• BMB Reports
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• 제29권5호
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• pp.417-422
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• 1996

In clonal sublines with different metastatic ability derived from Dunning rat prostate tumor, phosphoamino acid levels of cellular proteins were determined. Cell lines with high metastatic ability exhibited 5-fold higher phosphotyrosine level than did cell lines with low metastatic ability, while the contents of phosphoserine and phosphothreonine were similar among cell lines examined, All cell lines showed similar activities of protein tyrosine kinases as well as overall protein kinases. Phosphotyrosine protein phosphatase (PTPP) activities of the cells with high metastatic ability were very low, compared to those of the cells with low metastatic ability, suggesting that the different phosphotyrosine levels among the cell lines were due to the difference in PTPP activities rather than protein tyrosine kinase activities. Cellular activities of prostatic acid phosphatase (PAcP), which has been reported to possess phosphotyrosine protein phosphatase activity, were shown to be inversely related to the phosphotyrosine levels and metastatic abilities of the prostate tumor cells, These results suggest that cellular PAcP activity, regulating phosphotyrosine levels of cellular proteins, is closely connected with the metastatic process in prostate tumor cells and can be utilized as a good biochemical marker for the diagnosis of metastasis of prostate tumor.

• Mass Spectrometry Letters
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• 제11권2호
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• pp.25-29
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• 2020

Pseudopodia are dynamic actin cytoskeleton-based membrane protrusions of cells that enable directional cell migration. Pseudopodia of cancer cells play key roles in cancer metastasis. Recent studies using pseudopodial subcellular fractionation methodologies combined with mass spectrometry-based proteomic profiling have provided insight into the pseudopodiome that control the protrusions of invasive metastatic cancer cells. This review highlights how to characterize the protein composition of pseudopodia and develop strategies to identify biomarkers or drug candidates that target reduction or prevention of metastatic cancer.

• 대한세포병리학회지
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• 제18권2호
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• pp.133-142
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• 2007

Cytologic diagnosis of the metastatic tumors to the thyroid is important in the management of the patients. There have been rare reports analyzing fine-needle aspiration (FNA) cytology of metastatic tumors to the thyroid. This study examines comprehensive cytologic findings of metastatic tumors to the thyroid with radiologic findings. The FNA cytology slides obtained from 12 cases with metastatic tumors of the thyroid; lung cancer (n=5), tongue and tonsil cancer (n=3), esophageal cancer (n=2), and breast cancer (n=2) were reviewed. Radiological study showed single mass with heterogeneous texture or multiple masses without calcification. Metastatic tumor was easily considered in a differential diagnosis of FNA cytology because they had peculiar cytological features which were not seen in primary thyroid tumor. The smear background varied from predominantly necrotic, bloody, and inflammatory to colloid. The aspirates exhibited a mixture of benign follicular cells and malignant cells in 6 cases. The characteristic cytoplasmic features of the tumor cells, such as keratin, mucin and melanin, were found in 9 cases. Although some cases mimic primary thyroid neoplasm, a careful examination of the cytological characteristics may help cytopathologists to recognize a metastatic tumor in the thyroid by FNA, and may help the clinicians to establish a proper treatment plan.

• 대한세포병리학회지
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• 제7권2호
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• pp.185-191
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• 1996

Metastatic melanoma is often difficult to diagnose morphologically. However, the prognostic and therapeutic decision in cases of metastatic melanoma depends upon the morphologic documentation of the metastatic disease, which may rapidly and accurately be done by cytologic methods such as aspiration cytology of clinically suspicious lesion. Cytological features of 12 metastatic melanoma are described. Evaluation for melanin pigment, background composition, cytoplasmic vacuoles, intranuclear inclusions, bi- or multinucleated cells, eccentric nuclei, nucleoli, and degree of cellular cohesion were made. the presence of melanin pigment, prominent nucleoli, intranuclear cytoplasmic inclusions, lack of cell cohesion, and eccentric nuclei are the important and useful cytologic features in the diagnosis of metastatic melanoma. Bi or multinucleated cells, cytoplasmic vacuoles, and bloody background are also frequently found in smears from metastatic melanoma.

• 대한세포병리학회지
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• 제5권2호
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• pp.180-183
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• 1994

A case of metastatic mucoepidermoid carcinoma of the lung, originating from the hard palate, was diagnosed by sputum and bronchial washing cytology. Although the cytologic features of mucoepidermoid carcinoma have been well described, it is easy to confuse mucoepidermoid carcinoma with the more common primary adenocarcinoma or squamous cell carcinoma of the lung. The features distinguishing mucoepidermoid carcinoma from other primary neoplasms include 1) mucus-secreting cells individually and in clusters admixed with other cell components, 2) epidermoid cells identified by the presence of abundant spread-out cytoplasm and an oval dark nucleus and 3) intermediate cells resembling normal ductal epithelial cells with moderate-to-scanty cytoplasm, a central, round vesicular nucleus and a prominent nucleolus. The morphologic features of metastatic mucoepidermoid carcinoma in this case were similar to those of primary salivary mucoepidermoid carcinoma.

