1.Value of Ultrasonographic Features Combined With Immunohistochemistry in Predicting Axillary Lymph Node Metastasis in Middle-Aged Women With Breast Cancer.
Qian-Kun CHANG ; Wen-Ying WU ; Chun-Qiang BAI ; Zhi-Chao DING ; Wei-Fang WANG ; Ming-Han LIU
Acta Academiae Medicinae Sinicae 2025;47(4):550-556
Objective To investigate the value of ultrasonographic features combined with immunohistochemistry in predicting axillary lymph node metastasis in middle-aged women with breast cancer.Methods A retrospective analysis was conducted on 827 middle-aged female breast cancer patients who underwent surgical treatment at the Affiliated Hospital of Chengde Medical University from June 2017 to June 2023.Ultrasonographic and immunohistochemical information was collected,and the patients were randomly allocated into a training set(579 patients)and a validation set(248 patients).Univariate and multivariate Logistic regression analyses were performed to identify ultrasonographic and immunohistochemical risk factors associated with axillary lymph node metastasis in these patients,and a nomogram model was developed.Receiver operating characteristic curves and calibration curves were established to evaluate the performance of the nomogram model,and clinical decision curves were built to assess the clinical value of the model.Results The maximum diameter,morphology,boundary,calcification,and expression of human epidermal growth facor receptor 2 and Ki-67 in breast cancer lesions were identified as risk factors for predicting axillary lymph node metastasis in middle-aged women.The areas under the curve of the nomogram model on the training and validation sets were 0.747(0.707-0.787)and 0.714(0.647-0.780),respectively.Calibration curves and clinical decision curves indicated good consistency and performance of the model.Conclusion The nomogram model constructed based on ultrasonographic features and immunohistochemistry of the primary breast cancer lesion demonstrates high value in predicting axillary lymph node metastasis in middle-aged women with breast cancer.
Humans
;
Female
;
Breast Neoplasms/diagnostic imaging*
;
Middle Aged
;
Lymphatic Metastasis/diagnostic imaging*
;
Axilla
;
Retrospective Studies
;
Nomograms
;
Ultrasonography
;
Immunohistochemistry
;
Lymph Nodes/diagnostic imaging*
;
Risk Factors
;
Ki-67 Antigen
2.Clinical significance of tertiary lymphoid structure maturity in colorectal cancer patients.
Jiangjiang ZHENG ; Jingjing YU ; Jingjing XIE ; Dong CHEN ; Hong DENG
Journal of Zhejiang University. Medical sciences 2024;53(6):765-771
OBJECTIVES:
To explore the clinical significance of the tertiary lymphoid structure (TLS) maturity in colorectal cancer patients.
METHODS:
A total of 230 surgically removed colorectal cancer specimens with detailed follow-up data were collected from Yinzhou Second Hospital. The patients were divided into mature TLS group and immature TLS group according to immunohistochemical results. The patient age, gender, maximum tumor diameter, tumor location, differentiation degree, depth of invasion, lymph node metastasis, vascular tumor thrombus, liver metastasis, distant non-liver metastasis, mismatch repair status, expression of Ki-67, P53 and programmed death-ligand (PD-L) 1 were analyzed. The Kaplan-Meier method (Breslow test) was used to analyze the survival of patients, and multivariate Cox regression model was applied to analyze the prognostic factors.
RESULTS:
There were 128 cases of mature TLS and 102 cases of immature TLS. Compared to the immature TLS group, the mature TLS group showed a significantly lower rate of vascular tumor thrombus, lymph node metastasis, and liver metastasis. Additionally, the positive expression rate of Ki-67 was markedly reduced, while the rate of deficient mismatch repair and the positive rate of PD-L1 were significantly increased (all P<0.05). The overall survival rate of the mature TLS group was superior to that of the immature TLS group (Breslow=4.553, P<0.05). Cox regression analysis indicated that lymph node metastasis was an independent risk factor for the prognosis of colorectal cancer patients (P<0.01), while TLS maturation was a protective factor (P<0.05).
CONCLUSIONS
The formation of TLS may play a significant role in inhibiting lymph node metastasis, liver metastasis, and vascular tumor thrombus in colorectal cancer. In addition, patients with mature TLS have a favorable clinical prognosis.
