Irrelevance of Microsatellite Instability in the Epidemiology of Sporadic Pancreatic Ductal Adenocarcinoma

Background and Aims

Pancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.

Methods

MS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27) in 338 consecutive pancreatic ductal adenocarcinoma (PDAC), resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.

Results

Only one PDAC (0.3%) showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5%) LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.

Conclusions

MSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.     

Quantitative trends of zebra mussels in Lake Balaton (Hungary) in 2003–2005 at different water levels

During the extremely dry period between 2000 and 2003, the water level of Lake Balaton decreased by 82 cm and 80% of the stony littoral, an important habitat for the zebra mussel (Dreissena polymorpha), became dry. A recovery period started in 2004 due to intense precipitation, which increased water levels in the lake. Seasonal and spatial variations of the relative abundance, population density, population structure and biomass of the zebra mussel and the relative abundance of the amphipod Chelicorophium curvispinum were monitored in the period of 2003–2005 at four different shoreline sections and in two different portions (on the bottom and near the surface portion of the rip-rap) of Lake Balaton. Along with these studies, a quantitative survey of mussel larvae found in the plankton and of the abundance of mussel feeding diving ducks were made. As a consequence of the water level fall, on the dried part of the stony littoral, numerous zebra mussel druses perished. Following the dry period in early 2004, the relative abundance of the mussel on the bottom stones was smaller than in 2003 and the bottom community was dominated by C. curvispinum. By the end of 2004 and during 2005, the water level returned to normal and the surfaces of the reinundated stones were conducive to the successful colonization of zebra mussels. Hence, they returned as the dominant fauna in 2005. The stones near the surface might provide a new substrate for the recruitment of zebra mussels, probably offering more suitable substrata for the settlement in 2005 than in 2003. Therefore, the new substrata available in 2005 may have encouraged better and more rapid zebra mussel colonization than before. Zebra mussels may be better competitors for new space than C. curvispinum. A minor change of water-level fluctuation in 2005 and the reduction in population size of the mussel feeding waterfowl could have contributed to the intensive spread of zebra mussel by 2005.     

Conversion of oat (<Emphasis Type="Italic">Avena sativa</Emphasis> L.) haploid embryos into plants in relation to embryo developmental stage and regeneration media

Obtaining oat DH lines is only effective via wide crossing with maize. Seven hundred haploid embryos from 21 single F₁ progeny obtained from wide crosses with maize were isolated, divided into four groups according to their size (<0.5 mm, 0.5–0.9 mm, 1.0–1.4 mm, and ≥1.5 mm), and transferred into 190–2 regeneration medium with different growth regulators: 0.5 mg L^?1 kinetin (KIN) and 0.5 mg L^?1 1-naphthaleneacetic acid (NAA); 1 mg L^?1 zeatin (ZEA) and 0.5 mg L^?1 NAA; or 1 mg L^?1 dicamba (DIC), 1 mg L^?1 picloram (PIC), and 0.5 mg L^?1 kinetin (KIN). Among all isolated embryos, approximately 46.1% were between 1.0–1.4 mm, while the smallest group of embryos (7.1%) were those <0.5 mm. The ability of haploid embryos to germinate varied depending on oat genotypes and the size of embryos. Haploid embryos <0.5 mm were globular and did not germinate, whereas embryos ≥1.5 mm had clearly visible coleoptiles, radicles, and scutella, and were able to germinate. Germination of oat haploid embryos varied depending on growth regulators in the regeneration medium. Most haploid embryos germinated on medium with 0.5 mg L^?1 NAA and 0.5 mg L^?1 KIN, while the fewest germinated on medium with 1 mg L^?1 DIC, 1 mg L^?1 PIC, and 0.5 mg L^?1 KIN. One hundred thirty germinated haploid embryos converted into haploid plants. Fifty oat DH lines were obtained after colchicine treatment.     

Effect of S-methylmethionine on the photosynthesis in maize at different chilling temperatures

The effect of the natural compound S-methylmethionine (SMM) on the functioning of the photosynthetic apparatus, the efficiency of photosynthesis and the synthesis of stress-induced phenoloids and anthocyanins involved in defence was investigated in young maize plants exposed to moderate and severe chilling stress. Damage to PSII was observed as a reduction in the value of variable fluorescence (Fv/Fm) which could be detected even after few hours of mild chilling stress. At temperatures below 10°C, the reduction in Fv/Fm was more pronounced. Changes in the value of net photosynthesis exhibited a similar tendency. SMM has a moderating effect on this reduction and its protective effect was more pronounced under long-lasting chilling stress and at the lowest temperatures. Monitoring of fluorescence intensities and ratios correlated with the levels of stress defence compounds. The fluorescence intensities were found to increase over the course of chilling stress in response to SMM, with the highest values being recorded in plants exposed to the longest period of stress. A similar tendency was observed for the quantity of anthocyanins. The results confirm the complex role of SMM, which is manifested both in preserving the ability of the photosynthetic apparatus to function and in stimulating the synthesis of metabolites involved in stress defence.     

Decorin-TGFβ axis in hepatic fibrosis and cirrhosis

Hepatic fibrosis and cirrhosis are worldwide health care problems, especially in regions with a high rate of hepatitis infection. As these diseases affect a major part of the human population, the search for antifibrotic therapies has a high priority in medical research. Transforming growth factor β1 (TGF-β1) is one of the most powerful profibrotic cytokines. Thus, blocking TGF-β1 activity by natural inhibitors represents a valid and logical strategy to combat hepatic fibrosis. One of the natural inhibitors of TGF-β1 is decorin, a small leucine-rich proteoglycan that binds with high affinity to this cytokine and prevents its interaction with pro-fibrotic receptors. Recent evidence has shown that decorin has a protective role in liver fibrogenesis insofar as its genetic ablation in mice leads to enhanced matrix deposition, impaired matrix degradation, and "activation" of hepatic stellate cells, the main producers of fibrotic tissue. Moreover, TGF-β1 exerts a stronger effect when functional decorin is absent. These data provide robust genetic evidence for a direct role of endogenous decorin in preventing and retarding hepatic fibrosis. Thus, boosting the endogenous production of decorin or systemic delivery of recombinant decorin could represent an additional therapeutic modality against hepatic fibrosis.