INTRODUCTION: Single-agent oral vinorelbine is a standard of care for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) that has progressed on endocrine therapy. Metronomic administration may offer a better balance of efficacy and safety than standard regimens, but data from previous trials are scarce. METHODS: In this open-label, multicenter, phase II trial, patients were randomized to oral vinorelbine administered on a metronomic (50 mg three times weekly) or weekly (60 mg/m2 in cycle 1, increasing to 80 mg/m2 if well tolerated) schedule. Treatment was continued until disease progression or intolerance. The primary endpoint was disease control rate (DCR, the proportion of patients with a best overall confirmed response of CR, PR, or stable disease lasting 6 months or more). RESULTS: One-hundred sixty-three patients were randomized and treated. The DCR was 63.4% (95% confidence interval [CI]: 52.0-73.8) with metronomic vinorelbine and 72.8% (95% CI: 61.8-82.1) with weekly vinorelbine. Weekly vinorelbine was also associated with longer progression-free survival (5.6 vs 4.0 months) and overall survival (26.7 vs 22.3 months) than metronomic vinorelbine, but was associated with more adverse events. CONCLUSIONS: In this randomized phase II trial, single-agent metronomic oral vinorelbine was effective and well tolerated as first-line chemotherapy for patients with HR-positive/HER2-negative ABC. Formal comparisons are not done in this phase II study and one can simply observe that confidence intervals of all endpoints overlap. When deciding for a chemotherapy after failure of endocrine therapy and CDK 4/6 inhibitors, oral vinorelbine might be an option to be given with either schedule. CLINICAL TRIAL REGISTRATION NUMBER: EudraCT 2014-003860-19.

• MeSH
• doba přežití bez progrese choroby MeSH
• lidé MeSH
• metronomické podávání léků MeSH
• nádory prsu * MeSH
• protokoly protinádorové kombinované chemoterapie MeSH
• prsy metabolismus   MeSH
• receptor erbB-2 metabolismus   MeSH
• vinblastin MeSH
• vinorelbin MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Genetic and non-genetic factors contribute to breast cancer development. An epigenome-based signature capturing these components in easily accessible samples could identify women at risk. Here, we analyse the DNA methylome in 2,818 cervical, 357 and 227 matched buccal and blood samples respectively, and 42 breast tissue samples from women with and without breast cancer. Utilising cervical liquid-based cytology samples, we develop the DNA methylation-based Women's risk IDentification for Breast Cancer index (WID-BC-index) that identifies women with breast cancer with an AUROC (Area Under the Receiver Operator Characteristic) of 0.84 (95% CI: 0.80-0.88) and 0.81 (95% CI: 0.76-0.86) in internal and external validation sets, respectively. CpGs at progesterone receptor binding sites hypomethylated in normal breast tissue of women with breast cancer or in BRCA mutation carriers are also hypomethylated in cervical samples of women with poor prognostic breast cancer. Our data indicate that a systemic epigenetic programming defect is highly prevalent in women who develop breast cancer. Further studies validating the WID-BC-index may enable clinical implementation for monitoring breast cancer risk.

• MeSH
• cervix uteri cytologie   metabolismus   MeSH
• CpG ostrůvky MeSH
• epigenom MeSH
• epigenomika metody   MeSH
• epitelové buňky metabolismus   MeSH
• lidé MeSH
• metylace DNA * MeSH
• mutace MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádory prsu genetika   metabolismus   MeSH
• prognóza MeSH
• prsy cytologie   metabolismus   MeSH
• ROC křivka MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

Early detection of cancer is one of the unmet needs in clinical medicine. Peripheral blood analysis is a preferred method for efficient population screening, because blood collection is well embedded in clinical practice and minimally invasive for patients. Lipids are important biomolecules, and variations in lipid concentrations can reflect pathological disorders. Lipidomic profiling of human plasma by the coupling of ultrahigh-performance supercritical fluid chromatography and mass spectrometry is investigated with the aim to distinguish patients with breast, kidney, and prostate cancers from healthy controls. The mean sensitivity, specificity, and accuracy of the lipid profiling approach were 85%, 95%, and 92% for kidney cancer; 91%, 97%, and 94% for breast cancer; and 87%, 95%, and 92% for prostate cancer. No association of statistical models with tumor stage is observed. The statistically most significant lipid species for the differentiation of cancer types studied are CE 16:0, Cer 42:1, LPC 18:2, PC 36:2, PC 36:3, SM 32:1, and SM 41:1 These seven lipids represent a potential biomarker panel for kidney, breast, and prostate cancer screening, but a further verification step in a prospective study has to be performed to verify clinical utility.

