Michael Ang, UCLA David Geffen School of Medicine CT and MR ...
Michael Ang, UCLA David Geffen School of Medicine
CT and MR ImagingCharacteristicsof Hepatocellular Carcinoma:Correlation with Tumor Pathology,Gene
Expression,and Clinical Outcome.
Hepatocellular Carcinoma (HCC) is a primary liver tumor most commonly occurringin patients with hepatitis
and/or underlyingcirrhosis. Itis oneof the most lethal forms of cancer worldwide, particularly in theFar East, and
its incidenceis increasingin the United States. Left untreated, the 5-year survival rateis less than 5%and, even
with treatment, the 5-year survival rateis approximately 30%. One of the main reasons HCC is so deadly is dueto
the fact that early HCC is clinically silent. Therefore, the diseaseis often not detected until iti s very advanced. CT
and MRI have longbeen used to detect and diagnoseHepatocellular Carcinoma. However, recent advances in
technology, especially theuse of contrast-enhancingagents, have made itpossibleto detect HCC earlier in its
The purpose of this projectis to identify specific imagingcharacteristicsthatcorrespond with underlyingtumor
pathology and genetic expression profiling. Wewill then determine how this radiological evaluation affects
treatment and clinical outcome.
CT and MR images of patients diagnosed with Hepatocellular Carcinoma were obtained from the UCLA Department
of Radiology with IRB approval and in accordancewith HIPPA. All images were evaluated by a board certified
Radiologistand compared with biological markers thatwere provided by histological analysisand global gene
expression profiling. A specific algorithmis currently beingdeveloped and applied to correlatefindings on imaging
with well-documented histological features. Once we areable to characterizethe tumor by imaging,we will then
proceed to look at the clinical outcome of patients and determine whether there areany significantassociations
between these image features and patient outcomes vis-à-visdifferenttreatments options.
The results of this study are still ongoing,however preliminary outcomes have revealed that there is indeed a
correlation between specific imagingcharacteristics,underlyingpathology,and,in fact,genetic expression.
CT and MR arepowerful imagingmodalities employed in the diagnosisand stagingof many diseases,especially
HCC. These imagingmodalities can nowdo more than ever to help personalizemedicineand aid in the selection of
the most efficacioustreatment. By correlatingtumor pathogenesis and genetic expression profiles to well known
imagingcharacteristics,onecan non-invasively imagethe biochemical makeup of livingtissue. Sincegene
expression patterns in cancer often reveal its etiology, prognosis,and treatment, molecular imagingvia CTand MR
can soon be another powerful tool utilized in the treatment of all cancers,notjustHCC.
Kwan Hon Vincent Lau, Mount Sinai School of Medicine
A Multi-Institutional RetrospectiveStudy of Radiation Therapy in Patients with Oligometastases
BACKGROUND: Although cancer that has progressed to metastasis is generally treated with palliative
chemotherapy, recent evidence suggests benefit in high-doseimage-guided radiation therapy for metastatic
diseaselimited to fiveor fewer sites,a state termed oligometastasis.Two studies,conducted at Mount Sinai
School of Medicine and Rochester Medical Center, have validated this method. To date, there lacks cleardata
identifyingspecific diseaseand treatment parameters correlatingto greatest clinical benefit.
OBJECTIVE: The purposeof this study was to identify diseaseand treatment characteristicswhich serveas
prognostic factors for treating oligometastasis.
METHODS: We merged the datasets from the two studies above (n = 165), and evaluated thirty-fiveindependent
patient, diseaseand treatment parameters against four outcome factors usingmultivariateanalysis.
RESULTS: Patients with breastcancer had statistically significantly better overall survival (OS),progression-free
survival (PFS),local control (LC) and distantcontrol (DC) (p = 0.007, p = 0.011,p = 0.000, p = 0.033 respectively),
whilethose with head and neck cancers had worseOS and PFS (p = 0.002, p = 0.001). Patients with bone
metastases had significantly better OS and PFS (p = 0.004, p = 0.008), whilethose with adrenal metastases had
worse OS (p = 0.002). Patients with primary tumors with sarcoma histology had worsePFS and DF (p = 0.021, p =
0.014). Higher total dose for primary siteradiation corresponded with better PFS and LF (p = 0.007, p = 0.000).
