To date, 13 cases of sporadic renal hemangioblastoma have been reported. In this article, we report such a case that might cause the diagnostic pitfall. A 37-year-old Japanese was found to have a renal mass by periodic medical check-up. He underwent radical nephrectomy. Macroscopically, the tumor was well-defined without fibrous capsule and the cut surface of the tumor exhibited light brown to gray-tan color without hemorrhage or necrosis. Microscopically, the tumor was made up of large polygonal to short spindle cells with eosinophilic cytoplasm with occasional vacuolization and abundant arborizing capillary network. Immunohistochemically, neoplastic cells showed diffuse positivity for inhibin-alpha, S-100 protein, vimentin, CA9, PAX2 and PAX8, but negativity for cytokeratin CAM5.2, alpha smooth muscle actin, Melanosome, Melan A, TFE3 and cathepsin K. In genetic analyses, this tumor showed no changes of VHL gene mutation, hypermethylation and loss of heterozygosity of chromosome 3p. Additionally, G-band karyotype and array comparative genomic hybridization studies showed a normal chromosome. In conclusion, the positivity for CA9, PAX2 and PAX8 in sporadic renal hemangioblastoma may cause the critical diagnostic pitfall in the differential diagnosis from clear cell renal cell carcinoma. Pathologists need to pay attention to systemic evaluation including macroscopic, microscopic and immunohistochemical findings. In some cases, molecular genetic study may be necessary.

• Klíčová slova
• CA9, Hemangioblastoma, PAX2, PAX8, kidney,
• MeSH
• antigeny nádorové metabolismus   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• hemangioblastom diagnóza   metabolismus   patologie   MeSH
• karboanhydrasa IX MeSH
• karboanhydrasy metabolismus   MeSH
• karcinom z renálních buněk diagnóza   metabolismus   patologie   MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory ledvin diagnóza   metabolismus   patologie   MeSH
• transkripční faktor PAX2 metabolismus   MeSH
• transkripční faktor PAX8 MeSH
• transkripční faktory paired box metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• karboanhydrasa IX MeSH
• karboanhydrasy MeSH
• nádorové biomarkery MeSH
• PAX2 protein, human MeSH Prohlížeč
• PAX8 protein, human MeSH Prohlížeč
• transkripční faktor PAX2 MeSH
• transkripční faktor PAX8 MeSH
• transkripční faktory paired box MeSH

Specific antibodies interfere with the function of human tumor-associated carbonic anhydrase IX (CA IX), and show potential as tools for anticancer interventions. In this work, a correlation between structural elements and thermodynamic parameters of the association of antibody fragment Fab M75 to a peptide corresponding to its epitope in the proteoglycan-like domain of CA IX, is presented. Comparisons of the crystal structures of free Fab M75 and its complex with the epitope peptide reveal major readjustments of CDR-H1 and CDR-H3. In contrast, the overall conformations and positions of CDR-H2 and CDR-L2 remain unaltered, and their positively charged residues may thus present a fixed frame for epitope recognition. Adoption of the altered CDR-H3 conformation in the structure of the complex is accompanied by an apparent local stabilization. Analysis of domain mobility with translation-libration-screw (TLS) method shows that librations of the entire heavy chain variable domain (V(H)) decrease and reorient in the complex, which correlates well with participation of the heavy chain in ligand binding. Isothermal titration microcalorimetry (ITC) experiments revealed a highly unfavorable entropy term, which can be attributed mainly to the decrease in the degrees of freedom of the system, the loss of conformational freedom of peptide and partially to a local stabilization of CDR-H3. Moreover, it was observed that one proton is transferred from the environment to the protein-ligand complex upon binding. Molecular dynamics simulations followed by molecular mechanics/generalized Born surface area (MM-GBSA) calculations of the ligand (epitope peptide) binding energy yielded energy values that were in agreement with the ITC measurements and indicated that the charged residues play crucial role in the epitope binding. Theoretical arguments presented in this work indicate that two adjacent arginine residues (ArgH50 and ArgH52) are responsible for the observed proton transfer.

