Adults Ischium Age Estimation Based on Deep Learning and 3D CT Reconstruction.

OBJECTIVES: To develop a deep learning model for automated age estimation based on 3D CT reconstructed images of Han population in western China, and evaluate its feasibility and reliability. METHODS: The retrospective pelvic CT imaging data of 1 200 samples (600 males and 600 females) aged 20.0 to 80.0 years in western China were collected and reconstructed into 3D virtual bone models. The images of the ischial tuberosity feature region were extracted to create sex-specific and left/right site-specific sample libraries. Using the ResNet34 model, 500 samples of different sexes were randomly selected as training and verification set, the remaining samples were used as testing set. Initialization and transfer learning were used to train images that distinguish sex and left/right site. Mean absolute error (MAE) and root mean square error (RMSE) were used as primary indicators to evaluate the model. RESULTS: Prediction results varied between sexes, with bilateral models outperformed left/right unilateral ones, and transfer learning models showed superior performance over initial models. In the prediction results of bilateral transfer learning models, the male MAE was 7.74 years and RMSE was 9.73 years, the female MAE was 6.27 years and RMSE was 7.82 years, and the mixed sexes MAE was 6.64 years and RMSE was 8.43 years. CONCLUSIONS: The skeletal age estimation model, utilizing ischial tuberosity images of Han population in western China and employing the ResNet34 combined with transfer learning, can effectively estimate adult ischium age.

Clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in Chinese population with mismatch repair deficient urothelial carcinoma: a real-world study.

Urothelial carcinoma (UC) with deficient mismatch repair (dMMR) is a specific subtype of UC characterized by the loss of mismatch repair (MMR) proteins and its association with Lynch syndrome (LS). However, comprehensive real-world data on the incidence, clinicopathological characteristics, molecular landscape, and biomarker landscape for predicting the efficacy of PD-1/PD-L1 inhibitors in the Chinese patients with dMMR UC remains unknown. We analyzed 374 patients with bladder urothelial carcinoma (BUC) and 232 patients with upper tract urothelial carcinoma (UTUC) using tissue microarrays, immunohistochemistry, and targeted next-generation sequencing. Results showed the incidence of dMMR UC was higher in the upper urinary tract than in the bladder. Genomic analysis identified frequent mutations in KMT2D and KMT2C genes and LS was confirmed in 53.8% of dMMR UC cases. dMMR UC cases displayed microsatellite instability-high (MSI-H) (PCR method) in 91.7% and tumor mutational burden-high (TMB-H) in 40% of cases. The density of intratumoral CD8+ T cells correlated with better overall survival in dMMR UC patients. Positive PD-L1 expression was found in 20% cases, but some patients positively responded to immunotherapy despite negative PD-L1 expression. Our findings provide valuable insights into the characteristics of dMMR UC in the Chinese population and highlights the relevance of genetic testing and immunotherapy biomarkers for treatment decisions.

Delta and Notch-like epidermal growth factor-related receptor suppresses human glioma growth by inhibiting oncogene TOR4A.

Delta and Notch-like endothelial growth factor-related receptor (DNER) is a transmembrane protein that mediates signal communication between neurons and glial cells. This study was performed to elucidate the specific mechanism by which DNER inhibits human glioma growth. RNA sequencing was used to detect differentially expressed genes after DNER inhibition in glioma cells. The functions of the Torsin family 4 member A (TOR4A) gene were explored through cell proliferation and clonogenic assays, flow cytometric analysis, in vitro cell migration and invasion assays, in vivo glioma transplantation, and human glioma tissue analysis using the Chinese Glioma Genome Atlas database. Protein expression levels were determined using the western blot assay. We found that TOR4A was highly expressed after the inhibition of DNER in glioma cells. The prognosis of patients with gliomas that expressed high levels of TOR4A was worse than those with low levels of the protein. TOR4A promoted the proliferation of glioma cells and inhibited their apoptosis, likely by enhancing the expression of phosphorylated protein kinase B (p-AKT) and inhibiting that of antiapoptotic proteins. We confirmed that TOR4A is an oncogene and that DNER acts as a tumor suppressor gene by inhibiting TOR4A and its functions of promoting p-AKT and inhibiting antiapoptotic protein expression.

