studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1177A
lower in cancerous tissue compared with noncancerous tissue
(respectively: p < 0.01 and p < 0.01). There were no significant
differences between the expression of these five molecules
and any clinicopathologic factors, including PVI. Immunohistochemical
stain for RGS5 demonstrated that RGS5 expression
was higher in cancerous tissue than in paired noncancerous
tissue in 63.3% (38/60) of HCC. Furthermore, high expression
of RGS5 in cancerous tissue was significantly associated with
PVI (p < 0.01) and tended to be associated with intrahepatic
metastasis (p = 0.0626). The cases with high expression of
RGS5 in cancerous tissue were significantly frequent in simple
nodular type with extranodular growth or confluent multinodular
type than in simple nodular type (p < 0.01). Conclusion: By
using LMD and cDNA microarray, we detected molecules associated
with PVI. RGS5 expression in cancerous tissue was significantly
upregulated at mRNA and protein levels compared
with noncancerous tissue and was significantly associated with
PVI of HCC. RGS5 may be a useful prognostic biomarker as
well as a target of molecular therapy of HCC. In vitro functional
analysis of RGS5 in HCC is underway.
Disclosures:
The following authors have nothing to disclose: Yumi Umeno, Sachiko Ogasawara,
Jun Akiba, Hironori Kusano, Osamu Nakashima, Hironori Koga, Takuji
Torimura, Hirohisa Yano
1991
Correlation between Incidence Rate of Hepatocellular
Carcinoma and Chemical Air Pollution in the State of
Texas.
Ali Shirafkan 1 , Cristiana Rastellini 1 , Katherine Ensor 2 , Loren Raun 2 ,
Daria Zorzi 1 , Laura Campos 2 , Mauro Montalbano 1 , Tiziana Corsello
1 , Luca Cicalese 1 ; 1 Department of Surgery, University of Texas
Medical Branch, Galveston, TX; 2 Department of Statistics, Rice
University, Houston, TX
Introduction: Primary liver cancer is the third cause of cancer
death in the world and the seventh in the United States. The
known etiologies of Hepatocellular Carcinoma (HCC) are comprised
of nonspecific cirrhosis, alcohol induced liver disease,
hepatitis C (HCV) and B (HBV) infection. In addition, obesity
and diabetes mellitus type two (T2DM) have been shown to
increase the risk. Texas ranks third in the US with HCC incidence
rate of 9.9 per 100,000. This is being compared to
national average of 7.1 per 100,000, while distribution of the
known risk factors in the state of Texas is similar to the national
data. Texas has the largest oil and gas industry and is the
second largest agricultural producer in the nation. Chemicals,
fertilizers, herbicides and pesticides could potentially contribute
to HCC development. Methods: The mean concentration
value of Vinyl Chloride, Arsenic, Benzene and 1, 3 Butadiene
reported by EPA (Environmental Protection Agency). Incidence
rate of HCC in Texas by counties for the time period between
2002 and 2010 was obtained from the Texas Cancer Registry.
A scatter plot matrix, a logistic regression model and a generalized
additive (GAM) logistic regression model were used
to observe any correlation between these variables. Results:
Increases in vinyl chloride and total Benzene and 1, 3 Butadiene
were associated with an increased risk of HCC within a
county. Arsenic levels appear protective at low levels, but at
high levels the probability of HCC within a county increases.
Conclusion: It is possible that vinyl chloride, arsenic, BZ and 1,
3 BD produced in different areas of Texas probably contribute
to the high incidence rates of HCC observed in this state.
Disclosures:
The following authors have nothing to disclose: Ali Shirafkan, Cristiana Rastellini,
Katherine Ensor, Loren Raun, Daria Zorzi, Laura Campos, Mauro Montalbano,
Tiziana Corsello, Luca Cicalese
1992
MicroRNA profiling of human cholangiocarcinoma
Hong Joo Kim, Yong Kyun Cho, Woo Kyu Jeon, Byung Ik Kim;
Internal Medicine, Sungkyunkwan University Kangbuk Samsung
Hospital, Seoul, Korea (the Republic of)
Background and aims: Cholangiocarcinoma (CC) is a highly
malignant epithelial cancer of the biliary tract with high morbidity
and mortality. In the current study, we performed microR-
NAs (miRNAs) expression microarrays to identify the up- and
downregulated miRNAs in CC. Thereafter, we performed oligomer
and antagomir transfection experiments for the most prominently
up- and downregulated miRNA in CC to identify the
underlying molecular pathogenic mechanisms for proliferation,
invasion and metastasis of CC. Methods: Human hepatic duct
bifurcation site cancer cells SNU-1196 (KCLB No. 01196),
and human common bile duct cancer cells SNU-245 (KCLB No.
00245) were purchased from Korean Cell Line Bank and maintained
in RPMI1640 medium. Affymetrix miRNA expression
microarrays were used to determine the miRNA expression profile
of each CC cell line and normal control cells obtained from
primary culture of normal bile duct epithelium. Transfections
were performed using Lipofectamine RNAiMAX (Invitrogen).
Cell proliferation was determined by MTT assay after mimics
or antisense oligonucleotide transfection. Western blotting of
cell extracts was performed using rabbit monoclonal antibodies
against human SRGAP2, Rac1 (both from BD Bioscience) and
β-actin. Results: To profile the miRNA expression patterns in
human CC cells, we compared the miRNA expression profile
of 2 CC cell lines with that of normal control cells obtained
from primary culture of normal bile duct epithelium. MicroR-
NAs downregulated more than 10-folds log ratio in CC cell
lines than normal control cells were as follows: miR-145-5p,
miR-125b-5p, miR-125a-5p, and miR-100-5p. Upregulated
miRNAs more than 8-folds log ratio in CC cell lines than normal
control cells were as follows: miR-182-5p, miR-196a-5p,
miR-194-5p, miR-192-5p, and miR-182-5p. Thereafter, we
performed transfection experiments using the mimics and
antagomirs targeting miR-145-5p. There were no significant
differences in cell proliferation measured by MTT assay among
the CC and normal control cell lines transfected with mimics
and antagomirs. Downregulation of miR-145-5p by antagomir
transfection was associated with increase in protein expression
levels of SRGAP2 and Rac1. Conclusions: Our data identify
that miR-145-5p is the most profoundly downregulated miRNA
in human CC cells. SRGAP2 and Rac1 can be novel targets of
miR-145-5p, establishing a role for miR-145-5p in modulating
motility and metastasis of CC cells. Our data provide a possibility
for further investigations for future miR-145-5p targeted
approaches of anticancer treatment in.CC.
Disclosures:
The following authors have nothing to disclose: Hong Joo Kim, Yong Kyun Cho,
Woo Kyu Jeon, Byung Ik Kim
1993
Cholangiocarcinoma cells interact with cancer-associated
myofibroblasts in 3-D culture to provoke a strong
desmoplastic-like reaction mediated by TGF-β.
Alphonse E. Sirica, Akihiro Usui, Deanna J. Campbell; Pathology,
Virginia Commonwealth University School of Medicine, Richmond,
VA
Intrahepatic cholangiocarcinomas (ICC) typically exhibit
a prominent desmoplastic reaction marked by a dramatic
increase in α-smooth muscle actin-positive cancer-associated
fibroblasts (α-SMA+CAFs) together with the production of a