• 한국미생물·생명공학회지
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• 제47권4호
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• pp.651-661
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• 2019

Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3959-3962
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• 2016

The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our ndings indicated that promoter methylation of TET2 signi cantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was signi cantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to con rm our ndings.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.3159-3161
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• 2013

Aim: We designed this study to investigate the neutrophil lymphocyte ratio as a biomarker in distinguishing colonic polyps which are neoplastic or non-neoplastic. Materials and Methods: One hundred and twenty-five patients with colonic polyps were enrolled into the study. The following data were obtained from a computerized patient registry database: mean platelet volume (MPV), uric acid (UA), platelet count (PC), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT) and the neutrophil to lymphocyte ratio (NLR). Exclusion criteria were active infectious disease, hematological disorders, and malignancies. Colonic polyps divided into two groups as neoplastic polyps (tubular adenoma, villous adenoma, tubulovillous adenoma) and non-neoplastic polyps (hyperplastic polyps, inflammatory pseudopolyps etc). The relationship between colonic polyp type and NLR was evaluated with statistical analysis. Results: There were 67 patients (53.6%) with neoplastic and 58 (46.4%) patients with non-neoplastic polyps. Mean NLRs of neoplastic and non-neoplastic groups were respectively $3.32{\pm}2.54$ and $2.98{\pm}3.16$ (P<0.05). Conclusion: Although sensitivity and specificity are not high, NLR may be used as a biomarker of neoplastic condition of colonic polyps.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.157-164
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• 2022

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.

• Clinical and Experimental Pediatrics
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• 제45권8호
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• pp.1000-1006
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• 2002

목 적 : 혈액-종양 환자에서 항암화학요법으로 치료하는 과정 중에서 중증 폐 질환 합병증이 발생할 수 있다. 그 원인으로는 감염성 또는 비 감염성의 원인들이 있고 특히 이들 환자에서 폐 질환 합병증 또는 호흡부전으로 인한 인공환기 치료시에는 예후가 나쁘다고 알려져 있다. 저자들은 본원 소아 중환자실에 입원한 혈액-종양 환아에서 면역 저하상태(절대 호중구수 < $1,000/mm^3$)의 지표의 하나인 호중구 감소증과 폐합병증의 유무에 따른 원인과 예후를 분석하였다. 방 법: 1997년 1월부터 2001년 5월까지 서울중앙병원 소아 중환자실에 입원한 혈액-종양 환아 95명의 의무기록을 후향적으로 분석하여 폐 합병증의 원인과 진단 방법, 호중구 감소상태와 폐 합병증의 유무에 따른 사망률을 분석하였다. 결 과 : 연령 분포는 생후 2개월에서 18세까지 평균 8.5세였고, 원인 혈액-종양 질환으로는 급성 림프성 백혈병 31명, 급성 골수성 백혈병 9명, 림프선 종양 11명, 뇌종양 8명, 고형종양 25명, 그 외 혈액질환이 11명이었다. 95명의 환아 중 중환자실 입원당시의 원인으로는 패혈증 23명(24%), 패혈증을 동반한 폐렴 22명(23%), 급성 호흡부전 12명(12.5%), 의식소실 16명(17%), 급성 신부전, 심부전의 기타 질환이 15명(16%)이었다. 이들 중에서 폐 합병증을 동반한 환아는 42명(44%), 동반하지 않은 환아는 53명(56%)이었다. 폐 합병증으로는 폐렴, 늑막삼출, 급성호흡부전, 기흉이 있었다. 폐 합병증이 있는 환아 중 호중구 감소상태의 환아는 29명(69%), 호중구 감소상태가 아닌 환아는 13명(31%)이었다. 원인으로는 감염성인 경우가 37명(88%), 비 감염성인 경우가 2명(5%)이었고, 구분이 어려운 경우가 3명(7%)이었다. 시행된 각각의 검체에서 균이 검출된 빈도를 비교하면 혈액배양검사는 42명중 15명(36%), 객담검사는 42명 중 7명(16%), 소변 배양검사는 42명 중 3명(7%), 인공환기요법 중인 환아에서 시행한 기도내 분비물 배양검사는 28명 중 5명(18%)이었다. 주요 원인균으로는 Candida species 12명(33%), MRSA 6명(17%), Pseudomonas aeruginosa 4명(11%), Klebsiella pneumoniae 4명(11%)이었다. 골수이식술을 받은 환자는 모두 10명으로 이중 7명에서 폐 합병증이 있었고, 원인균이 동정된 경우는 모두 3명으로 각각 S.maltophilia, K.pneumoniae, Parainfluenza virus이었다. 10명의 환아 중 8명이 사망하였고 사망 원인으로는 폐혈증이 5명, 급성호흡부전 증후군이 2명, 뇌출혈이 1명이었다. 전체 사망률은 56.8%였고, 사망률을 보면 이중 폐 합병증이 있고 호중구 감소상태의 환아는 76%(22명), 폐 합병증이 있으나 호중구 감소상태가 아닌 환아는 69% (9명), 폐 합병증이 없으나 호중구 감소상태의 환아는 46%(7명), 폐 합병증이 없으며 호중구 감소상태가 아닌 환아는 43%(16명)이었다. 결 론 : 중환자실에 입원한 혈액-종양 환아에서 폐 합병증의 원인으로 감염성인 경우가 많았다. 사망률은 폐 합병증이 있는 경우가 없는 경우에 비해 높았으며, 특히 폐 합병증이 있는 환아 중 호중구 감소상태의 환아에서 사망률이 높았다. 이 결과로 미루어 폐 합병증이 있는 혈액-종양 환자에서 더 적극적인 원인 규명과 치료를 시도해야 할 것으로 생각된다.

