• Journal of Chest Surgery
• /
• v.29 no.11
• /
• pp.1223-1231
• /
• 1996

Immunohistochemical stains for RB and p53 tumor suppressor gene products were performed on 72 cases of resected primary lung cancer tissues to study the correlation between their expressions and the histologic types, the clinical stage, and the survival rate. The results were as follows. 1. The RB protein was altered or absent in 38 cases (52.8%), and the mutant p53 protein was detected in 35 cases (48.6%). 2. The incidences of RB and p53 protein expression were significantly different among the histologic types (p＜0.05) but were not correlated with the clinical stages of lung cancer (p＞0.05). 3. The two year survival rate of patients with alteration of both RB and p53 genes (RB-/p53＋) was 22. 4%, and that with no alteration of both genes (RB+/p53-) was 63.1%. This difference was statistically significant (p=0.01). 4. It was shown that alteration of RB protein greatly affects the prognosis of lung carcinoma by multivariate analysis of prognostic factors. The presence or absence of RB and mutant p53 protein in tumor cells is closely related to the survival of primary lung cancer patients, and it is suggested that RB gene expression is an independent prognostic factor of primary lung cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.9
• /
• pp.3959-3963
• /
• 2014

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2255-2258
• /
• 2013

The activity of Rb proteins is controlled by post-translational modifications, especially through phosphorylation. Acetylation of Rb2/p130 was reported recently in NIH3T3 cells but its physiological relevance in cell cycle control and tumorigenesis is still unknown. Efforts are underway to investigate possible interplay between Rb2/p130 phosphorylation and acetylation. Here we hypothesized that Rb2/p130 acetylation, like p53 acetylation, may play a role in development of the tumor phenotype. The proposed hypothesis regarding acetylation of Rb2/p130 in tumor VS normal cells was found to be true in our case study of 36 tumor samples. Statistical analysis of results suggest strong correlation among Rb2/p130 acetylation and cancer phenotype.

• Journal of Ginseng Research
• /
• v.43 no.3
• /
• pp.394-401
• /
• 2019

Background: Ginsenoside Rb1, a triterpene saponin, is derived from the Panax ginseng root and has potent antiinflammatory activity. In this study, we determined if Rb1 can increase macrophage phagocytosis and elucidated the underlying mechanisms. Methods: To measure macrophage phagocytosis, mouse peritoneal macrophages or RAW 264.7 cells were cultured with fluorescein isothiocyanate-conjugated Escherichia coli, and the phagocytic index was determined by flow cytometry. Western blot analyses were performed. Results: Ginsenoside Rb1 increased macrophage phagocytosis and phosphorylation of p38 mitogenactivated protein kinase (MAPK), but inhibition of p38 MAPK activity with SB203580 decreased the phagocytic ability of macrophages. Rb1 also increased Akt phosphorylation, which was suppressed by LY294002, a phosphoinositide 3-kinase inhibitor. Rb1-induced Akt phosphorylation was inhibited by SB203580, (5Z)-7-oxozeaenol, and small-interfering RNA (siRNA)-mediated knockdown of $p38{\alpha}$ MAPK in macrophages. However, Rb1-induced p38 MAPK phosphorylation was not blocked by LY294002 or siRNA-mediated knockdown of Akt. The inhibition of Akt activation with siRNA or LY294002 also inhibited the Rb1-induced increase in phagocytosis. Rb1 increased macrophage phagocytosis of IgG-opsonized beads but not unopsonized beads. The phosphorylation of p21 activated kinase 1/2 and actin polymerization induced by IgG-opsonized beads and Rb1 were inhibited by SB203580 and LY294002. Intraperitoneal injection of Rb1 increased phosphorylation of p38 MAPK and Akt and the phagocytosis of bacteria in bronchoalveolar cells. Conclusion: These results suggest that ginsenoside Rb1 enhances the phagocytic capacity of macrophages for bacteria via activation of the p38/Akt pathway. Rb1 may be a useful pharmacological adjuvant for the treatment of bacterial infections in clinically relevant conditions.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.42 no.8
• /
• pp.1197-1203
• /
• 2013

