Epidemiological trends and factors associated with survival in patients with medulloblastoma: A 45-year population-based retrospective study.

Medulloblastoma (MB) is a primary brain malignancy. However, updated epidemiological data and long-term outcomes are lacking.The clinical and epidemiological datasets of patients with MB in the current study were obtained from the Surveillance, Epidemiology, and End Results (SEER) databases. Joinpoint regression models were used to assess the rate of changes in the incidence, prevalence, and treatment trends in patients with MB. Cox hazard and competition risk model analyses were used to assess overall survival (OS) and cancer-specific survival (CSS).The age-adjusted incidence of MB remained relatively stable at 0.15 per 100,000 individuals in 2019. The annual percentage change (APC) of females remained stable, whereas that of males increased over time. The 20-year limited-duration prevalence of patients with MB increased significantly from 0.00016 % in 1999 to 0.00203 % in 2018. Patients aged 5-19 years accounted for 46.7 % of all age groups, and the trend for the three treatments was increased. Average annual percentage change (AAPC) for the chemotherapy group was increased in patients aged 20 + years MB [AAPC = 2.66 (95 % CI 0.93-6.31)]. Multivariate analysis revealed that OS and CSS varied significantly according to age, year of diagnosis, histology, stage, surgery, and radiotherapy. Subgroup analysis showed that chemotherapy was associated with a favorable prognosis in high-risk groups.The incidence of MB remained relatively stable, and its prevalence increased significantly. This current population-based study further identified the prognostic factors in patients with MB. Moreover, the use of chemotherapy was associated with better survival in high-risk groups.

Trends of incidence and mortality in metaplastic breast cancer and the effect of contralateral prophylactic mastectomy: A population-based study.

INTRODUCTION: Metaplastic breast cancer (MBC) is considered rare and aggressive. We examined the epidemiology of and prognostic factors for MBC and investigated the effect of contralateral prophylactic mastectomy (CPM), because neither had been thoroughly examined previously. METHODS: We obtained data from the Surveillance, Epidemiology, and End Results (SEER)-18(2000-2018) for epidemiological and survival analysis. RESULTS: The age-adjusted incidence per 100,000 persons of MBC increased significantly from 0.12 to 0.35 [annual percent change (APC):2.95%, 95% confidence interval [CI], 1.73-4.19]. The incidence-based mortality increased from 0.01 to 0.12 (APC: 5.01%, 95% CI: 2.50-7.58). The incidence of MBC patients who underwent CPM significantly increased from 0.003 to 0.039 with an APC of 10.96% (95%CI, 7.26-14.78). Older patients and those with higher T classification were less likely to receive CPM. The multivariate Cox model showed that CPM was not an independent predictor of good prognosis for both overall survival (OS) and breast cancer-specific survival (BCSS) (pre-propensity score matching (PSM): OS: P = 0.331; BCSS: P = 0.462. post-PSM: OS: P = 0.916; BCSS: P = 0.967). Subgroup analysis showed that CPM still did not provide a survival benefit to any risk groups. CONCLUSION: In this study, we demonstrated that the incidence and incidence-based mortality of MBC have increased over the past decades. Although the number of MBC patients who underwent CPM has significantly increased recently, CPM did not confer a survival benefit compared with unilateral mastectomy, indicating that the decision to undergo CPM should be considered carefully.

Effect of open versus video-assisted thoracoscopy on perioperative outcomes and survival for cases of thymic carcinomas and thymic neuroendocrine tumors.

