Journal of Oral Pathology & Medicine最新文献_第10页

Highly Expressed NELFE in Tumor Cells at the Invasive Tumor Front Was a Prognostic Biomarker for Oral Squamous Cell Carcinoma 侵袭性肿瘤前部肿瘤细胞中高表达的NELFE是口腔鳞状细胞癌的预后生物标志物。

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-08 DOI: 10.1111/jop.70025

Yizhuo Xue, Lingyun Liu, Liyuan Yu, Zihui Li, Xiaofeng Huang, Sheng Chen, Yue Jing, Xiaoxin Zhang, Liang Ding, Yuxian Song, Zhiyong Wang, Yanhong Ni

Background

Negative elongation factor E (NELFE) is a crucial subunit of the NELF complex, which plays pivotal roles in transcriptional regulation and cell fate. Despite the role of dysregulated NELFE in promoting the onset and progression of some kinds of tumors, its expression profile, prognostic value, and function in oral squamous cell carcinoma (OSCC) still remain unknown.

Methods

Immunohistochemistry (IHC) was utilized to analyze the NELFE expression profile in OSCC, and the prognostic values of NELFE were also evaluated. qRT-PCR and Western blot were used to compare the expression of NELFE in OSCC cell lines. NELFE expression was knocked down by small interfering RNA fragments, and functional experiments were conducted to investigate the impact of NELFE on the proliferation and migration of OSCC cell lines. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas (TCGA) data to explore potential mechanisms of NELFE in OSCC.

Results

NELFE was widely distributed throughout tumor cells (TCs), fibroblast-like cells (FLCs), and tumor infiltrating lymphocytes (TILs) in OSCC tissue. However, its expression was significantly upregulated in TCs at the invasive tumor front compared to the tumor center components (p = 0.027). Higher expression of NELFE in TCs at the invasive tumor front (ITF) was significantly associated with higher lymph node metastasis (p = 0.024), worse invasion pattern (p < 0.0001), and more advanced tumor node metastasis classification (p = 0.002). Additionally, higher expression of NELFE in TCs at the invasive tumor front was also linked to higher recurrence (p = 0.021) and shorter disease-free (HR = 2.045, p = 0.006) as well as relapse-free survival (HR = 2.369, p = 0.011). The NELFE mRNA and protein were generally expressed in OSCC cells. Functionally, silencing NELFE significantly inhibited the proliferation and migration capabilities of OSCC tumor cells in vitro. Finally, GSEA revealed a significant difference in the E2F pathway between NELFE high and low expression.

Conclusions

NELFE expression at the invasive front was associated with poor prognosis and could be a potential prognostic biomarker for OSCC.

背景：负伸长因子E （NELFE）是NELFE复合体的一个重要亚基，在转录调控和细胞命运中起着关键作用。尽管失调的NELFE在促进某些肿瘤的发生和发展中起作用，但其在口腔鳞状细胞癌（OSCC）中的表达谱、预后价值和功能仍不清楚。方法：采用免疫组化（IHC）方法分析NELFE在OSCC中的表达谱，并评价NELFE的预后价值。采用qRT-PCR和Western blot方法比较NELFE在OSCC细胞系中的表达。通过小干扰RNA片段敲低NELFE的表达，通过功能实验研究NELFE对OSCC细胞系增殖和迁移的影响。利用癌症基因组图谱（TCGA）数据进行基因集富集分析（GSEA），探讨NELFE在OSCC中的潜在机制。结果：NELFE在OSCC组织中广泛分布于肿瘤细胞（TCs）、成纤维细胞样细胞（FLCs）和肿瘤浸润淋巴细胞（TILs）。然而，与肿瘤中心成分相比，其在侵袭性肿瘤前部tc中的表达显著上调（p = 0.027）。侵袭性肿瘤前缘tc中NELFE的高表达与较高的淋巴结转移（p = 0.024）和较差的侵袭方式(p)显著相关。结论：侵袭性肿瘤前缘NELFE表达与预后不良相关，可能是OSCC潜在的预后生物标志物。

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引用次数: 0

Concordance of Oral and Anal Human Papillomavirus in Men Who Have Sex With Men Living With Human Immunodeficiency Virus 与人类免疫缺陷病毒感染者发生性行为的男性口腔和肛门人乳头瘤病毒的一致性。

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-08 DOI: 10.1111/jop.70023

Po-Chi Huang, Szu-I Lin, Na-Lee Sun, Shu-Yuan Li, Cheng-Pin Chen, Yi-Chun Lin, Chien-Yu Cheng, Fang-Yeh Chu, Shu-Hsing Cheng

Background

To detect human papillomavirus (HPV) at oral and anal sites and assess genotype concordance among men who have sex with men (MSM) living with human immunodeficiency virus (HIV) in Taiwan.

Methods

HIV-positive men aged 20 years or older attending outpatient clinics at Taoyuan General Hospital, Taiwan, were enrolled. Oral gargle and anal swab samples were collected for HPV genotyping using linear array testing. Multivariate logistic regression identified factors associated with oral-HPV and oral-anal genotype concordance. Significance was set at p < 0.05.

