Different Proteins Regulated Apoptosis, Proliferation and Metastasis of Lung Adenocarcinoma After Radiotherapy at Different Time.

INTRODUCTION: The biological changes after irradiation in lung cancer cells are important to reduce recurrence and metastasis of lung cancer. To optimize radiotherapy of lung adenocarcinoma, our study systematically explored the mechanisms of biological behaviors in residual A549 and XWLC-05 cells after irradiation. METHODS: Colony formation assay, cell proliferation assay, cell migration assay, flow cytometry, BALB/C-nu mice xenograft models and Western blot of pan-AKT, p-Akt380, p-Akt473, PCNA, DNA-PKCS, KU70, KU80, CD133, CD144, MMP2 and P53 were used in our study to assess biological changes after irradiation with 0, 4 and 8 Gy at 0-336 hr after irradiation in vitro and 20 Gy at transplantation group, irradiated transplantation group, residual tumor 0, 7, 14, 21, and 28 days groups in vivo. RESULTS: The ability of cell proliferation and radiosensitivity of residual XWLC-05 cells was better than A549 cells after radiation in vivo and in vitro. MMP-2 has statistical differences in vitro and in vivo and increased with the migratory ability of cells in vitro. PCNA and P53 have statistical differences in XWLC-05 and A549 cells and the changes of them are similar to the proliferation of residual cells within first 336 hr after irradiation in vitro. Pan-AKT increased after irradiation, and residual tumor 21-day group (1.5722) has statistic differences between transplantation group (0.9763, p=0.018) and irradiated transplantation group (0.8455, p=0.006) in vivo. Pan-AKT rose to highest when 21-day after residual tumor reach to 0.5 mm2. MMP2 has statistical differences between transplantation group (0.4619) and residual tumor 14-day group (0.8729, p=0.043). P53 has statistical differences between residual tumor 7-day group (0.6184) and residual tumor 28 days group (1.0394, p=0.007). DNA-PKCS has statistical differences between residual tumor 28 days group (1.1769) and transplantation group (0.2483, p=0.010), irradiated transplantation group (0.1983, p=0.002) and residual tumor 21 days group (0.2017, p=0.003), residual tumor 0 days group (0.5992) and irradiated transplantation group (0.1983, p=0.027) and residual tumor 21 days group (0.2017, p=0.002). KU80 and KU70 have no statistical differences at any time point. CONCLUSION: Different proteins regulated apoptosis, proliferation and metastasis of lung adenocarcinoma after radiotherapy at different times. MMP-2 might regulate metastasis ability of XWLC-05 and A549 cells in vitro and in vivo. PCNA and P53 may play important roles in proliferation of vitro XWLC-05 and A549 cells within first 336 hr after irradiation in vitro. After that, P53 may through PI3K/AKT pathway regulate cell proliferation after irradiation in vitro. DNA-PKCS may play a more important role in DNA damage repair than KU70 and KU80 after 336 hr in vitro because it rapidly rose than KU70 and KU80 after irradiation. Different cells have different time rhythm in apoptosis, proliferation and metastasis after radiotherapy. Time rhythm of cells after irradiation should be delivered and more attention should be paid to resist cancer cell proliferation and metastasis.

[Application of nuclear magnetic dispersion weighted imaging and apparent diffusion coefficient in the identification of benign].

Objective:To determine the diagnostic role of diffusionweighted imaging(DWI) and apparent diffusion coefficient（ADC） under different b values in differentiating benign and malignant thyroid nodules by using postoperative histopathological results were taken as the reference standard. Method: From January 2017 to June 2018, 64 patients with thyroid nodules diagnosed by ultrasound in the head and neck surgery of Shanxi Cancer Hospital were collected, and a total of 80 nodules were collected. The Philips 3.0T superconducting magnetic resonance imaging system was used for T1 weighting, T2 weighting, and DWI horizontal axis scanning imaging. The b values were 300, 500, 800 and 1 000 s/mm², respectively. Taking postoperative histopathological results as the reference standard, the ADC values of thyroid nodules of all subjects were calculated and compared, and the working characteristics(ROC) curves of all subjects with b values were drawn, the area under the curve was calculated, and the threshold value of differentiating benign and malignant thyroid nodules was obtained. Result:A total of 80 nodules, 33 malignant and 43 benign were excluded, including 1 diffuse b-cell non-hodgkin's lymphoma, 2 parathyroid cysts, and 1 pure cystic patient. A total of 76 nodules were included. When b values were 300, 500, 800 and 1 000 s/mm²î€‰, the average ADC values of malignant nodules were(1.498±0.210) ×10⁻³mm²î€‰/s, (1.311±0.190) ×10⁻³î€‰mm²/s, (1.134±0.170) ×10⁻³mm²î€‰/s, (0.972±0150) ×10⁻³mm²/s. The mean ADC values of benign nodules were(2.207±0.390) ×10⁻³mm²/s, (1.928±0.430) ×10⁻³î€‰mm²/s, (1.702±0.410) ×10⁻³mm²/s,(1.557±0.420) ×10⁻³mm²/s. At the same b value, the average ADC value of malignant nodules was lower than that of benign nodules, and the difference was statistically significant(t values were 9.279,7.641,7.301,7.569, P values were 0.000,0.000,0.000,0.000,0.000). The average ADC values of the benign and malignant nodules decreased with the increase of b value, and the difference was statistically significant(the F values of the benign and malignant groups were 210.091 and 353.822, respectively，P values are 0.000, 0.000). Under different b values, the area(AUC) of ROC curve is 0.927,0.884,0.878,0.901,and 95%CI are 0.862-0.993,0.804-0.956,0.794-0.962 and 0.829-0.972, respectively. When b value is 300 s/mm², AUC is the largest, indicating that it is the best indicator to distinguish benign and malignant thyroid nodules. The diagnostic threshold of benign and malignant nodules is 1.802×10⁻³mm²/s. Specificity, sensitivity, accuracy, positive predictive value, and negative predictive value were 95.00%,86.11%,90.79%,93.94% and 88.37%, respectively. Conclusion: DWI is a noninvasive diagnostic tool used to identify benign and malignant thyroid nodules. It can help to make a definite diagnosis before surgery and reduce the unnecessary burden of surgery.

