• Journal of Cancer Prevention
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• v.21 no.2
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• pp.88-94
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• 2016

Background: Breast cancer is the most common malignant disease in women. The patients with advanced breast cancer develop metastasis to bone. Bone metastasis and skeletal-related events by breast cancer are frequently associated with the invasiveness of breast cancer cells and osteoclasts-mediated bone resorption. Forsythia koreana is used in oriental traditional medicine to treat asthma, atopy, and allergic diseases. The aim of this study was to evaluate the inhibitory effects of F. koreana extracts on the invasion of breast cancer cells and bone resorption by osteoclasts. Methods: Cell viability was measured by an MTT assay and the migration and invasion of MDA-MB-231 cells were detected by a Boyden chamber assay. The formation of osteoclasts and pit was detected using tartrate-resistant acid phosphatase staining and calcium phosphate-coated plates, respectively. The activities of matrix metalloproteinases (MMPs) and cathepsin K were evaluated by gelatin zymography and a cathepsin K detection kit. Results: The fruit and leaf extracts of F. koreana significantly inhibited the invasion of MDA-MB-231 cells at noncytotoxic concentrations. The fruit extract of F. koreana reduced the transforming growth factor ${\beta}1-induced$ migration, invasion and MMPs activities of MDA-MB-231 cells. In addition, the fruit, branch, and leaf extracts of F. koreana also inhibited the receptor activator of nuclear factor kappa-B ligand-induced osteoclast formation and osteoclast-mediated bone-resorbing activity by reducing the activities of MMPs and cathepsin K. Conclusions: The extracts of F. koreana may possess the potential to inhibit the breast cancer-induced bone destruction through blocking invasion of breast cancer cells, osteoclastogenesis, and the activity of mature osteoclasts.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4871-4876
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• 2014

Background: We sought to evaluate the role of tumor associated macrophages (TAMs) on the promotion of coal tar pitch extract (CTPE)-induced tumorigenesis of human bronchial epithelial cells (BEAS-2B) and tumor metastasis in nude mice, and related mechanisms. Materials and Methods: BEAS-2B cells were first treated with 2.4 mg/mL CTPE for 72 hours. After removal of CTPE, the cells were continuously cultured and passaged using trypsin-EDTA. THP-1 cells were used as macrophage-like cells. BEAS-2B cells under different conditions (n=6/group) were injected into the back necks of nude mice, and alterations of tumor xenograft growth, indicative of tumorigenicity, and tumor metastasis were determined. Pathological changes (tumor nests and microvascular lesions) of HE-stained tumor tissues were also evaluated. The expression of AP-1(c-Jun) in xenografts and metastatic tumors was determined using immunohistochemistry. Results: Tumor size and weight in nude mice transplanted with the mixture of CTPE-induced passage 30 BEAS-2B and THP-1 cells (2:1) were increased compared to those from the CTPE-treated BEAS-2B cells at passage 30 alone at different observation time points. Tumor metastasis to lymph nodes and liver was only detected after transplantation of a mixture the two kinds of cells. The numbers of tumor nests and microvascular lesions, and the expression levels of AP-1 (c-Jun) in tumors from the mixture of two kinds of cells were increased apparently in contrast to those in tumor from the CTPE-treated BEAS-2B cells of passage 30 alone. In addition, there was positive correlation between AP-1 (c-Jun) expression level and the number of microvascular lesions, or between AP-1 (c-Jun) expression level and tumor metastasis in these two groups. Conclusions: TAMs not only facilitate tumorigenesis transformation of CTPE-induced BEAS-2B cells, but also promote tumor growth, angiogenesis and metastasis in nude mice in vivo, which may be mediated by AP-1.

• Journal of Nutrition and Health
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• v.53 no.4
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• pp.369-380
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• 2020

Purpose: It has been previously reported that breast tumor incidence, growth, and metastasis are stimulated by high-fat diet but reduced by caloric restriction. However, few studies have elucidated the effects of dietary change from a high-fat diet after breast cancer initiation. Therefore, in this study, we attempted to provide practical assistance to breast cancer prevention and management by investigating the effects of dietary change from a high-fat diet to normal diet on breast cancer growth and metastasis. Methods: The experimental animals were divided into 2 groups (high-fat diet control [HFC] group and diet restriction [DR] group) and consumed a high-fat diet for 8 weeks. 4T1 cells were transplanted into subcutaneous fat or tail vein to measure the growth and metastasis of breast cancer. The HFC and DR groups continuously ingested either high-fat diet or AIG-93G diet for 5 weeks or 3 weeks, respectively. Cell proliferation and apoptosis markers from tumor tissues were analyzed by Western blot analysis. The data were analyzed using the SPSS 25.0 package program. Results: The results show that the DR group significantly reduced breast tumor initiation, growth, and tumor tissue weight compared to the HFC group. The DR group suppressed tumor growth by decreasing proliferation and inducing apoptosis through down-regulation of Bcl-xL and up-regulation of caspase-3 activity. Furthermore, the DR group significantly reduced numbers of metastasized tumors in lung tissues. Conclusion: These results suggest that dietary change from a high-fat diet to normal diet decreased breast growth by reducing cell proliferation and inducing apoptosis and metastasis. Taken together, these results indicate that dietary change to a low-fat and balanced diet might suppress breast tumor growth and metastasis even after tumor diagnosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.2099-2102
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• 2015

