Cytojournal最新文献

{"title":"Aberrations in the glycosylation of receptor tyrosine kinases: A focus on lung adenocarcinoma.","authors":"Anna M Dmitrieva, Ilayda G Kocak, Lydia Meder","doi":"10.25259/Cytojournal_21_2025","DOIUrl":"10.25259/Cytojournal_21_2025","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer-related deaths worldwide, with genetic- and protein-based diagnostics playing a crucial role in disease detection and improving patient outcomes. Glycosylation, a major post-translational modification, has recently emerged as a factor influencing cancer progression, immune evasion, and therapeutic resistance. Aberrant glycosylation patterns, particularly among receptor tyrosine kinases (RTKs), have been shown to modulate oncogenic signaling pathways and influence tumor growth. This review provides a comprehensive overview of how glycosylation alterations affect the stability, function, and therapeutic targeting of key RTKs relevant in lung adenocarcinoma: Epidermal growth factor receptor, human epidermal growth factor receptor 2, and cellular mesenchymal-epithelial transition factor, rearranged during transfection, anaplastic lymphoma kinase, and ROS proto-oncogene 1 receptor tyrosine kinase. Despite substantial advances in targeted therapies, initial and acquired resistance remain a major challenge in the treatment of lung cancer. There is growing evidence that strategies targeting glycosylation can be combined with established treatment protocols to help overcome resistance. Finally, we propose future directions for the advancement of glycosylation-based approaches to improve precision medicine.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"62"},"PeriodicalIF":3.1,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microfibrillar-associated protein-2 facilitates aggressive progression of oral squamous cell carcinoma cells through Kelch-like E3 ubiquitin ligase-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling pathway.","authors":"Wanzhen Yang, Junyi Tu, Kaixi Dai, Kemin Jia","doi":"10.25259/Cytojournal_53_2025","DOIUrl":"10.25259/Cytojournal_53_2025","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to explore the role of microfibrillar-associated protein-2 (MFAP2) in oral squamous cell carcinoma (OSCC).</p><p><strong>Material and methods: </strong>Analysis of MFAP2 expression in diverse cancers and its relationship with head-and-neck squamous cell carcinoma (HNSC) prognosis. MFAP2 abundance was identified in OSCC cells and in human oral epithelial cells using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays. Knockdown and overexpression techniques were utilized to examine the mechanism by which MFAP2 and nuclear factor erythroid 2-related factor 2 (NRF2) affect OSCC malignancy. Cell viability, proliferation, and apoptosis were assessed using cell counting kit-8, colony formation, flow cytometry, wound healing, and Transwell tests. Messenger ribonucleic acid expression was detected using qRT-PCR, whereas protein level was analyzed using Western blot.</p><p><strong>Results: </strong>MFAP2 and Kelch-like E3 ubiquitin ligase (ECH)-associated protein 1 (KEAP1) had high expression levels in numerous tumors, including OSCC, and the high expression level of MFAP2 was associated with unfavorable HNSC outcomes. MFAP2 was abundantly expressed in five OSCC cell lines, with the peak expression observed in squamous cell carcinoma (SCC)-15 and SCC-9 cells, making them suitable for subsequent studies. MFAP2 knockdown hindered the proliferative and mobile capacity of OSCC cells, yet it supported cell apoptosis. MFAP2 silencing led to a notable drop in KEAP1 and NRF2 expression levels in OSCC cells. NRF2 overexpression could counteract the effects of MFAP2 knockout, which included diminished proliferation and movement and heightened apoptosis in OSCC cells.</p><p><strong>Conclusion: </strong>The results of this study indicated that MFAP2 facilitated the malignant progression of OSCC and provided insights into the downstream regulatory mechanism of the KEAP1/NRF2 axis, highlighting the potential application of MFAP2 in OSCC management.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"61"},"PeriodicalIF":3.1,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of 15-hydroxyprostaglandin dehydrogenase protein inhibiting cervical cancer cell proliferation through downregulation of the notch1 signaling pathway.","authors":"Suwen Chang","doi":"10.25259/Cytojournal_57_2025","DOIUrl":"10.25259/Cytojournal_57_2025","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aims to explore the modulatory effect of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) protein in the Notch1 signaling pathway in cervical cancer (CC) cells and assess how this modulation affects the proliferation and migration of CC cells. Moreover, this study offers fresh perspectives on the molecular mechanisms underlying CC by thoroughly analyzing the relationship between 15-PGDH and the Notch1 signaling pathway, and investigates the therapeutic potential of 15-PGDH.