Objective:To investigate the dosimetric impact of dwell position spacing in the design of three-dimensional (3D) interstitial brachytherapy plans for cervical cancer, and to provide a reference for selecting dwell spacing in clinical planning.Methods:A total of 15 patients with cervical cancer who underwent 3D interstitial brachytherapy at Tianjin Medical University Cancer Institute & Hospital between March 2022 and March 2024 were selected using simple random sampling. For each patient, 10 brachytherapy plans were generated with different dwell position spacings set at 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 mm, respectively. Key parameters among different dwell spacings compared included D 90%, V 100%, V 200%, and V 300% for the high-risk clinical target volume (HRCTV); D 90% for the intermediate-risk clinical target volume (IRCTV); D 2 cm3 for organs at risk (OARs) (bladder, small intestine, colon, and rectum); and the total dwell time. Statistical analyses were performed using repeated measurement ANOVA or the Friedman test. Results:Among different dwell spacings, there were no statistically significant differences in HRCTV D 90%, HRCTV V 100%, bladder D 2 cm3, and rectum D 2 cm3 among different dwell spacings ( P=0.075, 0.061, 0.480, 0.639). All plans with dwell spacings ≤ 3 mm met clinical dose requirements. When the dwell spacing was set to 1 mm, HRCTV V 200% and V 300% had the smallest mean values, while IRCTV D 90% and total dwell time had the largest mean values; all differences were statistically significant ( P<0.05). When the dwell spacing was ≥6 mm, an increase in spacing led to a decrease in mean small intestine D 2 cm3, and total dwell time, but an increase in HRCTV V 200% and a decrease in IRCTV D 90%, with statistically significant differences compared to spacings of 1-4 mm ( P<0.05). When the dwell spacing was ≥8 mm, the median colon D 2 cm3 decreased, with statistically significant differences compared to spacings of 1-3 mm ( P<0.05). Conclusions:For 3D interstitial brachytherapy planning in cervical cancer, dwell position spacings ≤ 3 mm can meet clinical dose requirements, with 1 mm providing optimal target coverage. Spacings ≥6 mm / ≥8 mm can reduce radiation dose to the small intestine and colon, respectively, while also shortening dwell time.

Objective:To investigate the dosimetric impact of dwell position spacing in the design of three-dimensional (3D) interstitial brachytherapy plans for cervical cancer, and to provide a reference for selecting dwell spacing in clinical planning.Methods:A total of 15 patients with cervical cancer who underwent 3D interstitial brachytherapy at Tianjin Medical University Cancer Institute & Hospital between March 2022 and March 2024 were selected using simple random sampling. For each patient, 10 brachytherapy plans were generated with different dwell position spacings set at 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 mm, respectively. Key parameters among different dwell spacings compared included D 90%, V 100%, V 200%, and V 300% for the high-risk clinical target volume (HRCTV); D 90% for the intermediate-risk clinical target volume (IRCTV); D 2 cm3 for organs at risk (OARs) (bladder, small intestine, colon, and rectum); and the total dwell time. Statistical analyses were performed using repeated measurement ANOVA or the Friedman test. Results:Among different dwell spacings, there were no statistically significant differences in HRCTV D 90%, HRCTV V 100%, bladder D 2 cm3, and rectum D 2 cm3 among different dwell spacings ( P=0.075, 0.061, 0.480, 0.639). All plans with dwell spacings ≤ 3 mm met clinical dose requirements. When the dwell spacing was set to 1 mm, HRCTV V 200% and V 300% had the smallest mean values, while IRCTV D 90% and total dwell time had the largest mean values; all differences were statistically significant ( P<0.05). When the dwell spacing was ≥6 mm, an increase in spacing led to a decrease in mean small intestine D 2 cm3, and total dwell time, but an increase in HRCTV V 200% and a decrease in IRCTV D 90%, with statistically significant differences compared to spacings of 1-4 mm ( P<0.05). When the dwell spacing was ≥8 mm, the median colon D 2 cm3 decreased, with statistically significant differences compared to spacings of 1-3 mm ( P<0.05). Conclusions:For 3D interstitial brachytherapy planning in cervical cancer, dwell position spacings ≤ 3 mm can meet clinical dose requirements, with 1 mm providing optimal target coverage. Spacings ≥6 mm / ≥8 mm can reduce radiation dose to the small intestine and colon, respectively, while also shortening dwell time.