• MeSH
• antigeny nádorové chemie   imunologie   MeSH
• epitopy chemie   imunologie   MeSH
• imunoglobuliny - Fab fragmenty chemie   MeSH
• izoenzymy chemie   imunologie   MeSH
• kalorimetrie MeSH
• karboanhydrasa IX MeSH
• karboanhydrasy chemie   imunologie   MeSH
• krystalografie rentgenová MeSH
• lidé MeSH
• molekulární sekvence - údaje MeSH
• monoklonální protilátky chemie   MeSH
• nádorové buněčné linie MeSH
• počítačová simulace * MeSH
• sekvence aminokyselin MeSH
• termodynamika MeSH
• vazebná místa protilátek * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• epitopy MeSH
• imunoglobuliny - Fab fragmenty MeSH
• izoenzymy MeSH
• karboanhydrasa IX MeSH
• karboanhydrasy MeSH
• monoklonální protilátky MeSH

Human carbonic anhydrase IX is a membrane enzyme that is significantly expressed in some types of cancer cells, while copper radioisotopes offer wide range of diagnostic, therapeutic and theranostic properties. The work was focused on a new approach to the labelling of antibody IgG M75 for epitope human carbonic anhydrase IX with copper radioisotopes 61Cu and 64Cu and its in vivo testing in mice with inoculated colorectal cancer. Monoclonal antibody IgG M75 for epitope human carbonic anhydrase IX was successfully conjugated with copper-specific chelator "phosphinate" and labelled with 61Cu and 64Cu The obtained molecule has considerable potential as a radioimmuno pharmaceutical suitable for imaging of tumours expressing carbonic anhydrase IX by positron emission tomography (PET).

• Klíčová slova
• Carbonic anhydrase IX, Cu-61, Cu-64, PET, Tumour diagnostics, “phosphinate”,
• MeSH
• antigeny nádorové imunologie   MeSH
• buňky HT-29 MeSH
• imunoglobulin G chemie   MeSH
• imunokonjugáty chemie   farmakokinetika   MeSH
• karboanhydrasa IX imunologie   MeSH
• kolorektální nádory diagnostické zobrazování   enzymologie   MeSH
• lidé MeSH
• monoklonální protilátky chemie   farmakokinetika   MeSH
• myši nahé MeSH
• myši MeSH
• pozitronová emisní tomografie MeSH
• radiofarmaka chemie   farmakokinetika   MeSH
• radioimunodetekce MeSH
• radioizotopy mědi chemie   farmakokinetika   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• Copper-61 MeSH Prohlížeč
• Copper-64 MeSH Prohlížeč
• imunoglobulin G MeSH
• imunokonjugáty MeSH
• karboanhydrasa IX MeSH
• M75 monoclonal antibody MeSH Prohlížeč
• monoklonální protilátky MeSH
• radiofarmaka MeSH
• radioizotopy mědi MeSH

Specific oncology diagnostics requires new types of the selective radiopharmaceuticals, particularly those suitable for the molecular PET imaging. The aim of this work is to present a new, specific PET-immunodiagnostic radiopharmaceutical based on the monoclonal antibody IgG M75 targeting human carbonic anhydrase IX labelled with 64Cu (T½ = 12.70h) and its in vitro and in vivo evaluation. The antibody IgG M75 was conjugated with a non-commercial copper-specific chelator "phosphinate" and then labelled with the positron emitter 64Cu. Stability of the labelled conjugated was tested in human serum. The immunoreactivity of the labelled conjugate was evaluated in vitro on a suitable cell cultures of the colorectal carcinoma (HT-29) and its imaging properties were estimated in vivo on a mouse model with inoculated colorectal carcinoma HT-29 imaged on a µPET/CT. The tested radioimmunoconjugate was obtained in a specific activity of 0.25-0.5 MBq/µg. In vitro uptake experiments revealed specific binding to the HT-29 cells (45 ± 2.8% of the total added activity) and the measured KD value was found to be 9.2nM. Imaging clearly demonstrated significant uptake of the labelled monoclonal antibody in the tumour at 18h post administration. The radioimmunoconjugate 64Cu-PS-IgG M75 seems to be a suitable candidate for PET diagnostics of hypoxic tumours expressing human carbonic anhydrase IX.

