Genetic susceptibility to pancreatic cancer and its functional characterisation: The PANcreatic Disease ReseArch (PANDoRA) consortium

Pancreatic cancer is the fourth leading cause of cancer deaths in the European Union and in the USA, but little is known about its genetic susceptibility. The PANcreatic Disease ReseArch (PANDoRA) consortium was established to unite the efforts of different research groups; its aim is to create a large bio-database to uncover new genetic factors for pancreatic cancer risk, response to treatment, and patient survival. So far 2220 cases of pancreatic adenocarcinoma, a smaller number of cases of endocrine pancreatic tumours (n = 86), chronic pancreatitis (n = 272) and 3847 healthy controls have been collected. As a collective effort of the consortium, SNPs associated with pancreatic adenocarcinoma risk from a genome-wide association study performed in Caucasians were replicated. The possibility that the same genetic polymorphisms may influence patient survival as well was also addressed. This collective effort is particularly important for pancreatic cancer because it is a relatively rare disease for which little is known about aetiopathogenesis and risk factors. The recruitment of additional collaborators and partner institutions is continuously on-going.     

Synthesis and structural studies of new copolyimides 2. Influence of pyromellitimide rings on copolymer structure

The reaction of pyromellitic dianhydride (1,2 : 4,5-benzenetetracarboxylic dianhydride) ( 1 ) with L - and D -alanine ( 2 L ) and ( 2 D ) leads to new monomers which were used to synthesize new copolymers. These copolymers were obtained as a product of the condensation of optical isomers of bis[N-(1-chloroformylethyl)]pyromellitimides (CFEP) with poly(ethylene glycol) PEG-2000 ( 5 ). The effect of monomer structure on the structure and thermal properties of the polymers was studied using X-ray diffraction, differential scanning calorimetry and thermogravimetry. The copolymers were compared with similar copolyimides obtained previously from bis(N-chloroformylmethyl)pyromellitimide and poly(ethylene glycol), PEG 2000. The dominating effect of poly(ethylene glycol) comonomer on the crystallinity, structure and thermal stability of these new copolymers is proven.     

Deciphering principles of morphogenesis from temporal and spatial patterns on the integument

Background : How tissue patterns form in development and regeneration is a fundamental issue remaining to be fully understood. The integument often forms repetitive units in space (periodic patterning) and time (cyclic renewal), such as feathers and hairs. Integument patterns are visible and experimentally manipulatable, helping us reveal pattern formative processes. Variability is seen in regional phenotypic specificities and temporal cycling at different physiological stages. Results: Here we show some cellular/molecular bases revealed by analyzing integument patterns. (1) Localized cellular activity (proliferation, rearrangement, apoptosis, differentiation) transforms prototypic organ primordia into specific shapes. Combinatorial positioning of different localized activity zones generates diverse and complex organ forms. (2) Competitive equilibrium between activators and inhibitors regulates stem cells through cyclic quiescence and activation. Conclusions: Dynamic interactions between stem cells and their adjacent niche regulate regenerative behavior, modulated by multi‐layers of macro‐environmental factors (dermis, body hormone status, and external environment). Genomics studies may reveal how positional information of localized cellular activity is stored. In vivo skin imaging and lineage tracing unveils new insights into stem cell plasticity. Principles of self‐assembly obtained from the integumentary organ model can be applied to help restore damaged patterns during regenerative wound healing and for tissue engineering to rebuild tissues. Developmental Dynamics 244:905–920, 2015. © 2015 Wiley Periodicals, Inc.     

Antimycobacterial action of a new glycolipid‐peptide complex obtained from extracellular metabolites of Raoultella ornithinolytica

In this paper, an antimycobacterial component of extracellular metabolites of a gut bacterium Raoultella ornithinolytica from D. veneta earthworms was isolated and its antimycobacterial action was tested using Mycobacterium smegmatis. After incubation with the complex obtained, formation of pores and furrows in cell walls was observed using microscopic techniques. The cells lost their shape, stuck together and formed clusters. Surface‐enhanced Raman spectroscopy analysis showed that, after incubation, the complex was attached to the cell walls of the Mycobacterium. Analyses of the component performed with Fourier transform infrared spectroscopy demonstrated high similarity to a bacteriocin nisin, but energy dispersive X‐ray spectroscopy analysis revealed differences in the elemental composition of this antimicrobial peptide. The component with antimycobacterial activity was identified using mass spectrometry techniques as a glycolipid–peptide complex. As it exhibits no cytotoxicity on normal human fibroblasts, the glycolipid–peptide complex appears to be a promising compound for investigations of its activity against pathogenic mycobacteria.     

