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Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

  • Singdong, Roongrudee;Siriboonpiputtana, Teerapong;Chareonsirisuthigul, Takol;Kongruang, Adcharee;Limsuwanachot, Nittaya;Sirirat, Tanasan;Chuncharunee, Suporn;Rerkamnuaychoke, Budsaba
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4647-4653
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    • 2016
  • Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9 mutations in 100 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load > 50.0%) was predominantly observed in PV when compared with ET. Although a high level of JAK2 (V617F) allele burden was strongly associated with high WBC counts in both PV and ET, several hematological parameters (hemoglobin, hematocrit, and platelet count) were independent of JAK2 (V617F) mutational load. MPL (W515K/L) mutations could not be detected whereas CALR exon 9 mutations were identified in 35.7% of patients with JAK2 negative ET and 33.3% with JAK2 negative PMF. Conclusions: The JAK2 (V617F) allele burden may be involved in progression of MPNs. Furthermore, a high level of JAK2 (V617F) mutant allele appears strongly associated with leukocytosis in both PV and ET.

Analysis on the Characteyistics of Consumer′s Consumption Types of Environmently Friendly Agricultural Products (친환경 농산물 소비자의 소비행태에 관한 특성분석)

  • Bae Sung Eui;Yoon Jun Sang;Lee Jong Sang;Kim Chang Ho;Yoon Gil Sun
    • The Korean Journal of Community Living Science
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    • v.15 no.4
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    • pp.149-163
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    • 2004
  • The purpose of this study is to present a plan to activate the production and consumption of environmently friendly agricultural products through an analysis on the understanding degree, the level and inclination of consumption, the satisfaction degree of consumption, and the comprehension degree of production and circulation process of the environmently friendly agricultural products. 1 reviewed the literature and did survey In this study. The results are as follows : (1) As a result of an analysis on the understanding degree of the environmently friendly agricultural products, it is shown to get 6.37 points out of 10 and also, there is a difference between age, educational background, and income level. (2) In the case of research on the method to distinguish the environmently friendly agricultural products from others, it is proved that consumers have a strong faith on quality guarantee marks and there is a difference between gender, income level, and consumption period. (3) It is also shown that consumers purchase environmently friendly agricultural products for the family member's health in the survey on the motivation for purchasing them. And also, there is a difference between men and women. (4) The result of the survey on the consumption scale of the environmently friendly agricultural products shows that 94 people(60.3%) spend more than 50% of their gloss foodstuffs cost purchasing them and 20 people(12.8%) spend 30-50%. (5) In the survey on the amount and the frequency of the purchasing items of the envirounently friendly agricultural products, respondents count livestock products mostly in amount while point out main cereals and a kinds of soy and pastes in frequency. (6) Consumers ask that the price of environmently friendly agricultural products is a little expensive or reasonable and there is no differences between individual groups. (7) In the case of the purchase of foreign environmently friendly agricultural products, there are more people who want to purchase domestic ones than those who want foreign ones. Therefore, it is shown that environmently friendly agricultural products have a counterpower after the market-open to import. (8) As a result of the analysis on the quality of environmently friendly agricultural products, it is proved that they have better quality than general agricultural products and also, it is found out that women feel larger differences than men in quality. (9) In the analysis on the satisfaction degree of the environmently friendly agricultural products, it is proved that respondents trust the safety and nutrition of them whereas they are not satisfied with the external shape of them. (10) It is analyzed that tile conversion of consumer's consciousness is the most critical factor for development of environmently friendly agriculture. (11) The factors to activate the consumption of environmently friendly agricultural products are proved in order of the enlargement of direct transaction, the conversion of consumer's consciousness, the easiness of purchase, activating consumers'unions, and publicity.