This study investigated the effects of endurance exercise and ginsenoside $Rb_1$ on AMP-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K) protein expression and glucose uptake in the skeletal muscle of rats. A total of 32 rats were randomly divided into four groups: CON (Control group, n=8), Ex (Exercise group; 25 m/min for 1 h, 6 days/week, 2 weeks, n=8), $Rb_1$ (Ginsenoside $Rb_1$ group; n=8), and $Rb_1/Ex$ ($Rb_1$+Exercise group, n=8). The $Rb_1$ and $Rb_1/Ex$ groups were incubated in ginsenoside $Rb_1$ (KRBP buffer, $100{\mu}g/mL$) for 60 min after a 2-week experimental treatment. After 2 weeks, the expression of phosphorylated $AMPK{\alpha}$ $Thr^{172}$, total $AMPK{\alpha}$, the p85 subunit of PI3K, pIRS-1 $Tyr^{612}$, and pAkt $Ser^{473}$ were determined in the soleus muscle. Muscle glucose uptake was measured using 2-deoxy-D-[$^3H$] glucose in epitroclearis muscle. Muscle glucose uptake was significantly higher in the three experimental groups (Ex, $Rb_1$, $Rb_1/Ex$) compared to the CON group (P<0.05). The expression of $tAMPK{\alpha}$ and $pAMPK{\alpha}$ $Thr^{172}$ was significantly higher in the Ex, $Rb_1$, and $Rb_1/Ex$ groups compared to the CON group (P<0.05). The expression of pAkt $Ser^{473}$ was significantly higher in the $Rb_1$ group compared to the CON and EX groups. However, the expression of pIRS-1 $Tyr^{612}$ and the p85 subunit of PI3K were not significantly different between the four groups. Overall, these results suggest that ginsenoside $Rb_1$ significantly stimulates glucose uptake in the skeletal muscle of rats through increasing phosphorylation in the AMPK pathway, similar to the effects of exercise.

• Proceedings of the KSAR Conference
• /
• 2001.03a
• /
• pp.21-21
• /
• 2001

일반적으로 세포는 방사능이나 항암제 등의 자극에 의해 DNA가 손상받았을 때 DNA를 합성하기 전, DNA변이를 복구하기 위해 cell cycle을 정지시키게 된다. pRB(retinoblatoma protein)는 이러한 cell cycle의 조절기작에서 중요한 역할을 담당하는 것으로 알려져 있다. G1기에서 S기로 진행하는 것을 조절하는 단백질인 pRB 은 E2F(cell cycle transcription factor)와 상호작용하여 cell cycle 진행에 필요한 전사활성을 억제, PCNA (proliferating cell nuclear antigen)의 합성을 저해한다. 또한, E2F와 결합된 pRB는 apoptosis를 제어하는 유전자를 조절하는 것으로 알려져 있다. Cell cycle에 영향을 미치는 항암제의 일종인 busulfan을 처리하면, 정소 내에 존재하는 대부분의 생식세포들은 사멸되고 spermatogonia만 남는 것으로 알려져 있다. 그러나 그 기작에 대해서는 자세히 연구된 바가 없다. 본 연구에서는 busulfan처리시 spermatogonial stem cell이 어떤 기작에 의해 손상받지 않고 유지되는지를 알아보고자 실험을 수행하였다. Busulfan을 처리한 마우스 (항암제 투여 후 5주)와 정상적인 13주령의 마우스의 정소로부터 각각 세포를 분리하였다. LSC (laser scanning cytometry)를 이용하여 처리군(busulfan treated mice)과 대조군(normal mature mice)에 대해 각각 DNA함량을 비교ㆍ분석한 결과 G0/G1(2N)에 머물러 있는 세포비율이 처리군에서 현저하게 증가했다 (79.3$\pm$5.5%:8.1$\pm$1.3%). Cell cycle의 G1/S check point인 pRB와 PCNA 발현을 Western blot과 면역조직학적인 방법(immunohisto-chemistry)을 이용하여 조사하였다 PCNA는 대조군과 비교해, 처리군에서 매우 낮은 수준으로 발현되었다. 면역염색된 정소단면을 살펴보면, 대조군에서는 모든 세정관에서 PCNA를 발현하는 세포가 높은 비율로 검출되었고, 처리군에서는 소수의 세정관에서 세포들이 낮은 수준으로 검출되었다. 반면에, pRB의 경우 PCNA와는 상반된 결과를 나타내어, 대조군에서는 거의 발현이 되지 않는 반면, 처리군에서는 대부분의 세정관내, 기저막을 따라 위치한 세포들에서 발현되었다. 이상의 결과는 busulfan에 의해 pRB의 인산화가 억제, pRB 와 결합된 E2F는 전사 활성이 억제되어, PCNA 합성을 저해하는 것으로 설명되어질 수 있다. 결론적으로, 인산화가 억제된 pRB (underphosphorylated RB protein)이 quiescent spermatogonial stem cell에서만 특이하게 발현하는 단백질이며, 이러한 pRB의 발현은 apoptosis를 제어하는 역할을 담당해 busulfan처리에 의해 손상받지 않고 남아있는 것으로 시사된다.