Humans
;
Colorectal Neoplasms/pathology*
;
Male
;
Female
;
Middle Aged
;
Tertiary Lymphoid Structures/pathology*
;
Prognosis
;
Aged
;
Adult
;
Lymphatic Metastasis
;
Ki-67 Antigen/metabolism*
;
B7-H1 Antigen/metabolism*
;
Clinical Relevance
3.Preoperative CT radiomics-based model for predicting Ki-67 expression in clear cell renal cell carcinoma patients.
Zhijun YANG ; Han HE ; Yunfeng ZHANG ; Jia WANG ; Wenbo ZHANG ; Fenghai ZHOU
Journal of Central South University(Medical Sciences) 2024;49(11):1722-1731
OBJECTIVES:
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), and developing personalized treatment strategies is crucial for improving patient prognosis. This study aims to develop and validate a preoperative computer tomography (CT) radiomics-based predictive model to estimate Ki-67 expression in ccRCC patients, thereby assisting in clinical treatment decisions and prognosis prediction.
METHODS:
A retrospective analysis was conducted on 214 ccRCC patients who underwent surgical treatment at Gansu Provincial Hospital between January 2018 and November 2023. Patients were classified into high Ki-67 expression (n=123) and low Ki-67 expression (n=91) groups based on postoperative immunohistochemical staining results. The dataset was randomly divided in a 7꞉3 ratio into a training set (n=149) and a validation set (n=65). Preoperative contrast-enhanced urinary CT images and clinical data were collected. After preprocessing, 5 mm arterial-phase CT images were manually segmented layer by layer to delineate the region of interest (ROI) using ITK-SNAP 3.8 software. Radiomic features were then extracted using the FeAture Explorer (FAE) package. Dimensionality reduction and feature selection were performed using the least absolute shrinkage and selection operator (LASSO) algorithm, yielding the optimal feature set. Three classification models were constructed using logistic regression (LR), multilayer perceptron (MLP), and support vector machine (SVM). The receiver operating characteristic (ROC) curve, area under the curve (AUC), decision curve analysis (DCA), and calibration curves were used for model evaluation.
RESULTS:
A total of 107 radiomic features were extracted from 5 mm arterial-phase CT images, and twenty-one features significantly associated with Ki-67 expression were selected using the LASSO algorithm. Predictive models were developed using LR, MLP, and SVM classifiers. In the training and validation sets, the AUC values for each model were 0.904 (95% CI 0.852 to 0.956) and 0.818 (95% CI 0.710 to 0.926) for the LR model, 0.859 (95% CI 0.794 to 0.923) and 0.823 (95% CI 0.716 to 0.929) for the MLP model, and 0.917 (95% CI 0.865 to 0.969) and 0.857 (95% CI 0.760 to 0.953) for the SVM model. DCA demonstrated that all models had good clinical net benefit, while calibration curves indicated high accuracy of the predictions, supporting the robustness and reliability of the models.
CONCLUSIONS
A CT radiomics-based model for predicting Ki-67 expression in ccRCC was successfully developed. This model provides valuable guidance for treatment planning and prognostic assessment in ccRCC patients.
Humans
;
Carcinoma, Renal Cell/surgery*
;
Kidney Neoplasms/surgery*
;
Tomography, X-Ray Computed/methods*
;
Ki-67 Antigen/metabolism*
;
Retrospective Studies
;
Female
;
Male
;
Middle Aged
;
Aged
;
Prognosis
;
Adult
;
Preoperative Period
;
Radiomics
4.Correlation between SWE parameters and histopathological features and immunohistochemical biomarkers in invasive breast cancer.
Xu LIU ; Jigang LI ; Ying HE ; Zhiyuan WANG
Journal of Central South University(Medical Sciences) 2024;49(12):1941-1952
OBJECTIVES:
Shear wave elastography (SWE) is a novel quantitative elastography technique that can assess the hardness of different tissues. This study introduces a novel shear wave parameter-frequency of mass characteristic (fmass)-and investigates its correlation, along with other shear wave parameters, with the histopathological features and immunohistochemical (IHC) biomarkers of invasive breast cancer (IBC). The study aims to explore whether SWE can provide useful information for IBC treatment and prognosis.
