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The controllable assembly of metal-organic frameworks (MOFs) nanomaterials is an effective means to enhance their application capabilities. In this paper, a novel method is reported to control MOFs assembly by using a DNA framework material, a tetrahedral DNA nanostructure (TDN) labeled with phosphate groups at the vertex. In particular, various well-defined superstructures can be tailored by regulating the number of phosphate groups that coordinate with catalytic Zr-MOFs to create polymeric MOFs superstructures (Poly(MOFs)), exhibiting excellent catalytic activities and molecular recognition ability as well as greatly amplified signal readout. Furthermore, based on the DNA framework-controlled Poly(MOFs), a colorimetric biosensor with excellent analytical performance is fabricated for improving the diagnosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. It is demonstrated that the quantification of HER2 protein can be achieved at molecular level with the limit of detection (LOD) of 12 pg L-1 and cellular level with the LOD of 10 cells. More importantly, the detection of HER2 in the serum of breast cancer patients have been achieved, thus HER2-positive and triple-negative breast cancer patients can be well distinguished. Considering the substitutability of the target, this study shows great potential in biomedical research as well as clinical applications. [Display omitted] • DNA framework-induced controllable self-assembly of metal-organic frameworks. • A simple colorimetric biosensor for the diagnosis of HER2-positive breast cancer. • Great application potential for detection in proteins, cells, and patient serum. • Effective for prognosis monitoring of tumor targeted therapy. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) hinders treatment efficacy in cancer therapy. One typical mechanism contributing to MDR is the overexpression of permeability-glycoprotein (P-gp) encoded by ATP-binding cassette subfamily B member 1 (ABCB1). Basic helix-loop-helix family member e40 (BHLHE40) is a well-known transcription factor that has pleiotropic effects including the regulation of cancer-related processes. However, whether BHLHE40 regulates MDR is still unknown. Chromatin immunoprecipitation-seq study revealed BHLHE40 occupancy in the promoter of ABCB1 gene. Adriamycin (ADM)-resistant human chronic myeloid leukemia cells (K562/A) and human breast cancer cells (MCF-7/A) were established. BHLHE40 expression was downregulated in the ADM-resistant cell lines. Overexpression of BHLHE40 resensitized resistant cells to ADM, promoted cell apoptosis in vitro and suppressed tumor growth in vivo, whereas BHLHE40 knockdown induced resistance to ADM in parental cells. Moreover, we found that BHLHE40 regulated drug resistance by directly binding to the ABCB1 promoter (-1605 to -1597) and inactivating its transcription. In consistence, the expression of BHLHE40 was negatively correlated with ABCB1 in various cancer cells, while positively with cancer cell chemosensitivity and better prognosis of patients with breast cancer. The study reveals the role of BHLHE40 as a transcriptional suppressor on the expression of ABCB1, major ABC transporter in chemoresistance. The findings extend the function of BHLHE40 in tumor progression and provides a novel mechanism for the reversal of multidrug resistance. BHLHE40 inhibits multidrug resistance through directly binding to ABCB1 promoter. Model is proposed to illustrate our findings. When BHLHE40 binds to ABCB1 promoter, transcription of ABCB1 is suppressed in sensitive cells. When expression of BHLHE40 is inhibited, ABCB1 transcription initiates and translates to P-gp that pumps ADM out in resistant cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to observe the changes of a transplanted heart with cardiac computed tomography (CT) and to evaluate the clinical application of the examination. Methods: Cardiac CT was performed on 12 heart transplant recipients, of which 4 cases were also examined by echocardiography. Coronary arteries, the cardiac chamber, and the wall were shown with three-dimensional imaging techniques, and their changes were analyzed and discussed. Results: Twelve heart transplant recipients were successfully examined by CT. All transplanted hearts were found with good anastomosis at the great vessels and atria. Coronary allograft vasculopathy was found in 7 cases, of which 4 cases were found with ventricular dilation or ventricular septum thickening and 1 with tricuspid regurgitation. Ventricular dilation was found in other 3 cases, of which 1 was found with ventricular septum thickening and 1 with tricuspid regurgitation. No abnormality was found by cardiac CT in the rest 2 cases, which were found with mitral regurgitation by echocardiography. Conclusion: Cardiac CT can clearly and directly display the changes in the shape of a transplanted heart and coronary artery abnormalities. It will become an ideal noninvasive follow-up method for the heart transplant recipients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer (NSCLC). Methods: Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity. Results: None of the patients achieved a complete response (CR), while 15 patients achieved a partial remission (PR) and 17 experienced a stable disease (SD). Thirteen patients continued to have a progressive disease (PD). The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash (53.3%) and diarrhea (33.3%). Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients. Conclusion: Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients. [Copyright &y& Elsevier]

