Immunolocalization of Androgen Receptor and Estrogen Receptors in Skin Tags

Abstract

Skin tags (STs) are benign connective tissue tumors of the dermis. Several clinical observations suggested the involvement of sex steroids in their development. This study aimed at investigating the possible role of androgen receptor (AR) and estrogen receptors (ERs) in STs pathogenesis through their immunohistochemical (IHC) localization in skin biopsies of this disease and to correlate their expression with different clinical and histopathological parameters. Using IHC techniques, we examined 62 cases with STs and 30 gender- and age-matched, healthy subjects, representing the control group. ERα, ERβ, and AR were upregulated in STs compared to normal skin in epidermis and dermis (p?<?.001 for all). Higher AR H score was significantly associated with axillary STs (p?=?.02), skin colored tags (p?=?.03), acanthosis, and papillomatosis (p?=?.04 for both). Higher ERα H score was significantly associated with hyperpigmented tags (p?<?.001) and positive family history (p?=?.003). Higher ERβ H score was significantly associated with female gender and obesity (p?=?.004 for both). Higher ERα and AR H scores were significantly associated with loose collagen arrangement (p?=?.02, p?=?.004, respectively). Higher AR, ERα, and ERβ H scores were significantly associated with the presence of mast cells (p?=?.01, p?=?.04, p?=?.002, respectively) and dilated blood vessels (p?=?.006, p?=?.04, p?=?.04, respectively). In conclusion, AR and ERs may share in STs pathogenesis through their effect on keratinocytes, fibroblasts, and mast cells.     

Immunohistochemical Evaluation of Leptin Role in Skin Tags

Skin tags (STs) are common benign dermal connective tissue neoplasms that are mainly composed of loose fibrous tissue. However, their exact etiology is not fully understood. Leptin is a major player in the biology and pathology of the skin and its appendages. It is linked to cell differentiation, proliferation, migration, and survival with pronounced effects on angiogenesis, blood flow, and tissue perfusion. This study aimed at investigating the possible role of leptin in STs pathogenesis and correlating its expression with different clinical and histopathological parameters. Using immunohistochemical techniques, we examined 90 subjects. These included 60 non-obese cases with STs and 30 age-, gender- and Body Mass Index-matched normal subjects as a control group.

Leptin was overexpressed in STs compared with normal skin (p?p?p?H score was significantly associated with female gender (p?=?.004) and haphazard collagen arrangement (p?H score was significantly associated with smooth skin tags (p?=?.01), dilated blood vessels (p?=?.04), presence of mast cells (MCs) (p?=?.002), presence of inflammatory cells (p?=?.004), and haphazard collagen arrangement (p?相似文献   

Immunolocalization of Glioma-Associated Oncogene Homolog 1 in Non Melanoma Skin Cancer

Glioma-associated oncogene homolog (GLI)1 is involved in controlling cell proliferation and angiogenesis. The aim of this work was to explore its possible role in non-melanoma skin cancer pathogenesis through its immunohistochemical (IHC) expression in skin biopsies of these diseases and correlating this expression with the clinico-pathological parameters of the studied cases. Seventy-six cutaneous specimens were studied; 30 cases with basal cell carcinoma (BCC), 30 cases with squamous cell carcinoma (SCC) and 16 normal skin samples, from age- and gender-matched subjects, as a control group. GLI1 was expressed in all BCC cases and in 60% of SCC cases. All SCC cases showed cytoplasmic, while 70% of BCC cases showed nucleocytoplasmic immunoreactivity. It was over expressed in BCC and SCC compared to normal skin (p?=?0.01 and 0.0006, respectively). Higher Histo (H) score in BCC cases was significantly associated with female gender (p?=?0.04), multiple lesions, desmoplastic stromal reaction and stromal angiogenesis (p?p?=?0.004 for all), inflammatory stromal reaction (p?=?0.01), lymph node involvement and absence of calcification (p?=?0.001 for both). In conclusion, GLI1 may play a role in BCC pathogenesis through its role in cell proliferation, migration, and angiogenesis. Its upregulation and cytoplasmic localization in SCC may suggest that its role in tumor pathogenesis is through mechanisms other than Hedgehog pathway activation. Further studies are needed to clarify the exact molecular basis of its oncogenic action.     

