The anti-diabetic effects of GLP-1-gastrin dual agonist ZP3022 in ZDF rats

Aims/hypothesisCombination treatment with exendin-4 and gastrin has proven beneficial in treatment of diabetes and preservation of beta cell mass in diabetic mice. Here, we examined the chronic effects of a GLP-1-gastrin dual agonist ZP3022 on glycemic control and beta cell dysfunction in overtly diabetic Zucker Diabetic Fatty (ZDF) rats.MethodsZDF rats aged 11 weeks were dosed s.c., b.i.d. for 8 weeks with vehicle, ZP3022, liraglutide, exendin-4, or gastrin-17 with or without exendin-4. Glycemic control was assessed by measurements of HbA1c and blood glucose levels, as well as glucose tolerance during an oral glucose tolerance test (OGTT). Beta cell dynamics were examined by morphometric analyses of beta and alpha cell fractions.ResultsZP3022 improved glycemic control as measured by terminal HbA1c levels (6.2 ± 0.12 (high dose) vs. 7.9 ± 0.07% (vehicle), P < 0.001), as did all treatments, except gastrin-17 monotherapy. In contrast, only ZP3022, exendin-4 and combination treatment with exendin-4 and gastrin-17 significantly improved glucose tolerance and increased insulin levels during an OGTT. Moreover, only ZP3022 significantly enhanced the beta cell fraction in ZDF rats, a difference of 41%, when compared to the vehicle group (0.31 ± 0.03 vs. 0.22 ± 0.02%, respectively, P < 0.05).ConclusionThese data suggest that ZP3022 may have therapeutic potential in the prevention/delay of beta cell dysfunction in type 2 diabetes.     

An in situ study of bioenergetic properties of human colorectal cancer: The regulation of mitochondrial respiration and distribution of flux control among the components of ATP synthasome

The aim of this study is to characterize the function of mitochondria and main energy fluxes in human colorectal cancer (HCC) cells. We have performed quantitative analysis of cellular respiration in post-operative tissue samples collected from 42 cancer patients. Permeabilized tumor tissue in combination with high resolution respirometry was used.Our results indicate that HCC is not a pure glycolytic tumor and the oxidative phosphorylation (OXPHOS) system may be the main provider of ATP in these tumor cells. The apparent Michaelis–Menten constant (K_m) for ADP and maximal respiratory rate (V_m) values were calculated for the characterization of the affinity of mitochondria for exogenous ADP: normal colon tissue displayed low affinity (K_m = 260 ± 55 μM) whereas the affinity of tumor mitochondria was significantly higher (K_m = 126 ± 17 μM). But concurrently the V_m value of the tumor samples was 60–80% higher than that in control tissue. The reason for this change is related to the increased number of mitochondria. Our data suggest that in both HCC and normal intestinal cells tubulin β-II isoform probably does not play a role in the regulation of permeability of the MOM for adenine nucleotides.The mitochondrial creatine kinase energy transfer system is not functional in HCC and our experiments showed that adenylate kinase reactions could play an important role in the maintenance of energy homeostasis in colorectal carcinomas instead of creatine kinase.Immunofluorescent studies showed that hexokinase 2 (HK-2) was associated with mitochondria in HCC cells, but during carcinogenesis the total activity of HK did not change. Furthermore, only minor alterations in the expression of HK-1 and HK-2 isoforms have been observed.Metabolic Control analysis showed that the distribution of the control over electron transport chain and ATP synthasome complexes seemed to be similar in both tumor and control tissues. High flux control coefficients point to the possibility that the mitochondrial respiratory chain is reorganized in some way or assembled into large supercomplexes in both tissues.     

