Combined Radiomics-Clinical Model to Predict Radiotherapy Response in Inoperable Stage III and IV Non-Small-Cell Lung Cancer.

Purpose: Radiotherapy is a promising treatment option for lung cancer, but patients' responses vary. The purpose of the study was to investigate the potential of radiomics and clinical signature for predicting the radiotherapy sensitivity and overall survival of inoperable stage III and IV non-small-cell lung cancer (NSCLC) patients. Materials: This retrospective study collected 104 inoperable stage III and IV NSCLC patients at the Yunnan Cancer Hospital from October 2016 to September 2020. They were divided into radiation-sensitive and non-sensitive groups. We used analysis of variance (ANOVA) to select features and support vector machine (SVM) to build the radiomic model. Furthermore, the logistic regression method was used to screen out clinically relevant predictive factors and construct the combined model of radiomics-clinical features. Finally, survival was estimated using the Kaplan-Meier method. Results: There were 40 patients in the radiation-sensitive group and 64 in the non-sensitive group. These patients were divided into training set (73 cases) and testing set (31 cases) according to the ratio of 7:3. Nine radiomics features and one clinical feature were significantly associated with radiotherapy sensitivity. Both the radiomics model and combined model have good predictive performance (the areas under the curve (AUC) values of the testing set were 0.864 (95% confidence interval [CI]: 0.683-0.996) and 0.868 (95% CI: 0.689-1.000), respectively). Only platelet level status was associated with overall survival. Conclusion: The combined model constructed based on radiomics and clinical features can effectively identify the radiation-sensitive population and provide valuable clinical information. Patients with higher platelet levels may have a poor prognosis.

Health-related quality of life measured by EQ-5D-3L for the spouses of breast cancer patients.

To explore factors influencing the health-related quality of life of spouses of breast cancer patients and the suitable questionnaires for this purpose. A cross-sectional study was conducted in the Third Affiliated Hospital of Kunming Medical University. The spouses of breast cancer patients were included and evaluated via face-to-face interviews. Self-designed demographic characteristics and disease-related questionnaires, the 12-item health survey questionnaire (SF-12), the three-level European five-dimensional health status scale (EQ-5D-3L), and the Social Support Rate Scale (SSRS) were used. The internal consistency reliability measure Cronbach's coefficient, criterion-related validity, construct validity, and sensitivity were used to evaluate the applicability of the EQ-5D-3L. Univariate and multivariate analyses were performed to analyze the factors associated with the health-related quality of life of spouses of breast cancer patients. We investigated a total of 100 spouses of breast cancer patients. Cronbach's α, the internal consistency reliability coefficient, was 0.502. The EQ-5D-3L health utility score was moderately correlated with PCS-12 (r=0.46, p=0.0001) and weakly correlated with MCS-12 (r=0.35, p=0.0001). The EQ-5D-3L health utility score for the spouses of breast cancer patients was 0.870, and the EQ-VAS was 78.3. In multivariate analysis, social support and cognition of the treatment effect were factors that influenced the EQ-5D-3L health utility score. The EQ-5D-3L has good reliability, validity, and sensitivity for measuring the physiological aspects of the health-related quality of life of spouses of BC patients. EQ-5D-3L was considered suitable for this study.

G9a Regulates Cell Sensitivity to Radiotherapy via Histone H3 Lysine 9 Trimethylation and CCDC8 in Lung Cancer.

PURPOSE: To investigate the role and underlying mechanism of G9a and CCDC8 in lung cancer radioresistance. METHODS: Western blotting assays were used for G9a, CCDC8, H3K9me3 expression detection. MTT assays and clone formation assays were used for measuring cell proliferation activities. Flow cytometry assays were used for cell apoptosis detection. The enrichment of H3K9me3 in CCDC8 promoter was measured by chromatin immunoprecipitation assay. RESULTS: G9a and G9a-mediated H3K9me3 are upregulated in radioresistant lung cancer cells (A549/IR cell and XWLC-05/IR cell). Blocking G9a not only promotes radiosensitivity of A549/IR cell and XWLC-05/IR cell but also reduces aggressive behavior of radioresistant A549 cell/IR and XWLC-05/IR cell. In addition, G9a-controlled H3K9me3 is able to binding to the promoter of tumor suppressor gene CCDC8 and suppresses CCDC8 expression. CCDC8 dysregulation is responsible for G9a-mediated radioresistance of A549/IR cell and XWLC-05/IR cell. CONCLUSION: G9a and H3K9me3 contribute to the lung cancer radioresistance via modulating CCDC8 expression.

ATAS Acupuncture Reduces Chemotherapy Induced Fatigue in Breast Cancer Through Regulating ADROA1 Expression: A Randomized Sham-Controlled Pilot Trial.