The −675 4G/5G PAI-1 polymorphism confers genetic susceptibility to systemic lupus erythematosus,its clinical manifestations,and comorbidities in Mexican-Mestizo population

Abstract

Systemic lupus erythematosus (SLE) involves a broad range of factors that contribute to the development of the disease and its comorbidities. Genetic predisposition influences the development of SLE, and the ?675 4G/5G PAI-1 polymorphism has been associated with several pathologies with a chronic inflammatory component. Our objective was to investigate the genetic association between the ?675 4G/5G PAI-1 polymorphism with SLE, its clinical manifestations, and comorbidities in a Mexican-Mestizo population. The ?675 PAI-1 polymorphism was determined by PCR-RFLP in 716 subjects: 293 SLE patients and 423 control subjects. Significant associations for SLE genetic susceptibility were found in carriers of 4G/5G (OR = 2.63; CI 1.81–3.87; p?<?.001) and 4G/4G (OR = 2.70; CI 1.62–4.51; p?<?.001) genotype in comparison with the 5G/5G genotype; 4G allele carriers also presented genetic risk for SLE (OR = 1.63; CI 1.31–2.03; p?<?.001) compared to the 5G allele. Following a dominant genetic model, a similar association was found with the 4G allele to SLE (OR = 2.66; CI1.84–3.84; p?<?.001). The 4G/5G genotype was associated with shorter disease duration (p?=?.039), as well as lower levels of haemoglobin (p?=?.001) and haematocrit (p?=?.009); the need for prednisone treatment (p?=?.001), higher BMI (p?=?.03), presence of type 2?DM (p?=?.015), clinical activity (Mex-SLEDAI = 57%; p?=?.047), Chronicity (SLICC-ACR = 0; p?=?.015) and CRP levels (p?=?.015) were associated with 5G/5G genotypes. In conclusion, the ?675 4G/5G and 4G/4G PAI-1genotypes were found as genetic risk markers of susceptibility for SLE in the Mexican-Mestizo population, and each genotype could influence the clinical manifestations and comorbidities differently in SLE.     

Immunohistochemical expression of ezrin in cutaneous basal and squamous cell carcinomas

Ezrin is a member of the ezrin-radixin-moesin family of proteins, which link the actin-containing cytoskeleton to the plasma membrane. Overexpression of ezrin protein is correlated with the metastatic potential in several cancers. Little is known about the distribution of ezrin in normal epidermis and nonmelanoma skin cancer; therefore, in the current study, we examined the immunohistochemical expression of ezrin in normal skin (10 biopsies) and epithelial skin tumors (25 basal cell carcinoma [BCC] and 20 squamous cell carcinoma [SCC]). Ezrin was expressed in epidermis of all normal controls with a prominent membranous pattern compared with 93.3% positivity in malignant cases with a significant higher intensity (assessed by H score) in favor of the latter (P = .002). Cytoplasmic expression of ezrin either alone or associated with membranous expression was both seen in BCC and SCC. The median value of H score in SCC (160) cases was higher than that in BCC (60). H score values of ezrin expression in BCC was significantly higher in tumors arising in sites other than the head and neck (P = .04). In SCC, the intensity of ezrin expression tended to be associated with advanced stage (P = .08). Our study demonstrated the probable tumorigenic role of ezrin in epithelial skin tumor formation. It may enhance local invasion or metastasis of epithelial skin tumors, which necessitates further larger study to clarify. The intensity rather than the pattern of ezrin expression had a more probable impact on the tumor behavior.     

Relationships between different nutritional anthropometric statuses and health-related fitness of South African primary school children

Background: A double burden of both under- and over-nutrition exists among South African children.

Aim: To describe associations between nutritional statuses and health-related fitness test performances.

Subjects and methods: Height and weight of 10 285 children (6–13 years; n?=?5604 boys and 4681 girls) were measured and used to calculate body mass index (BMI) and prevalence of overweight and obesity, stunting, wasting and underweight. Physical fitness scores for standing long jump, shuttle run, sit-and-reach, sit-up (EUROFIT) and cricket ball throw were assessed. Age- and gender-specific z-scores were calculated for these variables. Physical fitness for each nutritional status group was compared to children of normal weight.

