interferon-β
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The authors aim to understand how lymphocyte populations could predict the course of multiple sclerosis (MS) in people treated with interferon-β (IFN-β). Twenty-five male patients and 72 female patients were analyzed in the study. Peripheral blood samples were taken before and 5 years after the treatment with IFN-β. Lymphocyte subsets were analyzed by flow cytometry. The authors compared lymphocyte parameters between confirmed sustained progression (CSP) and non-CSP groups by using Welch's one-way analysis of means or a chi-square test of independence. A penalized (lasso) logistic regression model was fitted to identify the combination of lymphocyte parameters for potential biomarkers. The combination of lymphocyte counts, relative CD3+/CD25+ cells, absolute CD8 T cells, absolute CD8+/CD38+ cells, absolute CD38+ cells, and relative CD5+/CD19+ cells was identified as potential biomarker for the IFN-β treatment to monitor MS development in relation to CSP. The results suggest that other biomarkers aid in patient observation, predict a favorable outcome, and assist in the decision-making process for the early therapy escalation.
- Klíčová slova
- biomarkers, interferon-β, lymphocytes, multiple sclerosis,
- MeSH
- dospělí MeSH
- interferon beta terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfocyty patologie MeSH
- mladý dospělý MeSH
- počet lymfocytů MeSH
- roztroušená skleróza krev farmakoterapie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interferon beta MeSH
BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, which often causes progressive neurological disability. In addition to motor and sensory dysfunction, cognitive decline and fatigue are frequent manifestations of the disease. Fatigue is probably the most common symptom, with up to 90% of MS individuals reporting fatigue at some point. Cognitive impairment affects about 50% of patients and may be present at all MS stages. The aim of this observational study was to evaluate changes in cognition, fatigue, and disability status in 300 relapsing-remitting MS (RRMS) patients, treated with subcutaneous (sc) interferon (IFN) β-1a over 2 years. METHODS: The study was designed as an observational, multicentre, prospective, single-arm, phase IV study carried out in 13 MS centres in the Czech Republic. Cognition status was assessed using the Paced Auditory Serial Addition Task (PASAT), fatigue using the Fatigue Descriptive Scale (FDS), and disability using the Expanded Disability Status Scale (EDSS), at baseline, and after 6, 12 and 24 months. The percentage of patients with changed versus stable cognition, fatigue status and disability was calculated at each time point and the changes in these scores were evaluated. RESULTS: The proportion of patients with cognitive improvement was higher compared with those with a stable or decreased PASAT scores at all time points, and the average cognitive performance improved during the follow-up period. Also the proportion of patients with stable or improved fatigue and EDSS scores was higher compared with those in which FDS or EDSS scores declined, this was found at all time points of the analysed sample. However, the direct effect of IFN β-1a on cognition and fatigue cannot be concluded from this study. CONCLUSIONS: The results of this observational study have demonstrated a stable or improved cognitive performance, fatigue status, and disability level in the majority of RRMS patients treated with sc IFN β-1a over a two-year follow-up period, in a real life setting, in the Czech Republic.
- Klíčová slova
- cognitive impairment, fatigue, interferon β-1a, multiple sclerosis, treatment,
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This propensity score-matched analysis from MSBase compared the effectiveness of cladribine with interferon β, fingolimod or natalizumab. METHODS: We identified all patients with relapse-onset multiple sclerosis, exposure to the study therapies and ⩾1-year on-treatment follow-up from MSBase. Three pairwise propensity score-matched analyses compared treatment outcomes over 1 year. The outcomes were hazards of first relapse, disability accumulation and disability improvement events. Sensitivity analyses were completed. RESULTS: The cohorts consisted of 37 (cladribine), 1940 (interferon), 1892 (fingolimod) and 1410 patients (natalizumab). The probability of experiencing a relapse on cladribine was lower than on interferon ( p = 0.05), similar to fingolimod ( p = 0.31) and higher than on natalizumab ( p = 0.042). The probability of disability accumulation on cladribine was similar to interferon ( p = 0.37) and fingolimod ( p = 0.089) but greater than natalizumab ( p = 0.021). The probability of disability improvement was higher on cladribine than interferon ( p = 0.00017), fingolimod ( p = 0.0025) or natalizumab ( p = 0.00099). Sensitivity analyses largely confirmed the above results. CONCLUSION: Cladribine is an effective therapy for relapse-onset multiple sclerosis. Its effect on relapses is comparable to fingolimod and its effect on disability accrual is comparable to interferon β and fingolimod. Cladribine may potentially associate with superior recovery from disability relative to interferon, fingolimod and natalizumab.
