The Utility of Diffusion and Perfusion Magnetic Resonance Imaging in Target Delineation of High-Grade Gliomas.

BACKGROUND: The tumor volume of high-grade glioma (HGG) after surgery is usually determined by contrast-enhanced MRI (CE-MRI), but the clinical target volume remains controversial. Functional magnetic resonance imaging (multimodality MRI) techniques such as magnetic resonance perfusion-weighted imaging (PWI) and diffusion-tensor imaging (DTI) can make up for CE-MRI. This study explored the survival outcomes and failure patterns of patients with HGG by comparing the combination of multimodality MRI and CE-MRI imaging with CE-MRI alone. METHODS: 102 patients with postoperative HGG between 2012 and 2016 were included. 50 were delineated based on multimodality MRI (PWI, DTI) and CE-MRI (enhanced T1), and the other 52 were delineated based on CE-MRI as control. RESULTS: The median survival benefit was 6 months. The 2-year overall survival, progression-free survival, and local-regional control rates were 48% vs. 25%, 42% vs. 13.46%, and 40% vs. 13.46% for the multimodality MRI and CE-MRI cohorts, respectively. The two cohorts had similar rates of disease progression and recurrence but different proportions of failure patterns. The univariate analysis shows that characteristics of patients such as combined with epilepsy, the dose of radiotherapy, the selection of MRI were significant influence factors for 2-year overall survival. However, in multivariate analyses, only the selection of MRI was an independent significant predictor of overall survival. CONCLUSIONS: This study was the first to explore the clinical value of multimodality MRI in the delineation of radiotherapy target volume for HGG. The conclusions of the study have positive reference significance to the combination of multimodality MRI and CE-MRI in guiding the delineation of the radiotherapy target area for HGG patients.

Protective properties of Huperzine A through activation Nrf2/ARE-mediated transcriptional response in X-rays radiation-induced NIH3T3 cells.

Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation. Dose-dependent increase of antioxidant genes by HupA were associated with up-regulated Nrf2 and down-regulated Keap-1 expression, which was confirmed by increasing nuclear accumulation, and inhibiting of degradation of Nrf2. Notably, augmented luciferase activity of ARE may explained Nrf2/ARE-mediated signaling pathways behind HupA protective properties. Moreover, expression of Nrf2 HupA-mediated was significant attenuated by AKT inhibitor (LY294002), p38 MAPK inhibitor (SB202190) and ERK inhibitor (PD98059). Besides, HupA-mediated cell viability, and ROS production were dramatically bated by LY294002, SB202190, and PD98059. Taken together, HupA effectively ameliorated X-rays radiation-induced damage Nrf2-ARE-mediated transcriptional response via activation AKT, p38, and ERK signaling in NIH3T3 cells.

MicroRNA-125b inhibits cell proliferation and induces cell apoptosis in esophageal squamous cell carcinoma by targeting BMF.

MicroRNAs (miRNAs) have been reported to regulate the expression of genes by suppressing translation or facilitating mRNA decay. Their expression regulates a wide variety of cellular processes, including the development and progression of cancer. Esophageal squamous cell carcinoma (ESCC) is a malignant cancer with high morbidity and recurrence in Asia. In the present study, the biological function of miR-125b and its underlying mechanism in ESCC were explored. The results revealed that miR-125b expression was significantly decreased in ESCC tissues and cell lines. A decrease in miR-125b was markedly related to lymphatic metastasis in patients. Functional analysis revealed that the overexpression of miR-125b using miR-125b mimics significantly inhibited cell growth and induced cell apoptosis, and increased the G1 phase of the cell cycle in EC109 and EC9706 cells. Notably, the miR-125b inhibitors revealed the opposite effect. Additionally, overexpression of miR-125b significantly inhibited tumor growth in vivo. Furthermore, BCL-2-modifying factor (BMF) was considered to be a potential candidate target of miR-125b based on miRNA target databases. miR-125b negatively regulated BMF expression by directly binding to its 3'-untranslated region. BMF was a functional target of miR-125b in the regulation of cell proliferation, cell apoptosis and the cell cycle in EC109 and EC9706 cells. In clinical ESCC specimens, BMF expression was upregulated, and negatively correlated with that of miR-125b. In conclusion, miR-125b had an antitumor role in ESCC cells mediated by targeting BMF, which can be potentially useful for tumorigenesis in ESCC.

Emerging roles of circular RNA hsa_circ_0000064 in the proliferation and metastasis of lung cancer.

