• BMB Reports
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• v.56 no.11
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• pp.584-593
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• 2023

Hypoxia, a widespread occurrence observed in various malignant tumors, results from rapid tumor growth that outpaces the oxygen supply. Tumor hypoxia precipitates several effects on tumor biology; these include activating angiogenesis, intensifying invasiveness, enhancing the survival of tumor cells, suppressing anti-tumor immunity, and fostering resistance to therapy. Aligned with the findings that correlate CMGC kinases with the regulation of Hypoxia-Inducible Factor (HIF), a pivotal modulator, reports also indicate that hypoxia governs the activity of CMGC kinases, including DYRK1 kinases. Prolyl hydroxylation of DYRK1 kinases by PHD1 constitutes a novel mechanism of kinase maturation and activation. This modification "primes" DYRK1 kinases for subsequent tyrosine autophosphorylation, a vital step in their activation cascade. This mechanism adds a layer of intricacy to comprehending the regulation of CMGC kinases, and underscores the complex interplay between distinct post-translational modifications in harmonizing precise kinase activity. Overall, hypoxia assumes a substantial role in cancer progression, influencing diverse aspects of tumor biology that include angiogenesis, invasiveness, cell survival, and resistance to treatment. CMGC kinases are deeply entwined in its regulation. To fathom the molecular mechanisms underpinning hypoxia's impact on cancer cells, comprehending how hypoxia and prolyl hydroxylation govern the activity of CMGC kinases, including DYRK1 kinases, becomes imperative. This insight may pave the way for pioneering therapeutic approaches that target the hypoxic tumor microenvironment and its associated challenges.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.188-188
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• 2003

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a prototype of halogenated aromatic hydrocarbons, is a persistent environmental contaminant and one of the most powerful tumor promoters. The molecular mechanism underlying induction of tumor promotion by TCDD has not been elucidated.(omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.1
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• pp.173-177
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• 2013

Backgrounds: Tanshinone IIA (TIIA), a phenanthrenequinone derivative extracted from Salvia miltiorrhiza BUNGE, has been reported to be a natural anti-cancer agent in a variety of tumor cells. However, the effect of TIIA on gastric cancer cells remains unknown. In the present study, we investigated the influence of TIIA on the malignant phenotype of SGC7901 gastric cancer cells. Methods: Cells cultured in vitro were treated with TIIA (0, 1, 5, $10{\mu}g/ml$) and after incubation for different periods, cell proliferation was measured by MTT method and cell apoptosis and cell cycling were assessed by flow cytometry (FCM). The sensitivity of SGC7901 gastric cancer cells to anticancer chemotherapy was investigated with the MTT method, while cell migration and invasion were examined by wound-healing and transwell assays, respectively. Results: TIIA (1, 5, $10{\mu}g/ml$) exerted powerful inhibitory effects on cell proliferation (P < 0.05, and P < 0.01), and this effect was time- and dose-dependent. FCM results showed that TIIA induced apoptosis of SGC7901 cells, reduced the number of cells in S phase and increased those in G0/G1 phase. TIIA also significantly increased the sensitivity of SGC7901 gastric cancer cells to ADR and Fu. Moreover, wound-healing and transwell assays showed that TIIA markedly decreased migratory and invasive abilities of SGC7901 cells. Conclusions: TIIA can reverse the malignant phenotype of SGC7901 gastric cancer cells, indicating that it may be a promising therapeutic agent.

• Korean Journal of Head & Neck Oncology
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• v.36 no.2
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• pp.37-40
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• 2020

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare, low grade neoplasm which usually occurs in subcutaneous soft tissue. Histologically, it features ectatic blood filled vessels surrounded by hyalinized stroma and pleomorphic spindle cells. Clinically and histologically, PHAT could be misdiagnosed as such tumor as neurogenic tumor, malignant fibrous histiocytoma. About 100 cases of PHAT have been reported so far, and it is even rarer in head and neck area. We experienced a case of PHAT in 41-year-old male with several months of history of gradually enlarging neck mass which was surgically removed by wide excision.

• Molecules and Cells
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• v.43 no.9
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• pp.763-773
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• 2020

Recently, tumor microenvironment (TME) and its stromal constituents have provided profound insights into understanding alterations in tumor behavior. After each identification regarding the unique roles of TME compartments, non-malignant stromal cells are found to provide a sufficient tumorigenic niche for cancer cells. Of these TME constituents, adipocytes represent a dynamic population mediating endocrine effects to facilitate the crosstalk between cancer cells and distant organs, as well as the interplay with nearby tumor cells. To date, the prevalence of obesity has emphasized the significance of metabolic homeostasis along with adipose tissue (AT) inflammation, cancer incidence, and multiple pathological disorders. In this review, we summarized distinct characteristics of hypertrophic adipocytes and cancer to highlight the importance of an individual's metabolic health during cancer therapy. As AT undergoes inflammatory alterations inducing tissue remodeling, immune cell infiltration, and vascularization, these features directly influence the TME by favoring tumor progression. A comparison between inflammatory AT and progressing cancer could potentially provide crucial insights into delineating the complex communication network between uncontrolled hyperplastic tumors and their microenvironmental components. In turn, the comparison will unravel the underlying properties of dynamic tumor behavior, advocating possible therapeutic targets within TME constituents.

