Treatment of type 2 diabetes mellitus and risk of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most common cancer of the exocrine part of the pancreas with poor prognosis. Up to 85% of PDAC patients are diagnosed with diabetes or hyperglycaemia at the time of diagnosis indicating that impaired glucose homeostasis is a common event in this cancer. A mechanism of association between PDAC and diabetes is very complex and still not fully understood. Currently, the various classes of anti-diabetic drugs are used in diabetes treatment. It is possible that specific types of anti-diabetic drugs for diabetes may have different impacts on pancreatic cancer development. Moreover, the intriguing question of whether diabetes can facilitate PDAC development remains unanswered. This paper presents the results of recent studies on the effect of the anti-diabetic treatment used on pancreatic cancer risk in diabetic patients

Patients' opinions about Polish surgeons and surgical treatment

In Polish society Stereotypes about the surgeons are deeply rooted, which could really affect their relationship with the patient and the entire treatment process. The aim of the study was to evaluate the results of an opinion survey on the image of the surgeon and operative treatment. Material and methods. Between 1 January and 30 October 2012, 1000 patients were examined by use of a original questionnaire containing 25 questions. Results were analyzed statistically by STATISTICA test. Differences between groups were tested using Chi-square test (X²) with Yates modification, adopting the significance level α = 0.05. Results. The study group consisted of 1000 patients, including 56% of women (n = 560) and 44% of men (n = 440). The media image of Polish surgeon was identified as positive by 78% of respondents. A majority of patients (74%) considered that the Polish surgeons had equal level of competence and skills as foreign specialists. The greatest trust of the respondents (n = 537) had surgeons in middle age (40‑60 years). For the majority of patients (n = 649) a sex of the surgeon had no significance. Respondents clearly stated that a surgeon performing the operation should not have additional financial rewards. Almost all respondents in medical emergencies without hesitation declared their agreement to surgery (n = 974). Conclusions. Present knowledge of Polish patients about surgeons and surgical treatment is high. The surgeon has a high social prestige, respect and appreciation, and his image in the opinion of the vast majority of respondents is positive

Memorandum of understanding relating to the comprehensive, continuing and cooperative transportation planning process in the Boston Metropolitan Area

INTRODUCTION:We undertook a comparative survey of gastric emptying (GE) kinetics after two variants of bypass surgery for upper bowel obstruction. MATERIAL & METHODS:In 10 dogs with experimental upper bowel obstruction, five were randomized to obtain gastrojejunal anastomosis (GA), and the other five received Roux-en-Y duodenojejunal anastomosis (DA). Duplicate scintigraphic measurements of GE of a solid meal were accomplished in every animal before surgery and during the early (2-3 weeks), medium (3 months), and late (6 months) post-operative period. The GE curves were fitted with a power-exponential function to derive the GE half time T½, and the curve shape parameter S. RESULTS:Early after surgery T½ slightly decreased by -18±21 min in the DA group and lengthened by 91±37 min in the GA group (p = 0.042). In both groups an increase in the S parameter was found then. In either group T½ gradually declined towards the basal value during the medium and late post-operative period. On the other hand, net differences relative to the basal situation in the S values appeared to be positive in the GA group (0.32±0.11 at 3 months; 0.64±0.19 at six months), and negative in the DA group (-0.30±0.09 at 3 months; -0.01±0.20 at six months). Hence a statistically significant contrast was found between those differences: p = 0.0022 at 3 months, and p = 0.045 at six months after the surgery. CONCLUSION:Roux-en-Y duodenojejunal anastomosis appears to be superior to the classical gastrojejunal anastomosis while restoring patency of the gastrointestinal passage in the case of upper bowel obstruction

Clinical relevance of DNA microarray analyses using archival formalin-fixed paraffin-embedded breast cancer specimens