Results: Compared to normal weight children, overweight and obese children scored lower on all fitness tests (p?p?=?.235) and sit-and-reach (p?=?.015). Stunted and underweight children performed poorer than normal weight children on most fitness tests (p?p?=?.829; underweight: p?=?.538) and shuttle run (underweight: p?=?.017). Performance of wasted children was not as highly compromised as other under-nourished groups, but they performed poorer on the cricket ball throw (p?Conclusions: When compared to normal weight children, both under- and over-nourished children performed poorer on some, but not all, health-related fitness tests.     

Nailfold avascular score and coronary microvascular dysfunction in systemic sclerosis: A newsworthy association

Background and aims

We aimed to assess the relationship between nailfold videocapillaroscopy (NVC) abnormalities and coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD) in patients with systemic sclerosis (SSc).

Process and Outcome Evaluation of Vocational Rehabilitation Interventions in Patients with Prolonged Fatigue Complaints

Background

Prolonged fatigue can cause physical, mental and occupational disability. Fatigue often persists because of a combination of biopsychosocial factors.

Purpose

To evaluate the process and outcomes of three existing outpatient vocational rehabilitation interventions (VRI) in patients with prolonged fatigue complaints. The VRIs differ with regard to the content and treatment duration, enrolment procedure and financing.

Method

A pre-post design was used with repeated measurements before treatment, after treatment and 3 months after treatment. Primary outcomes (fatigue and work participation) and secondary outcomes (physical and social functioning, mental health and physiological indicators (heart rate variability)) were assessed over time using linear mixed models analysis. A process evaluation (i.e. patient reach, content completeness and patient satisfaction) was conducted as well.

Results

One hundred patients participated. Post-treatment, fatigue decreased (p?<?.001) and work participation (p?<?.010), physical functioning (p?<?.001) and mental health (p?<?.001) improved considerably in all three VRIs. Social functioning improved in one VRI (p?=?.022), but did not in the other two (p?=?.442, p?=?.196, respectively). Physiologically, heart rate variability improved in two VRIs (p?=?.044, p?=?.038, respectively). VRIs were administered according to the programme protocol. Almost all patients met their personal goals and the majority was satisfied with the outcomes of diminished constraints at work.

Conclusion

Three VRIs showed significant and clinically relevant outcomes over time regarding decreased fatigue and improved functioning and work participation in fatigued patients. The VRIs administered patient-tailored biopsychosocial interventions as planned and patients were satisfied with the interventions.     

Nuclear Factor Kappa B and Cyclo-Oxygenase-2: Two Concordant Players in Psoriasis Pathogenesis

Nuclear factor kappa B (NFκB) is a key regulatory element in a variety of immune and inflammatory pathways, cellular proliferation, differentiation and apoptosis. Cyclo-oxygenase 2 (COX2) is one of the downstream targets of NFκB. The current work aimed to explore the possible role of NFκB and COX2 in psoriasis pathogenesis through their immunohistochemical (IHC) expression in skin biopsies of this disease and correlating this expression with clinico-pathological parameters of studied cases. 103 subjects were studied; including 58 cases with psoriasis vulgaris (lesional and perilesional skin) and 45 normal, age- and gender-matched subjects, as a control group. NFκB and COX2 expressions were evaluated using standard IHC techniques. NFκB and COX2 were upregulated in psoriasis lesional skin compared to perilesional (p?p?p?=?0.02 for both), severe degree of perivascular inflammatory infiltrate (p?=?0.03 and 0.002, respectively) and thin suprapapillary epidermis (p?=?0.003 and 0.006, respectively). Significant positive correlation was noted between NFκB and COX2 H scores in epidermis (r?=?0.41, p?=?0.02) and dermis (r?=?0.6, p?=?0.04) of lesional skin. Significant positive correlation between NFκB H score and PASI score (r?=?0.38, p?=?0.04) and between COX2 H score and PASI score (r?=?0.52, p?相似文献   

Dasatinib prevent hepatic fibrosis induced by carbon tetrachloride (CCl4) via anti-inflammatory and antioxidant mechanism

Objectives: Dasatinib, a potent and broad-spectrum tyrosine kinase inhibitor, is approved for the treatment of imatinib-resistant chronic myelogenous leukemia. The aim of this study was to evaluate the anti-fibrotic, anti-inflammatory and antioxidant effects of this agent against CCl₄-induced hepatic fibrosis and oxidative status.

