COUP-TFII plays a role in cAMP-induced Schwann cell differentiation and in vitro myelination by up-regulating Krox20.

Schwann cells (SCs) are known to produce myelin for saltatory nerve conduction in the peripheral nervous system (PNS). Schwann cell differentiation and myelination processes are controlled by several transcription factors including Sox10, Oct6/Pou3f1, and Krox20/Egr2. Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan receptor that plays a role in the development and differentiation. However, the role of COUP-TFII in the transcriptional regulatory network of SC differentiation has not been fully identified yet. Thus, the objective of this study was to investigate the role and molecular hierarchy of COUP-TFII during cAMP-induced SC differentiation. Our results showed that dibutyryl-cAMP (db-cAMP) increased expression levels of COUP-TFII along with the expressions of Oct6, Krox20, and myelin-related genes known to be related to SC differentiation. Our mechanistic studies showed that COUP-TFII acted downstream of Hsp90/ErbB2/Gab1/ERK-AKT pathway during db-cAMP-induced SC differentiation. In addition, we found that COUP-TFII induced Krox20 expression by directly binding to Krox20-MSE8 as revealed by chromatin immunoprecipitation assay and promoter activity assay. In line with this, the expression of COUP-TFII was increased before up-regulation of Oct6, Krox20, and myelin-related genes in the sciatic nerves during early postnatal myelination period. Finally, COUP-TFII knockdown by COUP-TFII siRNA or via AAV-COUP-TFII shRNA in SCs inhibited db-cAMP-induced SC differentiation and in vitro myelination of sensory axons, respectively. Taken together, these findings indicate that COUP-TFII might be involved in postnatal myelination through induction of Krox20 in SCs. Our results present a new insight into the transcriptional regulatory mechanism in SC differentiation and myelination.

Secretory SERPINE1 Expression Is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis.

Contrary to many reports that antiplatelet agents inhibit cancer growth and metastasis, new solid tumors have been reported in patients receiving long-term antiplatelet therapy. We investigated the effects of these agents directly on cancer cells in the absence of platelets to mimic the effects of long-term therapy. When four antiplatelet agents (aspirin, clopidogrel, prasugrel, and ticagrelor) were administered to colon cancer cells, cancer cell proliferation was inhibited similarly to a previous study. However, surprisingly, when cells were treated with a purinergic P2Y12 inhibitor (purinergic antiplatelet agent), the motility of the cancer cells was significantly increased. Therefore, gene expression profiles were identified to investigate the effect of P2Y12 inhibitors on cell mobility, and Serpin family 1 (SERPINE1) was identified as a common gene associated with cell migration and cell death in three groups. Antiplatelet treatment increased the level of SERPINE1 in cancer cells and also promoted the secretion of SERPINE1 into the medium. Increased SERPINE1 was found to induce MMP1 and, thus, increase cell motility. In addition, an increase in SERPINE1 was confirmed using the serum of patients who received these antiplatelet drugs. With these results, we propose that SERPINE1 could be used as a new target gene to prevent the onset and metastasis of cancer in patients with long-term antiplatelet therapy.

High anemia prevalence in Korean older adults, an advent healthcare problem: 2007-2016 KNHANES.

BACKGROUND: Anemia is associated with high morbidity and mortality in older people. However, the prevalence and characteristics of anemia in older individuals are not fully understood, and national data on these aspects in older Korean adults are lacking. This study aimed to evaluate the prevalence and characteristics of anemia in older adults using data from the Korea National Health and Nutrition Examination Survey (KNHANES), which is a nationwide cross-sectional epidemiological study conducted by the Korean Ministry of Health and Welfare. METHODS: Data from a total of 62,825 participants of the 2007-2016 KNHANES were compiled and analyzed to investigate differences in participant characteristics and potential risk factors for anemia. Differences in clinical characteristics of participants were compared across subgroups using the chi-square test for categorical variables and independent t-test for continuous variables. Univariate and multivariate analyses using logistic regression were performed to identify related clinical factors. RESULTS: The prevalence of anemia was higher in the population aged ≥65 years than in the younger population. Anemia was also more prevalent among females than among males, but this difference was not significant in people aged > 85 years. Being underweight, receiving a social allowance, living alone, and having comorbidities such as hypertension, rheumatoid arthritis, diabetes mellitus (DM), cancer, and chronic renal failure (CRF) were more common among older adults with anemia than among the population without anemia. In univariate and multivariate analyses, older age, female sex, underweight, and presence of comorbidities including rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia. CONCLUSIONS: This study revealed that age, female sex, underweight, and the presence of comorbidities such as rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia in older Korean adults. Further study on causal relationships between anemia and other variables in the older population is necessary.

