• Title/Summary/Keyword: Hematologic Malignancies

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Characteristics of Cancer Stem Cells and Immune Checkpoint Inhibition (암줄기세포의 특성 및 면역관문억제)

  • Choi, Sang-Hun;Kim, Hyunggee
    • Journal of Life Science
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    • v.29 no.4
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    • pp.499-508
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    • 2019
  • Cancer stem cells (CSCs), which are primarily responsible for metastasis and recurrence, have self-renewal, differentiation, therapeutic resistance, and tumor formation abilities. Numerous studies have demonstrated the signaling pathways essential for the acquisition and maintenance of CSC characteristics, such as WNT/${\beta}$-catenin, Hedgehog, Notch, B lymphoma Mo-MLV insertion region 1 homolog (BMI1), Bone morphogenetic protein (BMP), and TGF-${\beta}$ signals. However, few therapeutic strategies have been developed that can selectively eliminate CSCs. Recently, neutralizing antibodies against Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1), immune checkpoint inhibitors (ICIs), have shown promising outcomes in clinical trials of melanoma, lung cancer, and pancreatic cancer, as well as in hematologic malignancies. ICIs are considered to outperform conventional anticancer drugs by maintaining long-lasting anti-cancer effects, with less severe side effects. Several studies reported that ICIs successfully blocked CSC properties in head and neck squamous carcinomas, melanomas, and breast cancer. Together, these findings suggest that novel and effective anticancer therapeutic modalities using ICIs for selective elimination of CSCs may be developed in the near future. In this review, we highlight the origin and characteristics of CSCs, together with critical signaling pathways. We also describe progress in ICI-mediated anticancer treatment to date and present perspectives on the development of CSC-targeting ICIs.

Causes of Hyperferritinemia and Red Blood Cell Transfusion (고페리틴혈증의 원인과 적혈구 수혈)

  • Kim, Mi Seon;Kim, Sun Hyung
    • The Korean Journal of Blood Transfusion
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    • v.29 no.3
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    • pp.273-281
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    • 2018
  • Background: Ferritin is used to detect iron overload in patients with chronic red blood cell transfusions. Although ferritin reflects the amount of iron storage in the body, it may increase nonspecifically in inflammation and infection. This study analyzed the cause of increased ferritin and the association with a red blood cell (RBC) transfusion. Methods: The medical records of patients who visited the authors' hospital from January to December 2017 and underwent a ferritin test were reviewed retrospectively. Hyperferritinemia was defined as a ferritin level more than 1,000 ng/mL. The causes of hyperferritinemia were investigated by examining the laboratory findings and medical records. Results: The results revealed 417 cases of hyperferritinemia in 238 patients during the period. The most common diseases were hematologic malignancies from 125 cases (30.0%) in 31 patients and infectious diseases were the second most common. Iron overload was suspected in 119 cases in 33 patients, and 12 patients (76 cases) were transfused with more than 8 units of RBC for 1 year before the test. Conclusion: In hyperferritinemia, the rate of iron overload is high considering the underlying diseases and chronic RBC transfusion. To determine iron storage status accurately, it will be helpful to measure the C-reactive protein (CRP) and iron saturation in the ferritin test. Careful attention should be paid to habitual iron formulations and frequent transfusions due to the possibility of iron overload.

A Case of Hemophagocytic Lymphohistiocytosis with Clonal Karyotype Abnormalities (클론성 염색체이상을 보인 혈구포식 림프조직구증 1예)

  • Choi, Gae-Ryung;Kim, Ha-Nui;Cho, Chi-Hyun;Yoo, Byoung-Joon;Kim, Myung-Han;Kim, Jang-Su;Lim, Chae-Seung;Lee, Kap No
    • Laboratory Medicine Online
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    • v.1 no.2
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    • pp.110-114
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    • 2011
  • There have been a few reports of hemophagocytic lymphohistiocytosis (HLH) with chromosomal abnormalities. Clonal chromosomal abnormalities in HLH patients are usually found in association with hematologic malignancies and rarely with epstein-barr virus (EBV) infection. Here, we report a fatal case of HLH with clonal karyotype abnormalities. A 75-yr-old man was admitted with persistent anorexia and high fever. Laboratory data revealed pancytopenia, hypofibrinogenemia, hyperferritinemia, prolonged prothrombin time and activated partial thromboplastin time, and marked elevated level of serum transaminases. In real time-PCR using whole blood, EBV DNA was not detected but cytomegalovirus (CMV) DNA was detected. The bone marrow aspiration smear showed hyperplasia of mature histiocytes with prominent hemophagocytosis. In chromosomal analysis of bone marrow aspirates, complex chromosomal abnormalities were found. In spite of steroid pulse therapy and antibiotic treatment, he died of disseminated intravascular coagulopathy.

