KLF8 is associated with poor prognosis and regulates glycolysis by targeting GLUT4 in gastric cancer.

Krüppel-like transcription factor (KLF) family is involved in tumorigenesis in different types of cancer. However, the importance of KLF family in gastric cancer is unclear. Here, we examined KLF gene expression in five paired liver metastases and primary gastric cancer tissues by RT-PCR, and immunohistochemistry was used to study KLF8 expression in 206 gastric cancer samples. The impact of KLF8 expression on glycolysis, an altered energy metabolism that characterizes cancer cells, was evaluated. KLF8 showed the highest up-regulation in liver metastases compared with primary tumours among all KLF members. Higher KLF8 expression associated with larger tumour size (P < 0.001), advanced T stage (P = 0.003) and N stage (P < 0.001). High KLF8 expression implied shorter survival outcome in both TCGA and validation cohort (P < 0.05). Silencing KLF8 expression impaired the glycolysis rate of gastric cancer cells in vitro. Moreover, high KLF8 expression positively associated with SUVmax in patient samples. KLF8 activated the GLUT4 promoter activity in a dose-dependent manner (P < 0.05). Importantly, KLF8 and GLUT4 showed consistent expression patterns in gastric cancer tissues. These findings suggest that KLF8 modulates glycolysis by targeting GLUT4 and could serve as a novel biomarker for survival and potential therapeutic target in gastric cancer.

Diastolic Dysfunction Occurs Early in HER2-Positive Breast Cancer Patients Treated Concurrently With Radiation Therapy and Trastuzumab.

BACKGROUND: Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular diastolic dysfunction (LVDD) and its relationship to the dose-volume of the heart irradiated were evaluated in HER2-positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT). MATERIALS AND METHODS: Data from 40 breast cancer patients treated with concurrent trastuzumab and left-sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right-sided adjuvant RT and 71 patients treated with left-sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified. RESULTS: Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left-sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. Dmean, D15-D40, D60-D70, and V3-V10 of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left-sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left-sided RT alone. CONCLUSION: Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose-volume of the heart contributes significantly to the risk of LVDD in patients with left-sided breast cancer treated concurrently with trastuzumab. IMPLICATIONS FOR PRACTICE: Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose-volume of the heart irradiated in patients with left-sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose-volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.

Differential diagnosis of B-mode ultrasound Breast Imaging Reporting and Data System category 3-4a lesions in conjunction with shear-wave elastography using conservative and aggressive approaches.

Background: The high false-positive rates of US Breast Imaging Reporting and Data System (BI-RADS) category 3-4a breast lesions leads to excessive biopsies of many benign lesions, and our aim was to investigate the diagnostic performance achieved by adding a maximum elasticity (Emax) of shear-wave elastography (SWE) to ultrasound (US) to evaluate US BI-RADS category 3-4a breast lesions using conservative and aggressive approaches. We explored the capacity of using this method to avoid unnecessary biopsies without increasing the probability of missing breast cancers. Methods: A total of 123 breast lesions of 120 patients classified as BI-RADS category 3 or 4a were enrolled from January 2019 to December 2019. The US features were evaluated according to the US BI-RADS lexicon. The maximum diameter measured on the US was defined as the size of the lesion. The Emax was assessed by SWE, and the average Emax of breast lesions on two images were calculated and recorded as the final maximum Young's modulus. The diagnostic performance of the combined B-mode US and SWE approach for BI-RADS category 3-4a breast lesions was tested using a conservative approach and an aggressive approach. In the conservative approach, the lesions were downgraded with Emax of 30 kPa or less and upgraded with Emax of 160 kPa or more. In the aggressive approach, the lesions were downgraded with Emax of 80 kPa or less and upgraded with Emax of 160 kPa or more. Pathologic results were defined as the reference standard. Results: Among all 123 breast lesions, there were 60 lesions classified as BI-RADS category 3 and 63 lesions classified as BI-RADS category 4a. Compared to the B-mode US, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic (ROC) curve (AUC) of the combined B-mode US and SWE with a conservative approach changed from 88.9% to 94.4%, 55.2% to 60.0%, 25.4% to 28.8%, 96.7% to 98.4%, 60.2% to 65.0%, and 0.721 to 0.772, respectively. The specificity, PPV, and accuracy of combined B-mode US and SWE with an aggressive approach increased from 55.2% to 72.4%, 25.4% to 29.3%, and 60.2% to 71.5%, respectively, but this was accompanied with decreases in the sensitivity from 88.9% to 66.7%, the NPV from 96.7% to 92.7%, and the AUC from 0.721 to 0.695. Conclusions: The addition of SWE improves the diagnostic performance of breast US. Adding the diagnostic criteria of SWE to the BI-RADS assessment of B-mode US, downgrading the lesions with Emax 30 kPa or less, and upgrading the lesions with Emax 160 kPa or more helped discriminate low suspicion lesions from benign lesions in order to decrease false-positive findings and avoid missing cancer diagnosis.

