BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is highly immunogenic and efficacious in adults ≥50 years of age. We evaluated (1) long-term immunogenicity of an initial 2-dose RZV schedule, by following up adults vaccinated at ≥60 years of age and by modeling, and (2) immunogenicity of 2 additional doses administered 10 years after initial vaccination. METHODS: Persistence of humoral and cell-mediated immune (CMI) responses to 2 initial RZV doses was assessed through 10 years after initial vaccination, and modeled through 20 years using a Piecewise, Power law and Fraser model. The immunogenicity and safety of 2 additional RZV doses were also evaluated. RESULTS: Seventy adults were enrolled. Ten years after initial vaccination, humoral and CMI responses were approximately 6-fold and 3.5-fold, respectively, above those before the initial vaccination levels. Predicted immune persistence through 20 years after initial vaccination was similar across the 3 models. Sixty-two participants (mean age [standard deviation], 82.6 [4.4] years) received ≥1 additional RZV dose. Strong anamnestic humoral and CMI responses were elicited by 1 additional dose, without further increases after a second additional dose. CONCLUSIONS: Immune responses to an initial 2-dose RZV course persisted for many years in older adults. Strong anamnestic immune responses can be induced by additional dosing 10 years after the initial 2-dose course. CLINICAL TRIALS REGISTRATION: NCT02735915.

• Klíčová slova
• adjuvanted recombinant zoster vaccine, herpes zoster, persistence of immune response, safety,
• MeSH
• adjuvancia imunologická aplikace a dávkování   škodlivé účinky   MeSH
• herpes zoster prevence a kontrola   MeSH
• imunogenicita vakcíny * MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• syntetické vakcíny aplikace a dávkování   škodlivé účinky   imunologie   MeSH
• vakcína proti pásovému oparu aplikace a dávkování   škodlivé účinky   MeSH
• vakcinace MeSH
• virus varicella zoster imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• syntetické vakcíny MeSH
• vakcína proti pásovému oparu MeSH

In two pivotal efficacy studies (ZOE-50; ZOE-70), the adjuvanted recombinant zoster vaccine (RZV) demonstrated >90% efficacy against herpes zoster (HZ).Adults aged ≥50 or ≥70 years (ZOE-50 [NCT01165177]; ZOE-70 [NCT01165229]) were randomized to receive 2 doses of RZV or placebo 2 months apart. Vaccine efficacy and safety were evaluated post-hoc in the pooled (ZOE-50/70) population according to the number and type of selected medical conditions present at enrollment.At enrollment, 82.3% of RZV and 82.7% of placebo recipients reported ≥1 of the 15 selected medical conditions. Efficacy against HZ ranged from 84.5% (95% Confidence Interval [CI]: 46.4-97.1) in participants with respiratory disorders to 97.0% (95%CI: 82.3-99.9) in those with coronary heart disease. Moreover, efficacy remained >90% irrespective of the number of selected medical conditions reported by a participant.As indicated by the similarity of the point estimates, this post-hoc analysis suggests that RZV efficacy remains high in all selected medical conditions, as well as with increasing number of medical conditions. No safety concern was identified by the type or number of medical conditions present at enrollment.

• Klíčová slova
• Varicella-zoster virus, adjuvanted recombinant zoster vaccine, comorbidity, underlying chronic disease, vaccine efficacy, vaccine safety,
• MeSH
• adjuvancia imunologická aplikace a dávkování   MeSH
• chronická nemoc MeSH
• herpes zoster prevence a kontrola   MeSH
• hostitel s imunodeficiencí MeSH
• interpretace statistických dat MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• postherpetická neuralgie imunologie   prevence a kontrola   MeSH
• potence vakcíny * MeSH
• rizikové faktory MeSH
• senioři MeSH
• syntetické vakcíny imunologie   MeSH
• vakcína proti pásovému oparu aplikace a dávkování   imunologie   MeSH
• vakcinace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adjuvancia imunologická MeSH
• syntetické vakcíny MeSH
• vakcína proti pásovému oparu MeSH

