Identification of circRNAs and circRNA-miRNA-mRNA regulatory network in radiation-induced heart disease.

OBJECTIVE: Radiation-induced heart disease (RIHD) is one of the most common and serious long-term adverse effect after thoracic radiotherapy. Our aim was to investigate the potential molecular mechanism underlying RIHD using RNA-sequencing (RNA-seq) and bioinformatics methods. MATERIALS AND METHODS: An RIHD rat model was established and transcription profiles were identified using RNA-seq. Differentially expressed circRNAs, miRNAs and mRNAs were identified. Enrichment of functions and signaling pathways analysis were performed based on GO and the KEGG database. Potential circRNA-miRNA-mRNA regulatory network underlying RIHD was established. qRT-PCR was used to validate the associated genes. RESULTS: In total, 21 circRNAs, 26 miRNAs, and 178 mRNA transcripts were differentially expressed in RIHD. GO and KEGG pathway analyses identified that differentially expressed mRNAs were most enriched in pathways referring to endothelial function and vascular pathological processes. Nine circRNAs, 10 miRNAs, and 6 mRNA transcripts were most likely involved in vascular function and a candidate competitive endogenous RNA (ceRNA) network of circRNA-miRNA-mRNA was established, which were further validated by qRT-PCR. CONCLUSIONS: Our study revealed that vascular pathology plays an important role in the early stage of RIHD. Furthermore, a circRNA-miRNA-mRNA ceRNA network was found that may be involved in the regulation of vascular function and RIHD.

Does the primary tumor site in stage I extranodal natural killer/T-cell lymphoma matter?

The purpose of this study was to investigate whether the primary tumor site in stage I extranodal natural killer/T-cell lymphoma (ENKTCL) had a prognostic value. Between January 2009 and December 2015, 152 stage I ENKTCL patients with primary disease in the nasal cavity and Waldeyer's ring were enrolled for this retrospective study. All patients received extended field intensity-modulated radiotherapy alone without prophylactic cervical node irradiation at a total dose of 50 Gy. In this study, there were 122 patients whose primary tumors were localized in the nasal cavity (NC group), and no adjacent structures were involved. A total of 18 patients had a primary disease involving the nasal cavity and Waldeyer's ring (NC-WR group), and the remaining 12 patients had primary tumors confined to Waldeyer's ring (WR group). We found that there was no significant difference in cervical lymph node failure rates among the NC, NC-WR, and WR groups. In terms of the 5-year overall survival (OS) rates, there was a significant difference among the NC, NC-WR, and WR groups (p=0.004), with the WR group having the worst OS. Multivariate analyses showed that the primary site (p=0.011) and ECOG (Eastern Cooperative Oncology Group) score (p=0.013) were independent prognostic factors for OS. In summary, patients with stage I ENKTCL had a good local control rate with radiotherapy alone and without prophylactic cervical node irradiation (PCNI), regardless of the site of the primary tumor. So, we think PCNI for stage I ENKTCL patients is not necessary. Patients with a primary tumor site located in Waldeyer's ring had the worst prognosis. And combined treatment with radiotherapy and chemotherapy should be considered in patients with primary tumors located outside the nasal cavity.

The efficacy of postoperative radiotherapy for patients with non-small cell lung cancer: An updated systematic review and meta-analysis.

The controversy over the efficacy of postoperative radiotherapy (PORT) has existed for a long time. The present study reassessed the overall survival (OS) and disease-free survival (DFS) data to investigate whether PORT can improve survival in resectable non-small cell lung cancer (NSCLC) patients. The following databases were used to perform literature search: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Embase (from January 1, 1986 to July 5, 2021). The results of overall survival (OS) and disease-free survival (DFS) were calculated as hazard ratio (HR). Confidence intervals are chosen with 95% confidence intervals. A total of 12 RCTs and 19 retrospective cohort studies were found to meet the inclusion criteria. A significant DFS improvement was detected in the PORT group (4111 patients from 15 studies), although statistical difference was not detected for OS between the non-PORT and PORT groups (31 studies, 49,342 total patients). PORT prolonged OS in patients undergoing PORT plus postoperative chemotherapy (POCT) and in pN2 patients. Patients with a median radiation dose of 50.4 Gy and a median radiation dose of 54 Gy had a better OS after PORT. However, if the total radiotherapy dose went up to 60 Gy, PORT increased the risk of death in NSCLC patients. Significant difference in OS was not found in the results of studies with regard to treatment methods, pathologic stages, study type, radiation beam quality, and radiation dose. Patients undergoing postoperative chemoradiotherapy and pN2 patients can benefit from PORT. Patients exposed to median radiation doses of 50.4 and 54 Gy demonstrated relatively good efficacy. For patients with non-small-cell lung cancer, PORT has not been proven to extend OS, but its effect on DFS remains strong.

