TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells

The TP53induced glycolysis and apoptosis regulator (TIGAR) is the protein product of the p53 target gene, C12orf5. TIGAR blocks glycolysis and promotes cellular metabolism via the pentose phosphate pathway; it promotes the production of cellular nicotinamide adenine dinucleotide phosphate (NADPH), which leads to enhanced scavenging of intracellular reactive oxygen species, and inhibition of oxidative stressinduced apoptosis in normal cells. Our previous study identified a novel nucleoside analog that inhibited cellular growth and induced apoptosis in nasopharyngeal carcinoma (NPC) cell lines via downregulation of TIGAR expression. Furthermore, the growth inhibitory effects of cMet tyrosine kinase inhibitors were ameliorated by the overexpression of TIGAR in the NPC cell lines. These results indicate a significant role for TIGAR expression in the survival of NPCs. The present study aimed to further define the function of TIGAR expression in NPC cells. In total, 36 formalinfixed, paraffinembedded NPC tissue samples were obtained for the immunohistochemical determination of TIGAR expression. The effects of TIGAR expression on cell proliferation, NADPH production and cellular invasiveness were also assessed in NPC cell lines. Overall, TIGAR was overexpressed in 27/36 (75%) of the NPC tissues compared with the adjacent noncancer epithelial cells. Similarly, TIGAR overexpression was also observed in a panel of six NPC cell lines compared with normal NP460 hTert and Het1A cell lines. TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness of the NPC cell lines, whereas a knockdown of TIGAR expression resulted in significant inhibition of cellular growth and invasiveness. The expression of the two mesenchymal markers, fibronectin and vimentin, was increased by TIGAR overexpression, but reduced following TIGARknockdown. The present study revealed that TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness, and the maintenance of a mesenchymal phenotype, in NPC tissues.published_or_final_versio

Clinical significance of frizzled homolog 3 protein in colorectal cancer patients

2013-2014 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Patients with treated indolent lymphomas immunized with BNT162b2 have reduced anti-spike neutralizing IgG to SARS-CoV-2 variants, but preserved antigen-specific T cell responses

Patients with indolent lymphoma undertaking recurrent or continuous B cell suppression are at risk of severe COVID-19. Patients and healthy controls (HC; N = 13) received two doses of BNT162b2: follicular lymphoma (FL; N = 35) who were treatment naïve (TN; N = 11) or received immunochemotherapy (ICT; N = 23) and Waldenström's macroglobulinemia (WM; N = 37) including TN (N = 9), ICT (N = 14), or treated with Bruton's tyrosine kinase inhibitors (BTKi; N = 12). Anti-spike immunoglobulin G (IgG) was determined by a high-sensitivity flow-cytometric assay, in addition to live-virus neutralization. Antigen-specific T cells were identified by coexpression of CD69/CD137 and CD25/CD134 on T cells. A subgroup (N = 29) were assessed for third mRNA vaccine response, including omicron neutralization. One month after second BNT162b2, median anti-spike IgG mean fluorescence intensity (MFI) in FL ICT patients (9977) was 25-fold lower than TN (245 898) and HC (228 255, p =.0002 for both). Anti-spike IgG correlated with lymphocyte count (r =.63; p =.002), and time from treatment (r =.56; p =.007), on univariate analysis, but only with lymphocyte count on multivariate analysis (p =.03). In the WM cohort, median anti-spike IgG MFI in BTKi patients (39 039) was reduced compared to TN (220 645, p =.0008) and HC (p <.0001). Anti-spike IgG correlated with neutralization of the delta variant (r =.62, p <.0001). Median neutralization titer for WM BTKi (0) was lower than HC (40, p <.0001) for early-clade and delta. All cohorts had functional T cell responses. Median anti-spike IgG decreased 4-fold from second to third dose (p =.004). Only 5 of 29 poor initial responders assessed after third vaccination demonstrated seroconversion and improvement in neutralization activity, including to the omicron variant