OBJECTIVE: To investigate the feasibility and effectiveness of ATAS acupuncture (Acupoints-Time-Space Acupuncture) as a non-pharmacological intervention to prevent or relieve chemotherapy-induced fatigue in breast cancer patients undergoing taxane chemotherapy. METHODS: A pilot study in Kunming center with the aim of evaluating 40 patients randomized to 3 groups: ATAS, sham and non-acupuncture with an unequal randomization of 2:1:1. Participants with stage I-III breast cancer were scheduled to receive adjuvant EC4P4 chemotherapy. Participants in the ATAS and sham acupuncture arms received 20 sessions of acupuncture over 20 weeks, non-acupuncture arm received usual care. Evaluation scales, including VAS-F, MFI-20, HDAS, ISI, and blood samples were collected at four timepoints (T1-T4). mRNA sequencing was performed to detect the mechanism of acupuncture. RESULTS: A total of 581 sessions of acupuncture were performed on patients in the acupuncture group. There was no difference between the three groups in terms of clinical characteristics. Patients randomized to ATAS acupuncture had improved symptoms including fatigue, anxiety and insomnia during the whole process of chemotherapy compared with the other two groups. The VAS-F score of ATAS acupuncture group was decreased compared with non-acupuncture group (P=0.004). The score of MFI-20 in ATAS acupuncture group was kept at low level, while the other two groups' scores kept climbing during chemotherapy (P=0.016; P=0.028, respectively). The mechanism of ATAS acupuncture which reduced fatigue and depression may be related to ADROA1, by regulating cGMP/PKG pathway. CONCLUSION: This pilot study has demonstrated that ATAS acupuncture can significantly reduce fatigue induced by chemotherapy. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR-IPR-17,013,652, registered Dec 3, 2017. http://www.chictr.org.cn/. PROTOCOL VERSION: Version 3.2 dated from 2018/04/20.

Cellular senescence in ionizing radiation (Review).

Radiotherapy (RT) is one of most common treatments for cancer. However, overcoming the failure and side effects of RT as well as radioresistance, recurrence and metastasis remains challenging in cancer treatment. Cellular senescence (CS) is permanent arrested state of cell division induced by various factors, including exposure to ionizing radiation (IR). CS induced by IR contributes to tumour cell control and often even causes side effects in normal cells. Improvement of the therapeutic RT ratio is dependent on more cancer cell death and less normal cell damage. In addition, the biological behaviour of tumour cells after IR has also been linked to CS. This review summarizes our understanding of CS in IR, which may be beneficial for providing new insight for improving the therapeutic outcomes of RT.

Microarray Analysis of Circular RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.

Preoperative 5-fluorouracil- (5-FU-) based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, the effect of 5-FU-based chemoradiotherapy on CRC is limited due to the development of chemoradiation resistance (CRR), and the molecular mechanisms underlying this resistance are yet to be investigated. Recently, circular RNAs (circRNAs), which can function as microRNA sponges, were found to be involved in the development of several cancers. In this study, we focused on clarifying the modulation of the expression profiles of circRNAs in CRR. Microarray analysis identified 71 circRNAs differentially expressed in chemoradiation-resistant CRC cells. Among them, 47 were upregulated and 24 were downregulated by more than twofold. Furthermore, expression modulation of five representative circRNAs was validated by quantitative reverse transcription PCR (qRT-PCR). Moreover, these modulated circRNAs were predicted to interact with 355 miRNAs. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most modulated circRNAs regulate several cancers and cancer-related pathways, and the possible mechanism underlying CRR was discussed. This is the first report revealing the circRNA modulations in 5-FU chemoradiation-resistant CRC cells by microarray. The study provided a useful database for further understanding CRR and presents potential targets to overcome CRR in CRC.

Influence of VEGFR single nucleotide polymorphisms on the efficacy of sunitinib therapy against renal cell carcinoma.

Single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor receptor (VEGFR) may have effects on the MAPK/ERK/STAT3 signaling pathway, and the resulting phenotypes may influence the response to sunitinib-targeted therapy for renal cell carcinoma. In order to test this hypothesis patients with advanced renal cell carcinoma treated with sunitinib, were enrolled in our study. Peripheral blood samples were used to run a polymerase chain reaction-restriction fragment length polymorphism protocol to type candidate nucleotide polymorphism loci (VEGFR1, VEGFR2 and VEGFR3). The samples were also used in western blots to determine p-MAPK/ERK/STAT3 protein expression levels. The clinical responses to treatment were recorded and then a logistic regression method was applied to analyze the correlation between polymorphism of loci and effectiveness of sunitinib therapy. According to a follow-up visit (on average after 15 months of treatment) there were 16 complete responses (CR), 29 partial responses (PR) and 23 stable disease (SD) and progression of disease (PD) cases. Tests were carried out for 5 SNPs: VEGFR1 (rs664393), VEGFR2 (rsl870377 and rs7667298) and VEGFR3 (rs448012 and rs72816988). Mutation rates of rsl870377 and rs448012 loci in the CR+PR group were lower than those in the SD+PD group. No such differences were found for the other 3 loci. Relative expression levels of p-MAPk, p-ERK and p-STAT3 in the CR+PR group were significantly lower than those in the SD+PD group (P<0.05). The median progression-free survival and overall survival (OS) in the CR+PR group were higher than those in the SD+PD group (P<0.001). The median OS of the TT rsl870377 genotype was higher than that of the AA genotype, and the median OS of the GG rs448012 genotype was higher than that of the CC genotype (P<0.001). It was concluded through a logistic regression model that rsl870377 (AA) and rs448012 (GG) are independent risk factors closely associated with the effectiveness of sunitinib-targeted therapy on renal cell carcinoma. VEGFR SNPs are able to mediate the MAPK/ERK/STAT3 signaling pathway and therefore influence the effectiveness of sunitinib-targeted therapy, which makes them possible new therapeutic targets.

