Useful Biomarker In Patients Research Articles

Hematopoietic lineage cell-specific protein 1 immunoreactivity indicates an increased risk of poor overall survival in patients with ovarian carcinoma.

Hematopoietic lineage cell-specific protein 1 (HS1) is a 75-kDa intracellular protein that is expressed primarily in hematopoietic cells. Several previous studies have demonstrated the association between HS1 expression and a poor prognosis in hematopoietic malignancies; however, in solid tumors, no studies not been reported. The present study examined the distribution and expression of HS1 in human epithelial ovarian carcinoma (EOC) to determine its clinical significance. Paraffin sections were obtained from EOC tissues and immunostained with HS1 antibody, and then the staining intensities were evaluated. Overall survival (OS) was determined using the Kaplan-Meier estimator method, and multivariate analysis was performed using the Cox proportional hazards analysis. In total, 195 patients with EOC (median age, 56 years) were enrolled into the present study. HS1 immunoreactivity was categorized based on expression levels: Low (89/195; 45.6%) and high (106/195; 54.4%). Results demonstrated no association between expression level(s) and any clinicopathological parameter including age, International Federation of Gynecology and Obstetrics (FIGO) staging, type of chemotherapy or type of surgery received. The 5-year OS rates of patients who demonstrated low (n=89) and high (n=106) HS1 expression were 90.4 and 66.7%, respectively. The OS times for patients with high HS1 expression were significantly shorter compared with those for patients exhibiting low HS1 expression (P=0.0065). Results obtained from the multivariate analysis demonstrated that the FIGO stage and the amount of HS1 expressed were significant independent prognostic markers for poorer OS (hazard ratio, 3.539; 95% confidence interval, 1.221-12.811; P=0.0187). High HS1 expression levels may serve as a useful biomarker in patients with EOC who are likely to exhibit an unfavorable clinical outcome.

Significance of Circulating Galectin-3 in Patients with Pancreatobiliary Cancer.

Pancreatobiliary cancer is a disease associated with a dismal prognosis and limited treatment options. The aim of the present study was to clarify the usefulness of circulating galectin-3 in pancreatobiliary cancer. We examined serum galectin-3 concentrations in 45 patients with pancreatobiliary cancer. Receiver operating characteristic curves were utilized to evaluate the accuracy of circulating galectin-3 to discriminate pancreatobiliary cancer patients from controls and predict the prognostic outcomes. Circulating galectin-3 had diagnostic value at the cut-off level of 6.2 ng/ml, and the patients' overall survival was predictable at the cut-off level of 10.3 ng/ml. Furthermore, circulating galectin-3 ≥10.3 ng/ml was an independent prognostic marker in pancreatobiliary cancer. Regarding biliary cancer, higher galectin-3 was associated with malnutrition. On the other hand, regarding pancreatic cancer, higher galectin-3 levels were associated with higher inflammatory parameters. Galectin-3 can be a useful biomarker in patients with pancreatobiliary cancer.

Liquid biopsy of PIK3CA mutations in cervical cancer in Hong Kong Chinese women

IntroductionCervical cancer is the fourth most common female cancer worldwide. The prognosis for women with advanced-stage or recurrent cervical cancer remains poor and response to treatment is variable. Standardized management protocols leave little room for individualization. We report on a novel blood-based liquid biopsy for specific PIK3CA mutations as a clinically useful biomarker in patients with invasive cervical cancer. MethodsOne hundred seventeen Hong Kong Chinese women with primary invasive cervical cancer and their pre-treatment plasma samples were investigated. Two PIK3CA mutations, p.E542K and p.E545K were measured in cell free DNA (cfDNA) extracted from plasma using droplet digital PCR. This liquid biopsy of PIK3CA in cervical cancer was correlated to clinico-pathological features to verify the potential of PIK3CA as a clinically useful molecular biomarker for predicting disease prognosis and monitoring for progression. ResultsPIK3CA mutations, either p.E542K or p.E545K, were detected in plasma cfDNA from 22.2% of the patients. PIK3CA mutation status was significantly correlated to median tumor size (p<0.01). PIK3CA mutations detected in the plasma were significantly associated with decreased disease-free survival and overall survival (p<0.05). ConclusionsAs a liquid molecular biopsy, analysis of circulating PIK3CA mutations shows promise as a way to refine risk stratification of individual patients with cervical cancer, and provides a platform for further research to offer individualized therapy with the purpose of improving outcomes.

