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1.
Ann Oncol ; 35(7): 588-606, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38834388

ABSTRACT

BACKGROUND: Advancements in the field of precision medicine have prompted the European Society for Medical Oncology (ESMO) Precision Medicine Working Group to update the recommendations for the use of tumour next-generation sequencing (NGS) for patients with advanced cancers in routine practice. METHODS: The group discussed the clinical impact of tumour NGS in guiding treatment decision using the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) considering cost-effectiveness and accessibility. RESULTS: As for 2020 recommendations, ESMO recommends running tumour NGS in advanced non-squamous non-small-cell lung cancer, prostate cancer, colorectal cancer, cholangiocarcinoma, and ovarian cancer. Moreover, it is recommended to carry out tumour NGS in clinical research centres and under specific circumstances discussed with patients. In this updated report, the consensus within the group has led to an expansion of the recommendations to encompass patients with advanced breast cancer and rare tumours such as gastrointestinal stromal tumours, sarcoma, thyroid cancer, and cancer of unknown primary. Finally, ESMO recommends carrying out tumour NGS to detect tumour-agnostic alterations in patients with metastatic cancers where access to matched therapies is available. CONCLUSION: Tumour NGS is increasingly expanding its scope and application within oncology with the aim of enhancing the efficacy of precision medicine for patients with cancer.


Subject(s)
High-Throughput Nucleotide Sequencing , Neoplasms , Precision Medicine , Humans , High-Throughput Nucleotide Sequencing/methods , High-Throughput Nucleotide Sequencing/standards , Precision Medicine/methods , Precision Medicine/standards , Neoplasms/genetics , Neoplasms/pathology , Neoplasms/therapy , Medical Oncology/methods , Medical Oncology/standards , Europe
2.
ESMO Open ; 7(3): 100522, 2022 06.
Article in English | MEDLINE | ID: mdl-35717681

ABSTRACT

BACKGROUND: Clear cell sarcoma (CCS) is a translocated aggressive malignancy with a high incidence of metastases and poor prognosis. There are few studies describing the activity of systemic therapy in CCS. We report a multi-institutional retrospective study of the outcomes of patients with advanced CCS treated with systemic therapy within the World Sarcoma Network (WSN). MATERIALS AND METHODS: Patients with molecularly confirmed locally advanced or metastatic CCS treated with systemic therapy from June 1985 to May 2021 were included. Baseline demographic and treatment information, including response by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, was retrospectively collected by local investigators. Descriptive statistics were carried out. RESULTS: Fifty-five patients from 10 institutions were included. At diagnosis, the median age was 30 (15-73) years and 24% (n = 13/55) had metastatic disease. The median age at diagnosis was 30 (15-73) years. Most primary tumours were at aponeurosis (n = 9/55, 16%) or non-aponeurosis limb sites (n = 17/55, 31%). The most common fusion was EWSR1-ATF1 (n = 24/55, 44%). The median number of systemic therapies was 1 (range 1-7). The best response rate was seen for patients treated with sunitinib (30%, n = 3/10), with a median progression-free survival of 4 [95% confidence interval (CI) 1-7] months. The median overall survival for patients with advanced/metastatic disease was 15 months (95% CI 3-27 months). CONCLUSIONS: Soft tissue sarcoma-type systemic therapies have limited benefit in advanced CCS and response rate was poor. International, multicentre prospective translational studies are required to identify new treatments for this ultra-rare subtype, and access to early clinical trial enrolment remains key for patients with CCS.


