ABSTRACT
Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva.
ABSTRACT
Radioresistance in the tumor and radiotoxicity in the nontumorous liver significantly restrict efficient radiotherapy of hepatocellular carcinoma (HCC). It is therefore important to study the radioresistance mechanism and development of radiosensitization to optimize the effect of irradiation on cancer cells. Emodin (1, 3, 8trihydroxy6methylanthraquinone) is a plantderived polyphenol, possessing anticancer properties. It is known to act as a radiosensitizer in human HCC cell lines. The aim of this study was to evaluate the role of emodin in radioresistance of human HCC cell lines as well as the underlying radiosensitization mechanism. The human HCC cell line (HepG2) was used in this study. Four different treatment groups, i.e., no treatment (control), irradiation (10 Gy, one fraction), emodin (10 µM), and a combination of irradiation and emodin (10 Gy+10 µM) were used for two environmental conditions: hypoxia (1% O2) and normoxia (20% O2). The cells were exposed to the respective treatments for 24 and 72 h. Following the treatment, the cell viability was determined by the 3(4,5dimethylthiazol2yl)2,5diphenyltetrazolium bromide (MTT) assay, and the radiosensitization mechanism was evaluated by western blotting. The proliferation of HepG2 cells was significantly suppressed in the treatment groups under hypoxic and normoxic conditions in the following order: combination of irradiation and emodin>irradiation only >emodin only. The combination of irradiation and emodin induced apoptotic signaling activities such as cleavage of poly (ADPribose) polymerase (PARP)1 as well as the downregulation of epigenetic signaling such as JMJD1A and JMJD2B. Emodin attenuated radioresistance in the HepG2 cells via upregulation of the apoptotic signals and down-regulation of the proliferative signals. These results suggested that emodin is a potential candidate for the radiosensitization of HCC cells and can aid in identifying novel therapeutic strategies for HCC radiotherapy.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Emodin/pharmacology , Hep G2 Cells/drug effects , Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors , Neoplasm Proteins/metabolism , Poly(ADP-ribose) Polymerases/metabolism , Radiation Tolerance/drug effects , Radiation-Sensitizing Agents/pharmacology , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Division/drug effects , Cell Division/radiation effects , Cell Hypoxia/physiology , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Drug Screening Assays, Antitumor , Gamma Rays , Gene Expression Regulation, Neoplastic , Hep G2 Cells/radiation effects , Humans , Jumonji Domain-Containing Histone Demethylases/biosynthesis , Jumonji Domain-Containing Histone Demethylases/genetics , Neoplasm Proteins/antagonists & inhibitors , Poly (ADP-Ribose) Polymerase-1 , Time FactorsABSTRACT
Extramedullary plasmacytoma involves organs outside the bone marrow; however, involvement of the pancreas is rare. We recently experienced a case of extramedullary plasmacytoma of the pancreas that was diagnosed by endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). EUS-FNA, which has a high diagnostic accuracy and an excellent safety profile, is the modality of choice for establishing tissue diagnosis. We report a case of extramedullary plasmacytoma of the pancreas diagnosed using EUS-FNA.