Late gadolinium enhancement MRI quantification to predict left ventricular remodeling after acute myocardial infarction

ObjectivesInfarct size is a major surrogate marker for prognosis in the context of myocardial infarction. There is a growing interest in validating a quantitative assessment approach in order to: (1) standardize these analyses; (2) to precise the individual prognosis of our patients. Several methods are available and were tested across their capacity to predict left ventricular (LV) remodeling at three months.Patients and methodsLate gadolinium enhancement-MRI was performed on day 5 and after a period of three months in 92 patients with STEMI. LV volumes and scar parameters were assessed visually (by using a four scale score) and quantitatively on day 5 and at three months. Dichotomous thresholds were defined first visually (VISUAL), then by 2, 5 and 6 standard deviations above remote myocardium, and by the full-width at half-maximum (FWHM) method.ResultsAll infarct sizing methods showed great relation to LV remodeling at three months (ROC analysis). Univariate predictors of an LV end-systolic volume index (LVESVi) superior to 70 mL/m² were: heart failure, creatin kinase peak and infarct size at day 5. FWHM was shown to be the best of all quantitative methods. An infarct size superior to 44 grams predicted a LVESVi > 70 mL/m² with a sensitivity of 90% and a specificity of 92.5%. FWHM reproducibility was good (r = 0.895, P < 0.0001, Bland Altman bias of 0.8 g).ConclusionIn the context of STEMI, FWHM is a tough and reproducible algorithm to quantitatively assess late gadolinium hyperenhancement, greatly related to functional prognosis at three months follow-up.     

Antileishmanial activity of essential oil from Chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in BALB/c mice

Chenopodium ambrosioides have been used during centuries by native people to treat parasitic diseases.Aims of the studyTo compare the in vivo anti-leishmanial activity of the essential oil (EO) from C. ambrosioides and its major components (ascaridole, carvacrol and caryophyllene oxide).Materials and methodsAnti-leishmanial effect was evaluated in BALB/c mice infected with Leishmania amazonensis and treated with the EO, main compounds and artificial mix of pure components by intralesional route at 30 mg/kg every 4 days during 14 days. Diseases progression and parasite burden in infected tissues were determined.ResultsEO prevented lesion development compared (p < 0.05) with untreated animals and treated with vehicle. In addition, the efficacy of EO was also statistically superior (p < 0.05) compared with the glucantime-treated animals. No potential effects were observed with pure components treatment. Mix of pure compounds cause death of animals after 3 days of treatment.ConclusionsOur results demonstrate the superiority of EO against experimental cutaneous leishmaniasis caused by L. amazonensis.     

Effects of praeruptorin C on blood pressure and expression of phospholamban in spontaneously hypertensive rats

BackgroundThe traditional Chinese medicine Praeruptorin c (Pra-c) has many physiological and pharmacological effects, including antagonistic effects on blood pressure and calcium levels, maintenance of cellular calcium homeostasis, and improved cardiac systolic and diastolic function. It is potentially a novel and versatile drug for the treatment and prevention of cardiovascular diseases.ObjectiveTo explore the possible impact of Pra-c on blood pressure in SHR and its mechanism of action.Materials and methodsTwenty SHR were randomly divided into a Pra-c group [Pra-c was administered intragastrically, 20 mg kg⁻¹ d⁻¹, n = 10] or an untreated control group (n = 10), containing 10 age-matched SD rats. Each group of rats was followed for 8 weeks. Before and during the treatment, tail artery systolic blood pressure was measured using a tail-cuff every 2 weeks. After 8 weeks, the rats were sacrificed and RNA was extracted from homogenates of cardiac tissue. Tissue from the left ventricle was fixed, sectioned and H&E stained to assess possible changes in myocardial cell structure and morphology. Semi-quantitative RT-PCR was used to assess changes in phospholamban gene expression in treated and untreated rats.ResultsSHR treated with Pra-c for 8 weeks had a lower systolic pressure than untreated SHR (p < 0.05), two measures of cardiac damage, the heart mass index and left ventricle mass index (HMI and LVMI, respectively) were improved, and the level of PLB mRNA expression was lower in the untreated SHR group (p < 0.05).Discussion and conclusionWith continuous hypertension, SHR gradually formed or developed cardiac hypertrophy and fibrosis. Pra-c had a clear effect on blood pressure in SHR, and reversed SHR ventricular remodeling by upregulating the gene expression of sarcoplasmic reticulum PLB.     

