Correlation Between Quantitative Spectral CT Parameters and Ki-67 Expression in Lung Adenocarcinomas Manifesting as Ground-glass Nodules.

OBJECTIVE: We assessed the feasibility of spectral CT imaging for diagnosing lung adenocarcinomas manifesting as ground-glass nodules (GGNs) with varying Ki-67 expression. METHODS: Spectral CT parameters in 116 patients with lung adenocarcinomas manifesting as GGNs were analyzed. Cases were grouped into pre-invasive/minimally invasive adenocarcinoma (pre/MIA) and invasive adenocarcinoma (IA) groups. The Ki-67 labeling index (Ki-67 LI) was measured and compared between the two groups. Ki-67 LI was divided into three grades based on the number of positive-stained cells. Spectral CT parameters (diameter, water, and iodine concentrations of the lesion [WCL and ICL], the slope of the spectral Hounsfield unit curve [λHU], and CT values from 40 to 140 keV [at 10 keV intervals]) were compared among the three different grades. The correlation between quantitative spectral CT imaging parameters and Ki-67 LI was analyzed using Spearman correlation analysis. RESULTS: Ki-67 LI in the IA group was significantly higher than in the pre/MIA group (p < 0.01). Grade 2 had higher diameter, WCL, and monochromatic CT values, and grade 1 had higher ICL and λHU. The WCL and monochromatic CT values were highly and positively correlated with Ki-67 LI. CT40keV had the highest correlation with Ki-67 LI, the diameter was moderately correlated with Ki- 67 LI, and ICL and λHU were weakly correlated with Ki-67 LI. CONCLUSION: Spectral CT, a noninvasive diagnostic method, is valuable for predicting Ki-67 expression higher in IA, thus allowing preoperative evaluation of lung adenocarcinomas manifesting as GGNs.

Association between quantitative spectral CT parameters, Ki-67 expression, and invasiveness in lung adenocarcinoma manifesting as ground-glass nodules.

BACKGROUND: Few studies about lung ground-glass nodules (GGNs) have been done using non-enhancement spectral computed tomography (CT) imaging. PURPOSE: To examine the association between spectral CT parameters, Ki-67 expression, and invasiveness in lung adenocarcinoma manifesting as GGNs. MATERIAL AND METHODS: Spectral CT parameters were analyzed in 106 patients with lung GGNs. The Ki-67 labeling index (Ki-67 LI) was measured, and patients were divided into low expression and high expression groups according to the number of positive-stained cells (low expression ≤10%; high expression >10%). Spectral CT parameters were compared between low and high expression groups. The correlation between spectral CT parameters and Ki-67 LI was estimated by Spearman correlation analysis. Cases were divided into a preinvasive and minimally invasive adenocarcinoma (MIA) group (atypical adenomatous hyperplasia, adenocarcinoma in situ, and MIA) and invasive adenocarcinoma (IA) group. Spectral CT parameters were compared between the two groups. The diagnostic performance was evaluated using receiver operating characteristic analysis. RESULTS: There were significant differences in water concentration of lesions (WCL) and monochromatic CT values between the low and high expression groups. CT 40 keV had the highest correlation coefficient with Ki-67 LI. WCL and monochromatic CT values were significantly higher in the IA group than in the pre/MIA group. The value of area under the curve of CT 40 keV was 0.946 (95% confidence interval=0.905-0.988) for differentiating the two groups; the cutoff was -280.66 Hu. CONCLUSION: Spectral CT is an effective non-invasive method for the prediction of proliferation and invasiveness in lung adenocarcinoma manifesting as GGNs.

Down-regulation of FOS-like antigen 1 enhances drug sensitivity in breast cancer.

OBJECTIVE: Multidrug resistance (MDR) to chemotherapeutic drugs is an important reason for clinical chemotherapy failure. So far, the relationship between FOS-like antigen1 (FOSL1) and chemotherapy sensitivity of breast cancer remains unclear. This study investigates the relationship between FOSL1 and chemotherapy sensitivity of breast cancer and its molecular mechanism. METHODS: Doxorubicin-resistant MCF-7/ADR breast cancer cells were transfected with NC (control) or FOSL1 siRNA and assayed for cell viability and relative colony number by MTT assay and colony formation, respectively. The expression level of FOSL1 was detected by immunohistochemistry (IHC). The relationship between FOSL1 and chemotherapy sensitivity was analyzed by a one-way of variance analysis and Pearson's chi-square test among a total of 50 patients with stage II and III breast cancer before and after they received epirubicin-based neoadjuvant chemotherapy (NCT) between 2012 and 2017. RESULTS: The expression of FOSL1 was increased in breast cancer tissues compared with normal breast tissues (P<0.05), and the expression of FOSL1 was decreased after NCT treatment compared with breast cancer tissues (or before NCT). This lower expression of FOSL1 was correlated with chemotherapy resistance or chemotherapy sensitivity (P<0.05). Moreover, the expression level of FOSL1 was markedly lower in NCT-sensitive patients than that of NCT-resistant patients (P<0.05). CONCLUSION: Down-regulation of FOSL1 potentiated chemotherapy sensitivity of breast cancer, and its lower expression attenuated chemotherapeutic drug resistance in human breast cancer cells. FOSL1 might be a drug target for predicting chemotherapy effect in breast cancer.