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Evaluation of Nutritional Improvement by Total Parenteral Nutrition Guideline in Early Malnourished Inpatients (입원초기 영양불량 환자의 TPN 지침에 따른 영양개선 평가)

  • Cha, Yun Young;Kim, Jung Tae;Lim, Sung Cil
    • Korean Journal of Clinical Pharmacy
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    • v.23 no.4
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    • pp.365-372
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    • 2013
  • Background: Malnutrition of inpatients has been associated with higher morbidity, mortality, cost, and longer hospital stay. Total parenteral nutrition (TPN) therapy plays an important role in decreasing morbidity and mortality among critical inpatients in hospitals, and has been commonly used to improve clinical outcomes. However, only a few studies were conducted regarding patients' nutritional improvement by TPN. Method: This study therefore evaluated the changes in nutritional parameters by TPN therapy for early malnourished inpatients. Data from early malnourished inpatients who were treated with TPN therapy between January 2012 and June 2013 at the ${\bigcirc}{\bigcirc}$ university Hospital were studied retrospectively. Information regarding sex, age, underlying diseases, division, TPN (peripheral and central), and changes in nutritional parameters were collected by reviewing electronic medical records. The criteria for evaluation of the changes in nutritional parameters were included physical marker, body mass index (BMI), and biochemical markers, including albumin (Alb), total lymphocyte count (TLC), and cholesterol. Nutritional parameters were collected three times: pre-TPN, mid-TPN and end-TPN. A total of 149 patients (peripheral, 97; central, 52) was evaluated. Results: In all patients, the malnutrition number was significantly decreased following the complete TPN therapy (peripheral patients, pre-TPN: $3.33{\pm}0.12$, mid-TPN : $3.06{\pm}0.17$, and end-TPN: $2.85{\pm}0.21$ (p < 0.05); central patients, pre-TPN: $3.38{\pm}0.11$, mid-TPN: $3.06{\pm}0.13$, and end-TPN: $2.75{\pm}0.21$ (p < 0.05). The malnutrition number means number of nutrition parameters below normal range of malnutrition. In addition, all of the four nutritional parameters (BMI, Alb, TLC and cholesterol) were increased with duration of TPN periods for all patients, and the changes in the early stage were larger than in the late stage (p < 0.05). The nutritional parameters of non-cancer patients were increased to a greater extent compared to cancer patients with longer TPN therapy, but it was not significant. The nutritional parameters of younger patients (50-60 years) were also increased more than of older patients (70-80 years), but it was not significant. Conclusion: In conclusion, the TPN therapy decreases malnutritional status and improves nutritional parameters in malnourished patients, thereby decreasing morbidity and mortality. The combined evaluation of all four nutritional parameters is more accurate for nutritional assessment than a single one.

Studies on the Maintenance of Bioluminescence from Stored Photobacterium phosphoreum (Photobacterium phosphoreum의 생체발광 유지도에 관한 연구)

  • 김현숙;정성제;전억한
    • Microbiology and Biotechnology Letters
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    • v.28 no.2
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    • pp.117-123
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    • 2000
  • The object of this work is to improve the maintenance of bioluminescence from stored Photobacterium phosphoreum in a view of developing continuous monitoring system for pollutants. The long-term experiments were performed to determine the effect of storage temperature and immobilization on the maintenance of bioluminescence and viability of P. phosphoreum. A naturally luminescent bacterium, P. phosphoreum was starved in 2.5% Nael solution at $20^{\circ}C$, $4^{\circ}C$, -$20^{\circ}C$ and -$70^{\circ}C$ for 30 days. In vivo luminescence was measured by luminometry, and total cell concentrations and concentrations of culturable and viable cells were determined by acridine orange staining, dilution plate counting, and direct viable counting, respectively. The bioluminescence emission from cells stored at 4De was maintained up to 10 days while those with starved cells at other temperature ranges decreased to background level within 3 days. In terms of viability of cells, concentrations of cells stored at $20^{\circ}C$ were rapidly decreased as a result of cell lysis, leading to a drop in culturable and viable counts while cells stored at $4^{\circ}C$ was shown viable but nonculturable state during starvation. With immobilized cells on strontium alginate, the bioluminescence showed higher maintenance than free cells and decreased with count number of nonculturable cells.