Abstract: Vascular endothelial growth factor (VEGF) has been implicated in breast tumor angiogenesis. And tumor necrosis factor-α (TNF-α) is a positive regulator of VEGF. This study was aimed to identify the signalling pathway of TNF-α in VEGF expression regulation in breast cancer cell line MCF7. Using luciferase reporter assays, we demonstrated that TNF-α significantly increased activator protein-1 (AP-1) transcriptional activity in the MCF7 cells. The expression of the AP-1 family members c-Jun, c-Fos and JunB and phosphorylation levels of c-Jun were upregulated by TNF-α, whereas other AP-1 family members Fra-1, Fra-2, and JunD were unaffected. The activation of AP-1 was associated with the formation of p-c-Jun-c-Jun and p-c-Jun-JunB homodimers. Furthermore, the phosphorylation levels of c-Jun N-terminal kinase (JNK) but not P38 and ERK were elevated by TNF-α in MCF7 cells. TNF-α potently upregulated the mRNA and protein levels of VEGF, which were significantly reversed by JNK inhibitor SP600125. Finally using chromatin immunoprecipitation (CHIP) assays, we found that p-c-Jun bound to the VEGF promoter and regulated VEGF transcription directly. These data suggest that the pro-inflammatory cytokine TNF-α is a critical regulator of VEGF expression in breast cancer cells, at least partially via a JNK and AP-1 dependent pathway. [Copyright &y& Elsevier]

Abstract: Background and objectives: TNF-α secreted by tumor cells and macrophages that have infiltrated into the micro-environment of a tumor may promote the metastasis of a variety of malignant cancers, including breast cancer. The present study was designed to detect gene expression changes in metastatic MCF-7 cells treated with a low dose of TNF-α (20ng/mL), and to further explore the mechanisms by which TNF-α can contribute to metastasis. Methods: Transwell assays were performed to evaluate the invasive phenotype of MCF-7 cells. Samples for cDNA array analysis were collected 3h and 24h after pre-treatment with TNF-α and changes in gene expression were quantitated. Results: The invasive phenotype of MCF-7 cells was enhanced by the exposure of MCF-7 cells to a low dose of TNF-α. Gene expression profiles of 39 genes significantly increased or decreased after treatment with TNF-α, 6 of which were genes not previously associated with regulation by TNF-α. Genes to promote metastasis, as well as to inhibit metastasis, were identified with some changes being time dependent. Conclusions: TNF-α can enhance the invasive capacity of MCF-7 cells by affecting the expression of a group of genes that have roles in various steps of metastasis. Mechanistic insights into the role of TNF-α in tumor cell metastasis are discussed. [Copyright &y& Elsevier]

Abstract: Objective: Studies have shown that TNF-α secreted by tumor cells and macrophages infiltrated into the tumor microenvironment might promote the metastasis of a variety of malignant cancers, including breast cancer. The present study was designed to detect global metastasis-related gene expression changes of MCF-7 cells treated by low dose TNF-α and to further explore the mechanisms by which TNF-α contributes to metastasis. Methods: MCF-7 cells were cultured and treated with low dose TNF-α (20 ng/ml). cDNA array analysis was applied to detect the metastasis related gene expressions. Results: A total of 36 gene expressions were significantly regulated by TNF-α. Functional analysis indicates that the altered genes belong to different functional group. Most of the genes changed may promote the metastasis of MCF-7 cells while the others may inhibit metastasis. The changes observed in gene expression following TNF-α were somewhat time dependent. Conclusion: TNF-α can enhance the invasive ability of MCF-7 cells, partly by regulating a series of metastasis related genes, and these genes may take part in every step of metastasis. Some of the genes deserve further study. [Copyright &y& Elsevier]