High resolution ArrayCGH and expression profiling identifies PTPRD and PCDH17/PCH68 as tumor suppressor gene candidates in laryngeal squamous cell carcinoma

Many classical tumor suppressor genes (TSG) were identified by delineation of bi-allelic losses called homozygous deletions. To identify systematically homozygous deletions in laryngeal squamous cell carcinoma (LSCC) and to unravel novel putative tumor suppressor genes, we screened 10 LSCC cell lines using high resolution array comparative genomic hybridization (arrayCGH) and array based expression analysis. ArrayCGH identified altogether 113 regions harboring protein coding genes that showed strong reduction in copy number indicating a potential homozygous deletion. Out of the 113 candidate regions, 22 novel homozygous deletions that affected the coding sequences of 15 genes were confirmed by multiplexPCR. Three genes were homozygously lost in two cell lines: PCDH17/PCH68, PRR20, and PTPRD. For the 15 homozygously deleted genes, four showed statistically significant downregulation of expression in LSCC cell lines as compared with normal human laryngeal controls. These were ATG7 (1/10 cell line), ZMYND11 (BS69) (1/10 cell line), PCDH17/PCH68 (9/10 cell lines), and PTPRD (7/10 cell lines). Quantitative real-time PCR was used to confirm the downregulation of the candidate genes in 10 expression array-studied cell lines and an additional cohort of cell lines; statistical significant downregulation of PCDH17/PCH68 and PTPRD was observed. In line with this also Western blot analyses demonstrated a complete absence of the PCDH17 and PTPRD proteins. Thus, expression profiling confirmed recurrent alterations of two genes identified primarily by delineation of homozygous deletions. These were PCDH17/PCH68, the protocadherin gene, and the STAT3 inhibiting receptor protein tyrosine phosphatase gene PTPRD. These genes are good candidates for novel TSG in LSCC.     

Transapical aortic valve implantation – a rescue procedure for patients with aortic stenosis and “porcelain aorta”

Surgical aortic valve replacement (AVR) still remains the treatment of choice in symptomatic significant aortic stenosis (AS). Due to technical problems, extensive calcification of the ascending aorta (“porcelain aorta”) is an additional risk factor for surgery and transapical aortic valve implantation (TAAVI) is likely to be the only rescue procedure for this group of patients. We describe the case of an 81-year-old woman with severe AS and “porcelain aorta”, in whom the only available life-saving intervention was TAAVI.     

Distribution of HBV genotypes and mutants among hepatitis B infected patients from northern Poland

Hepatitis B virus (HBV) infection is one of the major global epidemiological problems. The aim of our study was to determine the distribution of HBV genotypes in Poland since the data concerning the spread of HBV viruses in the central-eastern region of Europe is still very limited. HBV DNA was extracted from 58 serum samples. To quantify the level of HBV DNA the Roche Amplicor HBV Monitor Assay was used. To genotype and assign HBV subtypes DNA sequencing methods were performed. The HBV virus from 43 serum samples from hepatitis B infected patients was genotype A (74.1%), 12 cases had genotype D (20.7%), and 3 had the rare in Europe genotype F (5.2%). Prediction of HBV serological subtypes based on HBsAg sequencing showed almost 100% occurrence of subtype adw2 in the group of genotype A samples, three different subtypes in genotype D (ayw2, ayw3, and ayw4), and equal distribution of subtype adw4q- in all 3 cases of genotype F, also the most prevalent subtype in the Amerindians. Our results coincide with the general European HBV prevalence. However, HBV genotype F, which is not a common genotype in European countries, was detected and so was relatively high occurrence of genotype D, which may reflect historical and ethnical migration events in Poland in the past.     

10 years survival of patient with lung cancer and cerebral metastasis

The authors describe the case of survival for the period of 10 years after brain metastasis surgery and removal of the left lung upper lobe due to adeno-squamous cells carcinoma. Surgery did not generate any complications. Within 8 years after the surgery the radiological examination showed infiltrations resembling changes typical for tuberculosis. Microbiological analysis showed a culture of Mycobacterium kansasi leading to diagnosis of mycobacteriosis. Hence the antituberculous treatment was extended to 12 months to be interrupted due to liver damage. Two years later the patient experienced incident of haemoptysis. Detailed examination and assessment of the respiratory tract condition revealed COPD without features of renewal of the neoplastic process or infection by Mycobacterium tuberculosis or mycobacterium other than tuberculosis. This case demonstrates that aggressive surgical approaches to lung cancer with solitary cerebral metastasis significantly improve patient survival and justifies its widespread use.