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View the Table of Contents for the February 15 issue of Cancer Research
Page 1180
Multiphoton laser scanning microscopy (MPLSM) is a potentially attractive technique for the diagnosis of epithelial precancers and cancers. This technology can noninvasively generate three-dimensional fluorescence images deep within tissue with subcellular resolution. In this study, Skala et al. demonstrate the feasibility of using MPLSM to quantify the fluorescence intensity and morphological changes in epithelial precancers and cancers in an animal model. Features quantified from the MPLSM images (nuclear density, keratin layer thickness, epithelial thickness, and fluorescence in the keratin and epithelial layers) show statistically significant differences among normal, precancerous, and cancerous tissues. MPLSM does not require tissue biopsy, sectioning, or staining and, in the future, could be applied in vivo in a clinical setting with multiphoton fluorescence endoscopy.
Page 1259
The SWR mouse model for spontaneous ovarian granulosa cell tumorigenesis is an accurate disease model for juvenile-onset granulosa cell tumors that develop in infants and young girls. To identify genetic determinants of tumor susceptibility in the mouse model that could be further investigated in human cases, Dorward et al. performed a genome-wide genetic linkage analysis. A distal locus on mouse Chr 4 (Gct1) was verified as an important susceptibility locus for development of this ovarian tumor, along with new modifier loci on mouse Chr 1, 2, and 13, plus additional genetic interactions that contribute to this complex phenotype.
Page 1394
Nonmelanoma skin cancer is the most common malignancy among Caucasians. Human papillomaviruses (HPV) associated with skin cancer in epidermodisplasia verruciformis (EV) patients are prevalent in the general population. To explore their still-debated carcinogenic potential, Schaper et al. established transgenic mice with the complete early genome region of EV-HPV8 and targeted expression to the basal epithelial layer. The mice developed multifocal papillomas with varying degrees of dysplasia and squamous cell carcinomas. According to these results EV-associated HPV have to be further considered as relevant skin carcinogens in man.
Page 1471
Due to their rapid systemic clearance and improved tumor penetration, small, engineered antibody-based molecules may offer a particularly effective platform for the targeted ImmunoPET detection of solid tumors. Robinson et al. evaluated a 50 kDa anti-HER2 diabody molecule labeled with the positron emitting radioisotope Iodine-124 in immunodeficient mice bearing established human tumor xenografts that overexpress or lack HER2. In these studies, quantifiable HER2-dependent tumor imaging was observed using a clinical PET/CT scanner, indicating that diabodies may represent an effective molecular structure for the development of novel PET radiotracers.
Page 1479
The c-Met receptor is often up-regulated in cancer and plays a key role in tumor invasion and metastasis. To explore c-Met as a therapeutic target in non-small cell lung cancer (NSCLC), Ma et al. showed the functional expression of c-Met in NSCLC and determined that c-Met can sometimes be mutated, especially within the semaphorin and juxtamembrane domains. They successfully validated c-Met as a therapeutic target using siRNA inhibition and selective small molecule inhibitor SU11274 in NSCLC. This study shows promise for targeting c-Met and its mutated variants in therapeutic inhibition against NSCLC.