Tissue response to iodine-125 interstitial brachytherapy of cerebral gliomas.
ABSTRACT The purpose of this study was to investigate histopathological changes and the role of the microglia/macrophage cell system in the therapeutic effect of iodine-125 (125I) interstitial brachytherapy on cerebral gliomas. Out of a series of 60 cases harboring cerebral astrocytomas and other brain tumors treated with 125I interstitial brachytherapy, autopsy material was available in 10 cases between 0.75 and 60 months after irradiation. The patients were treated with 60-Gy maximum doses at the tumor periphery. Besides the routine HE and Mallory's PTAH trichrome staining, immunohistochemical reactions were carried out for CD15, CD31, CD34, CD45, CD68 (PG-M1), CPM, HAM 56 and HLA-DR antigens to study immunological characteristics of the reactive cell population around gliomas after 125I treatment. The present immunohistochemical study demonstrated that the early lesions following 125I interstitial brachytherapy of gliomas are characterized by migrating macrophages apparently concerned with the removal of necrotic debris. The established phase of reactive zone around the necrotic center disclosed a narrow inner rim of microglial accumulation, and a broad outer area consisting of astrocytic gliosis, vascular proliferation, activated microglia and infiltration by macrophages. In the burned-out phase, the necrosis undergoes liquefaction, the microglial rim is replaced by end-stage macrophages, and the reactive zone is transformed into astrocytic gliosis, which can be considered as equivalent to scar tissue formed around necrosis outside of the central nervous system.
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ABSTRACT: This review covers carboxypeptidase M (CPM) research that appeared in the literature since 2009. The focus is on aspects that are new or interesting from a clinical perspective. Available research tools are discussed as well as their pitfalls and limitations. Evidence is provided to suggest the potential involvement of CPM in apoptosis, adipogenesis and cancer. This evidence derives from the expression pattern of CPM and its putative substrates in cells and tissues. In recent years CPM emerged as a potential cancer biomarker, in well differentiated liposarcoma where the CPM gene is co-amplified with the oncogene MDM2; and in lung adenocarcinoma where coexpression with EGFR correlates with poor prognosis. The available data call for extended investigation of the function of CPM in tumor cells, tumor-associated macrophages, stromal cells and tumor neovascularisation. Such experiments could be instrumental to validate CPM as a therapeutic target.Clinica chimica acta; international journal of clinical chemistry 11/2012; · 2.54 Impact Factor
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ABSTRACT: Introduction: In the recent literature, carboxypeptidase M (CPM) emerged as a potential cancer biomarker. CPM modulates receptor signaling of kinins, anaphylatoxins, and chemokines. These CPM substrates affect proliferation, angiogenesis, and apoptosis of cancer cells. What is the evidence that CPM is a drug target for cancer therapy? Areas covered: The literature was searched using PubMed with the search terms "carboxypeptidase M" and/or "chromosome 12q13-15" eventually combined with general terms related to cancer. Information was retrieved from the GEO database and material of gene expression and proteomic studies. Expert opinion: CPM is a part of the molecular signature of many cancers. There is good evidence that it is useful for the discrimination and stratification of cancer types, possibly in combination with other markers such as EGFR and MDM2. Whether it is also a drug target remains to be determined. Lung, kidney, brain, and the reproductive system contain relatively high levels of CPM, but its functions in those tissues are largely unknown. CPM is expressed on tumor-associated macrophages. To facilitate the investigation of CPM in tumor-associated inflammation and in the other aspects of tumor biology, it is necessary to develop potent and selective CPM inhibitors.Expert Opinion on Therapeutic Targets 01/2013; · 4.90 Impact Factor
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ABSTRACT: Although the kidney generally has been regarded as an excellent source of carboxypeptidase M (CPM), little is known about its renal-specific expression level and distribution. This study provides a detailed localization of CPM in healthy and diseased human kidneys. The results indicate a broad distribution of CPM along the renal tubular structures in the healthy kidney. CPM was identified at the parietal epithelium beneath the Bowman’s basement membrane and in glomerular mesangial cells. Capillaries, podocytes, and most interstitial cells were CPM negative. Tumor cells of renal cell carcinoma subtypes lose CPM expression upon dedifferentiation. Tissue microarray analysis demonstrated a correlation between low CPM expression and tumor cell type. CPM staining was intense on phagocytotic tumor-associated macrophages. Immunoreactive CPM was also detected in the tumor-associated vasculature. The absence of CPM in normal renal blood vessels points toward a role for CPM in angiogenesis. Coexistence of CPM and the epidermal growth factor receptor (EGFR) was detected in papillary renal cell carcinoma. However, the different subcellular localization of CPM and EGFR argues against an interaction between these h proteins. The description of the distribution of CPM in human kidney forms the foundation for further study of the (patho)physiological activities of CPM in the kidney.Journal of Histochemistry and Cytochemistry 11/2012; · 2.40 Impact Factor