BACKGROUND: Detection of circulating tumor cells (CTC) in patients with castration-resistant prostate cancer (CRPC) may improve the estimate of chemotherapy response. We evaluated the AdnaTest® system in patients receiving docetaxel. PATIENTS AND METHODS: CTC analysis was carried out in 37 patients by immunomagnetic separation. Correlation between serum prostate-specific antigen (sPSA) change and CTC presence and the influence of each parameter on the overall survival (OS) were evaluated. RESULTS: We detected CTCs in 32 and 16 patients before and after three docetaxel cycles, respectively. The sPSA level correlated with CTC positivity during docetaxel therapy (p=0.0031). The longest OS was in patients negative for CTCs in both samples (p=0.0228). Change in sPSA levels was associated with treatment response (p=0.033). CONCLUSION: We detected CTCs in a considerable number of patients with CRPC. The absolute change of sPSA level correlated with OS. CTC presence during docetaxel therapy was associated with shorter OS.
- Klíčová slova
- AdnaTest, castration-resistant prostate cancer, chemotherapy, circulating tumor cells, prognosis,
- MeSH
- antitumorózní látky terapeutické užití MeSH
- docetaxel MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové cirkulující buňky * MeSH
- nádory prostaty rezistentní na kastraci krev patologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- prognóza MeSH
- prostatický specifický antigen krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- taxoidy terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky MeSH
- docetaxel MeSH
- prostatický specifický antigen MeSH
- taxoidy MeSH
UNLABELLED: Circulating tumor cells (CTCs) are an independent prognostic factor for patients with metastatic breast cancer (MBC). However, the role of CTCs in early breast cancer management is not yet clearly defined. The aim of this study was to assess the CTC-positivity rate in patients undergoing chemotherapy depending on breast cancer stage in the adjuvant and neoadjuvant setting. We evaluated the ability to confirm therapy response by CTC analysis. PATIENTS AND METHODS: CTCs isolated from blood by means of immunomagnetic separation were further characterized by means of reverse transcriptase - polymerase chain reaction (RT-PCR) for epithelial cell adhesion molecule (EPCAM), mucin 1 (MUC1) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2) transcripts with the AdnaTest™. This prospective study included 179 patients; altogether 419 blood samples were evaluated. Patients with primary tumors were divided into neoadjuvant (n=38), and adjuvant (n=100) groups. Forty-one patients with MBC were evaluated under palliative treatment. RESULTS: CTC positivity was described in 35% of patients with early breast cancer without detected metastases before neoadjuvant chemotherapy; similarly, a 26% positivity rate was found in the adjuvant group. In patients with MBC, we detected CTCs in 43% of them. After completing the therapy, the CTC positivity rate decreased to 5% in the neoadjuvant group, to 13% in the adjuvant group and to 12% in the MBC group. CTC positivity after the therapy may classify a subgroup of patients at high risk of developing metastatic disease. This was even true when a patient was evaluated as being CTC-negative before chemotherapy. The multivariate analysis evaluating the correlation of CTC positivity with clinicopathological characteristics such as tumor size, nodal involvement, hormone receptor status, HER2 expression and number of metastatic sites revealed no statistically significant relationships. CONCLUSION: CTC status may have a significant impact on early BC management.
- Klíčová slova
- CTC, breast cancer, chemotherapy, circulating tumor cells,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorové cirkulující buňky metabolismus patologie MeSH
- nádory prsu u mužů diagnóza genetika patologie terapie MeSH
- nádory prsu diagnóza genetika patologie terapie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- staging nádorů MeSH
- stupeň nádoru MeSH
- tumor burden MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- nádorové biomarkery MeSH
The major cause of death due to cancer is its metastatic deposit in numerous tissues and organs. The metastatic process requires the migration of malignant cells from primary sites to distant environments. Even for tumors initially spreading through lymphatic vessels, hematogenous transport is the most common metastatic pathway. The detachment of cancer cells from a primary tumor into the blood stream is called epithelial-mesenchymal transition (EMT). As these cells circulate further in the bloodstream they are known as circulating tumor cells (CTCs). The CTC population is highly resilient, enabling the cells to colonize a foreign microenvironment. Alternatively, cancer stem cells (CSCs) may arise from differentiated cancer cells through EMT and an embryonic transdifferentiation process. The presence of CTCs/CSCs in blood seems to be a determining factor of metastasis. This paper reviews various methods of clinical cancer detection as well as the biology and molecular characterization of CTCs/CSCs. Our goal was to summarize clinical studies which used CTC/CSCs for prognosis in patients with breast, colorectal, prostate, lung, ovarian, and bladder cancer.
