Objective To explore the effects of Caspase-3 and Glypicante1 (Gpc1) altered expressions on the proliferation of glioma cells and its mechanism.Methods Fifty-two glioma specimens and 13 normal cerebral tissues were collected in our hospital from October 2011 to October 2014;the protein expressions of Caspase-3 and Gpc1 in these tissues were detected with immunohistochemistry.The peDNA3.1/Gpc 1 high expression plasmids were constructed;human glioma A172 cell lines were routinely cultured in vitro;the signal path changes of Hedgehog (H-h) in the A172 cells after being transfected with 0.5,1,2 and 4 μg peDNA3.1/Gpc1 high expression plasmids were detected by Luciferase luciferase reporter gene kit.Gpc 1-1694 interference plasmids were transfected into the A172 cells to silence the Gpc1 expression and these A172 cells were given 8 iμg/mL Blasticidin (experimental group) for 24 h;normal A172 cells were given the same volume of solvent (control group);altered expressions of G-pc 1 were detected by immumohistochemical staining and proliferation activity of the cells were observed by MTT assay 24,48,72 and 96 h after transfection.Results The expressions of Caspase-3 and Gpc1 in the glioma specimens were significantly higher than those in the normal brain tissues (P＜0.05);in the glioma specimens,positive correlation between Caspase-3 and Gpc1 was noted (r=0.486,P=0.000).As compared with the control group,increased fluorescence intensity was observed in the 0.5,1,2 and 4 μg peDNA3.1/Gpc1 high expression plasmids groups (P＜0.05);immumohistochemical staining showed that CyclinD1 expression in the Hh pathway of in the peDNA 3.1/Gpc1 high expression plasmids groups was significantly lower than that in the control group;MTT assay showed that the proliferation activity of the A172 cells in the peDNA3.1/Gpc1 high expression plasmids groups at 24,48,72 and 96 h after transfection was significantly lower than that in the control group (P＜0.05).Conclusion Caspase-3 and Gpc1 play important roles in regulating the proliferation of glioma cells,which might be related to Hedgehog signaling pathway.

Objective:To investigate the ultrasonic characteristics of eccrine spiradenoma (ES) and to analyze the diagnostic value.Methods:Nineteen ES patients with 24 lesions confirmed by pathology in 3 grade-A tertiary hospitals from October 2011 to October 2021 were enrolled as study group, and in the same time, 46 patients with 46 masses in the skin and muscular tissues with clinical features of automatic pain and/or tenderness were selected as control group. The ultrasonographic characteristics of the two groups were analyzed retrospectively, including anatomical location, shape, boundary, internal echogenicity, echogenic distribution, calcification, posterior acoustic effect, and vascularity. The ultrasonographic characteristics of the two groups were compared, and the risk sonographic characteristics of ES were obtained by multivariate logistic regression analysis. The sensitivity and specificity of ultrasound characteristics for the diagnosis of ES were calculated.Results:The ultrasonic characteristics of the two groups had significant differences in lobulated shape, boundary, internal echogenicity and posterior acoustic effect (χ 2=32.65, 15.65, 5.77, 13.63; all P<0.01). Multivariate logistic regression analysis showed that lobulated shape and posterior acoustic enhancement were the risk ultrasonic characteristics of ES. The sensitivity and specificity of lobulated shape and posterior acoustic enhancement characteristics in the diagnosis of ES were 79.17%, 89.13%, 95.83% and 47.83%, respectively; and the sensitivity and specificity of the combination of lobulated shape and posterior acoustic enhancement characteristics in the diagnosis of ES were 79.17% and 97.83%, respectively. Conclusions:The lobulated shape and posterior acoustic enhancement characteristics are important for the identification of ES, which have higher diagnostic efficacy for ES.

Objective:To validate the Chinese version of Thyroid Imaging Report and Data System (C-TIRADS) for the malignancy risk stratification assessment of thyroid nodules, and compare with the American College of Radiology TIRADS(ACR-TIRADS) for diagnostic performance.Methods:A total of 1 306 patients with 1 389 thyroid nodules in the First Affiliated Hospital of Hainan Medical University from January 2015 to March 2021 were reviewed and assessed for diagnostic performance according to the C-TIRADS and the ACR-TIRADS, respectively, and the histopathological results were taken as golden standard.Results:The 1 389 thyroid nodules consisted of 973 benign nodules and 416 malignant nodules. The C-TIRADS 4C and ACR-TIRADS 5 had the highest accuracies and were taken respectively as the optimized cut-off values for diagnosis.The sensitivity, specificity, positive and negative predictive values and AUC by C-TIRADS 4C and ACR-TIRADS 5 for thyroid nodule evaluation were 87.39%, 89.92%, 75.00%, 95.38%, 0.89, and 85.58%, 91.88%, 81.84%, 93.71%, 0.89, respectively(all P>0.05). Conclusions:The C-TIRADS and ACR-TIRADS have good diagnostic performance for the malignancy risk stratification of thyroid nodules, and C-TIRADS 4C has comparable diagnostic performance to ACR-TIRADS 5.

