Reversing immunosuppression in the tumor microenvironment of fibrolamellar carcinoma via PD-1 and IL-10 blockade.

Fibrolamellar carcinoma (FLC) is a rare liver tumor driven by the DNAJ-PKAc fusion protein that affects healthy young patients. Little is known about the immune response to FLC, limiting rational design of immunotherapy. Multiplex immunohistochemistry and gene expression profiling were performed to characterize the FLC tumor immune microenvironment and adjacent non-tumor liver (NTL). Flow cytometry and T cell receptor (TCR) sequencing were performed to determine the phenotype of tumor-infiltrating immune cells and the extent of T cell clonal expansion. Fresh human FLC tumor slice cultures (TSCs) were treated with antibodies blocking programmed cell death protein-1 (PD-1) and interleukin-10 (IL-10), with results measured by cleaved caspase-3 immunohistochemistry. Immune cells were concentrated in fibrous stromal bands, rather than in the carcinoma cell compartment. In FLC, T cells demonstrated decreased activation and regulatory T cells in FLC had more frequent expression of PD-1 and CTLA-4 than in NTL. Furthermore, T cells had relatively low levels of clonal expansion despite high TCR conservation across individuals. Combination PD-1 and IL-10 blockade signficantly increased cell death in human FLC TSCs. Immunosuppresion in the FLC tumor microenvironment is characterized by T cell exclusion and exhaustion, which may be reversible with combination immunotherapy.

Ribosomal protein S3 associates with the TFIIH complex and positively regulates nucleotide excision repair.

In mammalian cells, the bulky DNA adducts caused by ultraviolet radiation are mainly repaired via the nucleotide excision repair (NER) pathway; some defects in this pathway lead to a genetic disorder known as xeroderma pigmentosum (XP). Ribosomal protein S3 (rpS3), a constituent of the 40S ribosomal subunit, is a multi-functional protein with various extra-ribosomal functions, including a role in the cellular stress response and DNA repair-related activities. We report that rpS3 associates with transcription factor IIH (TFIIH) via an interaction with the xeroderma pigmentosum complementation group D (XPD) protein and complements its function in the NER pathway. For optimal repair of UV-induced duplex DNA lesions, the strong helicase activity of the TFIIH complex is required for unwinding damaged DNA around the lesion. Here, we show that XP-D cells overexpressing rpS3 showed markedly increased resistance to UV radiation through XPD and rpS3 interaction. Additionally, the knockdown of rpS3 caused reduced NER efficiency in HeLa cells and the overexpression of rpS3 partially restored helicase activity of the TFIIH complex of XP-D cells in vitro. We also present data suggesting that rpS3 is involved in post-excision processing in NER, assisting TFIIH in expediting the repair process by increasing its turnover rate when DNA is damaged. We propose that rpS3 is an accessory protein of the NER pathway and its recruitment to the repair machinery augments repair efficiency upon UV damage by enhancing XPD helicase function and increasing its turnover rate.

Enhanced antimicrobial stewardship based on rapid phenotypic antimicrobial susceptibility testing for bacteraemia in patients with haematological malignancies: a randomized controlled trial.

