• BMB Reports
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• v.54 no.7
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• pp.344-355
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• 2021

Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this mini-review, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma.

• Journal of Life Science
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• v.25 no.12
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• pp.1415-1424
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• 2015

ICI 182, 780 (ICI) has been used as an estrogen receptor inhibitor in several mammalian species. This study was conducted to observe histological changes in the reproductive system of pubescent male mice following ICI treatment, as well as to investigate the recovery of the organs over time. To accomplish this, ICI at 5 mg/0.1 ml of castor oil was subcutaneously injected into 5-week-old male mice once per week for 4 weeks. The mice were then randomly divided into no-recovery, 150-day recovery, and 300-day recovery groups. The testis of the no-recovery group showed atrophy of the seminiferous tubules, with decreased Sertoli cell numbers and thickness of the germinal epithelium. In the epididymis, the cell height of epithelial tissues was altered, but these changes were not observed in the 300-day recovery group. In the efferent ductule, the luminal diameter was increased, but the cell height of the epithelial tissues was decreased. In the prostate and seminal vesicles, the cell height of the epithelial tissues was increased, and these changes were not observed in the 150-day recovery group. These results show that ICI causes histological changes in pubescent male reproductive organs but that these changes are resolved with time.

• Korean Journal of Veterinary Research
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• v.57 no.4
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• pp.215-222
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• 2017

Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350-400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.

• Development and Reproduction
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• v.14 no.4
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• pp.287-295
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• 2010

It was recently reported that nesfatin-1/NUCB2, which is secreted from the brain, controls appetite and energy metabolism. The purpose of this research was to confirm whether or not the protein and its binding site should have been expressed in the mouse reproductive organs and to know the possible effects of nesfatin-1 on the reproductive function. Using the ICR female mouse ovary and uterus, the expression of NUCB2 mRNA was confirmed with the conventional PCR and the relative amount of NUCB2 mRNA in the tissues was analyzed with real-time PCR. Immunohistochemical staining was performed using the nesfatin-1 antibody to investigate the nesfatin-1 protein expression and the biotin conjugated nesfatin-1 to confirm the binding site for nesfatin-1 in the ovary. Furthermore, in order to examine if the expression of NUCB2 mRNA in the ovary and uterus is affected by gonadotropin, its mRNA expression was analyzed after PMSG administration into mice. As a result, the expression level of NUCB2 mRNA in the ovary and the uterus was as much as the expression level in hypothalamus. As a result of the immunohistochemical staining, nesfatin-1 proteins were localized at the theca cells, the interstitial cells, and some of the luteal cells. However, the granulosa cells in the follicles did not stain. Interestingly, the oocytes in the some follicles were stained with nesfatin-1. On the other hand, nesfatin-1 protein binding sites were displayed at the theca cells and the interstitial cells near the tunica albuginea. After PMSG administration the expression level of NUCB2 mRNA was increased in the ovary and the uterus. These results demonstrate that for the first time the nesfatin-1 and its binding site were expressed in the ovary and NUCB2 mRNA expression was controlled by gonadotropin, suggesting an important role in the reproductive organs as a local regulator. Therefore, further study is needed to elucidate the functions of nesfatin-1 on the reproductive organs.

• The Journal of Internal Korean Medicine
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• v.35 no.1
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• pp.37-49
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• 2014

Objectives & Methods : The objective of this study was to evaluate the single oral dose toxicity of Chongmyung-tang (CMT) in ICR mice. Korean traditional herbal prescription CMT has traditionally been used as a neuroprotective for treatment of learning disability and memory improvement. CMT, lyophilized aqueous extracts (yield=9.7%) were administered to female and male mice with oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for mortality, changes in body weight, clinical signs and gross observation during 14 days after administration upon necropsy; organ weight and histopathology of 14 principle organs were examined. Results : We could not find any CMT extracts treatment related mortalities, clinical signs, changes in body and organ weight, or gross and histopathological observations against 14 principle organs up to 2,000 mg/kg in both female and male mice, except for some accidental sporadic findings which did not show any obvious dose-relations and most of which also demonstrated in both the female and male vehicle control mice in this experiments. Conclusions : Based on the results of this experiment, the 50% lethal dose ($LD_{50}$) and approximate lethal dose (ALD) of CMT extracts after single oral treatment in female and male mice can be considered to be over 2,000 mg/kg, and is likely to be safe in humans.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.483-489
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• 2002

APA-01, which is an aqueous extract of five Chinese herbs, is a modified formula of Huoxiang-Zhengqi-San. The effect of new herb extract on immune response was investigated. The parameter examined to assess apparent immune response of APA-01 in mice included changes of body weight, relative weight of immune organs, cell proliferation and cytokine gene expression. The body weight and relative weight of immune organs were not significantly changed among the tested groups. In the spleen cell prolijeration assay, APA-01 increased the cell proliferation in a dose-dependent manner. Methotrexate (MTX), an agent of immune suppression, inhibited the spleen cell proliferation (IC/sub 50/: 800㎍/㎖). However, APA-01 significantly inhibited the suppression of mouse spleen cell proliferation. Therefore, it seems that APA-01 has a reducing effect of immune suppression. Immunomodulatory effect of APA-01 was further investigated using reverse transcription polymerase chain reaction (RT-PCR) in mouse spleen cells. In RT-PCR test, APA-01 enhanced the expression of cyclooxygenase-2 (COX-2) mRNA in a dose-dependent manner. In spite of immune suppression by MTX, COX-2 mRNA was induced by co-treatment with APA-01. These results suggest that APA-01 stimulates the proliferation of spleen cells, regulates the expression of COX-2 mRNA, and accelerates the recovery of inhibition of spleen cell proliferation induced by MTX, thus providing the immunological basis for clinical benefit of APA-01.

