1.High Activities of Protein Kinases C and M in Fresh Human Stomach and Breast Tumors.
In Kyoung LIM ; Do Jong LEE ; Kee Ho LEE ; Taik Koo YUN
Yonsei Medical Journal 1987;28(4):255-260
The activities of Ca+2-PL dependent protein Kinase (PKC) and independent protein kinase(RKM) were measured in human stomach and breast tumors and in the respective counterparts of normal tissue. Expression of c-fos and c-myc of the tissues were also measured. RNAs of c-fos and c-myc were unexpectedly high in the tissue from normal stomach and breast as well as in all cancer tissue. On the other hand, cytosolic and particulate PKC activities were higher in the tumors as compared to those of normal controls. Notably, some cases exhibited. altered activities of PKC i.e. increased RKM activities as high as RKC, which might be related to the autocrine control of growth in the tumor mass.
Adenocarcinoma/enzymology*
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Breast Neoplasms/enzymology*
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Carcinoma, Intraductal, Noninfiltrating/enzymology*
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Human
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Protein Kinase C/metabolism*
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Stomach Neoplasms/enzymology*
2.Role of arginase-1 expression in distinguishing hepatocellular carcinoma from non-hepatocellular tumors.
Wei SANG ; Abulajiang GULINAR ; Cheng-hui WANG ; Wei-qi SHENG ; Ymijiang MAIWEILIDAN ; Wei ZHANG
Chinese Journal of Pathology 2013;42(8):538-542
OBJECTIVETo study the role of arginase-1 (Arg-1) expression in differential diagnosis of hepatocellular carcinoma (HCC), Arg-1 staining pattern in clear cell neoplasm (HCC and non-HCC) and Arg-1 expression in non-hepatocellular tumors.
METHODSSeventy-eight cases of HCC (including 8 cases of clear cell type and 70 cases of non- clear cell type) and 246 cases of non-hepatocellular neoplasms (including 29 cases of metastatic tumors such as breast cancer, nasopharyngeal carcinoma and neuroendocrine carcinoma, 77 cases of tumors with clear cell changes such as malignant melanoma, clear cell renal cell carcinoma and alveolar soft part sarcoma, and 140 cases of other types of tumors such as ovarian endometrioid adenocarcinoma, pituitary tumor and thyroid papillary carcinoma) were studied.Immunohistochemical study for Arg-1 was performed on the paraffin-embedded tumor tissue.
RESULTSIn HCC, Arg-1 demonstrated both cytoplasmic and nuclear staining, with an overall sensitivity of 96.2% (75/78).In well, moderately and poorly differentiated HCC, the sensitivity was 15/15, 100% (41/41) and 86.4% (19/22), respectively. That was in contrast to negative staining for Arg-1 in all the 29 cases of metastatic tumors studied. The sensitivity, specificity, positive predictive value and negative predictive value of Arg-1 in distinguishing HCC from metastatic tumors was 96.2%, 100%, 100% and 90.6%, respectively. Cytoplasmic and membranous staining was observed in clear cell type of HCC. The overall sensitivity of Arg-1 expression in the 77 cases of tumors with clear cell changes was 14.3% (11/77), including 8/15 for malignant melanoma, 2/4 for ovarian clear cell carcinoma and 1/1 gall bladder adenocarcinoma with clear cell component.In malignant melanoma and ovarian clear cell carcinoma, only cytoplasmic staining was demonstrated. There was no expression of Arg-1 in the 140 cases of other tumor types studied.
CONCLUSIONSArg-1 is a sensitive and specific marker for HCC.It is a potentially useful immunohistochemical marker in distinguishing HCC from metastatic tumors. Though also expressed in malignant melanoma and ovarian clear cell carcinoma, Arg-1 shows a different staining pattern as compared with that in HCC.