• MeSH
• časná detekce nádoru MeSH
• dospělí MeSH
• heparin chemie   MeSH
• hmotnostní spektrometrie MeSH
• ledviny metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidomika * MeSH
• lipidy chemie   MeSH
• mladý dospělý MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory prostaty metabolismus   MeSH
• nádory prsu metabolismus   MeSH
• plocha pod křivkou MeSH
• prospektivní studie MeSH
• prostata metabolismus   MeSH
• prsy metabolismus   MeSH
• regulace genové exprese u nádorů MeSH
• reprodukovatelnost výsledků MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• senioři MeSH
• statistické modely MeSH
• studie případů a kontrol MeSH
• superkritická fluidní chromatografie 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

The eleventh annual workshop of the European Network for Breast Development and Cancer, Methods in mammary gland biology and breast cancer, took place on the 16th to 18th of May 2019 in Weggis, Switzerland. The main topics of the meeting were high resolution genomics and proteomics for the study of mammary gland development and cancer, breast cancer signaling, tumor microenvironment, preclinical models of breast cancer, and tissue morphogenesis. Exciting novel findings in, or highly relevant to, mammary gland biology and breast cancer field were presented, with insights into the methods used to obtain them. Among others, the discussed methods included single-cell RNA sequencing, genetic barcoding, lineage tracing, spatial transcriptomics, optogenetics, genetic mouse models and organoids.

• MeSH
• genomika MeSH
• karcinogeneze genetika   metabolismus   patologie   MeSH
• lidé MeSH
• nádorové mikroprostředí * MeSH
• nádory prsu genetika   metabolismus   patologie   MeSH
• proteomika MeSH
• prsy metabolismus   patologie   MeSH
• signální transdukce MeSH
• společnosti vědecké MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

RATIONALE: The goal of this work is the comparison of differences in the lipidomic compositions of human cell lines derived from normal and cancerous breast tissues, and tumor vs. normal tissues obtained after the surgery of breast cancer patients. METHODS: Hydrophilic interaction liquid chromatography/electrospray ionization mass spectrometry (HILIC/ESI-MS) using the single internal standard approach and response factors is used for the determination of relative abundances of individual lipid species from five lipid classes in total lipid extracts of cell lines and tissues. The supplementary information on the fatty acyl composition is obtained by gas chromatography/mass spectrometry (GC/MS) of fatty acid methyl esters. Multivariate data analysis (MDA) methods, such as nonsupervised principal component analysis (PCA), hierarchical clustering analysis (HCA) and supervised orthogonal partial least-squares discriminant analysis (OPLS-DA), are used for the visualization of differences between normal and tumor samples and the correlation of similarity between cell lines and tissues either for tumor or normal samples. RESULTS: MDA methods are used for differentiation of sample groups and also for identification of the most up- and downregulated lipids in tumor samples in comparison to normal samples. Observed changes are subsequently generalized and correlated with data from tumor and normal tissues of breast cancer patients. In total, 123 lipid species are identified based on their retention behavior in HILIC and observed ions in ESI mass spectra, and relative abundances are determined. CONCLUSIONS: MDA methods are applied for a clear differentiation between tumor and normal samples both for cell lines and tissues. The most upregulated lipids are phospholipids (PL) with a low degree of unsaturation (e.g., 32:1 and 34:1) and also some highly polyunsaturated PL (e.g., 40:6), while the most downregulated lipids are PL containing polyunsaturated fatty acyls (e.g., 20:4), plasmalogens and ether lipids. Copyright © 2016 John Wiley & Sons, Ltd.

