Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Malignant Peripheral Nerve Sheath Tumour in the Urinary Bladder of a Dog.

A 15-year-old neutered male miniature pinscher was presented with a pedunculated mass (4 × 1 cm) in its urinary bladder. Exploratory cystotomy revealed that the mass was located at the trigone of the bladder and projected into the lumen. The cut surface of the mass was homogeneous grey to tan in colour with focal brown pigmentation. Microscopically, the mass was predominantly composed of neoplastic spindle cells characterized by moderate cellular pleomorphism, invasion into the muscular layer of the bladder wall and few mitotic figures. The neoplastic spindle cells formed interwoven bundles intersecting at various angles. Immunohistochemically, these cells were negative for cytokeratin 7 and α-smooth muscle actin, but strongly expressed S100 and vimentin, confirming a diagnosis of a malignant peripheral nerve sheath tumour (PNST). To the best of our knowledge, this is the first report of a primary malignant PNST in the urinary bladder of a dog.

A modified-live porcine reproductive and respiratory syndrome virus (PRRSV)-1 vaccine protects late-term pregnancy gilts against heterologous PRRSV-1 but not PRRSV-2 challenge.

The objective of this study was to determine the efficacy of a commercially available porcine reproductive and respiratory syndrome virus (PRRSV)-1 modified-live virus (MLV) vaccine against PRRSV-1 and PRRSV-2 challenge in late-term pregnancy gilts. Gilts were vaccinated with the PRRSV-1 MLV vaccine at 4 weeks prior to breeding and then challenged intranasally with PRRSV-1 or PRRSV-2 at 93 days of gestation. After PRRSV-1 challenge, vaccinated pregnant gilts had a significantly longer gestation period, significantly higher numbers of live-born and weaned piglets and a significantly lower number of stillborn piglets at birth compared to unvaccinated pregnant gilts. No significant improvement in reproductive performance was observed between vaccinated and unvaccinated pregnant gilts following PRRSV-2 challenge. Vaccinated pregnant gilts also exhibited a significantly improved reproductive performance after challenge with PRRSV-1 compared to vaccinated pregnant gilts following PRRSV-2 challenge. The PRRSV-1 MLV vaccine was able to reduce PRRSV-1 but not PRRSV-2 viremia in pregnant gilts. Vaccinated gilts also showed a significantly higher number of PRRSV-1-specific IFN-γ-secreting cells (IFN-γ-SC) compared to PRRSV-2-specific IFN-γ-SC. The data presented here suggest that the vaccination of pregnant gilts with a PRRSV-1 MLV vaccine provides good protection against PRRSV-1 but only limited protection against PRRSV-2 challenge in late-term pregnancy gilts based on improvement of reproductive performance, reduction in viremia and induction of IFN-γ-SC.

Inhibition of Porcine Endogenous Retrovirus by Multi-Targeting Micro RNA Against Long Terminal Region.

BACKGROUND: There might be much benefit in xenotransplantation, however, the risk of infections across species barriers remains, especially porcine endogenous retrovirus (PERV). To date, many attempts have been made to knock down active PERVs by inhibitory RNA (RNAi) and micro RNA (miRNA), which target different genes of PERV. There are a few studies that have explored whether targeting promoter regions of PERV could exert an inhibition effect. METHODS: miRNAs were automatically selected based on an online program BLOCK-iT RNAi Designer. The inhibition efficiency between miRNAs was compared based on their inhibition of different PERV genes: long terminal repeats (LTR), gag, and pol. Both relative quantitative real-time polymerase chain reaction (PCR) and C-type reverse transcriptase activity were performed. RESULTS: The results demonstrated that miRNA targeting the LTR region degraded the target sequence, and simultaneously inhibited the mRNA expression of both gag and pol genes of PERV. The LTR1, LTR2, and dual LTR1 + LTR2 miRNA inhibited 76.2%, 22%, and 76.8% of gag gene expression, respectively. Similarly, the miRNA was found to knock down the pol gene expression of 69.8%, 25.5%, and 77.7% for single targeting miRNA (LTR1 and LTR2) and multi-targeting miRNA (LTR1 + LTR2), respectively. A stable PK15 clone constitutively expressed dual LTR1 + LTR2 miRNA and exhibited higher inhibitory up to 82.8% and 92.7% of the expressions of the gag and pol genes, respectively. Also, the result of co-cultivation of dual LTR1 + LTR2 miRNA transfected PK15 cell with a human cell line inhibited expression of LTR, gag, and pol genes of PERV. CONCLUSIONS: In conclusion, this study suggested that the LTR might be an alternative target for gene silencing of PERV, and that multi-targeting miRNA had better inhibitory effect than single- targeting miRNA. In an in vitro model, the presence of miRNA was able to reduce PERV infectivity in a human cell line.

