@article {10747, title = {Activation of hepatic stem cells compartment during hepatocarcinogenesis in a HBsAg HBV-transgenic mouse model.}, journal = {Sci Rep}, volume = {8}, year = {2018}, month = {2018 Sep 03}, pages = {13168}, abstract = {

Chronic infection of Hepatitis B Virus (HBV) is one of the highest risk factors of hepatocellular carcinoma (HCC). The accumulation of HBV surface antigen (HBsAg) into hepatocytes induces inflammation and oxidative stress, impairing their replicative ability and allowing the activation of the hepatic stem cells (SC) compartment. This study aimed to understand the involvement of SC during hepatocarcinogenesis in HBsAg-related liver damage, from early injury until HCC. HBsAg-transgenic (TG) and wild type (WT) mouse were followed at several stages of the liver damage: inflammation, early hepatocytes damage, dysplasia, and HCC. Serum transaminases, liver histology, and diagnostic data were collected. The expressions of SC and cancer stem cells (CSC) markers was analyzed by RT-qPCR, immunohistochemistry and Western blot. Starting from 3 months, TG animals showed a progressive liver damage characterized by transaminases increase. The up-regulations of SCs markers Cd34 and Sca-1 started from the beginning of the inflammatory stage while progressive increase of Krt19 and Sox9 and CSCs markers Epcam and Cd133 from early hepatic injury. The expressions of Cd133, Cd34, and Afp were significantly higher in HCC compared to paired non-HCC tissue, in contrast to Epcam and Krt19. Western blot and IHC confirmed the positivity of Cd34 and Cd133 in small cells subpopulation.

}, issn = {2045-2322}, doi = {10.1038/s41598-018-31406-5}, author = {Anfuso, Beatrice and El-Khobar, Korri E and Ie, Susan I and Avellini, Claudio and Radillo, Oriano and Raseni, Alan and Tiribelli, Claudio and Sukowati, Caecilia H C} } @article {10847, title = {Serum Stem Cell Growth Factor Beta for the Prediction of Therapy Response in Hepatocellular Carcinoma.}, journal = {Biomed Res Int}, volume = {2018}, year = {2018}, month = {2018}, pages = {6435482}, abstract = {

Introduction: Chronic inflammatory response is one of major contributors in the development of hepatocellular carcinoma (HCC). Inflammatory molecules, such as cytokines and growth factors in the circulation, can be useful in the diagnosis and prognosis of the patients. The stem cell growth factor beta (SCGF), a newly found protein, is a secreted sulfated glycoprotein and it functions as a growth factor for primitive hematopoietic progenitor cells. The level of SCGF had been reported to be elevated in several cancer types. However, there is very few or even no information on this protein in the study of HCC, even more in clinical studies.

Methods: A multiplex immunoassay panel of 48 cytokines and growth factors were utilized to screen 68 sera from 29 HCC patients at pretreatment (T0), 1 month (T1), and 6 months (T6) after treatment by either radiofrequency ablation (RF) or transarterial chemoembolization (TACE). Treatment response was evaluated according to mRECIST criteria.

Results: Immunoassay screening showed that the levels of IL-17, CTACK, TNF, IL-2R, IL-8, and SCGF were different in Complete Responders (CR) and Nonresponders (NR) groups. At T0 and T1, the SCGF level was significantly the highest in NR (23.8 and 40.7 ng/mL, respectively), followed by early recurrence (25.4 and 25.0 ng/mL), and CR (6.7 and 5.3 ng/mL), independently from HCV, stages, and treatment type. Low basal SCGF level was associated with longer disease-free survival compared to high SCGF.

Conclusion: In this study, for the first time, we demonstrate that the high level of serum SCGF at pre- and posttreatment is associated with HCC nonresponsiveness.

}, keywords = {Aged, Carcinoma, Hepatocellular, Chemoembolization, Therapeutic, Female, Hematopoietic Cell Growth Factors, Humans, Liver Neoplasms, Male, Middle Aged, Neoplasm Recurrence, Local, Retrospective Studies, Stem Cells, Treatment Outcome}, issn = {2314-6141}, doi = {10.1155/2018/6435482}, author = {Sukowati, Caecilia H C and Patti, Riccardo and Pascut, Devis and Ladju, Rusdina B and Tarchi, Paola and Zanotta, Nunzia and Comar, Manola and Tiribelli, Claudio and Croc{\`e}, Lory S} }