• Toxicological Research
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• v.16 no.4
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• pp.269-274
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• 2000

Epoxidised soya bean oil (ESBO, 1000, 2000 or 4000 mg/kg) was orally administered to BALB/c mice daily for 28 consecutive days, and the control mice were exposed to vehicle (corn oil). Mice were immunized and challenged with sheep red blood cells (SRBC) or bovine serum albumin (BSA). In groups exposed to ESBO, the body weight gains and the relative lymphoid organ weights were not significantly changed as compared with control group. Secondary IgG antibody response to BSA was not significantly changed by ESBO, but plaque-forming cell (PFC) response to SRBC was significantly suppressed in mice treated with 4000 mg ESBO/kg/day. The mitogenic response of splenic B cells induced by LPS was not effected by ESBO in any of the groups. These results indicate that ESBO did not induce significant humoral immune response at a dose less than 2000 mg/kg/day in mice.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.287-292
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• 2017

Vitiligo is an intriguing depigmentary disorder and is notoriously difficult to be treated. The ultimate goal of vitiligo treatment is to replenish the lost melanocytes by immigration from hair follicle and to restore the normal function of melanogenesis by residual melanocytes. There are two types of topical calcineurin inhibitors called tacrolimus and pimecrolimus, and are recommended as the first-line treatments in vitiligo. Although pimecrolimus is efficacious for the repigmentation of vitiligo, its intrinsic mechanisms have never been investigated in vitro. This research aimed to study the ability of pimecrolimus on stimulating melanogenesis, melanocyte migration and MITF (microphthalmia associated transcription factor) protein expression. Results showed that pimecrolimus at the dosages of 1, 10, $10^2$nM were neither mitogenic nor cytotoxic to melanocytes. The addition of pimecrolimus at 10, $10^2$ and $10^3nM$ significantly increased intracellular tyrosinase activity, which was consistent with the elevated content of melanin content at the same concentrations. The peak effect was seen at 72 h in response to $10^2$nM pimecrolimus. Results of the wound scratch assay and Transwell assays indicate that pimecrolimus is effective in facilitating melanocyte migration on a collagen IV-coated surface. In addition, MITF protein yield reached the highest by pimecrolimus at $10^2nM$. In brief, pimecrolimus enhances melanin synthesis as well as promotes migration of melanocytes directly, possibly via their effects on MITF protein expression.

• BMB Reports
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• v.53 no.8
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• pp.419-424
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• 2020

Bee venom (BV), secreted from the venom gland of the honey bee, contains several biological active compounds. BV has been widely used as a traditional medicine for treating human disease, including cancer. In this study, we have shown the molecular mechanism underlying the therapeutic effect of BV on cancer. Treatment with BV reduced the proliferation of cervical-cancer cells in a dose- and time-dependent manner. Interestingly, the killing effect of BV was specific to HPV-positive cervical-cancer cell lines, such as Caski and HeLa cells, and not to HPV-negative cervical-cancer cells (C33A). BV reduced the expression of HPV E6 and E7 at RNA and protein levels, leading to an increase in the expression of p53 and Rb in Caski and HeLa cells. Further, BV decreased the levels of cell-cycle proteins, such as cyclin A and B, and increased the levels of cell-cycle inhibitors, such as p21 and p27. BV significantly induced apoptosis and inhibited wound healing and migration of cervical-cancer cells. It also upregulated the expression of pro-apoptotic BAX and downregulated the expression of anti-apoptotic Bcl-2 and Bcl-XL. Cleavage of caspase-3, caspase-9, and PARP were also induced by BV treatment, whereas the phosphorylation of mitogenic signaling-related proteins, such as AKT, JNK, p38, and ERK, were downregulated. Our results indicate that BV has a therapeutic selectivity for HPV-positive malignant cells, so further clinical studies are needed to assess its clinical application.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.771-776
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• 2003

