• Journal of Ginseng Research
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• 제45권2호
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• pp.295-304
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• 2021

Background: Acute promyelocytic leukemia (APL) is a hematopoietic malignancy driven by promyelocytic leukemia-retinoic acid receptor A (PML-RARA) fusion gene. The therapeutic drugs currently used to treat APL have adverse effects. 20(S)-ginsenoside Rh2 (GRh2) is an anticancer medicine with high effectiveness and low toxicity. However, the underlying anticancer mechanisms of GRh2-induced PML-RARA degradation and apoptosis in human APL cell line (NB4 cells) remain unclear. Methods: Apoptosis-related indicators and PML-RARA expression were determined to investigate the effect of GRh2 on NB4 cells. Z-VAD-FMK, LY294002, and C 87, as inhibitors of caspase, and the phosphatidylinositol 3-kinase (PI3K) and tumor necrosis factor-α (TNF-α) pathways were used to clarify the relationship between GRh2-induced apoptosis and PML-RARA degradation. Results: GRh2 dose- and time-dependently decreased NB4 cell viability. GRh2-induced apoptosis, cell cycle arrest, and caspase3, caspase8, and caspase9 activation in NB4 cells after a 12-hour treatment. GRh2-induced apoptosis in NB4 cells was accompanied by massive production of reactive oxygen species, mitochondrial damage and upregulated Bax/Bcl-2 expression. GRh2 also induced PML/PML-RARA degradation, PML nuclear bodies formation, and activation of the downstream p53 pathway in NB4 cells. Z-VAD-FMK inhibited caspase activation and significantly reversed GRh2-induced apoptosis and PML-RARA degradation. GRh2 also upregulated TNF-α expression and inhibited Akt phosphorylation. LY294002, an inhibitor of the PI3K pathway, enhanced the antitumor effects of GRh2, and C 87, an inhibitor of the TNF-α pathway, reversed NB4 cell viability, and GRh2-mediated apoptosis in a caspase-8-dependent manner. Conclusion: GRh2 induced caspase-dependent PML-RARA degradation and apoptosis in NB4 cells via the Akt/Bax/caspase9 and TNF-α/caspase8 pathways.

• 대한인간공학회지
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• 제33권1호
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• pp.1-14
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• 2014

Objective: The purpose of this study is to select the methodology for SMR HRA which has characteristics that are different from existing nuclear power plants and digital-based plants. Background: We must assure safety to preoccupy export of technology to developing countries or countries interested in nuclear application. And we can be an advanced country in nuclear technology by securing original technology in the field of SMR such as SMART. Method: THERP, which is the most representative HRA methodology among all, and RARA, which is the latest HRA methodology. This study compared and evaluated THERP and RARA. Results: As a result of applying THERP and RARA methodologies which are based on LOCA EOG task analysis result, this research concluded that RARA has higher personal errors than THERP. Conclusion: This study needs validation for LOCA, emergency operations, normal and abnormal scenarios since HRA methodology was only focused on LOCA scenario. Application: The results of this study can apply as base line data when designing MMIS, which is the main control room of SMART, and when building a simulator.

• 생명과학회지
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• 제17권1호
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• pp.143-149
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• 2007

Scutellaria baicalensis GEORGI(SB) is used in oriental medicine for the treatment of incipient strokes. Although it has been reported that SB is neuroprotective in a hypoxia model, its mechanism is poorly understood. Here, we investigated the effect of SB on the modulation of retinoic acid receptor a (RARa). Rat cerebrocortical cells were grown in neurobasal medium. On DIV12 cells were treated with SB $(20{\mu}g/ml)$ and given a hypoxic shock $(2%\;O_2/5%\;CO_2,\;3hr)$ on DIV14. In situ hybridization using cRNA probe revealed that RARa mRNA punctae are distributed, in addition to nucleus, throughout neuronal dendrites, where SB upregulated its density by 69.8% (p=0.001) and 129.8% (p=0.001) in both normoxia and hypoxia, respectively. At the protein level, SB upregulated RARa in the neuronal soma by 78.8% (p=0.004) and 23.6% (p=0.001) in both normoxia and hypoxia, respectively. These results indicate that SB upregulates RARa in both normoxia and hypoxia, which might contribute to the neuroprotection.

• 대한임상검사과학회지
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• 제45권3호
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• pp.120-123
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• 2013

Leukemia in pregnancy was first reported by Virchow in 1845, and acute Leukemia that occurs with pregnancy is extremely rare. About 350 pregnancies with leukemia have been reported in literature. The incident of acute leukemia during pregnancy has been reported in one case per 100,000 pregnancies case. A 40-year-old patient with 30 weeks of pregnancy, (by promyelocyte which is contained granules and auer rods in the bone marrow and biopsy) was diagnosed with acute promyelocyte leukemia WITH t (15;17) (q22;q12); PML-RARA. (M3) in peripheral blood and bone marrow examination, and gave a birth to the fetus normally, January 24, 2013, after receiving the complete remission decision from the bone marrow, complete blood cell count, PML-RARA PCR test, showed normal findings until March 2013. The treatment of acute leukemia during pregnancy should be considered as treatment of a pregnant mother and the impact on the fetus. Decisions about when and how birth takes place is difficult and has to consider both mother and fetus. It is preferable to start immediate treatment without delay so that the treatment time to achieve complete remission or full recovery of the pregnant mother is longer.

