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* ; Breast Neoplasms/enzymology* ; Carcinoma, Intraductal, Noninfiltrating/enzymology* ; Human ; Protein Kinase C/metabolism* ; Stomach Neoplasms/enzymology*

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

5-Lipoxygenase, one of lipoxygenase isozymes, is a well-studied oxidative metabolism enzyme. It widely exists in various human tissues and cells, participates in the oxidative metabolism of endogenous and exogenous chemicals, and produces a variety of metabolites, all of which contribute to the occurrence of human diseases, such as inflammation, asthma, atherosclerosis, and tumor and so on. The expression of 5-lipoxygenase is at low level in normal human tissues while at high level in abnormal tissues. 5-Lipoxygenase is closely related to many kinds of diseases in human ovary, brain, cardiovascular system, lung, liver, pancreas and other tissues. The abnormal expression of 5-lipoxygenase tends to promote the development of the disease.
Arachidonate 5-Lipoxygenase ; physiology ; Atherosclerosis ; enzymology ; Humans ; Inflammation ; enzymology ; Neoplasms ; enzymology

Nicotinamide phosphoribosyltransferase (Nampt) is a rate-limiting enzyme for synthesis of nicotinamide adenine dinucleotide in mammalian cells. Recent studies show that Nampt also works as a cytokine that exerts insulin-mimetic effects by binding to the insulin receptor, induces B-cell differentiation, inhibits neutrophil apoptosis, and affects immune and inflammatory functions. This review is focused on current knowledge regarding the structure and function of Nampt and its roles in carcinogenesis.
Humans ; Neoplasms ; enzymology ; Nicotinamide Phosphoribosyltransferase ; metabolism ; physiology

BACKGROUND: Helicobacter pylori (H. pylori) has been considered a definitive carcinogen in gastric cancer. Telomerase is activated in gastric cancer and some premalignant gastric lesions, including intestinal metaplasia (IM). In this study, we evaluated the relationships of both H. pylori infection and telomerase activity with endoscopic and histologic features in IM. The effects of H. pylori eradication on endoscopic, histologic and biochemical changes were evaluated. METHODS: Endoscopic biopsies were obtained from 43 patients with IM for rapid urease, histologic and telomerase tests. The endoscopic and histologic features, H. pylori infection and telomerase were assessed. After H. pylori eradication, 15 patients were re-evaluated and compared after 4 months. RESULTS: Thirty-four (79.1%) patients were infected with H. pylori. The incidence of H. pylori infection was borderline correlated to the severity of IM (p=0.076). Telomerase was elevated in eight (18.6%) patients. Telomerase tends to be high in subtype III and endoscopic grade III of IM. After H. pylori eradication, endoscopic extent (p=0.039) and histologic severity (p=0.074) showed improvements, and telomerase decreased significantly (p=0.0001). CONCLUSION: Our data suggest that telomerase is associated with the severity and extent of IM and that H. pylori eradication improves the endoscopic and histologic features in IM, and decreases telomerase activity. H. pylori eradication can be considered one of the methods to prevent gastric cancer in patients with H. pylori-infected IM. Further long-term and large-scaled study will be needed.
Female ; Helicobacter Infections/*enzymology ; *Helicobacter pylori ; Human ; Intestinal Mucosa/enzymology/microbiology/*pathology ; Male ; Metaplasia/enzymology/microbiology ; Middle Aged ; Precancerous Conditions/enzymology/microbiology ; Stomach Neoplasms/*enzymology/microbiology ; Telomerase/*metabolism

The protein encoded by TXNDC5 is a member the protein disulfide isomerase family, which has disulfide isomerase activity and can act as the molecular chaperone to reduce the synthesis of abnormal proteins. Its biological functions include anti-oxidation, promoting angiogenesis, taking part in cellular inflammation, and energy metabolism, etc. Studies have demonstrated that the expression of TXNDC5 is increased in many types of tumors including cervical carcinoma, gastric carcinoma and colorectal cancer. Moreover, TXNDC5 is also closely associated with rheumatoid arthritis, diabetes, hepatic steatosis and vitiligo. This paper aims to summarize the latest progress in research on TXNDC5 in terms of biochemical function, relationship with diseases and the underlying mechanism.
Animals ; Arthritis, Rheumatoid ; enzymology ; genetics ; Diabetes Mellitus ; enzymology ; genetics ; Humans ; Neoplasms ; enzymology ; genetics ; Protein Disulfide-Isomerases ; genetics