- Klíčová slova
- Cladribine, disability, fingolimod, interferon, natalizumab, relapses,
- MeSH
- dospělí MeSH
- fingolimod hydrochlorid terapeutické užití MeSH
- imunosupresiva terapeutické užití MeSH
- interferon beta terapeutické užití MeSH
- kladribin terapeutické užití MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- natalizumab terapeutické užití MeSH
- recidiva MeSH
- relabující-remitující roztroušená skleróza farmakoterapie MeSH
- tendenční skóre MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- fingolimod hydrochlorid MeSH
- imunosupresiva MeSH
- interferon beta MeSH
- kladribin MeSH
- natalizumab MeSH
OBJECTIVE: To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS). METHODS: The impact of alemtuzumab 12 mg vs SC IFN-β-1a 44 μg on MRI measures was evaluated in patients with RRMS who were treatment-naive (CARE-MS I) or who had an inadequate response, defined as at least one relapse, to prior therapy (CARE-MS II). RESULTS: Both treatments prevented T2-hyperintense lesion volume increases from baseline. Alemtuzumab was more effective than SC IFN-β-1a on most lesion-based endpoints in both studies (p < 0.05), including decreased risk of new/enlarging T2 lesions over 2 years and gadolinium-enhancing lesions at year 2. Reduced risk of new T1 lesions (p < 0.0001) and gadolinium-enhancing lesion conversion to T1-hypointense black holes (p = 0.0078) were observed with alemtuzumab vs SC IFN-β-1a in CARE-MS II. Alemtuzumab slowed brain volume loss over 2 years in CARE-MS I (p < 0.0001) and II (p = 0.012) vs SC IFN-β-1a. CONCLUSIONS: Alemtuzumab demonstrated greater efficacy than SC IFN-β-1a on MRI endpoints in active RRMS. The superiority of alemtuzumab was more prominent during the second year of both studies. These findings complement the superior clinical efficacy of alemtuzumab over SC IFN-β-1a in RRMS. CLINICALTRIALSGOV IDENTIFIER: NCT00530348 and NCT00548405. CLASSIFICATION OF EVIDENCE: The results reported here provide Class I evidence that, for patients with active RRMS, alemtuzumab is superior to SC IFN-β-1a on multiple MRI endpoints.
- MeSH
- alemtuzumab MeSH
- dospělí MeSH
- gadolinium MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- imunologické faktory terapeutické užití MeSH
- injekce subkutánní MeSH
- interferon beta 1a aplikace a dávkování MeSH
- kontrastní látky MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mozek diagnostické zobrazování účinky léků MeSH
- relabující-remitující roztroušená skleróza diagnostické zobrazování farmakoterapie MeSH
- velikost orgánu MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- alemtuzumab MeSH
- gadolinium MeSH
- humanizované monoklonální protilátky MeSH
- imunologické faktory MeSH
- interferon beta 1a MeSH
- kontrastní látky MeSH
OBJECTIVES: To investigate the associations of serum lipid profile with disease progression in high-risk clinically isolated syndromes (CIS) after the first demyelinating event. METHODS: High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were obtained in pretreatment serum from 135 high risk patients with CIS (≥ 2 brain MRI lesions and ≥ 2 oligoclonal bands) enrolled in the Observational Study of Early Interferon β-1a Treatment in High Risk Subjects after CIS study (SET study), which prospectively evaluated the effect of intramuscular interferon β-1a treatment following the first demyelinating event. Thyroid stimulating hormone, free thyroxine, 25-hydroxy vitamin D3, active smoking status and body mass index were also obtained. Clinical and MRI assessments were obtained within 4 months of the initial demyelinating event and at 6, 12 and 24 months. RESULTS: The time to first relapse and number of relapses were not associated with any of the lipid profile variables. Higher LDL-C (p=0.006) and TC (p=0.001) levels were associated with increased cumulative number of new T2 lesions over 2 years. Higher free thyroxine levels were associated with lower cumulative number of contrast-enhancing lesions (p=0.008). Higher TC was associated as a trend with lower baseline whole brain volume (p=0.020). Higher high density lipoprotein was associated with higher deseasonalised 1,25-dihydroxy vitamin D3 (p=0.003) levels and a trend was found for deseasonalised 25-hydroxy vitamin D3 (p=0.014). CONCLUSIONS: In early multiple sclerosis, lipid profile variables particularly LDL-C and TC levels are associated with inflammatory MRI activity measures.