• Klíčová slova
• Cu-64, IgG M75, Imaging, Immunoaffinity, Monoclonal antibody,
• MeSH
• aktivní transport MeSH
• antigeny nádorové imunologie   MeSH
• buňky HT-29 MeSH
• buňky NIH 3T3 MeSH
• imunokonjugáty farmakokinetika   farmakologie   MeSH
• inhibitory enzymů farmakokinetika   farmakologie   MeSH
• karboanhydrasa IX antagonisté a inhibitory   imunologie   MeSH
• kyseliny fosfinové MeSH
• lidé MeSH
• monoklonální protilátky farmakokinetika   farmakologie   MeSH
• myši nahé MeSH
• myši MeSH
• nádory diagnostické zobrazování   enzymologie   MeSH
• PET/CT MeSH
• protinádorové látky imunologicky aktivní farmakokinetika   farmakologie   MeSH
• radiofarmaka farmakokinetika   farmakologie   MeSH
• radioizotopy mědi farmakokinetika   farmakologie   MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• Copper-64 MeSH Prohlížeč
• imunokonjugáty MeSH
• inhibitory enzymů MeSH
• karboanhydrasa IX MeSH
• kyseliny fosfinové MeSH
• M75 monoclonal antibody MeSH Prohlížeč
• monoklonální protilátky MeSH
• protinádorové látky imunologicky aktivní MeSH
• radiofarmaka MeSH
• radioizotopy mědi MeSH

Solid tumors, including breast cancer, are characterized by the hypoxic microenvironment, extracellular acidosis, and chemoresistance. Hypoxia marker, carbonic anhydrase IX (CAIX), is a pH regulator providing a selective survival advantage to cancer cells through intracellular neutralization while facilitating tumor invasion by extracellular acidification. The expression of CAIX in breast cancer patients is associated with poor prognosis and metastases. Importantly, CAIX-positive hypoxic tumor regions are enriched in cancer stem cells (CSCs). Here we investigated the biological effects of CA9-silencing in breast cancer cell lines. We found that CAIX-downregulation in hypoxia led to increased levels of let-7 (lethal-7) family members. Simultaneously with the increase of let-7 miRNAs in CAIX-suppressed cells, LIN28 protein levels decreased, along with downstream metabolic pathways: pyruvate dehydrogenase kinase 1 (PDK1) and phosphorylation of its substrate, pyruvate dehydrogenase (PDH) at Ser-232, causing attenuation of glycolysis. In addition to perturbed glycolysis, CAIX-knockouts, in correlation with decreased LIN28 (as CSC reprogramming factor), also exhibit reduction of the further CSC-associated markers NANOG (Homeobox protein NANOG) and ALDH1 (Aldehyde dehydrogenase isoform 1). Oppositely, overexpression of CAIX leads to the enhancement of LIN28, ALDH1, and NANOG. In conclusion, CAIX-driven regulation of the LIN28/let-7 axis augments glycolytic metabolism and enhances stem cell markers expression during CAIX-mediated adaptation to hypoxia and acidosis in carcinogenesis.

• Klíčová slova
• LIN28/let-7 axis, carbonic anhydrase IX, hypoxia, metabolism,
• MeSH
• antigeny nádorové genetika   MeSH
• glykolýza MeSH
• hypoxie buňky MeSH
• karboanhydrasa IX genetika   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• mikro RNA genetika   MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky metabolismus   MeSH
• nádory prsu genetika   metabolismus   MeSH
• přeprogramování buněk MeSH
• proteiny vázající RNA genetika   MeSH
• stanovení celkové genové exprese MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• karboanhydrasa IX MeSH
• Lin28A protein, human MeSH Prohlížeč
• mikro RNA MeSH
• mirnlet7 microRNA, human MeSH Prohlížeč
• proteiny vázající RNA MeSH

