Himani, Bhankar;Meera, Sikka;Abhimanyu, Sharma;Usha, Rusia
Asian Pacific Journal of Cancer Prevention
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제17권5호
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pp.2559-2564
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2016
Purpose: To compare Ki-67 index and microvessel density MVD) in multiple myeloma and non-myeloma patients and their correlation with each other and other prognostic markers. Materials and Methods: Forty patients were enrolled in this study between 2011-2013, 30 with multiple myelomas and 10 with non-malignant disease as controls. Proliferative activity was analyzed by Ki-67 and microvessel density (MVC) was assessed by CD34 and compared between two groups. In myeloma patients, correlation between Ki-67, MVD and other prognostic factors was assessed by Pearson correlation coefficient. Results: According to Durie Salmon staging criteria, 13 patients were of stage 1, 5 of stage II and 12 of stage III. Ki-67 expression showed a positive correlation with MVD (r=0.729, p<0.001) and was significantly higher (p<0.0001) in myeloma patients (range 35-80%, mean 60.1 %) as compared to controls (range 8-25%, mean 18.1%). $MVD/mm^2$ was also significantly (p<0.0001) higher in myeloma patients (range $62-237/mm^2$, mean $178.0/mm^2$) than controls (range $5.2-50/mm^2$, mean $18.3/mm^2$). Ki-67 and MVD, both increased progressively with increasing stage of myeloma. Ki-67 showed significant positive correlation with blood urea and lactate dehydrogenase and a significant negative correlation with serum albumin. MVD showed a significant positive correlation with blood urea, lactate dehydrogenase, serum creatinine, ${\beta}2$ microglobulin and skeletal lesions. Conclusions: Ki-67 and MVD are indicators of aggressiveness and poor prognosis having significant correlation with each other and other prognostic markers of multiple myeloma. Routine assessment of these markers may help to identify high risk patients, who may benefit from with more aggressive therapy.
Background: Cadmium exposure may induce chronic intoxication with renal damage. Silver soldering may be a source of cadmium exposure. Methods: We analyzed working environment measurement data and periodic health screening data from a small-scale silver soldering company with ten workers. Concentrations of cadmium in air from working environment measurement data were obtained. Concentrations of blood and urinary cadmium, urine protein, and urine β2-microglobulin (β2M) were obtained. The generalized linear model was used to identify the association between blood and urine cadmium and urine β2M concentrations. Clinical features of chronic cadmium intoxication focused with toxicological renal effects were described. Results: The mean duration of work was 8.5 years (standard deviation [SD] = 6.9, range = 3-20 years). Cadmium concentrations in air were ranged from 0.006 to 0.015 mg/㎥. Blood cadmium concentration was elevated in all ten workers, with a highest level of 34.6 ㎍/L (mean = 21.288 ㎍/L, SD = 11.304, range = 9.641-34.630 ㎍/L). Urinary cadmium concentration was elevated in nine workers, with a highest level of 62.9 ㎍/g Cr (mean = 22.151 ㎍/g creatinine, SD = 19.889, range = 3.228-62.971 ㎍/g creatinine). Urine β2M concentration was elevated in three workers. Urinary cadmium concentration was positively associated with urine protein concentration (beta coefficient = 10.27, 95% confidence interval = [4.36, 16.18]). Other clinical parameters were compatible with renal tubular damage. Conclusion: Cadmium intoxication may occur at quite low air concentrations. Exposure limit may be needed to be lowered.
The purpose of this study was to investigate the effects of green tea catechin on renal dysfunction and blood presure change in chronic cadmium poisoned rats. Sprague-Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal group and three cadmium poisoned groups. Cadmium groups were classified to catechin free diet(Cd-0C group) 0.25% catechin diet(Cd-0.25C group) and 0.5% catechin diet(Cd-0.5C group) according to the levels of catechin supplement. Animals were raids for 20weeks. Cadmium were supplied as drinking water of 50ppm Cd2+ Morphological changes shown through a light microscope and an electro-microscope revealed the mitochondria and tubule epithelial cell edema in Cd -0C group but they were alleviated in catechin supplementation. The urinary $\beta$2-microglobulin that measured to observe the glomerular injury were higher in Cd-poisoned groups than in normal group but they was lowered by catechin supplementation. Glomerular filtration ratios(GFR) in Cd-poisoned groups were significantly lower than in normal group but that of catechin supplementation group was similar to normal group. This suggested that catechin protected the kidney from the functional damage. Angiotensin converting enzyme(ACE) activity and blood pressure(BP) in Cd-poisoned groups were significantly higher than in normal group. Heart rate was tended to increase in Cd-poisoned groups. The results indicate that green tea catechin supplementation on chronic cadmium-poisoned rats normalized the renal dysfunction and blood pressure system.
