• MeSH
• adjuvantní chemoterapie metody   MeSH
• časná diagnóza MeSH
• dospělí MeSH
• lidé MeSH
• nádory prsu patologie   terapie   MeSH
• neoadjuvantní terapie metody   MeSH
• přehledová literatura jako téma MeSH
• taxoidy farmakologie   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy MeSH

Paclitaxel is a valuable plant drug produced by Taxus species, showing anticancer activity in various cancer types. Its action consists in preventing depolymerization of tubulin in cell division. Unfortunately, its isolation from the bark of slow-growing yew trees is limited. Although paclitaxel has been totally synthesized, its production currently depends, completely or in part, on supply of Taxus sp. Plant cell cultures, endophytic and epiphytic microorganisms as well as chemical and biotechnological synthesis are currently investigated for the production of taxanes (paclitaxel and docetaxel).

• MeSH
• biotechnologie metody   MeSH
• financování organizované MeSH
• nádory farmakoterapie   MeSH
• paclitaxel analogy a deriváty   chemická syntéza   izolace a purifikace   MeSH
• toxoidy chemická syntéza   izolace a purifikace   terapeutické užití   MeSH
• vztahy mezi strukturou a aktivitou MeSH

Periférna neurotoxicita predstavuje najtypickejší nehematologický nežiaduci účinok taxánov. Z príznakov dominuje senzorická periférna neuropatia, ktorej výskyt a stupeň závisia na výške kumulatívnej dávky. Dopad neurotoxicity na kvalitu života pacienta je značný, preto je nevyhnutné zohľadňovať selekciu terapie a preexistujúce rizikové faktory pacienta k rozvoju neuropatie a oboznamovať sa s aktuálnymi možnosťami jej manažmentu vrátane genetickej predikcie polyneuropatie. Tento prehľadový článok informuje o veľmi častej komplikácii onkologickej terapie, s ktorou je možné sa stretnúť v ambulancii každého internistu.

Peripheral neurotoxicity is the most typical non-haematological adverse effect of taxanes. Symptoms are dominated by sensory peripheral neuropathy, the incidence and degree of which depend on the cumulative dose level. The impact of neurotoxicity on the patient´s quality of life is significant, therefore it is necessary to consider the selection of therapy and the patient´s pre-existing risk factors for developing neuropathy and to get acquainted with current management options, including genetic prediction of polyneuropathy. This review article reports on a very common complication of cancer therapy that can be encountered at each internist´s outpatient dispensary.

• MeSH
• antitumorózní látky škodlivé účinky   MeSH
• duloxetinum hydrochlorid terapeutické užití   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• paclitaxel * škodlivé účinky   MeSH
• parestezie etiologie   prevence a kontrola   MeSH
• polyneuropatie * etiologie   prevence a kontrola   terapie   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Taxane and platinum-based chemotherapy regimens are standard treatment for advanced ovarian carcinoma. Expression levels of putative markers of taxane resistance in carcinoma tissues and paired peritoneal samples (n=55) and in 16 samples of ovaries without signs of carcinoma were compared with clinical data and the patients' time to progression. KIF14, PRC1, CIT and ABCC1 genes were significantly overexpressed in carcinomas when compared with normal ovarian tissues, while ABCB1 and CASP9 expression was decreased. Associations of protein expression of the proliferation marker Ki-67 with KIF14, PRC1, ABCB1 and CASP2 were found. Lastly, it was discovered that ABCB1 and CASP2 levels associated with FIGO stage and that the CIT level associated with the time to progression of ovarian carcinoma patients (P<0.0001). In conclusion, ABCB1, CASP2, KIF14, PRC1 and CIT genes seem to associate with surrogate markers of ovarian carcinoma progression and CIT gene associates with therapy outcome.