Objective:To observe the expression patterns of miR-195 and DLL4 in colorectal cancer, and to explore the relationship between miR-195 and DLL4 and clinicopathological parameters and prognosis of patients with colorectal cancer.Methods:The relative expression of miR-195 in 56 colorectal cancer tissues was detected by real-time fluorescent quantitative PCR the expression of DLL4 protein and tumor microvessel density (MVD) were detected by bloting and immunohistochemistry. Colon cancer cell line SW480 was treated with miR-195. The expression of DLL4, Jagged1, (the intracellular domain of notch, NICD), CyclinD1, Hes1, Bcl-2 and NF-kB were detected by bloting.Results:The expression level of DLL4 protein in colorectal cancer tissues was significantly higher than that in normal intestinal mucosa (30/56 vs.16/56, t=5.323, P=0.018). The expression level of miR-195 was significantly lower than that in normal intestinal mucosa (36/56 vs.20/56, t=2.371, P=0.008). The expression of DLL4 was negatively correlated with the expression of miR-195 ( r=- 0.881, P=0.015) , which was closely related to the differentiation degree, lymph node metastasis and TNM stage . The prognosis of patients with high expression of DLL4 was significantly worse than that with low expression of DLL4 ( P=0.013). The prognosis of patients with low expression of miR-195 was worse than that with high expression of miR-195 ( P=0.009) . Conclusion:The antagonistic expression of miR-195 and Notch might be closely related to the occurrence and development of colorectal cancer, which can be used as a new reference index for prognosis of colorectal cancer.

AIM: To explore whether tumor necrosis factor-α (TNF-α) induces necroptosis in murine long bone osteocyte-like cell line MLO-Y4 and the possible mechanism.METHODS: The MLO-Y4 cells were divided into control group, TNF-α group, TNF-α+necrostatin-1 (Nec-1) group, TNF-α+Z-VAD group and TNF-α+receptor-interacting protein 3 (RIP3)-siRNA group.The death rate of MLO-Y4 cells was assessed by flow cytometry with Annexin V-FITC/PI staining.The morphological features of the cells were observed under transmission electron microscope (TEM).The protein levels of RIP1, RIP3 and cleaved caspase-3 were determined by Western blot.Finally, the numbers of total cells and RIP1-RIP3-positive cells were observed under laser scanning confocal microscope.The production of reactive oxygen species (ROS) in the cells was measured by DCFH-DA staining.RESULTS: Compared with control group, the apoptotic or necroptotic rate of the cells induced by TNF-α was increased significantly (P<0.01).The increased apoptotic or necroptotic rate was dramatically reduced by treating with Nec-1, Z-VAD or RIP3-siRNA transfection (P<0.01).In TNF-α group and TNF-α+Z-VAD group, a lot of MLO-Y4 cells with typical necroptotic morphological features were observed under TEM.However, obvious necroptotic cells were not found in Nec-1 or RIP3-siRNA treatment group.The protein level of RIP1 in the cells treated with Nec-1 was sharply lower than that in TNF-α group (P<0.01).However, Z-VAD did not reduce the elevated levels of RIP1 and RIP3.RIP3-siRNA effectively down-regulated the protein level of RIP3 compared with TNF-α group (P<0.01).Nec-1 effectively down-regulated the protein levels of RIP1 colocalized with RIP3 compared with TNF-α group (P<0.01).However, Z-VAD did not reduce the levels of RIP1 colocalized with RIP3.Nec-1, Z-VAD and RIP3 siRNA significantly decreased the ROS levels (P<0.01).CONCLUSION: TNF-α induces the necroptosis of MLO-Y4 cells.RIP3 play vital roles in the cell necroptotic signal pathway.ROS may be the executor of necroptosis of MLO-Y4 cells.

