18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making

Background

Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery.

Methods

From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy.

Results

156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490).

Conclusion

In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery.     

Evaluation of the prevalence and economic burden of adverse drug reactions presenting to the medical emergency department of a tertiary referral centre: a prospective study

Background  

Adverse drug reactions (ADRs) are now recognized as an important cause of hospital admissions, with a proportion ranging from 0.9–7.9%. They also constitute a significant economic burden. We thus aimed at determining the prevalence and the economic burden of ADRs presenting to Medical Emergency Department (ED) of a tertiary referral center in India     

Interannual variability of seasonal succession events in a temperate lake and its relation to temperature variability

The assessment of possible implications of anthropogenic climate change requires the evaluation of results obtained with complex climate models. Here we considered the problem of assessing the impact of climate variability on successional events in a lake (Plußsee) of the temperate region between January and May. We first established a statistical link between large-scale air temperature, at about 1500 m height, and the local temperature, in order to bridge the spatial gap of information obtained from global climate models and local climate which forces processes in the lake. Secondly, the local temperatures were statistically related to biologically induced dynamic features in the lake, derived from Secchi depths readings (as integrated measures). The observed relationships were compared with results from a phyto- and zooplankton population-dynamic model run under different temperature regimes. The local temperatures approximated closely the large-scale temperature. The timing of phyto- and zooplankton maxima (clearwater phase) were negatively related to the temperature. Thus, with a temperature increase both occurred earlier. The intensity of the spring algal maximum was negatively related to its timing, whereas no clear relation between the timing and intensity of the clearwater phase (zooplankton maximum) could be obtained.     

GC-1 mRHBDD1 knockdown spermatogonia cells lose their spermatogenic capacity in mouse seminiferous tubules

Background  

Apoptosis is important for regulating spermatogenesis. The protein mRHBDD1 (mouse homolog of human RHBDD1)/rRHBDD1 (rat homolog of human RHBDD1) is highly expressed in the testis and is involved in apoptosis of spermatogonia. GC-1, a spermatogonia cell line, has the capacity to differentiate into spermatids within the seminiferous tubules. We constructed mRHBDD1 knockdown GC-1 cells and evaluated their capacity to differentiate into spermatids in mouse seminiferous tubules.     

The cDNA cloning and molecular evolution of reptile and pigeon lactate dehydrogenase isozymes

The cDNAs encoding lactate dehydrogenase isozymes LDH-A (muscle) and LDH-B (heart) from alligator and turtle and LDH-A, LDH-B, and LDH-C (testis) from pigeon were cloned and sequenced. The evolutionary relationships among vertebrate LDH isozymes were analyzed. Contrary to the traditional belief that the turtle lineage branched off before the divergence between the lizard/alligator and bird lineages, the turtle lineage was found to be clustered with either the alligator lineage or the alligator-bird clade, while the lizard lineage was found to have branched off before the divergence between the alligator/turtle and bird lineages. The pigeon testicular LDH-C isozyme was evidently duplicated from LDH-B (heart), so it is not orthologous to the mammalian testicular LDH-C isozymes.      

Cell-to-cell and phloem-mediated transport of potato virus X. The role of virions

Movement-deficient potato virus X (PVX) mutants tagged with the green fluorescent protein were used to investigate the role of the coat protein (CP) and triple gene block (TGB) proteins in virus movement. Mutants lacking either a functional CP or TGB were restricted to single epidermal cells. Microinjection of dextran probes into cells infected with the mutants showed that an increase in the plasmodesmal size exclusion limit was dependent on one or more of the TGB proteins and was independent of CP. Fluorescently labeled CP that was injected into epidermal cells was confined to the injected cells, showing that the CP lacks an intrinsic transport function. In additional experiments, transgenic plants expressing the PVX CP were used as rootstocks and grafted with nontransformed scions. Inoculation of the PVX CP mutants to the transgenic rootstocks resulted in cell-to-cell and systemic movement within the transgenic tissue. Translocation of the CP mutants into sink leaves of the nontransgenic scions was also observed, but infection was restricted to cells close to major veins. These results indicate that the PVX CP is transported through the phloem, unloads into the vascular tissue, and subsequently is transported between cells during the course of infection. Evidence is presented that PVX uses a novel strategy for cell-to-cell movement involving the transport of filamentous virions through plasmodesmata.     