Relationship of arterial stiffness and early mild diastolic heart failure in general middle and aged population.

AIMS: The brachial-ankle pulse wave velocity (baPWV) has been recognized as a marker that reflects arterial stiffness. We conducted an investigation to evaluate whether baPWV is independently associated with early mild diastolic heart failure (DHF) in a general middle and aged population. METHODS AND RESULTS: From 1 July 2009 until 31 August 2009, we investigated 2095 subjects for the relevant factors of heart failure in the Lujiazui Community, Shanghai. The baPWV, echocardiography, and blood sampling were performed in the morning after a 12 h overnight fast. A total of 1929 subjects had the complete data, including questionnaire, age, gender, baPWV, brain natriuretic peptide, and E/A ratio. Early mild DHF was defined as a left ventricular ejection fraction >50%, E/A ratio <0.8, and E/E' ≤ 8; finally, 482 subjects with early mild DHF and 1282 subjects with non-DHF entered into analysis. Among 1764 subjects, 31.6% of the subjects were male (average age was 58.0 ± 12.3), 35.8% of the subjects had hypertension, the average body mass index (BMI) was 24.2 ± 3.3 kg/m(2), baPWV was 1513.0 (1329.1, 1763.5) cm/s, and the baPWV was significantly correlated with the E/A ratio (r = -0.39, P < 0.01). There was a difference of the baPWV [1456.0 (1295.3, 1698.3) vs. 1670.5 (1465.6, 1910.8) cm/s] between the non-DHF group and the early mild DHF group (P < 0.01). Multiple logistic-regression analyses demonstrated that age, male gender, BMI, baPWV, posterior left ventricular wall thickness (PVWT), interventricular septal thickness (IVST), E/E' ratio, left ventricular mass index (LVMI), systolic blood pressure (≥140 mmHg), and diastolic blood pressure (≥90 mmHg) were independently correlated with early mild DHF. CONCLUSIONS: The increased arterial stiffness is associated with early mild DHF in a general middle and aged population independently of age, male gender, BMI, PVWT, IVST, E/E' ratio, LVMI, and high blood pressure. The non-invasive techniques described may allow serial measurements to be made over time to monitor baPWV changes in arteries provided the introduction of anti-arteriosclerosis therapy.

Prediction of treatment responses to neoadjuvant chemotherapy in breast cancer using contrast-enhanced ultrasound.

BACKGROUND: Elucidation the efficacy of neoadjuvant chemotherapy (NAC) in breast cancer is important for informing therapeutic decisions. This study aimed at evaluating the potential value of contrast-enhanced ultrasound (CEUS) parameters in predicting breast cancer responses to NAC. METHODS: We performed CEUS examinations before and after two cycles of NAC. Quantitative CEUS parameters [maximum intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (mTT)], tumor diameter, and their changes were measured and compared to histopathological responses, according to the Miller-Payne Grading (MPG) system (score 1, 2, or 3: minor response; score 4 or 5: good response). Prediction models for good response were developed by multiple logistic regression analysis and internally validated through bootstrap analysis. The receiver operating characteristic (ROC) curve was used to evaluate the performance of prediction models. RESULTS: A total of 143 patients were enrolled in this study among whom 98 (68.5%) achieved a good response and while 45 (31.5%) exhibited a minor response. Several imaging variables including diameter, IMAX, changes in diameter (Δdiameter), IMAX (ΔIMAX) and TTP (ΔTTP) were found to be significantly associated with good therapeutic responses (P<0.05). The areas under the curve (AUC) increased from 0.748 to 0.841 in the multivariate model that combined CEUS parameters and molecular subtypes with a sensitivity and specificity of 0.786, 0.745, respectively. Tumor molecular subtype was the primary predictor of primary endpoint. CONCLUSIONS: CEUS is a potential tool for predicting responses to NAC in locally advanced breast cancer patients. Compared to the other molecular subtypes, triple negative and HER2+/ER- subtypes are more likely to exhibit a good response to NAC.