- Klíčová slova
- Clinical Neurology, Mri, Multiple Sclerosis, Neurobiology, Neuroradiology,
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- časná lékařská intervence MeSH
- cholesterol krev MeSH
- demyelinizační nemoci krev farmakoterapie MeSH
- dospělí MeSH
- HDL-cholesterol krev MeSH
- index tělesné hmotnosti MeSH
- injekce intramuskulární MeSH
- interferon beta 1a MeSH
- interferon beta terapeutické užití MeSH
- kalcifediol krev MeSH
- kohortové studie MeSH
- kouření škodlivé účinky krev MeSH
- LDL-cholesterol krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- mozek účinky léků patologie MeSH
- prospektivní studie MeSH
- roztroušená skleróza krev diagnóza farmakoterapie MeSH
- thyreotropin krev MeSH
- thyroxin krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- adjuvancia imunologická MeSH
- cholesterol MeSH
- HDL-cholesterol MeSH
- interferon beta 1a MeSH
- interferon beta MeSH
- kalcifediol MeSH
- LDL-cholesterol MeSH
- thyreotropin MeSH
- thyroxin MeSH
OBJECTIVES: To evaluate safety and efficacy of add-on low-dose azathioprine or interferon (IFN)-beta in patients with active multiple sclerosis despite monotherapy. METHODS: This retrospective observational study evaluated 5-year data from 85 patients with active multiple sclerosis despite monotherapy with either IFN-beta or azathioprine, who received add-on azathioprine or IFN-beta, respectively. In a subgroup of 23 patients, 10-year data were analysed. Clinical (relapse frequency, disability) and laboratory effects were compared preceding and following the addition of second drug and between the two treatment regimens. Potential serious adverse events were evaluated. RESULTS: The add-on treatment triggered a drop in annualised relapse rate by approximately 1.5 points sustained over 5 and 10 years. No effect on disability was observed. Simultaneously, white blood cell and lymphocyte counts decreased, being below the physiological levels in 8-26% and 13-52% of patients at each time point, respectively. The drop in relapse rate was independent from the dosage of azathioprine or changes in lymphocyte count. Comparison between the two treatment regimens showed that, with the exception of lymphocyte count, these effects were triggered by the add-on of interferon but not azathioprine. The combination therapy was well tolerated; however, after 5 years on treatment a moderately increased incidence of cancer was observed. CONCLUSIONS: IFN-beta as add-on to azathioprine decreases relapse activity in active multiple sclerosis. In contrast, azathioprine add-on in patients with suboptimal response to IFN-beta does not improve the control over the disease activity.
- MeSH
- azathioprin aplikace a dávkování MeSH
- dospělí MeSH
- interferon beta aplikace a dávkování MeSH
- kombinovaná farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- retrospektivní studie MeSH
- roztroušená skleróza krev farmakoterapie patologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- azathioprin MeSH
- interferon beta MeSH
BACKGROUND AND PURPOSE: Our aim was to identify early imaging surrogate markers of clinical progression in patients after the first demyelinating event suggestive of multiple sclerosis treated with weekly intramuscular interferon β-1a. In a prospective observational study, the predictive role of baseline and 6-month changes in magnetic resonance imaging outcomes was investigated with respect to relapse activity and development of confirmed disability progression in patients after 48 months. METHODS: This study examined 210 patients. Multivariate Cox proportional hazard models were used to analyse predictors of relapse activity and confirmed disability progression after 48 months. RESULTS: Greater T2 lesion volume [hazard ratio (HR) 1.81; P = 0.005] and the presence of contrast-enhancing lesions (HR 2.13; P < 0.001) at baseline were significantly associated with increased cumulative risk of a second clinical attack over 48 months. A greater decrease of the corpus callosum volume (HR 2.74; P = 0.001) and greater lateral ventricle volume enlargement (HR 2.43; P = 0.002) at 6 months relative to baseline were associated with increased cumulative risk of a second clinical attack between months 6 and 48. In addition, increased risk of confirmed disability progression over 48 months in patients with greater lateral ventricle volume enlargement between baseline and 6 months (HR 4.70; P = 0.001) was detected. CONCLUSIONS: A greater T2 lesion volume, the presence of contrast-enhancing lesions at baseline, decrease of corpus callosum volume and lateral ventricle volume enlargement over the first 6 months in patients after the first demyelinating event treated with weekly intramuscular interferon β-1a may assist in identification of patients with the highest risk of a second clinical attack and progression of disability.
