Drug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates resistance to chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant to chemotherapy-induced cell death than cells with lower DUSP16 expression. Overexpression of DUSP16 in cancer cells leads to increased resistance to cell death upon chemotherapy treatment. In contrast, knockdown of DUSP16 in cancer cells increases their sensitivity to treatment. Mechanistically, DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria to reduce apoptosis. Analysis of patient survival in head & neck cancer and breast cancer patient cohorts supports DUSP16 as a marker for sensitivity to chemotherapy and therapeutic outcome. This study therefore identifies DUSP16 as a prognostic marker for the efficacy of chemotherapy, and as a therapeutic target for overcoming chemoresistance in cancer.

Background. Asthma is a disease with airway hyperresponsive and airway inflammation. Platycodin D is a triterpenoid saponin extracted from Platycodon grandiflorus root, which has various pharmacological activities. The study mainly explored the effects of platycodin D3 (PD3) in airway remodeling and inflammation of asthma. Methods. The ovalbumin (OVA)-induced asthma mice were given PD3 (20 mg/kg, 40 mg/kg, and 80 mg/kg) in different groups. The asthma mice administrated with dexamethasone (DXM) were enrolled as the positive control group, and the normal control mice and asthma model mice separately received the same volume of saline. Mouse airway lung dynamic compliance (Cdyn) and total airway resistance (RL) were measured by the EMKA animal lung function analysis system. The inflammation factor levels were estimated by ELISA. Histopathological changes were tested by HE and PAS staining. The protein and phosphorylation levels of NF-κBp65, p38, ERK1/2, and JNK1/2 were detected by Western blot. Results. In asthmatic mice, PD3 enhanced the airway Cdyn and decreased RL to improve the airway hyperreactivity and alleviated the pathological injury of lung tissues. In addition, PD3 could reduce the infiltration of inflammatory cells in BALF and suppress the levels of eotaxin, IL-4, IL-5, IL-13, IFN-γ, and IgE. Furthermore, PD3 treatment inhibited the phosphorylation of NF-κBp65, p38, ERK1/2, and JNK1/2 proteins in asthma mice. Conclusion. PD3 treatment alleviated the airway remodeling and inflammation in asthmatic mice, which might be related to downregulating the phosphorylated proteins in the MAPK/NF-κB signaling pathway.

Background BI-RADS 4 breast lesions are suspicious for malignancy with a range from 2 to 95%, indicating that numerous benign lesions are unnecessarily biopsied. Thus, we aimed to investigate whether high-temporal-resolution dynamic contrast-enhanced MRI (H_DCE-MRI) would be superior to conventional low-temporal-resolution DCE-MRI (L_DCE-MRI) in the diagnosis of BI-RADS 4 breast lesions. Methods This single-center study was approved by the IRB. From April 2015 to June 2017, patients with breast lesions were prospectively included and randomly assigned to undergo either H_DCE-MRI, including 27 phases, or L_DCE-MRI, including 7 phases. Patients with BI-RADS 4 lesions were diagnosed by the senior radiologist in this study. Using a two-compartment extended Tofts model and a three-dimensional volume of interest, several pharmacokinetic parameters reflecting hemodynamics, including Ktrans, Kep, Ve, and Vp, were obtained from the intralesional, perilesional and background parenchymal enhancement areas, which were labeled the Lesion, Peri and BPE areas, respectively. Models were developed based on hemodynamic parameters, and the performance of these models in discriminating between benign and malignant lesions was evaluated by receiver operating characteristic (ROC) curve analysis. Results A total of 140 patients were included in the study and underwent H_DCE-MRI (n = 62) or L_DCE-MRI (n = 78) scans; 56 of these 140 patients had BI-RADS 4 lesions. Some pharmacokinetic parameters from H_DCE-MRI (Lesion_Ktrans, Kep, and Vp; Peri_Ktrans, Kep, and Vp) and from L_DCE-MRI (Lesion_Kep, Peri_Vp, BPE_Ktrans and BPE_Vp) were significantly different between benign and malignant breast lesions (P < 0.01). ROC analysis showed that Lesion_Ktrans (AUC = 0.866), Lesion_Kep (AUC = 0.929), Lesion_Vp (AUC = 0.872), Peri_Ktrans (AUC = 0.733), Peri_Kep (AUC = 0.810), and Peri_Vp (AUC = 0.857) in the H_DCE-MRI group had good discrimination performance. Parameters from the BPE area showed no differentiating ability in the H_DCE-MRI group. Lesion_Kep (AUC = 0.767), Peri_Vp (AUC = 0.726), and BPE_Ktrans and BPE_Vp (AUC = 0.687 and 0.707) could differentiate between benign and malignant breast lesions in the L_DCE-MRI group. The models were compared with the senior radiologist’s assessment for the identification of BI-RADS 4 breast lesions. The AUC, sensitivity and specificity of Lesion_Kep (0.963, 100.0%, and 88.9%, respectively) in the H_DCE-MRI group were significantly higher than those of the same parameter in the L_DCE-MRI group (0.663, 69.6% and 75.0%, respectively) for the assessment of BI-RADS 4 breast lesions. The DeLong test was conducted, and there was a significant difference only between Lesion_Kep in the H_DCE-MRI group and the senior radiologist (P = 0.04). Conclusions Pharmacokinetic parameters (Ktrans, Kep and Vp) from the intralesional and perilesional regions on high-temporal-resolution DCE-MRI, especially the intralesional Kep parameter, can improve the assessment of benign and malignant BI-RADS 4 breast lesions to avoid unnecessary biopsy.

