• Molecular & Cellular Toxicology
• /
• v.4 no.4
• /
• pp.267-277
• /
• 2008

Benzene and ethylbenzene (BE), the volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Chronic exposure of benzene is responsible for myeloid leukemia and also ethylbenzene is also recognized as a possible carcinogen. To evaluate the BE effect on human, whole human genome 35 K oligonucleotide microarray were screened for the identification of the differential expression profiling. We identified 280 up-regulated and 201 down-regulated genes changed by more than 1.5 fold by BE exposure. Functional analysis was carried out by using DAVID bioinformatics software. Clustering of these differentially expressed genes were associated with immune response, cytokine-cytokine receptor interaction, toll-like signaling pathway, small cell lung cancer, immune response, apoptosis, p53 signaling pathway and MAPKKK cascade possibly constituting alternative or subordinate pathways of hematotoxicity and immune toxicity. Gene ontology analysis methods including biological process, cellular components, molecular function and KEGG pathway thus provide a fundamental basis of the molecular pathways through BEs exposure in human lymphoma cells. This may provides a valuable information to do further analysis to explore the mechanism of BE induced hematotoxicity.

• Journal of Haehwa Medicine
• /
• v.10 no.2
• /
• pp.73-81
• /
• 2002

In the literal study of anti-tumor effects of Jakeumjung. the results were as follows. 1. Jakeumjung is a traditional oriental medical prescription which is composed of Cremastare appeniculatae tuber, Euphorbiae pekinensis radix, Toosendan fructus, Chinensis galla, Moschus, Realgar and Cinnabaris. 2. Jakeumjung is applied to patients by administering or external application. When it is administered for patients, pertinent dose is 0.6~1.5g twice or three times per one day. When it is applied by external application, we melt it by water or vinegar and apply it to patients. 3. Effects of Jakeumjung are expelling toxin and pestilence, counteracting pathogen and relieving stagnation, detumescence and stopping pain. So it is used for detoxification from ancient. In recent, it is often used for cancer such as breast cancer, pancreatic cancer, epigastric cancer, acute leukemia, lymphoma, thymus cancer and skin cancer. 4. From the various experiments, Jakeumjung has been proved to have antifungal and antitumor effects. It inhibits and kills L7212, L1210 cells of leukemia. Especially, it acts in S stage of cell period. 5. Jakeumjung includes mineral medicines such as Realgar, Cinnabaris. So if we execute progressive study for anticancer effects and safety, the boundary of oriental medicine of using mineral medicines for cancer therapy will magnify in the future.

• Journal of Korean Society of Occupational and Environmental Hygiene
• /
• v.29 no.3
• /
• pp.278-288
• /
• 2019

Objectives: The objectives of this study are to summary controversy over health risks among semiconductor workers, to review major cancer risk results conducted in semiconductor operation and to evaluate occupational health activities in Korea for controlling hazardous agents generated in semiconductor operations Methods: Major occupational health issues that has been social controversies among semiconductor workers since 2007 were reviewed through an extensive literature, report and article review. Results: Since a female semiconductor worker aged 22 died from leukemia in 2007, job-association of a number of former semiconductor workers with various types of cancer and rare diseases have been denied by the Korea Workers' Compensation and Welfare Service (KWCWS), but some of them were later awarded compensation as an occupational disease by the administrative court. Two epidemiologic cancer risk studies conducted in Korea found increased risks in leukemia and non-Hodgkin's lymphoma among semiconductor workers. Various legal occupational health activities taken in semiconductor industry were found to fail to assess a complex characteristics of semiconductor operations, such as drastic changes in chemical use, processes, and technology, multiple exposure. National compensation regulation also showed the limitation to evaluate job-association of semiconductor workers who had worked in semiconductor operation. Conclusions: National legal measures should be taken to improve several occupational health activities and duties for protecting workers. In addition, the KWCWS program should be revised so that all workers who meet minimal job or environment associations can be compensated.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.23 no.3
• /
• pp.443-452
• /
• 1994