Colorectal cancer is a highly malignant disease characterized by a poor prognosis. Although the targeted therapy based on chemotherapy improves the efficacy, the prognosis of advanced colorectal cancer patients is poor. Poly (ADP-ribose) polymerase (PARP) inhibitors, which act through a synergistic lethal mechanism, have been widely utilized in treating ovarian and breast cancer cases with homologous recombination deficiency and have demonstrated positive clinical outcomes. Recently, due to advancements in next-generation sequencing technology and the development of precision targeted therapy, an increasing number of clinical trials have started to investigate the potential of PARP inhibitors in colorectal cancer treatment. This review summarized the molecular mechanism of PARP inhibitors in the treatment of colorectal cancer and the application of several combined PARP inhibitors therapy regimens in colorectal cancer, in order to provide new insights for the treatment of colorectal cancer.

OBJECTIVETo investigate the effect of 17-AAG combined with paclitaxel (PTX) on the proliferation and apoptosis of esophageal squamous cell carcinoma cell line Eca-109 in vitro.

METHODSEca-109 cells were treated with 17-AAG and PTX either alone or in combination. The proliferation of Eca-109 cells was detected by MTT assay, and the cell cycle changes and cell apoptosis were determined by flow cytometry.

RESULTSCompared with the control group, both 17-AAG and PTX significantly inhibited the proliferation of Eca-109 cells. A combined treatment of the cells with 0.5 µmol/L PTX and 0.625 µmol/L 17-AAG produced an obviously stronger inhibitory effect on the cell proliferation than either of the agents used alone (P<0.01). Flow cytometry showed that, 17-AAG and PTX used alone caused Eca-109 cell cycle arrest in G2/M phase and S phase, respectively, and their combined use caused cell cycle arrest in both G2/M and S phases. The cell apoptosis rates of Eca-109 cells treated with 17-AAG, PTX and their combination were 4.52%, 10.91%, and 29.88%, respectively, all significantly higher than that in the control group (1.32%); the combined treatment resulted in a distinct apoptotic peak that was significantly higher than that caused by either of the agents alone.

CONCLUSION17-AAG and PTX can inhibit cell proliferation and promote apoptosis of Eca-109 cells, and their combination produces stronger effects in inhibiting cell proliferation and increasing cell apoptosis.

Apoptosis ; Benzoquinones ; pharmacology ; Carcinoma, Squamous Cell ; pathology ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Esophageal Neoplasms ; pathology ; Humans ; Lactams, Macrocyclic ; pharmacology ; Paclitaxel ; pharmacology

Objective To investigate the effect of 17-AAG combined with paclitaxel (PTX) on the proliferation and apoptosis of esophageal squamous cell carcinoma cell line Eca-109 in vitro. Methods Eca-109 cells were treated with 17-AAG and PTX either alone or in combination. The proliferation of Eca-109 cells was detected by MTT assay, and the cell cycle changes and cell apoptosis were determined by flow cytometry. Results Compared with the control group, both 17-AAG and PTX significantly inhibited the proliferation of Eca-109 cells. A combined treatment of the cells with 0.5μmol/L PTX and 0.625μmol/L 17-AAG produced an obviously stronger inhibitory effect on the cell proliferation than either of the agents used alone (P<0.01). Flow cytometry showed that, 17-AAG and PTX used alone caused Eca-109 cell cycle arrest in G2/M phase and S phase, respectively, and their combined use caused cell cycle arrest in both G2/M and S phases. The cell apoptosis rates of Eca-109 cells treated with 17-AAG, PTX and their combination were 4.52%, 10.91%, and 29.88%, respectively, all significantly higher than that in the control group (1.32%); the combined treatment resulted in a distinct apoptotic peak that was significantly higher than that caused by either of the agents alone. Conclusion 17-AAG and PTX can inhibit cell proliferation and promote apoptosis of Eca-109 cells, and their combination produces stronger effects in inhibiting cell proliferation and increasing cell apoptosis.

