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  • 1
    Language: English
    In: Journal of biomedical science, 2017-08-24, Vol.24 (1), p.60-17
    Description: To mimic systemic inflammation in humans, different animal models have been developed. Since these models are still discussed controversially, we aimed to comparatively evaluate the most widely used models with respect to the systemic effects, the influence on organ functions and to the underlying pathophysiological processes. Systemic inflammation was induced in C57BL/6N mice with lipopolysaccharide (LPS) treatment, peritoneal contamination and infection (PCI), or cecal ligation and puncture (CLP). Blood glucose and circulating cytokine levels were evaluated at 0, 2, 4, 6, 12, 24, 48, and 72 h after induction of inflammation. Additionally, oxidative stress in various organs and liver biotransformation capacity were determined. Markers for oxidative stress, apoptosis, infiltrating immune cells, as well as cytokine expression patterns, were assessed in liver and spleen tissue by immunohistochemistry. Treating mice with LPS and PCI induced a very similar course of inflammation; however, LPS treatment elicited a stronger response. In both models, serum pro-inflammatory cytokine levels rapidly increased whereas blood glucose decreased. Organs showed early signs of oxidative stress, and apoptosis was increased in splenic cells. In addition, liver biotransformation capacity was reduced and there was pronounced immune cell infiltration in both the liver and spleen. Mice exposed to either LPS or PCI recovered after 72 h. In contrast, CLP treatment induced comparatively fewer effects, but a more protracted course of inflammation. The LPS model of systemic inflammation revealed to be most suitable when being interested in the impact of new therapies for acute inflammation. When using the CLP model to mimic human sepsis more closely, a longer time course should be employed, as the treatment induces delayed development of systemic inflammation.
    Subject(s): Blood Glucose - analysis ; Oxidative Stress ; Liver - metabolism ; Mice, Inbred C57BL ; Male ; Organ Specificity ; Inflammation - etiology ; Animals ; Cecum - surgery ; Time Factors ; Biotransformation ; Lipopolysaccharides - pharmacology ; Peritoneal Diseases - immunology ; Mice ; Ligation - adverse effects ; Cecum - immunology ; Cytokines - blood ; Disease Models, Animal ; Inflammation - physiopathology ; Infection ; Cytokines ; Blood sugar ; Analysis ; Liver ; Inflammation ; Health aspects ; Mitogens ; Oxidative stress ; CLP ; PCI ; Research ; LPS ; Systemic inflammation
    ISSN: 1423-0127
    ISSN: 1021-7770
    E-ISSN: 1423-0127
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 2
    Language: English
    In: Journal of biomedical science, 2016-10-03, Vol.23 (1), p.68
    Description: Chemokine receptor 4 (CXCR4) is a multifunctional G protein-coupled receptor that is activated by its natural ligand, C-X-C motif chemokine 12 (CXCL12). As a likely member of the lipopolysaccharide (LPS)-sensing complex, CXCR4 is involved in pro-inflammatory cytokine production and exhibits substantial chemo-attractive activity for various inflammatory cells. Here, we aimed to characterize the effects of CXCR4 blockade in systemic inflammation and to evaluate its impact on organ function. Furthermore, we investigated whether CXCR4 blockade exerts deleterious effects, thereby substantiating previous studies showing a beneficial outcome after treatment with CXCR4 agonists in endotoxemia. The CXCR4 antagonist AMD3100 was administered intraperitoneally to mice shortly after LPS treatment. After 24 h, health status was determined and serum tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma), and nitric oxide (NO) levels were measured. We further assessed oxidative stress in the brain, kidney, and liver as well as liver biotransformation capacity. Finally, we utilized immunohistochemistry and immunoblotting in liver and spleen tissue to determine cluster of differentiation 3 (CD3), CD8, CD68, and TNF alpha expression patterns, and to assess the presence of various markers for apoptosis and oxidative stress. Mice treated with AMD3100 displayed impaired health status and showed enhanced serum levels of TNF alpha, IFN gamma and NO levels in endotoxemia. This compound also amplified LPS-induced oxidative stress in all tissues investigated and decreased liver biotransformation capacity in co-treated animals. Co-treatment with AMD3100 further inhibited expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), heme oxygenase-1 (HO-1), and various cytochrome P450 enzymes, whereas it enhanced expression of CD3, inducible nitric oxide synthase, and TNF alpha, as well as the total number of neutrophils in liver tissue. Spleens from co-treated animals contained large numbers of erythrocytes and neutrophils, but fewer CD3+ cells, and demonstrated increased apoptosis in the white pulp. AMD3100 administration in a mouse model of endotoxemia further impaired health status and liver function and mediated pro-inflammatory, pro-oxidative, and pro-apoptotic effects. This suggests that interruption of the CXCR4/CXCL12 axis is deleterious in acute inflammation and confirms previous findings showing beneficial effects of CXCR4 agonists in endotoxemia, thereby more clearly elucidating the role of CXCR4 in inflammation.
