Medicus
1. vydání 239 stran : ilustrace (převážně barevné) ; 24 cm
Publikace se zaměřuje na postupy molekulární diagnostiky v molekulární onkologii a v chirurgii. Určeno odborné veřejnosti.
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- onkochirurgie
- molekulární biologie, molekulární medicína
- NLK Publikační typ
- kolektivní monografie
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: The anti-PD-1 monoclonal antibody pembrolizumab has been shown to be associated with a good response in patients with metastatic gastric cancer. Excellent therapeutic results of pembrolizumab have been shown in patients with tumours showing a high microsatellite instability (MSI) and Epstein–Barr virus (EBV) positivity. GOAL: This is a retrospective study of 40 bioptic specimens from the patients, who underwent gastrectomy for gastric carcinoma. The goal of the study was to identify biomarkers (EBV, MLH-1, PDL-1 expression) that are potentially relevant for selecting the patients, who may benefit from PD-1 inhibition therapy. METHODS: Immunohistochemical (IHC) expression of PDL-1 and MSI, cytogenetic FISH amplification of the HER-2/neu gene and polymerase chain reaction of EBV RNA, including charge quantification, were performed in selected patients with metastatic or advanced gastric cancer. RESULTS: EBV-encoded RNA was detected in nine patients. None of them exhibited Her-2 overexpression or CMV infection. PD-L1 was detected in twelve patients. Ten patients were MLH1 positive. All nine cases of EBV infection showed a high expression of PD-L1 and MLH-1 (Tab. 1, Ref. 14).
- MeSH
- antigeny CD274 analýza imunologie MeSH
- biologické markery * analýza MeSH
- exprese genu MeSH
- infekce virem Epsteina-Barrové diagnóza imunologie MeSH
- klinické laboratorní techniky metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrosatelitní nestabilita MeSH
- MutL homolog 1 analýza imunologie MeSH
- nádory žaludku * imunologie patofyziologie MeSH
- odběr biologického vzorku MeSH
- receptor erbB-2 analýza imunologie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- výběr pacientů MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
Receptors of the large HER family play an important role in breast cancer, which is undergoing a gradual development in connection with biological development, both in the fi eld of diagnostics and therapy. Dimerization of HER-2 with other HER members, such as HER-3, is the biggest driver of tumor cell growth and survival. Numerous studies show that HER-3 gene overexpression correlates with poor prognosis. However, other studies have shown HER-3 overexpression to be a positive prognostic factor. HER-3 may confer resistance to certain EGFR or HER-2 receptor therapeutics. An interesting fact, however, is that HER-3 expression can serve as a marker in immunotherapy for triple-negative breast cancer (TNBC). It is thought to be involved not only in cell survival and proliferation, but also in the regulation of PD-L1 expression. In breast cancer, PD-L1 expression is heterogeneous and is generally associated with the presence of tumor-infi ltrating lymphocytes and a number of factors with poor prognosis such as young age, hormone receptor negativity, and high HER-2 expression and proliferation index. Our results showed amplifi cation of HER-3 (CERB3) in 2 out of a sample of 20 patients with TNBC, and 13 of 20 HER-2-positive patients. PD-L1 expression was demonstrated in 3 out of 13 HER-3-positive patients and 2 out of 2 HER-3-positive TNBC patients. There was a strong correlation between positive HER-3 and PD-L1 TNBC expression (p = < 0.001). Thus, the view of the HER-3 receptor will be much more complex, and the overexpression of this receptor appears to have both negative and positive prognostic and clinical impacts (Tab. 1, Ref. 17).
- MeSH
- amplifikace genu MeSH
- antigeny CD274 biosyntéza MeSH
- cytogenetické vyšetření MeSH
- dospělí MeSH
- erbB receptory škodlivé účinky MeSH
- imunoanalýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- proteosyntéza * MeSH
- senioři MeSH
- triple-negativní karcinom prsu * etiologie genetika imunologie patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- biomedicínské technologie etika MeSH
- důstojnost lidského života * MeSH
- genetické testování etika MeSH
- individualizovaná medicína etika metody MeSH
- infekční nemoci diagnóza MeSH
- informovaný souhlas pacienta etika MeSH
- klinické laboratorní techniky * etika MeSH
- lékařská etika MeSH
- lidé MeSH
- nádory diagnóza MeSH
- prenatální diagnóza etika MeSH
- Check Tag
- lidé MeSH
Receptory velké rodiny HER hrají v případě karcinomu prsu významnou roli, která prochází postupným rozvojem v souvislosti s biologickým vývojem, a to jak na poli diagnostickém tak terapeutickém. HER2 pozitivita u karcinomu prsu původně sama o sobě představovala nepříznivý prognostický faktor. To se změnilo díky moderní léčbě pomocí monoklonálních protilátek. Další mezník poté představuje konečná analýza dat ze studie CLEOPATRA. Tato studie se zaměřila na přínos přidání monoklonální protilátky pertuzumabu ke standardní terapii trastuzumabem a docetaxelem. Pertuzumab se váže na stejný cíl jako trastuzumab, avšak na jiném vazebném místě, inhibuje tak heterodimerizaci HER2 a HER3 receptorů. Dimerizace HER2 s dalšími členy skupiny HER je přitom největším hnacím mechanismem růstu a přežívání nádorových buněk. Pertuzumab má sám o sobě minimální protinádorovou účinnost, používá se proto výhradně v kombinaci s trastuzumabem. Tento kombinovaný přístup tedy zlepšuje blokádu HER2 signální dráhy porušením dimerizace HER3 a HER2 receptoru. Velice zajímavé se ovšem jeví využití exprese HER3, jako možného prognostického markeru u TNBC převážně ve spojitosti s graviditou a kojením. Dále se předpokládá, že HER-3 receptor se podílí nejen na přežití a proliferaci buněk, ale také na regulaci exprese PD-L1. Mohlo by se tedy jednat o potenciální cíl imunoterapie. Pohled na receptor HER-3 bude však daleko složitější a jak se zdá, nadměrná exprese tohoto receptoru, bude mít jak negativní, tak pozitivní prognostický význam.
