Hypermethylation of MGMT and DAPK gene promoters is associated with tumorigenesis and metastasis in oral squamous cell carcinoma

AbstractBackground/purposeOral squamous cell carcinoma (OSCC) is the fourth major cause of mortality among males in Asia. The tumorigenesis of OSCC is a multi-step process characterized by sequential morphological changes. The extent of lymph node metastasis is a major determinant in the prognosis of cancer. Hypermethylation is an important pathway for repression of gene transcription in cancer cells and a promising marker for cancer detection. It is also found in early metastatic cancer patients.Materials and methodsSixty-four histologically confirmed OSCC tissues and corresponding nontumorous tissues were enrolled in this study. DNA was extracted. The promoter methylation status of the p16, death-associated protein kinase (DAPK), MGMT, and glutathione S-transferase genes in OSCC tissues was evaluated by a methylation-specific polymerase chain reaction analysis.ResultsFrequencies of promoter hypermethylation of p16, DAPK, and MGMT in OSCC tissue were 67.2%, 45.3%, and 31.3%, respectively. No methylation was found in normal oral mucosa. Methylation rates of MGMT (50%) and DAPK (55.6%) in metastasized OSCC were higher than those of MGMT (23.9%) and DAPK (41.3%) in nonmetastasized OSCC. No glutathione S-transferase P methylation was found in any tissue samples.ConclusionsOur study supports the hypothesis that hypermethylation of p16 gene promoters may indicate a high risk of oral cancer, and hypermethylation of the MGMT and DAPK genes may be a major indicator of early OSCC metastasis

HLA typing in Taiwanese patients with oral squamous cell carcinoma

AbstractBackground/purposeThe human leukocyte antigen (HLA) system, which plays a vital role in immunity, is the most polymorphic gene complex found in the human genome. This study investigated HLA-related alleles and haplotypes in Taiwanese patients with oral squamous cell carcinoma (OSCC).Materials and methodsHLA class I (HLA-A and HLA-B) antigens and class II (HLA-DRB1) alleles were determined in 105 patients with OSCC and compared with those in 190 healthy controls. The antigens were measured serologically and the alleles by sequencing-based typing.ResultsCompared with the control group, patients with OSCC had higher frequencies of HLA-A24, HLA-B54, HLA-DRB1*0405, and HLA-DRB1*1201, while they had lower frequencies of HLA-B58 and HLA-DRB1*1302. Haplotype frequencies also varied significantly in individuals with OSCC, with certain haplotypes associated with lymph node metastases or a particular tumor stage.ConclusionThese results suggest that HLA genetic factors influence susceptibility to OSCC and perhaps to lymph node metastasis and tumor progression

Consecutive dual-vortex interactions between quadruple Typhoons Noru, Kulap, Nesat and Haitang during the 2017 North Pacific Typhoon season

© 2019 by the authors. This study utilizes remote sensing imagery, a differential averaging technique and empirical formulas (the \u27Liou-Liu formulas\u27) to investigate three consecutive sets of dual-vortex interactions between four cyclonic events and their neighboring environmental air flows in the Northwest Pacific Ocean during the 2017 typhoon season. The investigation thereby deepens the current understanding of interactions involving multiple simultaneous/sequential cyclone systems. Triple interactions between Noru-Kulap-Nesat and Noru-Nesat-Haitung were analyzed using geosynchronous satellite infrared (IR1) and IR3 water vapor (WV) images. The differential averaging technique based on the normalized difference convection index (NDCI) operator and filter depicted differences and generated a new set of clarified NDCI images. During the first set of dual-vortex interactions, Typhoon Noru experienced an increase in intensity and a U-turn in its direction after being influenced by adjacent cooler air masses and air flows. Noru\u27s track change led to Fujiwhara-type rotation with Tropical Storm Kulap approaching from the opposite direction. Kulap weakened and merged with Noru, which tracked in a counter-clockwise loop. Thereafter, in spite of a distance of 2000-2500 km separating Typhoon Noru and newly-formed Typhoon Nesat, the influence of middle air flows and jet flows caused an \u27indirect interaction\u27 between these typhoons. Evidence of this second interaction includes the intensification of both typhoons and changing track directions. The third interaction occurred subsequently between Tropical Storm Haitang and Typhoon Nesat. Due to their relatively close proximity, a typical Fujiwhara effect was observed when the two systems began orbiting cyclonically. The generalized Liou-Liu formulas for calculating threshold distances between typhoons successfully validated and quantified the trilogy of interaction events. Through the unusual and combined effects of the consecutive dual-vortex interactions, Typhoon Noru survived 22 days from 19 July to 9 August 2017 and migrated approximately 6900 km. Typhoon Noru consequently became the third longest-lasting typhoon on record for the Northwest Pacific Ocean. A comparison is made with long-lived Typhoon Rita in 1972, which also experienced similar multiple Fujiwhara interactions with three other concurrent typhoons