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Material and methods: &lt;/strong&gt;Human normal cervical epithelial cells and CC cell lines (human CC cell line [HeLa], human cervical squamous carcinoma cell line [Caski], and human cervical epidermoid carcinoma cells [ME180]) were selected as experimental models. Western blotting (WB) and quantitative reverse transcription polymerase chain reaction were performed to evaluate the protein and messenger RNA levels of 15-PGDH and Notch receptor 1 (Notch1) signaling pathway-related proteins (Jagged canonical Notch ligand 1 [Jagged1] and Hes family bHLH transcription factor 1 [Hes1]). Results suggested that the HeLa and Caski cells exhibited significant expression of 15-PGDH and Notch1 signaling-related proteins. A series of experiments, including WB, cell counting kit-8 assay, Transwell migration assay, and 5-ethynyl-2'-deoxyuridine assay, was conducted in the HeLa and Caski cells to obtain an extensive understanding of how 15-PGDH influences Notch1 signaling regulation. This study also utilized the 15-PGDH inhibitor SW033291 and a Notch1 overexpression vector to evaluate the effect of 15-PGDH on CC cell growth, motility, and Notch1 signaling pathway modulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Results demonstrated that in the normal human cervical epithelial cells, 15-PGDH was highly expressed, while the Notch1 signaling pathway-related proteins exhibited low expression quantities. However, in HeLa and Caski CC cells, 15-PGDH expression was significantly downregulated (&lt;i&gt;P&lt;/i&gt; &lt; 0.001 or &lt;i&gt;P&lt;/i&gt; &lt; 0.01), whereas the Notch1 signaling pathway was activated. Further studies revealed that 15-PGDH or its inhibitor influenced the stimulation of the Notch1 signaling pathway in the HeLa and Caski cells. Specifically, the 15-PGDH inhibitor SW033291 reduced 15-PGDH expression (&lt;i&gt;P&lt;/i&gt; &lt; 0.001 or &lt;i&gt;P&lt;/i&gt; &lt; 0.01) and promoted Notch signaling activation. Meanwhile, 15-PGDH upregulation suppressed Notch signaling activation. Furthermore, 15-PGDH successfully prevented the proliferation and migration of CC cells induced by Notch1 overexpression and reduced the activation of the Notch signaling pathway, as shown by the downregulation of Notch1 and its downstream effectors, Jagged1 and Hes1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;This study highlights the role of 15-PGDH in regulating the Notch1 signaling pathway in CC cells, focusing on its effect on cell proliferation and migration. The results demonstrate that 15-PGDH suppresses CC cell prolif","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"59"},"PeriodicalIF":3.1,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial autophagy inhibits nucleotide-binding oligomerization domain-like receptor protein 3-mediated pyroptosis and alleviates endothelial cell injury in pregnancy-induced hypertension.","authors":"Mengsi Zhang, Xiangzhen Zhang, Leilei Mao","doi":"10.25259/Cytojournal_52_2025","DOIUrl":"10.25259/Cytojournal_52_2025","url":null,"abstract":"<p><strong>Objective: </strong>Pregnancy-induced hypertension (PIH) is a common complication during pregnancy and is closely associated with vascular endothelial cell damage and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis. This study aimed to investigate whether mitophagy alleviates vascular endothelial cell damage in PIH by inhibiting NLRP3-mediated pyroptosis. The regulatory mechanisms of pyroptosis-related pathways were systematically investigated by establishing a cellular model of PIH and incorporating mitophagy intervention.