• IMMUNE NETWORK
• /
• 제21권4호
• /
• pp.31.1-31.16
• /
• 2021

Gastric cancer (GC) is the fourth most common cause of cancer-related death globally. The classification of advanced GC (AGC) according to molecular features has recently led to effective personalized cancer therapy for some patients. Specifically, AGC patients whose tumor cells express high levels of human epidermal growth factor receptor 2 (HER2) can now benefit from trastuzumab, a humanized monoclonal Ab that targets HER2. However, patients with HER2^negative AGC receive limited clinical benefit from this treatment. To identify potential immune therapeutic targets in HER2^negative AGC, we obtained 40 fresh AGC specimens immediately after surgical resections and subjected the CD45⁺ immune cells in the tumor microenvironment to multi-channel/multi-panel flow cytometry analysis. Here, we report that HER2 negativity associated with reduced overall survival (OS) and greater tumor infiltration with neutrophils and non-classical monocytes. The potential pro-tumoral activities of these cell types were confirmed by the fact that high expression of neutrophil or non-classical monocyte signature genes in the gastrointestinal tumors in The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases associated with worse OS on Kaplan-Meir plots relative to tumors with low expression of these signature genes. Moreover, advanced stage disease in the AGCs of our patients associated with greater tumor frequencies of neutrophils and non-classical monocytes than early stage disease. Thus, our study suggests that these 2 myeloid populations may serve as novel therapeutic targets for HER2^negative AGC.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권17호
• /
• pp.7431-7434
• /
• 2015

As an important component of innate immune system, neutrophil has been involved in many other physiological processes, including tumor-related diseases. In 2004, the phenomenon of NETs was reported for the first time. Extracellular decondensed chromatin, released from activated neutrophils, forms a network structure, which is NETs. This review focuses on the function of NETs in tumor cell proliferation, metastasis, and tumor-associated thrombosis; it also explores the application of NETs specific markers in the diagnosis of pre-thrombotic state and tumor associated diseases; it also explores NETs inhibitor for the treatment of tumor-related diseases. In view of the rapid development of NETs, it may provide new therapeutic targets for tumor-associated thrombosis, and even tumor itself.

• Journal of Applied Biological Chemistry
• /
• 제65권4호
• /
• pp.387-396
• /
• 2022

골격근은 체중의 약 40-50%를 차지하며 자세 유지, 연조직 지지, 체온 유지, 호흡 등 다양한 기능을 수행하는 중요한 조직이다. 전 세계적으로 광범위하게 발생하는 암은 근위축을 동반한 암 악액질을 일으켜 항암제의 효과를 떨어뜨리고 암환자의 삶의 질과 생존율을 크게 떨어뜨린다. 따라서 암 악액질을 개선하기 위한 연구가 진행 중이지만 암과 근육 위축 사이의 연관성에 관한 연구는 거의 없다. 암 세포는 종양 관련 대식세포(TAM), 종양 관련 호중구(TAN) 및 Warburg 효과로 인한 인슐린 저항성을 포함하여 독특한 미세 환경 및 대사를 나타낸다. 따라서 암세포의 미세환경과 대사적 특성, 사이토카인과 인슐린 저항성에 의해 영향을 받을 수 있는 근육 위축의 분자적 기전을 정리하였다. 또한 이는 TAM, TAN, Warburg 효과에 영향을 미치는 물질의 암 악액질 개선 가능성을 시사한다. 본 논문에서는 또한 암 악액질을 개선할 수 있는 단일 화합물 및 이들에 의해 매개되는 신호 전달 경로를 통해 지금까지 확인된 메커니즘을 정리하였다.