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Effect of misting and wallowing cooling systems on milk yield, blood and physiological variables during heat stress in lactating Murrah buffalo

  • Yadav, Brijesh;Pandey, Vijay;Yadav, Sarvajeet;Singh, Yajuvendra;Kumar, Vinod;Sirohi, Rajneesh
    • Journal of Animal Science and Technology
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    • v.58 no.1
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    • pp.2.1-2.10
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    • 2016
  • Background: Heat stress adversely affects the physiological and metabolic status, and the productive performance of buffalo. Methods: The present study was conducted to explicate the effect of misting and wallowing cooling strategies during heat stress in lactating Murrah buffalo. The study was conducted for three months (May-July) of which first two months were hot dry and last month was hot humid. Eighteen lactating buffaloes, offered the same basal diet, were blocked by days in milk, milk yield and parity, and then randomly allocated to three treatments: negative control (no cooling), cooling by misting, and cooling by wallowing. Results: The results showed higher (P < 0.05) milk yield in buffaloes of misting and wallowing group compared to control during the experimental period however wallowing was found more (P < 0.05) effective during July (hot humid period). Both the treatments resulted into significant (P < 0.05) reduction in rectal temperature (RT) and respiratory rate (RR) compared to control animals during study period whereas wallowing was found to be effective on pulse rate (PR) only during July. Both treatments were resulted in mitigating the heat stress mediated decrease in packed cell volume (PCV), lymphocytopnoea and neutrophilia whereas decrease in total erythrocyte count (TEC) and monocytes was only mitigated by wallowing. Heat load induced alteration in serum creatinine and sodium concentration was significantly (P < 0.05) ameliorated by misting and wallowing whereas aspartate aminotransferase, alkaline phosphatase and superoxide dismutase activity, and reactive oxygen species concentration could be normalized neither by misting nor by wallowing. The significant (P < 0.05) increment in serum cortisol and prolactin levels observed in June and July period in control animals was significantly (P < 0.05) prevented by misting and wallowing. Conclusions: It can be concluded that misting and wallowing were equally effective in May and June (hot dry period) whereas wallowing was more effective during hot humid period in preventing a decline in milk production and maintaining physiological, metabolic, endocrine and redox homeostasis.

Study of the determination of 226Ra in soil using liquid scintillation counter (액체섬광계수기를 이용한 토양 중 226Ra 분석 방법 연구)

  • Jung, Yoonhee;Kim, Hyuncheol;Chung, Kun Ho;Kang, Mun Ja
    • Analytical Science and Technology
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    • v.29 no.2
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    • pp.65-72
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    • 2016
  • This study presented an analytical method for detecting radium in soils using a liquid scintillation counter (LSC). The isotope 226Ra was extracted from soil using the fusion method and then separated from interfering radionuclides using the precipitation method. Radium was coprecipitated as sulfate salts with barium (Ba) and then converted into Ba(Ra)CO3, which is soluble in an acidic solution. The isotope 222Rn, the decay progeny of 226Ra, was trapped in a water immiscible cocktail and analyzed by LSC. The pulse shape analysis (PSA) level was estimated using 90Sr and 226Ra standard solutions. The figure of merit was the highest at PSA 80, while the alpha spillover was the lowest at PSA 80. The counting efficiency was 243 ± 2% in a glass vial. This analytical method was verified with International Atomic Energy Agency (IAEA) reference materials, including IAEA-312, IAEA-314, and IAEA-315. The recovery ranged from 60–82%, while the relative bias between the measured value and the recommended value was less than 10%. The minimum detectable activity was 2.1 Bq kg−1 with dry mass 1 g, the background count rate of 0.02 cpm, the recovery rate of 70% and counting time of 30 min.

Risk of Treatment Related Death and Febrile Neutropaenia with First Line Palliative Chemotherapy for De Novo Metastatic Breast Cancer in Clinical Practice in a Middle Resource Country