</p><p><strong>Material and methods: </strong>An Nω-nitro-L-arginine methyl ester (L-NAME)-induced gestational hypertension model was established, and the cell samples were grouped as follows: Control group (Control), L-NAME-induced gestational hypertension group (L-NAME), mitochondrial autophagy inhibition group (L-NAME+ 3-methyladenine [3-MA]), and mitochondrial autophagy activation group (L-NAME+ rapamycin [Rapa]). Cell viability was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, lactate dehydrogenase (LDH) levels were measured to evaluate cell damage, and reactive oxygen species (ROS) kits were used to quantify ROS accumulation. Cell death was evaluated using terminal deoxynucleotidyl transferase dUTP nick end labeling staining to detect apoptotic cells. Immunofluorescence, Western blot analysis, and quantitative real-time polymerase chain reaction were performed to assess the expression levels of proteins and genes associated with mitophagy (e.g., microtubule-associated protein 1 light chain 3 and sequestosome 1) and those linked to pyroptosis (e.g., NLRP3, gasdermin D (GSDMD), cysteinyl aspartate-specific proteinase 1 (caspase-1), interleukin (IL)-1β, and IL-18). The role of NLRP3 in pyroptosis regulation through mitochondrial autophagy was further examined using NLRP3 small interfering RNA (siNLRP3) transfection experiments.</p><p><strong>Results: </strong>L-NAME treatment substantially decreased vascular endothelial cell viability, elevated LDH release and ROS levels, and upregulated pyroptosis-related proteins (NLRP3, GSDMD, and caspase-1) and inflammatory factors (IL-1β and IL-18). The inhibition of mitochondrial autophagy with 3-MA further enhanced pyroptosis and aggravated cell damage, and its activation with Rapa reduced pyroptosis, improved cell survival, and decreased LDH release and ROS levels. NLRP3 silencing (siNLRP3) significantly inhibited pyroptosis and alleviated the cell damage caused by 3-MA. Meanwhile, Rapa enhanced the protective effect of NLRP3 silencing.</p><p><strong>Conclusion: </strong>This study demonstrates that mitophagy can effectively alleviate the vascular endothelial cell damage associated with PIH by inhibiting NLRP3-mediated pyroptosis. The findings provide new theoretical support for the treatment of PIH and suggest potential intervention targets.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"60"},"PeriodicalIF":3.1,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289115/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoscopic ultrasound-guided fine-needle aspiration value in suspected autoimmune pancreatitis malignancy diagnosis.","authors":"Yue Liu, Dongling Wan, Chang Wu, Deyu Zhang, Jiaheng Xu, Wanshun Li, Zhenghui Yang, Jiayu Li, Ying Chen, Zhendong Jin, Haojie Huang","doi":"10.25259/Cytojournal_214_2024","DOIUrl":"10.25259/Cytojournal_214_2024","url":null,"abstract":"<p><strong>Objective: </strong>Histopathology examination is important for diagnosing autoimmune pancreatitis (AIP), which is suspected to be pancreatic cancer based on imaging findings. Although the validity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in the diagnosis of AIP is still debated globally, this study aimed to evaluate the efficacy of EUS-FNA in the diagnosis of AIP with suspected pancreatic cancer.</p><p><strong>Material and methods: </strong>From January 2021 to June 2024, 30 AIP patients with radiographically diagnosed pancreatic cancer were enrolled and underwent EUS-FNA. Sex, age, symptoms, CA199, serum immunoglobulin G4 (IgG4), and treatment outcome were included. Tissue sampling conditions, puncture sites, storiform fibrosis, CD38- and IgG4-positive plasma cell counts, and obliterans phlebitis were evaluated.</p><p><strong>Results: </strong>Thirty patients, 24 males and six females, with an average age of 60.53 ± 11.72 years (32-79 years), were included in the study. Thirty patients had their serum IgG4 and CA199 levels tested. Tissue samples containing ≥10 were obtained from 19 (63.33%) patients. CD38+ plasma cell infiltration and laminar fibrosis were detected in 22 (73.33%) and 10 (33.33%) patients. According to the International Consensus Diagnostic Criteria ( ICDC), 12 patients had histopathological levels of Grade 1, 15 of Grade 2, and three patients could not be classified. The accuracy, sensitivity, and specificity of EUS-FNA in diagnosing AIP with suspected pancreatic cancer on imaging were 96.66% (29/30), 96.42% (27/28), and 100% (2/2), respectively. The area under the curve value of EUS-FNA for patients with AIP who were radiologically suspected of having pancreatic cancer was 0.957.</p><p><strong>Conclusion: </strong>Approximately 90% of patients with EUS-FNA results are diagnosed with an ICDC level of 2 or higher. Our results suggest that for cases where malignant tumors are suspected after imaging or cannot be ruled out, obtaining pancreatic tissue through EUS-FNA puncture for pathological diagnosis is recommended.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"58"},"PeriodicalIF":3.