[Overexpression of miR-382-5p Mediated Downregulation of PTEN on Malignant Biological Behavior of Human Glioma U251 Cells].

OBJECTIVE: To investigate the effect of overexpression of miR-382-5p overexpression on malignant biological behavior of human glioma U251 cells. METHODS: U251 cells were transfected with miR-382-5pmimic. Then miR-382-5p and PTEN mRNA levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) after transfection. Used bioinformatics to predicted the presence of base binding sites between miR-382-5p and PTEN, and constructed PTEN pcDNA vector overexpression plasmid was constructed. Luciluciase reporting experiment was used to detect the targeting relationship between miR-382-5p and PTEN. Cells were randomly divided into four groups: control group, mimics group, pc-PTEN group and mimics+pc-PTEN group for follow-up experiments. RT-PCR was carried out to detect the level of PTEN mRNA in each group. Cell proliferation was detected by clone formation method. The mRNA levels of Ki67, Survivin and c-Myc were detected by RT-PCR. Transwell experiment was used to assayed cell invasion ability. The expression levels of E-cadherin, N-cadherin and Vimentin were determined by Western blot. RESULTS: Results showed that miR-382-5p directly targeted PTEN. Compared with the control group, miR-382-5p and c-Myc mRNA levels and E-cadherin protein level were increased (P<0.05),PTEN, Ki67 and Survivin mRNA levels were decreased (P<0.05), cell clonal formation rate and cell invasion number were decreased (P<0.05), N-cadherin and Vimentin protein levels were decreased (P<0.05) in the mimics group; In pc-PTEN group, miR-382-5p mRNA and c-Myc mRNA levels and E-cadherin protein level were decreased (P<0.05),PTEN, Ki67 and Survivin mRNA levels were increased (P<0.05), cell clonal formation rate and cell invasion number were increased (P<0.05), N-cadherin and Vimentin protein levels were increased (P<0.05). Compared with pc-PTEN group, PTEN, Ki67 and Survivin mRNA levels, the cell clone formation rate, the number of invasion cells and the N-cadherin and Vimentin levels of mimics+PC-PTEN group decreased significantly (P<0.05), while the c-Myc mRNA level and E-cadherin protein level increased significantly (P<0.05). CONCLUSION: Overexpression of miR-382-5p mediates the downregulation of PTEN expression, causing the inhibition of the proliferation, invasion, growth and EMT of U251 glioma cells.

Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway.

Context: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle.Objective: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism.Materials and methods: Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25-80 µg/mL cisplatin and/or 5-80 µM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA.Results: NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 µg/mL NB and 40 µg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner.Discussion and conclusions: Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic.

CDCA7L promotes glioma proliferation by targeting CCND1 and predicts an unfavorable prognosis.

Cell division cycle associated 7 like (CDCA7L) belongs to the JPO protein family, recently identified as a target gene of c­Myc and is frequently dysregulated in multiple cancers. However, to the best of our knowledge, no studies to date have been carried out to investigate the functions of CDCA7L in glioma. Thus, in this study, the expression level of CDCA7L and its association with the prognosis in glioma were detected through the TCGA database. The mRNA expression levels of CDCA7L in glioblastoma (GBM) tissues and normal brain tissues were detected by RT­qPCR and western blot analysis. To explore the role of CDCA7L in glioma, CDCA7L siRNA was constructed and transfected into U87 glioma cells. The expression levels of CDCA7L and cyclin D1 (CCND1) in glioma U87 cells following transfection with CDCA7L siRNA were measured by RT­qPCR and western blot analysis. CCK­8, colony formation, EdU and Transwell assays were used to measure the effects of CDCA7L on U87 cell proliferation, and flow cytometry was used to monitor the changes in the cell cycle following transfection with CDCA7L siRNA. Xenograft tumors were examined in vivo for the carcinogenic effects, as well as the mechanisms and prognostic value of CDCA7L in glioma tissues. The results revealed that CDCA7L was highly expressed in human GBM tissues, and a high expression of CDCA7L was associated with a poor prognosis of glioma patients through the TCGA database. We demonstrated that CDCA7L was highly expressed in human GBM tissues and 3 glioma cell lines. The downregulation CDCA7L expression significantly inhibited the proliferation and colony formation ability of U87 cells by blocking cell cycle progression in the G0/G1 phase. In addition, we found that the mRNA and protein levels of CCND1 were markedly decreased following transfection with CDCA7L siRNA compared with NC siRNA in vitro. The downregulation CDCA7L expression reduced the number of invading cells. Consistent with the results of the in vitro assays, the xenograft assay, immunohistochemistry (IHC) assay and western blot analysis demonstrated that, in response to CDCA7L inhibition, tumor growth was inhibited, Ki­67 and CCND1 expression levels were decreased in vivo. On the whole, the results of the current study indicate that CDCA7L is highly expressed in human glioma tissues and that a high CDCA7L expression predicts a poor prognosis of glioma patients. CDCA7L promotes glioma U87 cell growth through CCND1.

