• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2631-2634
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• 2014

Background: p53 gene is a well-known tumor suppressor gene that has several polymorphisms in both its exons and introns. It has been suggested that intron 3 16 bp duplication polymorphism may affect the gene function resulting in reduction or suppression of p53 anti tumor activity. In most case control studies a duplicated allele has been noticeably more frequent in cases rather than controls but there are also conflicting results. The aim of this study was to assess the association of intron 3 16 bp duplication polymorphism of p53 with breast cancer risk among Iranian-Azeri population. We also analyzed the clinicopathological information of patients as an epidemiological description of breast cancer in the north-west of Iran. Materials and Methods: This case-control study was performed on 221 breast cancer patients and 170 controls. Genomic DNA was extracted from peripheral blood samples and tumor tissues. p53 PIN3 genotype was determined using electrophoresis of PCR products on 8% non-denaturing polyacrylamide gels and silver staining. Results: In the control and case groups, respectively, 62.9% and 61.1% had no 16 bp insertion (A1A1 genotype), 7.1% and 7.7% had insertion in both p53 alleles (A2A2) and 30% and 31.2% were heterozygous (A1A2). There was no significant difference between genotype frequencies as well as allelic frequencies in two case and control groups. Conclusions: According to the result of the present study, the intron 3 16 bp duplication polymorphism of p53 could not be assessed as a marker of risk factor for predisposition to breast cancer in Azeri population. However, a high frequency of A2 allele (22.1%) in our population suggested that intron 3 16 bp duplication polymorphism may be a valuable marker for study in other cancers with well designed large groups.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.76 no.1
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• pp.15-22
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• 2014

Background: Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion. Methods: A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30. Results: The M30 levels in pleural fluid were significantly higher in patients with tuberculosis ($2,632.1{\pm}1,467.3U/mL$) than in patients with lung cancer ($956.5{\pm}618.5U/mL$), parapneumonic effusion ($689.9{\pm}413.6U/mL$), and transudates ($273.6{\pm}144.5U/mL$; all p<0.01). The serum levels were not significantly different among the disease groups. Based on receiver operating characteristics analysis, the area under the curve of M30 for differentiating tuberculous pleural effusion from all other effusions was 0.93. In the immunohistochemical analysis of M30, all pathologic types of cancer cells showed moderate to high expression, and the epithelioid cells in granulomas showed high expression in tuberculous pleural tissues. Conclusion: Caspase-cleaved cytokeratin 18 was most prominently observed in tuberculous pleural effusion and showed utility as a clinical marker. The main source of M30 was found to be the epithelioid cells of granulomas in tuberculous pleural tissues.

• Clinical and Experimental Pediatrics
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• v.54 no.8
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• pp.340-344
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• 2011

Purpose: Brain natriuretic peptide (BNP) has been considered a biochemical marker for myocarditis in Kawasaki disease. We performed this study to determine its quantitative significance. Methods: We attempted to correlate log-transformed BNP concentrations (log-BNP) and clinical, laboratory, and echocardiographic variables in 81 children with Kawasaki disease. Stepwise multiple linear regression analysis was used to determine the variables independently associated with log-BNP concentration. Results: Serum C-reactive protein level (P<0.0001), serum alanine aminotransferase concentration (P =0.0032), white blood cell count (P=0.0030), and left ventricular mass index (P=0.0024) were positively related with log-BNP, and hemoglobin level (P<0.0001), serum albumin level (P<0.0001), $Na^+$ concentrations (P<0.0001), left ventricular fractional shortening (P=0.0080), and peak early diastolic tissue velocity of the left ventricular basal lateral segment (P=0.0045) were negatively related to the log-BNP concentration. Multiple regression analysis showed that serum albumin concentration ($R_2$=0.31, P=0.0098) and left ventricular mass index ($R_2$=0.09, P=0.0004) were significantly associated with the log-BNP concentration. Conclusion: Elevated BNP levels during the acute phase of Kawasaki disease may be attributable to cardiac dysfunction associated with the increase in left ventricular mass, and log-BNP concentration may be a quantitative biochemical marker of myocarditis in Kawasaki disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7351-7355
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• 2014