Clinical Manifestations of Norovirus Infection in Korean Pediatric Cancer Patients (한국 소아 암환자에서 노로바이러스 감염증의 임상 양상)

  • Choi, Hyunshin;Choi, Young Bae;Hwang, Ji-Young;Cheon, Doo-Sung;Jeong, Hye Sook;Choe, Yon Ho;Yoo, Keon Hee;Sung, Ki Woong;Koo, Hong Hoe;Kim, Yae-Jean
    • Pediatric Infection and Vaccine
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    • v.18 no.1
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    • pp.40-47
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    • 2011
  • Purpose : Norovirus infection, a common cause of community-acquired gastroenteritis, can also lead to severe illness in immunocompromised patients. We investigated clinical manifestations of norovirus infection in pediatric cancer patients. Methods : Stool specimens were collected from pediatric patients with gastrointestinal symptoms between November 2008 and September 2009 at Samsung Medical Center, Seoul, Korea. Norovirus infection was identified by reverse-transcription polymerase chain reaction (RT-PCR). A retrospective chart review was performed in pediatric cancer patients who were diagnosed with norovirus infection. Results : Ten patients were diagnosed with norovirus infection by RT-PCR in stool samples. The median age was 0.83 years (range 0.25-5.5 years) and the male to female ratio was 1.5:1 (6 males and 4 females). Underlying diseases were hematologic malignancies (4/10, 40%), neuroblastoma (4/10, 40%), and brain tumors (2/10, 20%). Three patients were infected before hematopoietic cell transplantation (HCT) and four patients after HCT. All patients had diarrhea (10/10, 100%), with a median frequency of diarrhea of 8.5 times/day (range 4-22 times/day). Median virus shedding duration was 72.5 days (range 19-299 days). Four patients with pneumatosis intestinalis were conservatively treated with bowel rest and total parenteral nutrition. One patient with severe diarrhea and bloody stool had concomitant chronic gut graft-versus-host disease (GVHD). Norovirus infection-related mortality was not observed. Conclusion : Norovirus infection can cause significant clinical manifestations with prolonged viral shedding in immunocompromised patients. Norovirus should be considered in pediatric cancer patients with severe gastrointestinal symptoms.

Stenotrophomonas maltophilia and Ventilator-Associated Pneumonia in Critically Ill Pediatric Patients: a Retrospective Analysis at a Single Center (소아 환자에서 Stenotrophomonas maltophilia와 인공 환기요법 관련 폐렴에 관한 연구)

  • Lee, Byung-Kee;Choi, Soo-Han;Kim, Soo Jin;Cho, Joong Bum;Ae, Hong;Yoo, So-young;Kim, Ji Hye;Lee, Nam Young;Kim, Yae-Jean
    • Pediatric Infection and Vaccine
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    • v.22 no.2
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    • pp.75-80
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    • 2015
  • Purpose: Ventilator-associated pneumonia (VAP) is a serious threat in critically ill pediatric patients. Data regarding Stenotrophomonas maltophilia VAP in pediatric population is limited. We evaluated the clinical data of S. maltophilia associated VAP in critically ill pediatric patients. Methods: A retrospective chart review was performed in pediatric patients 18 years old or younger who developed S. maltophilia associated VAP at Samsung Medical Center, Seoul Korea from January 2008 to December 2012. Results: A total of 31 patients were identified S. maltophilia associated VAP. Median age was 8 months (range, 0.5 month to 16.6 years) and 13 patients were male (40.6%). Underlying illnesses were cardiologic diseases (n=11, 34.4%), hematologic oncologic malignancies (n=7, 25%), neurologic diseases (n=4, 12.5%), pulmonary diseases (n=3, 9.4%), and others (n=4, 12.5%). The median duration of ventilator use before S. maltophilia VAP diagnosis was 14 days (range, 4-256 days). Overall mortality at 30 days was 12.5% (4/32). Conclusions: S. maltophilia should be also considered as a possible pathogen for VAP in critically ill pediatric patients. Empiric antibiotic choice should include agents that are active against S. maltophilia in patients who are deteriorating on broad spectrum beta-lactam antimicrobial agents.

