Defect Detection of MEMS Based on Data Augmentation, WGAN-DIV-DC, and a YOLOv5 Model.

Surface defect detection of micro-electromechanical system (MEMS) acoustic thin film plays a crucial role in MEMS device inspection and quality control. The performances of deep learning object detection models are significantly affected by the number of samples in the training dataset. However, it is difficult to collect enough defect samples during production. In this paper, an improved YOLOv5 model was used to detect MEMS defects in real time. Mosaic and one more prediction head were added into the YOLOv5 baseline model to improve the feature extraction capability. Moreover, Wasserstein divergence for generative adversarial networks with deep convolutional structure (WGAN-DIV-DC) was proposed to expand the number of defect samples and to make the training samples more diverse, which improved the detection accuracy of the YOLOv5 model. The optimal detection model achieved 0.901 mAP, 0.856 F1 score, and a real-time speed of 75.1 FPS. As compared with the baseline model trained using a non-augmented dataset, the mAP and F1 score of the optimal detection model increased by 8.16% and 6.73%, respectively. This defect detection model would provide significant convenience during MEMS production.

MicroRNA-409 regulates the proliferation and invasion of breast cancer cell lines by targeting special AT-rich sequence-binding protein 1 (SATB1).

This study aims to determine the cellular functions and clinical significance of microRNA-409 (miR-409) in breast cancer by targeting special AT-rich sequence-binding protein 1 (SATB1). Breast cancer tissues and adjacent normal tissues, breast cancer cell lines (MDA-MB-453, MDA-MB-231, BT-549, BR3, and MCF-7) were used. miR-409 mimics, miR-409 inhibitor, SATB1, and siSATB1 were transiently transduced into cancer cells independently or together. RT-qPCR, Western blot, Cell Counting Kit-8 (CCK8), and Transwell assays were carried out to analyze the expression, cellular proliferation, and invasion. The results showed that the expression of miR-409 in breast cancer tissues is lower than that in adjacent tissues. The application of a target prediction algorithm predicts that the candidate gene regulated by miR-409 may be SATB1. The expression level of miR-409 in MDA-MB-453 cells is lower, while in BT-549 cells it is higher, when compared with MDA-MB-231, BR3, and MCF-7. The proliferation rate and invasive ability of MDA-MB-453 cells transfected with the miR-409 mimic was significantly lower than that of the miRNA negative control (miR-NC) cells, while the proliferation rate and invasive ability of BT-549 cells transfected with the miR-409 inhibitor were significantly increased. Cell proliferation and invasion of miR-409 mimic and SATB1 co-transfected MDA-MB-453 cells increased compared with that of miR-409 mimic-transfected cells, while miR-409 inhibitor and siSATB1 co-transfected BT-549 cells showed the opposite result. All these results indicated that miR-409 regulates breast cancer proliferation and invasion by targeting SATB1 and might be a potential therapeutic target for the treatment of breast cancer.

Clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 & SATB1 in HER-2-Positive breast cancer patients.

Objective: To evaluate the clinical curative effect of neoadjuvant chemotherapy combined with immunotherapy and its impact on immunological function and the expression of ER, PR, HER-2 and SATB1 in HER-2-positive breast cancer patients. Methods: The subjects of study were 80 patients with HER-2-positive breast cancer. Enrolled patients were randomly divided into two groups, with 40 cases in each group at The Fourth Affiliated Hospital of Hebei Medical University from March 2018 from March 2021. Patients in the control group were provided with neoadjuvant chemotherapy using TAC regimen merely; while those in the study group received oral administration of Apatinib Mesylate (500mg/d; three weeks a cycle) on the basis of the TAC regimen. Further comparative analysis was performed focusing on the therapeutic effect and adverse drug reaction rate of the two groups; levels of CD3+, CD4+, CD8+ and CD4+/CD8+ of T lymphocyte subsets in the two groups before and after treatment; as well as the expressions of ER, PR, HER-2 and SATB1 in the two groups before and after treatment. Results: The total response rate was 77.5% and 55% in the study group and the control group, respectively, with an obviously better outcome in the former group than that in the latter group (p=0.03). Meanwhile, the incidence of adverse reactions was 40% in the study group and 45% in the control group, without statistical difference (p=0.65). There were statistically significant differences that the levels of CD3+, CD4+, and CD4+/CD8+ in the study group were significantly higher when compared with those in the control group after treatment (CD3+, p=0.00; CD4+, p=0.02; CD4+/CD8+, p=0.00); while no evident change was observed in the level of CD8+ (p=0.88). After treatment, the positive expression rates of ER, HER-2 and SATB1 were remarkably lower in the study group than those in the control group, showing statistically significant differences (ER, HER-2, p=0.03; SATB1, p=0.02). However, there was no statistically significant difference in the positive expression rate of PR between the study group and the control group (P=0.80). Conclusions: Neoadjuvant chemotherapy combined with immunotherapy has significant effect on the treatment of HER-2-positive breast cancer patients. It can result in the significant enhancement of T lymphocyte function, obvious improvement in the negative converse rates of ER, HER-2 and SATB1, and no evident increase in the adverse drug reactions. The proposed therapeutic approach is safe, effective, and have certain clinical value.

