1.MMP9 and ADNP Gene Expressions in Secondary Bone Metastasis of Locally Advanced Nasopharyngeal Cancer
Rahmat Cahyanur ; Cosphiadi Irawan ; Lisnawati Rachmadi ; Marlinda Adham ; Achmad Fauzi Kamal ; Achmad Rusdan Handoyo Utomo ; Mardiah Suci Hardianti ; Thariqah Salamah ; Muchtaruddin Mansyur
Acta Medica Indonesiana 2026;58(1):59-66
Abstract
Background: Nasopharyngeal cancer (NPC) is a malignancy of the nasopharyngeal mucosal epithelium. Primary and secondary metastases in nasopharyngeal cancer are generally prevalent in the bones. Gene expression plays a critical role in regulating fundamental cellular processes in cancer cells, including metastasis. Methods: A total of 29 patients with non-metastatic NPC were included in the study. Results: The mean age of the participants was 48.45±9.98 years old. Most participants were male (75.9%). More than half of the participants had T4 and N2, 52.7% and 51.0% respectively). Secondary metastasis was observed in 9 of the 29 participants within two years. Patients with secondary metastases had a higher proportion of T4 (7/9) and N2 (4/9) disease. Bone was the first site of secondary metastasis (6/9 patients). The median time to secondary bone metastasis was 14.0 (6.8-21.2) months. Based on the differential expression gene (DEG) analysis, the MMP9 gene was upregulated 12.50 (4.18–37.40), adjusted p <0.01, and the ADNP gene was downregulated 0.141 (0.04–0.43), adjusted p 0.04, among patients with secondary bone metastasis. Conclusion: Bones are the first site of metastasis, with a time to metastasis of 14.0 (6.8-21,2) months. MMP9 was upregulated, and ANDP was downregulated in patients with bone metastasis compared to those without metastasis.
MMP-9
;
ADNP
;
nasopharyngeal cancer
;
secondary bone metastasis
2.Ectopic Hepatocellular Carcinoma in the Mediastinum with Brain Metastasis: A Rare Case Report
Vidi Prasetyo Utomo ; Shinta Oktya Wardhani
Acta Medica Indonesiana 2026;58(1):88-93
Abstract
Ectopic hepatocellular carcinoma (EHCC) is an extremely rare neoplasm, especially in the mediastinum, which shares morphologic characteristics with intrahepatic hepatocellular carcinoma (HCC). Its clinical features remain unclear, posing significant diagnostic and therapeutic challenges. The prognosis is also unclear due to its rarity and potential variability. This study reports the first case of EHCC in the mediastinum with subsequent brain metastasis. A 50-year-old man presented with shoulder and chest discomfort persisting for 5 months, accompanied by progressive weight loss and fatigue over the preceding 2 years. Imaging showed a mediastinal mass initially suspected to be lymphoma due to its malignant characteristics. However, histopathological examination identified the lesion as HCC, supported by characteristic immunohistochemical markers, despite normal abdominal imaging. Two months later, the tumor progressed despite intensive radiotherapy, and the patient experienced recurrent seizures. Subsequent brain imaging confirmed multiple intracranial metastases. Unfortunately, the patient died 6 months after diagnosis. The ectopic liver is more susceptible to hepatocarcinogenesis than the main liver; this is attributed to its incomplete functional structure. EHCC can be considered as differential diagnosis of mediastinal masses, even when no intrahepatic HCC is found. The rarity of EHCC in the mediastinum poses difficulties in developing treatment protocols. This case emphasizes the diagnostic challenges and aggressive nature of ectopic HCC and the need for comprehensive management strategies. There are currently no definite guidelines regarding the diagnosis, treatment, and prognosis of EHCC.
ectopic hepatocellular carcinoma
;
mediastinum
;
metastasis
3.Potential molecular mechanism of lncRNAs HOTAIR in malignant metastasis of esophageal cancer.
