Acknowledgements - UCSF School of Dentistry - University of ...

#38 Title: Death Note against OSCC
F YANG (1), W XIAO (2), R LIU (2), R KRAMER (1), K LAM (2)
(1) UCSF School of Dentistry; (2) UC Davis Medical Center Department of Biochemistry
Background: Oral squamous cell carcinoma (OSCC) is a well-known malignancy that accounts for more than 90% of all oral
cancers. 5-years survival rates for OSCC decrease with delayed diagnosis. So far, there is no sensitive and specific clinical
screening method for OSCC . We therefore investigate a less invasive but more specific and sensitive method for screening OSCC.
Objective: Our goal is to find ligands that will specifically bind to OSCC cells but not to normal healthy oral cells for clinical
screening and subsequent treatment.
Method: In this study, we employed “one bead one compound” combinatorial library (OBOC) strategy to identify specific ligands for
OSCC. Briefly, 24 random libraries were screened with OSCC derived from lateral side of tongue for 1.5 hrs to identify library with
possible OSCC binding ability. One library named X1 with strong, and fast OSCC binding property was chosen for further study.
The selected libr ary has a permutation of 24.3 million compounds. Live OSCC were co-cultured with X1 OBOC libraries for 1.5 hrs.
These OSCC cell binding beads were isolated and co-cultured with normal keratinocytes derived from skin. Compound beads that
showed strong binding to OSCC but not to normal keratinocytes were identified. The chemical structures of the compounds were
determined using Edmund Chemistry.
Results: A final of 12 beads with strong OSCC binding, but no keratinocyte binding ability were identified and a motif was observed.
Conclusion: Current work is underway to evaluate these ligands’ cytotoxicity, and possible conjugation to imaging agents for visual
inspection of OSCC in vitro. In the future, these OSCC cell binding ligands will be reserved and generated on “one bead two
compound” libraries to induce apoptosis of OSCC.
III. POSTDOCTURAL/RESIDENT CATEGORY
#39 Title: “Meth Mouth”: The Effect of Drug-Use Patterns, Beliefs, and Knowledge
R BROWN-KIMBREW
UCSF Department of Preventive and Restorative Health Sciences
Objectives: Rampant dental caries, “meth mouth,” is characteristic of methamphetamine use; the second most widely abused drug
in the world. The author sought to investigate the impact of drug-use patterns and knowledge on “meth mouth” severity and
compared the number of teeth affected by caries between methamphetamine users (MA users) and nonusers using the DMFT
(decayed, missing and filled teeth) index.
Methods: A case-control study design was used amongst voluntary participants at the Sonoma County Main Adult Detention
Facility. A sample of 59 MA users and 40 nonusers completed a self-administered questionnaire to assess their dental health, druguse
patterns, and knowledge of “meth mouth.” Oral examinations were performed to obtain a DMFT index for each cohort. The data
was analyzed using descriptive statistics, t-tests and analysis of variance.
Results: MA users had higher DMFT scores (p=0.019) than nonusers and perceived that their oral health had declined (p=0.000)
since using. Two drug-use patterns, years of use (p=0.026) and dosage (p=0.031), impacted DMFT and missing scores,
respectively. Few participants
(6.1 percent) had received “meth mouth” information from dental professionals.
Conclusions: MA users have more permanent teeth affected by dental caries and the years of use and the dosage impacts the
severity of “meth mouth”. Dentists should consider methamphetamine abuse among patients with high DMFT scores and provide all
patients with information about “meth mouth” to prevent future or continued use of this drug.
#40 Title: Effect of hydrogel Modulus and RGD Ligand Density on Mesenchymal Stem Cell Proliferation and Differentiation
A JANG (1) A JHA (2), E CHEUNG (2), K HEALY (2)(3)
(1) UCSF Department of Preventive and Restorative Dental Sciences (2) UC Berkeley Department of Bioengineering (3) UC
Berkeley Department of Materials Science and Engineering
Background: Mesenchymal stem cells (MSCs) carry the potential to differentiate into multiple tissue types including osteoblasts,
chondrocytes, and adipocytes. These cells hold great promise for the regeneration of orthopedic joints including the periodontium.
Self-renewal and differentiation of these cells are thought to be directed, in part, by biomechanical microenvironment features of the
surrounding extracellular matrix (ECM).
Objectives: In this study, we report on a synthetic ECM system which is independently tunable for cell adhesion ligand presentation
and matrix stiffness for the purposes of guiding MSC proliferation and differentiation towards an osteoblastic state.
Methods: A semi interpenetrating network (sIPN) hydrogel containing p(N-isopropylacrylamide-co-AAc) was synthesized using a
radical addition reaction. Variation of crosslinking agent and polyacrylic acid-graft-[RGD] peptide concentration allowed for the
independent tuning of complex modulus and cell adhesion ligand presentation. A custom QPQGLAK diacrylate crosslinking agent
was utilized to facilitate osteoblastic differentiation by providing MMP-13 cleavage sites. Complex modulus was determined using
rheology. Responses of both rat mesenchymal stem cells (rMSCs) and human mesenchymal stem cells (hMSCs) were
School of Dentistry Research and Clinical Excellence Day 2011 Program 18