    Subject(s): Anti-HIV Agents - pharmacology ; Inflammation - chemically induced ; Liver - pathology ; Apoptosis - drug effects ; Endotoxemia - drug therapy ; Mice, Inbred C57BL ; Heterocyclic Compounds - pharmacology ; Injections, Intraperitoneal ; Male ; Spleen - drug effects ; Receptors, CXCR4 - metabolism ; Animals ; Chemokine CXCL12 - metabolism ; Liver - drug effects ; Endotoxemia - physiopathology ; Lipopolysaccharides - pharmacology ; Oxidation-Reduction - drug effects ; Spleen - pathology ; Antagonists (Biochemistry) ; Health aspects ; Chemokine receptors ; Lipopolysaccharides ; Oxidative stress ; CXCR4 ; CXCL12 ; Research ; AMD3100 ; Endotoxemia
    ISSN: 1423-0127
    ISSN: 1021-7770
    E-ISSN: 1423-0127
    Source: BioMedCentral Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 3
    Language: English
    In: Histopathology, 2015-09, Vol.67 (3), p.368-377
    Description: Aims Due to the growing number of somatostatin receptor (SSTR) targeting analogues and radiopeptides used for the diagnosis and therapy of neuroendocrine neoplasms (NEN), the assessment of SSTR subtype status has increasingly gained predictive value. In pathology, the SSTR protein levels are detected routinely by immunohistochemistry (IHC); however, a lack of a standardized evaluation system persists. Thus, in the present investigation, three well‐established semi‐quantitative scoring systems [immunoreactive score (IRS), human epidermal growth factor receptor 2 (HER2)/neu score, H score] used commonly for SSTR‐IHC evaluation in NEN were compared. Methods and results A total of 240 formalin‐fixed, paraffin‐embedded tumour samples from 90 patients with bronchopulmonary NEN were examined by IHC and quantitative reverse transcription–polymerase chain reaction (qRT–PCR) for SSTR1, 2A, 3, 4 and 5 expression. Using both methods, SSTR1, 2A and 5 were the most frequently expressed subtypes. For all SSTR subtypes, all three scores correlated well with each other and with qRT–PCR data. However, the IRS was the most meaningful score with the best correlation to mRNA levels. Conclusions Because a unified IHC scoring system for SSTR analysis is needed urgently to optimize the theranostics of NEN, among the scores tested, the IRS seems to be the most suitable according to our results. It provides sufficient accuracy combined with high practicability.
