecular hallmark that correlates with the growth and metastasis of head and neck squamous cell carcinoma, one of the most prevalent cancers worldwide. However, the molecular mechanisms by which angiopoietin-like 4 promotes head and neck squamous cell carcinoma tumorigenesis are unclear.
Methods
Using well-characterized cell lines of head and neck squamous cell carcinoma development, including human normal oral keratinocytes, dysplastic oral keratinocytes, oral leukoplakia-derived oral keratinocytes, and head and neck squamous cell carcinoma cell lines, HN13, HN6, HN4, HN12, and CAL27, we investigated the signaling pathways upstream and downstream of angiopoietin-like 4-induced head and neck squamous cell carcinoma tumorigenesis.
Results
We found that both epidermal growth factor receptor ligands, epithelial growth factor, and amphiregulin led to angiopoietin-like 4 upregulation in normal oral keratinocytes and dysplastic oral keratinocytes and cooperated with the activation of hypoxia-inducible factor-1 in this effect. Interestingly, amphiregulin and angiopoietin-like 4 were increased in dysplastic oral keratinocytes and head and neck squamous cell carcinoma cell lines, and amphiregulin-induced activation of cell proliferation was dependent on angiopoietin-like 4. Although both p38 mitogen-activated protein kinases (p38 MAPK) and protein kinase B (AKT) were activated by angiopoietin-like 4, only pharmacological inhibition of p38 MAPK was sufficient to prevent head and neck squamous cell carcinoma cell proliferation and migration. We further observed that angiopoietin-like 4 promoted the secretion of interleukin 11 (IL-11), interleukin 12 (IL-12), interleukin-1 alpha (IL-1α), vascular endothelial growth factor, platelet-derived growth factor (PDGF), and tumour necrosis factor alpha (TNF-α), cytokines and chemokines previously implicated in head and neck squamous cell carcinoma pathogenesis.
Conclusion
Our results demonstrate that angiopoietin-like 4 is a downstream effector of amphiregulin and promotes head and neck squamous cell carcinoma development both through direct activation of p38 kinase as well as paracrine mechanisms.
{"title":"Angiopoietin-like 4 is upregulated by amphiregulin and activates cell proliferation and migration through p38 kinase in head and neck squamous cell carcinoma","authors":"Ajay Kumar, Emmanuel Asiedu, Eman Hefni, Cheryl Armstrong, Deepak Menon, Tao Ma, Lauren Sands, Eberechi Mbadugha, Akrit Sodhi, Abraham Schneider, Silvia Montaner","doi":"10.1111/jop.13545","DOIUrl":"10.1111/jop.13545","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Angiopoietin-like 4 is a molecular hallmark that correlates with the growth and metastasis of head and neck squamous cell carcinoma, one of the most prevalent cancers worldwide. However, the molecular mechanisms by which angiopoietin-like 4 promotes head and neck squamous cell carcinoma tumorigenesis are unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using well-characterized cell lines of head and neck squamous cell carcinoma development, including human normal oral keratinocytes, dysplastic oral keratinocytes, oral leukoplakia-derived oral keratinocytes, and head and neck squamous cell carcinoma cell lines, HN13, HN6, HN4, HN12, and CAL27, we investigated the signaling pathways upstream and downstream of angiopoietin-like 4-induced head and neck squamous cell carcinoma tumorigenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that both epidermal growth factor receptor ligands, epithelial growth factor, and amphiregulin led to angiopoietin-like 4 upregulation in normal oral keratinocytes and dysplastic oral keratinocytes and cooperated with the activation of hypoxia-inducible factor-1 in this effect. Interestingly, amphiregulin and angiopoietin-like 4 were increased in dysplastic oral keratinocytes and head and neck squamous cell carcinoma cell lines, and amphiregulin-induced activation of cell proliferation was dependent on angiopoietin-like 4. Although both p38 mitogen-activated protein kinases (p38 MAPK) and protein kinase B (AKT) were activated by angiopoietin-like 4, only pharmacological inhibition of p38 MAPK was sufficient to prevent head and neck squamous cell carcinoma cell proliferation and migration. We further observed that angiopoietin-like 4 promoted the secretion of interleukin 11 (IL-11), interleukin 12 (IL-12), interleukin-1 alpha (IL-1α), vascular endothelial growth factor, platelet-derived growth factor (PDGF), and tumour necrosis factor alpha (TNF-α), cytokines and chemokines previously implicated in head and neck squamous cell carcinoma pathogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results demonstrate that angiopoietin-like 4 is a downstream effector of amphiregulin and promotes head and neck squamous cell carcinoma development both through direct activation of p38 kinase as well as paracrine mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"366-375"},"PeriodicalIF":2.7,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065906","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}
Sebastião Silvério Sousa-Neto, Allisson Filipe Lopes Martins, Victor Hugo Lopes de Oliveira Moreira, João Gabriel Batista Pereira, Nilceana Maya Aires Freitas, Maria Paula Curado, Claudio Rodrigues Leles, Elismauro Francisco Mendonça
Background
To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease-free survival and overall survival of patients with oral cancer.
