Efficacy and Safety of Bortezomib in Multiple Myeloma Patients with Hepatitis B: A Multicenter Retrospective Study

Background:

The efficacy and safety evidence of bortezomib in multiple myeloma (MM) patients with hepatitis B is vacant. This study aimed to investigate the efficacy and safety of bortezomib in MM patients with hepatitis B in China.

Methods:

From 2006 to 2011, 739 newly diagnosed MM patients were screened for serum hepatitis B virus (HBV) biomarkers. HBV-infected patients were followed for HBV reactivation by monitoring of serum alanine transaminase (ALT) and HBV DNA load. The pattern of HBV reactivation in relation to bortezomib was evaluated. Seven hundred thirty-nine MM patients were included in this study.

Results:

The prevalence of MM patients infected with HBV was 3.4% (n = 25), of which 17 cases were treated with bortezomib. Bortezomib had no significant influence on liver function (ALT before and after treatment: 36.69 ± 8.90 U/L vs. 11.31 ± 2.74 U/L, P = 0.19) and HBV DNA of MM patients with HBV (detectable HBV DNA percentage: 5.9% vs. 11.8%, P = 0.12).

Conclusions:

Bortezomib can be used safely and effectively in MM patients with hepatitis B. HBV prophylaxis and surveillance are recommended during the MM treatment.     

Proteomic Analysis of the Uterosacral Ligament in Postmenopausal Women with and without Pelvic Organ Prolapse

Background:

Pelvic organ prolapse (POP) is a major health problem in adult women that involves many factors. No proteomic analysis has been conducted exclusively in POP patients. This study aimed to identify the differential expression of proteins that may be involved in POP by proteomic analysis.

Methods:

Samples of the uterosacral ligament (USL) were collected from five POP patients and five non-POP patients matched according to age, parity, and menopausal status and analyzed using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the mRNA expression of proteins that showed differential expression in the proteomic analyses.

Results:

Proteins differentially expressed between POP and non-POP patients were detected. Eight proteins that were down-regulated in the POP group were identified by MALDI-TOF-MS. These proteins included electron transfer flavoprotein, apolipoprotein A-I, actin, transgelin, cofilin-1, cyclophilin A, myosin, and galectin-1, and their expression was verified by qRT-PCR.

Conclusion:

Using comparative proteomics, we identified eight differentially expressed proteins (including four cytoskeleton proteins and three proteins related to apoptosis) in the USL that may be involved in apoptosis associated with the tissue effects in POP pathophysiology.     

Melanoma: A new strategy to reduce morbidity and mortality

Background

Public awareness campaigns could address risk factors for melanoma to reinforce their sun protection message. The objective of this study is to prioritise risk factors associated with malignant melanoma (MM) to improve public awareness.

Method

Design: A cross-sectional study with retrospective data analysis from 2004 to 2010. Setting: Western Australian Melanoma Advisory Service (WAMAS), a tertiary referral multidisciplinary organisation providing MM management advice. WAMAS data files were analysed with histologically confirmed cutaneous MM. Forty- seven patients had two or more melanomas, but the patient file was counted only once. Six MM data files with missing or incomplete information were excluded. Main outcome measures: The number of naevi, blood relatives with MM, and previous sunburns were the primary variables collected.

Results

The results showed that 70.9 per cent (268/378) had previous sunburn; 40.2 per cent (152/378) had multiple naevi; and 22.5 per cent (85/378) had a positive family history. In the 110 MM data files not associated with sunburn, multiple naevi and a positive family history represented 34.5 per cent (38/110) and 20.0 per cent (22/110), respectively.

Conclusion

The results confirm the findings of previous studies that multiple naevi and a positive family history are important risk factors associated with MM. We suggest that MM can be detected earlier and its mortality decreased by focusing on these high-risk groups who are not targeted by current public awareness campaigns.     

Identification of Differentially Expressed MicroRNAs in the Ovary of Polycystic Ovary Syndrome with Hyperandrogenism and Insulin Resistance

Background:Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age.The patients often develop insulin resistance (IR) or hyperinsulinemia despite manifesting anovu...     

Identification of Biomarkers for Endometriosis Using Clinical Proteomics

Background:

We investigated possible biomarkers for endometriosis (EM) using the ClinProt technique and proteomics methods.

Methods:

We enrolled 50 patients with EM, 34 with benign ovarian neoplasms and 40 healthy volunteers in this study. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) combined with weak cationic exchange (WCX) magnetic beads. Possible biomarkers were analyzed by a random and repeat pattern model-validation method that we designed, and ClinProtools software, results were refined using online liquid chromatography-tandem MS.