• 대한임상검사과학회지
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• 제41권1호
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• pp.11-23
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• 2009

Chromosomal rearrangements are major pathology in hematological malignancies. The detection of minimal residual disease (MRD) for these gene rearrangements helps in monitoring treatment outcomes and predicting prognosis of patients. Recently, quantification of these gene transcripts based on real-time quantitative polymerase chain reaction (RQ-PCR) has been used as MRD detection. The purpose of this study is to ensure the usefulness of the RQ-PCR technique for detecting MRD in hamatological malignancy patients. The patients had been diagnosed to AML1-ETO positive AML, PML-RARa positive AML and BCR-ABL positive MPN at Chonnam National University Hwasun Hospital from Jan. 2006 to Aug. 2008. The fusion transcript was quntified by RQ-PCR and analyzed in comparison to conventional cytogenetics, FISH and RT-PCR. The fusion gene transcript was quantified by RQ-PCR in 57 samples from 14 patients with AML1-ETO positive AML, 79 samples from 27 patients with PML-RARa positive AML and 108 samples from 36 patients with CML. At diagnosis, the quantitative fusion transcripts for AM1-ETO, PML-RARa and BCR-ABL showed the range of 0.485552651~10.82233683 (mean 3.782217131, SD 2.998052348), 0.005300395~0.29267494 (mean 0.056901315, SD 0.080131381) and 0.1293929~12.94826849 (mean 1.701935665, SD 2.200913158). The increase of AML1-ETO fusion gene transcripts preceded morphologic relapse in two patients. Quantification of fusion gene transcripts by RQ-PCR could detected MRD in samples which were negative by in cytogenetic analysis or FISH. Our findings indicated that quantitative analysis of AML1-ETO, PML-RARa and BCR-ABL transcripts by RQ-PCR might be a useful tool for the monitoring of minimal residual disease in hematological malignancies.

• Asian Pacific Journal of Cancer Prevention
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• 제13권5호
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• pp.1809-1817
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• 2012

Background: Gastric cancer is frequently lethal despite aggressive multimodal therapies, and new treatment approaches are therefore needed. Retinoids are potential candidate drugs: they prevent cell differentiation, proliferation and malignant transformation in gastric cancer cell lines. They interact with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors, each with three subclasses, ${\alpha}$, ${\beta}$ and ${\gamma}$. At present, little is known about retinoid expression and influence on prognosis in gastric cancers. Patients and Methods: We retrospectively analyzed the expression of the subtypes RARa, $RAR{\beta}$, $RAR{\gamma}$, RXRa, $RXR{\beta}$, $RXR{\gamma}$ by immunohistochemistry in 147 gastric cancers and 51 normal gastric epithelium tissues for whom clinical follow-up data were available and correlated the results with clinical characteristics. In addition, we quantified the expression of retinoid receptor mRNA using real-time PCR (RT-PCR) in another 6 gastric adenocarcinoma and 3 normal gastric tissues. From 2008 to 2010, 80 patients with gastric cancers were enrolled onto therapy with all-trans-retinoic acid (ATRA). Results: RARa, $RAR{\beta}$, $RAR{\gamma}$ and $RXR{\gamma}$ positively correlated with each other (p < 0.001) and demonstrated significantly lower levels in the carcinoma tissue sections (p < 0.01), with lower $RAR{\beta}$, $RAR{\gamma}$ and RXRa expression significantly related to advanced stages (p < =0.01). Tumors with poor histopathologic grade had lower levels of RARa and $RAR{\beta}$ in different histological types of gastric carcinoma (p < 0.01). Patients whose tumors exhibited low levels of RARa expression had significantly lower overall survival compared with patients who had higher expression levels of this receptor (p < 0.001, HR=0.42, 95.0% CI 0.24-0.73), and patients undergoing ATRA treatment had significantly longer median survival times (p = 0.007, HR=0.41, 95.0% CI 0.21-0.80). Conclusions: Retinoic acid receptors are frequently expressed in epithelial gastric cancer with a decreased tendency of expression and RARa may be an indicator of a positive prognosis. This study provides a molecular basis for the therapeutic use of retinoids against gastric cancer.

• Journal of Chest Surgery
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• 제30권4호
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• pp.441-444
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• 1997

기관내 지방종은 문헌상 매우 희귀한 종양으로 알려져 있다 본 환자는37세의 건강한 남자로 간질성와 호흡곤란의 증상으로 지난 6개월간 기관지천식의 진단하에 치료받아 오던중,본원에서 흉부전산화 단층촬영과 기관지내시경검사상 흉부기관의 내강에 위치한 구형의 종양이 기관내강의 대부분을 막고 있음을 알고 기관지내시경검사하에 용종제거술루우프를 이용하여 전기소작과 더불어 종양을 완전히 제거하였다 환자는 수술후 3일 째 퇴원하였으며,수술후 1, 6개월에 시행한 기관지내시경상 재발없이 양호한 상태를 유지하고 있다.

