Expression of Wnt Target Genes in Solid Pseudopapillary Tumor of the Pancreas: A Pilot Study

Kang, Chang Moo,Kim, Hyun Ki,Kim, Hoguen,Choi, Gi Hong,Kim, Kyung Sik,Choi, Jin Sub,Lee, Woo Jung Lippincott Williams Wilkins, Inc. 2009 PANCREAS Vol.38 No.2

OBJECTIVES:: Solid pseudopapillary tumor (SPT) of the pancreas is very rare. This study was performed to analyze the expression of Wnt signal target genes (matrix metalloproteinase-7 [MMP-7], cyclin-D1, and c-myc) and Ki-67 in resected SPTs to determine their clinicopathologic characteristics according to their expression. METHODS:: From January 1995 to December 2005, 23 patients underwent pancreatic resections for SPT of the pancreas. Among 23 formalin-fixed, paraffin-embedded tissues, 12 were evaluated as a pilot study. Immunohistochemistry was performed using various detection and antigen retrieval methods to detect MMP-7, cyclin-D1, c-myc, and Ki-67. The expression of Wnt target genes was correlated with clinicopathologic features of the patients. RESULTS:: Solid pseudopapillary tumors of the pancreas always showed cytoplasmic/nuclear accumulation of &bgr;-catenin, frequent expression of cyclin-D1, and low proliferation index. MMP-7, cyclin-D1, c-myc, and Ki-67 were not correlated with microscopic features suggesting malignant potential (P > 0.05). Tumor size was closely related to microscopic features of malignant potential and apparently has an inverse relationship with the expression of cyclin-D1 and Ki-67 (P < 0.05). CONCLUSIONS:: Low proliferative index and associated MMP-7 expression may cause an unpredictable clinical course in this tumor. Subtle changes in the intracellular environment, not pathologic (morphologic) changes, may elucidate the unpredictable clinical course of this tumor.

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

Bing Chun Yan,Ki-Yeon Yoo,Joon Ha Park,Choong Hyun Lee,Jung Hoon Choi,Moo-Ho Won 대한해부학회 2011 Anatomy & Cell Biology Vol.44 No.3

Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2’-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 ㎎/㎏ EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice.

The high dosage of earthworm (Eisenia andrei) extract decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus.

Yan, Bing Chun,Yoo, Ki-Yeon,Park, Joon Ha,Lee, Choong Hyun,Choi, Jung Hoon,Won, Moo-Ho Korean Association of Anatomists 2011 Anatomy & Cell Biology Vol.44 No.3

<P>Earthworm extract has shown anticancer characteristics. In the present study, we examined the effect of chronic treatment with a high dose of earthworm (Eisenia andrei) extract (EE) on cell proliferation and neuroblast differentiation in the hippocampal dentate gyrus (DG) of 3-week-old mice using 5-bromo-2'-deoxyuridine (BrdU) and Ki-67 immunohistochemistry for cell proliferation and doublecortin (DCX) immunohistochemistry for neuroblast differentiation, respectively. BrdU-, Ki-67-, and DCX-immunoreactive cells were easily detected in the subgranular zone of the DG in vehicle (saline)-treated mice. However, BrdU-, Ki-67-, and DCX-immunoreactive cells in the 500 mg/kg EE-treated mice decreased distinctively compared to those in the vehicle-treated mice. In addition, brain-derived neurotrophic factor (BDNF) immunoreactivity and its protein level decreased markedly in the DG of the EE-treated group compared to those in the vehicle-treated group. These results indicate that chronic treatment with high dose EE decreased cell proliferation and neuroblast differentiation, and that BDNF immunoreactivity decreased in the DG of EE-treated mice.</P>

Effects of Streptozotocin-Induced Type 1 Diabetes on Cell Proliferation and Neuronal Differentiation in the Dentate Gyrus : Correlation with Memory Impairment

