• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권6호
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• pp.499-508
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• 2007

Background and Purpose: Some subtypes of malignant salivary gland tumors such as adenoid cystic carcinoma (ACC) frequently result in distant metastasis of vascular origin, which are main causes of treatment failure. The reasons for the affinity for vascular metastatic potential are unclear. Therefore, molecular characteristics that influence the dissemination of metastatic tumor cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of vascular metastasis related factors in orthotopic (parotid) murine models of parotid ACC and compared with those in ectopic (subcutis) tumors of athymic mice. Experimental Design: Using specimens from murine parotid (orthotopic, experimental group) and subcutaneous (ectopic, control group) tumors, which have developed via transplantation of tumor cells, originated from human parotid ACC, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF, FGF2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. We also performed immunohistochemical assays with VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and phosphorylated VEGFR-2. Results: Transplantation of human ACC tumor cell $(5{\times}10^5)$ into the parotid and subcutis successfully resulted in orthotopic (parotid) and ectopic (subcutaneous) tumors in athymic mice. Immunohistochemical staining demonstrated higher expression of major angiogenic factors (VEGF, bFGF, MMP-9) in the orthotopic tumors than in ectopic tumors (P<0.05). But the expression level of angiogenic receptors were same in orthotopic and ectopic tumors of parotid ACC. Conclusion: VEGF, bFGF, and MMP-9 could be a good candidates for antiangiogenic therapy for the contol of vascular metastatic lesions of salivary ACC.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제29권1호
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• pp.10-23
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• 2007

Hallmarks of clinical behaviors of adenoid cystic carcinoma(ACC) of salivary glands are the delayed onset of vascular metastasis and poor responses to classical chemotherapeutic agents. Poor prognoses from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, cellular and molecular characteristics that influence the dissemination of metastatic cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of angiogenic proteins in benign (pleomorphic adenoma) and malignant (ACC, mucoepidermoid carcinoma) tumors of salivary glands and compared each other and to those in oral squamous cell carcinoma. Using surgical specimens, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), phosphorylated VEGFR-2 (pVEGFR-2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. Most angiogenic factors were overexpressed in malignant salivary tumors than in pleomorphic adenoma which is benign nature. Moreover, ACC demonstrated more expression of VEGFR-2 than that of squamous cell carcinoma which used as control. Conclusively, these data show those angiogenic factors produced by salivary gland tumors may affect the propagation and metastasis of malignant cells of salivary tumors, and could be used as biomarkers for the malignant transformation of salivary gland tumors. Prospectively, although further studies will be needed, these biomarkers related to angiogenesis can be molecular targets for the therapy of salivary ACC, which has propensity for delayed vascular metastasis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3151-3154
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• 2013

Introduction: Colorectal cancers are in the top of the cancer-related causes of death in the world and lymph node metastasis is accepted as the primary prognostic factor. In this study, correlations of FGF19 staining pattern with local invasion and lymph node metastasis in a series of colorectal cancers were investigated. Methods: This studyincluded 81 colorectal cancer patients who underwent surgery in our hospital with no evidence of preoperative radiological distant metastasis. Routine pathological examination of the resection material was performed in order to identify vascular, perineural and serosal infiltration, regional lymph node metastasis and the degree of differentiation. Tumor tissue samples were stained with an immunohistochemistry method for FGF 19 evaluation and the staining pattern was statistically compared with the above mentioned characteristics of the tumors. Results: The patient population consisted of 47 females and 34 males with a median age of 70 years. In 40 patients regional lymph nodes were positive and 51%, 32% and 38% had serosal, perineural and vascular invasion. While 64 cases were moderately-differentiated, 11 cases were well-differentiated and 6 poorlydifferentiated, there was no association with FGF 19 staining, including intensity. Conclusion: No evidence of significant statistically correlation was found between FGF 19 staining pattern and serosal, perineural, vascular invasion, lymph node involvement and degree of differentiation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10509-10512
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• 2015

Objective: To investigate the differential features of CT images in children with neuroblastomas (N) and ganglioneuroblastomas (G). Materials and Methods: Clinical data of 12 children in group G and 15 in group N undergoing CT examination and definitely diagnosed by pathology were retrospectively analyzed. The focal conditions were observed and compared in the two groups, including location, size, boundaries, morphology, enhanced degree and mode, abdominal vascular involvement, presence or absence of spanning the midline, infiltration of peripheral organs, angiography manifestations in tumors or surroundings, presence or absence of calcification and vascular tumor emboli as well as metastases of distal organs and lymph nodes. Results: In group N, the incidence of tumors in the adrenal area was conspicuously higher than in group G (P<0.05), while that of tumors with regular morphology and clear boundaries was significantly lower than in group G (P<0.01); Angiography manifestation rate and incidences of vascular embedding, lymph node metastasis, infiltration and organic metastasis in group N were all markedly higher than in group G (P<0.05). There was no statistical significance between the two groups in terms of focal size, presence or absence of calcification and spanning the midline, and enhanced degree and mode, as well as vascular tumor emboli (P>0.05). Conclusions: Mostly located in adrenal areas and with vascular embedding as a primary manifestation, the neuroblastoma extremely readily metastases to lymph nodes and other organs as well as infiltrating local tissues, with dilation on angiography frequent in or around the tumors. With vascular displacement as a primary manifestation, ganglioneuroblastoma has a regular morphology and clear boundaries.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1677-1682
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• 2015

