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CIP1 inhibits P53 mediated apoptosis in hepatocellular carcinoma cell line
Hepatocellular
carcinoma, liver regeneration,
apoptosis
89
1 P/CO4/011 1
PREVALENCE AND PREDICTIVE FACTORS OF LARGE CELL DYSPLASIA (LCD) IN CHRONIC LIVER DISEASES. F~.&.rhotcarena. C. Guettier*. N. Ganne-Carrie. C. Christidis. JC. c et. M. Beaue a d, Services d’Hkpatolig?le ‘et d’Anatomopathologie*, HBpital Jean Verdier, 93143 Bondy-France. Liver LCD has a high independent predictive value for the occurrence of hepatocellular carcinoma. However, the prevalence of LCD in chronic liver diseases and the predictive factors of LCD occureence are poorly known. To assess these points, liver biopsies of 468 patients (286 with cirrhosis) were studied by an experienced liver pathologist. For each patient, 21 clinicobiological parameters and 8 histological parameters were recorded. According to the etiology of liver disease, 4 groups of patients with cirrhosis (HBV n=34, HCV n=117, alcohol n=55, PBC or hemochromatosis or auto-immune hepatitis n=80) and 3 groups of patients with non cirrhotic liver disease (HBV n=35, HCV n=116, alcohol n=31) were studied. The prevalence of LCD was higher in case of cirrhosis (20% vs 10.5%, p=O.O16) and was related to the etiology of chronic liver disease: HBV 38% and 26%, HCV 17% and 6%, alcohol 18% and 10% in patients with or without cirrhosis; the prevalence was only 5% in patients with cirrhosis from other cause. The level of fibrosis was predictive of the presence of LCD in every aetiological groups. Age had an independent predictive value in patients with alcoholic liver disease. The activity of liver disease had a highly predictive value in patients with HCV infection (p
mmmofHcc~uvma-
Coimbm,Pork@ Purpose: To determine the rob of mm reao~nw iMpin (MRI) parhInd with l ruparpam~ contmst a9ent (SPIO) for dwction of wMhh~csz, (HCC) in cintytic pdentf. ~Swwhenarrhotkp8hntswithsuspectedlii lMdWWMMRI,bOforOMdollOhwr8ftOr m,wstudw thoi~i~ot~ uip.lpMnugn(iccontrnt~~~~or 16 mmol Fe&l. Spin-who (SE) Tl-, ptondondty (W), T2- and 9mdiontwwepMommdon~1,5TesbMRunit. aoh (GRE) T2s v All~undsroocTPorbwPM,db~~wroioonphy(D8A) ~,inn~~,~~~bylipkdoCCT.I~~~ quanWM9thenumberofbsionson ~nddbyfwri~~, MRI md @lorkMT Dy mew~s of a conMenm mtlr~ rcrb. RecWer opamtin9 dundell8tta (Rot) Mdy8ls mr pafomw, awetin the AZ indexforwtlchseMr.~coontirwutionmr~iby peKsuw= tliop8yin dl pdbnts. Hcczy p&l= tansplwhtbn in four lnd pM&l ronogmphy, in cIv8; tumpnl nodubs. on. non-Surgkrl pdbflb war0 ~_~tobe~1thaywanldsntmsdby~lerathvoi~i~ ResuL: Seventy thma tumors! noduba m dotodd. After contm6t Mhnanwnt~nwn~indu~0.79t0.04(k~SEPDw~~ md 0.79 i 0.05 for the ORE T2-w v. both s&ikwUy hiihw &x01) thMthabnt PcMontna SE v (0.96 f 0.08 for T2-w). On MRI, 34 baionswemdatadodbdomoontlnterhw@md (47%). ad 58 clssc) dter dmiibtntion of SPIO (~~01). Two m WC warn only debctadonthe~ study ti, tier SPlQ ~~+=$y~ inmrmMyuJgcwd~nHCCnodub.UpkdoCCT babns(48%)wlth~mrrn&lnMxofO.6lt0.99. Conclutknr:in~dnhoJI.SPDm~MRIcontmst~for HccdewionttutcouldpertarmbetterthnlipiodoccT.How8ver.to inawwKMIcy,~i~shou~be~.