The movement protein of cucumber mosaic virus traffics into sieve elements in minor veins of nicotiana clevelandii

The location of the 3a movement protein (MP) of cucumber mosaic virus (CMV) was studied by quantitative immunogold labeling of the wild-type 3a MP in leaves of Nicotiana clevelandii infected by CMV as well as by using a 3a-green fluorescent protein (GFP) fusion expressed from a potato virus X (PVX) vector. Whether expressed from CMV or PVX, the 3a MP targeted plasmodesmata and accumulated in the central cavity of the pore. Within minor veins, the most extensively labeled plasmodesmata were those connecting sieve elements and companion cells. In addition to targeting plasmodesmata, the 3a MP accumulated in the parietal layer of mature sieve elements. Confocal imaging of cells expressing the 3a-GFP fusion protein showed that the 3a MP assembled into elaborate fibrillar formations in the sieve element parietal layer. The ability of 3a-GFP, expressed from PVX rather than CMV, to enter sieve elements demonstrates that neither the CMV RNA nor the CMV coat protein is required for trafficking of the 3a MP into sieve elements. CMV virions were not detected in plasmodesmata from CMV-infected tissue, although large CMV aggregates were often found in the parietal layer of sieve elements and were usually surrounded by 3a MP. These data suggest that CMV traffics into minor vein sieve elements as a ribonucleoprotein complex that contains the viral RNA, coat protein, and 3a MP, with subsequent viral assembly occurring in the sieve element parietal layer.     

Cloning and expression analysis of two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp,Ctenopharyngodon idellus

Background  

Hypoxia-inducible factors (HIFs) are involved in adaptive and survival responses to hypoxic stress in mammals. In fish, very little is known about the functions of HIFs.     

Increasement of Heterologous Expression of Recombinant Vit v 1 in Pichia pastoris KM71 by Nonionic Detergents as a Cost-effective Approach

Applied Biochemistry and Microbiology - Vit v 1 as a lipid-transfer protein is a major allergen of grapes (Vitis vinifera) that elicits food allergy in many patients in Iran. Todays, recombinant...     

Lymphocyte subsets and T(h)1/T(h)2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM stage and clinical outcome

Introduction Recent studies have indicated that the cytokines produced by CD4⁺ T helper type 1 (T_h1) and type 2 (T_h2) cells are critically important in antitumour immunity and perhaps clinical outcome. From this perspective, we investigated the immunocompetence of patients with previously untreated cancer of the oesophagus or oesophagogastric junction (OGJ) in relation to stage of disease and postoperative survival.Methods Blood samples were taken prior to surgery from 32 patients with adenocarcinoma of the oesophagus or OGJ. Ten healthy volunteers served as normal controls. T-cell and monocyte subpopulations were determined using flow cytometry. Monocyte as well as T_h1- and T_h2-lymphocyte cytokine levels were assessed in stimulated whole blood cultures.Results Absolute T-cell and monocyte (subset) counts as well as monocyte cytokine levels were similar among patients and controls. Production of T_h1-type cytokines was higher in patients than in controls (IFN-, p=0.01; IL-2, p=0.05), whereas T_h2-type cytokine levels were comparable (IL-4, p=0.5; IL-13, p=0.3). T-cell CD4⁺/CD8⁺ ratios decreased as pTNM stage worsened (stage I/II vs stage III/IV, p=0.009). Of all measured immunological parameters, only IL-2 production significantly affected both overall survival (p=0.015) and disease-free survival (p=0.0062). High IL-2 levels corresponded with a favourable prognosis.Conclusions Patients awaiting surgery for adenocarcinoma of the oesophagus or oesophagogastric junction demonstrated a shift in the T_h1/T_h2 balance—in favour of T_h1—compared with healthy volunteers. The ability of T cells to produce IL-2 was related to survival indicating a crucial role of T_h1-type cells in antitumour immunosurveillance.