Results

Of 196 eligible participants, the mean age was 32.2 years and over 95% were MSM. The mean CD4+ T cell count was 588 cells/μL (95% confidence interval [CI]: 551–626), and 73% (n = 143) had suppressed viral loads. Anal-HPV was detected in 184 participants (93.8%, 95% CI: 90.5%–97.2%), with 82.7% (n = 162) having oncogenic genotypes. Oral HPV was found in 20 participants (10.2%, 95% CI: 5.9%–14.4%), with 30% (n = 6) having oncogenic genotypes. Among those with oral HPV, 55% (n = 11) showed genotype concordance with anal sites. Only 30% reported condom use during oral sex. Concordance was significantly associated with the number of anal-HPV genotypes (adjusted odds ratio: 1.58, 95% CI: 1.08–2.32, p = 0.015), adjusting for drug use, internet-based partners, recent sexually transmitted infections, and anal oncogenic HPV count.

Conclusions

Oral HPV was common, and over half of the infections matched genotypes found anally. These results support targeted HPV vaccination promotion among MSM living with HIV in Taiwan.

背景：在台湾地区男男性行为者（MSM）中检测人类免疫缺陷病毒（HIV）在口腔和肛门部位的人乳头瘤病毒（HPV），并评估基因型一致性。方法：选取在台湾桃园总医院门诊就诊的年龄在20岁及以上的hiv阳性男性为研究对象。收集口腔含漱液和肛门拭子样本，采用线性阵列检测进行HPV基因分型。多因素logistic回归确定了与口腔- hpv和口腔-肛门基因型一致性相关的因素。结果：在196名符合条件的参与者中，平均年龄为32.2岁，超过95%是男男性行为者。平均CD4+ T细胞计数为588个/μL(95%可信区间[CI]: 551-626), 73% （n = 143）的病毒载量受到抑制。184名参与者（93.8%,95% CI: 90.5%-97.2%）检测到al- hpv，其中82.7% （n = 162）为致癌基因型。在20名参与者中发现了口腔HPV (10.2%, 95% CI: 5.9%-14.4%)，其中30% （n = 6）具有致癌基因型。在口腔HPV患者中，55% （n = 11）的基因型与肛门部位一致。只有30%的人报告在口交时使用避孕套。一致性与肛门HPV基因型数量显著相关（校正优势比：1.58,95% CI: 1.08-2.32, p = 0.015），校正了药物使用、网络伴侣、近期性传播感染和肛门致癌HPV计数。结论：口腔HPV是常见的，超过一半的感染与肛门发现的基因型匹配。本研究结果支持台湾爱滋病毒男同性恋者有针对性地推广HPV疫苗接种。

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引用次数: 0

Epstein–Barr Virus Serology Associated With Persistent Oral Human Papillomavirus Infections in Men eb病毒血清学与男性持续性口腔人乳头瘤病毒感染相关

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-07 DOI: 10.1111/jop.70015

Sanni Rinne, Birgitta Michels, Julia Butt, Kari Syrjänen, Seija Grenman, Tim Waterboer, Stina Syrjänen, Karolina Louvanto

Background

Most people acquire Epstein–Barr virus (EBV) and certain human papillomaviruses (HPVs) during their lifetime. HPV-related oropharyngeal carcinomas have increased in recent decades, particularly among men. The role of coinfection with viruses like EBV on HPV outcomes is unclear. We investigated potential associations between EBV serology and longitudinal outcomes of oral HPV infections in men.

Methods

This study included 119 men from the Finnish Family HPV Study who were followed up for 3 years. Blood and oral cavity samples were collected at baseline, 12-, 24-, and 36-month follow-up visits. HPV was genotyped with the Multimetrix assay, and the serum IgG antibodies of EBV proteins Zebra, EA-D, EBNA, and VCAp18 were measured with fluorescent bead-based multiplex serology. Univariate regression analysis was used to measure the strength of the association between different variables.

Results

Most participants (99.2%; n = 118) were EBV-seropositive with stable antibody titers throughout the follow-up. Self-reported history of atopy was positively associated with elevated EBNA-1 levels, with OR 7.43 (95% CI: 1.39–39.76). EBV seropositivity with high titers and elevated EA-D levels alone increased the risk of type-specific oral HPV persistence for Types 16, 18, 33, and 51, with OR 4.20 (95% CI: 1.09–16.19) and OR 6.23 (95% CI: 1.19–32.75), respectively.

Conclusions

Most of the participants were EBV-seropositive as expected. Elevated EA-D antibody levels and being EBV-seropositive with high titers significantly increased the risk of type-specific oral HPV persistence among these men.