Abstract AP01: HE4 IS A BIOMARKER FOR NEWLY DIAGNOSED AND RECURRENT HIGH–GRADE SEROUS OVARIAN CANCERS WITH NORMAL CA–125 VALUES

Abstract PURPOSE: CA125 is widely used for the diagnosis and monitoring of women with epithelial ovarian cancer. However, CA125 will not be elevated in ~20% of patients. Human epididymis protein 4 (HE4) was approved by the FDA in 2008 to monitor ovarian cancer. The objective of this study was to evaluate whether HE4 would serve as a useful biomarker in patients with a normal CA125 at either the time of diagnosis or at the time of recurrence. METHODS: Twenty–one patients with high–grade serous ovarian cancer and CA125 values &amp;lt;50U/ml at the time of diagnosis were identified from a bank of serum specimens collected between 2006–2012. Twenty patients with high–grade serous ovarian cancer and CA125 values &amp;gt;1000U/ml served as positive controls and 11 patients without disease served as negative controls. Fourteen patients with an elevated CA125 at diagnosis (&amp;gt;50 U/ml) and a normal CA125 at the time of recurrence were also identified. HE4 was measured using the Abbott Architect i2000 assay and validation was performed using the Fujirebio HE4 ELISA assay. Normal age–based HE4 values were obtained from the published literature (Urban N, et al.; PMID: 22962406). Data was compared between groups using standard two–sided statistical tests. RESULTS: At the time of diagnosis, the mean HE4 was 1082±437.9 in the positive control patients with elevated CA125, the mean HE4 was 50.96±11.43 in the patients without disease, and 214.4±236.9 in patients with a normal CA–125 (P = &amp;lt;.0001 compared to normal controls; Student's t–test). At the time of recurrence, the mean HE4 was 102.7±83.29 in patients with normal CA125 levels. For 12 of 14 (86%) patients, the HE4 value was greater than the expected normal age–based reference. CONCLUSIONS: These preliminary data suggest that HE4 values are elevated in newly diagnosed ovarian cancer patients with a normal CA125 value. HE4 also appears to be a potentially useful biomarker for detecting recurrent disease in patients with an elevated CA125 at the time of diagnosis who have a normal CA125 level at the time of recurrence. Citation Format: Katherine LaVigne, MD, Fanny Dao, MS, Nadeem Abu–Rustum, MD, Petar Jelinic, PhD, Lakshmi V. Ramanathan, PhD, Martin Fleisher, PhD, Douglas A. Levine, MD. HE4 IS A BIOMARKER FOR NEWLY DIAGNOSED AND RECURRENT HIGH–GRADE SEROUS OVARIAN CANCERS WITH NORMAL CA–125 VALUES [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP01.

Surfactant Protein D Inhibits Interleukin-12p40 Production by Macrophages Through the SIRPα/ROCK/ERK Signaling Pathway

ObjectiveInterleukin (IL)-12 has a pivotal profibrotic role in the development of idiopathic pulmonary fibrosis (IPF). Medical research trials based on IPF registry databases have actively recruited patients. Surfactant protein D (SP-D) is a useful biomarker in patients with IPF. SP-D binds to signal regulatory protein α (SIRPα), which acts as an inhibitory receptor, and this SP-D/SIRPα interaction may have an anti-inflammatory effect. Accordingly, the inhibitory effect of SP-D on IL-12p40 production by lipopolysaccharide (LPS)-stimulated macrophages was investigated. Materials and MethodsHuman granulocyte-macrophage colony-stimulating factor (GM-CSF)-stimulated macrophages (day 9 of culture) was used to investigate IL-12p40 production after stimulation with SP-D. ResultsGM-CSF was found to upregulate SIRPα expression by macrophages. PD98059 (an extracellular signal-regulated kinase [ERK] inhibitor) blunted induction of SIRPα expression by GM-CSF. SP-D significantly attenuated IL-12p40 production by macrophages after stimulation with LPS. Silencing of SIRPα/β/γ significantly reversed this inhibitory effect of SP-D. In contrast, neither SB023580 (a p38α/β MAPK inhibitor) nor BIRB796 (a p38γ/δ MAPK inhibitor) attenuated the inhibitory effect of SP-D on LPS-stimulated production of IL-12p40. Silencing of SHP also had no influence on this effect of SP-D. Interestingly, a Rho-associated protein kinase (ROCK) inhibitor (Y-27632) abolished the inhibition of LPS-stimulated IL-12p40 production by SP-D, whereas silencing of ERK 2 significantly blunted this effect of Y-27632. ConclusionsThese findings suggest that SP-D inhibits LPS-stimulated production of IL-12p40 via the SIRPα/ROCK/ERK signaling pathway.