BACKGROUND: The oncology-related indices between open and video-assisted thoracoscopic surgery (VATS) procedures for thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) remain unclear. METHODS: Propensity score matching (PSM) and multivariate Cox proportional risk models were used to evaluate the perioperative outcomes and survival rates of patients undergoing open and VATS for TCs and TNETs at the Second Affiliated Hospital of Air Force Military Medical University Hospital, between 2009 and 2018. RESULTS: Of the total 126 cases of TCs and TNETs, VATS treatment was used in 39 (30.9%). Advanced age and Masaoka-Koga staging were found to be independent prognostic factors for both TCs and TNETs, through a multifactorial Cox regression analysis. There was no significant difference in survival between the VATS and open groups before and after PSM; however, the VATS group had better perioperative-related indicators. There were no significant differences between the groups in terms of mortality at 30 days, mortality at 90 days, R0 resection rate, and 5-year survival rate (67.5% vs. 58.5% [P = 0.260] in the VATS group compared to the open group, in a PSM analysis of the 27 VATS and 27 open groups). Compared to the open group, the VATS group had a shorter length of hospital stay (13 days vs. 16 days, P = 0.015), a shorter level I care (0 days vs. 1 day, P = 0.016), and less intraoperative bleeding (50 mL vs. 300 mL, P < 0.001). CONCLUSIONS: In this single-center retrospective study of TCs and TNETs, survival rates were comparable between the VATS group and the open group, and the VATS group showed improved perioperative-related parameters.

Epidemiology of and factors associated with overall survival for patients with head and neck adenoid cystic carcinoma.

BACKGROUND: Updated epidemiologic and survival data of head and neck adenoid cystic carcinoma (HNACC) are lacking. This retrospective study aimed to clarify the incidence, prevalence, and overall survival (OS) of patients with HNACC and establish relevant nomogram. METHODS: Trends in incidence, limited-duration prevalence, and relative survival (RS) rates were evaluated using data from the Surveillance, Epidemiology, and End Results (SEER) database, and annual percent change (APC) in rates was calculated using joinpoint regression. Data on age, sex, site, stage, and surgery were used in construction and validation of the nomogram. RESULTS: The study included 6474 patients; 57.7% were female and 78.6% were white. The age-adjusted incidence rates of HNACC decreased significantly from 0.41 to 0.25 per 100,000 [1975-2018; average annual percent change (AAPC): - 1.37, P < 0.001], which was dominated by the localized stage. The 20-year limited duration prevalence increased from 0.00028% to 0.00262%. The 5- and 10-year RS rates of all HNACC patients were 80.0% and 65.5%, respectively. RS rates in HNACC showed a slight increase over time, with APC values of 0.03 for 5-year (P < 0.05) and 0.13 for 10-year (P < 0.05) RS. A prognostic model was constructed. The C-indices for the training and testing sets were both 0.734. The nomogram's discrimination efficiency was evaluated using the receiver operating characteristic curve and had moderate predictive power. CONCLUSIONS: Over the past 40 years, the incidence of HNACC decreased accompanied by slightly improved survival rates. Nomogram was capable of predicting the 5- and 10-year OS rates with moderate accuracy.

DNA repair pathways-targeted cyclovirobuxine inhibits castration-resistant prostate cancer growth by promoting cell apoptosis and cycle arrest.

BACKGROUND: Castration-resistant prostate cancer (CRPC) is a deadly malignancy without effective therapeutics. Cyclovirobuxine (CVB) can play an anticancer role by inhibiting mitochondrial function, regulating tumor cell apoptosis, dysregulating autophagy, and other mechanisms. This study aimed to examine the function and mechanism of CVB in CRPC to provide new insights into CRPC treatment. METHODS: The effect of CVB on PC3 and C4-2 cell viability was determined using a CCK8 assay. Core therapeutic targets of CVB in CRPC cells were identified using RNA sequencing, online database, and PPI network analyses. Western blotting, RT-qPCR and molecular docking were performed to evaluate the regulation of core targets by CVB. Utilizing GO and KEGG enrichment analyses, the probable anti-CRPC mechanism of CVB was investigated. Immunofluorescence, flow cytometry and colony formation assays were used to verify the potential phenotypic regulatory role of CVB in CRPC. RESULTS: CVB inhibited CRPC cell activity in a concentration-dependent manner. Mechanistically, it primarily regulated BRCA1-, POLD1-, BLM-, MSH2-, MSH6- and PCNA-mediated mismatch repair, homologous recombination repair, base excision repair, Fanconi anemia repair, and nucleotide excision repair pathways. Immunofluorescence, Western blot, flow cytometry and colony formation experiments showed that CVB induced DNA damage accumulation, cell apoptosis, and cell cycle arrest and inhibited CRPC cell proliferation. CONCLUSION: CVB can induce DNA damage accumulation in CRPC cells by targeting DNA repair pathways and then induce cell apoptosis and cell cycle arrest, eventually leading to inhibition of the long-term proliferation of CRPC cells.

