• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4263-4266
• /
• 2012

Colorectal cancer has become a major disease threatening human health. To establish animal models that exhibit the characteristics of human colorectal cancer will not only help to study the mechanisms underlying the genesis and development effectively, but also provide ideal carriers for the screening of medicines and examining their therapeutic effects. In this study, we established a stable, colon cancer nude mouse model highly expressing green fluorescent protein (GFP) for spontaneous metastasis after surgical orthotopic implantation (SOI). GFP-labeled colon cancer models for metastasis after SOI were successfully established in all of 15 nude mice and there were no surgery-related complications or deaths. In week 3, primary tumors expressing GFP were observed in all model animals under fluoroscopy and two metastatic tumors were monitored by fluorescent imaging at the same time. The tumor volumes progressively increased with time. Seven out of 15 tumor transplanted mice died and the major causes of death were intestinal obstruction and cachexia resulting from malignant tumor growth. Eight model animals survived at the end of the experiment, 6 of which had metastases (6 cases to mesenteric lymph nodes, 4 hepatic, 2 pancreatic and 1 mediastinal lymph node). Our results indicate that our GFP-labeled colon cancer orthotopic transplantation model is useful with a high success rate; the transplanted tumors exhibit similar biological properties to human colorectal cancer, and can be used for real-time, in vivo, non-invasive and dynamic observation and analysis of the growth and metastasis of tumor cells.

• Journal of Korean Neurosurgical Society
• /
• v.41 no.3
• /
• pp.186-189
• /
• 2007

Metastasizing mixed tumors [MMT] of salivary glands are inexplicably metastasize maintaining benign histology. There is no pathologic and flow cytometric analysis criteria to predict the metastasis. MMT is known to metastasize by local implantation, vascular and lymphatic embolization after multiple surgery to local recurrences of primary tumor. However, multiple metastasis including cranium and spine occurred even without surgery to the primary tumor in this case. No pathological evidence of malignancy could be found in both primary and metastatic tumor. MMT is considered as an low grade malignancy based on clinical behavior rather than histologic evidence, such as low mortality rate, long delay of metastasis after primary lesion. Cranial metastasis is also extremely rare and only two cases have been reported. We report this unusual case with a literature review.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.33 no.2
• /
• pp.81-93
• /
• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• Tuberculosis and Respiratory Diseases
• /
• v.50 no.6
• /
• pp.718-725
• /
• 2001

The implantation of malignant cells along the needle tract is an extremely rare complication after a percutaneous fine-needle aspiration biopsy(FNAB). However, it is very serious and may result in a change in the prognosis of lung cancer, especially in the curable early stage(T1-2,N0,M0). Recently, we experienced two cases of such complications. A 43 years old female underwent a fine needle aspiration biopsy and a right middle lobectomy with adjuvant chemotherapy due to an adenocarcinoma(T2N0M0). Two years later, a new tumor developed at the site of the needle aspiraton biopsy. It had the same pathological findings as the previous lung cancer. Therefore, it was concluded to be an implantation metastasis, and she was treated successfully by a right pneumonectomy and a resection of the chest wall mass with adjuvant radiotherapy. In another case, a 62 years old man was diagnosed with squamous cell lung cancer by a fine needle aspiration biopsy and underwent a right upper lobectomy(T2N0M0) with adjuvant chemotherapy. eight months later, a protruding chest wall mass developed at the aspiration site. It showed the same pathological findings as the previous lung cancer. Consequently, a total excision of the mass with adjuvant radiotherapy was done. Two years after the second operation, although the right lung was intact, a metachronous squamous cell lung cancer was found at the left lower lobe. The two patients were still alive 15 and 37months after thenresection of the chest wall mass, respectively.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.1
• /
• pp.407-411
• /
• 2014