Kaijin LU ; Jiangfeng SHEN ; Guang HAN ; Quan CHEN
Chinese Journal of Cellular and Molecular Immunology 2025;41(3):236-244
Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans
;
RNA, Long Noncoding/metabolism*
;
Esophageal Neoplasms/metabolism*
;
Cell Movement/genetics*
;
Cell Proliferation/genetics*
;
Cell Line, Tumor
;
Esophageal Squamous Cell Carcinoma
;
Exosomes/genetics*
;
Neoplasm Metastasis
;
Neoplasm Invasiveness
;
Gene Expression Regulation, Neoplastic
;
Glycolysis/genetics*
;
Cancer-Associated Fibroblasts/metabolism*
;
Carcinoma, Squamous Cell/metabolism*
;
Cadherins/genetics*
4.Phospholipase Cβ1 (PLCB1) promotes gastric adenocarcinoma metastasis by inducing epithelial mesenchymal transition and inhibiting tumour immune infiltration and is associated with poor patient prognosis.
Lingping YUE ; Junfeng CHEN ; Qianqian GAO
Chinese Journal of Cellular and Molecular Immunology 2025;41(5):444-449
Objective To investigate whether PLCB1 expression leads to gastric adenocarcinoma metastasis and poor prognosis, and to preliminarily analyze its mechanism. Methods 122 gastric adenocarcinoma patients and their adjacent non-cancerous tissues were selected, and tissue microarray technology was used to detect the expression levels of PLCB1, epithelial cadherin(E-cadherin), vimentin and CD8+ T cells by immunohistochemistry, and scored by two pathologists. According to the immunohistochemical score of PLCB1, the patients were divided into PLCB1 high expression group (IHC>90) and PLCB1 low expression group (IHC≤90). The clinical pathological characteristics, epithelial mesenchymal transition(EMT)-related proteins and CD8+ T cells expression differences between the two groups were compared. The overall survival of the patients was collected, and COX regression analysis and Kaplan-Meier curve were used to evaluate the relationship between PLCB1 expression level and prognosis. Results PLCB1 was highly expressed in 55 cases of gastric adenocarcinoma tissues, while only 12 cases in adjacent non-cancerous tissues. The tumor invasion depth, lymph node metastasis degree and TNM stage of the PLCB1 high expression group were higher than those of the PLCB1 low expression group. Chi-square test showed that PLCB1 expression level was negatively correlated with E-cadherin (r=-0.339), positively correlated with vimentin (r=0.211), and negatively correlated with CD8+ T cells (r=-0.343). Kaplan-Meier curve analysis showed that the overall survival and disease-free survival of gastric adenocarcinoma patients with high PLCB1 expression were significantly reduced. Multivariate COX regression analysis showed that except for lymph node metastasis, tumor invasion depth, TNM stage, E-cadherin and vimentin were also independent prognostic factors for gastric adenocarcinoma patients. Conclusion PLCB1 is highly expressed in gastric adenocarcinoma, and is closely related to tumor aggressiveness and prognosis. PLCB1 may induce EMT and inhibit CD8+ T cell infiltration to affect gastric adenocarcinoma metastasis and immune response.
Humans
;
Stomach Neoplasms/genetics*
;
Epithelial-Mesenchymal Transition
;
Male
;
Female
;
Middle Aged
;
Prognosis
;
Adenocarcinoma/genetics*
;
Cadherins/metabolism*
;
Aged
;
Adult
;
CD8-Positive T-Lymphocytes/immunology*
;
Vimentin/metabolism*
;
Lymphatic Metastasis
;
Neoplasm Metastasis
5.Wenxia Changfu Formula inhibits NSCLC metastasis by halting TAMs-induced epithelial-mesenchymal transition via antagonisticallymodulating CCL18.