Objective: To explore the expression of $laminin{\gamma}2$ in extrahepatic cholangiocarcinoma (EHCC) tissues and its influence on tumor invasion and metastasis. Materials and Methods: Paraffin embedding samples of cancer, para-cancer, lymph node metastatic and hepatic metastatic tissues from 79 patients undergoing EHCC resection were collected. Expression of $laminin{\gamma}2$ was detected by immunohistochemistry and its relationship with clinical pathological characteristics and the prognosis of EHCC patients were analyzed. Results: $Laminin{\gamma}2$ showed negative staining in para-cancer tissues, but demonstrated a 51.9% (41/79) positive expression rate in extracellular matrix (ECM) or cytoplasm of EHCC tissues. In lymph node metastatic and distant metastatic nidi, expression of $laminin{\gamma}2$ was significantly higher than in the primary nidi (${\chi}^2=7.4173$, P=0.0065; ${\chi}^2=4.0077$, P=0.0453). The expression was in obvious association with lymph node metastasis (P<0.01), but had no relevance with age, gender, tumor location, tumor stage, differentiation and distant metastasis in ECM (P>0.05), whereas it was in marked connection with lymph node and distant metastasis (P<0.05 or P<0.01), but had no relationship with age, gender, tumor location, tumor stage and differentiation in cytoplasm (P>0.05). However, the median survival time and median recurrent period of patients with positive expression of $laminin{\gamma}2$ in both cytoplasm and ECM of tumor cells, only in ECM and only in cytoplasm, were evidently lower than with negative expression of $laminin{\gamma}2$ in RCM and cytoplasm (P<0.05 or P<0.01). Further Cox regression analysis showed that the positive expression of $laminin{\gamma}2$ and the tumor differentiation were independent risk factors influencing the prognosis of EHCC patients. Conclusions: Abnormal expression of $laminin{\gamma}2$ may be closely associated with invasion and metastasis of tumor cells, and thus a potential molecular marker for prognosis of EHCC patients.

• Journal of Gastric Cancer
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• v.13 no.2
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• pp.93-97
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• 2013

Purpose: Endoscopic submucosal dissection has recently been practiced on a differentiated type of early gastric cancer. However, there is no clear evidence for endoscopic treatments of signet ring cell carcinoma. The aim of this study is to identify the predictive clinicopathological factors for lymph node metastasis in signet ring cell carcinoma for assisting endoscopic submucosal dissection trials. Materials and Methods: A total of 186 patients with early signet ring cell carcinoma who underwent radical curative gastrectomy between January 2001 and September 2009 were enrolled in this study. Retrospective reviews of their medical records are being conducted. Several clinicopathologic factors were being investigated in order to identify predictive factors for lymph nodes metastasis: age, gender, tumor size, type of operation, tumor location, gross type, ulceration, Lauren's classification, depth of invasion, and lymphatic invasion. Results: The lymph node metastasis rate for signet ring cell carcinoma was 4.3% (n=8). Of the 186 lesions with early signet ring cell carcinoma, 91 (48.9%) tumors were larger than 15 mm in size and 40 (21.5%) showed submucosal invasions in the resection specimens. In multivariate analysis, only the lymphatic invasion (P<0.0001) showed an association with lymph node metastasis. To evaluate cutoff values for tumor sizes in the presence of lymph node metastasis, early signet ring cell carcinomas with lymphatic invasions were excluded. In the absence of lymphatic invasion, mucosal cancer with tumor sizes <15 mm had no lymph node metastasis. Conclusions: Endoscopic submucosal dissection can be performed on patients with early signet ring cell carcinoma limited to the mucosa and less than 15 mm.

• Journal of Breast Cancer
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• v.21 no.4
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• pp.442-446
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• 2018

Purpose: The definition of nodal pathologic complete response (pCR) after a neoadjuvant chemotherapy (NAC) just included the evaluation of axillary lymph node (ALN) without internal mammary lymph node. This study aimed to evaluate the feasibility of internal mammary-sentinel lymph node biopsy (IM-SLNB) in patients with breast cancer who underwent NAC. Methods: From November 2011 to 2017, 179 patients with primary breast cancer who underwent operation after NAC were included in this study. All patients received radiotracer injection with modified injection technology. IM-SLNB would be performed on patients with internal mammary sentinel lymph node (IMSLN) visualization. Results: Among the 158 patients with cN+ disease, the rate of nodal pCR was 36.1% (57/158). Among the 179 patients, the visualization rate of IMSLN was 31.8% (57/179) and was 12.3% (7/57) and 87.7% (50/57) among those with $cN_0$ and cN+ disease, respectively. Furthermore, the detection rate of IMSLN was 31.3% (56/179). The success rate of IM-SLNB was 98.2% (56/57). The IMSLN metastasis rate was 7.1% (4/56), and all of them were accompanied by ALN metastasis. The number of positive ALNs in patients with IMSLN metastasis was 3, 6, 8, and 9. The pathology nodal stage had been changed from $pN_1/pN_2$ to $pN_{3b}$. The pathology stage had been changed from IIA/IIIA to IIIC. Conclusion: Patients with visualization of IMSLN should perform IM-SLNB after NAC, especially for patients with cN+ disease, in order to complete lymph nodal staging. IM-SLNB could further improve the definition of nodal pCR and guide the internal mammary node irradiation.

