Role of squamous cell carcinoma antigen 1 expression in the invasive potential of head and neck squamous cell carcinoma

BACKGROUND: Serine proteases have important roles in tumor invasion and metastasis, and their inhibitors, serine protease inhibitors (serpins), are attractive targets for therapeutic strategies. On chromosome 18q21, there is a cluster of serpins: maspin, headpin, and squamous cell carcinoma antigen 1 (SCCA1)/SCCA2. Others and we have reported that the expression of these serpins is down regulated in head and neck squamous cell carcinoma (HNSCC) cells compared with normal squamous epithelial cells. In this study, we hypothesized that expression of SCCA1 is biologically disadvantageous to HNSCC cells. METHODS: HNSCC cell lines were transfected with a mammalian expression vector with SCCA1 cDNA. In vitro proliferation, migration, or invasive potential (matrigel assay) of the transfectants were assayed. In addition, the in vivo growth and invasion was analyzed using the floor-of-mouth model of nude mice. RESULTS: SCCA1 expression did not alter the in vitro growth rate of established HNSCC cells. However, SCCA1 expression significantly inhibited the in vitro invasion in matrigel assays. Furthermore, the in vivo growth and invasion in nude mice was also inhibited by SCCA1 expression. CONCLUSIONS: Overexpression of SCCA1 in a HNSCC cell line inhibited its invasive potential. Loss of expression of the serpin SCCA1 may play a role in the malignant progression of HNSCC.     

Effects of a novel NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on growth, apoptosis, gene expression, and chemosensitivity in head and neck squamous cell carcinoma cell lines

BACKGROUND: Recent studies provide evidence that the constitutive activation of nuclear factor-kappa B, NF-kappaB plays a critical role in enhancing the growth of several types of malignancies, including head and neck squamous cell carcinoma (HNSCC). METHODS: In this study, we examined the effects of a newly synthesized NF-kappaB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on growth, induction of apoptosis, gene expression, and chemosensitivity in two HNSCC cell lines (YCU-H891 and KB), which expressed high levels of nuclear NF-kappaB protein. RESULTS: DHMEQ showed strong growth inhibitory effects on these two cell lines, with a 50% cell growth inhibition (IC50) concentration of approximately 20 microg/mL. These growth inhibitory effects were associated with inhibition of the NF-kappaB activity. Treatment with DHMEQ induced apoptosis in a dose-dependent manner accounting, at least in part, for the growth inhibition by DHMEQ. DHMEQ strongly inhibited cyclin D1 and vascular endothelial growth factor (VEGF) promoter activity and decreased the levels of cyclin D1 protein and VEGF mRNA in KB cells. In addition, low concentrations of DHMEQ (1.0 or 5.0 microg/mL) synergistically enhanced the cellular sensitivity of YCU-H and KB cells to cisplatin, which is a key chemotherapeutic agent in the treatment of HNSCC. CONCLUSIONS: These results suggest that DHMEQ may be effective when used alone or in combination with other agents in the treatment of HNSCC.     

The effect of cyclin D1 overexpression in human head and neck cancer cells

Overexpression of cyclin D1 in head and neck cancer has been suggested to be a poor prognostic factor. To understand the role of cyclin D1 expression in head and neck cancer, we overexpressed cyclin D1 in TU182 (a cell line derived from pharyngeal cancer) using a retroviral vector. Stable transfectants were isolated by neomycin (G418) selection. Compared to the parental and control-vector transfected cells, the cyclin D1 transfected cells revealed a decrease of the G1/G0 population and resulted in continuous proliferation under low serum conditions. Proliferation assays revealed an increase in resistance to cisplatin in cyclin D1 overexpressing cells. These observation suggest that deregulation of cyclin D1 may reduce growth factor requirements and contribute to the resistance to some chemotherapeutic agents among head and neck cancer patients.     

Arachnoid cyst of the quadrigeminal cistern

The case report of an infant girl with hydrocephalus due to an arachnoid cyst situated at the posterior end of the third ventricle is described. The mechanism of fluid accumulation in the cyst and the choice of surgical treatment are discussed.     