Esophageal Carcinosarcoma: Analysis of Clinical Features and Prognosis of 24 Cases and a Literature Review.

OBJECTIVE: Esophageal carcinosarcoma (ECS) is a rare malignant tumor that accounts for only 0.5%-2.8% of all esophageal malignancies. As most current studies are case reports, the relationship between clinical features and prognosis remains controversial. METHODS: We investigated the clinical features and prognosis of 24 patients with ECS in a single center from 2006 to 2018. There were 18 male and 6 female patients aged 52-82 years with a median age of 62.5 years. In addition, we included 9 studies on ECS from PubMed and a literature review. RESULTS: The median follow-up time of the 24 patients was 70.5 (range, 10-156)months. The 3-year and 5-year survival rates were 83.3% and 70.8%, respectively. Among the 24 patients, none of the 10 (41.7%) stage T1 cancer patients had lymph node metastasis; however, lymph node metastasis was noted in 8 (57.1%) stage T2-4 cancer patients. The literature review revealed that 211 patients had a 5-year survival rate of 11.8%-68.2%, and 54.5%-95.8% study participants had early stage ECS. Although the information provided in the literature review is limited, it appears to be a characteristic of the early stage of the disease and predicts better prognosis when ECS is diagnosed, which is similar to the result of the current study. CONCLUSION: Our results indicate that ECS has a favorable prognosis, even among patients with early stage ECS who undergo radical esophagectomy with lymph node dissection. Because of the low incidence of ECS, further studies with more cases need to investigate this rare malignancy.

Clinicopathological characteristics and survival outcomes in neuroendocrine prostate cancer: A population-based study.

OBJECTIVE: This study aimed to investigate the clinicopathological features and the survival outcomes of neuroendocrine prostate cancer (NEPC). METHODS: Within the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, we identified a total of 510 patients with NEPC between 2006 and 2015. Age-adjusted incidence rates were evaluated in the study by the SEER∗Stat Software version 8.3.6. Kaplan-Meier analysed assessed overall survival (OS) after stratification according to marital status, age, histologic subtype, metastatic status, and treatment. The significant differences were assessed in a log-rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS. RESULTS: From a total of 560,124 patients with prostate cancer diagnosed between 2006 and 2015, we identified 510 cases of de novo NEPC. Regarding histology, among all the NEPC, 329 (64.5%) patients were diagnosed as small cell carcinoma, 181 (39.8%) were nonsmall cell carcinoma. The overall age-adjusted incidence of NEPC statistically significantly increased from 0.321/1,000,000 person-years in 2006 to 0.587/1,000,000 person-years in 2015. The median OS in our study cohort was 9 months (95% CI, 8-10 months). Multivariate cox regression analysis showed that age, histologic subtype, and stage were independent prognostic factors for NEPC patients. The majority of NEPC (78.2%) were metastatic at diagnosis. In terms of treatment, for metastatic tumor patients, chemotherapy was the most effective therapy. Chemotherapy increased the OS of patients with regional (distant) metastases from 8 months (5 months) to 13.5 months (9 months). CONCLUSION: NEPC is extremely rare but the incidence of NEPC has been increasing in the past years. The prognosis of NEPC is poor because most cases are diagnosed at metastatic stage. The patients with metastases are typically treated with chemotherapy and chemotherapy shows survival benefits in both regional and distant metastatic tumor patients.

Inhibition of immune checkpoints prevents injury-induced heterotopic ossification.