Novel biomarkers for patients with idiopathic acute anterior uveitis: neutrophil to lymphocyte ratio and platelet to lymphocyte ratio.

To assess the levels of the neutrophil to lymphocyte ratio (N/L) and the platelet to lymphocyte ratio (P/L) in patients with idiopathic acute anterior uveitis (AAU) and to compare with healthy controls. Thirty-six male patients with idiopathic AAU and 36 male healthy subjects were enrolled in this retrospective study. Complete ophthalmological examination and complete blood count measurements results of all subjects were evaluated. There was a significant difference in N/L and P/L between idiopathic AAU and control groups (P=0.006, P=0.022). Also, correlation analysis revealed a significant correlation between C-reactive protein (CRP) and N/L (P=0.002; r=0.461). Our study for the first time provides evidence of N/L and P/L may be useful biomarkers in patients with idiopathic AAU. N/L is correlated with CRP, so it can be a useful biomarker to predict the prognosis in idiopathic AAU.

Preoperative multiplication of neutrophil and monocyte counts as a prognostic factor in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is leading cause of death in gynecologic cancer, and finding prognostic factors is important for establishing treatment plans. The aim of this study was to investigate the prognostic value of the multiplication of neutrophil and monocyte counts (MNM) in epithelial ovarian cancer (EOC). Data were retrospectively collected from Samsung Medical Center for EOC patients treated from January 2002 to December 2012. MNM was determined by multiplying neutrophil and monocyte counts and dividing by 10,000. Sensitivity and specificity of markers were assessed using receiver operating characteristic curves. We included 674 patients with EOC. For predicting overall survival (OS), the area under the curve for MNM was 0.607 (95% CI, 0.554-0.661) with sensitivity 55.2% and specificity 63.2% (cut-off value 197.40). The ability of MNM to determine OS was similar to that of the previously validated NLR and PLR. When the cohort was divided by cut-off values, poorer survival outcomes were observed in the group with higher MNM. Higher MNM was associated with advanced stage and presence of residual disease after primary treatment. Elevated pretreatment MNM is an independent predictor of poor survival and can be a useful biomarker in patients with EOC.

The expression and significance of heparanase in oral squamous cell carcinoma with different metastatic potentials

Objective: To detect the expression of heparanase (HPSE) in oral squamous cell carcinoma (OSCC) with different metastatic potentials and investigate its clinical significance. Methods: Transcriptional and translational status of HPSE in OSCC cell lines with different metastatic capacities, primary OSCC samples and their paired metastatic cancer tissues were determined using real-time polymerase chain reaction (PCR) and Western blotting analysis. Immunohistochemistry was used to evaluate HPSE expression in 131 OSCC samples. The correlation between HPSE expression pattern and clinicopathological parameters and clinical outcome in patients with OSCC were analyzed. HPSE level was reduced using HPSE-siRNAs in OSCC cell lines and its impact on cell migration and invasion was measured by scratch assay and matrigel invasion assay. Results: The mRNA and protein levels of HPSE were remarkably up-regulated in OSCC cell lines with highly metastatic capacity (P<0.000 1) and metastatic OSCC tissues (P<0.000 1). The protein levels of HPSE were strongly associated with lymph node metastasis (P<0.000 1) and tumor node metastasis stage (P=0.012). Survival analyses revealed that high HPSE expression was associated with worse overall survival (P=0.000 3). Multivariate Cox proportional analyses indicated that HPSE expression was strongly associated with clinical outcome in patients with OSCC (HR=2.203, 95% CI: 1.203-3.988, P=0.009). The siRNA-mediated silencing of HPSE could suppress the migration and invasion (P=0.008) of HN12 cells in vitro. Conclusions: The up-regulation of HPSE contributes to invasion and metastasis of OSCC. HPSE may serve as a useful biomarker for patients with OSCC.

Dynamics of microvesicle generation in B-cell chronic lymphocytic leukemia: implication in disease progression.

Previously, we reported that B-cell chronic lymphocytic leukemia (CLL) patients contained elevated levels of microvesicles (MVs). However, given the quiescent nature of CLL B-cells and the relative indolence of the disease, the dynamics of MV generation and their unique phenotypes are not clearly defined. In this study, we find that CLL B-cells generate MVs spontaneously and can be further induced by B-cell receptor-ligation. Most interestingly, CLL B-cells predominantly generate CD52+ MVs, but not CD19+ MVs in vitro, suggesting preferential usage of CD52 into leukemic-MVs and that the CLL plasma MV phenotypes corroborate well with the in vitro findings. Importantly, we detected increased accumulation of CD52+ MVs in previously untreated CLL patients with progressive disease. Finally, sequential studies on MVs in pre- and post-therapy CLL patients demonstrate that while the plasma CD52+ MV levels drop significantly after therapy in most and remain at low levels in some patients, a trend of increased accumulation of CD52+ MVs was detected in majority of post-therapy CLL patients (25 of 33). In total this study emphasizes that dynamic accumulation of CD52+ MVs in plasma can be used to study CLL progression and may be a useful biomarker for patients as they progress and require therapy.

Serum fibrinogen levels are positively correlated with advanced tumor stage and poor survival in patients with gastric cancer undergoing gastrectomy: a large cohort retrospective study.

BackgroundPlatelet and blood coagulation abnormalities frequently occur in cancer patients. Fibrinogen is an important hemostatic factor that regulates the hemostatic pathway. Hyperfibrinogenemia is increasing recognized as an important risk factor influencing cancer development and outcome. However, few reports have investigated the prognostic potential of fibrinogen for predicting the survival of gastric cancer (GC) patients. The primary aim of this study was to evaluate the usefulness of preoperative serum fibrinogen as a biomarker for predicating tumor progression and survival of patients with GC.Patients and methodsThis retrospective study was conducted in GC patients who underwent gastrectomy from 2005 to 2007. Patient demographics, clinicopathological characteristics, preoperative plasma fibrinogen levels and median survival time (MST) were analyzed. Univariate and multivariate proportional hazard analysis of risk factors were used.ResultsThis study included 1196 patients (885 males and 311 females) with GC, more than half of whom had advanced GCs. Radical lymph node dissection was performed in 71.6 % of these patients. MST was 41.9 ± 32.4 months. Patient survival was significantly affected by family GC history (p <0.05), lymph node dissection mode (p <0.001), tumor size (≥5 cm; p <0.001), tumor location (p < 0.001), poor tumor differentiation (p <0.001), tumor histologic classification (p <0.001), extent of tumor invasion (p <0.001), number of metastatic lymph nodes (p <0.001), advanced stage of disease (p <0.001), extended operation duration (>150 min; p <0.001), higher operative bleeding volume (>200 ml; p <0.001), postoperative transfusion, preoperative serum fibrinogen levels, CEA levels and CA 19-9 levels (p <0.001). Multivariate analysis indicated that the independent prognostic factors significantly associated with poor survival included non-radical lymph node dissection, palliative lymph node dissection, multi-organ involvement, advanced TNM stages, poor tumor differentiation, higher preoperative serum fibrinogen levelsand higher CA19-9 levels.ConclusionsSerum fibrinogen levels are positively correlated with advanced tumor stages and poor survival in GC patients undergoing gastrectomy. Preoperative plasma fibrinogen levels are an independent risk factor for survival in these patients. Serum fibrinogen is a useful biomarker for patients with clinically advanced GC.

Role of B-type natriuretic peptide (BNP) in heart failure

Abstract Introduction: Early clinical diagnosis of heart failure (HF) is challenging because the signs and symptoms are neither sensitive nor specific for diagnosis. B-type natriuretic peptide (BNP), a cardiac neurohormone is a useful biomarker for patients with HF. Objectives: The purpose of this review is to evaluate the role of BNP in HF as a diagnostic, prognostic, and therapeutic marker in both outpatient care and urgent care settings. Methodology: An extensive literature review was conducted for this study. Findings: Determination of BNP is particularly useful as a rule-out test for suspected cases of HF in patients with dyspnoea. HF is very unlikely in patients with levels of BNP &lt;100 pg/mL whereas BNP levels &gt;400 pg/mL strongly support the diagnosis of HF. Elevated level of BNP indicates a worse prognosis in patients with HF. Conclusion: Although, it is recommended in the diagnostic pathways of guidelines for HF, it is not well established to recommend measurement of BNP to titrate HF medications because of lack of enough evidence. It requires further in-depth research.

