A pilot study of low-dose CT perfusion imaging (LDCTPI) technology in patients with triple-negative breast cancer.

PURPOSE: To investigate associations between the clinicopathologic features and CT perfusion parameters of triple-negative breast cancer (TNBC) and non-TNBC using low-dose computed tomography perfusion imaging (LDCTPI), and to find potential clinical applications in the prognosis assessment of TNBC. MATERIALS AND METHODS: A total of 60 patients with breast cancer confirmed by pathological examination were studied prospectively using LDCTPI on a 64-slice spiral CT scanner. The acquired volume data were used for calculations, mapping, and analysis by using a tumor perfusion protocol in the CT perfusion software package to measure 2 parameters namely, blood flow (BF), and permeability surface (PS) area product. Patients were grouped into TNBC (n = 27) and non-TNBC (n = 33) subtypes. Associations between these two subtypes and clinicopathologic characteristics were evaluated by both univariate and multivariate logistic regression. CT perfusion parameters values were compared for clinicopathologic characteristics using independent 2-sample t test. RESULTS: TNBC displayed higher CT perfusion parameters values (BF: 57.56±10.94 vs 52.70±7.79 mL/100 g/min, p = 0.006; PS: 38.98±9.46 vs 33.39±8.07 mL/100 g/min, p = 0.001) than non-TNBC. In addition, breast cancer with poorly histologic grade or positive Ki-67 expression showed higher BF and PS values than those with well and moderately histologic grade or negative Ki-67 expression (p < 0.05). TNBC had poorer histologic grade (P = 0.032) and higher Ki-67 expression (P = 0.013) than non-TNBC. CONCLUSION: LDCTPI is a functional imaging technology from the perspective of hemodynamics with potential of clinical applications. The BF and PS values were higher in TNBC patient group than non-TNBC group. TNBC patients also have poorer clinicopathologic outcome.

Glycolysis is essential for chemoresistance induced by transient receptor potential channel C5 in colorectal cancer.

BACKGROUND: Elevated intracellular Ca2+ ([Ca2+] i ) level could lead to [Ca2+] i overload and promote apoptosis via different pathways. In our previously study, up-regulated expression of transient receptor potential canonical channel (TRPC5) was proven to increase [Ca2+] i level, and resulted in chemoresistance whereas not apoptosis in human colorectal cancer (CRC) cells. The ATP-dependent homeostatic maintenance of resting [Ca2+] i should be important in this process. Increased glycolysis was found to be an important adenosine triphosphate (ATP) source in cancer. This study aimed to explore the potential mechanism of aerobic glycolysis in transient receptor potential channel TRPC5 induced chemoresistance. METHODS: In this study, we examined glucose transporter 1 (GLUT1) expression, glucose consumption and celluar ATP production to determine glycolytic activity. Real-time PCR and western blot were analyzed to determine TRPC5 expression at the mRNA and protein levels in human CRC cells (HCT-8, LoVo), and fluorouracil (5-Fu) resistant CRC cells (HCT-8/5-Fu, LoVo/5-Fu). 3-bromopyruvate (3-BP) and 2-Deoxy-D-glucose (2DG) were used to inhibit glycolysis. Glycolytic activity, intracellular Ca2+ ([Ca2+] i ) and the half maximal inhibitory concentration of 5-Fu (5-Fu IC50) were measured. Western blot was analyzed to determine cleaved Caspase-3 protein level. Flow cytometry was performed to detect the apoptosis rates. Immunohistochemistry staining was performed to determine TRPC5 and GLUT1 expression level in human CRC tissues. RESULTS: Overproduced of TRPC5 and increased glycolysis were found in HCT-8/5-Fu and LoVo/5-Fu than in HCT-8 and LoVo cells. Compared to HCT-8 cells, the HCT-8/5-Fu cells showed higher [Ca2+] i levels which decreased after treated with TRPC5-specific shRNA. Furthemore, inhibition of glycolysis resulted in decreased ATP production, elevation of [Ca2+] i level and cleaved caspase-3, increased apoptotic cells rate, and a remarkable reversal of 5-Fu resistance in HCT-8/5-Fu cells, while showed no effect in HCT-8 cells. BAPTA-AM, a [Ca2+] i chelator, could reduce the elevation of cleaved caspase-3 and increased apoptotic cells rate due to glycolysis inhibition. Advanced CRC patients with high expression of TRPC5/GLUT1 displayed poorer chemotherapy outcome, and notably, the significant association between high TRPC5 expression and chemoresistance is GLUT1 expression level dependent. CONCLUSIONS: We demonstrated the essential role of glycolysis in TRPC5 induced chemoresistance in human CRC cells via maintaining [Ca2+] i homeostasis.

