Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A tumor-associated antigen-induced leukocyte adherence inhibition assay was used to evaluate the effect of serum from patients with adenocarcinoma of the prostate on the antitumor reactivity of normal leukocytes. Peripheral blood leukocytes from 53 normal (control) subjects were armed with serum from 22 patients with localized (Stage A) and metastatic (Stage D) prostatic cancer and reacted with allogenic extract of malignant prostate as specific tumor-associated antigen. Leukocytes pre-treated with serum from patients with Stage A cancer show significantly stronger responses to malignant prostate than do those pretreated with serum from patients with Stage D cancer, which induced little or no response. This may be attributed to an "arming factor" present in the sera of patients with an initial stage of prostatic cancer which appears to be capable of sensitizing normal leukocytes and making them specifically reactive to tumor extract. The specificity of arming with individual and pooled patient's sera was delineated by the use of extracts from other genitourinary tumors.
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PMID:Arming of normal leukocytes with sera from patients with adenocarcinoma of the prostate. 47 62

A unique mouse hybridoma, PR92, was obtained using human prostate adenocarcinoma cell line DU145. The monoclonal antibody produced by the PR92 clone was reactive with DU145, MCF-7 (breast adenocarcinoma), and CHAGO (lung carcinoma), but not with normal cell lines and 16 other cell lines of cancerous origin. A homologous solid-phase sandwich radioimmunoassay (PR92-RIA) was developed utilizing PR92 monoclonal antibody. The PR92-RIA recognized unique antigen present in DU145 cell extract but did not detect 16 other known tumor-associated markers. In preliminary studies, the PR92-RIA measured greater than 5 units/ml level of PR92 monoclonal antibody-binding antigen in 23 of 31 (74%) serum specimens of active prostate cancer and 27 of 31 (87%) active breast carcinoma patients. Only 1 of 79 (1%) sex-matched normal donors and 1 of 57 (2%) benign disease control patients showed the serum antigen level greater than 5 units/ml. A high degree of correlation was observed between the PR92 antigen activity and the clinical status of four prostate and four breast cancer patients during therapeutic treatment. Thus, the PR92-RIA detects new tumor-associated antigen which may be useful in detection and monitoring of prostate and breast carcinoma patients.
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PMID:Monoclonal antibody PR92 with restricted specificity for tumor-associated antigen of prostate and breast carcinoma. 339 7

To provide appropriate therapy for prostate cancer, accurate staging of the patient's disease is essential. Determination of tumor size, location, periprostatic extension and metastatic disease in the skeleton and soft tissue are needed to stage properly. Current diagnostic modalities may lead to understaging in 40%-70% of prostate cancer. Detection of metastatic disease, both at the time of initial diagnosis and in patients with suspected local recurrence, can significantly alter the type of therapy given. Clinical studies using the (111)In radiolabeled immunoconjugate, MAb 7E11-C5.3-GYK-DTPA (capromab pendetide), have shown the superiority of radioimmunoscintigraphy over other diagnostic modalities in the detection of both primary and metastatic prostate cancer. Radioimmunoscintigraphy with capromab pendetide depends on expression of tumor-associated antigen rather than lesion size. Earlier detection of extraprostatic invasion and metastases by means of radioimmunoscintigraphy provides valuable information for treatment decisions. A case of metastatic prostate cancer in the abdomen of a patient without local disease, in which the extent of disease was confirmed at autopsy after sudden cardiac arrest, is presented.
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PMID:Prostate cancer abdominal metastases detected with indium-111 capromab pendetide. 954 74

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.
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PMID:CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia. 1141 19

There is no standard effective therapy for metastatic renal-cell carcinoma (RCC) or prostate cancer. Both of these cancers may be immunogenic, so therapy targeted to a tumor-associated antigen may be effective. Transduction of the gene encoding granulocyte-macrophage colony-stimulating factor has shown promise in preclinical studies, and clinical trials are in their early stages. Both autologous cancer cells and partially HLA-matched allogenic cells are being studied. No dose-limiting side effects have been observed, and a few patients have had transient objective tumor regressions. Further trials with more frequent and, probably, longer immunization schedules are needed to define efficacy.
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PMID:Ex vivo gene therapy using granulocyte-macrophage colony-stimulating factor-transduced tumor vaccines. 1200 40

The realization that prostate cancer is an immunogenic tumor, in conjunction with the discovery of novel methods for priming the immune system to generate an antitumor response, has resulted in several new approaches for prostate cancer immunotherapy. Based on these various approaches, several human clinical trials have begun using immune-based therapies for prostate cancer. These approaches can be divided into cytokine-based therapies, tumor-associated antigen-based therapies, tumor vaccines, and dendritic cell-based therapies. This review summarizes the latest findings from each of these approaches and gives results from the few completed human clinical trials.
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PMID:Immunotherapy of prostate cancer. 1208 72

Despite early diagnosis and improved therapy, 31,500 men will die from prostate cancer (PC) this year. The HER2/neu oncoprotein is an important effector of cell growth found in the majority of high-grade prostatic tumors and is capable of rendering immunogenicity. The antigenicity of this oncoprotein might prove useful in the development of PC vaccines. Our goal is to prove the principle that a single DNA vaccine can provide reliable immunity against PC in the MatLyLu (MLL) translational tumor model. The parental rat MatLyLu PC cell line expresses low to moderate levels of the rat neu protein. To simulate in vivo human PC, MatLyLu cells were transfected with a truncated sequence of human HER2/neu cDNA cloned into the pCI-neo vector. This HER2/neu cDNA sequence encodes the first 433 amino acids of the extracellular domain (ECD). MatLyLu cells were also transfected with the same HER2/neu cDNA sequence cloned into the N1-terminal sequence of EGFP reporter gene to produce a fusion protein. The partial ECD sequence of HER2/neu includes five rat major histocompatibility (MHC)-II-restricted peptides with complete human-to-rat cross-species homology. The HER2/neu protein overexpression was documented by Western Blot analysis, and the expression of fusion protein was monitored by confocal microscopy and fluorimetry. Vaccination with a single injection of HER2/neu cDNA protected 50% of animals against HER2/neu-MatLyLu tumors (P < 0.01). When the tumor cells were engineered to express HER2/neu-EGFP fusion protein, the antitumor immunity was enhanced, as following vaccination with HER2/neu-EGFP cDNA, 80% of these rats rejected HER2/neu-EGFP-MatLyLu (P<0.001). Both vaccines induced HER2/neu-specific antibody titers. Rats vaccinated with EGFP-cDNA rejected 80% of EGFP-MatLyLu tumors and, interestingly, 40% of HER2/neu-MatLyLu tumors. None of the cDNA vaccines induced immunity against parental MatLyLu cells. Our data clearly demonstrate that a single injection of HER2/neu-EGFP cDNA is a very effective vaccine against PC tumors expressing the cognate tumor-associated antigen (TA). The antitumor immunity is significantly more pronounced if the tumors express xenogeneic HER2/neu-EGFP fusion protein as opposed to only the syngeneic HER2/neu oncoprotein. Our data suggests that the HER2/neu-EGFP-MatLyLu tumor is a potential animal tumor model for investigating therapeutic vaccine strategies against PC in vivo and demonstrates the limitations of a cDNA vaccine only encoding for MHC-II-restricted HER2/neu-ECD sequence peptides.
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PMID:Efficacy of vaccination with plasmid DNA encoding for HER2/neu or HER2/neu-eGFP fusion protein against prostate cancer in rats. 1209 69

Cancer sera contain antibodies which react with a unique group of autologous cellular antigens called tumor-associated antigens (TAAs). This study determines whether a mini-array of multiple TAAs would enhance antibody detection and be a useful approach to cancer detection and diagnosis. The mini-array of TAAs comprised full-length recombinant proteins expressed from cDNAs encoding c-myc, p53, cyclin B1, p62, Koc, IMP1, and survivin. Enzyme immunoassay was used to detect antibodies in 527 sera from six different types of cancer. Antibody frequency to any individual TAA was variable but rarely exceeded 15-20%. With the successive addition of TAAs to a final total of seven antigens, there was a stepwise increase of positive antibody reactions up to a range of 44-68%. Breast, lung, and prostate cancer patients showed separate and distinct profiles of reactivity, suggesting that uniquely constituted antigen mini-arrays might be developed to distinguish between some types of cancer. Distinct antibody profiles were not observed in gastric, colorectal, and hepatocellular carcinomas with this set of seven TAAs. Detection of autoantibodies in cancer can be enhanced by using a mini-array of several TAAs as target antigens. Additional studies in early cancer patients and high-risk individuals and the design of unique antigen panels for different cancers would help to determine whether multiple antigen mini-arrays for the detection of autoantibodies might contribute a clinically useful noninvasive approach to cancer detection and diagnosis.
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PMID:Enhancement of antibody detection in cancer using panel of recombinant tumor-associated antigens. 1258 23

The identification of tumor-associated/-specific antigens and an increased understanding of the ways in which antigens are processed and presented has led to a revived interest in cancer vaccines as a therapeutic strategy. BLP25 liposome (L-BLP25) vaccine is a cancer vaccine that targets the exposed core peptide of the MUC1 tumor-associated antigen. Studies in advanced-stage non-small cell lung cancer demonstrate that L-BLP25 vaccine has the potential to extend the survival of patients with Stage IIIB locoregional non-small cell lung cancer and maintain quality of life for longer. L-BLP25 vaccine also shows promise for prostate cancer patients, having the potential to prolong prostate-specific antigen doubling time in men with biochemical failure post prostatectomy. These clinically meaningful results with a relatively nontoxic therapeutic vaccine are very encouraging and suggest potential for L-BLP25 to fulfill an unmet medical need.
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PMID:Vaccination with BLP25 liposome vaccine to treat non-small cell lung and prostate cancers. 1602 41

Molecular changes are vital for the development of prognostic markers and therapeutic modalities of prostate cancer (CaP). There is growing interest in mucins as treatment targets in human malignancies, including CaP. The role of their expression in the progression of CaP is however unclear. We examined the expressions MUC1, MUC2, MUC4, MUC5AC and MUC6 in CaP tissues using tissue microarrays (TMAs) to look for tumor-associated antigens (TAAs) for targeted therapy. In this study, 120 paraffin-embedded specimens were selected from patients who underwent radical retro-pubic prostatectomy (RRP) or trans-urethral-resection of the prostate (TURP) for primary, untreated CaP and 10 matched lymph node metastases. A series of MUC monoclonal antibodies (mAbs) was used on TMAs by standard immunohistochemistry. Our results indicate that the over-expression of MUC1 was detected in 58% of primary CaP tissues and 90% of lymph node metastases but not in normal prostate or benign tissues, while the expression of MUC2, MUC4, MUC5AC and MUC6 was found to be negative in both normal and cancer tissues. Of the MUC1 positive tumors 86% were Gleason grade 7 or higher. Over-expression of MUC1 was found in late stage CaP while MUC2, 4, 5AC and 6 were negative in CaP. MUC1 is a TAA that is highly related to tumor progression in CaP patients. This antigen is ideal for targeted therapy to control micrometastases and hormone refractory disease but additional studies are necessary to assess its usefulness in patient biopsies and CaP bone metastases before clinical trial.
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PMID:MUC1, MUC2, MUC4, MUC5AC and MUC6 expression in the progression of prostate cancer. 1647 27


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