H3F3A K27M mutations in thalamic gliomas from young adult patients

Introduction

Mutations in H3F3A, which encodes histone H3.3, commonly occur in pediatric glioblastoma. Additionally, H3F3A K27M substitutions occur in gliomas that arise at midline locations (eg, pons, thalamus, spine); moreover, this substitution occurs mainly in tumors in children and adolescents. Here, we sought to determine the association between H3F3A mutations and adult thalamic glioma.

Methods

Genomic H3F3A was sequenced from 20 separate thalamic gliomas. Additionally, for 14 of the 20 gliomas, 639 genes—including cancer-related genes and chromatin-modifier genes—were sequenced, and the Infinium HumanMethylation450K BeadChip was used to examine DNA methylation across the genome.

Results

Of the 20 tumors, 18 were high-grade thalamic gliomas, and of these 18, 11 were from patients under 50 years of age (median age, 38 y; range, 17–46), and 7 were from patients over 50 years of age. The H3F3A K27M mutation was present in 10 of the 11 (91%) younger patients and absent from all 7 older patients. Additionally, H3F3A K27M was not detected in the 2 diffuse astrocytomas. Further sequencing revealed recurrent mutations in TP53, ATRX, NF1, and EGFR. Gliomas with H3F3A K27M from pediatric or young adult patients had similar, characteristic DNA methylation profiles. In contrast, thalamic gliomas with wild-type H3F3A had DNA methylation profiles similar to those of hemispheric glioblastomas.

Conclusion

We found that high-grade thalamic gliomas from young adults, like those from children and adolescents, frequently had H3F3A K27M.     

Identification of genes preferentially methylated in hepatitis C virus‐related hepatocellular carcinoma

Chronic infections by hepatitis B virus (HBV) and hepatitis C virus (HCV) appear to be the most significant causes of hepatocellular carcinoma (HCC). Aberrant promoter methylation is known to be deeply involved in cancer, including in HCC. In this study, we analyzed aberrant promoter methylation by methylated DNA immunoprecipitation‐on‐chip analysis on a genome‐wide scale in six HCCs including three HBV‐related and three HCV‐related HCCs, six matched noncancerous liver tissues, and three normal liver tissues. Candidate genes with promoter methylation were detected more frequently in HCV‐related HCC. Candidate genes methylated preferentially to HBV‐related or HCV‐related HCCs were detected and selected, and methylation levels of the selected genes were validated by quantitative methylation analysis using MALDI‐TOF mass spectrometry using 125 liver tissue samples, including 61 HCCs (28 HBV‐related HCCs and 33 HCV‐related HCCs) and 59 matched noncancerous livers, and five normal livers. Among analyzed genes, preferential methylation in HBV‐related HCC was validated in one gene only. However, 15 genes were found to be methylated preferentially in HCV‐related HCC, which was independent from age. Hierarchical clustering of HCC using these genes stratified HCV‐related HCC as a cluster of frequently methylated samples. The 15 genes included genes inhibitory to cancer‐related signaling such as RAS/RAF/ERK and Wnt/β‐catenin pathways. Methylation of dual specificity phosphatase 4 (DUSP4), cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1), and natriuretic peptide receptor A (NPR1) significantly correlated with recurrence‐free survival. It was indicated that genes methylated preferentially in HCV‐related HCC exist, and that DNA methylation might play an important role in HCV‐related HCC by silencing cancer‐related pathway inhibitors, and might perhaps be useful as a prognostic marker. (Cancer Sci 2010)     

New local hyperthermia using dextran magnetite complex (DM) for oral cavity: experimental study in normal hamster tongue

The possibility of dextran magnetite complex (DM) as a new hyperthermic material was examined in this study. DM suspension of 56 mg ml(-1) iron concentration was locally injected into the normal tongue of golden hamster. DM injected tongues were heated by 500 kHz alternating current (AC) magnetic field and its serial changes in temperature were recorded at 30-s intervals. The temperature of DM injected tongue was maintained at about 43.0-45.0 degrees C for 30 min by changing the AC magnetic field intensity. While temperature elevations of the contralateral tongue and the rectum were only of minor degree. In experiment on the extent of heating area, there was correlation between volume of black stain area and amount of the injected DM suspension (Y = - 18.1 + 1.94X, r = 0.931, P < 0.0001, n = 9 ). Histological examination after heating revealed brown uniform DM accumulation in the connective tissue between fibers of the tongue muscle. Except for vascular dilatations, no tissue damage was seen in the heated tongue. Thus, DM which has the possibility of selective and uniform heating in local hyperthermia might be useful for oral cancer therapy.     

Factor XIIIa expression in pseudo-Kaposi sarcoma.

A 39-year-old man had pseudo-Kaposi sarcoma on his left foot. A biopsy specimen obtained from a cutaneous lesion showed increased numbers of vascular spaces, proliferation of fibroblast-like spindle cells, and deposition of hemosiderin in the dermis. Immunohistochemically, proliferative fibroblast-like spindle cells around the vessels were positive for anti-factor XIIIa antibody. Excessive heat radiation was detected from the skin lesions by thermography.     