Non-local means filter denoising for DEXA images.

Dual high and low energy images of Dual Energy X-ray Absorptiometry (DEXA) suffer from noises due to the use of weak amount of X-rays. Denoising these DEXA images could be a key process to enhance and improve a Bone Mineral Density (BMD) map which is derived from a pair of high and low energy images. This could further improve the accuracy of diagnosis of bone fractures, osteoporosis, and etc. In this paper, we present a denoising technique for dual high and low energy images of DEXA via non-local means filter (NLMF). The noise of dual DEXA images is modeled based on both source and detector noises of a DEXA system. Then, the parameters of the proposed NLMF are optimized for denoising utilizing the experimental data from uniform phantoms. The optimized NLMF is tested and verified with the DEXA images of the uniform phantoms and real human spine. The quantitative evaluation shows the improvement of Signal-to-Noise Ratio (SNR) for the high and low phantom images on the order of 30.36% and 27.02% and for the high and low real spine images on the order of 22.28% and 33.43%, respectively. Our work suggests that denoising via NLMF could be a key preprocessing process for clinical DEXA imaging.

Randomized clinical trial of immersive virtual reality tour of the operating theatre in children before anaesthesia.

BACKGROUND: A virtual reality (VR) tour of the operating theatre before anaesthesia could provide a realistic experience for children. This study was designed to determine whether a preoperative VR tour could reduce preoperative anxiety in children. METHODS: Children scheduled for elective surgery under general anaesthesia were randomized into a control or VR group. The control group received conventional information regarding anaesthesia and surgery. The VR group watched a 4-min video showing Pororo, the famous little penguin, visiting the operating theatre and explaining what is in it. The main outcome was preoperative anxiety, assessed using the modified Yale Preoperative Anxiety Scale (m-YPAS) before entering the operating theatre. Secondary outcomes included induction compliance checklist (ICC) and procedural behaviour rating scale (PBRS) scores during anaesthesia. RESULTS: A total of 69 children were included in the analysis, 35 in the control group and 34 in the VR group. Demographic data and induction time were similar in the two groups. Children in the VR group had a significantly lower m-YPAS score than those in the control group (median 31·7 (i.q.r. 23·3-37·9) and 51·7 (28·3-63·3) respectively; P < 0·001). During anaesthesia, the VR group had lower ICC and PBRS scores than the control group. CONCLUSION: This preoperative VR tour of the operating theatre was effective in alleviating preoperative anxiety and increasing compliance during induction of anaesthesia in children undergoing elective surgery. Registration number: UMIN000025232 (http://www.umin.ac.jp/ctr).

Two Commercial Type 1 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-Modified Live Vaccines Reduce Seminal Shedding of Type 1 PRRSV but not Type 2 PRRSV in Infected Boars.

The objective of this study was to compare the effects of two commercial type 1 porcine reproductive and respiratory syndrome virus (PRRSV)-modified live vaccines on type 1 and type 2 PRRSV shedding in the semen of experimentally infected boars. Upon challenge with PRRSV, unvaccinated boars exhibited an increase in daily rectal temperature (39.4-39.7°C). Vaccination of boars with type 1 PRRSV significantly reduced the amount of type 1 PRRSV load in blood and semen after challenge with type 1 PRRSV, but barely reduced the amount of type 2 PRRSV load in blood and semen after the type 2 PRRSV challenge. There were no significant differences in the reduction of viremia and seminal shedding of type 1 and type 2 PRRSV between the two commercial vaccines. The seminal shedding of PRRSV is independent of viremia. The reduction of type 1 PRRSV seminal shedding coincided with the appearance of type 1 PRRSV-specific interferon-γ secreting cells (IFN-γ-SC) in vaccinated type 1 PRRSV-challenged boars. The frequencies of type 1 PRRSV-specific IFN-γ-SC induced by type 1 PRRSV vaccine are relatively high compared to type 2 PRRSV-specific IFN-γ-SC induced by the same vaccine which may explain why type 1 PRRSV vaccine is more effective in reducing seminal shedding of type 1 PRRSV when compared to type 2 PRRSV in vaccinated challenged boars. These results provide clinical information on how to reduce seminal shedding of type 1 PRRSV in boars using type 1 PRRSV-modified live vaccine.

