• Tuberculosis and Respiratory Diseases
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• v.87 no.1
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• pp.22-30
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• 2024

Tumor immune evasion is a complex process that involves various mechanisms, such as antigen recognition restriction, immune system suppression, and T cell exhaustion. The tumor microenvironment contains various immune cells involved in immune evasion. Recent studies have demonstrated that granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce immune evasion in lung cancer by modulating neutrophils and myeloid-derived suppressor cells. Here we describe the origin and function of G-CSF and GM-CSF, particularly their role in immune evasion in lung cancer. In addition, their effects on programmed death-ligand 1 expression and clinical implications are discussed.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4315-4320
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• 2012

Background: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis. Aim of the study: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk. Results: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR=6.807, 95% CI=1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value=0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML. Conclusion: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

• Biomolecules & Therapeutics
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• v.25 no.5
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• pp.490-496
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• 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
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• v.17 no.2
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• pp.815-821
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• 2016

Background: Development of chronic myeloid leukemia (CML) involves formation of double strand breaks (DSBs) which are initially sensed by the ataxia telangiectasia mutated (ATM) signal kinase to induce a DNA damage response (DDR). Mutations or single nucleotide polymorphisms in ATM gene are known to influence the signaling capacity resulting in susceptibility to certain genetic diseases such as cancers. Materials and Methods: In the present study, we have analyzed -5144A>T (rs228589) and C4138T (rs3092856) polymorphisms of theATM gene through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 925 subjects (476 CML cases and 449 controls). Results: The A allele of -5144A>T polymorphism and T allele of C4138T polymorphism which were known to be influencing ATM signaling capacity are significantly associated with enhanced risk for CML independently and also in combination (evident from the haplotype and diplotype analyses). Significant elevation in the frequencies of both the risk alleles among high risk groups under European Treatment and Outcome Study (EUTOS) score suggests the possible role of these polymorphisms in predicting the prognosis of CML patients. Conclusions: This study provides the first evidence of association of functional ATM gene polymorphisms with the increased risk of CML development as well as progression.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8149-8153
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• 2016

An oncopathological state assessment was conducted among adults, children and teenagers in Aktobe region for 2004-2013. Overall the burden of mortality was in the range of 94.8-100.2 per 100,000 population, without any obvious trend over time. Ranking by pathology, the highest incidences among women were registered for breast cancer (5.8-8.4), cervix uteri (2.9-4.6), ovary (2.4-3.6) and corpus uteri, stomach, esophagus, without any marked change over time except for a slight rise in cervical cancer rates. In males, the first place in rank was trachea, bronchus and lung, followed by stomach and esophagus, which are followed by bladder, lymphoid and hematopoietic tissues pathology. Agian no clear trends were apparent over time. In children, main localizations in cancer incidence blood (acute lymphocytic leukemia, lymphosarcoma, acute myeloid leukemia, Hodgkin's disease), brain and central nervous system, bones and articular cartilages, kidneys, and eye and it's appendages, in both sexes. Similarly, in young adults, the major percentage was in blood and lymphatic tissues (acute myeloid leukemia, acute lymphocytic leukemia, Hodgkin's disease) a significant percentage accruing to lymphosarcoma, lymphoma, other myeloid leukemia and hematological malignancies as well as tumors of brain and central nervous system, bones and articular cartilages. This initial survey provides the basis for more detailed investigation of cancer epidemiology in Aktobe, Kazakhstan.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4367-4372
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• 2014