CDK2 and CDK4 targeted liensinine inhibits the growth of bladder cancer T24 cells.

Bladder cancer (BCa) is a urinary tumor with limited treatment options and high mortality. Liensinine (LIEN), a natural bisbenzylisoquinoline alkaloid, has shown excellent anti-tumor effects in numerous preclinical studies. However, the anti-BCa effect of LIEN remains unclear. To the best of our knowledge, this is the first study to investigate the molecular mechanism of LIEN in the management of BCa. First, we identified the treatment-related targets of BCa; those that repeatedly occur in more than two databases, including GeneCards, Online Mendelian Inheritance in Man, DisGeNET, Therapeutic Target Database, and Drugbank. The SwissTarget database was used to screen LIEN-related targets, and those with a probability >0 were possible LIEN targets. The prospective targets of LIEN in the treatment of BCa were then determined using a Venn diagram. Second, we discovered that the PI3K/AKT pathway and senescence mediated the anti-BCa action of LIEN by using GO and KEGG enrichment analysis to explore the function of LIEN therapeutic targets. A protein-protein interaction network was created using the String website, and six algorithms of the CytoHubba plug-in were then used in Cytoscape to assess the core targets of LIEN for the therapy of BCa. The outcomes of molecular docking and dynamics simulation demonstrated that CDK2 and CDK4 proteins were the direct targets of LIEN in the management of BCa, among which CDK2 was more stable in binding to LIEN than CDK4. Finally, in vitro experiments showed that LIEN inhibited the activity and proliferation of T24 cells. The expression of p-/AKT, CDK2, and CDK4 proteins progressively decreased, while the expression and fluorescence intensity of the senescence-related protein, γH2AX, gradually increased with increasing LIEN concentration in T24 cells. Therefore, our data suggest that LIEN may promote senescence and inhibit proliferation by inhibiting the CDK2/4 and PI3K/AKT pathways in BCa.

Association between radiotherapy for surgically treated oral cavity cancer and secondary lung cancer.

Background: There is limited research on the incidence of secondary lung cancer (SLC) after radiotherapy (RT) for oral cavity cancer (OCC). Therefore, we investigated the association between RT for OCC and the risk of SLC and the overall survival of these patients. Methods: Patients diagnosed with OCC between 1975 and 2015 were selected from the Surveillance, Epidemiology, and End Results database. The cumulative incidence of SLC, relative risk (RR) of RT vs. no RT (NRT), standardized incidence ratios (SIR), and survival outcomes were assessed. Results: A total of 10,936 patients with OCC were included. Of these, 429 (3.92%) patients developed SLC, where 136 (5.02%) received RT and 293 (3.56%) did not. The cumulative incidence of SLC during follow-up was 6.89% and 4.84% in the RT and NRT patients, respectively. RT was associated with a higher risk of SLC. In the subset analysis, the results showed that a higher risk of developing SLC among patients with index OCC in most subgroups. Dynamic RR and SIR revealed a decreased risk of SLC with increasing latency time. No difference was observed in the 10-year survival rates for patients with SLC who received RT or not or compared with primary lung cancer. Conclusion: RT was associated with a higher risk of SLC, and patients diagnosed with OCC could be followed for 5-10 years after diagnosis.

Subtype-based analysis of cell-in-cell structures in non-small cell lung cancer.

