Perpendicular magnetic tunnel junction with a strained Mn-based nanolayer.

A magnetic tunnel junction with a perpendicular magnetic easy-axis (p-MTJ) is a key device for spintronic non-volatile magnetoresistive random access memory (MRAM). Co-Fe-B alloy-based p-MTJs are being developed, although they have a large magnetisation and medium perpendicular magnetic anisotropy (PMA), which make it difficult to apply them to a future dense MRAM. Here, we demonstrate a p-MTJ with an epitaxially strained MnGa nanolayer grown on a unique CoGa buffer material, which exhibits a large PMA of more than 5 Merg/cm(3) and magnetisation below 500 emu/cm(3); these properties are sufficient for application to advanced MRAM. Although the experimental tunnel magnetoresistance (TMR) ratio is still low, first principles calculations confirm that the strain-induced crystal lattice distortion modifies the band dispersion along the tetragonal c-axis into the fully spin-polarised state; thus, a huge TMR effect can be generated in this p-MTJ.

Effect of steroid add-back therapy on the proliferative activity of uterine leiomyoma cells under gonadotropin-releasing hormone agonist therapy.

Short-term treatment with gonadotropin-releasing hormone agonist (GnRHa) is a useful preoperative medical therapy of uterine leiomyomas. However, adverse effects caused by the hypo-estrogen state sometimes appear, suggesting the necessity of add-back therapy. In this study, we investigated effects of three kinds of add-back therapies on the proliferative activity of uterine leiomyoma cells by examining the expression of Ki-67 in leiomyoma cells by immunostaining. Thirty patients who were to undergo hysterectomy or myomectomy were injected with 3.75 mg depot leuprolide acetate every four weeks until the end of the 12th week. Twenty patients underwent add-back therapy from the 5th week to the end of the 12th week, 8 patients receiving 0.625 mg of conjugated equine estrogen (CEE) /day, 6 patients 5.0 mg of medroxyprogesterone acetate (MPA)/day, 6 patients 0.625 mg CEE plus 2.5 mg of MPA /day. The add-back of CEE or CEE plus MPA suppressed decreases in the proliferative activity of leiomyoma cells caused by GnRHa therapy, but that of MPA did not. These results suggest that the add-back therapy with MPA is of use in preventing the adverse effects caused by hypo-estrogen in the preoperative short-term GnRHa therapy.

Neuroendocrine differentiation of periodic-acid Schiff and Alcian blue-negative signet-ring cell-like cells and tubular adenocarcinoma cells within a gastric cancer.

A case of a Borrmann type 2 advanced gastric cancer with endocrine differentiation is described. Histologically, the cancer was either composed of cells arranged in a tubular pattern or formed solid nests of various sizes. The tubular pattern was composed of a moderately differentiated tubular adenocarcinoma. The histology showed partial carcinoid tumor-like features. Cancer cells inside solid nests had a signet-ring cell-like appearance. Periodic-acid Schiff (PAS) staining was positive in the cytoplasm of a few of the cells found in the tubular pattern and in the mucus in some lumens and on the apical surface of cells in some lumens, but PAS did not stain cancer cells in the solid nests. Neither cancer cells nor mucus in the lumens were stained with alcian blue. All cancer cells were strongly positive for Grimelius silver stain, and most of the cancer cells stained positively for chromogranin A. Electron microscopic examination showed electron dense neuroendocrine granules in the cytoplasm of cancer cells. Cancer cells were stained positively for pancytokeratin, cytokeratin 8/18 and carcinoembryonic antigen. Muc 1 mucin glycoprotein staining was positive along the cell surfaces of cancer cells, but Muc 2, 5AC and 6 stainings were negative, although Muc 3 stained positively in the cytoplasm of a few cancer cells. The present case is a gastric tubular adenocarcinoma with Muc 1-positive, neutral- and acid mucin-negative signet-ring cell-like cells, which is associated with neuroendocrine differentiation.

Characteristics and surgical outcomes of paediatric retinal detachment.

