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Target Concepts:
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Query: UMLS:C0019204 (
hepatocellular carcinoma
)
71,386
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hepatocellular carcinoma
(
HCC
) is the most common form of liver tumors. Although
HCC
is associated with chronic viral infections, alcoholic cirrhosis, and nonalcoholic fatty liver disease, genetic factors that contribute to the
HCC
risk remain unknown. The BRCA2 DNA repair associated (BRCA2) and
cyclin-dependent kinase inhibitor 1A
(
CDKN1A
) interacting protein, known as BCCIP, are essential for cell viability and maintenance of genomic stability. In this study, we established a new genetically engineered mouse model with Bccip deficiency. Mosaic or heterozygous Bccip deletion conferred an increased risk of spontaneous liver tumorigenesis and B-cell lymphoma development at old age. These abnormalities are accompanied with chronic inflammation, histologic features of nonalcoholic steatohepatitis, keratin and ubiquitin aggregates within cytoplasmic Mallory-Denk bodies, and changes of the intracellular distribution of high-mobility group box 1 protein. Our study suggests BCCIP dysregulation as a risk factor for
HCC
and offers a novel mouse model for future investigations of nonviral or nonalcoholic causes of
HCC
development.
...
PMID:Spontaneous Development of Hepatocellular Carcinoma and B-Cell Lymphoma in Mosaic and Heterozygous Brca2 and Cdkn1a Interacting Protein Knockout Mice. 3220 Dec 59
Prevention and treatment options for
hepatocellular carcinoma
(
HCC
) are presently limited, underscoring the necessity for further elucidating molecular mechanisms underlying
HCC
development and identifying new prevention and therapeutic targets. Here, we demonstrate a unique protumorigenic niche in the livers of Ncoa5
+/
-
mouse model of
HCC
, which is characterized by altered expression of a subset of genes including p21
WAF1
/CIP1
and proinflammatory cytokine genes, increased putative hepatic progenitors, and expansions of activated and tissue-resident memory (TRM) CD8+ T lymphocytes, myeloid-derived suppressor cells (MDSCs), and alternatively activated M2 macrophages. Importantly, prophylactic metformin treatment reversed these characteristics including aberrant p21
WAF1
/CIP1
expression and subsequently reduced
HCC
incidence in Ncoa5
+/-
male mice. Heterozygous deletion of the p21
WAF1
/CIP1
gene alleviated the key features associated with the protumorigenic niche in the livers of Ncoa5
+/-
male mice. Moreover, transcriptomic analysis reveals that preneoplastic livers of Ncoa5
+/-
mice are similar to the livers of nonalcoholic steatohepatitis patients as well as the adjacent noncancerous liver tissues of a subset of
HCC
patients with a relatively poor prognosis. Together, our results suggest that p21
WAF1
/CIP1
overexpression is essential in the development of protumorigenic microenvironment induced by NCOA5 deficiency and metformin prevents
HCC
development via alleviating p21
WAF1
/CIP1
overexpression and protumorigenic microenvironment.
...
PMID:NCOA5 deficiency promotes a unique liver protumorigenic microenvironment through p21
WAF1/CIP1
overexpression, which is reversed by metformin. 3220 60
Hepatocellular carcinoma
(
HCC
) represents one of the most frequent type of primary liver cancers. Decorin, a small leucine-rich proteoglycan of the extracellular matrix, represents a powerful tumor cell growth and migration inhibitor by hindering receptor tyrosine kinases and inducing p21
WAF1
/CIP1
. In this study, first we tested decorin expression in HCCs utilizing
in silico
data, as well as formalin fixed paraffin embedded tissue samples of
HCC
in a tissue microarray (TMA).
In silico
data revealed that DCN/SMA mRNA ratio is decreased in
HCC
compared to normal tissues and follows the staging of the disease. Among TMA samples, 52% of HCCs were decorin negative, 33% exhibited low, and 15% high decorin levels corroborating
in silico
results. In addition, applying conditioned media of
hepatoma
cells inhibited decorin expression in LX2 stellate cells
in vitro
. These results raise the possibility that decorin acts as a tumor suppressor in liver cancer and that is why its expression decreased in HCCs. To further test the protective role of decorin, the proteoglycan was overexpressed in a mouse model of hepatocarcinogenesis evoked by thioacetamide (TA). After transfection, the excessive proteoglycan amount was mainly detected in hepatocytes around the central veins. Upon TA-induced hepatocarcinogenesis, the highest tumor count was observed in mice with no decorin production. Decorin gene delivery reduced tumor formation, in parallel with decreased pEGFR, increased pIGF1R levels, and with concomitant induction of pAkt (T308) and phopho-p53, suggesting a novel mechanism of action. Our results suggest the idea that decorin can be utilized as an anti-cancer agent.
...
PMID:Protective Role of Decorin in Primary Hepatocellular Carcinoma. 3247 37
Wharton jelly mesenchymal stem cells (WJ-MSCs) are able to differentiate into different cell lineages upon stimulation. This ability is closely related to the perfect balance between the pluripotency-related genes, which control stem-cell proliferation, and genes able to orchestrate the appearance of a specific phenotype. Here we studied the expression of stemness-related genes, epigenetic regulators (
DNMT1, SIRT1
), miRNAs (
miR-145, miR-148
, and
miR-185
) related to stemness, exosomes, the cell-cycle regulators
p21
(
WAF1
/CIP1
) and
p53
, and the senescence-associated genes (
p16, p19
, and
hTERT
)
. Cells were cultured in the presence or absence of the human
hepatocarcinoma
cell line HepG2-exhausted medium, to evaluate changes in stemness, differentiation capability, and senescence sensibility. Our results showed the overexpression of
SIRT1
and reduced levels of
p21
mRNA. Moreover, we observed a downregulation of
DNMT1
, and a simultaneous overexpression of
Oct-4
and
c-Myc
. These findings suggest that WJ-MSCs are more likely to retain a stem phenotype and sometimes to switch to a highly undifferentiable proliferative-like behavior if treated with medium exhausted by human HepG2 cell lines.
...
PMID:Behavioral Changes in Stem-Cell Potency by HepG2-Exhausted Medium. 3280 9
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