50 research outputs found
Correction to: Balloon occluded TACE (B-TACE) vs DEM-TACE for HCC: a single center retrospective case control study
No full textFollowing publication of the original article, the authors identified an error in the author name of Stefania Brozzetti. • The incorrect author name is: Stefania Brozetti. • The correct author name is: Stefania Brozzetti. The author group has been updated above and the original article has been corrected.
Background:To compare oncological results and safety profile of balloon micro-catheter trans-arterial chemoembo-lization (b-TACE) and drug-eluting-microsphere (DEM-TACE) in patients with hepatocellular-carcinoma (HCC).Methods:This is a case–control, retrospective, single-center study. Between January-2015/March-2019, 149 patients (131 males [87.9%]) with 226 HCC were treated, 22 patients (35 HCC; 19 [86.4%] males) with b-TACE and 127 with DEM-TACE (191 HCC, 112 [88.2%] males). Embolization protocol was standardized (sequential 100 ± 25 and 200 ±25 μm microspheres). Results were evaluated by modified-response-evaluation-criteria-in-solid-tumor [mRE-CIST ] at 1, 3–6 and 9–12 months and time to recurrence after complete response [TTR] at 1 years. Cox’s regression weighted with tumor dimensions was performed. Adverse events (AEs) were recorded.Results:mRECIST oncological response at all time points (1, 3–6 and 9–12 months) for both treatments were similar, with the exception of Objective response rate at 9-12 months. Objective response at 1 and 3–6 months between b-TACE vs DEM-TACE [23/35 (65.7%) vs 119/191 (62.3%), 21/29 (72.4%) vs 78/136 (57.4%) (p > 0.05), respectively]. On the contrary, at 9–12 months, it was significantly higher in b-TACE subgroup than DEM-TACE (15/19 [78.9%] vs 48/89 [53.9%], p=0.05). TTR for complete response at 1 year had a better trend for b-TACE vs DEM-TACE (278.0 days [196.0–342.0] vs 219.0 days [161.0–238.0], OR 0.68 [0.4–1.0], p=0.10). The use of balloon micro-catheter reduced the relative risk of the event of recurrence by 0.63 [CI95% 0.38–1.04]; p=0.07). No significant differences were found in AEs rate.Conclusion:b-TACE showed a trend of better oncological response over DEM-TACE with and longer TTR with a simi-lar adverse events rate, in patients presenting with larger tumors
Author response: Phosphorylation of iRhom2 at the plasma membrane controls mammalian TACE-dependent inflammatory and growth factor signalling
No full textProteolytic cleavage and release from the cell surface of membrane-tethered ligands is an important mechanism of regulating intercellular signalling. TACE is a major shedding protease, responsible for the liberation of the inflammatory cytokine TNFα and ligands of the epidermal growth factor receptor. iRhoms, catalytically inactive members of the rhomboid-like superfamily, have been shown to control the ER-to-Golgi transport and maturation of TACE. Here, we reveal that iRhom2 remains associated with TACE throughout the secretory pathway, and is stabilised at the cell surface by this interaction. At the plasma membrane, ERK1/2-mediated phosphorylation and 14-3-3 protein binding of the cytoplasmic amino-terminus of iRhom2 alter its interaction with mature TACE, thereby licensing its proteolytic activity. We show that this molecular mechanism is responsible for triggering inflammatory responses in primary mouse macrophages. Overall, iRhom2 binds to TACE throughout its lifecycle, implying that iRhom2 is a primary regulator of stimulated cytokine and growth factor signalling
PROSEDUR PEMERIKSAAN CT SCAN ABDOMEN PADA KASUS HEPATOCELLULAR CARCINOMA (HCC) POST TACE DI INSTALASI RADIOLOGI RSUP DR. KARIADI SEMARANG
No full textBackground : Research on the CT scan of Abdominal examination on Hepatocellular Carcinoma (HCC) Post TACE. The purpose of this research is to know how the procedure of CT scan of Abdomen in case of Hepatocellular Carcinoma (HCC) Post TACE in Radiology Installation of Dr. Kariadi Semarang and the reason for using the four-phase technique.Metode : The research type is qualitative analytic research with case study approach. Subjects in this study were radiographers, radiology specialists and hepatologists. The author made observations on the examination and conducted in-depth interviews with subject, and perform documentation of the inspection conducted. The data is processed using open coding system, then the data is