• Food Science of Animal Resources
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• v.27 no.1
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• pp.95-101
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• 2007

We have investigated the immunomodulatory activity of water extracts of Acanthopanax divaricatus var. alveofructus in male ICR mice. Mice were administrated with fermented milk containing freeze-dried extract 3 mg/Kg (A), 9 mg/kg (B), 27 mg/Kg (C) per body weight with A. divaricatus var. alveofructus (loots : leaves : stem) : Codonopsis lanceolata = (5 : 2 : 1.5) : 1.5 for 7 and 10 weeks, respectively. Body weight, relative organ weight, cellularity of lymphoid organs, plaque- forming cell (PFC) assay, agglutination (AGG) test and lymphoproliferation were examined in various groups of animals. Any significant differences of body weight gain were not recorded in the tested ICR mice. There was significant different (p<0.05) in the spleen index in B group of 10 weeks and C group of 7 weeks fed mouse. The thymus gain weight was increased during administration of the extract, but there was no significant increase on other organs gain. Humoral immunity as measured by PFC showed more decreased PFC level in 10 weeks than in 7 weeks. In the HT, A. divaricatus var. albeofructus extract also showed a significant increase (p<0.05) in C group of 10 weeks. Administration of extracts from A. divaricatus var. albeofructus increased significantly in the production of IgG antibodies on the mice immunized with SRBC in B group of 7 and 10 weeks (p<0.05).

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.650-657
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• 2011

The object of this study was to obtain acute information (single oral dose toxicity) of Taraxaci Herba (Dried total parts of Taraxacum platycarpum. H.Dahlstedt (Compositae)), has been traditionally used in Korean medicine for treating various inflammatory diseases. In order to observe the 50% lethal dose (LD 50), approximate lethal dosage (ALD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 mg/kg according to the recommendation of Korea Food and Drug Administration Guidelines. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after single oral treatment of Taraxaci Herba aqueous extracts according to KFDA Guidelines with organ weights and histopathological observations of 12 types of principle organs. After single oral treatment of Taraxaci Herba aqueous extracts, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents at body and organ weights, clinical signs, gross and histopathological observations. Except for slight soft feces, which were detected in male mice treated with 2,000 mg/kg of Taraxaci Herba aqueous extracts at 1 day after end of treatment. The results obtained in this study suggest that the LD 50 and ALD of Taraxaci Herba aqueous extracts in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2000 mg/kg that was the highest dose recommended by KFDA and OECD. However, it also observed that the possibility of digestive disorders, like diarrhea when administered over 2,000 mg/kg of Taraxaci Herba aqueous extracts in the present study, but these possibilities of digestive disorders can be disregard in clinical use because they ate transient in the highest dosages male only.

• The Journal of Internal Korean Medicine
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• v.31 no.3
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• pp.539-553
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• 2010

Objectives : The object of this study was to obtain accurate information (single oral dose toxicity) of Lonicerae Flos (LF; Dried flower bud parts of Lonicera japonica Thunb (Caprifoliaceae)), which has traditionally been used in Korean medicine for treating various inflammatory diseases. Methods : In order to observe the 50% lethal dose (LD 50), approximate lethal dosage (ALD) and target organs, test articles were once orally administered to female and male ICR mice at dose levels of 2,000, 1,000, 500 and 0 (control) mg/kg (body weight.). The mortality and changes on body weight, clinical signs and gross observation were monitored for 14 days after single oral treatment of LF aqueous extracts with organ weights and histopathological observations of 12 types of principle organs. Results : 1. After single oral treatment of LF aqueous extracts, we could not find any mortality and toxicological evidences up to 2,000 mg/kg treated group, the limited dosages in rodents at body and organ weights, clinical signs, gross and histopathological observations. 2. Slight diarrhea was detected in most mice treated with 2,000 mg/kg of LF aqueous extracts and male mice of LF aqueous extracts 1,000 mg/kg within 2 days after end of treatment, respectively. Conclusion : The results obtained in this study suggest that the LD 50 and ALD of LF aqueous extracts in both female and male mice after single oral treatment were considered as over 2,000 mg/kg because no mortalities were detected up to 2000 mg/kg, the highest dose recommended by KFDA and OECD. However, we also observed the possibility of digestive disorders like diarrhea when over 1,000 mg/kg of LF aqueous extracts were administered in the present study.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.453-459
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• 2013

The objective of this study was to evaluate the single oral dose toxicity of Polygalae Radix (PR) in male and female mice. PR extract (yield = 18.6%) was administered to ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). Animals were monitored for the mortality and the changes in body weight, clinical signs and gross observation during 14 days after dosing. Upon necropsy, organ weight and histopathology of 14 principal organs were examined. It was observed that there were no mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs related to PR extract up to 2,000 mg/kg. Therefore, 50% lethal dose ($LD_{50}$) and approximate LD of PR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg the limited dosages recommended by KFDA Guidelines, respectively.