Subject(s)
Sarcoma, Clear Cell , Soft Tissue Neoplasms , Adolescent , Adult , Aged , Humans , Middle Aged , Prospective Studies , Retrospective Studies , Sarcoma, Clear Cell/diagnosis , Sarcoma, Clear Cell/drug therapy , Sarcoma, Clear Cell/pathology , Soft Tissue Neoplasms/drug therapy , Soft Tissue Neoplasms/pathology , Sunitinib/therapeutic use , Young Adult
3.
Sci Rep ; 10(1): 5379, 2020 03 25.
Article in English | MEDLINE | ID: mdl-32214151

ABSTRACT

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer. Prognosis for ccRCC is generally poor since it is largely resistant to chemo- and radiotherapy. Many studies suggested that cancer stem cells/tumor initiating cells (CSCs/TICs) are responsible for development of tumor, disease progression, aggressiveness, metastasis and drug resistance. However, tumorigenic potential of CSCs/TICs isolated from established RCC cell lines - basic ccRCC research model - has never been investigated in vivo. CD105+, CD105-, CD44+ and CD44- as well as CD44-/CD105- CD44+/CD105+ and CD44-/CD105+ cells were isolated from Caki-1 RCC cell line, confirming coexistence of multiple subpopulations of stem-related phenotype in stable cell line. Sorted cells were injected subcutaneously into NOD SCID mice and tumor growth was monitored with MRI and PET/CT. Tumor growth was observed after implantation of CD105+, CD44+, CD44-, CD44-/CD105+ and CD44-/CD105- but not CD105- or CD44+/CD105+. Implantation of CD44-/CD105- cells induced tumors that were characterized by longer T1 and distinct metabolic pattern than other tumors. All the tumors were characterized by low uptake of [18F]FDG. CD105+ and CD44- tumors expresses Nanog and Oct-4, while CD44- tumors additionally expressed endothelial cell marker - CD31.


Subject(s)
Carcinoma, Renal Cell/immunology , Endoglin/immunology , Hyaluronan Receptors/immunology , Animals , Biomarkers, Tumor/immunology , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Separation , Endoglin/metabolism , Humans , Hyaluronan Receptors/metabolism , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Male , Mice , Mice, Inbred NOD , Mice, SCID , Neoplastic Stem Cells/immunology , Neoplastic Stem Cells/metabolism , Positron Emission Tomography Computed Tomography , Prognosis
4.
Rev Sci Instrum ; 89(10): 10F111, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30399723

ABSTRACT

The paper reports on the optimization process of the soft X-ray pulse height analyzer installed on the Wendelstein 7-X (W7-X) stellarator. It is a 3-channel system that records X-ray spectra in the range from 0.6 to 19.6 keV. X-ray spectra, with a temporal and spatial resolution of 100 ms and 2.5 cm (depending on selected slit sizes), respectively, are line integrated along a line-of-sight that crosses near to the plasma center. In the second W7-X operation phase with a carbon test divertor unit, light impurities, e.g., carbon and oxygen, were observed as well as mid- to high-Z elements, e.g., sulfur, chlorine, chromium, manganese, iron, and nickel. In addition, X-ray lines from several tracer elements have been observed after the laser blow-off injection of different impurities, e.g., silicon, titanium, and iron, and during discharges with prefill or a gas puff of neon or argon. These measurements were achieved by optimizing light absorber-foil selection, which defines the detected energy range, and remotely controlled pinhole size, which defines photon flux. The identification of X-ray lines was confirmed by other spectroscopic diagnostics, e.g., by the High-Efficiency XUV Overview Spectrometer, HEXOS, and high-resolution X-ray imaging spectrometer, HR-XIS.

5.
Rev Sci Instrum ; 89(10): 10D131, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30399789

ABSTRACT

This paper reports on impurity behavior in a set of hybrid discharges with Ne seeding-one of the techniques considered to reduce the power load on reactor walls. A series of experiments carried out with light gas injection on JET with the ITER-Like-Wall (ILW) suggests increased tungsten release and impurity accumulation [C. Challis et al., Europhysics Conference Abstracts 41F, 2.153 (2017)]. The presented method relies mainly on the measurements collected by vacuum-ultra-violet and soft X-ray (SXR) diagnostics including the "SOXMOS" spectrometer and the SXR camera system. Both diagnostics have some limitations. Consequently, only a combination of measurements from these systems is able to provide comprehensive information about high-Z [e.g., tungsten (W)] and mid-Z [nickel (Ni), iron (Fe), copper (Cu), and molybdenum (Mo)] impurities for their further quantitative diagnosis. Moreover, thanks to the large number of the SXR lines of sight, determination of a 2D radiation profile was also possible. Additionally, the experimental results were compared with numerical modeling based on integrated simulations with COREDIV. Detailed analysis confirmed that during seeding experiments, higher tungsten release is observed, which was also found in the past. Additionally, it was noticed that besides W, the contribution of molybdenum to SXR radiation was greater, which can be explained by the place of its origin.

