The role of cytochrome c oxidase subunit Va in non-small cell lung carcinoma cells: association with migration, invasion and prediction of distant metastasis

BACKGROUND: Lung cancer is one of the most lethal malignancies worldwide, but useful biomarkers of lung cancer are still insufficient. The aim of this study is to identify some membrane-bound protein(s) associated with migration and invasion in human non-small cell lung cancer (NSCLC) cells. METHODS: We classified four NSCLC cell lines into high and low migration/invasion groups by Transwell and Matrigel assays. Using two-dimensional gel electrophoresis and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), we identified 10 membrane-associated proteins being significantly overexpressed in the high migration/invasion group. The expression of the target protein in the four NSCLC cell lines was then confirmed by reverse transcription polymerase chain reaction (RT-PCR), western blot and immunostaining. RNA interference technique was applied to observe the influence of the target protein on migration and invasion. Gelatin zymography was also performed to evaluate the activities of matrix metalloproteinase (MMP)-2 and MMP-9. Expression condition of the target protein on surgical specimens was further examined by immunohistochemical staining and the clinicopathologic data were analyzed. RESULTS: We identified a mitochondria-bound protein cytochrome c oxidase subunit Va (COX Va) because of its abundant presence found exclusively in tumorous areas. We also demonstrated that migration and invasion of NSCLC cells decreased substantially after knocking down COX Va by siRNA. Meanwhile, we found a positive correlation between COX Va expression, Bcl-2 expression and activities of MMP-2 and MMP-9 in NSCLC cells. Immunohistochemical staining of surgically resected lung adenocarcinomas in 250 consecutive patients revealed that strong COX Va expression was found in 54.8% (137/250) of patients and correlated positively with the status of lymph node metastasis (P = 0.032). Furthermore, strong COX Va expression was associated with the presence of distant metastasis (P = 0.033). CONCLUSIONS: Our current study showed that COX Va may play a role in migration and invasion of NSCLC cells and can be used as a biomarker to predict aggressiveness of NSCLC

Low temperature and high magnetic field spectroscopic ellipsometry system

We report on the design and implementation of a spectral ellipsometer at near-infrared wavelength (700-1000 nm) for samples placed in high magnetic fields (up to 14 T) at low temperatures (~4.2 K). The main optical components are integrated in a probe, which can be inserted into a conventional long-neck He dewar and has a very long free-space optical path (~1.8 m×2). A polarizer-sample-(quarter-wave plate)-rotating analyzer configuration was employed. Two dielectric mirrors, one before and one after the sample in the optical path, helped to reflect the light back to the analyzer and a two-axis piezo-driven goniometer under the sample holder was used to control the direction of the reflected light. Functional test results performed on an intrinsic GaAs wafer and analysis on the random error of the system are shown. We obtained both amplitude and phase ellipsometric spectra simultaneously and observed helicity transformation at energies near the GaAs exciton transitions in the phase spectra. Significant shifts of them induced by magnetic fields were observed and fitted with a simple model. This system will allow us to study the collective magneto-optical response of materials and spatial dispersive exciton-polariton related problems in high external magnetic fields at low temperatures

Efficient Prodrug Activator Gene Therapy by Retroviral Replicating Vectors Prolongs Survival in an Immune-Competent Intracerebral Glioma Model.

Prodrug activator gene therapy mediated by murine leukemia virus (MLV)-based retroviral replicating vectors (RRV) was previously shown to be highly effective in killing glioma cells both in culture and in vivo. To avoid receptor interference and enable dual vector co-infection with MLV-RRV, we have developed another RRV based on gibbon ape leukemia virus (GALV) that also shows robust replicative spread in a wide variety of tumor cells. We evaluated the potential of GALV-based RRV as a cancer therapeutic agent by incorporating yeast cytosine deaminase (CD) and E. coli nitroreductase (NTR) prodrug activator genes into the vector. The expression of CD and NTR genes from GALV-RRV achieved highly efficient delivery of these prodrug activator genes to RG-2 glioma cells, resulting in enhanced cytotoxicity after administering their respective prodrugs 5-fluorocytosine and CB1954 in vitro. In an immune-competent intracerebral RG-2 glioma model, GALV-mediated CD and NTR gene therapy both significantly suppressed tumor growth with CB1954 administration after a single injection of vector supernatant. However, NTR showed greater potency than CD, with control animals receiving GALV-NTR vector alone (i.e., without CB1954 prodrug) showing extensive tumor growth with a median survival time of 17.5 days, while animals receiving GALV-NTR and CB1954 showed significantly prolonged survival with a median survival time of 30 days. In conclusion, GALV-RRV enabled high-efficiency gene transfer and persistent expression of NTR, resulting in efficient cell killing, suppression of tumor growth, and prolonged survival upon CB1954 administration. This validates the use of therapeutic strategies employing this prodrug activator gene to arm GALV-RRV, and opens the door to the possibility of future combination gene therapy with CD-armed MLV-RRV, as the latter vector is currently being evaluated in clinical trials

Transforaminal Endoscopic Lumbar Discectomy with Foraminoplasty for Down-migrated Disc Herniation: A Single-center Observational Study

