Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin carcinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2-3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented lesions. Animal model studies have suggested that long-term PDT response involves an immune reaction in which CTLs play a crucial role. In this study, we have assessed: (a) HPV infection; (b) HLA expression; and (c) immune infiltrating cells in VIN biopsies from responders and nonresponders to determine whether these factors may limit response to topical 5-aminolevulinic acid-based PDT. Tissues from normal vulva (n = 9), vulval carcinoma (n = 11), and VIN (32 patients from which 19 pre- and 43 post-PDT biopsies were taken) were investigated for immune cell infiltration and HLA class I expression by immunohistochemistry and HPV infection by PCR. There was a greater likelihood of HPV positivity associated with a lack of response of VIN to PDT (P = 0.002), and VIN nonresponders were more likely to show HLA class I loss compared with responders (P = 0.030). HLA class I down-regulation was significantly greater in the carcinomas (82%, total loss) than the VIN (28%, 19%, total loss; and 9%, allele loss; P = 0.004). None of the cases with class I down-regulation responded to PDT, whereas 3 of 6 (50%) of cases that showed total class I loss subsequently developed superficial invasion. Compared with normal vulval skin, VIN lesions showed increased infiltration by CD4 (T-helper) and CD68 (macrophages) but not CD1a (Langerhans cells) or CD8 (CTLs). There was, however, a significant increase of CD8 infiltration in posttreatment VIN responders compared with nonresponders (P = 0.0001). These data clearly support the contention that high-risk HPV infection and lack of cell-mediated immunity may play a role in the observed poor response of lower genital lesions to topical PDT.
 ...
PMID:Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. 1119 60

The induction of apoptosis in dendritic cells (DC) is a key mechanism by which tumors escape immune recognition and elimination. In fact, a number of studies have showed the correlation between the number of DC within the tumor and the clinical prognosis, suggesting that increased infiltration of tumor tissue by DC was associated with better patient survival and low incidence of metastatic disease. We compared the number of DC and their distribution pattern in human small-cell lung carcinoma and bronchial carcinoid tumor (CT) tissues. Immunohistochemical analysis revealed the presence of cells expressing DC markers CD1a and CD83 in small-cell lung carcinoma tissues and the complete absence of these cells in CT samples. Next, we examined whether human lung tumor cells produce soluble factors that inhibit differentiation of hematopoietic precursors into mature DC. The addition of small-cell lung carcinoma-conditioned medium to CD34+ precursor cell cultures significantly inhibited colony-forming units of DC formation when compared with nontreated control DC cultures. Furthermore, DC generation and differentiation was completely abrogated in CD34+ cell cultures treated with CT-conditioned medium, suggesting that CT-derived factors blocked CD34+ cell differentiation into DC or induced their apoptosis. Finally, flow cytometry analysis of cultured DC confirmed these results. Thus, analysis of our data suggests that human lung tumors produce factors that inhibit DC generation or maturation and may also induce apoptotic death of DC precursors in vitro.
 ...
PMID:Human small cell lung carcinoma and carcinoid tumor regulate dendritic cell maturation and function. 1121 8

