To identify novel genes in castration-resistant prostate cancer (CRPC), we downloaded three microarray datasets containing CRPC and primary prostate cancer in Gene Expression Omnibus (GEO). R packages affy and limma were performed to identify differentially expressed genes (DEGs) between primary prostate cancer and CRPC. After that, we performed functional enrichment analysis including gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway. In addition, protein-protein interaction (PPI) analysis was used to search for hub genes. Finally, to validate the significance of these genes, we performed survival analysis. As a result, we identified 53 upregulated genes and 58 downregulated genes that changed in at least two datasets. Functional enrichment analysis showed significant changes in the positive regulation of osteoblast differentiation pathway and aldosterone-regulated sodium reabsorption pathway. PPI network identified hub genes like cortactin-binding protein 2 (CTTNBP2), Rho family guanosine triphosphatase (GTPase) 3 (RND3), protein tyrosine phosphatase receptor-type R (PTPRR), Jagged1 (JAG1), and lumican (LUM). Based on PPI network analysis and functional enrichment analysis, we identified two genes (PTPRR and JAG1) as key genes. Further survival analysis indicated a relationship between high expression of the two genes and poor prognosis of prostate cancer. In conclusion, PTPRR and JAG1 are key genes in the CRPC, which may serve as promising biomarkers of diagnosis and prognosis of CRPC.
Computational Biology/methods* ; Gene Ontology ; Humans ; Jagged-1 Protein/genetics* ; Male ; Prognosis ; Prostatic Neoplasms, Castration-Resistant/mortality* ; Protein Interaction Maps ; Receptor-Like Protein Tyrosine Phosphatases, Class 7/genetics*

Protein tyrosine phosphatases (PTPs) play an important role in regulating cell signaling events in coordination with tyrosine kinases to control cell proliferation, apoptosis, survival, migration, and invasion. Receptor-type protein tyrosine phosphatases (PTPRs) are a subgroup of PTPs that share a transmembrane domain with resulting similarities in function and target specificity. In this review, we summarize genetic and epigenetic alterations including mutation, deletion, amplification, and promoter methylation of PTPRs in cancer and consider the consequences of PTPR alterations in different types of cancers. We also summarize recent developments using PTPRs as prognostic or predictive biomarkers and/or direct targets. Increased understanding of the role of PTPRs in cancer may provide opportunities to improve therapeutic approaches.
Apoptosis ; Cell Proliferation ; Cell Survival ; Humans ; Neoplasm Invasiveness ; Neoplasms ; enzymology ; Receptor-Like Protein Tyrosine Phosphatases ; genetics ; physiology

Spontaneous gastric perforation is a rare complication of gastric lymphoma that is potentially life threatening since it can progress to sepsis and multi-organ failure. Morbidity also increases due to prolonged hospitalization and delay in initiating chemotherapy. Therefore prompt diagnosis and appropriate treatment is critical to improve prognosis. A 64-year-old man presented to the emergency department with severe abdominal pain. Chest X-ray showed free air below the right diaphragm. Abdominal CT scan also demonstrated free air in the peritoneal cavity with large wall defect in the lesser curvature of gastric lower body. Therefore, the patient underwent emergency operation and primary closure was done. Pathologic specimen obtained during surgery was compatible to diffuse large B cell lymphoma. Fifteen days after primary closure, the patient received subtotal gastrectomy and chemotherapy was initiated after recovery. Patient is currently being followed-up at outpatient department without any particular complications. Herein, we report a rare case of gastric lymphoma that initially presented as peritonitis because of spontaneous gastric perforation.
Abdominal Pain ; Antigens, CD20/metabolism ; Antigens, CD45/metabolism ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Gastrectomy ; Humans ; Intestinal Perforation/diagnostic imaging ; Lymphoma, Large B-Cell, Diffuse/*diagnosis/drug therapy/pathology ; Lymphoma, Non-Hodgkin/*diagnosis/drug therapy/pathology ; Male ; Middle Aged ; Positron-Emission Tomography ; Stomach Neoplasms/*diagnosis/drug therapy/pathology ; Tomography, X-Ray Computed

BACKGROUNDFetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKAL1, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.

METHODSTwelve single nucleotide polymorphisms (rs7756992/rs10946398 in CDKAL1, rs1111875 in HHEX, rs391300 in SRR, rs17584499 in PTPRD, rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5) were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.

RESULTSBirthweight was inversely associated with CDKAL1-rs10946398 (β = -41 g [95% confidence interval [CI]: -80, -3], P = 0.034), common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight (β = -36 g [95% CI: -72, -0.2], P = 0.048). The risk allele in SRR showed a trend toward a reduction of birthweight (P = 0.085).

CONCLUSIONSThis study identified the association between type 2 diabetes risk variants in CDKAL1 and birthweight in Chinese Han individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.

Adenylyl Cyclases ; genetics ; Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Birth Weight ; genetics ; Cyclin-Dependent Kinase 5 ; genetics ; Diabetes Mellitus, Type 2 ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Homeodomain Proteins ; genetics ; Humans ; Infant, Low Birth Weight ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Receptor-Like Protein Tyrosine Phosphatases, Class 2 ; genetics ; Transcription Factors ; genetics ; tRNA Methyltransferases

OBJECTIVES: Mesenchymal stem cells (MSCs) are adult stem cells which identified by adherence to plastic, expression of cell surface markers including CD44, CD90, CD105, CD106, CD166, and Stro-1, lack of the expression of hematopoietic markers, no immunogenic effect and replacement of damaged tissues. These properties led to development of progressive methods to isolation and characterization of MSCs from various sources for therapeutic applications in regenerative medicine. METHODS: We isolated MSC-like cells from testis biopsies, ovary, hair follicle and umbilical cord Wharton's jelly and investigated the expression of specific cell surface antigens using flow cytometry in order to verify stemness properties of these cells. RESULTS: All four cell types adhered to plastic culture flask a few days after primary culture. All our cells positively expressed common MSC-specific cell surface markers. Moreover, our results revealed the expression of CD19and CD45 antigens in these cells. CONCLUSION: According to our results, high expression of CD44 in spermatogonial stem cells (SSCs), hair follicle stem cells (HFSCs),granulosa cells (GCs)and Wharton's jelly-MSCs (WJ-MSCs)may help them to maintain stemness properties. Furthermore, we suggest that CD105+SSCs, HFSCs and WJ-MSCs revealed the osteogenic potential of these cells. Moreover, high expression of CD90 in SSCs and HFSCs may associate to higher growth and differentiation potential of these cells. Further, the presence of CD19 on SSCs and GCs may help them to efficiency in response to transmembrane signals. Thus, these four types of MSCs may be useful in clinical applications and cell therapy.
Adult Stem Cells* ; Antigens, CD45 ; Antigens, Surface ; Biopsy ; Cell- and Tissue-Based Therapy ; Female ; Flow Cytometry ; Hair Follicle ; Humans ; Mesenchymal Stromal Cells* ; Ovary ; Plastics ; Regenerative Medicine ; Stem Cells ; Testis ; Umbilical Cord ; Wharton Jelly

No abstract available.
Acute Disease ; Adult ; Antigens, CD4/metabolism ; Antigens, CD45/metabolism ; Antigens, CD56/metabolism ; Bone Marrow Cells/cytology ; Flow Cytometry ; Hematologic Neoplasms/*diagnosis/pathology ; Humans ; Interleukin-3 Receptor alpha Subunit/metabolism ; Lymph Nodes/metabolism/pathology ; Male ; Tomography, X-Ray Computed

This study was undertaken to identify genetic polymorphisms that are associated with the risk of an elevated fasting glucose (FG) level using genome-wide analyses. We explored a quantitative trait locus (QTL) for FG level in a genome-wide study from a Korean twin-family cohort (the Healthy Twin Study) using a combined linkage and family-based association analysis approach. We investigated 1,754 individuals, which included 432 families and 219 pairs of monozygotic twins. Regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2, were found to show evidence of linkage with FG level, and several markers in these regions were found to be significantly associated with FG level using family-based or general association tests. In particular, a single-nucleotide polymorphism (rs6138953) on the PTPRA gene in the 20p13 region (combined P = 1.8 x 10(-6)) was found to be associated with FG level, and the PRKCB1 gene (in 16p12.1) to be possibly associated with FG level. In conclusion, multiple regions of chromosomes 2q23.3-2q31.1, 15q26.1-15q26.3, 16p12.1, and 20p13-20p12.2 are associated with FG level in our Korean twin-family cohort. The combined approach of genome-wide linkage and family-based association analysis is useful to identify novel or known genetic regions concerning FG level in a family cohort study.
Adult ; Aged ; Asian Continental Ancestry Group/*genetics ; Blood Glucose/*genetics ; Chromosomes, Human, Pair 15/genetics ; Chromosomes, Human, Pair 16/genetics ; Chromosomes, Human, Pair 2/genetics ; Chromosomes, Human, Pair 20/genetics ; Cohort Studies ; Family ; Female ; *Genetic Linkage ; *Genome-Wide Association Study ; Genotype ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Protein Kinase C/genetics ; Quantitative Trait Loci ; Receptor-Like Protein Tyrosine Phosphatases, Class 4/*genetics ; Republic of Korea ; Twins, Monozygotic/*genetics

Mantle cell lymphoma (MCL) is a kind of mature B-cell neoplasms with significantly poor prognosis and is usually misdiagnosed. With the development of flow cytometry and cytogenetic technique, most patients were at leukemic phase when diagnosed. This study was purposed to investigate the immunophenotypes of MCL, the immunophenotype information of 22 leukemic MCL patients was analyzed retrospectively. All the patients were conformed t(11;14) translocation by fluorescence in situ hybridization. Immunophenotypes were detected by a four-color flow cytometry including CD3, CD4, CD5, CD8, CD10, CD19, CD20, CD22, CD23, CD25, CD38, CD103, CD148, CD200, FMC7, ZAP-70, κ, λ. The results showed that CD19, CD5, CD20 and monoclonal sIg expressed in all 22 patients with CD20 high expression; CD22 expressed weakly in 17 patients; CD23 expressed in 6 patients including 2 cases highly expressed; FMC7 expressed in 12 patients. 5 patients were 4-point score and 17 patients had a score less than 4 according to CLL scoring system. CD148 and CD200 were detected in 18 patients, in which CD200 expressed negatively in 11 patients, CD200 expressed weakly in 7 patients with median fluorescence intensity (MFI) 25.8 (6.6 - 254.26); CD148 expressed positively in all 18 patients with median MFI: 337 (73.4 - 1341.9). It is concluded that the atypical immunophenotype is common in leukemia MCL, thereby the diagnosis of MCL needs comprehensively analyze with morphocytology, immunophenotype and cytogenetic, CD200 and CD148 as new bio-markers can differentiate MCL from chronic B cell lymphoproliferative disease.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; metabolism ; Female ; Humans ; Immunophenotyping ; Karyotyping ; Lymphoma, Mantle-Cell ; genetics ; immunology ; metabolism ; Male ; Middle Aged ; Receptor-Like Protein Tyrosine Phosphatases, Class 3 ; metabolism ; Retrospective Studies

Myeloid sarcoma is a rare extramedullary myeloid tumor, which is frequently misdiagnosed when no evidence of leukemia is initially observed. Here, we report on a peculiar case of a 49-year-old man afflicted with multiple masses in the jejunum, the superior mesentery, and the serosa of the transverse colon, without leukemic manifestation. The tumor was composed of undifferentiated small round cells containing eosinophilic cytoplasm, which were negative for myeloperoxidase, nonspecific esterase, lysozyme, terminal deoxynucleotidyl transferase, leukocyte common antigen, CD3, CD4, CD15, CD20, CD30, CD43, CD56, CD68/PG-M1, CD79a, human melanoma black-45, c-kit, and CD34 with positivity only for CD68/KP1, CD99, and vimentin. Under electron microscopy, those cells had abundant membrane-bound cytoplasmic granules that measured 200 to 300 nm in diameter, which were consistent with granulocytic azurophilic granules. The tumor was finally diagnosed as a myeloid sarcoma. The presence of non-leukemic myeloid sarcomas showing immunonegativity for conventional myeloid-leukemic markers necessitated a diagnosis by ultrastructural observation.
Antigens, CD45 ; Carboxylesterase ; Colon, Transverse ; Cytoplasm ; Cytoplasmic Granules ; DNA Nucleotidylexotransferase ; Eosinophils ; Humans ; Intestinal Obstruction ; Jejunum ; Leukemia ; Melanoma ; Mesentery ; Microscopy, Electron ; Muramidase ; Peroxidase ; Sarcoma, Myeloid ; Serous Membrane ; Vimentin

BACKGROUND: Merkel cell carcinoma is a rare neuroendocrine tumor that typically presents as indurated nodules in elderly patients. It has an aggressive behavior and thus, such incidence has been increasing. OBJECTIVE: Our purpose was to analyze clinical and histological characteristics of Merkel cell carcinoma, and to obtain a better understanding of this rare malignancy. METHODS: We conducted a clinicopathologic evaluation of 11 patients from our center during 21 year period (1989~2010). We investigated personal and clinical information, including age, sex, time of onset, past history, histologic findings and clinical manifestations. RESULTS: The age of the 11 patients ranged from 48 to 84, and the mean age of onset was 62.3, with a slight female predominance (1:1.7). The most prevalent site was the face then followed by the extremities. Subcutaneous nodular lesion with overlying erythema was the most common finding (72.7%, 8/11). Protruding tumorous lesions were 18.2% (2/11) and palpable lymphadenopathy was 9.1% (1/11), respectively. Histopathologically, pleomorphic atypical cells and granular nuclear dots ("salt and pepper") were observed. Immunohistochemical study showed positivity for pan-cytokeratin (CK), cytokeratin (CK20), CD56, synaptophysin, chromogranin (90%, 81.8%, 100%, 85.7%, 83.3%) and negative result for leukocyte common antigen (LCA, 0/7), and thyroid transcription factor-1 (TTF-1, 0/4), S100 (0/4). CONCLUSION: Merkel cell carcinomas were more frequent in old females and were rare in immunocompromised patients in Korea. Histologic and immunohistochemical features were similar to previous studies, but there was a case of rare type (CK7+/CK20-) of Merkel cell carcinoma. Surgery is a treatment of choice in Merkel cell carcinoma. But radiation or chemotherapy can be used as an adjuvant therapy. Based on this study, characteristics of Merkel cell carcinoma in Korea can be elucidated with more future cases.
Age of Onset ; Aged ; Antigens, CD45 ; Carcinoma, Merkel Cell ; Erythema ; Extremities ; Female ; Humans ; Immunocompromised Host ; Incidence ; Keratins ; Korea ; Lymphatic Diseases ; Neuroendocrine Tumors ; Synaptophysin ; Thyroid Gland