    Subject(s): lung ; immunoreactive score ; H score ; receptors/somatostatin ; HER2/neu score ; neuroendocrine tumours ; immunohistochemistry ; Lung Neoplasms - genetics ; Neuroendocrine Tumors - pathology ; Neuroendocrine Tumors - metabolism ; Bronchial Neoplasms - genetics ; Humans ; Lung Neoplasms - metabolism ; RNA, Messenger - genetics ; Receptor, ErbB-2 - metabolism ; Lung Neoplasms - pathology ; RNA, Messenger - metabolism ; Receptors, Somatostatin - classification ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Neoplasm - metabolism ; Neuroendocrine Tumors - genetics ; Immunohistochemistry - methods ; Receptors, Somatostatin - genetics ; Bronchial Neoplasms - pathology ; Biomarkers, Tumor - metabolism ; RNA, Neoplasm - genetics ; Biomarkers, Tumor - genetics ; Receptors, Somatostatin - metabolism ; Bronchial Neoplasms - metabolism ; Immunohistochemistry ; Comparative analysis ; Tumors
    ISSN: 0309-0167
    E-ISSN: 1365-2559
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 4
    Language: English
    In: Journal of mammary gland biology and neoplasia, 2016-12, Vol.21 (3), p.89-98
    Description: Multicellular tumor spheroids are widely used models in tumor research. Because of their three dimensional organization they can simulate avascular tumor areas comprising proliferative and necrotic cells. Nonetheless, protocols for spheroid generation are still inconsistent. Therefore, in this study the breast cancer cell lines MCF-7, MDA-MB-231 and SK-BR-3 have been used to compare different spheroid generation models including hanging drop, liquid overlay and suspension culture techniques, each under several conditions. Experimental approaches differed in cell numbers (400–10,000), media and additives (25 % methocel, 25 % methocel plus 1 % Matrigel, 3.5 % Matrigel). In total, 42 different experimental setups have been tested. Generation of spheroids was evaluated by light microscopy and the structural composition was assessed immunohistochemically by means of Ki-67, cleaved poly (ADP-ribose) polymerase (cPARP) and mucin-1 (MUC-1) expression. Although the tested cell lines diverged widely in their capacity of forming spheroids we recommend hanging drops supplemented with 25 % methocel as the most reliable and efficient method with regard to success of generation of uniform spheroids, costs, experimental complexity and time expenditure in the different cell lines. MCF-7 cells formed spheroids under almost all analyzed conditions, and MDA-MB-231 cells under only one protocol (liquid overlay technique, 3.5 % Matrigel), while SK-BR-3 did not under neither condition. Therefore, we outline specific methods and recommend the use of adapted and standardized spheroid generation protocols for each cell line.
    Subject(s): SK-BR-3 ; Medicine & Public Health ; 3D cultures ; MCF-7 ; Oncology ; Cancer Research ; Tumor ; Breast cancer ; MDA-MB-231 ; Spheroids ; Mucin-1 - metabolism ; MCF-7 Cells ; Breast Neoplasms - pathology ; Humans ; Spheroids, Cellular - metabolism ; Spheroids, Cellular - pathology ; Cell Line, Tumor ; Female ; Ki-67 Antigen - metabolism ; Cell Culture Techniques - methods ; Breast Neoplasms - metabolism ; Comparative analysis ; Sugars ; Monosaccharides
    ISSN: 1083-3021
    E-ISSN: 1573-7039
    Source: Springer Online Journal Archives (DFG Nationallizenzen)
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Journal of cancer research and clinical oncology, 2019-10, Vol.145 (10), p.2481-2493
    Description: Pancreatic adenocarcinoma (PAC) represents one of the most fatal types of cancer with an exceptionally poor prognosis, underscoring the need for improved diagnostic and treatment approaches. An over-expression of somatostatin receptors (SST) as well as of the chemokine receptor CXCR4 has been shown for many tumour entities. Respective expression data for PAC, however, are scarce and contradictory.Overall, 137 tumour samples from 70 patients, 26 of whom were diagnosed with PAC and 44 with pancreatic neuroendocrine tumour (PanNET), were compared in terms of SST and CXCR4 expression by immunohistochemical analysis using well-characterized rabbit monoclonal antibodies.Only SST1 and CXCR4 expression was detected in PAC tumours, with SST1 present in 42.3% and CXCR4 in 7.7% of cases. However, the overall staining intensity was very weak. In contrast to the tumour cells, in many PAC cases, tumour capillaries exhibited strong SST3, SST5, or CXCR4 expression. In PanNETs, SST2 was the most-prominently expressed receptor, observed in 75.0% of the tumours at medium–strong intensity. SST5, SST1, and CXCR4 expression was detected in 20.5%, 15.9%, and 11.4% of PanNET cases, respectively, but the staining intensity was only weak. SST2 positivity in PanNET, but not in PAC, was associated with favourable patient outcomes.SST or CXCR4 expression in PAC is clearly of no therapeutic relevance. However, indirect targeting of these tumours via SST3, SST5, or CXCR4 on tumour microvessels may represent a promising additional therapeutic strategy.