Evaluation of neutrophil extracellular traps as the circulating marker for patients with acute coronary syndrome and acute ischemic stroke.

INTRODUCTION: Neutrophil extracellular traps (NETs) are known to be induced by various factors. In this study, we tried to identify circulating levels of NETs in patients with acute coronary syndrome (ACS) and acute ischemic stroke (AIS) and to confirm its suitability as a new circulating marker in their detection. METHODS: We prospectively enrolled 95 patients with a diagnosis of ACS (N = 37) or AIS (N = 58) in Dong-A University Hospital, Busan, Korea. The control group was selected from healthy adults (N = 25) who visited the hospital for health screening. Circulating levels of NETs were evaluated by measuring plasma concentrations of double-stranded DNA (dsDNA) and DNA-histone complex. RESULTS: The concentrations of dsDNA were statistically higher in patients with ACS or AIS than those in the control group (both P < .001). In the univariable and multivariable analyses, statistically significant risk factors were troponin I (TnI) level and dsDNA concentration in the ACS group (P = .046 and P = .015, respectively) and only dsDNA concentration in the AIS group (P = .002). In the receiver operating characteristic curve analyses, the area under the curve values for TnI level and dsDNA concentration in the ACS group were 0.878 and 0.968, respectively, and the value for dsDNA concentration in the AIS group was 0.859. CONCLUSIONS: In this study, it was confirmed that the circulating level of NETs was increased in patients with ACS and AIS at initial presentation. Findings in this study show that NETs could be used as a new circulating marker for the initial diagnosis of ACS or AIS.

Early prediction of severity in acute ischemic stroke and transient ischemic attack using platelet parameters and neutrophil-to-lymphocyte ratio.

BACKGROUND: It is still not easy to predict severity promptly in patients with acute ischemic stroke (AIS) and transient ischemic attack (TIA). We investigated that platelet parameters or combinations of them could be a useful tool for early prediction of severity of AIS and TIA at admission and after 3 months. METHODS: We prospectively recruited 104 patients newly diagnosed with AIS and TIA. We investigated their neutrophil-to-lymphocyte ratio (NLR) and platelet parameters. According to the Modified Rankin Scale scores, the patients were divided into two groups. RESULTS: In receiver operating characteristic (ROC) curve analyses, mean platelet volume (MPV), NLR/platelet count (PLT), MPV/PLT, MPV*NLR, and MPV*NLR/PLT showed statistically significant results in both at admission and after 3 months. Values of area under ROC curves for those tests at admission were 0.646, 0.697, 0.664, 0.708, and 0.722, respectively. Also, values after 3 months were 0.591, 0.661, 0.638, 0.662, and 0.689, respectively. CONCLUSION: MPV*NLR/PLT could be used as a relatively good tool for predicting severity at the time of admission and after 3 months than other parameters or combinations of them. Further studies have to be carried out to investigate the best parameter for predicting the severity of AIS and TIA.

Holotoxin A1 Induces Apoptosis by Activating Acid Sphingomyelinase and Neutral Sphingomyelinase in K562 and Human Primary Leukemia Cells.