Jung Hoon Choi,In Koo Hwang,Sun Shin Yi,Ki-Yeon Yoo,Choong Hyun Lee,Hyung-Cheul Shin,Yeo Sung Yoon,Moo-Ho Won 대한해부학회 2009 Anatomy & Cell Biology Vol.42 No.1

We examined the effects of steptozotocin (STZ)-induced type 1 diabetes on cell proliferation and neuroblasts in the subgranular zone of the hippocampal dentate gyrus (SZDG) of male Wistar rats. Change in memory function was also investigated using the passive avoidance test. In the SZDG, Ki67 (a marker for cell proliferation) positive nuclei were significantly decreased at 2 and 3 weeks and slightly decreased at 4 weeks after STZ treatment. Doublecortin (DCX, a marker for neuronal differentiation)-immunoreactive (+) neuroblasts with tertiary dendrites were significantly decreased in the STZ-treated group compared to those in the vehicle-treated group. However, DCX+ neuroblasts without tertiary dendrites were abundant at 4 weeks after STZ treatment. In addition, retention latency time in STZ-treated group was similar to that of vehicle-treated group at 2 and 3 weeks after STZ treatment. However, the retention latency time was significantly decreased at 4 weeks after STZ treatment. These results suggest that STZ significantly reduced cell proliferation and neuroblasts at 2~3 weeks after STZ treatment, but not at 4 weeks after STZ treatment although memory impairment was detected at 4 weeks after STZ treatment. The gradual reduction of DCX+ neuroblasts with tertiary dendrites may be associated with the impairment of hippocampus-related memory function.

Effects of pyridoxine on a high‐fat diet‐induced reduction of cell proliferation and neuroblast differentiation depend on cyclic adenosine monophosphate response element binding protein in the mouse dentate gyrus

Yoo, Dae Young,Kim, Woosuk,Yoo, Ki‐,Yeon,Nam, Sung Min,Chung, Jin Young,Yoon, Yeo Sung,Won, Moo‐,Ho,Hwang, In Koo Wiley Subscription Services, Inc., A Wiley Company 2012 JOURNAL OF NEUROSCIENCE RESEARCH - Vol.90 No.8

<P><B>Abstract</B></P><P>In this study, we challenged pyridoxine to mice fed a high‐fat diet (HFD) and investigated the effects of pyridoxine on HFD‐induced phenotypes such as blood glucose, reduction of cell proliferation and neuroblast differentiation in the dentate gyrus using Ki67 and doublecortin (DCX), respectively. Mice were fed a commercially available low‐fat diet (LFD) as control diet or HFD (60% fat) for 8 weeks. After 5 weeks of LFD or HFD treatment, 350 mg/kg pyridoxine was administered for 3 weeks. The administration of pyridoxine significantly decreased body weight in the HFD‐treated group. In addition, there were no significant differences in hepatic histology and pancreatic insulin‐immunoreactive (‐ir) and glucagon‐ir cells of the HFD‐treated group after pyridoxine treatment. In the HFD‐fed group, Ki67‐positive nuclei and DCX‐ir neuroblasts were significantly decreased in the dentate gyrus compared with those in the LFD‐fed mice. However, the administration of pyridoxine significantly increased Ki67‐positive nuclei and DCX‐ir neuroblasts in the dentate gyrus in both LFD‐ and HFD‐fed mice. In addition, the administration of pyridoxine significantly increased the protein levels of glutamic acid decarboxylase 67 (GAD67) and brain‐derived neurotrophic factor (BDNF) and the immunoreactivity of phosphorylated cyclic AMP response element binding protein (pCREB) compared with the vehicle‐treated LFD‐ and HFD‐fed mice. In contrast, the administration of pyridoxine significantly decreased HFD‐induced malondialdehyde (MDA) levels in the hippocampus. These results showed that pyridoxine supplement reduced the HFD‐induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus via controlling the levels of GAD67, pCREB, BDNF, and MDA. © 2012 Wiley Periodicals, Inc.</P>