The present study was conducted to evaluate the regulation mechanism of nitric oxide(NO) by water-extracted Cyperus rotundus (WCR) in RAW 264.7 macrophages. We investigated the effects of cell proliferation in mouse spleen cell and RAW 264.7 macrophages cells. WCR enhanced mitogenic activity in the dose-response manner in mouse spleen cells and RAW 264.7 macrophages cells. In nitric oxide (NO) synthesis by WCR, WCR alone had an effect on NO synthesis. It was found that the production of NO of RAW 264.7 cells stimulated with lipopolysaccharide (LPS) could be markedly inhibited by WCR. Inhibition of NO production was achieved by reducing inducible nitric oxide syntheses(iNOS) mRNA expression. The expression of IL-I gene by WCR was investigated using reverse transcription polymerase chain reaction (RT-PCR). In RT-PCR, IL-1 family(IL-1 α, IL-1β) expressions were induced by WCR. These finding suggested that regulation of NO production by WCR may be, at least in part, associated with the regulation of iNOS mRNA expression and IL-1 family gene expression.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6595-6599
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• 2013

Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future.

• Korean Journal of Veterinary Research
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• v.31 no.4
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• pp.441-447
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• 1991

In this study, effect of levamisole, selenium and tocopherol on the lymphocyte blastogenesis and antibody production in Korean native goat were evaluated in vitro and in vivo. Lymphocyte blastogenesis of goat blood increased significantly (p<0.01 and p<0.05) when the cells were treated in vitro with levamisole at the concentration of $50{\sim}500{\mu}g/ml$, with selenium at the concentration of $0.062{\sim}1.0{\mu}g$ and with tocopherol nt the concentration on $12.5{\mu}g$. Increased lymphocyte blastogenesis was detected from 2 to 24 hours after oral administration of levamisole (2.5mg/kg of body weight). After 7 days, increased mitogenic response of lymphocytes was not detected. Meanwhile increased blastogenesis of lymphocyte from goats given the selenium-tocopherol mixture (selenium $100{\mu}g$-tocopherol 200IU/head/day) was detected from 10 days after feeding, and the tendency continued throughout the entire experimental period. When immune responses of goats against PPD were subjected to test by ELISA, the mean IgG titers of levamisolc group (1 : 1,800) and selenium-tocopherol group (1 : 960) were higher than that of control group (1 : 600) at 2 weeks after lst inoculation. At 3 weeks after lst inoculation and 1 week after 2nd inoculation, the significant (p<0.05) differences in IgG titers were detected among the three groups. The mean IgG titers of levamisole group, selenium-tocopherol group and control at that time were 1 : 20,480, 1 : 5,120 and 1 : 2,640, respectively. The IgG production of levamisole group was significantly (p<0.01) higher than that of control group.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.9
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• pp.1341-1347
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• 2002

An experiment was conducted to determine effects of oral administration of $Diakur^{TM}$ (an additive of glucose and electrolytes for young calves) on growth performance and some physiological responses in male broilers reared in a high temperature. A 2 by 3 factorial arrangement test of 2 temperatures (24 and $36^{\circ}C$) and 3 levels of oral administration of the glucose and electrolytes additive, $Diakur^{TM}$, (0, 150 and 300 mg/day/100 gBW) were applied in the experiment. Male broiler chicks (2 weeks of age) were assigned to six groups and received dietary and temperature treatments for 7 days. The additive of glucose and electrolytes was suspended with water and intubated into crop twice a day (08:00 and 17:00). Oral administration of the additive prevented decreases in food intake and growth rates in broilers due to exposure of the hot environment. Oral administration of the additive also improved a lowered electrolyte ($Na^+$ + $K^+$ - $Cl^-$) balance in plasma, low mitogenic response of blood mononuclear cell and an increase in glucose concentration due to exposure to the high environmental temperature. Oral administration of the additive increased rectal temperature regardless of environmental temperatures. On the other hand, blood pH, $pCO_2$ and $HCO_3$ - concentration, and plasma creatine kinase activity were not affected by the oral administration. The results suggested that oral administration of the glucose and electrolytes additive, $Diakur^{TM}$ during heat stress did not only prevent decrease in growth performance, but also normalized some physiological and immunological responses in male broilers.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.8
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• pp.1199-1204
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• 2003