1 P/CO4/012 CLINICAL VALIDATION ON =T-MIBI
OF THE
INPLURNCR OF P-GLYWPROTRlN
UFTAKE IN =T-MIBI
SPECT
IN HEPATOCELLLJLAR
CARCINOMA s. w. &bJHJb& H. 1. !k3lw’. Y. M. ,m . . C. H. epdL+. Dues of Gastmenkol~y, Gaeral swgery’. Anatanic @bc.looy’* and Nuclear medicine’, Ajw University School of Medicine, Suwon, Korea. Drug
resistance
is
one
treatment of patients
of
the
as the ability of cells exposed transpmt
of dnws
vc-MIBI.
a
transport in
its
mediated
uptake
lipophilic to
in viva.
with
METHODS
specimens
was
RESZJLTS SPECT. uptake
:
of
Pep
diagnose in
to
has
shown is
that a
a
suitable
of MIBI would lie
the
presence
of
the association
hepatocellular
Pgp
of MD31
carcinoma(HCC).
with HCC were enrolled in the study. ten minutes after injection of ZOmCi
Du Pant
Merck
Immumobistochemical pt%fOIllEd
using
Pharma.
Co.,
staining
for
a
USA)
before
resected
mO”CIO”al
HCC
antibody
Lab. UK) and LSAB kit (Dako Co., Carpinteria, CA).
Thirty(85.7%)
while
the
that is encoded by
evidence
to determine
patients
of 35 patients
had no yc-MlBl was
in
is defined
due to enhanced outward
radiophannaceutical.
was performed
HCC.
JSB-l(Novocestra tissues
We sought
G4iolite@. of
Recent
noninvasively
expression
99”rc-MB31 SPECT resection
dr”gs
by P-glycoprotein(Pgp)
cationic
: Thiiy-five
ga*rc-MIBl
problems
for Pgp. The potential advantage
superiority
expression
““related
gene(MDR1).
substrate
unsolved
to a single dr”g to develop resistance
a broad range of struct”ndly multidrug-resistance
major
with cancer. Multidrug resistance(MDR~
in five
noted
uptake patients
in tumor
suggest that vc-MB1
without
lesions.
SPECT
with Pap expression
in tumor lesions Pgp
expression,
CONCLUSIONS
is useful
in tumor
0” Yc-MIBI VC-MIBI : Our
to noninvasively
the presence of MDRI gene product Pgp in patients with HCC.
results
determine
COMPARISON OF NON-
ENMNCED,SPtO-ENH&CEDMWOR-GT
1
SUPPRESSION OF P21wARINEIBIIS P53 MEDIATED APOPTOSIS IN BEPATocELLuLAR CARCINOMA CELL LINE FYamz.WLWamz Department of Pathology, Institute for Cancer Research, Fourth Military Medical University, Xian, 710032, P.R.China P21wAF1/cIp’is a downstream effector of the ~53 gene and a universal &in-dependent kinase (CDK) inhibitor. Postulated roles for in apoptosis remains controversial. Our previous studies P21wAF1/cIp’ showed stable overexpression wild type(wt>p53 by gene transfection in a ~53 mutant human hepatocellular carcinoma cell line (HCC-9204) could induce apoptosis accompanying p21wAF”c’p’protein expression. P21wAF’/cIplprotein, however, is negative in HCC-9204 cells. To determine the function of p21 wAF1’clp’in the ~53 dependent apoptosis, we used two eukaryotic expressions: LXSN containing wt-~53, PCEW containing antisense p21 wAF1/cIp’and , co-transfected into HCC-9204 cells. After selection with G418 and hygromycin, a positive clone was obtained and confirmed by Southern blotThe majority of these cells grow slower and did not exhibit apoptosis phenotype. The Western blot showed this particular cell line highly express wt-~53 protein but not express p2 1wAF1lclplprotein. The expression of antisense p21 wAF’lcIp’ led to inhibit wt-pS3 mediated apoptosis showing at two aspect: the v&p53 mediated spontaneous apoptosis disappeared and the sensitivity of cotransfection cells to adriamycin induced apoptosis decreased greatly as compared with cells subjected to only wt-~53 transfection. These finding suggested p21 wAF’/cIp’might play an important role in ~53 mediated