Methods
A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (n = 129), or (2) those referred by nonspecialized professionals (n = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease-free survival and overall survival.
Results
Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease-free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival.
Conclusion
Specialized oral diagnosis did not directly impact disease-free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis.
{"title":"The association between referral by specialists in oral diagnosis on survival rates of patients with oral cancer: A retrospective cohort study","authors":"Sebastião Silvério Sousa-Neto, Allisson Filipe Lopes Martins, Victor Hugo Lopes de Oliveira Moreira, João Gabriel Batista Pereira, Nilceana Maya Aires Freitas, Maria Paula Curado, Claudio Rodrigues Leles, Elismauro Francisco Mendonça","doi":"10.1111/jop.13546","DOIUrl":"10.1111/jop.13546","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To assess the influence of diagnosis and referral provided by specialists in oral diagnosis on disease-free survival and overall survival of patients with oral cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A cohort of 282 patients with oral cancer treated at a regional cancer hospital from 1998 to 2016 was analyzed retrospectively. The referral register of the patients was analyzed and assigned to two groups: (1) those referred by oral diagnosis specialists (<i>n</i> = 129), or (2) those referred by nonspecialized professionals (<i>n</i> = 153). The cancer treatment evolution was assessed from the patients' records, and the outcome was registered concerning cancer recurrence and death. Sociodemographic and clinicopathological variables were explored as predictors of disease-free survival and overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Group 1 exhibited lower T stages and a reduced incidence of regional and distant metastases. Surgery was performed in 75.2% of cases in Group 1, while in Group 2, the rate was 60.8%. Advanced T stages and regional metastases reduced the feasibility of surgery. Higher TNM stages and tumor recurrence were associated with decreased disease-free survival, while surgical intervention was a protective factor. Higher TNM stage had a negative impact on the overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Specialized oral diagnosis did not directly impact disease-free survival and overall survival and did not influence the indication of surgery in oral cancer; however, it was associated with the diagnosis of early tumors and better prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"358-365"},"PeriodicalIF":2.7,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922313","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}
Felipe Martins Silveira, Laura Borges Kirschnick, Bruna Barcelos Só, Lauren Frenzel Schuch, Vanesa Pereira Prado, Estefania Sicco, Rafael Rodrigues Lima, Ronell Eduardo Bologna-Molina, Adalberto Mosqueda-Taylor, Ana Carolina Uchoa Vasconcelos, Manoela Domingues Martins
Background
Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features.
Methods
This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report.
Results
A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases.
Conclusion
MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.
{"title":"Clinicopathological features of myofibromas and myofibromatosis affecting the oral and maxillofacial region: A systematic review","authors":"Felipe Martins Silveira, Laura Borges Kirschnick, Bruna Barcelos Só, Lauren Frenzel Schuch, Vanesa Pereira Prado, Estefania Sicco, Rafael Rodrigues Lima, Ronell Eduardo Bologna-Molina, Adalberto Mosqueda-Taylor, Ana Carolina Uchoa Vasconcelos, Manoela Domingues Martins","doi":"10.1111/jop.13537","DOIUrl":"10.1111/jop.13537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Myofibromas are rare benign neoplasms composed of myoid cells and myofibroblasts. This study aimed to systematically review case reports and a series of myofibromas (MF) and myofibromatosis (MFT) occurring in the oral and maxillofacial regions in order to describe their main clinicopathological features.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Electronic searches were conducted in 2023 in four databases: MEDLINE/PubMed, Web of Science, Scopus, and EMBASE. A manual search and a search in the grey literature were also conducted. The lesions were classified as MF or MFT according to their original report.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 169 cases were included in this systematic review. Men were slightly more affected, with a painless nodule. When occurring in soft tissue, MF usually developed in the gingiva (mean age:29.23 ± 21.93 years) and when it was intra-osseous, it occurred more frequently in the posterior mandible (mean age:14.33 ± 15.62 years). MFT occurred mainly in the mandible and was predominantly described as well-circumscribed masses of spindle cells organized in fascicles with a prominent vascular activity in a hemangiopericytoma-like pattern. The lesions were mainly positive for smooth muscle actin and vimentin immunomarkers. Surgical excision was the treatment of choice in the majority of cases and recurrence was observed in only three cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>MF and MFT affect more men, with an indolent clinical course. Intra-osseous tumors and MFT seem to occur more frequently in younger individuals. These lesions seem to have a good prognosis and low recurrence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 6","pages":"334-340"},"PeriodicalIF":2.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863991","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}
Farah Essgui Orellana Martinez, Thâmara Manoela Marinho Bezerra, Ana Paula Negreiros Nunes Alves, Isabelle Joyce Lima Silva Fernandes, Fabricio Bitu Sousa, Paulo Goberlânio de Barros Silva, Mário Rogério Lima Mota
Background
To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs).
Methods
Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-β, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann–Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05).
Results
ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-β (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047).
Conclusions
Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.
