• Journal of Food Hygiene and Safety
• /
• v.31 no.1
• /
• pp.59-66
• /
• 2016

It has been generally accepted that obesity and overweight are associated with metabolic diseases and cancer incidence. In fact, obesity increased risks of cancers i.e. breast, liver, pancreatic and prostate. Celastrol is a pentacyclic triterpenoid isolated from Thunder god vine, was used as a Chinese traditional medicine for treatment of inflammatory disorders such as arthritis, lupus erythematosus and Alzheimer's disease. Also, celastrol has various biological properties of chemo-preventive, neuro-protective, and anti-oxidant effects. Recent studies demonstrated that celastrol has anti-proliferation effects in different type of obesity-related cancers and suppresses tumor progression and metastasis. Anticancer effects of celastrol include regulation of $NF-{\kappa}B$, heat shock protein, JNK, VEGF, CXCR4, Akt/mTOR, MMP-9 and so on. For these reasons, celastrol has shown to be a promising anti-tumor agent. In this review, we will address the anticancer activities and multiple mechanisms of celastrol in obesity-related cancers.

• Journal of Life Science
• /
• v.24 no.1
• /
• pp.8-13
• /
• 2014

The moringa (Moringa oleifera Lam.) plant is used as food and as an anti-allergic agent. In this study, we studied the inhibitory effect of moringa root extract on the expression of PMA-induced matrix metalloproteinase-9 (MMP-9), which is the main factor implicated in the invasion and metastasis of cancer cells in MCF-7 cells. At first, various moringa extracts were examined in the MCF-7 cells. Both moringa root extract and leaf extracts inhibited PMA-induced MMP-9 activity, but the root extract suppressed PMA-induced MMP-9 activity to a greater extent than the leaf extract. The moringa root extract also inhibited PMA-induced MMP-9 protein expression and cell invasion. According to RT-PCR, the treatment of the MCF-7 cells with moringa root extract decreased levels of PMA-induced MMP-9 mRNA expression, but not the expression of TIMP-1 and -2, indicating that moringa root extract prevents the transcription of MMP-9 in response to PMA. In addition, moringa root extract specifically suppressed the phosphorylation of ERK/JNK, but not p38. We suggest that moringa root extract abolishes MMP-9 activity/expression through ERK/JNK. In conclusion, moringa root extract suppressed PMA-induced MMP-9 activity/expression by inhibiting the phosphorylation of ERK/JNK in MCF-7 cells. These results indicate that moringa root extract may be a potential antimetastatic and anti-invasive agent. Future clinical research is needed on the anticancer properties of moringa root extract.

• Journal of Life Science
• /
• v.29 no.4
• /
• pp.499-508
• /
• 2019

Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

• Radiation Oncology Journal
• /
• v.27 no.3
• /
• pp.140-144
• /
• 2009

Purpose: This study was performed to retrospectively analyze patient survival by weighting according to the primary tumor oncotype in 160 patients with brain metastasis and who underwent whole brain radiotherapy. Materials and Methods: A total of 160 metastatic brain cancer patients who were treated with whole brain radiotherapy of 30 Gy between 2002 and 2008 were retrospectively analyzed. The primary tumor oncotype of 20 patients was breast cancer, and that of 103 patients was lung cancer. Except for 18 patients with leptomeningeal seeding, a total of 142 patients were analyzed according to the prognostic factors and the Recursive Partitioning Analysis (RPA) class. Weighted Partitioning Analysis (WPA), with the weighting being done according to the primary tumor oncotype, was performed and the results were correlated with survival and then compared with the RPA Class. Results: The median survival of the patients in RPA Class I (8 patients) was 20.0 months, that for Class II (76 patients) was 10.0 months and that for Class III (58 patients) was 3.0 months (p<0.003). The median survival of patients in WPA Class I (3 patients) was 36 months, that for the patients in Class II (9 patients) was 23.7 months, that for the patients in Class III (70 patients) was 10.9 months and that for the patients in Class IV (60 patients) was 8.6 months (p<0.001). The WPA Class might have more accuracy in assessing survival, and it may be superior to the RPA Class for assessing survival. Conclusion: A new prognostic index, the WPA Class, has more prognostic value than the RPA Class for the treatment of patients with metastatic brain cancer. This WPA Class may be useful to guide the appropriate treatment of metastatic brain lesions.

