What is the optimal radiation dose for non-operable esophageal cancer? Dissecting the evidence in a meta-analysis.

The standard radiation dose 50.4 Gy with concurrent chemotherapy for localized inoperable esophageal cancer as supported by INT-0123 trail is now being challenged since a radiation dose above 50 Gy has been successfully administered with an observable dose-response relationship and insignificant untoward effects. Therefore, to ascertain the treatment benefits of different radiation doses, we performed a meta-analysis with 18 relative publications. According to our findings, a dose between 50 and 70 Gy appears optimal and patients who received ≥ 60 Gy radiation had a significantly better prognosis (pooled HR = 0.78, P = 0.004) as compared with < 60 Gy, especially in Asian countries (pooled HR = 0.75, P = 0.003). However, contradictory results of treatment benefit for ≥ 60 Gy were observed in two studies from Western countries, and the pooled treatment benefit of ≥ 60 Gy radiation was inconclusive (pooled HR = 0.86, P = 0.64). There was a marginal benefit in locoregional control in those treated with high dose (> 50.4/51 Gy) radiation when compared with those treated with low dose (≤ 50.4/51 Gy) radiation (pooled OR = 0.71, P = 0.06). Patients that received ≥ 60 Gy radiation had better locoregional control (OR = 0.29, P = 0.001), and for distant metastasis control, neither the > 50.4 Gy nor the ≥ 60 Gy treated group had any treatment benefit as compared to the groups that received ≤ 50.4 Gy and < 60 Gy group respectively. Taken together, a dose range of 50 to 70 Gy radiation with CCRT is recommended for non-operable EC patients. A dose of ≥ 60 Gy appears to be better in improving overall survival and locoregional control, especially in Asian countries, while the benefit of ≥ 60 Gy radiation in Western countries still remains controversial.

Kanglaite inhibits the expression of drug resistance genes through suppressing PVT1 in cisplatin-resistant gastric cancer cells.

Kanglaite (KLT) was shown to alleviate the development of multidrug resistance (MDR) clinically. The purpose of this study is to examine the mechanism of KLT for chemotherapy resistance in gastric cancer cells involving the regulation of MDR-related proteins. The cisplatin-resistant BGC823/DPP and SGC7901/DDP cells were treated with 1, 2.5 and 5 µl/ml of KLT for 24, 36 and 48 h. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were performed to detect the cell viability and cell apoptosis, respectively. The expression of MDR1 and multidrug resistance associated protein 1 (MRP1) were examined by quantitative PCR and western blotting in BGC823/DPP cells and SGC7901/DDP cells treated with KLT. The effect of KLT on the expression of PVT1 was investigated. PVT1-overexpression vector was constructed and transfected into BGC823/DPP cells and SGC7901/DDP cells which were treated with KLT. KLT inhibited the cell viability and promoted the cell apoptosis of BGC823/DPP cells and SGC7901/DDP cells in a concentration-dependent manner. KLT suppressed the expression of MDR1 and MRP1 and the level of PVT1. PVT1 overexpression reversed the increased percentage of apoptotic cells induced by KLT. Finally, we found that PVT1 overexpression also abrogated the effect of KLT on the mRNA level and protein level of MDR1 and MRP1 in BGC823/DPP and SGC7901/DDP cells. KLT inhibited the expression of MDR1 and MRP1 via suppressing the expression of PVT1, which suggested the potential mechanism of KLT involving in MDR in gastric cancer.

The effects of pprI gene of Deinococcus radiodurans R1 on acute radiation injury of mice exposed to 60Co γ-ray radiation.

The role of the pprI gene from Deinococcus radiodurans R1 in therapy of acute radiation injury of a mammalian host was investigated. We injected a plasmid containing the pprI gene into the muscle of mice exposed to total 6Gy of 60Co γ-ray radiation. After injection, we used in vivo gene electroporation technology to transfer the pprI gene into the cell. We found the PprI protein was expressed significantly at 1 d after irradiation, but there was no expression of pprI gene 7 d post-irradiation. The expression of pprI gene evidently decreased the death rate of mice exposed to lethal dose radiation, significantly relieved effects on blood cells in the acute stage, shortened the persistence time of the decrease of lymphocytes, and decreased the apoptotic rates of spleen cells, thymocytes and bone marrow cells. The expression of Rad51 protein in the lungs, livers, and kidneys was significantly higher in the mice treated with the pprI plasmid after irradiation. However, there were no obvious differences for Rad52 protein expression. We conclude that the prokaryotic pprI gene of D. radiodurans R1 first was expressed in mammalian cells. The expressed prokaryotic PprI protein has distinct effects of the prevention and treatment on acute radiation injury of mammal. The effects of radio-resistance may relate to expression of Rad51 protein which is homologous with RecA from D. radiodurans.

Analysis of the setup errors of medical image registration-based cone-beam CT for lung cancer.