Feruloyl esterase production by Aspergillus terreus CECT 2808 and subsequent application to enzymatic hydrolysis

Ferulic acid esterases (FAE) were produced by Aspergillus terreus CECT 2808 from vine trimming shoots (VTS) and corn cob. Later, the fungal extracts thus obtained were used to enzymatically release ferulic acid (FA) from both substrates. Our findings showed a higher FAE activity in the enzymatic extracts produced on corn cob (0.070 ± 0.004 U/mL). Nevertheless, the enzymatic extracts produced on VTS demonstrated a better performance for FA release from both corn cob (2.05 ± 0.01 mg/g) and VTS (0.19 ± 0.003 mg/g). This result was probably because of the higher xylanase/FAE ratio determined in VTS extract. Therefore, an additional assay was carried out by supplementing corn cob extract with a commercial xylanase to test the influence of FAE/xylanase ratio in FA release. The results revealed the relevance of the FAE/xylanase ratio for an optimal FA release.     

Prognostic impact of definitive local therapy of the primary tumor in men with metastatic prostate cancer at diagnosis: A population-based,propensity score analysis

BackgroundThis study investigated whether definitive local therapy [radical prostatectomy (RP) or brachytherapy (BT)] of the primary tumor improves survival in men with metastatic prostate cancer (PrCA) at diagnosis.MethodsData on newly diagnosed metastatic PrCA cases (stage IV, N = 7858) were obtained from the Surveillance Epidemiology and End Results (SEER) program. Conventional multivariable survival analysis and propensity score analysis were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (95% CI) comparing men who underwent definitive local therapy of the primary tumor to those who did not.ResultsAfter adjusting for sociodemographic and tumor attributes, having RP after diagnosis with metastatic PrCA was associated with 73% (HR = 0.27, 95% CI: 0.20–0.38) lower risk of all-cause mortality and 72% (HR = 0.28, 95% CI: 0.20–0.39) reduced risk of death from PrCA. Having BT also was associated with 57% (HR = 0.43, 95% CI: 0.31–0.59) and 54% (HR = 0.46, 95% CI: 0.33–0.64) lower risk of all-cause and PrCA-specific mortality. Similar results were observed in propensity score-adjusted analysis as well as when stratified by age and extent of tumor metastasis.ConclusionsThese findings suggest that definitive local therapy improves survival in men with metastatic PrCA at diagnosis. Future work should consider comorbidities, diet, physical activity and smoking status.     

Genetic factors in individual radiation sensitivity

Cancer risk and radiation sensitivity are often associated with alterations in DNA repair, cell cycle, or apoptotic pathways. Interindividual variability in mutagen or radiation sensitivity and in cancer susceptibility may also be traced back to polymorphisms of genes affecting e.g. DNA repair capacity. We studied possible associations between 70 polymorphisms of 12 DNA repair genes with basal and initial DNA damage and with repair thereof. We investigated DNA damage induced by ionizing radiation in lymphocytes isolated from 177 young lung cancer patients and 169 cancer-free controls. We also sought replication of our findings in an independent sample of 175 families (in total 798 individuals). DNA damage was assessed by the Olive tail moment (OTM) of the comet assay. DNA repair capacity (DRC) was determined for 10, 30 and, 60 min of repair.Genes involved in the single-strand-repair pathway (SSR; like XRCC1 and MSH2) as well as genes involved in the double-strand-repair pathway (DSR; like RAD50, XRCC4, MRE11 and ATM) were found to be associated with DNA damage. The most significant association was observed for marker rs3213334 (p = 0.005) of XRCC1 with basal DNA damage (B), in both cases and controls. A clear additive effect on the logarithm of OTM was identified for the marker rs1001581 of the same LD-block (p = 0.039): B_CC = −1.06 (95%-CI: −1.16 to −0.96), B_CT = −1.02 (95%-CI: −1.11 to −0.93) and B_TT = −0.85 (95%-CI: −1.01 to −0.68). In both cases and controls, we observed significantly higher DNA basal damage (p = 0.007) for carriers of the genotype AA of marker rs2237060 of RAD50 (involved in DSR). However, this could not be replicated in the sample of families (p = 0.781). An alteration to DRC after 30 min of repair with respect to cases was observed as borderline significant for marker rs611646 of ATM (involved in DSR; p = 0.055), but was the most significant finding in the sample of families (p = 0.009).Our data indicate that gene variation impacts measurably on DNA damage and repair, suggesting at least a partial contribution to radiation sensitivity and lung cancer susceptibility.     