• Radiation Oncology Journal
• /
• 제34권3호
• /
• pp.223-229
• /
• 2016

Purpose: This study is to investigate the effect of captopril when combined with irradiation. Materials and Methods: 4T1 (mouse mammary carcinoma) cells were injected in the right hind leg of Balb/c mice. Mice were randomized to four groups; control (group 1), captopril-treated (group 2), irradiated (group 3), irradiated and captopril-treated concurrently (group 4). Captopril was administered by intraperitoneal injection (10 mg/kg) daily and irradiation was delivered on the tumor-bearing leg for 15 Gy in 3 fractions. Surface markers of splenic neutrophils (G-MDSCs) and intratumoral neutrophils (tumor-associated neutrophils [TANs]) were assessed using flow cytometry and expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 alpha ($HIF-1{\alpha}$) of tumor was evaluated by immunohistochemical (IHC) staining. Results: The mean tumor volumes (${\pm}$standard error) at the 15th day after randomization were $1,382.0({\pm}201.2)mm^3$ (group 1), $559.9({\pm}67.8)mm^3$ (group 3), and $370.5({\pm}48.1)mm^3$ (group 4), respectively. For G-MDSCs, irradiation reversed decreased expression of CD101 from tumor-bearing mice, and additional increase of CD101 expression was induced by captopril administration. Similar tendency was observed in TANs. The expression of tumor-necrosis factor-associated molecules, CD120 and CD137, are increased by irradiation in both G-MDSCs and TANs. Further increment was observed by captopril except CD120 in TANs. For IHC staining, VEGF and $HIF-1{\alpha}$ positivity in tumor cells were decreased when treated with captopril. Conclusion: Captopril is suggested to have additional effect when combined to irradiation in a murine tumor model by modulation of MDSCs and angiogenesis.

• 한국임상수의학회지
• /
• 제19권3호
• /
• pp.353-356
• /
• 2002

A 9-year-old male Yorkshire terrior with recurrent chronic otitis externa and otitis interna was referred to the Veterinary Medical Teaching Hospital of Seoul National University. Radiographic findings indicated mineralization around the right ear canal. A tan nodular mats, 1 cm in diameter. was noted near the tympanum after total ear canal ablation. Cytologically. the imprint smear of the cut surface of the mass produced clusters of cells with abundant and weakly basophilic cytoplasm, one small round nucleus and one or two nucleoli, mixed with both degenerate and non degenerate neutrophils. The location of the nuclei was eccentric, and some cells contained somewhat coarse black granules in their cytoplasms, on which the mass was diagnoted as ceruminous gland adenoma or hyperplasia associated with inflammation. Histopathologic examination of the tumor was compatible with a diagnosit of ceruminous gland adenoma. The patient is responding well to sugery and antimicrobial treatment.

• 대한의생명과학회지
• /
• 제28권4호
• /
• pp.260-275
• /
• 2022

Sterile alpha motif (SAM) domains bind to various proteins, lipids, and RNAs. However, these domains have not yet been analyzed as prognostic biomarkers. In this study, SAM domain containing 13 (SAMD13), a member of the SAM domain, was evaluated to identify a novel prognostic biomarker in various human cancers, including hepatocellular carcinoma (HCC). Moreover, we identified a correlation between SAMD13 expression and immune cell infiltration in HCC. We performed bioinformatics analysis using online databases, such as Tumor Immune Estimation Resource, UALCAN, Kaplan-Meier plotter, LinkedOmics, and Gene Expression Profiling Interactive Analysis2. SAMD13 expression in HCC samples was significantly higher than that in normal liver tissue; additionally, SAMD13 was higher in primary tumors, various stages of cancer and grades of tumor, and status of nodal metastasis. Higher SAMD13 expression was also associated with poorer prognosis. SAMD13 expression positively correlated with CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. In the analysis of SAMD13 co-expression networks, positively related genes of SAMD13 were associated with a high hazard ratio in different types of cancer, including HCC. In biological function of SAMD13, SAMD13 mainly include spliceosome, ribosome biogenesis in eukaryote, ribosome, etc. These results suggest that SAMD13 may serve as a novel prognostic biomarker for HCC diagnosis and provide novel insights into tumor immunology in HCC.

• 대한바이러스학회지
• /
• 제30권2호
• /
• pp.141-150
• /
• 2000

The effectiveness of noninfectious recombinant adenovirus encoding murine granulocyte-macrophage colony stimulating factor (mGM-CSF) for the treatment of Meth A fibrosarcoma was investigated in syngeneic BALB/C model. Meth A and HeLa cells transduced with the recombinant adenovirus (Ad.mGM-CSF) produced substantial amounts of mGM-CSF, while WEH1164 cells transduced with the virus did not produce mGM-CSF. Mice inoculated subcutaneously with $1{\times}10^6$ Meth A cells, followed by injection of Ad.dE1 as a control, developed large tumors that reached a mean tumor size of 22 mm by day 30. However, tumor development and tumorigenicity were significantly inhibited in mice with a single intratumoral injection of Ad.mGM-CSF at $1{\times}10^8\;pfu$. Histological examination of the tumors injected with Ad.mGM-CSF revealed dense infiltrates of neutrophils, histiocytes, lymphocytes, and eosinophils associated with apoptotic cell death. The results suggest that the recombinant adenovirus encoding GM-CSF have a potential use for cancer gene therapy.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권17호
• /
• pp.7561-7566
• /
• 2015