[Comparison of 3 hand-carried ultrasound devices with comprehensive echocardiographic devices in elderly cardiac inpatient examinations].

In order to test the clinical capacity of hand-carried ultrasound (HCU) devices in elderly inpatients with heart disease, chamber sizes of heart structure, ventricular wall thickness and motion abnormality (WMA), mitral valve and tricuspid regurgitation evaluated by HCU devices in 401 elderly inpatients with heart disease were compared with those evaluated by comprehensive echocardiography (CE) devices. As a result, there was no significant difference in measurements of cardiac chamber dimensions or left ventricular ejection fraction between the two techniques. The HCU's WMA detection rate relative to the CE was 92.15%. Their conformable rates for detection of mitral and tricuspid regurgitation was 93% and 91.4% respectively. Therefore, we conclude that HCU is one of the practical modalities for diagnosis and monitoring in elderly inpatients with heart disease.

Predicting Treatment Response of Breast Cancer to Neoadjuvant Chemotherapy Using Ultrasound-Guided Diffuse Optical Tomography.

PURPOSE: To prospectively investigate ultrasound-guided diffuse optical tomography (US-guided DOT) in predicting breast cancer response to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: Eighty-eight breast cancer patients, with a total of 93 lesions, were included in our study. Pre- and post-last chemotherapy, size and total hemoglobin concentration (THC) of each lesion were measured by conventional US and US-guided DOT 1 day before biopsy (time point t0, THC THC0, SIZE S0) and 1 to 2 days before surgery (time point tL, THCL, SL). The relative changes in THC and SIZE of lesions after the first and last NAC cycles were considered as the variables ΔTHC and ΔSIZE. Receiver operating characteristic curve was performed to calculate ΔTHC and ΔSIZE cutoff values to evaluate pathologic response of 93 breast cancers to NAC, which were then prospectively used to predicate response of 61 breast cancers to NAC. RESULTS: The cutoff values of ΔTHC and ΔSIZE for evaluation of breast cancers NAC treatment response were 23.9% and 42.6%. At ΔTHC 23.9%, the predicted treatment response in 61 breast lesions for the time points t1 to t3 was calculated by area under the curve (AUC), which were AUC1 0.534 (P=.6668), AUC2 0.604 (P=.1893), and AUC3 0.674(P =. 0.027), respectively; for ΔSIZE 42.6%, at time points t1 to t3, AUC1 0.505 (P=.9121), AUC2 0.645 (P=.0115), and AUC3 0.719 (P=.0018). CONCLUSION: US-guided DOT ΔTHC 23.9% and US ΔSIZE 42.6% can be used for the response evaluation and earlier prediction of the pathological response after three rounds of chemotherapy.

miR-146a rs2910164 and hepatocellular carcinoma: a meta-analysis.

INTRODUCTION: Single nucleotide polymorphism in miRNAs can alter its expression, thus can lead to the development of cancers. Many studies have explored the association between miR-146a rs2910164 (G>C) polymorphism and hepatocellular carcinoma (HCC) risk, but the results remains inconsistent. So, we performed this pooled analyses in order to get a precise result. EVIDENCE ACQUISITION: Odds ratios (OR) with 95% confidence intervals (CI), calculated by STATA software, was used to determine whether miR-146a rs2910164 polymorphism contributes to the risk of HCC. A comprehensive literature search was conducted on PubMed, Embase, Web of Science, and China National Knowledge Infrastructure up to May 30, 2016. EVIDENCE SYNTHESIS: A total of 14 studies including 5921 cases and 7005 controls were included in this meta-analysis. When all the eligible studies were pooled into this meta-analysis, the miR-146a rs2910164 was associated with a decreased risk of hepatocellular carcinoma (OR=0.90; 95% CI=0.82-0.98, P=0.01, allele model). CONCLUSIONS: Our meta-analysis supports that the miR-146a rs2910164 polymorphism contributes to the risk of HCC from currently available evidence.