• Journal of Chest Surgery
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• v.44 no.2
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• pp.159-164
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• 2011

Background: Renal cell carcinoma has shown less response to systemic therapies including chemotherapy, radiation, and immunotherapy than other cancers. Surgery has therefore become an important treatment tool. The protocol for treatment is the same for pulmonary metastasis of renal cell carcinoma. We performed surgery for pulmonary metastatic renal cell carcinomas and analyzed the results. Materials and Methods: We retrospectively analyzed 15 patients who had undergone pulmonary metastasectomy from renal cell carcinoma at our hospital from January 2005 to December 2009. Results: No patients had extrathoracic metastatsis. The mean age was 60.2 years (range 35~73). There were 12 male and 3 female patients. The number of synchronous and metachronous patients were 8 and 7, respectively. The mean survival times of synchronous and metachronous patients were 32.6 and 42.9 months, respectively. 6 patients had single lesions and 9 patients had multiple (more than 3) lesions. The surgical procedures included wedge resection (10), lobectomy (2), wedge resection with segmentectomy (2), and segmentectomy (1). Median observation and survival time were 54.1 and 34.9 months. The 1-year and 3-year survival rates were 80% and 50%, respectively. Conclusion: Pulmonary resection for pulmonary metastatic renal cell carcinoma was found to be a safe and effective treatment modality when complete resection was performed.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.367-374
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• 2019

Euphorbia humifusa Willd (EuH), called Ttang-Bin-Dae in Korea, is a traditional medicinal plant widely used for its anti-inflammatory and antiviral activity. Ethyl acetate (EA) extracts of EuH (EA/EuH) inhibit invasion and metastasis by inhibiting tumor necrosis factor TNFá-induced matrix metalloproteinases (MMP)-9 expression in human breast cancer cells. However, the bioactive components of EA/EuH mediating the inhibition of MMP-9 expression have not been identified. In the present study, three bioactive constituents of EA/EuH were isolated using high-performance liquid chromatography. Nuclear magnetic resonance spectroscopy revealed isoquercetin, avicularin, and astragalin as the bioactive compounds responsible for preventing TNFα-induced MMP-9 mRNA expression in breast cancer cells. These findings suggest that isoquercetin, avicularin, and astragalin could be used as valuable anti-metastatic agents against metastatic cancers.

• Biomolecules & Therapeutics
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• v.29 no.1
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• pp.64-72
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• 2021

Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of Nigella sativa, has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells. We found that treatment with TQ reduced the proteolytic activity of matrix metalloproteinase-9 (MMP-9) in Caki-1 cells. TQ significantly repressed prostaglandin E2 (PGE2) production, its EP2 receptor expression as well as the activation of Akt and p38, the wellknown upstream signal proteins of MMP-9. In addition, treatment with butaprost, a PGE2 agonist, also induced MMP-9 activity and migration/invasion in Caki-1 cells. Moreover, pharmacological inhibitors of PI3K/Akt and p38 remarkably attenuated butaprost-induced Caki-1 cell migration and invasion, implying that activation of PI3K/Akt and p38 is a bridge between the PGE2-EP2 axis and MMP-9-dependent migration and invasion. Taken together, these data suggest that TQ is a promising anti-metastatic drug to treat advanced and metastatic RCC.

• Natural Product Sciences
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• v.28 no.2
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• pp.80-88
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• 2022

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.551-561
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• 2021