Objective To investigate the relationship between the expression of suppressor of zeste 12(SUZ12) and the clinicopathological parameters and prognosis in patients with gastric cancer. Methods SUZ12 protein expression levels in 97 cases of resected gastric cancer were detected by immunohitochemistry method, the relations between SUZ12 expression levels and the survival were estimated by Kaplan-Meier curve. Results The positive rate of SUZ12 expression in gastric cancer tissues was 43%, significantly higher than that (15%)in the adjacent noncancerous tissues( P = 0. 002). SUZ12-positive expression was significantly correlated with tumor differentiation ( P = 0. 018 ), lymph nodes metastasis ( P = 0. 023 ) and TNM staging(P = 0. 014). Gastric cancer patients with SUZ1 2-positive expression had worse prognosis than those with SUZ12-negative expression ( P = 0. 024). Conclusions SUZ12 is overexpressed in tissues of gastric carcinoma, SUZ12 is an independent prognosis factor of patients with gastric carcinoma.

Objective To investigate the expressions of Dapper1 in gastric carcinoma and elucidate its relationship with survivin and its role in tumor cell apoptosis. Methods Dapper1 mRNA was detected with RT-PCR using specimens from 30 cases of gastric carcinoma and the corresponding normal gastric mucosa.The pcDNA3.1-Dpr1 plasmid was transfected into SGC-7901 cells with LipofectamineTM 2000.The effect of upregulation of Dpr1 on SGC7901 cell apoptosis was determined by flow cytometry.The downregulation of survivin、Dvl-2 and β-catenin protein expression were detected by Western blot analysis.Results Downregulation of Dpr1 gene expression was observed in 17(57%)of 30 human gastric cancer and the downregulation was significantly correlated with the depth of invasion and the degree of differentiation (P＜0.05).Also,upregulation of Dpr1 mRNA and downregulation of survivin mRNA were detected after transfecting pcDNA3.1-Dpr1 plasmid in SGC7901 cells,which led to downregulation of survivin、Dvl-2、β-catenin protein and increase of the SGC7901 cell apoptosis rate from 2.89%to 13.96%.Conclusion Downregulation of Dp1l gene expression is common in human gastric carcinoma,and upregulation of Dpr1 results in significant inhibition of survivin expression which can induce apoptosis of SGC7901 cells.

OBJECTIVETo investigate the expressions of cyclin E, cyclin dependent kinase 2 (CDK-2) and cyclin-dependent kinase inhibitor p57(KIP2) in human gastric cancer, and to evaluate the relationships between protein levels and clinicopathological parameters.

METHODSWestern blot was used to measure the expressions of cyclin E, CDK-2 and p57(KIP2) proteins in the surgically resected gastric carcinoma, adjacent normal mucosa and metastatic lymph nodes from 36 patients.

RESULTSCyclin E and CDK-2 protein levels were higher in gastric cancer tissues in comparison with normal tissues (P < 0.05). Overexpression of cyclin E was correlated with lymph node involvement, poor histological grade and serosa invasion (P < 0.05). Overexpression of CDK-2 was correlated with lymph nodes involvement (P < 0.05). No statistically significant difference between cyclin E and CDK-2 expression was found when samples were stratified according to tumor size (P > 0.05). Expression of cyclin E and CDK-2 showed a positive linear correlation (r = 0.451, P = 0.01). Protein levels of p57(KIP2) were lower in gastric cancer tissues than in the normal mucosa (P < 0.05). Decreased expression of p57(KIP2) was correlated with lymph node involvement (P < 0.05). No statistically significant difference in p57(KIP2) expression was found when sample were stratified according to tumor size, histological grade or serosa invasion (P > 0.05). In metastatic lymph nodes, expression of cyclin E was increased and the expression of p57(KIP2) decreased.