Background: Laryngeal carcinogenesis is a multifactorial process that has not been fully elucidated. Despite extensive research, reliable markers with diagnostic and prognostic value are still lacking. It was recently reported that an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) may correlate with an increased risk of recurrence, tumor aggressiveness and poorer prognosis in various malignancies. The aim of this study was to examine whether NLR could be used as an inflammatory marker to differentiate laryngeal squamous cell carcinoma (LSCC) patients from benign laryngeal lesion (BLL) and precancerous laryngeal lesion (PLL) patients. Materials and Methods: This retrospective study was performed on 209 patients admitted to a tertiary referral center with laryngeal lesions and undergoing biopsies to establish their histopathological diagnosis. We reviewed the patient files for their clinical, histopathological and laboratory data. The patients were divided into three groups according to their histopathological findings, as BLL, PLL and LSCC groups. The patients in the PLL group were also divided into three subgroups as mild, moderate and severe dysplasia/carcinoma in situ (CIS) subgroups. The groups were compared for NLR and the other laboratory data. Results: The mean NLRs of the BLL, PLL and the LSCC groups were $2.12{\pm}0.86$, $2.32{\pm}0.68$ and $3.46{\pm}1.51$, respectively, and the difference was statistically significant (p=0.001). The mean NLRs of the patients with PLL and LSCC were significantly higher than the patients with BLL (p=0.031 and p=0.001, respectively). The mean NLRs were similar among mild dysplasia, moderate dysplasia and severe dysplasia / CIS groups (p>0.05). Conclusions: To our knowledge, this is the first study investigating NLR in BLL, PLL and LSCC. NLR is an inexpensive, reproducible and widely available blood test, and could be a useful inflammatory marker to differentiate LSCC from BLL and PLL.

• Development and Reproduction
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• v.5 no.2
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• pp.151-158
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• 2001

Genomic DNA from the blood of crucian carp(Carassius carassiu) from lake and aquaculture facility in Kunsan, Korea was extracted in order to identify genetic differences by polymerase chain reaction-randomly amplified polymorphic DNAs(PCR-RAPD). Out of 12 primers, 6 generated 266 highly reproducible RAPD markers, producing approximately 2.1 polymorphic bands per primer in crucian carp from lake. The degree of similarity varied from 0.18 to 0.76 as calculated by bandsharing analysis in crucian carp from lake. The RAPD outlines obtained with DNA of two different crucian carp populations from Kunsan were different(0.47 from lake and 0.70 from aquaculture facility, respectively). The electrophoretic analysis of polymerase chain reaction-randomly amplified polymorphic DNAs(PCR-RAPD) products showed high levels of similarity between different individuals in crucian carp from aquaculture facility. This result implies the genetic similarity due to raising in the same environmental condition or inbreeding within the crucian carp from aquaculture facility in Kunsan. In other words, crucian carp may have high levels of genome DNA diversity due to the introduction of the wild population from the other sites of Knsan even if it may be the geographical diverse distribution of this species. Generally, the RAPD polymorphism generated by these primers may be useful as a genetic marker for strain or population identification of important aquacultural fish species, crucian carp. However, in future, additional populations and sampling sites will be necessary to complement weak points.

• Journal of Trauma and Injury
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• v.20 no.2
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• pp.138-143
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• 2007

Purpose: $S100{\beta}$, a marker of traumatic brain injury (TBI), has been increasingly focused upon during recent years. $S100{\beta}$, is easily measured not only in cerebrospinal fluid (CSF) but also in serum. After TBI, serum S 10019, has been found to be increased at an early stage. The purpose of this study was to evaluate the clinical correlations between serum $S100{\beta}$, and neurologic outcome, and severity in traumatic brain injury. Methods: From August 2006 to October 2006, we made a protocol and studied prospectively 42 patients who visited the emergency room with TBI. Venous blood samples for $S100{\beta}$, protein were taken within six hours after TBI and vital signs, as well as the Glasgow Coma Scale (GCS), were recorded. The final diagnosis and the severity were evaluated using the Abbreviated Injury Score (AIS), and the prognosis of the patients was evaluated using the Glasgow Outcome Score (GOS). Results: Thirty-eight patients showed a favorable prognosis (discharge, recovery, transfer), and four showed an unfavorable prognosis. Serum $S100{\beta}$, was higher in patients with an unfavorable prognosis than in patients with a favorable prognosis, and a significant difference existed between the two groups ($0.74{\pm}1.50\;{\mu}g/L$ vs $7.62{\pm}6.53\;{\mu}g/L$ P=0.002). A negative correlation existed between serum $S100{\beta}$, and the Revised Traumatic Score (R2=-0.34, P=0.03), and a positive correlation existed between serum $S100{\beta}$, and the Injury Severity Score (R2=0.33, P=0.03). Furthermore, the correlation between serum $S100{\beta}$, and the initial GCS and the GCS 24 hours after admission to the ER were negative (R2=-0.62, P<0.001; R2=-0.47, P=0.005). Regarding the GOS, the mean serum concentration of $S100{\beta}$, was $7.62\;{\ss}{\partial}/L$ (SD=${\pm}6.53$) in the expired patients, $1.15\;{\mu}g/L$ in the mildly disable patient, and $0.727\;{\mu}g/L$ (SD=${\pm}0.73$) in the recovered patients. These differences are statistically significant (p<0.001). Conclusion: In traumatic brain injury, a higher level of serum concentration of $S100{\beta}$, has a poor prognosis for neurologic outcome.

