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View the Table of Contents for the December 1 issue of Clinical Cancer Research.
Parikh et al. Page 8512
Pregnancy is associated with reduced breast cancer risk. Parikh et al. report that a small peptide (AFPep), which mimics the active site of a naturally occurring, pregnancy-associated molecule (α-fetoprotein), prevents breast cancer in rats and blocks estrogen-stimulated human breast cancer xenograft growth in SCID mice. No host toxicity was found in animals treated with AFPep. Mechanistic studies showed that AFPep interfered with estrogen-dependent breast cancer growth, inhibited phosphorylation of the estrogen receptor, and activated phosphorylation of p53. They conclude that AFPep is a well-tolerated, mechanistically novel, chemopreventive agent in models of breast cancer and warrants further development for prevention and treatment of this disease in humans.
Li et al. Page 8312
Breast fluids potentially offer a superior source of biomarkers for breast cancer because the proteins present are released locally from breast tissue. Because of the limited specimen availability and protein yield, however, proteomic study of this important fluid remains preliminary. Among the few published studies, only differentially expressed protein spots (by two-dimensional gel analysis) or peaks (by mass spectrometry) have been reported. Li et al. examined breast fluids from patients at multiple institutions and developed a comprehensive proteomic approach that led to the discovery, identification, and validation of neutrophil peptides 1-3 (HNP 1-3) as potential biomarkers for breast cancer.
Nagato et al. Page 8250
Nasal NK/T-cell lymphoma is associated with Epstein-Barr virus and has peculiar clinical features. Little is known, however, about its genetic features. To determine which genes are expressed specifically in this lymphoma, Nagato et al. investigated the gene expression patterns and found that IL-9 was specifically expressed in SNK-6 and SNT-8, which were established from nasal NK/T-cell lymphoma, and that it plays a role as an autocrine growth factor. Moreover, IL-9 expression was detected in biopsies and sera from patients with nasal NK/T-cell lymphoma. These results suggest that the IL-9 signaling pathway may be a new target for the treatment of this lymphoma.
Nam et al. Page 8391
To evaluate new susceptibility genes for prostate cancer in a clinical setting, Nam et al. genotyped 13 polymorphisms among 2,088 men who underwent prostate biopsies for prostate cancer. Four of 13 genes (TNF, KLK2, GSTT1 and HOGG-SC) were found to be significantly associated with prostate cancer. When combined, patients with high-risk alleles from the four genes had an odds ratio of 9.33 (95% C.I.:2.4–35.8; P=0.0005) for having prostate cancer compared with patients with low-risk alleles. This shows promise of new susceptibility genes for prostate cancer being used in a clinical setting to enhance methods of diagnosing prostate cancer.
Karp et al. Page 8403
Flavopiridol targets cyclin-dependent kinases, induces checkpoint arrest, and interrupts transcriptional elongation. In a Phase I clinical trial of flavopiridol followed by ara-C and mitoxantrone for adults with relapsed and refractory acute leukemias, Karp et al. used flavopiridol for initial cytoreduction and to enhance cycle progression of remaining leukemic blasts. Flavopiridol killed leukemic blasts and, when followed by ara-C and mitoxantrone, induced clinical responses in refractory AML (31%) and ALL (12.5%). Flavopiridol downregulated diverse proteins in marrow blasts in vivo, including VEGF. The biological and clinical effects in adults with refractory acute leukemias warrant continuing development of flavopiridol combined with cytotoxic and biologic agents.