Heterotopic ossification (HO), true bone formation in soft tissue, is closely associated with abnormal injury/immune responses. We hypothesized that a key underlying mechanism of HO might be injury-induced dysregulation of immune checkpoint proteins (ICs). We found that the earliest stages of HO are characterized by enhanced infiltration of polarized macrophages into sites of minor injuries in an animal model of HO. The non-specific immune suppressants, Rapamycin and Ebselen, prevented HO providing evidence of the central role of the immune responses. We examined the expression pattern of ICs and found that they are dysregulated in HO lesions. More importantly, loss of function of inhibitory ICs (including PD1, PD-L1, and CD152) markedly inhibited HO, whereas loss of function of stimulatory ICs (including CD40L and OX-40L) facilitated HO. These findings suggest that IC inhibitors may provide a therapeutic approach to prevent or limit the extent of HO.

Molecular mechanisms of lncRNAs in regulating cancer cell radiosensitivity.

Radiotherapy is one of the main modalities of cancer treatment. However, tumor recurrence following radiotherapy occurs in many cancer patients. A key to solving this problem is the optimization of radiosensitivity. In recent years, long non-coding RNAs (lncRNAs), which affect the occurrence and development of tumors through a variety of mechanisms, have become a popular research topic. LncRNAs have been found to influence radiosensitivity by regulating various mechanisms, including DNA damage repair, cell cycle arrest, apoptosis, cancer stem cells regulation, epithelial-mesenchymal transition, and autophagy. LncRNAs are expected to become a potential therapeutic target for radiotherapy in the future. This article reviews recent advances in the role and mechanism of lncRNAs in tumor radiosensitivity.

Brucea javanica seed oil enhances the radiosensitivity of esophageal cancer by inhibiting hypoxia-inducible factor 1α, in vitro and in vivo.

Brucea javanica oil emulsion (BJOE) has been used clinically to treat esophageal cancer combined with radiotherapy for numerous years in China. However, the detailed mechanism remains unclear. Thus, the effects of BJOE on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) were evaluated in vitro and in vivo. The growth inhibitory effects of different BJOE concentrations were determined through an MTT assay. Radiosensitivity was evaluated through focal formation measurements and clone formation assays. The effects of BJOE on radiation-induced apoptosis were examined through flow cytometric analysis. The effects of BJOE on hypoxia-inducible factor 1α (HIF-1α) protein levels in vitro and in vivo were respectively analyzed through western blot analyses and enzyme-linked immunosorbent assays. BJOE significantly inhibited ECA109 cell proliferation in a dose- and time-dependent manner. Pretreatment with 2.5 mg/ml BJOE increased ECA109 radiosensitivity. BJOE in combination with radiation increased the DNA double-strand breaks. Compared with radiation alone, BJOE and radiation significantly increased the apoptotic rate of ECA109 cells. BJOE also decreased the HIF-1α protein levels in vitro and in vivo. The results from the present study demonstrated that BJOE enhanced the radiosensitivity of human ESCC. This finding was associated with the inhibition of HIF-1α expression. Therefore, BJOE may be a potential radiotherapy sensitization drug due to its significant anti-hypoxic activity.

Oroxylin a could be a Promising Radiosensitizer for Esophageal Squamous Cell Carcinoma by Inducing G2/M Arrest and Activating Apoptosis.

To evaluate the radiosensitization of Oroxylin A on esophageal carcinoma cell as well as the optimal scheduling of Oroxylin A and radiotherapy (RT). Cell proliferation was estimated by a CCK8 assay. Radiosensitization was evaluated by a clonogenic survival assay. The progressions of Cell apoptosis and Cell cycle were investigated by flow cytometry. Expressions of survivin and cell cycle regulators were evaluated by Western blot analysis. A dose-dependent cell survival reduction was found in response to radiation with or without Oroxylin A. The apoptosis rates were remarkably dose-dependent higher in combination groups than in either Oroxylin A or radiation alone group. Besides, Oroxylin A could obviously radiosensitize ESCC cells by arresting tumor cells in G2/M phase and regulating cyclin B1 and Cdc 2 protein expression. Oroxylin A could be a promising radiosensitizer for esophageal squamous cell carcinoma by inducing G2/M phase blocking and activating cell apoptosis.

Clinical significance of measuring reticulated platelets in infectious diseases.

