Journal of the Korean Association of Oral and Maxillofacial Surgeons
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제33권3호
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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.
Squamous cell carcinoma originating in the parotid gland has rare occurrence. The primary squamous cell carcinoma of the parotid gland comprise about 0.3% and 9.8% of all parotid malignant tumor. We investigated the clinical behavior and treatment outcome of patients with primary squamous cell carcinoma of the parotid gland. We reviewed all cases of possible primary squamous cell carcinoma of the parotid gland treated at Yonsei Cancer Center, Seoul, Korea, from 1981 through 1995. A total of 128 had primary parotid malignancy. Metastatic squamous cell carcinoma and mucoepidermoid carcinoma were excluded in this study. Ten cases of primary squamous cell carcinoma of the parotid gland were identified. 6 cases of them are men & 4 cases are women. The age of patients ranged from 31 to 68 years with median age of 55 years. On physical examination, 5 cases had palpated cervical neck node and 6 cases had facial nerve palsy. Staging was done according to the current guidelines established by the American Joint Committee on Cancer (1992). Two cases were stage I, 1 in stage III, and 7 in stage IV. Six cases were performed operation and postoperative radiation therapy. Four cases were treated by curative radiation therapy, dose of more than 65 Gy on parotid gland region. The 5 year actual survival rate and the 5 year disease free survival rate were 30.8%, and 40.0%. Initial complete response rate was 70% for all patients. Local failure were occurred 3 of 7 patients with local controlled cases, failure sites were primary site, ipsilateral cervical neck node, contralateral supraclavicular node. Most recurrences developed within 1 year of initial treatment. Distant metastasis was appeared 2 of 3 patients who did not achieved local control. Primary squamous cell carcinoma of the parotid gland occured infrequently. A retrospective study at the Yonsei Cancer Center indicates incidence of 7.8%. At diagnosis, advanced stage, neck node presentation, facial nerve paralysis were associated with a poor prognosis. These results may suggested that radical surgical excision may be treatment of choice and that planned postoperative radiotherapy may be bendicial for reducing locoregional recurrence rates.
Anti-proliferation of methanol extract of Curcuma rhizome on oral squamous cell carcinoma (KB) and osteosarcoma (HOS) cells were investigated. In order to elucidate the involvement of telomerase inhibitory activity as a part of anti-proliferative effect of Curcuma rhizome on cancer cells, we measured telomerase activity in Curcuma rhizome extract-treated cancer cells. The concentration inhibited cell proliferation to 50% $(IC_{50})$ of the methanol extract of Curcuma rhizome against oral squamous cell carcinoma (KB) cells and osteosarcoma (HOS) cells were 21.30 ${\mu}g/ml$ and 39.3${\mu}g/ml$, respectively. The methanol extract of Curcuma rhizome showed inhibitory telomerase inhibitory effect which is required for cancer cell immortality. Therefore, it seems that the anticancer effect of methanol extract of Curcuma rhizome is at least partially due to telomerase inhibitory effect. Five fraction samples were prepared according to its polarity differences and analyzed anti-proliferative effects of each fraction samples on oral squamous cell carcinoma and osteosarcoma cells. Anticancer effect was observed in dichloromethane, and ethylacetate fractions. The highest anticancer effect was found in dichloromethane fraction which had $IC_{50}$ value of 23.3 ${\mu}g/ml$ and 10.5${\mu}g/ml$ against oral squamous cell carcinoma (KB) cells and osteosarcoma (HOS) cells, respectively.
Mature cystic teratoma is a common ovarian lesion, approximately 10-20% of ovarian tumor. However, it can undergo a malignant transformation, but incidence of malignant transformation is very low. Squamous cell carcinoma is the most common type of malignant transformation in the mature cystic teratoma. Preoperative diagnosis of malignant transformation in the mature cystic teratoma is very difficult, because malignant transformed tissues are very small in the mature cystic teratoma components. And so most of the carcinoma arising in mature cystic teratoma were diagnosed after histologic examination. We experienced a case of squamous cell carcinoma arising in the mature cystic teratoma of the ovary and report a case with a brief review of the literatures.