Regulatory T cells (Treg) are important regulators of anti-cancer immune responses, and an increase in Treg frequency was observed in the blood of cancer patients. Blood samples from 112 patients with head and neck squamous cell carcinoma antigen (HNSCC) were obtained at the time of tumour diagnosis, and lymphocyte subpopulations (CD3(+); CD3(-)CD16(+)CD56(+); CD4(+); CD8(+); CD19(+); CD4(+)CD45RA(+)) with emphasis on Treg counts (CD3(+)CD4(+)CD25(+)), complete blood count and tumour markers (squamous cell carcinoma [SCC]; CEA; alpha-1-antitrypsin [AAT]; Cyfra 21-1; C-reactive protein [CRP]) were analysed. The data were grouped according to TNM classification, and their significance for the course of the disease at an interval of 1 year after the end of the therapy was determined. The percentage of CD8(+) cells increased and the CD/D8 ratio decreased with tumour grade. The ratio of B lymphocytes decreased in patients with locoregional metastases (11.25%versus 9.22%). Treg (15.2%) and CD4(+) cells (45.3%) increased, while NK cells (11.8%) decreased in HNSCC patients compared to controls (9.0%, 38.1% and 15.8%, respectively). The data obtained at time of diagnosis were used to assess the significance of tumour markers (SCC, Cyfra 21-1 and AAT) for evaluation of prognosis. The erythrocyte counts (4.64 x 10(12)/l versus 4.45 x 10(12)/l) and haemoglobin levels (14.58 g/dl versus 14.05 g/dl) decreased, while Treg counts (8.91%versus 15.70%) increased in patients with early recurrence. Our results show that examination of these parameters could be helpful for prognostication in HNSCC patients and aid improvement of treatment strategy.

• MeSH
• CD antigeny imunologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory hlavy a krku krev   diagnóza   imunologie   MeSH
• prognóza MeSH
• regulační T-lymfocyty metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom krev   diagnóza   imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CD antigeny MeSH
• nádorové biomarkery MeSH

PURPOSE: In vivo efficacy and safety of HPMA-based copolymers armed with doxorubicin via a spacer containing pH-sensitive linkage that can be prepared within a broad range of attached drug contents (1) was tested in murine tumor models. METHODS: Mice bearing T cell lymphoma EL4 or B cell lymphoma 38C13 were treated with a single dose of the conjugate (15, 25, and 75 mg Dox eq./kg i.v.) in a therapeutic regime. Anti-tumor resistance of the cured animals was proved by a second challenge with a lethal dose of tumor cells without additional treatment. RESULTS: The content of drug bound to the polymer is an important parameter in relation to the conjugate therapeutic efficacy. The best anti-tumor effects were produced by conjugates with 10 - 13 wt% of bound doxorubicin. Free doxorubicin up to 4.6% relative to total drug content had no impact on the treatment efficacy and acute toxicity. The conjugates induced a complete cure of mice and regular treatment-dependent development of specific anti-tumor resistance. No myelosuppression or organ damage was observed. CONCLUSIONS: A well-defined HPMA copolymer-doxorubicin conjugate with pH-sensitive drug release is a good candidate for clinical trials as it has remarkable anti-tumor efficacy and a favorable safety profile.

• MeSH
• antibiotika antitumorózní farmakokinetika   farmakologie   MeSH
• doxorubicin analogy a deriváty   chemická syntéza   farmakokinetika   farmakologie   MeSH
• imunomodulace účinky léků   MeSH
• koncentrace vodíkových iontů MeSH
• kyseliny polymethakrylové chemická syntéza   farmakokinetika   farmakologie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemická syntéza   farmakokinetika   farmakologie   MeSH
• polymery * chemická syntéza   farmakokinetika   farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• kyseliny polymethakrylové MeSH
• nosiče léků MeSH
• polymery * MeSH