OBJECTIVESTo detect telomerase activity in patients with mycosis fungoides (MF) and to study the role of telomerase in the tumorigenesis of MF.

METHODSThe technique of PCR-ELISA was employed to detect telomerase activity in 35 patients with various stages of MF.

RESULTS92.3% tumor stage of MF, 78.6% plaque stage of MF and 75.0% patch stage of MF had positive telomerase activity. The control samples had no telomerase activity. Telomerase activity in tumor stage of MF was significantly higher than that in plaque stage, while the latter was higher than that in patch stage. Telomerase activity was correlated with the stage of MF.

CONCLUSIONHigh level of telomerase activity frequently occurred in patients with MF, suggesting that telomerase might play an important role in the tumorigenesis of MF and is a useful marker for the diagnosis of MF possibly.

Humans ; Mycosis Fungoides ; enzymology ; pathology ; Neoplasm Staging ; Skin Neoplasms ; enzymology ; pathology ; Telomerase ; metabolism

Carcinoma, Hepatocellular ; enzymology ; pathology ; Glutathione Peroxidase ; Humans ; Liver Neoplasms ; enzymology ; pathology ; Thioredoxin-Disulfide Reductase

Aging ; genetics ; metabolism ; Animals ; Diabetes Mellitus ; enzymology ; metabolism ; Humans ; Longevity ; genetics ; physiology ; Neoplasms ; enzymology ; metabolism ; Neurodegenerative Diseases ; enzymology ; metabolism ; Obesity ; enzymology ; metabolism ; Sirtuins ; genetics ; metabolism

Thioredoxin reductase 1 (TrxR) is a homodimeric selenoenzyme catalyzing thioredoxin (Trx) in an NADPHdependent manner. With regard to carcinogenesis, these redox proteins have been implicated in cell proliferation, transformation and anti-apoptosis. In the present study, using a hamster cholangiocarcinoma (ChC) model, we evaluated the immunohistochemical expression pattern of TrxR in precancerous lesions and ChCs as well as in normal bile ducts. The goal of this study was to determine the potential role and importance of TrxR in cholangiocarcinogenesis. For the ChC model, we obtained liver tissue specimens with dysplastic bile ducts prior to the development of ChC 8 weeks after initiation of the experiment and ChC samples at 27 weeks. The immunohistochemical analysis showed diffuse cytoplasmic overexpression of TrxR in the dysplastic bile duct epithelial cells as well as in cholangiocarcinoma; this was comparable to the negative or weakly positive in normal and type 1 hyperplastic bile ducts. However, TrxR appeared to be considerably down-regulated in the ChCs when compared to the higher expression observed in the dysplastic bile ducts. Therefore, these results suggest that TrxR overexpression followed by down-regulation might be an important event in cholangiocarcinogenesis, especially at early stages including the cellular transformation of candidate bile ducts. Further studies are however required to determine whether TrxR may be a potential target molecule for chemoprevention against cholangiocarcinogenesis. In addition, the molecular mechanism as well as the importance of the loss of TrxR in the development of cholangiocarcinoma, following dysplastic transformation of bile duct cells, also remains to be clarified.
Animals ; Bile Duct Neoplasms/*enzymology/pathology ; Bile Ducts/enzymology/pathology ; Cholangiocarcinoma/*enzymology/pathology ; Cricetinae ; Disease Models, Animal ; Immunohistochemistry ; Mesocricetus ; Precancerous Conditions/*enzymology/pathology ; Thioredoxin Reductase (NADPH)/*biosynthesis