背景：大多数人在一生中感染eb病毒（EBV）和某些人乳头瘤病毒（hpv）。近几十年来，hpv相关的口咽癌有所增加，尤其是在男性中。与EBV等病毒合并感染对HPV结果的作用尚不清楚。我们调查了EBV血清学和男性口腔HPV感染纵向结果之间的潜在关联。方法：本研究纳入了来自芬兰家族HPV研究的119名男性，随访3年。在基线、12个月、24个月和36个月的随访中采集血液和口腔样本。采用Multimetrix法对人乳头瘤病毒（HPV）进行基因分型，采用荧光珠复合血清学检测EBV蛋白Zebra、EA-D、EBNA和VCAp18的血清IgG抗体。采用单变量回归分析来衡量不同变量之间的关联强度。结果：大多数参与者(99.2%；n = 118) ebv血清阳性，在整个随访期间抗体滴度稳定。自我报告的特应性病史与ena -1水平升高呈正相关，OR为7.43 （95% CI: 1.39-39.76）。EBV血清阳性、高滴度和EA-D水平升高单独增加了16型、18型、33型和51型口腔特异性HPV持续存在的风险，OR分别为4.20 （95% CI: 1.09-16.19）和6.23 （95% CI: 1.19-32.75）。结论：大多数受试者如预期的那样呈ebv血清阳性。在这些男性中，升高的EA-D抗体水平和高滴度的ebv血清阳性显著增加了类型特异性口腔HPV持续存在的风险。

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引用次数: 0

Investigation of PDGFRA Gene Pathogenic Variants in Nasal Polyps Associated With Chronic Rhinosinusitis 慢性鼻窦炎相关鼻息肉PDGFRA基因致病变异的研究。

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-07 DOI: 10.1111/jop.70027

Tamara da Silva Vieira, Letícia Martins Guimarães, Marina Gonçalves Diniz, Wilma Terezinha Anselmo-Lima, Edwin Tamashiro, Luiz Armando De Marco, Fabiana Cardoso Pereira Valera, Carolina Cavalieri Gomes

Background

Chronic rhinosinusitis (CRS) with nasal polyps is an inflammatory condition of the nasal mucosa accompanied by significant tissue remodeling. It is characterized by a type 2 inflammatory response and epithelial barrier dysfunction. Platelet-derived growth factor receptor alpha (PDGFRA) is a proto-oncogene that encodes a receptor tyrosine kinase for which platelet-derived growth factor-A (PDGFA) is a specific ligand. Immunoexpression of PDGFRA and upregulation of PDGFRA and PDGFA mRNAs have been demonstrated in CRS with nasal polyps, suggesting they participate in the pathophysiology of such lesions. PDGFRA pathogenic variants have been reported in inflammatory fibroid polyps, as well as in gastrointestinal stromal tumors. Although the pathogenesis of CRS with nasal polyps has been extensively studied, it remains unclear whether nasal polyps harbor genetic mutations. Therefore, herein we investigated the presence of PDGFRA pathogenic variants in nasal polyps occurring in the context of CRS.

Methods

Fourteen CRS with nasal polyp samples were Sanger sequenced, targeting PDGFRA exons 12 and 18.

Results

All samples exhibited wild-type sequences for the PDGFRA sequenced regions.

Conclusion

These findings suggest that, unlike inflammatory fibroid polyps occurring in the gastrointestinal tract, the pathogenesis of nasal polyps occurring in CRS does not involve PDGFRA mutations.

背景：慢性鼻窦炎（CRS）合并鼻息肉是一种伴有显著组织重塑的鼻黏膜炎症。其特点是2型炎症反应和上皮屏障功能障碍。血小板衍生生长因子受体α (PDGFRA)是一种原癌基因，其编码酪氨酸激酶受体，而血小板衍生生长因子- a （PDGFA）是其特异性配体。PDGFRA的免疫表达以及PDGFRA和PDGFA mrna的上调已在CRS鼻息肉中得到证实，提示它们参与了鼻息肉病变的病理生理过程。PDGFRA致病变异已在炎性肌瘤息肉和胃肠道间质瘤中报道。虽然CRS合并鼻息肉的发病机制已被广泛研究，但鼻息肉是否存在基因突变尚不清楚。因此，我们在此研究了在CRS背景下发生的鼻息肉中PDGFRA致病变异的存在。方法：对14例鼻息肉CRS进行Sanger测序，定位PDGFRA外显子12和18。结果：所有样品在PDGFRA测序区域均显示野生型序列。结论：这些研究结果表明，与胃肠道发生的炎性肌瘤息肉不同，CRS中发生的鼻息肉的发病机制与PDGFRA突变无关。

