• Biomolecules & Therapeutics
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• 제30권5호
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• pp.465-472
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• 2022

Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl₂ is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl₂-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl₂-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl₂ but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl₂, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

• Tuberculosis and Respiratory Diseases
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• 제75권4호
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• pp.165-169
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• 2013

An inflammatory myofibroblastic tumor (IMT) is a rare disease entity reported to arise in various organs. It is thought to be a neoplastic or reactive inflammatory condition, controversially. The treatment of choice for myofibroblastic tumor is surgery, and recurrence is known to be rare. The optimal treatment method is not well-known for patients ineligible for surgery. We report a 47-year-old patient with aggressive recurrent IMT of the lungs. The patient had been admitted for an evaluation of back-pain two years after a complete resection of pulmonary IMT. Radiation therapy was performed for multiple bone recurrences, and the symptoms were improved. However the patient presented again with aggravated back-pain six months later. High-dose steroid and non-steroidal anti-inflammatory drugs were administered, but the disease progressed aggressively, resulting in spinal cord compression and metastasis to intra-abdominal organs. This is a very rare case of aggressively recurrent pulmonary IMT with multi-organ metastasis.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.331-341
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• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.2031-2035
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• 2015

Intra-tumoral hypoxia is an environment that promotes tumor cell migration, angiogenesis and epithelial-mesenchymal transition that accounts for a major mechanism of metastasis. Chloroquine potentially offers a new therapeutic approach with an 'old' drug for effective and safe cancer therapies, as it exerts anti-metastatic activity. We investigated the inhibitory effect of chloroquine on cholangiocarcinoma (CCA) cell migration under cobalt chloride ($CoCl_2$)-stimulated hypoxia. We showed that chloroquine suppressed CCA cell migration under hypoxic-mimicking conditions on exposure to $100{\mu}M$ $CoCl_2$. Moreover, chloroquine stabilized the protein level of prolyl hydroxylase domain proteins (PHD-2) but reduced the levels of hypoxic responsive proteins such as hypoxia-inducible factor (HIF-$1{\alpha}$) and vascular endothelial growth factor (VEGF). It also suppressed epithelial mesenchymal transition (EMT) by increasing the ratio of E-cadherin to N-cadherin under hypoxic conditions. In conclusion, chloroquine can inhibit hypoxia-stimulated metastasis via HIF-$1{\alpha}$/VEGF/EMT which may serve as a useful additional strategy for CCA therapy.

• 대한한의학회지
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• 제30권3호
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• pp.61-69
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• 2009

Objectives : This experiment was conducted to evaluate the inhibitory effects against lung metastasis and promotion of splenocytes by water-soluble components from five mushrooms extracts (WEFM): Garnoderma frondosa, Corious versicolor, Codyceps militaris, Hericium erinaceus and Lentinula edodes. Methods : Colon 26-L5 carcinoma cells were injected through the tail vein to induce lung metastatic cancer. Changes in weight of lung were observed and cytokine level was analyzed to evaluate immunological changes. Results : Oral administration of WEFM resulted in a significant inhibition of lung metastasis after intravenous injection of colon 26-L5 cells in a dose-dependent manner. There was also a significant increase in T cell and B cell mitogenic stimuli and production of IFN-g by splenocytes stimulated with Con A compared to untreated controls. Conclusion : WEFM may have anti-tumor activities via Th1-type dominant immune responses.

• 생명과학회지
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• 제28권8호
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• pp.992-998
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• 2018

암세포는 종양의 성장을 지지하는 다양한 성분으로 구성되어 있는 환경에서 자란다. 암미세환경에 존재하는 주요 세포등은 섬유아세포, 내피세포, 면역세포들이며 이들세포들은 암세포들과 서로 소통을 하고 있다 종양조직에 유입된 면역세포중에서 대식세포가 종양미세환경의 주요성분으로서 다양한 면역현상들을 조절한다. 면역세포유입에 의한 암촉진과 항암효과 간의 복잡한 균형은 종양의 성장과 진행에 필요한 만성염증 환경을 생성시킬 수 있다. 대식세포는 M1과 M2 극성화로 규정된 미세환경 신호에 반응하여 기능적으로 다른 프로그램을 작동시킬 수 있다. 종양관련대식세포는 다양한 사이토카인, 케모카인, 단백질분해효소들을 분비함으로써 암 신생혈관형성, 증식, 전이 및 면역억제를 촉진시킨다. 최근에, 종양관련대식세포는 암줄기세포와 상호작용하여 종양의 진행, 전이 및 항암제 내성을 유도하는 것으로 알려져 있다. 종양관련대식세포는 암미세환경을 유지하기위해 면역억제 기능을 획득하며, 종양의 이질성과 가소성의 특성을 갖고 있어 암관련인자 및 감염등의 노출에 의해 서로 다른 극성형질로 리프로그래밍된다. 종양관련대식세포는 기질인자의 자극에 의해 암특이적인 케모카인들을 생성하기 때문에 케모카인은 질병의 활성을 반영하는 바이오마커로 작용할 수 있다. 종양조직에 종양관련대식세포가 많이 유입될수록 환자의 예후가 좋지 않으며 항암치료에 대한 저항성이 생긴다. 따라서 종양에서 대식세포를 표적화하는 항암치료는 유망한 치료전략이 될 수 있다.