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy.

Retraction to: Cell Death Differ 2016;23(9):1471­1482. doi:10.1038/cdd.2016.32

Randomized clinical trial of preoperative skin antisepsis with chlorhexidine gluconate or povidone-iodine.

BACKGROUND: Skin antiseptic agents are used to prevent surgical-site infection (SSI); few trials have reported the superiority of any specific agent in clean-contaminated abdominal surgery. This RCT was designed to compare the effectiveness of chlorhexidine gluconate and povidone-iodine. METHODS: Consecutive patients who underwent clean-contaminated upper gastrointestinal or hepatobiliary-pancreatic open surgery between 2011 and 2014 were assigned randomly to either chlorhexidine gluconate or povidone-iodine. The primary endpoint was the occurrence of SSI within 30 days of surgery. Secondary endpoints included causative organisms and risk factors for SSI. RESULTS: A total of 534 patients were randomized; 31 (5·8 per cent) developed an SSI. There was no difference in the overall SSI rate in the chlorhexidine gluconate and povidone-iodine groups: 15 of 267 (5·6 per cent) and 16 of 267 (6·0 per cent) respectively (P = 0·853). The most common causative organism was Enterococcus faecalis. In subgroup analysis, biliary-pancreatic surgery had a higher SSI rate (26 of 127, 20·5 per cent) than upper gastrointestinal (2 of 204, 1·0 per cent) and hepatic (3 of 203, 1·5 per cent) resection. Both age (60 years and over) and type of incision were associated with the risk of SSI. CONCLUSION: No difference was detected between chlorhexidine gluconate and povidone-iodine antiseptics for prevention of SSI. Registration number: NCT01495117 (http://www.clinicaltrials.gov).

Emergence of Panton-Valentine leucocidin-positive ST8-methicillin-resistant Staphylococcus aureus (USA300 clone) in Korea causing healthcare-associated and hospital-acquired bacteraemia.

Panton-Valentine leucocidin (PVL)-positive sequence type (ST)8-MRSA-SCCmec IVa (USA300) is the epidemic strain of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in North America. USA300 is extremely rare in South Korea, and PVL-negative ST72 SCCmec type IVc is the predominant CA-MRSA clone. In a multicentre, prospective cohort study of S. aureus bacteraemia, we identified PVL-positive ST8-MRSA isolates by performing multilocus sequence typing and PCR for PVL. We analyzed the clinical characteristics of patients with PVL-positive ST8-MRSA bacteraemia, and performed SCCmec, spa, and agr typing, PCR for arginine catabolic mobile element (ACME), virulence gene profiling, and pulsed-field gel electrophoresis (PFGE). Among a total of 818 MRSA isolates, we identified ten isolates of PVL-positive ST8-MRSA (USA300) (3 from Hospital D, 4 from Hospital G, and 3 from Hospital A), all of which involved exclusively healthcare-associated (5 isolates) and hospital-acquired bacteraemia (5 isolates). This strain accounted for 8~10 % of the hospital-acquired MRSA bacteraemia in Hospitals D and G. Bacteraemia of unknown origin was the most common type of infection followed by pneumonia. All the isolates were SCCmec type IVa, spa type t008, and agr group I. Eight of the isolates harboured ACME. In a PFGE analysis, four isolates were identical to the USA300 control strain, five differed by a single band, and the remaining one differed by two bands. All the isolates were pulsed-field type USA300. This is the first report of healthcare-associated and hospital-acquired bacteraemia caused by USA300 in South Korea. USA300 seems to be an emerging hospital clone in this country.

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy.