This study describes the effects of novel1, 25-dihydroxyvitamin D$_3$ analong[1,25(OH)$_2$-16ene-23yne-26, 27-F6-D$_3$] on proliferation of the human histiocytic lymphoma cell line U937 in vitro. We also examined the expression of c-myc oncogene in U937 cells was apparently inhibited to 62% and 87% of the control level after 4 days in the presence of 10-8M and 10-7 M of this analog, respectively. This compound morpholgically and functionally differentiated U937 cells to nonocyte-macrophage phenotype showing the increase of adherence ability to surface and a decrease of N/C ratio in Giemsa staining . Especially, nonspecific esterase activity which is a marker of cell differentiation to monocyte-macrophage was positive, and production of the positive stained cells increased in a dose dependent fashion . The expression of c-myc oncogene by 1, 25(OH)$_2$D$_3$ analog(10-7 M) was reduced by 60% at the mRNA level as determined by Northern blotting. The effects of this novel analog on cell proliferation and cell differentiation may open op new therapeutic strategies for human disorders such as psoriassis and may provide a tool to understand the mechanism of action of vitamin D$_3$ seco-steroids in malignancy.

• Journal of Chest Surgery
• /
• v.51 no.5
• /
• pp.350-355
• /
• 2018

Background: The complication rate of fungal disease is higher among patients with hematological malignancies. We investigated the clinicobacteriological outcomes of resected pulmonary fungal infections complicating hematological malignancies. Methods: Between 2001 and 2017, 21 patients with pulmonary fungal infections complicating hematological malignancies underwent resection, and their clinical records and survival were retrospectively reviewed. Results: The median age of the patients was 47 years, and 13 were male. The histological diagnoses were pulmonary aspergillosis (19 cases), mucormycosis (1 case), and cryptococcosis (1 case). The indications for surgery were resistance to antifungal therapy and the necessity of surgery before hematopoietic stem cell transplantation in 13 and 8 cases, respectively. The diagnoses of the hematological malignancies were acute myelogenous leukemia (10 cases), acute lymphocytic leukemia (5 cases), myelodysplastic syndrome (3 cases), and chronic myelogenous leukemia, malignant lymphoma, and extramedullary plasmacytoma (1 case each). The surgical procedures were partial resection (11 cases), segmentectomy (5 cases), lobectomy (4 cases), and cavernostomy (1 case). The size of the lesions was 0.9-8.5 cm. Fourteen cases had cavitation. There were no surgical-related deaths or fungal progression. Conclusion: Pulmonary fungal infections are resistant to treatments for hematological malignancies. Since the treatment of the underlying disease is extended and these infections often recur and are exacerbated, surgery should be considered when possible.

• Biomolecules & Therapeutics
• /
• v.25 no.5
• /
• pp.490-496
• /
• 2017

Imatinib resistance has become a major clinical problem for chronic myeloid leukemia. The aim of the present study was to investigate the involvement of MEG3, a lncRNA, in imatinib resistance and demonstrate its underlying mechanisms. RNAs were extracted from CML patients' peripheral blood cells and human leukemic K562 cells, and the expression of MEG3 was measured by RT-qPCR. Cell proliferation and cell apoptosis were evaluated. Western blotting was used to measure the protein expression of several multidrug resistant transporters. Luciferase reporter assay was performed to determine the binding between MEG3 and miR-21. Our results showed that MEG3 was significantly decreased in imatinib-resistant CML patients and imatinib-resistant K562 cells. Overexpression of MEG3 in imatinib-resistant K562 cells markedly decreased cell proliferation, increased cell apoptosis, reversed imatinib resistance, and reduced the expression of MRP1, MDR1, and ABCG2. Interestingly, MEG3 binds to miR-21. MEG3 and miR-21 were negatively correlated in CML patients. In addition, miR-21 mimics reversed the phenotype of MEG3-overexpression in imatinib-resistant K562 cells. Taken together, MEG3 is involved in imatinib resistance in CML and possibly contributes to imatinib resistance through regulating miR-21, and subsequent cell proliferation, apoptosis and expression of multidrug resistant transporters.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.5
• /
• pp.2257-2262
• /
• 2014

A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420T polymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a more precise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 available studies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significant association between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer, gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associated with decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838, 95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysis was performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverse association was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for the PB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association was only found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggest that SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decrease cancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis.