Qianyu BI ; Mengran WANG ; Li LUO ; Beiying ZHANG ; Siyuan LV ; Zengna WANG ; Xuming JI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(7):838-847
Our previous research demonstrated that the Wenxia Changfu Formula (WCF), as a neoadjuvant therapy, inhibits M2 macrophage infiltration in the tumor microenvironment and prevents lung cancer metastasis. Given tumor-associated macrophages (TAMs) in epithelial-mesenchymal transition (EMT), this study investigated whether WCF impedes lung cancer metastasis by attenuating TAM-induced EMT in non-small cell lung cancer (NSCLC) cells. Utilizing a co-culture model treated with or without WCF, we observed that WCF downregulated cluster of differentiation 163 (CD163) expression in macrophages, reduced CCL18 levels in the conditioned medium, and inhibited the growth, invasion, and EMT of NSCLC cells induced by macrophage co-culture. Manipulation of CCL18 levels and Src overexpression in NSCLC cells revealed that WCF's effects are mediated through CCL18 and Src signaling. In vivo, WCF inhibited recombinant CCL18 (rCCL18)-induced tumor metastasis in nude mice by blocking Src signaling. These findings indicate that WCF inhibits NSCLC metastasis by impeding TAM-induced EMT via antagonistic modulation of CCL18, providing evidence for its potential development and clinical application in NSCLC patients.
Epithelial-Mesenchymal Transition/drug effects*
;
Carcinoma, Non-Small-Cell Lung/metabolism*
;
Humans
;
Animals
;
Lung Neoplasms/metabolism*
;
Chemokines, CC/antagonists & inhibitors*
;
Mice
;
Mice, Nude
;
Drugs, Chinese Herbal/administration & dosage*
;
Cell Line, Tumor
;
Neoplasm Metastasis
;
Tumor-Associated Macrophages/drug effects*
;
Mice, Inbred BALB C
;
Signal Transduction/drug effects*
6.TSZAF monomer combination downregulates the Wnt/β-catenin signaling pathway and inhibits neutrophil recruitment to prevent lung cancer metastasis.
Pan YU ; Jialiang YAO ; Long ZHANG ; Yanhong WANG ; Xinyi LU ; Jiajun LIU ; Zujun QUE ; Yao LIU ; Qian BA ; Jiwei LIU ; Yan WU ; Jianhui TIAN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(9):1069-1079
Metastasis remains the primary cause of cancer-related mortality worldwide. Circulating tumor cells (CTCs) represent critical targets for metastasis prevention and treatment. Traditional Chinese medicine may prevent lung cancer metastasis through long-term intervention in CTC activity. Tiao-Shen-Zhi-Ai Formular (TSZAF) represents a Chinese medicine compound prescription utilized clinically for lung cancer treatment. This study combined three principal active ingredients from TSZAF into a novel TSZAF monomer combination (TSZAF mc) to investigate its anti-metastatic effects and mechanisms. TSZAF mc demonstrated significant inhibition of proliferation, migration, and invasion in CTC-TJH-01 and LLC cells, while inducing cellular apoptosis in vitro. Moreover, TSZAF mc substantially inhibited LLC cell growth and metastasis in vivo. Mechanistically, TAZSF mc significantly suppressed the Wnt/β-catenin signaling pathway and CXCL5 expression in lung cancer cells and tissues. Additionally, TAZSF mc notably reduced neutrophil infiltration in metastatic lesions. These findings indicate that TSZAF mc inhibits lung cancer growth and metastasis by suppressing the Wnt/β-catenin signaling pathway and reducing CXCL5 secretion, thereby decreasing neutrophil recruitment and infiltration. TSZAF mc demonstrates potential as an effective therapeutic agent for lung cancer metastasis.
Lung Neoplasms/genetics*
;
Wnt Signaling Pathway/drug effects*
;
Animals
;
Humans
;
Drugs, Chinese Herbal/pharmacology*
;
Mice
;
Neoplasm Metastasis/prevention & control*
;
Cell Proliferation/drug effects*
;
Cell Line, Tumor
;
Neutrophil Infiltration/drug effects*
;
Down-Regulation/drug effects*
;
Cell Movement/drug effects*
;
beta Catenin/genetics*
;
Apoptosis/drug effects*
;
Mice, Inbred C57BL
;
Male
;
Neoplastic Cells, Circulating/drug effects*
7.Multidisciplinary expert consensus on thermal ablation for benign thyroid diseases, low-risk thyroid carcinoma, and metastatic cervical lymph nodes (2025 edition).
