Hepatocellular carcinoma (HCC) is a major health problem worldwide and in the UnitedStates as its incidence has increased substantially within the past two decades. HCC therapy remains a challenge, primarily due to underlying liver disorders such as cirrhosis that determines treatment approach and efficacy. Activated hepatic stellate cells (A-HSCs) are the key cell types involved in hepatic fibrosis/cirrhosis. A-HSCs are important constituents of HCC tumor microenvironment (TME) and support tumor growth, chemotherapy resistance, cancer cell migration, and escaping immune surveillance. This makes A-HSCs an important therapeutic target in hepatic fibrosis/cirrhosis as well as in HCC. Although many studies have reported the role of A-HSCs in cancer generation and investigated the therapeutic potential of A-HSCs reversion in cancer arrest, not much is known about inactivated or quiescent HSCs (Q-HSCs) in cancer growth or arrest. Here we report that Q-HSCs resist cancer cell growth by inducing cytotoxicity and enhancing chemotherapy sensitivity. We observed that the conditioned media from Q-HSCs (Q-HSCCM) induces cancer cell death through a caspase-independent mechanism that involves an increase in apoptosis-inducing factor expression, nuclear localization, DNA fragmentation, and cell death. We further observed that Q-HSCCM enhanced the efficiency of doxorubicin, as measured by cell viability assay. Exosomes present in the conditioned media were not involved in the mechanism, which suggests the role of other factors (proteins, metabolites, or microRNA) secreted by the cells. Identification and characterization of these factors are important in the development of effective HCC therapy. K E Y W O R D Sapoptosis-inducing factor, cell death, doxorubicin, hepatic stellate cell, hepatocellular carcinoma Abbreviations: A-HSCCM, activated hepatic stellate cell-conditioned media; AIF, apoptosis inducing factor; HCC, hepatocellular carcinoma; HSC, hepatic stellate cell; LX2CM, LX2 cell-conditioned media; pHSCCM, primary hepatic stellate cell-conditioned media; Q-HSCCM, quiescent hepatic stellate cell-conditioned media; ROS, reactive oxygen species; TME, tumor microenvironment.
Using the latest technology and image processing tools enables significant reduction in radiation exposure during complex liver interventional procedures.
The spleen is a commonly injured organ in blunt abdominal trauma. Splenic preservation, however, is important for immune function and prevention of overwhelming infection from encapsulated organisms. Splenic artery embolization (SAE) for high-grade splenic injury has, therefore, increasingly become an important component of non-operative management (NOM). SAE decreases the blood pressure to the spleen to allow healing, but preserves splenic perfusion via robust collateral pathways. SAE can be performed proximally in the main splenic artery, more distally in specific injured branches, or a combination of both proximal and distal embolization. No definitive evidence from available data supports benefits of one strategy over the other. Particles, coils and vascular plugs are the major embolic agents used.Incorporation of SAE in the management of blunt splenic trauma has significantly improved success rates of NOM and spleen salvage. Failure rates generally increase with higher injury severity grades; however, current management results in overall spleen salvage rates of over 85%. Complication rates are low, and primarily consist of rebleeding, parenchymal infarction or abscess. Splenic immune function is felt to be preserved after embolization with no guidelines for prophylactic vaccination against encapsulated bacteria; however, a complete understanding of post-embolization immune changes remains an area in need of further investigation. This review describes the history of SAE from its inception to its current role and indications in the management of splenic trauma. The endovascular approach, technical details, and outcomes are described with relevant examples. SAE is has become an important part of a multidisciplinary strategy for management of complex trauma patients.
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