Suppression of CCT3 inhibits the proliferation and migration in breast cancer cells.

BACKGROUND: CCT3 is a subunit of chaperonin-containing TCP-1 (CCT), which folds many proteins involved in cancer development and plays an important role in many cancers. However, the role of CCT3 in breast cancer is still unclear. METHODS: CCT3 expression was knocked down by transfecting breast cancer cells with lentiviral shRNA. The proliferation of breast cancer cells (HCC1937 and MDA-MB-231) was detected by Celigo image cytometry and MTT assay, the migration of the cells was measured by Transwell analysis, cell cycle distribution and apoptosis was detected by flow cytometry, and changes in signal transduction proteins were detected by western blot analysis. RESULTS: The expression of CCT3 was significantly suppressed by transduction with lentiviral shRNA; CCT3 knockdown significantly reduced the proliferation and metastasis ability of breast cancer cells (HCC 1937 and MDA-MB-231), increased the proportion of cells in S phase, and decreased the proportion of cells in G1 phase compared to those in shControl cells. There was no significant change in the number of cells in the G2/M phase. Apoptosis analysis showed that knockdown of CCT3 induced apoptosis in breast cancer cells. Western blot analysis showed that the expression of many signal transduction proteins was changed after suppression of CCT3. A rescue experiment showed that overexpression of NFκB-p65 rescued the cell proliferation and migration affected by CCT3 in breast cancer cells. CONCLUSION: CCT3 is closely related to the proliferation and migration of breast cancer and may be a novel therapeutic target.

Dose-Response Relationship between Head and Neck Radiation and Damages to Gustatory Cells in Mice.

Objective: To investigate the dose-response relationship between radiation to the head and neck regions and damage observed in mice gustatory cells. Materials and Methods: A total number of 45 mice (C57BL/6) (aged 8-12 weeks) were enrolled in this study. The head and neck regions of the mice were irradiated at doses of 8 Gy (low-dose group, n = 15), 16 Gy (moderate-dose group, n = 15), and 24 Gy (high-dose group, n = 15). Each time, 3 mice from each group were sacrificed before radiation and then 2-day, 4-day, 7-day, and 14-day post the irradiation, respectively. The immune-histochemical staining method was employed to obtain gustatory papilla tissues and mark gustatory cells. Careful calculation of the numbers of proliferative cells, taste buds, and type II gustatory cells was conducted. Results: A decrease in the number of Ki-67-marked proliferative cells was noted at 2 days postirradiation (DPI), and the number of cells was recovered to the normal level at 4-DPI in each group. The number of Ki-67-marked proliferative cells was hypercompensation (significantly higher than normal) in the moderate-dose and high-dose groups at 7-DPI and insufficient compensation (significantly lower than normal) in the high-dose group at 14-DPI. There was a significant reduction of taste buds and type II gustatory cells at 2-DPI and is lowest at 4-DPI in the moderate-dose and high-dose groups, while little change was observed in the low-dose group. Conclusion: Damages to Gustatory Cells after head and neck radiation were dose-related and compensation occurred in 14-DPI and may be insufficient when overdosed.

Identification of novel lactate metabolism-related lncRNAs with prognostic value for bladder cancer.

Background: Bladder cancer (BCA) has high recurrence and metastasis rates, and current treatment options show limited efficacy and significant adverse effects. It is crucial to find diagnostic markers and therapeutic targets with clinical value. This study aimed to identify lactate metabolism-related lncRNAs (LM_lncRNAs) to establish a model for evaluating bladder cancer prognosis. Method: A risk model consisting of lactate metabolism-related lncRNAs was developed to forecast bladder cancer patient prognosis using The Cancer Genome Atlas (TCGA) database. Kaplan‒Meier survival analysis, receiver operating characteristic curve (ROC) analysis and decision curve analysis (DCA) were used to evaluate the reliability of risk grouping for predictive analysis of bladder cancer patients. The results were also validated in the validation set. Chemotherapeutic agents sensitive to lactate metabolism were assessed using the Genomics of Drug Sensitivity in Cancer (GDSC) database. Results: As an independent prognostic factor for patients, lactate metabolism-related lncRNAs can be used as a nomogram chart that predicts overall survival time (OS). There were significant differences in survival rates between the high-risk and low-risk groups based on the Kaplan‒Meier survival curve. decision curve analysis and receiver operating characteristic curve analysis confirmed its good predictive capacity. As a result, 22 chemotherapeutic agents were predicted to positively affect the high-risk group. Conclusion: An lactate metabolism-related lncRNA prediction model was proposed to predict the prognosis for patients with bladder cancer and chemotherapeutic drug sensitivity in high-risk groups, which provided a new idea for the prognostic evaluation of the clinical treatment of bladder cancer.

MiR-122 radiosensitize hepatocellular carcinoma cells by suppressing cyclin G1.