Incidental placental choriocarcinoma in a term pregnancy: a case report

<p>Abstract</p> <p>Introduction</p> <p>Gestational choriocarcinoma occurs in 1 in 40,000 pregnancies. Of all forms of gestational choriocarcinoma, placental choriocarcinoma is the most rare. Maternal choriocarcinoma is usually diagnosed in symptomatic patients with metastases. The incidental finding of a choriocarcinoma confined to the placenta with no evidence of dissemination to the mother, or infant is the least common scenario.</p> <p>Case presentation</p> <p>The patient is an 18 year-old Gravida 1 Para 1 African American female who delivered a viable 3641 g female infant at 39 weeks gestation. Her pregnancy course was complicated by gestational hypertension during the third trimester. Her placenta revealed intraplacental choriocarcinoma. She was then followed closely by the Gynecologic Oncology service with a weekly serum beta human chorionic gonadotropin value. Beta human chorionic gonadotropin values dropped from 3070 mIU/ml to less than 2 mIU/ml two months post partum. No chemotherapy was initiated. Metastasis was ruled out by chest x-ray and whole body computed tomography scan. To date, both mother and baby are well.</p> <p>Conclusion</p> <p>Due to the potential fatal outcome of placental choriocarcinoma, careful evaluation of both mother and infant after the diagnosis is made is important. The incidence of placental choriocarcinoma may actually be higher than expected since it is not routine practice to send placentas for pathological evaluation after a normal spontaneous delivery. The obstetrician, pathologist, and pediatrician should have an increased awareness of placental choriocarcinoma and its manifestations.</p

Transcriptional Regulation of Proteoglycans and Glycosaminoglycan Chain-synthesizing Glycosyltransferases by UV Irradiation in Cultured Human Dermal Fibroblasts

Various kinds of glycosaminoglycans (GAGs) and proteoglycans (PGs) have been known to be involved in structural and space-filling functions, as well as many physiological regulations in skin. To investigate ultraviolet (UV) radiation-mediated regulation of GAGs and PGs in cultured human dermal fibroblasts, transcriptional changes of many types of PGs and GAG chain-synthesizing enzymes at 18 hr after 75 mJ/cm2 of UV irradiation were examined using quantitative real-time polymerase chain reaction methods. Hyaluronic acid synthase (HAS)-1, -2, and -3 and hyaluronidase-2 mRNA expressions were significantly increased by UV irradiation. Expressions of lumican, fibromodulin, osteoglycin, syndecan-2, perlecan, agrin, versican, decorin, and biglycan were significantly decreased by UV irradiation, while syndecan-1 was increased. Expressions of GAG chain-synthesizing glycosyltransferases, xylosyltransferase-1, β1,3-glucuronyltransferase-1, β1,4-galactosyltransferase-2, -4, exostosin-1, chondroitin polymerizing factor, and chondroitin sulfate synthase-3 were significantly reduced, whereas those of β1,3-galactosyltransferase-6, β1,4-galactosyltransferase-3, -7, β-1,3-N-acetylglucosaminyltran sferase-2, and -7 were increased by UV irradiation. Heparanase-1 mRNA expression was increased, but that of heparanase-2 was reduced by UV irradiation. Time-course investigation of representative genes showed consistent results. In conclusion, UV irradiation may increase hyaluronic acid production through HAS induction, and decrease other GAG productions through downregulation of PG core proteins and GAG chain-synthesizing glycosyltransferases in cultured human dermal fibroblasts