• MeSH
• ABC transportéry genetika   MeSH
• adenokarcinom diagnóza   farmakoterapie   genetika   MeSH
• antitumorózní látky terapeutické užití   MeSH
• chemorezistence genetika   MeSH
• genetické asociační studie MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• kaspasy genetika   MeSH
• kineziny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory vaječníků diagnóza   farmakoterapie   genetika   MeSH
• onkogenní proteiny genetika   MeSH
• ovarium metabolismus   MeSH
• peritoneum metabolismus   MeSH
• přemostěné cyklické sloučeniny terapeutické užití   MeSH
• progrese nemoci MeSH
• protein-serin-threoninkinasy genetika   MeSH
• proteiny buněčného cyklu genetika   MeSH
• taxoidy terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A limited number of studies are devoted to regulating TRIP6 expression in cancer. Hence, we aimed to unveil the regulation of TRIP6 expression in MCF-7 breast cancer cells (with high TRIP6 expression) and taxane-resistant MCF-7 sublines (manifesting even higher TRIP6 expression). We found that TRIP6 transcription is regulated primarily by the cyclic AMP response element (CRE) in hypomethylated proximal promoters in both taxane-sensitive and taxane-resistant MCF-7 cells. Furthermore, in taxane-resistant MCF-7 sublines, TRIP6 co-amplification with the neighboring ABCB1 gene, as witnessed by fluorescence in situ hybridization (FISH), led to TRIP6 overexpression. Ultimately, we found high TRIP6 mRNA levels in progesterone receptor-positive breast cancer and samples resected from premenopausal women.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• AMP cyklický MeSH
• chemorezistence * genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádory * genetika   MeSH
• P-glykoproteiny * genetika   MeSH
• proteiny s doménou LIM * genetika   MeSH
• responzivní elementy MeSH
• taxoidy MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

BACKGROUND/AIM: Classical taxanes are routinely used in cancer therapy. In this study, mechanisms involved in death induction by the novel fluorine-containing taxane SB-T-12854 were investigated. MATERIALS AND METHODS: We employed breast cancer SK-BR-3, MCF-7 and T47D cell lines to assess activation of individual caspases, changes in the expression of proteins of the Bcl-2 family, and the release of pro-apoptotic factors from mitochondria into the cytosol after SB-T-12854 treatment. RESULTS: Caspase-2, -8, and -9 were activated in SK-BR-3 and MCF-7 cells. Only caspase-8 was activated in T47D cells. Caspase-7 and -6 were activated in all tested cells while caspase-3 was activated only in SK-BR-3 cells. Pro-apoptotic Bad protein seems to be important for cell death induction in all tested cells. Anti-apoptotic Bcl-2 and pro-apoptotic Bim, Bok, Bid and Bik seem to be also associated with cell death induction in some of the tested cells. The mitochondrial apoptotic pathway was significantly activated in association with the release of cytochrome c and Smac from mitochondria, but only in SK-BR-3 cells, not in MCF-7 and T47D cells. CONCLUSION: Cell death induced by SB-T-12854, in the tested breast cancer cells, differs regarding activation of caspases, changes in levels of pro-apoptotic and anti-apoptotic proteins of the Bcl-2 family and activation of the mitochondrial apoptotic pathway.

• MeSH
• apoptóza účinky léků   MeSH
• fluorované uhlovodíky farmakologie   MeSH
• kaspasy metabolismus   MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádorové buňky kultivované MeSH
• nádory prsu farmakoterapie   patologie   MeSH
• proliferace buněk účinky léků   MeSH
• taxoidy farmakologie   MeSH
• western blotting MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: In this study, the effect of novel taxane SB-T-1216 and paclitaxel on sensitive MDA-MB-435 and resistant NCI/ADR-RES human breast cancer cells was compared. MATERIALS AND METHODS: Cell growth and survival were evaluated after 96-hour incubation with tested concentrations of taxanes. The effect on the formation of microtubule bundles was assessed employing fluorescence microscopy and on the cell cycle employing flow cytometric analysis. The activity of caspases was assessed employing commercial colorimetric kits. RESULTS: The IC(50) (concentration resulting in 50% of living cells in comparison with the control) of SB-T-1216 in sensitive cells was 0.6 nM versus 1 nM for paclitaxel. However, the IC(50) of SB-T-1216 in resistant cells was 1.8 nM versus 300 nM for paclitaxel. Both SB-T-1216 and paclitaxel at death-inducing concentrations induced the formation of microtubule bundles in sensitive as well as resistant cells. Cell death induced in sensitive and resistant cells by paclitaxel was associated with the accumulation of cells in the G(2)/M phase. On the contrary, cell death induced by SB-T-1216 took place without the accumulation of cells in the G(2)/M phase but with a decreased number of G(1) cells and the accumulation of hypodiploid cells. Both SB-T-1216 and paclitaxel activated caspase-3, caspase-9, caspase-2 and caspase-8 in sensitive as well as resistant cells. CONCLUSION: Cell death induced by both paclitaxel and novel taxane SB-T-1216 in breast cancer cells is associated with caspase activation and with the formation of interphase microtubule bundles. Novel taxane SB-T-1216, but not paclitaxel, seems to be capable of inducing cell death without the accumulation of cells in the G(2)/M phase.