PURPOSE: This study aimed to investigate the feasibility of efficiently using a rigid image registration (RIR) algorithm or a deformable image registration (DIR) algorithm to match medical images and evaluate the impact of setup errors on intensity modulated radiation therapy of lung cancer patients. METHODS: Ten lung cancer patients were chosen randomly each day and were subjected to image-guided radiotherapy. The clinical registration between cone-beam computed tomography (CBCT) images and treatment planning system CT images was performed by applying both RIR and DIR; the clinical registration was evaluated on the basis of the contour index, including dice similarity coefficient, sensitivity, and positive predictive value; the optimal scheme of image registration was selected to ensure that the actual irradiation isocenter was consistent with the treatment planning isocenter. In each patient, the translational errors in the right-left (x), superior-inferior (y), and anterior-posterior (z) directions and the rotational errors in the u, υ, and w directions formed by the x, y, and z directions were calculated and analyzed daily in the whole course of treatment; margins were calculated according to this equation: M = 2.5∑+ 0.7δ. RESULTS: The tumors and the surrounding soft tissues of the patients are shown more clearly in the CBCT images than in the CT images. DIR can be applied more efficiently than RIR to determine the morphological and positional changes in the organs shown in the images with the same or different modalities in the different period. The setup errors in translation in the x, y and z axes were 0.05±0.16, 0.09±0.32 and -0.02±0.13 cm, respectively; by contrast, the setup errors in rotation in u, υ and w directions were (0.41±0.64)°, (-0.08±0.57)° and (-0.03±0.62)°, respectively. The setup errors in the x, y and z axes of the patients indicated that the margins expansions were 0.82, 1.15 and 0.72 cm, respectively. CONCLUSION: CBCT with DIR can measure and correct the setup errors online; as a result, setup errors in lung cancer treatments can be significantly reduced and the accuracy of radiotherapy can be enhanced.

Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance.

BACKGROUND: The development of multidrug resistance (MDR) is a crucial problem of therapy failure in gastric cancer, which results in disease recurrence and metastasis. Plasmacytoma variant translocation 1 (PVT-1), a long non-coding RNA (lncRNA), was previously found to be increased in gastric cancer patients and regulated the chemotherapy sensitivity in pancreatic cancer cells. However, the role of PVT1 in multidrug resistant Gastric cancer remains largely unexplored. METHODS: In this study, the mRNA levels of PVT1 in gastric cancer tissues of cisplatin-resistant patients and two kinds of cisplatin-resistant cells BGC823/DDP and SGC7901/DDP were detected by qRT-PCR. The influence of PVT1 knockdown or overexpression on anticancer drug resistance was assessed by measuring the cytotoxicity of cisplatin and the rate of apoptosis detected by CCK-8 assay and flow cytometry, respectively. Further, we investigated the expression levels of MDR1, MRP, mTOR and HIF-1α by qRT-PCR and western blotting. RESULTS: PVT-1 was highly expressed in gastric cancer tissues of cisplatin-resistant patients and cisplatin-resistant cells. In addition, BGC823/DDP and SGC7901/DDP cells transfected with PVT-1 siRNA and treated with cisplatin exhibited significant lower survival rate and high percentage of apoptotic tumor cells. While, PVT1 overexpression exhibit the anti-apoptotic property in BGC823 and SGC7901 cells transfected with LV-PVT1-GFP and treated with cisplatin. Moreover, qRT-PCR and western blotting revealed that PVT1 up-regulation increased the expression of MDR1, MRP, mTOR and HIF-1α. CONCLUSIONS: Overexpression of LncRNA PVT1 in gastric carcinoma promotes the development of MDR, suggesting an efficacious target for reversing MDR in gastric cancer therapy.

Meat consumption is associated with esophageal cancer risk in a meat- and cancer-histological-type dependent manner.

BACKGROUND: We conducted a systematic review and meta-analysis of meat intake and esophageal cancer risk, with subgroup analyses based on meat type and histological type of cancer. AIMS: The purpose of this study was to investigate the association between meat intake and risk of esophageal cancer. METHODS: We searched MEDLINE, EMBASE and Cochrane Library (April 2013) for cohort and case-control studies that assessed meat intake and esophageal cancer risk. Random-effect or fixed-effect models were used to pool relative risks (RRs) from individual studies with heterogeneity and publication bias analyses carried out. Seven cohort and 28 case-control studies were included. RESULTS: The summary RRs for esophageal cancer for the highest versus lowest consumption categories were 1.19 (95 % confidence interval [CI] 0.98-1.46) for total meat, 1.55 (95 % CI 1.22-1.96) for red meat, 1.33 (95 % CI 1.04-1.69) for processed meat, 0.72 (95 % CI 0.60-0.86) for white meat, 0.83 (95 % CI 0.72-0.96) for poultry, and 0.95 (95 % CI 0.76-1.19) for fish. When striated by histological subtype, positive associations were seen among esophageal squamous cell carcinoma and red meat, white meat and poultry, and esophageal adenocarcinoma with total meat and processed meat. CONCLUSIONS: Meat consumption is associated with esophageal cancer risk, which depends on meat type and histological type of esophageal cancer. High intake of red meat and low intake of poultry are associated with an increased risk of esophageal squamous cell carcinoma. High meat intake, especially processed meat, is likely to increase esophageal adenocarcinoma risk. And fish consumption may not be associated with incidence of esophageal cancer.