carcinoma, liver regeneration,
apoptosis
89
1 P/CO4/011 1
PREVALENCE AND PREDICTIVE FACTORS OF LARGE CELL DYSPLASIA (LCD) IN CHRONIC LIVER DISEASES. F~.&.rhotcarena. C. Guettier*. N. Ganne-Carrie. C. Christidis. JC. c et. M. Beaue a d, Services d’Hkpatolig?le ‘et d’Anatomopathologie*, HBpital Jean Verdier, 93143 Bondy-France. Liver LCD has a high independent predictive value for the occurrence of hepatocellular carcinoma. However, the prevalence of LCD in chronic liver diseases and the predictive factors of LCD occureence are poorly known. To assess these points, liver biopsies of 468 patients (286 with cirrhosis) were studied by an experienced liver pathologist. For each patient, 21 clinicobiological parameters and 8 histological parameters were recorded. According to the etiology of liver disease, 4 groups of patients with cirrhosis (HBV n=34, HCV n=117, alcohol n=55, PBC or hemochromatosis or auto-immune hepatitis n=80) and 3 groups of patients with non cirrhotic liver disease (HBV n=35, HCV n=116, alcohol n=31) were studied. The prevalence of LCD was higher in case of cirrhosis (20% vs 10.5%, p=O.O16) and was related to the etiology of chronic liver disease: HBV 38% and 26%, HCV 17% and 6%, alcohol 18% and 10% in patients with or without cirrhosis; the prevalence was only 5% in patients with cirrhosis from other cause. The level of fibrosis was predictive of the presence of LCD in every aetiological groups. Age had an independent predictive value in patients with alcoholic liver disease. The activity of liver disease had a highly predictive value in patients with HCV infection (p
mmmofHcc~uvma-
Coimbm,Pork@ Purpose: To determine the rob of mm reao~nw iMpin (MRI) parhInd with l ruparpam~ contmst a9ent (SPIO) for dwction of wMhh~csz, (HCC) in cintytic pdentf. ~Swwhenarrhotkp8hntswithsuspectedlii lMdWWMMRI,bOforOMdollOhwr8ftOr m,wstudw thoi~i~ot~ uip.lpMnugn(iccontrnt~~~~or 16 mmol Fe&l. Spin-who (SE) Tl-, ptondondty (W), T2- and 9mdiontwwepMommdon~1,5TesbMRunit. aoh (GRE) T2s v All~undsroocTPorbwPM,db~~wroioonphy(D8A) ~,inn~~,~~~bylipkdoCCT.I~~~ quanWM9thenumberofbsionson ~nddbyfwri~~, MRI md @lorkMT Dy mew~s of a conMenm mtlr~ rcrb. RecWer opamtin9 dundell8tta (Rot) Mdy8ls mr pafomw, awetin the AZ indexforwtlchseMr.~coontirwutionmr~iby peKsuw= tliop8yin dl pdbnts. Hcczy p&l= tansplwhtbn in four lnd pM&l ronogmphy, in cIv8; tumpnl nodubs. on. non-Surgkrl pdbflb war0 ~_~tobe~1thaywanldsntmsdby~lerathvoi~i~ ResuL: Seventy thma tumors! noduba m dotodd. After contm6t Mhnanwnt~nwn~indu~0.79t0.04(k~SEPDw~~ md 0.79 i 0.05 for the ORE T2-w v. both s&ikwUy hiihw &x01) thMthabnt PcMontna SE v (0.96 f 0.08 for T2-w). On MRI, 34 baionswemdatadodbdomoontlnterhw@md (47%). ad 58 clssc) dter dmiibtntion of SPIO (~~01). Two m WC warn only debctadonthe~ study ti, tier SPlQ ~~+=$y~ inmrmMyuJgcwd~nHCCnodub.UpkdoCCT babns(48%)wlth~mrrn&lnMxofO.6lt0.99. Conclutknr:in~dnhoJI.SPDm~MRIcontmst~for HccdewionttutcouldpertarmbetterthnlipiodoccT.How8ver.to inawwKMIcy,~i~shou~be~.