Lung cancer is ranked as the leading cause of cancer-related death worldwide, and the development of novel biomarkers is helpful to improve the prognosis of non-small cell lung cancer (NSCLC). Cell-in-cell structures (CICs), a novel functional surrogate of complicated cell behaviors, have shown promise in predicting the prognosis of cancer patients. However, the CIC profiling and its prognostic value remain unclear in NSCLC. In this study, we retrospectively explored the CIC profiling in a cohort of NSCLC tissues by using the "Epithelium-Macrophage-Leukocyte" (EML) method. The distribution of CICs was examined by the Chi-square test, and univariate and multivariate analyses were performed for survival analysis. Four types of CICs were identified in lung cancer tissues, namely, tumor-in-tumor (TiT), tumor-in-macrophage (TiM), lymphocyte-in-tumor (LiT), and macrophage-in-tumor (MiT). Among them, the latter three constituted the heterotypic CICs (heCICs). Overall, CICs were more frequently present in adenocarcinoma than in squamous cell carcinoma (P = 0.009), and LiT was more common in the upper lobe of the lung compared with other lobes (P = 0.020). In univariate analysis, the presence of TiM, heCIC density, TNM stage, T stage, and N stage showed association with the overall survival (OS) of NSCLC patients. Multivariate analysis revealed that heCICs (HR = 2.6, 95% CI 1.25-5.6) and lymph node invasion (HR = 2.6, 95% CI 1.33-5.1) were independent factors associated with the OS of NSCLC. Taken together, we profiled the CIC subtypes in NSCLC for the first time and demonstrated the prognostic value of heCICs, which may serve as a type of novel functional markers along with classical pathological factors in improving prognosis prediction for patients with NSCLC.

Association between a prior cancer history and prognosis in adult patients with high­grade glioma.

Patients with a prior cancer history are often excluded from clinical trials. This study aimed to investigate the prognostic impact of prior cancer history on patients with high-grade glioma. Data of patients with high-grade glioma as the first or second primary malignancy were obtained from the Surveillance, Epidemiology, and End Results database. Propensity score matching (PSM) was performed to balance the heterogeneity baseline characteristics. The survivals of patients with or without prior cancers were analyzed. A total of 46,200 patients were included in this study, 2471 (5.3 %) of whom carried a prior cancer history. Prostate (37.7 %), breast (12.2 %), colon and rectal (7.9 %), and skin (6.9 %) cancers were the most common types of prior cancers. Overall survival rates were similar between patients with and without a prior cancer history (hazard ratio [HR], 1.02; 95 % confidence interval [CI], 0.96-1.08; P = 0.525). However, a prior cancer history served as a protective factor against glioma-specific mortality (sub-distribution HR = 0.90; 95 % CI, 0.84-0.96; P = 0.001) in comparison with having no prior cancer history. The subgroup stratified by time intervals and types of prior cancer history showed that a prior cancer history was not a significant prognostic factor for survival in patients, except for breast cancers within 5 years and prostate cancers over 5 years. Our study shows that except for patients with high-grade gliomas with a history of stable tumors, the inclusion of patients with a prior history of tumors in clinical trials requires careful consideration.

The role of postoperative radiation therapy in stage I-III male breast cancer: A population-based study from the surveillance, epidemiology, and End Results database.

BACKGROUND: This study aimed to investigate the role of postoperative radiation therapy in a large population-based cohort of patients with stage I-III male breast cancer (MaBC). METHODS: Patients with stage I-III breast cancer treated with surgery were selected from the Surveillance, Epidemiology, and End Results cancer database from 2010 to 2015. Multivariate logistic regression identified the predictors of radiation therapy administration. Multivariate Cox regression model was used to evaluate the predictors of survival. RESULTS: We identified 1321 patients. Age, stage, positive regional nodes, surgical procedure, and HER2 status were strong predictors of radiation therapy administration. There was no difference between patients who received radiation therapy and those who did not (P = 0.46); however, after propensity score matching, it was associated with improved OS (P = 0.04). In the multivariate analysis of the unmatched cohort, the factors associated with better OS were administration of radiation therapy and chemotherapy. In the subset analysis of the unmatched cohort, postoperative radiation therapy was associated with improved OS in men undergoing breast-conserving surgery (BCS), with four or more node-positive or larger primary tumours (T3/T4). Furthermore, we found no benefit of radiation therapy, regardless of the type of axillary surgery in mastectomy (MS). In older MaBC patients with T1-2N1 who underwent MS, radiation therapy showed no significant effects, regardless of chemotherapy. CONCLUSION: Postoperative radiation therapy could improve the survival of MaBC patients undergoing BCS, with four or more node-positive or larger primary tumours. Moreover, it should be carefully considered in patients undergoing MS and older T1-2N1 patients.

ceRNA Networks: The Backbone Role in Neoadjuvant Chemoradiotherapy Resistance/Sensitivity of Locally Advanced Rectal Cancer.