Effects of <i>Ginkgo biloba</i> Extract on Promotion of Neurogenesis in the Hippocampal Dentate Gyrus in C57BL/6 Mice

YOO, Dae Young,NAM, YoonYi,KIM, Woosuk,YOO, Ki-Yeon,PARK, Jaeil,LEE, Choong Hyun,CHOI, Jung Hoon,YOON, Yeo Sung,KIM, Dong-Woo,WON, Moo-Ho,HWANG, In Koo Japanese Society of Veterinary Science 2011 The Journal of veterinary medical science Vol.73 No.1

<P><I>Ginkgo biloba </I>leaf extract (Gb) has been known to improve blood flow and preclude the tissue from free radical damage. Effects of Gb were examined by using Ki67, a specific proliferative marker for cellular proliferation, and doublecortin (DCX), a marker for immature neurons, indicating degree of neuroblast differentiation in the hippocampal dentate gyrus (DG) of adult C57BL/6 mice. The mice were fed with Gb at 40 and 100 mg/kg once daily for 28 days. The increase of Ki67- and DCX-immunoreactive cells in the DG was increased in a dose-dependent manner. Especially, the group having 100 mg/kg Gb showed a significant increase of DCX-immunoreactive neuroblasts with well-developed tertiary dendrites. Expression of DCX protein in the Gb groups was also significantly increased upon compared with the vehicle group. The results suggested that repeated intake of Gb would enhance cell proliferation and neuroblast differentiation in the mouse DG.</P>

Effects of High Cholesterol Diet on Newly Generated Cells in the Dentate Gyrus of C57BL/6N and C3H/HeN Mice

KIM, Il Yong,HWANG, In Koo,CHOI, Ji Won,YOO, Ki-Yeon,KIM, Yo Na,YI, Sun Shin,WON, Moo-Ho,LEE, In Se,YOON, Yeo Sung,SEONG, Je Kyung Japanese Society of Veterinary Science 2009 The Journal of veterinary medical science Vol.71 No.6

<P>In this study, we observed and compared the effects of a high cholesterol diet (HCD) on cell proliferation and differentiation in the subgranular zone of the dentate gyrus of C57BL/6N (B6, susceptible strain) and C3H/HeN (C3H, resistant strain) mice. Ki67 (a marker for cell proliferation) positive cells) were significantly decreased in HCD-fed B6 mice compared to those in B6 (49.7%) and C3H mice fed a low cholesterol diet (LCD). In addition, doublecortin (DCX, a marker for cell differentiation or neuroblasts)-immunoreactive cells in HCD-fed B6 mice were significantly decreased compared to those in LCD-fed B6 and C3H mice. These results suggest that B6 strains are sensitive to HCD, which impairs cell proliferation and differentiation.</P>

Effects of Cu,Zn-superoxide dismutase on cell proliferation and neuroblast differentiation in the mouse dentate gyrus.

Yoo, Dae Young,Shin, Bich Na,Kim, In Hye,Kim, Woosuk,Kim, Dae Won,Yoo, Ki-Yeon,Choi, Jung Hoon,Lee, Choong Hyun,Yoon, Yeo Sung,Choi, Soo Young,Won, Moo-Ho,Hwang, In Koo Kluwer Academic/Plenum Publishers 2012 Neurochem Res Vol.37 No.2