PURPOSE: Emerging evidence has shown that radiotherapy is an effective treatment for hepatocellular carcinoma (HCC), Micro(mi)RNAs are involved in regulating radiosensitivity in many cancers. MiR-122 accounts for approximately 70% of all cloned miRNAs in the liver, but there are few reports about whether it is involved in regulating of radiosensitivity in HCC cells. MATERIALS AND METHODS: HCC cells (HepG2 and Huh7) overexpressing miR-122 were constructed by transfecting them with lentiviral-miR-122. Then, their proliferation ability was analyzed by the MTT, and colony formation assays and a xenograft tumor model was used to detect their radiosensitivity. The expression of cyclin G1 mRNA and protein was detected by the quantitative real-time polymerase chain reaction and western blotting, respectively. RESULTS: Overexpression of miR-122 inhibited the proliferation of, and radiosensitized HCC cells. Cyclin G1 mRNA and protein level were suppressed in HepG2 tumors overexpression miR-122. CONCLUSION: MiR-122 may be useful as a potential radiosensitizer for HCC, and its mechanism is related to the regulation of cyclin G1.

Silencing the Expression of Cyclin G1 Enhances the Radiosensitivity of Hepatocellular Carcinoma In Vitro and In Vivo by Inducing Apoptosis.

Radiotherapy plays an important role in the treatment of hepatocellular carcinoma (HCC). Cyclin G1 is a novel member of the cyclin family, and it is abnormally expressed in HCC. In this study we investigated the role of cyclin G1 in the radiotherapy of HCC cells. The expression of cyclin G1 was silenced by transfection of cyclin G1-siRNA into HepG2 cells and Huh7 cells, and the expression of cyclin G1 mRNA and protein was measured by qRT-PCR and Western blot analysis. The proliferation was analyzed using MTT assay, and the radiosensitivity of HCC cells was detected using colony formation assay and a xenograft tumor model. The expression of apoptosis-related proteins (Bcl-2 and Bax) was detected by Western blot analysis, and caspase-3 was detected using fluorimetry. The expression of cyclin G1 mRNA and protein in HepG2/Huh7-cyclin G1-siRNA cells was found to be significantly decreased compared to that in HepG2/Huh7 cells. Silencing the expression of cyclin G1 inhibited the proliferation of HCC cells and enhanced radiosensitivity in HCC cells in vitro and in vivo. Knockdown of cyclin G1 expression significantly decreased Bcl-2 expression, and increased Bax expression and caspase-3 activity in HCC cells. Silencing of cyclin G1 expression enhances the radiosensitivity of HCC cells in vitro and in vivo. The mechanism for this may be related to the regulation of apoptosis-related proteins.

Nutritional Status and Its Association With Radiation-Induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma During Radiotherapy: A Prospective Study.

BACKGROUND AND AIMS: Malnutrition is a concern in patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy (CRT)/radiotherapy (RT), which is considered to be related with radiation-induced oral mucositis (ROM). The study aimed to evaluate the nutritional status of NPC patients during RT and investigate its association with ROM. METHODS: A prospective study was conducted in NPC patients. Patients were divided into three subgroups (mild, moderate, and severe groups) based on the duration of severe ROM (≥ grade 3). Body weight, body mass index (BMI), albumin, prealbumin, NRS2002, and ROM grade were assessed on a weekly basis before and during CRT/RT. The statistical analysis was performed in the overall group and between three subgroups. RESULTS: A total of 176 patients were included. In the overall group, body weight and BMI kept decreasing since week 1 of RT, and NRS2002 score and ROM grade increased (p < 0.001). NRS2002 score and prealbumin levels were significantly different between each subgroup (p ≤ 0.046). Significant differences were observed in the proportion of patients receiving enteral nutrition, duration of parenteral nutrition, and total calories provided by nutritional support among three subgroups (p = 0.045-0.001). CONCLUSIONS: Malnutrition occurred early in NPC patients and worsened continuously during RT. ROM was strongly associated with nutritional status. Nutritional support should be provided at the start of RT, especially in patients at high-risk of severe ROM.

[Prognostic factors and treatment of 74 patients with dermatofibro-sarcoma protuberans].

OBJECTIVE: To analyze treatment and prognostic factors of 74 patients with dermatofibro-sarcoma protuberans (DFSP). METHODS: From August 1990 to November 1999, 74 patients with DFSP confirmed pathologically were treated. There were 52 males and 22 females with a median age of 37 years (range 4 to 80 years) on diagnosis. Seventeen patients were treated by extensive excision and 2 by limited excision. Fifty-two patients had surgical resection alone (S), and 22 postoperative radiotherapy (S + R) of 50-70 Gy. The multivariate parameters were analyzed using Cox model. Kaplan-Meier and Log-Rank test were used to evaluate the results of the recurrence-free survival. RESULTS: The rate of recurrence was 28.4% for all patients. The 5-year recurrence-free survival rate (RFSR) was 66.6% and the 10-year RFSR was 52.5%. The 5-year and 10-year in the S group were 58.4% and 41.2%, compared with 90.0% and 83.3% in the S + R group (P < 0.05). The 5-year and 10-year RFSR in the pathologically positive margin group were 57.5% and 41.4% respectively, compared with the 75.0% and 56.6% in the pathologically negative group (P < 0.05). Multivariate analysis suggested radiotherapy and negative pathological margins were favorable prognostic factors. CONCLUSION: Post-operation radiotherapy and pathological margin are the independent prognostic factors.