Circular RNAs (circRNAs), a novel class of widespread and diverse endogenous RNAs, can regulate gene expression in mammals. CircRNAs have recently been identified as microRNA sponges and involved in the development of some human diseases. However, the role of circRNAs in the process of tumorigenesis and development of lung cancer remains vague. The purpose of this study is to investigate the role of circRNAs in the lung cancer. In this study, we chose hsa_circ_0000064 as a targeted circRNA to investigate its clinical significances in lung cancer patients. The result indicated that hsa_circ_0000064 was up-regulated in lung cancer tissues and lung cancer cell lines (A549 and H1229). Moreover, its aberrant expression was correlated with several clinical characteristics, including T stage, lymphatic metastasis, and TNM stage. Fluorescence in situ hybridization detected that hsa_circ_0000064 was mostly located in the cytoplasm in A549 and H1229 cells. In addition, knockdown of hsa_circ_0000064 with siRNA dramatically attenuated the proliferation, blocked cell cycle progression, and promoted cell apoptosis. Western blot analysis showed that the protein levels of caspase-3, caspase-9, bax, p21, CDK6 and cyclin D1 significantly restrained by si-hsa_circ_0000064, while the expression of bcl-2 notably increased in A549 and H1229 cells. Further, si-hsa_circ_0000064 also abated migration and invasion activities of A549 and H1229 cells, which may be associated with reduced expressions of MMP-2 and MMP-9. In general, our data suggest that hsa_circ_0000064 represents a novel potential biomarker and therapeutic target of lung cancer.

Prognostic value of chemotherapy in addition to concurrent chemoradiotherapy in T3-4N0-1 nasopharyngeal carcinoma: a propensity score matching study.

PURPOSE: The objective of this study is to evaluate the contribution of induction (IC) or adjuvant (AC) chemotherapy additional to concurrent chemoradiotherapy (CCRT) for patients with T3-4N0-1 nasopharyngeal carcinoma (NPC) in the era of intensity-modulate radiotherapy (IMRT). METHOD AND MATERIALS: We retrospectively reviewed the data on 685 patients with newly diagnosed T3-4N0-1 NPC. Propensity score matching (PSM) method was used to match patients. Survival outcomes between different groups were calculated by Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was adopted to establish independent prognostic factors. RESULTS: In total, 236 pairs were selected from the primary cohort. Univariate analysis revealed 3-year overall survival (OS) (90.8% vs. 90.3%, P = 0.820), distant failure-free survival (DFFS) (87.3% vs. 89.4%, P = 0.896) and locoregional failure-free survival (LRFFS) (95.4% vs. 93.0%, P = 0.311) rates were comparable between CCRT plus IC/AC and CCRT alone groups. Multivariate analysis found that treatment group was not an independent prognostic factors for OS (HR, 0.964; 95% CI, 0.620-1.499; P = 0.869), DFFS (HR, 1.036; 95% CI, 0.626-1.714; P = 0.890) and LRFFS (HR, 0.670; 95% CI, 0.338-1.327; P = 0.250). Further subgroup analysis according to overall stage also obtained similar results. CONCLUSION: Patients with T3-4N0-1 NPC receiving CCRT could not benefit from additional induction or adjuvant chemotherapy in the era of IMRT.

Influence of MDR1 gene codon 3435 polymorphisms on outcome of platinum-based chemotherapy for advanced non small cell lung cancer.

OBJECTIVE: To evaluate the influence of multi-drug resistance 1 (MDR1) gene codon 3435 polymorphisms on response to platinum-based chemotherapeutic regimens for advanced non small cell lung cancer (NSCLC). METHODS: Responses and overall survival were evaluated in a series of patients presenting between March 1, 2005 and December 31, 2010. MDR1 gene C3435T polymorphisms were genotyped using peripheral blood with real time polymerase chain reaction (RT-PCR) and relationships between the MDR1 C3435T genetic polymorphism and response rate of chemotherapy were analyzed by SPSS 13.0. RESULTS: Overall response to chemotherapy in the eligible 103 patients was 21.4%. Patients with C/C genotype in MDR1 codon 3435 had a significantly higher response rate (24.5%) than those for C/T(19.0%) and T/T(12.5%) (P<0.05). The overall median survival time (MST) of patients was 19 months, values with C/C, C/T and T/T genotype were 21, 15.5 and 17 months, respectively (P=0.487). CONCLUSION: Our research suggested that patents with the C/C genotype in MDR1 codon 3435 could be more sensitive to platinum-based chemotherapy than patients with C/T and T/T; however, no significant difference was found between overall survival and MDR1 codon 3435 genetic polymorphisms.

MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy.