Marine triterpene glycosides are attractive candidates for the development of anticancer agents. Holotoxin A1 is a triterpene glycoside found in the edible sea cucumber, Apostichopus (Stichopus) japonicus. We previously showed that cladoloside C2, the 25(26)-dihydro derivative of holotoxin A1 induced apoptosis in human leukemia cells by activating ceramide synthase 6. Thus, we hypothesized that holotoxin A1, which is structurally similar to cladoloside C2, might induce apoptosis in human leukemia cells through the same molecular mechanism. In this paper, we compared holotoxin A1 and cladoloside C2 for killing potency and mechanism of action. We found that holotoxin A1 induced apoptosis more potently than cladoloside C2. Moreover, holotoxin A1-induced apoptosis in K562 cells by activating caspase-8 and caspase-3, but not by activating caspase-9. During holotoxin A1-induced apoptosis, acid sphingomyelinase (SMase) and neutral SMase were activated in both K562 cells and human primary leukemia cells. Specifically inhibiting acid SMase and neutral SMаse with chemical inhibitors or siRNAs significantly inhibited holotoxin A1-induced apoptosis. These results indicated that holotoxin A1 might induce apoptosis by activating acid SMase and neutral SMase. In conclusion, holotoxin A1 represents a potential anticancer agent for treating leukemia. Moreover, the aglycone structure of marine triterpene glycosides might affect the mechanism involved in inducing apoptosis.

Platelet microRNA for predicting acute myocardial infarction.

Acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide, while early diagnosis still represents an upmost priority. While platelet activation is critical for AMI pathogenesis, the role of platelet microRNAs (pmiRNAs) as biomarkers for AMI is unclear. Furthermore, correlations between the levels of pmiRNAs and indices of platelet activity are also unknown. Expression of platelet miR-1, miR-21, miR-126, miR-150 and miR-223 were prospectively assessed in 20 ST-segment elevation myocardial infarction (STEMI) patients, and 40 healthy volunteers. Platelet reactive units (PRU) were assessed with cartridge analyzer, and vasodilator-stimulated phosphoprotein (VASP) was measured by flow cytometry. There were no significant changes in pmiR-1 expression. Expressions of pmiR-21 and pmiR-126 were decreased, while pmiR-150 and pmiR-223 were increased in STEMI patients when compared to controls (all p < 0.01). However, only pmiR-126 exhibited correlation with plasma cardiac troponin I (r = - 0.556, p = 0.011) in STEMI. There was no correlation between pmiRNAs with PRU or VASP during admission, or at 48 h post-stenting. Among tested pmiRNAs, pmiR-126 may serve as a potential novel biomarker for STEMI, while pmiR-1, pmiR-21, pmiR-150, and pmiR-223 were not particularly useful. Moreover, since assessed pmiRNA expression did not correlate well with platelet activity indices their potential diagnostic utility is quite limited.

Defining predictive values using three different platelet function tests for CYP2C19 phenotype status on maintenance dual antiplatelet therapy after PCI.

Published data suggests that the presence of CYP2C19*2 or *3 loss of function (LOF) alleles is indicative of increased platelet aggregation and a higher risk of adverse cardiovascular events after clopidogrel administration. We sought to determine cut-off values using three different assays for prediction of the CYP2C19 phenotype in Korean percutaneous coronary intervention (PCI) patients. We enrolled 244 patients with drug-eluting stent implantation who were receiving clopidogrel and aspirin maintenance therapy for one month or more. Platelet reactivity was assessed with light transmittance aggregometry (LTA), multiple electrode aggregometry (MEA) and the VerifyNow P2Y12 assay (VN). The CYP2C19 genotype was analyzed by polymerase chain reaction (PCR) and snapshot method. The frequency of CYP2C19 LOF allele carriers was 58.6%. The cut-off values from LTA, MEA and VerifyNow for the identification of LOF allele carriers were as follows: 10 µM ADP-induced LTA ≥ 48 %, VN>242 PRU and MEA ≥ 37 U. Between the three tests, correlation was higher between LTA vs. VN assays (r=0.69) and LTA vs. MEA (r=0.56), with moderate agreement (κ=0.46 and κ=0.46), but between VN assay and MEA, both devices using whole blood showed a lower correlation (r=0.42) and agreement (κ=0.3). Our results provide guidance regarding cut-off levels for LTA, VerifyNow and MEA assays to detect the CYP2C19 LOF allele in patients during dual antiplatelet maintenance therapy.

