Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first step of invasion and metastasis is the detachment of cancer cells in the primary tumor, which is mainly controlled by the function in the adherens junction, consisting of E-cadherin associated proteins (E-cadherin, alpha- and beta-catenins, vinculin, alpha-actinin, and actin). The cell-to-cell aggregation activity and the expressions of E-cadherin, and alpha- and beta-catenin mRNAs in Ishikawa cells of well-differentiated endometrial cancer were significantly suppressed by estrogen. These suppressions were reversed by progesterone, medroxyprogesterone acetate (MPA) and danazol. Proteins in the adherens junction appeared to be expressed intact and to be functional in Ishikawa cells. Persistent estrogen predominant milieu might contribute to the detachment of well-differentiated endometrial cancer cells, leading to spreading of those cells, while progestins and danazol protect estrogen-induced spreading of those cells.
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PMID:Progestins and danazol effect on cell-to-cell adhesion, and E-cadherin and alpha- and beta-catenin mRNA expressions. 863 63

Metastatic renal-cell carcinoma (RCC) is not responsive to conventional cytotoxic chemotherapy, but a subset of patients achieve a durable remission with the use of interleukin-2 (IL-2). IL-2 is currently the only Food and Drug Administration (FDA)-approved treatment for metastatic RCC, and it benefits 10-20% of those who receive it. However, it is accompanied by significant, occasionally life-threatening toxicity. Attempts to maintain the efficacy of IL-2 while minimizing systemic side effects have led to the development of IL-2 gene therapies. Leuvectin is a plasmid DNA/lipid complex composed of a plasmid DNA expression vector (VCL-1102, 30) encoding human IL-2 complexed in a 5:1 mass ratio with DMRIE/DOPE lipid (1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide/dioleoylphosphatidyl ethanolamine), which has been developed for the treatment of malignancy. DMRIE/DOPE is a cationic lipid that has been shown to facilitate in vitro transfection of plasmid DNA. It has been demonstrated that in vitro transfection with the IL-2 plasmid DNA/DMRIE/DOPE complex results in the expression of sustained levels of biologically active IL-2. Established human tumor cell lines and primary human tumor cells obtained from biopsies are readily transfected in vitro, resulting in the expression of IL-2. Following in vitro transfection, IL-2 expression has been found to persist for up to several weeks in primary tumor cells. In preclinical efficacy studies in a murine model of renal-cell carcinoma the direct intratumoral administration of an IL-2 plasmid DNA/DMRIE/DOPE complex resulted in complete tumor regression in the majority of mice. In preclinical animal-safety studies, repeated administration of Leuvectin was safe and well tolerated. Following these promising preclinical trials, Leuvectin has been taken into clinical trial. The results of two early studies indicate that Leuvectin is safe, is free of systemic toxicity, and has biologic activity.
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PMID:Intratumoral interleukin 2 for renal-cell carcinoma by direct gene transfer of a plasmid DNA/DMRIE/DOPE lipid complex. 1085 52

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.
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PMID:Technology evaluation: interleukin-2 gene therapy for the treatment of renal cell carcinoma. 1171 51

Mammary tumors are a major health threat to women and female dogs. In both, metastasis of the primary tumor to distant organs is the most common cause of tumor-related death. Nevertheless, the molecular mechanisms of tumor metastasis are far from being understood, and it is still unknown why some human and canine carcinomas metastasize and others do not. Using 2D-DIGE and MALDI-TOF-MS we identified 21 proteins with significant changes (fold change >1.5; p < 0.05) in protein expression between metastasizing (n = 6) and nonmetastasizing (n = 6) canine mammary carcinomas. Quantitative RT-PCR was used to identify transcriptional or post-transcriptional regulation of protein expression. Up-regulated proteins in metastatic carcinomas included proliferating cell nuclear antigen, ferritin light chain, bomapin, tropomyosin 3, thioredoxin-containing domain C5, adenosin, ornithine aminotransferase, coronin 1A, RAN-binding protein 1,3-phosphoglycerate dehydrogenase, and eukaryotic translation elongation factor 1. Down-regulated proteins in metastatic carcinomas included calretinin, myosin, light chain 2, peroxiredoxin 6, maspin, ibrinogen beta chain, vinculin, isocitrate dehydrogenase 1, tropomyosin 1, annexin A5, and Rho GTPase activating protein 1. Interestingly, 19 of these 21 proteins have been described with a malignancy-associated expression in human breast cancer and other human cancer types before. Further investigations are now necessary to test whether these markers are of prognostic value for canine mammary carcinomas and whether their expression is directly involved in canine mammary carcinogenesis or represent solely a secondary reactive phenotype.
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PMID:Proteome of metastatic canine mammary carcinomas: similarities to and differences from human breast cancer. 2093 60

Alternative splicing (AS) is a common mechanism which creates diverse RNA isoforms from a single gene, potentially increasing protein variety. Growing evidence suggests that this mechanism is closely related to cancer progression. In this study, whole transcriptome analysis was performed with GeneChip Human exon 1.0 ST Array from 80 samples comprising 23 normal colon mucosa, 30 primary colorectal cancer and 27 liver metastatic specimens from 46 patients, to identify AS events in colorectal cancer progression. Differentially expressed genes and exons were estimated and AS events were reconstructed by combining exon-level analyses with AltAnalyze algorithms and transcript-level estimations (MMBGX probabilistic method). The number of AS genes in the transition from normal colon mucosa to primary tumor was the most abundant, but fell considerably in the next transition to liver metastasis. 206 genes with probable AS events in colon cancer development and progression were identified, that are involved in processes and pathways relevant to tumor biology, as cell-cell and cell-matrix interactions. Several AS events in VCL, CALD1, B3GNT6 and CTHRC1 genes, differentially expressed during tumor development were validated, at RNA and at protein level. Taken together, these results demonstrate that cancer-specific AS is common in early phases of colorectal cancer natural history.
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PMID:An integrative framework identifies alternative splicing events in colorectal cancer development. 2418 47

Increases in nuclear calcium concentration generate specific biological outcomes that differ from those resulting from increased cytoplasmic calcium. Nuclear calcium effects on tumor cell proliferation are widely appreciated; nevertheless, its involvement in other steps of tumor progression is not well understood. Therefore, we evaluated whether nuclear calcium is essential in other additional stages of tumor progression, including key steps associated with the formation of the primary tumor or with the metastatic cascade. We found that nuclear calcium buffering impaired 4T1 triple negative breast cancer growth not just by decreasing tumor cell proliferation, but also by enhancing tumor necrosis. Moreover, nuclear calcium regulates tumor angiogenesis through a mechanism that involves the upregulation of the anti-angiogenic C-X-C motif chemokine 10 (CXCL10-IP10). In addition, nuclear calcium buffering regulates breast tumor cell motility, culminating in less cell invasion, likely due to enhanced vinculin expression, a focal adhesion structural protein. Together, our results show that nuclear calcium is essential for triple breast cancer angiogenesis and cell migration and can be considered as a promising strategic target for triple negative breast cancer therapy.
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PMID:Inositol 1, 4, 5-trisphosphate-dependent nuclear calcium signals regulate angiogenesis and cell motility in triple negative breast cancer. 2837 4