• 생명과학회지
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• 제15권3호
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• pp.406-414
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• 2005

암세포의 유전적 불안정성은 부적절하게 활성화된 DNA수복경로와 관련되어 있다. 전이성 암은 높은 유전적 불안정성을 나타내는데, 이와 관련하여 본 연구에서는 전이성 암세포에서의 중요한 DNA수복 단백질의 하나인 DN의존성 단백질 키나아제(DNA-PK)의 발현 변화를 조사하였다. 여러 종류의 전이도가 다른 암세포들을 대상으로 한 실험에서 전이성 암세포들은 각각의 모세포에 비하여 DNA-PK 성분의 조절 소단위인 Ku70/80의 발현 및 Ku의 DNA 결합 활성이 증강되어 있었다. 또한 DNA-PK의 촉매 소단위인 DNA-PKcs의 발현 및 whole DNA-PK복합체의 kinase의 활성도 전이도가 큰 암세포에서 그 모세포보다 증강되어 있음을 알 수 있어, 전이성 암세포의 증강된 DNA수복능은 부적절한 DNA수복을 일으켜 암의 진행 및 전이를 촉진시키는 원인이 될 수 있음을 시사하였다. 한편 암세포의 표피성장인자수용체의 신호전달의 증강은 암의 침윤과 전이에 관련되어 있으며, DNA-PK의 기 기능에도 영향을 줄 수 있는 가능성이 보고 된 바 있는데, 본 연구에서는 표피성장인자수용체의 신호전달과 DNA-PK의 관련성을 명확히 밝히기 위하여 새로 개발된 EGFR tyrosine kinase inhibitor인 PKI166의 DNA-PK의 활성에 미치는 영향을 조사하였다. PKI166는 Ku70/80 및 DNA-PKcs의 발현을 억제하였고 이와 관련하여 전이성 및 항암제 다제내성 암세포에서 PKI166에 의하여 항암제에 대한 감수성을 증가시켜 항암제 내성을 나타내는 전이성 암세포 대한 치료법 연구에 DNA-PK가 분자적 표적이 될 수 있음을 밝혔다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.581-590
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• 2016

Resistance to anoikis, a cell-detachment induced apoptosis, is one of the malignant phenotypes which support tumor metastasis. Molecular mechanisms underlying the establishment of this phenotype require further investigation. This study aimed at exploring protein expression profiles associated with anoikis resistance of a metastatic breast cancer cell. Cell survival of suspension cultures of non-metastatic MCF-7 and metastatic MDA-MB-231 cells were compared with their adherent cultures. Trypan blue exclusion assays demonstrated a significantly higher percentage of viable cells in MDA-MB-231 than MCF-7 cell cultures, consistent with analysis of annexin V-7-AAD stained cells indicating that MDA-MB-231 possess anti-apoptotic ability 1.7 fold higher than MCF-7 cells. GeLC-MS/MS analysis of protein lysates of MDA-MB-231 and MCF-7 cells grown under both culture conditions identified 925 proteins which are differentially expressed, 54 of which were expressed only in suspended and adherent MDA-MB-231 but not in MCF-7 cells. These proteins have been implicated in various cellular processes, including DNA replication and repair, transcription, translation, protein modification, cytoskeleton, transport and cell signaling. Analysis based on the STITCH database predicted the interaction of phospholipases, PLC and PLD, and 14-3-3 beta/alpha, YWHAB, with the intrinsic and extrinsic apoptotic signaling network, suggesting putative roles in controlling anti-anoikis ability. MDA-MB-231 cells grown in the presence of inhibitors of phospholipase C, U73122, and phospholipase D, FIPI, demonstrated reduced ability to survive in suspension culture, indicating functional roles of PLC and PLD in the process of anti-anoikis. Our study identified intracellular mediators potentially associated with establishment of anoikis resistance of metastatic cells. These proteins require further clarification as prognostic and therapeutic targets for advanced breast cancer.