MicroRNA-130a reduces drug resistance in breast cancer.

OBJECTIVE: Although the advent of chemotherapy has made some progress in the comprehensive treatment of breast cancer, drug resistance of tumor cells remains to be one of the main challenges for the treatment of breast cancers. Several microRNAs have been implicated in the resistant process, but the role of miR-130a in drug resistance in breast cancer remains unclear. The present study aims to investigate the role and mechanisms of miR-130a in drug resistance in breast cancer cells and tissues. PATIENTS AND METHODS: miR-130a mimics was used to up-regulate miR-130a expression in Doxorubicin-resistant MCF-7/Adr breast cancer cell line, followed by MTT assay and colony formation to determine cell viability and relative colony number. The relationship between the expression of miR-130a and drug resistance was detected by in situ hybridization in the formalin-fixed paraffin-embedded (FFPE) tissues from 50 breast cancer patients before and after Epirubicin-based neoadjuvant chemotherapy. RESULTS: Up-regulation of miR-130a level in MCF-7/Adr cells decreased the cell viability and colony number, and reversed Doxorubicin resistance of MCF-7/Adr cells. In breast cancer tissue from patients, the miR-130a level was lower before neoadjuvant chemotherapy than that after neoadjuvant chemotherapy (P < 0.05). Moreover, a significant increase in the expression of miR-130a was observed in breast tumor tissues from patients sensitive to neoadjuvant chemotherapy compared to the patients who were resistant to neoadjuvant chemotherapy (P < 0.05). CONCLUSION: We concluded that miR-130a might weaken drug resistance of human breast cancer cells, and act as an important factor in prediction of therapeutic responses in chemotherapy of breast cancer.

Expression of and correlation between BCL6 and ZEB family members in patients with breast cancer.

B-cell lymphoma 6 (BCL6), a proto-oncogene, is an evolutionarily conserved zinc finger protein that functions as a transcriptional repressor. BCL6 is the master regulator of B-lymphocyte development, and it has been reported that BCL6 may serve an important role in breast cancer progression. The aim of the present study was to investigate the expression of BCL6, zinc finger E-box-binding homeobox (ZEB)1 and ZEB2 and their associations in breast cancer. The mRNA and protein expression of BCL6, ZEB1 and ZEB2 was assessed using in situ hybridization and immunohistochemistry, respectively, in 228 patients with breast cancer and 80 patients with benign breast disease. In addition, the association between BCL6, ZEB1 and ZEB2 expression and the clinicopathological characteristics and survival of patients with breast cancer were analyzed. The mRNA and protein expression of BCL6, ZEB1 and ZEB2 were significantly higher in breast cancer tissues compared with benign breast disease tissues (P<0.05). The expression of BCL6, ZEB1 and ZEB2 were significantly positively correlated with tumor size, lymph node metastasis and a higher tumor stage (P<0.05). Furthermore, patients with BCL6, ZEB1 and ZEB2 protein-positive primary tumors had significantly lower overall survival (P=0.001, 0.002 and 0.001, respectively) and relapse-free survival (P=0.002, 0.001 and 0.003, respectively) rates. The mRNA expressions of ZEB1 (rs=0.326, P<0.001) and ZEB2 (rs=0.382, P<0.001) were significantly positively correlated with BCL6 mRNA expression, and the protein expressions of ZEB1 ((rs=0.449, P<0.001) and ZEB2 (rs=0.669, P<0.001) were significantly positively correlated with BCL6 protein expression. These results suggest that BCL6, ZEB1 and ZEB2 are potential biomarkers for the invasion, metastasis and prognosis of breast cancer, and that BCL6 may be a regulator of the ZEB family.