Materials and methods: Experimental fibrosis was induced in Wistar male rats by 12 weeks of CCl₄ administration (i.p.). During the last 8 weeks of injection, rats were gavaged daily with Dasatinib (10?mg/kg). To evaluate anti-inflammatory and anti-fibrotic effects of Dasatinib, histopathological examination of liver tissue was performed and serum ALT and AST activities, oxidant, antioxidant parameters and hepatic tumor necrosis factor alpha (TNF-α) were examined. Moreover, transforming growth factor (TGF-β₁), platelet derived growth factor (PDGF) and TNF-α mRNA expressions were also evaluated by real time polymerase chain reaction.

Results: Dasatinib administration induced a significant reduction of ALT and AST activities (p?4 injected rats (p?1 and PDGF were increased due to CCl₄ intoxication (p?p?p?4 administration which was significantly attenuated by Dasatinib (p?Discussion and conclusion: Our findings indicate that Dasatinib can be cautiously an anti-fibrotic, anti-inflammatory and anti-oxidative agent in clinical setting.     

Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study

Abstract

Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth.

Methods: In 10-year-old children (n?=?1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test.

Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p?<?.001) also having higher TPOAb levels at 10 years (p?=?.049). TPOAb was associated with GADA (p?=?.002), ZnT8R/W/QA (p?=?.001) and IA-2A (p?=?.001) while TGAb were associated with ZnT8R/W/QA (p?=?.021). In boys only, TPOAb were associated with GADA (p?=?.002), IA-2A (p?=?.001), ZnT8R/W/QA (p?=?.001) and IAA (p?=?.009), and TGAb with GADA (p?=?.013), IA-2A (p?=?.005) and ZnT8R/W/QA (p?=?.003). Levels of IA-2A correlated to both TPOAb (p?=?.021) and to TGAb (p?=?.011). In boys only, levels of GADA and TGAb correlated (p?=?.009 as did levels of IA-2A and TPOAb (p?=?.013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine.

Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.     

Vascular endothelial growth factor B inhibits lipid accumulation in C2C12 myotubes incubated with fatty acids

To investigate (1) the effect of vascular endothelial growth factor B (VEGFB) on lipid accumulation and the alteration of fatty acids and fatty acid-related enzymes in C2C12 myotubes incubated with fatty acids and (2) the regulatory effect of VEGFB on skeletal muscle lipid metabolism. Mouse C2C12 myotubes were incubated with oleic acid (OA) and palmitic acid (PA), and differentiated mature C2C12 myotubes were treated with VEGFB. Oil-red O staining, BODIPY staining and cell triglycerides (TG) content were examined. Total RNA was isolated, and real-time PCR analysis was performed. Treatment with 100?μM OA and 50?μM PA induced lipid droplet accumulation and increased TG content (p?<?.01), and 100?ng/mL VEGFB reduced lipid droplet accumulation and decreased TG content (p?<?.01). Treatment with 100?ng/mL VEGFB significantly induced the mRNA expression of fatty acid transport protein 1 (FATP1) (p?<?.01) and FATP4 (p?<?.01). Treatment with 100?ng/mL VEGFB significantly induced the mRNA expression of adipose TG lipase and hormone-sensitive lipase (p?<?.01) as well as carnitine palmitoyltransferase I (p?<?.01), peroxisome proliferator-activated receptor-γ coactivator-1α (p?<?.01), acyl-coa dehydrogenase very long chain (p?<?.05), acyl-coa synthetase long-chain family member 1 (p?<?.01), peroxisomal acyl-coenzyme A oxidase 1 (p?<?.05), and mitochondrial uncoupling protein 3 (p?<?.01). VEGFB enhanced FATP1and FATP4 expression, promoted C2C12 myotube fatty acid oxidation and TG decomposition, and inhibited C2C12 myotube fatty acid re-esterification, thus inhibiting lipid accumulation in C2C12 myotubes incubated with fatty acids.     