{"title":"Investigation of PDGFRA Gene Pathogenic Variants in Nasal Polyps Associated With Chronic Rhinosinusitis","authors":"Tamara da Silva Vieira, Letícia Martins Guimarães, Marina Gonçalves Diniz, Wilma Terezinha Anselmo-Lima, Edwin Tamashiro, Luiz Armando De Marco, Fabiana Cardoso Pereira Valera, Carolina Cavalieri Gomes","doi":"10.1111/jop.70027","DOIUrl":"10.1111/jop.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Chronic rhinosinusitis (CRS) with nasal polyps is an inflammatory condition of the nasal mucosa accompanied by significant tissue remodeling. It is characterized by a type 2 inflammatory response and epithelial barrier dysfunction. Platelet-derived growth factor receptor alpha (<i>PDGFRA</i>) is a proto-oncogene that encodes a receptor tyrosine kinase for which platelet-derived growth factor-A (<i>PDGFA</i>) is a specific ligand. Immunoexpression of <i>PDGFRA</i> and upregulation of <i>PDGFRA</i> and <i>PDGFA</i> mRNAs have been demonstrated in CRS with nasal polyps, suggesting they participate in the pathophysiology of such lesions. <i>PDGFRA</i> pathogenic variants have been reported in inflammatory fibroid polyps, as well as in gastrointestinal stromal tumors. Although the pathogenesis of CRS with nasal polyps has been extensively studied, it remains unclear whether nasal polyps harbor genetic mutations. Therefore, herein we investigated the presence of <i>PDGFRA</i> pathogenic variants in nasal polyps occurring in the context of CRS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Fourteen CRS with nasal polyp samples were Sanger sequenced, targeting <i>PDGFRA</i> exons 12 and 18.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All samples exhibited wild-type sequences for the <i>PDGFRA</i> sequenced regions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that, unlike inflammatory fibroid polyps occurring in the gastrointestinal tract, the pathogenesis of nasal polyps occurring in CRS does not involve <i>PDGFRA</i> mutations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 8","pages":"742-745"},"PeriodicalIF":2.3,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794760","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

Pyrimethamine Triggers the Apoptotic Pathway in Mucoepidermoid Carcinoma in Cell-Based Models 乙胺嘧啶触发黏液表皮样癌细胞凋亡通路

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-06 DOI: 10.1111/jop.70024

Hyun-Ji Kim, Dong-Guk Park, Su-Jung Choi, Jae-Jin Cho, Seong-Doo Hong, Sung-Dae Cho

Background

Mucoepidermoid carcinoma (MEC) is the most prevalent salivary gland malignancy, with a poor prognosis in high-grade tumors at diagnosis. This highlights the need for effective antitumor agents for treating MEC. Therefore, we aimed to investigate the antineoplastic efficacy of pyrimethamine (PYR), a Food and Drug Administration-approved antiparasitic medicine, to repurpose it as an alternative therapeutic option for treating human MEC.

Methods

The trypan blue exclusion assay, cell counting kit-8 assay, and live/dead assay were performed to assess the antiproliferative efficacy of PYR. PYR-induced apoptosis was confirmed with 4′,6-diamidino-2-phenylindole staining, cell cycle analysis, and annexin V/propidium iodide staining. A western blot assay was conducted to measure changes in cleaved caspase 8 and myeloid cell leukemia-1 (Mcl-1) expression after PYR treatment. Mcl-1 overexpression was used to further confirm the apoptosis-inducing activity of PYR. The hanging drop method was employed to assess the efficacy of PYR in a three-dimensional culture system.

Results

PYR-induced apoptotic cell death in the YD-15 high-grade MEC cell line by promoting apoptosis, as evidenced by MCl-1 proteasomal degradation and increased cleaved caspase 8 expression.

Conclusion

Our results indicate that PYR can effectively target human MEC by inducing both intrinsic and extrinsic apoptotic pathways.

背景：黏液表皮样癌（MEC）是最常见的唾液腺恶性肿瘤，在诊断为高级别肿瘤时预后较差。这突出了治疗MEC需要有效的抗肿瘤药物。因此，我们的目的是研究乙胺嘧啶（PYR）的抗肿瘤疗效，PYR是美国食品和药物管理局批准的抗寄生虫药物，旨在将其作为治疗人类MEC的替代治疗方案。方法：采用台盼蓝排除法、细胞计数试剂盒-8法、活/死法评价PYR的抗增殖作用。通过4′，6-二氨基-2-苯基吲哚染色、细胞周期分析和膜联蛋白V/碘化丙啶染色证实pyr诱导的细胞凋亡。western blot检测PYR治疗后裂解caspase 8和髓样细胞白血病-1 （Mcl-1）表达的变化。通过Mcl-1过表达进一步证实PYR的诱导凋亡活性。采用挂滴法评价PYR在三维培养体系中的效果。结果：pyr通过促进凋亡诱导YD-15高级别MEC细胞株凋亡细胞死亡，表现为MCl-1蛋白酶体降解和cleaved caspase 8表达增加。结论：PYR可通过诱导内源性和外源性凋亡途径有效靶向人MEC。

{"title":"Pyrimethamine Triggers the Apoptotic Pathway in Mucoepidermoid Carcinoma in Cell-Based Models","authors":"Hyun-Ji Kim, Dong-Guk Park, Su-Jung Choi, Jae-Jin Cho, Seong-Doo Hong, Sung-Dae Cho","doi":"10.1111/jop.70024","DOIUrl":"10.1111/jop.70024","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Mucoepidermoid carcinoma (MEC) is the most prevalent salivary gland malignancy, with a poor prognosis in high-grade tumors at diagnosis. This highlights the need for effective antitumor agents for treating MEC. Therefore, we aimed to investigate the antineoplastic efficacy of pyrimethamine (PYR), a Food and Drug Administration-approved antiparasitic medicine, to repurpose it as an alternative therapeutic option for treating human MEC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The trypan blue exclusion assay, cell counting kit-8 assay, and live/dead assay were performed to assess the antiproliferative efficacy of PYR. PYR-induced apoptosis was confirmed with 4′,6-diamidino-2-phenylindole staining, cell cycle analysis, and annexin V/propidium iodide staining. A western blot assay was conducted to measure changes in cleaved caspase 8 and myeloid cell leukemia-1 (Mcl-1) expression after PYR treatment. Mcl-1 overexpression was used to further confirm the apoptosis-inducing activity of PYR. The hanging drop method was employed to assess the efficacy of PYR in a three-dimensional culture system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>PYR-induced apoptotic cell death in the YD-15 high-grade MEC cell line by promoting apoptosis, as evidenced by MCl-1 proteasomal degradation and increased cleaved caspase 8 expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results indicate that PYR can effectively target human MEC by inducing both intrinsic and extrinsic apoptotic pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 8","pages":"723-732"},"PeriodicalIF":2.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789386","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}