Thyroid cancer is the most common endocrine malignancy. Patients with well-differentiated thyroid cancers, such as papillary and follicular cancers, have a favorable prognosis. However, poorly differentiated thyroid cancers, such as medullary, squamous and anaplastic advanced thyroid cancers, are very aggressive and insensitive to radioiodine treatment. Thus, novel therapies that attenuate metastasis are urgently needed. We found that both PDGFC and PDGFRA are predominantly expressed in thyroid cancers and that the survival rate is significantly lower in patients with high PDGFRA expression. This finding indicates the important role of PDGF/PDGFR signaling in thyroid cancer development. Next, we established a SW579 squamous thyroid cancer cell line with 95.6% PDGFRA gene insertion and deletions (indels) through CRISPR/Cas9. Protein and invasion analysis showed a dramatic loss in EMT marker expression and metastatic ability. Furthermore, xenograft tumors derived from PDGFRA geneedited SW579 cells exhibited a minor decrease in tumor growth. However, distant lung metastasis was completely abolished upon PDGFRA gene editing, implying that PDGFRA could be an effective target to inhibit distant metastasis in advanced thyroid cancers. To translate this finding to the clinic, we used the most relevant multikinase inhibitor, imatinib, to inhibit PDGFRA signaling. The results showed that imatinib significantly suppressed cell growth, induced cell cycle arrest and cell death in SW579 cells. Our developed noninvasive apoptosis detection sensor (NIADS) indicated that imatinib induced cell apoptosis through caspase-3 activation. In conclusion, we believe that developing a specific and selective targeted therapy for PDGFRA would effectively suppress PDGFRA-mediated cancer aggressiveness in advanced thyroid cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10557-10563
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• 2015

It is well known that conventional chemotherapy and radiation therapy can result in toxicity to both normal cells and tumor cells, which causes limitations in the application of these therapeutic strategies for cancer control. Novel and effective therapeutic strategies for cancers with no or low toxicity for normal cells are a high priority. Therefore, natural products with anticancer activity have gained more and more attention due to their favorable safety and efficacy profiles. Pre-clinical and clinical studies have demonstrated that several representative natural compounds such as resveratrol, epigallocatechin-3-gallate, curcumin, allicin and ginsenosides have obvious anticancer potential. In this article, we summarize autophagy-associated targeting pathways of such natural products for inducing the death of cancer cells, and discuss the core autophagic pathways involved in cancer treatments. Recent advances in the discovery, evaluation and exploitation of natural compounds as therapeutic agents for cancers will provide references and support in pre-clinical and clinical application of novel natural drugs for the treatment of primary and metastatic tumors in the future.

• Korean Journal of Head & Neck Oncology
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• v.25 no.2
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• pp.163-167
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• 2009

Sinonasal malignant tumors comprise less than 1% of all cancers and 3% of all malignant tumors of the head and neck, which explains a lack of large series addressing the clinical characteristics and management of these tumors. Neck node metastasis occurs in only about 7% to 15% of malignant tumors compared with other head and neck cancers. A 90-yr-old woman presented with left palpable neck mass and right nasal mass occupying nasal cavity. Fine needle aspiration biopsy of left neck mass results in metastatic squamous cell carcinoma(SCC). PET/CT shows intense FDG uptake in right nasal cavity with bone invasion. Histopathologic examination of excised lesion in the right nasal cavity revealed SCC. We report here on a primary sinonasal SCC with contralateral lymph node metastasis.

• The Korean Journal of Pain
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• v.34 no.4
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• pp.375-393
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• 2021

Percutaneous osteoplasty (POP) is defined as the injection of bone cement into various painful bony lesions, refractory to conventional therapy, as an extended technique of percutaneous vertebroplasty (PVP). POP can be applied to benign osteochondral lesions and malignant metastatic lesions throughout the whole skeleton, whereas PVP is restricted to the vertebral body. Common spinal metastases occur in the thoracic (70%), lumbosacral (20%), and cervical (10%) vertebrae, in order of frequency. Extraspinal metastases into the ribs, scapulae, sternum, and humeral head commonly originate from lung and breast cancers; extraspinal metastases into the pelvis and femoral head come from prostate, urinary bladder, colon, and uterine cervical cancers. Pain is aggravated in the dependent (or weight bearing) position, or during movement (or respiration). The tenderness and imaging diagnosis should match. The supposed mechanism of pain relief in POP is the augmentation of damaged bones, thermal and chemical ablation of the nociceptive nerves, and local inhibition of tumor invasion. Adjacent (facet) joint injections may be needed prior to POP (PVP). The length and thickness of the applied needle should be chosen according to the targeted bone. Bone cement is also selected by its osteoconduction, osteoinduction, and osteogenesis. Needle route should be chosen as a shortcut to reach the target bony lesions, without damage to the nerves and vessels. POP is a promising minimally invasive procedure for immediate pain relief. This review provides a technical survey for POPs in painful bony lesions.