• Radiation Oncology Journal
• /
• v.21 no.3
• /
• pp.216-221
• /
• 2003

Purpose: To investigate the modulation of radiosensitivity by celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on cancer cells over- and under-expressing COX-2. Materials and Methods: A clonogenic radiation survival analysis was performed on A549 human lung and MCF-7 human breast cancer cell lines incubated in both 1 and $10\%$ fetal bovine serum (FBS) containing media. The apoptosis in both cell lines was measured after treatment with radiation and/or celecoxib. Results: Celecoxib enhanced the radiation sensitivity of the A549 cells in the medium containing the $10\%$ FBS, with radiation enhancement ratios of 1.58 and 1.81 respectively, at surviving fractions of 0.1, with $30\muM\;and\;50\muM$ celecoxib. This enhanced radiosensitivity disappeared in the medium containing the $1\%$ FBS. Celecoxib did not change the radiation sensitivity of the MCF-7 cells in either media. The induction of apoptosis by celecoxib and radiation was not synergistic in either cell line. Conclwsion: Celecoxib, a selective COX-2 inhibitor, preferentially enhanced the effect of radiation on COX-2 over-expressing cancer cells compared to the cells with a low expression, and this effect disappeared on incubation of the cells during drug treatment in the medium with suboptimal serum concentration. Apoptosis did not appear to be the underlying mechanism of this radiation enhancement effect due to celecoxib on the A549 cells. These findings suggest radiosensitization by a selective COX-2 inhibitor is COX-2 dependent.

• The Journal of the Korean bone and joint tumor society
• /
• v.6 no.1
• /
• pp.1-9
• /
• 2000

Purpose : Spine is one of the most common sites of the metastatic bone tumors. Conservative management such as chemotherapy or radiotherapy has been preferred in most cases. However, the neurologic deficit has not been usually improved, and the quality of life was poor. The purpose of this study was to show the efficacy of the surgical treatments for metastatic spinal tumors in terms of postoperative improvements of neurologic deficit and survival time. Materials and Methods : Authors have reviewed the literatures and analyzed 14 patients of metastatic spinal tumors who were received operative treatments between August 1991 and June 1999 at the our department of orthopaedic surgery. Results : The most frequent primary tumor was breast cancer in women and lung cancer in men. The thoracic region was the most common site. There was a preponderance of females over males, and the age ranged between 4th and 8th decade. The indications of surgical treatment comprised instability, progressive neurologic findings, resistance to radiotherapy, pathological fracture, long life expectancy( >6weeks), isolated metastasis and need for pathological diagnosis. The degree of preoperative neurological deficit might influence on the improvement of clinical symptoms after surgery. Conclusion : The surgical treatment reduced the neurological deficit and pain regardless of the operative methods. In the early stage of neurological deficit, the surgical treatment was important for better prognosis. Recently early active operative treatment was performed for metastatic spinal tumor to minimize the intractable pain and to prevent the progression of the neurologic deficit. Early intervention can improve the quality of life and long term survival.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.14 no.2
• /
• pp.145-149
• /
• 2010

Purpose: Recently, $^{18}F$-FDG Fusion PET which has a high sensitivity for diagnosing cancer is being used for purpose of health examination. This study is to demonstrate that $^{18}F$-FDG fusion PET study is useful for diagnosing an early stage cancer. Materials and Methods: This research has been conducted with 2790 patients visited Seoul National University Hospital Healthcare System (SNUHHS) for $^{18}F$-FDG fusion PET study for a health examination from February, 2004 to December 2008. PET/CT images were acquired from skull base to femur after 1 hour from injecting $^{18}F$-FDG 0.14 mCi/kg to the patients. GEMINI GS (Philips, Netherlands) was used for scanning. Results: From February 2004 to December 2008, $^{18}F$-FDG Fusion PET study was performed for 99,009 patients among all patients who visited SNUHHS and 2,790 patients was performed. Diagnostic rate for malignant cancer was 0.95% for the patients who were not examined by $^{18}F$-FDG Fusion PET study. 1.94% was for the patients who were. The rate of malignant tumor was showed 10% and benign tumor was 90% among 542 patients who showed abnormality in the PET/CT images. Types and rates of malignant tumor showed thyroid cancer: 31.5%, lung cancer: 14.8%, stomach cancer: 9.3%, rectum cancer: 3.7%, breast cancer: 3.7%, metastasis cancer: 16.7%. Nonspecific lymph node in the mediastinum, physiologic uptake in the colon, diffuse mild hypermetabolism in bilateral thyroid gland were shown as a benign tumor. Conclusion: The diagnostic rate of malignant tumor with $^{18}F$-FDG Fusion PET for a purpose of health examination was relatively higher than general medical examination. Consequently, it is superior and useful for applying $^{18}F$-FDG Fusion PET study for health examination.

