Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eighty-five breast carcinomas were immunostained for CD3-, CD4-, CD8-, CD16-, CD22-, CD38- and CD57-positive lymphocyte subpopulations. The results were related to follow-up data (median follow-up 46 months) of 74 patients regarding overall survival and 73 patients in respect to disease-free survival. Whereas the number of axillary lymph node metastases (P less than 0.01) and the hormone receptor status (P less than 0.01) resulted in significantly different survival curves for overall survival, not one of the lymphocyte subset infiltrats correlated significantly which overall survival. For disease-free survival, pT stage (P less than 0.01) and nodal (P less than 0.01) and hormone receptor status (P less than 0.05) proved to be prognostically important. However, disease-free survival was not influenced by the infiltration of any lymphocyte subset.
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PMID:Study of the relationship between immunohistologically demonstrated lymphocytes infiltrating human breast carcinomas and patients' survival. 182 9

The FACS-analysis of diseases as different as cancer, autoimmune disorders and chronic (retro)viral infections, including HIV-infection, shows -at least temporarily- a common feature of lymphocyte hyperactivation, characterized by cellular activation markers (HLA-DR, CD26, CD38, CD69, CD2R and/or CD30), as well as by solubilized membrane structures, such as beta-2m, sICAM-I, sIL-2R/sCD25, sCD8, and by some oversecreted immunocyte products (e.g. neopterin, lysozyme and/or cathepsin D). We tested two potential approaches to down-regulate the pathologically elevated CD8+ and HLA-DR+ T cells: (a) In animal model, we tested the sensibility of these, disease inducing and maintaining T cell subsets to in vitro pretreated (cell death preprogrammed) semi-syngeneic and allogeneic donor T cells in tumor-bearing mice. (b) In the first clinical study, we used a novel combination of FDA-approved drugs which inhibits Ca(2+)-influx and concomitantly down-regulates cytosolic cAMP in patient's overstimulated immunocompetent cells. We could achieve a 94.6-100% long-term survival in tumor-bearing mice. In patients, large primary tumors and large metastases shrinked by 80-85% and small metastases disappeared completely. Since in HIV-infected persons, the increased number of HLA-DR+ CD38+T (T8) cells is associated with a fall in CD4-level and with development of AIDS, we are looking for the elimination of these HLA-DR+ targets by our novel technique in two AIDS-simulating (FIV/FeLV and SIV) animal models.
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PMID:Treatment of solid tumors should obligatorily be combined with the in vivo codepletion of tumor-protecting, CD8+/HLA-DR(+)-suppressor T cells by alloreactive donor T cells whose preprogrammed cell death allows a high GvL-effect before GvHD can be established. Results of animal experiments, including more than 6000 mice. 873 48

The presence and phenotype of lineage-committed hematopoietic progenitors in the normal adult human liver (AHL) were investigated and compared with the profiles of differentiating hematopoietic precursor populations detected in liver bearing metastases of colonic origin. Levels of hematopoietic stem cells (HSCs) (CD34(+)CD45(+)) detected in hepatic mononuclear cell (HMNC) populations were increased 6-fold when compared with matched peripheral blood samples. In normal liver, less than 5% of HSCs expressed the myeloid-associated antigen, CD33, whereas considerable proportions expressed lymphoid-associated markers (T cell, 33.39%; B cell, 17.39%; and natural killer [NK] cell, 37.17%). Significant increases were observed in the relative proportions of hepatic HSCs coexpressing CD33 (20.53%; P =.001), and the T-cell marker (CD7, 58. 13%; P =.02) in tumor-bearing liver compared with normal liver. HSCs with B-cell progenitor phenotype (CD19(+)) were significantly decreased in tumor-bearing liver (0.06%; P =.02). Despite these differences, the activation status of hematopoiesis, as measured by the coexpression of the differentiation and activation markers, CD38 and CD45RA, did not differ significantly between normal and tumor-bearing liver. These results indicate that the normal AHL harbors lineage-committed hematopoietic progenitors, and the vast majority of these progenitors express lymphoid-associated antigens with changes occurring in both the myeloid and lymphoid compartments of the hepatic hematopoietic pathway on tumor challenge. While tumor-bearing livers are enriched for intrahepatic myeloid precursors and T-cell progenitor cells, further studies are required to establish the origin and in situ development potential of hepatic HSCs in the adult human and their role in tumor immunity.
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PMID:Differential expression of lymphoid and myeloid markers on differentiating hematopoietic stem cells in normal and tumor-bearing adult human liver. 1082 50

