We have examined the combined anticancer effects of docetaxel (DOC) and cisplatin (CDDP) in vitro using the gastric cancer cell lines MKN-45, MKN-74, and TMK-1. Treatment of the cell lines with 30 µ µ µ µg/ml of DOC for 24 h followed by incubation with 3 or 10 µ µ µ µg/ml of CDDP for 24 h showed a clear synergistic effect. Sequence dependency of the agents was observed in these cell lines: DOC followed by CDDP (DC) showed a stronger antitumor effect than CDDP followed by DOC (CD) in all cell lines. To clarify the mechanism of action of the DC combination, total intracellular platinum (Pt) levels were evaluated after treatment with CDDP alone or combined with DC. ocetaxel (DOC) is derived from needles of the yew tree Taxus baccata as a semi-synthetic compound, and has been shown to be active against several kinds of cancer, including gastric cancer. Clinical studies using DOC alone against gastric cancer provided an efficacy rate of approximately 20%, 1) and the antitumor spectrum of DOC was different from those of conventional anticancer agents such as mitomycin C, doxorubicin, and cisplatin (CDDP). 2, 3) Therefore, it is thought that DOC may be useful as a potent agent in combination chemotherapies with conventional chemotherapy agents.Taxoids such as DOC bind to free tubulin and promote the formation of stable microtubules, inhibiting microtubule depolymerization. Recently, a relationship between bcl-2 phosphorylation, Raf-1 (Ras) signaling, and apoptosis during M phase cell cycle arrest induced by DOC was proposed. 4) A study that examined transcription factor levels found that DOC appeared to induce AP-1 activation, and that resistance to DOC was characterized by increased AP-1 levels. 5) Thus, DOC may possess potent ability to alter cell biology through the modification of transcription factor expression levels. We consider that DOC used in combination with conventional anticancer agents may be of considerable benefit in cancer therapy.While the combination chemotherapy of DOC and CDDP has already been applied to the clinical treatment of several types of cancer, with high efficacy rates and only moderate toxic effects in phase I and II studies, 6-9) the mechanism of action of this therapy remains to be clarified. Elucidation of this mechanism, including investigations into synergistic or additive antitumor effects, biochemical modulation, and the importance of sequence dependency, will assist the further clinical application of such combination chemotherapy.In the present study, we demonstrated the synergistic antitumor activity of the DOC and CDDP combination against three gastric cancer cell lines, MKN-45, MKN-74, and TMK-1. We also clarified the sequence dependency and the optimal timeschedule of the two agents, and analyzed the mechanism of DOC enhancement of CDDP antitumor activity in our cell line models by evaluating the amounts of intracellular platinum (Pt) and its intracellular scavenger, glutathione (GSH). Lastly, we examined the expression dynamics of multidrug resistance-associated protein-1 (...

Mucoepidermoid carcinoma (MEC) is one of the most frequently misdiagnosed tumors. Glycans are modulated by malignant transformation. Mucin 1 (MUC1) is a mucin whose expression is upregulated in various tumors, including MEC, and it has previously been investigated as a diagnostic and prognostic tumor marker. The present study aimed to reveal the differences in the mucin glycans between MEC and normal salivary glands (NSGs) to discover novel diagnostic markers. Soluble fractions of salivary gland homogenate prepared from three MEC salivary glands and 7 NSGs were evaluated. Mucins in MEC and NSGs were separated using supported molecular matrix electrophoresis, and stained with Alcian blue and monoclonal antibodies. The glycans of the separated mucins were analyzed by mass spectrometry. MUC1 was found in MEC but not in NSGs, and almost all glycans of MUC1 in MEC were sialylated, whereas the glycans of mucins in NSGs were less sialylated. The core 2 type glycans, (Hex) 2 (HexNAc) 2 (NeuAc) 1 and (Hex) 2 (HexNAc) 2 (NeuAc) 2 , were found to be significantly abundant glycans of MUC1 in MEC. MEC markedly produced MUC1 modified with sialylated core 2 glycans. These data were obtained from the soluble fractions of salivary gland homogenates. These findings provide a basis for the utilization of MUC1 as a serum diagnostic marker for the preoperative diagnosis of MEC.

Healing music and Musicotherapy attract attentions recently. They are beginning to be used in the medical treatment. On the other hand there are little practical utilization to relax with video images compared with music. Visual information is said to occupy about the whole of 80% humans receive from five senses. Therefore it has some potential that visual information affects human's mental and physical state as well as aural information does. This paper attempts to investigate the relation between characteristics of video images and mental relaxation. The one of characteristics we focus is motion speed of video images. It is considered that it might correspond to tempo of music. This paper investigates the relaxation effect by using the index calculated by heart rate variability analysis. The experimental results and analysis confirmed that viewing video images might have higher effect of reducing stress than eyes closed state and the relaxation effect might depend on motion speed.

Mucoepidermoid carcinoma (MEC) is the most frequent of the rare salivary gland malignancies. We previously reported high expression of Mucin 1 (MUC1) modified with sialylated core-2 O-glycans in MEC by using tissue homogenates. In this study, we characterised glycan structures of MEC and identified the localisation of cells expressing these distinctive glycans on MUC1. Mucins were extracted from the frozen tissues of three patients with MEC, and normal salivary glands (NSGs) were extracted from seven patients, separated by supported molecular matrix electrophoresis (SMME) and the membranes stained with various lectins. In addition, formalin-fixed, paraffin-embedded sections from three patients with MEC were subjected to immunohistochemistry (IHC) with various monoclonal antibodies and analysed for C2GnT-1 expression by in situ hybridisation (ISH). Lectin blotting of the SMME membranes revealed that glycans on MUC1 from MEC samples contained α2,3-linked sialic acid. In IHC, MUC1 was diffusely detected at MEC-affected regions but was specifically detected at apical membranes in NSGs. ISH showed that C2GnT-1 was expressed at the MUC1-positive in MEC-affected regions but not in the NSG. Conclusion: MEC cells produced MUC1 modified with α2,3-linked sialic acid-containing core 2 O-glycans. MUC1 containing these glycans deserves further study as a new potential diagnostic marker of MEC. (200 words)

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