CONCLUSIONOverexpressions of cyclin E, CDK-2 and downregulated expression of p57(KIP2) may play important roles in tumorigenesis and metastatic potential of gastric cancer.

Blotting, Western ; CDC2-CDC28 Kinases ; Cyclin E ; analysis ; physiology ; Cyclin-Dependent Kinase 2 ; Cyclin-Dependent Kinase Inhibitor p57 ; Cyclin-Dependent Kinases ; analysis ; physiology ; Humans ; Lymphatic Metastasis ; Nuclear Proteins ; analysis ; physiology ; Protein-Serine-Threonine Kinases ; analysis ; physiology ; Stomach Neoplasms ; chemistry ; pathology

OBJECTIVETo investigate the MEK and ERK expression and their relationship with clinicopathological parameters in human breast carcinoma, and the effect of preoperative chemotherapy on MEK and ERK protein expression.

METHODSSamples were obtained from 56 patients with breast carcinoma and 8 patients with benign tumors. Sixteen of the 56 patients received preoperative chemotherapy. Western blot and immunohistochemistry were used to measure the expression of MEK1, MEK2 and ERK1, ERK2 protein.

RESULTSMEK2 and ERK1, ERK2 protein levels were increased in breast carcinoma tissue compared with those in adjacent normal tissues (t = 7.244, 5.959, 3.735, P < 0.01) and benign tumors (t = 2.206, P < 0.05). The levels of MEK1 were decreased. The expression of MEK2 protein in ER negative patients was higher than that in ER positive ones. MEK2 protein levels were lower in patients who received preoperative chemotherapy than in those who did not.

CONCLUSIONOverexpression of MEK-ERK may play an important role in the development of human breast carcinoma. MEK and ERK protein expressions are inhibited by preoperative chemotherapy.

Adult ; Aged ; Blotting, Western ; Breast Neoplasms ; diagnosis ; enzymology ; metabolism ; Female ; Humans ; Immunohistochemistry ; MAP Kinase Kinase 1 ; MAP Kinase Kinase 2 ; MAP Kinase Signaling System ; physiology ; Middle Aged ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Mitogen-Activated Protein Kinases ; metabolism ; Prognosis ; Protein Kinases ; metabolism ; Protein-Serine-Threonine Kinases ; metabolism ; Protein-Tyrosine Kinases ; metabolism

Objective This study was to investigate the role of STAT3 signaling pathway in gastric cancer invasiveness. Methods Janus kinase 2 selective inhibitor AG490 was used to inhibit the activation of STAT3 signaling pathway. Matrigel-coated transwell was employed to estimate the invasiveness of BGG-823 cells. Alterations in the activity of STAT3 and expression of MMPs and TIMPs were measured by Western blot and RT-PCR. Results The activation of STAT3 signaling pathway was suppressed by AG490. AC490 significantly decreased the invasiveness of gastric cancer cell line BGC-823 through Matrigel-coated filters. Decreased invasion was associated with the inhibition of MMP-2, and MMP-9 at both mRNA and protein levels by RT-PCR and Western blot. Meanwhile, the expression of TIMP-1, and TIMP-2 were up-regulated at mRNA levels. Conclusion Inhibition of STAT3 signaling pathway in AG490 suppresses gastric cancer cell invasiveness through down-regulation of several invasion-related factors including MMP-2, and MMP-9 and up-regulation of their inhibitors.

Objective This study was to investigate the relationship between the activities of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) and clinicopathological parameters in human colorectal cancer,and the relationship between TP and/or DPD activity in tumor tissue and efficiency of chemotherapy. MethodsSixty-eight patients undergoing surgery for primary colorectal cancer were enrolled including 40 patients receiving postoperative adjuvant chemotherapy with 5-FU plus leucovorin(de Gramont regimen). The activities of TP and DPD both in tumor tissue and in normal tissue were determined by enzyme-linked immunosorbent assay(ELISA). Results The TP activity was significantly higher in tumor than in normal tissues(P