A Demodulation Algorithm for Periodically In-Plane Vibrating MEMS Based on a Stroboscopic Micro-Visual System.

A high-frequency short-pulsed stroboscopic micro-visual system was employed to capture the transient image sequences of a periodically in-plane working micro-electro-mechanical system (MEMS) devices. To demodulate the motion parameters of the devices from the images, we developed the feature point matching (FPM) algorithm based on Speeded-Up Robust Features (SURF). A MEMS gyroscope, vibrating at a frequency of 8.189 kHz, was used as a testing sample to evaluate the performance of the proposed algorithm. Within the same processing time, the SURF-based FPM method demodulated the velocity of the in-plane motion with a precision of 10−5 pixels of the image, which was two orders of magnitude higher than the template-matching and frame-difference algorithms.

Unsupervised anomaly detection of MEMS in low illumination based on polarimetric Support Vector Data Description.

Low illuminated images make it challenging to conduct anomaly detection on material surface. Adding polarimetric information helps expand pixel range and recover background structure of network inputs. In this letter, an anomaly detection method in low illumination is proposed which utilizes polarization imaging and patch-wise Support Vector Data Description (SVDD) model. Polarimetric information of Micro Electromechanical System (MEMS) surface is captured by a division-of-focal- plane (DoFP) polarization camera and used to enhance low illuminated images. The enhanced images without defects serve as training sets of model to make it available for anomaly detection. The proposed method can generate heatmaps to locate defects correctly. It reaches 0.996 anomaly scores, which is 22.4% higher than that of low illuminated images and even higher than normal illuminated images.

High sensitivity curvature sensor based on the long period fiber grating inscribed in the two-mode fiber.

The optical fiber curvature sensor is an important device that is widely used in the field of medical instruments. In this paper, we proposed a high sensitivity curvature sensor based on a long period fiber grating (LPFG), which is inscribed in the two-mode fiber (TMF) by CO2 laser pulses. Unlike the traditional LPFG in the single-mode fiber, TMF-LPFG couples the high-order mode LP11 in the core with the modes in the cladding. From the experiment results, the wavelength shifts to the short-wave direction as the sensor bends. This sensor offers a high curvature sensitivity of -23.67nm/m-1 in the range of 1.137-4.684m-1 and -18.95nm/m-1 in the range of 4.766-6.132m-1, respectively. Moreover, this sensor has the advantage of low transmission loss, which is less than -4dB.

Semen parameters in men recovered from COVID-19.

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

High-consistency fiber-optic Fabry-Perot sensor based on MEMS for simultaneous temperature and liquid refractive index measurement.

We proposed a hybrid Fabry-Perot fiber-optic sensor based on the microelectromechanical system (MEMS) technique for measuring temperature and liquid refractive index simultaneously, and we verify the consistency of four sensors in the same batch. The sensor consists of a groove-array structured glass wafer and two silicon wafers, which are connected by double-sided anodic bonding. The three parts form two independent Fabry-Perot cavities for temperature and liquid refractive index sensing, respectively. We randomly selected three sensors in the same batch and conducted temperature and refractive index experiments to establish the sensing equation. The experimental results demonstrate their high consistency with temperature sensitivities of 81.6, 81.8, and 81.4 pm/°C in the range of 10°C to 80°C, and refractive index sensitivities of 1040.11, 1044.24, 1042.91 nm/RIU in the range of 1.333-1.374. The sensors have low cross-sensitivities that are less than 5.86×10-6 RIU/°C and high precisions of 0.047°C, 2.14×10-6RIU, respectively. To verify the validity of the sensing equation, we made another sensor in the same batch and got maximum errors of 0.36°C and 7.7×10-5RIU, respectively.

Knockdown of FAM83D Enhances Radiosensitivity in Coordination with Irradiation by Inhibiting EMT via the Akt/GSK-3ß/Snail Signaling Pathway in Human Esophageal Cancer Cells.

PURPOSE: To explore the effects of FAM83D on the proliferation, invasion and radiosensitivity of human esophageal cancer cells and to elucidate the mechanism involved in the regulation of the growth and metastasis of esophageal cancer cells. METHODS AND MATERIALS: This study included sixty-nine patients with esophageal cancer. The expression levels of FAM83D in the esophageal cancer tissues and paracarcinoma tissues of the sixty-nine patients were measured. We also examined FAM83D expression in five cell lines. We analyzed the effects of FAM83D on the proliferation, invasion and radiosensitivity of human esophageal cancer cells via MTS, Transwell, and colony formation assays. The effect of FAM83D knockdown on cell apoptosis was assayed by flow cytometry. In addition, we also examined changes in the expression of metastasis-related molecules at the protein and mRNA levels by qRT-PCR and Western blotting after silencing FAM83D expression, and we detected the expression of PI3K/Akt signaling-related proteins by Western blotting. RESULTS: The results demonstrated that the expression of FAM83D was obviously higher in esophageal cancer tissues and cell lines than that in human adjacent normal tissues and normal esophageal epithelial cell lines. FAM83D overexpression was positively associated with tumor size, tumor-node-metastasis (TNM) stage, T classification, N classification, distant metastasis and relapse and was negatively associated with patient survival rates. FAM83D shRNA transfection suppressed its expression. Compared to that in the control group, the proliferation of tumor cells in the FAM83D shRNA group was hindered after exposure to radiation in vitro and in vivo; in addition, FAM83D knockdown inhibited cell invasion, induced apoptosis and regulated apoptosis-related protein expression. Moreover, the radiosensitivity of esophageal cancer cells was increased after depletion of FAM83D. In addition, FAM83D silencing was associated with the reversion of EMT, as reflected by an increase in the epithelial marker E-cadherin and a decrease in the mesenchymal markers N-cadherin and vimentin. Further study showed that FAM83D depletion suppressed the signaling pathway involving p-Akt, p-GSK-3ß and Snail. CONCLUSION: The results reveal that FAM83D may be a potential therapeutic target for esophageal squamous cell carcinoma (ESCC) and that lower expression of FAM83D in coordination with irradiation promotes the radiosensitization of ESCC by inducing EMT through the Akt/GSK-3ß/Snail signaling pathway.

Gap-matching algorithm with the impCEEMDAN in scanning white-light interference microscopy.

Coherence scanning interferometry (CSI) is a common optical measurement method for measuring three-dimensional surface profiles. However, batwings and ghost steps are common obstacles in CSI. In this paper, we proposed a gap-matching algorithm with the improved complete ensemble empirical mode decomposition with adaptive noise (impCEEMDAN) to solve the above two obstacles without any priori knowledge of the surface geometry from the tested sample. A micro-component with 500 nm and 1200 nm step heights and a 10 µm standard step of were used as test samples to evaluate the accuracy of the proposed method. Simulations and experimental results show that this approach can effectively suppress the batwings effect and eliminate the ghost steps. Experiments also confirm that the approach has good accuracy and repeatability.

BMI-1 suppression increases the radiosensitivity of oesophageal carcinoma via the PI3K/Akt signaling pathway.

B-cell­specific Moloney murine leukaemia virus integration site-1 (BMI-1) contributes to the growth of tumour cells post-irradiation (IR). The aim of the present study was to characterize the effects of BMI-1 on cell viability, radiosensitivity and its mechanisms of action in oesophageal squamous cell cancer (ESCC). Western blotting and immunohistochemistry were employed to evaluate the protein expression of BMI-1 in ESCC cells and specimens, respectively. Additionally, the protein expression levels of BMI-1, H2AK119ub and γH2AX in ESCC cells were detected following different doses of IR and at different times after IR. The protein expression levels of MDC1 and 53BP1 were also measured. Flow cytometry and MTT assays were used to determine cell cycle progression, apoptosis and cell viability. The phosphatidylinositol 3-kinase inhibitor LY294002 and the agonist IGF-1 were employed to suppress or induce the phosphorylation of Akt to determine whether BMI-1 induces radioresistance in ESCC cells via activation of the PI3K/Akt pathway. The expression of BMI-1 was higher in ESCC tissues and cells compared with that in normal oesophageal tissues and cells. In addition, BMI-1 was positively related to tumour size and lymph node metastases and negatively to the overall survival of ESCC patients. IR induced the expression of BMI-1, H2AK119ub and γH2AX in a dose- and time-dependent manner. BMI-1 knockdown lowered the expression of γH2AX, MDC1 and 53BP1, suppressed cell viability and increased radiosensitivity. G2/M phase arrest was eliminated; this was followed by an increased proportion of cells entering the G0/G1 phase after IR and BMI-1 knockdown via the upregulation of P16 and downregulation of cyclin D2 and cyclin-dependent kinase-4. Moreover, BMI-1 knockdown increased cell apoptosis, downregulated MCL-1 and p-Akt and upregulated Bax. Additionally, the inhibitory effect of the downregulation of p-Akt by LY294002 on tumour cell viability was identical to that of BMI-1 knockdown, while the kinase agonist IGF-1 reversed the effects of BMI-1 knockdown on cell viability and radiosensitivity. Taken together, BMI-1 knockdown induces radiosensitivity in ESCC and significantly inhibits cell viability, which may contribute to an increased proportion of cells in the G0/G1 phase and cell apoptosis via suppression of the PI3K/Akt signalling pathway.

A novel curcumin analogue is a potent chemotherapy candidate for human hepatocellular carcinoma.

Curcumin (CUR) has been demonstrated to protect against carcinogenesis and to prevent tumor development in cancer; however, the clinical application of CUR is limited by its instability and poor metabolic properties. The present study offers an strategy for a novel CUR analogue, (1E,4E)-1,5-bis(2-bromophenyl)penta-1,4-dien-3-one (GL63), to be used as a potential therapeutic agent for hepatocellular carcinoma (HCC) in vitro and in vivo. The current study demonstrated that GL63 exhibited more potent inhibition of proliferation of HCC cells than CUR. GL63 induced G0/G1 phase cell cycle arrest and apoptosis in SK-HEP-1 cells in a dose-dependent manner, and was more potent than CUR, according to the flow cytometry data. The present study demonstrated for the first time that the inhibition of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway by GL63 resulted in a protective effect against HCC cell growth. GL63 was more effective than CUR in regulating STAT3 downstream targets, which contributed to the suppression of cell proliferation and the induction of cell apoptosis. In addition, the effects of GL63 were tested in a model of N-nitrosodiethylamine (DEN)-induced HCC in Wistar rats. Although macroscopic and microscopic features suggested that both GL63 and CUR were effective in inhibiting DEN-induced hepatocarcinogenesis, GL63 exerted a stronger effect than CUR. Immunohistochemical analysis for proliferating cell nuclear antigen demonstrated significant differences among the DEN-bearing non-treated, DEN-bearing GL63-treated and DEN-bearing, CUR-treated groups (P=0.039). It was concluded that GL63 was a potent agent able to suppress the proliferation of HCC cells by inhibition of the JAK2/STAT3 signaling pathway, with more favorable pharmacological activity than CUR, and may be a more potent compound for the prevention of DEN-induced hepatocarcinogenesis in rats than CUR.

Radiosensitization of esophageal carcinoma cells by the silencing of BMI-1.