B7-H3, B7-H4, Foxp3 and IL-2 expression in cervical cancer: Associations with patient outcome and clinical significance.

The aim of this study was to determine the expression of B7-H3, B7-H4, Foxp3 and IL-2 in cervical cancer tissues, and evaluate the corresponding clinical significance. The expression of B7-H3, B7-H4, Foxp3 and IL-2 in 108 cervical cancer specimens was detected using immunohistochemistry, and their relationship with clinicopathologic parameters was determined. B7-H3, B7-H4 and Foxp3 had high levels of expression in cervical cancer cells (72.22, 80.56, and 91.56%, respectively). B7-H3 levels were only significantly associated with tumor size (P=0.013), while B7-H4, Foxp3 and IL-2 levels were significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.023, 0.014 and 0.036, respectively) and tumor size (P=0.045, 0.010 and 0.021, respectively). Their expression levels were not correlated with age, histologic type, differentiation and lymph node metastasis (all P>0.05). Cox regression multivariate analysis confirmed that B7-H3 or B7-H4 overexpression was an independent prognostic factor. In addition, there were significant positive relationships between the expression of B7-H3 and B7-H4 with Foxp3 (P<0.001). In contrast, the expression of B7-H3 and B7-H4 was negatively correlated with IL-2 (P<0.05). B7-H3, B7-H4 and Foxp3 may be useful biomarkers in patients with cervical cancer for predicting treatment.

Evaluation of TOP2A as a Predictive Marker for Endometrial Cancer With Taxane-Containing Adjuvant Chemotherapy.

Paclitaxel plus carboplatin and doxorubicin plus cisplatin are usually selected as adjuvant chemotherapy for endometrial cancer. However, biomarkers that can determine the appropriate chemotherapy regimen are not known. In the present study, we performed a retrospective investigation of the association between TOP2A, HER2 overexpression, and disease-free and overall survival in patients with endometrial cancer receiving taxane and platinum. Eligible patients had a diagnosis of endometrial cancer based on histology and treated with an adjuvant chemotherapy regimen comprising taxane-platinum after surgery, and the HER2 and TOP2A status of the endometrial cancer regions was determined. Overall survival and disease-free survival between HER2 status and TOP2A status were estimated by the Kaplan-Meier method and compared using the log-rank test. We identified 56 patients who fulfilled the previously described criteria. Median follow-up was 49 months (range, 18-110 months). HER2-positive tumors were detected in 11 patients (19.6%), and TOP2A-positive tumors were detected in 7 patients (12.5%). Overall survival was not significantly different between patients with HER2-positive tumors and those with HER2-negative tumors, although disease-free survival for patients with HER2-positive tumors was significantly lower than disease-free survival for patients with HER2-negative tumors (P = 0.049). In contrast, patients with TOP2A-positive tumors had significantly lower overall survival than did patients with TOP2A-negative tumors (P = 0.020), and disease-free survival for patients with TOP2A-positive tumors tended to be shorter than for those with TOP2A-negative tumors. Patients with TOP2A overexpression have a worse prognosis compared with those with TOP2A nonexpression, and TOP2A may be a useful biomarker in patients receiving adjuvant taxane-platinum regimens with moderate- to high-risk endometrial cancer.