{"title":"Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma","authors":"Farah Essgui Orellana Martinez, Thâmara Manoela Marinho Bezerra, Ana Paula Negreiros Nunes Alves, Isabelle Joyce Lima Silva Fernandes, Fabricio Bitu Sousa, Paulo Goberlânio de Barros Silva, Mário Rogério Lima Mota","doi":"10.1111/jop.13541","DOIUrl":"10.1111/jop.13541","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-β, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann–Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ACs showed higher number of α-SMA<sup>+</sup> MFs when compared to CG (<i>p</i> = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (<i>p</i> = 0.027). Areas of SE had lower deposits of collagen (<i>p</i> < 0.001), immunostaining for TGF-β (<i>p</i> < 0.001), and higher density of elastic fibers (<i>p</i> < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (<i>p</i> = 0.027). LLSCCs showed a higher number of α-SMA<sup>+</sup> MFs about CG (<i>p</i> = 0.034), as well as a reduction in the deposition of total collagen (<i>p</i> = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA<sup>+</sup> cells and the accumulation of total collagen (<i>p</i> = 0.041). Collagen and elastic density loss was higher in larger tumors (<i>p</i> = 0.045) with nodal invasion (<i>p</i> = 0.047).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 5","pages":"321-330"},"PeriodicalIF":3.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837467","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}
Various antigen-presenting cells and tumor cells-expressing PD-L1 inhibits antitumor immune responses in the tumor microenvironment. Recently, numerous studies have shown that tumor cell intrinsic PD-L1 also plays important roles in tumor growth and progression. On the other hand, oral squamous cell carcinoma (OSCC) cells overexpress epidermal growth factor receptor (EGFR) and EGFR signal pathway exacerbates tumor progression. Therefore, this study assessed whether tumor-intrinsic PD-L1 facilitates malignant potential of OSCC cells through regulation of EGFR signaling.
Methods
Two OSCC cell lines, SAS and HSC-3, were transfected with PD-L1 and EGFR-specific small interfering RNA (siRNA). Influences of PD-L1 knockdown on malignant potentials of OSCC cells were examined by Cell Counting kit-8 assay, transwell assay, sphere formation assay, flow cytometry, and Western blot. Effects of PD-L1 and EGFR knockdown on each expression were examined by quantitative real-time PCR (qRT-PCR), Western blot, and flow cytometry.
Results
Transfection of an PD-L1-siRNA into OSCC cells decreased the abilities of proliferation, stemness, and mobility of these cells significantly. PD-L1 knockdown also decreased EGFR expression through the promotion of proteasome- and lysosome-mediated degradation and following activation of the EGFR/protekin kinase B (AKT) signal pathway. Meanwhile, EGFR knockdown did not influence PD-L1 expression in SAS and HSC-3 cells, but treatment with a recombinant human EGF induced its expression. Treatment with erlotinib and cetuximab suppressed rhEGF-induced PD-L1 expression and localization in the cellular membrane of both OSCC cells.
Conclusion
OSCC cells-expressing PD-L1 induced by EGF stimulation may promote malignancy intrinsically via the activation of the EGFR/AKT signaling cascade.
{"title":"The involvement of epidermal growth factor receptor/protein kinase B signaling in the tumor intrinsic PD-L1-induced malignant potential of oral squamous cell carcinoma","authors":"Eri Sasabe, Ayumi Tomomura, Tetsuya Yamamoto","doi":"10.1111/jop.13540","DOIUrl":"10.1111/jop.13540","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Various antigen-presenting cells and tumor cells-expressing PD-L1 inhibits antitumor immune responses in the tumor microenvironment. Recently, numerous studies have shown that tumor cell intrinsic PD-L1 also plays important roles in tumor growth and progression. On the other hand, oral squamous cell carcinoma (OSCC) cells overexpress epidermal growth factor receptor (EGFR) and EGFR signal pathway exacerbates tumor progression. Therefore, this study assessed whether tumor-intrinsic PD-L1 facilitates malignant potential of OSCC cells through regulation of EGFR signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two OSCC cell lines, SAS and HSC-3, were transfected with <i>PD-L1</i> and <i>EGFR</i>-specific small interfering RNA (siRNA). Influences of PD-L1 knockdown on malignant potentials of OSCC cells were examined by Cell Counting kit-8 assay, transwell assay, sphere formation assay, flow cytometry, and Western blot. Effects of PD-L1 and EGFR knockdown on each expression were examined by quantitative real-time PCR (qRT-PCR), Western blot, and flow cytometry.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Transfection of an <i>PD-L1</i>-siRNA into OSCC cells decreased the abilities of proliferation, stemness, and mobility of these cells significantly. PD-L1 knockdown also decreased EGFR expression through the promotion of proteasome- and lysosome-mediated degradation and following activation of the EGFR/protekin kinase B (AKT) signal pathway. Meanwhile, EGFR knockdown did not influence PD-L1 expression in SAS and HSC-3 cells, but treatment with a recombinant human EGF induced its expression. Treatment with erlotinib and cetuximab suppressed rhEGF-induced PD-L1 expression and localization in the cellular membrane of both OSCC cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>OSCC cells-expressing PD-L1 induced by EGF stimulation may promote malignancy intrinsically via the activation of the EGFR/AKT signaling cascade.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"53 5","pages":"310-320"},"PeriodicalIF":3.3,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.13540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140837470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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