引用次数: 0

Immunohistochemical Expression of H3K9ac and H3K27ac in Premalignant and Malignant Tongue Lesions of Wild-Type and Nos2-Knockout Mice Treated With 4NQO H3K9ac和H3K27ac在野生型和nos2基因敲除小鼠舌癌前和舌癌中的免疫组化表达

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-06 DOI: 10.1111/jop.70021

Anaíra Ribeiro Guedes Fonseca Costa, Débora de Oliveira de Santos, Mariana Daiani Costa Silva, Ianca Daniele Oliveira de Jesus, Lúbia Cristina Fonseca, Sérgio Vitorino Cardoso, Paulo Rogério de Faria, Adriano Mota Loyola

Background

Nitric oxide is an important regulator of the epigenetic landscape of cellular homeostatic and pathological states, in which post-translational modifications of the epigenome-modulating enzymes are the most well described mechanism. Considering that alterations of the histone acetylation pattern were associated with oral cancer development and progression, the purpose of this study was to analyze the immunohistochemical expression of H3K9ac and H3K27ac at different stages of oral carcinogenesis induced by 4-nitroquinoline-N-oxide (4NQO) in Nos2^+/+ (wild-type) and Nos2^−/− (knockout) mice.

Methods

C57BL/6J and B6.129P2-Nos2^tm1Lau/J mice were treated with 4NQO in the drinking water at 50 μg/mL for 16 weeks and observed for 8 weeks. Tongues were submitted to histopathological analysis and immunohistochemistry for H3K9ac and H3K27ac expression. The antigen–antibody reaction was analyzed with quickscore (QS).

Results

Both histone acetylation marks were expressed in the normal epithelium. QS values were higher in moderate dysplasia of Nos2^−/− mice (p = 0.025) when compared to Nos2^+/+, and mild dysplasia had lower values for H3K9ac when compared to moderate and severe dysplasia in the Nos2^−/− group (p = 0.015). H3K27ac significantly increased from normal mucosa to mild dysplasia in Nos2^+/+ mice (p = 0.007). Additionally, Nos2^+/+ mice had a higher number of H3K27ac-positive mild dysplasias when compared to Nos2^−/− (p = 0.023).

Conclusion

The pattern of histone acetylation changes in murine oral carcinogenesis, mainly when the epithelial lining of the tongue becomes dysplastic, and such epigenetic modifications might be iNOS-mediated.

背景：一氧化氮是细胞内稳态和病理状态的表观遗传景观的重要调节剂，其中表观基因组调节酶的翻译后修饰是最清楚描述的机制。考虑到组蛋白乙酰化模式的改变与口腔癌的发生发展相关，本研究的目的是分析4-硝基喹啉-n -氧化物（4NQO）诱导的Nos2+/+（野生型）和Nos2-/-（敲除型）小鼠不同阶段H3K9ac和H3K27ac的免疫组织化学表达。方法：将C57BL/6J和B6.129P2-Nos2tm1Lau/J小鼠以50 μg/mL的浓度给予4NQO治疗16周，观察8周。对舌进行组织病理学分析和免疫组化，检测H3K9ac和H3K27ac的表达。采用quickscore （QS）分析抗原抗体反应。结果：两种组蛋白乙酰化标记均在正常上皮中表达。Nos2-/-中度发育不良小鼠的QS值高于Nos2+/+组（p = 0.025），轻度发育不良小鼠的H3K9ac值低于Nos2-/-组的中度和重度发育不良小鼠（p = 0.015）。Nos2+/+小鼠的H3K27ac从正常黏膜到轻度发育不良显著升高（p = 0.007）。此外，与Nos2-/-相比，Nos2+/+小鼠具有更高数量的h3k27ac阳性轻度发育不良（p = 0.023）。结论：组蛋白乙酰化模式在小鼠口腔癌发生过程中发生改变，主要发生在舌上皮发育异常时，这种表观遗传改变可能是由inos介导的。

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引用次数: 0

A Unique Plasma Protein Signature Characterizes Squamous Cell Carcinoma of the Oral Tongue in Young Adults 一个独特的血浆蛋白特征特征的口腔舌鳞状细胞癌的年轻人。

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-06 DOI: 10.1111/jop.70020

Xiaolian Gu, Philip J. Coates, Lixiao Wang, Sivakumar Vadivel Gnanasundram, Nicola Sgaramella, Nima Attaran, Baris Erdogan, Mustafa Magan, Karin Nylander

Background

The incidence of squamous cell carcinoma of the oral tongue (SCCOT) among young adults is increasing in several regions of the world. Age-dependent differences in the biology of SCCOT have been suspected.