OBJECTIVES: Recently, rapid phenotypic antimicrobial susceptibility testing (AST) based on microscopic imaging analysis has been developed. The aim of this study was to determine whether implementation of antimicrobial stewardship programmes (ASP) based on rapid phenotypic AST can increase the proportion of patients with haematological malignancies who receive optimal targeted antibiotics during early periods of bacteraemia. METHODS: This randomized controlled trial enrolled patients with haematological malignancies and at least one positive blood culture. Patients were randomly assigned 1:1 to conventional (n = 60) or rapid phenotypic (n = 56) AST. The primary outcome was the proportion of patients receiving optimal targeted antibiotics 72 hr after blood collection for culture. RESULTS: The percentage receiving optimal targeted antibiotics at 72 hr was significantly higher in the rapid phenotypic AST group (45/56, 80.4%) than in conventional AST group (34/60, 56.7%) (relative risk (RR) 1.42, 95% confidence interval (CI) 1.09-1.83). The percentage receiving unnecessary broad-spectrum antibiotics at 72 hr was significantly lower (7/26, 12.5% vs 18/60, 30.0%; RR 0.42, 95% CI 0.19-0.92) and the mean time to optimal targeted antibiotic treatment was significantly shorter (38.1, standard deviation (SD) 38.2 vs 72.8, SD 93.0 hr; p < 0.001) in the rapid phenotypic AST group. The mean time from blood collection to the AST result was significantly shorter in the rapid phenotypic AST group (48.3, SD 17.6 vs 83.1, SD 22.2 hr). DISCUSSION: ASP based on rapid phenotypic AST can rapidly optimize antibiotic treatment for bacteraemia in patients with haematological malignancy. Rapid phenotypic AST can improve antimicrobial stewardship in immunocompromised patients.

Early Vs Late Liver Retransplantation: Different Characteristics and Prognostic Factors.

BACKGROUND: East Asia is a known endemic area for hepatitis B, and living donor liver transplantation is mainly performed. Liver retransplantation (ReLT) is expected to become an increasing problem because of a shortage of organs. This study aimed to compare early and late ReLT with consideration of specific circumstances and disease background of East Asians. METHODS: Between October 1996 and January 2015, 51 patients underwent ReLT; we performed a retrospective analysis of data obtained from medical records of the patients. Clinical characteristics, indication, causes of death, survival rate, and prognostic factors were investigated. RESULT: The survival rate for early ReLT (n = 18) was 51.5% and that for late ReLT (n = 33) was 50.1% at 1 year postoperatively. Continuous venovenous hemodialysis and the use of mechanical ventilators were more frequent, and pre-retransplant intensive care unit stay and prothrombin time was longer in early ReLT than in late ReLT. Operation time was longer and the amount of intraoperative blood loss was greater in late ReLT than in early ReLT. Multivariate analysis showed that a higher C-reactive protein level increased mortality in early ReLT (P = .045), whereas a higher total bilirubin level increased the risk of death in late ReLT (P = .03). CONCLUSION: Patients with early ReLT are likely to be sicker pre-retransplantation and require adequate treatment of the pretransplant infectious disease. On the other hand, late ReLT is likely to be technically more difficult and should be decided before the total bilirubin level increases substantially.

Detection and classification of the breast abnormalities in digital mammograms via regional Convolutional Neural Network.

Automatic detection and classification of the masses in mammograms are still a big challenge and play a crucial role to assist radiologists for accurate diagnosis. In this paper, we propose a novel computer-aided diagnose (CAD) system based on one of the regional deep learning techniques: a ROI-based Convolutional Neural Network (CNN) which is called You Only Look Once (YOLO). Our proposed YOLO-based CAD system contains four main stages: mammograms preprocessing, feature extraction utilizing multi convolutional deep layers, mass detection with confidence model, and finally mass classification using fully connected neural network (FC-NN). A set of training mammograms with the information of ROI masses and their types are used to train YOLO. The trained YOLO-based CAD system detects the masses and classifies their types into benign or malignant. Our results show that the proposed YOLO-based CAD system detects the mass location with an overall accuracy of 96.33%. The system also distinguishes between benign and malignant lesions with an overall accuracy of 85.52%. Our proposed system seems to be feasible as a CAD system capable of detection and classification at the same time. It also overcomes some challenging breast cancer cases such as the mass existing in the pectoral muscles or dense regions.

Seropositivity and identification of paramyosin for sparganosis in the Kangwon and Incheon provinces of the Republic of Korea.

