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

Adenovirus-mediated gene therapy is hampered by severe virus-related toxicity, especially to the liver. The aim of the present study was to test the ability of a vascular exclusion technique to achieve transgene expression within selected liver segments, thus minimizing both viral and transgene product toxicity to the liver. An E1-E3-deleted replication-deficient adenovirus expressing a green fluorescent protein (GFP) reporter gene was injected into the portal vein of BDIX rats, with simultaneous clamping of the portal vein tributaries to liver segments II, III, IV, V, and VIII. GFP expression and inflammatory infiltrate were measured in the different segments of the liver and compared with those of the livers of animals receiving the viral vector in the portal vein without clamping. The GFP expression was significantly higher in the selectively perfused segments of the liver as compared with the non-perfused segments (p < 0.0001) and with the livers of animals that received the vector in the portal vein without clamping (p < 0.0001). Accordingly, the inflammatory infiltrate was more intense in the selectively perfused liver segments as compared with all other groups (p < 0.0001). Fluorescence was absent in lungs and kidneys and minimal in spleen. The clinical usefulness of adenovirus-mediated gene transfer to the liver largely depends on the reduction of its liver toxicity. Clamping of selected portal vein branches during injection allows for delivery of genes of interest to targeted liver segments. Transgene expression confined to selected liver segments may be useful in the treatment of focal liver diseases, including metastases.
 ...
PMID:Adenovirus-mediated gene transfer into selected liver segments using a vascular exclusion technique. 1180 95

Gestational trophoblastic disease (GTD) represents a spectrum of histologically distinct entities including molar pregnancy and choriocarcinoma. The incidence of GTD varies in different parts of the world with high incidences in countries like Japan (2 / 1000 pregnancies). With the advent of sensitive assays for detection of serum beta human chorionic gonadotrophin (HCG) and ultrasound, GTD can now be detected earlier in pregnancy. To date no studies have been reported from South Africa regarding the epidemiology, management, and outcome of patients with GTD. This study was a retrospective audit based on 112 patients with GTD treated at King Edward VIII Hospital, Durban, South Africa. Clinical records of patients were reviewed with regards to presentation, investigation, management and outcome. Of 112 patients, there were 78 patients (70%) with hydatidiform mole and 34 patients (30%) with choriocarcinoma. The mean age of patients was 28.5 years (SD 8.1 years). The majority of patients were Black females (94.6%) while 4.4% were Asian and 1% Coloured females. The most common presenting symptom was vaginal bleeding (93.8%). There were 74 patients (66.7%) who had a previous normal term pregnancy and only two patients (1.8%) had previous molar pregnancies. Suction curettage was the main treatment modality for patients with molar pregnancy while choriocarcinoma was treated primarily with chemotherapy. A total of 72 percent of patients with molar pregnancy and 28 percent with choriocarcinoma had complete remission after initial treatment. Twelve patients died during the course of treatment mainly due to late presentation and advanced metastatic disease. Complete cure was achieved in 89% of patients. Age, parity, previous history, initial uterine size, presence of theca-lutein cysts, and initial betaHCG concentration was not found to be prognostic for persistent trophoblastic disease. In the present study, the incidence of molar pregnancy and choriocarcinoma was 1.2 / 1000 and 0.5 / 1000 deliveries, respectively. This is much lower than those quoted from countries such as Japan. However, the incidence quoted from our study may be overestimated as this was a hospital-based study and most of the uncomplicated deliveries occur in referring centers. Only 20% of patients in this study were above the age of 35 years with a mean age of 28.5 years. The majority of patients were of Black African ethnic origin mainly due to the fact that our hospital is a referral center for Black patients. Similar to other studies, the majority of patients with molar pregnancy were treated with suction curettage while the majority of patients with choriocarcinoma were treated with chemotherapy. Overall, spontaneous remission was achieved in 60% of patients with molar pregnancy and an overall complete cure was achieved in 89% of patients.
 ...
PMID:Gestational trophoblastic syndrome: an audit of 112 patients. A South African experience. 1265 30

The authors describe a locally recurrent tumor of the mandible whose microscopic structure and immunohistochemical findings corresponded to an epithelioid hemangioendothelioma. The tumorous cells had an epithelioid character, they created rudimentary vascular lumina, and they focally expressed vascular markers CD 34, CD 31, and F VIII. Locally the tumor grew aggressively. During the last recurrence, the tumor even affected the already healed and rebuilt bone graft, which was incorporated after the primary resection of the mandibular body. From the histological point of view, the tumor approximated an angiosarcoma. No metastases occurred.
 ...
PMID:Epithelioid hemangioendothelioma of the mandible. 1276 86

The poor selective toxicity of chemotherapeutic anticancer drugs leads to dose-limiting side effects that compromise clinical outcome. Solid tumors recruit new blood vessels to support tumor growth, and unique epitopes expressed on tumor endothelial cells can function as targets for the anti-angiogenic therapy of cancer. An NGR peptide that targets aminopeptidase N, a marker of angiogenic endothelial cells, was coupled to the surface of liposomal doxorubicin (NGR-SL[DXR]) and was used to treat orthotopic neuroblastoma (NB) xenografts in SCID mice. Pharmacokinetic studies indicated that liposomes coupled to NGR peptide had long-circulating profiles in blood. Their uptake into NB tumor was time dependent, being at least 10 times higher than that of nontargeted liposomes (SL[DXR]) after 24 h, with DXR spreading outside the blood vessels and into the tumors. No uptake was observed into tumors of mice treated with the mismatched peptide ARA-targeted SL[DXR]. Tumor-specific DXR uptake was completely blocked when mice were coinjected with a 50-fold molar excess of the soluble NGR peptide. Adrenal tumor-bearing mice treated with 2 mg/kg/week/x3 of NGR-SL[DXR] partly outlived the control mice (P < 0.001), whereas doses > 3 mg/kg/week/x3 were toxic. Histopathological analysis of cryosections taken from treated mice revealed pronounced destruction of the tumor vasculature with a marked decreased in vessel density. Double staining of tumors with terminal deoxynucleotidyl transferase-mediated nick end labeling and antifactor VIII antibody or antihuman NB demonstrated endothelial cell apoptosis in the vasculature, as well as increased tumor cell apoptosis. Moreover, mice injected with 3 mg/kg/week/x3 of NGR-SL[DXR] displayed rapid tumor regression, as well as inhibition of metastases growth (P = 0.0002). One day after the third treatment, four of six mice showed no evidence of tumors, and the two others showed a >80% reduction in tumor mass and a >90% suppression of blood vessel density (P < 0.01). In contrast, mice treated with ARA-SL[DXR] formed large well-vascularized tumors. Finally, a metronomic administration of NGR-SL[DXR] (1 mg/kg/every other 2 days x 9) induced complete tumor eradication in all animals (P < 0.0001). Our strategy markedly enhanced the therapeutic index of DXR and enabled metronomic administration of therapeutic doses. A dual mechanism of action is proposed: indirect tumor cell kill via the destruction of tumor endothelium by NGR-targeted liposomes and direct tumor cell kill via localization of liposomal DXR to the tumor interstitial space. This combined strategy has the potential to overcome some major limitations of conventional chemotherapy.
 ...
PMID:Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. 1461 39

Liver resections for metastases of colorectal carcinomas are generally accepted. The 5-year survival rate is higher than 30 percent. Major resections can be performed safely with normal remnant liver. The liver regenerates following extended hepatectomies or other major resections. Authors operated on a 57-year-old man for a secondary liver tumor. The primary tumor was in the colon sigmoideum and sigma-resection was made at another hospital 16 months before. The metastasis was in the right lobe of the liver. Authors performed right extended hepatectomy. After systemic chemotherapy, 4.5 months later a new metastasis developed in the left lobe. Despite locoregional chemotherapy, chemoembolization and radiofrequency treatment, the tumor was still growing so a left lobectomy was performed. The patient is macroscopically tumor-free 17 months after the first hepatic resection. The interest in this case is that segments IV to VIII were removed first time, and segments II and III at the second liver resection. Liver regeneration after the first resection made the second operation possible. Only segment I of the original segments remained. Utilizing the regeneration of the liver we can make an effort to perform a complete tumor ablation in two steps.
 ...
PMID:Near total hepatectomy in two steps for surgical treatment of liver metastasis of colorectal tumor. 1469 91

Metastases of various malignancies have been shown to be inversely related to the abundance of nm23 protein expression. However, the downstream pathways involved in nm23-mediated suppression of metastasis have not been elucidated. In the present investigation, we used cDNA microarrays to identify novel genes and functional pathways in nm23-mediated spontaneous breast metastasis. Microarray experiments were performed in a pair of cell lines, namely, C-100 (only vector transfected; highly metastatic) and H1-177 (nm23 transfected; low metastatic), derived from human mammary carcinoma cell line MDA-MB-435. The cDNA microarray analysis using GeneSpring software revealed significant as well as consistent alterations in the expression (up- and downregulation) of 2158 genes in a total of 18889 genes between high and low metastatic cells. Some of these genes were grouped into 6 functional categories, namely, invasion and metastasis, apoptosis and senescence, signal transduction molecules and transcription factors, cell cycle and repair, adhesion, and angiogenesis to extrapolate an association between these genes and different functional pathways involved in nm23-regulated metastasis. The results suggest that nm23 gene plays a major role in metastasis and its mechanism of action of metastasis suppression may involve downregulation of genes associated with cell adhesion, motility (integrins alpha2, -8, -9, -L and -V, collagen type VIII alpha1, fibronectin 1, catenin, TGF-beta2, FGF7, MMP14 and 16, ErbB2) and possibly certain tumor/metastasis suppressors (2 members of SWI/SNF-related matrix-associated proteins 2 and 5 and PTEN).
 ...
PMID:Expression profile of genes associated with antimetastatic gene: nm23-mediated metastasis inhibition in breast carcinoma cells. 1473 69

Central hepatectomy (CH) is a major liver resection that removes Couinaud's segments IV, V and VIII, indicated for centrally located lesions and designed to preserve functional parenchyma and prevent liver failure. During an 8-year period between January 1995-November 2002, 507 liver resections were performed in Fundeni Center of General Surgery and Liver Transplantation (Bucharest). There were three CH performed for colorectal metastases (1 case) and inflammatory pseudotumor (2 cases). The mean duration of the procedure and the mean blood loss were, respectively, 231 minutes and 915 ml. The patients had a good post-operative course, with only minor complications.
 ...
PMID:[Central hepatectomy]. 1499 42

Patients with synchronous bilobar colorectal liver metastases usually have an extent or distribution of the metastases that precludes curative resection. Recently radiofrequency ablation has been proved to safely control liver metastases but a combination of radiofrequency ablation with more than liver resection is rarely performed. We report two patients with colorectal primary and synchronous classically unresectable bilobar liver metastases treated with a combination of bowel and liver resection plus radiofrequency ablation. In the first patient we performed left colectomy, left hepatic lobectomy and radiofrequency ablation of lesions in segments I and VII. In the second patient we performed low anterior resection, wedge resections for three superficially placed lesions in segments V and VIII, and radiofrequency ablation of five more deeply located lesions in segments III, IV, VI and VII. Both patients recovered uneventfully. At the eighth month, the first patient developed three new liver metastases that were treated with subsequent radiofrequency ablation and at the tenth and seventh months of follow-up respectively, both patients are disease free. In conclusion, combination of bowel and liver resection plus radiofrequency ablation expands the possibilities to treat more patients with colorectal cancer having synchronous bilobar unresectable liver metastases.
 ...
PMID:Treatment of colorectal cancer with synchronous bilobar liver metastases with simultaneous bowel and liver resection plus radiofrequency ablation. 1514 82

Reaction of one equivalent of vanadium(III) chloride with three equivalents of l-cysteine(H2Cys) in methyl alcohol affords a VIII-Cys compound that is formulated as [VIII(Hcys)3].2HCl.2.5H2O 1. The solid state characterization of 1 was performed by microanalysis, circular dichroism (CD) and infrared studies as well as room temperature magnetic susceptibility. These studies have shown coordination of each HCys- ligand to the VIII atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of 1 were carried out in water and methanol by UV-visible, CD and electron paramagnetic resonance (EPR) spectroscopies. According to these studies, it was evident that despite the progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were also present in solution after several hours. Compound 1, VIVOSO4.5H2O and l-cysteine were examined for their total antioxidant capacity (TAC) and lag time. Compound 1 exhibited significantly greater total antioxidant capacity and lag time values than l-cysteine. VIVOSO4.5H2O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, VIVOSO4.5H2O and thiorphan was also measured. Compound 1, at a concentration of 10(-3) M, showed inhibition of NEP activity as potent as thiorphan at 10(-6) M, while VIVOSO4.5H2O in the same concentration exhibited less than 50% inhibitory activity than that of thiorphan at 10(-6) M. Moreover, the antimetastatic effects of compound 1, l-cysteine and VIVOSO4.5H2O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that 1 prevents significantly lung metastases (only 9.5% of animals treated with 1 showed metastases), whereas 47-52% of the rats of the control group and those treated with l-cysteine and VIVOSO4.5H2O exhibited metastases.
 ...
PMID:Solid state and solution studies of a vanadium(III)-L-cysteine compound and demonstration of its antimetastatic, antioxidant and inhibition of neutral endopeptidase activities. 1514 2

The competitive inhibitory effects of NK4 (a specific hepatocyte growth factor (HGF)-antagonist) on the interaction between HGF and the c-Met/HGF receptor has been shown in HGF-mediated invasion of some distinct types of human cancer cells. Furthermore, NK4 has inhibitory effects on the angiogenic pathways driven by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), as well as by HGF. In this study, to evaluate the therapeutic efficacy of adenoviral-mediated NK4 gene treatment, we employed animal models of peritoneal metastasis using two gastric cancer cell lines, the strongly c-Met expressing MKN45 cell line and the weakly c-Met-expressing cell line, TMK1. In both models, the total number and weight of peritoneal tumours per mouse and ascites treated early with AxCANK4 (administered 3 times 2, 7 and 12 days after the tumour inoculation) were significantly reduced compared with those treated with phosphate-buffered solution (PBS) and AxCALacZ (P < 0.05). In Factor-VIII-related-antigen-stained sections from peritoneal metastatic tumours, the inhibition of intratumour vessels was observed in tissues from tumours of MKN45 and TMK1 treated with AxCANK4. We also compared the therapeutic effect of early AxCANK4 treatment with that of late treatment (at 7, 12 and 17 days). Peritoneal metastases and ascites treated late with AxCANK4 showed less of an improvement than those treated early with AxCANK4 in both models. In addition, the inhibitory effect of cisplatin (CDDP) on peritoneal metastasis was significantly enhanced by AxCANK4, suggesting that the combination of intraperitoneal (i.p.) chemotherapy with NK4 gene therapy might be effective, even in cases of advanced peritoneal metastasis from gastric cancer. To conclude, these results show clearly that NK4 gene therapy inhibits peritoneal metastases from gastric cancer, regardless of the level of c-Met/HGF receptor expression in the tumour cells, and especially in the early stages of peritoneal metastasis.
 ...
PMID:Adenoviral-mediated gene transduction of the hepatocyte growth factor (HGF) antagonist, NK4, suppresses peritoneal metastases of gastric cancer in nude mice. 1534 89


<< Previous 1 2 3 4 5 Next >>