Objective: To observe local and systemic toxicity after sustained-release 5-fluorouracil (5-Fu) implantation in canine peritoneum and para-aortic abdominalis and the changes of drug concentration in the local implanted tissue with time. Methods: 300 mg sustained-release 5-Fu was implanted into canine peritoneum and para-aorta abdominalis. Samples were taken 3, 5, 7 and 10 days after implantation for assessment of changes and systemic reactions. High performance liquid chromatography was applied to detect the drug concentrations of peritoneal tissue at different distances from the implanted site, lymphatic tissue of para-aortic abdominalis, peripheral blood and portal venous blood. Results: 10 days after implantation, the drug concentrations in the peritoneum, lymphatic tissue and portal vein remained relatively high within 5 cm of the implanted site. There appeared inflammatory reaction in the local implanted tissue, but no visible pathological changes such as cell degeneration and necrosis, and systemic reaction like anorexia, nausea, vomiting and fever. Conclusions: Sustained-release 5-Fu implantation in canine peritoneum and para-aortic abdominalis can maintain a relatively high tumour-inhibiting concentration for a longer time in the local implanted area and portal vein, and has mild local and systemic reactions. Besides, it is safe and effective to prevent or treat recurrence of gastrointestinal tumours and liver metastasis.

• Korean Journal of Pharmacognosy
• /
• v.35 no.4 s.139
• /
• pp.324-329
• /
• 2004

SKT is consisted of skullcap radix, knope-sedge radix and trametes mushroom. SKT mixture extract has been used for curing breast cancer and cervical cancer as a folk medicine without any kind of experimental evidence to support the rationales for its clinical use. This study was undertaken to investigate the antitumor effects and toxicity of SKT. Tumor was induced by implantation of B16F10 melanoma cells $(1{\times}10^6\;cells/mouse)$ into abdominal skin in ICR mice and SKT application (5 mg/mouse, p.o.) was initiated 4 days prior to tumor induction and lasted for 42 days. SKT significantly inhibited not only tumor growth but also metastasis of i.v. implanted melanoma cells into lung and showed prolonged life span of tumor bearing mice. The combined theraphy of SKT with doxorubicin was more effective against tumor metastasis into lung. SKT almostly recovered serum SGPT to normal level of galactosamine/LPS-induced hepatitis mice. High dose of SKT did not show any acute side effects. But, in vitro SKT did not inhibit the growth of melanoma cells, which suggests that the antitumor effects of SKT might be menifested by indirect mechanisms.

• Journal of Korean Neurosurgical Society
• /
• v.61 no.3
• /
• pp.415-423
• /
• 2018

Objective : To identify the perioperative factors associated with instrument failure in patients undergoing a partial corpectomy with instrumentation (PCI) for spinal metastasis. Methods : We assessed the one hundred twenty-four patients with who underwent PCI for a metastatic spine from 1987 to 2011. Outcome measure was the risk factor related to implantation failure. The preoperative factors analyzed were age, sex, ambulation, American Spinal Injury Association grade, bone mineral density, use of steroid, primary tumor site, number of vertebrae with metastasis, extra-bone metastasis, preoperative adjuvant chemotherapy, and preoperative spinal radiotherapy. The intraoperative factors were the number of fixed vertebrae, fixation in osteolytic vertebrae, bone grafting, and type of surgical approach. The postoperative factors included postoperative adjuvant chemotherapy and spinal radiotherapy. This study was supported by the National Research Foundation grant funded by government. There were no study-specific biases related to conflicts of interest. Results : There were 15 instrumentation failures (15/124, 12.1%). Preoperative ambulatory status and primary tumor site were not significantly related to the development of implant failure. There were no significant associations between insertion of a bone graft into the partial corpectomy site and instrumentation failure. The preoperative and operative factors analyzed were not significantly related to instrumentation failure. In univariable and multivariable analyses, postoperative spinal radiotherapy was the only significant variable related to instrumentation failure (p=0.049 and 0.050, respectively). Conclusion : When performing PCI in patients with spinal metastasis followed by postoperative spinal radiotherapy, the surgeon may consider the possibility of instrumentation failure and find other strategies for augmentation than the use of a bone graft for fusion.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.2
• /
• pp.759-764
• /
• 2013