Objective Full-endoscopic lumbar discectomy has evolved to be an alternative for the treatment of lumbar disc herniation. Regarding the techniques, the transforaminal approach remains the primary access. The indications of transforaminal endoscopic lumbar discectomy (TELD) have expanded following the evolution of the techniques, especially TELD with foraminoplasty. This study is to evaluate the efficacy of the TELD with foraminoplasty for downward migrated lumbar disc herniation. Methods The authors conducted a retrospective study with prospectively collected data in a single center. The study enrolled patients with downward migrated lumbar disc herniation undergoing TELD with foraminoplasty from May 2009 to June 2018. All procedures were performed under local anesthesia. Patients' demographics, clinical outcomes, and satisfaction with surgery were recorded. Results There were 126 patients included in the current study. The mean age was 50.7±17.4 years old. The leg pain and functional outcome scores significantly improved after the operation. There was no neurological deficit or iatrogenic instability requiring fusion surgery. The operation time was within 2 hours in most cases (92%). Thirteen patients reported minor complications, but symptoms were self-limited or responded to conservative treatment. The operation satisfied 94.4% of patients. Seven cases underwent revision surgery within six months due to recurrence. Conclusion TELD with foraminoplasty under local anesthesia can be an alternative for downward migrated lumbar disc herniation. Nerve root irritation can be detected without intraoperative neurophysiological monitoring when the patient is awake during the procedures. The clinical outcomes were favorable and the risk of complication was low with the current technique

The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics

<p>Abstract</p> <p>Background</p> <p>Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low.</p> <p>Methods</p> <p>¹⁸F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA) of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and ¹⁸F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature.</p> <p>Results</p> <p>Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (<it>p </it>= 0.043) and a higher TMA (<it>p </it>= 0.028) than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (<it>p </it>= 0.016).</p> <p>Conclusions</p> <p>Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.</p

THE USE OF MANDAMUS TO COMPEL EDUCATIONAL INSTITUTIONS TO CONFER DEGREES

Hispolon is an active phenolic compound of <i>Phellinus igniarius</i>, a mushroom that was recently shown to have antioxidant and anticancer activities in various solid tumors. Here, the molecular mechanisms by which hispolon exerts anticancer effects in acute myeloid leukemia (AML) cells was investigated. The results showed that hispolon suppressed cell proliferation in the various AML cell lines. Furthermore, hispolon effectively induced apoptosis of HL-60 AML cells through caspases-8, -9, and -3 activations and PARP cleavage. Moreover, treatment of HL-60 cells with hispolon induced sustained activation of JNK1/2, and inhibition of JNK by JNK1/2 inhibitor or JNK1/2-specific siRNA significantly abolished the hispolon-induced activation of the caspase-8/-9/-3. In vivo, hispolon significantly reduced tumor growth in mice with HL-60 tumor xenografts. In hispolon-treated tumors, activation of caspase-3 and a decrease in Ki67-positive cells were observed. Our results indicated that hispolon may have the potential to serve as a therapeutic tool to treat AML

Biomechanical investigation of flexor digitorum tendons in trigger finger patients using sonography

Trigger finger (TF) has generally been ascribed to primary changes in the first annular (A1) pulley. Repeated friction between the A1 pulley and flexor digitorum tendons could result in swelling of soft tissues, and thus it has been speculated that TF affects tendons’ biomechanical behaviors. However, the pathology mechanism related to these behaviors remains unclear. The purposes of this study are to understand (1) the variations in the morphologies of the flexor digitorum profundus (FDP) and flexor digitorum superficialis (FDS) between normal fingers and TFs, (2) the differences in the biomechanical behaviors of the FDP and FDS between normal fingers and TFs in various finger flexion positions, and (3) the effect of various finger positions on the biomechanical behaviors of the FDP and FDS

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

Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients

Background The dysregulation of transforming growth factor-β (TGF-β) signaling plays a crucial role in ovarian carcinogenesis and in maintaining cancer stem cell properties. Classified as a member of the ATP-binding cassette (ABC) family, ABCA1 was previously identified by methylated DNA immunoprecipitation microarray (mDIP-Chip) to be methylated in ovarian cancer cell lines, A2780 and CP70. By microarray, it was also found to be upregulated in immortalized ovarian surface epithelial (IOSE) cells following TGF-β treatment. Thus, we hypothesized that ABCA1 may be involved in ovarian cancer and its initiation. Results We first compared the expression level of ABCA1 in IOSE cells and a panel of ovarian cancer cell lines and found that ABCA1 was expressed in HeyC2, SKOV3, MCP3, and MCP2 ovarian cancer cell lines but downregulated in A2780 and CP70 ovarian cancer cell lines. The reduced expression of ABCA1 in A2780 and CP70 cells was associated with promoter hypermethylation, as demonstrated by bisulfite pyro-sequencing. We also found that knockdown of ABCA1 increased the cholesterol level and promoted cell growth in vitro and in vivo. Further analysis of ABCA1 methylation in 76 ovarian cancer patient samples demonstrated that patients with higher ABCA1 methylation are associated with high stage (P = 0.0131) and grade (P = 0.0137). Kaplan-Meier analysis also found that patients with higher levels of methylation of ABCA1 have shorter overall survival (P = 0.019). Furthermore, tissue microarray using 55 ovarian cancer patient samples revealed that patients with a lower level of ABCA1 expression are associated with shorter progress-free survival (P = 0.038). Conclusions ABCA1 may be a tumor suppressor and is hypermethylated in a subset of ovarian cancer patients. Hypermethylation of ABCA1 is associated with poor prognosis in these patients