[Evaluation of progression-free survival for locally advanced rectal cancer by MRI after neoadjuvant chemoradiotherapy and total mesorectal excision].

Objective: To evaluate the predictive value of MRI features and pathological parameters on local recurrence, metastasis and progression free survival (PFS) for locally advanced rectal cancer after neoadjuvant chemoradiotherapy and subsequent total mesorectal excision surgery. Methods: A retrospective analysis of 95 patients with locally advanced rectal adenocarcinoma who underwent total mesorectal excision after neoadjuvant chemoradiotherapy was performed. Univariate and multivariate analyses were performed to evaluate the predictive value of MRI features before chemoradiation and postoperative pathological parameters on progression free survival. Results: Among the 95 cases, 5 cases occured local recurrence, 21 cases developed, 3 cases including both locally recurrence and distant metastasis, 19 died and 47 had no recurrence or metastasis at the last of follow-up. Univariant analysis showed that MRI signs before chemoradiation, namely, mr circumferential resection margin, mr levator ani muscle invasion, mr lymphatic vessel invasion, mr tumor deposition and postoperative pathological parameters, yp circumferential resection margin, yp lymphatic vessel invasion were related to PFS (P<0.05). Multivariate analysis of Cox proportional hazard model showed that mr lymphatic vessel invasion and mr tumor deposition were independent factors for PFS (OR=2.774 and 3.029, P<0.05). Conclusions: Lymphatic vessel invasion and tumor deposition on MRI are independent prognostic factors for progression free survival of locally advanced rectal cancer after neoadjuvant chemoradiotherapy and TME surgery. To some extent, MRI signs can assess local recurrence and distant metastasis in locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy and mesorectal excision.

[MRI findings and pathological features of occult breast cancer].

Objective: To investigate the magnetic resonance imaging (MRI) findings and clinicopathological features of primary lesions in patients with occult breast cancer (OBC). Methods: The imaging reports from the Breast Imaging Reporting and Data System in 2013 were retrospectively analyzed to investigate the morphology and the time signal intensity curve (TIC) of breast lesions in patients with OBC. The clinical and pathological characteristics of these patients were also included. Results: A total of 34 patients were enrolled. Among these patients, 24 patients underwent modified radical mastectomy and 18 of them had primary breast carcinoma in pathological sections. MRI detected 17 cases of primary lesions, including six masse lesions with a diameter of 0.6-1.2 cm (average 0.9 cm), and 11 non-mass lesions with four linear distributions, three segmental distributions, three focal distributions, and one regions distribution. Five patients had TIC typeⅠprimary lesions, ten had TIC type Ⅱ primary lesions, and two had TIC type Ⅲ primary lesions. Among all 34 cases, 23 of them had complete results of immunohistochemistry: 11 estrogen receptor (ER) positive lesions (47.8%), tenprogesterone receptor (PR) positive lesions (43.5%), seven human epidermal growth factor receptor 2 (HER-2) positive lesions (30.4%), and 20high expression(>14%) of Ki-67 (87.0%). The proportion of type luminal A was 4.3%, type luminal B was 43.5%, triple negative breast cancer (TNBC) was 30.4%, and HER-2 over expression accounted for 21.7%. Conclusions: The primary lesions of OBC usually manifested as small mass lesions, or focal, linear or segmental distribution of non-mass lesions. The positive rate of ER and PR was low, but the positive rate of HER-2 and the proliferation index of Ki-67 was high. Type luminal B is the most common molecular subtype.

Measurement of shear strength for HOPG with scanning tunneling microscopy by thermal excitation method.

An experimental observation of force interactions in scanning tunneling microscopy (STM) is presented. A technique for measuring force interactions between a conventional STM probe and a sample by spectra analysis of its thermal fluctuations from tunneling current in STM is developed theoretically and experimentally. Thermally excited fluctuation of the STM probe is exactly discerned in air and then force gradient is determined from its corresponding eigen-frequency with a formula similar to that for a small-amplitude atomic force microscopy (AFM). The observed force interactions are consistent with forces in dynamic AFM. Shear strength of 7 GPa for highly oriented pyrolytic graphite (HOPG) under compressive stress is obtained from the experiment and using the elastic theory. We believe that this technique is of scientific significance as it enables accurate measurement of short-range force interactions at atomic scale under true STM conditions.