METHODS:
With the pathological results as the gold standard, 258 malignant breast lesions were collected, and all patients underwent conventional ultrasound and SWE examinations. The SWE parameters [maximum elastic value (Emax), minimum elastic value (Emin), mean elastic value (Emean), standard deviation of elastic value of the whole lesion (Esd)] and fmass] in the transverse and longitudinal orthogonal sections were measured, and their correlations with the prognostic factors of IBC [including tumor diameters, axillary lymph node (ALN) metastasis, lymphatic vessel invasion (LVI), calcification, histological type, histological grade, and IHC biomarkers (ER, PR, HER-2, Ki-67), and molecular subtypes] were analyzed. The correlations between the SWE parameters of the transverse and longitudinal sections of the tumors with different prognostic factors and the above indicators were analyzed. At the same time, the receiver operating characteristic (ROC) curve was used to analyze the efficacy of fmass in predicting ER and PR expression.
RESULTS:
Emean, Emax, Esd, and fmass were correlated with tumor diameters; Emean, Emax and Esd were correlated with histological types and histological grades. Emax and Esd were correlated with ALN metastasis, LVI and pathological types. In the IHC biomarker-labeled masses, fmass was correlated with ER and PR (both P<0.05), and Emean, Emax, and Esd were correlated with HER-2 and Ki-67 (all P<0.05). Emean, Emax, and fmass were all correlated with breast cancer subtypes (all P<0.05), and Emean and Emax were higher in Luminal B [HER-2(+)] breast cancer, while fmass was lower in HER-2(+) and triple-negative breast cancer. Among the statistically significant prognostic factors, the P values of the transverse sections of the masses were all less than or equal to those of the longitudinal sections. The AUC of fmass in the transverse sections of the masses for predicting ER and PR expression were 0.73 (95% CI 0.65 to 0.80) and 0.67 (95% CI 0.60 to 0.74), respectively, with the optimal cut-off values being 76.50 and 60.66, the sensitivities being 72.45% and 81.98%, the specificities being 66.13% and 45.35%, and the accuracies being 70.93% and 69.77%, respectively. The AUC of fmass in the longitudinal sections of the masses for predicting ER and PR expression were 0.74 (95% CI 0.67 to 0.81) and 0.65 (95% CI 0.58 to 0.72), respectively, with the optimal cut-off values being 131.8 and 137.5, the sensitivities being 69.90% and 66.28%, the specificities being 72.58% and 60.47%, and the accuracies being 70.54% and 64.34%, respectively. The fmass in the transverse sections of the masses was more statistically significant.
CONCLUSIONS
The poor prognosis factors of IBC are related to high Emean, Emin, Emax, Esd, and low fmass. The fmass can predict the expression of ER and PR, and the transverse cut data are more meaningful. SWE is helpful for predicting the invasiveness of IBC.
Humans
;
Breast Neoplasms/metabolism*
;
Female
;
Elasticity Imaging Techniques/methods*
;
Biomarkers, Tumor/metabolism*
;
Middle Aged
;
Adult
;
Prognosis
;
Immunohistochemistry
;
Neoplasm Invasiveness
;
Receptor, ErbB-2/metabolism*
;
Aged
;
Lymphatic Metastasis
;
Receptors, Estrogen/metabolism*
;
Receptors, Progesterone/metabolism*
;
Ki-67 Antigen/metabolism*
5.Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway.
Chu-Lan XIAO ; Zhi-Peng ZHONG ; Can LÜ ; Bing-Jie GUO ; Jiao-Jiao CHEN ; Tong ZHAO ; Zi-Fei YIN ; Bai LI
Journal of Integrative Medicine 2023;21(2):184-193
OBJECTIVE:
Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness.
METHODS:
A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected.
RESULTS:
Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin+/CD31+ ratio, rather than the number of CD31+ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group.
CONCLUSION
Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.
Humans
;
Animals
;
Mice
;
Carcinoma, Hepatocellular/drug therapy*
;
Proto-Oncogene Proteins c-akt/metabolism*
;
Proliferating Cell Nuclear Antigen/therapeutic use*
;
Mice, Nude
;
Glycogen Synthase Kinase 3 beta/genetics*
;
beta Catenin/therapeutic use*
;
Liver Neoplasms/drug therapy*
;
Desmin/therapeutic use*
;
Ki-67 Antigen
;
Cell Line, Tumor
;
Hypoxia
;
RNA, Messenger/therapeutic use*
;
Cell Proliferation
6.Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis.
P ZHU ; H LYU ; Q M BAI ; R H SHUI ; X L XU ; W T YANG
Chinese Journal of Pathology 2023;52(9):907-911
Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.