Torque-onset determination: Unintended consequences of the threshold method

Background: Compared with visual torque-onset-detection (TOD), threshold-based TOD produces onset bias, which increases with lower torques or rates of torque development (RTD). Purpose: To compare the effects of differential TOD-bias on common contractile parameters in two torque-disparate groups. Methods: Fifteen boys and 12 men performed maximal, explosive, isometric knee-extensions. Torque and EMG were recorded for each contraction. Best contractions were selected by peak torque (MVC) and peak RTD. Visual-TOD-based torque-time traces, electromechanical delays (EMD), and times to peak RTD (tRTD) were compared with corresponding data derived from fixed 4-N m- and relative 5%MVC-thresholds. Results: The 5%MVC TOD-biases were similar for boys and men, but the corresponding 4-N m-based biases were markedly different (40.3 ± 14.1 vs. 18.4 ± 7.1 ms, respectively; p < 0.001). Boys–men EMD differences were most affected, increasing from 5.0 ms (visual) to 26.9 ms (4 N m; p < 0.01). Men’s visually-based torque kinetics tended to be faster than the boys’ (NS), but the 4-N m-based kinetics erroneously depicted the boys as being much faster to any given %MVC (p < 0.001). Conclusions: When comparing contractile properties of dissimilar groups, e.g., children vs. adults, threshold-based TOD methods can misrepresent reality and lead to erroneous conclusions. Relative-thresholds (e.g., 5% MVC) still introduce error, but group-comparisons are not confounded.     

Magnolol inhibits colonic motility through down-regulation of voltage-sensitive L-type Ca2+ channels of colonic smooth muscle cells in rats

This study aimed to investigate the effect of magnolol (5,5′-diallyl-2,2′-biphenyldiol) on contraction in distal colonic segments of rats and the underlying mechanisms. Colonic segments were mounted in organ baths for isometric force measurement. Whole-cell voltage-sensitive L-type Ca²⁺ currents were recorded on isolated single colonic smooth muscle cells using patch-clamp technique. The spontaneous contractions and acetylcholine (ACh)- and Bay K 8644-induced contractions were inhibited by magnolol (3–100 μM). In the presence of Bay K8644 (100 nM), magnolol (10–100 μM) inhibited the contraction induced by 10 μM ACh. By contrast, tetrodotoxin (100 nM) and N_ώ-nitro-l-arginine methyl ester (l-NAME 100 μM) did not change the inhibitory effect of magnolol (10 μM). In addition, magnolol (3–100 μM) inhibited the L-type Ca²⁺ currents. The present results suggest that magnolol inhibits colonic smooth muscle contraction through downregulating L-type Ca²⁺ channel activity.     