Serum level of microRNA-147 as diagnostic biomarker in human non-small cell lung cancer

Objectives In this study, we intended to examine the gene expression level and the clinical significance of microRNA-147 (miR-147) in cancer tissues and sera of patients with non-small cell lung cancer (NSCLC).Methods Quantitative real-time PCR (qRT-PCR) was used to investigate the expression levels of miR-147 in 32 paired NSCLC tissues and their adjacent normal lung tissues, sera of 122 control and 87 NSCLC patients. The correlation of serum miR-147 expression level with clinicopathological characteristics, and the prognosis of NSCLC patients was statistically evaluated.Results MiR-147 was significantly down-regulated in NSCLC tissues than in paired adjacent normal tissues, and in sera of NSCLC patients than in sera of control patients. In addition, serum miR-147 was markedly down-regulated in advanced NSCLC patients and the patients with lymph node metastasis (LNM). Low serum miR-147 expression level was found to be significantly correlated with tumor, lymph node, metastasis stage, LNM, and tumor size. Statistical analysis showed that patients with low serum miR-147 had much worse overall survival, and low serum miR-147 expression level was an independent prognostic factor for poor prognosis for NSCLC.Conclusion Low serum miR-147 expression level may be a useful biomarker for patients with NSCLC.

Human Epididymis Protein 4 is a Useful Biomarker in Patients with Dilated Cardiomyopathy

Human Epididymis Protein 4 is a Useful Biomarker in Patients with Dilated Cardiomyopathy

Abstract 3404: NDRG2 suppresses growth and invasion of gallbladder carcinoma via regulation of matrix metalloproteinase 19/slug interaction

Abstract Background: Gallbladder cancer is a relatively uncommon tumor worldwide but it has a feature of highly invasive and malignant tumor with poor prognosis. However, relevant molecules and/or genes associated with growth and metastasis of gallbladder carcinoma are poorly understood. Although NDRG2 is known as a tumor suppressor gene, its exact role in gallbladder carcinoma remains unknown. Materials and method: For deciphering biological roles of NDRG2 in gallbladder carcinoma, first, we examined the expression of NDRG2 in tumor specimens from 86 gallbladder carcinoma patients by immunostaining and analyzed the correlation between NDRG2 expression and clinicopathologic parameters as well as patient survival. Second, we investigated the functional significance of NDRG2 in gallbladder carcinoma progression by stable knock-down or overexpression of NDRG2 in in vitro and in vivo studies. Results: NDRG2 was differentially expressed in gallbladder carcinoma tissues. The negative expression of NDRG2 was significantly associated with a pathological T stage (P = 0.015), high histological grade (P = 0.020), and perineural invasion (P = 0.016). Multivariate analyses clearly showed that the loss of NDRG2 expression was an independent poor prognostic factor for cancer-specific survival. The stable expression of NDRG2 shRNA in gallbladder carcinoma cell lines significantly increased cell proliferation, anchorage-independent growth, migration and invasion. In addition, NDRG2 shRNA remarkably increased metastasis from the spleen to the liver in mice. Furthermore, loss of NDRG2 expression in cells caused an epithelial-mesenchymal transition through Slug induction by MMP-19 interaction with Slug promoter. Conclusions: In the present study, we showed that loss of NDRG2 expression leads to poor prognosis and enhanced metastasis in gallbladder carcinoma. NDRG2 suppresses MMP-19 which causes an epithelial-mesenchymal transition through Slug induction. These data indicate that NDRG2 suppresses tumor progression via regulating MMP19/Slug axis in gallbladder carcinoma. The loss of NDRG2 is a novel prognostic factor suggesting it could be a useful biomarker in patients with gallbladder carcinoma and a potential therapeutic target. Citation Format: Nayoung Kim, Jeong-Ki Min, Jin-Man Kim, Hyo Jin Lee. NDRG2 suppresses growth and invasion of gallbladder carcinoma via regulation of matrix metalloproteinase 19/slug interaction. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3404. doi:10.1158/1538-7445.AM2015-3404

Dynamic contrast enhanced MRI-derived parameters are potential biomarkers of therapeutic response in bladder carcinoma

ObjectivesTo evaluate the performance of dynamic contrast enhanced (DCE) magnetic resonance (MR) imaging to assess the histological response after chemotherapy on bladder carcinoma. MethodsFrom 2008 to 2010, 12 patients presenting localized urothelial carcinoma of the bladder were prospectively evaluated by DCE-MR imaging before and after two courses of cisplatin-based neoadjuvant chemotherapy. Size and thickness of tumours were measured. Relative enhancement at the arterial (rSI35s) and venous phases (rSI80s) of each tumour was obtained. Histological response was assessed and outcomes were recorded. ResultsHistological examination after neoadjuvant chemotherapy concluded as pathological complete response (pCR) for 6 out of 12 patients. Five patients developed recurrences (4/6 no pCR and 1/6 pCR). Significant differences, between before and after treatment, were found for patients with complete pathological response after chemotherapy for all MR quantitative values. Tumours decreased in size and thickness (both P=0.03). After treatment, rSI80s was significantly different between pCR and non-pCR patients (P=0.04) with a cut-off value of 40%. For this cut-off, sensitivity, specificity and accuracy were 83.33%. Similar recurrence free survivals were obtained if applying the MR cut-off value or the histopathological findings. ConclusionOur results suggest that DCE-MR imaging may be a useful biomarker for patients with localized bladder carcinoma, improving selection before surgery.

