• Biomedical Science Letters
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• v.24 no.1
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• pp.50-54
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• 2018

N-nitroso-N-methylurea (NMU) and N-nitroso-N-ethylurea (NEU), direct alkylating chemical mutagens and carcinogens, are shown to be the upregulators of cellular $NF-{\kappa}B$, regulating various genes that mediate tumorigenesis and carcinogenesis. Nitric oxide (NO), a toxic reactive radical gas, has been known to induce programmed cell death or apoptosis in various cells. Therefore, the assessment of NO production was examined to elucidate the possible contribution of NO release to the chemical carcinogenic potency of NMU and NEU in human skin cells. NMU and NEU did not alter the NO production, but they caused a significant downregulation of the NO generation on lipopolysaccharide (LPS)-induced NO production at concentrations ranging from $2{\sim}5{\mu}M$. The degree of downregulation of NO by NMU and NEU decreased up to 15% and 20%, respectively, compared to the control. These results demonstrate that the LPS-inducible keratinocytes NO synthase is involved in modulating carcinogenic potency by NMU and NEU, and the regulation of the cellular $NF-{\kappa}B$ activity by NMU and NEU is negatively correlated with the level of LPS-induced NO production in human skin cells. The findings of this study suggest the hypothesis that NMU and NEU-induced carcinogenesis may be associated with the downregulation of NO production, and the inducible NO may play an important role in NMU and NEU-induced carcinogenicity in human epidermal keratinocytes.

• Korean Journal of Environmental Biology
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• v.20 no.2
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• pp.173-179
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• 2002

N-nitrosoethylurea (NEU) -induced changes of lipid peroxide content, aldehyde metabolic enzyme activities and antioxidant enzyme activities were examined in cultured rat liver cell. Aldehyde metabolic enzymes tested in this investigation were alcohol dehydrogenase and aldehyde dehydrogenase. Several antioxidant enzymes tested were glutathione transferase, superoxide dismutase, glutathione reductase and catalase. When the cell was exposed with various concentrations of NEU, lipid peroxide content increased about 2.5 fold with 6.25 mM NEU. Maximun 2.3 times higher alcohol dehydrogenase activity was found after NEU treatment. About 2 times higher aldehyde dehydrogenase activity could also be observed. Only slight increases of glutathione transferase and catalase activities occurred with NEU treatment. In addition mnximun 1.5 times higher superoxide dismutase activities and 3 times higher glutathione reductase activities were found after NEU treatment. Therefore, it is likely that the increases of superoxide dismutase and glutathione reductase could contribute in a antioxidative process against NEU toxicity.

• The Journal of Korean Physical Therapy
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• v.23 no.2
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• pp.45-52
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• 2011

Purpose: The purpose of this study was to investigate the effect of electroacupuncture on NeuN expression in ventral horn motor neurons of spinal cord, changes in pain thresholdchanges in motor function in rats with partially dissected sciatic nerves. Method: A total of 120 male Sprague-Dawley rats were randomly divided into two groups, a control group and a group administered electroacupuncture at ST36, LI11 and SP9 with 120 Hz and 0.5 mA. Animals were sacrificed on days 1, 3, 7, 14 and 28 after nerve injury (the sciatic nerve was partially dissected). The pain threshold was recorded by an Analgesia? meter and a BBB? score was calculated for motor function. After preparing lumbar spinal cord slide sections, they were immunostained with NeuN antisera (1:2,500). Results: The numbers of NeuN immunoreactive neuronsin the electroacupuncture group was increased compared to the control group. The numbers of NeuN immunoreactive neurons on days 14 and 28 day were different (p<0.05), as were the numbers on days 3 and 7 (p<0.01). The pain threshold BBB score for the electroacupuncture group was higher than for controls. Conclusion: The increase in pain threshold, BBB-score and number of NeuN immunoreactive neurons inventral horn motor neurons of spinal cord in rats withnerve dissection showed that electroacupuncture can attenuate pain transduction and increase motor function. Also, NeuN was a good marker for identifying the degree of nerve cell loss after nervous system injury.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3733-3736
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• 2016

HER2/neu is a well-established prognostic and predictive factor for invasive breast cancer. However, the role of HER2/neu in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that it is mainly linked to in situ local recurrence. Although molecular data suggest that atypical ductal hyperplasia (ADH) and duct carcinoma in situ (DCIS) are related lesions, albeit with vastly different clinical implications, the role of HER2/neu expression in atypical ductal hyperplasia is not well defined either. The aim of this study was to evaluate over expression of HER2/neu in DCIS and cases of ADH in comparison with invasive breast carcinoma. Archival primary breast carcinoma paraffin blocks (n=15), DCIS only (n=10) and ductal epithelial hyperplasia and other breast benign lesions (n=25) were analyzed for HER2/neu immunoexpression. Follow up was available for 40% of the patients. HER2/neu was positive in 80%of both DCIS and invasive carcinoma, and 67% of atypical ductal hyperplasia (ADH) cases. Thus at least a subset of patients with preinvasive breast lesions were positive, which strongly suggests a role for Her2/neu in identifying high-risk patients for malignant transformation. Although these are preliminary data, which need further studies of gene amplification within these patients as well as a larger patient cohort with longer periods of follow up, they support the implementation of routine Her2/neu testing in patients diagnosed as pure DCIS and in florid ADH.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.3903-3909
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• 2016