Effectiveness of Varicella Zoster Immune Globulin Administration within 96 Hours versus more than 96 Hours after Exposure to the Varicella-Zoster Virus (수두 바이러스에 노출 후 96시간 이내와 96시간 이후에 수두 면역 글로불린 투여시 수두 예방 효과에 관한 연구)

  • Kim, Sun-Ja;Lee, Byung-Kee;Kim, Yang-Hyun;Kim, Soo-Jin;Kim, Yae-Jean
    • Pediatric Infection and Vaccine
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    • v.22 no.2
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    • pp.55-62
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    • 2015
  • Purpose: Varicella Zoster Immune Globulin (VZIG) is available in Korea for post-exposure prophylaxis of the Varicella-zoster virus (VZV) in high-risk patients. In July 2013, the United States Centers for Disease Control and Prevention (US CDC) recommended extending the time for administration of VariZIG$^{(R)}$ from within 96 hours up to 10 days after VZV exposure. This study was performed to analyze the effectiveness of VZIG prophylaxis between the two groups of patients who received VZIG within 96 hours and more than 96 hours of exposure to varicella. Methods: A retrospective chart review was performed in pediatric patients who received VZIG at Samsung Medical Center, Seoul, Korea from January 2001 to December 2012. Results: A total of 91 patients were identified. Fifty-seven patients were male (62.6%) and the median age was 5.91 years. Thirty-nine patients (42.9%) were exposed to VZV in the hospital. Underlying diseases were solid tumors (41.8%), hematologic malignancies (40.7%), and others (17.5%). Forty-five patients (49.5%) were hematopoietic cell transplant recipients. Seventy-four patients (81.3%) received VZIG within 96 hours after VZV exposure. There was no significant difference in the development of chickenpox between the two groups (2.7% vs. 5.9%, P=0.4664). In 22 seronegative patients, we also observed no significant difference between the groups in terms of the development of chickenpox (6.6% vs. 0%, P=0.667). Conclusions: This study showed that the effectiveness of VZIG for the prevention of chickenpox was comparable between patients who received VZIG within 96 hours and those who received VZIG more than 96 hours after exposure to VZV.

Evaluation of Cell Death and the Reduction of ERK Phosphorylation in Non-Small Cell Lung Cancer Cells after Exposure to Sodium Butyrate (Sodium butyrate 노출에 의한 비소세포폐암 세포의 세포사멸과 extracellular signal-regulated kinase 인산화의 감소)

  • Park, Ji-Eun;Lee, Seung-Gee;Lim, Hyun-Ju;Kim, Ji-Young;Chung, Jin-Yong;Kim, Yoon-Jae;Lee, Chang-Hun;Lee, Min-Ki;Yoo, Ki-Soo;Yoo, Young-Hyun;Kim, Jong-Min
    • Journal of Life Science
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    • v.19 no.9
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    • pp.1314-1320
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    • 2009
  • Histone deacetylase inhibitor (HDACI) is a new promising candidate as an antineoplastic agent for the treatment of solid and hematologic malignancies. In order to evaluate cell death and to elucidate the related mechanism(s) in NSCLC cells after HDACI, sodium butyrate (SB), a representative HDACI, was used to treat H460 cells for 48 hrs. SB exposure resulted in a significant reduction of cell viability at concentrations below 7.5 mM, and about 50% of cell death occurred at 20 mM. The types of cell death induced by SB were both apoptosis and necrosis, evaluated by Annexin-V staining combined with propidium iodide. SB treatment significantly evoked G2/M cell cycle arrest and subsequently induced cell death with caspase-dependent manner. While ERK protein content was not altered after SB, phosphorylated forms of ERK were markedly reduced. Taken together, SB is significantly able to induce cell death in NSCLC cell line H460, and it is suggested that the reduction of ERK phosphorylation might be closely involved in the cancer cell death mechanism initiated by HDACI.