This study aimed to explore the association between the percentage of reticulated platelets (RP%) and infection, and analyze the value of combined measurement of RP% with other inflammatory indicators in diagnosing infection. A total of 190 patients with signs and symptoms suspicious of infection were included in the infection group, and 70 healthy subjects with comparable percentages of gender and age were included in the control group. Peripheral white blood cell (WBC) count, percentage of neutrophils (N%), platelet count, C-reactive protein (CRP), procalcitonin (PCT), RP%, and axillary temperature were recorded. Dynamic changes in RP% with infection were measured to analyze the association between RP% and infection. The receiver operating characteristic curve was used to evaluate the value of each inflammatory indicator in diagnosing infection and analyze the diagnostic value of the combined adoption of multiple inflammatory indicators. RP% was significantly higher in the infection group than in the noninfection and control groups. The sensitivity and specificity for diagnosing infection were, respectively, 91.78% and 93.18% when RP% and CRP were used in combination, 90.41% and 90.90% when RP% and PCT were used in combination, and 100% and 100% when RP%, CRP, and PCT were used in combination. RP% changed dynamically with the progression of infection and recovered to lower than 5.5% at 2 to 7 days before the body temperature recovered to a normal level. The diagnostic value of RP% was the highest. A combined use with CRP/PCT could improve the sensitivity and specificity in the early diagnosis of infectious diseases.

Esophageal cancer stem cells and implications for future therapeutics.

Esophageal carcinoma (EC) is a lethal disease with high morbidity and mortality worldwide, and the incidence has been increasing in recent years. Although the diagnosis and treatment of EC have improved considerably, EC has rapidly progressed in the clinical setting and has a poor prognosis for its metastasis and recurrence. The general idea of cancer stem cells (CSCs) is primarily based on clinical and experimental observations, indicating the existence of a subpopulation of cells that can self-renew and differentiate. The EC stem cells, which can be isolated from normal pluripotent stem cells by applying similar biomarkers, may participate in promoting esophageal tumorigenesis through renewal and repair. In this review, major emphasis is given to CSC markers, altered CSC-specific pathways, and molecular targeting agents currently available to target CSCs of esophageal cancer. The roles of numerous markers (CD44, aldehyde dehydrogenase, CD133, and ATP-binding cassette subfamily G member 2) and developmental signaling pathways (Wnt/ß-catenin, Notch, hedgehog, and Hippo) in isolating esophageal CSCs are discussed in detail. Targeting CSCs can be a logical strategy to treat EC, as these cells are responsible for carcinoma recurrence and chemoradiation resistance.

Potential biomarkers for esophageal cancer.

Esophageal cancer, which consist of esophageal adenocarcinoma and esophageal squamous cell carcinoma, is one of the most common malignant tumors in the world, especially in the south of Iran and China. To find and investigate the biomarkers in the initiation, development and progression of esophageal cancer will help us predict the prognosis of esophageal cancer patients and improve the curative effect and survival rate. Here, we reviewed the potential biomarkers of esophageal cancer in three aspects: Immunohistochemical markers, blood-based markers, miRNA markers and Gene expression profiling. All these biomarkers provided promising therapeutic targets for the diagnosis, treatment, and prognosis of esophageal cancer.

Long-term clinical outcome of intensity-modulated radiation therapy for locally advanced esophageal squamous cell carcinoma.

PURPOSE: This study evaluated the effectiveness and safety of intensity-modulated radiation therapy (IMRT) for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Between August 2009 and December 2011, 112 patients with pathologically confirmed ESCC treated with IMRT at Jiangsu Province People's Hospital and Nantong Tumor Hospital were included in a retrospective analysis. Patients received either IMRT alone (group A) or concurrent chemoradiotherapy (CRT) (group B). A radiation dose of 60-66 Gy administered in 30-33 fractions was delivered to the tumor. The patients in group B simultaneously received 2 cycles of cisplatin-based doublets with either 5-fluorouracil or taxotere. The Kaplan-Meier method was used to compute the survival time. Early and late toxicities were scored according to CTCAE v.3.0. RESULTS: The response rate of group B (91.07%) was not significantly greater than that of group A (89.29%) (χ2 = 0.10, p = 0.75). The 1- and 3-year survival rates of group B (87.5% and 57.14%, respectively) were greater than those of group A (69.64% and 37.50%, respectively). The difference in overall survival was statistically significant between groups A and B (χ2 = 5.30, p = 0.02; χ2 = 4.33, p = 0.04). Hematological toxicity, gastrointestinal toxicity, and treatment-related esophagitis were significantly higher in group B than group A (16.07% vs. 33.93%, p = 0.04; 10.71% vs. 26.79%, p = 0.03; 19.64% vs. 44.64%, p = 0.01). However, intergroup differences in terms of late toxicity were not significant. CONCLUSIONS: IMRT was a practical and feasible technique to treat ESCC. Concurrent CRT could increase local tumor control and long-term survival. The CRT regimen was associated with a higher incidence of acute gastrointestinal and hematological toxicity.