At the ISAC 2000 Congress, the Clinical Cytometry Society organized a meeting of international experts to reach consensus on the minimum number of antibodies required for a full evaluation of hematologic and lymphoid neoplasias. A questionnaire was distributed prior to the meeting to numerous experts from US and European institutions and 13 responses were received. At the meeting, 25 individuals, including most of those who returned responses, participated in the discussions and voted on the issues presented. In chronic lymphoproliferative disorders (CLD), 9 antibodies (anti-CD5, CD19, kappa, lambda, CD3, CD20, CD23, CD10, and CD45) were deemed essential for initial evaluation by 75% of the participants. There was near unanimity that additional markers (selected from CD22, FMC7, CD11c, CD103, CD38, CD25, CD79b and heavy chains for B-cell disorders, and CD4, CD7, CD8, CD2, CD56, CD16, TCRa/b, and TCRg/d for T-cell disorders) would be needed to fully characterize CLD, although not every marker would be useful in all cases. Tissue lymphomas were believed to be similar to CLD, needing a minimum of 12--16 markers. However, for some cases, CD30, bcl-2, TdT, CD71, CD1a, and CD34 were cited as useful by the participants. Markers mentioned for plasma cell disorders included kappa, lambda, CD38, CD45, CD56, CD19, CD20, CD138, and heavy chains. Of 17 voting participants, 16 agreed that between 5 to 8 markers would be essential reagents for plasma cell disorders. For acute leukemia (AL), 10 markers (CD10, CD19, CD13, CD33, CD34, CD45, CD7, CD14, CD3, and HLADR) were considered essential by 75% of participants for initial characterization of the leukemia lineage. Most (>75%) agreed that at least one more B (CD20, CD22, CD79a, IgM), T (CD1a, CD2, CD4, CD5, CD8), myeloid (CD11b, CD15, CD64, CD117, myeloperoxidase), erythroid (CD36, CD71, glycophorin A), and megakaryocytic (CD41, CD61) reagents should be included in the essential panel. However, there was no agreement as to which was optimal. Thus, approximately 13--15 of those reagents would be considered essential in all cases of AL, whereas others (CD16, CD56, CDw65, TdT, and cytoplasmic CD3) were mentioned as useful in some cases. Almost all voting participants believed that the appropriate number of markers for complete characterization of AL would average 20--24. The majority of the responders (11 of 13) indicated that fewer reagents could be used in monitoring or staging patients with previously characterized disease, but not all ventured a specific number of reagents. From the above results, we conclude that the phenotypic analysis of hematologic and lymphoid neoplasia requires a rather extensive panel of reagents. Supplementary reagents might even be necessary if they prove to become relevant for diagnostic purposes. Reducing the number of antibodies could significantly compromise the diagnostic accuracy, appropriate monitoring, or therapy of these disorders.
 ...
PMID:Optimal number of reagents required to evaluate hematolymphoid neoplasias: results of an international consensus meeting. 1124 3

Dendritic cells (DC) are important antigen-presenting cells in the development of an anti-tumor T cell response. To extend the range of current immuno / gene therapies, we tested luciferase-expressing RGD-adenovirus (Ad) (Ad5lucRGD)-mediated transduction into DC. Phenotypically characterized DC were generated from peripheral blood CD14(+) cells by incubation with granulocyte-macrophage colony-stimulating factor, interleukin-4 and tumor necrosis factor alpha. On the 7th day of culture, the cells became mature DC with a CD1a(+), CD11c(+), CD80(+), CD83(+), CD86(+), human leukocyte antigen (HLA)-DR(+), CD14- phenotype. The expression of alpha( v)beta(3) integrin was enhanced on day 3 and returned to the basal level on day 7. We then compared the transduction efficiency of an Ad5lucRGD system to that using conventional Ad, in cells harvested on days 1, 3 and 7 of culture. Luciferase activity was negligible in AdCMVLuc, but remarkable in cells processed with Ad5lucRGD. Activity was maximal in cells that had been cultured for 3 days. Recombinant Ad5 fiber knob protein blocked AdCMVLuc- and Ad5lucRGD-mediated gene transduction by 90% and 20%, respectively. Surface markers and cytokine production were not affected by Ad5lucRGD-mediated transduction.
 ...
PMID:Efficient gene transduction by RGD-fiber modified recombinant adenovirus into dendritic cells. 1126 43

To better define the clinical and pathologic features of interdigitating dendritic cell sarcoma (IDCS), we report 4 cases, including the first reported in the tonsil. There were 2 male and 2 female patients (mean age, 70 years). Sites of tumor included 1 case each in the right cervical lymph node, left axillary lymph node, right tonsil, and right inguinal lymph node. Histologically, all showed diffuse effacement of the lymphoid tissue by pleomorphic round to spindled cells with convoluted nuclei and abundant eosinophilic cytoplasm. All were immunoreactive for S-100, CD68, lysozyme, and vimentin. CD45 was positive in 3 cases and CD1a in 1 case. Fascin was positive in 3 cases. Other immunostains, including CD3, CD20, CD21, CD30, actin, cytokeratin, and HMB-45, were negative. Ultrastructurally, the tumor cells were elongated and showed indented nuclei, variable numbers of lysosomes, and interdigitating cytoplasmic processes. Follow-up was available for all cases. One patient died of widespread disease 2 months after diagnosis. One was alive with metastatic lung disease at 12 months. Two patients were disease free at 5 and 9 months.
 ...
PMID:Interdigitating dendritic cell sarcoma. A report of four cases and review of the literature. 1129 8