Background: The high recurrence rate after hepatic resection in hepatocellular carcinoma (HCC) is a major obstacle to improving prognosis. The objective of the present study was to explore the function of genistein, a soy-derived isoflavone, in enhancing the inhibitory effect of cisplatin on HCC cell proliferation and on tumor recurrence and metastasis in nude mice after curative hepatectomy. Methods: Proliferation of human HCC cells (HCCLM3) was detected by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Synergistic effects of genistein and cisplatin were evaluated with the median-effect formula. Nude mice bearing human HCC xenografts underwent tumour resection (hepatectomy) 10 days post implantation, then received intraperitoneal administration of genistein or cisplatin alone or the combination of the two drugs. 33 days after surgery, recurrent tumours and pulmonary metastasis were evaluated individually. MMP-2 level in recurrent tumours was detected by immunohistochemistry and real-time PCR; MMP-2 expression in HCCLM3 was detected by immunocytochemistry. Results: Genistein and cisplatin both suppressed the growth and proliferation of HCCLM3 cells. The two drugs exhibited synergistic effects even at relatively low concentrations. In vivo, mice in the combined genistein and cisplatin group had a smaller volume of liver recurrent tumors and fewer pulmonary metastatic foci compared with single drug treated groups. Cisplatin upregulated the expression of MMP-2 in both recurrent tumours and HCCLM3, while genistein abolished cisplatin-induced MMP-2 expression. Conclusions: Genistein reinforced the inhibitory effect of cisplatin on HCC cell proliferation and tumour recurrence and metastasis after curative hepatectomy in nude mice, possibly through mitigation of cisplatin-induced MMP-2 upregulation.

• Molecules and Cells
• /
• v.43 no.5
• /
• pp.479-490
• /
• 2020

Interleukin-9 (IL-9) is well known for its role in allergic inflammation. For cancer, both pro- and anti-tumor effects of IL-9 were controversially reported, but the impact of IL-9 on tumor metastasis has not yet been clarified. In this study, IL-9 was expressed as a secretory form (sIL-9) and a membrane-bound form (mbIL-9) on B16F10 melanoma cells. The mbIL-9 was engineered as a chimeric protein with the transmembrane and cytoplasmic region of TNF-α. The effect of either mbIL-9 or sIL-9 expressing cells were analyzed on the metastasis capability of the cancer cells. After three weeks of tumor implantation into C57BL/6 mice through the tail vein, the number of tumor modules in lungs injected with IL-9 expressing B16F10 was 5-fold less than that of control groups. The percentages of CD4⁺ T cells, CD8⁺ T cells, NK cells, and M1 macrophages considerably increased in the lungs of the mice injected with IL-9 expressing cells. Among them, the M1 macrophage subset was the most significantly enhanced. Furthermore, peritoneal macrophages, which were stimulated with either sIL-9 or mbIL-9 expressing transfectant, exerted higher anti-tumor cytotoxicity compared with that of the mock control. The IL-9-stimulated peritoneal macrophages were highly polarized to M1 phenotype. Stimulation of RAW264.7 macrophages with sIL-9 or mbIL-9 expressing cells also significantly increased the cytotoxicity of those macrophages against wild-type B16F10 cells. These results clearly demonstrate that IL-9 can induce an anti-metastasis effect by enhancing the polarization and proliferation of M1 macrophages.

• Radiation Oncology Journal
• /
• v.5 no.2
• /
• pp.105-110
• /
• 1987

Fourty nine patients with squamous cell carcinoma of oral tongue were reviewed retrospectively for the evaluation of clinical manifestation and for the comparison between therapeutic modalites. The gross shape of the tumor was infiltrative in 22, ulcerative in 12, ad ulcer-oinfiltrative type in 10 patients. Direct extension of the tumor was most commonly to the floor of the mouth. The incidence of nodal metastasis generally increased with tumor stage. $55\%$ of the patients showed neck nodal metastasis at the time of diagnosis. Ipsilateral subdigastric node were most commonly involved, followed by submandibular nodes. The 5-year survival rate of patients treated with surgery and radiotherapy was $58.7\%$ in contrast to $21.6\%$ in radiation alone group. Overall 5-year survival rate was $31\%$ In radiation alone group, half of the patients in stage I, II were locally controlled. But the local control In stage III, IV was much inferior to early lesions. Especially, of 4 patients combined with implantation technique, 3 were completely controlled. 5-year survival rate of these implanted patients was $50\%,\;49.4\%$ of patients treated over 7,000cGy survived 5 years. This was significant in contrast to $6.4\%$ of the group treated below 7,000cGy. The most common sites of failures were primary sites. In early lesions primary radiotherapy with implantation would be an appropriate treatment in cancer of oral tongue, operation reserved for radiation failure. Operation and adjuvant radiotherapy is recommended in cases of advanced disease.