Cell division cycle associated 7 like predicts unfavorable prognosis and promotes invasion in glioma.

BACKGROUND: Cell division cycle associated 7 like (CDCA7L) belongs to the JPO protein family, which is recently identified as a target gene of c-Myc and is frequently dysregulated in multiple cancers. This study aimed to explore the clinicpathological value and biological role of CDCA7L in glioma. METHODS: CDCA7L expression in glioma patients was determined using the Oncomine database, and the prognostic role of CDCA7L expression was assessed in a retrospective cohort study. Moreover, the relationship of CDCA7L expression with the clinicopathological characteristics in glioma patients, including age, gender, tumor size, cystic change, Karnofsky performance scale (KPS) score, tumor location, extent of resection, WHO grade, adjuvant therapy and tumor recurrence, was analyzed in this study. In addition, the CDCA7L small interfering (si) RNA was constructed and transfected into the glioma U251 cells, so as to examine the role of CDCA7L in glioma patients. Besides, the changes in U251 cell invasion after transfection with CDCA7L siRNA were also monitored through Transwell assay. RESULTS: Our results suggested that CDCA7L expression was up-regulated in different glioma types, including glioblastoma, oligodendroglioma, diffuse astrocytoma and anaplastic astrocytoma. Moreover, the current retrospective cohort study indicated that high CDCA7L expression was associated with tumor size, WHO grade, adjuvant therapy and recurrence, as well as the poor overall survival (OS) and recurrence-free survival (RFS) in glioma patients. Lastly, CDCA7L expression was knocked down using CDCA7L siRNA, which could block the invasion abilities of glioma U251 cells. CONCLUSIONS: CDCA7L is highly expressed in human glioma tissues and a high CDCA7L expression level predicts the dismal prognosis for glioma patients. Moreover, CDCA7L can promote glioma invasion, which can serve as an independent potential prognostic biomarker for glioma patients.

CD44 collaborates with ERBB2 mediate radiation resistance via p38 phosphorylation and DNA homologous recombination pathway in prostate cancer.

CD44, a glycoprotein, has been reported to have relationship with resistance to radiation in prostate cancer (Cap) cells. However, its molecular mechanism remains unknown. In this study, we demonstrated that inhibited CD44 enhanced the radiosentivity in Cap cells. It has been hypothesized that CD44 combine with ERBB2 and activate downstream phosphated protein to mediate DNA damage repair. Therefore, we conducted a detailed analysis of effects of radiation by clonogenic assay and immunofluorescence stain for p-H2AX foci. The downstream of CD44/ERBB2 and DNA damage repair proteins was detected by western blot. The results reveal that CD44 interacted with ERBB2, the downstream of CD44/ERBB2 was p-p38 when Cap cells were irradiated. Among the pathways, homologous recombination (HR) related proteins Mre11 and Rad50 were involved in CD44/ERBB2/p-p38 mediated radioresistance in Cap. In conclusion, CD44 could stabilize ERBB2 and co-activate p-p38 expression then promote the DNA damage repair by HR pathway, which finally contribute to the radioresistance of CaP.

[Effects of centella asiatica granule on the expression of TGF-ß1 and related down-stream signals in rats with early diabetic nephropathy].

