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In this work, high‐performance ZnO–SnO2 binary ceramic targets for magnetron sputtering of transparent conductive oxide (TCO) films were prepared by pressureless oxygen atmosphere sintering. The sintering behavior and densification mechanism of the ZnO–SnO2 binary targets were analyzed by systematically studying the oxide powder state, formation process of the solid reaction phase, and evolution of the target microstructure. The data revealed that the ZnO–SnO2 powder treatment improved the sintering activity and the powder dispersion; furthermore, it promoted a mutual reaction between the different components during sintering and the homogeneity of the target composition. The densification of the pure SnO2 ceramic target was difficult to achieve, and the addition of ZnO led to a continuous interaction between the ZnO and SnO2 components. The Zn2SnO4 phase started to form, and a temporary shrinkage of the target occurred above 800°C. After formation of the stable Zn2SnO4 and SnO2 phases, the target shrunk rapidly with increasing temperature, densification occurred during growth, and the two phases started to interact. The sintering temperature provided the driving force for the target densification, with the densification activation energy of the ZnO–SnO2 binary ceramic target estimated to be 580 kJ/mol based on the master sintering curve. A binary ceramic target with a high density (99.78% relative density), a fine grain size, and a homogeneous phase structure was achieved at a temperature of 1600°C. These findings are promising for the further improvement and performance enhancement of SnO2‐based materials. [ABSTRACT FROM AUTHOR]

T‐cell‐based immunotherapy and immune checkpoint blockade have been successfully used to treat several human solid cancers. The present study attempted to investigate the feasibility and efficacy of the antitumor effect of adoptive cell therapy along with programmed cell death protein 1 (PD‐1) inhibitor on triple‐negative breast cancer (TNBC). Tumor infiltration lymphocytes (TILs) from TNBC mouse tumor tissues were isolated and expanded, and TILs for adoptive cell therapy (TILs‐ACT) were applied in combination with a PD‐1 inhibitor to the TNBC mouse model. The pre‐ and post‐therapy antitumor efficacy, cytokine secretion, and pathological changes were assessed both in vitro and in vivo. We found that TILs exhibited higher IFN‐γ and TNF‐α secretion than conventional T cells. The TILs‐ACT combined with PD‐1 inhibitor promoted active T‐cell infiltration into the tumor tissue and exerted a strong antitumor effect in an in vivo model. Additionally, the strategy could downregulate the expression of inhibitory marker PD‐1 on TILs. In conclusion, PD‐1 blockade regulated T‐cell exhaustion that synergized with adoptive TIL transfer immunotherapy, leading to eradication of established TNBC tumors. These findings might be useful in developing a feasible and effective therapeutic approach for TNBC. [ABSTRACT FROM AUTHOR]

Lipids play crucial biological roles in health and disease, including in cancers. The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pivotal promoter of cell growth and proliferation in various types of cancer. The somatic mutations in PIK3CA , the gene coding for the catalytic subunit p110α of PI3K, are frequently present in cancer cells, including breast cancer. Although the most prominent mutants, represented by single amino acid substitutions in the helical domain in exon 9 (E545K) and the kinase domain in exon 20 (H1047R) are known to cause a gain of PI3K function, activate AKT signaling and induce oncogenic transformation, the effect of these mutations on cellular lipid profiles has not been studied. We carried out untargeted lipidomics using liquid chromatography-tandem mass spectrometry to detect the lipid alterations in mammary gland epithelial MCF10A cells with isogenic knockin of these mutations. A total of 536 species of lipids were analyzed. We found that the levels of monosialogangliosides, signaling molecules known to enhance cell motility through PI3K/AKT pathway, were significantly higher in both mutants. In addition, triglycerides and ceramides, lipid molecules known to be involved in promoting lipid droplet production, cancer cell migration and invasion, were increased, whereas lysophosphatidylcholines and phosphatidylcholines that are known to inhibit cancer cell motility were decreased in both mutants. Our results provide novel insights into a potential link between altered lipid profile and carcinogenesis caused by the PIK3CA hotspot mutations. In addition, we suggest untargeted lipidomics offers prospects for precision/personalized medicine by unpacking new molecular substrates of cancer biology.