China
;
In Situ Hybridization, Fluorescence
;
Ki-67 Antigen
;
Neoadjuvant Therapy
;
Retrospective Studies
;
Trastuzumab
;
Humans
;
Female
;
Breast Neoplasms/drug therapy*
7.The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients.
Yuan LI ; Lei GUO ; Chang Yuan GUO ; Chu Qi LEI ; Ke ZHANG ; Nian Chang WANG ; Zhong Zhao WANG ; Li Xue XUAN
Chinese Journal of Oncology 2023;45(12):1057-1064
Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.
Humans
;
Female
;
Prognosis
;
Breast Neoplasms/surgery*
;
Ki-67 Antigen/analysis*
;
Neoadjuvant Therapy/methods*
;
gamma Catenin
;
Neoplasm, Residual
;
Disease-Free Survival
;
Retrospective Studies
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
8.The Clinical-Biological Features and Prognosis of Patients with Mantle Cell Lymphoma.
Journal of Experimental Hematology 2023;31(6):1726-1732
OBJECTIVE:
To analyze the clinical-biological features and outcomes of patients with mantle cell lymphoma (MCL).
METHODS:
The clinical and laboratory data of 104 patients with newly diagnosed MCL who were admitted to the Department of Hematology, Fujian Medical University Union Hospital from January 2011 to December 2019 were retrospectively analyzed, and the efficacy was observed through survival analysis.
RESULTS:
Among 104 MCL patients, 88 were male and 16 were female. The median age was 54 (25-79) years old, 93.0% (93/100) of the patients with advanced stage (III and IV stages) and 48.08% (50/104) of the patients with bone marrow infiltration. Patients with Ki-67≥50% had higher WBC counts and LDH levels. Univariate analysis showed that the patients with WBC≥15×109/L, bone marrow involvement, high LDH, high β2-MG levels, Ki-67≥50%, SOX11-, had lower OS and EFS rates (P =0.005, 0.049, 0.033, 0.025, 0.042, 0.018 and 0.001, 0.021, 0.024, 0.035, 0.014, 0.026). The OS rate and EFS rate of patients in R-CHOP and R-Hyper-CVAD treatment groups were significantly higher than those in other treatment groups (P =0.02, 0.002 and P =0.001, 0.001). Patients with autologous stem cell transplantation (ASCT) had higher OS rate and EFS rate (P =0.037, 0.013). Multivariate COX analysis showed that only WBC count, SOX11 expression and whether achieved CR after 4 courses treatment were the independent factors affecting the prognosis.
CONCLUSION
MCL mainly occur in elderly men. There are many factors affecting patients' survival, while WBC≥15×109/L, negative expression of SOX11 and failure to achieve CR after 4 courses of treatment are adverse factors for MCL patients.
Adult
;
Humans
;
Male
;
Female
;
Aged
;
Middle Aged
;
Lymphoma, Mantle-Cell/pathology*
;
Hematopoietic Stem Cell Transplantation
;
Retrospective Studies
;
Ki-67 Antigen
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use*
;
Transplantation, Autologous
;
Prognosis
9.Effect of LINC00174 on the Malignant Proliferation of Multiple Myeloma Cells and Its Related Mechanism.
Jing-Jing WANG ; Cui-Ping ZHAO ; Shi-Guang WANG
Journal of Experimental Hematology 2023;31(4):1085-1092
OBJECTIVE:
To explore the biological function of LINC00174 in multiple myeloma (MM).
METHODS:
Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expressions of LINC00174 and miR-150 in peripheral blood of MM patients and MM cell lines. EdU staining and flow cytometry were used to detect the effects of LINC00174 and miR-150 on the proliferation and apoptosis of MM cells. Western blot was used to detect the expressions of proliferation marker nuclear-related antigen Ki67, apoptosis-related protein cleaved caspase-3 and transcription factor forkhead box protein P1 (FOXP1). Bioinformatics and dual-luciferase reporter assay were used to verify the targeting relationship between LINC00174 and miR-150 and the targeting relationship between miR-150 and FOXP1.