Radiotherapy (RT) has been widely used to treat cancer patients, particularly esophageal cancer patients. B-cell-specific Moloney murine leukemia virus integration site-1 (BMI-1) plays an important role in promoting the growth of cancer cells after exposure to irradiation. The present study aimed to characterize the effects of BMI-1 on the proliferation and invasion of cancer cells, as well as the mechanism involved in the regulation of the growth of esophageal cancer ECA109 and TE13 cells. The expression levels of the BMI-1 gene and protein in esophageal cancer ECA109 and TE13 cells were determined by quantitative PCR and western blotting after transfection. Co-immunoprecipitation (Co-IP) assay was employed to detect the interaction of BMI-1 with r-H2AX and H2AK119ub. We used flow cytometry to analyze the cell cycle distribution and apoptosis of transfected cells after irradiation or not, and examined cellular growth and invasion in vitro by MTS and Transwell assays. The results revealed that shRNA targeting the BMI-1 gene and protein downregulated BMI-1 expression after transfection for 24 h. The proliferation and invasion of tumor cells in the BMI-1­shRNA group were suppressed after RT. In addition, the interaction of BMI-1, H2AK119ub and r-H2AX was increased after exposure to IR, followed by an increased apoptosis rate and decreased percentage of cells arrested at the G2/M phase after irradiation and silencing of BMI-1 by shRNA. Knockdown of BMI-1 expression decreased the phosphorylation of H2AX, upregulated p16, and induced the radiosensitivity of esophageal cancer ECA109 and TE13 cells in vitro and significantly inhibited the growth and invasion of tumor cells. The mechanisms were found to be abrogation of cell cycle arrest at the G2/M stage and promotion of apoptosis.

Radiosensitization of esophageal carcinoma cells by knockdown of RNF2 expression.

Radiotherapy has been widely used for the treatment of cancer patients, especially for esophageal cancer patients. Ring finger protein 2 (RNF2) plays an important role in promoting the growth of cancer cells after exposure to irradiation. The present study aims to characterize the proliferative effects of RNF2 on cancer cells, and its mechanisms on the growth of esophageal cancer cells. We demonstrate that expression of RNF2 was markedly upregulated in esophageal cancer cell lines and surgically resected cancer specimens. In addition, RNF2 expression level is positively correlated with the presence of tumor size, lymph node metastases and negatively correlated with patient survival rates, suggesting that it plays an important role in the progression of esophageal cancer. Furthermore, the expression of RNF2 at both mRNA and protein levels in esophageal cancer ECA109 and TE13 cells was detected by real-time PCR and western blot assay after shRNA targeting RNF2. Co-immunoprecipitation (Co-IP) assay and western blot analysis were employed to detect the interaction between RNF2 and r-H2AX, H2AK119ub, and the expression of proteins associated with cell cycle and apoptosis, respectively. We used flow cytometry assay to analyze cell cycle and apoptosis of transfected cells, and further examined cellular growth in vitro and in vivo. shRNA targeting RNF2 gene and protein downregulated RNF2 expression after transfection for 24 h. The proliferation of tumor cells in RNF2-shRNA group was suppressed after radiotherapy. In addition, the interaction of RNF2, H2AK119ub, r-H2AX was increased after exposure to IR, followed by increasing apoptosis rates and inducing the arrest at G0/G1 phase after irradiation and shRNA targeting RNF2. Expression of the short-hairpin RNA is also correlated with the upregulation of p16 and Bax, and the downregulation of cyclin D2, cyclin-dependent kinase (CDK)-4, H2AX and Bcl-2. RNF2 gene knockdown induces radiosensitivity of esophageal cancer cells in vitro and significantly inhibits the growth of tumor cells. The mechanisms include inducing the cell cycle arrest at G0/G1 phase and promoting apoptosis.

The tumor-suppressive function of miR-1 by targeting LASP1 and TAGLN2 in esophageal squamous cell carcinoma.