Methods

We used the Olink Explore 3072 high-throughput platform to comprehensively quantify plasma proteins in 24 young (≤ 40 years of age) and 50 old (> 50 years of age) individuals. Eight young and 20 old individuals were diagnosed with SCCOT, four young and nine old individuals with SCC at other oral subsites (SCCOO), and the remaining 12 young and 21 old individuals were healthy controls. Dimension reduction analysis, differential expression analysis, and functional enrichment analysis were performed to characterize young patient-specific biological signatures.

Results

Plasma levels of 2923 proteins were obtained. Principal component analysis indicated age-related expression patterns. Comparing young patients to young controls/old patients/old controls, differential abundance analysis showed that increases in protein levels of Peroxiredoxin 2 (PRDX2) and C-C motif chemokine ligand 26 (CCL26) and a decrease in Kallikrein related peptidase 4 (KLK4) were young patient-specific. Reactome pathway enrichment analysis identified “Cellular response to chemical stress,” “Detoxification of reactive oxygen species” and “Cellular responses to stimuli” as the top altered pathways in young patients with SCCOT.

Conclusions

Abnormal cellular stress and aberrant immune regulation could thus be linked to cancer development in young patients. The unique plasma proteomic signature observed in young patients with SCCOT suggests that they constitute a specific group with distinct underlying pathophysiological processes.

背景：在世界上的一些地区，年轻成人口腔舌鳞癌（SCCOT）的发病率正在增加。年龄依赖性的SCCOT生物学差异已被怀疑。方法：采用Olink Explore 3072高通量平台对24例年轻人（≤40岁）和50例老年人（≤50岁）的血浆蛋白进行综合定量。8名年轻人和20名老年人被诊断为SCCOT， 4名年轻人和9名老年人在其他口腔亚位（SCCOO）患有SCC，其余12名年轻人和21名老年人为健康对照。通过降维分析、差异表达分析和功能富集分析来表征年轻患者特异性的生物学特征。结果：获得血浆2923蛋白水平。主成分分析显示了与年龄相关的表达模式。将年轻患者与年轻对照组/老年患者/老年对照组进行比较，差异丰度分析显示，过氧化物氧还蛋白2 （PRDX2）和C-C基序趋化因子配体26 （CCL26）蛋白水平的升高和钾化因子相关肽酶4 （KLK4）蛋白水平的降低是年轻患者特异性的。Reactome通路富集分析发现，“细胞对化学应激的反应”、“活性氧解毒”和“细胞对刺激的反应”是年轻SCCOT患者中最重要的改变通路。结论：异常的细胞应激和异常的免疫调节可能与年轻患者的癌症发展有关。在年轻SCCOT患者中观察到的独特血浆蛋白质组学特征表明，他们构成了一个具有不同潜在病理生理过程的特定群体。

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引用次数: 0

Clinicopathological Study of Oncocytomas of Head and Neck Region: A Systematic Review 头颈部肿瘤细胞瘤的临床病理研究：系统综述。

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-06 DOI: 10.1111/jop.70022

João Paulo Gonçalves de Paiva, Laura Borges Kirschnick, Daniela Giraldo Roldán, Manoela Domingues Martins, Alan Roger Santos-Silva, Ciro Dantas Soares, Jacks Jorge

Background

Salivary gland oncocytomas are infrequent benign salivary gland tumors with few reported cases.

Aims

This study aimed to systematically review case reports and case series studies on oncocytomas in the head and neck region.

Materials & Methods

Electronic searches were performed in PubMed, Scopus, Web of Science, Embase, and LILACS databases. The risk of bias was assessed using the Joanna Briggs Institute—University of Adelaide tool for case reports and case series.

Results

A total of 99 studies (145 cases) were included. Oncocytomas predominantly affected women, typically presenting as solitary, asymptomatic parotid masses in patients over 51 years of age. Some cases reported multiple or bilateral tumors, occasionally associated with other salivary gland lesions. Histologically, the tumors were primarily composed of eosinophilic oncocytes with minimal pleomorphism, arranged in diverse architectural patterns. Immunohistochemical analysis revealed positivity for PTAH, antimitochondrial antigen, CK5/6, CK8/18, CK10/13, CK19, EMA, along with a low Ki67 index, while being negative for S100 and actin. Surgical excision was the primary treatment, with rare instances of recurrence.

Conclusion

Oncocytoma is a rare, benign neoplasm that most commonly arises in the parotid gland, with a predilection for female patients. Complete surgical excision constitutes the standard treatment and is associated with an excellent prognosis.