Adenocarcinoma ; enzymology ; Adult ; Aged ; Arginase ; metabolism ; Carcinoma, Hepatocellular ; enzymology ; pathology ; secondary ; Cell Differentiation ; Diagnosis, Differential ; Female ; Gallbladder Neoplasms ; enzymology ; Humans ; Liver Neoplasms ; enzymology ; pathology ; secondary ; Male ; Melanoma ; enzymology ; Middle Aged ; Ovarian Neoplasms ; enzymology ; Stomach Neoplasms ; enzymology ; pathology
4.Comparison of DNA-dependent protein kinase catalytic subunit expression in two lung adenocarcinoma cell lines with different radiosensitivity.
Wei-Jian CEN ; Yi PAN ; Wei-Xiong LI ; Su-Qing YANG
Journal of Southern Medical University 2009;29(11):2241-2243
OBJECTIVETo investigate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) content and activity in lung adenocarcinoma cell lines and its correlation with radiosensitivity.
METHODSThe content and activity of DNA-PKcs were analyzed in two lung adenocarcinoma cell lines A549 and H1299 by Western blotting and the Signa TECT DNA-PK assay kit. The dose-survival relationship for two cell lines was analyzed using clonogenic formation assay.
RESULTSA549 was more radiosensitive than H1299. The survival fractions at 2 Gy (SF2) were 0.7412 in A549 cell line and 0.2473 in H1299 cell line. The content of DNA-PKcs was significantly higher in A549 cells than in H1299 cells (t=10.37, P<0.001). The integrated optical densities were 3.29-/+0.44 in A549 cells and 0.50-/+0.17 in H1299 cells. DNA-PKcs activities in A549 and H1299 cells were 8.29-/+1.37 and 2.47-/+1.09, respectively, showing a significant difference between them (t=5.76, P=0.005).
CONCLUSIONDNA-PKcs is an important factor to affect the radiosensitivity of lung adenocarcinoma cell lines.
Adenocarcinoma ; enzymology ; pathology ; Calcium-Binding Proteins ; genetics ; metabolism ; Cell Line, Tumor ; Humans ; Lung Neoplasms ; enzymology ; pathology ; Radiation Tolerance
5.Morphologic diagnosis and clinical significance of prostatic atypical small acinar proliferation suspicious but not diagnostic of cancer.
Huai-yin SHI ; Li-xin WEI ; Zhen-hong ZHOU ; Zai-lü WEN
Chinese Journal of Pathology 2006;35(11):660-663
OBJECTIVETo study the morphologic features and clinical significance of atypical small acinar proliferation (ASAP) suspicious but not diagnostic of cancer in prostatic biopsies.
METHODSThe slides of 11 cases of prostatic needle biopsies collected during a two-year period with the diagnosis of ASAP were reviewed. Immunohistochemical study for 34betaE12, p63 and P504S was performed on the archival paraffin sections.
RESULTSAll the 11 ASAP cases were characterized by the presence of a few compacted small acini in the prostatic stroma. Six cases had acini of less than three in number. The acini were round or slightly irregular in shape. The nuclei were enlarged, round or irregular, arranged in single layer and focally separated by broad interval. The nucleoli were usually prominent. Cytoplasm was amphophilic or pale and the lumen border was often well-defined. Basophilic mucus was also seen in some of the lumen. Immunohistochemical study for 34betaE12 and p63 was negative, while that for P504S was positive. In 4 of the 11 cases, the acini were more than three in number, round or slightly irregular, but without cytologic atypia. The nuclei were slightly enlarged with small or inconspicuous nucleoli. Immunohistochemical study for 34betaE12 and p63 was negative or at most focally positive. P504S staining was either negative or weakly positive. Second repeat biopsy was carried out in all cases, and 4 of them (36%) showed definite adenocarcinomatous changes. The positive cases were those with fewer acini but definite cytologic atypia in the initial biopsy.
CONCLUSIONSASAP is a morphologic interpretation closely associated with prostatic adenocarcinoma. The histologic features are suspicious of but not diagnostic of cancer, due to insufficient criteria in terms of acinar number, cytologic or architectural abnormalities. The positive rate in subsequent repeat biopsy is higher than that for cases with usual nodular hyperplasia.