Sparganosis is one of the top three tissue-dwelling heterologous helminthic diseases, along with cysticercosis and paragonimiasis, in Korea. Due to a lack of effective early diagnosis and treatment methods, this parasitic disease is regarded as a public health threat. This study evaluated reactivity, against sparganum extracts, of sera from inhabitants of Cheorwon-gun, Goseong-gun and Ongjin-gun in Korea. The sera from 836 subjects were subjected to enzyme-linked immunosorbent assay and immunoblot analysis. The sera from 18 (5.8%) and 15 (5.1%) inhabitants in Cheorwon-gun (n = 312) and Goseong-gun (n = 294), respectively, exhibited highly positive reactions to the sparganum antigen, whereas only two (0.9%) inhabitants in Ongjin-gun (n = 230) showed positivity. We sought antigenic proteins for serodiagnosis of positive sera by immunoproteomic approaches. Total sparganum lysates were separated by two-dimensional electrophoresis and then subjected to immunoblot analysis with mixed sparganosis-positive sera. We found seven antigenic spots and identified paramyosin as an antigenic protein by liquid chromatography-mass spectrometry. By two-dimensional (2D)-based mass analysis and immunoblotting against sparganosis-positive sera, paramyosin was identified as a candidate antigen for serodiagnosis of sparganosis.

LincRNA-p21 acts as a mediator of ING1b-induced apoptosis.

ING1b is a tumor suppressor that affects transcription, cell cycle control and apoptosis. ING1b is deregulated in disease, and its activity is closely linked to that of p53. In addition to regulating protein-coding genes, we found that ING1b also influences the expression of large intergenic non-coding RNAs (lincRNAs). In particular, lincRNA-p21 was significantly induced after DNA-damage stress or by ING1b overexpression. Furthermore, lincRNA-p21 expression in response to DNA damage was significantly attenuated in cells lacking ING1b. LincRNA-p21 is also a target of p53 and can trigger apoptosis in mouse cell models. We found that this function of lincRNA-p21 is conserved in human cell models. Moreover, ING1b and p53 could function independently to influence lincRNA-p21 expression. However, their effects become more additive under conditions of stress. In particular, ING1b regulates lincRNA-p21 levels by binding to its promoter and is required for induction of lincRNA-p21 by p53. The ability of ING1b to cause apoptosis is also impaired in the absence of lincRNA-p21. Surprisingly, deletion of the ING1b plant homeodomain, which allows it to bind histones and regulate chromatin structure, did not alter regulation of lincRNA-p21. Our findings suggest that ING1b induces lincRNA-p21 expression independently of histone 3 lysine 4 trimethylation mark recognition and that lincRNA-p21 functions downstream of ING1b. Thus, regulation at the level of lincRNA-p21 may represent the point at which ING1b and p53 pathways converge to induce apoptosis under specific stress conditions.

Development progresses of radio frequency ion source for neutral beam injector in fusion devices.

A large-area RF (radio frequency)-driven ion source is being developed in Germany for the heating and current drive of an ITER device. Negative hydrogen ion sources are the major components of neutral beam injection systems in future large-scale fusion experiments such as ITER and DEMO. RF ion sources for the production of positive hydrogen (deuterium) ions have been successfully developed for the neutral beam heating systems at IPP (Max-Planck-Institute for Plasma Physics) in Germany. The first long-pulse ion source has been developed successfully with a magnetic bucket plasma generator including a filament heating structure for the first NBI system of the KSTAR tokamak. There is a development plan for an RF ion source at KAERI to extract the positive ions, which can be applied for the KSTAR NBI system and to extract the negative ions for future fusion devices such as the Fusion Neutron Source and Korea-DEMO. The characteristics of RF-driven plasmas and the uniformity of the plasma parameters in the test-RF ion source were investigated initially using an electrostatic probe.

Monitoring and treatment for BK virus after kidney transplantation.

