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1.
Int J Mol Sci ; 24(14)2023 Jul 12.
Article in English | MEDLINE | ID: mdl-37511126

ABSTRACT

Pulmonary adenocarcinomas (pADCs) with an ALK rearrangement are a rare cancer subtype, necessitating comprehensive molecular investigations to unravel their heterogeneity and improve therapeutic strategies. In this pilot study, we employed spatial transcriptomic (NanoString GeoMx) and proteomic profiling to investigate seven treatment-naïve pADCs with an ALK rearrangement. On each FFPE tumor slide, 12 smaller and 2-6 larger histopathologically annotated regions were selected for transcriptomic and proteomic analysis, respectively. The correlation between proteomics and transcriptomics was modest (average Pearson's r = 0.43 at the gene level). Intertumoral heterogeneity was more pronounced than intratumoral heterogeneity, and normal adjacent tissue exhibited distinct molecular characteristics. We identified potential markers and dysregulated pathways associated with tumors, with a varying extent of immune infiltration, as well as with mucin and stroma content. Notably, some markers appeared to be specific to the ALK-driven subset of pADCs. Our data showed that within tumors, elements of the extracellular matrix, including FN1, exhibited substantial variability. Additionally, we mapped the co-localization patterns of tumor microenvironment elements. This study represents the first spatially resolved profiling of ALK-driven pADCs at both the gene and protein expression levels. Our findings may contribute to a better understanding of this cancer type prior to treatment with ALK inhibitors.


Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Humans , Anaplastic Lymphoma Kinase/genetics , Anaplastic Lymphoma Kinase/metabolism , Lung Neoplasms/pathology , Receptor Protein-Tyrosine Kinases/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Adenocarcinoma/pathology , Transcriptome , Pilot Projects , Proteomics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Gene Rearrangement , Tumor Microenvironment/genetics
2.
Molecules ; 28(3)2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36770697

ABSTRACT

The Inverse Method is a widely used technique for the determination of adsorption isotherms in liquid chromatography. In this method, isotherm is determined from the overloaded peak profile of the component by the iterative solution of the mass balance equation of liquid chromatography. Successful use of this method requires a prior assumption of equation of isotherm (Langmuir, BET etc.). In this work, we have developed an inverse method that gives results of similar accuracy to the frontal analysis without assuming the equation of the isotherm. The oversaturated peaks were calculated using a spline fitted to data points instead of the derivative of the isotherm. The distribution of the isotherm points were optimized for minimizing the difference between the measured and calculated overloaded peaks. The accuracy of the developed method was verified with synthetic benchmark peaks and by the determination of isotherm of buthyl-benzoate under real conditions. The results confirmed that the accuracy of the developed method is similar to that of Frontal Analysis.

3.
J Chromatogr A ; 1651: 462331, 2021 Aug 16.
Article in English | MEDLINE | ID: mdl-34153736

ABSTRACT

Modern analytical applications of liquid chromatography require more and more efficient columns. In this work, the possibility of utilizing particle size gradient in the chromatographic column was studied by a theoretical approach. In the course of our work three different scenarios of particle size gradients were considered with different shapes (linear, convex and concave). The evolution of bandwidth inside the column was plotted for each scenario. As a reference point, the bandwidth of the uniform column was used, which had the same pressure drop as the non-uniform column. According to our calculations, in isocratic elution mode, the non-uniform column does not offer any advantage compared to the uniform column, regardless the type of the particle size gradient. In gradient elution mode, however, extra band compression occurs was found. For negative particle size gradients, the final physical bandwidth was found to be approximately 1-4 % smaller than for uniform columns. This slight gain in efficiency in terms of bandwidth compression can be expanded to 5-8 % by the optimization of the limiting particle sizes. These optimized results are obtained when the final particle size is approximately 40% of the initial particle diameter.


Subject(s)
Chromatography, Liquid/instrumentation , Chromatography, Liquid/standards , Models, Theoretical , Particle Size
4.
Sensors (Basel) ; 19(16)2019 Aug 15.
Article in English | MEDLINE | ID: mdl-31443164

ABSTRACT

The recent trend in plastic production dictated by Industry 4.0 demands is to acquire a great deal of data for manufacturing process control. The most relevant data about the technological process itself come from the mold cavity where the plastic part is formed. Manufacturing process data in the mold cavity can be obtained with the help of sensors. Although many sensors are available nowadays, those appropriate for in-mold measurements have certain peculiarities. This study presents a comprehensive overview of in-mold process monitoring tools and methods for injection molding process control. It aims to survey the recent development of standard sensors used in the industry for the measurement of in-mold process parameters, as well as research attempts to develop unique solutions for solving certain research and industrial problems of injection molding process monitoring. This review covers the established process monitoring techniques-direct temperature and pressure measurement with standard sensors and with the newly developed sensors, as well as techniques for the measurement of indirect process parameters, such as viscosity, warpage or shrinkage.

5.
Molecules ; 24(15)2019 Aug 06.
Article in English | MEDLINE | ID: mdl-31390734

ABSTRACT

Modern analytical applications of liquid chromatography require columns with higher and higher efficiencies. In this work, the general rate model (GRM) of chromatography is used for the analysis of the efficiency of core-shell phases having two porous layers with different structures and/or surface chemistries. The solution of the GRM in the Laplace domain allows for the calculation of moments of elution curves (retention time and peak width), which are used for the analysis of the efficiency of bi-layer particles with and without a non-porous core. The results demonstrate that bi-layer structures can offer higher separation power than that of the two layers alone if the inner layer has smaller surface coverage (retentivity) and the pore size and pore diffusion of the outer layer is either equal to or higher than that of the inner layer. Even in the case of core-shell phases, there is an increase in resolution by applying the bi-layer structure; however, we can always find a mono-layer core-shell particle structure with a larger core size that provides better resolution. At the optimal core size, the resolution cannot be further improved by applying a bi-layer structure. However, in case of the most widely produced general-purpose core-shell particles, where the core is ∼70% of the particle diameter, a 15-20% gain of resolution can be obtained by using well-designed and optimized bi-layer core-shell phases.


Subject(s)
Chromatography, High Pressure Liquid , Macromolecular Substances/analysis , Macromolecular Substances/chemistry , Models, Theoretical , Algorithms , Chromatography, High Pressure Liquid/methods , Particle Size
6.
Front Immunol ; 10: 650, 2019.
Article in English | MEDLINE | ID: mdl-31024530

ABSTRACT

There is far less information available about the tumor infiltrating B (TIL-B) cells, than about the tumor infiltrating T cells. We focused on discovering the features and potential role of B lymphocytes in solid tumors. Our project aimed to develop innovative strategies to define cancer membrane structures. We chose two solid tumor types, with variable to considerable B cell infiltration. The strategy we set up with invasive breast carcinoma, showing medullary features, has been introduced and standardized in metastatic melanoma. After detecting B lymphocytes by immunohistochemistry, VH-JH, Vκ-Jκ immunoglobulin rearranged V region genes were amplified by RT-PCR, from TIL-B cDNA. Immunoglobulin variable-region genes of interest were cloned, sequenced, and subjected to a comparative DNA analysis. Single-chain variable (scFv) antibody construction was performed in selected cases to generate a scFv library and to test tumor binding capacity. DNA sequence analysis revealed an overrepresented VH3-1 cluster, represented both in the breast cancer and the melanoma TIL-B immunoglobulin repertoire. We observed that our previously defined anti GD3 ganglioside-binder antibody-variable region genes were present in melanoma as well. Our antibody fragments showed binding potential to disialylated glycosphingolipids (GD3 ganglioside) and their O acetylated forms on melanoma cancer cells. We conclude that our results have a considerable tumor immunological impact, as they reveal the power of TIL-B cells to recognize strong tumor-associated glycosphingolipid structures on melanomas and other solid tumors. As tumor-derived gangliosides affect immune cell functions and reduce the B lymphocytes' antibody production, we suspect an important B lymphocyte and cancer cell crosstalk mechanism. We not only described the isolation and specificity testing of the tumor infiltrating B cells, but also showed the TIL-B cells' highly tumor-associated GD3 ganglioside-revealing potential in melanomas. The present data help to identify new cancer-associated biomarkers that may serve for novel cancer diagnostics. The two-direction regulation mechanism between immune B cells and the tumor could eventually be developed into an innovative cancer treatment strategy.


Subject(s)
B-Lymphocytes/immunology , Breast Neoplasms/immunology , Gangliosides/immunology , Lymphocytes, Tumor-Infiltrating/immunology , Melanoma/immunology , Single-Chain Antibodies/immunology , Cell Line, Tumor , Humans
7.
Magy Seb ; 71(3): 126-133, 2018 09.
Article in Hungarian | MEDLINE | ID: mdl-30231634

ABSTRACT

INTRODUCTION: Surgical removal is the gold standard method for the treatment of pulmonary sequestration (PS); nowadays, video-assisted thoracoscopic lobectomy (VATS) is more frequently applied in the surgical treatment of malignant pulmonary tumours and appears to be suitable also in case of benign pulmonary diseases. We are the first in Hungary, who report three, radiologically identified intralobar PS treated with VATS. METHOD: Surgeries were performed in general anaesthesia with double-lumen separated ventilation in lateral decubitus position through two ports (1.5 cm camera port and 5-6 cm axillary working port, protected by a plastic ring). Results and cases: Two of the patients presented with the symptoms of haemoptysis and pneumonia, and the third patient after radiological screening (one 37 years old woman and 2 men, 39 and 46 years old). The nutritive artery was identified on the CT scans in all cases. We removed the right lower lobe in two cases and the left lower lobe in one case without major complications. CONCLUSION: We recommend the video-thoracoscopic lobectomy for the treatment of PS as a suitable treatment option.


Subject(s)
Bronchopulmonary Sequestration/surgery , Pneumonectomy/methods , Thoracic Surgery, Video-Assisted/methods , Adult , Bronchopulmonary Sequestration/diagnostic imaging , Female , Humans , Male , Middle Aged
8.
Contemp Oncol (Pozn) ; 22(1A): 41-47, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29628793

ABSTRACT

AIM OF THE STUDY: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells. MATERIALS AND METHODS: As a novel approach, we investigated B cells infiltrating breast carcinomas and melanomas (TIL-B) in terms of their tumour antigen binding potential. By developing the TIL-B phage display technology we provide here a new technology for the specific detection of highly tumour-associated antigens. Single chain Fv (scFv) antibody fragment phage ELISA, immunofluorescence (IF) FACS analysis, chamber slide technique with IF confocal laser microscopy and immunohistochemistry (IHC) in paraffin-embedded tissue sections were set up and standardized. RESULTS: We showed strong tumour-associated disialylated glycosphingolipid expression levels on various cancer cells using scFv antibody fragments, generated previously by uniquely invasive breast carcinoma TIL-B phage display library technology. CONCLUSIONS: We report herein a novel strategy to obtain antibody fragments of human origin that recognise tumour-associated ganglioside antigens. Our investigations have the power to detect privileged molecules in cancer progression, invasiveness, and metastases. The technical achievements of this study are being harnessed for early diagnostics and effective cancer therapeutics.

9.
Perit Dial Int ; 38(4): 251-256, 2018.
Article in English | MEDLINE | ID: mdl-29674408

ABSTRACT

BACKGROUND: Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases, including renal failure, and often poorer outcomes for patients with such conditions. The aim of this study was to investigate the effect of deprivation on peritonitis episodes following peritoneal dialysis (PD)-catheter insertion. METHODS: The Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes following 233 consecutive first PD-catheter insertions from a single institution in the United Kingdom, performed between 2010 and 2015. The primary outcome measure was the presence of peritonitis episodes. RESULTS: Peritoneal dialysis catheters were inserted in 243 patients, of which data were available for 233. Fifty-four patients experienced at least 1 episode of peritonitis. Overall, more patients in the most deprived group (vs least deprived) experienced peritonitis, although this was not statistically significant. When analyzing the severity of the peritonitis, within the 'Education' domain of the WIMD, significantly more patients from the most deprived group (compared with the least deprived group) experienced '2 or more peritonitis' episodes (p = 0.04) and were hospitalized for antibiotics (p = 0.02). CONCLUSION: This study has shown that patients who live in more 'educationally' deprived areas are more likely to have multiple episodes of peritonitis requiring hospital admission following PD-catheter insertions.


Subject(s)
Educational Status , Kidney Failure, Chronic/therapy , Peritoneal Dialysis/adverse effects , Peritonitis/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Catheters, Indwelling , Female , Hospitalization , Humans , Kidney Failure, Chronic/epidemiology , Male , Middle Aged , Retrospective Studies , Risk Factors , Socioeconomic Factors , United Kingdom , Young Adult
10.
Int J Surg ; 46: 21-26, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28803997

ABSTRACT

BACKGROUND: Following transplantation, many patients travel long distances for follow-up care. Many studies have examined the influence of distance from transplant centre on access to transplantation, but few have examined post-transplant outcomes. MATERIALS AND METHODS: Distance from transplant centre was calculated for all kidney transplant recipients transplanted over a 5-year period. Outcomes measured were rates of acute rejection, graft and patient survival. RESULTS: Complete follow up data was available for 571 of the 585 kidney transplants performed over the study period. Distance from home to transplant centre ranged from 1.3 to 257.4 km (median 33.7 km). Patients were divided into quartiles according to their distance from the transplant centre. Distance from the transplant centre did not influence rates of acute rejection (p = 0.102). One-year graft survival for 'nearest' and 'farthest' quartiles was 99% and 97% respectively and five-year graft survival was 78% and 89% respectively (log rank p-value of 0.212). There were no differences in patient survival at 1 and 5 years between the 'nearest' and 'farthest' groups. CONCLUSION: Distance from transplant centre does not affect early outcomes following kidney transplantation. The centralized practice which involves a low threshold for rapid assessment and readmission of patients post-transplantation appears to provide good outcomes for kidney transplant recipients.


Subject(s)
Aftercare/statistics & numerical data , Health Services Accessibility/statistics & numerical data , Kidney Transplantation/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Databases, Factual , Female , Graft Survival , Humans , Male , Middle Aged , Prospective Studies , Time Factors , Treatment Outcome , Young Adult
11.
J Chromatogr A ; 1483: 80-85, 2017 Feb 03.
Article in English | MEDLINE | ID: mdl-28062080

ABSTRACT

The effect of axial temperature gradient on the chromatographic efficiency was studied under adiabatic conditions by a modeling approach. The equilibrium-dispersive model of chromatography was used for the calculations. The model was extended by taking into account the axial temperature gradient. The results show that due to the temperature gradient, there are retention and migration velocity gradients in the column. Since the retention factor, k, is not constant in the column, k cannot be calculated as the ratio of net retention and hold-up times. As a result of the gradual increase of migration velocity, the retention times of solutes decrease as the slope of temperature gradient increases. In addition, the band in the column have extra broadening due to larger migration velocity of the front of band. The width of bands becomes larger at larger change of temperature. In the same time, however, the release velocity of the compounds from the column is increasing as ΔT increases. Accordingly, an apparent peak compression effect makes the peaks thinner. As a result of the two counteracting effects (peak expansion, apparent peak compression) the column efficiency does not change significantly in case of axial temperature gradient under adiabatic conditions. The resolutions, however, decrease slightly due to the decrease of retention times.


Subject(s)
Chromatography, Liquid/methods , Models, Theoretical , Temperature , Time Factors
12.
Magy Onkol ; 60(1): 64-71, 2016 03 02.
Article in Hungarian | MEDLINE | ID: mdl-26934353

ABSTRACT

The rapidly growing field of gene therapy techniques to modify T cells with chimeric antigen receptors (CARs) for cancer care solutions, reached considerable achievements. However, there is an urgent need of reliable, well tolerable tumor-associated antigen specific antibodies. Tumor-infiltrating B (TIL-B) cell originated single chain Fv (scFv) gene regions could be selected with tumor specificity. DNA sequences of these antibody variable regions were subjects to get engineered into new CAR constructs. Our novel strategy harnesses tumor-infiltrating B cells' unique capacity to reveal highly tumor-associated disialylated glycosphingolipids (GD3 gangliosides). We used these human antibody fragments for generating GD3 ganglioside specific CAR gene constructs for potential usage in solid tumors.


Subject(s)
Genetic Therapy/methods , Neoplasms/immunology , Receptors, Antigen, B-Cell/metabolism , Receptors, Antigen, T-Cell/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Humans , Lymphocytes, Tumor-Infiltrating , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
13.
J Vasc Access ; 16(6): 480-5, 2015.
Article in English | MEDLINE | ID: mdl-26070094

ABSTRACT

INTRODUCTION: Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, and often poorer outcomes for patients with such conditions. The influence of deprivation on outcomes following vascular access surgery has not previously been reported. METHODS: The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes following 507 consecutive first upper limb arteriovenous (AV) fistulas from a single institution in the United Kingdom, performed between 2011 and 2014. The primary outcome measures were early failure and maturation into a working fistula. RESULTS: Four hundred and five (80%) patients had a patent AV fistula at the 2-week follow-up clinic. Three hundred and fifty-nine (71%) patients developed a functionally mature AV fistula as determined by clinical assessment and a Doppler scan. There were no differences in either early failure rates (p = 0.95) or maturation rates (p = 0.77) between the least and most deprived groups of patients. CONCLUSIONS: In conclusion, this study has shown that socioeconomic deprivation does not influence outcomes following vascular access surgery.


Subject(s)
Arteriovenous Shunt, Surgical/economics , Health Status Disparities , Healthcare Disparities/economics , Kidney Diseases/economics , Kidney Diseases/therapy , Poverty , Process Assessment, Health Care/economics , Renal Dialysis/economics , Upper Extremity/blood supply , Adolescent , Adult , Aged , Aged, 80 and over , Arteriovenous Shunt, Surgical/adverse effects , Comorbidity , Female , Humans , Kidney Diseases/diagnosis , Kidney Diseases/epidemiology , Male , Middle Aged , Renal Dialysis/adverse effects , Risk Factors , Time Factors , Treatment Failure , Ultrasonography, Doppler , Vascular Patency , Wales/epidemiology , Young Adult
14.
Transplantation ; 99(1): 226-31, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25099703

ABSTRACT

INTRODUCTION: To expand the donor pool, kidney transplants are being performed using donors who were previously considered unacceptable. We applied the United Network for Organ Sharing criteria to define expanded criteria donors (ECD) within the donation after cardiac death (DCD) and donation after brain stem death (DBD) cohorts. We compared outcomes of DCD and DBD transplants with and without (standard criteria donor [SCD]) the ECD criteria. METHODS: This was a single-center retrospective study of all deceased donor transplants from 2004 to 2010 (n=359). Four groups were identified--DBD-SCD (n=154), DBD-ECD (n=93), DCD-SCD (n=78), and DCD-ECD (n=34). Kaplan-Meier analysis of graft and patient survival and multiple regression analysis of 1-year graft function were performed. RESULTS: One-year and two-year uncensored graft survivals were similar between DCD-ECD and DCD-SCD cohorts (1 year, 90% and 93%; 2 years, 81% and 93% respectively; log-rank test P=0.2). Median estimated glomerular filtration rate (eGFR) was lower in DCD-ECD recipients at 12 months (41 vs. 53 mL/min, P=0.003) and 24 months (33 vs. 54 mL/min, P<0.001) compared with DCD-SCD recipients. Compared with DBD-ECD recipients also at 24 months, DCD-ECD recipients showed a lower graft function (median, eGFR 33 vs. 47 mL/min; P=0.007) but similar graft survival. Expanded criteria donor status (B=-9.7, P=0.01) was associated with a lower 1-year eGFR within the DCD cohort, with donor age (B=-0.42, P=0.002) being the only significant ECD variable. CONCLUSION: Short-term graft survival in DCD-ECD transplants was comparable to DCD-SCD and DBD-ECD transplants albeit with poorer allograft function at 2 years. Quality-of-life studies are needed to determine the true value of these transplants, particularly when performed to older recipients.


Subject(s)
Brain Death , Donor Selection , Heart Diseases/mortality , Kidney Transplantation , Tissue Donors/supply & distribution , Adolescent , Adult , Age Factors , Aged , Female , Glomerular Filtration Rate , Graft Survival , Humans , Kaplan-Meier Estimate , Kidney Transplantation/adverse effects , Kidney Transplantation/mortality , Male , Middle Aged , Postoperative Complications/mortality , Postoperative Complications/physiopathology , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome , Wales , Young Adult
15.
Immunol Res ; 61(1-2): 11-23, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25480739

ABSTRACT

We aim to harness the natural humoral immune response by various technologies to get novel biomarkers. A complex antibody analysis in sera and in the tumor microenvironment leads to reveal tumor-specific antibodies. More strategies were introduced to select the most effective one to identify potential tumor antigen-binding capacity of the host. Epstein-Barr virus transformation and cloning with limiting dilution assay, magnetic cell sorting and antibody phage display with further methodological improvements were used in epithelial and neuroectodermal cancers. Column-purified sera of patient with melanoma were tested by immunofluorescence assay, while sera of further melanoma patients were processed for membrane-binding enzyme-linked immunosorbent assay. Some supernatants of selected B cell clones and purified antibodies showed considerable cancer cell binding capacity by immunofluorescence FACS analysis and confocal laser microscopy. Our native tumor cell membrane preparations helped to test soluble scFv and patients' sera for tumor binder antibodies. A complex tumor immunological study was introduced for patients with melanoma (ethical permission: ETT TUKEB 16462-02/2010); peripheral blood (n = 57) and surgically removed primary or metastatic tumors (n = 44) were gathered and processed at cellular immunological level. The technological developments proved to be important steps forward to the next antibody profile analyses at DNA sequence level. Cancer cell binding of patient-derived antibodies and natural immunoglobulin preparations of pooled plasma product intravenous immunoglobulins support the importance of natural human antibodies. Important cancer diagnostics and novel anticancer strategies are going to be built on these tools.


Subject(s)
Antibodies, Neoplasm/immunology , Antigens, Neoplasm/immunology , Melanoma/immunology , Melanoma/pathology , Antibodies, Neoplasm/blood , Antibodies, Neoplasm/isolation & purification , Antibody Formation , Antibody Specificity/immunology , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Biomarkers , Cell Line, Transformed , Cell Line, Tumor , Cell Proliferation , Flow Cytometry , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Melanoma/blood , Neoplasm Metastasis , Tumor Microenvironment/immunology
17.
Orv Hetil ; 154(22): 850-6, 2013 Jun 02.
Article in Hungarian | MEDLINE | ID: mdl-23708985

ABSTRACT

The life expectancy of patients with type 1 diabetes mellitus is inferior to that of patients with some malignancies. Simultaneous pancreas-kidney transplantation is the procedure providing the best survival results among all options of renal replacement therapy. The operative techniques and immunosuppresion have been standardized in the last decade. Although the number of transplantable organs falls behind the need, simultaneous pancreas-kidney transplantation is the method of choice for the eligible patients. The results of the two Hungarian simultaneous pancreas-kidney transplantation programs are in accordance with data published in the international literature.


Subject(s)
Diabetes Mellitus, Type 1/surgery , Diabetic Nephropathies/surgery , Immunosuppressive Agents/administration & dosage , Kidney Transplantation , Pancreas Transplantation , Tissue and Organ Procurement , Cytomegalovirus Infections/prevention & control , Diabetes Mellitus, Type 1/complications , Diabetic Nephropathies/etiology , Humans , Immunosuppression Therapy/methods , Kidney Transplantation/methods , Kidney Transplantation/trends , Outcome and Process Assessment, Health Care , Pancreas Transplantation/methods , Pancreas Transplantation/trends , Patient Selection , Program Development , Program Evaluation , Tissue and Organ Procurement/organization & administration , Tissue and Organ Procurement/trends
18.
J Transl Med ; 11: 43, 2013 Feb 18.
Article in English | MEDLINE | ID: mdl-23418928

ABSTRACT

BACKGROUND: Besides being a preferential site of early metastasis, the sentinel lymph node (SLN) is also a privileged site of T-cell priming, and may thus be an appropriate target for investigating cell types involved in antitumor immune reactions. METHODS: In this retrospective study we determined the prevalence of OX40+ activated T lymphocytes, FOXP3+ (forkhead box P3) regulatory T cells, DC-LAMP+ (dendritic cell-lysosomal associated membrane protein) mature dendritic cells (DCs) and CD123+ plasmacytoid DCs by immunohistochemistry in 100 SLNs from 60 melanoma patients. Density values of each cell type in SLNs were compared to those in non-sentinel nodes obtained from block dissections (n = 37), and analyzed with regard to associations with clinicopathological parameters and disease outcome. RESULTS: Sentinel nodes showed elevated amount of all cell types studied in comparison to non-sentinel nodes. Metastatic SLNs had higher density of OX40+ lymphocytes compared to tumor-negative nodes, while no significant difference was observed in the case of the other cell types studied. In patients with positive sentinel node status, high amount of FOXP3+ cells in SLNs was associated with shorter progression-free (P = 0.0011) and overall survival (P = 0.0014), while no significant correlation was found in the case of sentinel-negative patients. The density of OX40+, CD123+ or DC-LAMP+ cells did not show significant association with the outcome of the disease. CONCLUSIONS: Taken together, our results are compatible with the hypothesis of functional competence of sentinel lymph nodes based on the prevalence of the studied immune cells. The density of FOXP3+ lymphocytes showed association with progression and survival in patients with positive SLN status, while the other immune markers studied did not prove of prognostic importance. These results, together with our previous findings on the prognostic value of activated T cells and mature DCs infiltrating primary melanomas, suggest that immune activation-associated markers in the primary tumor may have a higher impact than those in SLNs on the prognosis of the patients. On the other hand, FOXP3+ cell density in SLNs, but not in the primary tumor, was found predictive of disease outcome in melanoma patients.


Subject(s)
Forkhead Transcription Factors/metabolism , Lymph Nodes/immunology , Melanoma/immunology , Sentinel Lymph Node Biopsy , Adult , Aged , Disease Progression , Female , Humans , Immunohistochemistry , Lymph Nodes/pathology , Male , Melanoma/pathology , Middle Aged , Retrospective Studies , Survival Analysis
19.
Transplantation ; 94(12): 1218-23, 2012 Dec 27.
Article in English | MEDLINE | ID: mdl-23154212

ABSTRACT

BACKGROUND: Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. METHODS: We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. RESULTS: Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). CONCLUSION: Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.


Subject(s)
Death , Delayed Graft Function/mortality , Graft Rejection/mortality , Graft Survival , Kidney Transplantation/mortality , Tissue Donors/statistics & numerical data , Acute Disease , Adolescent , Adult , Aged , Cadaver , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Survival Rate , Young Adult
20.
Histol Histopathol ; 26(7): 821-30, 2011 07.
Article in English | MEDLINE | ID: mdl-21630212

ABSTRACT

Intraperitoneal surgical mesh implantation is required for laparoscopic ventral hernia repair. Composite meshes are well known in animal models and human practice. The aim of our study is to compare the biological behaviour of two different textured silicone-covered polypropylene meshes. Transmural abdominal wall defect was created in 40 rabbits and treated as follows: In 20 animals a polypropylene mesh with a laminar silicone covering (LSPP) and in the rest a macroporous textured mesh knitted of silicone-impregnated polypropylene filaments (MSPP) was applied. One and three weeks after implantation we evaluated the intraperitoneal adhesion formation of the mesh macroscopically, histologically and immunohistochemically to detect the reactive cells, especially inflammatory, endothelial and mesothelial cells, as well as their proliferative activity, and with Scanning Electron microscopy to visualize the surface of the meshes. The adhesion formation caused by the composites showed no statistical difference after one week although in the three weeks old samples the LSPP adhesion was significantly weaker than that of MSPP. As complications, serome formation in both groups, fistulas, abscesses, and sc. haematoma in the LSPP group were found. Only in MSPP containing tissues was the decrease of Ki-67 positive proliferating cells significant. A significant increase in VEGF expressing cells was observed only in MSPP containing three week old samples, suggesting better regulation of vascular growth in tissues surrounding the implants. In one week old specimens we observed an irregular proliferation of cytokeratin containing mesothelial cells in both group. The intraperitoneal surface of MSPP mesh was covered with neoperitoneum, while it was not regularly seen on LSPP mesh after three week.


Subject(s)
Hernia, Ventral/surgery , Surgical Mesh , Animals , Biocompatible Materials , Coated Materials, Biocompatible , Humans , Immunohistochemistry , Keratins/metabolism , Ki-67 Antigen/metabolism , Materials Testing , Microscopy, Electron, Scanning , Models, Animal , Polypropylenes , Rabbits , Silicones , Time Factors , Tissue Adhesions/metabolism , Tissue Adhesions/pathology , Tissue Adhesions/prevention & control , Vascular Endothelial Growth Factor A/metabolism , Wound Healing
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