1 P/CO4/012 CLINICAL VALIDATION ON =T-MIBI
OF THE
INPLURNCR OF P-GLYWPROTRlN
UFTAKE IN =T-MIBI
SPECT
IN HEPATOCELLLJLAR
CARCINOMA s. w. &bJHJb& H. 1. !k3lw’. Y. M. ,m . . C. H. epdL+. Dues of Gastmenkol~y, Gaeral swgery’. Anatanic @bc.looy’* and Nuclear medicine’, Ajw University School of Medicine, Suwon, Korea. Drug
resistance
is
one
treatment of patients
of
the
as the ability of cells exposed transpmt
of dnws
vc-MIBI.
a
transport in
its
mediated
uptake
lipophilic to
in viva.
with
METHODS
specimens
was
RESZJLTS SPECT. uptake
:
of
Pep
diagnose in
to
has
shown is
that a
a
suitable
of MIBI would lie
the
presence
of
the association
hepatocellular
Pgp
of MD31
carcinoma(HCC).
with HCC were enrolled in the study. ten minutes after injection of ZOmCi
Du Pant
Merck
Immumobistochemical pt%fOIllEd
using
Pharma.
Co.,
staining
for
a
USA)
before
resected
mO”CIO”al
HCC
antibody
Lab. UK) and LSAB kit (Dako Co., Carpinteria, CA).
Thirty(85.7%)
while
the
that is encoded by
evidence
to determine
patients
of 35 patients
had no yc-MlBl was
in
is defined
due to enhanced outward
radiophannaceutical.
was performed
HCC.
JSB-l(Novocestra tissues
We sought
G4iolite@. of
Recent
noninvasively
expression
99”rc-MB31 SPECT resection
dr”gs
by P-glycoprotein(Pgp)
cationic
: Thiiy-five
ga*rc-MIBl
problems
for Pgp. The potential advantage
superiority
expression
““related
gene(MDR1).
substrate
unsolved
to a single dr”g to develop resistance
a broad range of struct”ndly multidrug-resistance
major
with cancer. Multidrug resistance(MDR~
in five
noted
uptake patients
in tumor
suggest that vc-MB1
without
lesions.
SPECT
with Pap expression
in tumor lesions Pgp
expression,
CONCLUSIONS
is useful
in tumor
0” Yc-MIBI VC-MIBI : Our
to noninvasively
the presence of MDRI gene product Pgp in patients with HCC.
results
determine
COMPARISON OF NON-
ENMNCED,SPtO-ENH&CEDMWOR-GT
1
SUPPRESSION OF P21wARINEIBIIS P53 MEDIATED APOPTOSIS IN BEPATocELLuLAR CARCINOMA CELL LINE FYamz.WLWamz Department of Pathology, Institute for Cancer Research, Fourth Military Medical University, Xian, 710032, P.R.China P21wAF1/cIp’is a downstream effector of the ~53 gene and a universal &in-dependent kinase (CDK) inhibitor. Postulated roles for in apoptosis remains controversial. Our previous studies P21wAF1/cIp’ showed stable overexpression wild type(wt>p53 by gene transfection in a ~53 mutant human hepatocellular carcinoma cell line (HCC-9204) could induce apoptosis accompanying p21wAF”c’p’protein expression. P21wAF’/cIplprotein, however, is negative in HCC-9204 cells. To determine the function of p21 wAF1’clp’in the ~53 dependent apoptosis, we used two eukaryotic expressions: LXSN containing wt-~53, PCEW containing antisense p21 wAF1/cIp’and , co-transfected into HCC-9204 cells. After selection with G418 and hygromycin, a positive clone was obtained and confirmed by Southern blotThe majority of these cells grow slower and did not exhibit apoptosis phenotype. The Western blot showed this particular cell line highly express wt-~53 protein but not express p2 1wAF1lclplprotein. The expression of antisense p21 wAF’lcIp’ led to inhibit wt-pS3 mediated apoptosis showing at two aspect: the v&p53 mediated spontaneous apoptosis disappeared and the sensitivity of cotransfection cells to adriamycin induced apoptosis decreased greatly as compared with cells subjected to only wt-~53 transfection. These finding suggested p21 wAF’/cIp’might play an important role in ~53 mediated