Metastatic relapse remains largely incurable and a major challenge of clinical management in breast cancer, but the underlying mechanisms are poorly understood. Herein, we report that CGI-99 is overexpressed in breast cancer tissues from patients with metastatic recurrence within 5 years. High CGI-99 significantly predicts poorer 5-year metastasis-free patient survival. We find that CGI-99 increases breast cancer stem cell properties, and potentiates efficient tumor lung colonization and outgrowth in vivo. Furthermore, we demonstrate that CGI-99 activates the autocrine interleukin-6 (IL-6)/STAT3 signaling by increasing the accumulation and activity of RNA polymerase II and p300 cofactor at the proximal promoter of IL-6. Importantly, delivery of the IL-6-receptor humanized monoclonal antibody tocilizumab robustly abrogates CGI-99-induced metastasis in vivo. Finally, we find that high levels of CGI-99 are significantly correlated with STAT3 hyperactivation in breast cancer patients. These findings reveal a potential mechanism for constitutive activation of autocrine IL-6/STAT3 signaling and may suggest a novel target for clinical intervention in breast cancer.

SFTPB variants are associated with COPD susceptibility and lung function in the Chinese Han population.

Purpose: Liver SBRT patients unable to tolerate breath‐hold for radiotherapy are treated free‐breathing with image guidance. Target localization using 3D CBCT requires extra margins to accommodate the respiratory motion. The purpose of this study is to evaluate the accuracy and reproducibility of 4D CT‐on‐rails in target localization for free‐breathing liver SBRT. Methods: A Siemens SOMATOM CT‐on‐Rails 4D with Anzai Pressure Belt system was used both as the simulation and the localization CT. Fiducial marker was placed close to the center of the target prior to the simulation. Amplitude based sorting was used in the scan. Eight or sixteen phases of reconstructed CT sets (depends on breathing pattern) can be sent to Velocity to create the maximum intensity projection (MIP) image set. Target ITV and fiducial ITV were drawn based on the MIP image. In patient localization, a 4D scan was taken with the same settings as the sim scan. Images were registered to match fiducial ITVs. Results: Ten liver cancer patients treated for 50Gy over 5 fractions, with amplitudes of breathing motion ranging from 4.3–14.5 mm, were analyzed in this study. Results show that the Intra & inter fraction variability in liver motion amplitude significantly less than the baseline inter‐fraction shifts in liver position. 90% of amplitude change is less than 3 mm. The differences in the D99 and D95 GTV dose coverage between the 4D CT‐on‐Rails and the CBCT plan were small (within 5%) for all the selected cases. However, the average PTV volume by using the 4D CT‐on‐Rails is 37% less than the CBCT PTV volume. Conclusion: Simulation and Registration using 4D CT‐on‐Rails provides accurate target localization and is unaffected by larger breathing amplitudes as seen with 3D CBCT image registration. Localization with 4D CT‐on‐Rails can significantly reduce the PTV volume with sufficient tumor

Purpose: Careful selection of beam number and orientation is of critical importance for external beam treatment planning. The utilization of well‐chosen non‐coplanar beams could allow the generation of high‐quality plans. This study is to evaluate the quality of the IMRT plans generated with the non‐coplanar (NCP) beams selected with our in‐house program by comparing it with coplanar (CP) IMRT and RapidArc (ARC) plans for prostate and pancreatic cancer treatments. Methods: Ten patients with prostate and pancreas cancer treated previously were selected for this study. A set of 13 non‐coplanar beams was selected with our in‐house program based on the CT data of one patient and was used to generate NCP plans for the ten cases. For each case we also generated an eight‐beam CP and a double‐arc ARC plan. All plans were generated with the Varian Eclipse TPS. For individual cases, the same dose‐volume constraints and weightings were used for all three plans. Results: All plans provided conformal and complete converge of the PTV and led to clinically acceptable doses to the organs‐at‐risk. The NCP plans show the best quality in terms of PTV Dmean, Dmax and HI, while the ARC plans are best in terms of PTV Dmin and CI. For the prostate cases, the NCP plans show the best V40 and V60 for rectum and bladder, and best D2% for the right‐femoral head, while the ARC plans show the best left‐femoral head D2%. For the pancreas cases, the NCP plans show the best sparing of the left‐and right‐kidney as well as the spinal cord. However, the NCP plans lead to slightly worse Dmean and D1/3 to the liver than the CP plans. Conclusion: We have shown that the non‐coplanar beams selected with our program allow the generation of high‐quality IMRT plans, by comparing them with the conventional IMRT and RapidArc plans.

No abstract