[Retracted] SIRT3 regulates cell proliferation and apoptosis related to energy metabolism in non­small cell lung cancer cells through deacetylation of NMNAT2.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the control ß­actin western blots shown in Fig. 4C were strikingly similar to data appearing in different form in Fig. 9B in a previously published paper featuring one author in common; moreover, the immunoblotting experiments shown in Figs. 1B and D and 2B appeared to have been derived, either wholesale or in part, from data that had already appeared in the following publication: Lei Y, Liu H, Yang Y, Wang X, Ren N, Li B, Liu S, Cheng J, Fu X and Zhang J: Interaction of LHBs with C53 promotes hepatocyte mitotic entry: A novel mechanism for HBV­induced hepatocellular carcinoma. Oncol Rep 29: 151­159, 2012. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Oncology, and due to a lack of overall confidence in the presented data, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 43: 1420­1430, 2013; DOI: 10.3892/ijo.2013.2103].

Influence of computed tomography contrast agent on radiotherapy dose calculation for pancreatic carcinoma: A dosimetric study based on tomotherapy and volumetric-modulated arc therapy techniques.

The main purpose of our investigation was to quantify the dosimetric influence of intravenous contrast agent for pancreatic cancer radiotherapy treatment. This study focused on complex modulated irradiation techniques of tomotherapy (TOMO) and volumetric-modulated arc therapy (VMAT) to investigate if novel conformal treatment methods could reduce the influence of contrast agent. In our study, patients with pancreatic cancer were enrolled to have 2 computed tomography (CT) scans in the same position without and with intravenous contrast agent for treatment planning. Then tumors and organ at risks were countered on contrast-enhanced CT (CECT) images. Each patient's CECT was assigned a TOMO plan and a VMAT plan. Then these plans were copied onto the non-CECT image and dose distribution was calculated with the same algorithm and structure sets. Finally, the dose distribution and the dose difference were analyzed for the target volume and organs at risk between the 2 sets of images. The statistic dosimetric result showed that for both TOMO and VMAT, no significant dose difference between CECT and non-CECT-based plan was observed. Dose difference was clinically negligible because the average relative percentage dose difference was 1% ± 1% for target volume, except a blurring effect at the higher dose region of the target volume. It implied that intravenous contrast agent will not affect dose calculation for pancreatic cancer radiotherapy significantly. Also the dose deviation based on TOMO showed no statistical difference compared with that on VMAT. For both superposition/conversation algorithm used by TOMO and Monte Carlo algorithm used by VMAT, the dosimetric difference was nonsignificant. A full analysis demonstrated a negligible dose difference of less than 1% between CECT-based plan and non-CECT-based plan. Therefore, contrast-enhanced CT image can be used directly for dose calculation of TOMO and VMAT plans for pancreatic cancer. It is unnecessary to scan twice then make a fusion of CECT and non-CECT, which would result to additional unnecessary radiation dose to patient and decrease work efficiency.

Outcome Study of Cobalt Based Stereotactic Body Radiation Therapy for Patients with Inoperable Stage III Non-small Cell Lung Cancer.

Aim of this paper is to retrospectively evaluate the efficacy and toxicity of specialized Body Cobalt based system (BCBS) treatment in the senior patients group (.65 years) with Stage III non-small cell lung carcinoma (NSCLC). A total of 49 patients (41 males and 8 females) with Stage III NSCLC according to UICC TNM classification (6(th) edition) were treated using OUR-QGD™ BCBS which was designed and manufactured in China. Post treatment evaluation with follow-up information was collected from April 2001 to December 2006 in our department. Median age of enrolled patients was 71 years old (65-85). Among those patients, 36 patients were pathologically identified with squamous cell carcinoma, and the other 13 patients were confirmed as adenocarcinoma. All patients were immobilized by vacuum based immobilization mold and then performed slow CT scan without any respiration gating devices. The daily radiation prescription dose was defined at 50% isodose line covering primary lesions and metastatic lymph nodes with doses from 2.5 to 6 Gy in 5 fractions per week according to the tumor stage and internally approved treatment protocols by the Institutional Review Board (IRB). Median daily dose and total delivery dose of 50% isodose line were 4 Gy and 41 Gy, respectively. In this study group, total of 3 patients received neoadjuvant cisplatin-based chemotherapy. Tumor response evaluated 12 weeks after radiation has demonstrated 13 complete responses (26.5%), 21 partial responses (42.9%). The overall survival (OS) rate of 1-year, 2-year and 3-year was 63.3%, 40.8% and 20.4%, respectively. The median and mean survival time was 22 and 24 months. All 49 patients tolerated the treatment well and have completed the planned therapy regiment. Body Cobalt based system treatment of those over 65 years old patients with Stage III NSCLC had reasonable and superior curative effect as well as local control, and at the same time without severe radiation side effects.