Approximately 40% of rectal cancers during initial diagnosis are identified as locally advanced rectal cancers (LARCs), for which the standardized treatment scenario is total mesorectal excision following neoadjuvant chemoradiotherapy (nCRT). nCRT can lead to discernible reductions in local relapse rate and distant metastasis rate in LARC patients, in whom previously inoperable tumors may potentially be surgically removed. However, only 4% to 20% cases can attain pathological complete response, and the remaining patients who are unresponsive to nCRT have to suffer from the side effects plus toxicities and may encounter poor survival outcomes due to the late surgical intervention. As such, employing potential biomarkers to differentiate responders from nonresponders before nCRT implementation appears to be the overarching goal. Well-defined competing endogenous RNA (ceRNA) networks include long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA and circRNA-miRNA-mRNA networks. As ceRNAs, lncRNAs, and circRNAs sponge miRNAs to indirectly suppress miRNAs downstream of oncogenic mRNAs or tumor-suppressive mRNAs. The abnormal expression of mRNAs regulates the nCRT-induced DNA damage repair process through pluralistic carcinogenic signaling pathways, thereby bringing about alterations in the nCRT resistance/sensitivity of tumors. Moreover, many molecular mechanisms relevant to cell proliferation, metastasis, or apoptosis of cancers (eg, epithelial-mesenchymal transition and caspase-9-caspase-3 pathway) are influenced by ceRNA networks. Herein, we reviewed a large group of abnormally expressed mRNAs and noncoding RNAs that are associated with nCRT resistance/sensitivity in LARC patients and ultimately pinpointed the backbone role of ceRNA networks in the molecular mechanisms of nCRT resistance/sensitivity.

Stereotactic Biopsy for Brainstem Lesions: A Meta-analysis with Noncomparative Binary Data.

OBJECTIVES: To evaluate the diagnostic yield and safety of brainstem stereotactic biopsy for brainstem lesions. METHODS: We performed a meta-analysis of English articles retrieved from the PubMed, Web of Science, Cochrane Library, and APA psycInfo databases up to May 12, 2021. A binary fixed-effect model, the inverse variance method, or a binary random-effect model, the Dersimonian Laird method, were utilized for pooling the data. This meta-analysis was registered with INPLASY, INPLASY202190034. FINDINGS: A total of 41 eligible studies with 2792 participants were included. The weighted average diagnostic yield was 97.0% (95% confidential interval [CI], 96.0-97.9%). The weighted average proportions of temporary complications, permanent deficits, and deaths were 6.2% (95% CI, 4.5-7.9%), .5% (95% CI, .2-.8%), and .3% (95% CI, .1-.5%), respectively. The subgroup analysis indicated a nearly identical weighted average diagnostic yield between MRI-guided stereotactic biopsy and CT-guided stereotactic biopsy (95.9% vs 95.8%) but slightly increased proportions of temporary complications (7.9% vs 6.0%), permanent deficits (1.9% vs .2%), and deaths (1.1% vs .4%) in the former compared to the latter. Moreover, a greater weighted average diagnostic yield (99.2% vs 97.6%) and lower proportions of temporary complications (5.1% vs 6.8%) and deaths (.7% vs 1.5%) were shown in the pediatric patient population than in the adult patient population. CONCLUSIONS: Brainstem stereotactic biopsy demonstrates striking accuracy plus satisfying safety in the diagnosis of brainstem lesions. The diagnostic yield, morbidity, and mortality mildly vary based on the diversity of assistant techniques and subject populations.

Breast Cancer Subtypes and Mortality of Breast Cancer Patients With Brain Metastasis at Diagnosis: A Population-Based Study.

BACKGROUND: Brain metastasis is an important cause of breast cancer-related death. AIM: We evaluated the relationships between breast cancer subtype and prognosis among patients with brain metastasis at the initial diagnosis. METHODS: The Surveillance, Epidemiology, and End Results database was searched to identify patients with brain metastasis from breast cancer between 2010 and 2015. Multivariable Cox proportional hazard models were used to identify factors that were associated with survival among patients with initial brain metastases. The Kaplan-Meier method was used to compare survival outcomes according to breast cancer subtype. RESULTS: Among 752 breast cancer patients with brain metastasis at diagnosis, 140 patients (18.6%) underwent primary surgery and 612 patients (81.4%) did not undergo surgery, while 460 patients (61.2%) received chemotherapy and 292 patients (38.8%) did not receive chemotherapy. Multivariable analysis revealed that, relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with significantly poorer overall survival (hazard ratio: 2.52, 95% confidence interval: 1.99-3.21), independent of age, sex, race, marital status, insurance status, grade, liver involvement, lung involvement, primary surgery, radiotherapy, and chemotherapy. The median overall survival intervals were 12 months for HR+/HER2-, 19 months for HR+/HER2+, 11 months for HR-/HER2+, and 6 months for HR-/HER2- (P < .0001). Relative to HR+/HER2- breast cancer, HR-/HER2- breast cancer was associated with a significantly higher risk of mortality among patients, and the association was stronger among patients who received chemotherapy (p for interaction = .005). CONCLUSIONS: Breast cancer subtype significantly predicted overall survival among patients with brain metastasis at diagnosis.

Subtype-Based Analysis of Cell-in-Cell Structures in Esophageal Squamous Cell Carcinoma.

Cell-in-cell (CIC) structures are defined as the special structures with one or more cells enclosed inside another one. Increasing data indicated that CIC structures were functional surrogates of complicated cell behaviors and prognosis predictor in heterogeneous cancers. However, the CIC structure profiling and its prognostic value have not been reported in human esophageal squamous cell Carcinoma (ESCC). We conducted the analysis of subtyped CIC-based profiling in ESCC using "epithelium-macrophage-leukocyte" (EML) multiplex staining and examined the prognostic value of CIC structure profiling through Kaplan-Meier plotting and Cox regression model. Totally, five CIC structure subtypes were identified in ESCC tissue and the majority of them was homotypic CIC (hoCIC) with tumor cells inside tumor cells (TiT). By univariate and multivariate analyses, TiT was shown to be an independent prognostic factor for resectable ESCC, and patients with higher density of TiT tended to have longer post-operational survival time. Furthermore, in subpopulation analysis stratified by TNM stage, high TiT density was associated with longer overall survival (OS) in patients of TNM stages III and IV as compared with patients with low TiT density (mean OS: 51 vs 15 months, P = 0.04) and T3 stage (mean OS: 57 vs 17 months, P=0.024). Together, we reported the first CIC structure profiling in ESCC and explored the prognostic value of subtyped CIC structures, which supported the notion that functional pathology with CIC structure profiling is an emerging prognostic factor for human cancers, such as ESCC.

Cistanoside of Cistanche Herba ameliorates hypoxia-induced male reproductive damage via suppression of oxidative stress.

Increasing evidence shows that hypoxia is a cause of male infertility, and hypoxia may be related to oxidative stress (OS). Cistanoside (Cis) is a phenylethanoid glycoside compound that can be extracted from Cistanches Herba and possesses various biological functions. This study aimed to investigate the protective effects of Cis on reproductive damage induced by hypoxia and explore the specific underlying mechanisms. Cell and animal hypoxia experimental models were constructed, and the protective effects of different subtypes of Cis on the male reproductive system were assessed both in vitro and in vivo. The results indicated that hypoxia significantly reduced the viability of GC-1 cells through cell cycle arrest and apoptosis activation, which were associated with increased OS. Moreover, Cis showed strong antioxidative effects both in vitro and in vivo, significantly restoring antioxidant enzyme activities and downregulating reactive oxygen species (ROS) levels while increasing cell viability and decreasing apoptosis. Importantly, the Cis subtypes (Cis-A, Cis-B, Cis-C and Cis-H) studied herein all showed certain antioxidant effects, among which the effects of Cis-B were the most significant. This study demonstrates that Cis markedly attenuates the harmful effects of hypoxia-induced OS by affecting antioxidant enzyme activities in testes and GC-1 cells.

Comparison of the Oncological Efficacy Between Intraoperative Radiotherapy With Whole-Breast Irradiation for Early Breast Cancer: A Meta-Analysis.