Radioresistance is a major obstacle in successful clinical cancer radiotherapy, and the underlying mechanisms are not clear. Here we show that IKKα-mediated miR-196a biogenesis via interaction with Drosha regulates the sensitivity of nasopharyngeal carcinoma (NPC) cells to radiotherapy. Phosphorylation of IKKα at T23 site (p-IKKαT23) promotes the binding of IKKα to Drosha that accelerates the processing of miR-196a primary transcripts, leading to increased expressions of both precursor and mature miR-196a. Dephosphorylation of p-IKKαT23 downregulates miR-196a expression and promotes the resistance of NPC cells to radiation treatment. The miR-196a mimic suppresses while its inhibitor promotes the resistance of NPC to radiation treatment. Importantly, the expression of p-IKKαT23 is positively related to the expression of miR-196a in human NPC tissues, and expression of p-IKKαT23 and miR-196a is inversely correlated with NPC clinical radioresistance. Thus, our studies establish a novel mechanistic link between the inactivation of IKKαT23-Drosha-miR-196a pathway and NPC radioresistance, and de-inactivation of IKKαT23-Drosha-miR-196a pathway would be an efficient way to restore the sensitivity of radioresistant NPC to radiotherapy.

Comparison of commercial type 1 and type 2 PRRSV vaccines against heterologous dual challenge.

This study was to compare the effect of vaccination of pigs with either type 1 or type 2 porcine reproductive and respiratory syndrome virus (PRRSV) against heterologous dual challenge of both genotypes. Pigs were administered type 1 (UNISTRAIN PRRS) or type 2 (Fostera PRRS) PRRSV vaccine at 28 days of age and inoculated intranasally with both genotypes at 63 days of age. Vaccination of pigs with type 1 PRRSV was able to reduce the levels of type 1 but not type 2 PRRSV viraemia, whereas vaccination of pigs with type 2 PRRSV was able to reduce the levels of type 1 and type 2 PRRSV viraemia against a dual challenge. Vaccination of pigs with type 2 PRRSV significantly reduced lung lesions after dual challenge compared with vaccination of pigs with type 1 PRRSV. Vaccination of pigs with type 2 PRRSV induced higher numbers of type 1 and type 2 PRRSV-specific interferon-γ secreting cells compared with vaccination of pigs with type 1 PRRSV after dual challenge. The results of this study demonstrated that vaccination of pigs with type 2 PRRSV is efficacious in protecting growing pigs from respiratory disease after heterologous dual type 1 and type 2 PRRSV challenge compared with vaccination of pigs with type 1 PRRSV.

Differential Expression of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Open Reading Frame 5, but not Apoptogenic Cytokines, Contribute to Severe Respiratory Disease in Pigs Infected with Type 2 PRRSV Compared with Pigs Infected with Type 1 PRRSV.

The aim of this study was to compare the expression of open reading frame 5 (ORF5) of porcine reproductive and respiratory syndrome virus (PRRSV) and apoptogenic cytokines in the lungs from pigs infected with type 1 and type 2 PRRSV. Microscopical lung lesion scores and the mean number of apoptotic cells were significantly (P <0.05) higher in pigs with type 2 PRRSV infection than in those with type 1 PRRSV infection. The score for the mean number of PRRSV ORF5-positive cells per unit area of lung was significantly (P <0.05) higher in pigs with type 2 PRRSV infection. There were no significant differences in the expression of tumour necrosis factor-α and interleukin-1 in lung tissues between type 1 and type 2 PRRSV-infected pigs. The severity of microscopical lung lesions and the number of apoptotic cells correlated well with the number of PRRSV ORF5-positive cells. Therefore, differential expression of PRRSV ORF5, but not apoptogenic cytokines, may attribute to the severity of lung lesions and apoptosis in lungs in PRRSV infection. These results suggest that expression of PRRSV ORF5 may be a critical determinant for different virulence between PRRSV genotypes in terms of respiratory disease.

Impact of Intra-Abdominal Adhesion on Living Donor Right Hepatectomy.

The impact of intra-abdominal adhesion (IAA) on living donor right hepatectomy (LDRH) remains to be clarified. The purpose of this study was to compare both the donor and recipient outcomes of right lobe living donor liver transplantation according to IAA detected intraoperatively. LDRH donors were identified through a prospectively maintained database at the authors' institution between March 2008 and February 2014. IAA was graded according to Beck et al (Dis Colon Rectum 2000; 43: 1749-1753). LDRH donors with IAA (group A) were matched 1:3 to those without IAA (group B) based on age, gender, and BMI. Perioperative data, complications by the Clavien classification, and the outcomes with at least 12 months follow-up were compared. Thirty-two (7.6%) of a total of 420 LDRH donors had IAA around the liver. Nineteen donors had previous abdominal surgery. LDRH was successfully completed under upper midline laparotomy in all donors. Compared with group B, group A had a longer operative time (270 vs. 172 min; p < 0.001), a higher wound complication rate (28.1% vs. 4.2%; p = 0.009), and a longer postoperative stay (10 vs. 7 days; p = 0.009). All donors recovered completely to their previous activities. The 1-year graft and recipient survivals of recipients were comparable between two groups. These findings support the feasibility and safety of LDRH in patients with IAA.