Report of the International Council for Standardization in Haematology working group for standardization of reticulocyte parameters.

INTRODUCTION: The International Council for Standardization in Haematology convened a working group to assess and propose improvements upon the state of standardization and harmonization of reticulocyte parameters among commercial hematology analyzers. METHODS: An international group of laboratory hematologists prospectively collected and analyzed clinical samples using locally available IVD commercial hematology analyzers. Eight hundred and fifty-five total samples were collected at 6 sites using 9 distinct analyzer types. Samples were assessed for reticulocyte percent (RET%), immature reticulocyte fraction (IRF), and reticulocyte hemoglobin content (RHC). Method comparison and regression statistics were calculated. These analyses were used to determine whether statistical recalibration offered a potential avenue for increasing comparability between these methods. RESULTS: While methods producing reticulocyte percent were the most comparable in this study, the state of harmonization for the IRF and RHC was reduced with pearson correlation coefficients ranging from 0.955 to 0.77 and 0.927 and 0.680, respectively. Nevertheless, use of parameters from the Passing Bablok regression substantially improved the comparability of the results. In addition, precision data was derived which also demonstrated substantial differences between analyzer systems. CONCLUSION: While reticulocyte counting is correlated between the automated methods evaluated in this study, the current state of harmonization of other reticulocyte parameters is not as strong. A major challenge in moving this field forward is the need for commutable materials to facilitate comparisons between analyzers not co-located. A potential alternate approach to improve the current state would be instrument re-calibration. However, this is challenging both technically and due to national regulatory frameworks.

Current Status of Flow Cytometric Immunophenotyping of Hematolymphoid Neoplasms in Korea.

Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCI-HLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization. Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey. We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positive/negative criteria, and reporting. Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positive/negative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included. Conclusions: This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Clinical significance of preoperative serum vascular endothelial growth factor, interleukin-6, and C-reactive protein level in colorectal cancer.

BACKGROUND: Angiogenesis is a multistep process in which many growth factors and cytokines have an essential role. Vascular endothelial growth factor (VEGF) is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells through specific cell surface receptors. The interleukin-6 (IL-6) pathway is another mechanism linking angiogenesis to malignancy. C-reactive protein (CRP), a representative marker for inflammation, is known for its association with disease progression in many cancer types. The aim of this study was to determine preoperative serum levels of VEGF, IL-6, and CRP in colorectal carcinoma, and to correlate them with disease status and prognosis. METHODS: A 132 of 143 patients who underwent curative resection for colorectal cancer were enrolled in this study. 11 patients with resection margin positive were excluded. Factors considered in analysis of the relationship between VEGF, IL-6, and CRP and histological findings. Patient prognosis was investigated. Serum levels of VEGF and IL-6 were assessed using Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured using immunoturbidimetry. RESULTS: Median follow-up duration was 18.53 months (range 0.73-43.17 months) and median age of the patients was 62 years (range, 26-83 years). Mean and median levels of VEGF and CRP in colorectal cancer were significantly higher than in the normal control group; 608 vs. 334 pg/mL and 528 (range 122-3242) vs. 312 (range 16-1121) (p < 0.001); 1.05 mg/dL vs. 0.43 mg/dL and 0.22 (range 0.00-18.40) vs. 0.07 (range 0.02-6.94) (p = 0.002), respectively. However mean and median level of IL-6 in patients were not significantly higher than in control; 14.33 pg/mL vs. 5.65 pg/mL and 6.00 (range 1.02-139.17) vs. 5.30 (4.50-13.78) (p = 0.327). Although IL-6 and CRP levels were not correlated with other pathological findings, VEGF level was significantly correlated with tumor size (p = 0.012) and CEA (p = 0.038). When we established the cutoff value for VEGF (825 pg/mL), IL-6 (8.09 pg/mL), and CRP (0.51 mg/dL) by Receiver Operating Characteristic (ROC) curve, we noted that high VEGF levels tended to reduce overall survival (p = 0.053), but not significantly. However, IL-6 and CRP demonstrated no significance with regard to disease free survival (p = 0.531, p = 0.701, respectively) and overall survival (p = 0.563, p = 0.572, respectively). Multivariate analysis showed that VEGF (p = 0.032), CEA (p = 0.012), lymph node metastasis (p = 0.002), and TNM stage (p = 0.025) were independently associated with overall survival. CONCLUSIONS: Preoperative serum VEGF and CRP level increased in colorectal cancer patients. High VEGF level has been proposed as a poor prognostic factor for overall survival in patients with colorectal cancer.

