Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antigenic profile of basal cell carcinoma (BCC) cells was analyzed by immunoperoxidase staining of 27 surgically removed BCC lesions with antiganglioside, antiadhesion molecule, and antihistocompatibility locus antigen (HLA) monoclonal antibodies (MoAb). The large majority of BCC lesions were stained by antiganglioside MoAb; among the latter the anti-GD3 ganglioside MoAb R24 displayed the broadest reactivity. The GD3 ganglioside expression by BCC cells, which was corroborated by thin layer chromatography immunostaining with MoAb R24, appears to be a proliferation dependent phenomenon. Among the adhesion molecules tested vitronectin receptor and CDw44 were found in up to 70% of the lesions tested, while intercellular adhesion molecule 1 (ICAM-1) was detected in only a low percentage of BCC cells in one lesion. ICAM-1 was not induced on BCC cells in five and three lesions removed 24 and 48 h, respectively, following the intralesional injection of gamma-interferon. The latter enhanced HLA Class I antigen expression and induced ICAM-1 expression by the surrounding keratinocytes; furthermore gamma-interferon induced HLA Class II antigen expression by a small percentage of BCC cells in three lesions. These results suggest that malignant transformation of keratinocytes is associated with a selective loss of susceptibility to induction by cytokines of ICAM-1 expression. Besides confirming the low HLA Class I and Class II antigen expression by BCC cells, the present investigation has shown a differential expression of distinct monomorphic determinants of HLA Class I antigens and a lower expression of HLA-A antigens than of HLA-B antigens by BCC cells. Furthermore, the present study has shown that HLA Class II antigens can be induced on BCC cells by cytokines.
Cancer Res 1992 Jun 01
PMID:Ganglioside, adhesion molecule, and HLA antigen expression in basal cell carcinoma lesions. 135 May 11

Two new human cholangiocarcinoma (CC) cell lines (CC-SW-I and CC-LP-I) were established and maintained in culture for 2 years. Histologically, both original liver tumors were adenocarcinomas, and the cell lines exhibited morphologic features of moderately differentiated adenocarcinoma. Immunohistochemistry showed that both cell lines were strongly positive for cytokeratin AEI but negative for carbohydrate tumor-associated antigen, CA19-9. Ultrastructural analysis of both cell lines showed the presence of tight junctional complexes and focally formed microvilli. Both CC cell lines were tumorigenic in nude mice. Cytogenetic analysis showed that both cell lines expressed highly aneuploid karyotypes with numerous structural and numerical deviations. CC-SW-I was hypodiploid with numerous chromosome losses and structural rearrangements, while CC-LP-I was hyperdiploid and displayed multiple additional chromosomes. Doubling times for the CC-SW-I and CC-LP-I cell lines in the presence of 15% fetal bovine serum were 72 hr and 180 hr, respectively. Growth of the CC-SW-I cell line was significantly stimulated in the presence of insulin, while that of the CC-LP-I cell line was significantly augmented by epidermal growth factor (EGF). In contrast, dexamethasone strongly inhibited proliferation of both cell lines in a dose-dependent manner. Among various recombinant cytokines examined for effects on growth or surface antigen expression on CC cell lines, only interleukin I-beta (ILI-beta) strongly inhibited growth of the CC-LP-I cell line, while interferons (IFNs) or tumor necrosis factor-alpha (TNF-alpha) were mildly inhibitory. Both tumor cell lines were resistant to natural killer (NK) cells but sensitive to lymphokine-activated killer (LAK) cells. Preincubation of tumor cells with IFN-gamma, IFN-alpha or TNF-alpha significantly decreased the susceptibility of each tumor cell line to lysis by LAK cells, and the change in sensitivity did not correlate with the expression of HLA antigens or intercellular adhesion molecule-I (ICAM-I) on the surface of tumor cells. These 2 CC cell lines are expected to provide valuable information about cell biology of human CC.
Int J Cancer 1992 Sep 09
PMID:Two new human cholangiocarcinoma cell lines and their cytogenetics and responses to growth factors, hormones, cytokines or immunologic effector cells. 135 57