- Klíčová slova
- MRI, brain atrophy, clinically isolated syndrome, lesions, multiple sclerosis, predictors,
- MeSH
- adjuvancia imunologická aplikace a dávkování MeSH
- biologické markery * MeSH
- demyelinizační nemoci diagnóza farmakoterapie patologie patofyziologie MeSH
- dospělí MeSH
- injekce intramuskulární MeSH
- interferon beta 1a aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- následné studie MeSH
- progrese nemoci * MeSH
- recidiva MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adjuvancia imunologická MeSH
- biologické markery * MeSH
- interferon beta 1a MeSH
BACKGROUND: Cognitive impairment is a well-recognized symptom of multiple sclerosis (MS) that can manifest early in the disease course. Deficits in cognitive function can have a major impact on daily life. However, cognitive decline is often under-examined in clinical trials and clinical practice due to lack of adequate data. The objective of this study was to examine the longitudinal effect of ocrelizumab vs interferon beta (IFNβ)-1a on cognitive impairment in 2 phase 3 studies in relapsing MS (RMS). METHODS: The pooled population of participants with RMS (n = 1656) from the OPERA I/II clinical trials received subcutaneous IFNβ-1a (44 μg; n = 829) 3 times weekly or intravenous ocrelizumab (600 mg; n = 827) every 24 weeks. Cognition was assessed with a Symbol Digit Modalities Test (SDMT), administered in written or oral form according to each site investigator's choice, that primarily measured cognitive processing speed at baseline and every 12 weeks until the end of the double-blind treatment (96 weeks). Treatment effects were investigated based on longitudinal linear models for the change from baseline in SDMT and Cox regression for the time to 12- or 24-week confirmed decline of ≥4 points. RESULTS: Among the participants with an SDMT assessment at baseline and ≥1 postbaseline time point (IFNβ-1a, n = 749; ocrelizumab, n = 766), ocrelizumab treatment was associated with a greater mean SDMT improvement over 96 weeks than IFNβ-1a treatment (5.4 [95 % CI, 4.4-6.5] vs 4.0 [95 % CI, 3.0-5.1]; adjusted mean difference, 1.4 [95 % CI, 0.05-2.72]; P = 0.042). The risk of a clinically meaningful SDMT decline (≥4 points) was lower for those treated with ocrelizumab for both ≥12 weeks (IFNβ-1a, 18.4 %; ocrelizumab, 12.7 %; hazard ratio, 0.63 [95 % CI, 0.47-0.85]; P = 0.003) and ≥24 weeks (IFNβ-1a, 12.9 %; ocrelizumab, 7.9 %; HR, 0.57 [95 % CI, 0.39-0.82]; P = 0.003). CONCLUSION: Ocrelizumab treatment resulted in better cognitive outcomes as measured by SDMT in participants with RMS compared with IFNβ-1a treatment. However, methodological limitations need to be considered when interpreting these data. CLINICALTRIALS: gov: NCT01247324, NCT01412333.