PURPOSE: To report the clinical features and surgical and visual outcomes of rhegmatogenous retinal detachment (RRD) in the paediatric population. METHODS: A retrospective review of children (aged 0-15 years) who underwent primary surgical repair for RRD at the Hiroshima University Hospital between 1988 and 2001. RESULTS: In all 53 eyes of 49 patients were identified; paediatric RRD accounted for 3.1% of 1779 eyes with RRD operated on during this period. The causes of RRD included blunt trauma (27%), myopia (25%), idiopathic (20%), familial exudative vitreoretinopathy (13%), and others. Among 55 eyes, 12 (22%) already had proliferative vitreoretinopathy (PVR) of grade C or D preoperatively. The median initial visual acuity (VA) was 0.3. Retinal reattachment was achieved with a single operation in 78%. Final retinal reattachment was achieved in 87%. Retinal reattachment rates with and without PVR were 42% and 100%, respectively (P<0.01). Median final VA was 0.7. Final VA was > or =0.1 in 73% and > or =0.5 in 53%; four eyes had a final VA of no light perception. The presence of preoperative PVR (P=0.03) and the initial VA (P<0.0001) significantly affected final VA. CONCLUSIONS: Paediatric RRD is characterised by a delay in diagnosis, as evidenced by the high rate of PVR at presentation. Retinal reattachment was adversely affected by the presence of PVR. Final VA correlated with the initial VA and was significantly affected by preoperative PVR. Early diagnosis may improve the visual prognosis of paediatric retinal detachment.

Induction of apoptosis by castration in epithelium of the mouse seminal vesicles.

Castration on days 0, 5, 10, 20, 40, and 60 caused increases in an apoptotic index (% of apoptotic cells) in seminal vesicle (SV) epithelium, peaking 1-3 days after castration. The peak apoptotic indices after castration on days 0, 5, 10, and 20 were significantly lower than peak apoptotic indices observed after castration on days 40 and 60. DNA extracted from mouse SVs 2 days after castration on days 0, 5, 10, and 60 showed a ladder pattern on agarose gel electrophoresis. The secretion of androgen by testes was confirmed by the growth retardation of the SVs after castration on days 0, 5, 10, and 20. It would appear that a proportion of SV epithelial cells dependent on testicular androgens for survival is smaller before day 20 than after day 20.

Superior vena cava syndrome after bone marrow transplantation caused by aspergillosis: a case report.

Aspergillosis is known for the variety of unusual presentations in immuno-suppressed patients. We report a patient in whom aspergillosis caused the superior vena cava (SVC) syndrome. A 37-year-old woman became febrile soon after bone marrow transplantation (BMT). Chest radiography demonstrated a 5-cm mass extending from the right lung apex to the right supraclavicular fossa beside her Hickman catheter. She then developed SVC syndrome, which progressed despite treatment. Despite recovery of the white blood cell count, the patient continued to deteriorate, became comatose, suffered a cardiac arrest and died 31 days after BMT. Autopsy revealed Aspergillus infection at the apex of the right lung associated with innominate artery thrombosis.

Interleukin-18 and interleukin-12 synergistically inhibit osteoclastic bone-resorbing activity.

The effect of interleukin (IL)-18 on osteoclastic bone-resorbing activity was investigated in vitro. Osteoclast-enriched cells, about 70% of which were tartrate-resistant acid phosphatase (TRAP)-positive, were cultured on dentine slices, and then the total volume of resorption pits on each dentine slice was measured as bone-resorbing activity. When the effects of IL-18 alone at 1, 10, 100, and 1000 ng/mL were examined, bone-resorbing activity was significantly reduced only at 1000 ng/mL, by about 50%. However, IL-18 plus IL-12 (10 ng/mL each) reduced bone-resorbing activity by about 70%, whereas IL-12 alone had no significant effect. When the concentration of interferon (IFN)-gamma in the medium was measured, IL-18 or IL-12 was found to increase it slightly, and the combination of these two cytokines synergistically increased it. The inhibitory effect of the combination of the two cytokines was completely abolished by the addition of an anti-IFN-gamma neutralizing antibody to the medium, but IFN-gamma by itself did not inhibit osteoclastic bone resorption. IL-18 alone or in combination with IL-12 did not affect the number of TRAP-positive cells in culture of osteoclast-enriched cells. Osteoclasts prepared from osteoclast-enriched cells expressed mRNAs of IL-18 receptor, MyD88, and cathepsin K. Furthermore, IL-18 receptor protein was detected on the cell surface of osteoclasts. The present results indicate that the combination of IL-18 and IL-12 synergistically inhibits osteoclastic bone-resorbing activity, suggesting that IFN-gamma participates in the mechanism underlying this inhibition.