CD31, an adhesion molecule expressed by endothelial cells, leukocytes, and platelets, is used in surgical pathology as a marker of normal and neoplastic vascularization. During the assessment of angiogenesis in breast carcinomas, CD31 expression was observed in a single case of large (5.2 cm diameter) high nuclear grade ductal carcinoma in situ (HG-DCIS) associated with poorly differentiated invasive ductal carcinoma (G3-IDC). Expression was limited to the cell membrane. This study focused on 32 HG-DCIS> or = 2 cm, either pure or associated with IDC. Cancer cells wereCD31(+) in 11 cases. Double staining using anti-CD31 monoclonal antibody (MAb) and anti-CD44 MAb, the anti-hyaluronate receptor, showed that foci of CD31(+) and CD44(-) tumour cells could be traced throughout the glandular tree, marking the intraductal diffusion of tumour up to Paget's cells at the nipple. The associated G3-IDC and their lymph node metastases were instead CD31(+) and CD44(+). CD31(+) tumours were oestrogen receptor (ER)(-), frequently p53(+) and c-erb-B2(+), and infiltrated by CD4(+) T lymphocytes. Normal and hyperplastic epithelia were constantly CD31(-). Other endothelial markers (e.g Factor VIII-RA and CD34) were not expressed by carcinoma cells, as was CD38, the CD31 ligand. In conclusion, CD31 expression is a feature acquired by breast cancer cells in the DCIS model. CD31 expression mainly correlates with tumour cells spreading within the ductal system. Finally, the invasive phenotype requires the co-expression of CD31 and CD44.
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PMID:Expression of CD31 by cells of extensive ductal in situ and invasive carcinomas of the breast. 1185 2

The therapy of metastatic melanoma has not given satisfactory results. Single chemo- or immunotherapeutic agents in the adjuvant setting or combined chemoimmunotherapy for metastatic disease have generally been evaluated only in terms of clinical benefit. Considering that dacarbazine (DTIC) and interferon-alpha (IFN-alpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFN-alpha monotherapy, as well as by their combination in metastatic disease. The evaluated immunological parameters showed significant early increase in the activity of NK (natural killer) cells, CD4/CD8 ratio, CD4+ T cell number in patients treated with combined chemoimmunotherapy and an increase in expression of the early activation antigen CD38 on CD8+ cytotoxic T cells, both, in patients treated with combined chemoimmunotherapy and with IFN-alpha alone, while, no significant change in any one parameter was detected in the group of patients receiving DTIC. The kinetics of the observed immunological changes, restricted to combined chemoimmunotherapy, indicate that the engagement of antitumor immune response appears early but is short-lived and that this favorable effect should be augmented and prolonged by the timely introduction of additional immunomodulating agents.
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PMID:Therapeutic implications of the kinetics of immunomodulation during single or combined treatment of melanoma patients with dacarbazine and interferon-alpha. 1158 85