Recent studies have suggested that certain oncogenes, in particular members of the myc family, may be involved in the down-regulation of HLA class-I antigen expression observed in many types of tumor. We report that constitutive expression of an OK10 v-myc gene in human monoblastic U-937 cells results in a reduced expression of HLA class-I cell-surface expression and decreased levels of HLA class-I protein and mRNA. All class-I alleles, with the possible exception of HLA A3, were affected, as shown by one-dimensional isoelectric focusing (ID-IEF). Basal expression of the beta 2m chain was also reduced, although to a lesser extent. In addition, we show that the PMA-, and at least partially the IFN-alpha-induced increase in HLA class-I antigen expression, was inhibited in U-937-myc cells both at the protein and the mRNA level. In contrast, the response to IFN-gamma was normal. Another important difference in the response to IFN-gamma and alpha was that, while IFN-gamma abrogated the v-myc block of PMA-induced differentiation of U-937 cells, as previously reported, IFN-alpha did not. Our data show that v-myc negatively affects the regulation of both basal and inducible HLA class-I antigen expression.
Int J Cancer 1992 Nov 11
PMID:Suppression of basal, PMA- and IFN-alpha-, but not IFN-gamma-induced expression of HLA class I in v-myc-transformed U-937 monoblasts. 135 27

Chronic myelogenous leukemia (CML) is a lethal malignancy of the human hematopoietic stem cell. Here we report that coexistent benign, primitive hematopoietic progenitors can be distinguished from their malignant counterparts in CML bone marrow by differences in cell surface antigen expression. Selection of bone marrow cells expressing the CD34 antigen but lacking the HLA-DR antigen results in recovery of small lymphocyte-like blasts, which initiate and sustain production of myeloid clonogenic progeny in vitro. Secondary clonogenic cells derived at week 1, 5, and 8 from long-term bone marrow cultures (LTBMCs) initiated with primitive progenitors, which lack HLA-DR antigens, exhibit neither the Philadelphia chromosome (Ph1) nor the corresponding bcr/abl mRNA characteristic of CML. In contrast, clonogenic cells recovered at week 1, 5, and 8 from LTBMCs initiated with the CML HLA-DR+ population contain Ph1 and express bcr/abl mRNA. This observation indicates that it may be possible to select a population of viable, exclusively benign hematopoietic stem cells from CML bone marrow capable of repopulating the hematopoietic compartment following autologous bone marrow transplantation.
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PMID:Selection of benign primitive hematopoietic progenitors in chronic myelogenous leukemia on the basis of HLA-DR antigen expression. 137 Oct 77

Specific T lymphocyte lines and T cell clones were established from peripheral blood mononuclear cells of asymptomatic seropositive individuals employing synthetic peptides which correspond to the sequence of the human papillomavirus (HPV) type 16 transforming protein E7. Specificity analysis of T cells as determined by means of [3H] thymidine incorporation after stimulation with individual peptides revealed three immunogenic determinants of E7 that are recognised in association with at least two different HLA haplotypes. One N-terminal region (aminoacids 5-18) was recognised by one T cell line. T cell clones and the corresponding T cell line established from another donor responded to a different N-terminal (17-38) and to a C-terminal region (69-86). The N-terminal sequence 5-18 and the C-terminal determinant contain a periodicity of hydrophilic and hydrophobic residues that have been found in many T cell epitopes. Phenotypic characterisation of T cell clones by indirect immunofluorescence revealed that the T cell clones expressed the CD4 surface glycoprotein suggesting that the specific E7 determinants were recognised in association with major histocompatibility complex (MHC) class II molecules. With regard to functional properties, at least three T cell clones exhibited specific cytotoxic activity towards autologous B lymphocytes transformed by Epstein-Barr virus in the presence of the relevant HPV16 E7 peptides. The implications of these results regarding the development of vaccination strategies and host-virus interaction are discussed.
Eur J Cancer 1992
PMID:Definition of immunogenic determinants of the human papillomavirus type 16 nucleoprotein E7. 137 81