OBJECTIVE: To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-ß1(TGF-ß1) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-ß1 expression and related down-stream signals. METHODS: Sixty male SD rats were divided into control group(n=10) and DN model group(n=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-ß1, TßR1, TßR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The expressions of mRNA and protein of TGF-ß1, TßR1, TßR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN. CONCLUSIONS: CA plays an important role in preventing and curing DN through regulating the TGF-ß1/Smad signaling pathways.

[Effects of centellaasiatica granule on the expression of Smad 2/3, Smad 7 and collagen â £ in the mesangial cells stably expressed TGF-ß1].

OBJECTIVES: Stably expressed transforming growth factor -beta 1(TGF-ß1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed. METHODS: Lipofectin method was used to transfect TGF-ß1 vector into MC, and the stably expressed TGF-ß1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-ß1 group:stably expressed TGF-ß1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-ß1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-ß1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-ß1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot. RESULTS: The contents of TGF-ß1 and collagen Ⅳ in the culture medium of stably-expressed TGF-ß1 MC were increased significantly, and the CA could reverse the effects of TGF-ß1. The expressions of mRNA and protein of TGF-ß1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-ß1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-ß1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-ß1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression. CONCLUSIONS: The MCs stably-expressed TGF-ß1 can activate the TGF-ß1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-ß1/Smad signal pathway.

Tetrandrine inhibits glioma stem-like cells by repressing ß-catenin expression.

Cancer stem cells (CSCs) in glioma are often responsible for relapse and resistance to therapy. The purpose of the present study was to confirm the self-renewal and migration inhibitory effects of tetrandrine (Tet), which is a compound extracted from the dried root of Stephania tetrandra S. Moore, toward glioma stem-like cells (GSLCs) and to examine the associated molecular mechanisms. Using a neurosphere culture technique, we enriched the GSLC population from the human glioblastoma cell lines U87 and U251. Cells were analyzed using cell counting kit-8 (CCK-8), western blotting, flow cytometry, transwell assay and immunofluorescence staining. GSLCs displayed properties of neural stem cells, including elevated expression of the cancer stem cell marker ALDH1 and ß-catenin. We found that Tet treatment decreased sphere formation in GSLCs in a dose-dependent manner using tumor spheroid formation assay. The GSK3ß inhibitor BIO maintained sphere formation and migration capacity in GSLCs, whereas the ß-catenin/TCF transcription inhibitor ICG-001 decreased sphere formation and the migration capacity of GSLCs. The proportion of apoptotic GSLCs also increased in response to ICG-001 treatment. These results indicate that ß-catenin activity is vital in maintaining neural stem cell traits of GSLCs. Tet inhibits cell viability, neurosphere formation and migration of GSLCs in vitro. Importantly, Tet treatment significantly repressed the nuclear translocation and expression of ß-catenin and induced apoptosis in GSLCs, as indicated in part by the upregulation of Bax, the cleavage of PARP and the downregulation of Bcl-2. The present study demonstrates that the inhibition of ß-catenin in CSCs by Tet could be an effective strategy for the treatment of glioma.

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation.

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.

Tetrandrine suppresses human glioma growth by inhibiting cell survival, proliferation and tumour angiogenesis through attenuating STAT3 phosphorylation.

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to possess anti-tumour activity. However, its effects on human glioma remain unknown. In this study, we demonstrated that Tet inhibited human glioma cell growth in vitro and in vivo. It has been hypothesised that Tet inhibits glioma growth by affecting glioma cell survival, proliferation and vasculature in and around the xenograft tumour in the chick CAM model and signal transducer and activator of transcription 3 (STAT3) mediated these activities. Therefore, we conducted a detailed analysis of the inhibitory effects of Tet on cell survival using a TUNEL assay and flow cytometric analysis; on cell proliferation based on the expression of proliferating cell nuclear antigen; and on angiogenesis using a CAM anti-angiogenesis assay. We used western blotting to investigate the role of STAT3 on the anti-glioma activities of Tet. The results revealed that Tet inhibited survival and proliferation in human glioma cells, impaired tumour angiogenesis and decreased the expression of phosphorylated STAT3 and its downstream proteins. In sum, our data indicate that STAT3 is involved in Tet-induced the regression of glioma growth by activating tumour cell apoptosis, inhibiting glioma cell proliferation and inhibiting angiogenesis.