Objective To investigate the effect of 17-AAG combined with paclitaxel (PTX) on the proliferation and apoptosis of esophageal squamous cell carcinoma cell line Eca-109 in vitro. Methods Eca-109 cells were treated with 17-AAG and PTX either alone or in combination. The proliferation of Eca-109 cells was detected by MTT assay, and the cell cycle changes and cell apoptosis were determined by flow cytometry. Results Compared with the control group, both 17-AAG and PTX significantly inhibited the proliferation of Eca-109 cells. A combined treatment of the cells with 0.5μmol/L PTX and 0.625μmol/L 17-AAG produced an obviously stronger inhibitory effect on the cell proliferation than either of the agents used alone (P<0.01). Flow cytometry showed that, 17-AAG and PTX used alone caused Eca-109 cell cycle arrest in G2/M phase and S phase, respectively, and their combined use caused cell cycle arrest in both G2/M and S phases. The cell apoptosis rates of Eca-109 cells treated with 17-AAG, PTX and their combination were 4.52%, 10.91%, and 29.88%, respectively, all significantly higher than that in the control group (1.32%); the combined treatment resulted in a distinct apoptotic peak that was significantly higher than that caused by either of the agents alone. Conclusion 17-AAG and PTX can inhibit cell proliferation and promote apoptosis of Eca-109 cells, and their combination produces stronger effects in inhibiting cell proliferation and increasing cell apoptosis.

Objective To investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia. Methods Hyperthermic HepG2 cell models established by exposure of the cells to 42 ℃ for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed. Results ROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001). Conclusion The intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.

Objective To investigate the mechanism by which heat shock protein 90 (HSP90) regulates 26S proteasome in hyperthermia. Methods Hyperthermic HepG2 cell models established by exposure of the cells to 42 ℃ for 3, 6, 12, and 24 h were examined for production of reactive oxygen species (ROS) and cell proliferation, and the changes in Hsp90α and 26S proteasome were analyzed. Results ROS production in the cells increased significantly after hyperthermia (F=28.958, P<0.001), and the cell proliferation was suppressed progressively as the heat exposure time extended (F=621.704, P<0.001). Hyperthermia up-regulated Hsp90α but decreased the expression level (F=164.174, P<0.001) and activity (F=133.043, P<0.001) of 26S proteasome. The cells transfected with a small interfering RNA targeting Hsp90α also showed significantly decreased expression of 26S proteasome (F=180.231, P<0.001). Conclusion The intracellular ROS production increases as the hyperthermia time extends. Heat stress and ROS together cause protein denature, leading to increased HSP90 consumption and further to HSP90 deficiency for maintaining 26S proteasome assembly and stability. The accumulation of denatured protein causes unfolded protein reaction in the cells to eventually result in cell death.

OBJECTIVE: To investigate the difference of tumor formation in different mouse strains bearing patient-derived xenograft of esophageal squamous cell carcinoma(ESCC) and establish a better animal model for preclinical study of individualized treatment of ESCC. METHODS: The tumor tissues collected from 22 ESCC patients were used to establish tumor-bearing mouse models in B-NDG (NSG) mice and BALB/c nude mice. The tumor formation rate and tumor formation time were compared between the two mouse models, and HE staining, immunohistochemistry and genome sequencing were carried out to assess the consistency between transplanted tumor tissues in the models and patient-derived tumor tissues. RESULTS: The tumor-bearing models were established successfully in both NSG mice (50%, 11/22) and BALB/c nude mice (18.18%, 4/22). The average tumor formation time was significantly shorter in NSG mice than in BALB/c nude mice (75.95 91.67 days, < 0.001). In both of the mouse models, the transplanted tumors maintained morphological characteristics identical to those of patient-derived ESCC tumors. Genetic analysis showed that the xenografts in NSG mice had a greater genetic similarity to the patients' tumors than those in BALB/c nude mice ( < 0.0001). CONCLUSIONS Mouse models bearing xenografts of patient-derived ESCC can be successfully established in both NSG mice and BALB/c nude mice, but the models in the former mouse strain can be more reliable.
Animals ; Cell Line, Tumor ; Cell Proliferation ; Esophageal Neoplasms ; Esophageal Squamous Cell Carcinoma ; Heterografts ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays