Cochlea sparing with a stratified scheme of dose limitation employed in intensity-modulated radiotherapy for nasopharyngeal carcinoma: A dosimetry study.

Hearing loss is 1 of the major complications after radiotherapy in nasopharyngeal carcinoma (NPC) patients, how to minimize dose to cochlea in order to reduce the incidence of sensorineural hearing loss is a critical task. This study is to investigate a stratified scheme of cochlea sparing based on T stage in intensity-modulated radiotherapy. We designed a comparison between 2 plans of cochlea sparing plan (C-Plan) and regular noncochlea sparing plan (R-Plan) from 19 NPC patients with 2, 3, 8, and 6 cases of T1, T2, T3, and T4 stage, respectively. The outcomes showed that target coverage parameters and dose-volume histogram features were of no significant difference, with a significant difference in dose distribution between C-Plan and R-Plan in cochlea and eustachian, e.g., ipsilateral cochlea Dmean 4619.75 ± 1134.09 cGy in C-Plan and 5061.03 ± 1121.09 cGy in R-Plan (p = 0.000), contralateral cochlea Dmean 4386.73 ± 945.14 cGy in C-Plan and 4991.38 ± 961.21 cGy in R-Plan (p = 0.000). Meanwhile, there was no significant difference in dose distribution in spinal cord, brainstem, and other OARs. Our dosimetry study showed cochlea sparing in intensity-modulated radiotherapy for NPC reduced cochlea dose to different extent, so we suggested a stratified scheme of cochlea sparing based on T stage could be a useful and practical tool for both physicists and radiation doctors.

Plumbagin from Plumbago Zeylanica L induces apoptosis in human non-small cell lung cancer cell lines through NF- κB inactivation.

OBJECTIVE: To detect effects of plumbagin on proliferation and apoptosis in non-small cell lung cancer cell lines, and investigate the underlying mechanisms. MATERIALS AND METHODS: Human non-small cell lung cancer cell lines A549, H292 and H460 were treated with various concentrations of plumbagin. Cell proliferation rates was determined using both cell counting kit-8 (CCK-8) and clonogenic assays. Apoptosis was detected by annexin V/propidium iodide double-labeled flow cytometry and TUNEL assay. The levels of reactive oxygen species (ROS) were detected by flow cytometry. Activity of NF-κB was examined by electrophoretic mobility shift assay (EMSA) and luciferase reporter assay. Western blotting was used to assess the expression of both NF-κB regulated apoptotic-related gene and activation of p65 and IκBκ. RESULTS: Plumbagin dose-dependently inhibited proliferation of the lung cancer cells. The IC50 values of plumbagin in A549, H292, and H460 cells were 10.3 µmol/L, 7.3 µmol/L, and 6.1 µmol/L for 12 hours, respectively. The compound concentration-dependently induced apoptosis of the three cell lines. Treatment with plumbagin increased the intracellular level of ROS, and inhibited the activation of NK-κB. In addition to inhibition of NF-κB/p65 nuclear translocation, the compound also suppressed the degradation of IκBκ. ROS scavenger NAC highly reversed the effect of plumbagin on apoptosis and inactivation of NK-κB in H460 cell line. Treatment with plumbagin also increased the activity of caspase-9 and caspase-3, downregulated the expression of Bcl-2, upregulated the expression of Bax, Bak, and CytC. CONCLUSIONS: Plumbagin inhibits cell growth and induces apoptosis in human lung cancer cells through an NF-κB-regulated mitochondrial-mediated pathway, involving activation of ROS.

The impact of chemokine receptor CXCR4 on breast cancer prognosis: a meta-analysis.

BACKGROUND: C-X-C chemokine receptor type 4 (CXCR4) has been implicated in the invasiveness and metastasis of diverse cancers. However, the published data remain controversial on the correlation between CXCR4 expression level, as well as its subcellular distribution in tumor cells, and the clinical outcome of patients with breast cancer. METHODS: To identify the precise role of CXCR4 in the clinical outcome of breast cancer, we performed a meta-analysis including 15 published studies. Original data included the hazard ratios (HRs) of overall survival (OS) and disease-free survival (DFS) in breast cancer with high CXCR4 expression versus low expression. We pooled hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the hazard. RESULTS: A total of 15 published studies (including 3104 patients) were eligible. Overall survival (OS) and disease-free survival (DFS) of breast cancer were found to be significantly related to CXCR4 expression level, with the HR being 1.65 (95%CI: 1.34-2.03; P<0.00001) and 1.94 (95%CI: 1.42-2.65; P<0.00001) respectively. Stratified analysis according to subcellular distribution of CXCR4 showed that high expression in whole cells, cytoplasm and nucleus could predict unfavorable OS, with the HR of 2.02 (95%CI: 1.43-2.85; P<0.0001), 1.57 (95%CI: 1.13-2.18; P=0.007), and 1.47 (95%CI: 1.19-1.81; P=0.0004) respectively. As for DFS, elevated expression level of CXCR4 both in whole cells and cytoplasm predicted a poor outcome, with the HR being 2.23 (95%CI: 1.48-3.37; P=0.0001) and 1.76 (95%CI: 1.11-2.80; P=0.02), while high expression in the nucleus had no statistical significance, with HR 1.15 (95%CI: 0.52-2.55; P=0.73). CONCLUSIONS: Increased CXCR4 expression, especially in whole cells and cytoplasm, may serve as a poor prognostic indicator in patients with breast cancer. Future studies are warranted to investigate the relationship between CXCR4 expression and survival of patients with breast carcinoma, which could help predict the clinical outcome and guide clinical decision-making for therapy.

Association of ERCC1-C118T and -C8092A polymorphisms with lung cancer risk and survival of advanced-stage non-small cell lung cancer patients receiving platinum-based chemotherapy: a pooled analysis based on 39 reports.

The published data on the predictive role of ERCC1 polymorphisms in lung cancer risk and survival of patients with advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy remains inconsistent. The aim of this meta-analysis was to determine the role of ERCC1 gene polymorphisms (C118T and C8092A) in this clinical situation. Eligible studies were included and assessed for quality using multiple search strategies. Thirty-nine published papers involving 9615 cases (4606 with Stage III/IV disease) and 5542 controls were included in the analysis. Pooled odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate risk. ERCC1-C118T was associated with lung cancer risk. The OR was 0.90 (95% CI: 0.81-0.99, p=0.043) in an additive genetic model (C allele vs. T allele) and 0.77 (95% CI: 0.63-0.95, p=0.013) in a recessive genetic model (CC/CT vs. TT). The corresponding risk was 0.74 (95% CI: 0.58-0.94, p=0.013) based on a homozygous comparison (CC vs. TT). No significant correlation was found for ERCC1 C8092A and there was no obvious relationship between ERCC1 C118T/C8092A polymorphisms and objective response to platinum-based chemotherapy. Overall survival (OS) of patients with non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy was significantly related to ERCC1 C118T (HR: 1.29, 95% CI: 1.07-1.56, p=0.007, CT/TT vs. CC). There was no relationship between ERCC1 C8092A and survival (HR: 1.32, 95% CI: 0.84-2.10, p=0.23, CA/AA vs. CC). These findings suggest that ERCC1 C118T polymorphisms may serve as a biomarker for lung cancer risk and have prognostic value in patients with advanced non-small cell lung cancer (NSCLC) undergoing platinum-based treatment. Further studies with larger numbers of subjects from a worldwide arena are needed to validate the associations.

MicroRNA-155 expression has prognostic value in patients with non-small cell lung cancer and digestive system carcinomas.

OBJECTIVE: Published data have shown that microRNAs (miRNAs) could play a potential role as diagnostic and prognostic indicators in cancers. Data for the predictive value of microRNA-155 are inconclusive. The aim of the present analysis was therefore to evaluate the role of miR-155 in prognosis for patients with a variety of carcinomas. METHODS: Relevant studies were identified by searching PubMed and EMBASE. Data were extracted from studies comparing overall survival (OS), recurrence-free survival (RFS) or cancer-specific survival (CSS) in patients with carcinoma with higher miR-155 expression and those with lower levels. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miR-155 for clinical outcome were calculated. RESULTS: A total of 15 studies were included. The pooled hazard ratio (HR) for OS of higher miR-155 expression in cancerous tissue was 1.89 (95% CI: 1.20-2.99, P =0.006), which could markedly predict poorer survival in general cancer. For RFS/CSS, elevated miR-155 was also associated with poor prognosis of cancer (HR= 1.50, 95% CI: 1.10-2.05, P = 0.01). On subgroup analysis, the pooled HR for OS in non-small cell lung cancer (NSCLC) was 2.09 (95% CI: 0.68-6.41, P > 0.05), but for RFS/CSS was 1.28 (95% CI: 1.05-1.55, P = 0.015), with statistical significance; the pooled HRs for OS and RFS/CSS in digestive system neoplasms were 3.04 (95% CI: 1.48-6.24, P =0.003) and 2.61 (95% CI: 1.98-3.42, P<0.05), respectively. CONCLUSIONS: The results indicated that the miR-155 expression level plays a prognostic role in patients with cancer, especially NSCLCs and digestive system carcinomas.

MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies.

OBJECTIVE: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. METHODS: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. RESULTS: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. CONCLUSIONS: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.

The effect of endostatin and gemcitabine combined with HIFU on the animal xenograft model of human pancreatic cancer.

OBJECTIVE: To investigate the influence of the recombinant human endostatin and gemcitabine combined with HIFU on the mouse xenograft model of pancreatic cancer. METHODS: Use human pancreatic cancer cell line PANC-1 to set up the mouse xenograft model, then randomized into four arms. Each arm was treated with gemcitabine, endostatin, gemcitabine combined with endostatin and normal saline respectively. Observe the volume of the tumor, the serum VEGF level and MVD in the tumor tissue among the different arms. All mice were treated with HIFU, then pathological examination was done. RESULTS: The tumor volume, serum VEGF level and MVD in the combined-therapy arm are all lower than the monotherapy arms and the control arm. The coagulation necrosis occurred in tumors after HIFU treatment. CONCLUSION: Endostatin and gemcitabine has better effect than gemcitabine or endostatin monotherapy on the animal xenograft model of human pancreatic cancer. HIFU combined with chemotherapy and/or targeted therapy may enhance the effect for pancreatic cancer.