    Subject(s): Immunohistochemistry ; Somatostatin receptor ; Medicine & Public Health ; Hematology ; Pancreatic neuroendocrine tumour ; Pancreatic adenocarcinoma ; Oncology ; Cancer Research ; Internal Medicine ; CXCR4 ; Life Sciences & Biomedicine ; Science & Technology ; Adenocarcinoma ; Monoclonal antibodies ; Analysis ; Pancreatic cancer
    ISSN: 0171-5216
    E-ISSN: 1432-1335
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: Alma/SFX Local Collection
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  • 6
    Language: English
    In: Nature neuroscience, 2020-03, Vol.23 (3), p.351-362
    Description: Monocyte-derived and tissue-resident macrophages are ontogenetically distinct components of the innate immune system. Assessment of their respective functions in pathology is complicated by changes to the macrophage phenotype during inflammation. Here we find that Cxcr4-CreER enables permanent genetic labeling of hematopoietic stem cells (HSCs) and distinguishes HSC-derived monocytes from microglia and other tissue-resident macrophages. By combining Cxcr4-CreER-mediated lineage tracing with Cxcr4 inhibition or conditional Cxcr4 ablation in photothrombotic stroke, we find that Cxcr4 promotes initial monocyte infiltration and subsequent territorial restriction of monocyte-derived macrophages to infarct tissue. After transient focal ischemia, Cxcr4 deficiency reduces monocyte infiltration and blunts the expression of pattern recognition and defense response genes in monocyte-derived macrophages. This is associated with an altered microglial response and deteriorated outcomes. Thus, Cxcr4 is essential for an innate-immune-system-mediated defense response after cerebral ischemia. We further propose Cxcr4-CreER as a universal tool to study functions of HSC-derived cells.
    Subject(s): Cerebral Infarction - immunology ; Mice, Inbred C57BL ; Immunity, Innate - genetics ; Hematopoietic Stem Cells - pathology ; Treatment Outcome ; Monocytes - immunology ; Brain Ischemia - immunology ; Mice, Knockout ; Receptors, CXCR4 - metabolism ; Stroke - pathology ; Cell Lineage ; Thrombosis - pathology ; Hematopoietic Stem Cells - immunology ; Animals ; Microglia - immunology ; Receptors, CXCR4 - immunology ; Brain Ischemia - pathology ; Monocytes - pathology ; Microglia - pathology ; Receptors, CXCR4 - genetics ; Ischemic Attack, Transient - immunology ; Stroke - immunology ; Cerebral Infarction - pathology ; Ischemic Attack, Transient - pathology ; Medical research ; Monocytes ; Immune response ; Ischemia ; Physiological aspects ; Medicine, Experimental ; Research ; Macrophages ; Health aspects ; Identification and classification
    ISSN: 1097-6256
    E-ISSN: 1546-1726
    Source: Nature Journals Online
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  • 7
    Language: English
    In: International journal of molecular sciences, 2019-11-01, Vol.20 (21), p.5261
    Description: GPR68 (OGR1) belongs to the proton-sensing G protein-coupled receptors that are involved in cellular adaptations to pH changes during tumour development. Although expression of GPR68 has been described in many tumour cell lines, little is known about its presence in human tumour entities. We characterised the novel rabbit monoclonal anti-human GPR68 antibody 16H23L16 using various cell lines and tissue specimens. The antibody was then applied to a large series of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. Antibody specificity was demonstrated in a Western blot analysis of GPR68-expressing cells using specific siRNAs. Immunocytochemical experiments revealed pH-dependent changes in subcellular localisation of the receptor and internalisation after stimulation with lorazepam. In normal tissue, GPR68 was present in glucagon-producing islet cells, neuroendocrine cells of the intestinal tract, gastric glands, granulocytes, macrophages, muscle layers of arteries and arterioles, and capillaries. GPR68 was also expressed in neuroendocrine tumours, where it may be a positive prognostic factor, in pheochromocytomas, cervical adenocarcinomas, and endometrial cancer, as well as in paragangliomas, medullary thyroid carcinomas, gastrointestinal stromal tumours, and pancreatic adenocarcinomas. Often, tumour capillaries were also strongly GPR68-positive. The novel antibody 16H23L16 will be a valuable tool for basic research and for identifying GPR68-expressing tumours during histopathological examinations.