OBJECTIVE: This study determined the expression of microRNA-1 in esophageal squamous cell carcinoma (ESCC) tissue and cell lines to evaluate its effects on clinicopathological parameters and its target genes LASP1 and TAGLN2. METHODS: The expression of miR-1, lasp1, and tagln2 was detected in 55 ESCC tissues and adjacent normal tissues by reverse transcription-polymerase chain reaction (RT-PCR). The association between miR-1, lasp1, and tagln2 expression and clinicopathological characteristics was observed. MicroRNA-1 (mimics-miR-1) and its inhibitor (Inhibitor-miR-1) were transfected into esophageal cancer cells KYSE 510 and Eca 109; cell proliferation, migration, and invasion assays were carried out. Plasmid construction and dual-luciferase reporter assay were also carried out to indicate whether LASP1 and TAGLN2 were miR-1 target genes. The expression of LASP1 and TAGLN2 was detected with Western blot methods in cell lines, by immunohistochemistry in ESCC tissue. RESULTS: The gene expression level of microRNA-1 in cancer tissues was significantly lower than that in adjacent normal tissues (P < 0.01). The expression of miR-1 in ESCC was correlated with involvement of lymph nodes (P = 0.002), histologic classification (P = 0.000), and vessel invasion (P = 0.022). The expression of lasp1 and tagln2 increased in cancer tissues compared with in adjacent normal tissues (P < 0.05). MiR-1 suppresses the cell growth, migration, and invasion in vitro. The expression of LASP1 and TAGLN2 decreased in mimics-miR-1 transfected cells, and increased in inhibitor-miR-1 transfected cells. Luciferase reporter assay confirmed that LASP1 and TAGLN2 mRNA actually had the target sites of miR-1. CONCLUSIONS: miR-1 suppresses cell proliferation, invasiveness, metastasis, and progression of ESCC by binding its targeted genes LASP1 and TAGLN2.

Biomarkers for EMT and MET in breast cancer: An update.

Metastasis and recurrence are the leading cause of mortality due to breast cancer, but the underlying mechanisms are still poorly understood. Understanding the breast cancer metastasis mechanism is important for early diagnosis and treatment of breast cancer. The seeding and growth of breast cancer cells at sites distinct from the primary tumor is a complex and multistage process. Recently, it has been reported that the epithelial-mesenchymal transition (EMT) and the mesenchymal-epithelial transition (MET) are the main mechanisms for breast cancer metastasis. During EMT, carcinoma cells shed their differentiated epithelial characteristics, including cell-cell adhesion, polarity and lack of motility, and acquire mesenchymal traits, including motility and invasiveness. This review has summarized the studies of known EMT biomarkers in the context of breast cancer progression. These biomarkers include EMT-related genes, proteins, microRNAs and kinases. In general, the findings of these studies suggest that EMT markers are associated with the invasion and metastasis of breast cancer. Further studies on the link between EMT markers and breast cancer will contribute to identify biomarkers for predicting early breast cancer metastasis as well as to provide new ideas for the treatment of breast cancer.

Low-dose decitabine induces MAGE-A expression and inhibits invasion via suppression of NF-κB2 and MMP2 in Eca109 cells.

Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic syndromes and gains better overall survival, which is based on epigenetic mechanism. Activated by promoter demethylation, melanoma-associated antigens-A (MAGE-A), cancer-testis antigens are attractive targets for immunotherapy. Our purpose was to investigate whether decitabine could show anti-tumor effects for esophageal cancer and explore its mechanism. In addition, we aimed to examine its modulation for most MAGE-A members. The results showed the baseline expression were MAGE-A2, -3,-9, and -10 in Eca109 cells and decitabine (0.5 µM) could induce MAGE-A8 and -A4 whereas reduce MAGE-A9 and -A10. Moreover, decitabine (0.5 µM) inhibited cell proliferation, migration and invasive ability by 15%, 34% and 47.2%, respectively and decreased expressions of NF-κB2 and MMP2. Our results demonstrated that low-dose decitabine induced the expression of MAGE-A8 and -A4, and inhibited cell invasion through decreasing expression of MMP2 and NF-κB2, which provides possibilities for combing decitabine with immunotherapy targeting MAGE-A to treat advanced esophageal squamous cell carcinoma.

Expressions of MAGE-A9 and MAGE-A11 in breast cancer and their expression mechanism.