BACKGROUND: The BK nephropathy (BKN) shows a 10% prevalence among cases of kidney transplantation (KT). We assessed the incidence of BK replication in KT recipients as well as our updated screening strategy and the impact of interventions on BK virus infections. METHODS: Since September 2007, our screening protocol for BK virus included examination of urine cytology or BK virus DNA real-time polymerase chain reaction (PCR) detection on postoperative days 1, 5, 9, 16, 24, 36, 48 weeks up to 1 year. IR present, we tested urine BK virus DNA PCR quantitation. We applied the updated screening protocol from August 2010. It urine BK DNA PCR quantification was above 10(7) copies/mL, we checked regularly blood the BK virus DNA PCR quantification. In addition, if the blood BK virus DNA load was above 10(4) copies/mL and the serum creatinine elevated, we was performed an allograft biopsy. Between September 2007 and December 2011, the 58 recipients who showed BK viremia were enrolled in the present study in 2 groups according to the period of screening protocol (era I, era II). RESULTS: The time between kidney transplantation and BK viremia detection of era II was shorter than that of era I (16 vs 29 weeks; P = .001). Viremia clearance rate at 6 months in era II was significant higher than that of era I (82% vs 36.8%; P = .001) as well as at 12 months (100% vs 61.1%, P < .001) after intervention. Interestingly, viremia clearance at 12 months after intervention was 100% in era II. CONCLUSION: An updated screening protocol for BK virus allowed early detection and accurate diagnosis of BKN. Early detection of BK virus infection enabled early intervention and improved viral clearance rate.

Presence of vesicoureteral reflux in the graft kidney does not adversely affect long-term graft outcome in kidney transplant recipients.

INTRODUCTION: We studied the incidence of vesicoureteral reflux (VUR) in the graft kidney and its effect on the occurrence of urinary tract infection (UTI) and long-term graft function. METHODS: We performed a retrospective analysis of 64 adult kidney transplant recipients based upon voiding cystourethrography at 12 months post-transplantation. Patients underwent analysis of survival, incidence of UTIs beyond 1 year, and graft function. RESULTS: Thirty-seven male and 27 female patients in the study populations showed a mean age 42 years. VUR in the transplanted kidney at 12 months post-transplant occurred among 78.1% (50/64) of subjects: grade I (n = 6), grade II (n = 30), or grade III (n = 14) reflux. Patients followed for a median 61 months (range 44-74s) showed 11 cases of UTIs in 9 subjects. There were no significant differences in clinical characteristics or incidence of, UTIs according to the presence or severity of VUR (P = .81) or the Serum creatinine and estimated glomerular filtration rate values at 12, 36, 48, or 60 months post-transplantation. CONCLUSIONS: VUR present in 78.1% of patients after kidney transplantation affected neither graft functions or graft survival. The incidence of UTI did not differ according to the presence of VUR.

Comparison between resection and transplantation in combined hepatocellular and cholangiocarcinoma.

OBJECTIVE: The treatment of choice for combined hepatocellular and cholangiocarcinoma (cHCC-CC) is surgical resection. However, the efficacy of liver transplantation is not clear. We compared the surgical outcome of hepatic resection and liver transplantation for cHCC-CC. PATIENTS AND METHODS: From 1995 to 2012, 89 patients were diagnosed with cHCC-CC after hepatic resection and 8 patients diagnosed with cHCC-CC after liver transplantation. We excluded 21 patients who were American Joint Committee on Cancer Staging Stage III or IV and lost to follow-up. The outcomes were reviewed retrospectively. RESULTS: The poor prognostic factors in cHCC-CC patients who underwent hepatectomy were large tumor size (>5 cm), small safety margin (<2 cm), and low preoperative albumin level. The disease-free survival (DFS) and overall survival (OS) between the hepatectomy group (n = 68) and the liver transplant group (n = 8) was not statistically different (5-year DFS: 26.2% vs 37.5%, P = .333; 5-year OS: 42.1% vs 50%, P = .591). In the small tumor subgroup (tumor size <5 cm), the DFS and OS between the 2 surgical procedures was not different, and in the adequate resection margin subgroup (safety margin >2 cm), survival was comparable. CONCLUSIONS: In well-selected cases with small tumor size and with preserved liver function, liver resection should be considered when complete resection is possible.

Optimal device and method for transportation of isolated porcine islet.