BACKGROUND: Intraoperative radiotherapy (IORT) and whole-breast irradiation (WBI) are both effective radiotherapeutic interventions for early breast cancer patients undergoing breast-conserving surgery; however, an issue on whether which one can entail the better prognosis is still controversial. Our study aimed to investigate the 5-year oncological efficacy of the IORT cohort and the WBI cohort, respectively, and compare the oncological efficacy between the cohorts. MATERIALS AND METHODS: We conducted a computerized retrieval to identify English published articles between 2000 and 2021 in the PubMed, the Web of Science, the Cochrane Library, and APA PsycInfo databases. Screening, data extraction, and quality assessment were performed in duplicate. RESULTS: A total of 38 studies were eligible, with 30,225 analyzed participants. A non-comparative binary meta-analysis was performed to calculate the weighted average 5-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) in the two cohorts, respectively. The LRFS, DMFS, and OS (without restriction on the 5-year outcomes) between the two cohorts were further investigated by a comparative binary meta-analysis. The weighted average 5-year LRFS, DMFS, and OS in the IORT cohort were 96.3, 96.6, and 94.1%, respectively, and in the WBI cohort were 98.0, 94.9, and 94.9%, respectively. Our pooled results indicated that the LRFS in the IORT cohort was significantly lower than that in the WBI cohort (pooled odds ratio [OR] = 2.36; 95% confidential interval [CI], 1.66-3.36). Nevertheless, the comparisons of DMFS (pooled OR = 1.00; 95% CI, 0.76-1.31), and OS (pooled OR = 0.95; 95% CI, 0.79-1.14) between the IORT cohort with the WBI cohort were both not statistically significant. CONCLUSIONS: Despite the drastically high 5-year oncological efficacy in both cohorts, the LRFS in the IORT cohort is significantly poorer than that in the WBI cohort, and DMFS and OS do not differ between cohorts.

MicroRNA-152 inhibits tumor cell growth by directly targeting RTKN in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common form of adult liver cancer and accounts for approximately 90% of all cases of primary liver cancer annually. Rhotekin (RTKN), which functions as a cancer promoter, can be frequently detected in many human cancers, including gastric cancer, colorectal carcinoma and bladder carcinoma. The aim of this study was to investigate the role of RTKN in HCC. Using HCC cells and tissues from patients with liver cancer, we demonstrated that RTKN was significantly increased in HCC. To examine the effect of RTKN on HCC, RTKN overexpressed or silenced HepG2 and Hep3B cells were constructed. Cell proliferation and apoptosis were measured by RT-PCR and flow cytometry. The results showed that RTKN can function as an oncogene and promote the proliferation, while inhibiting apoptosis, of HepG2 and Hep3B cells. Furthermore, we identified that RTKN is a direct gene target of miR-152. miR-152 can reverse the growth promoting effect of RTKN on HCC cells through G2/M phase arrest and nuclear factor-κB (NF-κB) signal inhibition. In conclusion, our research identified that miRNA-152 can inhibit tumor cell growth by targeting RTKN in HCC.

miR-144 reverses chemoresistance of hepatocellular carcinoma cell lines by targeting Nrf2-dependent antioxidant pathway.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Chemoresistance occurrence is a major cause of treatment failure in HCC. Currently, extensive research has revealed diverse mechanisms for chemoresistance, but the molecular mechanisms underlying the role of miRNAs in resistance to 5-FU are not confirmed in HCC cells. By quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we found that miR-144 was significantly decreased in HCC cell lines. It has been further demonstrated that miR-144 were significantly down-regulated in Bel-7402/5-FU cells compared with parental Bel-7402 cells by qRT-PCR and western blot. The expression of Nrf2 was reversely correlated to that of miR-144 in HCC cells. Moreover, Enhancement of 5-FU-induced cytotoxicity and apoptosis are resulted from the transfection with miR-144 mimics in Bel-7402/5-FU cells. Mechanically, miR-144 promoted nuclear factor erythroid-2-related factor-2 (Nrf2) mRNA degradation by directly targeting the Nrf2 3'untranslated region (3'UTR). In addition, ectopic expression of miR-144 in Bel-7402/5-FU cells reduced the levels of Nrf2 and inhibited the transcription of Nrf2-dependent HO-1 gene, thus contributing to 5-FU sensibilization. Conversely, re-expression of Nrf2 partly attenuated the chemosensibilization of miR-144. Our study showed that miR-144 serves as a potential chemoresistance-reversal agent in hepatocellular carcinoma cells, which is at least partly due to the down-regulation of Nrf2-dependent antioxidant pathway.