Results:

We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity. We selected 4210 and 5904 m/z, which differed most between patients with EM and controls, and identified them as fragments of ATP1B4, and the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor, respectively.

Conclusions:

ClinProt can identify EM biomarkers, which – most notably – distinguish even early-stage or minimal disease. We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.     

Phosphoproteomics Analysis of Endometrium in Women with or without Endometriosis

Background:

The molecular mechanisms underlying the endometriosis are still not completely understood. In order to test the hypothesis that the approaches in phosphoproteomics might contribute to the identification of key biomarkers to assess disease pathogenesis and drug targets, we carried out a phosphoproteomics analysis of human endometrium.

Methods:

A large-scale differential phosphoproteome analysis, using peptide enrichment of titanium dioxide purify and sequential elution from immobilized metal affinity chromatography with linear trap quadrupole-tandem mass spectrometry, was performed in endometrium tissues from 8 women with or without endometriosis.

Results:

The phosphorylation profiling of endometrium from endometriosis patients had been obtained, and found that identified 516 proteins were modified at phosphorylation level during endometriosis. Gene ontology annotation analysis showed that these proteins were enriched in cellular processes of binding and catalytic activity. Further pathway analysis showed that ribosome pathway and focal adhesion pathway were the top two pathways, which might be deregulated during the development of endometriosis.

Conclusions:

That large-scale phosphoproteome quantification has been successfully identified in endometrium tissues of women with or without endometriosis will provide new insights to understand the molecular mechanisms of the development of endometriosis.     

Variants of Interferon Regulatory Factor 5 are Associated with Neither Neuromyelitis Optica Nor Multiple Sclerosis in the Southeastern Han Chinese Population

Background:

Neuromyelitis optica (NMO) and multiple sclerosis (MS) are demyelinating disorders of the central nervous system. Interferon regulatory factor 5 (IRF5) is a common susceptibility gene to different autoimmune disorders. However, the association of IRF5 variants with NMO and MS patients has not been well studied. Therefore, we aimed to evaluate whether IRF5 variants were associated with NMO and MS in the Southeastern Han Chinese population.

Methods:

Four single nucleotide polymorphisms (SNPs) were selected and genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry in 111 NMO patients, 145 MS patients and 300 controls from Southeastern China.

Results:

None of these 4 SNPs was associated with NMO or MS patients.

Conclusions:

Our preliminary study indicates that genetic variants in IRF5 may affect neither NMO nor MS in the Southeastern Han Chinese population. Further studies with a large sample size and diverse ancestry populations are needed to clarify this issue.     

Identification of Human Serum Protein Targets of Qianggu Decoction (强骨饮) in Primary Type Ⅰ Osteoporosis Based on Tandem Mass Tag Labeling and Liquid Chromatography-Tandem Mass Spectrometry Technology

Objective: To investigate the serum protein targets of Qianggu Decoction (强骨饮, QGD) on treating osteoporosis by the proteomics analysis using tandem mass tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: Twenty serum protein samples were recruited (10 patients with primary type Ⅰ osteoporosis before and after QGD treatment) and the high abundance ratios protein was removed, two serum samples were extracted and labeled with TMT reagent. Then, mass spectrometric detection, identification of differentially expressed proteins and bioinformatics analysis of differentially expressed proteins were carried out. Results: A total of 60 proteins were identified, within a 99% confidence interval, to be differentially regulated of which, 34 proteins were up-regulated and 26 proteins were down-regulated. Differentially expressed proteins analyzed by Gene Ontology (GO) annotation mainly get involved in 12 different biological processes, 7 types of cellular components, and 6 kinds of molecular functions. Angiotensinogen (AGT), stromelysin-1 (MMP3), heparanase (HPSE) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were screened as candidate protein targets of QGD treatment, which were related to metabolic mechanism of bone remodeling and/or bone collagen of osteoporosis. By the utilization of the protein-protein interaction network analysis tool named STRING10.0, it showed that AGT, MMP3, HPSE and GAPDH were located in the key node of the protein-protein interactions network. Furthermore, AGT, MMP3, HPSE and GAPDH were found to be directly related to BMP, MAPK, Wnt, SMAD and tumor necrosis factor ligand superfamily member 11 (TNFSF11) families. Conclusions: The proteomics analysis by using TMT combined with LC-MS/MS was a feasible method for screening the potential therapeutic targets associated with QGD treatment. It suggests that AGT, MMP3, HPSE and GAPDH may be candidate protein targets of QGD treatment which can be used as therapeutic effect monitor and early diagnosis of primary type Ⅰ osteoporosis.     

