Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metastatic disease represents the most common hepatic neoplasm in the Western world. The most common primary malignancies to spread to the liver are those that originate in the gastrointestinal tract. Of non-gastrointestinal malignancies, breast, lung, and melanoma malignancies are most likely to develop hepatic metastases. Some solid tumors, such as renal cell carcinoma, may cause liver-related abnormalities in the absence of hepatic metastases, presumably by way of cytokine-mediated mechanisms. Physical examination, laboratory testing, histologic evaluation, and various radiographic studies are useful in the detection and diagnosis of liver metastases. Multiple treatment modalities are available, including hepatic resection, hepatic arterial chemotherapy, systemic chemotherapy, chemoembolization, cryotherapy, ethanol injection, and radiofrequency ablation.
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PMID:Liver involvement in patients with solid tumors of nonhepatic origin. 1251 5

We have determined the crystal structure of a novel regulatory protein (MGP-40) from the mammary gland. This protein is implicated as a protective signaling factor that determines which cells are to survive the drastic tissue remodeling that occurs during involution. It has been indicated that certain cancers could surreptitiously utilize the proposed normal protective signaling by proteins of this family to extend their own survival and thereby allow them to invade the organ and metastasize. In view of this, MGP-40 could form an important target for rational structure-based drug design against breast cancer. It is a single chain, glycosylated protein with a molecular mass of 40 kDa. It was isolated from goat dry secretions and has been cloned and sequenced. It was crystallized by microdialysis from 20 mg ml(-1) solution in 0.1 m Tris-HCl, pH 8.0, and equilibrated against the same solution containing 19% ethanol. Its x-ray structure has been determined by molecular replacement and refined to a 2.9 A resolution. The protein adopts a beta/alpha domain structure with a triose-phosphate isomerase barrel conformation in the core and a small alpha+beta folding domain. A single glycosylation site containing two N-acetylglucosamine units has been observed in the structure. Compared with chitinases and chitinase-like proteins the most important mutation in this protein pertains to a change from Glu to Leu at position 119, which is part of the so-called active site sequence in the form of Asp(115), Leu(119), and Asp(186) and in this case resulting in the loss of chitinase activity. The orientations of two Trp residues Trp(78) and Trp(331) in the beta barrel reduces the free space, drastically impairing the binding of saccharides/polysaccharides. However, the site and mode of binding of this protein to cell surface receptors are not yet known.
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PMID:Crystal structure of a novel regulatory 40-kDa mammary gland protein (MGP-40) secreted during involution. 1252 29

A nonhydrolyzable ether analogue of RRR-alpha-tocopherol, 2,5,7,8-tetramethyl-2R-(4R, 8R, 12-trimethyltridecyl)chroman-6-yloxyacetic acid, called RRR-alpha-tocopheryloxyacetic acid or RRR-alpha-tocopherol ether-linked acetic acid analogue (alpha-TEA), exhibits antitumor activity in vitro and in vivo using a syngeneic BALB/c mouse mammary tumor model (line 66 clone 4 stably transfected with green fluorescent protein). Treatment of cells with 5, 10, and 20 micro g/ml alpha-TEA for 3 days produced 6, 34, and 50% apoptosis, respectively, and treatment of cells with 10 micro g/ml for 2, 3, 4, and 5 days produced 20, 35, 47, and 58% apoptosis, respectively. A liposomal formulation of alpha-TEA administered by aerosol reduced s.c. tumor growth and lung metastasis. Alpha-TEA-treated animals showed a significant decrease in tumor volumes over 17 days of aerosol treatment (P < 0.001). Forty percent of aerosol as well as untreated control mice had visible, macroscopic lung metastases versus none (0%) of the alpha-TEA-treated mice. On the basis of fluorescence microscopic examination of the surface (top and bottom) of flattened whole left lung lobes, an average of 60 +/- 15 and 102 +/- 17 versus 11 +/- 4 fluorescent microscopic metastases was observed in aerosol control and untreated control versus alpha-TEA-treated animals, respectively. Alpha-TEA formulated in ethanol + peanut oil (5 mg/mouse/day) delivered by gavage did not reduce s.c. primary tumor burden; however, fluorescent microscopic lung metastases were significantly reduced (P < 0.0021). In summary, alpha-TEA formulated in liposomes and delivered by aerosol is a potent antitumor agent and reduces lung metastasis.
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PMID:Novel vitamin E analogue decreases syngeneic mouse mammary tumor burden and reduces lung metastasis. 1274 5

