Cancer: Towards a general theory of the target

General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality‐inhibition, and ‘acausal’ recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable.     

Abnormal Whole Blood Thrombi in Humans with Inherited Platelet Receptor Defects

To delineate the critical features of platelets required for formation and stability of thrombi, thromboelastography and platelet aggregation measurements were employed on whole blood of normal patients and of those with Bernard-Soulier Syndrome (BSS) and Glanzmann’s Thrombasthenia (GT). We found that separation of platelet activation, as assessed by platelet aggregation, from that needed to form viscoelastic stable whole blood thrombi, occurred. In normal human blood, ristocetin and collagen aggregated platelets, but did not induce strong viscoelastic thrombi. However, ADP, arachidonic acid, thrombin, and protease-activated-receptor-1 and -4 agonists, stimulated both processes. During this study, we identified the genetic basis of a very rare double heterozygous GP1b deficiency in a BSS patient, along with a new homozygous GP1b inactivating mutation in another BSS patient. In BSS whole blood, ADP responsiveness, as measured by thrombus strength, was diminished, while ADP-induced platelet aggregation was normal. Further, the platelets of 3 additional GT patients showed very weak whole blood platelet aggregation toward the above agonists and provided whole blood thrombi of very low viscoelastic strength. These results indicate that measurements of platelet counts and platelet aggregability do not necessarily correlate with generation of stable thrombi, a potentially significant feature in patient clinical outcomes.     

Lipocalin-2: pro- or anti-apoptotic?

Survival and apoptosis signaling pathways are altered concomitantly in response to numerous endogenous and exogenous stressors. The lipocalin family of small soluble proteins has been implicated in modulating apoptosis. However, the overall effect of these proteins has been variable, showing both pro- and anti-apoptotic activities. The goal of this minireview is to summarize the studies on lipocalins and apoptosis and consider what roles lipocalin-2 may play in cell death and survival.     

Mediators of ocular angiogenesis

Angiogenesis is the formation of new blood vessels from pre-existing vasculature. Pathologic angiogenesis in the eye can lead to severe visual impairment. In our review, we discuss the roles of both pro-angiogenic and anti-angiogenic molecular players in corneal angiogenesis, proliferative diabetic retinopathy, exudative macular degeneration and retinopathy of prematurity, highlighting novel targets that have emerged over the past decade.     

Facial Skin Coloration Affects Perceived Health of Human Faces

Numerous researchers have examined the effects of skin condition, including texture and color, on the perception of health, age, and attractiveness in human faces. They have focused on facial color distribution, homogeneity of pigmentation, or skin quality. We here investigate the role of overall skin color in determining perceptions of health from faces by allowing participants to manipulate the skin portions of color-calibrated Caucasian face photographs along CIELab color axes. To enhance healthy appearance, participants increased skin redness (a*), providing additional support for previous findings that skin blood color enhances the healthy appearance of faces. Participants also increased skin yellowness (b*) and lightness (L*), suggesting a role for high carotenoid and low melanin coloration in the healthy appearance of faces. The color preferences described here resemble the red and yellow color cues to health displayed by many species of nonhuman animals.     

Scale dependent effects of native prey diversity,prey biomass and natural disturbance on the invasion success of an exotic predator

There is growing support for the general notion that the drivers of invasion success often shift from biotic to abiotic factors with increasing spatial scale. Most of this research, however, has been conducted on a single trophic level; i.e. it has primarily looked at how the diversity of native competitors may influence invasion success. Less attention has been paid to understanding how native prey diversity may influence the invasion success of exotic predators and whether such biotic factors are scale-dependent. We used a hierarchical spatial survey of 17 stream communities to test whether native prey diversity, along with native prey biomass, algal resource abundance and annual stream discharge, influenced the abundance of an exotic crayfish predator, and whether the importance of these factors were scale-dependent. We used a hierarchical generalized linear model to evaluate the influence of these community and stream characteristics on exotic crayfish abundance at both the transect scale (1 m²) and the stream scale (400 m²). Our results indicated that at the stream scale, high stream discharge significantly limited invader abundance. However, at the smaller transect scale, native prey biomass was a significant driver of invasion success and positively correlated with invader abundance. We suggest that our results add to the emerging pattern that abiotic processes are stronger determinants of invasion success at large spatial scales, whereas biotic processes become more important with decreasing spatial scale. However, for predator invasions, prey biomass, not prey diversity may be a more important for driver of invasion success at small spatial scales.     

Cytogenetic effects of nine <Emphasis Type="Italic">Helichrysum</Emphasis> taxa in human lymphocytes culture

Helichrysum Mill. (Asteraceae) species have been used in folk medicine for thousands of years in the world. The in vitro cytogenetic effects in human lymphocytes of nine Helichrysum taxa used in Turkey folk medicine were investigated. Blood samples were obtained from healthy donors, non-smoking volunteers, which were incubated and exposed to increasing concentrations of methanol extracts of Helichrysum taxa (0.01, 0.05, 0.1, 0.5 and 1 mg/mL). The inhibitory effects of H. stoechas (L.) Moench subsp. barrelieri (Ten.) Nyman, H. armenium DC. subsp. armenium, H. armenium DC. subsp. araxinum (Kirp.) Takht., H. plicatum DC. subsp. plicatum, H. compactum Boiss. and H. artvinense P.H.Davis & Kupicha on the mitotic index and replication index indicate that these taxa can have genotoxic and mutagenic effects. They should therefore not be used freely in alternative medicine although their antiproliferative activity may suggest anticarcinogenic properties. Increase effects of H. stoechas subsp. barrelieri, H. armenium subsp. armenium, H. armenium subsp. araxinum, H. chasmolycicum P.H.Davis, H. plicatum subsp. plicatum, H. compactum and H. artvinense on the micronucleus rates showed that these taxa can have genotoxic and carcinogenic effects.     

Direction of Temperature Control in the Thermal Biofeedback Treatment of Vascular Headache

In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA), 70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received 12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4 weeks after treatment, HA Index was significantly (p=.003) reduced as was HA medication consumption. There were no differential reducations in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a specific effect of TBF for hand warming on vascular HA activity.