Clinicopathological Study of Sporadic Burkitt Lymphoma in Children

Background:

Non-Hodgkin lymphoma is the fourth most common malignant tumors in children, Burkitt lymphoma (BL) accounts for 30–50% of all pediatric lymphomas. The aim of this study was to investigate the clinicopathologic features, immunophenotype, Epstein-Barr virus (EBV) infection and c-myc gene rearrangement of sporadic BL in children.

Methods:

Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features, immunohistochemistry, EBV-encoded RNA (EBER) status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.

Results:

In the 92 cases, male is predominant in sex distribution (M: F = 3.38:1). The average age at diagnosis was 4.97 years. Polypoid BL showed a lower clinical stage (P = 0.002), and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome (P = 0.024 and 0.053, respectively). The positive expression of CDl0, B-cell lymphoma-6, MUMl and EBER were 95.7% (88 cases), 92.4% (85 cases), 22.8% (21 cases), 41.3% (38 cases), respectively. The expression of MUM1 were not associated with EBV infection status (P = 1.000). c-myc gene rearrangement was detected in 94.6% (87/92). Clinical treatment information for 54 cases was collected, 21 patients died of tumor after surgery alone, 33 patients received surgery and chemotherapy, and of which six patients died shortly afterwords (MUM1 positive expression in 3 cases, P = 0.076).

Conclusions:

The anatomical location, growth pattern and serum albumin level of BL were associated with biological behavior. MUM1 may be a potential adverse prognostic marker, and not associated with EBV infection status.     

Preterm delivery and low maternal serum cholesterol level: Any correlation?

Background:

The study assessed whether low maternal serum cholesterol during early pregnancy is associated with preterm delivery.

Patients and Methods:

It was a prospective observational cohort study involving pregnant women at gestational age of 14-20 weeks over a period of 12 months. Blood samples were obtained to measure total serum cholesterol concentrations and the sera were then analysed enzymatically by the cholesterol oxidase: p-aminophenazone (CHOD PAP) method.

Results:

The study showed an incidence of 5.0% for preterm delivery in the low risk study patients. Preterm birth was 4.83-times more common with low total maternal cholesterol than with midrange total cholesterol (11.8% versus 2.2%, P = 0.024).

Conclusion:

Low maternal serum cholesterol (hypocholesterolaemia) is associated with preterm delivery. Optimal maternal serum cholesterol during pregnancy may have merit, therefore pregnant women should be encouraged to follow a healthy, balanced diet.     

Diagnostic Values of Vascular Endothelial Growth Factor and Epidermal Growth Factor Receptor for Benign and Malignant Hydrothorax

Background:Hydrothorax,as one of the common complications of malignant tumors,still cannot be sensitively detected in clinical practice,thus requiring a sensitive,specific method for diagnosis.The aim ...     

Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background:

Lenalidomide has emerged as an important treatment for patients with multiple myeloma (MM). However, its role in the management of MM is still controversial and requires further clarification. The aim of this study was to evaluate efficacy and safety of lenalidomide for MM using a meta-analysis.

Methods:

We searched the electronic databases including: PubMed, EMBASE and the Cochrane Center Register of Controlled Trials. Seven randomized clinical trials were identified, which included a total of 2357 patients with MM who received lenalidomide-containing, noncontaining lenalidomide regimens or placebo as induction therapy or maintenance therapy. The outcomes included overall response (OR) rate, complete response (CR) rate, 3-year progression-free survival (PFS) rate, 3-year overall survival (OS) rate, and different types of treatment-related adverse events. We calculated the risk ratios (RRs) as well as their 95% confidence intervals of these outcomes and pooled the results using RevMan 5.2 software.

Results:

For patients with previously untreated MM, OR rate and CR rate was significantly higher in lenalidomide-containing group than the control group. For relapsed or refractory MM patients, lenalidomide-containing regimens significantly improved the OR rate, CR rate, 3-year PFS rate and 3-year OS rate. With regard to MM patients after autologous stem cell transplantation, lenalidomide maintenance therapy significantly improved 3-year PFS rate but did not result in improved 3-year OS rate. In terms of toxicities, lenalidomide therapy has a higher rate of Grade 3–4 grade cytopenias, infection, deep-vein thrombosis, and diarrhea. Furthermore, the incidence of second primary malignancies was significantly higher in the lenalidomide group.