Comparison of Amphotericin B and Itraconazole as Empirical Antifungal Therapy in Children with Acute Leukemia with Neutropenic Fever (발열을 동반한 호중구감소 상태의 급성백혈병 환아에서 경험적 항진균제로 투여한 Amphotericin B와 Itraconazole의 효과와 이상 반응 비교)

  • Lee, Sang-Yun;Park, Jong-Sun;Kim, Sun-Young;Yang, Keum-Jin;Park, Kyung-Deok;Kim, Hack-Ki
    • Pediatric Infection and Vaccine
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    • v.12 no.1
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    • pp.75-85
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    • 2005
  • Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

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Rarely Observed Jumping Translocation in Spontaneous Abortion (자연 유산에서 드물게 관찰된 Jumping translocation 2례)

  • Lee, Yeon-Woo;Lee, Bom-Yi;Park, Ju-Yeon;Choi, Eun-Young;Oh, Ah-Rum;Lee, Shin-Young;Ryu, Hyun-Mee;Kang, Inn-Soo;Yang, Kwang-Moon;Park, So-Yeon
    • Journal of Genetic Medicine
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    • v.7 no.1
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    • pp.82-86
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    • 2010
  • Jumping translocations (JT) are chromosomal rearrangements involving one donor chromosome and several recipient chromosomes. While JTs are frequently observed as acquired chromosomal abnormalities in hematologic malignancies, constitutional JTs are only rarely reported. We report two cases of constitutional JT in chorionic villi derived from the products of conception. The karyotype of the first case was 46,XY,add(18)(p11.1)[61]/45,XY,der(18;21)(q10;q10)[32]/46,XY,-18,+mar[16]/46,XY,i(18)(q10)[9]/45,XY,der(15;18)(q10;q10)[6]/46,XY,+1,dic(1;18)(p22;p11.1)[2]/45,XY,der(13;18)(q10;q10)[1]/46,XY[32]. The donor was a chromosome 18. The recipient chromosomes were chromosomes 1, 13, 15, 18 and 21. In the second case, the karyotype was 46,XY,der(22)t(9;22)(q12;q13)[22]/46,XY,der(22)t(1;22)(q21;q13)[13]/46,XY,add(22)(q13)[5]/46 XY[23]. The donor was a chromosome 22 and recipients were chromosomes 1 and 9. Both cases were de novo. The breakpoints of chromosomes were mostly in centromeric regions, pericentromeric regions, or telomeric regions. Normal cell lines were observed in both cases. This report supports the prior findings that the unstable nature of JT, resulting in chromosomal imbalance, most likely contributed to these early miscarriages.

Usefulness of Serum Thymidine Kinase 1 as a Biomarker for Aggressive Clinical Behavior in B-cell Lymphoma (B세포림프종의 임상적 악성도 표지자로서 혈청 Thymidine Kinase 1의 유용성)

  • Kim, Heyjin;Kang, Hye Jin;Lee, Jin Kyung;Hong, Young Jun;Hong, Seok-Il;Chang, Yoon Hwan
    • Laboratory Medicine Online
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    • v.6 no.1
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    • pp.25-30
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    • 2016
  • Background: The cell cycle-dependent enzyme thymidine kinase 1 (TK1) is known to increase during cancer cell proliferation and has been reported as a prognostic marker for various hematologic malignancies and solid tumors. This study aimed to determine the reference interval in Korean healthy controls and to evaluate the usefulness of TK1 as a biomarker for aggressive clinical behavior in B-cell lymphoma patients. Methods: We enrolled 72 previously untreated patients with B-cell lymphoma and 143 healthy controls. Serum TK1 levels were measured by chemiluminescence immunoassay ($Liaison^{(R)}$, DiaSorin, USA). We established the reference intervals in healthy controls. The diagnostic performance of serum TK1 was studied using receiver operating characteristic (ROC) analysis, and the correlation between the cutoff level for serum TK1 and clinical characteristics of B-cell lymphoma was evaluated. Results: The reference range (95th percentile) of serum TK1 in healthy controls was 5.4-21.8 U/L. There was a clear difference in TK1 levels between patients with B-cell lymphoma and healthy controls ($40.6{\pm}68.5$ vs. $11.8{\pm}4.4U/L$, P <0.001). The area under the curve of serum TK1 for the diagnosis of B-cell lymphoma was 0.73 (cutoff, 15.2 U/L; sensitivity, 59.7%; specificity, 83.2%). An increased TK1 level (${\geq}15.2U/L$) correlated with the advanced clinical stage (P <0.001), bone marrow involvement (P =0.013), international prognostic index score (P =0.001), lactate dehydrogenase level (P =0.001), low Hb level (<12 g/dL) (P =0.028), and lymphocyte count (P =0.023). Conclusions: The serum TK1 level could serve as a useful biomarker for aggressive clinical behavior in B-cell lymphoma patients.