Purpose: To evaluate the expression of Her2/neu and Ki-67 in benign and malignant gallbladder lesions, and to establish correlations with clinico-pathologic parameters. Materials and Methods: A retrospective analysis was conducted on formalin fixed paraffin embedded (FFPE) benign (n=25) and malignant gallbladder (n=25) tissue samples. Hematoxylin and eosin stained slides of each case were reviewed for: type of malignancy (whether adenocarcinoma, squamous cell carcinoma, or any other type), grade (well, moderate, and poor), depth of invasion, pre-neoplastic changes in adjacent mucosal epithelium like metaplasia and dysplasia. Immunohistochemistry for Her 2 neu and Ki-67 was performed and data analysis was conducted using SPSS 17 software. Chi-square test was used to compare categorical/dichotomous variables. P value of ${\leq}0.05$ was considered significant. Results: The difference of Her 2 neu expression and Ki67 index between benign and malignant groups was found to be statistically significant. Her2/neu positivity did not have any significant correlation with various clinicopathological parameters other than liver involvement. 5 cases of gallbladder cancer showed both Her2/neu and Ki67 positivity. Ten cases were Ki67 positive but Her2/neu negative while one case was Her2/neu positive but Ki67 negative. Conclusions: The present study demonstrated overexpression of Her2/neu and Ki67 in gallbladder cancer. A trend of decreasing Her2/neu expression with increasing grade of tumor was observed. Furthermore, greater Ki67 positivity was found in cases with lymph node metastasis and distant metastasis. Future studies with a larger number of patients will be required to precisely define the correlation of Her2/neu expression and Ki67 positivity with clinicopathological parameters. The results however are encouraging and suggest evaluation of Her2/neu as a candidate for targeted therapy.

• Food Science of Animal Resources
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• v.42 no.3
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• pp.426-440
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• 2022

The bioactive functions of oligosaccharides from human milk have been reported by many studies. Many of oligosaccharides isolated from colostrum and/or milk of dairy animals have been reported to have similar chemical structures with those in human colostrum and/or milk. It has been proved by several studies that the oligosaccharides with similar chemical structure shared common bioactivities. Among domesticated dairy animals, bovine/cattle, caprine/goat, and ovine/sheep are the most commonly used species to isolate oligosaccharides from their colostrum and/or milk. Several studies on the oligosaccharides from goat colostrum and milk have revealed similar properties to that of human milk and possess the highest content of sialyl oligosaccharides (SOS) as compared to other ruminants. Indonesia ranks first in Association of Southeast Asian Nations (ASEAN) for goat milk production. Therefore, goat milk is the second most consumed milk in the country. The most reared dairy goat breed in Indonesia is Etawah Grade. However, oligosaccharides from Indonesia dairy animals including goat, have not been characterized. This is the first study to characterize oligosaccharides from Indonesia dairy animals. The present study was aimed to isolate and characterize oligosaccharides, specifically SOS from the colostrum of Etawah Grade goats by using proton/¹H-nuclear magnetic resonance. The SOS successfully characterized in this study were: Neu5Ac(α2-3)Gal(β1-4)Glc (3'-N-acetylneuraminyllactose), Neu5Ac(α2-6)Gal(β1-4)Glc (6'-N-acetylneuraminyllactose), Neu5Gc(α2-3)Gal(β1-4)Glc (3'-N-glycolylneuraminyllactose), Neu5Gc(α2-6)Gal(β1-4)Glc (6'-N-glycolylneuraminyllactose), Neu5Ac(α2-6)Gal(β1-4) GlcNAc (6'-N-acetylneuraminyllactosamine) and Neu5Gc(α2-6)Gal(β1-4)GlcNAc (6'-N-glycolylneuraminyllactosamine). This finding shows that Etawah Grade, as a local dairy goat breed in Indonesia, is having significant potential to be natural source of oligosaccharides that can be utilized in the future food and pharmaceutical industries.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5773-5777
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• 2015