Expression of CA IX is normally restricted to the mucosa of alimentary tract, but on the other hand, it takes place in a high percentage of human cancers derived from tissues which are normally CA IX-negative. It is a transmembrane protein with two extracellular domains: carbonic anhydrase (CA) with a high catalytic activity and a proteoglycan-like segment (PG), mediating cell-cell adhesion. Both CA and PG domains interact with the microenvironment and they could play a role in tumorigenesis, but their roles are poorly understood. The present work characterizes some newly recognized properties of the PG. One of them is a prevalently negative charge, caused by a high proportion of dicarboxylic amino acids. This is reflected by easy dissociation of complexes formed by PG either with monoclonal antibody M75 or with the cell surface receptor already at slightly acidic pH. This property might facilitate separation of cells from the primary tumor. Released cells may subsequently attach elsewhere in the organism and eventually start metastatic growth. Another aim of the present study was to identify human tumor cell lines which are expressing the presumed CA IX receptor molecule. The same cell lines were also tested for the presence of CA IX protein; we found that expression of CA IX and of the receptor is independent of each other. In addition, we examined the species specificity of CA IX receptors. The PG domain, which contains the epitope of mAb M75 -PGEEDLP- overlapping with the binding site for putative receptor is relatively conserved in evolution: human and rat CA IX cross-react with M75 antibody on western blots. Consistently with this, human and rat cells can attach to purified human CA IX protein. On the other hand, murine CA IX contains an entirely different equivalent of PG sequence and it does not react with M75 antibody or attach to human CA IX protein. This is suggestive of the co-evolution of CA IX protein together with its receptor.

• MeSH
• antigeny nádorové metabolismus   MeSH
• buněčná adheze MeSH
• buňky 3T3 MeSH
• ELISA MeSH
• HeLa buňky MeSH
• karboanhydrasa IX MeSH
• karboanhydrasy metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• monoklonální protilátky MeSH
• myši MeSH
• nádory enzymologie   MeSH
• referenční hodnoty MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• karboanhydrasa IX MeSH
• karboanhydrasy MeSH
• monoklonální protilátky MeSH

BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.

• Klíčová slova
• Complex II, Metabolism, Mitochondria, Organoids, Renal cell carcinoma, Succinate dehydrogenase,
• MeSH
• antigeny nádorové MeSH
• dospělí MeSH
• karboanhydrasa IX metabolismus   genetika   MeSH
• karcinom z renálních buněk * patologie   metabolismus   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondriální DNA genetika   metabolismus   MeSH
• mitochondrie * metabolismus   patologie   genetika   MeSH
• mutace MeSH
• nádorový supresorový protein VHL genetika   metabolismus   MeSH
• nádory ledvin * patologie   metabolismus   genetika   MeSH
• respirační komplex II * metabolismus   genetika   MeSH
• senioři MeSH
• sukcinátdehydrogenasa genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• karboanhydrasa IX MeSH
• mitochondriální DNA MeSH
• nádorový supresorový protein VHL MeSH
• respirační komplex II * MeSH
• respiratory complex II MeSH Prohlížeč
• SDHB protein, human MeSH Prohlížeč
• sukcinátdehydrogenasa MeSH
• VHL protein, human MeSH Prohlížeč

We have designed, synthesized, and characterized peptides containing four repeats of the sequences VAALEKE (peptide E) or VAALKEK (peptide K). While the peptides alone adopt in aqueous solutions a random coil conformation, their equimolar mixture forms heterodimeric coiled coils as confirmed by CD spectroscopy. 5-Azidopentanoic acid was connected to the N-terminus of peptide E via a short poly(ethylene glycol) spacer. The terminal azide group enabled conjugation of the peptide with a synthetic drug carrier based on the N-(2-hydroxypropyl)methacrylamide copolymer containing propargyl groups using "click" chemistry. When incorporated into the polymer drug carrier, peptide E formed a stable noncovalent complex with peptide K belonging to a recombinant single-chain fragment (scFv) of the M75 antibody. The complex thereby mediates a noncovalent linkage between the polymer drug carrier and the protein. The recombinant scFv antibody fragment was selected as a targeting ligand against carbonic anhydrase IX-a marker overexpressed by tumor cells of various human carcinomas. The antigen binding affinity of the polymer-scFv complex was confirmed by ELISA. This approach offers a well-defined, specific, and nondestructive universal method for the preparation of protein (antibody)-targeted polymer drug and gene carriers designed for cell-specific delivery.