To compare the efficacies of exemestane and fulvestrant as first-line monotherapies for postmenopausal Chinese women having advanced oestrogen-receptor positive (ER+)/ human epidermal growth factor receptor 2 (HER2)-breast cancer (ER+/HER2- ABC) after a previous treatment for ≥2 years with an adjuvant non-steroidal aromatase inhibitor. In this randomised, open-label, multi-centre, parallel-controlled phase 2 FRIEND study, 145 postmenopausal ER+/HER2- ABC patients were assigned into fulvestrant (500 mg on days 0, 14 and 28, and then at every 28 ± 3 days, n = 77) and exemestane (25 mg/day, n = 67) groups. The primary outcome was progression-free survival (PFS), while the secondary outcomes were disease control rate, objective response rate, time to treatment failure, duration of response and overall survival. Exploratory end-points included gene mutation-related outcomes and safety. Fulvestrant was superior to exemestane regarding median PFS times (8.5 versus 5.6 months, p = 0.014, HR = 0.62, 95% confidence intervals: 0.42–0.91), objective response rates (19.5% versus 6.0%, p = 0.017) and time to treatment failure (8.4 versus 5.5 months, p = 0.008). The incidence of adverse or serious adverse events in the two groups was virtually identical. The most frequent mutations in 129 analysed patients were detected in the o estrogen receptor gene 1 (ESR1) (18/14.0%), PIK3CA (40/31.0%) and TP53 (29/22.5%) genes. Fulvestrant produced significant longer PFS times compared to exemestane but only for patients with an ESR1 -wild type (8.5 versus 5.8 months) (p = 0.035), although there was a similar trend also for the ESR1 mutation without statistical significance. All patients with c-MYC and BRCA2 mutations had longer PFS times in the fulvestrant versus the exemestane group (p = 0.049, p = 0.039). Fulvestrant significantly increased overall PFS for ER+/HER2- ABC patients and was well tolerated. NCT02646735, https://clinicaltrials.gov/ct2/show/NCT02646735. • The novel selective oestrogen receptor down regulator fulvestrant is administered to hormone receptor positive advanced breast cancer patients. • Exemestane, a steroidal aromatase inhibitors , is used to treat early and advanced breast cancer patients. • Fulvestrant was superior to exemestane regarding median progression-free survival times and time to treatment failure. • c-MYC and BRCA2 mutations led to longer progression-free survival times in the fulvestrant group. [ABSTRACT FROM AUTHOR]

Abstract: Non-small cell lung cancer (NSCLC) represents the most common cause of cancer mortality worldwide and counts for the greatest number of deaths from lung cancer in both men and women over age 60. Pemetrexed is a multi-targeted anti-metabolite and has shown comparable activity for Caucasian patients with advanced NSCLC. In this single-center retrospective study, we analyzed the outcome in 75 Chinese non-squamous NSCLC patients treated with pemetrexed as first-line therapy and assessed its efficacy and tolerability. The overall response rate was 9.3% (7/75) with 7 partial response s and no complete response. There were 44 (58.7%) stable diseases and 24 progressive diseases (32.0%). The median progression-free survival (PFS) was 6.79months (95% CI 5.69–7.90months), and the median overall survival (OS) was 11.67months (95% CI 9.98–13.36months). Good performance status and negative smoke history predicted better PFS and OS. Most side effects were generally mild and well tolerated. Taken together, pemetrexed was safe and effective in Chinese patients with non-squamous NSCLC. Pemetrexed alone or in combination with other efficacious drugs may serve as first-line therapy for this disease. [Copyright &y& Elsevier]