<P>Oxidative stress is one of the most important factors in reducing adult hippocampal neurogenesis in the adult brain. In this study, we observed the effects of Cu,Zn-superoxide dismutase (SOD1) on lipid peroxidation, cell proliferation, and neuroblast differentiation in the mouse dentate gyrus using malondialdehyde (MDA), Ki67, and doublecortin (DCX), respectively. We constructed an expression vector, PEP-1, fused PEP-1 with SOD1, and generated PEP-1-SOD1 fusion protein. We administered PEP-1 and 100 or 500 관g PEP-1-SOD1 intraperitoneally once a day for 3 weeks and sacrificed at 30 min after the last administrations. PEP-1 administration did not change the MDA levels compared to those in the vehicle-treated group, while PEP-1-SOD1 treatment significantly reduced MDA levels compared to the vehicle-treated group. In the PEP-1-treated group, the number of Ki67-positive nuclei was similar to that in the vehicle-treated group. In the 100 관g PEP-1-SOD1-treated group, the number of Ki67-positive nuclei was slightly decreased; however, in the 500 관g PEP-1-SOD1-treated group, Ki67-positive nuclei were decreased to 78.5% of the vehicle-treated group. The number of DCX-positive neuroblasts in the PEP-1-treated group was similar to that in the vehicle-treated group. However, the arborization of DCX-positive neuroblasts was significantly decreased in both the 100 and 500 관g PEP-1-SOD1-treated groups compared to that in the vehicle-treated group. The number of DCX-positive neuroblasts with tertiary dendrites was markedly decreased in the 500 관g PEP-1-SOD1-treated group. These results suggest that a SOD1 supplement to healthy mice may not be necessary to modulate cell proliferation and neuroblast differentiation in the dentate gyrus.</P>

Cell proliferation and neuroblast differentiation in the rat dentate gyrus after intrathecal treatment with adipose-derived mesenchymal stem cells.

Choi, Jung Hoon,Chung, Jin Young,Yoo, Dae Young,Hwang, In Koo,Yoo, Ki-Yeon,Lee, Choong Hyun,Yan, Bing Chun,Ahn, Jin Ok,Youn, Hwa Young,Won, Moo-Ho Kluwer Academic/Plenum Publishers 2011 Cellular and molecular neurobiology Vol.31 No.8

<P>Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin (DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma. However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain.</P>

Systemic administration of low dosage of tetanus toxin decreases cell proliferation and neuroblast differentiation in the mouse hippocampal dentate gyrus

Bing Chun Yan,In Hye Kim,Joon Ha Park,Ji Hyeon Ahn,Jeong-Hwi Cho,Bai Hui Chen,Jae-Chul Lee,Jung Hoon Choi,Ki-Yeon Yoo,Choong Hyun Lee,Jun Hwi Cho,Jong-Dai Kim,Moo-Ho Won 한국실험동물학회 2013 Laboratory Animal Research Vol.29 No.3

In the present study, we investigated the effect of Tetaus toxin (TeT) on cell proliferation and neuroblast differentiation using specific markers: 5-bromo-2-deoxyuridine (BrdU) as an exogenous marker for cell proliferation, Ki-67 as an endogenous marker for cell proliferation and doublecortin (DCX) as a marker for neuroblasts in the mouse hippocampal dentate gyrus (DG) after TeT treatment. Mice were intraperitoneally administered 2.5 and 10 ng/kg TeT and sacrificed 15 days after the treatment. In both the TeT-treated groups, no neuronal death occurred in any layers of the DG using neuronal nuclei (NeuN, a neuron nuclei maker) and Fluoro-Jade B (F-J B, a high-affinity fluorescent marker for the localization of neuronal degeneration). In addition, no significant change in glial activation in both the 2.5 and 10 ng/kg TeT-treated-groups was found by GFAP (a marker for astrocytes) and Iba-1 (a marker for microglia) immunohistochemistry. However, in the 2.5 ng/kg TeT-treated-group, the mean number of BrdU, Ki-67 and DCX immunoreactive cells, respectively, were apparently decreased compared to the control group, and the mean number of each in the 10 ng/kg TeT-treated-group was much more decreased. In addition, processes of DCX-immunoreactive cells, which projected into the molecular layer, were short compared to those in the control group. In brief, our present results show that low dosage (10 ng/kg) TeT treatment apparently decreased cell proliferation and neuroblast differentiation in the mouse hippocampal DG without distinct gliosis as well as any loss of adult neurons.