• Title/Summary/Keyword: Chronic leukemia

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Proactive Consultation by a Clinical Pathologist Prevents Diagnostic Delay in Hematological Malignancies

  • Chang, Chih-Chun;Su, Ming-Jang;Ho, Jung-Li;Sun, Jen-Tang;Tsai, Huang-Wen;Tang, Hui-Fei;Chu, Fang-Yeh
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1019-1022
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    • 2016
  • Background: Diagnostic difficulties in hematological malignancies may lead to unacceptably prolonged help-seeking to diagnostic interval as well as increased complications and poor outcomes. Proactive consultation by a clinical pathologist (PCCP) may help clinical diagnosis and therapeutic strategy. Hence, the aim of this investigation was to evaluate the effect of PCCP on the help-seeking to diagnostic interval in hematological cancer cases. Materials and Methods: From January to November, 2015, abnormal results of hematological laboratory testing with added laboratory comment were selectively screened out, and patients with such abnormalities in hematological laboratory testing and accompanied laboratory comment with PCCP were enrolled. Results: A total of 125 aberrant results of hematological laboratory testing were given with accompanied laboratory comments with PCCP and 40.8% (n=51) of these patient-oriented comments had an effect on clinical diagnosis and therapeutic strategy. Twelve of the subjects belonged to newly diagnosed hematological malignancies with the assistance of PCCP, and the help-seeking to diagnostic interval was also shortened from 42 days to 26 days in chronic lymphoid leukemia (CLL), from 83 days to 11 days in multiple myeloma (MM), and from 128 days to 15 days in myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). During the monitoring interval, neither complication events nor deaths were reported in the study group. Conclusions: It was seemingly that PCCP prevented diagnostic delay in hematological malignancies via shortening the help-seeking to diagnostic interval, particularly in CLL, MM and MDS/MPN cases. PCCP can be considered to play an essential role in prompt establishment of diagnosis in hematological malignancies for those who newly present.

Financial Burden of Cancer Drug Treatment in Lebanon

  • Elias, Fadia;Khuri, Fadlo R;Adib, Salim M;Karam, Rita;Harb, Hilda;Awar, May;Zalloua, Pierre;Ammar, Walid
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3173-3177
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    • 2016
  • Background: The Ministry of Public Health (MOPH) in Lebanon provides cancer drugs free of charge for uninsured patients who account for more than half the total case-load. Other categories of cancer care are subsidized under more stringent eligibility criteria. MOPH's large database offers an excellent opportunity to analyze the cost of cancer treatment in Lebanon. Materials and Methods: Using utilization and spending data accumulated at MOPH during 2008-2013, the cost to the public budget of cancer drugs was assessed per case and per drug type. Results: The average annual cost of cancer drugs was 6,475$ per patient. Total cancer drug costs were highest for breast cancer, followed by chronic myeloid leukemia (CML), colorectal cancer, lung cancer, and Non-Hodgkin's lymphoma (NHL), which together represented 74% of total MOPH cancer drug expenditure. The annual average cancer drug cost per case was highest for CML ($31,037), followed by NHL ($11,566). Trastuzumab represented 26% and Imatinib 15% of total MOPH cancer drug expenditure over six years. Conclusions: Sustained increase in cancer drug cost threatens the sustainability of MOPH coverage, so crucial for socially vulnerable citizens. To enhance the bargaining position with pharmaceutical firms for drug cost containment in a small market like Lebanon, drug price comparisons with neighboring countries which have already obtained lower prices may succeed in lowering drug costs.

Association of TAP1 and TAP2 Gene Polymorphisms with Hematological Malignancies

  • Ozbas-Gerceker, Filiz;Bozman, Nazli;Gezici, Sevgi;Pehlivan, Mustafa;Yilmaz, Mehmet;Pehlivan, Sacide;Oguzkan-Balci, Sibel
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.5213-5217
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    • 2013
  • Transporter associated with antigen presenting (TAP) 1 and TAP2 genes are localized in the major histocompatability complex (MHC) class II region and form a heterodimer playing a key role in endogenous pathways for antigen presentation. Defects of these genes have been reported to be common in different types of cancer. Polymorphisms identified in these loci have also been investigated and reported to be associated with several autoimmune disorders, viral infections and neoplasms. In the present study, for the first time, the allele and genotype frequencies of TAP1-333, TAP2-565, TAP2-651 and TAP2-665 were determined in patients with hematological malignancies (HM) using a PCR-RFLP method and compared with the frequencies in the control group. Our results suggested an association of TAP1-333 polymorphism with multiple myeloma-MM and TAP2-565 polymorphism with chronic lymphoid leukemia-CLL. In addition, it could be concluded that the TAP2-665 GG genotype might be a risk factor for all types of hematological malignancies included in this study.