The purpose of this study was to investigate the effects of vitamin E on the oxidative damage and glomerular filteration rates(GFR) of kidney in streptozotocin(STZ) induced diabetic rats. Sprague-Dawley male rats weihing 100$\pm$10gm were randomly assigned to one normal and three STZ-induced diabetic groups which were subdivided into vitamin E free diet(DM-0E group)40mg vitamin E per kg diet(DM-40E group) and 400mg vitamin E per kg diet (DM-400E group), Vitamin E level of normal group was 40mg per kg diet. diabetes was experimentally induced by intravenous injection of 55mg/kg of body weight of STZ in citrate buffer(pH 4.3) after 4 weeks feeding of experimental diets. Animals were sacrificed at the 6th day of diabetic states. Activities of xanthine oxidase(XOD) in DM-0E DM-40 and DM-400E groups were significantly increased by 133%, 110%, and 74% respectively compared to normal group. The contents of microsomal superoxide radical(O2) in kidney were 106% and 119% higher of DM-0E and DM-40E groups than normal group respectively but that of DM-400E group was similar to normal group. The level of urnary microalbumin in DM-0E group was increased as 5 times much as normal group at the 6th day. Those of DM-40E and DM-400E groups were decreased to 16% and 36% respectively compared to DM-0E group. The content of urinary $\beta$2-microglobulin in DM-0E DM-40E and DM-400E group were increased by 268%, 181% and 163% respectively compared to normal group. GFR in DM-0E and DM-40E were significantly increased but was nor significantly different from DM-400E groups compared to normal group. In conclusion the supplementation of dietary vitamin E reduced peroxidative damage of renal glomerular and renal dysfunction in diabetic rats.
Background: Even though rarely found in Indonesia, the incidence of multiple myeloma (MM) is increasing every year. Bone involvement of MM is the most often a clinical disorder which leads to worsening clinical conditions and low quality of life of patients. Purpose: To determine the clinicopathology profile of bone involvement of MM patients in Indonesia. Materials and Methods: The cross-sectional study of MM conducted at Dharmais National Cancer Hospital (DNCH) by collecting data from medical records of MM patients who came to DNCH in period 2008-2012. Results: There were 39 MM patients all with age above 60 years. There were 56.4% male and 43.6% female patients. Most were diagnosed at stage III (32.4%), and 41% had obesity. The comorbid conditions were anemia (82.9%), hypoalbuminemia (60%), increased creatinine level (38.5%), increased ${\beta}2$ microglobulin level (94.1%), increased LDH level (23.1%) and plasmocytes above 30% (65%), but only 4.2% patients presented with hypercalcemia. Meanwhile, bone involvement occurred in 76.9% of MM patients with 4 lesions on average and a maximum of 16 lesions. The locations of bone lesions were spine (70%), skull (70%), pelvis (33.3%), humerus (30%), and femur (30%). Conclusions: The incidence of MM in Indonesia is increasing annually with bone involvement in more than three-fourths, but interestingly without hypercalcemia.
Kim, Hyun-Pyo;Jin, Mi-Rim;Kim, Ick-Young;Ahn, Byung-Yoon;Kang, Seong-Man;Choi, Eui-Ju;Kim, Joon;Kim, Ik-Hwan;Ahn, Kwang-Seog
Journal of Microbiology and Biotechnology
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제9권3호
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pp.346-351
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1999
Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition and elimination by cytotoxic T cells. In order to investigate whether the major histocompatibility complex (MHC) class I-mediated antigen processing machinery is preserved in human lung cancer cell lines, we examined the expression of multiple components of the MHC class I antigen processing pathway, including transporter associated with antigen processing (TAP), $\beta_2$-microglobulin, MHC class I molecules, and chaperones which have not been previously examined in this context. Row cytometry analysis showed that the cell surface expression of MHC class I molecules was downregulated in all of the cell lines. While some cell lines showed no detectable expression of MHC class I molecules, pulse-chase experiments showed that MHC class I molecules were synthesized in the other cell lines but not transported from the endoplasmic reticulum to the cell surface. Low or nondetectable levels of TAP1 and/or TAP2 expression were demonstrated by Western blot analysis in all of the cell lines, representing a variety of lung tissue types. In some cases, this was accompanied by loss of tapasin expression. Our findings suggest that downregulation of antigen processing may be one of the strategies used by tumors to escape immune surveillance. This study provides further information for designing the potential therapeutic applications such as immunotherapy and gene therapy against cancers.
