Role Of TACE Research Articles

Transcatheter arterial chemoembolization of hepatocellular carcinoma on liver cirrhosis in patients awaiting liver transplantation

Transcatheter arterial chemoembolization of hepatocellular carcinoma on liver cirrhosis in patients awaiting liver transplantation OBJECTIVE. To evaluate the role of TACE as a method of neoadjuvant antitumor therapy of HCC before LT.METHODS AND MATERIALS. From January 1998 to April 2020, we performed 245 OLTs in 229 patients, among them in 25 (10.2 %) for HCC associated with LC. We analyzed treatment results of 16 patients who received 49 TACE sessions as neoadjuvant therapy. 10 (62.5 %) patients fell under Milan criteria, 6 (37.5 %) – beyond them. According to the Child – Pugh score of LC, two (12.5 %) patients matched A stage, 12 (75 %) – B stage, two (12.5 %) – C stage. According to the BCLC (Barcelona Clinic Liver Cancer) staging system, 10 patients matched A1–A4 stage and 6 – B stage. Totally, we performed 49 TACE sessions, both classical with lipiodol and hemostatic sponge, and with drug-eluting beads from 1 to 7 (on average 3) times. In all cases Doxorubicin was used.RESULTS. Technical success was 100 %. There were no complications. We performed RFA in three patients as an adjunct, in two patients – laparoscopic RFA-assisted atypical liver resection and in one patient – sequential resection and RFA. According to the m-Recist criteria, a complete response was observed in 6 (37.5 %), partial – in 7 (43.75 %), and stabilization – in 3 (18.75 %) patients. It was possible to achieve a tumor response to the treatment in 4 patients and return them to the Milan criteria. LT was performed in all 16 patients, among them – 14 (87.5 %) within the Milan criteria. The waiting periods for LT from the beginning of TACE were from 2 to 30 (on average 12.5) months. According to the histological studies, in 13 (81 %) patients, total and subtotal necrosis of HCC was revealed in excised organs.CONCLUSION. The results of the performed study indicate that neoadjuvant TACE delays the growth of HCC masses and prolongs (up to 30 months) a safe waiting period for the donor liver.

Role of TACE in LPS‐induced Production of Soluble Tumor Necrosis Factor‐α in Astrocytes

The pro‐inflammatory cytokine tumor necrosis factor alpha (TNF‐α) in the brain has been implicated in the neurohumoral activation in cardiovascular diseases like heart failure and hypertension. TNF‐α is originally synthesized as a membrane bound protein, the transmembrane TNF‐α (tmTNF‐α). TNF‐α converting enzyme (TACE) proteolytically cleaves the extracellular domain of tmTNF‐α) to release the fully functional form of soluble TNF‐α (sTNF‐α), the major form that contributes to the sympathetic excitation‐induced by cytokine TNF‐α. Our previous work has demonstrated a significant contribution of cytokine synthesis within the central nervous system in mediating neurohumoral excitation and the progression of heart failure in rats, and that both TNF‐α and TACE are increased within cardiovascular regulatory brain nuclei in rats with heart failure. However, the molecular mechanisms regulating TNF‐α and TACE expression within the brain and the specific cell types contributing to this process are currently unknown. The present study sought to determine whether astrocytes might contribute to central nervous system inflammation as a significant source of TNF‐α and TACE. We isolated and cultured astrocytes from male and female neonatal rat brains. Cells were maintained in culture for 28 days prior to treatment with lipopolysaccharide (LPS) alone or in combination with a matrix metalloproteinase inhibitor. Cells and conditioned media were collected after 8 hours to measure RNA expression as well as TNF‐α secretion. Primary astrocytes expressed TACE mRNA at baseline, and LPS increased mRNA levels of TNF‐α (2.8±0.6 vs 3.8±2.1‐fold change), interleukin‐1β (IL‐1β) (19.9±12.3 vs 22.2±7.6‐fold change), and TACE (1.8±0.2 vs 2.2±0.3‐fold change) to a similar extent in astrocytes from male and female rats. Neither the specific TACE inhibitor TAPI‐1 nor the broad range metalloproteinase inhibitor GM6001 significantly attenuated the LPS‐induced increase in TNF‐α at the mRNA level, and in fact we observed a trend towards increased TNF‐α expression specifically in astrocytes from male animals co‐treated with LPS and either inhibitor. This was in contrast to protein expression of sTNF‐α. LPS significantly increased TNF‐α secretion into the media in astrocytes from male (677±28 vs 5±1pg/ml) and female (658±42 vs 6±4pg/ml) animals to a similar extent. Interestingly, this was attenuated by treatment with TAPI‐1 (169±14 male and 108±11pg/ml female) but not GM6001 (526±51 male and 667±44pg/ml female). However, the LPS‐induced increase in TACE expression was attenuated in cells treated with GM6001 but not those treated with TAPI‐1. These data suggest that astrocytes in the brain may contribute to the production of cytokines and TACE in pathophysiological conditions, and TACE plays an important role in releasing the inflammatory sTNF‐α from its precursor tmTNF‐α.Support or Funding InformationSupported by R01‐HL139521 and T32 HL007121.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The ten commandments of chemoembolization: expert discussion and report from Mediterranean Interventional Oncology (MIOLive) congress 2017.

Transarterial therapies in the setting of primary and secondary liver malignancies are becoming an essential part of the oncology landscape. The mechanism of action of c-TACE is the induction of tumor necrosis due to the high concentration of the chemotherapeutic that is delivered only locally and to the embolic effect that causes ischemia and increased dwell time of the chemotherapeutic in the tumor. Recently, DEB-TACE has emerged as a variation of c-TACE with the potential for the selective delivery of large amounts of drugs to the tumor for a prolonged period, thereby decreasing plasma levels of the chemotherapeutic agent and related systemic effects. There is an increasing consensus that compared with conventional lipiodol-based regimen, DEB-TACE offers standardized methodology, is more reproducible and is associated with improved response and significantly better safety profile. Using an easy to access point by point format, this manuscript summarizes the expert discussion from the Mediterranean Interventional Oncology Live Congress (MIOLive 2017) about the role of TACE in the treatment of liver tumors.

Mice Heterozygous for Tumor Necrosis Factor-α Converting Enzyme Are Protected From Obesity-Induced Insulin Resistance and Diabetes

Tumor necrosis factor (TNF)-alpha is known to affect insulin sensitivity, glucose, and lipid metabolism through alternative and redundant mechanisms at both translational and post-translational levels. TNF-alpha exerts its paracrine effects once the membrane-anchored form is shed and released from the cell membrane. TNF-alpha cleavage is regulated by TNF-alpha converting enzyme (TACE), which regulates the function of several transmembrane proteins, such as interleukin-6 receptor and epidermal growth factor receptor ligands. The role of TACE in high-fat diet (HFD)-induced obesity and its metabolic complications is unknown. To gain insights into the role of TACE in metabolic disorders, we used Tace(+/-) mice fed a standard or high-fat diet for 16 weeks. We observed that Tace(+/-) mice are relatively protected from obesity and insulin resistance compared with wild-type littermates. When fed an HFD, wild-type mice exhibited visceral obesity, increased free fatty acid and monocyte chemoattractant protein (MCP)1 levels, hypoadiponectinemia, glucose intolerance, and insulin resistance compared with Tace(+/-) mice. Interestingly, Tace(+/-) mice exhibited increased uncoupling protein-1 and GLUT4 expression in white adipose tissue. Our results suggest that modulation of TACE activity is a new pathway to be investigated for development of agents acting against obesity and its metabolic complications.