A case of progressive muscular dystrophy with pulmonary hypertension

A case of progressive muscular dystrophy of the limb girdle type is reported. The patient, a 37-year-old man, showed severe hypoxemia upon blood gas analysis, which had been predicted by pulmonary function tests, together with elevated pulmonary arterial pressure revealed by cardiac catheterization. He showed abnormal symptoms of respiration during the night, and so a sleep study was performed. The results revealed central type apnea not only during REM sleep but also frequently during NREM sleep. Acidosis and hypoxemia induced by sleep apnea caused vasoconstriction of the pulmonary artery and long-term repetition of this had caused pulmonary hypertension.     

Role of individual ionic current systems in the SA node hypothesized by a model study

This paper discusses the development of a cardiac sinoatrial (SA) node pacemaker model. The model successfully reconstructs the experimental action potentials at various concentrations of external Ca2+ and K+. Increasing the amplitude of L-type Ca2+ current (I(CaL)) prolongs the duration of the action potential and thereby slightly decreases the spontaneous rate. On the other hand, a negative voltage shift of I(CaL) gating by a few mV markedly increases the spontaneous rate. When the amplitude of sustained inward current (I(st)) is increased, the spontaneous rate is increased irrespective of the I(CaL) amplitude. Increasing [Ca2+](o) shortens the action potential and increases the spontaneous rate. When the spontaneous activity is stopped by decreasing I(CaL) amplitude, the resting potential is nearly constant (-35 mV) over 1-15 mM [K+](o) as observed in the experiment. This is because the conductance of the inward background non-selective cation current balances with the outward [K+](o)-dependent K+ conductance. The unique role of individual voltage- and time-dependent ion channels is clearly demonstrated and distinguished from that of the background current by calculating an instantaneous zero current potential ("lead potential") during the course of the spontaneous activity.     

Effects of IFN-alpha on alpha-fetoprotein expressions in hepatocellular carcinoma cells.

We investigated the effects of pegylated (PEG)-IFN-alpha2b on alpha-fetoprotein (AFP) expression as demonstrated by protein and mRNA levels in six human hepatocellular carcinoma (HCC) cell lines. The number of KIM-1 cells in culture with PEG-IFN-alpha2b decreased between 24 amd 240 h, whereas the levels of intracellular and secreted AFP per cellular protein increased (except at 192 h), with levels 1.9-fold and 2.9-fold higher at maximum, respectively, than cells without PEG-IFN-alpha2b (control). The mRNA level increased between 72 and 192 h, when the level was 3-fold higher than that of the control. In the 72-h culture with 40-5000 IU/mL PEG-IFN-alpha2b, there were dose-dependent increases in AFP protein and mRNA expression and dose-dependent decrease in cell number resulting from apoptosis and blockage of the cell cycle at the S-phase. The rate of fucosylated AFP in the cell lysate decreased in a dose-dependent and time-dependent manner. In the PEG-IFN-alpha2b culture of the other five HCC cell lines, cell proliferation was suppressed, but the expressions of AFP protein and mRNA increased in only two cell lines, and suppression of cell proliferation was not related to the increase in AFP expressions. Our findings demonstrated that PEG-IFN-alpha2b induces an increase in AFP expression at both the protein and mRNA levels.     

Clonidine-evoked selective P1-purinoceptor antagonism of contraction of guinea-pig urinary bladder

The effect of clonidine on P1- and P2-purinoceptors of guinea-pig urinary bladder was compared to that of alpha, beta-methylene ATP, a selective P2-purinoceptor desensitizer. After, alpha, beta-methylene ATP, 10 microM, vesical contraction produced by ATP was eliminated while that caused by acetylcholine was unaffected. Clonidine, however, failed to antagonize ATP-induced contraction of the segment even at 100 microM. Electrically evoked contraction of the bladder was partly attenuated by 0.3 microM atropine and the remainder was markedly reduced by 3-30 microM alpha, beta-methylene ATP, suggesting an important role of ATP as an excitatory transmitter in this tissue. This stimulus-evoked contraction was also suppressed by adenosine, a P1-purinoceptor agonist, in a concentration-dependent fashion, and the suppression was greatly antagonized by 50 microM clonidine. These results suggest that the antagonistic property of clonidine is substantially selective for presynaptic P1-purinoceptors in contrast with that of alpha, beta-methylene ATP for postsynaptic P2-purinoceptors.