IL1β, IL18, NFKB1 and IFNG gene interactions are associated with severity of rheumatoid arthritis: A pilot study

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease which can lead to progressive and functional disability. Literature data suggest that some inflammatory proteins are dysregulated in RA patients and its genetic polymorphisms may contribute to the aetiology and pathogenesis of disease in different ethnic groups. Polymorphisms in IL1β, IL18, NFKB1 and IFNG genes were studied in different populations with RA, but the analysis indicated contradictory results. Thereby, we hypothesised that polymorphisms in these genes could have a combined effect on susceptibility to and severity of disease. We evaluated the +3953?C/T IL1β (rs1143634), –137?G/C IL18 (rs187238), –94 ins/del ATTG NFKB1 (rs28362491) and +874?T/A IFNG (rs2430561) polymorphisms in the northeastern Brazilian population. Peripheral blood samples were collected and DNA extraction was conducted. The polymorphisms were evaluated by RFLP and ARMS–PCR. An association was observed in rs1143634 which showed a protective effect against development of RA in carriers of the T allele (OR?=?0.58; 95% CI 0.36–0.92; p?=?.020). In addition, we found an association among genotypes of the rs1143634 with the HAQ index (p?=?.021) and rs2430561 with DAS28 (p?=?.029) and CDAI (p?=?.029). In relation to combined effects of these SNPs (C/C to rs1143634, G/G to rs187238, I/I to rs28362491 and AA to rs2430561) we found a significant association with decreased functional disability (HAQ index p?<?.001) and ESR (p?=?.034), indicating a lower disease activity in carriers of these genotypes. GLM analysis confirmed these associations (HAQ (F?=?5.497; p?<?.001) and ESR (F?=?2.727; p?=?.032)). Our analysis indicated that in the studied population +3953?C/T IL-1β (rs1143634), –137?G/C IL-18 (rs187238), –94 ins/del ATTG NFKB1 (rs28362491) and +874?T/A IFNG (rs2430561) polymorphisms can together contribute to RA severity although they do not individually influence the disease.     

A meta-analysis of the relationship between symptom severity of Posttraumatic Stress Disorder and executive function

Introduction: Some studies of Posttraumatic Stress Disorder (PTSD) find executive dysfunction, whereas others do not. We meta-analytically examined the association between executive function and PTSD and used meta-regression to examine the potential moderating effect of PTSD severity on executive function.

Methods: We conducted a meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We identified published peer-reviewed articles containing measures of executive function and PTSD symptom severity in subjects with PTSD compared to trauma-unexposed controls or trauma-exposed controls without PTSD, or both. We calculated an effect size for each study containing at least one measure of executive function and PTSD symptom severity.

Results: PTSD subjects for whom the Clinician-Administered PTSD Scale (CAPS) score was available had worse executive function compared to both trauma-unexposed controls (g?=?0.464, p?<?.001) and to trauma-exposed controls without PTSD (g?=?0.414, p?=?.001), as did PTSD subjects for whom the Mississippi Scale for Combat-Related PTSD (M-PTSD) score was available (g?=?0.390, p?<?.001). Neither CAPS nor M-PTSD scores significantly moderated the effect size of executive function.

Conclusions: PTSD is associated with executive dysfunction, but this association was not moderated by PTSD symptom severity, suggesting that once PTSD occurs, executive dysfunction may occur regardless of PTSD severity.     

Patients with Primary Immunodeficiencies in Pediatric Intensive Care Unit: Outcomes and Mortality-Related Risk Factors

Purposes

The aims of this study were to review the frequency, characteristics, and the clinical course of primary immunodeficiency (PID) patients admitted to pediatric intensive care unit (PICU) and attempt to identify factors related with mortality that might predict a poor outcome.

Methods

We performed a retrospective review of children with PID aged 1 month to 18 years and admitted to PICU from January 2002 to January 2012 in our tertiary teaching children’s hospital.