Background: Oral squamous cell carcinoma (OSCC) is thought to develop from precancerous dysplastic lesions through multistep processes of carcinogenesis involving activation of oncogenes and loss of tumor suppressor genes. The human epidermal growth factor receptor 2 (Her-2/neu [erbB-2]), a cell membrane glycoprotein, is a growth factor receptor that has receptor tyrosine kinase activity. Her2/neu activation plays a central role in cell proliferation and survival. It has been shown that overexpression of Her2/neu increases the rate of cell division and growth, leading to precancerous changes. The aim of the present study was to compare the serum and salivary Her2/neu levels between cases with premalignant and malignant oral lesions. Materials and Methods: Fasting blood samples and unstimulated saliva by passive drooling were collected from three groups of healthy control (n=20), premalignant disorder (PMD) (n=20) and OSCC (n=25) subjects. The HER2 extracellular domain (HER2 ECD) levels were measured using ELISA. Results: The levels of serum Her2/neu showed no significant differences between any of the groups but on the other hand salivary Her2/neu levels were found to be significantly (p<0.05) higher when compared between control (median 68.7 pg/ml, range: 21.5 - 75.8) and OSCC (median 145.6 pg/ml, range: 45.1-191.1). A similar trend was observed when comparing between PMD (median 43.3, range: 22.1 -94.7) and OSCC with a statistical significance of p<0.05. Conclusions: Our study provided evidence of increased salivary Her2/neu in OSCC when compared to PMD and control which was not the case for serum levels. This suggests that probably Her2/neu is not highly amplified as in breast cancer so as to be reflected in serum. Since saliva is in local vicinity of the OSCC, even a mild increase might be mirrored. On the whole, this study proposes Her2/neu as marker for distinguishing premalignant and malignant conditions.

• Applied Microscopy
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• v.30 no.1
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• pp.101-111
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• 2000

In this study, the distribution of lectin receptors in Paragonimus westermani tissue was explored using colloidal gold label complexed with lectin WGA purified from wheat germ (Triticum vulgare). The lectin WGA gold complex, shown to recognize GlcNAc (N-acetylgalactosamine) and NeuNAc (N-acetylneuraminic acid) regions, was applied to detect binding sites in Lowicryl HM 20 sections viewed under electron microscope. Labeled sections of the metacercaria revealed gold particles specifically distributed on the tegumental syncytium and lamella of the excretory canal. Labeling of young adult tissue was then quantified and compared to that of adult worm tissue. Adult worm tissue sections resulted in specific gold particle distribution on the lamella of caecal epithelium and excretory canal. These results indicate that lectin WGA receptors are located in the tegumental syncytium and lamella of the excretory canal of the metacercariae, and in the lamella of the caecum and excretory canal of the young adult and adult. Therefore, the GlcNAc and NeuNAc regions in the tegumental syncytium appear to be functionally associated with cell-recognition and protection from the immune system of the host, and linked with membrane transport and absorption of nutrients in the lamella of the excretaory canal and caecal epithelia.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.3
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• pp.215-218
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• 2000

Sialytrisaccharides based on $\beta$-galactosyldisaccharides were synthesized using $\beta$-galactosidase and trans-sialidase in one pot. Using $\beta$-galactosidase from Bacillus Ciculans and trans-sialidase from Trypanosoma cruzi simulaneously, 6mM sialyltrisaccharides composed of about 95% NeuAc$\alpha$(2,3)Gal$\beta$(1,4)GlcNAc and 5% NeuAc$\alpha$(2,3)Gal$\beta$(1,6)GlcNAc were produced from a reaction mixture containing 25mM o-nitropheny1-$\beta$-D-galsctolneuraminic acid. One beauty of this reaction was that a secondary hydrolysis of the disaccharide intermediate occurring between the activated galactopyranoside and N-acetylgucosamine was prevented. Using $\beta$-galactosidase from Escherichia cloi and the same trans-sialidase, 15mM sialyltrisaccharides composed of about 90% NeuAc$\alpha$(2,3)Gal$\beta$(1,6)GlcNac and 10% NeuAc$\alpha$(2,3)Gal$\beta$(1,4)GlcNAc were produced from a reaction misture containing 400nM galactose, 800nM N-acetylglucosylation rection between galactose and N-actylgucosamine was diminant since the disaccharide intermediate mainly resulted sreulted in the silylated product.

• BMB Reports
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• v.41 no.1
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• pp.72-78
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• 2008

Human NeuNAc-9-P synthase is a two-domain protein with ability to synthesize both NeuNAc-9-P and KDN-9-P. Its mouse counterpart differs by only 20 out of 359 amino acids but does not produce KDN-9-P. By replacing the AFL domain of the human NeuNAc-9-P synthase which accommodates 12 of these differences, with the mouse AFL domain we examined its importance for the secondary KDN-9-P synthetic activity. The chimeric protein retained almost half of the ability of the human enzyme for KDN-9-P synthesis while the NeuNAc-9-P production was reduced to less than 10%. Data from the homology modeling and the effect of divalent ions and temperature on the enzyme activities suggest conformational differences between the human and mouse AFL domains that alter the shape of the cavity accommodating the substrates. Therefore, although the AFL domain itself does not define the ability of the human enzyme for KDN-9-P synthesis, it is important for both activities by aiding optimal positioning of the substrates.