Fenofibrate enhances radiosensitivity of esophageal squamous cell carcinoma by suppressing hypoxia-inducible factor-1α expression.

Radiation therapy is widely used in esophageal squamous cell carcinoma (ESCC). Promoting radiation sensitivity is important. Recent studies have shown that fenofibrate can inhibit the growth of several cancer lines and hypoxia-inducible factor-1α (HIF-1α) expression in MCF-7 cells. However, few studies on the radiosensitive effect of fenofibrate on ESCCs under hypoxic condition have been conducted. In this study, we assessed the radiosensitive effects of fenofibrate on human ESCC cells. In vitro experiments showed the inhibition of cytotoxic effects after ionizing irradiation. We measured cell viability and clonogenic survival rate. Flow cytometry showed that fenofibrate pretreatment promoted apoptosis. The in vivo data also suggest that fenofibrate had radiosensitizing effects in ECA-109 cells xenografted into nude mice. Western blot and immunohistochemical analyses revealed that the HIF-1α and vascular endothelial growth factor (VEGF) protein content decreased by fenofibrate. Thus, the inhibition of HIF-1α and VEGF expression in ESCC cells contributed to the radiosensitive effect. These data suggest that fenofibrate may be a potential radiosensitive drug.

Berberine inhibits the expression of hypoxia induction factor-1alpha and increases the radiosensitivity of prostate cancer.

BACKGROUND: The radiation resistance of prostate cancer remains the primary obstacle to improve patient survival. This study aimed to investigate the effects of berberine, a commonly used natural product, on the radiosensitivity of prostate cancer. METHODS: Prostate cancer cell line LNCaP and DU-145 were subjected to hypoxia and/or ionizing radiation (IR), in the presence or absence of berberine treatment. Cell growth and colony formation, and apoptosis were evaluated. Moreover, LNCaP cells were xenografted into nude mice and subjected to IR and/or berberine treatment. The expression of HIF-1α and VEGF in prostate cancer cells and xenografts was detected by Western blot analysis. RESULTS: Berberine increased radiosensitivity of prostate cancer cells and xenografts in a dose dependent manner, and this was correlated with the inhibition of HIF-1α and VEGF expression. CONCLUSIONS: Berberine may inhibit the expression of HIF-1α and VEGF and thus confer radiosensitivity on prostatic cancer cells. Berberine has potential application as an adjuvant in radiotherapy of prostatic cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1519827543125021.

Ginsenoside Rg3 enhances radiosensitization of hypoxic oesophageal cancer cell lines through vascular endothelial growth factor and hypoxia inducible factor 1α.

OBJECTIVE: To determine if the pretreatment of hypoxic human oesophageal carcinoma cell lines (EC109, TE1 and KYSE170) with ginsenoside Rg3 (Rg3) increases their radiosensitivity to X-rays. METHODS: The growth inhibitory effect of different Rg3 concentrations was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Radiation sensitivity was measured using a clone formation assay and flow cytometry was used to measure the effects of Rg3 on radiation-induced apoptosis. Western blot analysis was used to measure the effects of Rg3 on the levels of hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF). RESULTS: Rg3 inhibited EC109, TE1 and KYSE170 cell growth in a dose- and time-dependent manner. Pretreatment with 10 µmol/ml Rg3 increased EC109, TE1 and KYSE170 radiosensitivity. Rg3 plus radiation significantly increased the apoptosis rate compared with radiation alone. Rg3 also decreased VEGF and HIF-1α protein levels in EC109 cells in a dose-dependent manner. The combination of Rg3 and radiation increased the fragmentation of double-stranded DNA. CONCLUSION: Rg3 enhanced the radiosensitivity of human oesophageal carcinoma cell lines cultured under hypoxic conditions possibly by downregulating VEGF and HIF-1α protein levels.

Berberine radiosensitizes human nasopharyngeal carcinoma by suppressing hypoxia-inducible factor-1α expression.

