Stopping drinking and risk of oesophageal cancer.

OBJECTIVE--To examine the effect of stopping drinking on the risk of oesophageal cancer. DESIGN--Hospital based case-control study. SETTING--Surgical departments of four district general hospitals and general practices in Hong Kong. SUBJECTS--Cases were 400 consecutive admissions of patients with histologically confirmed diagnosis of oesophageal cancer during a 21 month period in 1989-90 (87% response rate). Controls were 1598 patients selected from the same surgical departments as the cases and from the general practices from which the cases were originally referred (95% response rate). MAIN OUTCOME MEASURE--Relative risk of developing oesophageal cancer after stopping drinking (adjusted for age, education, place of birth, smoking, and diet). RESULTS--Current light drinking (< 200g ethanol/week) was not associated with significant increase in risk. Among former drinkers risk fell more quickly in moderate (200-599 g/week) than heavy (> or = 600 g/week) drinkers. Even among heavy drinkers, however, risk had dropped substantially after five to nine years of not drinking. The results suggest that the time taken for risk to return to that in subjects who never drink was 10-14 years for moderate drinkers and 15 years or more, if ever, for heavy drinkers. CONCLUSION--Risk of oesophageal cancer decreases fairly rapidly with time after abstaining from drinking. This new finding could be used in health promotion to encourage behavioural changes, especially in heavy drinkers, who have a very high risk of developing oesophageal cancer. It also suggests that alcoholic beverages have a strong effect on the late stage of carcinogenesis.     

Stopping the beating heart of cancer: KRAS reviewed

It has taken four decades of research to see the first major breakthrough for KRAS-driven cancers. In particular, the last decade has seen a paradigm shift with the discovery of druggable pockets on KRAS and clinical efficacy with covalent KRAS^G12C inhibitors, culminating in the first approval of sotorasib monotherapy as second-line treatment in KRAS^G12C-driven non–small-cell lung cancer. Nevertheless, 85% of all KRAS-mutated cancers still lack novel agents. In this review, we will outline the structure, function, and post-translational modifications of KRAS and highlight the various approaches being adopted to drug KRAS, ranging from selective to pan concepts. The range of molecular modalities being explored, including PROTACs and glues, will also be described. Finally, an outlook toward the next wave of KRAS drugs and the challenges of resistance will be given.     

Azorhizobium caulinodans ORS571 colonizes the xylem of Arabidopsis thaliana

Improved conditions were used for the aseptic growth of Arabidopsis thaliana to investigate whether xylem colonization of A. thaliana by Azorhizobium caulinodans ORS571 might occur. When seedlings were inoculated with ORS571 (pXLGD4) tagged with the lacZ reporter gene, nearly all of the plants showed blue regions of ORS571 colonization at lateral root cracks (LRC). The flavonoids naringenin and liquiritigenin significantly stimulated colonization of LRC by ORS571. Blue bands of ORS571 (pXLGD4) bacteria were observed histochemically in the xylem of intact roots of inoculated plants. Detailed microscopic analysis of sections of primary and lateral roots from inoculated A. thaliana confirmed xylem colonization. Xylem colonization also occurred with an ORS571 nodC mutant deficient in nodulation factors. There was no significant difference in the percentage of plants with xylem colonization or in the mean length of xylem colonized per plant between plants inoculated with either ORS571 (pXLGD4) or ORS571::nodC (pXLGD4), with or without naringenin.     

Pseudomonas syringae colonizes distant tissues in Nicotiana benthamiana through xylem vessels

The ability to move from the primary infection site and colonize distant tissue in the leaf is an important property of bacterial plant pathogens, yet this aspect has hardly been investigated for model pathogens. Here we show that GFP‐expressing Pseudomonas syringae pv. syringae DC3000 that lacks the HopQ1‐1 effector (PtoDC3000ΔhQ) has a strong capacity to colonize distant leaf tissue from wound‐inoculated sites in N. benthamiana. Distant colonization occurs within 1 week after toothpick inoculation and is characterized by distant colonies in the apoplast along the vasculature. Distant colonization is blocked by the non‐host resistance response triggered by HopQ1‐1 in an SGT1‐dependent manner and is associated with an explosive growth of the bacterial population, and displays robust growth differences between compatible and incompatible interactions. Scanning electron microscopy revealed that PtoDC3000ΔhQ bacteria are present in xylem vessels, indicating that they use the xylem to move through the leaf blade. Distant colonization does not require flagellin‐mediated motility, and is common for P. syringae pathovars that represent different phylogroups.     

Discovering an epidemic before it has reached a certain level of prevalence

In this communication we calculate the probability of discovering a simple epidemic in a large population before the epidemic has reached a given level of prevalence, by regularly taking a small random sample from the population for microbiological screening. Apart from the general formula which has to be evaluated numerically, we derive various simple approximation formulae which shed light on the properties of various monitoring regimes. These formulae are, moreover, rather robust against deviations from the model specifications. The results are applied to the evaluation of the efficiency of an infection-monitoring program in an animal breeding centre.     

Stopping ras in its tracks

Ras interacts with many downstream effectors that regulate complex cytoplasmic signaling networks. In this issue, Gupta et al. (2007) use mouse models of Ras-mediated tumorigenesis to show that the interaction of Ras with a single isoform of phosphatidylinositol 3-kinase (PI3K), called p110alpha (PIK3CA), is critical for tumor formation. This result will stimulate re-evaluation of pharmacological approaches to target Ras for cancer treatment.     

Eriophyid mite Floracarus perrepae readily colonizes recovering invasive vine Lygodium microphyllum following herbicide treatment

Lygodium microphyllum (Cav.) R. Br. (Schizaeales: Lygodiaceae) is among the most damaging invasive plant species in Florida, USA. Following mechanical and herbicide treatment, the plant typically recovers to pre-treatment levels within 1–2 years through regrowth from the adult rhizome and recruitment of new sporelings. A classical biocontrol agent, the gall-inducing mite Floracarus perrepae Knihinicki & Boczek (Acariformes: Eriophyidae), could attack recovering L. microphyllum, thereby reducing the need for repeated treatments. Here, we investigated natural F. perrepae colonization of recovering L. microphyllum following treatment using two field experiments. First, we monitored F. perrepae colonization on adult regrowth and sporelings on tree islands that were clipped and treated with herbicide (glyphosate or triclopyr). At 24 months post-treatment, mite galls were most abundant on glyphosate treated islands where?>?50% of adult rachises and?>?80% of sporelings exhibited galls and were rare on untreated islands. Second, we investigated the separate effects of clipping and herbicide (triclopyr) treatment on F. perrepae colonization of regrowth within small-scale plots at four heavily invaded sites. Galls were most prevalent following cutting and least prevalent following herbicide seven months post-treatment, but, on a per pinna (i.e., leaflet) basis, were equivalent across treatments. Taken together, we report that both L. microphyllum regrowth and especially sporelings were highly susceptible to colonization by F. perrepae. Our findings suggest that biological control of L. microphyllum is compatible with herbicide treatment, and future research is needed to determine how best to integrate these management tactics.