Ziziphus jujuba (ZJ) fruit is rich in bioactive functional components such as polysaccharides, triterpenoid acid, flavonoids and oleamide. It has been commonly used in the treatment of various diseases including diabetes, digestive disorders, diarrhea, skin infections, liver and urinary diseases. However, its dietary effect on chemoprevention of colon cancer has never been studied. The present study was to evaluate the protective effects of dietary ZJ on colitis-associated colon carcinogenesis in azoxymethane (AOM)-dextran sodium sulphate (DSS)-treated mice. AOM was injected (10 mg/kg b.wt., i.p.) and three cycles of 2% DSS in drinking water for 7 days with 14 days of normal drinking water in-between was administered to induce colitis-associated colon cancer. ZJ fruit was supplemented in feed as 5 and 10%. Dietary ZJ significantly attenuated aberrant crypt foci (ACF) formation thereby decreasing the progression of hyperplasia to dysplasia. In addition, it significantly reduced circulating white blood cells, lymphocytes, neutrophils, monocytes, eosinophils, basophils and platelets compared to colon cancer mice. We conclude that ZJ supplementation delayed the progression of colon cancer from hyperplasia to dysplasia and ultimately adenocarcinoma and cancer. In addition, it decreased circulating tumor-related leucocytes, main regulators of cancer inflammation. Therefore, dietary consumption of ZJ fruit attenuated the formation of ACF and delayed the progression of colon cancer.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제29권6호
• /
• pp.538-542
• /
• 2007

Sweet syndrome is characterized by acute onset of fever. neutrophilic leukocytosis, painful erythematous plaque on the face and extremities, infiltration of mature neutrophils in the dermis. Cutaneous lesion and clinical symptoms rapidly improve after treatment with systemic corticosteroids. The cause of sweet syndrome is unknown but the associations with hypersensitivity to bacteria, virus, or tumor antigen have been reported. Sweet syndrome itself can be a premonitory manifestation of malignancy, so diagnostic work up for other internal malignancy is recommended. Because of fever and leukocytosis, cutaneous infections are important differentials. Sweet syndrome can be divided into 4 categories according to associated disease and symptom. (Idiopathic Sweet syndrome, Parainflammatory Sweet syndrome, Paraneoplastic Sweet syndrome, Pregnacy associated Sweet syndrome.) Sweet syndrome is relatively rare disease and the association with myelodisplastic syndrome has been reported. We report a case of Sweet syndrome associated with myelodisplastic syndrome which has initial manifestation of odontogenic buccal cellulites.

• 대한의생명과학회지
• /
• 제29권1호
• /
• pp.11-25
• /
• 2023

In hepatocellular carcinoma (HCC), chromosome 4 open-reading frame 47 (C4orf47) has not been so far investigated for its prognostic value or association with infiltrating immune cells. We performed bioinformatics analysis on HCC data and analyzed the data using online databases such as TIMER, UALCAN, Kaplan-Meier plotter, LinkedOmics, and GEPIA2. We found that C4orf47 expression in HCC was higher compared to normal tissues. High C4orf47 expression was associated with a worse prognosis in HCC. The correlation between C4orf47 and infiltrating immune cells is positively associated with CD4+T cells, B cells, neutrophils, macrophages, and dendritic cells in HCC. Moreover, high C4orf47 expression was correlated with a poor prognosis of infiltrating immune cells. Analysis of C4orf47 gene co-expression networks revealed that 12501 genes were positively correlated with C4orf47, whereas 7200 genes were negatively correlated. The positively related genes of C4orf47 are associated with a high hazard ratio in different types of cancer, including HCC. Regarding the biological functions of C4orf47 gene, it mainly regulates RNA metabolic process, DNA replication, and cell cycle. The C4orf47 gene may play a prognostic role by regulating the global transcriptome process in HCC. Our findings demonstrate that high C4orf47 expression correlates with poor prognosis and tumor-infiltrating immune cells in HCC. We suggest that C4orf47 is a novel prognostic biomarker and potential immune therapeutic target for HCC.