IL-2 is potent imunostimulatory molecule that plays a key role in T and NK cell activation and expansion. IL-2 is approved by the FDA to treat metastatic renal cancer and melanoma, but its extremely short half-life and serious toxicities are significant limitations of its use. It was reported that in vivo biological activity of IL-2 can be increased by association of IL-2 with anti-IL-2 mAb (S4B6). IL-2/S4B6 mAb immunocomplexes were described to be highly stimulatory for NK and memory CD8(+) T cells and intermediately also for regulatory T cells. IL-2/JES6-1 mAb immunocomplexes are stimulatory solely for regulatory T cells. In this study we show that although both mentioned IL-2 immunocomplexes are less potent than free IL-2 in vitro, they possess extremely high stimulatory activity to expand activated naive CD8(+) T cells in vivo. IL-2 immunocomplexes expand activated naive CD8(+) T cells several hundred-fold times after four doses and more than 1000-fold times after six doses (1.5 microg/dose of IL-2), whereas free IL-2 given at the same dosage shows negligible activity. IL-2/S4B6 mAb immunocomplexes also induce massive expansion of NK cells (40% of DX5(+)NK1.1(+) cells in spleen). Importantly, activated naive CD8(+) T cells expanded by IL-2 immunocomplexes form robust population of functional memory cells. We also demonstrate in two distinct tumor models that IL-2/S4B6 mAb immunocomplexes possess considerable antitumor activity. Finally, by using radioactively labeled IL-2, we provide for first time direct evidence that IL-2 immunocomplexes have much longer half-life in circulation than free IL-2, being approximately 3 h vs <15 min, respectively.

• MeSH
• buňky NK imunologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• imunokomplex terapeutické užití   MeSH
• imunoterapie MeSH
• interleukin-2 terapeutické užití   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši transgenní MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory imunologie   terapie   MeSH
• poločas MeSH
• převzatá imunita MeSH
• rekombinantní proteiny farmakologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunokomplex MeSH
• interleukin-2 MeSH
• monoklonální protilátky MeSH
• rekombinantní proteiny MeSH

Synthesis, physicochemical behavior, tumor accumulation and preliminary anticancer activity of a new biodegradable graft copolymer-doxorubicin (DOX) conjugates designed for passive tumor targeting were investigated. In the graft high-molecular-weight conjugates the multivalent N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer was grafted with a similar but semitelechelic HPMA copolymer; both types of polymer chains were bearing doxorubicin attached by hydrazone bonds enabling intracellular pH-controlled drug release. The polymer grafts were attached to the main chain through spacers, degradable enzymatically or reductively, facilitating, after the drug release, intracellular degradation of the graft polymer carrier to short fragments excretable from the organism by glomerular filtration. The graft polymer-DOX conjugate exhibited prolonged blood circulation and enhanced tumor accumulation in tumor-bearing mice indicating the important role of the EPR effect in the anticancer activity. The graft polymer-DOX conjugates showed a significantly higher antitumor activity in vivo than DOX.HCl or the linear polymer conjugate when tested in mice bearing 38C13 B-cell or EL4 T-cell lymphoma, with a significant number of long-term-surviving (LTS) mice with EL4 T-cell lymphoma treated with a single dose 15 mg DOX equiv./kg on day 10.

• MeSH
• akrylamidy aplikace a dávkování   chemická syntéza   farmakokinetika   farmakologie   MeSH
• antibiotika antitumorózní aplikace a dávkování   chemická syntéza   farmakokinetika   farmakologie   MeSH
• biologický transport MeSH
• buněčné linie MeSH
• chemie farmaceutická MeSH
• doxorubicin aplikace a dávkování   chemická syntéza   farmakokinetika   farmakologie   MeSH
• hydrolýza MeSH
• injekce intravenózní MeSH
• koncentrace vodíkových iontů MeSH
• léky s prodlouženým účinkem MeSH
• lymfom farmakoterapie   metabolismus   patologie   MeSH
• molekulová hmotnost MeSH
• myši inbrední C3H MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nosiče léků * MeSH
• xenogenní modely - testy antitumorózní aktivity MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• antibiotika antitumorózní MeSH
• doxorubicin MeSH
• léky s prodlouženým účinkem MeSH
• N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate MeSH Prohlížeč
• nosiče léků * MeSH