A major obstacle in understanding the etiology of malignant melanoma is the lack of mouse models and transplantable cell lines. We have recently developed a model of primary melanoma in C3H mice induced by ethanol and UV light. The present study characterizes three cell lines, SM190.2, SM190.626, and SD0302, derived from two melanomas produced in the dorsal skin of two C3H mice treated thrice weekly for 28-33 weeks with UV radiation and ethanol. In both tumors, the N-ras oncogene was mutated. Tumor SM190 lacked exon 2 of the p16(INK4a) tumor suppressor gene. Cell line SM190.2, which was derived from tumor SM190, produced pigmented tumors when transplanted into syngeneic severe combined immunodeficient mice and normal mice. None of the cell lines produced metastases. All three cell lines were highly aneuploid, even at low passage numbers. SM190.2 and SD0302 cells contained an interstitial deletion in the long arm of chromosome 4, where the p16(INK4a) gene resides, and SM190.2 had an additional segment in chromosome 6. The third cell line, SM190.626, had three consistent Robertsonian translocation markers involving chromosomes 7, 14, and 17. The translocation involving mouse chromosome 14 may prove especially valuable because translocations in this chromosome are associated with metastatic behavior. These reagents will provide opportunities to search for new tumor suppressor genes that may contribute to the growth and metastasis of primary melanoma.
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PMID:Molecular characterization of new melanoma cell lines from C3H mice induced by ethanol plus ultraviolet radiation. 1283 34

Early detection of tumors and their metastases is crucial for the prognosis of cancer treatment. Traditionally, tumor detection is achieved by various methods, including magnetic resonance imaging and computerized tomography. With the recent cloning, cellular expression, and real-time imaging of light-emitting proteins, such as Renilla luciferase (Ruc), bacterial luciferase (Lux), firefly luciferase (Luc), green fluorescent protein (GFP), or Ruc-GFP fusion protein, significant efforts have been focused on using these marker proteins for tumor detection. It has also been demonstrated that certain bacteria, viruses, and mammalian cells (BVMC), when administered systemically, are able to gain entry and replicate selectively in tumors. In addition, many tissue/tumor specific promoters have been cloned which allow transgene expression specifically in tumor tissues. Therefore, when light-emitting protein encoded BVMC are injected systemically into rodents, tumor-specific marker gene expression is achieved and is detected in real time based on light emission. Consequently, the locations of primary tumors and previously unknown metastases in animals are revealed in vivo. In the future it will likely be feasible to use engineered light-emitting BVMC as probes for tumor detection and as gene-delivery vehicles in vivo for cancer therapy.
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PMID:Optical imaging: bacteria, viruses, and mammalian cells encoding light-emitting proteins reveal the locations of primary tumors and metastases in animals. 1287 98

The liver is the second only to lymph nodes as the most common site of metastatic disease irrespective of the primary tumor. Up to 50% of all patients with malignant diseases will develop liver metastases with a significant morbidity and mortality. Although the surgical resection leads to an improvement of the survival time, only approximately 20% of the patients are eligible for surgical intervention. Radiofrequency (RF) ablation represents one of the most important alternatives as well as complementary methods for the therapy of liver metastases. RF ablation can lead in a selected patient group to a palliation or to an increased life expectancy. RF ablation appears either safer (vs. cryotherapy) or easier (vs. laser) or more effective (percutaneous ethanol instillation [PEI], transarterial chemoembolisation [TACE]) in comparison with other minimal invasive procedures. RF ablation can be performed percutaneously, laparoscopically or intraoperatively and may be combined with chemotherapy as well as with surgical resection. Permanent technical improvements of RF systems, a better understanding of the underlying electrophysiological principles and an interdisciplinary approach will lead to a prognosis improvement in patients with liver metastases.
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PMID:[Radiofrequency ablation of liver metastases]. 1504 92

Hepatocellular carcinoma (HCC) and metastases from colorectal carcinoma are two most common malignant tumors affecting liver. Of all patients presenting with a malignant hepatic tumor, few are surgical candidates. Contraindications to hepatic resection include too many tumors, tumors in unresectable locations, insufficient hepatic reserve to tolerate resection, and other medical conditions that make the patient a poor surgical risk. A number of alternative therapies have been used for the treatment of malignant hepatic tumors. These include chemoembolization, ethanol injection therapy, and thermal ablation techniques. In this article are described chemoembolization and ethanol injection therapy.
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PMID:[Chemoembolization and ethanol ablation of primary hepatic carcinoma and metastatic tumors]. 1507 29

Two cases are presented in which molecular analyses of cytologic material obtained by fine-needle aspiration were helpful in establishing relationships between morphologically similar neoplasms in the same patient. For appropriate clinical management, it is important to ascertain whether the tumors represent independent primaries or metastases. Alcohol-fixed cytologic material prepared as cell blocks and formalin-fixed paraffin-embedded tissue were microdissected and analyzed for allelic loss of heterozygosity at multiple preselected genetic loci. The first case illustrates a 69-yr-old man with multiple intrapulmonary nodules involving the upper and lower lobes of the left lung. Genomic analysis showed that the neoplasms in the left upper and lower lung lobes were independent primaries, because the loss of heterozygosity (LOH) patterns were substantially different. By contrast, the second case is that of a 58-yr-old man with a right thyroid nodule and multiple pulmonary tumors. LOH analysis confirmed that a sampled pulmonary tumor represented a metastasis from the thyroid primary, as similar LOH patterns involving locus D9S252 were observed on comparison of the thyroid and pulmonary neoplasms. These cases illustrate the practical diagnostic utility of genomic analysis using cytologic material in the assessment of primary and metastatic malignancies.
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PMID:Molecular profiling of primary and metastatic neoplasms in the lung using cytologic material obtained by fine-needle aspiration: report of two cases. 1510 33

Lymph node (LN) metastases during operation for hepatocellular carcinoma (HCC), but not during operations for other cancer, as many surgeons can attest. We performed partial hepatectomy with LN dissection in a man with LN metastasis from HCC, and long-term survival was achieved. In December 1993, at another hospital, a tumor, 4.2 cm in diameter, in this 73-year-old patient had been diagnosed as HCC. Transcatheter arterial embolization (TAE) was performed three times. Eighteen months after the operation, a swollen LN was discovered at the hepatic hilum and was treated by TAE once and by transcatheter arterial infusion (TAI) twice. However, the level of alpha-fetoprotein gradually increased and so percutaneous ethanol injection therapy (PEIT) was performed. Nevertheless, serum PIVKA-II (protein induced by vitamin K absence or antagonist II) continued to rise. The patient was referred to our hospital for further treatment. He underwent S5 subsegmentectomy with LN dissection. Histologically, the primary lesion consisted entirely of necrotic tissue. However, in the resected LN, there was residual cancer tissue near its periphery. We concluded that dissection of the affected LN offered the only chance for long-term survival, and that PEIT should be avoided for a metastatic lymph node.
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PMID:Long-term survival in a patient with hepatocellular carcinoma with resection of a metastatic lymph node after percutaneous ethanol injection therapy. 1554 91

The development of malignant lesions in the acetabulum can lead to painful and disabling bone destruction. Lytic metastases of the acetabulum are frequent, causing pathologic fractures, pain and disability. The literature is sparse in relation to the exact indications and technique for this procedure. Percutaneous injection of methylmethacrylate or ethanol may provide marked pain relief or bone strengthening in patients, with malignant acetabular destruction, who are unable to tolerate surgery. Injection of methylmethacrylate is usually indicated when the weight-bearing part of the acetabulum is involved. The goals of treatment are pain relief and mechanical strengthening of the acetabulum. Radiography and computed tomography must be performed prior to therapeutic percutaneous injection to assess the location and extent of the lytic process, the presence of cortical destruction or fracture, and the presence of soft-tissue involvement. We report a case of a 39-year-old woman with a secondary acetabular lesion, which was treated successfully with percutaneous acetabular cementoplasty. We describe a novel technique used to inject cement into the lesion, allowing for greater cement volume and pressurisation within the lesion.
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PMID:Percutaneous cementoplasty of acetabular bony metastasis. 1557 Jul 72


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