6.
Rev Sci Instrum ; 87(11): 11D304, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27910389

ABSTRACT

Wendelstein 7-X, a superconducting optimized stellarator built in Greifswald/Germany, started its first plasmas with the last closed flux surface (LCFS) defined by 5 uncooled graphite limiters in December 2015. At the end of the 10 weeks long experimental campaign (OP1.1) more than 20 independent diagnostic systems were in operation, allowing detailed studies of many interesting plasma phenomena. For example, fast neutral gas manometers supported by video cameras (including one fast-frame camera with frame rates of tens of kHz) as well as visible cameras with different interference filters, with field of views covering all ten half-modules of the stellarator, discovered a MARFE-like radiation zone on the inboard side of machine module 4. This structure is presumably triggered by an inadvertent plasma-wall interaction in module 4 resulting in a high impurity influx that terminates some discharges by radiation cooling. The main plasma parameters achieved in OP1.1 exceeded predicted values in discharges of a length reaching 6 s. Although OP1.1 is characterized by short pulses, many of the diagnostics are already designed for quasi-steady state operation of 30 min discharges heated at 10 MW of ECRH. An overview of diagnostic performance for OP1.1 is given, including some highlights from the physics campaigns.

7.
Neuroscience ; 324: 92-106, 2016 Jun 02.
Article in English | MEDLINE | ID: mdl-26964686

ABSTRACT

Since the discovery of the role of the ubiquitin-proteasome system (UPS) in the pathogenesis of Parkinson's disease, UPS inhibitors, such as lactacystin have been used to investigate the relationship between UPS impairment and degeneration of dopamine (DA) neurons. However, mostly long-term neurotoxic effects of lactacystin have been studied in animal models. Therefore, the aim of our study was to investigate behavioral and biochemical changes related to the DA system during the first week following unilateral intranigral injection of lactacystin to rats. We found that lactacystin produced early spontaneous contralateral rotations which were inhibited by combined administration of DA D1 and D2 receptor antagonists. Simultaneously, an increase in the extracellular level of DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) was found in the ipsilateral striatum. In contrast, one week after lesion, when turning behavior was no longer visible, a decrease in the extracellular level of DA, DOPAC and HVA was demonstrated. It was accompanied by a substantial reduction in the tissue levels of DA and its metabolites in the lesioned substantia nigra and striatum. We concluded that unilateral intranigral administration of lactacystin produces an early increase in DA neurotransmission which precedes a decrease in the striatal and nigral tissue DA content. It is manifested by the appearance of spontaneous contralateral rotations and an elevation of the extracellular DA level in the ipsilateral striatum. Since similar behavior was previously observed after intranigral administration of rotenone and MPP(+) but not 6-hydroxydopamine (6-OHDA), it may indicate a common mechanism of action shared by these neurotoxins.


Subject(s)
Acetylcysteine/analogs & derivatives , Central Nervous System Agents/pharmacology , Corpus Striatum/drug effects , Dopamine/metabolism , Functional Laterality/drug effects , Movement/drug effects , 3,4-Dihydroxyphenylacetic Acid/metabolism , Acetylcysteine/pharmacology , Amphetamine/pharmacology , Animals , Benzazepines/pharmacology , Corpus Striatum/physiology , Dopamine Antagonists/pharmacology , Functional Laterality/physiology , Glutamic Acid/metabolism , Haloperidol/pharmacology , Homovanillic Acid/metabolism , Male , Movement/physiology , Parkinsonian Disorders , Rats, Wistar , Receptors, Dopamine/metabolism , Rotation , Substantia Nigra/drug effects , Substantia Nigra/physiology
8.
Endocr Relat Cancer ; 22(5): R253-64, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26330483