Conclusions:

The lenalidomide-containing regimens as induction therapy clearly increased response rates and improved intervals of survival with acceptable toxicity rates for patients with MM. However, when physicians choose to use the lenalidomide as maintenance therapy, whether the benefits outweigh the risks should be taken into account.     

Role of MicroRNAs in Malignant Glioma

Objective:

This overview seeked to bring together the microRNA (miRNA) researches on biogenesis and bio-function in these areas of clinical diagnosis and therapy for malignant glioma.

Data Sources:

Using the keyword terms “glioma” and “miRNA,” we performed the literature search in PubMed, Ovid, and web.metstr.com databases from their inception to October 2014.

Study Selection:

In screening out the quality of the articles, factors such as clinical setting of the study, the size of clinical samples were taken into consideration. Animal studied for verification and reviews article were also included in our data collection.

Results:

Despite many advance in miRNA for malignant glioma, further studies were still required to focus on the following aspects: (i) Improving the understanding about biogenesis of miRNA and up-down regulation; (ii) utilizing high-throughput miRNA expression analysis to screen out the core miRNA for glioma; (iii) Focusing related miRNAs on the signal transduction pathways that regulate the proliferation and growth of glioma.

Conclusions:

We discussed the most promising miRNA, correlative signaling pathway and their relation with gliomas in the way of prompting miRNA target into being a clinical therapeutic strategy.     

Renal Doppler and Novel Biomarkers to Assess Acute Kidney Injury in a Swine Model of Ventricular Fibrillation Cardiac Arrest

Background:

Majority of the research on cardiac arrest (CA) have focused on post-CA brain injury and myocardial dysfunction, the renal dysfunction and acute kidney injury (AKI) in other critical illnesses after CA have not been well described. This study was designed to assess AKI with renal Doppler and novel AKI biomarkers in a swine model of ventricular fibrillation cardiac arrest (VFCA).

Methods:

Thirty healthy piglets were divided into VFCA group (n = 22) and Sham group (n = 8) in a blinded manner. Mean arterial pressure, heart rate, and cardiac output were recorded continuously. Cardiac arrest (CA) was induced by programmed electric stimulation in the VFCA group, and then cardiopulmonary resuscitation was performed. Twenty piglets returned of spontaneous circulation (ROSC) and received intensive care. Blood and urine samples were collected for AKI biomarkers testing, and Color Doppler flow imaging was performed at baseline, 6 h, 12 h, and 24 h, respectively after ROSC. At ROSC 24 h, the animals were sacrificed and a semi-quantitative evaluation of pathologic kidney injury was performed.

Results:

In the VFCA group, corrected resistive index (cRI) increased from 0.47 ± 0.03 to 0.64 ± 0.06, and pulsatility index (PI) decreased from 0.82 ± 0.03 to 0.68 ± 0.04 after ROSC. Cystatin C (CysC) in both serum and urine samples increased at ROSC 6 h, but neutrophil gelatinase-associated lipocalin (NGAL) in serum increased to 5.34 ± 1.68 ng/ml at ROSC 6 h, and then decreased to 3.16 ± 0.69 ng/ml at ROSC 24 h while CysC increasing constantly. According to the renal histopathology, 18 of 20 animals suffered from kidney injury. The grade of renal injury was highly correlated with RI, cRI, NGAL, and CysC. Linear regression equation was established: Grade of renal injury = 0.002 × serum CysC + 6.489 × PI + 4.544 × cRI – 8.358 (r² = 0.698, F = 18.506, P < 0.001).

Conclusions:

AKI is common in post-CA syndrome. Renal Doppler and novel AKI biomarkers in serum and urine are of significant importance as early predictors of post-CA AKI.     

Natural History of Small Renal Masses

Objective:

To review the natural history and growth kinetics of small renal masses (SRMs).

Data Sources:

The literature concerning natural history and growth kinetics of SRMs was collected from PubMed published from 1990 to 2014.

Study Selection:

We included all the relevant articles on the active surveillance (AS) or delayed treatment for SRMs in English, with no limitation of study design.

Results:

SRMs under AS have a slow growth potential in general. The mean linear growth rate is 0.33 cm/year, the mean volumetric growth rate is 9.48 cm³/year. The rate of metastasis during AS is below 2%. Some factors are associated with the growth rate of SRMs, including tumor grade, histological subtype, initial tumor size, age, radiographic characteristics, and molecular markers. No definite predictor of growth rate of SRMs is defined at present. SRMs with high tumor grade and the subtype of clear cell renal cell carcinoma may have aggressive growth potential.