Malignant cells may escape from the immune response in vivo because of a defective differentiation of professional antigen-presenting cells (APCs), i.e., dendritic cells (DCs). We recently reported that tumor cells release interleukin (IL)-6 and macrophage colony stimulating factor (M-CSF), which inhibit the differentiation of CD34+ cells into DCs and promote their commitment toward monocytic lineage with a poor APC function. The results presented here show that both IL-4 and IL-13 reverse the inhibitory effects of renal cell carcinoma conditioned media (RCC CM) or IL-6+M-CSF on the phenotypic and functional differentiation of CD34+ into DCs. IL-4 was found to act through a rapid blockade of the expression of M-CSF and the IL-6 receptor-transducing chain (gp130), along with a decrease of the secondary production of M-CSF, thereby preventing the loss of granulocyte macrophage colony stimulating factor (GM-CSF) receptor alpha chain expression on differentiating CD34+ cells. Consistent with these observations, the differentiation of DCs from monocytes cultured with GM-CSF and IL-4 was also impaired by RCC CM, but the minimal inhibitory concentrations of RCC CM were 10-fold higher than for CD34+ cells. In these conditions, monocytes cultured with GM-CSF and IL-4 also exhibited profound phenotypic changes (CD14+ D32+ CD86+ HLA-DR+ CD115(low) CD23(low) CD1a-) and a poor APC function. These alterations were overcome in a dose-dependent manner by IL-4 (5-500 IU/ml), although not beyond a 40% final concentration of RCC CM. The capacity of RCC CM to block DC differentiation from monocytes strongly correlated with IL-6 and M-CSF concentrations in medium. Taken together, these results demonstrate that IL-4 and IL-13 reverse the inhibitory effect of tumor cells on DC differentiation.
 ...
PMID:IL-4 prevents the blockade of dendritic cell differentiation induced by tumor cells. 1130 93

Effective presentation of tumor antigens is fundamental to strategies aimed at enrolling the immune system in eradication of residual disease after conventional treatments. Myeloid malignancies provide a unique opportunity to derive dendritic cells (DCs), functioning antigen-presenting cells, from the malignant cells themselves. These may then co-express leukemic antigens together with appropriate secondary signals and be used to generate a specific, antileukemic immune response. In this study, blasts from 40 patients with acute myeloid leukemia (AML) were cultured with combinations of granulocyte-macrophage colony-stimulating factor, interleukin 4, and tumor necrosis factor alpha, and development to DCs was assessed. After culture, cells from 24 samples exhibited morphological and immunophenotypic features of DCs, including expression of major histocompatibility complex class II, CD1a, CD83, and CD86, and were potent stimulators in an allogeneic mixed lymphocyte reaction (MLR). Stimulation of autologous T-cell responses was assessed by the proliferative response of autologous T cells to the leukemic DCs and by demonstration of the induction of specific, autologous, antileukemic cytotoxicity. Of 17 samples, 11 were effective stimulators in the autologous MLR, and low, but consistent, autologous, antileukemic cytotoxicity was induced in 8 of 11 cases (mean, 27%; range, 17%-37%). This study indicates that cells with enhanced antigen-presenting ability can be generated from AML blasts, that these cells can effectively prime autologous cytotoxic T cells in vitro, and that they may be used as potential vaccines in the immunotherapy of AML.
 ...
PMID:Stimulation of autologous proliferative and cytotoxic T-cell responses by "leukemic dendritic cells" derived from blast cells in acute myeloid leukemia. 1131 69