In the case of breast cancer, receptors of the large HER family play an important role that undergoes gradual evolution in association with the biological development, both in the diagnostic and therapeutic fields. Originally, HER-2 positivity in breast cancer was an unfavourable prognostic factor in itself. This has changed due to modern treatment with monoclonal antibodies. The final analysis of data from the CLEOPATRA trial has been another landmark. This trial focused on the benefit of adding the monoclonal antibody pertuzumab to standard treatment with trastuzumab and docetaxel. Pertuzumab binds to the same target as trastuzumab, yet at a different binding site, thus inhibiting heterodimerization of the HER-2 and HER-3 receptors. In fact, dimerization of HER-2 and of other members of the HER family is the major driving mechanism of tumour cell growth and survival. Pertuzumab itself has minimal anticancer efficacy; therefore, it is used exclusively in combination with trastuzumab. Hence, this combined approach improves HER-2 signalling pathway inhibition by disrupting the dimerization of HER-3 and HER-2 receptors. What appears to be intriguing, however, is the use of HER-3 expression as a possible prognostic marker in TNBC predominantly in association with pregnancy and breast-feeding. The HER-3 receptor is supposed to be involved not only in cell survival and proliferation, but also in the regulation of PD-L1 expression. It could thus be a potential target for immunotherapy. Indeed, the view of the HER-3 receptor is likely to be much more complex and, as it seems, overexpression of this receptor will have both negative and positive prognostic significance.
- MeSH
- erbB receptory fyziologie MeSH
- exprese genu MeSH
- klinická studie jako téma MeSH
- lidé MeSH
- nádorové komplikace v těhotenství MeSH
- nádory prsu * diagnóza epidemiologie etiologie farmakoterapie MeSH
- prognóza MeSH
- receptor erbB-2 MeSH
- receptor erbB-3 * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Head and neck squamous cell carcinomas (HNSCC) are a highly heterogenous disease which can be induced by two main carcinogens – tobacco and/or alcohol, or by HR HPV infection. This work examined 60 paraffin-embedded biopsies of head and neck carcinomas after histological verification. HPV infection, including its specific types in various HNSCC areas, was studied using multiplex qPCR. Expression levels of p16INK4A and p53 were detected by subsequent IHC analysis as being potential diagnostic markers. Based on the assumption that patients with HNSCC could benefit from anti-EGFR therapy (cetuximab), but the predictors are not yet defined, analyses of point mutations of ras genes (Kras, Nras) were carried out using multiplex qPCR and sequence analysis of the Braf gene. All statistical data were processed by Chí-x2 test. HPV infection was detected in 23.34 % of cases with HNSCC, of which 100 % were HPV 16, which is the most frequently infection found in the oropharyngeal region. Using IHC analysis, a positive expression of P16INK4A was detected in 100 % of HPV-positive HNSCC while this expression was discovered to be highly correlated with HPV infection. Furthermore, a correlation between p53 and HPV-negative HNSCC was proved. The mutation incidence was the highest in the Kras gene (codon 12 and codon 146), Nras (codon 12) and Braf. A correlation between tumor location in the oropharyngeal region and Kras mutations was proved. The HPV infection correlated with Kras mutations in case of codon 146 but on the grounds of low amount of output data, these figures could be irrelevant. In one case, c.1808 G>A, protein 603 Arg>Gln mutation was found in the Braf gene but its correlation with head and neck carcinomas has not been described yet (Tab. 2, Fig. 2, Ref. 24).
- MeSH
- biopsie metody MeSH
- dlaždicobuněčné karcinomy hlavy a krku * genetika imunologie MeSH
- genetické testování metody MeSH
- imunohistochemie * metody MeSH
- infekce papilomavirem * komplikace patologie MeSH
- inhibitor p16 cyklin-dependentní kinasy analýza škodlivé účinky MeSH
- klinická studie jako téma metody MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádorový supresorový protein p53 analýza škodlivé účinky MeSH
- nádory hlavy a krku genetika imunologie patologie MeSH
- onkogenní proteiny imunologie škodlivé účinky MeSH
- prognóza MeSH
- Ras proteiny analýza genetika MeSH
- Check Tag
- lidé MeSH