• Journal of Digestive Cancer Research
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• v.1 no.1
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• pp.6-16
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• 2013

Recent estimates for colon cancer incidence in Korea have been increased and continue to rank as the second most common in male and the third in female. Although colonoscopy has been known as the best screening tool for colon cancer, 20-25% of patients with colon cancer was diagnosed with stage IV cancer. During the past 10 years, intensive clinical studies helped to establish the value of palliative treatment for colon cancer with metastasis. The introduction of new chemotherapeutic agents such as irinotecan and oxaliplatin has led to a significant increase in tumor response and median survival. In advanced colon cancer, impressive prolongation or overall survival can be achieved through sequential application of combined systemic chemotherapy. In addition, targeted manipulation of molecular tumor mechanisms with new substances such as monoclonal antibodies against the epidermal growth factor receptor or vascular endothelial growth factor shows promising effects. Progress in the systemic treatment of colon cancer is evident, not only because of the significant increase in life expectancy in advanced colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2473-2476
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• 2012

Background: In papillary and follicular thyroid cancers (PTC, FTC), nodal and distant metastasis are generally considered important determinants of recurrence and survival, respectively. However, there is no consensus about the threshold primary tumour size (PTS) for these determinants. The aim of this study was to assess size relationships for developing nodal, pulmonary, bone and overall distant metastases. Methods: This prospective study covered 139 (93 females and 46 males) consecutive biopsy proven patients with PTC (114/139, mean age $41.0{\pm}15.7$ years, M: F, 35%:65%) and FTC (25/139, mean age $39.2{\pm}14.3$ years, M: F: 24%:76%). Results: Average primary tumor size was $23.4{\pm}11.1$ mm and $26.5{\pm}13.1$ mm for PTC and FTC respectively (p value=0.223). Nodal metastasis was found more common in PTC than FTC (49% vs 28%, p value <0.05), whereas overall distant metastasis was approximately the same (13% and 24%, p value=0.277); however, bone metastasis was significantly higher in FTC than PTC (24% vs 5%, p value <0.05). Cumulative risk for nodal and distant metastases for FTC and PTC starts at PTS <20 mm and may indicate an unusual aggressive tumor behavior in the studied population. Highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC was found to be ${\geq}50$ mm PTS. Conclusion: We conclude that a PTS of <20 mm may indicate an unusual aggressive tumor behavior with highest cumulative risk for nodal and pulmonary metastases in PTC and for bone metastasis in FTC with a cutoff of ${\geq}50$ mm.

• BMB Reports
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• v.50 no.8
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• pp.401-410
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• 2017

The protein disulfide isomerase (PDI) family is a group of multifunctional endoplasmic reticulum (ER) enzymes that mediate the formation of disulfide bonds, catalyze the cysteine-based redox reactions and assist the quality control of client proteins. Recent structural and functional studies have demonstrated that PDI members not only play an essential role in the proteostasis in the ER but also exert diverse effects in numerous human disorders including cancer and neurodegenerative diseases. Increasing evidence suggests that PDI is actively involved in the proliferation, survival, and metastasis of several types of cancer cells. Although the molecular mechanism by which PDI contributes to tumorigenesis and metastasis remains to be understood, PDI is now emerging as a new therapeutic target for cancer treatment. In fact, several attempts have been made to develop PDI inhibitors as anti-cancer drugs. In this review, we discuss the properties and diverse functions of human PDI proteins and focus on recent findings regarding their roles in the state of diseases including cancer and neurodegeneration.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.116-120
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• 2008

Prostate cancer is the second leading cause of cancer death of men in western countries and the death related to this disease in Korea is also getting increased. Although anatomic imaging tools such as transrectal US or MRI have been playing a great role in detection of primary prostate lesion, the evaluation of regional lymph node or distant organ metastasis using these modalities is not successful. $^{18}F-FDG-PET$ scan is emerging diagnostic tool for various malignancies. Considering the usual characteristics of prostate cancer such as slow growing and osteoblastic metastasis, the application of FDG PET scan to this disease might be limited. However, in advanced prostate cancer refractory to chemotherapy, FDG PET scan show strong FDG uptake and SUV changes in serial PET scan can be a good indicator of treatment response. Although FDG PET can be useful only in limited cases of prostate cancer, its indication can be widened in future owing to rapid technical improvement and accumulated experiences in this field.