Caspase-3 expression in metastatic lymph nodes of esophageal squamous cell carcinoma is prognostic of survival.

AIM: To assess whether differential expression of caspase-3 in paired metastatic lymph nodes (LNs) is prognostic of survival in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: Capases-3 expression was evaluated immunohistochemically in 122 pairs of primary ESCCs and regional metastatic LNs assembled on tissue microarrays. The impact of caspase-3 expression on survival outcomes was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model. RESULTS: The level of caspase-3 expression was significantly higher in LN metastases than in primary tumors (P < 0.001). Caspase-3 expression in the primary tumors was associated with longer median survival (23 mo vs 21 mo, P = 0.033), whereas higher expression in paired metastatic LNs was associated with shorter median survival (20 mo vs 22 mo, P = 0.043). Multivariate analysis showed that both were independent prognostic factors. CONCLUSION: Caspase-3 expression in metastatic LNs may be a potential independent predictor of poorer overall survival in patients with resected ESCC and LN metastasis. Protein expression in metastatic tumors may be a biomarker prognostic of survival.

[Effect of concurrent chemoradiotherapy on serum vascular endothelial growth factor in esophageal squamous cell carcinoma patients--a report of 43 cases].

BACKGROUND & OBJECTIVE: The prognosis of esophageal cancer is not only affected by TNM stage but also by the level of serum vascular endothelial growth factor (S-VEGF). This study was to investigate the effect of concurrent chemoradiotherapy on S-VEGF in esophageal squamous cell carcinoma (ESCC), and to explore the correlation of S-VEGF to the prognosis of ESCC. METHODS: Serum samples were obtained from ESCC patients, treated with concurrent chemoradiotherapy in Cancer Center of Sun Yat-sen University from Dec. 2002 to May 2004, before treatment and 1 month after treatment. The serum samples from sex- and age-matched healthy donors were used as controls. Two courses of chemotherapy, comprised of cisplatin and 5-fluorouracil, were given during radiotherapy at 4-week intervals. S-VEGF level was measured by ELISA. The changes of S-VEGF level before and after treatment were observed, and its correlation to progress-freely survival rate of ESCC patients was analyzed. RESULTS: S-VEGF level was significantly higher in ESCC patients before and 1 month after treatment than in healthy controls [(516.27+/-67.89) ng/L and (347.19+/-35.42) ng/L vs. (294.20+/-23.40) ng/L, P<0.01, P=0.002]; concurrent chemoradiotherapy significantly reduced S-VEGF level (P<0.01). S-VEGF level before treatment was significantly lower in the patients achieved complete remission than in those achieved partial remission or had progressive disease [(345.82+/-76.29) ng/L vs. (669.37+/-99.04) ng/L, P =0.020]. The 1-year progress-freely survival rate was 0 in the patients with S-VEGF level of > 516.27 ng/L before treatment and >347.19 ng/L after treatment, 17% in the patients with S-VEGF level of > 516.27 ng/L and <347.19 ng/L, respectively, 57% in the patients with S-VEGF level of < 516.27 ng/L and >347.19 ng/L, respectively, and 72% in the patients with S-VEGF level of < 516.27 ng/L and <347.19 ng/L, respectively (P= 0.005). CONCLUSIONS: S-VEGF level is higher in ESCC patients than in healthy control. Concurrent chemoradiotherapy could reduce S-VEGF level in ESCC. The changes of S-VEGF level before and after treatment may provide prognostic information for ESCC patients.

[External radiation and combined transcatheter arterial chemoembolization for unresectable primary liver cancer].

BACKGROUND & OBJECTIVE: Transcatheter arterial chemoembolization (TACE) is the routine treatment for unresectable primary liver cancer, but 3-year survival rate of patients received TACE alone is only about 20%. This research was to evaluate efficacy of external radiotherapy (RT) combined with TACE on unresectable primary live cancer. METHODS: From Jun. 1994 to Apr. 2002, 114 patients with unresectable primary liver cancer were non-randomized to receive TACE plus RT (54 patients), or TACE alone (60 patients) as control. For TACE, after skiagram confirmed catheterization, suspension of 300 mg of carboplatin, 50-60 mg of epirubicin, 14-20 mg of mitomycin, and 10-30 ml of iodized oil was perfused into hepatic arteries, 1-2 mm of Gelfoam particles was given to embolize hepatic arteries according to blood supply conditions of tumors, this process was repeated every 4-8 weeks. Either group was treated with 1-4 sessions of TACE. In TACE+RT group, patients received radiation on tumor and generous margin 21-28 days after TACE. The radiation dose was 46-60 Gy in daily 2 Gy fractions. RESULTS: In TACE+RT group, response rate (AFP titer decrease of >50%) was 61.1%, and 1-, 2-, 3-year survival rates of TACE+RT group were significantly higher than those of TACE group (66.5% vs. 53.9%, 48.4% vs. 37.2%, and 37.4% vs. 17.8%, P<0.05). Three-year survival rate correlated with tumor size, liver function grade, and portal vein embolus. CONCLUSION: TACE combined with RT may prolong survival time of patients with unresectable primary live cancer.