Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy in KRAS Wild-Type Patients

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit. KRAS mutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction of KRAS wild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation of BRAF, NRAS, PIK3CA, and PTEN status could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.

Multiple stable reference points in oyster populations: biological relationships for the eastern oyster (Crassostrea virginica) in Delaware Bay

Abstract—In the first of two companion papers, a 54-yr time series for the oyster population in the New Jersey waters of Delaware Bay was analyzed to develop biological relationships necessary to evaluate maximum sustainable yield (MSY) reference points and to consider how multiple stable points affect reference point-based management. The time series encompassed two regime shifts, one circa 1970 that ushered in a 15-yr period of high abundance, and a second in 1985 that ushered in a 20-yr period of low abundance. The intervening and succeeding periods have the attributes of alternate stable states. The biological relationships between abundance, recruitment, and mortality were unusual in four ways. First, the broodstock–recruitment relationship at low abundance may have been driven more by the provision of settlement sites for larvae by the adults than by fecundity. Second, the natural mortality rate was temporally unstable and bore a nonlinear relationship to abundance. Third, combined high abundance and low mortality, though likely requiring favorable environmental conditions, seemed also to be a self-reinforcing phenomenon. As a consequence, the abundance –mortality relationship exhibited both compensatory and depensatory components. Fourth, the geographic distribution of the stock was intertwined with abundance and mortality, such that interrelationships were functions both of spatial organization and inherent populatio

Biological response to changes in climate patterns: population increases of gray snapper (Lutjanus griseus) in Texas bays and estuaries

The increase in the abundance of gray snapper (Lutjanus griseus) in Texas bays and estuaries over the past 30 years is correlated to increased wintertime surface water temperatures. Trends in the relative abundance of gray snapper are evaluated by using monthly fishery-independent monitoring data from each of the seven major estuaries along the Texas coast from 1978 through 2006. Environmental conditions during this period demonstrated increasing annual sea surface temperatures, although this increase was not seasonally uniform. The largest proportion of temperature increases was attributed to higher winter temperature minimums since 1993. Positive phases of the North Atlantic Oscillation, resulting in wetter, warmer winters in the eastern United States have occurred nearly uninterrupted since the late 1970s, and unprecedented positive index values occurred between 1989 and 1995. Increases in water temperature in Texas estuaries, beginning in the early 1990s, are postulated to provide both favorable over-wintering conditions for the newly settled juveniles and increased recruitment success. In the absence of cold winters, this species has established semipermanent estuarine populations across the entire Texas coast. A shift to negative phases of the North Atlantic Oscillation will likely result in returns to colder winter temperature minimums that could reverse any recent population gains.

Modification of the biological intercept model to account for ontogenetic effects in laboratory-reared delta smelt (Hypomesus transpacificus)*

We investigated age, growth, and ontogenetic effects on the proportionality of otolith size to fish size in laboratory-reared delta smelt (Hypomesus transpacificus) from the San Francisco Bay estuary. Delta smelt larvae were reared from hatching in laboratory mesocosms for 100 days. Otolith increments from known-age fish were enumerated to validate that growth increments were deposited daily and to validate the age of fish at first ring formation. Delta smelt were found to lay down daily ring increments; however, the first increment did not form until six days after hatching. The relationship between otolith size and fish size was not biased by age or growth-rate effects but did exhibit an interruption in linear growth owing to an ontogenetic shift at the postflexon stage. To back-calculate the size-at-age of individual fish, we modified the biological intercept (BI) model to account for ontogenetic changes in the otolith-size−fish-size relationship and compared the results to the time-varying growth model, as well as the modified Fry model. We found the modified BI model estimated more accurately the size-at-age from hatching to 100 days after hatching. Before back-calculating size-at-age with existing models, we recommend a critical evaluation of the effects that age, growth, and ontogeny can have on the otolith-size−fish-size relations

Biological characteristics and mortality of western butterfish (Pentapodus vitta), an abundant bycatch species of prawn trawling and recreational fishing in a large subtropical embayment

The western butterfish (Pentapodus vitta) is numerous in the bycatch of prawn trawling and recreational fishing in Shark Bay, Western Australia. We have thus determined crucial aspects of its biological characteristics and the potential impact of fishing on its abundance within this large subtropical marine embayment. Although both sexes attained a maximum age of 8 years, males grow more rapidly and to a larger size. Maturity is attained at the end of the first year of life and spawning occurs between October and January. The use of a Bayesian approach to combine independent estimates for total mortality, Z, and natural mortality, M, yielded slightly higher point estimates for Z than M. This result indicates that P. vitta is lightly impacted by fishing. It is relevant that, potentially, the individuals can spawn twice before recruitment into the fishery and that 73% of recreationally caught individuals are returned live to the water.

The half-lives of biological activity of some pesticides in water

In the absence of analytical methods, the half-lives of biological activity of pesticides can be estimated by bioassays. To determine the half-lives of biological acivity of pesticides to fish, static bioassays were conducted in the laboratory with ten different formulations of pesticides using Labeo rohita as a bio-indicator. The half-lives of biological activity for ten different pesticides in soft water at pH 7.5 and 27°C, ranged from 4.6 days to 11.8 days. The half-life of biological activity of Sumithion 50% EC was only 4.6 days. In contrast, Dimecron 50% EC degraded very slowly and its half-life of biological activity on L. rohita was about 11.8 days. Sumithion 50% EC, Padan 50% SP, EPN 45% EC, Diazinon 40% EC and Diazinon 10 G degraded in less than five to seven days indicating that these pesticides are desirable for rice-fish culture. Contamination by pesticides with long-term residual toxicity in waters may eventually cause high levels of fish mortality.