The feasibility of low-dose CT perfusion imaging in gastric cancer.

PURPOSE: To investigate feasibility of applying low-dose CT perfusion imaging (CTPI) to diagnose gastric cancer. MATERIALS AND METHODS: Twenty patients with gastric cancer confirmed by endoscopic biopsy were undergone routine dose (120 kV, 100 mA) and low-dose (120 kV, 50 mA) CTPI examination, respectively. The original data were processed by body perfusion software, and the perfusion parameters values including blood flow (BF), blood volume (BV) and permeability surface (PS) of gastric cancer were measured. Statistical data analyses including paired-samples t test, Pearson correlation analysis and Bland-Altman consistency test were used to compare the perfusion parameters values between the routine dose and low-dose CTPI examinations. Radiation dosage, which the patients received during two CTPI examinations, was also calculated and compared. RESULTS: There were no statistical differences in the BF, BV and PS values between routine dose group and low-dose group (P > 0.05), and there were significant correlation in the BF, BV and PS values between two groups (P <  0.01). The consistency of BF and BV values between the two groups was preferable to that of PS value. The radiation dosage of the low-dose group was much less than that of routine dose group, and the CTDIvol and DLP values of low-dose CTPI were decreased by 50%, respectively. CONCLUSION: The parameters BF and BV values may play a valuable role in the diagnosis and assessment of gastric cancer in low-dose CTPI examination.

Can low-dose CT perfusion imaging accurately assess response of advanced gastric cancer with neoadjuvant chemotherapy?

PURPOSE: To explore the value of low-dose CT perfusion imaging (LDCTPI) technology and its perfusion parameters in assessing response of neoadjuvant chemotherapy (NAC) in patients with advanced gastric cancer (AGC). METHODS: Thirty patients with AGC were studied prospectively by LDCTPI to measure two parameters including blood flow (BF) and blood volume (BV) of tumor area before and after chemotherapy, respectively. All of the patients received two courses of NAC and surgical resection of gastric tumor within one week after chemotherapy, and then obtained the result of postoperative pathology response for chemotherapy. The comparisons of BF and BV values of AGC before and after chemotherapy were analyzed by paired-samples t-test, respectively; and the correlations between BF as well as BV decrease rates after NAC and the pathology response grade were analyzed by Spearman statistical test. Thirty patients were divided into effective and ineffective groups according to different pathology response grade. Comparisons of BF as well as BV decrease rates between effective and ineffective groups were analyzed by independent-samples t-test, respectively. Receiver operating characteristic (ROC) curves were used to determine the cutoff values of BF and BV decrease rates as evaluation indicators of AGC after NAC and calculate area under the curve (AUC). RESULTS: There were significant differences in BF and BV values of AGC between before and after NAC (p < 0.001), respectively, and there were obvious correlations between BF as well as BV decrease rates and pathology response grade (r = 0.660, p < 0.001; r = 0.706, p < 0.001), respectively. There were also significant differences in BF and BV decrease rates of AGC between effective and ineffective groups (P = 0.001), respectively. If BF decrease rate of 12.1% (AUC was 0.816, P = 0.005) was used as the cutoff value for chemotherapy effectiveness of AGC, the sensitivity of 82% and specificity of 84% were achieved, and if BV decrease rate of 32.8% (AUC was 0.844, P = 0.002) was used as the cutoff value for chemotherapy effectiveness of AGC, the sensitivity of 82% and specificity of 89% were achieved. CONCLUSIONS: BF and BV decrease rates have potential to be used as effective indicators to assess chemotherapy efficacy of AGC from the hemodynamics.

Role of CT perfusion imaging in patients with variously differentiated gastric adenocarcinoma.

