• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.191-198
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• 2007

The p53 which is well known as tumor suppressor gene is located at 17p13. p53 is a sequence-specific DNA binding transcription factor that responds to certain cytotoxic stresses, such as DNA damage, by enhancing the transcription of genes that regulate cell-cycle progression as well as programmed cell death. The p63 gene that is located at 3q27-29, is recognized members of the p53 family, and responsible for the transcription of 6 isoforms. Three isoforms ($TAp63{\alpha}$, $TAp63{\beta}$, $TAp63{\gamma}$) contain an N-terminal transactivation (TA) domain and can induce apoptosis. The other 3 isoforms (${\Delta}Np63{\alpha}$, ${\Delta}Np63{\beta}$, ${\Delta}Np63{\gamma}$) lack the TA domain and may function in a dominant-negative fashion by inhibiting the transactivation functions of p53 and TAp63 proteins, and thus act as oncoproteins. A number of studies have investigated the role of p63 in human squamous cell carcinomas from different organs. Only a few studies have examined ${\Delta}Np63$ isoform in oral squamous cell carcinoma including normal epithelium. This study aimed to evaluate expression of ${\Delta}Np63$ isoform in human oral squamous cell carcinoma tissue and normal mucosa. The 3 cases of well differenciated oral squamous cell carcinoma specimen including adjacent normal mucosa were examined, and immunohistochemical study with monoclonal antibody(4A4) and tumor cell apoptosis analysis with Transmission Electon Microscopy were studied. And, RT-PCR analysis was done for expression of ${\Delta}Np63$ isoform. The results were as followed. 1. Normal gingiva showed the restricted p63 expression in basal cell layer. 2. Well differentiated squamous cell carcinoma showed mainly p63 expression in overall area of malignancy, especially in basal cell layer to adjacent stromal tissue. 3. Tumor cells around keratinized area with no p63 expression disclosed less micro-organelle in decreased size cytoplasm and severe chromatin margination with nuclear destruction that means apoptosis. 4. Comparison of mRNA expression of ${\Delta}Np63$ isoform by RT-PCR showed variable expression of ${\Delta}Np63$ isoform, but ${\Delta}Np63{\alpha}$ was most highly expressed in all 3 tumor specimen. From theses results, it should be suggested that ${\Delta}Np63$ isoform expression in well differentiated squamous cell carcinoma was closely related to tumor oncogenesis, expecially overexpression of ${\Delta}Np63{\alpha}$ is a most important factor in tumor genesis of oral squamous cell carcinoma.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.167-173
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• 2007

Purpose: Mistletoe (Viscum album L.) extract is one of the most widely used agents in alternative cancer therapeutic regimens in Europe. This study was conducted to determine the effect of mistletoe extract on immune function in gastric cancer patients. Materials and Methods: Ten patients that had undergone a curative gastrectomy were enrolled in the prospective study. ABNOBAviscum $Q^{(R)}$ was injected subcutaneously three times a week from postoperative-day 7 to week 16 with an increasing dose. All of the patients simultaneously received chemotheraphy with mitomycin, oral 5-FU and a cisplatin regimen. The WBC count, differential count, lymphocyte/WBC ratio and the level of cytokines (IL-$1{\beta}$, IL-2, IL-6, IFN-$\gamma$, TNF-$\alpha$) were checked in the peripheral blood preoperatively, at postoperative week 8 and at postoperative week 16. Results: The WBC and neutrophil counts significantly decreased after treatment on week 8 and week 16 (P=0.001), but the total eosinophil count was slightly increased (P=0.15). The total lymphocyte count also decreased during treatment but the lymphocyte/WBC ratio was slightly increased without statistical significance (P=0.91). The cytokine levels did not significantly change during treatment. Conclusion: It is somewhat difficult to determine the direct effect of mistletoe therapy on immune function as the effect may be compromised by the concurrent chemotherapy. It can be assumed that the slightly increased lymphocyte/WBC ratio and eosinophil count may be a result of the immunomodulatory effect of the mistletoe extract.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.747-752
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• 2013

Oncostatin M (OSM) is a multifunctional cellular regulator acting on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. Previous studies have shown that OSM can induce morphological and/or functional differentiation and maturation of many tumor cells. However, the action of OSM on the induction of differentiation of human hepatocellular carcinoma (HCC) has not been reported. Here, we investigated the effects of different concentrations of OSM on human HCC cell line SMMC-7721 growth, proliferation, cell cycling, apoptosis and differentiation in vitro. Cell growth was determined via MTT assay, proliferation by cell cycle analysis, apoptosis by flow cytometry, morphology by transmission electronic microscopy, and cell function by detection of biochemical markers. Our results demonstrated that OSM strongly inhibited the growth of SMMC-7721 cells in a dose-dependent manner, associated with decreased clonogenicity. Cell cycle analysis revealed a decreased proportion of cells in S phase, with arrest at G0/G1. The apotosis rate was increased after OSM treatment compared to the control. These changes were associated with striking changes in cellular morphology, toward a more mature hepatic phenotype, accompanied by significant reduction of the expression of AFP and specific activity of ${\gamma}$-GT, with remarkable increase in secretion of albumin and ALP activity. Taken together, our findings indicate that OSM could induce the differentiation and reduce cell viability of SMMC-7721 cells, suggesting that differentiation therapy with OSM offers the opportunity for therapeutic intervention in HCC.