INTRODUCTION: We investigated the optimal method for transportation of isolated porcine islets from an isolation facility to a transplant hospital or research center in terms of temperature, oxygen supply, and shaking effect. METHODS: Commercially available insulator boxes with thermoregulators exposed for 5 hours under two external temperatures (4°C and 37°C) were monitored using HOBO temperature loggers. To find the optimal transport device, we compared islet counts, viability, quality, and function in conical tubes, gas-permeable bags (GPB) and gas-permeable flasks (GPF) after 1, 3 and 5 hours. To evaluate the effects of shaking on islets, we also analyzed the difference between a control and a shaking group in each device with time. RESULTS: Commercially available Styrofoam insulators with thermoregulators maintained the internal temperature near the target. Islet recovery rate for GPF, which was higher than other devices, was maintained, while those decreased with time for conical tube and GPB containers adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio for GPF was lower than other devices, albeit not significantly fluoroscein acrimide/propidium iodide (AO/PI) ratio for GPF was higher than other devices after 5 hours. Glucose stimulated index was not different among the devices. In comparison with the control group, shaking yielded comparable islet survival, viability and function. CONCLUSION: Our study demonstrated that the use of commercially available insulator boxes with thermoregulators maintained internal temperature close to the target value and that GPF was more favorable for islet oxygenation during transportation. This study also suggested negligible impact of shaking on isolated porcine islets during transportation.

Jejunal artery can be a useful option for arterial reconstruction in living donor liver transplantation when the suitable arterial inflow is absent.

Successful arterial reconstruction is essential for liver transplantation. In the case of inadequate arterial inflow, an arterial conduit from the aorta using artery graft or re-establishment of arterial flow through other arteries such as the splenic artery, gastroepiploic, or sigmoid artery is considered. Herein we report our experience of 27 cases of hepatic artery reconstruction using alternative methods. The most common cause of hepatic artery reconstruction requiring alternative methods was intimal dissection for which we usually used the gastroepiploic artery. Many patients had a previous operation or transarterial chemoembolization history. Among these cases, hepatic artery reconstruction using the jejunal artery was performed for 2 cases of living donor liver transplantation due to the absence of suitable alternatives. These patients have been followed up with patent hepatic arterial flow until now. Thus, the jejunal artery can be a useful option for arterial reconstruction in living donor liver transplantation when suitable arterial inflow is absent.

High TOP2B/TOP2A expression ratio at diagnosis correlates with favourable outcome for standard chemotherapy in acute myeloid leukaemia.

BACKGROUND: Cytosine arabinoside-based chemotherapy coupled with anthracycline is currently the first-line treatment for acute myeloid leukaemia (AML), but diverse responses to the regimen constitute obstacles to successful treatment. Therefore, outcome prediction to chemotherapy at diagnosis is believed to be a critical consideration. METHODS: The mRNA expression of 12 genes closely involved in the actions of cytosine arabinoside and anthracycline was evaluated by real-time reverse transcriptase PCR (RT-PCR), in 54 diagnostic bone marrow specimens of M2-subtype AML. RESULTS: Low expression levels of ribonucleotide reductase M2 (RRM2) and high expression levels of topoisomerase 2 beta (TOP2B) were correlated with longer survival in a univariate analysis. Another interesting finding is that high ratios of TOP2B/RRM2 and TOP2B/TOP2 alpha (TOP2A) in a combined analysis were also shown to have a prognostic impact for longer survival with improved accuracy. Among the four markers, when adjusted for the influence of other clinical factors in multivariate analysis, the TOP2B/TOP2A ratio was significantly correlated with treatment outcomes; patients with high ratios trended toward longer disease-free survival (HR, 0.24; P=0.002) and overall survival (HR, 0.29; P=0.005). CONCLUSION: Genes with distinct expression profiles such as TOP2B/TOP2A expression ratio at diagnosis can be employed for outcome prediction after the treatment with standard regimens in AML patients with M2 subtype.

Histologically benign but clinically malignant neoplasms in the thorax: CT-pathological overview.