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-determining region Y-Box 4 promotes the progression of advanced hepatocellular carcinoma and enhances regulatory T-cell infiltration and immune suppression.","authors":"Yingxia Jing, Yunlong Wu","doi":"10.25259/Cytojournal_27_2025","DOIUrl":"10.25259/Cytojournal_27_2025","url":null,"abstract":"<p><strong>Objective: </strong>This study examined the role of sex-determining region Y-box 4 (SOX4) in sorafenib-resistant hepatocellular carcinoma (HCC) cells and its potential therapeutic relevance by focusing on the effects of SOX4 knockdown on tumor growth, apoptosis, and immune infiltration.</p><p><strong>Material and methods: </strong>A sorafenib-resistant HCC cell line (sorafenib-resistant HepG2 [SR-HepG2]) was established by gradually increasing the sorafenib dose (1-7 μM) over 12 months. The messenger RNA and protein expression levels of SOX4 in HepG2 and SR-HepG2 cells were analyzed by a quantitative reverse transcription-polymerase chain reaction and Western blot. Small interfering RNA (SOX4) or SOX4 overexpression plasmids were introduced into SR-HepG2 cells through transfection, and the effects on cell proliferation, colony formation, and apoptosis were evaluated using 5-ethynyl-2'-deoxyuridine staining, colony formation assays, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. For <i>in vivo</i> experiments, HepG2 or SR-HepG2 cells were subcutaneously injected into BALB/c nude mice to monitor tumor growth. In the sorafenib-resistant HCC mouse model, SOX4 knockdown (small-interfering RNA SOX4 [si-SOX4]) was delivered through lentiviral vectors to assess its effect on tumor growth. Immune cell infiltration was assessed by immunofluorescence staining, and the influences on immune escape markers were evaluated by Western blot.</p><p><strong>Results: </strong>Compared with those in the parental HepG2 cells, the transcriptional and translational expression levels of SOX4 were significantly elevated in the SR-HepG2 cells (<i>P</i> < 0.001). Si-SOX4 markedly suppressed the proliferation and colony formation of SR-HepG2 cells and increased their cell apoptosis (<i>P</i> < 0.001). <i>In vivo</i> experiments revealed that si-SOX4 inhibited tumor growth in the sorafenib-resistant HCC model, accompanied by a significant reduction in tumor volume and weight (<i>P</i> < 0.001). Histological analysis showed that si-SOX4 disrupted the tumor structure, characterized by increased necrosis and reduced collagen fibers. In addition, si-SOX4 decreased the infiltration of Forkhead box P3+regulatory T cells and cluster of differentiation 11b + myeloid-derived suppressor cells while increasing the number of cluster of differentiation 8 (CD8)+ T cells and granzyme B + CD8+ cytotoxic T cells (<i>P</i> < 0.001). SOX4 knockdown also reduced the expression of two immune escape markers, programmed cell death ligand 1 and C-C motif chemokine ligand 12 (<i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>SOX4 overexpression drives sorafenib resistance in HCC cells by promoting cellular growth, inhibiting apoptosis, and enhancing immune evasion. Conversely, SOX4 knockdown inhibits tumor growth, alters immune cell infiltration, and reduces immune escape. Hence, targeting SOX4 is a promising therapeutic approach to overcome sorafenib resistan","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"56"},"PeriodicalIF":3.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic accuracy of fine-needle aspiration cytology for extrathyroidal head-and-neck lesions performed by a cytopathologist with the assistance of radiologist: A single-center study.","authors":"Busra Yaprak Bayrak, Nadir Paksoy","doi":"10.25259/Cytojournal_247_2024","DOIUrl":"10.25259/Cytojournal_247_2024","url":null,"abstract":"<p><strong>Objective: </strong>In recent years, several publications have described the use of ultrasound-guided fine-needle aspiration (FNA) by cytopathologists to achieve better diagnostic accuracy. Some cytopathologists enroll in courses to learn and apply ultrasound (US) guidance themselves. However, no standard procedure has been established that cytopathologists can follow to perform US for FNA. Alternatively, FNA can be a useful tool when cytopathologists collaborate with radiologists. Here, we aimed to evaluate the diagnostic accuracy of FNA for non-thyroidal head-and-neck masses retrieved by a cytopathologist with US guidance provided by a radiologist.</p><p><strong>Material and methods: </strong>The FNA results for non-thyroidal head-and-neck masses at a private clinic using the Scandinavian FNA model with radiologist‒cytopathologist collaboration were compared with the histopathology results.