Chinese Journal of Internal Medicine 2025;64(7):614-624
Thermal ablation has proven an effective treatment modality for certain thyroid diseases. However, its indications remain the subject of significant debate both domestically and internationally. Over recent years, several international academic organizations have issued consensus statements, position papers, and guidelines concerning thyroid thermal ablation. In China, the Chinese College of Interventionalists (CCI), in collaboration with other relevant academic organizations, released the "Expert consensus on thermal ablation for thyroid benign nodes, microcarcinoma and metastatic cervical lymph nodes (2018 edition)". This consensus statement received widespread recognition within the field and contributed significantly to the standardization of thyroid thermal ablation therapy in China. With the continuous accumulation of evidence-based medical data, the need for a more stringent and standardized approach to thyroid thermal ablation has become evident. Accordingly, the Interventional Ultrasound Committee of the CCI, in collaboration with multiple academic organizations and experts, conducted extensive discussions and multiple revisions before finalizing the "Multidisciplinary expert consensus on thermal ablation for benign thyroid diseases, low-risk thyroid carcinoma, and metastatic cervical lymph nodes (2025 edition)". This updated consensus builds on the framework of the 2018 edition, refining indications and contraindications, emphasizing standardized treatment, and outlining future directions for research and clinical applications of thyroid thermal ablation technology.
Humans
;
Thyroid Neoplasms/surgery*
;
Consensus
;
Lymphatic Metastasis
;
Lymph Nodes/pathology*
;
Thyroid Diseases/surgery*
8.miR-302a-3p targeting lysosomal-associated membrane protein 5 inhibits the invasion and metastasis of oral squamous cell carcinoma.
Li YU ; Tiejun ZHOU ; Xiao WU ; Xinhong LIN ; Xiaoyan ZHANG ; Yongxian LAI ; Xinyue LIAO ; Hang SI ; Yun FENG ; Jie JIAN ; Yan FENG
West China Journal of Stomatology 2025;43(4):547-558
OBJECTIVES:
This study aimed to explore the expression of lysosomal-associated membrane protein 5 (LAMP5) and microRNA (miR)-302a-3p in oral squamous cell carcinoma (OSCC) and their functional mechanism on the invasion and metastasis of OSCC.
METHODS:
The expression of LAMP5 in OSCC and its sensitivity as a prognostic indicator were analyzed on the basis of The Cancer Genome Atlas database. Western blot, quantitative reverse transcription polymerase chain reaction, and cell immunocytochemistry were used to detect the expression of LAMP5 in OSCC tissues and cells. The effect of LAMP5 on the proliferation, migration, and invasion of OSCC cells was evaluated through cell counting kit-8, immunocytochemistry, migration, and invasion assays, respectively. The miRNA targeting prediction websites were used to predict the miR that regulates LAMP5 and verify the targeted regulatory effect of miR-302a-3p on LAMP5. The effect of LAMP5 knockdown on OSCC tumor growth was evaluated in a nude mouse tumorigenesis model.
RESULTS:
LAMP5 was highly expressed in OSCC tissues and cells. It showed high sensitivity in the early diagnosis of OSCC. LAMP5 knockdown significantly inhibited the proliferation, migration, and invasion of OSCC cells, whereas LAMP5 overexpression increased these cell activities. The expression of LAMP5 was regulated by miR-302a-3p. In vivo, LAMP5 knockdown significantly inhibited the growth of OSCC tumor.
CONCLUSIONS
LAMP5 promotes the malignant progression of OSCC by enhancing the proliferation, migration, and invasion of OSCC cells. The expression of LAMP5 is negatively regulated by miR-302a-3p.
MicroRNAs/metabolism*
;
Mouth Neoplasms/metabolism*
;
Humans
;
Animals
;
Carcinoma, Squamous Cell/genetics*
;
Neoplasm Invasiveness
;
Cell Proliferation
;
Mice, Nude
;
Cell Movement
;
Lysosomal Membrane Proteins/genetics*
;
Mice
;
Cell Line, Tumor
;
Neoplasm Metastasis
9.Lymphatic and Venous Contrast-Enhanced Ultrasound Imaging for Differential Diagnosis of Cervical Lymph Node Metastasis in Thyroid Cancer.
