Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IFNs were the first new therapeutic products resulting from recombinant DNA technology. IFNs were also the first human proteins effective in cancer treatment. There is however much to be discovered which will lead to new clinical applications. Areas which represent major research challenges for full understanding and application of the IFN system are: (i) the diversity of the IFN family; (ii) the role of induction; (iii) molecular mechanism of action; (iv) cellular modulatory effects; (v) advantages of combinations, and (vi) identification of new therapeutic indications. This review will emphasize the diversity of the IFN family and chemical modifications which will result in second-generation IFNs. Pre-clinical and clinical findings form the basis for new therapeutic directions in chronic myelogenous leukemia, lymphomas, myelomas, melanoma, urologic malignancies, primary brain tumors, and ovarian carcinoma.
 ...
PMID:Second-generation interferons for cancer: clinical targets. 1093 63

More than 4 decades after their discovery, interferons are used now in daily clinical practice for the treatment of chronic viral hepatitis, multiple sclerosis, chronic granulomatous disease, and malignant disease such as hairy cell leukaemia, chronic myeloid leukaemia, Kaposi's sarcoma, multiple myeloma and malignant melanoma. In general, treatment with interferons is successful in only a fraction of the patients suffering from these diseases. The reasons for treatment failures in many patients are not understood a present. The discovery of the Jak-Stat pathway as the principal signalling pathway for interferons opens new research options for a better understanding of interferon resistance in various diseases. Defective Jak-Stat signal transduction has now been described in cells expressing HBV proteins, in cells expressing HCV proteins, and in cell lines derived from malignant melanomas. A better understanding of these signalling defects might lead to new therapeutic strategies making interferons more effective in a larger percentage of patients.
 ...
PMID:Intracellular signalling and antiviral effects of interferons. 1097 79

This is a case of granulocytic sarcoma presenting as bilateral breast masses in a 40-yr-old woman with concurrent unsuspected chronic myeloid leukemia diagnosed by fine-needle aspiration. The granulocytic differentiation was recognized on Diff-Quik-stained cytology smears and confirmed rapidly on flow cytometry on the same day. The breast has been reported to be an uncommon site for granulocytic sarcoma. We found that 38.8% of granulocytic sarcomas diagnosed by fine-needle aspiration in the English-language literature occurred in the breast. In the absence of clinical history or hematological abnormality, granulocytic sarcoma may be misdiagnosed, depending on the degree of myeloid differentiation present within the tumor. The differential diagnosis includes large-cell non-Hodgkin's lymphoma, lobular carcinoma of the breast, undifferentiated carcinoma, malignant melanoma, extramedullary hemopoiesis and inflammation. The key morphological features and useful ancillary tests are discussed.
 ...
PMID:Unusual presentation of granulocytic sarcoma in the breast: a case report and review of the literature. 1113 70

Depressed natural killer (NK) cell activity has been showed in family members of patients with different types of cancer. The present work aimed to evaluate T cell subsets and NK cell cytotoxic activity in 15 members of a family with high incidence of tumors, such as glioblastoma, gastric, pancreas and colon rectal carcinoma, chronic myelocitic leukemia, melanoma and osteoblastoma. As controls, 19 healthy subjects with the age range equivalent were studied. The enumeration of CD3+ lymphocytes and their CD4+ and CD8+ subsets were defined by monoclonal antibodies and NK cell cytotoxicity towards K562 target cells were evaluated by single cell-assay. The results showed in family members low percentage of total T cells (CD3+), and their CD4+ subset and impairment of CD4/CD8 ratio in relation to control group. All family members presented percentage of NK-target cell conjugate formation below the minimum value observed in control group. Thirteen people were examined and followed up during five years, in order to assure that there was no undiagnosed or unsuspected disease at the moment of evaluation. One of them developed osteoblastoma and other malignant melanoma. Two cancer patients, with glioblastoma and chronic myelocytic leukemia were studied during illness. All the corresponding values were comparable. The persistence of low percentage of conjugate formation may be related to a defect on adhesion molecules expression in the surface of NK cells that was probably responsible for the low activity of these cells presented by the family group. Thus, the inheritance mechanism of low adherence of NK cells should have a prognostic value in determining the risk of developing tumors.
 ...
PMID:Familial cancer: depressed NK-cell cytotoxicity in healthy and cancer affected members. 1129 23

This report describes a tumor-associated antigen, termed CML66, initially cloned from a chronic myelogenous leukemia (CML) cDNA expression library. CML66 encodes a 583-aa protein with a molecular mass of 66 kDa and no significant homology to other known genes. CML66 gene is localized to human chromosome 8q23, but the function of this gene is unknown. CML66 is expressed in leukemias and a variety of solid tumor cell lines. When examined by Northern blot, expression in normal tissues was restricted to testis and heart, and no expression was found in hematopoietic tissues. When examined by quantitative reverse transcription-PCR, expression in CML cells was 1.5-fold higher than in normal peripheral blood mononuclear cells. The presence of CML66-specific antibody in patient serum was confirmed by Western blot and the development of high titer IgG antibody specific for CML66 correlated with immune induced remission of CML in a patient who received infusion of normal donor lymphocytes for treatment of relapse. CML66 antibody also was found in sera from 18-38% of patients with lung cancer, melanoma, and prostate cancer. These findings suggest that CML66 may be immunogenic in a wide variety of malignancies and may be a target for antigen-specific immunotherapy.
 ...
PMID:CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia. 1141 19

