Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The management of locally advanced prostate cancer remains controversial. Cause-specific survival rates are high for organ-confined disease, but there is a disturbingly high incidence of positive margins in radical prostatectomy specimens. Thus, there has been much interest in neoadjuvant hormonal therapy as a means of shrinking the primary tumor. Both nonrandomized and randomized trials have revealed reductions in tumor size, but the effect on tumor stage and patient survival is less clear. Because the long-term value is not clear, and because neoadjuvant hormonal therapy does have side effects and increases treatment costs, it is at present not advisable outside the clinical research setting.
Mol Urol 1999
PMID:Neoadjuvant Hormonal Therapy and Radical Prostatectomy for Locally Advanced Prostate Cancer. 1085 33

This report describes two cases of recurrent retroperitoneal dedifferentiated liposarcoma characterized by an extensive leiomyomatous component that prevented the correct diagnosis before the last recurrence. Strong immunoreactivity with smooth muscle and desmin antibodies and ultrastructural features consistent with leiomyosarcoma were observed in the spindle-cell and/or myxoid-like components in all four recurrences in case 1, and in the spindle-cell component of the primary tumor and the first recurrence in case 2. In case 1, the correct diagnosis was suggested by the cytogenetic evidence of ring markers, a hallmark of well-differentiated/dedifferentiated liposarcoma. In case 2, tumor type was yielded mainly by the morphology of the second recurrence, which consisted entirely of a well-differentiated liposarcoma, a sclerosing inflammatory variant, as confirmed by the karyotype. Reevaluation of the first two surgical specimens of each case revealed small areas consistent with well-differentiated liposarcoma that had been previously overlooked. Despite the smooth-muscle antigen profile, both cases retained an mdm2+/p53+/cdk4+ immunophenotype consistent with the genotype.
Appl Immunohistochem Mol Morphol 2000 Sep
PMID:Morphologic-cytogenetic analysis of dedifferentiated liposarcomas with an extensive misleading leiomyosarcomatous component. 1098 74

CD44 is a widely distributed set of cell surface glycoproteins expressed in several types of cells and tissues, implicated in cell-cell and cell-substrate interactions. This molecule plays a major role in cell differentiation, development and activation and has also been described as a potential marker of malignancy and metastasis. In the present study we investigated by RT-PCR followed by exon specific amplification the expression of CD44 splice variants in four different murine tumors as well as in the invaded organs in order to correlate the expression of CD44 variants with potential tumor invasiveness and their implications for growth. Our data showed deregulation in the expression of CD44 isoforms but no discernible correlation in isoform expression pattern. However, in all tumors studied isoforms presented by the primary tumor were detected in the invaded organs before metastasis could be demonstrated by histopathological analysis.
Int J Mol Med 2001 May
PMID:Expression of CD44 splice variants in spontaneous murine tumors. 1129 21

The MYCN gene is often amplified but rarely rearranged in neuroblastoma. We report, for the first time, a rearrangement within the MYCN coding region in a metastatic neuroblastoma in a 3-year-old boy with MYCN amplification in his primary tumor. The rearrangement occurred 46 nucleotides downstream from the ATG codon in exon 2 of MYCN. The amplification level of the rearranged copies of the MYCN gene was lower than that of the unrearranged copies of MYCN. These results indicate that the rearrangement occurred after initial MYCN gene amplification. Monochromosomal somatic cell hybrid mapping of the novel region fused to exon 2 of MYCN localized it to chromosome 2, suggesting that this rearrangement resulted from an interstitial deletion, presumably within the MYCN amplicon itself.
Diagn Mol Pathol 2001 Jun
PMID:Rearrangement in the coding region of the MYCN gene in a subset of amplicons in a case of neuroblastoma with MYCN amplification. 1138 18

We examined the involvement of the cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in the pathogenesis of ultraviolet (UV) radiation-induced melanomas in an opossum (Monodelphis domestica) melanoma model in which suckling young were exposed to UVB to produce melanocytic lesions. Monodelphis CDKN2A and alternated reading frame (ARF) cDNAs were cloned and sequenced, and the expression patterns of these genes were determined by reverse transcription-polymerase chain reaction in normal tissues, 39 primary melanocytic skin lesions, and two tumor-derived cell lines, one nonmetastatic and one metastatic. Primary melanocytic lesions, including hyperplasias, benign melanomas, melanomas metastatic to lymph nodes, and melanomas metastatic to nodes and additional visceral organs, were categorized accordingly as types I-IV. Levels of CDKN2A transcripts were most abundant in type III tumor samples and the metastatic cell line but absent in the nonmetastatic cell line. ARF transcripts were expressed in all tumors and cell lines. A UV-signature mutation was detected with the wild-type allele at the CDKN2A locus in type II and III primary tumor samples and in the nonmetastatic cell line. Interestingly, in the metastatic cell line, only the mutant allele was present and expressed. These data suggest dynamic changes in the expression and/or structure of the CDKN2A and ARF genes represent one molecular defect associated with the etiology of melanoma formation and progression in the Monodelphis model system.
Mol Carcinog 2001 May
PMID:Characterization of the CDKN2A and ARF genes in UV-induced melanocytic hyperplasias and melanomas of an opossum (Monodelphis domestica). 1139 94

Several elements such as circulating DNA and metastatic cells, containing the same primary tumor mutations, oncogenic proteins, cytokines, and other tumor related not yet identified factors, can be found in the blood stream of cancer patients. In this study we have shown that serum factors presented in lung cancer patients can modify the protein profile of the lung adenocarcinoma cell line (A549). This alteration in cellular protein profile can be an important event in the cell phenotype modification necessary for the advance of the disease. There have been no similar studies regarding cancer cell protein synthesis induction by human cancer serum.
Int J Mol Med 2001 Aug
PMID:Alteration of A549 carcinoma cell protein synthesis profile induced by lung cancer patient serum. 1144 77

Improved treatment and supportive care have increased the survival of children diagnosed with cancer. This success has resulted in a growing population at risk of long-term complications of therapy, including secondary malignancy. These neoplasms may result from the direct effect of the modalities used in treatment of the primary tumor, more indirect effects of the treatment or supportive care, the genetic predisposition of the patient, or to interactions among these factors. The increasing success of cancer therapy is producing a rapidly growing population of patients at risk of second malignancy. This is a result of the increasing intensity of treatments and the increasing duration of survival, which provides the time to manifest the late effects of therapy. The concept that a patient is "cured" at some arbitrary time after treatment does not diminish the need for follow-up of all cancer survivors to identify and treat secondary malignancies. These risks have led to an increased effort to define phenotypic and genotypic categories of patients that may be cured with less intensive therapy and to develop molecularly targeted drugs that have fewer noxious effects on normal tissues.
Blood Cells Mol Dis
PMID:Second malignant neoplasms after successful treatment of childhood cancers. 1148 81

Leuvectin is a plasmid DNA/lipid complex comprised of a plasmid DNA expression vector (VCL-1102, 30) encoding human interleukin (IL)-2 complexed in a 5:1 mass ratio with DMRIE/DOPE lipid that has been developed for the treatment of cancer. DMRIE/DOPE is a cationic lipid, which facilitates in vitro and in vivo transfection of plasmid DNA. In vitro transfection with the IL-2 plasmid DNA/DMRIE/DOPE complex results in the expression of sustained levels of biologically active IL-2. Human tumor cell lines and primary human tumor cells established from biopsies were readily transfected in vitro resulting in the expression of IL-2. Following in vitro transfection, IL-2 expression continued up to several weeks post-transfection in primary tumor cells. In preclinical efficacy studies in a murine model of renal cell carcinoma (RCC), the direct intratumoral administration of an IL-2 plasmid DNA/DMRIE/DOPE complex resulted in the generation of tumor specific lymphocytes and complete tumor regression in the majority of the mice. In preclinical animal safety studies, repeated administration of Leuvectin was safe and well-tolerated. Following these promising preclinical results, Leuvectin has entered clinical trials and two pilot phase I/II trials are described.
Curr Opin Mol Ther 1999 Apr
PMID:Technology evaluation: interleukin-2 gene therapy for the treatment of renal cell carcinoma. 1171 51

Fas ligand (FasL) is a type II transmembrane tumor necrosis factor family protein, known to trigger apoptosis in cells that bear the FasL receptor, Fas. The authors found that normal prostate, benign hyperplasia, and most prostatic carcinoma cells at the primary site did not express FasL, whereas metastatic prostatic carcinoma cells in lymph nodes and bone marrow displayed almost uniform, immunohistochemically detectable, FasL expression. However, small foci of FasL-positive prostatic carcinoma cells amid a vast majority of FasL-negative tumor cells were noted at the primary sites in patients with distant metastases. Analysis of the FasL gene and its mRNA by polymerase chain reaction and reverse transcriptase-polymerase chain reaction, respectively, suggested that the expression of immunohistochemically detectable FasL in metastatic tumor cells was not due to mutation in the FasL gene with resulting overexpression. Further, FasL expression was detectable in the acinar epithelial cells of prostates with morphologic atrophic changes, suggesting that FasL also plays a role in the physiologic apoptosis process of noncancerous prostate. The current data suggest that a subpopulation of prostate carcinoma cells clonally expresses FasL, and this subpopulation may have metastatic potential. Evaluation of FasL expression in the primary tumor thus may provide a useful parameter for predicting metastatic potential of the tumor.
Diagn Mol Pathol 2001 Dec
PMID:Expression of fas ligand in metastatic prostatic carcinoma: suggestive of possible clonal expansion of subpopulation with metastatic potential. 1176 14

Maspin has been shown to possess tumor-suppressing activity against breast tumor growth and metastasis. To test the therapeutic value of the maspin gene (SERPINB5) in breast cancer, we established a syngeneic breast tumor metastasis model. This model involved the implantation of mammary tumor cells orthotopically to mammary gland and allowed tumors to grow within the gland and become metastatic to other organs. The mammary tumor cells were initially isolated from MMTV-polyoma virus middle T transgenic mice and were selected in vitro for high invasiveness. Here, we demonstrate that the mammary tumor cells were highly invasive and metastatic. Overall, 100% of tumor-transplanted mice developed lung metastasis. Using nonviral liposome as a carrier, we delivered SERPINB5 to mice bearing mammary tumors. Our data showed that both primary tumor growth and metastasis were significantly inhibited in this syngeneic metastasis model. Such inhibition is mediated by SERPINB5 transgene through increased apoptosis in SERPINB5-treated tumors. Thus, SERPINB5 can be used in gene therapy against breast tumor growth and metastasis.
Mol Ther 2002 Jun
PMID:Inhibition of breast tumor progression by systemic delivery of the maspin gene in a syngeneic tumor model. 1202 60


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