IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.

Purpose To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I–III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-β1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-β1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

This study examined the value of a novel 1-step labeled integrin α v β 3 -targeting 18 F-AlF-NOTA-PRGD2 (denoted as 18 F-RGD) scan in assessing sensitivity to concurrent chemoradiotherapy (CCRT) in patients with newly diagnosed glioblastoma multiforme (GBM). Methods: Twenty-five patients with newly diagnosed GBM were enrolled in this study 3-5 wk after surgical resection. All participants were investigated with 18 F-RGD PET/CT on baseline (T1) and at the third week (T2) after the start of CCRT. Tumor volume, maximal and mean standardized uptake value of the tumor (SUV max , SUV mean ), and tumor-to-nontumor ratios of the tumor volume were obtained. The MRI treatment response was assessed at the 11th week (T3). The change in the lesion volume from T1 to T3 on MRI was used as an endpoint to evaluate the predictive ability of 18 F-RGD PET/CT. Results: With 18 F-RGD PET/CT imaging, we successfully visualized the residual lesions of GBM. Twenty-five and 23 18 F-RGD PET/CT scans at baseline and the third week, respectively, were available for analysis. We found that 18 F-RGD PET/CT parameters, both pretreatment SUV max on baseline (P , 0.05) and intratreatment SUV max at the third week (SUV maxT2 ) (P , 0.05) and tumor-to-nontumor ratios at the third week (P , 0.05), were predictive of treatment sensitivity to CCRT. Additionally, the change of volume from T1 to T2 on MRI was also predictive (P , 0.05). According to receiver-operating-characteristic curve analysis, the most significant parameter was SUV maxT2 (area under the curve, 0.846). The threshold of SUV maxT2 was 1.35, and its sensitivity, specificity, and accuracy were 84.6%, 90.0% and 87.0%, respectively. Conclusion: 18 F-RGD PET/CT allows for the noninvasive visualization of GBM lesions and the prediction of sensitivity to CCRT as early as 3 wk after treatment initiation.

MicroRNAs (miRs) are involved in the development and progression of hepatocellular carcinoma (HCC), but the regulatory mechanism of miR-98 in HCC still remains unclear. Here we found that miR-98 was significantly downregulated in HCC tissues compared to matched adjacent normal tissues (ANTs). Low miR-98 expression was associated with tumor size, metastasis, portal vein tumor embolus, and poor overall survival. Ectopic expression of miR-98 decreased the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. SALL4 was identified as a novel target of miR-98, and the protein expression of SALL4 was inhibited by miR-98 in HCC cells. Overexpression of SALL4 reversed the suppressive effects of miR-98 on the malignant phenotypes of HCC cells. Besides, SALL4, upregulated in HCC tissues compared to the matched ANTs, was inversely correlated to the miR-98 levels in HCC tissues. In addition, overexpression of miR-98 markedly suppressed the tumor growth as well as tumor-induced death in nude mice. In summary, miR-98 plays a suppressive role in the proliferation, migration, invasion and EMT of HCC cells, partly at least, via directly inhibition of SALL4. Therefore, the miR-98/SALL4 axis may become a promising therapeutic target for HCC.

Hypoxia plays an important role in the development of solid tumors and is associated with their therapeutic resistance. There exist three major forms of hypoxia: acute, chronic, and intermittent hypoxia. Previous studies have shown that cancer cells could behave in the form of adaptation to hypoxia in tumor growth, which could result in their biological changes and determine their responses to the therapies. To investigate the tumor cells' adaptation to hypoxia, we recreated two models using two lung cancer cell lines in the presence of intermittent hypoxia, which is characterized by changes in oxygen pressure within the disorganized vascular network. We investigated biological behaviors such as cell cycle, proliferation, radiation sensitivity, apoptosis and migration, hypoxia signal pathway in the lung cancer cells treated with chronic intermittent hypoxia, as well as the role of hypoxia inducible factor 1 there, hypoxia-inducible genes analyzed by real-time RT-PCR chip in H446 cells treated with the model. The results indicated the changes of some hypoxia target gene expressions of those induced by hypoxia, some of which were confirmed by real-time RT-PCR. The cells mediated by irradiation induced resistance to radiation and apoptosis and increased metastasis in lung cancer cells. It was found that such changes were related to hypoxia inducible factor 1, alpha subunit (HIF-1α).