• 생약학회지
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• 제41권2호
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• pp.115-121
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• 2010

The present study was designed to explore an immunostimulating activity of crude extracts of Macrolepiota procera, and a combination therapy of cisplatin and Macrolepiota procera extracts which can potentiate the anti-cancer activity of cisplatin. For these, water extraction of Macrolepiota procera were performed at $4^{\circ}C$(MPE-4) and $100^{\circ}C$(MPE-100). In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of MPE ($80-2,000{\mu}g$/mouse) inhibited tumor metastasis compared with tumor control. Peritoneal macrophages stimulated with MPE produced IL-12 as well as induced tumoricidal activity. In an analysis of NK-cell activity, i.v. administration of MPE ($200{\mu}g$/mouse) significantly augmented NK cytotoxicity to YAC-1 tumor cells. The combination treatments of cisplatin ($20{\mu}g$) and MPE ($100{\mu}g$) exhibited prolongation of lifespan in colon26-M3.1 tumor bearing mouse. These results suggested that MPE stimulate immune system non-specifically and application as adjuvant in cancer treatment.

• Journal of Gastric Cancer
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• 제21권4호
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• pp.439-456
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• 2021

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions: Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1253-1259
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• 2012

The 14-3-3 proteins are highly conserved, ubiquitous molecules involved in a variety of biologic phenomena, such as cell cycle control, and apoptosis. However, their expression in cholangiocarcinoma has not been previously characterized. In this paper, immunohistochemistry using specific anti-14-3-3 monoclonal antibodies was performed on formalin-fixed;, paraffin embedded archival tissue from 86 patients of cholangiocarcinoma. We also examined the correlation between expression and survival rate and clinicopathologic factors such as tumor location, tumor size, pathologic differentiation, lymphatic permeation, lymph node metastasis, and tumor stage. Positive 14-3-3 proteins expression was observed for 6 isoforms (${\beta}$, ${\sigma}$, ${\gamma}$, ${\theta}$, ${\delta}$, ${\eta}$) of these proteins in 86 patients of cholangiocarcinoma. ${\beta}$ and ${\sigma}$ isoform immunoreactivity was correlated with lymph node metastasis, tumor stage and patients' survival rate. In addition, ${\delta}$ isoform immunoreactivity showed trends with tumor location, tumor size, pathologic differentiation and tumor stage, while the ${\theta}$ isoform was correlated with pathologic differentiation. These results indicated that upregulated expression of some isoforms of 14-3-3 may be a common mechanism for evading apoptosis in cholangiocarcinoma, so that targeting 14-3-3 may be a novel promising strategy for the treatment of this tumor.

• BMB Reports
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• 제57권6호
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• pp.273-280
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• 2024

Cancer cells metastasize to distant organs by altering their characteristics within the tumor microenvironment (TME) to effectively overcome challenges during the multistep tumorigenesis. Plasticity endows cancer cell with the capacity to shift between different morphological states to invade, disseminate, and seed metastasis. The epithelial-to-mesenchymal transition (EMT) is a theory derived from tissue biopsy, which explains the acquisition of EMT transcription factors (TFs) that convey mesenchymal features during cancer migration and invasion. On the other hand, adherent-to-suspension transition (AST) is an emerging theory derived from liquid biopsy, which describes the acquisition of hematopoietic features by AST-TFs that reprograms anchorage dependency during the dissemination of circulating tumor cells (CTCs). The induction and plasticity of EMT and AST dynamically reprogram cell-cell interaction and cell-matrix interaction during cancer dissemination and colonization. Here, we review the mechanisms governing cellular plasticity of AST and EMT during the metastatic cascade and discuss therapeutic challenges posed by these two morphological adaptations to provide insights for establishing new therapeutic interventions.