A Tissue Biomarker Panel Predicting Systemic Progression after PSA Recurrence Post-Definitive Prostate Cancer Therapy

Many men develop a rising PSA after initial therapy for prostate cancer. While some of these men will develop a local or metastatic recurrence that warrants further therapy, others will have no evidence of disease progression. We hypothesized that an expression biomarker panel can predict which men with a rising PSA would benefit from further therapy.A case-control design was used to test the association of gene expression with outcome. Systemic (SYS) progression cases were men post-prostatectomy who developed systemic progression within 5 years after PSA recurrence. PSA progression controls were matched men post-prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years. Using expression arrays optimized for paraffin-embedded tissue RNA, 1021 cancer-related genes were evaluated-including 570 genes implicated in prostate cancer progression. Genes from 8 previously reported marker panels were included. A systemic progression model containing 17 genes was developed. This model generated an AUC of 0.88 (95% CI: 0.84-0.92). Similar AUCs were generated using 3 previously reported panels. In secondary analyses, the model predicted the endpoints of prostate cancer death (in SYS cases) and systemic progression beyond 5 years (in PSA controls) with hazard ratios 2.5 and 4.7, respectively (log-rank p-values of 0.0007 and 0.0005). Genes mapped to 8q24 were significantly enriched in the model.Specific gene expression patterns are significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence

Mollusc harvesting in the Pre - European contact Pacific Islands: investigating resilience and sustainability

Mollusc shells, which are often quite numerous in archaeological sites throughout the Pacific Islands, offer good proxies for assessing environmental change as well as human impact. Documented changes in species size, richness, and abundance have often been interpreted as evidence of resource abuse by shellfish gatherers. While this may be valid in some cases, archaeologists need to consider other variables to explain change (or stability) in shell distribution. A better understanding of ecological and biological (life history) characteristics associated with shell midden deposits, as well as greater awareness of ethnographic and ethnoarchaeological data on the interaction between people and varieties of marine resources, may result in a reinterpretation of past human behavior. A growing interest in indigenous resource management among contemporary Pacific Island communities has led some archaeologists to seek tangible evidence of community resilience and sustainable use of resources in the past. This chapter draws primarily from direct observations and semi-structured interviews among mollusc gatherers in Kiribati, eastern Micronesia, and examines selected case studies of archaeological shell deposits from the Pacific Islands that could shed new light on marine resource management to complement the more widespread research conclusions that depict human impact in largely negative terms