OBJECTIVE: To evaluate the impact of the multi-drug resistance 1(MDR1) C3435T polymorphism on clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. METHODS: From January 2005 to December 2008, 102 patients with surgically resected gastric cancers were enrolled into this study in the Affiliated Jiangsu Cancer Hospital of Nanjing Medical University. The polymorphism was tested using real time polymerase chain reaction (RT-PCR) cycling probes and the relationship with clinical outcomes after postoperative adjuvant chemotherapy was analyzed by SPSS 17.0. RESULTS: The CT/TT genotype of C3435T was significantly associated with a shorter progression-free survival (PFS) and overall survival (OS) compared with the CC genotype [PFS: adjusted hazard ratio (HR) = 2.01, 95% confidence intervals (CI): 1.17-3.45, P = 0.012; OS: adjusted HR = 2.37, 95% CI: 1.31-4.28, P = 0.004]. TNM stage was also associated with PFS (adjusted HR = 2.33, 95% CI: 1.34-4.05, P = 0.003) and OS (adjusted HR = 2.62, 95% CI: 1.44-4.76, P = 0.002) in gastric cancer patients treated with postoperative adjuvant chemotherapy. CONCLUSION: Our results suggest that the MDR1 gene C3435T polymorphism is associated with clinical outcomes in gastric cancer patients treated with postoperative adjuvant chemotherapy. This now needs to be confirmed by a randomized prospectively controlled study.

Validation of treatment efficacy of a computer-assisted program for breast cancer patients receiving postoperative adjuvant chemotherapy.

AIM: To validate the clinical value of a computer assisted program (CAP), (visit website; http://xinenhuang.blog.sohu.com for details) for breast cancer patients who receive postoperative adjuvant chemotherapy. METHODS: Patients with histologically confirmed breast cancer after mastectomy who received postoperative chemotherapy in Jiangsu Cancer Hospital and Research Institute were recruited in this study. All eligible patients are divided into three groups: group A, regimen of practical chemotherapy consistent with CAP prediction; group B, partly consistent with CAP prediction; group C, inconsistent with CAP prediction. Overall survival (OS) was compared among groups A, B and C to determine the efficacy of CAP. RESULTS: From November 1992 to July 2007, 310 female breast cancer patients were recruited into this study, with 112, 106 and 89, respectively, in groups A, B, and C. Prognosis of group A was better than both group B and C, with significantly different survival curves between group A and B (p=0.0004) and group A and C (p=0.0046). CONCLUSION: Validation showed our CAP to provide clinically valuable information on adjuvant chemotherapy for postoperative breast cancer patients.

Clinical comparison of safety and efficacy of vinorelbine/epirubicin (NE) with fluorouracil/epirubicin/cyclophosphamide (FEC).

OBJECTIVE: To compare the safety and efficacy of a combination of vinorelbine and epirubicin (NE) with fluorouracil/epirubicin/cyclophosphamide (FEC) as a postoperative adjuvant chemotherapy for breast cancer. METHODS: Breast cancer patients were treated postoperatively in Jiangsu Cancer Hospital and Research Institute from 1997 to 2006 with either the NE regimen (vinorelbine 40 mg/m2 iv on day 1 and day 8, epirubicin 50 mg/m2 iv on day 1 and day 2, and a cycle repeated every 21-28 days for totally 4-6 cycles) or the FEC regimen (5-Fu 500 mg/m2 iv gtt on day 1, epirubicin 50 mg/m2 iv on day 1 and day 2, CTX 500 mg/m2 iv on day 1 and a cycle repeated every 21-28 days for totally 4-6 cycles). Toxicity was evaluated after each cycle of chemotherapy. RESULTS: Main side effects in both NE and FEC groups were neutropenia and gastrointestinal syndrome, with a 5 year survival rate of 87.9% in the NE and 85.2% in the FEC group. CONCLUSIONS: NE regimen is safe with good long-term survival rate, and thus could be recommended as a postoperative chemotherapy regimen for breast cancer.

Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors.

PURPOSE: Endostar is a proteolytic fragment of collagen XVIII that has been shown to have antitumor activity, with a favorable toxicological profile. We conducted this study to investigate its efficacy and safety when combined with chemotherapy in patients with advanced solid tumors. METHODS: From July 2006 to September 2008, 45 patients with histologically or cytologically confirmed solid tumors were enrolled into this study. All received Endostar at a dose of 7.5 mg/m2 /day as an intravenous infusion for more than 7 days, in combination with chemotherapy. Patients were treated until tumor progression or unacceptable toxicity. RESULTS: No treatment related death occurred in this study. Main reported toxicities included: myelosuppression (82.2%), hepatic impairment (42.2%), anorexia (20.0%), nausea (24.4%), vomiting (22.2%), diarrhea (20.0%), febrile (20.0%) and fatigue (24.4%). No complete response was observed. Two patients (2/42) had partial response, twenty-one (21/42) remained stable, and nineteen (19/42) had progressive disease. Median time to tumor progression was 3.0 months (range, 0.5-12.0). Median overall survival was 30.0 months (95% confidence interval: 20.0-40.0) and 1 year survival rate was 81.0%. CONCLUSION: Our study revealed that toxicity of Endostar combined with chemotherapy in the treatment of solid tumors was tolerable with moderate efficacy.