Cutaneous horn is a morphologic designation for a projectile, conical, dense hyperkeratotic nodule that resembles the horn of an animal. The lesion varies in size from only a few millimeters to several centimeters, in color(white or yellowish) and in form (straight, curved, or twisted). It arises from a wide range of epidermal lesions, which include benign lesions, premalignant lesions and malignant lesions. An 83-year-old women came to our clinic with a giant cutaneous horn on the right chin and a small horn on the left upper eyelid. The patient had no palpable cervical lymph node. A wide elliptical skin incision was made and the horn was totally excised. In pathology, the giant cutaneous horn on the right chin revealed a moderately differentiated squamous cell carcinoma with subcutis invasion at its base. "Giant cutaneous horns" have often been associated with invasive squamous cell carcinoma. Cutaneous horns are common lesions usually found on the face, rarely larger than 2 cm. As large cutaneous horns are often associated with underlying malignancy, histopathologic examination of the base of the lesion is necessary to rule out carcinoma and full excision is recommended.
The concurrence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in a single tumor is rarely encountered. We report a case of BCC and SCC in a single tumor in the anterior auricular area. A 70-year-old woman had been diagnosed with BCC by a punch biopsy performed at a dermatology clinic. We performed wide excision of the tumor with an ulcer in the anterior auricular area. Analysis of the biopsy specimen revealed the presence of both BCC and SCC in the tumor. This case illustrates that it is necessary to establish a precise diagnosis and formulate appropriate surgical and treatment plans considering the possibility that two carcinomas may coexist, although the possibility is low in patients with skin cancer.
Oral squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its high metastasis and recurrent rates and poor prognosis. Taxol is an anticancer agent which is microbial products extracted from jew tree. It combines with the tubulin and induces apoptosis by inhibiting mitosis of cell with microtubule stabilization. Recently, it was reported to be effective in various solid tumors, but only very slight effect has been seen in oral squamous cell carcinomas due to its cell-specific potencies. Cyclosporin A is used as immune suppressant and is being applied in anticancer therapy as its mechanism of induction of change of apoptotic process in various cells have been known. In this study, oral squamous cell carcinoma HN22 cell line was used for in vitro experiment and as for the experimental group taxol and cyclosporin A were applied alone and to observe the synergistic effect of apoptosis, Taxol and cyclosporin A were coadministered with different concentration of taxol for comparison. The results were obtained as follow: 1. There was no difference in Bcl-2, Bax, caspase 3, 8, 9 mRNA expression when cyclosprin A or taxol was applied alone to HN 22 cell line. 2. Caspase 3, 9 mRNA expression was prominently increased when cyclosprin A and taxol were applied together to cancer cell. 3. No significant difference was observed when cyclosporin A and taxol($1{\mu}g/ml$ and $3{\mu}g/ml$) were applied together to cancer cell line. 4. No significant difference was seen in Bcl-2, Bax, and caspase 8 mRNA expression in all the groups of in vitro experiments. 5. When cyclosporin A was applied alone in vivo study on the nude mice, histopathologi cal findings was similar to those of the control group. Oral squamous cell carcinoma induced by inoculation of HN 22 cell line was not reduced after treatment of cyclosporin A. 6. When taxol was applied alone, the islands of squamous cell carcinoma still remained, which meant insignificant healing effect. There was a lesser volume increase compared with the cyclosporin A alone. 7. When taxol and cyclosporin A were applied together, the connective tissue and calcification were seen in the histopathologic findings. Oral squamous cell carcinoma was decreased and cancer cell was disappeared. In observing the tumor mass change with time, there was a gradual decreased size and healing features. As the results of the in vitro experiment, it could conclud that only when the two agents are applied together, mitochondria-mediated apoptosis occurred by considerable increase of caspase 3, 9 mRNA expression, irrespectable of the concentration of taxol. In vivo experiment, there was a discrete synergistic effect when the two agents were applied together. But single use of cyclosporin A was not effective in this study. Based on the results of this experiment, if further clinical studies are done, taxol and cyclosporin A could be effectively used in treatment of oral squamous cell carcinomas.