Screening of Korean Medicinal and Food Plants with Antitumoral Activity (국내 약용 및 식용식물중 항종양활성 식물탐색)

  • Chung, Ill-Min;Kim, Kwang-Ho;Ahn, Joung-Kuk;Ahn, Jong-Seog;Ahn, Soon-Cheol
    • Korean Journal of Medicinal Crop Science
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    • v.7 no.1
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    • pp.37-44
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    • 1999
  • This study was conducted to screen antitumoral activity by in vitro bioassay method using 60 Korean medicinal and food plants extracted by 80% EtOH. Antitumor activity test was applied by the PKC(protein kinase C) and antibleb formation, PLC (Phospholipase C), and colorimetric tetrazolium assay (MTT assay) methods. Chenopodjum album and black Glycine max showed high antitumoral activity by 73.5% and 81.0%, respectively, against PKC by bleb-forming assay and PKC enzyme assay on human chronic leukemia K562 cell. Black Glycine max also showed 91.2% antitumoral activity in the PLC method and the lowest $IC_{50}$ $value(4.7{\mu}g/ml)$ by MTT method against P-338 cell line. In the effect of the concentration treatment on antitumoral test, the more concentration indicated the more activity value.

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Synthesis and Antitumor Evaluation of Acyclic 1-[${\omega}$-(N^I-2-chloroethyl-N^I-nitrosoureido)alkyl]thymidine Nucleoside Analogues

  • Kim, Jack-C.;Kim, Young-Hyun;Park, Jin-Il;Kim, Seon-Hee;Choi, Soon-Kyu
    • Archives of Pharmacal Research
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    • v.20 no.3
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    • pp.259-263
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    • 1997
  • In the preparation of acyclic thymidine nucleoside analogues, $K_2CO_3$(or NaH) treated thymine in DMSO was alkylated with .omega.-chloroalkyl nitrite (Cl-(CH_2)n-CN; n=1, 2, 3, 4) to provide an isomeric mixture of 1-(${\omega}$-cyanoalkyl)thymine (2a-d) and 1,3-bis(${\omega}$-cyanoalkyl)thymine in approximately 5:1 ratios. Reduction of the cyano function 2a-d with $NaBH_{4}/CoCl_{2}$ center dot$ 6H_{2}O$gave the corresponding 1-(${\omega}$aminoalkyl)thymine (3a-d). The newly formed primary amino function in 3a-d was directly reacted with 2-chloroethylisocyanate to afford the 1-[.omega.($N^{I}$-2-chloroethylureido) alkyl]thymine (4a-d) in good yields. Nitrosation of 1-[5-($ N^{I}-2$-chloroethylureido)pentyl] thymine (4d) with glacial acetic acid and dry $NaNO_{2}$-powder in anhydrous $CH_{2}Cl_{2}$gave two types of regioisomeric nitrosoureas, 1-[5-($N^{I}$--chloroethyl-$N^{I}$--nitrosoureido)pentylithymine (5d) and 1-[5-($N^{I}-2$-chloroethyl-N-nitrosoureido)pentyllthymine in approximately 5 :1 ratios. The in vitro cytotoxicity of the synthesized compounds (2a-d, 3a-d, 4a-d and 5a-d) against three cell lines (K-562, P-388 and FM-3A) are measured as $IC^{50}$ values. Compounds 3b and 4c showed moderate activities against all three cell lines, and all other compounds were found to be not active.