• BMB Reports
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• v.53 no.12
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• pp.664-669
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• 2020

Breast cancer is one of the most frequently diagnosed cancers. Although biomarkers are continuously being discovered, few specific markers, rather than classification markers, representing the aggressiveness and invasiveness of breast cancer are known. In this study, we used samples from canine mammary tumors in a comparative approach. We subjected 36 fractions of both canine normal and mammary tumor plasmas to high-performance quantitative proteomics analysis. Among the identified proteins, LCAT was selectively expressed in mixed tumor samples. With further MRM and Western blot validation, we discovered that the LCAT protein is an indicator of aggressive mammary tumors, an advanced stage of cancer, possibly highly metastatic. Interestingly, we also found that LCAT is overexpressed in high-grade and lymph-node-positive breast cancer in silico data. We also demonstrated that LCAT is highly expressed in the sera of advanced-stage human breast cancers within the same classification. In conclusion, we identified a possible common plasma protein biomarker, LCAT, that is highly expressed in aggressive human breast cancer and canine mammary tumor.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4791-4795
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• 2015

Purpose: This study was conducted to observe the efficacy and safety of pemetrexed based chemotherapy in treating patients with locally advanced or metastatic cancers as first-line, second-line or third-line therapy. Materials and Methods: From May 2011 to January 2015, we recruited 29 patients with advanced breast cancer, 19 patients with advanced ovary cancer, 17 patients with advanced esophageal cancer,5 patients with advanced gallbladder cancer,5 patients with advanced cervical cancer and 1 patient with advanced tongue cancer in Jiangsu Cancer Hospital and Research Institute.All of them were pathologically confirmed and treated with pemetrexed based chemotherapy. After two cycles of treatment,efficacy and safety can be evaluated. Results: For pemetrexed based regimens,including 76 patients with 6 kinds of advanced cancer were considered eligible for inclusion. Complete remission represents CR, partial remission represents PR, stable disease represents SD, progressive disease represents PD. Among 29 patients with advanced breast cancer, 4 patients chose pemetrexed based regimens as second-line treatment,1 of them was PR,the other 3 got SD. The last 25 patients made use of this chemotherapy as third-line treatment, except one patient could not be assessed, 2 of them got PR,6 of them got SD,the remaining 16 of them finally were PD.19 patients with advanced ovary cancer,5 patients used this regimens as second-line treatment, 3 of them got PD,the remaining patients got SD, respectively. The last 14 patients made use of pemetrexed based regimens as third-line treatment,. RR (CR+PR) was 28.5%. Among 17 patients with advanced esophageal cancer, 2 patients made use of pemetrexed based regimens as first-line treatment,both of them got PR.4 of them used this chemotherapy as second-line regimen, except 2 patients could not be assessed,the remaining 2 was PD at last. The last 11 patients was third-line users, RR (CR+PR) was 18.2%. Among 5 patients with advanced gallbladder cancer, pemetrexed based regimens was used in 1 patient as first-line treatment and 1 patient as second-line treatment. The curative effect was SD and PD, respectively. 3 patients accepted pemetrexed based regimens as third-line treatment, 2 of them got PD as results and another was SD. Among 5 patients with advanced cervical cancer, just 1 patient adopted pemetrexed based regimens as first-line treatment, whose curative effect was PR.2 patients chose this chemotherapy regimens as second-line treatment. Both of them got PD as their consequence. The last 2 patients made use of the regimens as third-line treatment, the effect of them was PD and SD, respectively. The one who with advanced tongue cancer, pemetrexed based regimens was used as second-line treatment, and the consequence was PD. About 71.1% patients experienced bone marrow suppression. Among them, 5 patients reached 4 grade. Other toxicity of pemetrexed were neurotoxicity, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusions: Pemetrexed based chemotherapy has considerable effect in patients with advanced cancers such as breast cancer,esophageal cancer and ovary cancer. More randomly clinical trials are needed to verify the results.