• Journal of Korean Neurosurgical Society
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• v.63 no.5
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• pp.566-578
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• 2020

Objective : Radiation is known to induce autophagy in malignant glioma cells whether it is cytocidal or cytoprotective. Dexamethasone is frequently used to reduce tumor-associated brain edema, especially during radiation therapy. The purpose of the study was to determine whether and how dexamethasone affects autophagy in irradiated malignant glioma cells and to identify possible intervening molecular pathways. Methods : We prepared p53 mutant U373 and LN229 glioma cell lines, which varied by phosphatase and tensin homolog (PTEN) mutational status and were used to make U373 stable transfected cells expressing GFP-LC3 protein. After performing cell survival assay after irradiation, the IC₅₀ radiation dose was determined. Dexamethasone dose (10 μM) was determined from the literature and added to the glioma cells 24 hours before the irradiation. The effect of adding dexamethasone was evaluated by cell survival assay or clonogenic assay and cell cycle analysis. Measurement of autophagy was visualized by western blot of LC3-I/LC3-II and quantified by the GFP-LC3 punctuated pattern under fluorescence microscopy and acridine orange staining for acidic vesicle organelles by flow cytometry. Results : Dexamethasone increased cell survival in both U373 and LN229 cells after irradiation. It interfered with autophagy after irradiation differently depending on the PTEN mutational status : the autophagy decreased in U373 (PTEN-mutated) cells but increased in LN229 (PTEN wild-type) cells. Inhibition of protein kinase B (AKT) phosphorylation after irradiation by LY294002 reversed the dexamethasone-induced decrease of autophagy and cell death in U373 cells but provoked no effect on both autophagy and cell survival in LN229 cells. After ATG5 knockdown, radiation-induced autophagy decreased and the effect of dexamethasone also diminished in both cell lines. The diminished autophagy resulted in a partial reversal of dexamethasone protection from cell death after irradiation in U373 cells; however, no significant change was observed in surviving fraction LN229 cells. Conclusion : Dexamethasone increased cell survival in p53 mutated malignant glioma cells and increased autophagy in PTEN-mutant malignant glioma cell but not in PTEN-wildtype cell. The difference of autophagy response could be mediated though the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway.

• The Journal of the Korean bone and joint tumor society
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• v.2 no.1
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• pp.33-37
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• 1996

From January 1994 to August 1995 we performed 270 cases of fine needle aspiration cytology for bone and soft tissue lesions. Among them 137 cases were diagnosed histologically. Sixty-seven cases were benign and 70 cases were malignant. We analysed these on the aspect of sensitivity, specifity, positive predictive value, negative predictive value of the cytologic examination. Malignant cases consisted of bone tumor 29 cases; soft tissue tumor 25 cases; and metastatic tumor 16 cases. The sensitivity and specifity of the aspiration cytology for malignant tumor were 67.8% and 97%, respectively. The positive and negative predictive value of aspiration cytology were 97.4% and 72.7%, respectively. Among them 40 cases were primary bony lesions; 14 benign lesions, 26 malignamt bone tumors. Sensitivity of aspiration cytology for these primary bony lesion was 90%(18/20) and its specifity was 100%(13/13). Three cases showed atypical cells in cytology but with biopsy we could find them as one benign and two malignancies. Two cases of manignancy showed negative result in cytology; one was parosteal sarcoma of proximal femur and the other was osteosarcoma of proximal tibia which was biopsied already at other hospital. Although the overall sensitivity and specifity for malignant bone and soft tissue tumors were relatively low and not so predictable, the fine needle aspiration cytology for primary bony lesion was useful in the differential diagnosis of benign or malignancy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3561-3568
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• 2012

The calcium sensing receptor (CaSR) is a member of the largest family of cell surface receptors, the G protein-coupled receptors involved in calcium homeostasis. The role of the CaSR in neoplasia appears to be homeostatic; loss of normal CaSR-induced response to extracellular calcium is observed in cancers of the colon and ovary, while increased release of PTHrP is observed in cancers of the breast, prostate and Leydig cells. Currently CaSR can be considered as a molecule that can either promote or prevent tumor growth depending on the type of cancer. Therefore, recognition of the multifaceted role of CaSR in gliomas and other malignant tumors in general is fundamental to elucidating the mechanisms of tumor progression and the development of novel therapeutic agents. Emphasis should be placed on development of drug-targeting methods to modulate CaSR activity in cancer cells.