Shifts in thermoregulatory strategy during ontogeny in harp seals (Pagophilus groenlandicus)

Heat balance can be difficult for young and/or small animals in polar regions because environmental conditions in combination with small body size or physiological immaturity can increase heat loss. We investigated how thermoregulatory patterns change with ontogeny in 5 age classes of harp seal (Pagophilus groenlandicus) from birth to post-molt to further understand the timing of thermoregulatory development in relation to their potential vulnerability to ongoing fluctuations in the extent and stability of Arctic pack ice. We measured changes in the amount, conductivity, and resistance of the seal pups׳ insulative layers (blubber and fur), the potential for endogenous heat-generation by shivering (muscle enzyme activity), and nonshivering thermogenesis (NST; brown adipose tissue (BAT) uncoupling protein 1 (UCP1) expression and mitochondrial density). There was no significant difference in blubber conductivity among age classes, though the amount of blubber insulation significantly increased from birth to weaning. Pelage conductivity was low (0.12±0.01 W m⁻¹ °C⁻¹) except in 9-day old pups (0.40±0.08 W m⁻¹ °C⁻¹); the significantly higher conductivity may signal the beginning of the molt, and this age group may be the most vulnerable to early water entry. Citrate synthase activity significantly increased (49.68±3.26 to 75.08±3.52 μmol min⁻¹ g wet weight⁻¹) in the muscle; however it is unlikely that increasing a single enzyme greatly impacts heat generation. BAT of younger pups contained UCP1, though expression and mitochondrial density quickly declined, and the ability of pups to produce heat via NST was lost by weaning. While total thermal resistance did not differ, neonatal and early nursing animals gained the majority of their thermal resistance from lanugo (82.5±0.03%); however, lanugo is not insulative when wet, and NST may be important to maintain euthermia and dry the coat if early immersion in water occurs. By late nursing, blubber seems sufficient as insulation (75.87±0.01% of resistance after 4 weeks), but high conductivity of fur may be responsible for retention of UCP1 expression. Weaned animals rely on blubber insulation, and no longer need NST, as wetted fur is no longer a threat to euthermia.     

Kososan,a standardized traditional Japanese herbal medicine,reverses sleep disturbance in socially isolated mice via GABAA-benzodiazepine receptor complex activation

PurposeKososan (KSS), a traditional Japanese medicine with a distinct aroma, is clinically used to treat affective disorders but its antidepressant-like effect has not been thoroughly investigated. In this study, we investigated the effects of inhaled and orally administered KSS on sleep disturbances in socially isolated mice.MethodsFour-weeks-old male ddy mice were housed either in social isolation or in groups for 4–6 weeks before the experiment. KSS was orally administered (0.5 or 1.0 g/kg) or inhaled (0.5, 1.0, or 2.5 g/0.125 m³) 60 min before pentobarbital administration. Stress levels in mice were evaluated by the duration of pentobarbital-induced sleeping time.ResultsSleeping time was shorter in socially-isolated mice than in group-housed mice. Oral and inhaled KSS prolonged sleeping time in stressed mice, but had no effect on sleeping time of group-housed mice. Prolonged sleeping time after oral KSS was significantly inhibited (p < 0.05) by bicuculline (3 mg/kg, i.p.), a GABA_A antagonist, but not by flumazenil (3 mg/kg, i.p.), a selective benzodiazepine antagonist. Prolonged sleeping time after KSS inhalation was significantly inhibited (p < 0.05) by flumazenil but not by bicuculline.ConclusionsOur findings suggest that KSS activates GABA_A-benzodiazepine receptor complex and reverses shortened pentobarbital-induced sleep caused by social isolation.     

Pentraxin 3 is an anti-inflammatory protein associated with lipid-induced interleukin 10 in vitro

Pentraxin 3 (PTX3) is an acute phase protein expressed in response to pro-inflammatory stimuli during atherosclerosis. However, recent findings suggest that PTX3 is a counter-regulatory protein which enhances the anti-inflammatory response.ObjectiveTherefore, the capacity of PTX3 to alter the inflammatory milieu following in vitro stimulation of PBMCs with the pro-inflammatory lipid, palmitate, was examined.MethodsPBMCs from 17 healthy male donors were isolated and cultured under four separate conditions; 200 μmol/L palmitate, a physiologically relevant concentration of PTX3, in combination (pal + PTX3), and an unstimulated time-course control.ResultsPalmitate-induced production of the counter-regulatory protein PTX3 was positively associated with the production of the anti-inflammatory cytokine interleukin 10 (IL-10) following in vitro stimulation of human PBMCs. Furthermore, stimulation of PBMCs in vitro with 500 pg/mL PTX3 elicited a significantly greater increase in IL-10 production compared to the palmitate stimulated conditions. However, PTX3 stimulation did not result in the production of the pro-inflammatory cytokines IL-1β, IL-6, and tumor necrosis factor alpha, and when combined with palmitate, did not alter the pro-inflammatory milieu from PBMCs in this study.ConclusionThese findings provide evidence supporting the role of PTX3 as a mediator of the anti-inflammatory response in physiologically relevant conditions, and suggests that PTX3 counter regulates the development of atherosclerosis by enhancing the production of IL-10.     