    Subject(s): Biochemistry & Molecular Biology ; Physical Sciences ; Chemistry ; Life Sciences & Biomedicine ; Chemistry, Multidisciplinary ; Science & Technology ; Pancreatic Neoplasms - metabolism ; Receptors, G-Protein-Coupled - metabolism ; Humans ; Lung Neoplasms - metabolism ; Middle Aged ; Lung Neoplasms - pathology ; Male ; Receptors, G-Protein-Coupled - immunology ; Sensitivity and Specificity ; HEK293 Cells ; Aged, 80 and over ; Biomarkers, Tumor - metabolism ; Immunoassay - methods ; Adult ; Female ; Antibodies, Monoclonal - immunology ; Lung Neoplasms - genetics ; Rabbits ; Immunoassay - standards ; Pancreatic Neoplasms - pathology ; Antibody Affinity ; Pancreatic Neoplasms - genetics ; Animals ; Adolescent ; Cell Line, Tumor ; Aged ; Biomarkers, Tumor - genetics ; Receptors, G-Protein-Coupled - genetics ; Biomarkers, Tumor - immunology ; OGR1 ; antibody ; neuroendocrine ; immunohistochemistry ; GPR68 ; tumours ; ogr1 ; gpr68
    ISSN: 1422-0067
    E-ISSN: 1422-0067
    Source: Academic Search Ultimate
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 8
    Language: English
    In: Journal of cancer research and clinical oncology, 2018-10, Vol.144 (10), p.1921-1932
    Description: Lung cancer is highly prevalent and has an especially poor prognosis. Thus, new diagnostic and therapeutic targets are necessary. Two potential targets are somatostatin receptors (SST), which are overexpressed in well-differentiated neuroendocrine neoplasms, and the chemokine receptor CXCR4, which is present mainly in highly proliferative and advanced tumours. Although their expression is relatively well characterized in small cell lung cancer (SCLC), in non-small cell lung cancer (NSCLC), data on SST and CXCR4 expression are scarce and contradictory.We comparatively evaluated 83 tumour samples from a total of 57 lung cancer patients, of which 22 had adenocarcinoma (ADC), 21 had squamous cell carcinoma (SQC), and 15 had SCLC. Samples were evaluated for SST and CXCR4 expression using immunohistochemistry with well-characterized rabbit monoclonal antibodies.In the samples investigated, the most prominently expressed receptors were CXCR4 and SST5. Specifically, CXCR4 was detected with high expression intensity in more than 60% of ADC samples, about 90% of SQC, and 100% of SCLC. SST5 was present in about 75% of ADC and SQC samples and in more than 90% of SCLC. Although not noticeably expressed in ADC and SQC samples, SST2 was detected in 50% of SCLC cases, with a subset of patients displaying exceptionally high expression. The comparison of the three tumour entities revealed that SCLC samples had higher SST2, SST5, and CXCR4 expression, but lower SST3 and SST1 relative to ADC or SQC samples.CXCR4 may be a promising target for diagnostics and therapy in both SCLC and NSCLC.
    Subject(s): Small cell lung cancer ; Medicine & Public Health ; Hematology ; Non-small cell lung cancer ; Oncology ; Cancer Research ; Internal Medicine ; CXCR4 ; Chemokine receptor ; Somatostatin receptors ; Adenocarcinoma - pathology ; Prognosis ; Follow-Up Studies ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Humans ; Lung Neoplasms - metabolism ; Middle Aged ; Carcinoma, Squamous Cell - surgery ; Lung Neoplasms - pathology ; Male ; Small Cell Lung Carcinoma - metabolism ; Adenocarcinoma - metabolism ; Aged, 80 and over ; Biomarkers, Tumor - metabolism ; Adult ; Female ; Somatostatin - metabolism ; Signal Transduction ; Small Cell Lung Carcinoma - surgery ; Survival Rate ; Receptors, CXCR4 - metabolism ; Small Cell Lung Carcinoma - pathology ; Lung Neoplasms - surgery ; Aged ; Adenocarcinoma - surgery ; Adenocarcinoma ; Immunohistochemistry ; Squamous cell carcinoma ; Analysis ; Monoclonal antibodies ; Lung cancer, Small cell ; Lung cancer, Non-small cell
    ISSN: 0171-5216
    E-ISSN: 1432-1335
    Source: Alma/SFX Local Collection
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  • 9
    Language: English
    In: Scientific reports, 2019-03-13, Vol.9 (1), p.4339