Pluralitas Agama dalam Keluarga Jawa

Dalam masyarakat Jawa terdapat pemahaman dan pemaknaan sendiri terhadap agama yaitu â€agami ageming ajiâ€. Artinya apa pun agama yang dipeluk sama saja karena semua agama mengajarkan keselamatan. Oleh sebab itu menjadi sebuah fenomena menarik di kalangan masyarakat Jawa karena mereka cenderung lebih toleran dalam menyikapi perbedaaan dan keragaman beragama. Salah satu contoh masyarakat yang menghargai pluralitas agama adalah masyarakat Desa Getas Kaloran Temanggung. Tujuan penelitian ini adalah untuk menjelaskan tentang sejumlah keluarga yang dapat menerima pluralitas agama dan toleransi terhadap pluralitas agama dalam keluarga Jawa. Tulisan ini merupakan hasil penelitian yang menggunakan pendekatan deskriptif kualitatif. Subyek penelitian adalah masyarakat Desa Getas yang memiliki keragaman agama dalam keluarganya. Berdasarkan hasil penelitian dapat disimpulkan bahwa masyarakat Desa Getas dapat menerima pluralitas agama karena menurut mereka agama adalah urusan pribadi seseorang jadi tidak ada pihak yang dapat memaksakan suatu keyakinan kepada individu lain. Pluralitas agama tersebut tidak menimbulkan masalah berarti karena masyarakat memiliki derajat toleransi yang tinggi antar anggota keluarga, yang ditunjukkan melalui saling menghargai dan mengormati dan tidak mencampuri urusan keagamaan orang lain, serta saling membantu antar anggota keluarga untuk memperlancar kegiatan ibadah masing – masing. In Javanese community there is a specific principle on the meaning of religion, namely â€agami ageming ajiâ€. This pilosophy means whatever religion people believe, it doesn’t matter because they all teach salvation. This is an interesting phenomenon among the Javanese community because they tend to be tolerant in dealing with differences and diversity of religion that happen in one household. The objective of this article is to discuss the practices of religious tolerance found in a rural community of Getas, Kaloran, Temanggung Central Java. Techniques of data collection is done by interviews and observation. The study subjects were villagers of Getas, which has a diversity of religion in families. Based on the research results, it can be concluded that the villagers embrace a tradition of religious pluralism because they think religion is one’s personal affairs so that no party can impose a conviction for another individual. The plurality of religion does not cause significant problems because the public has a high degree of tolerance among family members, which is demonstrated through mutual respect and attitude not to interfere in religious affairs of others, and mutual help among family members to facilitate the worship activities of their relatives

Identification of Hub Genes Related to the Recovery Phase of Irradiation Injury by Microarray and Integrated Gene Network Analysis

BACKGROUND: Irradiation commonly causes long-term bone marrow injury charactertized by defective HSC self-renewal and a decrease in HSC reserve. However, the effect of high-dose IR on global gene expression during bone marrow recovery remains unknown. METHODOLOGY: Microarray analysis was used to identify differentially expressed genes that are likely to be critical for bone marrow recovery. Multiple bioinformatics analyses were conducted to identify key hub genes, pathways and biological processes. PRINCIPAL FINDINGS: 1) We identified 1302 differentially expressed genes in murine bone marrow at 3, 7, 11 and 21 days after irradiation. Eleven of these genes are known to be HSC self-renewal associated genes, including Adipoq, Ccl3, Ccnd1, Ccnd2, Cdkn1a, Cxcl12, Junb, Pten, Tal1, Thy1 and Tnf; 2) These 1302 differentially expressed genes function in multiple biological processes of immunity, including hematopoiesis and response to stimuli, and cellular processes including cell proliferation, differentiation, adhesion and signaling; 3) Dynamic Gene Network analysis identified a subgroup of 25 core genes that participate in immune response, regulation of transcription and nucleosome assembly; 4) A comparison of our data with known irradiation-related genes extracted from literature showed 42 genes that matched the results of our microarray analysis, thus demonstrated consistency between studies; 5) Protein-protein interaction network and pathway analyses indicated several essential protein-protein interactions and signaling pathways, including focal adhesion and several immune-related signaling pathways. CONCLUSIONS: Comparisons to other gene array datasets indicate that global gene expression profiles of irradiation damaged bone marrow show significant differences between injury and recovery phases. Our data suggest that immune response (including hematopoiesis) can be considered as a critical biological process in bone marrow recovery. Several critical hub genes that are key members of significant pathways or gene networks were identified by our comprehensive analysis

A histological comparison of micropulse and standard laser treatment in threshold and sub-threshold modes

Session 548: Laser TherapyConference Theme: Leading Eye and Vision ResearchPurpose: Laser photocoagulation is a common treatment for diabetic macular edema but not without side effects and can damage the neurosensory retina. Sub-threshold micropulse laser produces therapeutic effects without inducing detectable clinical visible changes. However, sub-threshold standard (continuous wave) laser can produce detectable changes in optical coherent topography. We aim to compare the effects of the 577nm (yellow) micropulse laser, 577nm (yellow) standard mode laser and 532nm (green) standard mode laser on the retina by histological examination. Methods: Twelve Dutch-belted rabbits received laser treatment in their left eyes. The 532nm and 577nm laser photocoagulation in standard mode were used in six rabbit eyes. The other six rabbits received sub-threshold 577nm micropulse laser photocoagulation at 5% and 10% duty cycle. Treatment was given at threshold and sub-threshold (approximately 50% of threshold) powers in different areas of the retina. At 1 week and 1 month post-laser photocoagulation, histology of the retinal sections was analyzed and compared. Results: In the treated areas by threshold mode, extensive retinal damage was present with all 4 treatment modalities. In the sub-threshold-treated areas, at 1 week and 1 month post-laser treatment, retinae treated by 532nm laser photocoagulation in standard mode exhibited more retinal morphological changes than the ones treated by 577nm laser in standard mode. Increased extent of retinal fold, retinal pigment epithelium disruption and outer retinal cell death occurred. In general, the overall appearance of the retinae treated with 577nm micropulse laser in both 5% and 10% duty cycles were better preserved when compared with the ones using standard setting with either 577nm or 532nm laser. Most importantly, cellular morphology appeared best preserved in the retinae using the 5% duty cycle, with slight or minimal disruption by histological examination. Conclusions: This study confirmed the clinical findings that no matter what modality is used, if there was a threshold treatment, extensive retinal damage occurs. However, by reducing power to 50% of threshold power, less damage incurred by using the 5% duty cycle micropulse laser