• Environmental Mutagens and Carcinogens
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• v.25 no.2
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• pp.66-70
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• 2005

Telomerase, a specialized RNA-directed DNA polymerase that extends telomeres of eukaryotic chromosomes, has activity in most malignant tumors and provides a mechanism for the unlimited potential for division of neoplastic cells. Although telomerase is known to be a regulated enzyme, the factors and mechanisms involved in telomerase regulation are not well understood. In the present study, we compared the effect of 12-O­tetradecanoyl-phorbol-13-acetate (TPA) and non-phorbol ester tumor promoters such as okadaic acid, anthralin and benzoyl peroxide on the expression of telomerase in the mouse skin carcinogenesis system, a well characterized model for studying pre-malignant and malignant progression. We found that most early papillomas harvested after 10 weeks of TPA promotion showed telomerase activity. Other papillomas harvested after 10 weeks of okadaic acid, anthralin and benzoyl peroxide promotion and after single treatment of DMBA only also showed telomerase activity, respectively. On the other hand, normal and all skins surrounded by papillomas harvested after 10 weeks of these promoters has no telomerase activity. Taken together these results, there appears to be no clear association between the level of telomerase activity and protein phosphorylation in mouse skin papillomas and telomerase may be useful as bio-markers in early detection of tumors.

• The Korean Journal of Cytopathology
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• v.12 no.2
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• pp.121-125
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• 2001

Primary small cell carcinoma of the urinary bladder is a rare malignant tumor. A more rapidly fatal course may be seen in advanced stages of small cell carcinoma as compared to similar stages of urothelial carcinoma. It is very important to recognize this distinct form of bladder cancer by urinary cytology The differential diagnosis of small cell carcinoma of the urinary bladder includes metastatic small cell carcinoma, urothelial carcinoma, and primary or secondary malignant lymphoma. This article highlights the urinary cytologic diagnosis of a case of primary small cell carcinoma. A 59-year-old male presented with gross hematuria for five months. Urinary cytology showed high cellularity consisting of tiny monotonous tumor cells in the necrotic background. The tumor cells occurred predominantly singly, but a few in clusters. The cytoplasm was so scanty that only a very narrow rim of it was seen. The nuclei were oval or round and had finely stippled chromatin. Rarely, the nuclei contain visible nucleoli. Frequently cell molding was noted in clusters. Many single cells demonstrated nuclear pyknosis or karyorrhexis. The histologic findings of transurethral resection and partial cystectomy specimen were those of small cell carcinoma. Cytologic distinction may be very difficult but careful attention to clinical features and cellualr details can classify these neoplasms correctly.

• Journal of Veterinary Clinics
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• v.28 no.5
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• pp.522-525
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• 2011

A 14 year old female Siberian tiger presented for postmortem examination. A large mass attached to sublumbar area was found to be circumscribing aorta with metastases to mesenteric lymph nodes, uterus, kidney, adrenal gland, lung and thymus. The tumor cells were arranged in clusters or nests separated by well-developed fibrovascular stroma. The individual cells were plump and polygonal with granular eosinophilic cytoplasms and had distinct cell borders. The tumor cells were positive for synaptophysin, chromogranin A and neuron-specific enolase, and negative for cytokeratins, S100 and glial fibrillary acidic protein. The primary tumor was diagnosed as a malignant retroperitoneal paraganglioma.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.1
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• pp.10-23
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• 2007

