• Molecules and Cells
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• v.46 no.3
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• pp.142-152
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• 2023

Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the cellular antioxidant response, allowing adaptation and survival under conditions of oxidative, electrophilic and inflammatory stress, and has a role in metabolism, inflammation and immunity. Activation of Nrf2 provides broad and long-lasting cytoprotection, and is often hijacked by cancer cells, allowing their survival under unfavorable conditions. Moreover, Nrf2 activation in established human tumors is associated with resistance to chemo-, radio-, and immunotherapies. In addition to cancer cells, Nrf2 activation can also occur in tumor-associated macrophages (TAMs) and facilitate an anti-inflammatory, immunosuppressive tumor immune microenvironment (TIME). Several cancer cell-derived metabolites, such as itaconate, L-kynurenine, lactic acid and hyaluronic acid, play an important role in modulating the TIME and tumor-TAMs crosstalk, and have been shown to activate Nrf2. The effects of Nrf2 in TIME are context-depended, and involve multiple mechanisms, including suppression of proinflammatory cytokines, increased expression of programmed cell death ligand 1 (PD-L1), macrophage colony-stimulating factor (M-CSF) and kynureninase, accelerated catabolism of cytotoxic labile heme, and facilitating the metabolic adaptation of TAMs. This understanding presents both challenges and opportunities for strategic targeting of Nrf2 in cancer.

• Proceedings of the KSCN Conference
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• 2005.04a
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• pp.72-72
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• 2005

• The Korean Journal of Physiology
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• v.3 no.2
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• pp.17-23
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• 1969

Oxygen consumption rate $(QO_2)$ and protein content of liver and kidney of the Ehrlich ascites tumor-bearing mouse were measured from 6th till 14th day after the inoculation of $4{\times}10^6$ Ehrlich ascites tumor cells. The results thus obtained were compared with those of the groups in which; 1) Whole body x-irradiation with 400 r was done to mouse prior to the inoculation of $4{\times}10^6$ Ehrlich ascites tumor cells, 2) Same number of the irradiated tumor cells were inoculated after subjecting the tumor cells to x-irradiation with 400 r or 900 r in vitro, and 3) the normal, and the following results were obtained; 1. $QO_2$ of the liver and kidney of the tumor-bearing mouse were all lower than the normal and a gradual decrease of $QO_2$ in both liver and kidney was noted as the ascites tumor was progressively developing. 2. In the groups where whole body x-irradiation with 400 r was done, or x-irradiation of ascites tumor cells in vitro with either 400 r or 900 r, $QO_2$ of the liver and kidney were lower than the normal, and the pattern of the decrease was similar in the case of the tumor-bearing mouse. 3. Protein contents in all the groups showed lower values than the normal, and the decrease was gradual as the ascites tumor was developing. 4. $QO_2$ and protein levels in the liver were generally lower than those in the kidney. 5. A certain cancerous metabolism was, therefore, noted in the remote organs of Ehrlich ascites tumor-bearing animal.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.5
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• pp.685-691
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• 2008

An experiment was conducted to determine the effect of dietary copper (Cu) on performance, carcass characteristics and lipid metabolism in lambs. Fifty DorperMongolia wether lambs (approximately 3 month of age; 23.80.6 kg of body weight) were housed in individual pens and were assigned randomly to one of five treatments. Treatments consisted of 1) control (no supplemental Cu), 2) 10 mg Cu/kg DM from Cu-lysine, 3) 20 mg Cu/kg DM from Cu-lysine, 4) 10 mg Cu/kg DM from tribasic copper chloride (Cu2(OH)3Cl; TBCC), 5) 20 mg Cu/kg DM from tribasic copper chloride. The Cu concentration was 6.74 mg/kg DM in the basal diet. Body weight was measured on two consecutive days at the start and the end of the 60-day experimental period. Blood samples were collected and then the lambs were slaughtered on d 60. Performance was not affected (p>0.05) by dietary Cu treatment. Cu-supplemented and control lambs had similar hot carcass weight, dressing percentage and longissimus muscle area, but Cu supplementation, regardless of source and level, reduced (p<0.01) 12th rib backfat and kidney fat in lambs. Plasma tumor necrosis factor-alpha (TNF-) and serum triglyceride concentrations were increased (p<0.05), total cholesterol concentrations were decreased (p<0.05) and nonesterified fatty acids (NEFA) concentrations tended to be increased (p<0.07) by Cu supplementation. However, Serum concentrations of HDL-cholesterol and LDL-cholesterol were not affected (p>0.05) by dietary treatment. Fatty acid profile of longissimus muscle was similar across treatments. These results indicate that Cu-lysine and TBCC are of similar availability in lambs. Cu supplementation given to DorperMongolia wether lambs altered lipid metabolism. The reduction in backfat depth may be due to copper altering TNF- metabolism in lambs. Supplementation of 10 or 20 mg Cu/kg DM showed similar effects on lipid metabolism in lambs.

• BMB Reports
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• v.32 no.2
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• pp.173-180
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• 1999

The effects of agmatine on the enzymes responsible for the biosynthesis of polyamines, the resultant levels of polyamines, and their effect on the growth of DU145 human prostate tumor cells were investigated. When agmatine was added to the medium, ornithine decarboxylase (ODC, EC 4.1.1.17) activity was substantially reduced, but S-adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.50) activity increased markedly. These changes in ODC and SAMDC activities were the result of an induction of ODC-antizyme and a decreased turnover rate of SAMDC in the presence of agmatine. Accordingly, there was a decrease in the intracellular levels of putrescine and spermidine but an increase in the intracellular level of spermine. Cell growth was markedly inhibited by agmatine treatment and this inhibition was not recovered by the addition of putrescine or spermidine. Our results suggest that agmatine alters the intracellular amounts of polyamine in the cells, closely related to the inhibition of cell growth.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.sup1
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• pp.1-5
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• 2008

Primary brain tumor accounts for 1.4% of entire cancer. For males between the ages of 15 and 34 years, central nervous system tumors account for the leading cause of cancer death. $^{18}F-FDG$ PET has been reported that it can provide important diagnostic information relating to tumor grading and differentiation from non- tumorous condition. In addition, the degree of FDG metabolism carries prognostic significance. By mapping the metabolic pattern of heterogeneous tumors, $^{18}F-FDG$ PET can aid in targeting for stereotactic biopsy by selecting the subregions within the tumor that are most hypermetabolic and potentially have the highest grade. According to clinical research data, FOG PET is expected to be a helpful diagnostic tool in the management of brain tumors.