Clinical significances of preoperative serum interleukin-6 and C-reactive protein level in operable gastric cancer.

BACKGROUND: The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy. Because the C-reactive protein (CRP) is a representative marker for inflammation, CRP has recently been associated with the progression of disease in many cancer types. The principal objective of this study was to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and to correlate them with disease status and prognosis. METHODS: A total of 115 patients who underwent gastrectomy were enrolled in this study. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumor size, depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (6th AJCC Stage Groupings: The staging systems; Primary tumor, regional LN, metastasis). RESULTS: Increases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels were correlated with invasion depth (P < 0.001, P = 0.001), LN metastasis (P < 0.001, P = 0.024) and TNM stage (P < 0.001, P < 0.001). The presence of peritoneal seeding metastasis is associated with IL-6 levels (P = 0.012). When we established the cutoff value for IL-6 level (6.77 pg/dL) by ROC curve, we noted significant differences in time to progression (TTP; P < 0.001) and overall survival (OS; P = 0.010). However, CRP evidenced no significance with regard to patients' TTP and OS levels. Serum IL-6 levels were correlated positively with CRP levels (r2 = 0.049, P = 0.018). CONCLUSION: Preoperative serum IL-6 and CRP levels might be markers of tumor invasion, LN metastasis, and TNM stage. Preoperative high IL-6 levels were proposed as a poor prognostic factor for disease recurrence and overall survival in patients with gastric cancers.

Cytogenetic characterizations of central nervous system tumors: the first comprehensive report from a single institution in Korea.

The World Health Organization (WHO) classification of central nervous system (CNS) tumors incorporates morphology, cytogenetics, molecular genetics, and immunologic markers. Despite the relatively large number of CNS tumors with clonal chromosome abnormalities, only few studies have investigated cytogenetic abnormalities for CNS tumors in Korea. Thus, we investigated 119 CNS tumors by conventional G-banded karyotypes to characterize patterns of chromosomal abnormalities involving various CNS tumors, and 92.4% of them were cultured and karyotyped successfully. Totally, 51.8% of karyotypable CNS tumors showed abnormal cytogenetic results, including neuroepithelial tumors (75.0%), meningeal tumors (71.1%), pituitary adenomas (4.2%), schwannomas (44.4%), and metastatic tumors (100.0%). Glioblastomas had hyperdiploid, complex karyotypes, mainly involving chromosomes Y, 1, 2, 6, 7, 10, 12, 13, and 14. Monosomy 22 was observed in 56.4% of meningiomas. There was a significant increase in the frequencies of karyotypic complexity according to the increase of WHO grade between grades I and II (P=0.0422) or IV (P=0.0101). Abnormal karyotypes were more complex at high-grade tumors, suggesting that the karyotype reflects the biologic nature of the tumor. More detailed cytogenetic and molecular characterizations of CNS tumors contribute to better diagnostic criteria and deeper insights of tumorigenesis, eventually resulting in development of novel therapeutic strategies.

Recent advances in cytogenetic characterization of multiple myeloma.