Castration induces apoptosis in the male accessory sex organs of Fas-deficient lpr and Fas ligand-deficient gld mutant mice.

The role of the Fas ligand-Fas system in castration-induced apoptosis in the epithelia of the ventral prostate (VP), seminal vesicle (SV), coagulating gland (CG) and epididymis (Ep) was investigated using lpr/lpr, and gld/gld mutant mice which are deficient in Fas and Fas ligand, respectively. The degree of apoptosis in the epithelium was quantitatively estimated by an apoptotic index (a percentage of apoptotic cells). The weights (mg/10 g body weight) of the VP, SV, CG and Ep of lpr/lpr and gld/gld mice were similar to those of normal +/+ mice and castration decreased the weights of the VP, SV, CG and Ep in these three kinds of mice to similar levels. Castration also increased the apoptotic indices in these organs reaching maximum on days 2-6 after castration. There was no significant difference in the apoptotic index of these organs among +/+, lpr/lpr and gld/gld mice on days 0-8 after castration. Agarose gel electrophoresis of DNAs extracted from the VP, SV, CG and Ep of +/+, lpr/lpr and gld/gld mice on day 4 after castration showed a ladder pattern. The present results suggest that the Fas ligand-Fas system plays little role in castration-induced apoptosis in the mouse male accessory sex organs such as the VP, SV, CG and Ep.

A novel alpha-amino-acid esterase from Bacillus mycoides capable of forming peptides of DD- and DL-configurations.

A novel alpha-amino-acid esterase possessing some properties favorable for the synthesis of D-amino acid-containing peptides has been purified from the culture broth of Bacillus mycoides. The enzyme consisted of 4 subunits of 39 kDa, had an isoelectric point of 7.0, and showed its maximum activity at around 47 degrees C and pH 7.6. The enzyme activity was strongly depressed by phenylmethanesulfonyl fluoride, but not by penicillin G or ampicillin, suggesting that the protein is a serine enzyme lacking penicillin-binding ability. The enzyme hydrolyzed a variety of D- and L-amino acid methyl esters with concomitant formation of homooligomers from D-Phe, D-Trp, D-Tyr, and D-Asp(OCH(3)) methyl esters, but it did not act on the D- or L-amino acid amides tested. Incubation of a mixture of Ac-D-Phe-OMe and D-/L-Leu-NH(2) with the enzyme yielded Ac-D-Phe-D-/L-Leu-NH(2) together with Ac-D-Phe-OH, the hydrolysate of the carboxyl component. To its credit, the enzyme failed to hydrolyze casein as well as peptides including diastereomers of diphenylalanine and dialanine, indicating that the enzyme would not cause secondary hydrolysis of once-formed peptides. These observations indicate the potential utility of the newly isolated enzyme for the synthesis of D-amino acid-containing peptides.

Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal.

It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype.

Expression of osteopontin by exudate macrophages in inflammatory tissues of the middle ear: a possible association with development of tympanosclerosis.

Tympanosclerosis is a condition leading to a calcification process in the middle ear, and often develops after chronic inflammation of the middle ear. Since osteopontin (OPN) has been shown to participate in the pathological calcification, we here investigated whether OPN is involved in the process of calcification in tympanosclerosis. The tympanic membrane and middle ear mucosa, obtained from patients of tympanosclerosis and chronic otitis media, were histologically classified depending on the calcification degree. In hyalinized tissues with macroscopic calcification and fibrous tissues with microscopic calcification, OPN was immunohistochemically found in the calcification sites. In inflammatory tissues with microscopic calcification, OPN was also found in the calcifying foci, and many OPN mRNA-expressing cells, determined by in situ hybridization, located around their foci. Moreover, immunohistochemical double staining of OPN and CD68 showed that the OPN-expressing cells were CD68-positive, indicating these cells were macrophages. In inflammatory tissues without calcification, immunohistochemistry of CD68 and in situ hybridization of OPN mRNA revealed that most OPN mRNA-expressing cells were CD68-positive. The expression of OPN mRNA in inflammatory tissues was also shown by reverse transcriptase polymerase chain reaction. These results suggest that OPN secreted by exudate macrophages might be an important regulator in the calcification of tympanosclerosis.

Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells.

Osteoprotegerin (OPG) and osteoclast differentiation factor (ODF) are crucial regulators of osteoclastogenesis. To determine the biological role of interleukin (IL)-18 produced by stromal/osteoblastic cells in osteoclastogenesis, we examined the effects of IL-18 on the OPG and ODF mRNA levels in these cells. When bone marrow stromal ST2 cells, osteoblastic MC3T3-E1 cells, and mouse calvarial osteoblasts were stimulated with IL-18, the expression of OPG mRNA, but not ODF mRNA, was transiently increased, its expression reaching a maximal level at 3 h after the beginning of the culture. In accordance with this observation, all these cells expressed the mRNAs of two IL-18 receptor components and MyD88, an adapter molecule involved in IL-18 signaling. Moreover, in these cells, mitogen-activated protein kinase was phosphorylated after stimulation with IL-18. These results suggest that stromal/osteoblastic cells are IL-18-responsive cells and that IL-18 may inhibit osteoclastogenesis by up-regulating OPG expression, without stimulation of ODF production, in stromal/osteoblastic cells.

Enzymatic purification of polyunsaturated fatty acids.

Polyunsaturated fatty acids (PUFAs) have various physiological functions. Of these, ethyl eicosapentaenoate is industrially purified and used as a medicine. Other PUFAs, such as docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), and arachidonic acid (AA), are also expected to be used as pharmaceutical agents; however, their industrial purification processes have not been established. Because PUFAs are highly unstable against heat and oxidation, we attempted to purify them by taking advantage of their enzymatic reactions. When free fatty acids (FFAs) originating from PUFA-containing oil were selectively esterified with lauryl alcohol (LauOH) using a lipase acting on a desired PUFA very weakly, the PUFA was efficiently enriched in the FFA fraction. In addition, when selective alcoholysis of ethyl esters originating from PUFA-containing oil with LauOH was carried out, the PUFA ethyl ester (EtPUFA) was enriched to a desired purity in the unreacted ethyl ester fraction. These reaction mixtures contain LauOH, PUFA (EtPUFA), and lauryl esters, and their molecular weights are different from one another. Hence, PUFA or EtPUFA can be easily separated by conventional distillation. Selective esterification increased the purity of DHA, GLA, and n-6 PUFAs rich in AA to 91, 98, and 96 wt%, respectively. Selective alcoholysis was also effective for increasing the purity of ethyl docosahexaenoate to 90 wt%.

Ethyl esterification of docosahexaenoic acid in an organic solvent-free system with immobilized Candida antarctica lipase.

Ethyl docosahexaenoate (EtDHA) is regarded as a potentially useful pharmaceutical substance on account of its beneficial physiological activities. We attempted the ethyl esterification of docosahexaenoic acid (DHA) in an organic solvent-free system using Candida antarctica lipase, which acts strongly on DHA and ethanol. Esterification of 88% was attained by shaking a mixture of DHA/ethanol (1:1, mol/mol) and 2 wt% immobilized C. antarctica lipase at 30 degrees C for 24 h. However, even in the presence of an excess amount of ethanol, the extent of esterification could not be raised above 90%. To attain a higher level of esterification, a two-step reaction was found to be effective. The first step was performed in a mixture of DHA/ethanol (1:1, mol/mol), and the reaction mixture was then dehydrated. In the second step, the resulting mixture was shaken at 30 degrees C for 24 h with 5 molar equivalents of ethanol against the remaining DHA using 2 wt% immobilized lipase. By means of this two-step procedure, 96% esterification was attained. Repetition of the first and second reactions showed that the immobilized lipase was reusable for at least 50 cycles. In addition, DHA remaining in the second-step reaction mixture was removed by a conventional alkali refining process, giving purified EtDHA with a high yield.