</p><p><strong>Results: </strong>In all, 1890 patients who underwent FNA were identified, among whom 1435 (76%) also had histopathological results. Non-cystic lesions were obtained from lymph nodes (LNs), salivary glands, and soft tissue, while the other lesions were cystic in nature. For FNA, the accuracy was 99.4%, the sensitivity was 99.6%, the specificity was 99.3%, the positive predictive value was 99.3%, and the negative predictive value was 99.6%. No FNA results were non-diagnostic. Surgical follow-up revealed that only eight of the 1435 assessments (0.5%), all performed for LN lesions, yielded false-negative or false-positive results.</p><p><strong>Conclusion: </strong>The present study is based on single-center observations. The use of FNA, when performed by a specialized cytopathologist and with US assistance from a radiologist, produces accurate results and sufficient material for analysis, especially for LNs in extrathyroidal head-and-neck lesions. This study also reveals that the technique is a low-cost and effective process. The way in which FNA is presented here indicates that this procedure would be useful and ideal for any health service.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"57"},"PeriodicalIF":3.1,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proposal for including risk of malignancy and clinical management in the Japanese system for reporting thyroid cytopathology - A multi-institutional study.","authors":"Mitsuyoshi Hirokawa, Ryohei Katoh, Takashi Amano, Tomohiro Chiba, Naoko Yamazaki, Shinya Satoh, Miyuki Towata, Yasuyo Ohi, Yukari Maeda, Mitsuhiro Fukushima, Eiji Sasaki, Hironao Yasuoka, Miyoko Higuchi, Ayana Suzuki, Takashi Akamizu","doi":"10.25259/Cytojournal_229_2024","DOIUrl":"10.25259/Cytojournal_229_2024","url":null,"abstract":"<p><strong>Objective: </strong>The Japanese System for Reporting Thyroid Cytopathology (JSRTC) does not include the risks of malignancies (ROMs) or recommended clinical management. This multi-institutional study aimed to determine the frequency, re-aspiration rate, resection rate, ROM, and clinical management options in seven different categories.</p><p><strong>Material and methods: </strong>For 15,495 cases of thyroid fine-needle aspiration performed at seven Japanese institutions without molecular testing, the frequency, re-aspiration rate, resection rate, ROM, and clinical management options of each diagnostic category were examined. The categorization was based on JSRTC, and cases were subdivided into those with nuclear atypia and other subtypes for undetermined significance.</p><p><strong>Results: </strong>Re-aspiration of unsatisfactory and undermined significance diagnostic categories was mainly performed for cases of suspected malignancy on ultrasound. The median re-aspiration rate of cyst fluid nodules was 4.9%, which was significantly different from that (17.8%) of unsatisfactory cases (<i>P</i> < 0.05). The resected ROMs for nodules that were suspicious for malignancy and malignant were 94.2% and 99.6%, respectively. The low resection rates of nodules that were suspicious for malignancy (77.8%) and malignant (70.8%) could be attributed to active surveillance for low-risk papillary microcarcinoma. The overall ROMs of unsatisfactory, cyst fluid, benign, undetermined significance, and follicular neoplasms were 4.5%, 0.4%, 0.7%, 16.7%, and 11.4%, respectively. In the subtype of undetermined significance, the overall ROM of nuclear atypia (27.6%) was higher than that of the others (6.7%).</p><p><strong>Conclusion: </strong>Overall, this study determines the frequency, ROM, and recommended clinical management for thyroid cytopathology in Japan. These results were different from those proposed by the Bethesda System for Reporting Thyroid Cytopathology. In the future, our results will be helpful in the revision of JSRTC and will contribute to improving the outcomes among Japanese patients with thyroid nodules.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"55"},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of forkhead box protein P2-mediated activation of myosin light-chain kinase on the invasion and migration of endometrial cancer cells.","authors":"Suwen Chang","doi":"10.25259/Cytojournal_31_2025","DOIUrl":"10.25259/Cytojournal_31_2025","url":null,"abstract":"<p><strong>Objective: </strong>Endometrial cancer (EC) ranks among the most prevalent malignant tumors affecting women, with metastasis and dissemination as the major contributors to poor prognosis. This study explores the involvement of forkhead box protein P2 (FOXP2) in EC cell invasion and migration, which is mediated through the activation of myosin light-chain kinase (MYLK).</p><p><strong>Material and methods: </strong>Bioinformatic analysis was conducted to determine whether FOXP2 is expressed in EC. FOXP2 overexpression was achieved using a FOXP2 overexpression vector (oeFOXP2), and negative control (NC) was used for cell transfection. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, enzyme-linked immunosorbent assay, colony formation, wound healing, and Transwell assay were used to assess the capabilities of cell viability, invasion, migration, and proliferation. Western blot and quantitative real-time polymerase chain reaction (qRTPCR) analysis were used to measure the expression levels of proteins linked to the epithelial-mesenchymal transition. The correlation between FOXP2 and MYLK was analyzed using bioinformatics and validated by Western blot and qRT-PCR analysis. The MYLK-specific inhibitor ML-7 was employed to study the impact of MYLK-mediated FOXP2 on regulating the malignant biological processes of EC.</p><p><strong>Results: </strong>The oeFOXP2 group of EC cells exhibited a significant decrease in cell viability, colony formation, migration rate, and metastatic cell count compared with the NC group (<i>P</i> < 0.05). FOXP2 overexpression markedly increased caspase-3, caspase-8, caspase-9 activity (<i>P</i> < 0.05). Significant changes were detected in the expression of epithelial-mesenchymal transition marker proteins, with vimentin and N-cadherin expression noticeably declining and E-cadherin expression sharply rising (<i>P</i> < 0.05). The addition of the MYLK-specific inhibitor ML-7 reversed the effect of FOXP2 overexpression on the invasion and migration of EC cells.</p><p><strong>Conclusion: </strong>FOXP2 suppresses the proliferation, invasion, and migration of EC cells through the activation of MYLK.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"54"},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178083/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration on the potential predictive value of regulator of G-protein signaling 2 in the efficacy of concurrent chemoradiotherapy on cervical squamous cell carcinoma.","authors":"Yi Liu, Jie Xu, Xiaofeng Zou, Li Li","doi":"10.25259/Cytojournal_225_2024","DOIUrl":"10.25259/Cytojournal_225_2024","url":null,"abstract":"<p><strong>Objective: </strong>Concurrent chemotherapy and radiotherapy (CCRT) has been applied as a therapeutic modality for cervical squamous cell carcinoma (CESC). Our aim is to investigate the potential marker(s) of the efficacy of CCRT in CESC.</p><p><strong>Material and methods: </strong>Potential candidates predictive of the efficacy of CCRT in CESC were identified. Differentially expressed genes (DEGs) were screened, followed by performing functional enrichment analyses. CCRT-related biomarkers were identified. In addition, the CIBERSORT algorithm was employed to determine the immune cell infiltration. Immune cell subsets from donors and specific cytokines were evaluated, and the biological functions of CESC cells following cisplatin treatment or coculture with M2 macrophages were explored.</p><p><strong>Results: </strong>A total of 56 DEGs were singled out. These DEGs were enriched in pathways relevant to CESC and CCRT. They were narrowed down to eight CCRT-related biomarkers with good predictive values. Notably, most of the biomarkers were negatively correlated with M2 macrophages (<i>P</i> < 0.05), and regulator of G-protein signaling 2 (RGS2) exhibited low expression in CESC (<i>P</i> < 0.05). Flow cytometry results revealed that patients with CCRT-resistant CESC had high percentages of M2 macrophages, CD4 T cells, regulatory T cells and T helper 2 cells but low percentages of T helper 1 cells, and T helper 17 cells, M1 macrophages, and CD8 T cells (<i>P</i> < 0.05). Aside from interleukin (IL4) and IL-10, the remaining specific cytokines exhibited low expression in patients with CCRT-resistant CESC (<i>P</i> < 0.05). Furthermore, the cell cycle progression and metastasis of CESC cells were evidently promoted by M2 macrophages but were suppressed by cisplatin intervention (<i>P</i> < 0.05). Moreover, in CESC cells, cisplatin repressed the levels of IL-4 and IL-10 yet boosted those of the remaining cytokines, whereas M2 macrophages had the opposite effects (<i>P</i> < 0.05). RGS2 silencing promoted the phosphorylation of phosphatidylinositol 3-kinase/protein kinase B/transcriptional signal transducer and activator 6 in macrophages, whereas RGS2 overexpression had the opposite effect (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>This study interpreted and explored the possible predictive values of RGS2 in the efficacy of CCRT in CESC. It may provide other insights for the management of CESC.</p>","PeriodicalId":49082,"journal":{"name":"Cytojournal","volume":"22 ","pages":"53"},"PeriodicalIF":2.5,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}