• Journal of Yeungnam Medical Science
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• 제20권1호
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• pp.79-84
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• 2003

Pyoderma gangrenosum is uncommon neutrophilic dermatosis characterized by richness of the mature neutrophilic polynuclear dermal infiltrate. Pyoderma gangrenosum is associated with variable diseases, most commonly inflammatory bowel disease, hematological diseases, malignancies, but it is reported rarely in rheumatoid arthritis. We report a case of pyoderma gangrenosum in rheumoid arthritis patient. A 50-year-old woman admitted to our hospital due to painful pretibial ulcerative skin lesions. She had been treated as rheumatoid arthritis for 8 years. At admission, body temperature was $36.5^{\circ}C$ and other vital sign was unremarkable. Physical examination revealed right pretibial ulceration, multiple pustules on left pretibial area and both palms. Laboratory studies revealed WBC count 7,600/uL (neutrophils 60.3%, eosinophil 3.2%), hemoglobin 11.4 g/dL, platelet count 319,000/uL, ESR 65 mm/hour. Other lab findings were also unremarkable. Skin biopsy was done, which showed dense dermal infiltrate of neutrophils and wound culture were negative. By 8 weeks after systemic high dose corticosteroid (1 mg/kg/day), cyclosporine A (5 mg/kg/day), sulfasalazine 2 g therapy, symptoms and skin ulceration were being improved. Without skin relapse, she is followed up our hospital with low dose corticosteroid and sulfasalazine.

• Journal of Korean Neurosurgical Society
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• 제51권3호
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• pp.127-134
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• 2012