BALB/c mice bearing syngeneic BCL1 leukemia, a mouse model of human chronic lymphocytic leukemia, were treated with polymer-bound doxorubicin conjugate targeted with BCL1-specific monoclonal antibody. Such treatment can cure up to 100% of mice and the cured mice show long-lasting resistance to BCL1 leukemia. We show that both CD4+ and CD8+ T cells are required for establishment of the resistance, but only CD8+ T cells are necessary for its maintenance. BCL1 cells express MHC class I and II and also costimulatory molecules CD80 and CD86, which can aid eliciting of antitumor response. On the other hand, BCL1 cells also use several immunoescape mechanisms, such as expression of PD-L1, PD-L2, and interleukin-10. BCL1 cells thus can be recognized by BCL1-specific T cells, but instead of effective priming, such T cells are anergized or deleted by apoptosis. Moreover, BCL1 leukemia progression is accompanied by robust expansion of CD4+CD25+Foxp3+ regulatory T (Treg) cells. Although it has been shown that depletion of Treg cells in tumor-bearing mice can retard tumor growth, direct evidence that expansion of Treg cells can promote tumor growth was lacking. In this study, we provide first direct evidence that expanded Treg cells can indeed promote tumor progression by using mice with selectively expanded Treg cells before inoculation of BCL1 leukemia. Finally, we have also shown that elimination of some immunoescape mechanism (e.g., deletion of Treg) can significantly improve the therapeutic outcome of chemotherapy.

• MeSH
• antibiotika antitumorózní farmakologie   MeSH
• CD8-pozitivní T-lymfocyty imunologie   MeSH
• doxorubicin analogy a deriváty   farmakologie   MeSH
• imunokonjugáty imunologie   farmakologie   MeSH
• kyseliny polymethakrylové farmakologie   MeSH
• leukemie B-buněčná farmakoterapie   imunologie   MeSH
• monoklonální protilátky imunologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• regulační T-lymfocyty imunologie   MeSH
• únik nádoru z imunitní kontroly účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• imunokonjugáty MeSH
• kyseliny polymethakrylové MeSH
• monoklonální protilátky MeSH

Synthesis and preliminary anticancer activity of new star-shaped immunoglobulin-containing polymer-doxorubicin (DOX) conjugates were investigated. The polymer precursors used for the synthesis of immunoglobulin-polymer-drug conjugates are based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, the anticancer drug DOX is attached to the immunoglobulin-modified polymer via a pH-sensitive hydrazone linkage. Such polymer-DOX conjugates are stable in aqueous solution at pH 7.4 (pH of blood plasma) and the drug is released in mildly acid environment at pH 5-5.5 (pH in endosomes or lysosomes of target cells). Semitelechelic copolymer chains are linked to the immunoglobulin via one-point attachment to avoid branching of the conjugate observed in our earlier studied systems. The cytostatic activity of the conjugates tested on several cancer cell lines was similar to that of free DOX.HCl and correlated with the sensitivity of a particular cell line to DOX. The star-shaped conjugates containing immunoglobulin showed a significantly higher antitumor activity in vivo than immunoglobulin-free non-targeted polymer conjugates when tested in mice bearing EL4 T-cell lymphoma.

• MeSH
• antibiotika antitumorózní aplikace a dávkování   chemie   farmakologie   MeSH
• doxorubicin aplikace a dávkování   analogy a deriváty   chemie   farmakologie   MeSH
• imunoglobuliny aplikace a dávkování   chemie   MeSH
• imunokonjugáty aplikace a dávkování   chemie   MeSH
• kyseliny polymethakrylové aplikace a dávkování   chemie   farmakologie   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• lymfom T-buněčný farmakoterapie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nosiče léků aplikace a dávkování   chemická syntéza   chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• imunoglobuliny MeSH
• imunokonjugáty MeSH
• kyseliny polymethakrylové MeSH
• nosiče léků MeSH

Doxorubicin is one of the most potent anti-tumor drugs with a broad spectrum of use. To reduce its toxic effect and improve its pharmacokinetics, we conjugated it to an HPMA copolymer carrier that enhances its passive accumulation within solid tumors via the EPR effect and decreases its cytotoxicity to normal, noncancer cells. In this study, we compared the antiproliferative, pro-survival, and death signals triggered in EL-4 cancer cells exposed to free doxorubicin and doxorubicin conjugated to a HPMA copolymer carrier via either enzymatically (PK1) or hydrolytically (HYD) degradable bonds. We have previously shown that the intracellular distribution of free doxorubicin, HYD, and PK1 is markedly different. Here, we demonstrated that these three agents greatly differ also in the antiproliferative effect and cell death signals they trigger. JNK phosphorylation sharply increased in cells treated with HYD, while treatment with free doxorubicin moderately decreased and treatment with PK1 even strongly decreased it. On the other hand, treatment with free doxorubicin greatly increased p38 phosphorylation, while PK1 and HYD increased it slightly. PK1 also significantly increased ERK phosphorylation, while both the free doxorubicin and HYD conjugate slightly decreased it. Long-term inhibition of JNK significantly increased both proliferation and viability of EL-4 cells treated with free doxorubicin, showing that the JNK signaling pathway could be critical for mediating cell death in EL-4 cells exposed to free doxorubicin. Both activation of caspase 3 and decreased binding activity of the p50 subunit of NFkappaB were observed in cells treated with free doxorubicin and HYD, while no such effects were seen in cells incubated with PK1. Analysis of the expression of genes involved in apoptosis and regulation of the cell cycle demonstrated that free doxorubicin and HYD have very similar mechanisms of action, while PK1 has very different characteristics.