The detection of cytogenetic abnormalities in multiple myeloma (MM) has received more importance over last years for risk stratification and the new risk-adapted treatment strategies. Conventional G-banding analysis should be included in a routine procedure for the initial diagnostic workup for patients suspected of MM. However, the detection of chromosomal abnormalities in MM by conventional cytogenetics is limited owing to the low proliferative activity of malignant plasma cells as well as the low number of plasma cells in bone marrow specimens. Fluorescence in situ hybridization (FISH) or microarray-based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.

Performance evaluation of new Abbott Alinity hq hematology analyzer.

INTRODUCTION: Abbott Alinity hq is a next-generation automated hematology analyzer providing complete blood count (CBC) with 6-part white blood cells (WBC) differential counts. The purpose of this study was to evaluate the performance of the analyzer to verify the diagnostic and clinical utility of the Abbott Alinity hq automated system. METHODS: We evaluated specimen stability, precision, linearity, carry-over, and method comparison to assess the performance of Alinity hq. For comparison of the Alinity hq with Sysmex XN-9000, totally 314 samples from adult and pediatric patients including both normal and abnormal hematology profiles were analyzed in parallel. The Alinity hq was also compared with the manual differential counts for the same 314 samples. RESULTS: At 4°C, the Alinity hq analyzer showed no significant changes in CBC and WBC differential count up to 48 hours. When stored at room temperature (18-25°C), all parameters except the mean platelet volume (MPV) were stable up to 36 hours. The Abbott Alinity hq analyzer demonstrated excellent reproducibility and between-batch precision for all CBC and WBC differential parameters. WBC, red blood cells (RBC), hemoglobin (HGB), and platelets showed good linearity and acceptable carry-over. Comparison with a Sysmex XN-9000 analyzer and manual 400-cell differential showed excellent correlation for CBC and WBC differential count parameters (correlation coefficient = 0.815-0.999) except for mean corpuscular hemoglobin concentration (MCHC) and basophils. CONCLUSION: We performed initial validation studies and confirmed performance specifications on specimen stability, precision, linearity, carry-over, and method comparison. The Abbott Alinity hq analyzer showed good analytical performance for all standard CBC parameters.

Recent progress in laboratory diagnosis of thalassemia and hemoglobinopathy: a study by the Korean Red Blood Cell Disorder Working Party of the Korean Society of Hematology.

Genetic hemoglobin disorders are caused by mutations and/or deletions in the α-globin or ß-globin genes. Thalassemia is caused by quantitative defects and hemoglobinopathies by structural defect of hemoglobin. The incidence of thalassemia and hemoglobinopathy is increased in Korea with rapid influx of people from endemic areas. Thus, the awareness of the disease is needed. α-thalassemias are caused by deletions in α-globin gene, while ß-thalassemias are associated with decreased synthesis of ß-globin due to ß-globin gene mutations. Hemoglobinopathies involve structural defects in hemoglobin due to altered amino acid sequence in the α- or ß-globin chains. When the patient is suspected with thalassemia/hemoglobinopathy from abnormal complete blood count findings and/or family history, the next step is detecting hemoglobin abnormality using electrophoresis methods including high performance liquid chromatography and mass spectrometry. The development of novel molecular genetic technologies, such as massively parallel sequencing, facilitates a more precise molecular diagnosis of thalassemia/hemoglobinopathy. Moreover, prenatal diagnosis using genetic testing enables the prevention of thalassemia birth and pregnancy complications. We aimed to review the spectrum and classification of thalassemia/hemoglobinopathy diseases and the diagnostic strategies including screening tests, molecular genetic tests, and prenatal diagnosis.

Clinicopathologic significance of HIF-1alpha, p53, and VEGF expression and preoperative serum VEGF level in gastric cancer.