Cancer progression is attained by uncontrolled cell division and metastasis. Increase in tumor size triggers different vascular channel formation to address cell nutritional demands. These channels are responsible for transferring of nutrients and gaseous to the cancer cells. Cancer vascularization is regulated by numerous factors including vascular endothelial growth factors (VEGFs). These factors play an important role during embryonic development. Members included in this group are VEGFA, VEGFB, VEGFC, PIGF and VEGFD which markedly influence cellular growth and apoptosis. Being freely diffusible these proteins act in both autocrine and paracrine fashions. In this review, genetic characterization these molecules and their putative role in cancer staging has been elaborated. Prognostic significance of these molecules along with different stages of cancer has also been summarized. Brief outline of ongoing efforts to target hot spot target sites against these VEGFs and their cognate limitations for therapeutic implications are also highlighted.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.271-274
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• 2015

Background: To explore vascular endothelial growth factor C (VEGF-C) and VEGF-D expression and its correlation with lymph node metastasis in esophageal squamous cell cancer (ESCC) tissue. Materials and Methods: Immunohistochemical methods were applied to detect the levels of VEGF-C and VEGF-D expression in 64 surgicall removal ESCC tissues, tissues adjacent to cancer and normal tissues, and the relationship between VEGF-C and VEGF-D expression and lymph node metastasis was analyzed. Results: Both VEGF-C and VEGF-D were expressed by varying degrees in esophageal cancer tissue, the tissue adjacent to cancer and normal tissue, and the positive expression rate went down successively. The positive expression rates of VEGF-C (59.4%) and VEGF-D (43.8%) in esophageal cancer tissue were significantly higher than in the tissue adjacent to cancer (34.4%, 15.6%) and normal tissue (20.3%, 12.5%), respectively, in which significant differences were manifested (p<0.01). Positive expression rates of VEGF-C and VEGF-D in esophageal cancers with lymph node metastasis were markedly higher than without such metastasis (p<0.01), while those in the tissue with TNM staging I~II were markedly lower than that with TNM staging III~IV (p<0.01). Conclusions: Both VEGF-C and VEGF-D are highly expressed in ESCC tissue, which may be related to the lymph node metastasis of cancer cells. Hence, VEGF-C and VEGF-D can be clinically considered as important reference indexes of lymph node metastasis in esophageal cancer.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권2호
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• pp.110-122
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• 2005

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

• Journal of Gastric Cancer
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• 제18권4호
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• pp.379-391
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• 2018

Purpose: Gastric cancer (GC) patients with peritoneal metastasis (PM) have poor prognosis. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) in combination with systemic chemotherapy is a novel treatment option for patients in stage IV of the disease. Materials and Methods: Between November 2015 and June 2018, prospective data collection was performed in 24 patients with GC and PM (median age, 57; range, 44-75 years). These patients underwent 46 PIPAC procedures with a median number of 2 interventions per patient (range, 1-6). A laparoscopic access was used and a combined therapy of cisplatin and doxorubicin aerosol was administered. Results: The median peritoneal carcinomatosis index before the 1st PIPAC was 14 (range, 2-36), and the median ascites volume in patients before the 1st PIPAC was 100 mL (range, 0-6 mL, 300 mL). Eleven patients, who received 2 or more PIPAC procedures, had decreased and stable volumes of ascites, while only 3 patients displayed increasing volume of ascites. The median overall survival was 121 days (range, 66-625 days) after the 1st PIPAC procedure, while 8 patients who received more than 3 PIPAC procedures had a median survival of 450 days (range, 206-481 days) (P=0.0376). Conclusions: Our data show that PIPAC is safe and well tolerated, and that the production of ascites can be controlled by PIPAC in GC patients. Patients, who received 2 or more PIPAC procedures, reported a stable overall quality of life. Further studies are required to document the significance of PIPAC as a palliative multimodal therapy.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권1호
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• pp.59-70
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• 2008

Purpose: We evaluated the therapeutic effect of AEE788, a dual inhibitor of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on human salivary adenoid cystic carcinoma (ACC) cells growing in nude mice. Experimental Design: We examined the effects of AEE788 on salivary ACC cell growth and apoptosis. To determine the in vivo effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 (50 mg/kg) three times per week, injected paclitaxel ($200{\mu}g$) once per week, AEE788 plus paclitaxel, or placebo. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. Results: Treatment of salivary ACC cells with AEE788 led to growth inhibition and induction of apoptosis. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. Furthermore, AEE788 potentiated growth inhibition and apoptosis of ACC tumor cells mediated by paclitaxel. Tumors of mice treated with AEE788 and AEE788 plus paclitaxel exhibited down-regulation of activated EGFR and its downstream mediators (Akt and MAPK), increased tumor and endothelial cell apoptosis, and decreased microvessel den-sity, which correlated with a decrease in the level of MMP-9, MMP-2 and bFGF expression and a decrease in the incidence of vascular metastasis. Conclusions: These data show that tumor-associated endothelial cells are important in the process of tumor-metastasis. And VEGFR can be a molecular target for therapy of metastatic lung lesion of salivary ACC.

• Journal of Korean Neurosurgical Society
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• 제41권3호
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• pp.186-189
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• 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.