• MeSH
• antibiotika antitumorózní farmakologie   MeSH
• antitumorózní látky fytogenní farmakologie   MeSH
• apoptóza účinky léků   MeSH
• buněčné dělení účinky léků   MeSH
• chemorezistence MeSH
• doxorubicin farmakologie   MeSH
• fluorescenční mikroskopie MeSH
• G1 fáze účinky léků   MeSH
• G2 fáze účinky léků   MeSH
• kaspasa 2 metabolismus   MeSH
• kaspasa 3 metabolismus   MeSH
• kaspasa 8 metabolismus   MeSH
• kaspasa 9 metabolismus   MeSH
• lidé MeSH
• mikrotubuly účinky léků   MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• paclitaxel farmakologie   MeSH
• proliferace buněk účinky léků   MeSH
• taxoidy farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• srovnávací studie MeSH

• Publikační typ
• abstrakt z konference MeSH

Platinum and taxane chemotherapy is associated with the risk of hypersensitivity reactions (HSRs), which may require switching to less effective treatments. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen. Therefore, we aimed to investigate the current management of HSRs to platinum and/or taxane chemotherapy in patients with gynecologic cancers. We conducted an online cross-sectional survey among gynecological and medical oncologists consisting of 33 questions. A total of 144 respondents completed the survey, and 133 respondents were included in the final analysis. Most participants were gynecologic oncologists (43.6%) and medical oncologists (33.8%), and 77.4% (n = 103) were involved in chemotherapy treatment. More than 73% of participants experienced >5 HSRs to platinum and taxane per year. Premedication and a new attempt with platinum or taxane chemotherapy were used in 84.8% and 92.5% of Grade 1-2 HSRs to platinum and taxane, respectively. In contrast, desensitization was used in 49.4% and 41.8% of Grade 3-4 HSRs to platinum and taxane, respectively. Most participants strongly emphasized the need to standardize the management of platinum and taxane HSRs in gynecologic cancer. Our study showed that HSRs in gynecologic cancer are common, but management is variable and the use of desensitization is low. In addition, the need for guidance on the management of platinum- and taxane-induced HSRs in gynecologic cancer was highlighted.

• Publikační typ
• časopisecké články MeSH

We tested the effect of substituents at the (1) C3 ́, C3 ́N, (2) C10, and (3) C2-meta-benzoate positions of taxane derivatives on their activity against sensitive versus counterpart paclitaxel-resistant breast (MCF-7) and ovarian (SK-OV-3) cancer cells. We found that (1) non-aromatic groups at both C3 ́ and C3 ́N positions, when compared with phenyl groups at the same positions of a taxane derivative, significantly reduced the resistance of ABCB1 expressing MCF-7/PacR and SK-OV-3/PacR cancer cells. This is, at least in the case of the SB-T-1216 series, accompanied by an ineffective decrease of intracellular levels in MCF-7/PacR cells. The low binding affinity of SB-T-1216 in the ABCB1 binding cavity can elucidate these effects. (2) Cyclopropanecarbonyl group at the C10 position, when compared with the H atom, seems to increase the potency and capability of the derivative in overcoming paclitaxel resistance in both models. (3) Derivatives with fluorine and methyl substituents at the C2-meta-benzoate position were variously potent against sensitive and resistant cancer cells. All C2 derivatives were less capable of overcoming acquired resistance to paclitaxel in vitro than non-substituted analogs. Notably, fluorine derivatives SB-T-121205 and 121,206 were more potent against sensitive and resistant SK-OV-3 cells, and derivatives SB-T-121405 and 121,406 were more potent against sensitive and resistant MCF-7 cells. (4) The various structure-activity relationships of SB-T derivatives observed in two cell line models known to express ABCB1 favor their complex interaction not based solely on ABCB1.

• MeSH
• antitumorózní látky farmakologie   chemie   MeSH
• benzoáty farmakologie   chemie   MeSH
• chemorezistence * účinky léků   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   patologie   MeSH
• nádory vaječníků farmakoterapie   patologie   MeSH
• P-glykoproteiny * metabolismus   genetika   MeSH
• paclitaxel farmakologie   MeSH
• taxoidy farmakologie   chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH