Pancreatic cancer cells infiltrate nerves through TGFbeta1-driven perineural epithelial-to-mesenchymal-like transdifferentiation.

Neural invasion is a prognostic hallmark of pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms behind the disruption of perineural barriers and access of cancer cells into intrapancreatic nerves remain poorly understood. This study aimed to investigate the role of epithelial-mesenchymal transformation (EMT) in perineural epithelial cells during neural invasion.Histopathological analysis of human and murine primary tumors using perineurium-specific GLUT1 antibody revealed a reduction in perineural integrity, which positively correlated with the extent of neural invasion in human PDAC cases.

Correlation of intratumoral mast cell quantity with psychosocial distress in patients with pancreatic cancer: the PancStress study.

Mast cells are commonly found in pancreatic ductal adenocarcinoma (PDAC), yet their role in the disease remains uncertain. Although mast cells have been associated with depression in several diseases, their connection to PDAC in this context remains unclear. This study explored the correlation between mast cells and psychosocial stress in patients with PDAC.

Noninvasive assessment and quantification of tumor vascularization using [18F]FDG-PET/CT and CE-CT in a tumor model with modifiable angiogenesis-an animal experimental prospective cohort study.

Background: This study investigated the noninvasive assessment of tumor vascularization with clinical F-18-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography ([18F]FDG-PET/CT and CE-CT) in experimental human xenograft tumors with modifiable vascularization and compared results to histology. Tumor xenografts with modifiable vascularization were established in 71 athymic nude rats by subcutaneous transplantation of human non-small-cell lung cancer (NSCLC) cells. Four different groups were transplanted with two different tumor cell lines (either A549 or H1299) alone or tumors co-transplanted with rat glomerular endothelial (RGE) cells, the latter to increase vascularization.

Transcriptome 3'end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma.

Diversification at the transcriptome 3'end is an important and evolutionarily conserved layer of gene regulation associated with differentiation and dedifferentiation processes. Here, we identify extensive transcriptome 3'end-alterations in neuroblastoma, a tumour entity with a paucity of recurrent somatic mutations and an unusually high frequency of spontaneous regression. Utilising extensive RNAi-screening we reveal the landscape and drivers of transcriptome 3'end-diversification, discovering PCF11 as critical regulator, directing alternative polyadenylation (APA) of hundreds of transcripts including a differentiation RNA-operon.

Noninvasive assessment and quantification of tumour vascularisation using MRI and CT in a tumour model with modifiable angiogenesis - An animal experimental prospective cohort study.

Background: To investigate vascular-related pathophysiological characteristics of two human lung cancers with modifiable vascularisation using MRI and CT.

Methods: Tumour xenografts with modifiable vascularisation were established in 71 rats (approval by the Animal Care Committee was obtained) by subcutaneous transplantation of two human non-small-cell lung cancer (NSCLC) cells (A549, H1299) either alone or co-transplanted with vascular growth promoters. The vascularity of the tumours was assessed noninvasively by MRI diffusion-weighted-imaging (DWI), T2-weighted, and time-of-flight (TOF) sequences) as well as contrast-enhanced CT (CE-CT), using clinical scanners.

Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice.

Background And Purpose: Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether inhibition of dipeptidyl peptidase-4 (DPP-4) and supplementation with glucagon-like peptide-1 (GLP-1) receptor agonists improved endotoxaemia-associated microvascular thrombosis via immunomodulatory effects.

Experimental Approach: Endotoxaemia was induced in C57BL/6J mice by a single injection of LPS (17.

Radiosensitization of p53-deficient lung cancer cells by pre-treatment with cytostatic compounds.

Background/aim: This study specifies a strategy to improve radiotherapy by partial synchronization of p53-deficient cancer cells (FaDu and H1299) in mitosis using taxol, with protecting p53 wild-type cells (A549) by the prior administration of cytostatic compounds. Cytotoxic and cytostatic effects of ionizing radiation, cisplatin, doxorubicin and taxol, administrated alone or in combination were investigated in vitro by flow cytometry.

Results: A protective effect of doxorubicin but not cisplatin was found after administration of triple sequence with ionizing radiation and taxol.

Radiation-induced cell cycle arrests in Ehrlich ascites carcinoma cells in vivo.

Radiation-induced progression delay in G(1)/S, S and G(2)/M phases of p53 wild-type Ehrlich ascites carcinoma (EAC) cells growing in vivo was investigated by DNA flow cytometry. Different behavior patterns of EAC cells at the time after irradiation with low (2, 4, 6, 8 Gy) and high (10, 15, 20 Gy) doses were evaluated. While EAC cells showed a small progression delay in S phase and a dose-dependent block in G(2)/M phase after the irradiation with low doses, a clear additional block in G(1)/S phase was observed after irradiation with high doses.

Tumour bed irradiation of human tumour xenografts in a nude rat model using a common X-ray tube.

Studies that investigate the radiation of human tumour xenografts require an appropriate radiation source and highly standardized conditions during radiation. This work reports on the design of a standardized irradiation device using a commercially available X-ray tube with a custom constructed lead collimator with two circular apertures and an animal bed plate, permitting synchronous irradiation of two animals. Dosimetry and the corresponding methodology for radiotherapy of human non-small cell lung cancer xenograft tumours transplanted to and growing subcutaneously on the right lower limb in a nude rat model were investigated.

Protection of p53 wild type cells from taxol by genistein in the combined treatment of lung cancer.

This study specifies the basic principles to selectively kill p53-deficient cells (H1299, FaDu) by taxol and to protect p53 wild type cells (A549) by the prior administration of structurally related flavonoids (apigenin, genistein, and quercetin). Cytotoxic and cytostatic properties of flavonoids were investigated in vitro by flow cytometry and were compared to known anticancer drugs (cisplatin, doxorubicin, etoposide). It was confirmed that doxorubicin induced growth arrest and protected A549 cells from taxol while simultaneously killing or blocking H1299 and FaDu cancer cells.

Preliminary assessment of dynamic contrast-enhanced CT implementation in pretreatment FDG-PET/CT for outcome prediction in head and neck tumors.

Background: Recently published data show some controversy concerning the impact of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in predicting head and neck tumors (HNT) outcome. Assessment of tumor blood supply parameters using dynamic contrast-enhanced CT (DCE-CT) may deliver additional information concerning this important question.

Purpose: To evaluate the contribution of DCE-CT implemented in pretherapeutic FDG-PET/CT protocol for prognosis prediction in patients with HNT.

Usefulness of dynamic contrast enhanced computed tomography in patients with non-small-cell lung cancer scheduled for radiation therapy.

Objective: The goal of this study was to investigate the local tumor blood supply parameters relative tumor blood volume (rTBV) and transfer coefficient (K(trans)) measurable with dynamic contrast enhanced computed tomography (DCE-CT) in patients with non-small-cell lung cancer (NSCLC) scheduled for radiation therapy (RT).

Materials And Methods: rTBV and K(trans) were measured before RT in 31 patients with clinically inoperable NSCLC (Stages I-III), which received (n=19) or did not receive (n=12) induction chemotherapy (IChT). Possible links between rTBV and K(trans) and time-to-progression (TTP), overall survival (OS) and maximum standardized uptake value (SUV(max)) from fluorodeoxyglucose positron emission tomography as well as histology were analyzed.

Improvement of radiation-mediated immunosuppression of human NSCLC tumour xenografts in a nude rat model.

Human tumour xenografts in a nude rat model have consistently been used as an essential part of preclinical studies for anticancer drugs activity in human. Commonly, these animals receive whole body irradiation to assure immunosuppression. But whole body dose delivery might be inhomogeneous and the resulting incomplete bone marrow depletion may modify tumour behaviour.

Protection of p53 wild type cells from taxol by nutlin-3 in the combined lung cancer treatment.

Background: Mutations within the tumor suppressor TP53 gene are one of the most common genetic alterations present at high frequency in human tumors and have been shown to be associated with resistance to radio-chemotherapy. The lack of the wild type TP53 gene in cancer cells could be exploited for therapeutic advantage using a sequence of two antagonistic drugs. The aim of this study was to selectively kill p53 deficient cells (FaDu and H1299) by taxol and to protect p53 wild type cells (A549) by the prior administration of nutlin-3 in comparison to certain known anticancer drugs (5-fluorouracil, camptothecin, roscovitine).

Distribution of fluorescent microspheres in vascular space and parenchymal organs of intact nude rats.

Purpose: To assess kinetics of elimination of different sized microspheres (MS) from the blood pool and tendency of their distribution in parenchymal organs of intact nude rats.

Materials And Methods: A mixture of 1 microm and 3 microm MS in phosphate-buffered saline was injected intravenously into eight rats under intraperitoneal anaesthesia. Blood samples were collected before, just after and in 2, 5 and 10 min after MS injection.

Fusion of images in multistep analysis of neovascularisation.

Purpose: The aim of our study was to develop a method for the fusion of images received after repeated staining of the same sample taking into account spatial differences between the images.

Material And Methods: A method of objective fusion performance was investigated on the images receiving during multistep staining of the xenograft tumour cross-sections.

Results: It was shown that several images receiving from different steps of staining procedures may be successfully fused by fluorescent marking of slide position with Trout red blood cells before analysis.

Is pre-therapeutical FDG-PET/CT capable to detect high risk tumor subvolumes responsible for local failure in non-small cell lung cancer?

Background And Purpose: Local failure is a significant issue following radiotherapy (RT) for patients with non-small cell lung cancer (NSCLC). The aim of this study was to find out whether FDG-PET/CT is capable to predict tumor relapse location in patients with NSCLC, in particular to determine high risk tumors' subvolumes responsible for local failure.

Material And Methods: Ten patients with locoregional relapse of NSCLC underwent FDG-PET/CT before, during, and in the 4-12 months following curative chemoradiotherapy (ChRT, 66 Gy) using a combined PET/CT scanner.

Retrospective analysis of radiation load during examination of cancer patients by (68)Ga-DOTATOC and (18)F-FDG positron emission tomography.

We present retrospective analysis of the results of examinations of 1,338 cancer patients by (68)Ga-DOTATOC and (18)F-FDG positron emission and computer-aided tomography. It was shown that complex devices for positron emission and computer-aided tomography provide more informative data than individual methods. The protocol for examination by methods of positron emission and computer-aided tomography in each case is determined by clinical requirements and risk of extra exposure of the patient.

[Main milestones of development and application of ductal cytometry at the Russian Federal Research Center for Radiology and Surgical Technology, St. Petersburg].

Ductal cytometry provides data on cellular DNA and RNA levels and overall profile of specific proteins identifiable by monoclonal antibodies. Results of its long-term use in clinical and oncological research are presented. Application of dosage ranging 0.

A number of bone marrow mesenchymal stem cells but neither phenotype nor differentiation capacities changes with age of rats.

Bone marrow (BM) derived mesenchymal stem cells (MSC) are pluripotent cells which can differentiate into osteogenic, adipogenic and other lineages. In spite of the broad interest, the information about the changes in BM cell composition, in particularly about the variation of MSC number and their properties in relation to the age of the donor is still controversial. The aim of this study was to investigate the age associated changes in variations of BM cell composition, phenotype and differentiation capacities of MSC using a rat model.

Age-related changes in the frequency of mesenchymal stem cells in the bone marrow of rats.

Mesenchymal stem cells (MSCs) are pluripotent cells that can differentiate into endothelial, osteogenic, adipogenic, and other lineages. In spite of the broad interest, little is known about the variation of MSC number in relation to the age of the donor. The aim of this study was to investigate the age-associated variations of bone marrow (BM) MSCs using a rat model.

Varying responses of human cells with discrepant p53 activity to ionizing radiation and heat shock exposure.

Objectives: Both heat shock (HS) and ionizing radiation have an impact on the cell cycle and may induce cell cycle arrest or apoptosis. Mutations of the p53 gene are observed at a high frequency in human tumours and are recognized in about half of all human cancers. Sensitivity to radiation, heat and anticancer agents has been observed in p53(+/+) cells, but not in mutated or p53-deficient cells.

Lectin-binding pattern as tool to identify and enrich specific primary testis cells of the tilapia (Oreochromis niloticus) and medaka (Oryzias latipes).

Cell type-specific lectin binding is a useful tool for the analysis of developing systems. We describe the binding pattern of 21 different fluorescein isothiocyanate (FITC)-labelled lectins to the testis of two model teleost species, the medaka (Oryzias latipes) and the tilapia (Oreochromis niloticus). The analysis of the binding pattern was carried out on tissue sections (medaka and tilapia) and using primary culture cells (only tilapia).