• Korean Journal of Pharmacognosy
• /
• v.47 no.3
• /
• pp.197-203
• /
• 2016

Decursin is a major component of the root of Angelica gigas(Umbelliferae), which has been traditionally used in Korea as a tonic and to treat anemia, hemiplegia, and women's diseases. The objective of this study is to identify the anti-cancer mechanism induced by decursin on apoptosis of human leukemia and lymphoma cells. Cytotoxicity of decursin on U937, HL-60, MOLT-4, THP-1 cells showed the significant effects. First of all, $IC_{50}$ of decursin on four cell lines was 27.1, 32.4, 17.4, $15.1{\mu}M$, respectively. So $IC_{50}$ in THP-1 cells was the smallest among 4 cell lines treated with decursin($15.1{\mu}M$). In order to understand the apoptosis-mechanism by decursin, we examined the gene expression of bcl-2(anti-apoptotic), bax(pro-apoptotic) and p53(tumor suppressor)after treating the THP-1 cells with decursin(10, 50 and $100{\mu}M$). It was found bcl-2 gene was decreased dose dependently, the expression level of bax gene of THP-1 cells treated with $100{\mu}M$ of decursin was about 3 times higher than those of control, and p53 gene was increased In the same concentration($100{\mu}M$), p53 gene was increased dose dependent manner. In protein express, bcl-2 and p53 protein showed a tendency to decrease. bax was increased about 4 fold. Therefore decursin is a useful chemotherapeutic agent against leukemia.

• International Journal of Oncology
• /
• v.56 no.1
• /
• pp.368-378
• /
• 2020

Meridianin C is a marine natural product with anticancer activity. Several meridianin C derivatives (compounds 7a-j) were recently synthesized, and their inhibitory effects on pro-viral integration site for Moloney murine leukemia virus (PIM) kinases, as well as their antiproliferative effects on human leukemia cells, were reported. However, the anti-leukemic effects and mechanisms of action of meridianin C and its derivatives remain largely unknown. The aim of the present study was to investigate the effects of meridianin C and its derivatives on MV4-11 human acute myeloid leukemia cell growth. The parent compound meridianin C did not markedly affect the viability and survival of MV4-11 cells. By contrast, MV4-11 cell viability and survival were reduced by meridianin C derivatives, with compound 7a achieving the most prominent reduction. Compound 7a notably inhibited the expression and activity of PIM kinases, as evidenced by reduced B-cell lymphoma-2 (Bcl-2)-associated death promoter phosphorylation at Ser112. However, meridianin C also suppressed PIM kinase expression and activity, and the pan-PIM kinase inhibitor AZD1208 only slightly suppressed the survival of MV4-11 cells. Thus, the anti-survival effect of compound 7a on MV4-11 cells was unrelated to PIM kinase inhibition. Moreover, compound 7a induced apoptosis, caspase-9 and -3 activation and poly(ADP-ribose) polymerase (PARP) cleavage, but did not affect death receptor (DR)-4 or DR-5 expression in MV4-11 cells. Compound 7a also induced the generation of cleaved Bcl-2, and the downregulation of myeloid cell leukemia (Mcl)-1 and X-linked inhibitor of apoptosis (XIAP) in MV4-11 cells. Furthermore, compound 7a increased eukaryotic initiation factor (eIF)-2α phosphorylation and decreased S6 phosphorylation, whereas GRP-78 expression was unaffected. Importantly, treatment with a pan-caspase inhibitor (z-VAD-fmk) significantly attenuated compound 7a-induced apoptosis, caspase-9 and -3 activation, PARP cleavage, generation of cleaved Bcl-2 and downregulation of Mcl-1 and XIAP in MV4-11 cells. Collectively, these findings demonstrated the strong anti-survival and pro-apoptotic effects of compound 7a on MV4-11 cells through regulation of caspase-9 and -3, Bcl-2, Mcl-1, XIAP, eIF-2α and S6 molecules.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.8
• /
• pp.3555-3560
• /
• 2012

The tumour lysis syndrome (TLS) is a group of metabolic abnormalities caused by rapid and unexpected release of cellular components into the circulation as a result of massive destruction of rapidly proliferating malignant cells. It usually develops in patients with hematologic malignancies like acute lymphoid leukemia, non-Hodgkin and Burkitt's lymphoma after initiation of chemotherapy or may, rarely, occur spontaneously. Though TLS is seldom observed in relation to solid tumours, there have been reports of connections with examples such as lung, liver, breast, gastric carcinomas. The clinical manifestations of TLS include hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These indications if untreated lead to life-threatening complications such as acute renal failure, cardiac arrhythmias, seizures, and eventually death due to multiorgan failure. Therefore early detection of TLS is of vital importance. This can be accomplished by identification of high risk patients, implementation of suitable prophylactic measures andmonitoring of the electrolyte levels in patients undergoing chemotherapy.