• MeSH
• akrylamidy analýza   chemie   farmakologie   MeSH
• apoptóza genetika   MeSH
• buněčný cyklus genetika   MeSH
• doxorubicin analýza   chemie   farmakologie   MeSH
• exprese genu účinky léků   MeSH
• fosforylace MeSH
• inhibiční koncentrace 50 MeSH
• kaspasa 3 metabolismus   MeSH
• lymfom T-buněčný chemie   metabolismus   MeSH
• mitogenem aktivované proteinkinasy kinas antagonisté a inhibitory   metabolismus   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• NF-kappa B metabolismus   MeSH
• proliferace buněk účinky léků   MeSH
• průtoková cytometrie MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• akrylamidy MeSH
• doxorubicin MeSH
• kaspasa 3 MeSH
• mitogenem aktivované proteinkinasy kinas MeSH
• N-(2-hydroxypropyl)methacrylamide co-polymer-doxorubicin conjugate MeSH Prohlížeč
• NF-kappa B MeSH

Linkage of doxorubicin (Dox) to a water-soluble synthetic N-(2-hydroxypropyl)methacrylamide copolymer (PHPMA) eliminates most of the systemic toxicity of the free drug. In EL-4 lymphoma-bearing C57BL/6 mice, a complete regression of pre-established tumours has been achieved upon treatment with Dox-PHPMA-HuIg conjugate. The treatment was effective using a range of regimens and dosages, ranging from 62.5 to 100% cured mice treated with a single dose of 10-20 mg of Dox eq./kg, respectively. Fractionated dosages producing lower levels of the conjugate for a prolonged time period had substantial curative capacity as well. The cured mice developed anti-tumour protection as they rejected subsequently re-transplanted original tumour. The proportion of tumour-protected mice inversely reflected the effectiveness of the primary treatment. The treatment protocol leading to 50% of cured mice produced only protected mice, while no mice treated with early treatment regimen (i.e. starting on day 1 after tumour transplantation) rejected the re-transplanted tumour. Exposure of the host to the cancer cells was a prerequisite for developing protection. The anti-tumour memory was long lasting and specific against the original tumour, as the cured mice did not reject another syngeneic tumour, melanoma B16-F10. The immunity was transferable to naïve recipients in in vivo neutralization assay by spleen cells or CD8(+) lymphocytes derived from cured animals. We propose an effective treatment strategy which eradicates tumours without harming the protective immune anti-cancer responses.

• MeSH
• antibiotika antitumorózní terapeutické užití   MeSH
• doxorubicin analogy a deriváty   terapeutické užití   MeSH
• imunoglobuliny terapeutické užití   MeSH
• imunologická tolerance * MeSH
• kyseliny polymethakrylové terapeutické užití   MeSH
• lidé MeSH
• lymfom T-buněčný farmakoterapie   imunologie   prevence a kontrola   MeSH
• melanom experimentální farmakoterapie   imunologie   metabolismus   MeSH
• míra přežití MeSH
• myši inbrední C57BL MeSH
• myši nahé MeSH
• myši MeSH
• nádorové buňky kultivované transplantace   MeSH
• nádory kůže farmakoterapie   imunologie   metabolismus   MeSH
• nosiče léků MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• doxorubicin-N-(2-hydroxypropyl)methacrylamide copolymer conjugate MeSH Prohlížeč
• doxorubicin MeSH
• imunoglobuliny MeSH
• kyseliny polymethakrylové MeSH
• nosiče léků MeSH