- Klíčová slova
- Cognitive impairment, DMT, Multiple sclerosis, Ocrelizumab, SDMT,
- MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- humanizované monoklonální protilátky * farmakologie aplikace a dávkování terapeutické užití MeSH
- imunologické faktory * farmakologie aplikace a dávkování terapeutické užití MeSH
- interferon beta 1a * farmakologie terapeutické užití aplikace a dávkování MeSH
- kognitivní dysfunkce * etiologie farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- relabující-remitující roztroušená skleróza * farmakoterapie komplikace MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- humanizované monoklonální protilátky * MeSH
- imunologické faktory * MeSH
- interferon beta 1a * MeSH
- ocrelizumab MeSH Prohlížeč
Fluorescent nanodiamonds (NDs) coated with therapeutics and cell-targeting structures serve as effective tools for drug delivery. However, NDs circulating in blood can eventually interact with the blood-brain barrier, resulting in undesired pathology. Here, we aimed to detect interaction between NDs and adult brain tissue. First, we cultured neuronal tissue with ND ex vivo and studied cell prosperity, regeneration, cytokine secretion, and nanodiamond uptake. Then, we applied NDs systemically into C57BL/6 animals and assessed accumulation of nanodiamonds in brain tissue and cytokine response. We found that only non-neuronal cells internalized coated nanodiamonds and responded by excretion of interleukin-6 and interferon-γ. Cells of neuronal origin expressing tubulin beta-III did not internalize any NDs. Once we applied coated NDs intravenously, we found no presence of NDs in the adult cortex but observed transient release of interleukin-1α. We conclude that specialized adult neuronal cells do not internalize plain or coated NDs. However, coated nanodiamonds interact with non-neuronal cells present within the cortex tissue. Moreover, the coated NDs do not cross the blood-brain barrier but they interact with adjacent barrier cells and trigger a temporary cytokine response. This study represents the first report concerning interaction of NDs with adult brain tissue.
- MeSH
- biokompatibilní potahované materiály chemie farmakologie MeSH
- interferon gama metabolismus MeSH
- interleukin-6 metabolismus MeSH
- kultivované buňky MeSH
- mozek patologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nanodiamanty chemie toxicita MeSH
- neurony cytologie účinky léků metabolismus MeSH
- regenerace účinky léků MeSH
- tubulin genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biokompatibilní potahované materiály MeSH
- interferon gama MeSH
- interleukin-6 MeSH
- nanodiamanty MeSH
- tubulin MeSH
Programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) blockade is a promising therapy for various cancer types, but most patients are still resistant. Therefore, a larger number of predictive biomarkers is necessary. In this study, we assessed whether a loss-of-function mutation of the interferon (IFN)-γ receptor 1 (IFNGR1) in tumor cells can interfere with anti-PD-L1 therapy. For this purpose, we used the mouse oncogenic TC-1 cell line expressing PD-L1 and major histocompatibility complex class I (MHC-I) molecules and its TC-1/A9 clone with reversibly downregulated PD-L1 and MHC-I expression. Using the CRISPR/Cas9 system, we generated cells with deactivated IFNGR1 (TC-1/dIfngr1 and TC-1/A9/dIfngr1). In tumors, IFNGR1 deactivation did not lead to PD-L1 or MHC-I reduction on tumor cells. From potential inducers, mainly IFN-α and IFN-β enhanced PD-L1 and MHC-I expression on TC-1/dIfngr1 and TC-1/A9/dIfngr1 cells in vitro. Neutralization of the IFN-α/IFN-β receptor confirmed the effect of these cytokines in vivo. Combined immunotherapy with PD-L1 blockade and DNA vaccination showed that IFNGR1 deactivation did not reduce tumor sensitivity to anti-PD-L1. Thus, the impairment of IFN-γ signaling may not be sufficient for PD-L1 and MHC-I reduction on tumor cells and resistance to PD-L1 blockade, and thus should not be used as a single predictive marker for anti-PD-1/PD-L1 cancer therapy.
- Klíčová slova
- IFN-α, IFN-β, IFNGR1, MHC class I, PD-1/PD-L1, cancer, immune checkpoint therapy,
- MeSH
- antigeny CD274 antagonisté a inhibitory MeSH
- antigeny CD279 antagonisté a inhibitory MeSH
- experimentální nádory farmakoterapie imunologie metabolismus patologie MeSH
- imunoterapie MeSH
- interferon gama antagonisté a inhibitory MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- protinádorové látky imunologicky aktivní farmakologie MeSH
- transformované buněčné linie účinky léků imunologie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny CD274 MeSH
- antigeny CD279 MeSH
- Cd274 protein, mouse MeSH Prohlížeč
- interferon gama MeSH
- Pdcd1 protein, mouse MeSH Prohlížeč
- protinádorové látky imunologicky aktivní MeSH