Adenocarcinoma ; enzymology ; pathology ; Aged ; Biopsy ; Diagnosis, Differential ; Humans ; Male ; Middle Aged ; Prostate ; enzymology ; pathology ; Prostatic Hyperplasia ; enzymology ; pathology ; Prostatic Intraepithelial Neoplasia ; enzymology ; pathology ; Prostatic Neoplasms ; enzymology ; pathology ; Racemases and Epimerases ; metabolism
6.Tripartite-motif protein 25 and pyruvate kinase M2 protein expression in non-small cell lung cancer.
Huai-Zhi JING ; Feng QIU ; Shi-Zhi CHEN ; Lin SU ; Can QU
Journal of Southern Medical University 2015;35(3):437-441
OBJECTIVETo investigate the expression of tripartite-motif protein 25 (TRIM25) and pyruvate kinase M2 (PKM2) protein in non-small cell lung cancer (NSCLC) and explore their role in the occurrence and progression of NSCLC.
METHODSThe expressions of TRIM25 and PKM2 protein were detected in 60 NSCLC specimens and 20 adjacent normal lung tissue (>5 cm from the lesions) with immunofluorescence histochemical method and in 10 fresh specimens of NSCLC with Western blotting. The results were analyzed in relation with the clinicopathological features of the patients.
RESULTSThe positivity rates of TRIM25 expression was 45% in the 60 lung carcinoma specimens, significantly higher than that in the 20 normal lung tissues (10%, P=0.005). TRIM25 protein was expressed in 28.6% of lung adenocarcinoma tissues and in 59.4% of squamous carcinoma tissues (P=0.017). TRIM25 protein expression was positively correlated with the TNM stages and lymph node metastasis of NSCLC (P<0.05). The expressions of PKM2 protein in 60 cases of lung carcinoma was 73.3%,while in 20 cases of normal lung tissues the expressions was 30%(P=0.001). The positivity rates of PKM2 expression differed significantly between lung adenocarcinoma and squamous carcinoma (57.1% vs 87.5%, P=0.008). An inverse correlation was noted between TRIM25 and PKM2 expressions (P=0.026).
CONCLUSIONTRIM25 and PKM2 protein may participate in the occurrence and progression of NSCLC, and their expressions are inversely correlated.
Adenocarcinoma ; enzymology ; Carcinoma, Non-Small-Cell Lung ; enzymology ; Carcinoma, Squamous Cell ; enzymology ; Carrier Proteins ; metabolism ; Humans ; Lung ; pathology ; Lung Neoplasms ; enzymology ; Lymphatic Metastasis ; Membrane Proteins ; metabolism ; Thyroid Hormones ; metabolism ; Transcription Factors ; metabolism ; Tripartite Motif Proteins ; Ubiquitin-Protein Ligases ; metabolism
7.Telomerase Expression in Colorectal Tubular Adenoma Determined by Immunohistochemical Staining.
Ho Dong KIM ; Young Sang OH ; Soo Hyun KIM ; Sang Pil KIM ; Hyun Hak SHIN ; Ju Yong PARK ; Hyeuk PARK ; Bo Hyun MYOUNG ; Do Hyun KIM ; Young Jik LEE ; Hyung Rag KIM ; Young Do JUNG
The Korean Journal of Gastroenterology 2007;50(3):164-169
BACKGROUND/AIMS: Telomeres are simple repeat elements located at each chromosome end of eukaryotic cells. The main function of telomeres is to cap the chromosome end and protect it from enzymatic attack. Telomerase that facilitates the synthesis of telomere has been detected in not only cancer but also precancerous lesion. In this study, we compared the telomerase expression between low grade and high grade colorectal tubular adenoma. METHODS: Among thissues from forty eight patients with colorectal tubular adenoma (23 low grade and 25 high grade colorectal dysplasia), telomerase expressions were evaluated by immunohistochemical staining. RESULTS: We classified 48 patients into two groups by the extent of nuclei staining pattern. High telomerase expression was a group which showed staining nucleus pattern above 50% in tubular adenoma. Low telomerase expression was a group which showed staining pattern nucleus below 50%. Twelve in 25 high grade colorectal dysplasia showed high telomerase expression (48%). Only one in 23 low grade colorectal dysplasia showed high telomerase expression (4%). Telomerase expression was much higher in the tissues from the patients with high grade than in those with low grade colorectal dysplasia (p<0.05). CONCLUSIONS: Activation of telomerase may be related to the malignant potential in colorectal epithelial cells. Further studies are needed to define the role of telomerase in colorectal tumorigenesis.