  • Phua, Chee Ee;Tang, Weng Heng;Yusof, Mastura Md.;Saad, Marniza;Alip, Adlinda;See, Mee Hoong;Taib, Nur Aishah
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.23
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    • pp.10263-10266
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    • 2015
  • Background: The risk of febrile neutropaenia (FN) and treatment related death (TRD) with first line palliative chemotherapy for de novo metastatic breast cancer (MBC) remains unknown outside of a clinical trial setting despite its widespread usage. This study aimed to determine rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). Materials and Methods: Patients who were treated with first line palliative chemotherapy for de novo MBC from 2002-2011 in UMMC were identified from the UMMC Breast Cancer Registry. Information collected included patient demographics, histopathological features, treatment received, including the different chemotherapy regimens, and presence of FN and TRD. FN was defined as an oral temperature > $38.5^{\circ}C$ or two consecutive readings of > $38.0^{\circ}C$ for 2 hours and an absolute neutrophil count < $0.5{\times}10^9/L$, or expected to fall below $0.5{\times}10^9/L$ (de Naurois et al, 2010). TRD was defined as death occurring during or within 30 days of the last chemotherapy treatment, as a consequence of the chemotherapy treatment. Statistical analysis was performed using the SPSS version 18.0 software. Survival probabilities were estimated using the Kaplan-Meier method and differences in survival compared using log-rank test. Results: Between $1^{st}$ January 2002 and $31^{st}$ December 2011, 424 patients with MBC were treated in UMMC. A total of 186 out of 221 patients with de novo MBC who received first line palliative chemotherapy were analyzed. The mean age of patients in this study was 49.5 years (range 24 to 74 years). Biologically, ER status was negative in 54.4% of patients and Her-2 status was positive in 31.1%. A 5-flourouracil, epirubicin and cyclophosphamide (FEC) chemotherapy regimen was chosen for 86.6% of the cases. Most patients had multiple metastatic sites (58.6%). The main result of this study showed a FN rate of 5.9% and TRD rate of 3.2%. The median survival (MS) for the entire cohort was 19 months. For those with multiple metastatic sites, liver only, lung only, bone only and brain only metastatic sites, the MS was 18, 24, 19, 24 and 8 months respectively (p-value= 0.319). Conclusions: In conclusion, we surmise that FEC is a safe regimen with acceptable FN and TRD rates for de novo MBC.

Roles of Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratios in the Early Diagnosis of Malignant Ovarian Masses

  • Yildirim, Mem Arjen;Seckin, Kerem Doga;Togrul, Cihan;Baser, Eralp;Karsli, Mehmet Fatih;Gungor, Tayfun;Gulerman, Hacer Cavidan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6881-6885
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    • 2014
  • Background: The present study aimed to investigate the utility and importance of the various parameters of complete blood count panel for benign-malignant differentiation of adnexal masses. Materials and Methods: This retrospective study involved 316 patients with documented benign and 253 patients with malignant adnexal masses who underwent primary surgical treatment at a tertiary referral center. Prior to the study, all benign and malignant cases were compared within their own groups and then the benign and malignant cases were compared to each other. For all cases, cut-off, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), neutrophil, lymphocyte, platelet and CA-125 parameters, and the results were compared in regards to the groups. Results: NLR, PLR, neutrophil, CA-125, and platelet values were higher in the malignant compared to the benign cases (p<0.01). The lymphocyte value was lower in the malignant cases (p<0.01). No significant differences were found for basophils and eosinophils (p > 0.05). For CA-125, the sensitivity, specificity, PPV and NPV for all cases were 78%, 62%, 62% and 78%, respectively. For NLR, they were 65.6%, 72.1%, 65.3%, and 72.3%, and for PLR, 48%, 81%, 67%, and 66%. Additionally, the sensitivity and specificity were 55% and 77% for CA-125, 66% and 58% for NLR, and 61% and 58% for PLR in early malignant cases. Conclusions: NLR and PLR appear to be useful methods that can be applied together with CA-125 due to the relatively high sensitivity values for the malign-benign differentiation of ovarian masses. Although the specificity of these parameters is lower than CA-125, especially in cases with early malignant ovarian pathology, their sensitivity being higher is promising for the early diagnosis of ovarian cancer. It can be used to detect ovarian malignancies in the early stages, and it will increase the treatment options and improve survival rates.