• The Korean Journal of Nuclear Medicine
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• v.36 no.4
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• pp.209-223
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• 2002

By considering the biological properties of a tumor, it should be possible to realize better results in cancer therapy. PET imaging offers the opportunity to measure tumor growth non-invasively and repeatedly as an early assessment of response to cancer therapy. Measuring cellular growth instead of energy metabolism showed offer significant advantages in evaluating therapy. Thymidine and its derivative nucleoside compounds can be changed to mono, di- and tri- phosphate compounds by thymidine kinase and then be incorporated into DNA. Their bindings are increased in highly proliferating cells due to the high DNA synthesis rate. To evaluate cell proliferation, many kinds of thymidine and uridine derivatives have been labeled with positron emitter and radioactive iodine. Compared to radiopharmaceuticals which have radioisotope labeled base ring such as pyirmidine, the radiopharmacuticals which have radioisotope labeled sugar ring are more stable in vivo and have metabolic resistance. The biological properties such as DNA incorporation ratios are highly dependent on their chemical structures and metabolic processes. This overview describes synthesis of radiopharmaceuticals and their biological properties for imaging of tumor cell proliferation.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.664-670
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• 1998

The role of intracellular $Ca^{2+}$, in the regulation of tumor cell proliferation by products of arachidonic acid (AA) metabolism was investigated using U-373 MG human as trocytoma cells. Treatment with nordihydroguaiaretic acid (NDGA), a lipoxygenase (LOX) inhibitor, or caffeic acid (CA), a specific 5-LOX inhibitor, suppressed proliferation of the tumor cells in a dose-dependent manner. However, indomethacin (indo), a cyclooxygenase (COX) inhibitor, did not significantly alter proliferation of the tumor cells. At anti-proliferative concentrations, NDGA and CA significantly inhibited intracellular $Ca^{2+}$ release induced by carbachol, a known intracelluar $Ca^{2+}$ agonist in the tumor cells. Exogenous administration of leukotriene $B_4(LTB_4)$, an AA metabolite of LOX pathway, enhanced proliferation of the tumor cells in a concentration-dependent fashion. In addition, $LTB_4$, induced intracelluar $Ca^{2+}$ release. Intracellular $Ca^{2+}$-inhibitors, such as an intracellular $Ca^{2+}$ chelator (BAPTA) and intracellular $Ca^{2+}$-release inhibitors (dantrolene and TMB-8), significantly blocked the LTB4-induced enhancement of cell proliferation and intracellular $Ca^{2+}$ release. These results suggest that LOX activity may be critical for cell proliferation of the human astrocytoma cells and that intracelluar $Ca^{2+}$ may play a major role in the mechanism of action of LOX.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7031-7038
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• 2015

Background: Arginine may play important roles in tumor progression by providing ornithine for polyamine biosynthesis, required for cell growth. The aim of this work was to determine the expression of arginine metabolic pathway enzymes in head and neck squamous cell carcinoma (HNSCC) in northeast India. Materials and Methods: The expressions of arginase isoforms (ARG1 and ARG2), ornithine aminotransferase (OAT) and ornithine decarboxylase (ODC) were examined in fifty paired HNSCC and adjacent non-tumor tissues by immunohistochemistry. Immunocytochemistry, semiquantitative reverse transcription sq-PCR and quantitative real-time qPCR were used to assess protein and mRNA expressions in peripheral blood of fifty HNSCC patients and hundred controls. Results: ARG1 and ODC protein and mRNA were strongly expressed in peripheral blood from HNSCC patients. No ARG2 expression was observed. In vivo, expression of ARG1, ARG2 and ODC was significantly higher in tumor than in non-tumor tissues. Most tumors expressed low levels of OAT, with no difference in tissues or blood, compared to controls. The absolute extent of maximal ARG1 upregulation with qPCR showed 6.23 fold increase in HNSCC. Conclusions: These findings strongly suggest that in HNSCCs, the ARG1 pathway is stimulated leading to the formation of polyamines as indicated by higher ODC expression, which promote tumor growth.

• Archives of Pharmacal Research
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• v.28 no.11
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• pp.1302-1310
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• 2005

Glucosylated polyethylenimine (GPEI) was synthesized as a tumor-targeting gene carrier through facilitative glucose metabolism by tumor glucose transporter. Particle sizes of GPEI/DNA complex increased in proportion to glucose content of GPEI, whereas surface charge of the complex was not dependent on glucosylation, partially due to inefficient shielding of the short hydrophilic group introduced. GPEI with higher glucosylation (36 mol-$\%$) had no cytotoxic effect on cells even at polymer concentrations higher than 200 $\mu$g/mL. Compared to unglucosylated PEl. glucosylation induced less than one-order decrease of transfection efficiency. Transfection of GPEI/DNA complex into tumor cells possibly occurred through specific interaction between glucose-related cell receptors and glucose moiety of GPEI. Gamma imaging technique revealed GPEI/DNA complex was distributed in liver. spleen. and tumors.