• Herbal Formula Science
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• v.24 no.2
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• pp.80-99
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• 2016

Objectives : Instrumental chemical analysis was utilized to investigate the effect of Add-Omit-Saenghyeoryunbu-eum(AO-SHU) on diabetic treatment. One of the most exciting, yet also controversial, arguments is the safety and biological mechanisms of the natural medicine on human body. Therefore, the aim of this study is to provide a better understanding on bioactive chemical components, hazards of heavy metal contamination and biological mechanism of the diabetic medicine composed of 12 different natural herbs. Methods : To study bioactive compound and metallic component in the diabetic medicine in detail, LC-MS/MS (Liquid Chromatography-Mass/Mass), GC (Gas Chromatography) and ICP (Inductively Coupled Plasma) were utilized to characterize the extract of the diabetic medicine and the result was compared with 18 marker substances selected from literature survey. In addition, in vitro assay experiments including GPR 119 activity and human DGAT-1 inhibition, and OGTT (Oral Glucose Tolerance Test) were performed to verify the effectiveness of this medicine on diabetic treatment. Results : Out of 18 marker substances, 9 bioactive compounds were identified from LC-MS/MS analysis which include Citruline, Catalpol, Berberine, Ginsenoside Rb1, Ginsenoside Rg1, Oleanolic acid, β-Sitosterol, Mangiferin, and Schizandrin. ICP study on 245 residual pesticides revealed that 239 species were not detected but 6 species, Dimethomorph, Trifloxystrobin, Pyraclostrobin, Isoprocarb, Carbaryl and Flubendiamide, while the amounts are trace levels, below permitted concentrations. The biological activity was observed in vitro assay and Oral Glucose Tolerance Test(OGTT), which are consistent with a preliminary clinical test result, a drop in blood sugar level after taking this herbal medicine. Conclusions : Instrumental chemical analysis using LC-MS/MS, GC, and ICP was conducted successfully to identify bioactive compounds in AO-SHU for the treatment of diabetes, finding 9 bioactive compounds. Furthermore, in vitro assay experiments and OGTT show that AO-SHU has its biological activities, which imply that it can be a candidate for the future diabetes remedy.

• The Korea Journal of Herbology
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• v.27 no.5
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• pp.99-107
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• 2012

Objectives : This study was conducted to investigate the anti-obesity effects of mixed water extract of Plantaginis Semen & Poria (CJB) on obese rats induced with high fat diet. Method: Male Sprague-Dawley rats were divided into three groups; Normal group, high-fat (HF) group, HF+CJB(100 mg/kg, P.O.) for 8 weeks. The body weight, food intake and weights of adipose tissues were measured, respectively. Lipid profiles in serum were analyzed by automatic analyzer of blood. Obese marker proteins and the changes of NPY and LR immunoreactivities in hypothalamus were analyzed by Western blot and immunohistochemistry. Results : CJB significantly reduced body weight, food intake, adipose tissue weights compared to HF group. Serum triglyceride and total cholesterol were significantly higher in HF group than in Normal group however, CJB significantly lowered those of HF group. HDL-cholesterol level in CJB groups was elevated compared to HF group. The pAMPK in hypothalamus were decreased in that of HF group and that of CJB group decreased. Inversely, ACC was increased in HF group and that of CJB groups decrease. Expression of $PPAR{\gamma}$ in hypothalamus was increased by CJB treatment. However, $PPAR{\alpha}$ levels in CJB group were decreased compared to HF group. The expressions of NPY and LR in PVN and ARC of hypothalamus were decreased in CJB group, respectively. Conclusion : Administration of CJB can play anti-obesity through regulations of NPY and LR activities and obesity marker proteins in obese rat's hypothalamus.

• Journal of Life Science
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• v.21 no.12
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• pp.1726-1731
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• 2011

Human Stem Cell Factor (hSCF) is a cytokine that binds to the c-Kit receptor and plays an important role in hematopoiesis, spermatogenesis, and melanogenesis. To produce the human Stem Cell Factor (hSCF) recombinant protein, we constructed a germline transgenic silkworm using the piggyback vector. The expression of the hSCF gene was driven by the Drosophila heat shock protein 70 (dHsp70) promoter. 3XP3 promotor-driven EGFP was used as a marker which allowed us to rapidly distinguish the transgenic silkworm. A mixture of the donor and helper vector was micro-injected into 1,020 eggs of bivoltin silkworms, Keomokjam. We obtained approximately 22 G1 broods that were EGFP-positive. The expression of the hSCF gene in the transgenic silkworm was analyzed by SDS-PAGE and immunoblotting. Also, analysis of insertion sites into the silkworm genome using inverse PCR showed that exogenous DNA was inserted into the transgenic silkworm genome. These results show that successfully constructed transgenic silkworm expresses the hSCF recombinant protein.