RESULTS:
The level of LINC00174 was significantly increased in peripheral blood of MM patients and MM cell lines (P <0.05). Compared with NC-siRNA group, the expression of LINC00174 was significantly reduced in LINC00174-siRNA group, the proliferation of U266 cells was reduced, the apoptosis rate was significantly increased, the level of Ki67 protein was reduced, and the level of cleaved caspase-3 protein was increased (all P <0.05). LINC00174 targeted regulation of the expression of miR-150. Compared with LINC00174-siRNA+NC inhibitor group, the expression of miR-150 in U266 cells in LINC00174-siRNA+miR-150 inhibitor group was significantly reduced, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05). FOXP1 is the target gene of miR-150. Compared with NC mimic group, the expression of FOXP1 protein in miR-150 mimic group was significantly reduced, the cell proliferation was reduced, the apoptosis rate was significantly increased, Ki67 protein level was decreased, and the level of cleaved caspase-3 was increased. Compared with miR-150 mimic + vector group, the expression of FOXP1 protein in miR-150 mimic + pcDNA-FOXP1 group was significantly increased, the cell proliferation was enhanced, the apoptosis rate was reduced, the level of Ki67 protein was increased, and the level of cleaved caspase-3 was decreased (all P <0.05).
CONCLUSION
LINC00174 promotes the proliferation of MM cells and inhibits cell apoptosis by regulating the miR-150/ FOXP1 axis.
Humans
;
Apoptosis
;
Caspase 3
;
Cell Line, Tumor
;
Cell Proliferation
;
Forkhead Transcription Factors
;
Ki-67 Antigen
;
MicroRNAs/genetics*
;
Multiple Myeloma/pathology*
;
Repressor Proteins
;
RNA, Small Interfering
;
RNA, Long Noncoding/genetics*
10.Tumor antigen-loaded dendritic cells combined with cytokine-induced killer (CIK) enhance the killing activity of human esophageal cancer cells by promoting ASK1 activation.
Zheng DUAN ; Honglin LI ; Bin HU ; Yun LI ; Li HUANG
Chinese Journal of Cellular and Molecular Immunology 2023;39(6):501-508
Objective To clarify the effect and mechanism of tumor antigen-loaded dendritic cells (Ag-DCs) combined with cytokine-induced killers (CIKs) on the killing of esophageal cancer tumor cells. Methods Peripheral blood DCs and CIKs were induced and cultured, and the DCs were loaded with tumor antigen to obtain Ag-DCs, and Ag-DCs were co-cultured with CIKs. The experiment was divided into CIK group, DC combined with CIK group, Ag-DC combined with CIK group. Flow cytometry was used to detect the phenotype of cells. MTT assay was employed to determine the killing activity against EC9706 cells. Annexin V-FITC/PI double staining was used to detect the apoptosis rate of cells, immunofluorescence staining to detect the expression of phosphorylated apoptotic signal-regulated kinase 1 (p-ASK1) and Western blot analysis to detect the expression of ASK1 pathway related proteins. A nude mouse model of esophageal cancer transplantation tumor was constructed and divided into control group, DC combined with CIK group and Ag-DC combined with CIK group. The corresponding immune cells were injected into the tail vein for treatment and the tumor volume was measured every 2 days. After 21 days, all nude mice were sacrificed with the tumors taken out. HE staining was used to observe the tumor pathological changes and immunohistochemical staining was performed to detect the expression of ki67 and ASK1 in the tumor tissue. Results Comparedwith the CIK group alone and the DC combined with CIK group, the ratio of CD3+ CD8+ and CD3+ CD56+ in the cells significantly increased after Ag-DCs and CIKs co-culture, along with the increased killing rate of EC9706 cells, increased apoptosis rate of EC9706 cells, and the improved activation level of ASK1. Compared with the CIK group and the DC combined with CIK group, the growth of the transplanted tumor in nude mice treated with Ag-DCs combined with CIKs was significantly inhibited, and after 21 days, it was observed that the tumor tissue mass in this group was relatively smaller, with sparsely arranged cells in the tumor tissue and a decline in the positive rate of ki67 in tumor tissue, while the positive rate of ASK1 was significantly increased. Conclusion Co-cultivation of tumor antigen-loaded DCs with CIKs can significantly increase the killing activity of esophageal cancer tumor cells. The mechanism of action may be related to the activation of the ASK1 pathway.
Animals
;
Humans
;
Mice
;
Antigens, Neoplasm
;
Cytokine-Induced Killer Cells
;
Cytokines/metabolism*
;
Cytotoxicity, Immunologic
;
Dendritic Cells
;
Esophageal Neoplasms/therapy*
;
Ki-67 Antigen
;
Mice, Nude

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