• MeSH
• akrylamidy chemie   MeSH
• antigeny nádorové imunologie   metabolismus   MeSH
• bakteriální transformace MeSH
• cirkulární dichroismus MeSH
• click chemie metody   MeSH
• dimerizace MeSH
• ELISA MeSH
• Escherichia coli MeSH
• imunokonjugáty chemie   imunologie   farmakologie   MeSH
• karboanhydrasa IX MeSH
• karboanhydrasy imunologie   metabolismus   MeSH
• karcinom farmakoterapie   enzymologie   imunologie   patologie   MeSH
• klonování DNA MeSH
• lidé MeSH
• molekulární konformace MeSH
• monoklonální protilátky chemie   genetika   imunologie   MeSH
• nádorové biomarkery imunologie   metabolismus   MeSH
• nosiče léků chemická syntéza   farmakologie   MeSH
• oligopeptidy chemická syntéza   imunologie   farmakologie   MeSH
• plazmidy MeSH
• polyethylenglykoly chemie   MeSH
• rekombinantní proteiny chemie   genetika   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• imunokonjugáty MeSH
• karboanhydrasa IX MeSH
• karboanhydrasy MeSH
• M75 monoclonal antibody MeSH Prohlížeč
• monoklonální protilátky MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nádorové biomarkery MeSH
• nosiče léků MeSH
• oligopeptidy MeSH
• polyethylenglykoly MeSH
• rekombinantní proteiny MeSH

Simple molecular descriptors of extensive series of 1,3,5-triazinyl sulfonamide derivatives, based on the structure of sulfonamides and their physicochemical properties, were designed and calculated. These descriptors were successfully applied as inputs for artificial neural network (ANN) modelling of the relationship between the structure and biological activity. The optimized ANN architecture was applied to the prediction of the inhibition activity of 1,3,5-triazinyl sulfonamides against human carbonic anhydrase (hCA) II, tumour-associated hCA IX, and their selectivity (hCA II/hCA IX).

• Klíčová slova
• 1,3,5-triazinyl sulfonamide derivatives, ANN, Carbonic anhydrase, Structural descriptors,
• MeSH
• antigeny nádorové metabolismus   MeSH
• inhibitory karboanhydras chemie   metabolismus   MeSH
• karboanhydrasa II antagonisté a inhibitory   metabolismus   MeSH
• karboanhydrasa IX antagonisté a inhibitory   metabolismus   MeSH
• lidé MeSH
• neuronové sítě * MeSH
• racionální návrh léčiv MeSH
• sulfonamidy chemie   metabolismus   MeSH
• triaziny chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• inhibitory karboanhydras MeSH
• karboanhydrasa II MeSH
• karboanhydrasa IX MeSH
• sulfonamidy MeSH
• triaziny MeSH

Oxygen is absolutely essential for correct functioning of living organisms and alterations in its concentration lead to serious consequences. In tumor tissues, oxygen plays an important role in energy production and modulation of red- ox balance. Insufficient oxygen supply within tissues results in hypoxia that is a characteristic feature of the tumor microenvironment. Hypoxia- inducible transcriptional factor represents a key executor of a cellular and molecular response to hypoxia and can activate the expression of more than hundred genes involved in various essential cellular processes. From the clinical point of view, phenotypic alterations caused by hypoxia are serious. Tumor hypoxia has been associated with resistance to therapy, disease progression and recurrence as well as increased mortality. Therefore, intratumoral hypoxia represents a clinically relevant problem, and its detection within tumors is very important for patient stratification for a suitable treatment. Currently available strategies directed towards the detection of hypoxic regions within tumor tissue suffer from numerous limitations e. g. invasiveness, inaccessibility of tumor tissue, low sensibility, inaccurate interpretation etc. On the other hand, the use of an intrinsic endogenous hypoxic marker, which can be detected through immunohistochemistry, is relatively simple, routinely available, and reproducible and can be performed on both prospective and retrospective samples. These include carbonic anhydrase IX (CA IX), one of the most strongly hypoxia-induced proteins and a prominent indicator of chronic hypoxia. Moreover, hypoxia-induced proteins (including CA IX) are also potential targets of anticancer therapy, and their practical application is a subject of intense research.

• MeSH
• antigeny nádorové MeSH
• hypoxie buňky fyziologie   MeSH
• karboanhydrasa IX MeSH
• karboanhydrasy MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery analýza   biosyntéza   MeSH
• nádorové mikroprostředí MeSH
• nádorové proteiny biosyntéza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antigeny nádorové MeSH
• CA9 protein, human MeSH Prohlížeč
• karboanhydrasa IX MeSH
• karboanhydrasy MeSH
• kyslík MeSH
• nádorové biomarkery MeSH
• nádorové proteiny MeSH