Breast cancer is the most common cancer in women worldwide. Triple-negative breast cancer is one of the most aggressive types of breast cancer as it has the worst clinical outcome for patients. microRNAs are a type of small non-coding RNA and play an important role in breast cancer. The purpose of this study was to explore the potential function and mechanism of miR-143-3p in triple-negative breast cancer (TNBC). MTT and colony formation assays, the effect of miR-143-3p modulation on MDA-MB-231 cell proliferation, revealed that increased miR-143-3p expression inhibited the proliferation of MDA-MB-231 TNBC cells. Moreover, miR-143-3p overexpression inhibited the movement of MDA-MB-231 TNBC cells in wound healing and transwell assays. To identify a potential miR-143-3p target, we investigated the effect of miR-143-3p modulation on LIMK1 expression level. Increased miR-143-3p expression caused a reduction in LIMK1 mRNA and protein, suggesting that LIMK1 is a target of miR-143-3p. In addition, dual-luciferase reporter assays showed that LIMK1 is a target gene of miR-143-3p. Flow cytometry analysis indicated that miR-143-3p arrested MDA-MB-231 TNBC cells at the G0/G1 phase. The TCGA (The Cancer Genome Atlas) database demonstrated that miR-143-3p was down-regulated in breast cancer tissues compared with normal breast tissues. These data demonstrated that miR-143-3p functioned as a suppressor gene in TNBC and that miR-143 targeted therapy may be a new strategy for TNBC treatment., Competing Interests: None.

MicroRNAs (miRNAs) are a small class of non-coding RNAs that are extensively deregulated in various cancers. They can act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to investigate the crucial role of miR-506 in breast cancer and to validate whether miR-506 could regulate proliferation of breast cancer cells by targeting YAP (Yes-associated protein) gene. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to quantify the expression levels of miR-506 in breast cancer and adjacent non-cancerous breast tissues. To characterize the miR-506 function, MTT assays, colony formation assays, cell migration assays, cell invasion assays and cell cycle assays were used. Finally, luciferase reporter assays were performed to validate the regulation of a putative target of miR-506, in corroboration with western blot assays. We found that expression of miR-506 was commonly down-regulated in breast cancer cells and breast cancer specimens when compared with that in non-malignant breast epithelial cells and adjacent normal tissues. Up-regulation of miR-506 inhibited cellular proliferation, migration and invasion as well as disrupt the cell cycle of breast cancer cells. Luciferase assays revealed that miR-506 directly bound to the 3'-untranslated region (3'-UTR) of YAP. Western blot analysis verified that miR-506 regulated the expression of YAP at the protein levels. These findings suggest that miR-506 exerts as a tumor suppressor in breast cancer and up-regulation of miR-506 expression inhibits cellular growth, cell migration and invasion as well as disrupt the cell cycle by targeting YAP. Our study demonstrates that the miR-506/YAP axis may help us better understand the molecular mechanisms of breast cancer progression.

Background: Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells (MDA-MB-231 cell) and to determine whether the suppression of DUSP6 by small interfering RNA (siRNA) and mircroRNA (miRNA) inhibits the growth of human MDA-MB-231 breast cancer cells., Methods: DUSP6-siRNA was used to inhibit the expression of DUSP6 directly and miR-145 to inhibit the expression of DUSP6 either in MDA-MB-231 breast cancer cells and successful transfection being confirmed by Real-time PCR and Western Blotting. Down regulation of DUSP6 in MDA-MB-231 cells suppressed the cell proliferation as investigated by MTT assay and colony form assay. Transwell test and Scratch assay were conducted to investigate the migration and invasion of MDA-MB-231 cells. T-test (two-tailed) was used to compare differences between groups, and the significance level was set at P<0.05., Results: DUSP6 mRNA expression and protein expression were reduced after transfection with DUSP6-siRNA directly and similar trend with transfection with miR-145. The treated group with DUSP6-siRNA or miR-145 suppressed MDA-MB-231 cells proliferation, migration and invasion, and meanwhile the cells were arrested at G0/G1 phase., Conclusions: DUSP6 plays a role in triple-negative breast cancer cells that might promote growth in MDA-MB-231 triple-negative breast cancer cells.

Many studies have demonstrated that microRNAs (miRNAs) may play vital roles in the development of breast cancer. The aim of this study was to examine the expression levels of miR-497 in human breast cancer and investigate whether its potential roles involved targeting Bcl-2. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to examine the expression levels of miR-497 in 48 breast cancer specimens and six breast cancer cell lines. MTT assay, colony formation assay, and flow cytometry were conducted to explore the potential functions of miR-497 in human MDA-MB-231 breast cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether Bcl-2 was a direct target of miR-497. The effects of modulating miR-497 on endogenous levels of Bcl-2 were subsequently confirmed via qRT-PCR and western blot. MTT assay, colony formation assay and flow cytometry were used to indicate the roles of endogenous Bcl-2 in breast cancer cells. miR-497 expression levels were significantly decreased in human breast cancer specimens and cell lines (P<0.05). Overexpression of miR-497 in breast cancer cells suppressed cell proliferation and induced apoptosis. Correlation analysis indicated that miR-497 was highly inversely correlated with Bcl-2 protein expression in breast cancer specimens. Dual-luciferase reporter assays confirmed that Bcl-2 was a direct target of miR-497. qRT-PCR and western blot showed that miR-497 negatively regulated Bcl-2 protein expression but had no impact on mRNA expression of Bcl-2. Knockdown of Bcl-2 expression in MDA-MB-231 cells significantly suppressed cell proliferation and promoted apoptosis. Our study suggests that miR-497 may act as a breast cancer suppressor through negative regulation of Bcl-2 protein expression at the posttranscriptional levels. Therefore, targeting miR-497 may provide a novel strategy for the diagnosis and treatment of patients with this lethal disease.