[Investigation of field width and pitch in tomotherapy treatment plans for brain metastases from lung cancer].

Tomotherapy plans were produced using a combination of field widths (1 cm, 2.5 cm and 5 cm) and pitches (0.15, 0.30, and 0.45) for seven patients with brain metastases from lung cancer, the plans were compared with dosimetric parameters, protection of organs at risk (OAR) dose and treatment times. All plans were defined that CTV with 30Gy and GTV 50 Gy by ten fraction synchronously. The results showed that the mean dose and CI for GTV was statistical difference (P = 0.002 1, P = 0.012 8), OARs were within the normal range, the treatment time increased inversely proportional to the jaw width, but had lesser impact on the pitch. This study showed plans produced with 5 cm jaw was an effective method for patients with brain metastases from lung cancer.

The application of gamma stereotactic body radiation therapy in stage I/II non-small-cell lung cancer. Promising and encouraging outcome.

OBJECTIVE: To further evaluate the efficacy and toxicity of the gamma-ray stereotactic body radiation therapy (SBRT) in patients with stage I/II non-small-cell lung cancer (NSCLC). METHODS: Twenty-nine newly diagnosed patients with stage I/II NSCLC who had no previous treatments, underwent OUR-QGD type of the gamma-SBRT at the Radiation Oncology Department, People's Liberation Army Airforce General Hospital, Beijing, China from January 2007 to July 2010. All patients were immobilized by vacuum bag, and then a slow CT scan was performed without any respiration gating. The total radiation dose of 50%, 60%, and 70% isodose line were prescribed in 50, 60, and 70 Grey (Gy) correspondingly, covering 100% of the planning target volume (PTV), 90% of the clinical target volume (CTV), and 80% of the gross target volume (GTV) in 10 fractions. The CT scans of the chest were required at one, 3, 6, 12, 18, and 24 months to evaluate the efficacy of the treatment. RESULTS: The median follow-up duration was 24 months, and the final follow-up rate is 96.6%. Local control rates of one and 2 years were all 93.1%. The progression-free survival rates versus overall survival rate of one year was 89.7% versus 96.6%, and 2 years was 86.1% versus 89.4%. Acute radiation reactions was diagnosed in 34.5%, and late radiation reactions in 37.9% of patients. CONCLUSION: The gamma-SBRT results in a good curative effects, and minimal toxicity in the treatment of stage I/II NSCLC.

SIRT3 regulates cell proliferation and apoptosis related to energy metabolism in non-small cell lung cancer cells through deacetylation of NMNAT2.