presented in quote form. The discussion is done by analyzing the results of research according to the references to take a decisionResults : The results of a four-phase contrast CT scan in the post TACE hepatocellular carcinoma (HCC) case, patient position supine on the examination table, feet first, spiral scanning, using double syringe injectors, 80 ml injected contrast medium for lactated ringer copy (RL) 40 ml, 15 min before the drinking water test 150 ml to fill the gastric mucosa, There are four phases to assess the enhancement patterns in the liver, imaging morphological changes in the picture between pre- and post-TACE actions.Conclusion : Early artery / early artery phase and late artery / stage artery phase are aimed at seeing the fiding artery to the tumor, the venous phase and delay phase are intended to look at the liver pattern, and the vascularization characteristics of whether it is enhanced or was out. Modality of CT Scan is used because it is a standard gold that is kreadible used for evaluation of TACE action without having the patient biops
Overexpression of TNF-α-converting enzyme in fibroblasts augments dermal fibrosis after inflammation
No full textTNF-α converting enzyme (TACE) can cleave transmembrane proteins, such as TNF-α, TNF receptors, and epidermal growth factor receptor (EGFR) ligands, to release the extracellular domains from the cell surface. Recent studies have suggested that overexpression of TACE may be associated with the pathogenesis of inflammation and fibrosis. To determine the roles of TACE in inflammation and fibrosis, TACE transgenic (TACE-Tg) mice, which overexpressed TACE systemically, were generated. Since the transgene-derived TACE was expressed as an inactive form, no spontaneous phenotype developed in TACE-Tg mice. However, the transgene-derived TACE could be converted to an active form by furin in vitro and by phorbol myristate acetate (PMA) in vivo. Subcutaneous injection of PMA into mice induced inflammatory cell infiltration 1 day later and subsequent dermal fibrosis 7 days later. Interestingly, the degree of dermal fibrosis at day 7 was significantly higher in TACE-Tg mice than in wild-type mice. Correspondingly, PMA increased the expression of type I collagen in the primary culture of dermal fibroblasts derived from TACE-Tg mice. Furthermore, phosphorylated EGFR was increased in the fibroblasts by the PMA treatment. The collective findings suggest that TACE overexpression and activation in fibroblasts could shed off putative EGFR ligands. Subsequently, the soluble EGFR ligands could bind and activate EGFR on fibroblasts, and then increase the type I collagen expression resulting in induction of dermal fibrosis. These results also suggest that TACE and EGFR on fibroblasts may be novel therapeutic targets of dermal fibrosis, which is induced after diverse inflammatory disorders of the skin
Overexpression of TNF-α converting enzyme promotes adipose tissue inflammation and fibrosis induced by high fat diet
No full textObesity is a state in which chronic low-grade inflammation persists in adipose tissues. Pro-inflammatory cytokines, including TNF-α, produced by adipose tissues have been implicated as active participants in the development of obesity-related diseases. Since TNF-α converting enzyme (TACE) is the major factor that induces soluble TNF-α, TACE has been noted as a pivotal regulator in this field. To reveal the role of TACE in adipose tissue inflammation, TACE-transgenic (TACE-Tg) and wild type (WT) mice were fed with high fat diet (HFD) or control diet for 16 weeks. At 13 weeks after the beginning of the diet, serum TNF-α and macrophage-related cytokine/chemokine levels were elevated in TACE-Tg mice fed with HFD (Tg-HFD mice), and the number of the so-called crown-like adipocyte was significantly increased in adipose tissues of Tg-HFD mice at the end of the experiment. Although macrophage infiltration was not detected in the adipose tissues at this time, fibrosis was observed around the crown-like adipocytes. These findings suggested that TACE overexpression induced macrophage infiltration and subsequent fibrosis in adipose tissues under HFD regimen. The collective evidence suggested that TACE could be a therapeutic target of HFD-induced obesity-related adipose tissue inflammation
A BETTER WORLD IS POSSIBLE: AGROECOLOGY AS A RESPONSE TO SOCIO-ECONOMIC AND POLITICAL CONDITIONS IN CUBA
