Komplexní sdělení o současných možnostech léčby karcinomu štítné žlázy v závislosti na jeho histologickém typu a rozsahu postižení se zaměřením na lokálně pokročilé a hraničně operabilní nálezy. Léčba této heterogenní skupiny nádorů vyžaduje multidisciplinární spolupráci. Popis 6 zajímavých kazuistik s obrazovou dokumentací, popisem léčby a průběhem.
Comprehensive information about current thyroid carcinoma treatment options depending on its histology and extent of the disease, focusing on locally advanced findings at the limit of operability. Treatment of such a heterogeneous group requires interdisciplinary cooperation. We provide 6 unique case reports including imaging scans, description of the therapy and description of development of the condition.
- Klíčová slova
- resekce trachey,
- MeSH
- chirurgie operační metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory štítné žlázy * chirurgie farmakoterapie MeSH
- protokoly protinádorové léčby MeSH
- senioři MeSH
- trachea chirurgie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- přehledy MeSH
Allogeneic cancer cell lines serve as universal source of tumor-associated antigens in cancer vaccines. Immunogenic high hydrostatic pressure-killed cancer cells derived from cell lines can be used for the generation of dendritic cell (DC)-based active cellular immunotherapy of non-small cell lung cancer (NSCLC). We investigated the expression of 12 known NSCLC tumor-associated antigens (TAA) (CEA, MAGE-A1, MAGE-A3, MAGE-A4, PRAME, hTERT, HER2, MUC1, Survivin, STEAP1, SOX2 and NY-ESO-1) in 6 NSCLC cell lines as candidates for the generation of DC-based lung cancer vaccine. We showed that the selected antigenic profile of these cell lines overlaps to various degrees with that of primary NSCLC tumors (n = 52), indicating that 4 out of 6 NSCLC cell lines would be suitable for DC-based vaccine generation. We further investigated the presence of TAA-specific T cells in blood of NSCLC patients (n = 32) using commercially available peptide mixes in an in vitro stimulation assay. IFN-γ+CD8+ and IFN-γ+CD4+ T cell responses to all antigens were detected in NSCLC patients. Interestingly, despite higher TAA expression in squamous cell carcinoma (SCC) the responsiveness of patients' T cells to stimulation was significantly lower in SCC patients than in adenocarcinoma (AC) patients. This suggests qualitative differences in T cell functionality between NSCLC subtypes. Based on this study, and in order to maximize the amount of treatable patients, we selected a mix of H520 and H522 NSCLC cell lines for DC-based vaccine preparation. We also established a minimal panel of antigenic peptide mixes (CEA, hTERT, PRAME, HER2) for immunomonitoring of T cell responses during the DC-based lung cancer immunotherapy in Phase I lung cancer clinical trial (NCT02470468).
- MeSH
- antigenní specifita receptorů T-buněk * MeSH
- antigeny nádorové imunologie MeSH
- cytotoxické T-lymfocyty imunologie metabolismus MeSH
- dendritické buňky imunologie metabolismus MeSH
- imunoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory plic imunologie metabolismus patologie terapie MeSH
- nemalobuněčný karcinom plic imunologie metabolismus patologie terapie MeSH
- protinádorové vakcíny MeSH
- senioři MeSH
- staging nádorů MeSH
- T-lymfocyty imunologie metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
INTRODUCTION: Lung cancer is the leading cause of cancer mortality worldwide; therefore, understanding the biological or clinical role of tumor-associated antigens and autoantibodies is of eminent interest for designing antitumor immunotherapeutic strategies. METHODS: Here we prospectively analyzed the serum frequencies of New York esophageal squamous cell carcinoma 1 (NY-ESO-1), human epidermal growth factor 2/neu, and melanoma-associated antigen A4 (MAGE-A4) antibodies and expression of the corresponding antigens in tumors of 121 patients with NSCLC undergoing an operation without prior neoadjuvant chemotherapy and compared them with those in 57 control age-matched patients with no history of a malignant disease. RESULTS: We found that only antibodies specific for NY-ESO-1 (19.8% [n = 24 of 121]) were significantly increased in the group of patients with NSCLC compared with in the controls. NY-ESO-1 seropositivity was significantly positively associated with an active smoking history in patients with NSCLC but not in smokers from the control group. In tumors, the frequency of NY-ESO-1 mRNA expression was 6.3% (in four of 64 patients), the frequency of human epidermal growth factor 2/neu (HER 2/neu) expression was 11.9% (five of 42), and the frequency of MAGE-A4 expression was 35.1% (20 of 57). MAGE-A4 expression in tumors correlated with smoking status and male sex in patients with NSCLC. Patients with squamous cell carcinoma displayed higher expression of NY-ESO-1 and MAGE-A4 in tumors than did patients with adenocarcinoma. On the other hand, 94.7% of nonsmoking patients in our study had adenocarcinoma (of whom 73.7% were women). CONCLUSION: These results confirm the reported high immunogenicity of NY-ESO-1 and suggest that a smoking-induced chronic inflammatory state might potentiate the development of NY-ESO-1-specific immune responses. Moreover, smoking might contribute to the expression of other cancer/testis antigens such as MAGE-A4 at early stages of NSCLC development.