Lung cancer is the leading cause of death worldwide and associated with dismal prognoses. As a major mitochondrial deacetylase, SIRT3 regulates the activity of enzymes to coordinate global shifts in cellular metabolism and has important implications for tumor growth. Its role as a tumor suppressor or an oncogene in lung cancer is unclear, especially in non-small cell lung carcinoma (NSCLC). To identify the mechanism of SIRT3-interacting proteins, we performed a yeast two-hybrid screen using a human lung cDNA library. One of the positive clones encoded the full-length cDNA of the nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) gene and the interaction between SIRT3 and NMNAT2 was identified. The interaction on growth, proliferation, apoptosis of NSCLC cell lines, and energy metabolism related to SIRT3 were investigated. Screening from the library resulted in NMNAT2 gene. We found that NMNAT2 interacts with SIRT3 both in vitro and in vivo; SIRT3 binds to NMNAT2 deacetylating it. Downregulation of SIRT3 inhibited acetylation of NMNAT2 and NAD+ synthesis activity of the enzyme. Low expression of SIRT3 significantly inhibited mitotic entry, growth and proliferation of NSCLC cell lines and promoted apoptosis, which was related to energy metabolism involving in the interaction between SIRT3 and NMNAT2. Taken together, our results strongly suggest that the binding of SIRT3 with NMNAT2 is a novel regulator of cell proliferation and apoptosis in NSCLC cell lines, implicating the interaction between SIRT3 and NMNAT2, energy metabolism associated with SIRT3.

[Dosimetric comparison of treatment plans of pancreatic carcinoma treated with body gamma knife and tomotherapy].

Fourteen patients with pancreatic carcinoma were selected. Two treatment plans were designed for each patient, including gamma knife and Tomotherapy. The dose characteristics were evaluated by DVH and were compared. The results showed that the gamma knife plan had the higher maximal and mean target dose than Tomotherapy. Body gamma knife can increase the target dose significantly, and decrease the OAR dose. Tomotherapy had excellent dose-target conformality, and it can control doses of duodenum and stomach easily, but it had larger low dose region.

[Verification of the couch automatic movement accuracy for Hi-ART tomotherapy].

The QUASAR Penta-guide Phantom with fiducial markers was scanned, and the CT images were transferred to Pinnacle workstation. Skin and target volumes were contoured and transferred to TomoPlan treatment planning system. The phantom was scanned with Megavoltage CT (MVCT). MVCT images were matched to the planning CT. Automatic adjustment of treatment couch was completed. It was found that the green laser coincided with the etched center crosshairs in lateral and longitudinal directions with an error less than 2 mm. However 2 mm vertical tabletop lag was found, but could be eventually corrected. Verifications for specific patients with head and pelvic tumors were also completed, the residual setup error were analyzed. The automatic movement of tabletop after image match is satisfactory.

Prospective study of epidermal growth factor receptor tyrosine kinase inhibitors concurrent with individualized radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer.

PURPOSE: To establish the safety profile and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) concurrent with individualized radiotherapy (RT) in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between June 2007 and January 2010, 26 patients with Stage III/IV NSCLC were enrolled in this prospective study. These patients were treated with EGFR-TKIs (gefitinib 250 mg or erlotinib 150 mg, oral daily) concurrent with individualized RT with curative intent. The thoracic RT plans were individually designed on the basis of tumor size and normal tissue volume constraints. All patients were assessed for toxicity, and 25 patients were available for efficacy. The primary endpoints were acute toxicity, overall survival, and median survival time. The secondary endpoints included local control rate, time to tumor progression, and progression-free survival (PFS). RESULTS: Median gross tumor volume, mean lung dose, and lung V20 were 56 cm(3), 8.6 Gy, and 14%, respectively. Median thoracic radiation dose was 70 Gy at a margin of gross tumor volume (range, 42-82 Gy), and median biological equivalent dose was 105 Gy (range, 60-119 Gy). Acute skin, hematologic, esophageal, and pulmonary toxicities were acceptable and manageable. Severe adverse events included neutropenia (Grade 4, 4%) and thrombocytopenia (Grade 4, 8%), esophagitis (Grade 3, 4%), and pneumonitis (Grade 3, 4%). With a median follow-up of 10.2 months, a local control rate of 96% was achieved for thoracic tumor. Median time to progression, median PFS, and median survival time were 6.3, 10.2, and 21.8 months, respectively. The 1- and 2-year PFS rates were both 42%, and 1-, 2-, and 3-year overall survival rates were 57%, 45%, and 30%, respectively. CONCLUSION: Concurrent EGFR-TKIs with individualized RT shows a favorable safety profile and promising outcome, therefore serving as a therapeutic option for patients with locally advanced or metastatic NSCLC.