• 대한세포병리학회지
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• 제9권1호
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• pp.21-28
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• 1998

Cytologic evaluation of cerebrospinal fluid(CSF) is an effective tool in diagnosing many disorders involving the central nervous system(CNS). CSF examination has been found to be of particular value in the diagnosis of metastatic carcinoma, lymphomatous or leukemic involvement of CNS and certain primary CNS tumors. As a survey of metastatic tumors to CSF and an evaluation of the preparation techniques increasing cellular yield in our laboratory, 713 CSF specimens examined between July 1995 and April 1997(1 year 10 months), were reviewed. There were 75 positive and 5 suspicious cases, the latter have had no evidence of tumors clinically. Primary tumors of 75 positive cases were classified as follows; 4(5.3%) as primary brain tumors, 40(53.3%) as secondary carcinomas, 13(17.3%) as leukemias, and 18 (24.0%) as lymphomas. The most common primary site of metastatic carcinomas was the lung in 17 cases(42.5%) followed by the stomach in 13(32.5%), breast in 8 (20.0%), and unknown primary in 2(5.0%). Four primary brain tumors were 3 cerebellar medulloblastomas and a supratentorial primitive neuroectodermal tumor (PNET). All 40 metastatic carcinomas were adenocarcinoma presented as single cells or cell clusters. Although signet ring cells were frequent in the cases of gastric primary cancers, no significant cytologic differences according to the primary site were observed. The cytologic features of leukemia and lymphoma were characterized by hypercellular smears presenting as individual atypical cells with increased N/C ratio, presence of nucleoli, and nuclear protrusions. In medulloblastomas and PNET, the principal cytologic findings were small undifferentiated cells arranged singly or in loose clusters with occasional rosettoid features. This study suggests that the CSF cytology is useful in the diagnosis of malignancy, especially metastatic extracranial tumors and the diagnostic accuracy can be improved by increasing cellular yield using cytocentrifuge.

• 대한세포병리학회지
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• 제9권1호
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• pp.1-14
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• 1998

The cytologic distinction of carcinoma cells from reactive mesothelial cells can be difficult, especially in specimens containing abundant reactive mesotheilal cells and inflammatory cells with scant carcinoma cells. This study evaluates the usefulness of mucin and immunocytochemistry for discrimination between reactive mesotheilal cells and carcinoma cells, and sensitivity and specificity of these stains for the detection of metastatic carcinoma in serous effusions. Immunocytochemical panel including mucin cytochemistry with the periodic acid-Schiff(PAS) reaction after or without diastase digestion was undertaken on 127 serous effusion specimens with histologically confirmed diagnoses. The specimens including cell smears and cell blocks were stained with PAS and antibodies to carcinoembryonic antigen(CEA), epithelial membrane antigen(EMA), cytokeratln(CK), and vimentin. The sensitivities of these stains for metastatic carcinoma(127 cases) were 49%(46/94) in PAS, 48%(60/124) in CEA, 89%(97/109) in EMA, 88%(93/106) in CK, and 25%(20/81) in vimentin. The sensitivities of stains for reactive mesothelial cells(36 cases) were 19%(7/36) in EMA, 78%(28/36) in CK, and 75%(27/36) in vimentin. The PAS and CEA stains were not reacted with all cases of benign reactive serous effusions containing abundant reactive mesothelial cells. The specificities of stains for metastatic carcinoma(127 cases) were 100% in PAS, 100% in CEA, 81% in EMA, 22% in CK, and 25% in vimentin. The optimal combination of stains for use in a panel was PAS and CEA. Combined results from these two stains yielded an advanced sensitivity of 8% in PAS and 4% in CEA for metastatic carcinoma. EMA was also cosiderably useful for identification of carcinoma cells. CK and vimentin were not suitable for distinguishing between reactive mesothelial cells and carcinoma cells.

• 대한세포병리학회지
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• 제2권2호
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• pp.79-89
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• 1991

Metastatic tumors occur more frequently in the liver than in any other organ. Guided percutaneous fine-needle aspiration (FNA) of the liver is often recommended for confirmative diagnosis of the metastatic lesion, because of its simplicity, high yield, and reasonable safety. The authors studied retrospectively cytologic findings of 110 cases of metastatic tumors to the liver. The frequent primary sites were the stomach (23 cases), pancreas(19 cases), gallbladder(12 cases), and periampullary lesions(6 cases). Most of the metastases were carcinoma (106 cases). There were only 4 cases of sarcoma. The characteristic cytologic findings of FNA of meatastatic tumors were dirty background, abrupt change between hepatocytes and malignant cells, and desmoplasia. Some tumors displayed rather distinctive cytologic appearance that suggests primary sites. For example, the colonic adenocarcinoma showed tall columnar cells with a palisading arrangement, adenocarcinoma of gallbaldder showed focal squamous differentiation in some cases, and metastatic renal cell carcinoma and neuroblastoma showed also distinctive cytologic findings. Because the cytologic features of metastatic tumor are very similar to those of primary tumor, correct cytologic typing may be helpful in pursuit of an occult primary site of metastatic liver lesions, reducing extensive diagnostic investigation in poor prognostic patients.