- MeSH
- adenokarcinom krev etiologie patologie MeSH
- antigeny nádorové krev imunologie MeSH
- dospělí MeSH
- kouření škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové proteiny krev imunologie MeSH
- nádorové biomarkery krev MeSH
- nádorové proteiny krev MeSH
- nádory plic krev etiologie patologie MeSH
- následné studie MeSH
- nemalobuněčný karcinom plic krev etiologie patologie MeSH
- prognóza MeSH
- prospektivní studie MeSH
- receptor erbB-2 krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocelulární karcinom krev etiologie patologie MeSH
- staging nádorů MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Publikační typ
- abstrakt z konference MeSH
High hydrostatic pressure (HHP) induces immunogenic death of tumor cells which confer protective anti-tumor immunity in vivo. Moreover, DC pulsed with HHP-treated tumor cells induced therapeutic effect in mouse cancer model. In this study, we tested the immunogenicity, stability and T cell stimulatory activity of human monocyte-derived dendritic cell (DC)-based HHP lung cancer vaccine generated in GMP compliant serum free medium using HHP 250 MPa. DC pulsed with HHP-killed lung cancer cells and poly(I:C) enhanced DC maturation, chemotactic migration and production of pro-inflammatory cytokines after 24h. Moreover, DC-based HHP lung cancer vaccine showed functional plasticity after transfer into serum-containing media and stimulation with LPS or CD40L after additional 24h. LPS and CD40L stimulation further differentially enhanced the expression of costimulatory molecules and production of IL-12p70. DC-based HHP lung cancer vaccine decreased the number of CD4+CD25+Foxp3+ T regulatory cells and stimulated IFN-γ-producing tumor antigen-specific CD4+ and CD8+ T cells from non-small cell lung cancer (NSCLC) patients. Tumor antigen specific CD8+ and CD4+ T cell responses were detected in NSCLC patient's against a selected tumor antigens expressed by lung cancer cell lines used for the vaccine generation. We also showed for the first time that protein antigen from HHP-killed lung cancer cells is processed and presented by DC to CD8+ T cells. Our results represent important preclinical data for ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa) in combination with chemotherapy and immune enhancers.
- MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- dendritické buňky imunologie MeSH
- hydrostatický tlak MeSH
- imunoterapie metody MeSH
- interferon gama metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory plic terapie MeSH
- nemalobuněčný karcinom plic terapie MeSH
- protinádorové vakcíny imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: Střelná poranění hrudníku nejsou v dnešní době v naší geografické poloze tak četná a vyskytují se nejčastěji v souvislosti s kriminální činností nebo jsou následkem suicidálního chování. Kazuistika: Autoři uvádějí případ pacienta, který si v sebevražedném pokusu způsobil kombinované penetrující střelné poranění hrudníku s lacerací plíce a průstřelem srdce, který byl diagnostikován až peroperačně. Závěr: Terapie střelných poranění v éře moderní medicíny by měla být komplexní v multioborové spolupráci.
Introduction: Gunshot thoracic injuries are not very common in our geographical location, occurring most frequently in the context of criminal activity or as a result of suicidal behavior. Case report: The authors report the case of a patient who, in a suicidal attempt, caused himself a combined penetrating gunshot injury of the chest with laceration of the lung and a heart gunshot hole, which was diagnosed peroperatively. Conclusion: Therapy of gunshot injuries in the era of modern medicine should be comprehensive in multidisciplinary cooperation.
- MeSH
- dospělí MeSH
- hemotorax MeSH
- incidence MeSH
- lidé MeSH
- pneumotorax MeSH
- pokus o sebevraždu MeSH
- poranění hrudníku * diagnostické zobrazování chirurgie terapie MeSH
- poranění srdce diagnóza etiologie terapie MeSH
- poškození plic diagnóza etiologie MeSH
- prognóza MeSH
- střelné rány * diagnóza etiologie chirurgie MeSH
- torakotomie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