Results

There were a total of 51 patients accounting for 71 admissions to the PICU. The most common diagnosis was severe combined immunodeficiency. Respiratory problems were the leading cause for admission. A total of 20 patients received hematopoietic stem cell transplantation. Immune reconstitution was achieved in 9 (45 %) patients and eight of them did survive. In all 56 % of all admission episodes resulted in survival. Risk factors for mortality included requirement of mechanical ventilation (P?<?.001), number of organ system failure (P?=?.013), need for renal replacement therapy (P?<?.001), use of inotropes (P?<?.001), higher Pediatric Logistic Organ Dysfunction (PELOD) score (P?=?.005), and length of PICU stay (P?<?.001).

Conclusions

This is the first study regarding the outcome and mortality-related risk factors for PID patients requiring PICU admission. We suggest that PICU management is as important as early diagnosis and treatment for these patients. Prediction of those at risk for poorer outcome might be beneficial for accurate intensive care management and survival.     

Identification of discrepancy between CTLA4 expression and CTLA4 activation in gastric cancer

Objective: Recently, immune checkpoints blockers showed higher anti-tumor activity for advanced gastric cancer (GC). The purpose of the study is to find out predictive biomarkers related to anti-cytotoxic lymphocyte antigen 4 (CTLA4) therapy.

Materials and methods: Datasets of gene expression omnibus (GEO), the cancer genome atlas (TCGA), and gene set enrichment analysis (GESA) were extracted. Differential expression of CTLA4 between cancer tissues and normal mucosa, enrichment of WT (wild type) vs. CTLA4_KO (knockout) upregulated gene set and clinical significance were analyzed. The expression of CTLA4, CD3, and granzyme A (GZMA) were validated on 30 cases of Chinese GC. Microsatellite instability (MSI) marker MLH1 and Epstein-Barr virus (EBV) marker EBER were examined on 30 cases of Chinese GC by immunohistochemistry and in situ hybridization.

Results: CTLA4 was upregulated in GC tissue relative to normal mucosa in datasets of GSE27342 (fold change?=?1.586, p?<?.001) and GSE63089 (fold change?=?1.365, p?<?.001). Increased CTLA4 expression was positively related to CTLA4 activation. EBV-associated GC (EBVaGC) and microsatellite instability GC (MSIGC) disclosed higher CTLA4 levels than other GCs. Genomic stability GC (GSGC) also showed higher enrichment score of CTLA4 activation. CTLA4 activation resulted in shorter overall survival in GC. The expression level of CTLA4 was well correlated to expression levels of GZMA (R?=?0.701, p?<?.001) and CD3 (R?=?0.750, p?<?.001).

Conclusions: Based on bioinformatics analysis, GSGC should be worth noticed as a potential GC subtypes responsive to anti-CTLA4 treatment.     

The prognostic role of tumor associated glycoprotein 72 (TAG-72) in stage II and III colorectal adenocarcinoma

Tumor associated glycoprotein 72 (TAG-72) is a membrane-bound glycoprotein complex that is overexpressed in many adenocarcinomas. Recently, monoclonal antibody targeting TAG72, minretumomab, have been introduced as a potential therapeutic target in colorectal cancers (CRC) as well as breast and lung cancers. However, the detailed expression profile of TAG72 and its prognostic effect in CRC are not clear yet. We investigated the relationship between tumor associated glycoprotein 72 (TAG-72) expression and clinicopathologic characteristics in CRC using 3E8 antibody, a fully humanized antibody with the highest affinity to TAG-72. Immunohistochemical staining for TAG-72 was performed in 578 CRC patients, and the results were analyzed using a modified Remmele scoring system (score: 0–12). Of the 578 patients, 144 (24.9%) composed the TAG-72 overexpression (TAG-72^high) group. TAG-72^high was significantly associated with microsatellite stable tumor (P?=?.002), lymphatic invasion (P?=?.001), venous invasion (P?=?.005), and high pN status (P?<?.001). In survival analyses, TAG-72^high group showed shorter disease-free survival in univariate analysis (P?=?.001), and TAG-72^high was found to be an independent prognostic factor in multivariate analysis (P?=?.028), in addition to TNM stage. In conclusion, TAG-72 is thought to be the factors involved in the progression of CRC and may be considered as one of the potential therapeutic target.     