Objective: Quantitative polymerase chain reaction (qPCR) has been extensively used in the field of mesenchymal stem cell (MSC) research to elucidate their characteristics and clinical potential by normalization of target genes against reference genes (RGs), which are believed to be stably expressed irrespective of various experimental conditions. However, the expression of RGs is also variable depending on the experimental conditions, which may lead to false or contradictory conclusions upon normalization. Due to the current lack of information for a clear list of stable RGs in bovine MSCs, we conducted this study to identify suitable RGs in bovine MSCs. Methods: The cycle threshold values of ten traditionally used RGs (18S ribosomal RNA [18S], beta-2-microglobulin [B2M], H2A histone family, member Z [H2A], peptidylprolyl isomerase A [PPIA], ribosomal protein 4 [RPL4], succinate dehydrogenase complex, subunit A [SDHA], beta actin [ACTB], glyceraldehyde-3-phosphate dehydrogenase [GAPDH], TATA box binding protein [TBP], and hypoxanthine phosphoribosyltrasnfrase1 [HPRT1]) in bovine bone marrow-derived MSCs (bBMMSCs) were validated for their stabilities using three types of RG evaluation algorithms (geNorm, Normfinder, and Bestkeeper). The effect of validated RGs was then verified by normalization of lineage-specific genes (fatty acid binding protein 4 [FABP4] and osteonectin [ON]) expressions during differentiations of bBMMSCs or POU class 5 homeobox 1 (OCT4) expression between bBMMSCs and dermal skins. Results: Based on the results obtained for the three most stable RGs from geNorm (TBP, RPL4, and H2A), Normfinder (TBP, RPL4, and SDHA), and Bestkeeper (TBP, RPL4, and SDHA), it was comprehensively determined that TBP and RPL4 were the most stable RGs in bBMMSCs. However, traditional RGs were suggested to be the least stable (18S) or moderately stable (GAPDH and ACTB) in bBMMSCs. Normalization of FABP4 or ON against TBP, RPL4, and 18S presented significant differences during differentiation of bBMMSCs. However, although significantly low expression of OCT4 was detected in dermal skins compared to that in bBMMSCs when TBP and RPL4 were used in normalization, normalization against 18S exhibited no significance. Conclusion: This study proposes that TBP and RPL4 were suitable as stable RGs for qPCR study in bovine MSCs.
Ahmadzadeh, Ahmad;Yekaninejad, Mir Saeed;Saffari, Mohsen;Pakpour, Amir H;Aaronson, Neil K
Asian Pacific Journal of Cancer Prevention
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제17권1호
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pp.255-259
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2016
Background: Reliable and validated instruments are needed in order to study the quality of life in myeloma patients. This study aimed to translate and explore the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) myeloma module (QLQ-MY20) in Iranian patients. Materials and Methods: Two hundred and fifteen patients with multiple myeloma (MM) were recruited from Imam Khomeini Hospital, Tehran. A standard forward-backward translation procedure was implemented. Participating patients were asked to complete the EORTC QLQ-C30 and the QLQ-MY20 three times, at study entry, after two weeks, and again after three months. Data were tested for the range of measurement, internal consistency, test-retest reliability, known group comparison, responsiveness and factor structure. Results: Mean age of the patients was 60.7 years. No floor and ceiling effects were seen for the QLQ-MY20. Cronbach's ${\alpha}$ was greater than 0.80 for all three multi-item scales (ranging from 0.82 to 0.93). All four scales had test-retest reliability of 0.85 or greater. Results of the confirmatory factor analysis that the hypothesized 3-scale measurement model of the QLQ-MY20. Moreover, the Persian version for the QLQ-MY20 differentiated between subgroups of the patients in terms of beta-2 microglobulin, fracture and performance status. The responsiveness of the QLQ-MY20 to change over time was confirmed within 3 months. Conclusions: the results of our study indicate that our Iranian version of the QLQ-MY20 is a feasible, reliable and valid questionnaire for assessing the condition-specific quality of life of patients with MM.
Lee, Jung-Min;Han, Young-Hwan;Choi, Su-Jeong;Park, Ju-Seong;Jang, Jeong-Jun;Bae, Re-Ji-Na;Lee, Mi Ju;Kim, Myoung Jun;Lee, Yong-Hoon;Kim, Duyeol;Lee, Hye-Young;Park, Sun-Hee;Park, Cheol-Beom;Kang, Jin Seok;Kang, Jong-Koo
Toxicological Research
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제30권4호
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pp.305-309
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2014
Recently, there has been an increase in the use of several nephrotoxicity biomarkers in preclinical experiments. In addition, it has been indicated that the result may have been influenced by secondary factors, such as sample storage condition or storage period. In this study, we have assessed the variation in urinary nephrotoxicity biomarkers as a result of urine storage conditions and storage period of the urine. Urine was sampled from specific pathogen-free Sprague-Dawley rats (19 weeks old), which were housed individually in hanged stainless steel wire mesh cages. Urine was stored at $20^{\circ}C$, at $4^{\circ}C$, or at $-70^{\circ}C$ after sampling. The levels of the biomarkers such as beta-2 microglobulin (B2M), cystatin-C (Cys-C), N-acetyl-${\beta}$-D-glucosaminidase (NAG), micro albumin (MA), micro protein (MP) were measured at 6, 24, 48 and 144 hr after sampling. The B2M level was significantly decreased at 6, 24, 48, and 144 hr compared to 0 hr at $-70^{\circ}C$ (p < 0.05, p < 0.01, p < 0.05, and p < 0.05, respectively) and 24 and 144 hr at $20^{\circ}C$ (p < 0.01, p < 0.01, respectively). The Cys-C level was significantly decreased at 144 hr compared to 0 hr at $4^{\circ}C$ (p < 0.01), at $20^{\circ}C$ (p < 0.05) and at $70^{\circ}C$ (p < 0.01). MP and MA levels were not different for 144 hr in all storage conditions. Taken together, B2M and Cys-C levels were modulated by storage temperature and period. For the enhancement of test accuracy, it is suggested that strict protocols be established for samples to minimize the effects of the storage conditions on the detected levels of biomarkers.
Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.
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