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Tumor-associated macrophages and monocytes are the major stromal cell types found in the tumor immune microenvironment (TIME), which modulates tumor progression, invasion, and chemoresistance. To address the need for an in vitro three-dimensional tumor model for understanding the complex cellular interactions within the TIME, we propose a TIME-mimetic co-culture matrix composed of photo-crosslinked poly(ethylene glycol) hydrogels mimicking the characteristics of the tumor and stroma. Desmoplasia-mimetic microgels encapsulating lung adenocarcinoma cells (A549) were embedded with monocyte- or macrophage-type U937 cells in normal stroma-mimetic hydrogel, increasing the proximity between the two cell types. By modulating the proteolytic degradability of the hydrogels, we could separate different cell types with high purities for use in orthogonal assays. In addition, we demonstrated that U937 cells had distinct influences on A549 cell death depending on their activation states (i.e. monocyte, M0, or M1 phenotype). M1 macrophages suppressed tumor growth and increased the susceptibility of A549 cells to cisplatin. In contrast, monocytes upregulated cancer stem cell markers (OCT4, SOX2, and SHH) of A549 cells, showing M2-like features, such as downregulated expression of proinflammatory markers (IL6 and TNFα). These findings suggest that this co-culture system is potentially used for investigation of heterotypic cellular interactions in the TIME. The developed co-culture model successfully reproduces complex tumor immune microenvironment. The model is composed of tumor- and stroma-mimetic matrices containing tumor and immune cells. Sequential matrix degradation enabled the independent cell collection. [ABSTRACT FROM AUTHOR]

Background: The clinical relevance of Mycobacterium szulgai respiratory isolates has been controversial. The aim of this study was to determine the clinical significance of M. szulgai isolates from respiratory specimens and to identify the clinical features and outcomes of M. szulgai lung disease. Methods: We reviewed the medical records of 30 patients from whom M. szulgai was isolated between 2001 and 2010 at the Samsung Medical Center (Seoul, Korea). Results: Of the 30 patients, 13 (43%) met the American Thoracic Society diagnostic criteria and were thus likely to have true M. szulgai lung disease. Approximately 57% (17/30) of M. szulgai isolates were recovered only once from patients with other pulmonary diseases, such as pulmonary tuberculosis and other non-tuberculous mycobacterial lung diseases. The 13 patients with M. szulgai lung disease included 12 men (92%), and the median age was 63 y. Among them, 7 (54%) were current smokers and 7 (54%) had a history of previous treatment for tuberculosis. Eight (62%) patients had the fibrocavitary form of M. szulgai lung disease. Nine (69%) patients received anti-mycobacterial treatment for a median duration of 8 months. Conversion to negative cultures was documented in all patients. There was no recurrence or disease-related mortality. Conclusions: Because the isolated M. szulgai from respiratory specimens could be regarded as pathogenic in less than 50% of cases, strict adherence to the recommended diagnostic criteria of non-tuberculous mycobacterial lung disease is essential. [ABSTRACT FROM AUTHOR]

Background: Occult hepatitis B infection (OBI) is the presence of hepatitis B virus (HBV) DNA in serum or hepatic tissue without detectable hepatitis B surface antigen (HBsAg) in serum. Kidney disease patients in the post-renal transplantation period are in a specific situation as a result of the high pre-transplantational risk of HBV infection and post-transplantational immunosuppression. We studied the pre-transplantational prevalence and post-transplantational influence of OBI on kidney transplantation patients. Methods: We investigated pre-transplantational serum samples of 217 HBsAg-negative patients of post-renal transplant status for the presence of HBV DNA by real-time quantitative polymerase chain reaction. Serologic markers for HBV and hepatitis C virus (HCV) infection as well as liver enzymes were analyzed. Results: We detected HBV DNA in 2.3% (5/217) of HBsAg-negative patients, and the median HBV DNA titer was 33.15 copies/ml (range 30.6-144.6 copies/ml). Among the 5 OBI patients, 2 had hepatitis B surface antibodies (anti-HBs) and 1 had hepatitis B core antibodies (anti-HBc IgG). None of the patients with OBI were co-infected with HCV. There was no evidence of reactivation of OBI during the 36-month (range 27-63 months) follow-up monitoring period after transplantation, in spite of immune suppression to prevent rejection. Conclusions: The prevalence of occult HBV in the setting of renal transplantation was higher than that in the general population of Korea, and no reactivation of hepatitis B was observed in patients with OBI in the post-renal transplantation period. [ABSTRACT FROM AUTHOR]

In the present study, the authors analyzed the tyrosine hydroxylase (TH) expression in peripheral blood (PB) of neuroblastoma (NB) patients and investigated the clinical implications. From April 2005 to October 2008, a total of 683 PB specimens (64 at diagnosis, 244 during chemotherapy, 355 during off-therapy follow-up, and 20 at relapse) acquired from141 patients were investigated. TH expression was measured by quantitative reverse transcriptase-polymerase chain reaction (RTPCR). TH-positive rate at diagnosis (21.4%) was higher than those during chemotherapy (0.8%) or off-therapy follow-up (1.7%). TH expression at diagnosis was associated with high-risk features (ie, advanced stage, older age, unfavorable pathology, and amplified N-myc) and the probability of 3- year relapse-free survival in the TH-positive patients was lower than in the TH-negative patients (45.8% ± 27.8% versus 95.8% ± 5.7%, P < .001). TH expression was positive in only 6 specimens during off-therapy follow-up. However, tumor relapse occurred in only 2 out of 6 TH-positive patients. In addition, TH expression was negative during previous off-therapy follow-up, prior to relapse, in 8 out of 10 relapsed patients. Whereas TH expression in PB at diagnosis was associated with high-risk features and a poorer outcome, TH expression during off-therapy follow-up had very limited value for the prediction of a subsequent relapse. [ABSTRACT FROM AUTHOR]

A letter to the editor commenting on a case study of 34 year old woman diagnosed with Germline TP53 mutation and later with Therapy-related myeloid neoplasm is presented.

We investigated the value of Epstein-Barr virus (EBV) DNA load in unfractionated whole blood for the diagnosis and prognosis of EBV-associated lymphoma. From July 2004 to July 2007, we compared EBV DNA loads in 101 patients with lymphoma and 105 control individuals. The median copy number of EBV was higher in patients with EBV-positive lymphoma (p<0.001). In patients with natural killer (NK)/T-cell lymphomas, the median EBV DNA load at presentation was significantly related to the stage (p = 0.011) and response (p = 0.026). The newly proposed classification model for NK/T cell lymphoma showed EBV DNA load differed significantly between patients with upper and extra-upper aerodigestive tracts (p = 0.017). In 16 patients with NK/T-cell lymphoma monitored serially, EBV DNA load correlated well with the treatment response and clinical course. Further prospective studies are required to evaluate the diagnosing and monitoring role of whole blood EBV DNA for uniformly treated patients. [ABSTRACT FROM AUTHOR]

Familial ALS (FALS) is mostly inherited as an age-dependent autosomal dominant trait. Since the discovery of mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1), testing for SOD1 gene mutations has become a routine part of the investigation into ALS patients with a family history. This study reports the results of mutation evaluation and clinical features examination in a Korean family with ALS. The clinical symptoms, signs and neurological findings of a four-generation pedigree with 34 members were collected. Five exons of the Cu/Zn SOD gene were analyzed by polymerase chain reaction. The clinical signs and symptoms of ALS patients began in the lower extremities and spread to the upper extremities and bulbar muscles. The mode of transmission was determined to be autosomal dominant, and low penetrance was seen in females. The age at onset varied from 37 to 77 years. ALSFRS-R testing showed variability in the clinical progression of the disease. A point mutation in exon 1 of the SOD1 gene, resulting in an amino acid change from phenylalanine 20 to cysteine (F20C), was identified. This is the first report of clinical features resulting from the Phe20Cys mutation in the SOD1 gene. [ABSTRACT FROM AUTHOR]