The authors present 18 cases of a hitherto unrecognized variant of cutaneous neurofibroma. The tumors presented in adults (10 occurred in men and eight occurred in women) as a solitary, well-circumscribed, superficial lesion located in the dermis measuring 3 to 17 mm (mean size, 6.2 mm). The tumors formed oval-shaped masses that ran perpendicular to the epidermis. In the deep part of the tumor there was multinodular arrangement with two types of cells: Type I cells were small, dark, lymphocyte-like cells with a slightly irregular nucleus and inconspicuous cytoplasm. Type II cells were larger, with pale-staining vesicular nuclei, with frequent invaginations and intranuclear inclusions, and had copious clear eosinophilic cytoplasm that formed a stellate growth pattern, which was poorly visible on hematoxylin and eosin staining. Type I cells were grouped concentrically around type II cells and formed pseudorosettes. Most of the type I and type II cells were S-100 protein and CD57 positive, and various proportions of both cell types were CD56 and PGP9.5 positive. All cells were chromogranin A, synaptophysin, glial fibrillary acidic protein, cytokeratins, CD1a, CD21, CD31, alpha-smooth muscle actin, muscle-specific actin, desmin, and HMB-45 negative. CD34 stained intralesional fibroblasts. Antibody to epithelial membrane antigen stained only the perineurium around the tumor masses, suggesting that the tumors arose inside the nerve sheath. No signs of neurosecretory granules were present at ultrastructural level. None of the lesions recurred and none metastasized over a mean follow-up of 8.1 years.
 ...
PMID:Dendritic cell neurofibroma with pseudorosettes: a report of 18 cases of a distinct and hitherto unrecognized neurofibroma variant. 1245 33

We describe a 58-year-old male with multiple histiocytic tumors in the liver and spleen. Multiple tumors in the liver and spleen were seen by image analysis, and splenectomy showed a large splenic tumor with a small nodule and a swelling lymph node in the hilus. Histological features of the tumors in the liver and spleen revealed proliferation of histiocytic cells with large and clear cytoplasm and a horseshoe-shaped nucleus. Immunohistochemical studies revealed the presence of S-100 protein and CD1a antigen in the tumor cells, and neither lymphocytic marker nor lysozyme was detected. No definite Birbeck granules were seen ultrastructurally, thus the tumor cells could be classified into Langerhans cell type without Birbeck granules. Administration of adriamycin, vincristine, cyclophosphamide and prednisolone reduced size and number of the liver tumors, and the histiocytic cells could not be detected in repeatedly biopsied tissue from liver tumor. We present the clinical, immunohistological and cytological features in a visceral type of adult Langerhans cell histiocytosis, which responded well to chemotherapy.
 ...
PMID:Langerhans cell histiocytosis of an adult with tumors in liver and spleen. 1137 59

Dendritic cells (DCs) are the most potent antigen-presenting cells and are thought to reflect the interaction between the host immune system and tumor cells. In a retrospective study, we analyzed the presence of DCs and memory lymphocytes in tumor biopsy specimens of 18 patients with ovarian cancer. These patients were followed up for 10 to 37 months. Within this period, 9 patients had no evidence of disease (NED, group A), and 9 patients had recurrence (group B). In group A, 5 cases were stage III, 1 was stage I, and 1 was stage II. In group B, 5 cases were stage III, 1 was stage III-IV, and 3 were stage IV. Our results show that the mean number of cells expressing the DC phenotype, HLA-DR(+) CD1a(+), in tumor biopsies was substantially higher in group A than in group B (HLA-DR(+): 37.8 +/- 18.2 v. 10.7 +/- 2.2, respectively; P <.005; CD1a(+): 9.5 +/- 11.3 v 2.1 +/- 3.7). On the other hand, the number of cells expressing the DC phenotype S-100 protein was substantially lower in group A than in group B (S-100(+): 9.7 +/- 9.9 v 16.2 +/- 12.7), although the difference was not statistically significant. There was no difference in the number of tumor-infiltrating CD45RO(+) cells between groups A and B (CD45RO(+): 39.1 +/- 28.5 v 34.2 +/- 19.1). Our results show that the presence of relatively high numbers of defined DC subpopulations may have prognostic value in ovarian tumors.
 ...
PMID:Expression of dendritic cells in ovarian tumors correlates with clinical outcome in patients with ovarian cancer. 1152 Dec 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>