MicroRNAs (miRNAs) are small, non-coding RNAs that modulate gene expression by negatively regulating the stability or translational efficiency of their target mRNAs. The aim of this study was to investigate the expression of microRNA-145 (miR-145) in human papillary thyroid cancer and its potential function. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-145 in ten papillary thyroid cancer and adjacent normal specimens. The function of miR-145 overexpression on the proliferation of human TPC1 thyroid cancer cells was conducted by MTT assays and by colony-formation assays. Western blot was used to validate the impact of miR-145 on the protein expression of the target gene. Luciferase reporter assays were employed to validate a putative target of miR-145. MiR-145 expression was relatively decreased in papillary thyroid cancer specimens compared with adjacent normal tissues (P<0.05). MTT assays and colony-formation assays showed that overexpression of miR-145 suppressed TPC1 cell growth. Luciferase assays using a reporter carrying a putative miR-145 target site in the 3' untranslated region of DUSP6 revealed that miR-145 directly targets DUSP6. Overexpression of miR-145 led to downregulation of DUSP6 at protein level as assessed by Western blot. Targeted knockdown of DUSP6 by siRNA significantly inhibited the proliferation of TPC1 cells. The overexpression of miR-145 inhibited TPC1 cellular growth by targeting DUSP6; this finding implies a better understanding of initiation and progression of papillary thyroid cancer.

MicroRNAs (miRNAs) are a small class of non-coding RNAs that are widely deregulated in various cancers. They act as either oncogenes or tumor suppressor genes in human cancer. The purpose of this study was to examine the potential role of miR-181b in human thyroid papillary cancer. The expression levels of different miRNAs were measured by micro array analysis in 10 thyroid papillary cancer specimens and adjacent normal thyroid cancer tissues. MTT assays, colony formation assays, apoptosis assays were used to explore the potential function of miR-181b inhibitor in TPC1 human thyroid papillary cancer cells. Luciferase reporter assays were performed to validate the regulation of a putative target of miR-181b, in corroboration with qPCR and western blot assays. We found that the expression of miR-181b was higher in thyroid papillary cancer specimens compared with adjacent normal tissues (P < 0.05). Downregulation of miR-181b inhibited cellular growth and promoted cellular apoptosis. Luciferase assays indicated that miR-181b can bind with its putative target site in the 3'-untranslated region (3'-UTR) of CYLD, suggesting that CYLD is a direct target of miR-181b. Western blot analysis indicated that downregulation of miR-181b results in the upregulation of CYLD at protein levels. Taken together, downregulation of miR-181b expression causes cellular growth inhibition, promoting cellular apoptosis by targeting CYLD. These findings suggest that downregulation of the expression of miR-181b may be a therapeutic target for the treatment of human thyroid papillary cancer.

Background and Aim: Protein Kinase (casein kinase 2, CK2) is a pleiotropic serine-threonine kinase that is frequently dysregulated in many human tumors; microRNAs (miRNAs) are a class of small noncoding RNAs which play important roles in human cancers. This study aimed to investigate the role of CK2 and miRNA expression in breast cancer., Methods: Casein kinase 2 in MCF-7 breast cancer cell line was inhibited by the CK2 inhibitor TBB (4,5,6,7-tetrabromobenzotriazole), then cell proliferation was studied using MTT assay, and cell cycle distribution and apoptosis were detected by flow cytometry. The alteration of microRNAs expression profile was determined by microarray technology, followed by RT-PCR confirmation., Results: Here, we for the first time showed that inhibition of CK2 in MCF-7 breast cancer cells causes suppressed cell growth, which was related with dysregulation of the miRNA profile and altered expression. CK2 inhibition induced the up-regulated expression of 17 miRNAs and 10 down-regulated microRNAs which contributed to the impaired growth, inhibited cell cycle progress and increased apoptosis of MCF-7 cells by a CK2 inhibitor., Conclusions: These findings highlight the potential role of dysregulated miRNA expression regulated by CK2 in breast cancer.