Nodal deposits of melanoma may present many years after resection of the primary tumour, implying initial suppression of tumour growth with subsequent immune escape. Using immunocytochemical techniques on frozen sections, the cellular types and activation status of infiltrating cells within a series of 19 clinically apparent nodal metastases of melanoma were studied. Infiltrating cells were assessed using a semiquantitative grading system. Macrophages (CD68+) and T-lymphocytes (CD3+) (including both CD8+ and probably also CD4+ T-cells) were the predominant cells infiltrating the tumours. B-lymphocytes (CD20+) were generally present in low numbers. CD1a+ putative dendritic cell density and expression of the early lymphocyte activation markers interleukin-2 receptor alpha (IL2Ralpha) and CD69 was low. However, greater evidence of intermediate lymphocyte activation (CD38) was identified. Expression of interleukin-2 (IL2) by tumour-infiltrating cells was not detected. The paucity of staining for IL2 and IL2Ralpha, with greater expression of CD38 by infiltrating cells, suggests that the usual pathways of lymphocyte activation via IL2 were bypassed or impaired within the lymph node metastases. Low numbers of CD1a+ putative dendritic cells may result in reduced effector cell activation. These findings provide evidence to support the hypothesis that antitumour immune responses within clinically involved lymph nodes are reduced in metastatic melanoma. This also has possible implications for micrometastases to the sentinel lymph node.
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PMID:Dendritic cell density and activation status of tumour-infiltrating lymphocytes in metastatic human melanoma: possible implications for sentinel node metastases. 1277 81

Considering that well-defined and comprehensive immunological monitoring is the basis for the evaluation of the obtained immunmodulatory effects, we evaluated NK-cell activity, the number of CD3+ CD4+, CD3+ CD8+ T cells and CD16+ CD56+ NK cells, as well as the expression of activation antigens, CD69, CD38 and HLA-DR on CD56+ NK cells, CD8+ and CD3+ T cells, simultaneously with IL-2 and TNF-alpha production, during chemoimmunotherapy with dacarbazine (DTIC) and interferon-alpha (IFN-alpha) in 39 patients with metastatic melanoma. In the first cycle of therapy, there was a significant rise in NK-cell activity, CD4+ T helper cell number, CD4/CD8 T-cell ratio, and the expression of activation antigens CD69 and CD38, on NK and T cells, respectively. However, in the following cycles there was a significant increase only in activation antigens without an increase in the percent or activity of NK cells. The early, but transient, immunopotentiation, present only in the first cycle of combined DTIC and IFN-alpha therapy, suggests that, in spite of increased IL-2 level, associated with augmented NK-cell activity, this therapy has a limited effect probably owing to the adverse effect of persistently high level of TNF-alpha in metastatic disease.
Clin Exp Metastasis 2003
PMID:IL-2-mediated augmentation of NK-cell activity and activation antigen expression on NK- and T-cell subsets in patients with metastatic melanoma treated with interferon-alpha and DTIC. 1466 96

Cluster designation (CD) antigens are cell surface markers that can be used to identify constituent cell populations of an organ. We have previously determined the CD phenotype of normal prostate parenchymal cells and are now extending this analysis to prostate cancer. Since expression of CD antigens is associated with cellular differentiation, cancer cells may differ from their normal counterpart in their CD profile. Compared with luminal secretory cells, prostate adenocarcinoma cells are frequently negative for CD10 and CD13, express increased levels of the cell activation molecule CD24, and decreased levels of the apoptosis-associated multifunctional enzyme CD38. Expression of CD57, CD63, CD75s, CD107a, CD107b, CD164, and CD166 by cancer cells is similar to that of secretory cells. Prostate basal epithelial cells do not express the CD antigens characteristic of prostate secretory cells; and the basal cell CD markers, CD29, CD44, CD49b, CD49f, CD104, and nerve growth factor receptor (NGFR) are not expressed by cancer cells. The preferential expression of secretory cell-associated CD markers by prostate cancer cells suggests a closer lineage relationship between cancer cells and secretory cells than basal cells. Although the above cancer CD phenotype was the most frequently seen, some prostate cancers contained populations of CD10- and/or CD13-positive cells, and CD57-negative cells. Furthermore, the cancer phenotype of tumor metastasis is different. Despite its low frequency in primary tumors, CD10 is expressed by virtually all of the nodal metastases of prostate cancer. In addition, stromal fibromuscular cells associated with primary prostate cancer differ from stromal cells in benign prostate tissue by an increased level of expression of the cell activation molecule, CD90. In summary, our data show that the CD marker expression profile of prostate cancer cells most closely resembles that of secretory prostate epithelial cells and that some prostate cancers consist of heterogeneous cell populations as distinguished by CD-marker expression profiles.
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PMID:Heterogeneity in primary and metastatic prostate cancer as defined by cell surface CD profile. 1550 25

