• Journal of Yeungnam Medical Science
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• 제29권2호
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• pp.96-101
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• 2012

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the optimal curative treatment for acute myeloid leukemia (AML), but some patients develop bone marrow relapse due to remnant leukemia, and few patients develop extramedullary relapse without bone marrow relapse. Isolated extramedullary relapse (IMER) is defined as extramedullary relapse without bone marrow relapse. IMER has been reported in various sites, including the skin, soft tissue, and central nervous system(CNS). Isolated CNS relapse is relatively rare and is associated with poor prognosis due to the absence of an optimal treatment for it. Reported herein is a case involving an adult AML woman who suffered from isolated extramedullary relapse in the CNS after allogeneic HSCT. She was treated with intrathecal chemotherapy and whole-brain and spine radiotherapy, followed by systemic chemotherapy. She is currently well, with no evidence of leukemia recurrence for over six years.

• BLOOD RESEARCH
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• 제53권4호
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• pp.320-324
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• 2018

Background Recent studies have devoted much attention to non-protein-coding transcripts in relation to a wide range of malignancies. MALAT1, a long non-coding RNA, has been reported to be associated with cancer progression and prognosis. Thus, we here determined MALAT1 gene expression in chronic lymphocytic leukemia (CLL), a genetically heterogeneous disease, and explored its possible relationships with cytogenetic abnormalities. Methods MALAT1 expression level was evaluated using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) on blood mononuclear cells from 30 non-treated CLL patients and 30 matched healthy controls. Cytogenetic abnormalities were determined in patients by fluorescence in situ hybridization (FISH). Results MALAT1 expression level was up-regulated in the CLL group compared to healthy controls (P=0.008). Del13q14, followed by Del11q22, were the most prevalent cytogenetic abnormalities. We found no association between the FISH results and MALAT1 expression in patients. Conclusion Altered expression of MALAT1 is associated with CLL development. Further investigations are required to assess the relationship between this long non-coding RNA and CLL patient survival and prognosis.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.11.1-11.12
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• 2018

USP15 has been shown to stabilize transcription factors, to be amplified in many cancers and to mediate cancer cell survival. However, the underlying mechanism by which USP15 regulates multiple myeloma (MM) cell proliferation and apoptosis has not been established. Here, our results showed that USP15 mRNA expression was upregulated in MM patients. USP15 silencing induced MM cell proliferation inhibition, apoptosis, and the expression of nuclear and cytoplasmic NF-${\kappa}Bp65$, while USP15 overexpression exhibited an inverse effect. Moreover, in vivo experiments indicated that USP15 silencing inhibited MM tumor growth and NF-${\kappa}Bp65$ expression. PDTC treatment significantly inhibited USP15 overexpression-induced cell proliferation, apoptosis inhibition, and NF-${\kappa}Bp65$ expression. USP15 overexpression promoted NF-${\kappa}Bp65$ expression through inhibition of its ubiquitination, whereas NF-${\kappa}Bp65$ promoted USP15 expression as a positive regulator. Taken together, the USP15-NF-${\kappa}Bp65$ loop is involved in MM tumorigenesis and may be a potential therapeutic target for MM.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1119-1124
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• 2012

Background: The effect and possible mechanism of traditional Chinese medicine, baicalin, on the PI3K/Akt signaling pathway in drug-resistant human myeloid leukemia HL-60/ADR cells have been investigated in this current study. Methods: HL-60/ADR cells were treated by 20, 40, $80\;{\mu}mol/L$ baicalin followed by cell cycle analysis at 24h. The mRNA expression level of the apoptosis related gene, Bcl-2 and bad, were measured by RT-PCR on cells treated with $80\;{\mu}mol/L$ baicalin at 12, 24 and 48hr. Western blot was performed to detect the changes in the expression of the proteins related to HL-60/ADR cell apoptosis and the signaling pathway before and after baicalin treatment, including Bcl-2, PARP, Bad, Caspase 3, Akt, p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR. Results: Sub-G1 peak of HL-60/ADR cells appeared 24 h after $20\;{\mu}mol/L$ baicalin treatment, and the ratio increased as baicalin concentration increased. Cell cycle analysis showed 44.9% G0/G1 phase cells 24 h after baicalin treatment compared to 39.6% in the control group. Cells treated with $80\;{\mu}mol/L$ baicalin displayed a trend in decreasing of Bcl-2 mRNA expression over time. Expression level of the Bcl-2 and PARP proteins decreased significantly while that of the PARP, Caspase-3, and Bad proteins gradually increased. No significant difference in Akt expression was observed between treated and the control groups. However, the expression levels of p-Akt, NF-${\kappa}B$, p-NF-${\kappa}B$, mTOR and p-mTOR decreased significantly in a time-dependent manner. Conclusions: We conclude that baicalin may induce HL-60/ADR cell apoptosis through the PI3K/AKT signaling pathway.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2153-2158
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• 2014