Objective: To analyze the prognostic factors thought to be related with survival time after a spinal metastasis operation. Methods: We retrospectively analyzed 217 patients who underwent spinal metastasis operations in our hospital from 2001 to 2009. Hematological malignancies, such as multiple myeloma and lymphoma, were excluded. The factors thought to be related with postoperative survival time were gender, age (below 55, above 56), primary tumor growth rate (slow, moderate, rapid group), spinal location (cervical, thoracic, and lumbo-sacral spine), the timing of radiation therapy (preoperative, postoperative, no radiation), operation type (decompressive laminectomy with or without posterior fixation, corpectomy with anterior fusion, corpectomy with posterior fixation), preoperative systemic condition (below 5 points, above 6 points classified by Tomita scoring), pre- and postoperative ambulatory function (ambulatory, non-ambulatory), number of spinal metastases (single, multiple), time to spinal metastasis from the primary cancer diagnosis (below 21 months, above 22 months), and postoperative complication. Results: The study cohort mean age at the time of surgery was 55.5 years. The median survival time after spinal operation and spinal metastasis diagnosis were 6.0 and 9.0 months. In univariate analysis, factors such as gender, primary tumor growth rate, preoperative systemic condition, and preoperative and postoperative ambulatory status were shown to be related to postoperative survival. In multivariate analysis, statistically significant factors were preoperative systemic condition (p=0.048) and postoperative ambulatory status (p<0.001). The other factors had no statistical significance. Conclusion: The factors predictive for postoperative survival time should be considered in the surgery of spinal metastasis patients.

• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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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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• 제17권12호
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• pp.5217-5221
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• 2016

Objective: A study of primary cancer morbidity among children and subsequent calculation of average annual incidence were carried out for boys and girls, and young men and women in Kazakhstan. Methods: The investigated population lived in three areas of the Aral Sea region: designated catastrophe (Aral, Kazalt, Shalkar regions), crisis (Zhalagash, Karmakshy, Shiely regions), pre-crisis (Irgiz, Arys, Ulytau regions). Zhanaarka region of Karaganda oblast was applied as a control. Parameters were retrospective analyzed for the 10 years from 2004 to 2013. Result: The results indicate that indices of children cancer morbidity were slightly higher in the Aral Sea region than in the control district, but they were comparable with similar data from studies in other regions. In all areas of the Aral Sea region, except for Ulytau, primary cancer morbidity exceeded the control level by 1.3-2.7 times (4.7%000). Hematological malignancies, including solid tumors - tumors of musculoskeletal system and skin, digestive system, brain and central nervous system predominated. Stress levels in zones of the Aral Sea region were slightly higher in the crisis zone than in the catastrophe zone that can be explained by the phenomenon of wave-like dynamics of disease growth risk. Gender differences in characteristics of malignancy formation were not more pronounced in the studied region. Conclusion: Indices of children cancer are slightly higher in the Aral Sea region than in the control area of Kazakhstan, but they are comparable to results for other regions.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.629-635
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• 2014

Background: Acute myeloid leukemia (AML) is a fatal hematological malignancy which is resistant to a variety of chemotherapy drugs. Myeloid cell leukemia-1 (Mcl-1), a death-inhibiting protein that regulates apoptosis, has been shown to be overexpressed in numerous malignancies. In addition, it has been demonstrated that the expression level of the Mcl-1 gene increases at the time of leukemic relapse following chemotherapy. The aim of this study was to target Mcl-1 by small interference RNA (siRNA) and analyze its effects on survival and chemosensitivity of acute myeloid leukemia cell line HL-60. Materials and Methods: siRNA transfection was performed with a liposome approach. The expression levels of mRNA and protein were measured by real-time quantitative PCR and Western blot analysis, respectively. Trypan blue assays were performed to evaluate tumor cell growth after siRNA transfection. The cytotoxic effects of Mcl-1 siRNA (siMcl-1) and etoposide were determined using MTT assay on their own and in combination. Apoptosis was quantified using a DNA-histone ELISA assay. Results: Transfection with siMcl-1 significantly suppressed the expression of Mcl-1 mRNA and protein in a time-dependent manner, resulting in strong growth inhibition and spontaneous apoptosis. Surprisingly, pretreatment with siMcl-1 synergistically enhanced the cytotoxic effect of etoposide. Furthermore, Mcl-1 down-regulation significantly increased apoptosis sensitivity to etoposide. No significant biological effects were observed with negative control siRNA treatment. Conclusions: Our results suggest that specific suppression of Mcl-1 by siRNA can effectively induce apoptosis and overcome chemoresistance of leukemic cells. Therefore, siMcl-1 may be a potent adjuvant in leukemia chemotherapy.