Temporal changes in breast cancer incidence in South Asian women

BackgroundBreast cancer in the UK resident population of South Asian ethnicity has been lower than that in indigenous women. Leicester has a large South Asian population and a breast cancer unit with comprehensive data on diagnosed cancers. This study analysed the annual incidence of new breast cancer diagnoses in females from 1998 to 2009 to determine any changes in recent years.MethodsEthnicity was known in over 98% of cases. Population denominators were based on published figures for 2001 and 2011, projected back to 1998. Age-adjusted directly standardised incidence rates were determined by ethnicity and broken down by invasive status and screening classification. Incidence rates were analysed using logistic regression in order to identify statistically significant effects of age, ethnicity, deprivation and year of diagnosis. Interactions with invasive status and screening classification were also investigated.ResultsAt the start of the study period South Asian incidence was estimated to be 45% of that of the white population (p < 0.001); by the end of the period the difference was still significant (p = 0.022) but smaller, at 17%.ConclusionSouth Asians should no longer be considered at low risk of breast cancer.     

Retrospective assessment of a single fiducial marker tracking regimen with robotic stereotactic body radiation therapy for liver tumours

AimTo investigate tumour motion tracking uncertainties in the CyberKnife Synchrony system with single fiducial marker in liver tumours.BackgroundIn the fiducial-based CyberKnife real-time tumour motion tracking system, multiple fiducial markers are generally used to enable translation and rotation corrections during tracking. However, sometimes a single fiducial marker is employed when rotation corrections are not estimated during treatment.Materials and methodsData were analysed for 32 patients with liver tumours where one fiducial marker was implanted. Four-dimensional computed tomography (CT) scans were performed to determine the internal target volume (ITV). Before the first treatment fraction, the CT scans were repeated and the marker migration was determined. Log files generated by the Synchrony system were obtained after each treatment and the correlation model errors were calculated. Intra-fractional spine rotations were examined on the spine alignment images before and after each treatment.ResultsThe mean (standard deviation) ITV margin was 4.1 (2.3) mm, which correlated weakly with the distance between the fiducial marker and the tumour. The mean migration distance of the marker was 1.5 (0.7) mm. The overall mean correlation model error was 1.03 (0.37) mm in the radial direction. The overall mean spine rotations were 0.27° (0.31), 0.25° (0.22), and 0.23° (0.26) for roll, pitch, and yaw, respectively. The treatment time was moderately associated with the correlation model errors and weakly related to spine rotation in the roll and yaw planes.ConclusionsMore caution and an additional safety margins are required when tracking a single fiducial marker.     

Peripheral arterial stiffness is associated with higher baseline plasma uric acid: A prospective cohort study

This prospective cohort study aimed at identifying association between uric acid (UA) and peripheral arterial stiffness. A prospective cohort longitudinal study was performed according to an average of 4.8 years’ follow-up. The demographic data, anthropometric parameters, peripheral arterial stiffness (carotid-radial pulse-wave velocity, cr-PWV) and biomarker variables including UA were examined at both baseline and follow-up. Pearson’s correlations were used to identify the associations between UA and peripheral arterial stiffness. Further logistic regressions were employed to determine the associations between UA and arterial stiffness. At the end of follow-up, 1447 subjects were included in the analyses. At baseline, cr-PWV (r = 0.200, p < 0.001) was closely associated with UA. Furthermore, the follow-up cr-PWV (r = 0.145, p < 0.001) was also strongly correlated to baseline UA in Pearson’s correlation analysis. Multiple regressions also indicated the association between follow-up cr-PWV (β = 0.493, p = 0.013) and baseline UA level. Logistic regressions revealed that higher baseline UA level was an independent predictor of arterial stiffness severity assessed by cr-PWV at follow-up cross-section. Peripheral arterial stiffness is closely associated with higher baseline UA level. Furthermore, a higher baseline UA level is an independent risk factor and predictor for peripheral arterial stiffness.     

