Chemokine receptors are infrequently expressed in malignant and benign mesothelial cells

We studied chemokine receptor expression in malignant mesothelioma (MM), reactive mesothelium (RM), and leukocytes in effusions. The expression of leukocyte markers (CD3, CD4, CD8, CD14, CD16, and CD19) and chemokine receptors (CXCR1, CXCR4, CCR2, CCR5, and CCR7) was studied in 11 MM and 16 RM specimens using flow cytometry. RM specimens showed higher lymphocyte counts (mean rank, 17.6 vs 8.8; P = .004), whereas monocyte numbers were higher in MM (mean rank, 19.5 vs 10.2; P = .002). CXCR1 (P =.006) and CXCR4 (P = .036) expression was higher in MM monocytes. Chemokine receptors were infrequently expressed in MM (0-2/11 effusions per receptor), whereas RM specimens were uniformly negative. Chemokine receptors are widely expressed on leukocytes in MM and RM effusions but are infrequently found on cells of mesothelial origin. This finding suggests a major role for an autocrine chemokine pathway in leukocytes but not in MM cells. The increased monocyte infiltration and their higher chemokine receptor expression in MM effusions may have a tumor-promoting rather than tumor-inhibiting effect.     

The novel colorectal cancer biomarkers CDO1, ZSCAN18 and ZNF331 are frequently methylated across gastrointestinal cancers

We have previously shown that gastrointestinal cancers display similar epigenetic aberrations. In a recent study, we identified frequently methylated genes for cholangiocarcinoma (CDO1, DCLK1, SFRP1 and ZSCAN18), where one of these genes, DCLK1, was also confirmed to be highly methylated in colorectal cancer. The aim of the present study was to determine whether these four genes, in addition to one gene found to be methylated in colon cancer cell lines (ZNF331), are commonly methylated across gastrointestinal malignancies, as well as explore their role as potential biomarkers. Quantitative methylation specific PCR (qMSP) of colorectal cancer (n = 164) and normal colorectal mucosa (n = 106) samples showed that all genes were frequently methylated in colorectal cancer (71–92%) with little or no methylation in normal mucosa (0–3%). Methylation of minimum two of these five genes identified 95% of the tumors with a specificity of 98%, and an area under the receiver operating characteristics curve (AUC) of 0.98. For gastric (n = 25) and pancreatic (n = 20) cancer, the same panel detected 92% and 90% of the tumors, respectively. Seventy‐four cancer cell lines were further analyzed by qMSP and real time RT‐PCR. In addition to the previously reported DCLK1, a high negative correlation between promoter DNA methylation and gene expression was observed for CDO1, ZNF331 and ZSCAN18. In conclusion, the high methylation frequency of these genes in colorectal‐ as well as in gastric‐, pancreatic‐ and bile duct cancer confirmed an epigenetic similarity between gastrointestinal cancer types, and simultaneously demonstrated their potential as biomarkers, particularly for colorectal cancer detection.     

Preserved granulocyte formation and function, as well as bone marrow innervation, in subjects with complete spinal cord injury

Patients with a spinal cord injury are at risk of infections and is partly attributed to immobilization. Their lymphocyte-mediated immunity is impaired and the growth of blood progenitor cells is reduced. An adequate immune response depends on granulocytes being mobilized rapidly and activated properly, at the inflammatory site. Possibly this requires a coordinated interaction between the autonomous nervous system and cells within the haematopoietic bone marrow. Granulocyte function in the spinal cord injured has not been evaluated. Although there is evidence that the bone marrow in rodents is innervated, it is uncertain whether human bone marrow is similarly affected. Microscopy and immunolabelling followed by flow cytometry, showed that blood and bone marrow counts of leucocyte subsets were similar in paraplegic, tetraplegic and control subjects (P > 0.05). Neutrophilic migration and oxygen consumption, as well as eosinophil activation, assayed as release of eosinophilic cationic protein or CD69 expression, were not altered after spinal cord injury (P > 0.05). Cryostat sections of human bone marrow biopsies stained positive with glyoxylic acid, indicating the presence of catecholamine-containing nerves in both the patients and the controls. We conclude that terminal differentiation and formation of granulocytes, as well as their functional capacity, do not depend appreciably on supraspinal nervous regulation.     

Gene expression signatures differentiate uterine endometrial stromal sarcoma from leiomyosarcoma

ObjectiveEndometrial stromal sarcoma (ESS) and leiomyosarcoma (LMS) are the two most common uterine sarcomas, but both are rare tumors. The aim of the present study was to compare the global gene expression patterns of ESS and LMS.MethodsGene expression profiles of 7 ESS and 13 LMS were analyzed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry.ResultsUnsupervised hierarchical clustering using all 54,675 genes in the array separated ESS from LMS samples. We identified 549 unique probes that were significantly differentially expressed in the two malignancies by greater than 2-fold with 1% FDR cutoff using one-way ANOVA with Benjamini–Hochberg correction, of which 336 and 213 were overexpressed in ESS and LMS, respectively. Genes overexpressed in ESS included SLC7A10, EFNB3, CCND2, ECEL1, ITM2A, NPW, PLAG1 and GCGR. Genes overexpressed in LMS included CDKN2A, FABP3, TAGLN, JPH2, GEM, NAV2 and RAB23. The top 100 genes overexpressed in LMS included those coding for myosin light chain and caldesmon, but not the genes coding for desmin or actin. CD10 was not overexpressed in ESS. Results for selected genes were validated by quantitative real-time PCR and immunohistochemistry.ConclusionsWe present the first study in which gene expression profiling was shown to distinguish between ESS and LMS. The molecular signatures unique to each of these malignancies may aid in expanding the diagnostic battery for their differentiation, and may provide a molecular basis for prognostic studies and therapeutic target discovery.     

Postoperative wound infection: Relation to different types of operation and wound contamination categories in orthopaedic surgery

During one year, 1,407 operations were performed on inpatients in an orthopaedic department. The presence or absence of postoperative wound infection was recorded during the hospital stay, at discharge and at follow up. Wound infections were linked to operations of different contamination categories and to the different types of operation performed. Better information about the risk for postoperative wound infection and the need for antibiotic prophylaxis was provided by considering the different operation types.