背景：唾液腺癌细胞瘤是罕见的良性唾液腺肿瘤，报道病例很少。目的：本研究旨在系统回顾头颈部肿瘤的病例报告和病例系列研究。材料与方法：在PubMed、Scopus、Web of Science、Embase和LILACS数据库中进行电子检索。使用乔安娜布里格斯研究所-阿德莱德大学的案例报告和案例系列工具评估偏倚风险。结果：共纳入99项研究（145例）。肿瘤细胞瘤主要影响女性，典型表现为孤立的，无症状的腮腺肿块，患者年龄超过51岁。一些病例报告多发性或双侧肿瘤，偶尔伴有其他唾液腺病变。组织学上，肿瘤主要由嗜酸性肿瘤细胞组成，具有最小的多形性，排列成不同的结构模式。免疫组化分析显示PTAH、抗线粒体抗原、CK5/6、CK8/18、CK10/13、CK19、EMA阳性，Ki67指数低，S100和actin阴性。手术切除是主要的治疗方法，很少有复发的情况。结论：嗜酸细胞瘤是一种罕见的良性肿瘤，常见于腮腺，多见于女性患者。完全手术切除是标准的治疗方法，预后良好。

{"title":"Clinicopathological Study of Oncocytomas of Head and Neck Region: A Systematic Review","authors":"João Paulo Gonçalves de Paiva, Laura Borges Kirschnick, Daniela Giraldo Roldán, Manoela Domingues Martins, Alan Roger Santos-Silva, Ciro Dantas Soares, Jacks Jorge","doi":"10.1111/jop.70022","DOIUrl":"10.1111/jop.70022","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Salivary gland oncocytomas are infrequent benign salivary gland tumors with few reported cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study aimed to systematically review case reports and case series studies on oncocytomas in the head and neck region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials & Methods</h3>\u0000 \u0000 <p>Electronic searches were performed in PubMed, Scopus, Web of Science, Embase, and LILACS databases. The risk of bias was assessed using the Joanna Briggs Institute—University of Adelaide tool for case reports and case series.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 99 studies (145 cases) were included. Oncocytomas predominantly affected women, typically presenting as solitary, asymptomatic parotid masses in patients over 51 years of age. Some cases reported multiple or bilateral tumors, occasionally associated with other salivary gland lesions. Histologically, the tumors were primarily composed of eosinophilic oncocytes with minimal pleomorphism, arranged in diverse architectural patterns. Immunohistochemical analysis revealed positivity for PTAH, antimitochondrial antigen, CK5/6, CK8/18, CK10/13, CK19, EMA, along with a low Ki67 index, while being negative for S100 and actin. Surgical excision was the primary treatment, with rare instances of recurrence.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Oncocytoma is a rare, benign neoplasm that most commonly arises in the parotid gland, with a predilection for female patients. Complete surgical excision constitutes the standard treatment and is associated with an excellent prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":16588,"journal":{"name":"Journal of Oral Pathology & Medicine","volume":"54 8","pages":"635-646"},"PeriodicalIF":2.3,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jop.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794758","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}

引用次数: 0

Tumor Cells-Derived FGF-2 Promotes Lymphangiogenesis as a Prognostic Marker in OSCC 肿瘤细胞来源的FGF-2促进淋巴管生成作为OSCC的预后标志物。

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-05 DOI: 10.1111/jop.70019

Jia Kang, Aoming Cheng, Guanzheng Chen, Lin Zhu, Zhengxue Han, Qiaoshi Xu

Background

The “cold” tumor microenvironment of oral squamous cell carcinoma (OSCC), where tumor-associated lymphatic vessels play a critical role in the transport of immune cells, is associated with a poor prognosis. However, the effect of tumor-induced lymphangiogenesis on CD8+ T cell infiltration and its role in the formation of the tumor immune microenvironment remain unclear.

Methods

We analyzed the prognostic significance of several lymphangiogenesis factors in OSCC with The Cancer Genome Atlas dataset, and confirmed the impact of fibroblast growth factor-2 (FGF-2) on prognosis in tissue specimens. Subsequently, we investigated the effects of FGF-2 on the proliferation, migration, and tube formation capacities of lymphatic endothelial cells, and CD8+ T cell infiltration through in vivo and in vitro experiments. Survival analysis was performed by Kaplan–Meier analysis and log-rank tests. The hazard ratio was calculated by Cox proportional hazards model.

Results

Patients with high FGF-2 levels and increased numbers of peritumoral lymphatic vessels were associated with a worse prognosis. Furthermore, we demonstrated that tumor cell-derived FGF-2 promoted lymphangiogenesis by regulating the FGFR1/PTEN/AKT axis and increased the secretion of CXCL9 to recruit and egress CD8+ T cells via neo-lymphatic vessels. PD-166866, an inhibitor of FGFR1, suppressed lymphangiogenesis and the secretion of CXCL9 to increase CD8+ T cell infiltration and inhibit tumor progression.

Conclusions

Our data suggest that FGF-2 is a significant prognostic factor that induces lymphangiogenesis and affects intratumoral CD8+ T cells, contributing to the formation of a “cold” tumor microenvironment in OSCC. FGF-2/FGFR1 could serve as an effective target for improving the prognosis of OSCC.