Noninvasive acoustic radiation force impulse (ARFI) elastography for assessing the severity of fibrosis in the post-operative patients with biliary atresia

Purpose

Liver biopsy (LB) is still considered the “gold standard” for hepatological evaluation, but recently noninvasive methods have attempted to replace this invasive procedure. Recently, acoustic radiation force impulse (ARFI) imaging has been developed as a noninvasive modality to evaluate the stiffness of tissues. ARFI imaging theoretically measures liver stiffness of all the segments independently. The aim of this study was to determine whether ARFI elastography is a reliable method for predicting the severity of fibrosis in the post-operative patients with biliary atresia.

Methods

ARFI elastography was performed 21 times in eight patients with biliary atresia over the last 2?years. At the same time, we measured serum hyaluronic acid (H value), which is one of the serum elastic makers, to compare ARFI versus values in these patients. We obtained ARFI versus values as the median of S2 to S8 by three consecutive measurements acquired with a Siemens Acuson S2000 (Siemens Medical Systems, Germany).

Results

Histological evaluation of fibrosis is graded from F0 (normal) to F4. The normal H value is under 50?mg/dl. One patient had F0 (H value 29.2?mg/dl), four had F1 (H value 11.5–18.1?mg/dl), one had F3 (H value 61.3?mg/dl), two had F4 (H value 29.2, 112?mg/dl). One patient with F4 whose ARFI versus value (3.56?m/s) was the highest, needed liver transplantation and her liver was cirrhotic.

Conclusion

These findings suggest that ARFI measurement may be a reliable method for predicting the severity of fibrosis after a Kasai operation.     

Identification of serum proteins that bind with S100A8, S100A9 and S100A8/A9: Clinical significance of using proteins for monitoring the postoperative condition of liver recipients

BackgroundSerum proteins that non-specifically bind with human S100A8/A9 (h-S100A8/A9) have been proposed. Our aim was to isolate and identify these proteins, and verify their clinical significance for monitoring the postoperative condition of liver recipients, and further to discuss the transportation of human fibronectin (h-FN) with h-S100A8/A9 and its functional role in vivo.MethodsTo isolate the serum proteins, recombinant human S100A8, S100A9 and S100A8/A9 affinity columns were used. Proteins were identified by mass spectrometry. Two enzyme-linked immunosorbent assays (ELISA) were used to measure h-S100A8/A9 and h-FN in the sera of liver recipients. Flow cytometry was employed to detect h-S100A8/A9 and h-FN on immunological cells. Western blotting was used to confirm serum constituents using antibodies specific to each constituent.ResultsOne of the proteins was identified with h-FN, and its fluctuation pattern in the serum of the recipient was in contrast to that of CRP. Flow cytometry showed a positive reaction for h-S100A8/A9 and h-FN on neutrophils and monocytes, indicating that both proteins exist on these cells.ConclusionsThe h-FN could be transported with S100A8/A9 in blood and/or on immunological cells, and effectively prevent further attack by various internal oxidants or repair damaged liver tissue in vivo.     

Local staging with magnetic resonance imaging after neoadjuvant hormonal therapy for prostate cancer]

We retrospectively studied the staging accuracy of magnetic resonance (MR) imaging after neoadjuvant hormonal therapy (NAH) for 21 localized prostate cancers. MR imaging was performed using a 1.5-Tesla magnetic resonance system with a pelvic phased array coil. T2-weighted MR images were obtained on axial and coronal planes, and T1-weighted MR images using the dynamic technique with Gd-DTPA bolus enhancement were obtained in axial planes for each patient. On T2-weighted imaging, the signal intensity of the normal tissue in the peripheral zone became lower after NAH. Therefore, it was more difficult to detect residual malignant lesions in many cases than before NAH. The accuracy of T staging for prostate cancer after NAH in MRI was 71%. The accuracy, sensitivity, and specificity of the extracapsular invasion was 76%, 0% and 94%, respectively, and those of the seminal vesicular invasion 85%, 0% and 100%, respectively. While 2 of the 4 patients judged as downstaged cases in MRI showed corresponding pathological findings, 5 of the 21 cases (23.8%) were underdiagnosed. Local staging with only MRI for prostate cancer after NAH seems to have limits in applicability.     

Early bladder wall changes after creation of obstructive uropathy in the fetal lamb

Vesico-amniotic shunting of obstructive uropathy in fetal lambs produced a thick-walled, poorly compliant bladder. We report the early histological changes in the obstructed bladder wall. We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. Vesicostomy or vesico-amniotic shunt tube insertion and biopsy of the bladder wall were performed 21 days later. The fetuses were delivered at term (145 days) and the kidneys and bladder sampled for histology. Colloidal iron (Col Fe), and alpha-smooth muscle actin (α-SMA) immunohistochemical stains were used for these samples. Seventeen fetuses were shunted with 15 biopsies taken at that time. Six (shunt failure or missed urachal ligation) were excluded. All biopsies taken at shunting had positive Col Fe and α-SMA. Term lambs had mild multicystic dysplastic kidney (MCDK) in five, severe MCDK in two, and hydronephrosis in four. All bladders had small volume and were severely fibrotic. Fetal shunt operations 3 weeks after the creation of obstructive uropathy provided partial preservation of renal histology but did not preserve normal bladder histology. We suggest that the high hyaluronic acid synthesis activity or hyperplasia of the myofibroblasts in the dilated fetal bladder wall at the time of shunting results in irreversible damage to the developing bladder muscle and fibrosis.