No full textI hereby declare that I am the sole author of this thesis. This is a true copy of the thesis, including any required final revisions, as accepted by my examiners. I understand that my thesis may be made electronically available to the public. iii Over the past century global agriculture has come to be characterized by high levels of industrial inputs, as well as increasing consolidation of land ownership and a focus on export-oriented monocrop production. In spite of its dominance, this conventional model of food production has faced growing criticism for being environmentally, socially, and economically unsustainable, and alternatives such as organic agriculture are becoming increasingly popular. The rapid growth of these alternative modes of production raises questions regarding how sustainable food systems should be defined, how they might best be implemented, and how they can contribute to the overall goals of sustainable development. Cuba is a recognized leader in the adoption of sustainable agriculture. This researc
Sorafenib in combination with transarterial chemoembolisation in patients with unresectable hepatocellular carcinoma (TACE 2): a randomised placebo-controlled, double-blind, phase 3 trial
No full text\ua9 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license Background Transarterial chemoembolisation (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma, while the multikinase inhibitor sorafenib improves survival in patients with advanced disease. We aimed to determine whether TACE with sorafenib improves progression-free survival versus TACE with placebo. Methods We did a multicentre, randomised, placebo-controlled, phase 3 trial (TACE 2) in 20 hospitals in the UK for patients with unresectable, liver-confined hepatocellular carcinoma. Patients were eligible if they were at least aged 18 years, had Eastern Cooperative Oncology Group performance status of 1 or less, and had Child-Pugh A liver disease. Patients were randomised 1:1 by computerised minimisation algorithm to continuous oral sorafenib (400 mg twice-daily) or matching placebo combined with TACE using drug-eluting beads (DEB-TACE), which was given via the hepatic artery 2–5 weeks after randomisation and according to radiological response and patient tolerance thereafter. Patients were stratified according to randomising centre and serum α-fetoprotein concentration (<400 ng/mL and ≥400 ng/mL). Only the trial coordinator was unmasked to treatment allocation before patient progression during the study. The primary endpoint was progression-free survival defined as the interval between randomisation and progression according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1) or death due to any cause, and was analysed by intention-to-treat. Safety was analysed by intention-to-treat. The trial has been completed and the final results are reported. The trial is registered at EudraCT, number 2008-005073-36, and ISRCTN, number ISRCTN93375053. Findings Between Nov 4, 2010, and Dec 7, 2015, the trial enrolled 399 patients and was terminated after a planned interim futility analysis. 86 patients failed screening and 313 remaining patients were randomly assigned: 157 to sorafenib and 156 to placebo. The median daily dose was 660 mg (IQR 389\ub72–800\ub70) sorafenib versus 800 mg (758\ub72–800\ub70) placebo, and median duration of therapy was 120\ub70 days (IQR 43\ub70–266\ub70) for sorafenib versus 162\ub70 days (70\ub70–323\ub75) for placebo. There was no evidence of difference in progression-free survival between the sorafenib group and the placebo group (hazard ratio [HR] 0\ub799 [95% CI 0\ub777–1\ub727], p=0\ub794); median progression-free survival was 238\ub70 days (95% CI 221\ub70–281\ub70) in the sorafenib group and 235\ub70 days (209\ub70–322\ub70) in the placebo group. The most common grade 3–4 adverse events were fatigue (29 [18%] of 157 patients in the sorafenib group vs 21 [13%] of 156 patients in the placebo group), abdominal pain (20 [13%] vs 12 [8%]), diarrhoea (16 [10%] vs four [3%]), gastrointestinal disorders (18 [11%] vs 12 [8%]), and hand–foot skin reaction (12 [8%] and none). At least one serious adverse event was reported in 65 (41%) of 157 patients in the sorafenib group and 50 (32%) of 156 in the placebo group, and 181 serious adverse events were reported in total, 95 (52%) in the sorafenib group and 86 (48%) in the placebo group. Three deaths occurred in each group that were attributed to DEB-TACE. Four deaths were attributed to study drug; three in the sorafenib group and one in the placebo group. Interpretation The addition of sorafenib to DEB-TACE does not improve progression-free survival in European patients with hepatocellular carcinoma. Alternative systemic therapies need to be assessed in combination with TACE to improve patient outcomes. Funding Bayer PLC and BTG PLC