Conclusions:

AS is a reasonable choice for elderly patients with SRMs, who are at high risk from surgery. Progression during observation is the biggest concern while performing AS. There is no definite predictor of progression for SRMs under AS. Percutaneous renal biopsy providing immunohistological and genic biomarkers may improve the understanding of natural history of SRMs.     

Analysis of Serum Metabolic Profile by Ultra-performance Liquid Chromatography-mass Spectrometry for Biomarkers Discovery: Application in a Pilot Study to Discriminate Patients with Tuberculosis

Background:Tuberculosis (TB) is a chronic wasting inflammatory disease characterized by multisystem involvement,which can cause metabolic derangements in afflicted patients.Metabolic signatures have be...     

Long Non-coding RNAs Expression Profile in HepG2 Cells Reveals the Potential Role of Long Non-coding RNAs in the Cholesterol Metabolism

Background:Green tea has been shown to improve cholesterol metabolism in animal studies,but the molecular mechanisms underlying this function have not been fully understood.Long non-coding RNAs (lncRNA...     

Elevation of serum pancreatic amylase and distortion of pancreatic cyto-architecture in type 1 diabetes mellitus rats treated with Ocimum gratissimum

Background:

Diabetes mellitus has been shown to cause severe impairment in exocrine pancreatic function and cyto-architecture. Ocimum grattissimum has been reported to lower blood glucose levels in experimental diabetic animals. This study, therefore, aims to investigate if treatment with O. grattissimum can alleviate these pancreatic complications of diabetes mellitus. The phytoconstituents and median lethal dose of the plant extract were determined.

Materials and Methods:

Eighteen rats were divided into three groups of six rats each. Diabetes mellitus was induced by single intraperitoneal injection of 65 mg/kg streptozotocin. Group 1 was the control and were given normal feed only; Group 2 was of diabetic untreated rats, while Group 3 was O. grattissimum-treated diabetic rats at a dose of 1,500 mg/kg. After 28 days, blood was collected by cardiac puncture of the anaesthetised animals and the serum was obtained for analysis of serum pancreatic amylase. Permanent preparations using routine biopsy method were employed for histological preparations.

Results:

Results showed that the level of pancreatic serum amylase in the test groups (diabetic and diabetic-treated) were significantly higher (P < 0.05) than the control group, while the diabetic-treated group was significantly lower than the diabetic group. Atrophic acinar tissue without β-cells was noted in the diabetic and diabetic-treated groups. Patchy areas of necrosis, oedematous interstitium, haemorrhagic and necrotic acinar cells were present in diabetic-treated groups.

Conclusion:

Direct association exists between the hyperglycaemic state caused by diabetes mellitus and the elevation of the serum pancreatic amylase and distortion of pancreatic cyto-achitecture. O. grattissimum-treatment reduced serum pancreatic amylase level to near normal and limit the extent of structural damage.     

Significance of serum butyrylcholinesterase levels in oral cancer

Background

Oral squamous cell carcinoma (OSCC) is a relatively common epithelial malignancy, and thus represents a significant public health problem. Early detection improves quality of life for affected patients. Identification of molecular markers (or biomarkers) which can predict disease progression is necessary for better management of these disorders. A correlation of cholinesterase with tumourigenesis, cell proliferation and cell differentiation has been observed. Butyrylcholinesterase (BChE; pseudocholinesterase) has been shown to be a biochemical marker for cervical cancer which is also an epithelial malignancy. In this study, we sought to estimate and compare serum BChE levels in healthy controls and patients with biopsy-proven oral squamous cell cancer (also an epithelial malignancy) before definitive therapy as radiotherapy or chemotherapy may alter the levels of BChE and may act as a confounding variable.

Method

After obtaining consent from biopsy proven oral cancer patients (n= 39) (before onset of any definitive treatment), and from age- and sex-matched healthy controls (n = 20), 2ml of blood was collected. After clot formation samples were centrifuged, serum was collected for estimation of BChE.

Results

Pre-treatment serum BChE levels were significantly elevated (p < 0.0001) in oral cancer patients compared to that of controls. BChE levels showed a significant increase (p = 0.005) with advancing stage in oral cancer patients.

Conclusion

Our results show there could be a role for serum BChE in determining the prognosis of oral cancer.