We here document discovery of expression profile of myeloid derived suppressor cells (MDSCs) in chronic hepatitis B (CHB) patients and changes in the course of disease. The study population was composed of 75 outpatient HBV cases and 15 healthy control cases. Peripheral blood samples were collected for separation of mononuclear cells. Levels of MDSCs labeled with Lin-DR-CD11b+CD33+ obtained from peripheral blood mononuclear cells (PBMC), were revealed to have significant differences between the CHB and other groups. They were 0.414% for health control cases and 0.226% for CHB cases (Z=-2.356, p=0.0189). It also observed that the group of HBeAg positive cases had significant difference in MDSCs/PBMC median ($X^2=11.877$, p=0.003), compared with group of HBeAg negative cases and the healthy control group. It suggested considerable MDSCs might be involved in HBeAg immune tolerance. In addition, negative correlations between MDSCs/PBMC and parameters of ALT, AST and TBil, while positive correlation between MDSCs/PBMC and ALB parameter were found. Multiple comparisons between the four phases and health control phase again, there was a statistically sifnificant difference ($X^2=17.198$, p=0.002). Taken together, these findings may provide a new immunotherapy strategy for reduced the expression levels of MDSCs in CHB patients, through induction of an autoimmune response to virus removal.

• Korean Journal of Clinical Pharmacy
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• v.19 no.2
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• pp.153-158
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• 2009

Background: Patients with chronic myeloid leukemia(CML) have different health status according to their disease conditions such as chronic phase(CP), accelerated phase(AP), blast crisis(BC), stage with MCyR(Major Cytogenetic Response); therefore, every patient has different quality of life related to their disease condition. Objectives: To measure the quality of life, this study compared and analyzed the utility weight in patients with CML. This study also evaluated the utility weight in order to view comparisons between the quality of life in a patient with CML to a patient with diabetes, which is a representative chronic disease. Methods: The disease scenario described 5 symptoms of the CP, AP, BC of the CML, the CML which gets the MCyR and the diabetes. Utility weight was developed using the EQ-5D method. All statistical data were analyzed by STATA 10.0 Results: 57 nurses(95%) out of 60 answered the questionnaire. In CP, the utility weight was 0.7946. In AP, it was 0.5301. and in BC, it was -0.2793. Survey data indicate that the worse the condition of a disease, the lower the utility weight. In case of the CML which gets the MCyR, the result was 0.7731(95% CI : 0.7384 - 0.8079). The general diabetes which has no complicating disease, the utility weight was 0.7481(95% CI : 0.6983 - 0.7978). Based on the result, it is evident that those with MCyR are not significantly different from people with general diabetes (p=0.4096) in views of the quality of life.

• Pediatric Infection and Vaccine
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• v.27 no.2
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• pp.134-139
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• 2020

Staphylococcus epidermidis is a part of the normal skin flora of humans. However, it can cause serious infections in people exposed to foreign bodies or in immunocompromised patients. A 13-year-old boy was hospitalized with fever and myalgia. Painful nodular lesions were detected on the scalp, arms, and legs. Pancytopenia and blasts were present in the peripheral blood. He was diagnosed with acute myeloid leukemia. Magnetic resonance imaging of the whole body showed multiple peripheral rim-enhancing, cyst-like lesions. Ultrasonography showed echogenic nodules inside the cystic lesions in the intramuscular space of the arms and legs. Therefore, cysticercosis was strongly suggested initially. However, an abscess was confirmed on sono-guided biopsy and S. epidermidis was isolated from a microbial culture of the tissue. We report a case of multiple disseminated lesions caused by S. epidermidis in a leukemia patient, initially mistaken for cysticercosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3793-3797
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• 2015

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder of pluripotent stem cells, caused by reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11), known as the Philadelphia chromosome. Materials and Methods: A total of 51 CML patients were recruited in this study. Complete blood counts of all CML patients were performed to find out their total leukocytes, hemoglobin and platelets. FISH was performed for the detection of BCR-ABL fusion and cryptogenic tests using bone marrow samples were performed for the conformation of Ph (9;22)(q34;q11) and variant translocation mechanisms. Results: In cytogenetic analysis we observed that out of 51 CML patients 40 (88.9%) were Ph positive and 4 (8.88%) had Ph negative chromosomes. Mean values of WBC 134.5 $10^3/{\mu}l$, hemoglobin 10.44 mg/dl, and platelets 288.6 $10^3/{\mu}l$ were observed in this study. Conclusions: In this study, Ph positive translocation between chromosome (9:22)(q34;q11) were observed in 40 (88.9%) CML patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4095-4101
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• 2015

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces $172^{nd}$ arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients.