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At least 19 recordsLinked to original sources
PubMed1997

Prognostic significance of angiogenesis in clinically localized prostate cancer (staining for Factor VIII-related antigen and CD34 Antigen.

Tumour angiogenesis is widely considered to be an important phenomenon in the process of tumour growth and metastasis. We investigated the prognostic significance of the microvascular count (MVC) in prostate cancer of each Gleason grade and compared the results to other established pathologic parameters and progression probability. We also compared the staining of Factor VIII-related antigen (FVIII-RA) with CD34 antigen (CD34 Ag) staining for determination of the MVC. We examined 101 radical prostatectomy specimens from patients who underwent curative therapy for clinically localized adenocarcinoma of the prostate as the first form of therapy. To identify microvessels, immunohistochemical staining of endothelial cells was performed using antibodies to FVIII-RA and CD34 Ag in formalin-fixed, paraffin-embedded tissue. Microvessels were counted in fivex200 fields (0.785 mm(2) on each Gleason grade in the 'hot' areas. We used the highest number of five fields in the worst Gleason grade on each staining for statistical analysis. MVC using FVIII-RA and CD34 Ag staining correlated with pathologic stage, Gleason score and preoperative serum prostate-specific antigen level. In addition, MVC using CD34 Ag staining also correlated with DNA ploidy and total tumour volume. The Gleason score was found to be the best prognostic indicator using Cox proportional hazards regression analysis. In this study, MVC in prostate cancer was predictive of pathologic stage and Gleason grade, but MVC by either FVIII-RA and CD34 Ag staining was not an independent prognostic predictor. The best prognostic indicator in this study was Gleason score.

Journal Article↗
PubMed2004

[Analysis of prognostic factors for the extent of vascularity of serous ovarian cancer on the basis of CD34 antigen expression].

OBJECTIVES: Ovarian neoplasms are very important problem in medicine, because they account for 23% of all female genital neoplasms, and they are the cause of 47% deaths among women suffering from gynecological cancers. Progression of neoplasmatic disease depends also on dynamism of angiogenesis, because better oxygen and nutrition substances supply increase tumor growth. To increase the tumor volume of 1 mm3, the development of new vessels is needed, and that also increases the risk of distant metastases. AIM: The aim of the study was the evaluation of clinical parameters compared with histological and laboratory findings in serous carcinomas. The research analyzed of angiogenesis level (antigen CD34) in patients with ovarian cancers and in control group. MATERIALS AND METHODS: The material consisted of 41 cases of serous ovarian cancer. For clinical examinations we chose only patients who underwent primary surgical operation. The control group for CD34 levels were 15 patients with benign serous adenomas. The microscopic (200x) evaluation of blood vessel in paraffin samples were made by showing the reaction of endothelial CD34 antigen with DAKO serum (Monoclonal Mouse Anti Human CD34 class 1-N 1574 LSAB). RESULTS: The level of statistical significance for grading and total vessels' area was p = 0.01 (G1--0.037 mm2, G2--0.019 mm2, G3--0.015 mm2). No difference in vascularity was observed at the level of total vascularisation of serous ovarian cancers (0.021 mm2) and in benign serous adenomas (0.023 mm2). CONCLUSIONS: Among analysed clinical and laboratory parameters only histological grade (G) correlates significantly with the level of vascularisation of ovarian serous cancers.

Adult↗
PubMed1994

Regulation of the expression of the hematopoietic stem cell antigen CD34: role of c-myb.

The CD34 antigen defines a subset of hematopoietic progenitor cells with self-renewal capacity and the ability to reconstitute hematopoiesis in irradiated primates and marrow-ablated humans, but its function remains unknown. The c-myb protooncogene plays a fundamental role in hematopoiesis, most likely via its transcriptional regulator function. We report that c-myb protein transactivates the CD34 promoter via specific interaction with multiple Myb binding sites in the 5' flanking region of the gene and induces expression of the endogenous CD34 mRNA in rodent fibroblasts. Also, constitutive expression of c-myb in CD34-negative human glioblastoma cells induces expression of CD34 mRNA and synthesis of the surface membrane antigen. These data directly demonstrate that c-myb regulates the expression of the hematopoietic stem cell antigen CD34 and raise the possibility that c-myb regulates hematopoiesis inducing a cascade of differentiation-related events.

Animals↗
PubMed2002

Expression of the CD34 antigen in pleomorphic xanthoastrocytomas.

Pleomorphic xanthoastrocytoma (PXA) is a rare, superficially located astrocytic glioma of children and young adults, which is associated with a relatively favorable prognosis. Here we report on the expression of the hematopoietic progenitor cell and vascular endothelial cell associated antigen CD34 in PXAs. We found CD34 immunoreactivity in various fractions of tumor cells in 44 of 60 PXAs investigated (73%). CD34 expression was more common in PXAs of WHO grade II (37 of 44 tumors, 84%) than in PXAs with anaplastic features (7 of 16 tumors, 44%). Immunoreactivity for CD34 was also commonly detected in single or clustered dysplastic neural cells within the cerebral cortex adjacent to the PXAs. Reverse transcription-PCR revealed that PXAs express the full-length CD34 transcript and a known splice variant encoding a truncated form of CD34. Both transcripts were detectable at higher levels in PXAs as compared to diffuse astrocytomas and non-neoplastic brain tissue. Taken together, our findings demonstrate that PXAs frequently express CD34 not only in vascular endothelial cells but also in tumor cells and in dysplastic cells of the adjacent cortex. Therefore, immunostaining for CD34 may be a helpful tool for the histological differential diagnosis of PXAs.

Adolescent↗
PubMed2003

Overexpression of dominant-negative Ikaros 6 protein is restricted to a subset of B common adult acute lymphoblastic leukemias that express high levels of the CD34 antigen.

Ikaros is a critical regulator of hematopoiesis. Its effects result in part from the balance between the isoforms that are produced by differential splicing of the pre-mRNA. Short isoforms that lack the DNA-binding domain act as dominant negatives by binding long isoforms through the C-terminal zinc-finger domain, which allows for the homo- or heterodimerization of the proteins. There are a number of evidences that different subsets of murine hematopoietic progenitors - as defined by phenotype - have different patterns of Ikaros expression. Forced expression of short isoforms (Ik5, Ik6 or Ik7) in murine or human hematopoietic progenitors alters the differentiation capacities of these cells. Human leukemias provide additional information: because of the blockade in differentiation, leukemias represent an equivalent of a particular stage of human hematopoietic hierarchy. We and others have shown that human acute leukemias are heterogeneous for the pattern of Ikaros isoform expression. The present study focused on adult de novo B ALLs and the Ikaros 6 isoform. ProB (BI, n=3), common B (BII, n=15) and preB (BIII, n=3) ALL were identified by their phenotype. RT-PCR and Western blot analyses of blast cell protein lysates suggest that approximately 50% of BII leukemias overexpress Ikaros 6 RNA and protein. Comparison of BII cells with high or normal levels of Ik6 shows a higher level of expression for the membrane stem cell antigen CD34 in the former, as detected with flow cytometry and confirmed with DNA arrays.

Adolescent↗
PubMed2003

Human dental pulp vasculogenesis evaluated by CD34 antigen expression and morphological arrangement.

Vasculogenesis describes the process by which endothelial precursor cells form new blood vessels. To characterize the topography and the cellular processes underlying vascularization of human dental pulp, we examiend the expression of the human hematopoietic progenitor cell antigen CD34. Dental pulps, obtained from deciduous and permanent teeth, were morphologically examined at light- and electron-microscope levels and by expression of CD34. The findings indicate that vasculogenesis of dental pulp is a complicated process starting from single CD34(+) cells. These subsequently coalesce to form solid vascular cords inside the developing connective tissue, which later hollows. Pericytes were embedded within the fully formed microvessels' basement membrane. The presence of CD34(+) endothelial cells in permanent teeth reveals that the process of vasculogenesis persists into adult life, where it contributes to continuous adjustment of vessel and network structures in response to functional needs and dental tissue homeostasis.

Adolescent↗
PubMed1996

Primitive hematopoietic cells in murine bone marrow express the CD34 antigen.

The CD34 antigen is expressed on most, if not all, human hematopoietic stem cells (HSCs) and hematopoietic progenitor cells, and its use for the enrichment of HSCs with repopulating potential is well established. However, despite homology between human and murine CD34, its expression on subsets of primitive murine hematopoietic cells has not been examined in full detail. To address this issue, we used a novel monoclonal antibody against murine CD34 (RAM34) to fractionate bone marrow (BM) cells that were then assayed in vitro and in vivo with respect to differing functional properties. A total of 4% to 17% of murine BM cells expressed CD34 at intermediate to high levels, representing a marked improvement over the resolution obtained with previously described polyclonal anti-CD34 antibodies. Sixty percent of CD34+ BM cells lacked lineage (Lin) markers expressed on mature lymphoid or myeloid cells. Eighty-five percent of Sca-1+Thy-1(10)Lin-/10 cells that are highly enriched in HSCs expressed intermediate, but not high, levels of CD34 antigen. The remainder of these phenotypically defined stem cells were CD34-. In vitro colony-forming cells, day-8 and -12 spleen colony-forming units (CFU-S), primitive progenitors able to differentiate into B lymphocytes in vitro or into T lymphocytes in SCID mice, and stem cells with radioprotective and competitive long-term repopulating activity were all markedly enriched in the CD34+ fraction after single-parameter cell sorting. In contrast, CD34-BM cells were depleted of such activities at the cell doses tested and were capable of only short-term B-cell production in vitro. The results indicate that a significant proportion of murine HSCs and multilineage progenitor cells express detectable levels of CD34, and that the RAM34 monoclonal antibody is a useful tool to subset primitive murine hematopoietic cells. These findings should facilitate more direct comparisons of the biology of CD34+ murine and human stem and progenitor cells.

Animals↗
PubMed1997

Expression of the hematopoietic stem cell antigen CD34 on blood and bone marrow monoclonal plasma cells from patients with multiple myeloma.

Monoclonal plasma cells (CD38+CD45-/dim) are typically present in the blood of patients with active myeloma and can contaminate stem cell harvests. This has led to strategies that select CD34+ cells for use in autologous stem cell transplantation with the goal of decreasing tumor cell contamination. The aim of this study was to learn if the CD34 antigen is expressed on monoclonal plasma cells in the blood or marrow of patients with multiple myeloma. We used three-color flow cytometry (surface CD38;CD45 and cytoplasmic kappa or lambda) to identify monoclonal plasma cells in the blood (n = 24) and marrow (n = 37) from patients with plasma cell proliferative disorders. In each case the CD38+CD45- and CD38+CD45dim+ monoclonal populations were then analyzed for CD34 expression. In all 24 blood and 37 marrow samples, the CD38+CD45-monoclonal plasma cells were negative for CD34 expression. CD38+CD45dim+ monoclonal cells were documented in the blood of 11 patients and in the marrow of 33 patients and this cell population was also CD34-negative in all cases. These results indicate that CD34 is usually not expressed on the CD38+CD45-CD45dim+ monoclonal plasma cells in the blood or marrow of patients with plasma cell proliferative disorders. CD34 selection methods should therefore decrease the chance of tumor cell contamination of the stem cell product.

ADP-ribosyl Cyclase↗
PubMed1995

The stem cell antigen CD34 functions as a regulator of hemopoietic cell adhesion.

Although the CD34 antigen is widely used in the identification and purification of hemopoietic stem and progenitor cells, its function within hemopoiesis is unknown. We have investigated this issue by ectopically expressing human (hu) CD34 on the surface of murine hemopoietic cells. Forced expression of hu-CD34 in the thymocytes of transgenic mice did not appear to affect the development, maturation, or distribution of murine T cells but did significantly increase their ability to adhere to bone marrow stromal layers of human but not mouse origin. Ectopic expression of hu-CD34 on murine 416B cells, a multipotential progenitor that expresses murine CD34, yielded similar results. In both cases hu-CD34-dependent adhesion was enhanced by molecular engagement of the hu-CD34 protein using anti-CD34 antibodies. These results provide evidence that CD34 promotes the adhesive interactions of hemopoietic cells with the stromal microenvironment of the bone marrow thereby implicating CD34 in regulation and compartmentalization of stem cells. We propose that CD34 regulates these processes in part via an indirect mechanism, signaling changes in cellular adhesion in response to molecular recognition of an as yet unidentified stromal CD34 counterreceptor or ligand.

Animals↗
PubMed1999

Angiogenesis in the human temporomandibular joint studied by immunohistochemistry for CD34 antigen.

The CD34 antigen is a sensitive marker of vascular endothelium and angiogenesis. Thus, we examined the expression of CD34 in 20 human temporomandibular joint (TMJ) samples with internal derangement and in 10 control specimens by an immunohistological technique using paraffin-embedded tissue and specific anti-human CD34 monoclonal antibody. In the control specimens, CD34 was observed sporadically within the TMJ discs. On the other hand, in the internal derangement specimens, CD34 was found frequently in the walls of blood capillaries within the TMJ discs. In the synovial membrane, CD34 was detected frequently in the walls of many blood capillaries in both the controls and the internal derangement specimens. Indeed, CD34 expression in internal derangement specimens was more intense than in control specimens. In the posterior loose connective tissue of the bilaminar zone, and in the anterior loose connective tissue between the upper and lower lamellae of the anterior capsular wall, CD34 was detected in abundance in the walls of blood capillaries both of the controls and the internal derangement specimens. Generally, CD34 was found rarely in the walls of large blood vessels. The presence of CD34 is suggested to be correlated with the process of angiogenesis induced by internal derangement of the TMJ.

Adult↗
PubMed1988

Antigen CD34+ marrow cells engraft lethally irradiated baboons.

The CD34 antigen is present on 1-4% of human marrow cells including virtually all hematopoietic progenitors detected by in vitro assays. Since the anti-CD34 monoclonal antibody 12-8 reacts with a similar marrow population in baboons, it was possible to test whether this antigen is expressed by stem cells responsible for hematopoietic reconstitution in vivo. CD34+ cells were enriched from marrows of five baboons using avidin-biotin immunoadsorption. After lethal irradiation, the five animals were given 15-27 X 10(6) autologous marrow cells (3.2-4.4 X 10(6) cells/kg) containing 65-91% CD34+ cells. All animals achieved granulocyte counts greater than 1,000/mm3 and platelet counts greater than 20 X 10(3)/mm3 by 13-24 d posttransplant and subsequently developed normal peripheral blood counts. Two additional animals received 184 and 285 X 10(6) marrow cells/kg depleted of CD34+ cells. One animal died at day 29 without engraftment, while the other had pancytopenia for greater than 100 d posttransplant. The data suggest that stem cells responsible for hematopoietic reconstitution are CD34+.

Animals↗
PubMed1999

Comparative evaluation of commonly used clones and fluorochrome conjugates of monoclonal antibodies for CD34 antigen detection.

CD34+ cell enumeration is currently the most appropriate technique for hematopoietic graft quality control. At the same time, numerous CD34 mAb have become commercially available. This study was designed to compare the commonly used clones 8G12 and QBEND-10 with the new clones 581 and BIRMA-K3. All available fluorochrome conjugates were tested: FITC, PE, and PE-Cy5 or PerCP for QBEND, BIRMA, 581, and 8G12 and FITC and PE for 581. Bone marrow from healthy donors (n = 5) and leukapheresis samples (n = 16) were stained, according to each manufacturer's protocol and analyzed using the FACScan. The following parameters were evaluated: % CD34+ cells detected and percentage of deviation from the median within each sample; mean channel fluorescence intensity of the CD34+ cells; resolution index (median channel fluorescence intensity of CD34+ cells/monocytes), % overlapping of CD34+ cell and monocyte fluorescence; proportion of CD34+ events after blocking with the same unlabeled clone; values of compensation requirements. Tables with results for each evaluated parameter separately were created, and rank points were applied. These scores represented the quality performance of the studied clones and fluorochrome conjugates and may be summarized as follows: 581 and 8G12 produced the best results, followed by BIRMA-K3 and QBEND10. The fluorochrome sequence was PE, PE-Cy5, PerCP, and FITC. However, all PE conjugates of the studied clones provided highly comparable results and conditions for CD34+ cell enumeration. When antigen coexpression must be studied and another dye than PE must be applied for CD34+ cell discrimination, the PE-Cy5 conjugates should be preferred.

Antibodies, Monoclonal↗
PubMed1996

The CD34 antigen: potential clinical advantages of CD34 selection.

The availability of monoclonal antibodies directed towards the haemopoietic cell surface antigen CD34 has facilitated accurate measurement, by flow cytometry, of CD34 positive cell frequencies in bone marrow and peripheral blood. In addition, a range of CD34 selection techniques, to purify peripheral blood progenitor cells or bone marrow prior to transplantation, have been developed. CD34 positive stem and progenitor cells may be selected with final purities in excess of 90%. Such pure populations of CD34 positive stem cells may be useful in several clinical areas, including tumour cell purging and T-cell depletion, and as a basis for gene therapy and stem cell expansion.

Antigens, CD34↗
PubMed1991

The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia.

The human hematopoietic progenitor cell antigen CD34 is synthesized and expressed by early normal hematopoietic progenitor cells and by many acute leukemias. Anti-CD34 antibodies also have been reported to stain blood vessels in tissue sections, and, more recently, CD34 mRNA has been detected in vascular endothelial cells. Therefore, the authors studied the diagnostic utility of immunohistochemical CD34 antigen detection in tumors of endothelial cell derivation and compared the results with stains for von Willebrand (vW) factor. A wide variety of epithelial and mesenchymal neoplasms also were examined to assess the specificity of CD34 for vascular neoplasia. Seven cases of angiosarcoma (seven of seven), five cases of Kaposi's sarcoma (five of five), and eight cases of epithelioid hemangioendothelioma (eight of eight) were moderately to strongly positive for CD34. This reactivity was equally intense in frozen sections, alcohol-fixed tissue, and formalin-fixed specimens. In many cases, the malignant endothelial cells stained more strongly than adjacent benign endothelium. Moreover, in most cases CD34 positivity was quantitatively and qualitatively stronger than staining for vW factor. Two cases of hemangiopericytoma (two of two) were CD34 positive but stained less intensely than the angiosarcomas, Kaposi's sarcomas, or hemangioendotheliomas. Five of six cases of hemangioma also stained positively for CD34; the nonreactive tumor in this group was the only one among 28 vascular neoplasms studied that was not reactive for CD34. In comparison, 9 of the 28 vascular tumors did not stain for vW factor. Three hundred fifty-seven tumors of nonvascular derivation also were examined for CD34 antigen expression. Focal light staining was seen in one pulmonary squamous cell carcinoma; moderate to intense staining was observed in half of the epithelioid sarcomas studied (8 of 16) and in a minority of leiomyosarcomas (3 of 22). These findings indicate that CD34 is a sensitive and relatively specific marker for neoplasms of vascular origin.

Antibodies, Monoclonal↗
PubMed1996

The expression of the endothelial cell antigen CD34 in demyelinating disease.

In this study, the antigenic expression of CD34, a 110 kDa glycoprotein which is expressed on human haemopoietic progenitor cells and vascular endothelium, has been assessed in a variety of neuropathological conditions, including infectious and demyelinating disease. Using immunoperoxidase staining on paraffin sections, the immunohistochemical results show that CD34 antigen is expressed widely on human CNS endothelium in grey and white matter, in the eye including retina, and in the anterior and posterior lobes of the pituitary. In demyelinating disease CD34 antigen expression was not detected in acute lesions, whereas strong expression was observed in old lesions. CD34 endothelial positivity was observed in areas of gliosis, vasogenic oedema, vascular disease and in Alzheimer's and Parkinson's disease pathology. A general pattern emerged, with CD34 antigen reactivity predominantly negative in areas of inflammation with demyelination but positive in adjacent non-inflamed tissue, irrespective of myelin pathology. We conclude that perivascular inflammation is a key factor in the absence of immunoreactivity of CD34 in the CNS in demyelinating disease.

Antigens, CD34↗
PubMed1997

Immunoreactivity for the human hematopoietic progenitor cell antigen (CD34) in lipomatous tumors.

The human hematopoietic progenitor cell antigen (CD34) recently was shown to react with a variety of nonhematopoietic tissues and their tumors, including vascular endothelium, dendritic interstitial fibroblastic cells, and endoneurial cells as well as with the neoplastic cells in a variety of mesenchymal neoplasms of unknown etiology, such as Kaposi's sarcoma, dermatofibrosarcoma protuberans, epithelioid sarcoma, gastrointestinal stromal tumors, and solitary fibrous tumors. Additionally, it has been claimed that normal adipocytes may also react with this antibody. We studied a series of 90 lipomatous lesions to examine the pattern of immunoreactivity of the CD34 antigen in adipose tissue neoplasms. The study included 14 lipomas, 19 angiolipomas, 4 atypical lipomas, 18 spindle cell lipomas, 3 renal angiomyolipomas, 1 intramuscular lipoma, and 31 liposarcomas. Immunostains identified a network of CD34+ spindle cells admixed with the adipose tissue elements in all cases of lipoma, angiolipoma, angiomyolipoma, intramuscular lipoma, and well-differentiated lipoma-like liposarcoma. Additionally, the spindle cell component in all cases of spindle cell lipoma were strongly positive for this antigen. Atypical, stellate spindle cells and multinucleated "floret" cells in all cases of atypical lipoma as well as in six of 12 cases of well-differentiated lipoma-like liposarcoma of deep soft tissue were also positive for CD34. Scattered spindle cells in all cases of myxoid liposarcoma and in one case of round cell liposarcoma, as well as the sarcomatous component in one case of "dedifferentiated" liposarcoma, were strongly positive for this antigen. The round cells in myxoid liposarcoma and round cell liposarcoma, the signet-ring and multivacuolated lipoblasts in well-differentiated liposarcoma, and the pleomorphic atypical cells in pleomorphic liposarcoma were uniformly negative. The results of this study appear to indicate that lipomatous tumors may harbor a population of CD34+ interstitial dendritic spindle cells. Overgrowth or clonal expansion of this dendritic cell subpopulation may account for the development of spindle cell lipomas and for the spindle cell component in some cases of "dedifferentiated" liposarcoma.

Antigens, CD34↗
PubMed1990

Activated protein kinase C directly phosphorylates the CD34 antigen on hematopoietic cells.

The CD34 antigen is a human leukocyte membrane protein expressed specifically by lymphohematopoietic progenitor cells. We found that CD34 is a phosphoprotein and therefore examined the regulation of its phosphorylation. Activation of protein kinase C (PKC) enhanced CD34 phosphorylation. The PKC activators, 12-O-tetradecanoylphorbol-13-acetate and bryostatin-1, induced rapid, stoichiometric hyperphosphorylation of CD34 protein in cells, resulting in a 5-fold increase in CD34 phosphorylation. In vitro kinase studies revealed that purified PKC could directly phosphorylate purified CD34. Only serine phosphorylation was detected in the CD34 molecule. Two-dimensional phosphopeptide mapping experiments indicated that PKC induces the phosphorylation of identical serine residue(s) in vitro and in vivo (in KG1 cells). These are newly phosphorylated serine residue(s), which are not detectably phosphorylated in CD34 from exponentially growing KG1 cells. These data indicate that the developmental stage-specific molecule, CD34, is a phosphorylation target for activated PKC. Furthermore, these findings raise the possibility that PKC activation and phosphorylation of the CD34 molecule may play a role in signal transduction during early lymphohematopoiesis.

Antigens, CD↗