Immunogenicity of branched polyethylene glycol modified interferon alpha

Aim: To assess the immunogenicity of Peginterferon alpha-2?b(Pegberon) and its effect on the efficacy and safety in phase III clinical trial, by comparing it with the control drug Pegasys.

Methods: 770 patients were recruited in total. 509 were treated with Pegberon plus ribavirin and 261 were treated with Pegasys plus ribavirin. After treatment of 12 and 24?weeks, plasma samples were collected from individual patients for detecting the anti-therapeutic antibodies (ATA) and hepatitis C RNA(HCV RNA), to evaluate the production of antibodies and their adverse effect on the efficacy and safety of the treatments. With data obtained from the treatments with Pegberon or Pegasys, gross comparison analysis was performed.

Results: The incidence of treatment-induced neutralizing antibodies (NAb) of Pegberon group (0.7%, 3/454) was significantly lower than Pegasys group (5.0%,12/238)(p?p?=?.010), between baseline NAb positive (36.0%,9/25) and baseline NAb negative patients (76.4%,569/745)(p?p?=?.034). The incidence of potential immunogenicity-related adverse reactions (AR) showed no significant difference between Pegberon (55.6%,283/509) and Pegasys groups (53.6%,140/261)(p?=?.605) and the profiles of these AR were also similar between the two groups.

Conclusion: The incidence of treatment-induced Nab in Pegasys group was significantly higher than the Pegberon group. Baseline ATA, induced ATA and baseline NAb all affected the efficacy. The profiles of potential immunogenicity-related AR were similar between two drug groups, indicating the immunogenicity had no significant adverse effect on safety.     

Differential expression of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer: implications for tumour progression

AIMS: To investigate the expression of matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in non-melanoma skin cancer (NMSC) and to compare their expression between different tumour types and with clinicopathological factors. METHODS AND RESULTS: A study of 11 normal skin, 29 Bowen's disease (BD), 40 squamous cell carcinoma (SCC) and 38 basal cell carcinoma (BCC) samples for MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out using immunohistochemistry and in situ hybridization. The expression of all metalloproteinases was greater in tumours than in normal skin. MMP-2 and MMP-9 expression was more extensive in the stroma of SCC than of BCC or BD. TIMP-1 expression was greater in the stroma of BCC than of SCC or BD and TIMP-2 expression was greater in the stroma of SCC than of BD. There was a correlation between increased metalloproteinase expression and depth of lesion (MMP-2 and TIMP-2), inflammation (MMP-2, MMP-9, TIMP-1 and TIMP-2) and microvessel density (MMP-2, MMP-9 and TIMP-2). CONCLUSIONS: MMP-2, MMP-9, TIMP-1 and TIMP-2 play an important role in the pathogenesis of non-melanoma skin cancer, but differ significantly in their expression levels between the tumour types examined. The immunoexpression of these proteins may be useful indicators of cutaneous cancer invasion and progression.     

Involvement of IL-1β and IL-6 in antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in rats

Purpose: Evidence show that statins possess wide beneficial cardioprotective and anti-inflammatory effects; therefore, in the present experiment, we investigated the antiarrhythmic properties of atorvastatin in ouabain-induced arrhythmia in isolated rat atria and the role of several inflammatory cytokines in this effect.

Materials and methods: Male rats were pretreated with either of atorvastatin (10?mg/kg) or vehicle, orally once daily for 6 weeks. After induction of anesthesia, we isolated the atria and after incubation with ouabain, time of onset of arrhythmia and asystole as well as atrial beating rate and contractile force were recorded. We also measured the atrial levels of IL-1β, IL-6, and TNF-α after the injection of ouabain to animals.

Results: Pretreatment with atorvastatin significantly delayed the onset of arrhythmia and asystole compared with vehicle-treated group (p?p?p?p?>?.05). Injection of ouabain elevated the atrial levels of IL-1β, IL-6, and TNF-α, while pretreatment of animals with atorvastatin could reverse the ouabain-induced increase in atrial IL-1β and IL-6 (p?p?Conclusions: It is concluded that observed antiarrhythmic effects of atorvastatin might be attributed to modulation of some inflammatory cytokines, at least IL-1β and IL-6.