Serological identification of tumor antigens by cDNA expression cloning is a technique used to isolate cDNAs encoding tumor antigens that are recognized by IgG antibodies in sera from cancer patients. It is also useful for the isolation of tumor antigens recognized by T cells. We applied this method to identify melanoma antigens recognized by the serum from a patient with a good prognosis who had T-cell-infiltrated melanoma and vitiligo. By screening a lambda phage cDNA library constructed from a highly pigmented melanoma cell line, SKmel23, with the patient's serum, 50 positive cDNA clones consisting of 26 distinct antigens were isolated. Of these, 20 encoded known proteins, and 6 encoded previously uncharacterized ones. The most frequently isolated clone, which we named KU-MEL-1, was unknown previously but was homologous to partial cDNA sequences registered in the expressed sequence tag database. Reverse transcription-PCR and Northern blot analysis demonstrated that KU-MEL-1 was strongly expressed in most melanoma cell lines, melanoma tissue samples, and cultured melanocytes and weakly expressed in cell lines derived from other types of tumors, as well as in some normal tissues, including testis. Western blot analysis with polyclonal murine antibody generated by immunization with the recombinant KU-MEL-1 protein demonstrated that the KU-MEL-1 protein was preferentially expressed in melanoma cells and melanocytes. IgG antibodies against KU-MEL-1 were detected in the sera from 9 of 26 melanoma patients and from some patients with other cancers, including brain tumor, esophageal cancer, colon cancer, and chronic myelogenous leukemia, but were not detected in sera from 30 healthy individuals. Although the IgG specific for KU-MEL-1 was not detected in sera from 12 vitiligo patients, it was detected in sera from 7 of 11 patients with Vogt-Koyanagi-Harada disease that is thought to be an autoimmune disease against melanocytes. These results suggest that KU-MEL-1 may be a useful target for the development of diagnostic and therapeutic methods for patients with various cancers, particularly with melanoma, as well as patients with autoimmune diseases against melanocytes.
 ...
PMID:Tumor antigens isolated from a patient with vitiligo and T-cell-infiltrated melanoma. 1218 44

ELISPOT assays are increasingly used for a direct detection and quantification of single antigen-specific T cells in freshly isolated peripheral blood mononuclear cells (PBMC). They are particularly attractive for the monitoring of specific T lymphocyte responses in clinical trials assessing antigen-specific immunizations in patients with cancer or chronic viral infections. However, one major limitation for the broad clinical implementation of ELISPOT assays is the lack of an inexhaustible source of suitable HLA-matched antigen-presenting cells (APC). Currently available allogeneic or xenogeneic APC (such as the human lymphoid hybrid T2 or HLA-transfected insect cells) can either lead to strong background spot production by APC-reactive T lymphocytes or have a low antigen presentation capability. Both phenomena can prevent the detection of low frequency T cell responses in PBMC. In search of alternative APC for ELISPOT assays, the human chronic myelogenous leukemia cell line K562 that per se does not express HLA class I and class II molecules on the cell surface was transfected with the HLA-A*0201 gene. Clonal HLA-A*0201-expressing K562 (K562/A*0201) cells were able to process and present endogenously expressed and exogenously loaded melanoma peptide antigens to HLA-A*0201-restricted cytolytic T lymphocyte clones in cytotoxicity and IFN-gamma ELISPOT assays. K562/A*0201 cells were then used as APC in IFN-gamma spot assays to detect ex vivo CD8(+) T lymphocytes responsive to known HLA-A*0201-binding peptide epitopes derived from cytomegalovirus, Epstein-Barr virus, influenza virus and melanoma in PBMC from HLA-A*0201-positive donors. In the majority of cases, peptide-pulsed K562/A*0201 cells were similarly efficient in the ability to visualize single antigen-specific CD8(+) T lymphocytes when compared to T2 cells. However, in contrast to T2, background reactivity of CD8(+) T cells responsive to unpulsed K562/A*0201 was regularly found to be negligible, thereby enhancing the sensitivity of the ELISPOT assay, particularly in donors with strong anti-T2 reactivity. K562 cells transfected with HLA-A*0201 or other HLA genes can serve as standard APC for monitoring T lymphocyte responses against tumor and viral peptide antigens.
 ...
PMID:The use of HLA-A*0201-transfected K562 as standard antigen-presenting cells for CD8(+) T lymphocytes in IFN-gamma ELISPOT assays. 1173 Aug 45

Kermit is a Xenopus orthologue of human GIPC1/GIPC, which interacts with Frizzled-3 (FZD3) class of WNT receptor to modulate WNT signaling. GIPC1 interacts with TGFbeta type III receptor to enhance TGFbeta signaling. We have recently cloned and characterized a novel GIPC1-related gene, GIPC2. During isolation of GIPC2, we identified another novel GIPC1-related gene, GIPC3, by using bioinformatics. In this study, we isolated GIPC3 cDNAs from poly(A)+ RNA of human fetal lung. GIPC3 encoded a 312-amino-acid protein with a central PDZ domain, which showed 59.9% total-amino-acid identity with GIPC1, 55.3% total-amino-acid identity with GIPC2, and 57.2% total-amino-acid identity with Xenopus Kermit. GIPC3 gene on human chromosome 19p13.3 was found to consist of 6 exons, just like GIPC1 gene and GIPC2 gene. The 4.5-kb GIPC3 mRNA was almost ubiquitously expressed in normal adult tissues as well as in normal fetal tissues. Expression level of GIPC3 mRNA was relatively higher in jejunum, followed by lymph node, parietal lobe in brain, fetal spleen, and fetal thymus. GIPC3 mRNA was expressed in cervical cancer cell line HeLa S3, chronic myelogenous leukemia cell line K-562, and melanoma cell line G-361. GIPC3 mRNA was also expressed in gastric cancer cell lines TMK1 and MKN7; however, expression level of GIPC3 mRNA in TMK1 and MKN7 cells were significantly lower than that in normal stomach. This is the first report on molecular cloning of GIPC3, the third member of the GIPC gene family.
 ...
PMID:Molecular cloning and characterization of human GIPC3, a novel gene homologous to human GIPC1 and GIPC2. 1183 71

An important goal of cancer immunology is the identification of antigens associated with tumor destruction. Vaccination with irradiated tumor cells engineered to secrete granulocyte/macrophage colony-stimulating factor (GM-CSF) generates potent, specific, and long-lasting antitumor immunity in multiple murine tumor models. A phase I clinical trial of this vaccination strategy in patients with advanced melanoma demonstrated the consistent induction of dense CD4(+) and CD8(+) T lymphocyte and plasma cell infiltrates in distant metastases, resulting in extensive tumor destruction, fibrosis, and edema. Antimelanoma antibody and cytotoxic T cell responses were associated with tumor cell death. To characterize the targets of these responses, we screened an autologous cDNA expression library prepared from a densely infiltrated metastasis with postvaccination sera from a long-term responding patient. High-titer IgG antibodies detected ATP6S1, a putative accessory unit of the vacuolar H(+)-ATPase complex. A longitudinal analysis of this patient revealed an association between the vaccine-induced increase in antibodies to ATP6S1 and tumor destruction. Three additional vaccinated melanoma patients and three metastatic non-small cell lung carcinoma patients vaccinated with autologous GM-CSF-secreting tumor cells similarly showed a correlation between humoral responses to ATP6S1 and tumor destruction. Moreover, a chronic myelogenous leukemia patient who experienced a complete remission after CD4(+) donor lymphocyte infusions also developed high-titer antibodies to ATP6S1. Lastly, vaccination with GM-CSF-secreting B16 melanoma cells stimulated high-titer antibodies to ATPS1 in a murine model. Taken together, these findings demonstrate that potent humoral responses to ATP6S1 are associated with immune-mediated destruction of diverse tumors.
 ...
PMID:ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction. 1198 66

Xenopus Strabismus (Stbm) is a negative regulator of the WNT - beta-catenin signaling pathway. Strabismus 1 (STB1/VangL2) and Strabismus 2 (STB2/Vangl1) are human homologues of Xenopus Stbm and Drosophila Stbm/ Van Gogh (Vang) STB1 and STB2 are four-transmembrane-type proteins with Dishevelled-binding motif. STB2 and CASQ2 genes are located on human chromosome 1p13.3-p11 with an interval less than 5 kb. Here, STB1 gene and CASQ1 gene were found to be located on human chromosome 1q21-q23 with an interval of about 210 kb including Nicastrin, COPA, PXF, H326 and PEA15 genes. Exon-intron structure was well conserved between STB1 and STB2 genes. STB1-CASQ1 gene cluster and STB2-CASQ2 gene cluster might be generated due to duplication of ancestral gene cluster, and several genes might be inserted into the STB1-CASQ1 intergenic region during or after gene-cluster duplication. STB1 mRNA was relatively highly expressed in prostate, trachea, thymus, lymph node, placenta, fetal kidney, fetal brain, and fetal lung. In adult brain, STB1 mRNA was more highly expressed in cerebellum, corpus callosum, amygdala, and medulla oblongata. STB1 mRNA was moderately expressed in K-562 (chronic myelogenous leukemia), G-361 (melanoma), and MKN7 (gastric cancer). On the other hand, STB1 mRNA was almost undetectable in several human cancer cell lines, and was down-regulated in 4 out of 14 cases of primary kidney tumors, and in 2 out of 3 cases of primary lung cancer. Loss-of-function mutation of STB1 gene might lead to carcinogenesis through activation of the WNT - beta-catenin signaling pathway.
 ...
PMID:Structure and expression of Strabismus 1 gene on human chromosome 1q21-q23. 1201 99


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