• Applied Microscopy
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• 제29권1호
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• pp.25-41
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• 1999

종양의 치료제로 많이 사용되고 있는 대표적인 항암제 가운데 대사길항제인 5-fluorouracil과 항암항생제인 mitomycin C가 콩팥토리에 미치는 영향을 미세구조적으로 비교 관찰하고자 이 실험을 시행하였다. Mitomycin C는 $LD_{50}$의 1/20 이하인 $400{\mu}g/kg$를, 5-fluorouracil는 $LD_{50}$의 1/4 정도인 60mg/kg를 격일 간격으로 계속 투여하였다. 각 항암제투여군은 처음 주사후 4일 (2회 투여)과 7일 (3회 투여) 째에 희생시킨 후 콩괄겉질부위의 조직을 메어 JEM 100CX-II 전자 현미경으로 관찰하였다. 1. 5-fluorouracil 및 mitomycin C 투여후 4일군에서는 다같이 혈관사이막이 증가하여 모세혈관과 주머니공간이 매우 좁아 보이는 부분이 많았는데, 그 현상은 mitomycin C 투여군에서 더 심했다. 2. 5-fluorouracil 투여 7일군은 토리의 미세구조가 거의 정상군의 모습과 비슷하게 회복되어 보였으나 mitomycin C 투여 7일군은 토리의 미세구조가 정상군의 모습과 비슷하게 회복된 모습을 거의 관찰할 수 없었다. 3. Mitomycin C 투여 4일군과 7일군에서는 내피세포의 종창현상(swelling) 이 심해서 내강으로 돌출되었을 뿐만 아니라 혈관사이세포가 모세혈관내강으로 돌출되어 내강을 거의 막고 있는 경우가 자주 관찰되었다. 4. Mitomycin C 투여 4일군에서는 토리모세혈관바닥막의 속투명판과 바깥투명판의 전자밀도가 높아서 치밀판과의 경계가 뚜렷하지 못한 부분이 많았는데, 부위에 따라서는 속투명판이 넓어진 부분이 관찰되기도 하였다. 이상의 결과를 종합해 보면 mitomycin C를 투여하였을 경우에는 마우스의 콩팥토리는 모세혈관의 내강이 좁아지고 혈관사이막이 증가하며 내피세포는 종창현상을 보이는 등의 미세구조적 변화를 보였다. 그러나 5-fluorouracil을 투여하였을 경우, 초기 (4일)에는 발세포와 혈관사이막의 경우 mitomycin C 투여군에서와 비슷한 미세구조적 변화를 보였으나, 7일군에서는 거의 정상군의 소견과 비슷한 모습을 보였다. 이와 같은 결과는 콩팥토리를 비롯한 콩팥조직에 미치는 세포독성은 mitomycin C가 5-fluorouracil에 비하여 훨씬 더 강하기 때문이라고 생각된다.

• Applied Microscopy
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• 제27권4호
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• pp.373-389
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• 1997

Morphological difference of the renal glomerulus at different age groups have been studies in one week-old, five weeks-old, eight weeks-old, six months-old, twelve months-old, eighteen months-old, twenty-four months-old, and thirty months-old ICR mice. Pieces of the tissue taken from the renal corticies were fixed in 2.5% glutaraldehyde-1.5% paraformaldehyde solution (0.1 Millonig's phosphate buffer pH 7.3), and 1% osmium tetroxide solution (0.1 M Millonig's phosphate buffer, pH 7.3), and were embedded in araldite mixture. The ultrathin sections were stained with uranyl acetate and lead citrate solution, and were observed under a JEM 100CX-II electron microscope. The results were as follows: 1 In the one week-old mouse, thicknesses of the three layers of the glomeluar basal lamina (lamina densa, lamina rara interna and lamina rara externa) are similar, but in the five weeks-old mouse, thick lamina densa becomes a greater portion of the thickness of whole glomerular basal lamina. 2. No difference was noticed between thickness of the renal glomerular basal lamina of the five weeks-old mouse compare with that of the one week-old one, but basal lamina of the eight weeks-old one is thickened considerably and thicknesses were maintained through twelve months-old one. After eighteen months, the thickness of the glomerular basal lamina is increased remarkably. 3. After eighteen months, electron dense deposits within the basal lamina of the renal glomeruli are observed frequently. 4. Amount of the microfilaments in the mesangial cells and the mesangial matrices are increasing during aging. 5. The thicknesses of the basal laminae of the Bowman's capsule are increasing during aging. 6. After twenty four months, the proximal tubular cell-like parietal cells with well developed microvilli are observed frequently. From the above results, it was suggested that the renal glomerulus matures structurally in five weeks, and the function of the glomerulus is suppressed after eighteen months.

• Clinical and Experimental Pediatrics
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• 제54권3호
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• pp.95-105
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• 2011

Since the successful introduction of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL) has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70-89%. Moreover, arsenic trioxide (ATO), which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leu-kemia/retinoic acid receptor-alpha (PML/$RAR{\alpha}$) isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.