Beclin 1 is a key factor for initiation and regulation of autophagy, which is a cellular catabolic process involved in tumorigenesis. To investigate the role of alternative splicing of Beclin1 in the regulation of autophagy in leukemia cells, Beclin1 mRNA from 6 different types of cell lines and peripheral blood mononuclear cells from 2 healthy volunteers was reversely transcribed, subcloned, and screened for alternative splicing. New transcript variants were analyzed by DNA sequencing. A transcript variant of Beclin 1 gene carrying a deletion of exon 11, which encoded a C-terminal truncation of Beclin 1 isoform, was found. The alternative isoform was assessed by bioinformatics, immunoblotting and subcellular localization. The results showed that this variable transcript is generated by alternative 3' splicing, and its translational product displayed a reduced activity in induction of autophagy by starvation, indicating that the spliced isoform might function as a dominant negative modulator of autophagy. Our findings suggest that the alternative splicing of Beclin 1 might play important roles in leukemogenesis regulated by autophagy.

• Journal of Yeungnam Medical Science
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• 제35권1호
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• pp.76-83
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• 2018

Background: Elderly patients with multiple myeloma (MM) are vulnerable to adverse events (AEs). This study evaluated adherence to chemotherapy and treatment outcomes in elderly patients treated with a frontline bortezomib (BTZ), melphalan, and prednisone (VMP) regimen and regimens without BTZ. Methods: One-hundred and forty elderly patients who were diagnosed with MM from March 2007 to March 2015 were included in this retrospective study. To evaluate regimen adherence, patients who were treated with more than 4 cycles were assigned to the good adherence group. Results: Among the 140 patients, 71 were treated with a frontline VMP and 69 with non-BTZ regimens. The median age was 71 years (range, 65-90 years). The VMP group showed a higher complete response rate than the non-BTZ group: 26.8% vs. 7.2%. More patients in the VMP group achieved ${\geq}$very good partial response (VGPR) and ${\geq}PR$. In the VMP group, 27 patients (38.0%) received less than 4 cycles. The VMP good adherence group showed a higher 3-year overall survival (OS) rate (70.9%) than the poor adherence group (60.2%, p=0.059). In the multivariate analysis, treatment with ${\geq}4$ cycles of VMP was a favorable factor for OS. Conclusion: A good adherence to a frontline VMP regimen resulted in favorable long-term survival. Adequate management of AEs will be needed to achieve favorable outcomes in elderly patients with MM.

• 대한핵의학회지
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• 제14권2호
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• pp.1-9
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• 1980

혈액질환(血液疾患), 특히 용혈성빈혈(溶血性貧血)을 수반(隨伴)한 경우(境遇)에 적혈구(赤血球)의 생성(生成), 파괴과정(破壞過程)을 정확히 파악하는 것은 빈혈(貧血)의 발생기전(發生機轉) 및 병인(病因), 치료(治療), 예후(豫後) 결정(決定)에 매우 중요(重要)하다. 적혈수명측정법(赤血壽命測定法)은 최근(最近) 방사성(放射性)동위원소(同位元素)를 이용(利用)한 방법(方法)이 소개된 이래 널리 시행(施行)되어 왔다. 그러나 그 방법(方法) 및 결과(結果) 해석(解釋)에 표준화(標準化)가 되어 있지 않았던 중 1971년 ICSH (International Committee for Standardization in Hematology)에서 expert panel을 갖고 ICSH 추천 방법(方法)을 발표(發表)하였고, 본지(本誌)에서도 그 내용(內容)을 게재(揭載)한 바 있다. 1980년 ICSH는 전문기관 및 전문가의 협조(協調)를 얻어 다시 expert panal을 갖은 후 1971년에 추진한 적혈구수명측정법(赤血球壽命測定法)의 일부(一部)를 수정(修正)하여 ICSH의 표준방법(標準方法)으로 발표(發表)하였다. 개정(改正)된 표준방법(標準方法)과 1971년 ICSH추친 방법(方法)과의 차이(差異)는 다음과 같다. $^{51}Cr$표지방법중(標識方法中) 참고방법(參考方法)(Reference method)인 ACD법(法)에 수정(修正)을 가하여, ACD solution 구성성분(構成成分)이 차이(差異)가 있으며, 표지(標識)$^{51}Cr$의 양(量)을 체중당(體重當) $1.5{\mu}Ci$에서 $0.5{\mu}Ci$로 제한(制限)시켰다. 투여방법(投與方法)에 대한 언급 특히 투여하는 표지적혈구(標識赤血球)의 용적을 정확하게 측정 하기 위한 방법 4가지를 추가하였고, 검체준비(檢體準備) 과정중(過程中)의 pipet error를 방지(防止)하기위해 일정(一定)한 형태의 pipet을 사용(使用)하며, 1ml의 tuterculin syringe는 사용(使用)하지 않기로 하였다. 또한 결과분석시(結果分析時) 혈구용적(血球容積)의 항정성(恒定性)을 위해 Sodium pertectnetate($^{99m}Tc$)를 이용(利用)해 혈구용적(血球容積)을 반복(反復)해 측정(測定)하도록 하였으며 이때 사용(使用)하는 방사성동위원소(放射性同位元素)는 $^{32}P$ 대신 $^{99m}Tc$로 하였다. 결과해석시(結果解釋時) IgG 항체(抗體) 또는 IgM 항체(抗體)에 따른 차이점(差異點)에 대한 고려가 추가(追加)되었다. ICSH와 국제혈액학회(國際血液學會)에서 수정(修正)된 ICSH 표준방법(標準方法)에 의한 적혈수명측정법(赤血壽命測定法)을 널리 소개(紹介)하여 결과(結果)의 표준화(標準化)를 기하고자 연관잡지(聯관(關)雜誌)에 게재(揭載)할 것을 요청(要請)하였기에 전문(全文)을 본지(本誌)에 소개(紹介)하고자 한다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2525-2528
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• 2013