The purpose of this article is to review the computed tomography (CT) and histopathological features of uncommon primary neoplasms of the thorax that can manifest clinically malignant features (multiplicity of pulmonary nodules, an invasive nature, and metastases or recurrence after surgery) with little evidence of histological malignancy.

Can immune function assay predict infection or recovery?

BACKGROUND: Recently, the ImmuKnow assay (Cylex Inc., Columbia, Md) has been reported to be a global immune monitoring tool for organ transplants recipients. We assessed whether immunKnow ATP values predicted infectious syndromes. METHODS: We prospectively enrolled 71 kidney transplant patients between September 2008 and May 2011. lmmuKnow assay monitoring was performed at one dav before as well as 4, 8, 12, 16, 20, 24, 36, and 52 weeks after the operation. ImmuKnow assay values were compared as well as BK viral infection pre-infection(PI), at first detection of infectious syndrome (DI), 4 weeks there after (4W), 8 weeks there after (8W) and 12 weeks there after (12W) and pre-recovery (PR), recovery (R) times. RESULTS: Serial ImmuKnow assays showed significant differences over time and BK viral infectious state (P = .026). Interestingly, PI was significantly lower than DI and PR but PR significant greater than PI, 8W and 12W. However, we did not observe an adequate or absolute cutoff value of ImmuKnow by ROC curve: 377 ng/mL ImmuKnow showed 0.471 of AUC and 57.1% and 56.2%, of sensitivity and specificity. CONCLUSION: Longitudinal evaluation and adjustment of the value of ImmuKnow assay seemed to be a favorable modality to monitor infectious syndromes especially those involving BK virus.

An Outbreak of Onion Center Rot Caused by Pantoea ananatis in Korea.

Symptoms typical of center rot of onion (Allium cepa L.) were observed in farmers' fields in spring of 2009 and 2010 in Hamyang, South Korea, at an incidence of 30 to 50% (five affected fields representing approximately 6 ha). The symptoms were identical to those reported from infected onions in Georgia in 1997 (1). Harvested bulbs of symptomatic plants had reddish, collapsed scales near the neck. Symptomatic bulb tissues were surface-sterilized by immersing sections of the tissue for 30 s in 1% NaOCl, then rinsing the sections with sterilized, distilled water. Tissues were then macerated in 1 ml of sterilized, distilled water in a 1.5 ml Eppendorf tube using a sterile scalpel. The macerated tissue was left to soak for 10 min, after which a 5 µl suspension from each section was streaked onto plates of nutrient agar (NA). Gram-negative, rod-shaped, yellow bacteria were consistently recovered on NA. Three bacterial isolates recovered were each facultative anaerobes and induced a hypersensitive reaction on tobacco leaves. The biochemical test, API 20E (Biomérieux, Marcy l'Etoile, France), was also used for identification. All three strains tested positive for ß-D-galactosidase, utilization of citrate, and production of acetoin, catalase, and indole. All three strains tested negative for ornithine decarboxylase, lysine decarboxylase, urease, and oxidase. All produced acid from arabinose, glucose, mannitol, and sorbitol; while none produced acid from melibiose, inositol, and rhamnose. These characteristics are consistent with those of P. ananatis (1,2). Five bulbs were each surface-disinfested with 70% ethanol, dried, and injected with 50 µl of the appropriate bacterial suspension containing ~108 CFU/ml, using a syringe. The bulbs were placed in plastic boxes with four sheets of wet paper towel to maintain the relative humidity at 100%, and incubated at 25°C for 2 weeks. Three onion bulbs treated similarly but injected with sterilized, distilled water served as replicates of the control treatment. After 1 week of incubation, inoculated onion bulbs developed a brown discoloration and decay of the internal, fleshy scales matching those observed in the original farmers' fields. The control onion bulbs remained asymptomatic. Bacteria reisolated from lesions in the fleshy bulb scales of the inoculated bulbs had the same characteristics as the original isolates inoculated, proving Koch's postulates. Bacteria were not reisolated from any of the control bulbs. To confirm identity of the isolated bacteria, 16S rRNA and recA genes were amplified with primers 27mF: 5'-AGAGTTTGATCMTGGCTCAG-3' and 1492mR: 5'-GGYTACCTTGTTACGACTT-3', and PAGRECA21: 5'-GGTGAAGACCGCTCAATGGA-3' and PAGRECA621: 5'-CACCGATACGGCGGATATCA-3', respectively (3). Amplification of the 16S rRNA gene generated a 1,506-bp consensus sequence (GenBank Accession No. JQ762264), and amplification of the recA gene generated a consensus sequence of 601 bp (JQ762265). The 16S rRNA and recA gene sequences shared 99% nucleotide identity with those of a P. ananatis strain in GenBank (DQ195523 and AY219004, respectively). Based on symptoms, biochemical tests, and molecular analyses, the bacterium responsible for the onion symptoms in Korea was identified as P. ananatis. To our knowledge, this is the first report of center rot of onion caused by P. ananatis in Korea. References: (1) R. D. Gitaitis and J. D. Gay. Plant Dis. 81:1096, 1997. (2) H. G. Truper and L. de Clari. Int. J. Syst. Bacteriol. 47:908, 1997. (3) A. Wensing et al. Appl. Environ. Microbiol. 76:6248, 2010.

