IL-32 Promotes the Radiosensitivity of Esophageal Squamous Cell Carcinoma Cell through STAT3 Pathway.

OBJECTIVE: This study is set out to determine the relationship between IL-32 and radiosensitivity of esophageal squamous cell carcinoma (ESCC). METHODS: Western blot was adopted for measuring IL-32 expression in Eca-109 and TE-10 cells. Eca-109 and TE-10 cells with interference or overexpression of IL-32 were treated with the presence or absence of X-ray irradiation. Then, the use of CCK8 assay was to detect proliferation ability, and effects of IL-32 expression on radiosensitivity of ESCC were tested by colony formation assay. The cell apoptosis was detected using flow cytometry. STAT3 and p-STAT expression, and apoptotic protein Bax were detected by western blot. RESULTS: Colony formation assay and CCK8 assay showed that compared with the NC group without treatment, the growth of the ESCC cells, that is Eca-109 and TE-10, was significantly inhibited in the OE+IR group with highly expressed IL-32 and irradiation. In flow cytometry analysis, in Eca-109 and TE-10 cells, highly expressed IL-32 combined with irradiation significantly increased apoptosis compared with the control group. Highly expressed IL-32 has a synergistic effect with irradiation, inhibiting STAT3 and p-STAT3 expression and increasing apoptotic protein Bax expression. CONCLUSION: IL-32 can improve the radiosensitivity of ESCC cells by inhibiting the STAT3 pathway. Therefore, IL-32 can be used as a new therapeutic target to provide a new attempt for radiotherapy of ESCC.

PBX1 Increases the Radiosensitivity of Oesophageal Squamous Cancer by Targeting of STAT3.

The radioresistance of oesophageal squamous cell carcinoma (OSCC) is a critical factor leading to a poor prognosis among patients. The expression of PBX1 is abnormally high in a broad range of human tissues, and this gene plays a key role in tumour proliferation. This research intended to explore the radiosensitization of OSCC by silencing PBX1. The OSCC cell lines KYSE450 and KYSE150 were subjected to PBX1 silencing and/or irradiation (IR). Cell proliferation, colony formation, and apoptosis were tested to evaluate the radiosensitization ability of PBX1 silencing. The levels of STAT3 and p-STAT3 in the OSCC cells were tested by Western blotting. Furthermore, KYSE150 cells with or without PBX1 silencing were xenografted into nude mice with or without radiation exposure. Concomitant PBX1 silencing and IR can obviously suppress growth and enhance radiosensitivity in OSCC cells and xenografts. Moreover, the downregulation of PBX1 inhibits the expression of STAT3 and p-STAT3. The downregulation of PBX1 may increase radiosensitivity in OSCC cells and xenografts via the PBX1/STAT3 pathway. Our findings demonstrate that PBX1 may be a potential target for promoting the effect of radiation therapy in OSCC patients.

MiR-450a-5p inhibits autophagy and enhances radiosensitivity by targeting dual-specificity phosphatase 10 in esophageal squamous cell carcinoma.

Radioresistance reduces the success of therapy for patients with ESCC. Enhancing our understanding of the cardinal principles of radioresistance may improve the response of patients to irradiation. MicroRNAs perform a key role in posttranscriptional regulation, which is linked with the response of tumors to irradiation. Here, we successfully constructed a radioresistant cell line model, ECA109R, from parental esophageal cancer cell line ECA109. We used RNA-Seq analysis and qRT-PCR to compare the miRNA expression profiles of the ECA109 and ECA109R cell lines. The results revealed that miR-450a-5p was downregulated in the radioresistant cells. Functional analysis indicated that miR-450a-5p increases cellular radiosensitivity and suppresses autophagy in ESCC cells. We utilized a luciferase reporter assay to identify the target gene, DUSP10, as an indispensable regulator of the p38 and SAPK/JNK signaling pathways. Upregulation or downregulation of DUSP10 expression could reverse the effects of miR-450a-5p overexpression or inhibition. Tumor xenograft experiments verified that miR-450a-5p overexpression could increase sensitivity to radiation therapy in vivo. In general, our findings indicate that miR-450a-5p is a latent radiosensitizer and may represent a potential novel therapeutic target for radioresistance in ESCC.

Long-Term Results and Predictors of Survival After Conservative Breast Surgery for Breast Cancer During Pregnancy.

BACKGROUND Breast cancer is one of the most frequently encountered malignancies in women. Although the prognosis is good for most breast cancer patients, little is known about the outcomes of breast carcinoma during pregnancy. The long-term results and predictors of survival of conservative breast surgery for breast cancer during pregnancy are especially unclear. MATERIAL AND METHODS Patients with primary diagnosis of breast cancer during pregnancy who received conservative breast surgery were recruited in this study from October 2009 to January 2015. Clinical data were collected and compared to individuals without associated pregnancies. The primary outcome disease-free survival (DFS) and the secondary outcome, overall survival (OS), were compared between the 2 groups (pregnant vs. nonpregnant women). Cox proportional hazards regression analysis was used to assess the potential predictors of survival for breast cancer patients during pregnancy. RESULTS Sixty-three pregnant patients underwent conservative breast carcinoma. The median gestational age was 26 weeks and the median age was 34 years. The nonpregnant group consists of 82 individuals with median age of 37 years. All the patients received chemotherapy after surgery. The follow-up period was 3 years. The 3-year DFS was 79.3% in the pregnant group and 81.7% in the nonpregnant group. The 3-year OS was 87.3% (pregnant) and 89% (nonpregnant), respectively. Multivariable analysis revealed that tumor stage and chemotherapy were independent predictors for survival. CONCLUSIONS Our study showed that conservative breast surgery is a reliable therapy for breast cancer patients during pregnancy, with similar DFS and OS compared to nonpregnant patients.