Comparison of protein expression patterns between hepatocellular carcinoma cell lines and a hepatoblastoma cell line

Hepatocellular carcinoma (HCC) and hepatoblastoma (HB) are malignancies of the liver with different etiologies, but the HB cell line HepG2 has been frequently used in various studies of HCC. In this study, we compare the protein expression patterns between HepG2 cells and three HCC cell lines, HKCI-2, HKCI-3, and HKCI-4, respectively. The cell lysates of individual cell lines were separated by two-dimensional polyacrylamide gel electrophoresis. The protein spots in the gel images were quantified and compared by image analysis software. The differentially expressing proteins were then identified by tryptic peptide mass fingerprinting. Compared with the HepG2 cells, the normalized quantities of 49 and 58 protein spots were found to be at least twofold higher and twofold lower, respectively, in all three HCC cell lines. The differentially expressed proteins can be grouped into structural proteins (annexins, transgelin, laminin receptor), stress-induced proteins (HSP27, 60, and 70), enzymes (aldehyde dehydrogenase, pyruvate kinase, α-enolase, etc.), and transcription factors (far upstream element binding protein 2, GTP-binding nuclear protein RAN). Some of these proteins play important roles in regulating homeostasis, drug resistance, apoptosis, cell differentiation, cell growth, and metastasis. In conclusion, our proteomic data indicate that there are considerable differences in the protein expression patterns between HepG2 cells and the HCC cells, suggesting differences m cellular properties. Hence, HepG2 may not be a good cell line model for studying HCC. Copyright © Humana Press Inc. All rights of any nature whatsoever are reserved.link_to_subscribed_fulltex

Proteomic comparison of nasopharyngeal cancer cell lines C666-1 and NP69 identifies down-regulation of annexin II and β 2-tubulin for nasopharyngeal carcinoma

Context. - Nasopharyngeal carcinoma (NPC), common in southern China and North Africa, has a complex etiology involving interplay between viral, environmental, and hereditary factors and is almost constantly associated with the Epstein-Barr virus. Since the prognosis of locally advanced and metastatic diseases is poor, increased understanding of the pathogenesis of NPC would be important for discovering novel markers for patients' management. Objectives. - To compare the proteomic expression profile between an Epstein-Barr virus-associated NPC cell line (C666-1) and a normal NP cell line (NP69). The proteins with differential expression were analyzed in 40 undifferentiated NPC paraffin-embedded specimens. Design. - Differentially expressed proteins discovered between the two cell lines were identified by mass spectrometry. After confirmation by immunocytochemical staining, their expression in patient samples was measured using 40 pairs of undifferentiated NPCs together with their adjacent normal epithelia. Results. - Proteomic findings indicated that adenosine triphosphate synthase α chain was up-regulated, whereas annexin II, annexin V, β 2-tubulin, and profilin 1 were down-regulated. After confirming the results in agar-processed cell lines, annexin II and β 2-tubulin expression were found to be lower in tumor cells than in adjacent normal epithelial cells in 100% and 90% of the patients' specimens, respectively. Finally, annexin II down-regulation was positively associated with lymph node metastasis, suggesting that it may be a prognostic factor in NPC. Conclusions. - The results suggest that annexin II and β 2- tubulin down-regulation is important in NPC formation and may represent potential targets for further investigations.link_to_subscribed_fulltex

An audit of the safety of an acute pain service

We audited and analysed the adverse effects and safety of postoperative pain management on 2509 consecutive patients under care of the Acute Pain Service at a tertiary referral teaching hospital over a 32-month period. Our standard respiratory monitoring consisted of continuous pulse oximetry, hourly respiratory rate counting, sedation scoring and intermittent arterial blood gas sampling. This protocol was reliable and detected six episodes of bradypnoea, 13 of hypercapnia and 23 of oxygen desaturation occurring in 39 patients (1.8% of all spontaneously breathing patients). Two patients required naloxone injection and none had long-term sequelae, Hypotension due to epidural bupivacaine 0.0625% and fentanyl 3.3 μg.ml-1 infusion occurred in four patients (1.2%), all with a sensory block higher than T5. They readily responded to fluid infusion and ephedrine (two patients). Postoperative nausea or vomiting occurred in 723 (28.8%) and 380 (15.1%) patients, respectively. Odds ratio analysis showed that the risk factors for postoperative nausea and vomiting were: female gender, gynaecological operations, nongeriatric patients and systemic analgesia. Postoperative nausea and vomiting decreased analgesic efficacy by discouraging the use of patient-controlled analgesia and was regarded as equally distressing as pain. Other side-effects included: pruritus in 182 patients; dizziness in 333 and lower limb weakness in 73 (21.2% of patients receiving epidural local anaesthetics). It is concluded that a standard monitoring and management protocol, an experienced nursing team and reliable Acute Pain Service coverage is mandatory for the safe use of modern analgesic techniques.link_to_OA_fulltex