Head and neck squamous cell carcinoma(HNSCC) still has poor outcome, and laryngeal cancer is the most frequent subtype of HNSCC. Therefore, there is a need to develop novel treatments to improve the outcome of patients with HNSCC. It is critical to gain further understanding on the molecular and chromosomal alteration of HNSCC to identify novel therapeutic targets but genetic etiology of squamous cell carcinoma of the larynx is so complex that target genes have not yet been clearly identified. Array based CGH(array-CGH) allows investigation of general changes in target oncogenes and tumor suppressor genes, which should, in turn, lead to a better understanding of the cancer process. In this study, We used genomic wide array-CGH in tissue specimens to map genomic alterations found in laryngeal squamous cell carcinomas. As results, gains of MAP2, EPHA3, EVI1, LOC389174, NAALADL2, USP47, CTDP1, MASP1, AHRR, and KCNQ5, with losses of SRRM1L, ANKRD19, FLJ39303, ZNF141, DSCAM, GPR27, PROK2, ARPP-21, and B3GAT1 were observed frequently in laryngeal squamous cell carcinoma tissue specimens. These data about the patterns of genomic alterations could be a basic step for understanding more detailed genetic events in the carcinogenesis and also provide information for diagnosis and treatment in laryngeal squamous cell carcinoma. The high resolution of array-CGH combined with human genome database would give a chance to find out possible target genes which were gained or lost clones.
Purpose: FGF4 (fibroblast growth factor 4) is a newly characterized gene which was found to be a transforming gene in several cancerous cells. FGF4 expression and amplification has been subsequently observed in several human cancers including stomach cancer, breast cancer, head and neck squamous cell carcinoma, lung cancer and bladder cancer. This study was designed to measure the protein expression of FGF4 in malignant skin cancers. Methods: We examined 8 normal skin tissues and 24 malignant skin tumor tissues which were 8 malignant melanomas, 8 squamous cell carcinomas and 8 basal cell carcinomas. The specimens were analyzed for the protein expression of FGF4 using immunohistochemical staining. To evaluate the amount of expression of FGF4, the histochemical score (HSCORE) was used. Results: FGF4 was expressed more intensely in malignant melanoma, followed by SCC and BCC in immunohistochemistry. The average HSCORE was 0.01 for normal skin, 2.02 for malignant melanoma, 1.28 for squamous cell carcinoma, and 0.27 for basal cell carcinoma, respectively. The expression of FGF4 in malignant melanoma and squamous cell carcinoma was increased in comparison with normal tissues and basal cell cancer, and the difference was statistically significant (p<0.05). The difference between malignant melanoma and squamous cell carcinoma was not statistically significant. Conclusion: These findings provide evidences that the expression of FGF4 plays an important role in malignant melanoma and squamous cell carcinoma progressions. This article demonstrates expression of FGF4 in human skin malignant tumors, and suggests that FGF4 is more expressed in highly aggressive skin tumors.
Journal of the Korean Association of Oral and Maxillofacial Surgeons
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제33권2호
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pp.103-108
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2007
Cyclooxygenase-2 (Cox-2) is known as one of the critical factor in carcinomas of various organs. However, the importance of Cox-2 in oral squamous cell carcinoma has not been fully described yet. The purpose of this study is to evaluate the anti-cancer effect of selective cox-2 inhibitor, celecoxib in an oral squamous cell carcinoma cell line, KB with respect to cytotoxicity test, in vitro invasion and MMP-2 expression. In cytotoxicity test, celecoxib treated group showed definitely concentration dependent cytotoxicity. In addition, administration of celecoxib reduced the invasive potential of KB cell line significantly in invasion assay. However, there was no remarkable difference of the MMP-2 expression between the celecoxib treated group and the control group. Considering these data, celecoxib had a potential cytotoxic agent to oral squamous cell carcinoma cells. Also, it had anti-invasive property without acting on the MMP-2 expression mechanism. Therefore, it was postulated that celecoxib had the possibility of anti-cancer agent in treatment strategies of oral squamous cell carcinoma.
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