CONCLUSION: Patients with specific disease and treatment characteristics, especially thosewith breastcancers or
bone metastases who had received high doses of radiation for their primary tumor, may benefit most from
radiation for oligometastatic disease.These patient groups can be identified and treated for their metastatic
lesions beforefurther diseaseprogression.Theprognostic factors identified may be validated in future prospective
Hillary Lin,Stanford University School of Medicine
Southeast Asian Ethnicity a Predictor for Hepatitis C-Associated Hepatocellular Carcinoma
Objective: The incidenceof hepatocellular carcinoma (HCC) is growingin the U.S. due to increasingrates of
hepatitis B (HBV) and C (HCV). Increased immigration fromAsian countries with endemic viral hepatitis isa major
causeof this phenomenon. Our goal was to identify and compare the etiologies of HCC in different Asian American
Methods: We performed a cross-sectional retrospectivestudy on 510 Asians diagnosed with HCC at a university-
affiliated liver clinicin theUnited States between November 1992 and December 2009. Comparisons were made
among Southeast Asian (n = 270), Chinese(n = 206), and Korean (n = 36).
Results:The Chinesecohort had the highestpercentage of HBV-associated HCC, followed by the Korean and
Southeast Asian cohort (78.4% vs. 61.1% vs.47.4%, P < 0.0001). HCV-associated HCC was significantly higher
among the Southeast Asian cohortcompared to the Korean and Chinese cohorts (37.8% vs. 27.8% vs.13.7%, P <
0.0001). There was no significantdifferencein the rates of HBV and HCV co-infection (3.9%). The Korean cohort
had a significantly higher rated of cirrhosis compared to the Southeast Asian and Chinesecohort (77.8% vs. 66.3%
vs. 52.0%, P <0.0001). Furthermore, prevalence rates of hemochromatosis- and cryptogenic-associated HCC were
not significantly different(0.4% and 2.4%, respectively).
Conclusions:Chinesepatients have a much higher percentage of HCC associated with HBV rather than HCV (78.4%
vs. 13.7%). Korean patients also havea strong majority of HBV-associated HCC cases (61.1%vs. 27.8% HCV-
associated cases).However, Southeast Asian patients have an even distribution of HBV- and HCV-associated cases
(47.4% vs. 37.8%). These statistics may beuseful in identifyingat-risk individualsfor HCC screening.
Philip Song,Johns Hopkins University School of Medicine
The Clinical Profileof Merkel Cell Carcinoma in Mainland China
Little is known about the presence or characteristics of Merkel cell carcinoma (MCC) inmainland China.
To describethe clinical profileof MCC in China.
At 18 cancer hospitalsin metropolitan centers from the six geographical regions of mainland China,approximately
3,100,000 pathology databaseand medical records were reviewed for eligibility criteriaof havinga pathological
diagnosisof MCC between 1970 and 2009. A caseseries was compiled from retrospective chartreviews of
identified MCC patients.
Eight out of 18 participatinghospitals reported at leastone record of a patient with a pathological diagnosisof
MCC, and a total of 22 cases were identified. The median age of patients was 65.5, and 59% were female. The
median time from the appearanceof a lesion to the time of biopsy was 6 months, and the most common location
of lesions was the head and neck. The most common treatment used was surgery alone.
MCC appears to be uncommon in mainland China.Patients in this series areelderly,often had lesions on the
head/neck region, and most commonly received surgery alone as treatment. In contrastwith MCC in Western
countries,the current series’patients were all of Asian ethnicity,had larger lesions atpresentation,and none were
documented as havingHIV or other forms of immunosuppression.
MicheleYunZu Wang, Washington University School of Medicine in St. Louis
Trends in utilization and donor attrition atthe SingaporeBone Marrow Donor Programme
Trends in utilization and donor attrition atthe SingaporeBone Marrow Donor Programme
Introduction:Growing bone marrow donor registries,developments in the useof cord blood stem cell utilization,
and increasingcollaboration between donor registries havecontributed to an increasein hematopoietic stem cell
(HSC) transplants performed worldwidein the lastdecade. Rates of growth and attrition from bone marrow donor
registries in the U.S. and Europe have both been clearly documented, but there is notyet any published data for
Asia.A more family-centered orientation and traditional superstitions may play a larger rolein an Asian’s decision
to donate HSCs. The purpose of this firststudy of HSC donor trends in Singaporeis to analyzethe impactof these
changes and explorethe reasons behind donor attrition in a pan-Asian context.