Abstract Background The ability of gene profiling to predict treatment response and prognosis in breast cancers has been demonstrated in many studies using DNA microarray analyses on RNA from fresh frozen tumor specimens. In certain clinical and research situations, performing such analyses on archival formalin fixed paraffin-embedded (FFPE) surgical specimens would be advantageous as large libraries of such specimens with long-term follow-up data are widely available. However, FFPE tissue processing can cause fragmentation and chemical modifications of the RNA. A number of recent technical advances have been reported to overcome these issues. Our current study evaluates whether or not the technology is ready for clinical applications. Methods A modified RNA extraction method and a recent DNA microarray technique, cDNA-mediated annealing, selection, extension and ligation (DASL, Illumina Inc) were evaluated. The gene profiles generated from FFPE specimens were compared to those obtained from paired fresh fine needle aspiration biopsies (FNAB) of 25 breast cancers of different clinical subtypes (based on ER and Her2/neu status). Selected RNA levels were validated using RT-qPCR, and two public databases were used to demonstrate the prognostic significance of the gene profiles generated from FFPE specimens. Results Compared to FNAB, RNA isolated from FFPE samples was relatively more degraded, nonetheless, over 80% of the RNA samples were deemed suitable for subsequent DASL assay. Despite a higher noise level, a set of genes from FFPE specimens correlated very well with the gene profiles obtained from FNAB, and could differentiate breast cancer subtypes. Expression levels of these genes were validated using RT-qPCR. Finally, for the first time we correlated gene expression profiles from FFPE samples to survival using two independent microarray databases. Specifically, over-expression of ANLN and KIF2C, and under-expression of MAPT strongly correlated with poor outcomes in breast cancer patients. Conclusion We demonstrated that FFPE specimens retained important prognostic information that could be identified using a recent gene profiling technology. Our study supports the use of FFPE specimens for the development and refinement of prognostic gene signatures for breast cancer. Clinical applications of such prognostic gene profiles await future large-scale validation studies

3T3 Cell Lines Stably Expressing Pax6 or Pax6(5a) – A New Tool Used for Identification of Common and Isoform Specific Target Genes

Pax6 and Pax6(5a) are two isoforms of the evolutionary conserved Pax6 gene often co-expressed in specific stochiometric relationship in the brain and the eye during development. The Pax6(5a) protein differs from Pax6 by having a 14 amino acid insert in the paired domain, causing the two proteins to have different DNA binding specificities. Difference in functions during development is proven by the fact that mutations in the 14 amino acid insertion for Pax6(5a) give a slightly different eye phenotype than the one described for Pax6. Whereas quite many Pax6 target genes have been published during the last years, few Pax6(5a) specific target genes have been reported on. However, target genes identified by Pax6 knockout studies can probably be Pax6(5a) targets as well, since this isoform also will be affected by the knockout. In order to identify new Pax6 target genes, and to try to distinguish between genes regulated by Pax6 and Pax6(5a), we generated FlpIn-3T3 cell lines stably expressing Pax6 or Pax6(5a). RNA was harvested from these cell lines and used in gene expression microarrays where we identified a number of genes differentially regulated by Pax6 and Pax6(5a). A majority of these were associated with the extracellular region. By qPCR we verified that Ncam1, Ngef, Sphk1, Dkk3 and Crtap are Pax6(5a) specific target genes, while Tgfbi, Vegfa, EphB2, Klk8 and Edn1 were confirmed as Pax6 specific target genes. Nbl1, Ngfb and seven genes encoding different glycosyl transferases appeared to be regulated by both. Direct binding to the promoters of Crtap, Ctgf, Edn1, Dkk3, Pdgfb and Ngef was verified by ChIP. Furthermore, a change in morphology of the stably transfected Pax6 and Pax6(5a) cells was observed, and the Pax6 expressing cells were shown to have increased proliferation and migration capacities

DAN (NBL1) promotes collective neural crest migration by restraining uncontrolled invasion

Neural crest cells are both highly migratory and significant to vertebrate organogenesis. However, the signals that regulate neural crest cell migration remain unclear. Here, we test the function of DAN, a BMP antagonist we detected by analysis of chick cranial mesoderm. Our analysis shows that, prior to neural crest cell exit from the hindbrain, DAN is expressed in the mesoderm, then it becomes absent along cell migratory pathways. Cranial neural crest and metastatic melanoma cells avoid DAN protein stripes in vitro. Addition of DAN reduces the speed of migrating cells, in vivo and in vitro respectively. In vivo loss-of-function of DAN results in enhanced neural crest cell migration by increasing speed and directionality. Computer model simulations support the hypothesis that DAN restrains cell migration by regulating cell speed. Taken together, our results identify DAN as a novel factor that inhibits uncontrolled neural crest and metastatic melanoma invasion and promotes collective migration in a manner consistent with inhibition of BMP signaling