• Archives of Craniofacial Surgery
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• v.20 no.2
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• pp.109-111
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• 2019

Intravascular papillary endothelial hyperplasia or Masson's hemangioma is a rare vascular tumor. The reactive proliferation of endothelial cells in this disease mimics other benign or malignant vascular proliferation such as angiosarcoma or Kaposi's sarcoma. It is important to make an accurate distinction to avoid confusion with these malignant tumors. This would facilitate a proper diagnosis, which is essential so that the patient is not subjected to unnecessarily aggressive or inappropriate treatment.

• The Korean Journal of Cytopathology
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• v.17 no.1
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• pp.51-55
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• 2006

The plasmacytoid variant is an extremely rare form of urothelial carcinoma in which the malignant cells resemble those of plasmacytoma. We report the cytologic features of 3 cases of this disorder. All 3 patients were male and presented with painless macroscopic hematuria. The voided urine cytology revealed a few scattered clusters of tumor cells in a bloody background. Each tumor cell had an abundant amount of cytoplasm that was clear or densely stained and characterized by eccentrically located nuclei. A histological examination of tissue obtained from a radical cystectomy confirmed the cytologic diagnosis in each 3 case, revealing a diffusely infiltrating tumor composed of round, noncohesive tumor cells demonstrating a high nuclear grade. These cells had infiltrated the tunica propria in 2 cases, but were limited to the submucosa in 1 case. The tumor cells were plasmacytoid in appearance, each demonstrating an eccentric nucleus and dense cytoplasm, as seen in the cytologic findings. All of the tumors were immunoreactive for pancytokeratin, CK7, CK20; negative for epithelial membrane antigen (EMA), leukocyte common antigen (LCA), kappa, lambda, and CD79a. Thus, it is important to consider the plasmacytoid variant of urothelial carcinoma in addition to plasmacytoma or lymphoma as a diagnosis when encountering plasmacytoid tumor cells in a voided urine sample.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.8
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• pp.3307-3312
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• 2015

The papillary patterned lesion of thyroid may be challenging with many diagnostic pitfalls. Tumor stroma plays an important part in the determination of the tumor phenotype. CD34 is thought to be involved in the modulation of cell adhesion and signal transduction as CD34(+) fibrocytes are potent antigen-presenting cells. Smooth muscle actin (SMA) positivity could be diagnostic for fibroblast activation during tumorigenesis. We aimed to examine the expression of CD34 and alphaSMA in the stroma of papillary thyroid hyperplasia, papillary thyroid carcinoma and papillary tumors of uncertain malignant potential in order to elucidate their possible differential distribution and roles. A total number of 54 cases with papillary thyroid lesions were studied by routine H&E staining, CD34 and ASMA immunostaining. ASMA was not expressed in benign papillary hyperplastic lesions while it was expressed in papillary carcinoma, indicating that tumors have modulated stroma. Although the stroma was not well developed in papillary lesions with equivocal features of uncertain potentiality, CD34 was notable in such cases with higher incidence in malignant cases. So ASMA as well as CD34 could predict neoplastic behavior, pointing to the importance of the stromal role. Differences between groups suggest that the presence of CD34 + stromal cells is an early event in carcinogensis and is associated with neoplasia, however ASMA+ cells are more likely to be associated with malignant behavior and metastatic potential adding additional tools to the light microscopic picture helping in diagnosis of problematic cases with H&E.

• Analytical Science and Technology
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• v.23 no.6
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• pp.579-586
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• 2010

Commercially widely used antitumor agents such as hydroxy urea, 6-mercaptopurine monohydrate, cytosine arabinoside, cyclophosphamide monohydrate and uracil were reacted with 3-(triethoxysilyl)propyl isocyanate and the product hydrolyzed to give silica nanoparticles bound antitumor agents ranging from 10 nm to micron-sized aggregates. The silyl isocyanate derivative was also reacted neat with water to give hybrid organicsilicananoparticles containing $-CH_2-CH_2-CH_2-NH-COOH$ or the corresponding decarboxylated propylamine groups depending on solvent and temperature employed. In vitro tests these functionalized silica nanoparticles were effective in the treatment of malignant tumor cells but had little or no effect on normal cells. Malignant human lung, ovarian, melanoma, CNS(Central nervous system) and colon tumor cells were used in this research. The use of silica as a carrier medium in the present research serves as a model material due to its ready functionalization via silation. The proof of concept established by the results suggests that the technique may be applied to other, more biocompatible carrier nanoparticles.

• Molecules and Cells
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• v.40 no.7
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• pp.515-522
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• 2017

CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-$1{\beta}$ and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133. In addition, the clinical relevance between CD133 expression and IL-$1{\beta}$ gene signature was established in patients with malignant gliomas. Thus, these results imply that glioma cells expressing CD133 are capable of modulating tumor microenvironment through the IL-$1{\beta}$ signaling pathway.