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Chracterization of THP-1 Cell Death Induced by Porphyromonas gingivalis Infection

  • Song, YuRi;Kim, SeYeon;Park, Mee Hee;Na, Hee Sam;Chung, Jin
    • International Journal of Oral Biology
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    • v.42 no.1
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    • pp.17-23
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    • 2017
  • Background: Periodontitis is generally a chronic disorder characterized by the breakdown of tooth-supporting tissues. P. gingivalis, a Gram-negative anaerobic rod, is one of the major pathogens associated with periodontitis. Frequently, P. gingivalis infection leads to cell death. However, the correlation between P. gingivalis-induced cell death and periodontal inflammation remains to be elucidated. Among cell deaths, the death of immune cells appears to play a significant role in inflammatory response. Thus, the aim of this study was to examine P. gingivalis-induced cell death, focusing on autophagy and apoptosis in THP-1 cells. Methods: Human acute monocytic leukemia cell line (THP-1) was used for all experiments. Autophagy induced by P. gingivalis in THP-1 cells was examined by Cyto ID staining. Intracellular autophagic vacuoles were observed by fluorescence microscopy using staining Acridine orange (AO); and 3-methyladenine (3-MA) was used to inhibit autophagy. Total cell death was measured by LDH assay. Cytokine production was measured by an ELISA method. Results: P. gingivalis induced autophagy in an MOI-dependent manner in THP-1 cells, but 3-MA treatment decreased autophagy and increased the apoptotic blebs. P. gingivalis infection did not increase apoptosis compared to the control cells, whereas inhibition of autophagy by 3-MA significantly increased apoptosis in P. gingivalis-infected THP-1 cells. Inhibition of autophagy by 3-MA also increased total cell deaths and inflammatory cytokine production, including $IL-1{\beta}$ and $TNF-{\alpha}$. Conclusion: P. gingivalis induced autophagy in THP-1 cells, but the inhibition of autophagy by 3-MA stimulated apoptosis, leading to increased cell deaths and pro-inflammatory cytokines production. Hence, the modulation of cell deaths may provide a mechanism to fight against invading microorganisms in host cells and could be a promising way to control inflammation.

Diagnostic and Prognostic Relevance of Bone Marrow Microenvironment Components in Non Hodgkin's Lymphoma Cases Before and After Therapy

  • Soliman, Amira H
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.12
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    • pp.5273-5280
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    • 2016
  • Objective: To evaluate stromal cells of the bone marrow microenvironment (BMM) in bone marrow trephine biopsy (BMTB) specimens, with a focus on fibronectin, tumor necrosis factor- alpha (TNF-${\alpha}$) and L-selectin in Non-Hodgkin's lymphoma (NHL) patients, before and after therapy. Materials and Methods: A total of 80 de novo NHL patients, 64 with B-cell lymphomas 80%, (follicular cell lymphoma (FCL) in 32, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in 12, and diffuse large cell lymphoma in 20) and 16 with T-cell lymphomas (20%) all diagnosed as T-Lymphoblastic lymphomas, were evaluated before and after therapy. For comparison, 25 age and sex matched BM donors, were included as a control group. BMTB material and BM aspirates were taken for morphological assessment of stromal cells, the plasma of these samples being examined for $TNF{\alpha}$ and L-selectin by ELISA, and fibronectin by radial immunodiffusion (RID). Results: BM stromal cells comprising reticular macrophages and fibroblasts were elevated in 53.3% of NHL cases at diagnosis, while BM fibronectin levels were decreased and BM $TNF{\alpha}$ and L-selectin were higher than in controls (p<0.05). In NHL cases, elevated values of BM $TNF{\alpha}$ and BM L-selectin were associated with signs of aggressive disease, including >1 extra nodal sites, detectable B symptoms, high grade, BM and CNS invasion, and a high International prognostic index (IPI) (p<0.05). Conclusion: BMM components, $TNF{\alpha}$, L-selectin and fibronectin, in NHL can be useful in evaluating disease activity, extent and response to treatment and as prognostic markers according to the IPI.

Anti-growth Effects of Imatinib and GNF5 via Regulation of Skp2 in Human Hepatocellular Carcinoma Cells

  • Kim, Sung Hyun;Kim, Myoung-Ok;Kim, Ki-Rim
    • Journal of Cancer Prevention
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    • v.23 no.4
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    • pp.170-175
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    • 2018
  • Background: Human hepatocellular carcinoma (HCC) is a common liver tumor and the main cause of cancer-related death. Tyrosine kinase inhibitors, such as imatinib and GNF5 which were developed to treat chronic myelogenous leukemia, regulate the progression of various cancers. The aim of this study was to confirm the anti-tumor activity of tyrosine kinase inhibitors through regulation of S-phase kinase-associated protein 2 (Skp2), an important oncogenic factor in various cancer cells, in human hepatocarcinoma SK-HEP1 cells. Methods: Cell viability and colony formation assays were conducted to evaluate the effects of imatinib, GNF5 and GNF2 on the growth of SK-HEP1 cells. Using immunoblot analysis, we assessed change of the activation of caspases, PARP, Akt, mitogen-activated protein kinases, and Skp2/p27/p21 pathway by imatinib and GNF5 in SK-HEP1 cells. Using sh-Skp2 HCC cells, the role of Skp2 in the effects of imatinib and GNF5 was evaluated. Results: Imatinib and GNF5 significantly inhibited the growth of SK-HEP1 cells. Treatment of imatinib and GNF5 decreased Skp2 expression and Akt phosphorylation, and increased the expression of p27, p21, and active-caspases in SK-HEP1 cells. In sh-Skp2 HCC cells, cell growth and the expression of Skp2 were inhibited by more than in the mock group treated with imatinib and GNF5. Conclusions: These results suggest that the anti-growth activity of tyrosine kinase inhibitors may be associated with the regulation of p27/p21 and caspases through Skp2 blockage in HCC cells.