• MeSH
• analýza hlavních komponent MeSH
• chromatografie kapalinová metody   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• hydrofobní a hydrofilní interakce MeSH
• lidé MeSH
• lipidy analýza   MeSH
• multivariační analýza MeSH
• nádorové buněčné linie MeSH
• nádory prsu chemie   metabolismus   MeSH
• prsy chemie   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The tumor suppressor p53 plays a key role in malignant transformation and tumor development. However, the frequency of p53 mutations within individual types of cancer is different, suggesting the existence of other mechanisms attenuating p53 tumor suppressor activity. Changes in upstream regulators of p53 such as MDM2 amplification and overexpression, expression of viral oncoproteins, estrogen receptor signaling, or changes in p53 transcriptional target genes were previously described in wild-type p53 tumors. We identified a novel pathway responsible for attenuation of p53 activity in human cancers. We demonstrate that AGR2, which is overexpressed in a variety of human cancers and provides a poor prognosis, up-regulates DUSP10 which subsequently inhibits p38 MAPK and prevents p53 activation by phosphorylation. Analysis of human breast cancers reveals that AGR2 specifically provides a poor prognosis in ER+ breast cancers with wild-type p53 but not ER- or mutant p53 breast cancers, and analysis of independent data sets show that DUSP10 levels also have prognostic significance in this specific sub-group of patients. These data not only reveal a novel pro-oncogenic signaling pathway mediating resistance to DNA damaging agents in human tumors, but also has implications for designing alternative strategies for modulation of wild-type p53 activity in cancer therapy.

• MeSH
• aktivace enzymů účinky léků   MeSH
• chemorezistence MeSH
• dospělí MeSH
• fosfatasy MAP kinas metabolismus   MeSH
• fosfatasy s dvojí specifitou metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorový supresorový protein p53 metabolismus   MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• nádory farmakoterapie   metabolismus   patologie   MeSH
• proteiny metabolismus   MeSH
• protinádorové látky farmakologie   MeSH
• prsy účinky léků   metabolismus   patologie   MeSH
• senioři MeSH
• signální transdukce * účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epidemiological studies have revealed that high consumption of soy products is associated with low incidences of hormone-dependent cancers, including breast and prostate cancer. Soybeans contain large amounts of isoflavones, such as the genistein and daidzain. Previously, it has been demonstrated that genistein, one of the predominant soy isoflavones, can inhibit several steps involved in carcinogenesis. It is suggested that genistein possesses pleiotropic molecular mechanisms of action including inhibition of tyrosine kinases, DNA topoisomerase II, 5α-reductase, galectin-induced G2/M arrest, protein histidine kinase, and cyclin-dependent kinases, modulation of different signaling pathways associated with the growth of cancer cells (e.g., NF-κB, Akt, MAPK), etc. Moreover, genistein is also a potent inhibitor of angiogenesis. Uncontrolled angiogenesis is considered as a key step in cancer growth, invasion, and metastasis. Genistein was found to inhibit angiogenesis through regulation of multiple pathways, such as regulation of VEGF, MMPs, EGFR expressions and NF-κB, PI3-K/Akt, ERK1/2 signaling pathways, thereby causing strong antiangiogenic effects. This review focuses on the antiangiogenic properties of soy isoflavonoids and examines their possible underlying mechanisms.

• MeSH
• genistein chemie   farmakologie   terapeutické užití   MeSH
• Glycine max chemie   MeSH
• inhibitory angiogeneze chemie   farmakologie   terapeutické užití   MeSH
• isoflavony chemie   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádory prsu krevní zásobení   farmakoterapie   metabolismus   patologie   MeSH
• patologická angiogeneze farmakoterapie   metabolismus   patologie   MeSH
• prsy krevní zásobení   účinky léků   metabolismus   patologie   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

