Citations

AbstractRecent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I–based vaccines. In this study, the goal was to identify an HLA-DR–degenerate epitope pool derived from insulin-like growth factor binding protein 2 (IGFBP-2). IGFBP-2, a regulator of insulin-like growth factor action, is overexpressed in the majority of breast and ovarian cancers. Using algorithms, we predicted 29 HLA-DR1–binding epitopes. Binding assays targeting 15 different HLA-DRs revealed that 10 epitopes were degenerate, binding to at least four different HLA-DR variants. An IFN-γ enzyme-linked immunosorbent spot assay was used to assess immunity to these 10 epitopes in 48 patients with either breast or ovarian cancer and 18 controls. Elevated T-cell immunity in patients was detected in 4 of the 10 epitopes (IGFBP2.17, IGFBP2.22, IGFBP2.249, and IGFBP2.293). The cumulative T-cell frequency of these four epitopes was elevated in patients relative to controls. All four peptides are naturally processed and presented to CD4 T-cells. The degenerate pool of peptides covers nearly 80% of patients and may be useful for augmenting CD4 T-cell immunity in patients undergoing immunization. [Cancer Res 2008;68(12):4893–901]

Considerable interest in the elastic properties of soft tissue has increased in medicine due to their clinical relevance for monitoring various diseases as well as a biomarker for cancer. A recent emerging field is the use of acoustic radiation force for imaging and estimating the elastic properties of tissue. Newly developed imaging modalities include shear wave elasticity imaging, supersonic shear wave imaging, acoustic radiation force impulse imaging, and vibro-acoustography. In these new methods, the shear wave is used to estimate the elasticity of tissue. We have developed a novel surface wave method for noninvasively estimating the elasticity of tissue [X. Zhang et al., J. Acoust. Soc. Am., 122, 2522-2525 (2007)]. In this method, a localized ultrasound radiation force is remotely and noninvasively applied inside the tissue. The surface wave speed is used to estimate the elasticity of tissue. This method has been further developed and applied to estimate the viscoelasticity of animal myocardium tissue. In this abstract, we report our recent results of in vitro studies on animal myocardium tissue. Both the surface wave and shear wave are measured and analyzed. Noninvasive characterization of viscoelastic properties of myocardium tissue may be a very important tool for assessing heart function.

Abstract Metaplastic breast carcinoma, a rare tumor composed of adenocarcinomatous and nonglandular growth patterns, is characterized by a propensity for distant metastases and resistance to standard anticancer therapies. We sought confirmation that this tumor is a basal-like breast cancer, expressing epidermal growth factor receptor (EGFR) and stem cell factor receptor (KIT). EGFR activating mutations and high copy number (associated with response to tyrosine kinase inhibitor gefitinib) and KIT activating mutations (associated with imatinib sensitivity) were then investigated. Seventy-seven metaplastic cases were identified (1976-2006); 38 with tumor blocks available underwent pathologic confirmation before EGFR and KIT immunohistochemical analyses. A tissue microarray of malignant glandular and metaplastic elements was constructed and analyzed immunohistochemically for cytokeratin 5/6, estrogen receptor, progesterone receptor, and p63, and by fluorescence in situ hybridization for EGFR and HER-2/neu. DNA isolated from individual elements was assessed for EGFR and KIT activating mutations. All assessable cases were negative for estrogen receptor, progesterone receptor, and (except one) HER2. The majority were positive for cytokeratin 5/6 (58%), p63 (59%), and EGFR overexpression (66%); 24% were KIT positive. No EGFR or KIT activating mutations were present; 26% of the primary metaplastic breast carcinomas were fluorescence in situ hybridization-positive, displaying high EGFR copy number secondary to aneusomy (22%) and amplification (4%). We report here that metaplastic breast carcinoma is a basal-like breast cancer lacking EGFR and KIT activating mutations but exhibiting high EGFR copy number (primarily via aneusomy), suggesting that EGFR tyrosine kinase inhibitors should be evaluated in this molecular subset of breast carcinomas. [Mol Cancer Ther 2008;7(4):944–51]

Abstract The cyclooxygenase (COX)-2 enzyme appears to be an important target for cancer chemoprevention. Given the recent emergence of potentially serious cardiovascular toxicity associated with selective COX-2 inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), which inhibit both COX-1 and COX-2, have received renewed attention as candidate chemoprevention agents. Sulindac has shown consistent chemopreventive potential in preclinical studies as well as in a limited number of clinical trials reported to date. For the current pharmacokinetic study, sulindac capsules were prepared to facilitate ample agent supplies for future intervention studies. Encapsulation of the parent compound (sulindac sulfoxide) can be readily accomplished, but the effects of alternate formulations on bioavailability have not been rigorously examined. In the present single-dose, two-period crossover trial, we conducted pharmacokinetic analyses of sulindac in capsule (test) versus tablet (reference) formulations. Overall, bioavailability appeared to be higher for the capsule compared with the tablet formulation based on test-to-reference pharmacokinetic variable ratios for the parent compound alone. However, additional analyses based on the sulfide and sulfone metabolites of sulindac with the same pharmacokinetic variables indicated similar chemopreventive exposures between the capsule and tablet formulations. These data support the use of sulindac capsules, which can be readily prepared with matching placebos, in future blinded chemoprevention trials. (Cancer Epidemiol Biomarkers Prev 2008;17(3):674–9)