IL-18 and IL-12 induce intestinal inflammation and fatty liver in mice in an IFN-gamma dependent manner.

BACKGROUND: In murine models of inflammatory bowel disease, colonic inflammation is considered to be caused by an aberrant Th1-type immune response. AIM: To investigate if systemic administration of interleukin (IL)-12 and IL-18 to wild-type BALB/c mice induces liver injury and intestinal inflammation, and if pathological changes are observed, what cytokines are involved. METHODS: Mice (BALB/c-wild-type (wt), MRL-lpr/lpr, BALB/c-interferon gamma knock out (IFN-gamma KO), C57BL/6-inducible nitric oxide synthase (iNOS) KO, and BALB/c tumour necrosis factor alpha (TNF-alpha) KO) were injected intraperitoneally each day with IL-12 (20 ng/g/mouse) and/or IL-18 (200 ng/g/mouse). RESULTS: Administration of IL-12 and IL-18 to BALB/c-wt mice induced prominent intestinal mucosal inflammation and fatty liver, leading to piloerection, bloody diarrhoea, and weight loss. IL-12 and IL-18 induced striking elevations in serum levels of IFN-gamma that caused NO production, although increased NO had no exacerbating effect on mice. Moreover, iNOS KO mice, or MRL lpr/lpr mice lacking functional Fas were equally susceptible to IL-12 and IL-18. Administration of IL-12 and IL-18 did not induce TNF-alpha production in wild-type mice, and the same treatment to TNF-alpha KO mice induced intestinal mucosal inflammation. Furthermore, they had diffuse and dense infiltration of small fat droplets in their hepatocytes associated with an increase in serum levels of liver enzymes. In contrast, the same treatment in IFN-gamma KO BALB/c mice and iNOS KO mice did not induce these changes. CONCLUSIONS: Our study strongly indicates that IL-18 together with IL-12 induces intestinal mucosal inflammation in an IFN-gamma dependent but TNF-alpha, NO, and Fas ligand independent manner, and fatty liver is dependent on IFN-gamma and NO.

Promotive effects of a silk film on epidermal recovery from full-thickness skin wounds.

We examined the effects of the transparent fibroin film (silk film) on full-thickness skin wounds. Full-thickness dermatotomies (15 mm x 9 mm) were prepared on the dorsal wall of CRJ:CD-1 nu/nu (ICR nu/nu) mice. The area of the wounds dressed with silk film was reduced to 10% of that made by the dermatotomy 14 days after the dermatotomy and were covered with regenerated epidermis 21 days after the dermatotomy. In contrast, less recovery and epidermal regeneration were found 14 days after dermatotomy in the wounds dressed with a conventional hydrocolloid dressing (Duro Active). Furthermore, only partial incomplete epidemal growth was obtained 21 days after dermatotomy. Most importantly, the healing time of wounds dressed with silk film was 7 days shorter than those dressed with DuoActive dressing. The silk film showed an almost similar or slightly better promotive effect as the lyophilized porcine dermis (Alloask D), which is used as a dressing for burns, ulcers, and decubitis. Histologic findings revealed that there was greater collagen regeneration and less inflammation and neutrophil-lymphocyte infiltration of the wounds dressed with silk film than with DuoActive dressing. It is clear that regeneration of the epidermis and dermis of the wound beds covered with silk film was faster than with DuoActive dressing. Finally, silk film is easily obtainable, sterilizable, and transparent, and it allows easy observation of tissue recovery. Therefore, silk film offers advantages over other dressings and may be clinically useful for wound treatment.

The role of oval cells in rat hepatocyte transplantation.