    Description: Somatostatin receptors (SST), especially SST2A, are known for their overexpression in well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). The chemokine receptor CXCR4, in contrast, is considered to be present mainly in highly proliferative and advanced tumors. However, comprehensive data are still lacking on potential differences in SST or CXCR4 expression pattern in GEP-NEN in dependence on the place of origin. Overall, 412 samples from 165 GEP-NEN patients, comprising both primary tumors (PT) and metastases (MTS), originating from different parts of the gastrointestinal tract or the pancreas were evaluated for SST and CXCR4 expression by means of immunohistochemistry using monoclonal antibodies. SST2A was present in 85% of PT with a high intensity of expression, followed by SST5 (23%), CXCR4 (21%), SST3 (10%), SST1 (9%), and SST4 (4%). PT displayed higher SST2A and chromogranin A (CgA) expression levels than MTS. In both PT and MTS lower SST2A and CgA expression levels were found in tumors originating from the appendix or colon, compared to tumors from other origins. Tumors derived from appendix or colon were associated with significantly worse patient outcomes. Positive correlations were noted between SST2A and CgA as well as between CXCR4 and Ki-67 expression levels. SST2A and CgA negativity of the tumors was significantly associated with poor patient outcomes. All in all, SST2A was the most prominent receptor expressed in the GEP-NEN samples investigated. However, expression levels varied considerably depending on the location of the primary tumor.
    Subject(s): Science & Technology - Other Topics ; Multidisciplinary Sciences ; Science & Technology ; Neuroendocrine Tumors - pathology ; Pancreatic Neoplasms - metabolism ; Neuroendocrine Tumors - metabolism ; Humans ; Middle Aged ; Pancreatic Neoplasms - pathology ; Male ; Receptors, CXCR4 - metabolism ; Young Adult ; Gastrointestinal Neoplasms - pathology ; Adolescent ; Aged, 80 and over ; Adult ; Female ; Aged ; Receptors, Somatostatin - metabolism ; Child ; Gastrointestinal Neoplasms - metabolism ; Immunohistochemistry ; Gastrointestinal tract ; Appendix ; CXCR4 protein ; Clinical outcomes ; Metastases ; Monoclonal antibodies ; Somatostatin ; Colon ; Pancreas ; Chemokines ; Somatostatin receptors ; Tumors
    ISSN: 2045-2322
    E-ISSN: 2045-2322
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: PubMed Central
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  • 10
    Language: English
    In: Translational oncology, 2020-09, Vol.13 (9), p.100801
    Description: BACKGROUND: Prostate cancer (PCa) is the most common type of cancer among men in Western countries. Despite numerous therapeutic options, few treatments are available for patients with end-stage disease. In the present study, different somatostatin receptors (SSTs) and the chemokine receptor CXCR4 were evaluated for their suitability as novel therapeutic targets in PCa. MATERIALS AND METHODS: The expression of SST subtypes 1, 2A, 3, and 5 and of CXCR4 was evaluated in 276 PCa tumor samples on a tissue microarray (TMA) in 23 whole-block tumor samples and in 3 PCa cell lines by immunohistochemistry using well-characterized monoclonal antibodies. RESULTS: Overall, the frequency and intensity of expression of SSTs and CXCR4 were very low among the PCa samples investigated. Specifically, SST5, SST2A, and SST3 were expressed, albeit at low intensity, in 10.5%, 9.1%, and 0.7% of the TMA samples, respectively. None of the TMA samples showed SST1 or CXCR4 expression. Only a single small-cell-type neuroendocrine carcinoma that was coincidentally included among the whole-block samples exhibited strong SST2A, SST5, and CXCR4 and moderate SST3 expression. Independent of the tumor cells, the tumor capillaries in many of the PCa samples were strongly positive for SST2A, SST3, SST5, or CXCR4 expression. SST expression in the tumor cells was associated with advanced tumor grade and stage. CONCLUSION: Overall, SST and CXCR4 expression levels are clearly of no therapeutic relevance in PCa. SST- or CXCR4-based therapy might be feasible, however, in rare cases of small-cell-type neuroendocrine carcinoma of the prostate.
    Subject(s): Original article
    ISSN: 1936-5233
    E-ISSN: 1936-5233
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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