Marked differences of haplotype tagging SNP distribution,linkage, and haplotype profile of IL23 receptor gene in Roma and Hungarian population samples

Polymorphisms of the interleukin-23 receptor (IL23R) gene have been found to play an important role in the development of several autoimmune diseases. We examined five susceptible (rs10889677, rs1004819, rs2201841, rs11805303, rs11209032), one protective (rs7517847) and two neutral variants (rs7530511, rs1884444) of the IL23R gene in pooled DNA of healthy Roma (Gipsy) and Hungarian population samples. Our aim was to determine the genetic variability of the major haplotype tagging polymorphisms, and the haplotype profile of IL23R between the two groups. We analyzed 273 healthy Roma and 253 Hungarian DNA samples using PCR/RFLP assay. Comparing the five susceptible conferring alleles, there were significant increase (p < 0.05), while in the protective alleles, there were decrease in the allele frequencies in Roma population (p < 0.05). One of the neutral alleles showed increase, the another one did not differ between the two groups. The haplotype analysis of the SNPs revealed fundamentally different association types of SNPs in the two groups; moreover, the frequencies of the various haplotypes also exhibited strong differences, as of ht4 and ht5 haplotypes were significantly higher, whereas the frequencies of ht2 and ht3 haplotypes were significantly lower in the Roma population than in Hungarians (p < 0.05). The data presented here show profound differences in the IL23R genetic profiles in the Roma population, that likely has also clinical implications in respect their possible role in the development of certain immunological diseases.     

Value of 111In-Pentetreotide scintigraphy and 18F-FDG PET for clinical prognosis of patients with neuroendocrine neoplasms

Despite the existence of biological markers of aggressiveness, the clinical course of gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NEN) remains difficult to predict. Discrepancies between imaging data generated with ¹¹¹In-pentetreotide scintigraphy and ¹⁸F-FDG-PET could reflect the degree of cellular de-differentiation. NEN patients with both types of studies were identified retrospectively from the SwissNET database, which is collecting information on Swiss NEN patients since 2008. Progression free survival (PFS) and overall survival (OS) were assessed depending on functional imaging results. Correlation between histological grading (according to the WHO 2010 classification) and functional imaging status was also assessed. We identified 31 patients with both imaging studies, either on the primary tumor site (21/31) or for metastases (21/31), with 12/31 on both sites. Mean follow-up was 36 months (95% CI 27–45). 21 patients had a metastatic disease at diagnosis and 11 died at follow-up. 7/31 (22%) were NET G1, 16/31 (52%) were NET G2 and 8/31 (26%) were NEC G3. Only ¹⁸F-FDG PET status almost reached statistical significance (P = 0.054) with histological grading. Progression free-survival was significantly poorer in the ¹⁸F-FDG positive group (n = 21), with a median time for progression of 8 months, compared to 51 months in the negative group (n = 10) with a HR of 3.2 (97.5% CI 1.1–9.5, P = 0.04). Overall survival tended to be worse with a positive PET and a negative ¹¹¹In-pentetreotide scintigraphy status with a HR 1.63 (97.5%CI 0.11–21, P = 0.08). ¹¹¹In-pentetreotide scintigraphy status was not found to be predictive of survival nor progression.ConclusionThese data demonstrate the poorer prognostic value of a positive ¹⁸F-FDG-PET imaging in this cohort of patients.