The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI3 kinase) and the mitogenactivating protein (MAP) kinase pathway on the differentiation of ovine preadipocytes. In order to investigate this issue, we monitored glycerol 3-phosphate dehydrogenase (GPDH) activity during differentiation with specific inhibitors of PI3 kinase and MAP kinase-Erk kinase, LY294002 and PD098059, respectively. The preadipocytes, which were obtained from ovine subcutaneous adipose tissues, were proliferated to confluence and then differentiated to adipocytes in differentiation medium with each inhibitor for 10 days. The confluent preadipocytes and differentiated adipocytes at days 3, 7 and 10 were harvested for assay of GPDH activity. LY294002 inhibited the differentiation program in dose- and day-dependent manners during 10 days of differentiation. PD098059 did not affect GPDH activity during differentiation. Furthermore, the expression of peroxisome proliferator-activated receptor ${\gamma}2$ (PPAR-${\gamma}2$), the representative early gene of differentiation, was markedly reduced by LY294002 treatment, although PD098059 did not change it. Our results demonstrated that the activation of PI3 kinase contributes to the differentiation process of ovine preadipocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4945-4948
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• 2015

Background: Adiponectin is a protein, synthesized by adipose tissue, which has a questionable role in breast cancer pathogenesis. This study focused on serum levels of adiponectin among cases and controls, and its possible association with breast cancer risk. Materials and Methods: This case-control study covered 175 diagnosed breast cancer patients with positive histopathology from Breast Clinic, surgical unit-1, Civil Hospital, Karachi and 175 healthy controls from various screening programs. Blood samples were obtained after an overnight fast and later analyzed. Results: Fasting blood glucose was significantly raised, while serum adiponectin was significantly decreased in breast cancer cases when compared to control subjects. To find the precise influence of serum adiponectin on the risk of breast cancer, subjects were divided in to quartiles based on serum levels of adiponectin. It is observed that risk of breast cancer decreased with rising quartile. Q2 (25th-50th) had the highest OR=1.76 (CI: 0.93- 3.34), Q3 (50th-75th) has OR= 0.89 (CI: 0.48-1.64), while subjects in the highest quartile Q4 (>75th) had significantly (p< 0.05) decreased risk of breast cancer having OR=0.06 (CI: 0.02-0.15), when compared to the lowest quartile. Conclusions: We demonstrated a statistically significant association of elevated serum adiponectin with decreased risk of breast cancer. This signifies a protective role of adiponectin via an intricate mechanism of masking mitogenic growth factors in breast carcinogenesis.

• Biomedical Science Letters
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• v.20 no.2
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• pp.85-95
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• 2014

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the head and neck tumors. To investigate the mechanism of antiproliferation to EGFR inhibition in oral cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$). We have demonstrated that ZD1839 induces growth arrest and apotosis in oral cancer cell lines by independent of EGFR-mediated signaling. An exposure of oral cancer cells to ZD1839 resulted in a dose dependent up-regulation of the cyclin-dependent kinase inhibitor p21 and p27, down regulation of cyclin D1, inactivation of GSK-$3{\beta}$ and of active MAPK. In resistant cells, GSK-$3{\beta}$ is constitutively active and its activity is negatively regulated primarily through Ser 9 phosphorylation and further enhanced by Tyr216 phosphorylation. These results showed that the resistance to the antiproliferative effects of ZD1839, in vitro was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-$3{\beta}$ activation and degradation of its target cyclin D1 were indicators of high cell sensitivity to ZD1839. In conclusion, our data show that the uncoupling of EGFR with mitogenic pathways can cause resistance to EGFR inhibition in oral cancer.