Correlation between epidermal growth factor receptor tyrosine kinase inhibitor efficacy and circulating tumor cell levels in patients with advanced non-small cell lung cancer.

OBJECTIVE: The aim of this study was to investigate the correlation between the efficacy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and circulating tumor cell (CTC) levels in patients with advanced non-small cell lung cancer (NSCLC). The efficacy of EGFR-TKIs in reducing CTC counts in patients with advanced NSCLC was studied. PATIENTS AND METHODS: A total of 66 patients with advanced NSCLC were enrolled and divided into two groups (those with high CTC counts and those with low CTC counts) based on the patients' median CTC counts. All the patients were treated with an EGFR-TKI, and the treatment efficacy and prognoses were compared. RESULTS: The treatment efficacies were 53.3% (16/30) and 27.8% (10/36) for the low CTC group and high CTC group, respectively, and this difference was statistically significant (P<0.05). The median overall survival was 22.8 months (95% confidence interval [CI]: 18.9-26.8 months) for the low CTC group and 18.3 months (95% CI: 2.9-8.2 months) for the high CTC group. The median progression-free survival was 11.5 months (95% CI: 8.1-15 months) and 5.6 months (95% CI: 2.9-8.2 months) for the low and high CTC groups, respectively, and the difference was statistically significant (P<0.05). CONCLUSION: The CTC count can be used as an index for predicting the EGFR-TKI effect on patients with advanced NSCLC. Efficacy and prognosis of EGFR-TKI treatment and CTC count were considered important, and the CTC count could be used to predict the efficacy of EGFR-TKI treatment and prognosis of advanced NSCLC. The change in CTC expression levels can be used as an index for evaluating the prognosis of patients with advanced NSCLC.

Radiotherapy concurrent versus sequential with endocrine therapy in breast cancer: A meta-analysis.

INTRODUCTION: This study compared treatment outcomes of radiotherapy concurrent with endocrine therapy and radiotherapy sequential with endocrine therapy in breast cancer. MATERIALS AND METHODS: Eligible studies of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were retrieved through extensive searches of the PubMed, Medline, Embase, Cochrane library, FEBM, FMJS, Web of science, Wiley, CBM, CNKI, Wang fang, Cqvip databases from 2000 to 2014. Original English and Chinese publications of radiotherapy concurrent and sequential with endocrine therapy in breast cancer were included. The primary endpoint was radiation-induced toxicity including upper than grade 2 skin related toxicity, radiation pneumonia and pulmonary fibrosis; the second endpoint was survival date, including local recurrence, distant metastasis, 5-year OS, 10-year OS. RESULTS: Eleven eligible trials were identified, six in English and five in Chinese. Totally, there were 1291 women in concurrent groups, and 1179 in sequential groups. Statistical analysis showed that there was no statistical difference between concurrent and sequential groups in skin related toxicity (RR 1.20, 95% CI 0.92-1.56, P = 0.17), radiation pneumonia (RR 1.11, 95% CI 0.46-2.70, P = 0.81) and pulmonary fibrosis (RR 1.35, 95% CI 0.75-2.41, P = 0.32). Meanwhile, no statistical difference was found in survival data, (RR 0.97, 95% CI 0.79-1.28, P = 0.26), (RR 0.86, 95% CI 0.66-1.12, P = 0.27) in local recurrence and distant metastasis respectively, (RR 1.01, 95% CI 0.96-1.06, P = 0.65), (RR 0.98, 95% CI 0.93-1.02, P = 0.32) in 5-year and 10-year overall survival respectively. Stratification analysis was proceeded, grouped by tamoxifen and AI in different treatment timing, however, no statistical difference was found in radiation-induced toxicity and survival outcomes. CONCLUSION: Radiotherapy concurrent with endocrine therapy didn't increase or decrease neither the incidence of radiation-induced toxicity nor the survival rate compared with that of sequential group; Endocrine therapy drugs didn't influence outcomes in different treatment timing.

Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells.

BACKGROUND: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. MATERIALS AND METHODS: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. RESULTS: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak- STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. CONCLUSIONS: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.