CXCL13 as a new biomarker of systemic lupus erythematosus and lupus nephritis - from bench to bedside?

Different studies over the last decade have linked the B cell-attracting chemokine CXC ligand 13 (CXCL13) to the autoimmune disease systemic lupus erythematosus (SLE). A pathogenetic role of this chemokine for disease manifestation in SLE was described initially in mouse models for SLE. Mechanisms of CXCL13 actions were also identified in SLE patients. Moreover, various clinical studies have identified CXCL13 serum levels as a useful biomarker in patients with SLE of different ethnicities for disease activity. In addition, CXCL13 seems to be a promising marker for the diagnosis of lupus nephritis, one of the most severe complications of SLE. However, its exact place within the mechanisms that lead to SLE remains to be defined. Further research is needed to resolve more details of the pathomechanism and the signalling pathway of CXCL13 in SLE. Blocking CXCL13 or the signal pathways of CXCL13 is seen as a promising therapeutic approach for SLE and will be addressed in the near future. This review summarizes all papers that linked CXCL13 to SLE and highlights its importance in the pathogenesis and diagnosis of SLE.

Anemia as a useful biomarker in patients with diffuse large B-cell lymphoma treated with R-CHOP immunochemotherapy.

The aim of the current study is to evaluate the prognostic value of anemia, an easily estimable parameter in patients with diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) immunochemotherapy. A total of 157 patients with newly diagnosed diffuse large B-cell lymphoma treated with ≥1 cycle of R-CHOP were included. Hemoglobin level without red cell transfusion within 7 days of initiation of treatment was chosen as a parameter of baseline cancer-induced anemia. To investigate the clinical significance of chemotherapy-induced anemia and its recovery after completion of treatment, 87 patients in complete remission for ≥6 months from the time of the last cycle of R-CHOP were grouped and analyzed separately. Patients with a cancer-induced anemia of hemoglobin <10 g/dL showed inferior event-free and disease-free survival compared to those with hemoglobin ≥10 g/dL. This finding was observed irrespective of the status of pre-treatment bone marrow involvement. In multivariate analysis, hemoglobin <10 g/dL was found to be an international prognostic index-independent prognostic factor. Risk of relapse was significantly higher for patients who were still anemic at 6 months after R-CHOP, compared to those who achieved complete recovery from chemotherapy-induced anemia within 6 months.

Fraction of immature granulocytes reflects severity but not mortality in sepsis

Objective. In order to validate immature granulocytes as a universal biomarker, we have compared the clinical relevance of the proportion of immature granulocytes (IG%), measured using Sysmex XE-2100, with other biomarkers (white blood cell, C-reactive protein, lactate and procalcitonin). Methods. This single center, retrospective study included 184 patients with sepsis admitted to an emergency department. Patients were classified into two groups: Uncomplicated sepsis and complicated sepsis (severe sepsis and septic shock). IG% and other biomarkers were evaluated and compared for predicting sepsis severity, overt disseminated intravascular coagulation (DIC) and 28 day mortality. Results. In multivariate analysis, only IG% (odd ratio [OR] 2.530, p = 0.004) and lactate (OR 4.500, p < 0.001) could discriminate between complicated and uncomplicated sepsis. The optimal cut-off value for IG% and lactate was 0.5% and 2.0 mmol/L, respectively. In subgroup analyses of complicated sepsis, IG% was related to overt DIC. However, no single biomarker could predict 28-day mortality. Conclusions. Given that IG% reflected sepsis severity and overt DIC without additional cost, IG% could be a useful biomarker in patients with sepsis. However, there is a limitation for using it as a novel biomarker in sepsis due to the disability of prediction for 28-day mortality.