ABSTRACT

Insulin and IGFs play a significant role in cancer development and progression, including renal cell carcinoma (RCC). RCC is the most frequent type of kidney cancer in adults and the tenth most common malignancy worldwide. Insulin is normally associated with metabolism control, whereas IGFs are defined as proliferation regulators. Today, there is convincing evidence of an association between obesity and the risk of RCC. Indicated risk factors together with type 2 diabetes are irreversibly connected with circulating insulin and IGF levels. The interplay between these molecules, their receptors, and IGF-binding proteins might be crucial for RCC cell biology and RCC progression. Given the potent activity IGF/IGF receptor 1 (IGF1R) inhibitors demonstrate against RCC in basic research, some type of combination therapy may prove to be beneficial clinically in the management of RCC. This review addresses not only molecular but also clinical associations between insulin and IGF1 signaling pathways and both RCC biology and clinical course. Revealing these interactions may improve our understanding of basic molecular oncology processes in RCC and improve treatment strategies.


Subject(s)
Diabetes Mellitus, Type 2/complications , Insulin-Like Growth Factor Binding Proteins/metabolism , Insulin-Like Growth Factor I/metabolism , Insulin/metabolism , Kidney Neoplasms/etiology , Kidney Neoplasms/pathology , Adult , Diabetes Mellitus, Type 2/physiopathology , Disease Progression , Humans , Kidney Neoplasms/metabolism , Risk Factors
9.
Rev Sci Instrum ; 85(11): 11D818, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25430231

ABSTRACT

An overview of the diagnostics which are essential for the first operational phase of Wendelstein 7-X and the set of diagnostics expected to be ready for operation at this time are presented. The ongoing investigations of how to cope with high levels of stray Electron Cyclotron Resonance Heating (ECRH) radiation in the ultraviolet (UV)/visible/infrared (IR) optical diagnostics are described.

10.
Neuroradiology ; 55(9): 1061-9, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23728070

ABSTRACT

INTRODUCTION: Stasis filling, defined as delayed, weak, and persistent opacification of proximal segments of the cerebral arteries, is frequently found in brain dead patients. This phenomenon causes a major problem in the development of reliable computed tomographic angiography (CTA) protocol in the diagnosis of brain death (BD). The aim of our study was to characterize stasis filling in the diagnosis of BD. To achieve this, we performed a dynamic evaluation of contrast enhancement of the cerebral and extracranial arteries in patients with BD and controls. METHODS: Study population included 30 BD patients, who showed stasis filling in computed tomographic perfusion (CTP) series. Thirty patients, after clipping of an intracranial aneurysm, constituted the control group. The study protocol consisted of CTA, CTP, and angiography. Time-density curves (TDCs) of cerebral and extracranial arteries were generated using 40-s series of CTP. RESULTS: Cerebral TDCs in BD patients represented flat curves in contrast to TDCs in controls, which formed steep and narrow Gaussian curves. We found longer time to peak enhancement in BD patients than in controls (32 vs. 21 s; p < 0.0001). In BD patients, peak enhancement in the cerebral arteries occurred with a median delay of 14.5 s to peak in extracranial arteries, while no delay was noted in controls (p < 0.0001). Cerebral arteries in BD patients showed lower peak enhancement than controls (34.5 vs. 81.5 HU; p < 0.0001). In all BD patients, CTP revealed zero values of cerebral blood flow and volume. Angiography showed stasis filling in 14 (46.7 %) and non-filling in 16 (53.3 %) cases. CONCLUSION: A confrontation of stasis filling with CTP results showed that stasis filling is not consistent with preserved cerebral perfusion, thus does not preclude diagnosis of BD.


Subject(s)
Brain Death , Cerebral Angiography/methods , Cerebral Arteries/diagnostic imaging , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Young Adult
11.
Tissue Cell ; 44(6): 391-400, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22939219

ABSTRACT

Porous titanium is one of the most widely used implant materials because of its mechanical properties, however, it is also characterised by low bioactivity. To improve the above parameter we prepared three modifications of the porous (30 wt%) titanium (Ti) surface by covering it with bioactive hydroxyapatite (HA), bioglass (BG) and calcium silicate (CS). Subsequently we tested the impact of the modifications on macrophages directing the inflammatory response that might compromise the implant bioactivity. In the study we investigated the in vitro effects of the materials on murine cell line RAW 264.7 macrophage adherence, morphology and activation (production/release of metalloproteinase MMP-9 and pro- and anti-inflammatory cytokines). CS Ti decreased the macrophage adherence and up-regulated the release of several pro-inflammatory mediators, including TNF-α, IL-6, IL-12. Also HA Ti reduced the cell adherence but other parameters were generally not increased, except of TNF-α. In contrast, BG Ti improved macrophage adherence and either decreased production of multiple mediators (MMP-9, TNF-α, IFN-γ, MCP-1) or did not change it in comparison to the porous titanium. We can conclude that analyzing the effects on the inflammatory response initiated by macrophages in vitro, calcium silicate did not improve the biological properties of the porous titanium. The improved bioactivity of titanium was, however, achieved by the application of the hydroxyapatite and bioglass layers. The present in vitro results suggest that these materials, HA Ti and especially BG Ti, may be suitable for in vivo application and thus justify their further investigation.


Subject(s)
Ceramics/pharmacology , Macrophage Activation/drug effects , Macrophages/cytology , Titanium/pharmacology , Animals , Cell Adhesion/drug effects , Cell Line , Cell Shape/drug effects , Cytokines/biosynthesis , Inflammation Mediators/metabolism , Macrophages/drug effects , Macrophages/enzymology , Macrophages/ultrastructure , Matrix Metalloproteinase 9/metabolism , Mice , Porosity
12.
J Biomater Sci Polym Ed ; 23(6): 715-38, 2012.
Article in English | MEDLINE | ID: mdl-21375810

ABSTRACT

There is a constant search for biodegradable polymers with biocompatible characteristics. However, the reported materials are rarely tested for their immunostimulatory properties, which is an important issue as immune cells activated by the polymers might cause their rejection and lead to further injury to the host tissues. Therefore, the aim of the present study was to determine if biodegradable polymers are able to activate RAW 264.7 macrophages. Aliphatic polyesters, poly(L-lactide) (PLLA), poly(L-lactide-co-trimethylene carbonate) (PLTMC), poly(glycolide-co-L-lactide) (PGLA), poly(glycolide-co-L-lactide-co-ε-caprolactone) (PGLCap) and poly(glycolide-co-ε-caprolactone) (PGCap), processed into foils by slip-casting, were characterized in terms of their structure ((1)H-NMR, GPC, DSC) and surface properties (chemical composition, water contact angle, surface free energy, topography and roughness). RAW 264.7 cells were cultured on the materials for 3 or 5 days and their adherence, numbers of apoptotic/necrotic cells, as well as production of several cytokines/chemokines and other inflammation-related molecules (matrix metalloproteinases, nitric oxide) was evaluated. The study demonstrated that PLLA and PGLA did not influence macrophage activation and survival. In contrast, PLTMC, PGLCap and PGCap significantly decreased macrophage adherence, increased ratio of apoptosis and up-regulated synthesis/release of numerous inflammatory mediators. Thus, the latter materials might initiate an undesired inflammatory reaction. The above effects of the polymers were attributed to their high hydrophobicity and low polarity due to the presence of ε-caproyl blocks (PGLCap and PGCap), and/or high flexibility and susceptibility to mechanical deformation due to low glasstransition temperature (PLTMC, PGLCap and PGCap). In conclusion, while PLLA and PGLA do not affect macrophage functioning, the other materials (PLTMC, PGLCap, PGCap) up-regulate macrophage activity.


Subject(s)
Biocompatible Materials , Macrophages/immunology , Polyesters , Animals , Apoptosis , Biocompatible Materials/chemical synthesis , Biocompatible Materials/chemistry , Cell Adhesion , Cell Proliferation , Cell Survival , Cytokines/metabolism , Hydrophobic and Hydrophilic Interactions , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Necrosis , Nitrates/metabolism , Nitric Oxide/metabolism , Nitrites/metabolism , Polyesters/chemical synthesis , Polyesters/chemistry , RAW 264.7 Cells , Surface Properties , Time Factors
13.
Eur J Histochem ; 52(4): 221-8, 2008.
Article in English | MEDLINE | ID: mdl-19109096

ABSTRACT

Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS) has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3) and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma) cells were exposed to various concentrations of hydrogen peroxide (H2O2) for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt) p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cells.


Subject(s)
Carcinoma, Mucoepidermoid/metabolism , Caspase 3/metabolism , Chaperonin 60/metabolism , Lung Neoplasms/metabolism , Oxidative Stress , Apoptosis/drug effects , Blotting, Western , Carcinoma, Mucoepidermoid/drug therapy , Carcinoma, Mucoepidermoid/pathology , Cell Line, Tumor , Cell Survival/drug effects , Comet Assay , DNA/drug effects , DNA Damage , Formazans/metabolism , Gene Expression/drug effects , Humans , Hydrogen Peroxide/pharmacology , Immunohistochemistry , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Tetrazolium Salts/metabolism , Trypan Blue/metabolism , Tumor Suppressor Protein p53/biosynthesis , Tumor Suppressor Protein p53/genetics
14.
Histopathology ; 52(2): 203-12, 2008 Jan.
Article in English | MEDLINE | ID: mdl-18184269

ABSTRACT

AIMS: CD1a is a molecule belonging to the highly conserved group of CD1 proteins. Its expression in dendritic cells is related to the presentation of tumour-derived glycolipid antigens to T cells and, consequently, the development of a successful antitumour response. The aim was to investigate the presence of CD1a+ cells in both primary tumours and lymph nodes (LN) of a series of 35 invasive ductal carcinomas by both immunohistochemistry and reverse transcription-polymerase chain reaction. METHODS AND RESULTS: CD1a antigen was more expressed in N0 than N1 breast cancer (P < 0.0001) in both primary lesions and LN metastases and correlated positively and significantly with oestrogen (ER) (P = 0.0025) and progesterone (P = 0.0226) receptor (PR) status, as well as CD4+ and CD8+ T-lymphocyte infiltration. CONCLUSIONS: This is the first report to show a link between CD1a+ mononuclear cells in breast cancer and in paired LN metastases. The positive and significant correlations between the number of CD1a+ cells and positivity of the primary tumour for ER and PR suggest a possible role for CD1a as a prognostic marker for breast cancer, raising the possibility that hormone receptor-positive breast cancer patients may have a better prognosis in the presence of greater dendritic cell infiltration.


Subject(s)
Antigens, CD1/metabolism , Breast Neoplasms/metabolism , Carcinoma, Ductal, Breast/metabolism , Down-Regulation , Lymphatic Metastasis/diagnosis , Adult , Aged , Antigens, CD1/genetics , Breast Neoplasms/genetics , Breast Neoplasms/pathology , CD4-Positive T-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Carcinoma, Ductal, Breast/genetics , Carcinoma, Ductal, Breast/pathology , Dendritic Cells , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Lymphatic Metastasis/pathology , Middle Aged , Predictive Value of Tests , Prognosis , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism
15.
Eur J Histochem ; 50(1): 25-34, 2006.
Article in English | MEDLINE | ID: mdl-16584982

ABSTRACT

This review addresses the significance of the expression of proliferating cell nuclear antigen (PCNA), p53 and some heat shock proteins (Hsps) in prostate carcinoma (PC). In fact, PCNA and p53 are two widely discussed tools in PC diagnosis, mainly because of the controversy regarding the significance of their expression during prostate cancer development and progression. At the same time, only few studies have shown the potential role of Hsps in carcinogenesis and their overexpression in pre-neoplastic and neoplastic lesions of the prostate. We briefly describe the physiological roles of Hsps in normal cells, and the significance of their immunohistochemical detection in PC as well as in pre-cancerous lesions of the prostate. We will also discuss the possible functional interactions of these molecules in both dysplastic and neoplastic cells.


Subject(s)
Biomarkers, Tumor/metabolism , Heat-Shock Proteins/metabolism , Proliferating Cell Nuclear Antigen/metabolism , Prostate/metabolism , Prostatic Neoplasms/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Biomarkers, Tumor/analysis , Cell Transformation, Neoplastic/metabolism , Heat-Shock Proteins/analysis , Humans , Immunohistochemistry , Male , Precancerous Conditions/metabolism , Proliferating Cell Nuclear Antigen/analysis , Prostate/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/etiology , Prostatic Neoplasms/pathology , Tumor Suppressor Protein p53/analysis
16.
Immunol Lett ; 101(2): 185-92, 2005 Nov 15.
Article in English | MEDLINE | ID: mdl-15979727

ABSTRACT

We have shown that supplementation of proinflammatory agent with a high dose of morphine not only abolishes inflammation-related pain symptoms but also inhibits influx of leukocytes to the inflamed peritoneal cavity. Present investigations focused on effects of morphine on proopiomelanocortin and prodynorphin systems during zymosan-induced peritonitis. Males of SWISS mice were ip injected with zymosan (Z, 40 mg/kg) or zymosan with morphine (ZM, 20 mg/kg). At time 0 (controls) and 4 and 24h after stimulation, peritoneal leukocytes (PTLs) were counted, PTL levels of opioid peptides (beta-endorphin and dynorphin) measured by radioimmunoassays, while mRNAs coding their respective precursors (POMC and PDYN) and receptors (MOR and KOR) determined by QRT-PCR. Influx of inflammatory PTLs, mainly PMNs, was significantly delayed by morphine co-injection. Total levels of beta-endorphin and dynorphin corresponded with PTL numbers, while levels per cell were similar in all groups except of beta-endorphin, decreased in ZM at 4h. Levels of both peptides in peritoneal fluid were increased in Z and ZM groups at 4h, while at 24h only in case of beta-endorphin in Z group. POMC was increased only in ZM group at 4h of peritonitis, while PDYN in both Z and ZM groups at the same time. MOR mRNA was increased 24h after injection in Z and ZM groups, while KOR mRNA was similar in all groups except of decrease in Z at 24h. In conclusion, endogenous opioids and their receptors are involved in zymosan-induced peritonitis and affected in various ways by morphine co-injection.


Subject(s)
Enkephalins/metabolism , Morphine/pharmacology , Peritonitis/metabolism , Pro-Opiomelanocortin/metabolism , Protein Precursors/metabolism , Animals , Cell Proliferation/drug effects , Leukocytes/cytology , Leukocytes/drug effects , Leukocytes/metabolism , Male , Mice , Peritonitis/chemically induced , Peritonitis/genetics , Pro-Opiomelanocortin/genetics , RNA, Messenger/genetics , Receptors, Opioid, kappa/genetics , Receptors, Opioid, mu/genetics , Zymosan/pharmacology
17.
Pol J Pharmacol ; 53(6): 715-8, 2001.
Article in English | MEDLINE | ID: mdl-11985352

ABSTRACT

Zymosan- or thioglycollate-induced experimental peritoneal inflammation in mice may serve as a convenient model for investigations of involvement of opioid peptides derived from exudatory leukocytes in the inflammatory processes. During peritonitis, the influx of neutrophils and monocytes/macrophages correlated with a sequential appearance of proinflammatory cytokines (IL-1beta and TNFalpha). After both kinds of stimulation, the expression of PENK mRNA was much higher in exudatory peritoneal leukocytes than its basal level in steady state.


Subject(s)
Enkephalins/metabolism , Leukocytes/metabolism , Peritonitis/metabolism , Protein Precursors/metabolism , RNA, Messenger/metabolism , Animals , Ascitic Fluid/cytology , Ascitic Fluid/immunology , Ascitic Fluid/metabolism , Enkephalins/genetics , Enzyme-Linked Immunosorbent Assay , Interleukin-1/metabolism , Leukocytes/cytology , Male , Mice , Neutrophils/cytology , Neutrophils/metabolism , Peritoneal Cavity/cytology , Peritonitis/chemically induced , Peritonitis/immunology , Protein Precursors/genetics , Reverse Transcriptase Polymerase Chain Reaction , Thioglycolates , Tumor Necrosis Factor-alpha/metabolism , Zymosan
18.
Fish Shellfish Immunol ; 10(6): 531-42, 2000 Aug.
Article in English | MEDLINE | ID: mdl-11016587

ABSTRACT

Acute peritonitis induced in the goldfish by intraperitoneal injection of a sterile Thioglycollate solution shows a typical pattern with intraperitoneal exudation of serum proteins followed by influx of leucocytes (mainly heterophils/macrophages) correlated with elevated levels of chemotactic factors in peritoneal fluid and blood plasma. Supplementation of Thioglycollate with morphine (20 mg kg(-1) b.w.) does not affect the leakage of serum proteins into peritoneum. In contrast, it reduces the number of exudate peritoneal leucocytes (among them heterophils/macrophages) to the control level and decreases the level of peritoneal fluid/plasma chemoattractants, both effects being reversed by naltrexone pretreatment. Morphine itself acts as a chemokinetic factor for fish leucocytes as it increases their random movements. Therefore inhibitory effects of morphine on accumulation of exudate cells might be explained by inhibition of the production/release of chemotactic factors and/or reduced sensitivity of leucocytes to chemotactic signals. The effects of morphine on the goldfish peritonitis are in concordance with those described recently in Atlantic salmon and CB6 mice.


Subject(s)
Analgesics, Opioid/therapeutic use , Fish Diseases/immunology , Goldfish/immunology , Morphine/therapeutic use , Peritonitis/veterinary , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/immunology , Animals , Chemotaxis , Coloring Agents/chemistry , Evans Blue/chemistry , Exudates and Transudates , Fish Diseases/drug therapy , Injections, Intraperitoneal/veterinary , Leukocyte Count/veterinary , Morphine/administration & dosage , Morphine/immunology , Naltrexone/administration & dosage , Narcotic Antagonists/administration & dosage , Peritonitis/drug therapy , Peritonitis/immunology , Thioglycolates/administration & dosage
19.
Pneumonol Alergol Pol ; 61(11-12): 637-40, 1993.
Article in Polish | MEDLINE | ID: mdl-8148766

ABSTRACT

The authors discuss the etiology, pathomechanisms, radiological features of lipid pneumonia. The role of bronchoalveolar lavage is stressed in determining this diagnosis. A case is presented of a patient receiving paraffin oil for chronic constipation. The diagnosis was made after identifying the lipid droplets (Sudan III stain) in alveolar macrophages sampled by BAL.


Subject(s)
Pneumonia, Lipid/diagnosis , Aged , Bronchoalveolar Lavage Fluid/cytology , Humans , Male , Pneumonia, Lipid/etiology
20.
Pneumonol Alergol Pol ; 61(5-6): 298-303, 1993.
Article in Polish | MEDLINE | ID: mdl-8348097

ABSTRACT

A case of chronic necrotic aspergillosis was discussed. Diagnostic and therapeutic difficulties were described in patient with an insufficiency of immune response mainly in polymorphonuclear leukocytes function.


Subject(s)
Aspergillosis/diagnosis , Lung Diseases, Fungal/diagnosis , Aspergillosis/immunology , Chronic Disease , Humans , Immune Tolerance , Lung Diseases, Fungal/immunology , Male , Middle Aged , Necrosis
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