Effect of palonosetron and dexamethasone administration on the prevention of gastrointestinal symptoms in hepatic arterial chemoembolization with epirubicin
No full textPurpose There are several studies on premedication to prevent postembolization syndromes which occurs after transcatheter arterial chemoembolization (TACE), but the medication to be used is still not established. This study aimed to examine the effect of palonosetron and dexamethasone on the prevention of gastrointestinal symptoms induced by TACE. Methods Patients with hepatocellular carcinoma who were treated with TACE with epirubicin were retrospectively evaluated. The complete response rate of antiemetic drugs and incidence and severity of gastrointestinal symptoms were compared between the antiemetic group (AE group), which includes 51 patients prophylactically administered with palonosetron 0.75 mg and dexamethasone 9.9 mg intravenously before TACE on day 1 and dexamethasone 6.6 mg intravenously on days 2 and 3, and control group with 101 patients without antiemetic premedication. Results Complete response rate in the entire evaluation period was significantly higher in the AE group compared with that in the control group. In the acute phase, the incidence and severity of nausea, vomiting, and anorexia significantly decreased in the AE group, but only anorexia improved in the delay phase. Additionally, postembolization syndromes, such as abdominal pain and fever, were significantly attenuated in the AE group; however, constipation worsened in this group. Conclusions Premedication of palonosetron and dexamethasone significantly prevents the incidence and reduces the severity of gastrointestinal symptoms especially in the acute phase. Further studies will be needed to determine the most recommended 5-HT3 antagonist or dosage of dexamethasone in establishing the optimal antiemetic regimen
Risk Factors for Local Recurrence of Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization with Drug‑eluting Beads (DEB‑TACE)
No full textTranscatheter treatment of hepatocellular carcinoma with doxorubicin-loaded dc bead (DEBDOX): Technical recommendations
No full textTranarterial chemoembolization (TACE) has been established by a meta-analysis of randomized controlled trials as the standard of care for nonsurgical patients with large or multinodular noninvasive hepatocellular carcinoma (HCC) isolated to the liver and with preserved liver function. Although conventional TACE with administration of an anticancer-in-oil emulsion followed by embolic agents has been the most popular technique, the introduction of embolic drug-eluting beads has provided an alternative to lipiodol-based regimens. Experimental studies have shown that TACE with drug-eluting beads has a safe pharmacokinetic profile and results in effective tumor killing in animal models. Early clinical experiences have confirmed that drug-eluting beads provide a combined ischemic and cytotoxic effect locally with low systemic toxic exposure. Recently, the clinical value of a TACE protocol performed by using the embolic microsphere DC Bead loaded with doxorubicin (DEBDOX; drug-eluting bead doxorubicin) has been shown by randomized controlled trials. An important limitation of conventional TACE has been the inconsistency in the technique and the treatment schedules. This limitation has hampered the acceptance of TACE as a standard oncology treatment. Doxorubicin-loaded DC Bead provides levels of consistency and repeatability not available with conventional TACE and offers the opportunity to implement a standardized approach to HCC treatment. With this in mind, a panel of physicians took part in a consensus meeting held during the European Conference on Interventional Oncology in Florence, Italy, to develop a set of technical recommendations for the use of DEBDOX in HCC treatment. The conclusions of the expert panel are summarized. © 2011 The Author(s)