A case is reported of an adult male patient with acute leukemia characterized by the presence of the novel cytogenetic abnormality, t(2;9)(p12;p23), in addition to a t(4;11)(q21;q23). The immunophenotype of the blast cell population was consistent with immature early pre-B cell acute lymphoblastic leukemia (ALL) (TdT+,HLA-DR+,CD19+,CD24 +/-,CD10-) expressing myelo-monocytic antigens (CDw65,CD15). The genotype showed a clonal rearrangement of the immunoglobulin heavy chain locus. Because the immunoglobulin kappa (kappa) light chain gene is located on chromosome 2 at band p12 and interferon alpha (alpha) and beta (beta) map to chromosome 9p21-p22, rearrangements of these loci as a result of the t(2;9) were studied. There was no evidence for rearrangement of the region covering about 40 kilobases around the kappa locus when hybridized to C(kappa), the 3' kappa enhancer or the kappa deleting element. Only germline size restriction fragments were also found for the interferon alpha and beta genes. The patient's clinical features were typical for ALL associated with the t(4;11), including a high white blood cell count at presentation, hepatosplenomegaly, and a poor outcome. The potential significance of 2p and 9p abnormalities in addition to t(4;11) is discussed.
Cancer Genet Cytogenet 1992 May
PMID:Translocation (2;9)(p12;p23) in a case of acute leukemia with t(4;11)(q21;q23). Lack of rearrangement of the kappa and interferon gene loci. 137 31

Conjugate formation between cytotoxic T lymphocytes (CTL) and target B cells, as observed in vitro, is mediated by interactions between adhesion molecules on the two cell surfaces rather than involving immune recognition through the T cell receptor. It is still not clear to what extent such adhesive contacts facilitate the process of immune recognition and target cell lysis. However, work on the Epstein-Barr virus (EBV)-associated malignancy Burkitt's lymphoma (BL) has suggested that down-regulation of one particular adhesion molecule, the lymphocyte function-associated antigen LFA-3, on the tumor cell surface is a key factor in allowing these target cells to escape EBV-specific T cell surveillance. To examine this directly, we used a cDNA for the full-length transmembrane form of LFA-3 to construct a recombinant vaccinia virus (Vacc-LFA 3), which is capable of restoring surface LFA-3 in adhesion molecule-negative BL cell lines to levels as high as seen in EBV-transformed lymphoblastoid cell lines (LCL); biochemical studies confirmed expression of the authentic N-glycosylated protein. The recombinant vaccinia-encoded LFA-3 was functional as an adhesion molecule since BL cells acutely infected with Vacc-LFA-3 then acquired the ability to form conjugates with activated T cells in vitro. However, there was no clear dependence upon LFA-3 when such BL cell lines were tested as targets for cytotoxic T lymphocytes (CTL). Firstly, LFA-3- BL cells could be killed by allospecific CTL recognizing HLA class I alloantigens, in some cases as efficiently as the corresponding LCL. In other cases where lysis was slightly below that of the LCL, Vacc-LFA-3 infection of the BL cells increased lysis up to, but never beyond, LCL values. Secondly, we studied the sensitivity of BL to EBV-specific HLA class I-restricted CTL using a BL target line which was LFA-3- but which expressed the same spectrum of EBV target proteins as an LCL. This line was not recognized by appropriately HLA-matched effectors, even after restoration of LFA-3 expression. We conclude that the LFA-3 status of BL cells influences their conjugate forming ability in in vitro assays but not necessarily their sensitivity to immune T cell-mediated cytolysis.
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PMID:Restoration of the LFA-3 adhesion pathway in Burkitt's lymphoma cells using an LFA-3 recombinant vaccinia virus: consequences for T cell recognition. 137 14