AIM: The liver is the site of breast cancer metastasis in 50% of patients with advanced disease. Tumour markers have been demonstrated as being useful in follow-up of patients with breast cancer, in early detection of recurrence of breast cancer after radical surgical treatments, and in assessing oncologic therapy effect, but no study has been carried out on their usefullness in distinguishing benign liver lesions from breast cancer metastases. The aim of this study was therefore to evaluate the importance of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen CA19-9 (CA19-9), thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin 19 fragment (CYFRA 21-1) in differential diagnosis between benign liver lesions and liver metastases of breast cancer. PATIENTS AND METHODS: The study includes 3 groups: 22 patients with liver metastases of breast cancer; 39 patients with benign liver lesions (hemangioma, focal nodular hyperplasia, liver cyst, hepatocellular adenoma); and 21 patients without any liver disease or lesion that were operated on for benign extrahepatic diseases (groin hernia, varices of lower limbs) as a control group. The serum levels of tumour markers were assessed by means of immunoanalytical methods. RESULTS: Preoperative serum levels of CYFRA 21-1, TPA, TPS and CEA were significantly higher in patients with liver metastases of breast cancer in contrast to healthy controls and patients with benign liver lesions (p-value<0.05). Serum levels of CA19-9 and TK were higher in patients with malignancy in comparison with benign liver disease and healthy controls but these differences were not statistically significant. CONCLUSION: Tumour markers CEA, CYFRA 21-1, TPA and TPS can be recommended as a good tool for differential diagnosis between liver metastases of breast cancer and benign liver lesions.

• MeSH
• antigen CA-19-9 krev   MeSH
• antigeny nádorové krev   MeSH
• časná diagnóza MeSH
• diferenciální diagnóza MeSH
• karcinoembryonální antigen krev   MeSH
• keratin-19 krev   MeSH
• kohortové studie MeSH
• lidé MeSH
• nádorové biomarkery krev   MeSH
• nádory jater krev   diagnóza   sekundární   MeSH
• nádory prsu krev   diagnóza   MeSH
• prognóza MeSH
• prsy metabolismus   MeSH
• retrospektivní studie MeSH
• studie případů a kontrol MeSH
• thymidinkináza krev   MeSH
• tkáňový polypeptidový antigen krev   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

Recent studies have suggested that genetic polymorphisms in the TP53 pathway influence tumour formation, progression and response to therapy. We analysed the three most common TP53 gene polymorphisms as potential genetic markers to predict the development and prognosis of breast cancer. The incidence of R72P, PIN3 Ins 16bp and PIN6 G13494A polymorphisms was determined in a cohort of 117 breast cancer tissues and 108 control specimens by PCR-RFLP. No significant difference was observed in the polymorphism variants in breast cancer specimens compared to controls. Furthermore, no statistically significant association of these polymorphisms with the outcome of the patients was observed. On the other hand we found positive correlation of lymph node metastases with both PIN3 Ins 16bp and PIN6 G13494A polymorphisms. The association of intronic TP53 variants with an aggressive breast cancer phenotype may represent a useful predictive biomarker, particularly in patients of clinical stage I with low or intermediate risk.

• MeSH
• dospělí MeSH
• duktální karcinom prsu genetika   metabolismus   sekundární   MeSH
• frekvence genu MeSH
• imunoenzymatické techniky MeSH
• introny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lobulární karcinom genetika   metabolismus   sekundární   MeSH
• lymfatické metastázy MeSH
• mladý dospělý MeSH
• mutace genetika   MeSH
• nádorové biomarkery genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory prsu genetika   metabolismus   patologie   MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus délky restrikčních fragmentů MeSH
• polymorfismus genetický MeSH
• prognóza MeSH
• prsy metabolismus   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

The resistance to interferons (IFNs) limits their anticancer therapeutic efficacy. Here we studied the antiproliferative effect of interferon gamma in relation to SOCS3 expression in a panel of breast cancer cell lines and normal mammary epithelial cells. Compared to normal cells most breast cancer lines (7/8) were highly resistant to IFN-gamma. Using Northern blot and real time RT-PCR we investigated transcription of SOCS3 genes. All normal epithelial cells (4/4) showed SOCS3 induction (2-14 fold) while most breast cancer lines did not or weakly activated SOCS3 after the interferon gamma treatment. Among the cancer lines, the MDA-MB-468 cells showed increased sensitivity to IFN-gamma and relatively high level of SOCS3 induction (2-3 fold). Together, there was a good correlation

• MeSH
• chemorezistence MeSH
• fosforylace MeSH
• interferon gama farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• proteiny SOCS genetika   MeSH
• prsy metabolismus   účinky léků   MeSH
• transkripční faktor STAT1 metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH