Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New interventional options especially for patients with HCC and BCLC scores B and C give rise to disputes about the optimal therapeutic management. CT-guided brachytherapy complements established interventional techniques like RFA and TACE since it may also be used successfully in tumors much greater than 5 cm in diameter. In addition, unlike thermal ablation, the brachytherapy technique may be applied in tumors located nearby risk structures such as liver hilum or gallbladder and it is independent of cooling effects such as through large blood vessels or strong tumor perfusion. Depending on tumor size, geometry and visibility, MRI or CT guidance may be used. 15 Gy minimal target dose can be applied safely in a single or--in case of very large tumors--a sequential approach targeting different tumor portions. Local recurrence rates will be very low, and the rate of complications is moderate despite the fact that most patients present with underlying cirrhosis and related comorbidities. Preliminary data suggest a positive impact on overall survival. Randomized controlled trials are on their way to assess combination schemes with systemic treatments such as sorafenib.
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PMID:Image-guided interstitial high-dose-rate brachytherapy in hepatocellular carcinoma. 1954 56

Regulating TGF-beta receptor presentation provides an avenue to alter a cell's responsiveness to TGF-beta. We report that activation of the Erk MAP kinase pathway decreases the TGF-beta-induced Smad3 activation due to decreased cell surface levels of the type I receptor TbetaRI, but not the type II receptor. Inhibition of TACE activity or expression enhanced the cell surface TbetaRI levels and TGF-beta-induced Smad3 and Akt activation. Accordingly, silencing TACE expression in cancer cells enhanced the TbetaRI presentation and TGF-beta responsiveness, including the antiproliferative effect of TGF-beta, and epithelial-to-mesenchymal transition. These results establish a mechanism for downregulating TGF-beta signaling through TACE activation by the Erk MAP kinase pathway and a strategy for evasion of tumor suppression and modulation of epithelial-to-mesenchymal transition during cancer progression. The decreased growth inhibition by TGF-beta, due to elevated TACE activity, complements the growth stimulation resulting from increased release of TGF-alpha family ligands.
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PMID:TACE-mediated ectodomain shedding of the type I TGF-beta receptor downregulates TGF-beta signaling. 1959 13

A 83-year-old man was admitted to our hospital with a large hepatic tumor located in lateral segment. Alpha-fetoprotein was 7ng/ml, and protein induced by vitamin K deficiency and antagonist-II (PIVKA-II) was 50792mAU/ml. The tumor was diagnosed as hepatocellular carcinoma (HCC) by angiographically assisted CT. No ascites was detected and major serological findings were T-Bil 0.7mg/dl, Alb 4.2g/dl, and PT 129%. Because of advanced age and a history of heart disease, he was treated with transarterial chemoembolization using cisplatin (Lip-TACE). The total dose was 128mg of cisplatin and 15ml of lipiodol. No adverse effects appeared. After the third session of Lip-TACE, the levels of PIVKA-II became negative and continued within the normal range for 26 months. We confirmed a decrease of HCC with lipiodol accumulation by abdominal CT, and the response rate was PR. He has been well for 3 years since the first Lip-TACE procedure.
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PMID:[Large hepatocellular carcinoma successfully treated with transarterial chemoembolization using cisplatin]. 1965 67

Understanding the underlying mechanisms by which a normal cell avoids the oncogenic potential of MUC1 signaling requires further definition of the pathways by which the MUC1 cytoplasmic tail is processed in both normal and tumor-derived cells. In the present study we describe the processing pathway initiated by TACE/ADAM17 cleavage of MUC1. Utilizing the human uterine epithelial cell line, HES, derived from normal endometrium, we show that endogenous full length MUC1 undergoes regulated intramembranous proteolysis mediated by presenillin-dependent gamma-secretase. Cytokine-stimulated HES cells exposed to gamma-secretase inhibitors accumulated a membrane-associated 15 kDa fragment of the MUC1 C-terminal subunit (CTF15). Inhibitors of TACE/ADAM17-mediated shedding inhibited accumulation of MUC1-CTF15 and MUC1 ectodomain release to a similar extent consistent with MUC1-CTF15 being a product of TACE/ADAM17 action. Reduction of catalytically active gamma-secretase complex by nicastrin siRNA treatment also resulted in CTF15 accumulation. Furthermore, mature nicastrin, the substrate receptor for gamma-secretase, co-immunoprecipitated with CTF15 in the presence of gamma-secretase inhibitors indicating the formation of CTF15: nicastrin complexes. MUC1-CTF15 accumulation in response to gamma-secretase inhibition was demonstrated in both normal and tumor-derived cells from humans and mice indicating that this processing pathway exists in many cell contexts. We did not detect products of MUC1 cleavage by gamma-secretase in the presence of various proteasomal inhibitors indicating that subsequent degradation is either non-proteasomal or extremely efficient. We suggest that this efficient pathway attenuates potential signaling mediated by cytoplasmic tail fragments.
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PMID:MUC1 is a substrate for gamma-secretase. 1971 67

Drug Eluting Microsphere-Transarterial Chemoembolization (DEM-TACE) is a new delivery system to administrate drugs in a controlled manner useful for application in the chemoembolization of colorectal cancer metastases to the liver. DEM-TACE is focused to obtain higher concentrations of the drug to the tumor with lower systemic concentrations than traditional cancer chemotherapy. Therefore a specific, precise and sensitive LC-ESI-MS/MS assay procedure was properly designed to detect and quantify epirubicin at the concentrations expected from a transarterial chemoembolization with microspheres. Serum samples were kept acidic (pH approximately of 3.5) and sample preparation consisted of a solid phase extraction (SPE) procedure with HLB OASIS cartridges using a methylene chloride/2-propanol/methanol mixture solution to recover epirubicin. The analyses consisted of reversed-phase high-performance liquid chromatography (rp-HPLC) coupled with tandem mass spectrometry (MS/MS). Accuracy, precision and matrix effect of this procedure were carried out by analyzing four quality control samples (QCs) on five separate days. The validation parameters were assessed by recovery studies of spiked serum samples. Recoveries were found to vary between 92 and 98% at the QC levels (5, 40, 80 and 150 microg/L) with relative standard deviation (RSD) always less than 3.7%. The limit of detection (LOD) was set at 1 microg/L. The developed procedure has been also applied to investigate the different capability of two types of commercially available microspheres to release epirubicin into the human circulatory system.
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PMID:Validation of an LC-MS/MS method for the determination of epirubicin in human serum of patients undergoing drug eluting microsphere-transarterial chemoembolization (DEM-TACE). 1978 35

Hepatocellular carcinoma (HCC) is one of the most critical global health issues. With frequent association of viral liver disease, HCC is highly complex, harboring both cancer and chronic liver disease. The tumor stage and underlying liver function are both major determinants of the treatment selection as well as prognosis in HCC patients, thus allowing no more than a 20% chance for potentially curative therapies. Radiotherapy technology has been evolved remarkably during the past decade, and radiation can be precisely delivered, thereby permitting higher doses to the tumour and reduced doses to surrounding normal tissues. There has been increasing interest in the merits of radiotherapy in HCC over the past few years, as indicated by a Pub Med search. Radiotherapy has been used as the definitive therapy with curative intent in early stage tumours. It has been used also in combination with TACE for intermediate stage tumours. In locally advanced tumours, radiotherapy has been combined with systemic agents. Despite its efficacy, radiotherapy has not yet been incorporated into the standard management guidelines of HCC. The lack of high evidence level data, especially randomized controlled trials, has posed an obstacle in including radiotherapy into the routine treatment schema of HCC. Therefore, well-designed prospective studies are strongly recommended using developing technology for radiotherapy alone or combination therapies. Also, many issues such as the optimal dose-fractionation, intra- or extrahepatic metastasis after radiotherapy, and radiation-induced hepatic dysfunction remain to be solved. In this review, current status of radiotherapy for HCC will be discussed with regard to technical consideration and combination strategy. The limitation and future perspectives will also be discussed.
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PMID:Challenge and hope in radiotherapy of hepatocellular carcinoma. 1988 61

Superselective TACE is defined as TACE from the distal portion of the feeding subsegmental hepatic artery to evoke strong ischemic effects on a small area of the liver, thus avoiding damage to liver function. Lipiodol (iodized oil) is semi-fluid, and it can flow into the surrounding portal venules and hepatic sinusoids through peribiliary plexus (PBP) and the drainage route from the hypervascular HCC. Therefore, the reversed flow from the hepatic sinusoids and portal venules to the peripheral portion of the tumor and daughter nodules can be blocked by Lipiodol injected before a particulate embolus (such as gelatin sponge particles). Common complications of superselective TACE are mild local pain and fever and temporary minimal changes of liver function. Reported CR ratio of definitely hypervascular HCC are around 30-60% by superselective TACE with Lipiodol for hypervascular HCC less than 5 cm. According to a nationwide survey by the Liver Cancer Study Group of Japan (LCSGJ), overall 5-year survival rate was 26% in patients with HCCs not indicated for surgery or RFA (PEI), mainly treated by segmental or subsegmental TACE using Lipiodol. Therefore, this TACE technique should be widely introduced as the first line technique for TACE therapy of HCC.
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PMID:Interventional oncology: new options for interstitial treatments and intravascular approaches: superselective TACE using iodized oil for HCC: rationale, technique and outcome. 1988 39

In the EASL and AASLD guidelines, hepatic resection (HR) is considered the first option for patients in stage 0 (very early HCC). This statement was not based on randomized controlled trials (RCTs) versus other therapies, but on the oncological assumption that HR is the better procedure for obtaining complete tumor ablation including a safety margin. Subsequently, three RCTs compared percutaneous radiofrequency ablation (RFA) versus HR in patients with early HCC. All failed to demonstrate better survival in favor of HR, even though the larger size of the early stage needs a larger area of necrosis. A recent study focused on stage 0 demonstrated a sustained local complete response after RFA comparable with that of HR. All these trials established that RFA is less invasive and associated with lower complication rates and lower costs. These data suggest that RFA can be considered the first option for operable patients with very early HCC. Other options (HR, PEI, selective TAE/TACE) can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible.
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PMID:Single HCC smaller than 2 cm: surgery or ablation: interventional oncologist's perspective. 1989 Jun

Hepatic portal vein embolization and transcatheter arterial chemoembolization are well-defined procedures respectively introduced to increase the future remnant liver and to avoid tumor progression before a scheduled hepatectomy. If used alone, both this approaches do not always improve surgical outcome, sometimes resulting in drop out from definitive surgery because of progression of disease. Since the late 1980s, sequential approach with TACE and PVE has been introduced as a preoperative treatment in order to: prevent tumor progression during the weeks intervening before operation; strengthen the effects of PVE by embolizing possible arterio-portal shunts; improve the FRL volumetric increase through the acceleration of hepatocytes proliferation. The risk of liver parenchymal necrosis, related to the double occlusion of blood supply, is usually avoided by maintaining an interval of weeks between the two procedures (PVE performed 2-3 weeks after TACE and surgery performed 4-6 weeks after PVE), but during this period the tumor may grow, nullifying the results obtained. We herein report a literary review and our initial experience with one patient affected by hepatocellular carcinoma involving the whole right liver, treated with TACE and right PVE, both performed in the same session. Although this technique still needs validation after the treatment of a wider number of patients, it seems to be feasible and effective.
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PMID:Simultaneous transarterial and portal embolization for unresectable tumors of the liver. 2042 90

Percutaneous radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) was introduced in Japan in 1999. It has been established as a main local treatment method worldwide including Japan. On comparing outcomes between resection and RFA, they were comparable when cases were limited to those with 3 or fewer tumors 3 cm or smaller in many reports, based on which RFA has become the main treatment for small HCCs. The 5-year survival rate following RFA was as high as 57% in patients registered in the Liver Cancer Study Group of Japan, 73% when cases were limited to liver damage A (Child-Pugh A), and 83.8 and 76.3% in liver damage A (Child-Pugh A) cases with a single 2-cm or smaller and 2- to 5-cm liver tumor, respectively, showing outcomes equivalent to those of resection. The outcomes at our facility were also favorable: the 5-year survival rates of Child-Pugh A liver function HCC cases with 3 or fewer tumors 3 cm or smaller following RFA and resection were 84 and 78%, respectively. Various complications and limitations of RFA have previously been reported, but the advances of physicians' skills and development of various techniques have reduced complications and expanded the indications for RAF. TACE-combined, artificial pleural effusion- and ascites-combined, and contrast-enhanced ultrasonography-guided RFAs are good examples. Adjuvant therapy, such as interferon and molecular targeted therapies following curative therapy, is expected to further improve survival after RFA.
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PMID:Radiofrequency ablation for hepatocellular carcinoma: updated review in 2010. 2061 93


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