BACKGROUND: Oval cells are liver cells capable of differentiating into either hepatocytes or biliary epithelial cells. We compared growth of hepatocytes and biliary epithelial cells between spleens transplanted with oval cell-free and oval cell-enriched rat liver cells. METHODS: Oval cell-enriched liver cells were obtained from livers of adult rats that had undergone treatment with acetylaminofluorene and partial hepatectomy, although oval cell-free liver cells were obtained from livers of untreated rats. Hepatocyte and biliary epithelial cell growth in the spleen was evaluated by counting periodic acid-Schiff-positive cells and cytokeratin 19-positive cells respectively in sections from transplanted spleens. RESULTS: Spleens transplanted with oval cell-free liver cells and spleens transplanted with oval cell-enriched liver cells contained similar numbers of hepatocytes after 2 weeks. Numbers of hepatocytes in spleens transplanted with oval cell-free liver cells decreased markedly at 4 and 8 weeks, then increasing slightly until 32 weeks. In spleens transplanted with oval cell-enriched liver cells, numbers of hepatocytes decreased only slightly at 4 weeks and then increased markedly. At 4, 8, 12, 16, 24, and 32 weeks, numbers of hepatocytes in spleens transplanted with oval cell-enriched liver cells respectively were 2.3, 3.5, 4.5, 6.7, 6.3, and 15.1 times hepatocyte numbers in spleens transplanted with oval cell-free liver cells. Numbers of biliary epithelial cells in spleens receiving oval cell-enriched liver cells showed changes similar to those in spleens transplanted with oval cell-free liver cells, increasing markedly at 4 weeks and then markedly and rapidly decreasing. CONCLUSIONS: Intrasplenic transplantation of oval cell-enriched liver cells enhanced growth of hepatocytes compared with transplantation of oval cell-free liver cells; this was not true for biliary epithelial cells.

Intrathyroid thyroglossal duct cyst simulating a thyroid nodule.

A case of intrathyroid thyroglossal duct cyst is reported. A 50-year-old woman presented with a right lateral neck mass that was clinically indistinguishable from a thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) revealed normal-looking squamous cells. Right thyroid lobectomy was performed and microscopic examination revealed a cyst lined by squamous epithelium that was consistent with a thyroglossal duct cyst. The lesion was completely surrounded by normal thyroid tissue. Our experience suggests that intrathyroid thyroglossal duct cyst should be remembered in the differential diagnosis of a thyroid nodule. Detection of benign squamous cells by US-FNAB may be useful for ruling out the possibility of a cystic thyroid tumor.

Inhibition by an angiogenesis inhibitor, TNP-470, of the growth of a human hepatoblastoma heterotransplanted into nude mice.

BACKGROUND/PURPOSE: The effect of TNP-470, an angiogenesis inhibitor, on the growth of a hepatoblastoma transplanted into nude mice was examined. METHODS: A hepatoblastoma obtained from a 3-year-old girl was serially transplanted into nude mice subcutaneously, and the transplant tumors of the seventh and eighth generations were used for experiments. Expression of various markers in the tumors was examined immunohistochemically. TNP-470 was injected subcutaneously every other day into tumor-bearing mice from 3 weeks after tumor transplantation. The proliferation of tumor cells and endothelial cells was estimated by means of the bromodeoxyuridine labeling index. RESULTS: The original hepatoblastoma showed the histology of the epithelial type, consisting of both the fetal and embryonal subtypes and was positively stained with anti-alpha-fetoprotein (AFP), anti-cytokeratin-19 and polyclonal anticarcinoembryonic antigen antibodies, and an antihuman hepatocyte antibody (hepatocyte paraffin 1). The transplant tumors consisted of solid nests of tumor cells with numerous vascular lakes of various sizes, and showed positive staining with all antibodies that reacted positively with the original hepatoblastoma. Injections of TNP-470 at the doses of 15 mg and 30 mg/kg body weight suppressed the tumor growth and the increase in the serum level of AFP dose dependently. Injections of TNP-470 also suppressed the proliferation of tumor cells and endothelial cells in the tumors. CONCLUSIONS: Hepatoblastomas maintained in nude mice retained the immunohistochemical characteristics of the original hepatoblastoma, and TNP-470 suppressed the growth of hepatoblastomas transplanted into nude mice. TNP-470 may be worth investigating further as to its usefulness as a therapy for hepatoblastomas.