Lack of Prognostic Value of Mean Corpuscular Volume with Capecitabine Therapy in Metastatic Breast Cancer

  • Bozkurt, Oktay;Berk, Veli;Kaplan, Muhammed Ali;Cetin, Bulent;Ozaslan, Ersin;Karaca, Halit;Inanc, Mevlude;Duran, Ayse Ocak;Ozkan, Metin
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2501-2504
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    • 2014
  • Background: Capecitabine is an oral fluoropyrimidine derivative which is frequently used alone or in combination regimens for the treatment of metastatic breast cancer. Although overall and progression free survivals have increased in recent years with the use of new generation drugs, predictive factors that would further improve the outcomes are needed. Previous studies have demonstrated the relation between post-treatment increase in mean corpuscular volume (MCV) and predicting therapy response as well as survival. The present study investigated the clinical impact of MCV elevation in metastatic breast cancer patients treated with capecitabine. Materials and Methods: The data of a total of 82 patients from three centers followed between June 2005 and June 2013 were retrospectively analyzed. The demographic data and hormone receptor status of the patients, as well as initial examination before and after treatment and data concerning progression were recorded. MCV ${\geq}100$ fl was considered as macrocytosis. Capecitabine was given at a dose of $2500mg/m^2$ daily for 14 days every three weeks. Pre-treatment and post-treatment MCV and other parameters of complete blood count were recorded. Post-treatment initial evaluation was performed after 2 cycles of therapy. Results: The median age of the patients was 46.5 years (range 26-72 years) and 54% were premenopausal. Performance status was ECOG 0 and 1 in 81 (99%) patients. The median number of cycles for capecitabine therapy was 5 (min-max: 2-18). The median ${\Delta}MCV$ level (post-treatment values at sixth week - baseline) was 6.4. Whilst ${\Delta}MCV$ was ${\geq}6.4$ in 42 patients, it was <6.4 in 40 patients. Clinical benefit (complete response+partial response+stable disease) was observed in 37 (88%) of 42 patients with a median ${\Delta}MCV$ ${\geq}6.4$ and in 30 (75%) of 40 patients with ${\Delta}MCV$ <6.4 with no statistically significant difference (p=0.158). No significant difference was determined between the group with ${\Delta}MCV$ ${\geq}6.4$ and the group with ${\Delta}MCV$ <6.4 in terms of progression-free survival (11 vs 12 months) (p=0.55) and overall survival (20 months vs. 24 months) (p=0.11). Conclusions: The identification of new predictive markers in metastatic breast cancer is very important. In some recent studies, increase in MCV has been suggested as a marker in tumor response. In the present study, however, no significant difference was determined between tumor response and increase in MCV. Further studies including higher numbers of patients are needed to determine whether increase in MCV is a predictive marker or not.

Validity and Necessity of Sub-classification of N3 in the 7th UICC TNM Stage of Gastric Cancer

  • Li, Fang-Xuan;Zhang, Ru-Peng;Liang, Han;Quan, Ji-Chuan;Liu, Hui;Zhang, Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.2091-2095
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    • 2013
  • Background: The $7^{th}$ TNM staging is the first authoritative standard for evaluation of effectiveness of treatment of gastric cancer worldwide. However, revision of pN classification within TNM needs to be discussed. In particular, the N3 sub-stage is becoming more conspicuous. Methods: Clinical data of 302 pN3M0 stage gastric cancer patients who received radical gastrectomy in Tianjin Medical University Cancer Institute and Hospital from January 2001 to May 2006 were retrospectively analyzed. Results: Location of tumor, depth of invasion, extranodal metastasis, gastric resection, combined organs resection, lymph node metastasis, rate of lymph node metastasis, negative lymph nodes count were important prognostic factors of pN3M0 stage gastric cancers. TNM stage was also associated with prognosis. Patients at T2N3M0 stage had a better prognosis than other sub-classification. T3N3M0 and T4aN3aM0 patients had equal prognosis which followed the T2N3M0. T4aN3bM0 and T4bN3aM0 had lower survival rate than the formers. T4bN3bM0 had worst prognosis. In multivariate analysis, TNM stage group and rate of lymph node metastasis were independent prognostic factors. Conclusions: The sub-stage of N3 may be useful for more accurate prediction of prognosis; it should therefore be applied in the TNM stage system.