Methods: Data from 1999-2009 was obtained from donor search files and other records at the Bone Marrow
Donor Programme (BMDP) and the SingaporeCord Blood Bank (SCBB). Donor recruitment and donor attrition
rates by racial groups werecompared by chi-squareanalysis.
Results:The BMDP and SCBB have been recruitingapproximately 3,800 additional bone marrowdonors and cord
blood units annually,with a significant(χ2 =2657) overrepresentation of ethnic Chinese donors in the BMDP. There
has been nearly threefold growth in the number of HSC procurements for BMDP patients from 2005-2009 alone.
Of the 126 potential donors registered through BMDP that were contacted between 2004 and 2009 57 refused to
donate, of which 29% did so due to family objections.
Conclusions:Overall,thecurrent status of hematopoietic stem cell transplants in Singaporeis healthy.Strategies
to improve minority recruitment appear to be effective. By addressingpreconceptions early and involvingfamily
from the beginningof the recruitment process,we seek to reduce BMDP donor attrition.We also hopethat the
findings of this study extend beyond Singaporeto benefit other registries with Asian donors that are also
confrontingthe problem of donor attrition,specifically for family reasons.
Brandon Yim, Northwestern University Feinberg School of Medicine
In vitro evaluation of the effects of a Malaysian herb, Vernonia amygdalina, on MCF-7 human breastcancer cells
Abstract: In Malaysian traditional and folkloricmedicine,a particular herb,Vernonia amygdalina (VA), commonly
known as “bitter leaf”, is used for various therapeutic and nutritional purposes.The aimof this study was to assess
leaf extracts of VA for anti-cancer properties and to determine the mechanism(s) by which itcauses cancer cell
death. In this study, MCF-7 human breastadenocarcinoma cellswere treated with different doses of VA leaf
extract for 48 and 72 hours, and subjected to the MTT cell viability assay.Additionally,cell cycleand cell
discrimination analysiswas conducted on VA-treated cells,usingthe flowcytometer. Data generated from the MTT
assay indicated IC50 values for the 48- and 72-hour incubation periods of 110 μg/ml and 83 μg/ml, respectively.
Dose-response curves indicated thatthe VA extract had a dose-dependent inhibitory action on the growth of MCF-
7 breastadenocarcinoma cells.Results fromcell cycleanalysisshowed an accumulation of cells in thesub-G1
phaseafter VA treatment, suggestingapoptotic cell death. Results from cell discrimination analysisalso suggested
cell death by apoptosis.More detailed studies need to be done to determine the molecular targets of VA on the
apoptotic pathway. In conclusion,VA leaf extract induced a dose-dependent apoptotic effect on MCF-7 breast
adenocarcinoma cells.These very preliminary findings raisethe possibility thatVA may contain activecompound(s)
with the potential for development into a drug(s) for the treatment of human breast cancer.
Li Zhou, VanderbiltMedical School
Effect of DMH1 on the Differentiation of mouse ES and iPS Cells
DMH1 is a selectivesmall moleculeinhibitor of the BMP pathway that was discovered in our lab.As an essential
component in the differentiation of embryos, the modulation of levels of BMP4 can commit stem cells to
different lineages. Ithas previously been shown that treatment of CGR8 mouse ES (mES) cells with dorsomorphin,
a relatively non-selectiveBMP4 inhibitor,increases thenumber of ES cells thatdifferentiate into beating
cardiomyoctes by 20-fold1. We investigated the effect of DMH1 on both mES and H11 mouse iPS (mIPS) cells for
two reasons. The firstwas to test the efficacy of DMH1 on differentiatingmES cells into cardiomyoctes. The
second was to compare the intrinsic characteristicsof mES and mIPS, cells to see whether they respond similarly to
the same treatments. Our results showthat >90% of our mES samples differentiated into spontaneously beating
cardiomyocytes when treated with DMH1. However, the protocol applied to miPS cells revealed ~4% spontaneous
cardiomyocytes when a identical protocol was applied. These results showthat DMH1 is effective at committing
mES cells to a cardiomyoctelineage. Furthermore, our results suggest an intrinsicdifferencebetween mES and
mIPS cells in their ability to respond to BMP4 inhibitors,though other cell lines mustbe tested in order to
strengthen this hypothesis.