Adenocarcinoma/*enzymology/pathology
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Adult
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Aged
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Colorectal Neoplasms/*enzymology/pathology
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Female
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Humans
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Immunohistochemistry
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Male
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Middle Aged
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Neoplasm Staging
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Retrospective Studies
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Telomerase/immunology/*metabolism
8.Overexpression of tissue inhibitors of metalloproteinase-1 and -2 in the stroma of gastric cancer.
Seok Il HONG ; In Chul PARK ; Weon Seon HONG ; Young Sook SON ; Seung Hoon LEE ; Jong Inn LEE ; Dong Wook CHOI ; Nan Mo MOON ; Tae Boo CHOE ; Ja Jun JANG
Journal of Korean Medical Science 1996;11(6):474-479
The fundamental event of cancer invasion and metastasis is the complicated interaction of cancer cells with host cells, in which event, a number of proteases and their inhibitors are involved. Matrix metalloproteinases are the potent proteases in degrading the basement membrane and extra cellular matrix and are inhibited by specific endogeneous inhibitors, tissue inhibitors of metalloproteinases-1(TIMP-1) and TIMP-2. The expression of mRNA for TIMP-1 and -2 was investigated by Northern blot analysis in specimens taken from 27 patients with primary gastric adenocarcinoma; 25 samples from the primary site, six from the metastatic lymph nodes and two from the peritoneal fluids. The expression for TIMP-1 and -2 was compared in primary gastric cancer tissues, metastatic lymph nodes and normal gastric mucosae. TIMP-1 mRNA was overexpressed in 24 (96%) out of 25 primary cancer tissues compared with the paired normal mucosae, while TIMP-2 was in 10 (40%). In six specimens of metastatic lymph nodes, TIMP-1 and -2 were overexpressed in 6 (100%) and 4 (67%) specimens, respectively. Of two specimens prepared from the peritoneal fluids, all specimens overexpressed TIMP-1 compared with the those of primary cancer tissues, while one (50%) specimen overexpressed TIMP-2. Immunohistochemical staining was done to investigate the localization of TIMP-1 and -2, demonstrating that the immunoreactivity for TIMP-1 and -2 was clearly detected in the cytoplasm of the stromal cells. These results suggest that both TIMP-1 and -2 are overexpressed by stromal cells in most of primary and some metastatic gastric cancer tissues and that TIMP-1 and TIMP-2, produced by stromal cells, may play an important role in inhibiting the proteolytic activity of matrix metalloproteinases originated from cancer cells, in gastric cancer.
Adenocarcinoma/*enzymology
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Blotting, Northern
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Glycoproteins/*biosynthesis/genetics
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Human
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Proteins/*biosynthesis/genetics
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RNA, Messenger/biosynthesis
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Stomach Neoplasms/*enzymology
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Support, Non-U.S. Gov't
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Tissue Inhibitor of Metalloproteinases
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Tissue Inhibitor-of Metalloproteinase-2
9.Overexpression of tissue inhibitors of metalloproteinase-1 and -2 in the stroma of gastric cancer.