Peripheral compressing artifacts in brain tissue from stereotactic biopsy with sidecutting biopsy needle: a pitfall for adequate glioma grading.

AIMS: The stereotactic brain biopsy is an essential diagnostic procedure in modern neurologic patient management. A side-cutting biopsy needle is one of the most widely used needle types. Recently we found a characteristic tissue artifact named "peripheral compressing artifact" in the brain tissues biopsied using a side-cutting needle of Leksell's system. We investigate prevalence, possible cause and its clinical implication of this type of artifact. MATERIALS AND METHODS: We examined the biopsies from 80 patients (44 cases of gliomas, 13 lymphomas, 7 germ cell tumors, 2 other tumors, 1 metastatic carcinoma, 4 non-tumorous conditions such as demyelinating disease and 8 non-diagnostic) in the stereotactic biopsy group with a suspected brain tumor, who underwent a stereotactic brain biopsy using side-cutting needle of Leksell's system. We also evaluated 16 cases of open brain biopsies without Leksell's system as a control group. RESULTS: The artifact is a semi-circular or band-like tissue compression in the periphery of the biopsied tissue. This artifact was found in 30 (37.5%) out of 80 cases and 57 (11.9%) out of 477 biopsied pieces. It might be produced during rotating of the inner cannula of the biopsy needle. Histologically, it might be misinterpreted as "hypercellular", "spindle", "well circumscribed", or rarely as "pseudopalisading" especially in glioma. CONCLUSIONS: Awareness of this artifact would help making the appropriate pathological diagnosis for glioma.

Aberrant ribosome biogenesis activates c-Myc and ASK1 pathways resulting in p53-dependent G1 arrest.

The largest energy consumer in the cell is the ribosome biogenesis whose aberrancy elicits various diseases in humans. It has been recently revealed that p53 induction, along with cell cycle arrest, is related with abnormal ribosome biogenesis, but the exact mechanism still remains unknown. In this study, we have found that aberrant ribosome biogenesis activates two parallel cellular pathways, c-Myc and ASK1/p38, which result in p53 induction and G1 arrest. The c-Myc stabilizes p53 by rpL11-mediated HDM2 inhibition, and ASK1/p38 activates p53 by phosphorylation on serine 15 and 33. Our studies demonstrate the relationship between these two pathways and p53 induction. The changes caused by impaired ribosomal stress, such as p53 induction and G1 arrest, were completely disappeared by inhibition of either pathway. These findings suggest a monitoring mechanism of c-Myc and ASK1/p38 against abnormal ribosome biogenesis through controlling the stability and activity of p53 protein.