Apoptotic Cell Death and Inhibition of Wnt/β-Catenin Signaling Pathway in Human Colon Cancer Cells by an Active Fraction (HS7) from Taiwanofungus camphoratus

Aberrant activation of Wnt/β-catenin signaling plays an important role in the development of colon cancer. HS7 is an active fraction extracted from Taiwanofungus camphoratus, which had been widely used as complementary medicine for Taiwan cancer patients in the past decades. In this study, we demonstrated the effects of HS7 on the growth inhibition, apoptosis induction, and Wnt/β-catenin signaling suppression in human colon cancer cells. HS7 significantly inhibited proliferation of HT29, HCT116, and SW480 colon cancer cells in a dose- and time-dependent manner. The apoptosis induction was evidenced by DNA fragmentation and subG1 accumulation, which was associated with increased Bax/Bcl-2 ratio, activation of caspase-3 and cleavage of PARP. By using Tcf-dependent luciferase activity assay, HS7 was found to inhibit the β-catenin/Tcf transcriptional activities. In addition, HS7 strongly suppressed the binding of Tcf complexes to its DNA-binding site shown in electrophoretic mobility shift assay. This inhibition was further confirmed by the decreased protein levels of Tcf-4 and β-catenin. The β-catenin/Tcf downstream target genes, such as survivin, c-myc, cyclin D1, MMP7, and MT1-MMP involved in apoptosis, invasion, and angiogenesis were also diminished as well. These results indicate that Taiwanofungus camphoratus may provide a benefit as integrative medicine for the treatment of colon cancer

Pengembangan Suplemen Pembelajaran Fisika Gelombang Elektromagnetik Cahaya Sebagai Partikel Memanfaatkan Virtual Laboratorium

This research has been done to make a supplement for physics learning about light electromagnetic wave as a particle using virtual laboratory. The population of this research was the second year science-students at SMA Muhammadiyah 1 Metro. This development is begun by needs analysis, then identification of resource which is the background of this developmental research. The next step is, identifying the product specification then developing products which contained a tutorial book for teacher and a work sheet for student (LKS). The material and design expert test result is that those products were approved. The external test resulted by users show that the LKS was attractive, very easy to use, and useful. It also was effective to be used as a learning resource because 80% of students reached the passing grade.Telah dilakukan penelitian untuk mengembangkan suplemen pembelajaran fisika gelombang elektromagnetik cahaya sebagai partikel dengan memanfaatkan virtual laboratorium. Populasi penelitian pengembangan ini adalah siswa kelas XI IPA di SMA Muhammadiyah 1 Metro. Pengembangan ini diawali dengan analisis kebutuhan, kemudian identifikasi sumber daya yang melatar belakangi pengembangan. Langkah selanjutnya identifikasi spesifikasi produk yang dilanjutkan dengan mengembangkan produk berupa LKS untuk siswa dan buku panduan untuk guru. Hasil uji internal oleh ahli materi dan ahli desain menyatakan produk yang dikembangkan layak digunakan sebagai media pembelajaran. Hasil uji eksternal oleh pengguna menunjukkan kualitas media pembelajaran menarik, sangat mudah digunakan, dan bermanfaat serta efektif digunakan sebagai media pembelajaran dengan presentase hasil belajar sebesar 80% siswa telah memenuhi KKM

A Nanopore Structured High Performance Toluene Gas Sensor Made by Nanoimprinting Method

Toluene gas was successfully measured at room temperature using a device microfabricated by a nanoimprinting method. A highly uniform nanoporous thin film was produced with a dense array of titania (TiO2) pores with a diameter of 70∼80 nm using this method. This thin film had a Pd/TiO2 nanoporous/SiO2/Si MIS layered structure with Pd-TiO2 as the catalytic sensing layer. The nanoimprinting method was useful in expanding the TiO2 surface area by about 30%, as confirmed using AFM and SEM imaging. The measured toluene concentrations ranged from 50 ppm to 200 ppm. The toluene was easily detected by changing the Pd/TiO2 interface work function, resulting in a change in the I–V characteristics

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/ β

Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such as β-catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β-catenin degradation promoting kinase GSK-3α/β was increased. Consistently, the protein levels of β-catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the β-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT

Afatinib Exerts Immunomodulatory Effects by Targeting the Pyrimidine Biosynthesis Enzyme CAD

13 páginas, 7 figurasCurrent clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)-bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non-small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs. SIGNIFICANCE: This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3270/F1.large.jpg.This study was supported by Taiwan Ministry of Science and Technology grants MOST 104-2320-B-002-044-MY3, MOST 106-2320-B-002-046-MY3, and MOST 108-2320-B-002-024-MY3, National Health Research Institutes grants NHRI-EX106-10401BI and NHRI-EX109-10725BI, National Taiwan University grants NTU107L890504 and NTU110L893503 to M.-S. Lee, and National Taiwan University Hospital grants 106-003451, 107-003849, 108-004269, and 109-004720 to C.-C. Ho. This work was also supported by MINECO grants BFU2016-80570-R and RTI2018-098084-B-I00 (AEI/FEDER, UE). The authors would like to thank the Laboratory Animal Core Facility at the College of Medicine, National Taiwan University for their servicesPeer reviewe

Detection of SARS-associated Coronavirus in Throat Wash and Saliva in Early Diagnosis

Early detection of SARS-CoV in throat wash and saliva suggests that these specimens are ideal for SARS diagnosis