背景：口腔鳞状细胞癌（OSCC）的“冷”肿瘤微环境与预后不良有关，肿瘤相关淋巴管在免疫细胞的运输中起着关键作用。然而，肿瘤诱导的淋巴管生成对CD8+ T细胞浸润的影响及其在肿瘤免疫微环境形成中的作用尚不清楚。方法：利用the Cancer Genome Atlas数据集分析几种淋巴管生成因子在OSCC中的预后意义，并在组织标本中证实成纤维细胞生长因子-2 （FGF-2）对预后的影响。随后，我们通过体内和体外实验研究了FGF-2对淋巴内皮细胞增殖、迁移和成管能力以及CD8+ T细胞浸润的影响。生存分析采用Kaplan-Meier分析和log-rank检验。采用Cox比例风险模型计算风险比。结果：高FGF-2水平和瘤周淋巴管数量增加的患者预后较差。此外，我们证明肿瘤细胞来源的FGF-2通过调节FGFR1/PTEN/AKT轴促进淋巴管生成，并增加CXCL9的分泌，通过新淋巴管招募和输出CD8+ T细胞。PD-166866是FGFR1的抑制剂，可抑制淋巴管生成和CXCL9的分泌，从而增加CD8+ T细胞浸润，抑制肿瘤进展。结论：我们的数据表明，FGF-2是一个重要的预后因子，可诱导淋巴管生成并影响肿瘤内CD8+ T细胞，促进OSCC“冷”肿瘤微环境的形成。FGF-2/FGFR1可作为改善OSCC预后的有效靶点。

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引用次数: 0

Daughter Cells Budding From PGCCs and Their Clinicopathological Significances in Oral Squamous Cell Carcinoma 口腔鳞状细胞癌中pgcc出芽的子细胞及其临床病理意义。

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

Journal of Oral Pathology & Medicine

Pub Date : 2025-08-05 DOI: 10.1111/jop.70014

Shanshan Zhuo, Chao Jing, Xiaonan Liu, Jiuling Yue, Wenchao Zhang, Shiwu Zhang

Objective

Polyploid giant cancer cells (PGCCs) have emerged as a focal point in tumorigenesis and progression research. Present across various tumor tissues, PGCCs are considered a potential target for anti-tumor strategies. Nonetheless, their presence and role in oral squamous cell carcinoma (OSCC) remain undocumented. This study investigated the presence and count of PGCCs in OSCC tissues, evaluated their association with clinicopathological factors, and preliminarily examined the mechanisms underlying their formation alongside their influence on OSCC proliferation, drug resistance, and migratory capacity.

Methods

The correlation between PGCC counts and clinical outcomes in OSCC was evaluated. CoCl₂ treatment was used to induce PGCC formation in OSCCUM1 cells, and alterations in HIF-1α, SOX-2, E-cadherin, and N-cadherin expression, along with changes in cellular proliferation, drug resistance, and migratory capacity, were assessed.

Results

Among 76 OSCC patients, PGCC counts were linked to clinical stage, histological grade, and chemotherapy response. Patients with > 3 PGCCs/HP exhibited significantly poorer overall and disease-free survival compared to those with ≤ 3 PGCCs/HP. Following the induction of polyploid giant cancer cells with budding cells, miRNA analysis revealed upregulated SOX-2 expression, while Western blot demonstrated increased protein levels of HIF-1α, SOX-2, and N-cadherin, accompanied by reduced E-cadherin expression. Induced PGCCs with budding cells also exhibited enhanced proliferation, resistance to chemotherapy, and migratory capacity.

Conclusion

Hypoxic conditions may promote OSCC proliferation, chemoresistance, and migration through the formation of PGCCs with budding cells characterized by epithelial-mesenchymal transition and stemness phenotypes.

目的：多倍体巨细胞（Polyploid giant cancer cells, PGCCs）已成为肿瘤发生发展研究的热点。存在于多种肿瘤组织中，pgcc被认为是抗肿瘤策略的潜在靶点。尽管如此，它们在口腔鳞状细胞癌（OSCC）中的存在和作用仍未得到证实。本研究调查了鳞癌组织中pgcc的存在和计数，评估了它们与临床病理因素的关系，并初步探讨了它们形成的机制以及它们对鳞癌增殖、耐药性和迁移能力的影响。方法：评价鳞癌患者PGCC计数与临床预后的相关性。使用CoCl2处理诱导OSCCUM1细胞形成PGCC，并评估HIF-1α、SOX-2、E-cadherin和N-cadherin表达的变化，以及细胞增殖、耐药性和迁移能力的变化。结果：在76例OSCC患者中，PGCC计数与临床分期、组织学分级和化疗反应有关。与≤3 PGCCs/HP的患者相比，bbb3 PGCCs/HP患者的总生存期和无病生存期明显较差。在诱导多倍体巨细胞出芽后，miRNA分析显示SOX-2表达上调，而Western blot显示HIF-1α、SOX-2和N-cadherin蛋白水平升高，同时E-cadherin表达降低。带出芽细胞的诱导pgcc也表现出增强的增殖、化疗抗性和迁移能力。结论：缺氧条件可能通过形成以上皮间质转化和干性表型为特征的出芽细胞pgcc，促进OSCC增殖、耐药和迁移。

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引用次数: 0