Seok Il HONG ; In Chul PARK ; Weon Seon HONG ; Young Sook SON ; Seung Hoon LEE ; Jong Inn LEE ; Dong Wook CHOI ; Nan Mo MOON ; Tae Boo CHOE ; Ja Jun JANG
Journal of Korean Medical Science 1996;11(6):474-479
The fundamental event of cancer invasion and metastasis is the complicated interaction of cancer cells with host cells, in which event, a number of proteases and their inhibitors are involved. Matrix metalloproteinases are the potent proteases in degrading the basement membrane and extra cellular matrix and are inhibited by specific endogeneous inhibitors, tissue inhibitors of metalloproteinases-1(TIMP-1) and TIMP-2. The expression of mRNA for TIMP-1 and -2 was investigated by Northern blot analysis in specimens taken from 27 patients with primary gastric adenocarcinoma; 25 samples from the primary site, six from the metastatic lymph nodes and two from the peritoneal fluids. The expression for TIMP-1 and -2 was compared in primary gastric cancer tissues, metastatic lymph nodes and normal gastric mucosae. TIMP-1 mRNA was overexpressed in 24 (96%) out of 25 primary cancer tissues compared with the paired normal mucosae, while TIMP-2 was in 10 (40%). In six specimens of metastatic lymph nodes, TIMP-1 and -2 were overexpressed in 6 (100%) and 4 (67%) specimens, respectively. Of two specimens prepared from the peritoneal fluids, all specimens overexpressed TIMP-1 compared with the those of primary cancer tissues, while one (50%) specimen overexpressed TIMP-2. Immunohistochemical staining was done to investigate the localization of TIMP-1 and -2, demonstrating that the immunoreactivity for TIMP-1 and -2 was clearly detected in the cytoplasm of the stromal cells. These results suggest that both TIMP-1 and -2 are overexpressed by stromal cells in most of primary and some metastatic gastric cancer tissues and that TIMP-1 and TIMP-2, produced by stromal cells, may play an important role in inhibiting the proteolytic activity of matrix metalloproteinases originated from cancer cells, in gastric cancer.
Adenocarcinoma/*enzymology
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Blotting, Northern
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Glycoproteins/*biosynthesis/genetics
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Human
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Proteins/*biosynthesis/genetics
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RNA, Messenger/biosynthesis
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Stomach Neoplasms/*enzymology
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Support, Non-U.S. Gov't
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Tissue Inhibitor of Metalloproteinases
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Tissue Inhibitor-of Metalloproteinase-2
10.Contribution of eukaryotic initiation factor-4E inhibition to heparanase expression and activity in human colon adenocarcinoma cell line LS-174T.
Yu-jie YANG ; Ya-li ZHANG ; Zhuo-sheng LAI ; Ji-de WANG ; Bao-ping WU ; Ya-dong WANG
Chinese Journal of Oncology 2003;25(6):542-545
OBJECTIVETo determine whether the eukaryotic initiation factor-4E (eIF-4E) is involved in the cap-dependent translational regulation of heparanase and study the correlation between heparanase expression and metastatic potential of LS-174T cells.
METHODSThe protein and mRNA levels of inhibited eIF-4E were tested by Western blot and RT-PCR. Heparanase activity was defined as the ability to degrade high molecular weight (40-100 000) radiolabeled ((35)S) heparan sulfate (HS) substrate into low molecular weight (5-15 000) HS fragments. The invasive potential of tumor cells in vitro was observed by Matrigel invasion assay system.
RESULTSThe 20-mer antisense oligonucleotide (asODN) against eIF-4E specifically and significantly inhibited eIF-4E expression at both transcriptional and translational levels. The expression and the activity of heparanase were effectively lowered, which further decreased the invasive potential of LS-174T.
CONCLUSIONeIF-4E, probably being involved in translational regulation of heparanase in colon adenocarcinoma cell line LS-174T, can be a particularly interesting target for heparanase regulation, based on of its critical function.
Adenocarcinoma ; enzymology ; pathology ; Cell Line, Tumor ; Colonic Neoplasms ; enzymology ; pathology ; Eukaryotic Initiation Factor-4E ; antagonists & inhibitors ; genetics ; physiology ; Glucuronidase ; metabolism ; Humans ; Neoplasm Invasiveness