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View the Table of Contents for the November 15 issue of Cancer Research.
Seftor et al. Page 10164
The clinical management of cutaneous melanoma would benefit significantly from a better understanding of the molecular changes that occur during melanocytic neoplasia. To gain unique insights into this process, Seftor et al. developed a 3-D in vitro model that allows observations of normal human melanocytes interacting with a metastatic melanoma matrix to determine whether these normal cells could be reprogrammed by inductive cues in the tumor cell microenvironment. This novel approach identified specific genes involved in the epigenetic transdifferentiation of melanocytes to an aggressive melanoma-like phenotype, which may offer significant therapeutic value in the earliest detection of melanocytic transformation.
Jackson et al. Page 10280
Roughly half of all human tumors have missense mutations in the p53 tumor suppressor gene. To compare the effects of different p53 mutations in vivo, Jackson et al. examined the effects of several alleles within a single tumor type. Interestingly, they observed a dominant-negative effect by the p53R270H allele on lung tumor size and grade, which was not observed with the p53R172H or null allele, and found that both missense alleles promote the formation of sinonasal carcinomas. Their findings demonstrate tissue-specific effects of different p53 mutations and show that individual alleles can have different effects within the same tumor.
Rossi et al. Page 10555
Humans have high titers of natural complement fixing anti-αGal antibodies as a result of constant stimulation by αGal+ bacteria of the pulmonary and intestinal flora. Rossi et al. exploited this naturally acquired immunity as a new adjuvant to induce antitumor immunity. By using αGal knockout mice with anti-αGal antibodies, the authors demonstrate that vaccination with αGal+ tumor cells effectively treated pre-existing αGal-negative subcutaneous or pulmonary melanoma tumors, inducing a long-lasting T-cell–mediated antitumor immunity. This study provides the basis for anovel immunotherapy using αGal+ whole cell vaccines in clinical trials for the treatment of cancer patients.
Honda et al. Page 10613
Multivariate analyses using proteomic data obtained by SELDI-MS have been reported to be highly successful in serum detection of malignancies of various organs, including ovarian cancer. However, there has been concern about the reproducibility of the results obtained with the SELDI-MS system. Honda et al. reviewed various aspects of SELDI-MS and showed the high reproducibility and robustness of plasma protein profiling using a high-resolution MS instrument. They carefully compared the plasma proteomic profiles of a large number of pancreatic cancer patients and healthy controls, and its discriminating performance was validated in two cohorts of different medical institutions.
Ju et al. Page 10623
Ju et al. investigated the effects of two main constituents of green tea, (-)-epigallo-catechin-3-gallate (EGCG) and caffeine, on intestinal tumorigenesis in Apcmin/+ mice. EGCG significantly inhibited intestinal tumorigenesis, whereas caffeine did not. EGCG decreased nuclear β-catenin levels and increased E-cadherin levels in small intestinal tumors, and these effects were recapitulated in HT29 human colon cancer cells under EGCG treatment. EGCG decreased phosphorylation levels of Akt and Erk1/2 in small intestinal tumors. These results indicate that EGCG effectively inhibited intestinal tumorigenesis in Apcmin/+ mice, possibly through the attenuation of aberrant nuclear β-catenin and activated Akt and Erk signaling.