Renal denervation for treatment of uncontrolled hypertension in an Asian population: results from the Global SYMPLICITY Registry in South Korea (GSR Korea).

Reports detailing the response of hypertensive patients to renal denervation (RDN) in Asian patients are limited. We evaluated 6- and 12-month outcomes after RDN in an Asian population and compared outcomes to a primarily Caucasian population. The Global SYMPLICITY Registry (GSR) is a prospective, all-comer, worldwide registry that evaluates the safety and effectiveness of RDN and includes the Korean registry substudy (GSR Korea) and a Caucasian subset (GSR Caucasian). Given differences in baseline characteristics among GSR Korea (n=93) as compared with GSR Caucasian (n=169) patients, including lower baseline office systolic blood pressure (SBP), lower body mass index and differences in medications, propensity score adjustment was performed when comparing the change in SBP between subsets. The 6- and 12-month change in SBP in GSR Korea was -19.4±17.2 and -27.2±18.1 mm Hg, respectively (P<0.001 for both vs baseline). GSR Caucasian had a SBP change similar to GSR Korea at 6 months (-20.9±21.4 mm Hg, unadjusted P=0.547, adjusted P=0.998), whereas at 12 months the change was significantly less pronounced (-20.1±23.9 mm Hg, unadjusted P=0.004, adjusted P=0.002). There were no protocol-defined procedure-related adverse events and no chronic adverse events associated with the device in an Asian population. RDN provided a significant reduction in 6- and 12-month office SBP among Asian patients, with a favorable safety profile. The 12-month SBP reduction was larger than that observed in Caucasian patients.

Risk factors for sepsis in Korean trauma patients.

PURPOSE: Sepsis in severely injured patients is one of the leading causes of death in hospitals. The incidence of and risk factors for sepsis after trauma have been studied outside, but not within Korea. Therefore, this study investigated the incidence of sepsis and the independent risk factors for sepsis in moderately to severely injured patients in Korea. METHODS: The electronic medical records of patients who visited the emergency department from January 2010 to December 2012 were reviewed retrospectively. Patients older than 18 years of age with an Injury Severity Score (ISS) greater than or equal to nine points were included. RESULTS: A total of 183 patients met the study inclusion criteria. The median ISS was 14 (range 9-17) points and 15 (8 %) patients developed sepsis. The patients' age [adjusted OR, 1.053; 95 % confidence intervals (CI), 1.015-1.094], ISS (adjusted OR, 1.114; 95 % CI, 1.046-1.187), and emergency surgery (adjusted OR, 3.727; 95 % CI, 1.051-13.221) were independent risk factors for post-traumatic sepsis. CONCLUSIONS: Among the risk factors identified in the literature, our research confirmed only the patients' age and ISS as risk factors for sepsis after trauma, and, additionally, identified emergency surgery as a risk factor in Korean patients. Therefore, trauma patients who have any of the risk factors mentioned above have a high risk of post-traumatic sepsis, which requires certain precautionary clinical measures.

MacroH2A1 downregulation enhances the stem-like properties of bladder cancer cells by transactivation of Lin28B.

The histone variant, macroH2A1, has an important role in embryonic stem cell differentiation and tumor progression in various types of tumors. However, the regulatory roles of macroH2A1 on bladder cancer progression have not been fully elucidated. Here, we show that macroH2A1 knockdown promotes stem-like properties of bladder cancer cells. The knockdown of macroH2A1 in bladder cancer cells increased tumorigenicity, radioresistance, degeneration of reactive oxygen species, increased sphere formation capability and an increase in the proportion of side populations. We found that macroH2A1 is required for the suppression of Lin28B identified as a novel downstream target of macroH2A1 in bladder cancer. Loss of macroH2A1 expression significantly correlated with the elevated levels of Lin28B expression and subsequently inhibited the mature let-7 microRNA expression. Furthermore, the stable overexpression of Lin28B enhances the several phenotypes, including tumorigenicity and sphere-forming ability, which are induced by macroH2A1 depletion. Importantly, Lin28B expression was regulated by macroH2A1-mediated reciprocal binding of p300 and EZH2/SUV39H1. Our results suggest that Lin28B/let-7 pathway is tightly regulated by macroH2A1 and its cofactors, and have a pivotal role in the bladder tumor progression and the regulation of stem-like characteristics of bladder cancer cells.

