Increased Expression of trk Proto-oncogene by γ-Interferon in Human Neuroblastoma Cell Lines

Three human neuroblastoma cell lines were examined to determine the effect of recombinant γ-interferon (IFN-γ) treatment on the expression of trk proto-oncogene. Increased levels of trk proto-oncogene mRNA were observed in two neuroblastoma cell lines (KP-N-RT and KP-N-SI(FA)) after IFN-γ treatment. The levels of trk mRNA increased with growth inhibition and morphological change in a time- and dose-dependent manner. The decreased level of N- myc mRNA after IFN-γ-treatment in KP-N-RT was inversely correlated with trk mRNA. Our results suggest that IFN-γ can modulate the signal transduction of nerve growth factor in human neuroblastoma cells.     

Surgical Treatment of Malignant Fibrous Histiocytoma in the Left Atrium and Pulmonary Veins: Report of a Case

This report describes the case of a 16-year-old boy who underwent surgical treatment of a cardiac malignant fibrous histiocytoma (MFH). He was admitted to our hospital for exertional dyspnea. An ultracardiogram (UCG) revealed a tumor about 10 cm in diameter, in the left atrium. Extirpation of the left atrial tumor, including the part extending into the pulmonary veins, was performed under cardiopulmonary bypass. Histological examination confirmed a diagnosis of MFH. No adjuvant chemotherapy or radiotherapy was given. While there has been no evidence of local recurrence or metastasis in the 9 months since his operation, strict follow-up is being done by UCG and computed tomography. A few reviews of this entity have been reported; however, they have confused autopsy cases with surgical cases. Therefore, we reviewed only the surgical cases of this type of cardiac tumor documented in the literature. According to our review of the literature, this patient is the youngest among the 42 cases of surgically treated cardiac MFH reported to date. Received: December 28, 2000 / Accepted: September 11, 2001     

The nitric oxide donor NOC12 protects cultured astrocytes against apoptosis via a cGMP-dependent mechanism

We examined the effect of 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene (NOC12), a nitric oxide (NO) donor, on apoptosis in cultured astrocytes. Reperfusion after hydrogen peroxide (H2O2) exposure caused a decrease in cell viability, loss of mitochondrial membrane potential, caspase-3 activation, DNA ladder formation, and nuclear condensation. NOC12 at 10-100 microM significantly attenuated these apoptotic changes, while the NO donor at 1 mM caused cell injury and exacerbated the H202-induced cell injury. NOC12 increased intracellular cGMP levels in a dose dependent manner with the maximal effect at 100 microM. The protective effect of NOC12 was mimicked by the NO-independent guanylate cyclase activator 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole, and was attenuated by the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and the cGMP-dependent protein kinase inhibitor KT5823. ODQ and KT5823 did not block but rather exacerbated the cytotoxic effect of NOC12 at 1 mM. These findings demonstrate that lower concentrations of NOC12 inhibit the H2O2-induced apoptosis of astrocytes in a cGMP-dependent way, but higher concentrations of NOC12 show a toxic effect on astrocytes in a cGMP-independent way.     

Mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia

X-linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is characterized by sparse hair, abnormal teeth and decreased sweating as a result of abnormal development of the sweat glands. Mutations in the ED1 gene, which encodes ectodysplasin-A (EDA), are responsible for XLHED. Ectodysplasin-A, a ligand for the EDA receptor, plays an important role in epidermal morphogenesis. We identified ED1 mutations including three novel mutations by sequencing genomic DNAs from eight unrelated Japanese XLHED families. Data from all reported mutations revealed that codon 156 in the furin subdomain is the most frequent site of change in EDA.     

Isoforms changes of tau protein during development in various species

Tau protein is one of the major microtubule-associated proteins of the vertebrate nervous system. Some kinds of isoforms, for example, six isoforms in humans, are generated from a single gene by alternative mRNA splicing. The expression of tau protein is widely believed to be developmentally and pathologically regulated. We examined developmental changes in tau protein from humans, rats, mice, and guinea pigs to determine the universal function of each isoform. Tau isoforms, composed of variants in the amino terminal and carboxyl terminal regions, gradually shifted through development in protein. The developmental changes in the carboxyl terminal region were found to be conserved in all species in which three-repeat tau isoforms were dominant in the fetus or neonate, while four-repeat tau isoforms were dominant in adult brain. On the other hand, the changes in the amino terminal region were not identical in these species. These observations were confirmed using isoform-specific antibodies which could discriminate the numbers of amino-terminus insertions and carboxy-terminus repeat insertions. Developmental regulation of 3- and 4-repeat tau isoforms may contribute to axonal development and neural plasticity.     

Significance of plasminogen-activation system in the formation of macroscopic types and invasion in esophageal carcinoma

BACKGROUND: The roles of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) in the formation of macroscopic types and invasion were investigated. MATERIALS AND METHODS: A total of 40 surgically-resected esophageal carcinoma tissues were immunohistochemically stained, and the expression of uPA, PAI-1 and the uPA/PAI-1 ratio, were evaluated. RESULTS: The expression of uPA was significantly stronger in the macroscopically infiltrative type (n = 20: p = 0.0027), whereas PAI-1 was significantly stronger in the localized type (n = 20: p = 0.0005). The uPA/PAI-1 ratio was significantly higher in the infiltrative type (p < 0.0001). A significant correlation was found between the U/P ratio and the depth of tumor invasion (r = 0.511, p = 0.0014). Analysis of tumors of uniform size (4.0-6.0 cm in length), showed that the depth of invasion was significantly greater in the infiltrative type (p = 0.0038). CONCLUSION: The results demonstrated that uPA and PAI-1 play important roles in invasion and formation of macroscopic types of esophageal carcinoma.     

Successive cultures of mature hepatocytes for hepatocyte autotransplantation to assist liver function after liver resection for cancer

We developed a method for the rapid successive cultures of adult rat mature hepatocytes on plastic dishes while avoiding viral transformation or co-culture with other cell lines. This method also allows for culturing adult human mature hepatocytes up to the secondary culture. These can be expected to provide a good source for hepatocyte autotransplantation, and, combined with the previously reported methods for the transplantation of hepatocytes into the spleen, a promising option for the support of liver function after liver resection for cancer without the need for immunosuppressive agents.     

Nonsurgical treatment of hepatocellular carcinoma: from percutaneous ethanol injection therapy and percutaneous microwave coagulation therapy to radiofrequency ablation

Treatment of hepatocellular carcinoma (HCC) is different from that of other solid tumors, in that surgery plays a limited role while nonsurgical therapies are very instrumental. At our institute, 90% of previously untreated patients have received image-guided percutaneous tumor ablations, such as percutaneous ethanol injection therapy (PEIT), percutaneous microwave coagulation therapy (PMCT) and radiofrequency ablation (RFA). We performed PEIT in 756 patients with HCC. Their survival rates were 89% at 1 year, 64% at 3 years, 39% at 5 years, and 18% at 10 years. With PMCT, survival rates of 122 new patients with HCC were 90% at 1 year, 87% at 2 years, and 68% at 3 years. We performed RFA in 324 patients. RFA required fewer treatment sessions and a shorter hospital stay than PEIT or PMCT to achieve complete necrosis of the lesions. By virtue of their local curability, minimal effect on liver function, and easy repeatability for recurrence, image-guided percutaneous tumor ablations, especially RFA, will be increasingly important in the treatment of HCC.