HLA antigen expression, cell ploidy determined by DNA content with flow cytometry, and tumor metastasis were analysed and studied in 51 cases of human colorectal cancer samples. It was observed that the pattern of HLA expression and lymph node metastasis varied significantly when the cancer cells were categorized into distinct ploidies. For tetraploid cancer cells, the percentage of positive expression of class I and II antigens were all 90.0% with no detectable metastasis. On the contrary, the expression of class I and II antigens were as low as 13.3% and 40.0% with metastasis in 26.7% of the samples from diploid group. or 20.0% and 40.0% with a metastasis percentage of 60.0% for heteroploid group. The relevant patterns for triploidy and aneuploidy were between the above three groups. The significance of the unexpected low metastasis of the tetraploid cancer cells both in clinical prognosis and mechanism studies is further discussed.
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PMID:[Relationship among expression of HLA antigen, cell ploidy and metastasis in human colorectal cancer]. 139 54

T-cell-enriched lymphocyte populations derived from the malignant exudate of a patient with ovarian carcinoma were exposed to autologous tumor cells in the mixed lymphocyte-tumor-cell culture (MLTC) and propagated for 42 days. Proliferation of lymphocytes depended on exposures to autologous tumor cells and on the presence of IL-2. After 7 days, the MLTC-lymphocytes lysed K562 and the autologous tumor cells. The latter effect was not inhibited by monoclonal antibodies (MAbs) reactive with MHC class-I antigens or with CD3. After 7 restimulations, the culture was enriched in CD8+ cells (92%) and showed selective lytic activity against the autologous tumor. This function was inhibited by the alpha-class I or alpha-CD3 MAbs, and also by antibodies reactive with the HLA B locus or B5 allele products. The antibodies reactive with HLA A molecules had no such effect. It seems therefore that the function of the CTLs was restricted by HLA B5. Analysis of the TCR beta genes indicated clonal T-cell expansion in this culture. This MLTC was 1 of 21 initiated with 11 blood- and 10 tumor-derived lymphocyte (TIL) populations prepared from the malignant effusions of ovarian carcinoma patients. None of these ex-vivo lymphocytes lysed autologous tumor cells. In 17 MLTCs the lymphocytes did not proliferate, and in 3 cultures the proliferation was maintained only for 2-3 weeks. In 3 of 4 cultures auto-tumor cytotoxicity was induced.
Int J Cancer 1992 Oct 21
PMID:HLA-B5-restricted auto-tumor-specific cytotoxic T cells generated in mixed lymphocyte-tumor-cell culture. 139 29

Peripheral blood lymphocytes from 146 patients with metastatic melanoma undergoing interleukin 2 (IL-2)-based immunotherapy were characterized for HLA A, B, Cw, DR, DQw, and DRw specificities. Patients had been enrolled into sequential treatment protocols with either IL-2 alone (28) or in combination with tumor-infiltrating lymphocytes (TILs) (86), alpha-interferon (26), lymphokine-activated killer cells (16), radiation therapy (7), cyclophosphamide (3), tumor necrosis factor (1), and interleukin 4 (1) for a total of 168 courses of therapy. HLA phenotype was then correlated with response rate and toxicity to IL-2. We noted: (a) a significant difference in the frequency of A11 (20.5% versus 10.2%; P < 0.05) allele between melanoma patients and the North American Caucasian population; (b) a significantly higher frequency of A11 phenotype among responders (40.5%) than in the melanoma patient population (20.5%; P < 0.01), which was even more obvious among patients responding to TIL therapy (47.4% versus 22.1%; P < 0.05); within TIL patients, responders also had an increased frequency of A19 (42.1% versus 25.6%; P < 0.05); (c) a correlation between the number of TILs received and response rate (P < 0.005); and (d) an association between DR4 haplotype and decreased tolerance to IL-2 among the patients receiving TILs (P = 0.01). These results suggest that, in melanoma patients, some HLA Class I specificities may predict for a greater likelihood of response to IL-2-based therapy, while HLA Class II phenotype correlates with tolerance to the combination of TIL and IL-2 therapy.
Cancer Res 1992 Dec 01
PMID:HLA association with response and toxicity in melanoma patients treated with interleukin 2-based immunotherapy. 142 1


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