Malignant melanoma is well known for its poor response to chemotherapy, radiotherapy and its susceptibility to immunotherapy. Considering that dacarbazine (DTIC) and interferon alpha (IFNalpha) are among the most frequently used agents in the treatment of melanoma, the aim of this study was to evaluate the kinetics of immunological changes during adjuvant treatment of melanoma patients with DTIC or with IFNalpha monotherapy, as well as with their combination in metastatic disease. Pre-therapy values of immunological parameters showed significantly decreased NK cell activity, altered in vitro production of TNFalpha, IL-2 and proliferative response of peripheral blood lymphocytes (PBL), while percentage of PBL subpopulations was unchanged. During therapy, NK cell activity was significantly increased after the 1st cycle of combined chemoimmunotherapy (DTIC + IFNalpha), followed by a significant decrease after the 2nd cycle of therapy. Furthermore, in this group, there was a significant increase in CD4+ T helper cell percentage after the 1st cycle of therapy. Serial monitoring of activation antigens also showed a significant increase in the expression of CD38 on CD8+ cytotoxic T cells, after the 1st and 2nd cycle in combined chemoimmunotherapy group and, after 30 days, in the group of patients treated with IFNalpha, only. The increase in the expression of HLA-DR activation antigen on CD3+ and CD8+ T cells had a gradual increase and significant rise after the 2nd cycle of combine chemoimmunotherapy, only. The dynamic of immunological changes, mostly observed in combined chemoimmunotherapy, and rarely in IFNalpha monotherapy gives valuable insight into induced immunomodulation, suggesting early, but transient favourable changes, that could be prolonged by timely introduction of other immunotherapeutic agents.
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PMID:[Correlation between functional capability and phenotypic characteristics of peripheral blood lymphocytes in patients with malignant melanoma]. 1607 47

Diagnosis of two distinct malignant entities existing concurrently and at the same location (synchronous malignancy) by fine- needle aspiration (FNA) is unusual but may occur. Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) in particular is associated with an increased incidence of secondary tumor, likely due to associated immunodeficiency. Co-occurrence of some carcinomas such as squamous cell carcinoma (SCC), may show especially aggressive behavior. A 57-year-old Caucasian male presented with recurrent upper extremity lymphedema and diffuse lymphadenopathy of the axillary and cervical regions. FNA of a large cervical lymph node was diagnostic for both atypical lymphocytic proliferation and SCC. Flow cytometric analysis showed the atypical lymphocytic proliferation to be positive for CD5, CD23, CD19, CD20, HLA-DR, CD38, and the population was kappa light chain restricted. These cells were negative for CD-10 and FMC-7 antigens, suggesting a phenotype of B-cell SLL/CLL. We report a rare occurrence of metastatic SCC to a lymph node infiltrated by SLL/CLL. The diagnosis was achieved by a combination of cytomorphologic examination of FNA smears, immunohistochemical staining of cell block material, and flow cytometry on the sample obtained by FNA. To the best of our knowledge, only three cases of SCC metastasis to SLL/CLL diagnosed by FNA have been reported in the English literature. Though rare, awareness of such a possibility and careful cytological examination under the appropriate clinical conditions is warranted.
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PMID:Fine-needle aspiration diagnosis of squamous cell carcinoma in a lymph node involved with small lymphocytic lymphoma: case report and review of the literature. 1897 26


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