- Klíčová slova
- Cancer stem cells, Circulating tumor cells, Clinical significance, Detection methods, Epithelial–mesenchymal transition,
- MeSH
- epitelo-mezenchymální tranzice MeSH
- lidé MeSH
- nádorové cirkulující buňky patologie MeSH
- nádorové kmenové buňky metabolismus MeSH
- nádory diagnóza etiologie mortalita patologie terapie MeSH
- prognóza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
AIMS: The identification of growth factors and cytokines with angiogenic activity has enabled new therapeutic treatments for a variety of diseases; this concept is called therapeutic angiogenesis. The vascular endothelial growth factor (VEGF) is the most critical regulator of vascular formation. In the present study, we were interested in the therapeutic angiogenesis effect using plasmid transfer of human complementary DNA VEGF(165) (phVEGF(165)) in experimental skin and cartilage trauma. METHODS: Ten BALB/c mice were used for cartilage injury model. At 6 weeks of age, all mice were ear-punched, resulting in 2-mm-diameter puncture through the center of both pinnae. Each mouse got phVEGF(165) injection into the first ear and vector without insert or saline injection into the second one. The healing process was followed. The hollow diameter was measured on days 0, 14, and 42. Histological sections of experimental and control pinnae were taken from days 1, 3, 5, 7, 9, 11, 13, 15, 20, and 30 after experimental injury for hematoxylin and eosin and periodic acid Schiff staining and for human VEGF immunocytochemistry. The expression of human VEGF was also checked by real-time polymerase chain reaction in formalin-fixed, paraffin-embedded tissue sections. KEY FINDINGS: In BALB/c mouse strain, a significant angiogenesis promotion and cartilage repair were observed after phVEGF(165) injection into the punched ear area. SIGNIFICANCE: We suggest that administering phVEGF(165) leads to faster cartilage regeneration even if not only on the angiogenic basis.
- MeSH
- analýza rozptylu MeSH
- chrupavka zranění MeSH
- fyziologická neovaskularizace účinky léků MeSH
- hojení ran účinky léků MeSH
- imunohistochemie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- plazmidy MeSH
- regenerace MeSH
- studie proveditelnosti MeSH
- vaskulární endoteliální růstový faktor A farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- vaskulární endoteliální růstový faktor A MeSH
Circulating tumor cells (CTCs) are potential precursors of metastasis. They are also of use in diagnosing malignancy and for prognostic purposes. Our laboratory has previously isolated CTCs from orthotopic nude mouse models of human prostate cancer cells where the PC-3 cancer cells express green fluorescent protein (GFP). It was found that orthotopic tumors produced CTCs and not subcutaneous tumors, which may explain why orthotopic tumors metastasize and subcutaneous tumors do not. However, in this previous study, CTCs were observed only after culture. In the present study, using the GFP-expressing PC-3 orthotopic model and immunomagnetic beads coated with anti-epithelial cell adhesion molecule (EpCAM) and anti-prostate specific membrane antigen (PSMA), GFP-expressing CTC were isolated within 15 minutes and were readily visualized by GFP fluorescence. It was possible to immediately place the immunomagnetic-bead-captured GFP-expressing PC-3 CTCs in 3-dimensional sponge cell culture, where they proliferated. The combination of GFP expression and the use of immunomagnetic beads is a very powerful method to obtain CTCs for either immediate analysis or for biological characterization in vivo or in 3-dimensional culture.
- MeSH
- adhezní molekula epiteliálních buněk MeSH
- antigeny nádorové imunologie MeSH
- glutamátkarboxypeptidasa II imunologie MeSH
- imunomagnetická separace * MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- molekuly buněčné adheze imunologie MeSH
- myši nahé MeSH
- myši MeSH
- nádorové buňky kultivované MeSH
- nádorové cirkulující buňky patologie MeSH
- nádory prostaty metabolismus patologie MeSH
- zelené fluorescenční proteiny metabolismus 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
- adhezní molekula epiteliálních buněk MeSH
- antigeny nádorové MeSH
- glutamátkarboxypeptidasa II MeSH
- molekuly buněčné adheze MeSH
- zelené fluorescenční proteiny MeSH