PURPOSE: To explore the characteristics of variously differentiated gastric cancers on computed tomography (CT) perfusion imaging, including specific perfusion parameter values, and potential clinical applications in the prognosis assessment of gastric cancer. MATERIALS AND METHODS: Fifty patients with gastric cancer confirmed by gastroscope pathology were studied prospectively using CT perfusion imaging examinations on a 64-slice spiral CT scanner. The acquired volume data were used for calculations, mapping, and analysis by using an abdominal tumor perfusion protocol (deconvolution method) in the CT perfusion software package to measure 4 parameters: blood flow (BF), blood volume (BV), mean transit time (MTT), and the permeability surface (PS) area product. The different differentiated Gastric cancers with CT perfusion values were divided into 3 groups: well-differentiated, moderately differentiated and poorly differentiated gastric adenocarcinoma, and compared statistically with one another by statistical software. RESULTS: The mean perfusion values of 10 patients with well-differentiated gastric adenocarcinoma were as follows: BF, 75.28 ± 6.81 mL/100 g/min; BV, 9.01 ± 0.94 mL/100 g; MTT, 9.89 ± 1.65 s; and PS, 10.05 ± 0.71 mL/100 g/min. The mean perfusion values of 24 patients with moderately differentiated gastric adenocarcinoma were as follows: BF, 110.01 ± 31.90 mL/100 g/min; BV, 18.18 ± 5.62 mL/100 g; MTT, 9.81 ± 3.69 s; and PS, 40.08 ± 15.82 mL/100 g/min. The mean perfusion values of 16 patients with poorly differentiated gastric adenocarcinoma were as follows: BF, 138.59 ± 38.09 mL/100 g/min; BV, 21.08 ± 4.11 mL/100 g; MTT, 9.47 ± 1.80 s; and PS, 57.50 ± 13.28 mL/100 g/min. Comparing the 3 groups, differences between the well-differentiated group and the moderate differentiation group were all statistically significant for BF, BV, and PS (p < 0.05, respectively), differences between the well-differentiated group and the poor differentiation group were all statistically significant for BF, BV, and PS (p < 0.05,respectively) as well; While MTT value showed no statistical difference among the 3 groups (p > 0.05). CONCLUSION: Stomach CT perfusion imaging is a functional imaging technology from the perspective of hemodynamics with potential clinical applications. The BF, BV and PS values could serve as indicators of the degree of malignancy and aid in prognostic assessment of gastric cancer.

Vestigial like family member 3 is a novel prognostic biomarker for gastric cancer.

BACKGROUND: Vestigial like family member 3 (VGLL3) is associated with the prognosis of epithelial ovarian cancer and soft tissue sarcoma, but its role in gastric cancer (GC) is unclear. AIM: To explore the expression pattern and clinical significance of VGLL3 in GC. METHODS: Integrative analysis was performed on the GC transcriptome profiles and survival information deposited in the ONCOMINE, GEPIA, and ONCOLNC databases. The expression levels of VGLL3 mRNA and protein were analyzed in the freshly resected tumor and normal gastric tissues from GC patients by quantitative RT-PCR and Western blot, respectively. In addition, the in situ expression of VGLL3 in the GC tissues was determined by immunohistochemistry (IHC), and the patients were accordingly classified into the high and low expression groups. The correlation of VGLL3 expression status with patient prognosis was then determined by univariate and multivariate Cox regression analyses. RESULTS: Analysis of the ONCOMINE and GEPIA databases showed that VGLL3 was significantly up-regulated in GC tissues (P = 0.003), and associated with the tumor TNM stage (P = 0.0163). The high VGLL3 expression group had a significantly worse prognosis compared to the low expression group, as per both GEPIA (P = 0.0057) and ONCOLNC (P = 0.01). The bioinformatics results were validated by the significantly higher VGLL3 mRNA and protein levels in the GC tissues compared to the adjacent normal tissues (P < 0.001) in a cohort of 30 GC patients. Furthermore, high in situ expression of VGLL3 protein was associated with more advanced N and TNM stages and HER2 mutation (P < 0.05) in a cohort of 172 patients. Kaplan-Meier analysis showed that the high VGLL3 expression group had a worse prognosis compared to the low expression group (P = 0.019). Multivariate analysis showed that VGLL3 expression status was an independent risk factor for prognosis. In addition, the prognostic risk model nomogram showed that VGLL3 was the most important indicator, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.613 for 3-year survival and 0.706 for 5-year survival. Finally, the protein interaction network analysis revealed that VGLL3 is likely involved in the Hippo signaling pathway. CONCLUSION: VGLL3 is overexpressed in GC tissues and associated with a poor prognosis, indicating its potential as a novel prognosis biomarker and therapeutic target for GC.