Mutations in the Wnt signalling cascade are believed to cause aberrant proliferation of colorectal cells through T-cell factor-4 (TCF4) and its downstream growth-modulating factors. HOXB13 is exclusively expressed in prostate and colorectum. In prostate cancers, HOXB13 negatively regulates b-catenin/TCF4-mediated transactivation and subsequently inhibits cell growth. To study the role of HOXB13 in colorectal tumorigenesis, we evaluated the expression of HOXB13 in 53 colorectal tumours originated from the distal left colon to rectum with their matching normal tissues using quantitative RT -PCR analysis. Expression of HOXB13 is either lost or diminished in 26 out of 42 valid tumours (62%), while expression of TCF4 RNA is not correlated with HOXB13 expression. TCF4 promoter analysis showed that HOXB13 does not regulate TCF4 at the transcriptional level. However, HOXB13 downregulated the expression of TCF4 and its target gene, c-myc, at the protein level and consequently inhibited b-catenin/TCF-mediated signalling. Functionally, forced expression of HOXB13 drove colorectal cancer (CRC) cells into growth suppression. This is the first description of the downregulation of HOXB13 in CRC and its mechanism of action is mediated through the regulation of TCF4 protein stability. Our results suggest that loss of HOXB13 may be an important event for colorectal cell transformation, considering that over 90% of colorectal tumours retain mutations in the APC/b-catenin pathway.

Purpose: To evaluate the characteristics of new thin 125I source Model 9011 in prostate implants and compare the dosimetric coverage between Model 6711 and 9011 sources. Methods: TG43 parameters of Model 9011 125I source were entered into a commercial treatment planning system to generate the new dose distributions in two patients who were originally implanted with Model 9011 thin sources but calculated with Model 6711 125I source data. Additionally, the Model 9011 source data were also used in randomly selected 16 prostate patients who were originally implanted with the model 6711 sources. The results of these calculations are compared side by side in the terms of the isodose covering 100% (D100) and 90% (D90) of prostate volume, and the percentages of volumes of prostate, bladder, rectum and urethra covered by 200% (V200), 150% (V150), 100% (V100), 50% (V50) and 20% (V20) of the prescribed dose as well. Results: The comparisons show that with the source strength suggested by Model 6711 source data, D100 would lower by 7% if Model 9011 source data are used. The percentage of volumes covered by different percentages of prescription dose (V200, V150, V100, V50 and V20) for prostate, bladder, rectum and urethra are also found to have changed significantly, in some cases up to 80% change could be expected. Conclusions: The differences of dosimetric characteristics between Model 9011 and 6711 sources are too large to be simply neglected. An oversimplified use of Model 6711 source data for Model 9011 source implant will create significant error in dose calculation. The source strength of Model 9011 source should be increased by 7% if the calculation is based on the 6711 source data and the same dose coverage is pursued. It is concluded that actual TG43 data of model 9011 thin seed should be used in treatment planning systems.

Background Our efforts to prevent and treat breast cancer are significantly impeded by a lack of knowledge of the biology and developmental genetics of the normal mammary gland. This ignorance has been the consequence of the lack of access to richly annotated, high quality normal breast specimens. The Susan G. Komen for the Cure® Tissue Bank at the IU Simon Cancer Center (KTB) was established expressly to remedy this deficiency. The KTB is a repository of specimens from volunteer donors with no clinical evidence of breast malignancy. The Bank's mission is to make available specimens that will enable an understanding of the developmental biology of the normal breast, to provide insight into breast oncogenesis, and to provide a normal control for breast cancer research. The purpose of this presentation is to increase the awareness of this unique and rich research resource and to actively solicit the use of its specimens. Methods: The KTB has been prospectively banking fresh frozen breast tissue since mid-2006. Coincident with the tissue donation two tubes of blood are obtained, which are processed for lymphocyte DNA, serum and plasma. These specimens are richly annotated with detailed information regarding the donors’ reproductive history, medical history, family history, and medications. Standard Operating Procedures have been constructed so as to control, limit and identify potential sources of bias. All of this information is recorded in an Oracle-based, searchable database. Results: As of June 2011, the KTB and its predecessor bank, Mary Ellen's Bank, have available fresh frozen breast tissue (10 gauge cores) from 1469 donors; formalin-fixed, paraffin-embedded tissue from 1055; DNA from 7507; serum from 2382; and plasma from 3771 donors. The KTB has also established 28 epithelial and 33 stromal cell lines from the cores; 4 of the epithelial cell lines have been immortalized using hTERT. Donors range in age from 18–86 years of age. 9% of donors to the KTB describe themselves as Hispanic/Latino. 5.2% of donors are Black or African-American. Using the Gail Risk Model, there is a bimodal distribution of life-time breast cancer risk among the donors: the largest peak is at 10% and a smaller one at 18%. Conclusions: The KTB is a unique and invaluable research resource which is now open for business and accessible to researchers across the globe. We encourage researchers to avail themselves of this unique tissue resource and to also acquaint themselves with other sources of healthy breast tissue, i.e., the Love/Avon Army of Women [http://www.armyofwomen.org/]. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-21-02.

HDR 192Ir source dose enhancement by a high-Z material thin layer is similar to that reported from a kilo-voltage X-ray beam. Attention should be paid for high-Z thin layers with HDR source clinically as it could cause significant dose enhancement.