Although many efforts have been made to improve management strategies and diagnostic methods in the past several decades, the prevention of anastomotic complications, such as anastomotic leaks and strictures, remain a major clinical challenge. Therefore, new molecular pathways need to be identified that regulate anastomotic healing and to design new treatments for patients after anastomosis to reduce the occurrence of complications. Rabbits were treated with a MST1/2 inhibitor XMU-XP-1, a Chinese medicine formula Shenhuang Plaster (SHP) or a control vehicle immediately after surgery. The anastomotic burst pressure, collagen deposition and hydroxyproline concentration were evaluated at 3 and 7 days after the surgery, and qRT-PCR and western-blot analyses were used to characterize mRNA and protein expression levels. Both XMU-XP-1 and SHP significantly increased anastomotic burst pressure, collagen deposition and the concentration of hydroxyproline in intestinal anastomotic tissue at postoperative day 7 (POD 7). Importantly, SHP could induce TGF-b1 expression, which activated its downstream target Smad-2 to activate the TGF-b1signaling pathway. Moreover, SHP reduced the phosphorylation level of YAP and increased its active form, and treatment with verteporfin, a YAP-TEAD complex inhibitor, significantly suppressed the effects induced by SHP during anastomotic tissue healing. This study demonstrated that activation of the Hippo-YAP pathway enhances anastomotic healing, and that SHP enhances both the TGF-b/Smad and YAP signaling pathways to promote rabbit anastomotic healing after surgery. These results suggest that SHP could be used to treat patients who underwent anastomosis to prevent the occurrence of anastomotic complications.

Background Breast cancer is the most common cancer in women worldwide, high-resolution dynamic contrast-enhanced MRI (DCE-MRI) can better evaluate the tissue microenvironment and texture characteristics. The purpose of this study was to investigate the value of the texture-based analysis for breast DCE-MRI in the diagnosis of breast lesions and background enhancement. Methods This study prospectively enrolled 128 patients with clinically suspected breast lesions in our hospital from April 2015 to June 2017. Among them, 62 patients underwent preoperative high temporal resolution DCE-MRI (1 + 26 phases) scan with 39 malignant and 23 benign lesions. The control group retrospectively and randomly contained 78 patients who underwent preoperative low temporal resolution DCE-MRI (1 + 5 phases) scans with 46 malignant and 32 benign lesions. Quantitative parameters were obtained using a two-compartment Extended Tofts and volume of interest model for the lesion center, surrounding peripheral area and background enhancement, including pharmacokinetic parameters (Ktrans, Kep, Ve and Vp) and texture features based on the Ktrans map. The Student’s t-test was used to compare the differences of means. LASSO was used for dimension reduction and logistic regression analysis was used for model construction. A receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance. Results Pharmacokinetic parameters were significantly different between high temporal resolution and low temporal resolution DCE-MRI (P < 0.05). In the malignant group, the average Ktrans of the lesion area on high temporal resolution DCE-MRI was significantly correlated to the pathological grading (r = 0.400, P = 0.012). In the differentiation between benign and malignant lesions, the ROC analysis demonstrated that the diagnostic value of high temporal resolution DCE-MRI offered slightly significant advantages in the realms of the lesion, peripheral areas and background enhancement. Conclusions The use of texture analysis based on high temporal resolution DCE-MRI may potentially improve breast cancer diagnostic performance. Specifically, combining the lesion, peripheral, BE area, and Ktrans-mean parameters can contribute to the diagnosis of breast lesions, background enhancement and the pathological grading of malignant tumors.