Short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and safety observation.

OBJECTIVE: To evaluate the short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and to observe the safety. METHODS: A total of 120 elderly patients with trigeminal nerve tumor were divided into a treatment group and a control group by random draw (n=60), and both groups were subjected to resection by stereotactic image-guided endoscopic nasal surgery. Afterwards, the control group was administered with high-dose cytarabine while the treatment group was given low-dose cytarabine for 14 days. RESULTS: Both groups completed treatment, but the effective rate of the treatment group (96.7%) was significantly higher than that of the control group (83.3%) (P < 0.05). The pain scores of the two groups were similar at T0, T1 and T2, but the score of the treatment group at T2 was significantly different from those at T0 and T1 (P < 0.05). During treatment, the treatment group was significantly less prone to complications such as headache, vomiting, vision impairment, nausea and local swelling than the control group (P < 0.05). During three months of follow-up, the appetite, sleep and daily living scores were significantly higher than those of the control group (P < 0.05). CONCLUSION: Stereotactic image-guided surgery was able to treat trigeminal nerve tumor well, and the effect was enhanced by low-dose cytarabine that improved postoperative outcomes and quality of life by dramatically decreasing complications.

EGCG inhibits properties of glioma stem-like cells and synergizes with temozolomide through downregulation of P-glycoprotein inhibition.

RATIONAL: Combination therapy to inhibit cancer stem cells may have important clinical implications. Here, we examine the molecular mechanisms by which epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea, inhibits the stem cell characteristics of glioma stem-like cells (GSLCs) and synergizes with temozolomide (TMZ), a DNA-methylating agent commonly used as first-line chemotherapy in gliomas. GSLCs were enriched from the human glioblastoma cell line U87 using neurosphere culture. Cells were analyzed using flow cytometry, quantitative PCR, and western blotting. Compared to U87 cells, a higher percentage of U87 GSLCs remained in the G0/G1 phase, with downregulation of the cell-cycle protein CylinD1 and overexpression of stem cell markers CD133 and ALDH1. The drug-resistance gene ABCB1 (but not ABCG2 or MGMT) also showed high mRNA and protein expression. The resistance index of U87 GSLCs against TMZ and carmustine (BCNU) was 3.0 and 16.8, respectively. These results indicate that U87 GSLCs possess neural stem cell and drug-resistance properties. Interestingly, EGCG treatment inhibited cell viability, neurosphere formation, and migration in this cell model. EGCG also induced apoptosis, downregulation of p-Akt and Bcl-2, and cleaving PARP in a dose-dependent manner. Importantly, EGCG treatment significantly downregulated P-glycoprotein expression but not that of ABCG2 or MGMT and simultaneously enhanced sensitivity to TMZ. Our study demonstrates that the use of EGCG alone or in combination with TMZ may be an effective therapeutic strategy for glioma.

Epithelial-to-mesenchymal transition is involved in BCNU resistance in human glioma cells.

Chemotherapy has been considered as an effective treatment for malignant glioma; however, it becomes increasingly ineffective with tumor progression. Epithelial-to-mesenchymal transition (EMT) is a process whereby cells acquire morphologic and molecular alterations that facilitate tumor metastasis and progression. Emerging evidence associates chemoresistance with the acquisition of EMT in cancer. However, it is not clear whether this phenomenon is involved in glioma. We used the previously established human glioma cell lines SWOZ1, SWOZ2 and SWOZ2-BCNU to assess cellular morphology, molecular changes, migration and invasion. We found that BCNU-resistant cells showed multiple drug resistance and phenotypic changes consistent with EMT, including spindle-shaped morphology and enhanced pseudopodia formation. Decreased expression of the epithelial adhesion molecule E-cadherin and increased expression of the mesenchymal marker vimentin were observed in BCNU-resistant SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. Migratory and metastatic potentials were markedly enhanced in SWOZ1 and SWOZ2-BCNU cells compared to SWOZ2 cells. These data suggest that there is a possible link between drug resistance and EMT induction in glioma cells. Gaining further insight into the mechanisms underlying chemoresistance and EMT may enable the restoration of chemosensitivity or suppression of metastasis.