The Homer protein family, also known as the family of cytoplasmic scaffolding proteins, which include three subtypes (Homer1, Homer2, Homer3). Homer3 can regulate transcription and play a very important role in the differentiation and development for some tissues (e.g. muscle and nervous systems). The current studies showed that Homer3 abnormal expression changes in acute myeloid leukemia (AML). Forced expression of Homer3 in transfected K562 cells inhibited proliferation, influenced the cell cycle profile, affected apoptosis induced by $As_2O_3$ through inhibition of Bcl2 expression, and also promoted cell differentiation induced by 12-O-tetra decanoylphorbol-acetate (TPA). These results showed that Homer3 is a novel gene which plays a certain role in the occurrence and development of AML.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.1553-1564
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• 2016

Identification of novel therapeutics in glioblastoma remains crucial due to the devastating and infiltrative capacity of this malignancy. The current study was aimed to appraise effect of arsenic trioxide (ATO) in U87MG cells. The results demonstrated that ATO induced apoptosis and impeded proliferation of U87MG cells in a dose-dependent manner and also inhibited classical NF-${\kappa}B$ signaling pathway. ATO further upregulated expression of Bax as an important proapoptotic target of NF-${\kappa}B$ and also inhibited mRNA expression of survivin, c-Myc and hTERT and suppressed telomerase activity. Moreover, ATO significantly increased adhesion of U87MG cells and also diminished transcription of NF-${\kappa}B$ down-stream targets involved in cell migration and invasion, including cathepsin B, uPA, MMP-2, MMP-9 and MMP-14 and suppressed proteolytic activity of cathepsin B, MMP-2 and MMP-9, demonstrating a possible mechanism of ATO effect on a well-known signaling in glioblastoma dissemination. Taken together, here we suggest that ATO inhibits survival and invasion of U87MG cells possibly through NF-${\kappa}B$-mediated inhibition of survivin and telomerase activity and NF-${\kappa}B$-dependent suppression of cathepsin B, MMP-2 and MMP-9.

• Journal of Yeungnam Medical Science
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• 제29권1호
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• pp.42-44
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• 2012

Plasma cell myelomas generally manifest as bone or soft-tissue tumors with variable mass effects, pain, and infiltrative behavior. Extramedullary involvement occurs most commonly in the spleen, liver, lymph nodes, and kidneys, but intracranial involvement in plasma cell myeloma is a rare extramedullary manifestation. These authors recently encountered a case of intracranial involvement of plasma cell myeloma. A 69-year-old man was hospitalized for headache and mental changes. Brain CT showed subdural hemorrhage caused by plasma cell myeloma. Plasma cell myeloma with intracranial involvement has poor prognosis, and the patient in this case died from acute complications, such as subdural hemorrhage. Based on this case report, it is suggested that more effective treatment regimens of plasma cell myeloma with intracranial involvement be developed. Moreover, a screening method and decision on the appropriate time for intracranial involvement are needed for plasma cell myeloma patients.