Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: HUMANGGP:010955 (mda-7)
 464 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Forty-one patients with histologically proven hepatic lesions (6 cysts, 6 hemangiomas, 8 hepatomas, 19 metastases and 2 negative cases) were studied with Magnetic Resonance (MR) imaging at 1.5 T, and with US and CT. This prospective study was aimed at evaluating: the comparative accuracy of MR, US and CT; the sensitivity and specificity of spin-echo (SE) vs FISP pulse sequences; the efficacy of T1 and T2 relaxation time values in differentiating hemangiomas from hepatomas and metastases. MR diagnostic accuracy was 94.7% vs 89.4% of CT and 84.2% of US. FISP sequences provided 60% sensitivity and 66% specificity. T2 relaxation time values were statistically significant (p less than 0.05) in differentiating hemangiomas (T2 range: 80.9-218.9 ms) from hepatomas (T2 range: 59.4-83.2 ms). The differences in mean T2 values between hemangiomas and metastases (T2 range 54.3-177.3 ms) were not statistically significant (p greater than 0.25).
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PMID:[Magnetic resonance in hepatic lesions. Experience with a 1.5-T magnetic field]. 256 May 78

To date, magnetic resonance angiography (MRA) has been used in neuroradiology mainly to study vascular malformations and atherosclerotic changes of the carotid bifurcation. Our study was aimed at investigating the role of MRA with the time-of-flight technique in the study of intracranial neoplasms; a superconductive 1.5 T magnet was used, and FLASH and FISP 2D and 3D pulse sequences were acquired before and after Gd-DTPA administration. Fifty-five MRA examinations were performed. Our series consists in 32 meningiomas, 14 glial tumors, 3 hypophysis adenomas, 2 metastases, 1 NF2, 2 craniopharyngiomas, 1 lymphoma and 1 rhinopharyngeal carcinoma with intracranial involvement. In 27 patients MRA results were compared with DSA findings. The results showed high agreement relative to indirect angiographic patterns (dislocations, encasement, dural sinuses involvement) and poor accuracy in the demonstration of tumor vascularization (inflow and outflow, vascular neoformation).
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PMID:[Magnetic resonance angiography in the study of neoplastic cerebral pathology]. 848 47

The melanoma differentiation associated gene-7 (mda-7) has a potential inhibitory role in melanoma progression, although the mechanisms underlying this effect are still unknown. mda-7 mRNA has been found to be present at higher levels in cultured normal melanocytes compared with metastatic melanoma cell lines. Furthermore, levels of mda-7 message have shown an inverse correlation with melanoma progression in human tumor samples, suggesting that mda-7 may be a novel tumor suppressor gene. We have designed this study to investigate MDA-7 protein expression in different stages of melanoma progression and to examine its antiproliferative effects in vitro. Our data demonstrate that MDA-7 protein can be found in normal melanocytes and early stage melanomas. It is also observed in smooth muscle cells in the skin. However, in keeping with a possible role as a tumor suppressor, MDA-7 expression is decreased in more advanced melanomas, with nearly undetectable levels in metastatic disease. We also investigated antitumor effects of overexpressed MDA-7 on human melanoma cells in vitro. Our results demonstrate that Ad-mda-7 induces apoptosis and G2/M cell cycle arrest in melanoma cells, but not in normal human melanocytes.
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PMID:Down-regulated melanoma differentiation associated gene (mda-7) expression in human melanomas. 1166 78

Limitations of current viral-based gene therapies for malignant tumors include lack of cancer-specific targeting and insufficient tumor delivery. To ameliorate these problems and develop a truly effective adenovirus gene-based therapy for cancer, we constructed a conditionally replication competent adenovirus (CRCA) manifesting the unique properties of tumor-specific virus replication in combination with production of a cancer-selective cytotoxic cytokine, melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), which embodies potent bystander antitumor activity. Cancer cell selective tropism was ensured by engineering the expression of the adenoviral E1A protein, necessary for viral replication, under the control of a minimal promoter region of progression elevated gene-3 (PEG-3), which functions selectively in diverse cancer cells with minimal activity in normal cells. In the E3 region of this CRCA, we introduced the mda-7/IL-24 gene, thereby mediating robust production of this cytokine as a function of adenovirus replication. Infection of this CRCA (designated Ad.PEG-E1A-mda-7) in normal mammary epithelial cells and breast cancer cells confirmed cancer cell selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 into human breast cancer xenografts in athymic nude mice completely eradicated not only the primary tumor but also distant tumors (established on the opposite flank of the animal) thereby implementing a cure. This dual cancer-specific targeting strategy provides an effective approach for treating breast and other human neoplasms with the potential for eradicating both primary tumors and metastatic disease. Additionally, these studies support the potential use of mda-7/IL-24 in the therapy of malignant cancers.
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PMID:Dual cancer-specific targeting strategy cures primary and distant breast carcinomas in nude mice. 1617 3

Comprehensive bowel examination results from the combined use of T2-weighted single-shot and breath hold T1-weighted gradient echo, minus/plus fat suppression, and gadolinium-enhanced 3D gradient echo (3D VIBE, T1 FAME, 3D THRIVE). Gadolinium-enhanced imaging should be performed dynamically, but the venous 60- to 90-second delayed phase images with fat suppression are generally the most valuable. Removal of fat signal for detection of enhancing normal and abnormal structures is critical. Newly available True-FISP (FIESTA, BFFE) sequences obtained in the 2D form can be very helpful in delineation of bowel wall pathology and overall bowel anatomy, particularly when combined with a water-based intraluminal distending agent. Advantages include rapid acquisition, high signal-to-noise, and motion insensitivity. Generalized protocol for comprehensive evaluation of the entire abdomen and pelvis can be used for the following bowel indications: type and severity of inflammatory bowel disease (IBD); identifying enteric abscesses and fistulae; preoperative staging of malignant neoplasms, including rectal carcinoma; differentiating postoperative and radiation therapy changes from recurrent carcinoma; follow-up evaluation of metastases response to localized ablative or systemic chemotherapy. For improved visualization of bowel wall in dedicated examinations, bowel distension should be achieved using either orally or rectally delivered contrast agents to produce either bright or dark lumen. We have found 2D True-FISP without fat suppression superior to 3D True-FISP and to single-shot echo-train sequences to provide a T2-weighted image of bowel morphology. Strengths include: performed without fat suppression results in the very dark bowel wall being sandwiched between intermediate high signal fat adjacent to bowel serosa, and very high lumen signal from water-distending agent; 2D True-FISP provides motion insensitivity that is lost if 3D is used; True-FISP produces better edge sharpness than single-shot echo-train, higher contrast, and resists flow void artifacts commonly seen with single-shot echo-train imaging combined with a water distending agent. Drawbacks of this technique include: artifacts related to extreme sensitivity to field inhomogeneity, including air-soft tissue interfaces at the patient skin surface, and from retained bowel gas; retained bowel gas is dark against dark bowel wall, impairing bowel wall assessment; and True-FISP does not provide sensitivity for edema, which is superior on single-shot echo-train imaging. Small/large bowel indications for MRI include: inflammatory bowel disease, infectious disease including abscess evaluation or for appendicitis, inflammatory conditions including ischemia, and partial obstruction, malnutrition, and neoplasm search.
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PMID:Magnetic resonance imaging of the gastrointestinal tract. 1631 98

Despite recent advances in treatment strategies, the overall 5-year survival rate for patients with common epithelial cancers is poor largely because of the difficulty in treating metastatic cancers. Therefore, therapeutic agents are urgently needed that can effectively inhibit both primary epithelial tumors and their metastases. One such agent that has shown promise in preclinical studies is the tumor suppressor/cytokine, melanoma differentiation associated gene-7 also known as interleukin-24 (mda-7/IL-24). Preclinical studies from our and other laboratories have shown that overexpression of MDA-7/IL-24 causes a strong tumor- suppressive effect in many human cancer cells but spares normal cells. This gene therapy also enhances the tumor-suppressive activity of radiotherapy and chemotherapy. Secreted MDA-7 protein that is glycosylated also has been shown to have potent antiangiogenic activity both in vitro and in vivo. Studies examining the immune properties of mda-7 have shown that MDA-7/IL-24 unlike the related IL-10, functions as a Th1 cytokine. Recently, an MDA-7 protein-mediated "bystander effect" on tumor cells has been documented. Building on these findings we successfully completed a Phase I clinical trial of adenovirus-based mda-7 cancer therapy that confirmed the safety of this gene therapy. Phase II trials evaluating the efficacy of mda-7-based gene therapy are warranted. The outcome of such ongoing mda-7-based gene therapy trials will allow us to better understand this therapy's clinical utility.
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PMID:MDA-7/IL-24-based cancer gene therapy: translation from the laboratory to the clinic. 1647 47

Terminal prostate cancer is refractory to conventional anticancer treatments because of frequent overexpression of antiapoptotic proteins Bcl-2 and/or Bcl-x(L). Adenovirus-mediated delivery of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), a secreted cytokine having cancer-selective apoptosis-inducing properties, profoundly inhibits prostate cancer cell growth. However, forced overexpression of Bcl-2 or Bcl-x(L) renders prostate cancer cells resistant to Ad.mda-7. We constructed a conditionally replication-competent adenovirus in which expression of the adenoviral E1A gene, necessary for replication, is driven by the cancer-specific promoter of progression elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/IL-24 in the E3 region of the adenovirus (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV). This CTV generates large quantities of MDA-7/IL-24 as a function of adenovirus replication uniquely in cancer cells. Infection of Ad.PEG-E1A-mda-7 (CTV) in normal prostate epithelial cells and parental and Bcl-2- or Bcl-x(L)-overexpressing prostate cancer cells confirmed cancer cell-selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 (CTV) into xenografts derived from DU-145-Bcl-x(L) cells in athymic nude mice completely eradicated not only primary tumors but also distant tumors (established in the opposite flank), thereby implementing a cure. These provocative findings advocate potential therapeutic applications of this novel virus for advanced prostate cancer patients with metastatic disease.
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PMID:Eradication of therapy-resistant human prostate tumors using a cancer terminator virus. 1754 25

Despite significant progress in early cancer detection and aggressive therapies, effective treatments for metastatic disease frequently fall short of producing the desired effect of engendering a 'cure.' This can be attributed in part to inherent and acquired resistance of primary and evolving tumor cells to conventional therapeutic approaches. Agents that can interfere with critical aberrant cell signaling and survival pathways in tumor cells while displaying minimal or preferably no toxicity to normal cells represent potentially powerful tools for cancer therapy. A recently identified cancer gene therapeutic is melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) that has the unique ability of inducing apoptosis in diverse cancer cells without harming normal cells or tissues. As a secreted cytokine mda-7/IL-24 also exerts anti-angiogenic, radiosensitizing and immunomodulatory effects and the therapeutic benefits of an adenovirus expressing mda-7/IL-24 (Ad.mda-7) in human xenograft animal models has been successfully recapitulated in a Phase I clinical trial in patients with advanced cancers. However, as with most treatment modalities, particular subsets of tumor cells might be inherently resistant to mda-7/IL-24, as observed in pancreatic and specific colorectal cancer cells, or they might acquire resistance because of repeated exposure to this cytokine. Pataer et al. have developed Ad.mda-7-resistant lung cancer cells in vitro and demonstrated that the combination of Ad.mda-7 with bcl-2 siRNA or 17AAG could overcome this resistance. Indeed, previous studies have also demonstrated that combinatorial approaches employing Ad.mda-7 and diverse other modalities, such as chemo- or radiotherapy, small molecule inhibitors and monoclonal antibodies, can either augment the therapeutic effect of Ad.mda-7 or overcome resistance to this gene. In these contexts, should resistance to monotherapy with mda-7/IL-24 occur, combinatorial therapies with this cytokine might provide a viable path for potentially curing patients of primary and metastatic cancer.
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PMID:Acquired and innate resistance to the cancer-specific apoptosis-inducing cytokine, mda-7/IL-24: not insurmountable therapeutic problems. 1805 75

The prognosis and response to conventional therapies of malignant melanoma inversely correlate with disease progression. With increasing thickness, melanomas acquire metastatic potential and become inherently resistant to radiotherapy and chemotherapy. These harsh realities mandate the design of improved therapeutic modalities, especially those targeting metastases. To develop an approach to effectively treat this aggressive disease, we constructed a conditionally replication-competent adenovirus in which expression of the adenoviral E1A gene, necessary for replication, is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/IL-24 in the E3 region of the adenovirus (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV). This CTV produces large quantities of MDA-7/IL-24 protein as a function of adenovirus replication uniquely in cancer cells. Infection of Ad.PEG-E1A-mda-7 (CTV) in normal human immortal melanocytes and human melanoma cells demonstrates cancer cell-selective adenoviral replication, mda-7/IL-24 expression, growth inhibition and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 CTV into xenografts derived from MeWo human metastatic melanoma cells in athymic nude mice completely eliminated not only primary treated tumors but also distant non-treated tumors (established in the opposite flank), thereby implementing a cure. These provocative findings advocate potential therapeutic applications of this novel virus for treating patients with advanced melanomas with metastases.
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PMID:A cancer terminator virus eradicates both primary and distant human melanomas. 1832 53

Intratumoral injections of a replication-incompetent adenovirus (Ad) expressing melanoma differentiation-associated gene-7/interleukin-24 (Ad.mda-7), a secreted cytokine displaying cancer-selective, apoptosis-inducing properties, profoundly inhibits prostate cancer (PC) growth in immune-incompetent animals. In contrast, Ad.mda-7 is ineffective in PCs overexpressing antiapoptotic proteins such as Bcl-2 or Bcl-x(L). However, intratumoral injections of a conditionally replication-competent Ad (CRCA) in which expression of the adenoviral E1A gene is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/interleukin (IL)-24 in the E3 region of the Ad (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV), is highly active in these cells. A major challenge for gene therapy is systemic delivery of nucleic acids directly into an affected tissue. Ultrasound (US) contrast agents (microbubbles-MBs) are viable candidates for gene delivery/therapy. Here, we show that MB/Ad.mda-7 complexes targeted to DU-145 cells using US dramatically reduced tumor burden in xenografted nude mice. Additionally, US-guided MB/CTV delivery completely eradicated not only targeted DU-145/Bcl-x(L)-therapy-resistant tumors, but also nontargeted distant tumors (established in the opposite flank), thereby implementing a cure. These findings highlight potential therapeutic applications of this novel image-guided gene therapy technology for advanced PC patients with metastatic disease.
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PMID:Eradication of therapy-resistant human prostate tumors using an ultrasound-guided site-specific cancer terminator virus delivery approach. 1988 95


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