Inhibitory Effects of Scrophulariae Radix on β-hexosaminidase release and cytokine production in RBL-2H3 cells (현삼(玄蔘) 추출물이 RBL-2H3 비만세포에서 β-hexosaminidase 및 cytokine 분비에 미치는 효과)

  • Kim, Se-Gie
    • The Korea Journal of Herbology
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    • v.32 no.6
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    • pp.9-15
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    • 2017
  • Objectives : Traditional medicines isolated from natural products often have positive effects in the prevention and healing of various immune disorders, such as allergy and atopic inflammation. Scrophulariae Radix (SR) been used in oriental medicine used for treatment of acute and chronic inflammatory diseases. Mast cells are known to play important roles in the initiation of allergic reactions. In this study, we investigated the effects of SR ethanol extract on inflammatory responses in IgE-stimulated RBL-2H3 mast cells. Methods : Rat basophilic leukemia RBL-2H3 cells were purchased from Korean Cell Line Bank (KCLB No. 22256). Cell viability was measured by MTT assay. Assays for ${\beta}-Hexosaminidase$ Secretion : RBL-2H3 cells were sensitized with dinitrophenyl-ImmunoglobulinE (DNP IgE). The next antigen DNP-BSA ($25ng/m{\ell}$) was added for 10 minutes and the reaction was terminated after 5 minutes in the ice bath. To determine ${\beta}-Hexosaminidase$ release, supernatants were aliquoted into 96-well plates. Samples were mixed with substrate solution and incubated for 1 h at $37^{\circ}C$. Absorbance was measured with a spectrophotometer at 405 nm. IL-4 and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) concentrations in cell culture supernatants were measured using enzyme-linked immunosorbent assay (ELISA) kits. Results : The cytotoxicity of SRE in RBL-2H3 cells was less than 5%. SRE inhibited DNP-IgE-imduced degranulation of mast cells in RBL-2H3 cells. Also significantly decreased the levels of inflammatory cytokine, IL-4 and TNF-alpha. In this study, the SRE showed potential anti-allergic and antiinflammatory. Conclusions : These results indicate that SRE could be inhibit the allergic response through suppressing the mast cell activation.

Imaging Features of Various Benign and Malignant Tumors and Tumorlike Conditions of the Pleura: A Pictorial Review (흉막의 여러 가지 양성 및 악성 종양 혹은 종양 같은 질환들의 영상 소견: 임상 화보)

  • June Young Bae;Yookyung Kim;Hyun Ji Kang;Hyeyoung Kwon;Sung Shine Shim
    • Journal of the Korean Society of Radiology
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    • v.81 no.5
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    • pp.1109-1120
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    • 2020
  • Pleural masses may be caused by various conditions, including benign and malignant neoplasms and non-neoplastic tumorlike conditions. Primary pleural neoplasms include solitary fibrous tumor, malignant mesothelioma, and primary pleural non-Hodgkin's lymphoma. Metastatic disease is the most common neoplasm of the pleura and may uncommonly occur in patients with hematologic malignancy, including lymphoma, leukemia, and multiple myeloma. Pleural effusion is usually associated with pleural malignancy. Rarely, pleural malignancy may arise from chronic empyema, and the most common cell type is non-Hodgkin's lymphoma (pyothorax-associated lymphoma). Non-neoplastic pleural masses may be observed in several benign conditions, including tuberculosis, pleural plaques caused by asbestos exposure, and pleural loose body. Herein, we present a review of benign and malignant pleural neoplasms and tumorlike conditions with illustrations of their computed tomographic images.