• The Journal of the Korean bone and joint tumor society
• /
• v.9 no.1
• /
• pp.12-17
• /
• 2003

Purpose: In this report we are going to discuss about the functional evaluation and the outcome of treatment of metastatic tumor in the lower extremities treated with tumor prosthetic arthroplasty. Materials and Methods: This report is based on nine patients diagnosed as a metastatic tumor and treated by tumor prosthetic arthroplasty, from June 1998 to December 2001. Age of the patients ranged from 49 to 63 with the average of 56.3. The average follow up period was 23.4 months. Two patients had lung cancer, three had breast cancer, two had renal cancer, one colon cancer, and one had multiple myeloma. All these were primary cancers. The site of metastasis were six in proximal femur, two in distal femur, and one in proximal tibia. Tumor excision was performed after biopsy in following the principle of primary tumor management. Excision with wide surgical margin was tried as possible could. Six cases were treated with tumor prosthesis, and the other three cases were reconstructed with bone cement and arthroplasty. Results: The functional evaluation in the extremities at the last follow up was performed on Enneking evaluation score with 6 categories. The highest scored 26, and the lowest scored 10, with an average of 19.5. A case in which the patient died 15 days after the operation was excluded from the evaluation. Among the categories, emotional acceptance to postoperative function and pain relief were highly scored. At the final follow up, seven patients survived, and one colon cancer patient died 68 days after operation. Conclusion: Metastatic tumor occurring in joints of lower extremities could be treated in accordance to the treatment principle of primary tumor. By insertion of tumor prosthesis, we can get satisfactory results of function in the lower extremity and pain relief especially. So, this aspect of medical favor must be considered in treating patients.

• The Journal of the Korean bone and joint tumor society
• /
• v.9 no.1
• /
• pp.1-11
• /
• 2003

Purpose: To analysis of the result of the treatment of metastatic diaphyseal fracture of the humerus with closed interlocking intrameduallry nailing. Materials and Methods: Among surgically treated 29 patients with pathologic or impending fracture of diaphysis of the humeurs, 13 patients (16 cases) treated with closed intramedullary interlocking nail were selected for the study. The final result of pain relief and functional recovery was evaluated by modified rating system of Perez et al. Results: Primary cancer was diagnosed after fracture was developed in 2 patients and pathologic or impending fracture was occurred average period of 28.9 months after primary cancer was diagnosed. The main primary malignancies were multiple myeloma, lung cancer and breast cancer. Mean survival after humeral metastasis was 11.7 months. The final result was superior to fair in 13 of 16 cases, and poor in 3 cases with progression of tumor spread or distant dissemination to the ipsilateral fingers. Except the latter 3 patients and other 3 patients, who died before 3 months postoperatively, bony union was achieved in 10 cases. There were no complications related to surgery. Conclusion: Closed interlocking intrameduallry nailing is accomplished with brief operative time, small amount of bleeding and provides immediate stability with resultant early return of function to the arm. Additionally it allows early postoperative irradiation. However, some of our cases shows that intramedullary nailing can accelerate tumor spread and metastases elsewhere, so that serious consideration must be given in planning this treatment. In conclusion, the functional status before fracture, life expectancy, type of tumor and extent of involvement should be carefully considered to decide operative treatment of metastatic disease.

• Radiation Oncology Journal
• /
• v.21 no.4
• /
• pp.291-298
• /
• 2003

Purpose: We report upon a web-based system for Patterns of Care Study (PCS) devised for Korean radiation oncology. This PCS was designed to establish standard tools for clinical quality assurance, to determine basic parameters for radiation oncology processes, to offer a solid system for cooperative clinical studies and a useful standard database for comparisons with other national databases. Materials and Methods: The system consisted of a main server with two back-ups in other locations. The program uses a Linux operating system and a MySQL database. Cancers with high frequencies in radiotherapy departments in Korea from 1998 to 1999 were chosen to have a developmental priority. Results: The web-based clinical PCS .system for radiotherapy in www.pcs.re.kr was developed in early 2003 for cancers of the breast, rectum, esophagus, larynx and lung, and for brain metastasis. The total number of PCS study items exceeded one thousand. Our PCS system features user-friendliness, double entry checking, data security, encryption, hard disc mirroring, double back-up, and statistical analysis. Alphanumeric data can be input as well as image data. In addition, programs were constructed for IRB submission, random sampling of data, and departmental structure. Conclusion: For the first time in the field of PCS, we have developed a web-based system and associated working programs. With this system, we can gather sample data in a short period and thus save, cost, effort and time. Data audits should be peformed to validate input data. We propose that this system should be considered as a standard method for PCS or similar types of data collection systems.