Advances, practice, and clinical perspectives in high-throughput sequencing.

Remarkable advances in high-throughput sequencing technologies have fundamentally changed our understanding of the genetic and epigenetic molecular bases underlying human health and diseases. As these technologies continue to revolutionize molecular biology leading to fresh perspectives, it is imperative to thoroughly consider the enormous excitement surrounding the technologies by highlighting the characteristics of platforms and their global trends as well as potential benefits and limitations. To date, with a variety of platforms, the technologies provide an impressive range of applications, including sequencing of whole genomes and transcriptomes, identifying of genome modifications, and profiling of protein interactions. Because these applications produce a flood of data, simultaneous development of bioinformatics tools is required to efficiently deal with the big data and to comprehensively analyze them. This review covers the major achievements and performances of the high-throughput sequencing and further summarizes the characteristics of their applications along with introducing applicable bioinformatics tools. Moreover, a step-by-step procedure for a practical transcriptome analysis is described employing an analytical pipeline. Clinical perspectives with special consideration to human oral health and diseases are also covered.

Pretransplant serum levels of C-reactive protein predict prognoses in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: Preoperative absolute C-reactive protein (CRP) has been shown to correlate with prognoses in various malignancies, including hepatocellular carcinoma (HCC). METHODS: The aim of this study was to investigate whether pretransplant CRP levels predict prognoses in patients undergoing liver transplantation (LT) for HCC. We retrospectively analyzed clinicopathological factors in 211 patients with available pretransplant serum CRP levels who underwent LT for HCC between January 2005 and April 2012. RESULTS: By means of receiver operating characteristic curve analysis, a CRP level of >0.3 mg/dL was considered to be elevated. By multivariate analysis, the high CRP level, the maximal tumor size >5 cm, the presence of intrahepatic metastasis, and positive findings in pretransplant (18)fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) were related to tumor recurrence, whereas the high CRP level, the presence of intrahepatic metastasis, and positive findings in pretransplant (18)F-FDG PET/CT were related to poor overall survival. When subgroup analysis was conducted according to the Milan criteria, the high CRP level was an independent factor for predicting poor outcomes in patients with HCC beyond the Milan criteria (P = .001 for recurrence-free survival and P = .010 for overall survival), and not for patients within the criteria. CONCLUSIONS: Pretransplant serum CRP levels can predict prognoses in patients undergoing LT for HCC, especially in patients with HCC exceeding the Milan criteria.

Comparison of LTBI treatment regimens for patients receiving anti-tumour necrosis factor therapy.

SETTING: A tertiary referral centre in South Korea. OBJECTIVE: To compare the completion rates and adverse drug reactions of three latent tuberculous infection (LTBI) treatment regimens for patients receiving anti-tumour necrosis factor (anti-TNF) therapy. DESIGN: A total of 408 patients were diagnosed with LTBI before receiving anti-TNF therapy between December 2004 and December 2013. Nine months of isoniazid (9H), 4 months of rifampicin (4H) or 3 months of isoniazid/rifampicin (3HR) were prescribed. The results were analysed retrospectively. RESULTS: The mean age of the 408 study subjects was 44 years; 258 (63.2%) were male. The 9H, 4R and 3HR treatment regimens were given to respectively 61 (15.0%), 139 (34.1%) and 208 (51.0%) patients. A total of 362 (88.7%) patients completed the treatment. The treatment completion rate was highest in patients receiving 3HR (94.2%). Of the 408 patients, 54 (13.2%) had one or more adverse drug reactions; their frequency was similar in the three groups. CONCLUSIONS: In patients receiving anti-TNF therapy, 3HR seems to be the most acceptable treatment regimen for LTBI, given its high completion rate and acceptable rate of adverse drug reactions.