Treating malignant tumor through the induction of cell differentiation has been an attractive concept, but clinical development of differentiation-inducing agents to treat malignant tumor, especially for solid tumors has been limited to date. Nerve growth factor, all trans retinoic acid, dimethyl sulfoxide, active form vitamin D(3), peroxisome proliferator-activated receptorgamma, 12-0-tetradecanoylphorbol 13-acetate, hexamethylene-bis-acetamide, transforming growth factor-beta, butyric acid, cAMP, and vesnarinone are known to have a differentiation-inducing capability on solid tumors in vitro and/or in vivo. Moreover some of the differentiation-inducing agents have been used for treating patients with solid tumor, but the therapeutic effect of the differentiation-inducing agents on solid tumor is not strong when compared with that of conventional chemotherapeutic agents. However, because most of the differentiation-inducing agents can potentiate the effect of conventional chemotherapy or radiation therapy, combination of differentiation-inducing therapy with conventional chemotherapy or radiation therapy might be used as a second- or third-line therapy in patients with advanced cancer. Furthermore, analysis of the molecular mechanisms of the tumor differentiation therapy might provide selective and targeted molecules for novel cancer therapy.

sophageal squamous cell carcinoma (SCC) is one of the most aggressive cancers. Esophageal SCC is relatively common in countries in Eastern Asia, such as China and Japan, and is characterized by poor prognosis and rapid clinical progression, with a high frequency of lymph node metastasis and recurrence. The 5-year survival rate of patients with esophageal SCC showing submucosal invasion is low (40-75%) 1-5) compared with that for patients with colon cancer (over 80%). 4,5) In addition, lymph node metastasis is commonly found in esophageal SCC, even when the tumor invades only the submucosa. Lymph node metastasis is the main cause of the poor prognosis for the patients with esophageal SCC.Consequently, the identification of the genes associated with metastasis of esophageal SCC is very important. Microarray analysis has been used to investigate the gene expression profiles of esophageal SCC tissues and esophageal cancer cell lines with various characteristics.6-10) When clinical materials are used for microarray analysis, it might be necessary to look at the overall expression profiles of genes (if possible) by clustering analysis in the different pathological stages, such as dysplasia, carcinoma in situ, and invasive cancer with or without metastasis. However, to isolate gene(s) related to metastasis, it would be convenient to use cell lines with different metastatic potentials derived from the same parental cells, and a reliable model system is therefore required for examining the metastatic potential of cancer cells.In our previous experiments, we established in vitro and in vivo model systems for studying invasion and metastasis of esophageal SCC cells. 11,12) We first clarified in detail the molecular and genetic characteristics of a human non-metastasizing esophageal SCC cell line, T.Tn, 12) and then developed an orthotopic inoculation model for esophageal cancer cells in nude mice.11) In the present study, we isolated a metastasizing subclone from the parental non-metastasizing T.Tn cell line by in vitro selection and by the use of a nude mouse orthotopic inoculation model. Then, we compared the expression profiles of 9206 genes in the parental T.Tn cells and the metastasizing subclone by cDNA microarray analysis, and identified several genes differentially expressed in the metastasizing subclone. Materials and MethodsCell line. A human esophageal SCC cell line, T.Tn 13) was obtained from JCRB (Japanese Collection of Research Bioresources, Osaka). T.Tn cells were grown in 1:1 mixture of Dulbecco's modified Eagle's medium (Nissui, Tokyo) and F-12 (Life Technologies, Inc., Gaithersburg, MD) supplemented with 10% fetal calf serum (FCS; Sigma, St. Louis, MO), 100 µg/ml streptomycin, 100 units/ml penicillin (Life Technologies, Inc.), and 0.25 µg/ml amphotericin B (Life Technologies, Inc.) in a humidified atmosphere of 95% air and 5% CO 2 at 37°C. HT1080 cells are derived from a human fibrosarcoma cell line known to secrete a large amount of several matrix-degrading enzymes (purchased from Dai-Nippon Seiyaku, Osa...

This combined navigations of fluorescence and 3-D imaging revealed more easy and effective to detect SLN intraoperatively than fluorescence imaging alone.

We present a successful laparoscopic treatment of paraesophageal hiatal hernia with an incarceration of the pancreas and jejunum. The patient was a 75-year-old woman who had complaints of epigastric pain and dysphasia. A chest x-ray revealed a mediastinal air-fluid level. Chest computed tomography showed intestinal contents, body and tail of the pancreas, and the splenic artery within the mediastinum. At laparoscopy, jejunum was incarcerated into the mediastinal cavity through the internal hernia of transverse mesocolon. Body and tail of the pancreas and the splenic artery were also dislocated within the hernia sac. The operation time took 115 minutes. The patient tolerated a regular diet on the first postoperative day and was discharged uneventfully. There were no recurrence or abdominal symptoms during the 29-month follow-up period. In the case of asymptomatic paraesophageal hiatal hernia with incarcerating pancreas on diagnostic imagings, elective surgical treatment is required to prevent a critical outcome.

A p53 functional analysis system, which can identify the types of abnormality of p53, such as loss of function, dominant negative function, or gain of oncogenic function, is now required. In this study, we examined the functional diversity of several mutations of p53 derived from human head and neck cancer cells. The entire open reading frame of p53 cDNA was subcloned into a mammalian expression vector, pEGFP-C3, and genetic mutations were determined. Then, intracellular localization and transcriptional activity of the tumor-derived p53 proteins were examined in Saos-2 cells. A mutant-p53 (Glu17Lys, His193Leu) or a truncated p53 (Δ121) did not activate the reporters containing p53 responsive elements from p21waf1, BAX, MDM2, p53AIP1, and PUMA genes at all. However, a mutant-p53 (Asn30Ser) showed the transcriptional activity on all of the reporters as wild-type p53 did. On the other hand, a mutant-p53 (Asp281His) activated the p21waf1 promoter strongly and the MDM2 promoter faintly, but did not activate the BAX promoter. Interestingly, this mutant-p53 prevented Saos-2 cells from undergoing apoptosis after treatment with a DNA damaging agent, adriamycin. This mutant-p53 induced cell cycle arrest but not apoptosis. Furthermore, another mutant-p53 (Glu17Lys, His193Leu) also prevented the cells from undergoing apoptosis after DNA damage probably in a transcriptionindependent manner. These results suggest that some cancer cells may contain the oncogenic mutation of the p53 gene, and the oncogenic p53 protein prevents cancer cells from undergoing apoptosis after DNA damage. Detailed information for mutated p53 gene in cancer cells might provide useful suggestions for the therapeutic strategy.