BACKGROUND AND AIMS: The MAGE gene encodes cancer/testis antigens that are selectively expressed in various types of human neoplasms but not in normal tissues other than testis and placenta. However, the expression pattern of MAGE-A9 and MAGE-A11 in breast cancer patients is still unclear. The purpose of our study is to investigate the expression pattern and mechanism of MAGE-A9 and MAGE-A11 in breast cancer patients. METHODS: The expression of MAGE-A9 and MAGE-A11 was investigated in 60 breast benign diseases specimens, 60 tumor-free breast specimens and 60 breast cancer specimens by RT-PCR, and their correlation with clinicopathological parameters was elucidated. We examined the influence of the DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) together with the histone deacetylase inhibitor trichostatin A (TSA) on the expression of MAGE-A9 and MAGE-A11 genes in two breast cancer cell lines. RESULTS: The expression rates of MAGE-A9 and MAGE-A11 in breast cancer specimens were 45 and 66.7%, respectively. MAGE-A9 and MAGE-A11 expression was positively associated with estrogen-receptor (ER) and HER-2 expression (p <0.05). 5-Aza-CdR treatment alone could induce the expression of MAGE-A9 and MAGE-A11 in cell lines that did not express this antigen. TSA treatment alone had no influence on MAGE-A9 and MAGE-A11 gene expression. However, TSA was able synergistically to enhance 5-aza-CdR-mediated MAGE-A transcription (p <0.05). CONCLUSIONS: Our data show that MAGE-A9 and MAGE-A11 are tumor-specific antigens and not only DNA hypermethylation but also histone deacetylation is responsible for the mechanism underlying MAGE-A9 and MAGE-A11 gene silencing.

Ku70 functions in addition to nonhomologous end joining in pancreatic ß-cells: a connection to ß-catenin regulation.

The genesis of ß-cells predominantly occurs through self-replication; therefore, understanding the regulation of cell proliferation is essential. We previously showed that the lack of nonhomologous end joining (NHEJ) DNA repair factor ligase IV leads to an accumulation of DNA damage that permanently halts ß-cell proliferation and dramatically decreases insulin production, causing overt diabetes in a hypomorphic p53(R172P) background. In the present study, to further delineate the function of NHEJ, we analyzed mice deficient for another key NHEJ factor, Ku70, to discover the effect of cellular responses to DNA damage in pancreatic ß-cells on cellular proliferation and glucose homeostasis. Analysis of Ku70(-/-) pancreatic ß-cells revealed an accumulation of DNA damage and activation of p53-dependent cellular senescence similar to the results found in our earlier ligase IV deficiency study. To our surprise, Ku70(-/-) mice had significantly increased ß-cell proliferation and islet expansion, heightened insulin levels, and decreased glycemia. This augmented ß-cell proliferation was accompanied by an increased ß-catenin level, which we propose to be responsible for this phenotype. This study highlights Ku70 as an important player not only in maintaining genomic stability through NHEJ-dependent functions, but also in regulating pancreatic ß-cell proliferation, a novel NHEJ-independent function.

An ester extract of Cochinchina momordica seeds induces differentiation of melanoma B16 F1 cells via MAPKs signaling.

Cochinchina momordica seeds (CMS) have been widely used due to antitumor activity by Mongolian tribes of China. However, the details of the underlying mechanisms remain unknown. In the present study, we found that an EtOAc (ethyl ester) extract of CMS (CMSEE) induced differentiation and caused growth inhibition of melanoma B16 F1 cells. CMSEE at the concentration of 5-200 µg/ml exhibited strongest anti-proliferative effects on B16 F1 cells among other CMS fractions (water or petroleum ether). Moreover, CMSEE induced melanoma B16 F1 cell differentiation, characterized by dendrite-like outgrowth, increasing melanogenesis production, as well as enhancing tyrosinase activity. Western blot analysis showed that sustained phosphorylation of p38 MAP accompanied by decrease in ERK1/2 and JNK dephosphorylation were involved in CMSEE-induced B16 F1 cell differentiation. Notably, 6 compounds that were isolated and identified may be responsible for inducing differentiation of CMSEE. These results indicated that CMSEE contributes to the differentiation of B16 F1 cells through modulating MAPKs activity, which may throw some light on the development of potentially therapeutic strategies for melanoma treatment.