Self-floating graphitic carbon nitride/zinc phthalocyanine nanofibers for photocatalytic degradation of contaminants.

The effective elimination of micropollutants by an environmentally friendly method has received extensive attention recently. In this study, a photocatalyst based on polyacrylonitrile (PAN)-supported graphitic carbon nitride coupled with zinc phthalocyanine nanofibers (g-C3N4/ZnTcPc/PAN nanofibers) was successfully prepared, where g-C3N4/ZnTcPc was introduced as the catalytic entity and the PAN nanofibers were employed as support to overcome the defects of easy aggregation and difficult recycling. Herein, rhodamine B (RhB), 4-chlorophenol and carbamazepine (CBZ) were selected as the model pollutants. Compared with the typical hydroxyl radical-dominated catalytic system, g-C3N4/ZnTcPc/PAN nanofibers displayed the targeted adsorption and degradation of contaminants under visible light or solar irradiation in the presence of high additive concentrations. According to the results of the radical scavenging techniques and the electron paramagnetic resonance technology, the degradation of target substrates was achieved by the attack of active species, including photogenerated hole, singlet oxygen, superoxide radicals and hydroxyl radicals. Based on the results of ultra-performance liquid chromatography and mass spectrometry, the role of free radicals on the photocatalytic degradation intermediates was identified and the final photocatalytic degradation products of both RhB and CBZ were some biodegradable small molecules.

Expression and correlation of Twist and gelatinases in breast cancer.

Altered expression of Twist, matrix metalloproteinase (MMP)-2 and MMP-9 proteins has been identified in various types of human cancers. However, the correlation between Twist and these gelatinases in breast cancer remains unclear. In this study, immunohistochemical analysis of Twist, MMP-2 and MMP-9 expression was performed on tissue microarrays from 200 breast cancer cases. The association of Twist and gelatinase expression with clinicopathological factors and patient survival was analyzed. Altered expression of Twist, MMP-2 and MMP-9 proteins was observed in breast cancer tissue. The positive rates of Twist, MMP-2 and MMP-9 protein expression were 75.5, 97.0 and 96.0%, respectively. Increased expression of Twist was positively correlated with the status of axillary lymph node metastasis and higher tumor-node-metastasis (TNM) stage (P<0.01). Moreover, increased expression of Twist was correlated with poor overall survival (OS) and post-operative relapse-free survival (RFS), compared with those for the patients with reduced expression levels of Twist (P<0.05, P<0.01). The expression of MMP-2 and MMP-9 was positively correlated with Twist expression (P<0.001). Our results indicate that Twist may play an important role in the invasion, metastasis and prognosis of breast cancer. Additionally, our results suggest that Twist may be a regulator of gelatinases (MMP-2 and MMP-9).

[Evaluation of dosimetric variance in forward intensity modulated radiotherapy of the breast based on 4D CT and 3D CT during free breathing].

OBJECTIVE: To explore the dosimetric variance in forward intensity modulated radiotherapy (IMRT) based on 4D CT and 3D CT after breast conserving surgery. METHODS: Seventeen patients after breast conserving surgery underwent 3D CT simulation scans followed by respiration-synchronized 4D CT simulation scans at free breathing state. The treatment plan constructed using the end inspiration (EI) scan was then copied and applied to the end expiration (EE), and 3D scans and dose distribution were calculated separately. Dose-volume histograms (DVHs) parameters for the CTV, PTV, ipsilateral lung and heart were evaluated and compared. RESULTS: The CTV volume difference was biggest between T0 and 3D CT, and the volume difference was 4.10 cm(3). Mean dose of PTV at EE was lower than that at EI (P = 0.019), but there were no statistically significant difference between 3D and EI, EE (all P > 0.05). The homogeneity index (HI) at EI, EE, 3D plans were 0.149, 0.159 and 0.164, respectively, and a significant difference was only between EI and EE (P = 0.039). The highest conformal index (CI) was at EI phase (P < 0.05), and there was no significant difference between EE and 3D (P = 0.758). The V(40) and V(50) of ipsilateral lung at EE phase were lower than that at EI (P < 0.05). There were no significant differences in all the indexes for heart (P > 0.05). CONCLUSIONS: The breast deformation during respiration may be disregarded in whole breast IMRT. PTV dose distribution is significantly changed between EI and EE phases, and the differentiation of the lung high dose area between EI and EE phases may be induced by thorax expansion. 3D treatment planning is sufficient for whole breast forward IMRT, but 4D CT scans assisted by respiratory gating ensures more precise delivery of radiation dose.