CONCLUSION: Berberine confers radiosensitivity on nasopharyngeal carcinoma (NPC) and this is associated with the down-regulation of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression. Berberine could be a promising radiosensitizer for NPC radiotherapy. OBJECTIVES: NPC has a poor prognosis. Radiotherapy as first-line therapy significantly increases patient survival but radioresistance is a problem. This study aimed to investigate the radiosensitizing effects of berberine on NPC and explore the underlying mechanisms. METHODS: CNE-1 and CNE-2 cells were exposed to hypoxia and treated with berberine at different concentrations. The MTT assay, clonogenic assay, and flow cytometry were performed to analyze cell proliferation, colony formation, and apoptosis. The expression of HIF-1α and VEGF was assessed by Western blot and immunofluorescence analysis. Male nude mice inoculated subcutaneously with CNE-2 cells were used to examine the sensitizing effects of berberine in vivo. RESULTS: Berberine efficiently radiosensitized NPC cells and xenografts in mice, and inhibited hypoxia/radiation-induced up-regulation of HIF-1α and VEGF expression.

Polymorphisms in XPD gene could predict clinical outcome of platinum-based chemotherapy for non-small cell lung cancer patients: a meta-analysis of 24 studies.

OBJECTIVE: Xeroderma pigmentosum group D (XPD) is an essential gene involved in the nucleotide excision repair (NER) pathway. Two commonly studied single nucleotide polymorphisms (SNPs) of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793) are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients. METHODS: A comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS) and overall survival (OS). The pooled and 95% confidence intervals (CIs) of ORs (odds ratios) and HRs (hazard ratios) were estimated using the fixed or random effect model. RESULTS: Twenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C) polymorphism was not significantly associated with increased response in Caucasians (OR=1.35, 95%CI=1.0-1.83, P=0.122 for heterogeneity) but was associated with decreased PFS in Asians (HR=1.39, 95%CI=1.07-1.81, P=0.879 for heterogeneity). Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P=0.014 for TR; P<0.001 for PFS). CONCLUSIONS: XPD Lys751Gln (A>C) may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings.

Prognostic role of microRNA-21 in colorectal cancer: a meta-analysis.

BACKGROUND: To date, many studies have shown that microRNAs (miRNA) exhibit altered expression in various cancers and may play an important role as prognostic biomarker of cancers. The present meta-analysis summarizes the recent advances in the use of microRNA-21 (miR-21) in the assessment of colorectal cancer and analyzes the prognostic role of miR-21 for survival outcome. METHODOLOGY/PRINCIPAL FINDINGS: The present meta-analysis was performed by searching PubMed through multiple search strategies. Data were extracted from studies comparing overall survival (OS) in patients with colorectal cancer who showed higher expression of miR-21 than similar patients. Pooled hazard ratios (HRs) of miR-21 for survival and 95% confidence intervals (CI) were calculated. Seven studies with a total of 1174 patients were included this meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-21 expression in colorectal cancer was 1.76 (95% CI: 1.34-2.32, P=0.000). After elimination of heterogeneity, the pooled HR was 2.32 (95% CI: 1.82-2.97, P=0.000), which was found to significantly predict poorer survival. The subgroup analysis suggested that elevated miR-21 level and patients' survival correlated with III/IV stage (HR=5.35, 95% CI: 3.73-7.66). CONCLUSIONS/SIGNIFICANCE: The present findings suggest that high expression of miR-21 might predict poor prognosis in patients with colorectal cancer.

Berberine enhances radiosensitivity of esophageal squamous cancer by targeting HIF-1α in vitro and in vivo.

Radiation therapy is an important treatment approach for esophageal squamous cell carcinoma (ESCC). However, how to promote radiation sensitivity in ESCC remains a challenge. This study aimed to evaluate the effects of berberine, a common used Chinese medicine, on the radiosensitivity of ESCC. ECSS cell line ECA109 and TE13 were subjected to hypoxia and/or ionizing radiation (IR), in the presence or absence of berberine treatment. Cell growth and survival, and apoptosis were evaluated. In addition, ECA109 cells were xenografted into nude mice and subjected to IR and/or berberine treatment. The expression of HIF-1α and VEGF was detected by western blot and immunohistochemical analysis. Our results showed that berberine increased radiosensitivity of ESCC cells and xenografts, and this was associated with the inhibition of HIF-1α and VEGF expression. These data suggest that berberine may be a potential radiotherapy sensitization drugs due to its significant anti-hypoxia activity.