MicroRNA-381 increases radiosensitivity in esophageal squamous cell carcinoma.

BACKGROUND: Radiation resistance poses a major clinical challenge in treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms of radioresistance has not been fully elucidated. Since accumulating evidence demonstrates that aberrant expression of microRNAs (miRNAs) contributes to cancer sensitivity to radiation, we aimed to identify miRNAs associated with radioresistance of ESCC. METHODS: In this study, we used GeneChip miRNA Array to perform an comparison of miRNAs expression in tissues from primary ESCC and recurrent ESCC in situ after radiotherapy. Differential expressions of miRNAs were comfirmed by quantitative Real-Time PCR in tissues and six ESCC cell lines. Cell radiosensitivity were determined by colony formation assay. Functional analyses of miRNA-381 in ESCC cells growth and metastasis were performed by MTT and Transwell Assays. In vivo assays of the functions of miRNA-381 were performed in tumor xenografts. RESULTS: One miRNA candidate, miRNA-381, was found to be downregulated in radiation resistance tissues and cells. Enforced expression of miRNA-381 increased radiosensitivity of ESCC cells and promoted nonaggressive phenotype including decreased cellular proliferation and migration. In contrast, inhibition of miRNA-381 in ESCC cells promoted radiation resistance and development of an aggressive phenotype. In vivo assays extended the significance of these results, showing that miRNA-381 overexpression decreased the tumor growth and the resistance to radiation treatment in tumor xenografts. CONCLUSIONS: Together, our work reveals miRNA-381 expression as a critical determinant of radiosensitivity in esophageal cancer cells.

Meta-analysis of MTHFR C677T and A1298C gene polymorphisms: association with the risk of hepatocellular carcinoma.

OBJECTIVE: Several studies have indicated an association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and the risk of hepatocellular carcinoma (HCC). However, the conclusions are inconsistent. Therefore, a meta-analysis was performed. METHODS: Databases like Pubmed, EMBASE, and EBSCO (up to September 2012) were searched to retrieve case-control trials about MTHFR (C677T or A1298C) polymorphisms and HCC. Literatures were independently screened by two researchers according to the inclusion and exclusion criteria. Data were extracted and analyzed by software STATA 11.0. RESULTS: Nine studies were included with 10 datasets and 5132 cases. C677T polymorphism was associated with HCC risk in a heterozygous model (TT vs. CT: OR=1.20, 95% CI: 1.02-1.40). For the A1298C polymorphism, a significantly decreased HCC risk was found in the dominant, heterozygous and homozygous models (CC vs. AA+AC: OR=0.52, 95% CI: 0.33-0.80; CC vs. AC: OR=0.50, 95% CI: 0.32-0.79; CC vs. AA: OR=0.52, 95% CI: 0.33-0.81). Subgroup analysis stratified by ethnicity and type of control further indicated decreased HCC risks in Asians (CC vs. AA+AC: OR=0.47, 95% CI: 0.26-0.84; CC vs. AC: OR=0.41, 95% CI: 0.24-0.71; CC vs. AA: OR=0.46, 95% CI: 0.27-0.78), studies with controls of healthy people (CC vs. AA: OR=0.54, 95% CI: 0.31-0.93; CC vs. AC: OR=0.54, 95% CI: 0.31-0.94; CC vs. AA+AC: OR=0.55, 95% CI: 0.32-0.94), and controls of non-HCC patients (CC vs. AC: OR=0.43, 95% CI: 0.19-0.96). CONCLUSIONS: Homozygous carriers of MTHFR C677T mutation are more susceptible to HCC, but homozygous mutations of MTHFR A1298C may play a protective role for developing HCC.