Hallmarks of clinical behaviors of adenoid cystic carcinoma(ACC) of salivary glands are the delayed onset of vascular metastasis and poor responses to classical chemotherapeutic agents. Poor prognoses from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, cellular and molecular characteristics that influence the dissemination of metastatic cells are important for the design of more effective treatment of salivary ACC. Tumor angiogenesis has been known to be essential for the distant metastasis of malignant cells. So, we determined expressions of angiogenic proteins in benign (pleomorphic adenoma) and malignant (ACC, mucoepidermoid carcinoma) tumors of salivary glands and compared each other and to those in oral squamous cell carcinoma. Using surgical specimens, we performed immunohistochemical assays with anti-vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), phosphorylated VEGFR-2 (pVEGFR-2), matrix metalloproteinase (MMP)-9, and interleukin (IL)-8 antibodies. Most angiogenic factors were overexpressed in malignant salivary tumors than in pleomorphic adenoma which is benign nature. Moreover, ACC demonstrated more expression of VEGFR-2 than that of squamous cell carcinoma which used as control. Conclusively, these data show those angiogenic factors produced by salivary gland tumors may affect the propagation and metastasis of malignant cells of salivary tumors, and could be used as biomarkers for the malignant transformation of salivary gland tumors. Prospectively, although further studies will be needed, these biomarkers related to angiogenesis can be molecular targets for the therapy of salivary ACC, which has propensity for delayed vascular metastasis.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.1-17
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• 2020

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exert suppressive function on the immune response. MDSCs expand in tumor-bearing hosts or in the tumor microenvironment and suppress T cell responses via various mechanisms, whereas a reduction in their activities has been observed in autoimmune diseases or infections. It has been reported that the symptoms of various diseases, including malignant tumors, can be alleviated by targeting MDSCs. Moreover, MDSCs can contribute to patient resistance to therapy using immune checkpoint inhibitors. In line with these therapeutic approaches, diverse oligonucleotide-based molecules and small molecules have been evaluated for their therapeutic efficacy in several disease models via the modulation of MDSC activity. In the current review, MDSC-targeting oligonucleotides and small molecules are briefly summarized, and we highlight the immunomodulatory effects on MDSCs in a variety of disease models and the application of MDSC-targeting molecules for immuno-oncologic therapy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.22 no.3
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• pp.334-339
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• 1993

Antitumor activities of tannin extract and chloroform fraction extract from the persimmon leaves, and 2, 4-decadienal identified as an antimutagenic compound in persimmon leaves were examined in sarcoma 180 implanted tumor in mice by using both light and transmission electron microscopes. Among them, tannin extracted from the persimmon leaves delayed the progression of malignant tumor but the other two did not show any noticeable effect. The antitumorigenic activity of tannin extract might not come from the selective cytotoxicity against tumor cells, but might be, in an anaerobic environment, from the inhibitory action against oncogenic protein synthesis or from the proteolysis of the preformed oncogenic proteins by autophagocytic granules. therefore, the tannin from persimmon leaves might protect cells from fast progression of malignant tumorigensis.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.186-191
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• 2002

A malignant fibrous histiocytoma is a malignant soft tissue neoplasm that occurs frequently in the metaphyseal ends of the long bones of adults. The lung is a common site for metastasis but it is a rare site for a primary malignant fibrous histiocytoma. Here we report a case of a primary malignant fibrous histiocytoma of the lung. The patient was a 53-year-old man who presented with a moderate amount of a left pleural effusion and an illdefined mass in the left lower lobe on a chest radiograph and a local invasion to the left 10th and 11th rib on chest CT. Under the strong suspicion of lung cancer with a pleural invasion, a serial diagnostic thoracentesis was performed. The cytologic examination of the pleural effusion revealed no malignant cells. Consequently, a thoracoscopic pleural biopsy was performed. The histological examination revealed slender spindle cells and scattered epitheloid cells arranged in a vague storiform or a whirling pattern. Immunohistochemicaily, the tumor cells tested positive for vimentin and negative for cytokeratin, desmin, CD 34 and PAS. These features were consistent with a malignant fibrous histiocytoma. This case is an unusual addition to the small number of published reports on a primary malignant fibrous histiocytoma of the lung.