Anesthetic experience in patient for single lung transplantation with previous contralateral pneumonectomy -A case report-

A 48-year-old woman with cystic fibrosis and a previous left pneumonectomy had surgery planned for single lung transplantation under general anesthesia. Due to progressive dyspnea and recurrent respiratory infection, she could not maintain her normal daily life without lung transplantation. The anesthetic management and surgical procedure was expected to be difficult because of the left mediastinal shift and an asymmetric thorax after the left pneumonectomy, but the single lung transplantation was successfully done under cardiopulmonary bypass

Comparison of flat and hollow-fiber mixed-matrix composite membranes for CO2 separation with temperature

Zeolite A/poly (1-trimethylsilyl-1-propyne) (zeoliteA/PTMSP) and [emim][Ac]/chitosan (IL/CS) are mixed-matrix membrane (MMM) materials with enhanced CO2/N2 permselectivity even at higher temperature. The scalability to asymmetric flat and hollow-fiber geometry by a simple dip-coating method was analyzed. The CO2/N2 separation performance was evaluated at different temperatures. The resulting composite membranes exhibit a significantly enhanced CO2permeation flux because the MMM layer thickness is reduced by 97?% from flat to hollow-fiber geometries in IL-CS composite membranes, while the selectivity is maintained similar to the self-standing membranes, thus proving that compatibility between the membrane component materials leads to a defect-free composite membrane, regardless the geometry and temperature.Financial support from the Spanish Ministry of Economyand Competitiveness (MINECO) under project CTQ2012-31229 at the Universidad de Cantabria is gratefully acknowl-edged. A.F.B. and C.C.C. also thank the MINECO for theEarly Stage Researcher (BES2013-064266) and ‘‘Ramón yCajal’’ (RYC2011-0855) contracts, respectively. The authorsthank F. Noboru Ramirez-Matsumoto for his contribution inthe synthesis and permeation experiments of the CS andIL-CS composite flat membranes by the modified IP method

Elimination of head and neck cancer initiating cells through targeting glucose regulated protein78 signaling

<p>Abstract</p> <p>Background</p> <p>Head and neck squamous cell carcinoma (HNSCC) is a highly lethal cancer that contains cellular and functional heterogeneity. Previously, we enriched a subpopulation of highly tumorigenic head and neck cancer initiating cells (HN-CICs) from HNSCC. However, the molecular mechanisms by which to govern the characteristics of HN-CICs remain unclear. GRP78, a stress-inducible endoplasmic reticulum chaperone, has been reported to play a crucial role in the maintenance of embryonic stem cells, but the role of GRP78 in CICs has not been elucidated.</p> <p>Results</p> <p>Initially, we recognized GRP78 as a putative candidate on mediating the stemness and tumorigenic properties of HN-CICs by differential systemic analyses. Subsequently, cells with GRP78 anchored at the plasma membrane (^memGRP78⁺) exerted cancer stemness properties of self-renewal, differentiation and radioresistance. Of note, xenotransplantation assay indicated merely 100 ^memGRP78⁺HNSCCs resulted in tumor growth. Moreover, knockdown of GRP78 significantly reduced the self-renewal ability, side population cells and expression of stemness genes, but inversely promoted cell differentiation and apoptosis in HN-CICs. Targeting GRP78 also lessened tumorigenicity of HN-CICs both <it>in vitro </it>and <it>in vivo</it>. Clinically, co-expression of GRP78 and Nanog predicted the worse survival prognosis of HNSCC patients by immunohistochemical analyses. Finally, depletion of GRP78 in HN-CICs induced the expression of Bax, Caspase 3, and PTEN.</p> <p>Conclusions</p> <p>In summary, ^memGRP78 should be a novel surface marker for isolation of HN-CICs, and targeting GRP78 signaling might be a potential therapeutic strategy for HNSCC through eliminating HN-CICs.</p