Li XU ; Wen-Bo WAN ; Tian GAO ; Tao-Hua GOU ; Yan ZHANG
Acta Academiae Medicinae Sinicae 2025;47(1):16-22
Objective To investigate the value of the novel lymphatic contrast-enhanced ultrasound(LCEUS)and conventional venous contrast-enhanced ultrasound(VCEUS)in the differential diagnosis of benign and malignant cervical lymph nodes in patients with thyroid cancer. Methods Patients with suspected thyroid cancer underwent conventional ultrasound,VCEUS,and LCEUS examinations of cervical lymph nodes before biopsy.The diagnostic abilities of conventional ultrasound,VCEUS,and LCEUS were compared with pathological results as the golden standard. Results Forty-four patients with 52 lymph nodes were included in the final data.Thirty-eight metastatic lymph nodes were confirmed by pathological results,and 14 were benign.The diagnostic sensitivity,specificity,and accuracy were 97.37%,71.43%,and 90.38% for LCEUS,92.11%,35.71%,and 76.92% for VCEUS,and 94.74%,21.43%,and 75.00% for conventional ultrasound,respectively.The area under the curve of LCEUS analyzed by the receiver operating characteristic curve was greater than that of VCEUS(P=0.020)and conventional ultrasound(P<0.001). Conclusion LCEUS could significantly improve the differential diagnosis of cervical lymph node metastasis in the patients with thyroid cancer,providing a basis for precise clinical treatment.
Humans
;
Thyroid Neoplasms/diagnostic imaging*
;
Lymphatic Metastasis/diagnostic imaging*
;
Diagnosis, Differential
;
Female
;
Male
;
Middle Aged
;
Ultrasonography
;
Adult
;
Lymph Nodes/pathology*
;
Contrast Media
;
Neck
;
Aged
;
Young Adult
;
Adolescent
;
Sensitivity and Specificity
10.Ultrasound Characteristics of Secondary Squamous Cell Carcinoma of the Thyroid.
Dong LIU ; Yan-Jia GOU ; Quan WEN ; Su-Ting ZONG
Acta Academiae Medicinae Sinicae 2025;47(3):390-395
Objective To analyze the ultrasonographic features of secondary squamous cell carcinoma of the thyroid(SSCC-T)and evaluate the diagnostic value of ultrasound.Methods A retrospective analysis was conducted on clinical and ultrasonographic data from 12 patients with pathologically confirmed SSCC-T treated at Beijing Friendship Hospital,Capital Medical University between January 2016 and January 2025.Evaluated parameters included lesion size,echogenicity,edge,vascularity,calcification,and cervical lymph node metastasis.Descriptive statistical analysis was performed to analyze the ultrasonographic features of SSCC-T,and Fisher's exact test was conducted to analyze the correlation between different ultrasound classifications and thyroid dysfunction.Results The 12 patients showed the following ultrasound classifications:nodular type(50.0%,6/12),diffuse type(33.3%,4/12),and mixed type(16.7%,2/12).All diffuse-type patients exhibited a characteristic cord-like hypoechoic pattern.Cervical lymph node metastasis was observed in all the patients,with 75.0%(9/12)showing lymph nodes >2 cm in maximum diameter.Thyroid dysfunction occurred in 66.7%(8/12)of patients,including 2 patients with dynamic shifts from hyperthyroidism to hypothyroidism.Diffuse and mixed types were associated with hypothyroidism(P=0.038).Conclusions SSCC-T demonstrates specific ultrasonographic features,particularly the cord-like hypoechoic pattern in the diffuse type.For patients with squamous cell carcinoma,regular ultrasound examinations of the thyroid and cervical lymph nodes combined with changes in thyroid function are conducive to the timely detection of thyroid metastasis of squamous cell carcinoma.
Humans
;
Retrospective Studies
;
Ultrasonography
;
Carcinoma, Squamous Cell/diagnostic imaging*
;
Thyroid Neoplasms/diagnostic imaging*
;
Lymphatic Metastasis
;
Male
;
Female
;
Middle Aged
;
Thyroid Gland/diagnostic imaging*
;
Adult


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