• Korean Journal of Veterinary Pathology
• /
• v.2 no.2
• /
• pp.85-94
• /
• 1998

This study was performed to evaluate whether the loss or overexpression of Rb, and overexpression of p53 were prognostic indicators for bladder neoplasia, 52 tumor specimens from transitional cell carcinoma of the urinary bladder were from 42 male and 10 female patients whose age ranged from 30 to 83 years old(mean age; 63,5 years old), This group included 36 superficial and 16 invasive stage bladder tumors, and grades 16-25, p53 was significantly associated with tumor stage and grade(p＜0,05 in each), but not with tumor recurrence. Loss of Rb gene expression or Rb overexpression was correlated with stage, but not grade. These results suggested that changes of Rb and p53 expression might play an important role in assessing the aggressiveness of human neoplasms.

• Journal of Ginseng Research
• /
• v.6 no.1
• /
• pp.25-29
• /
• 1982

This investigation was carried out to study the influence of pH and heat treatment on the ginsenosides in the white ginseng extract. Changes in ginsenosides (Rb1, Rb2, ,Rc, Rd) and free sugar were measured by the peak area variation of HPLC chromatogram during 25 hours heat treatment at the various level of pH. It was found that :(1) The peak areas of Rb1. Rb2, Rc and Rd on the HPLC chromatogram were decreased remarkably below pH 4.0 and more decrease was found as the temperature and heating time increased. (2) Those of glucose and arabinose were increased remarkably. It is considrered that the increase of glucose and the formation of arabinose result from the hydrolysis of ginsenoside( Rb1, Rb2, Rc, Rd) linked with sugars.

• Journal of Life Science
• /
• v.19 no.7
• /
• pp.871-877
• /
• 2009

We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

• Korean Journal of Animal Reproduction
• /
• v.27 no.3
• /
• pp.269-274
• /
• 2003

The purpose of this study was to determine the effect of rbST treatment on progesterone concentration, volume of luteal tissue and pregnancy rate following embryo transfer. Recipient cows were assigned to control and rbST group, of which was given a single injection of rbST (500 mg. sc) at estrus detection. The concentration of progesterone was not significantly different between control and at 0, 3, 6 days after rbST treatment. However, the concentration of progesterone at 9, 12 days was significantly higher than in control group (4.6 and 6.8 vs. 3.9 and 4.5 ng/ml P4). The pregnancy rate after embryo transfer in rbST treatment was significantly higher than in control group (64.0 vs. 47.1 %; p<0.05). The results indicated that rbST treatment in recipient cows could be improved the efficiency of pregnancy rate after embryo transfer.