BACKGROUND: Hypoxia influences tumor growth by inducing angiogenesis and genetic alterations. Hypoxia-inducible factor 1alpha (HIF-1alpha), p53, and vascular endothelial growth factor (VEGF) are all important factors in the mechanisms inherent to tumor progression. In this work, we have investigated the clinicopathologic significance of HIF-1alpha, p53, and VEGF expression and preoperative serum VEGF (sVEGF) level in gastric cancer.We immunohistochemically assessed the HIF-1alpha, p53, and VEGF expression patterns in 114 specimens of gastric cancer. Additionally, we determined the levels of preoperative serum VEGF (sVEGF). RESULTS: The positive rates of p53 and HIF-1alpha (diffuse, deep, intravascular pattern) were 38.6% and 15.8%, respectively. The VEGF overexpression rate was 57.9%. p53 and HIF-1alpha were correlated positively with the depth of invasion (P = 0.015, P = 0.001, respectively). Preoperative sVEGF and p53 levels were correlated significantly with lymph node involvement (P = 0.010, P = 0.040, respectively). VEGF overexpression was more frequently observed in the old age group (> or = 60 years old) and the intestinal type (P = 0.013, P = 0.014, respectively). However, correlations between preoperative sVEGF level and tissue HIF-1alpha, VEGF, and p53 were not observed. The median follow-up duration after operation was 24.5 months. HIF-1alpha was observed to be a poor prognostic factor of disease recurrence or progression (P = 0.002). CONCLUSION: p53, HIF-1alpha and preoperative sVEGF might be markers of depth of invasion or lymph node involvement. HIF-1alpha expression was a poor prognostic factor of disease recurrence or progression in patients with gastric cancers.

Characterization of complex chromosome aberrations in a recurrent meningioma combining standard cytogenetic and array comparative genomic hybridization techniques.

Meningiomas were among the first solid tumors recognized as having cytogenetic alterations. The most consistent changes reported in grade I meningiomas were monosomy 22 or partial 22q deletion. The vast majority of meningiomas are histologically benign, but the prognosis is determined by risk of recurrence after surgical treatment. Despite important advances in the identification of prognostic factors in the past decade, the exact nature of tumor recurrence remains largely unknown. In the present study, a recurrent transitional meningioma deriving from the anterior portion of the falx cerebri was characterized by combining conventional cytogenetics and array comparative genomic hybridization (CGH). Cytogenetic analysis at diagnosis revealed the following complex numerical and structural aberrations: 42,XY,der(1)t(1;?)(p12;?),-6,der(12;15)(q10;q10),-18, -22. Additional clonal evolutions were further identified with disease relapse. Array CGH corroborated the cytogenetic findings. The presence of a complex cytogenetic profile and progression-associated chromosomal abnormalities in a benign meningioma suggests the existence of underlying molecular events.

Plasma levels of prothrombin fragment F1+2, D-dimer and prothrombin time correlate with clinical stage and lymph node metastasis in operable gastric cancer patients.

OBJECTIVE: The principal objective of this study was to determine the relationship between preoperative coagulation tests and the extent of tumor involvement in gastric cancer patients. METHOD: A total of 110 patients with adenocarcinoma of the stomach were studied in order to evaluate this relationship. Platelet count (P), prothrombin time (PT), activated partial thromboplastin time, D-dimer, fibrinogen degradation product, thrombin-antithrombin complex and prothrombin fragment F1+2 (F1+2) were evaluated. RESULTS: The D-dimer levels were positively correlated with the depth of invasion (P =0.007). Plasma D-dimer and PT were highly correlated with degree of lymph node involvement (P = 0.006, 0.004, respectively). D-dimer level, PT and plasma F1+2 level were correlated with clinical stage (P = 0.001, 0.017, 0.031, respectively). PT and F1+2 levels were significant in the prediction of the presence of lymph node involvement on the multivariate logistic regression models (odds ratio 2502.081 (5.977-1047425.4); P = 0.010 and odds ratio 19.487 (1.495-253.936); P = 0.023, respectively). CONCLUSION: PT and plasma levels of F1+2 and D-dimer could be markers of degree or presence of lymph node involvement and clinical stage in patients with operable gastric cancer.