Fluoropyrimidine-associated cardiotoxicity: revisited

Saif, Muhammad Wasif; Shah, Mudasir Ahmad; Shah, Anuj R.

doi:10.1517/14740330902733961

Cited by 231 publications

(200 citation statements)

References 79 publications

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“…U pacjentów leczonych analogami pirimidyn często obserwuje się dławicę piersiową, nieprawidłowości w EKG związane z niedokrwieniem, zaburzenia rytmu serca i zawał serca, nawet u chorych z prawidłowymi tętnicami wieńcowymi [120,287]. Ryzyko zwiększa się znacznie u pacjentów z CAD w wywiadach, a ponieważ profilaktyczne podawanie azotanów i/lub antagonistów wapnia może nie być skuteczne, należy odradzać stosowanie analogów pirimidyn u tych osób [288][289][290].…”

Section: Analogi Pirimidynunclassified

“…Podczas gdy pierwotna prewencja kardiotoksyczności jest wciąż w fazie badań naukowych, prewencja wtórna została już ujęta w wytycznych dotyczących praktyki klinicznej mimo istotnych niewyjaśnionych kwestii [287]. Uzyskano pewne dowody, że dobra kontrola częstych czynników ryzyka CV w momencie rozpoczynania chemioterapii ogranicza niekorzystne konsekwencje leczenia onkologicznego w układzie CV u pacjentów z wywiadami nadciśnienia tętniczego, cukrzycy lub HF [83,117].…”

Section: Perspektywy I Kierunki Przyszłych Badań Naukowychunclassified

See 1 more Smart Citation

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

Zamorano¹,

Lancellotti²,

Muñoz³

et al. 2016

Kardiol Pol

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Section: Analogi Pirimidynunclassified

Section: Perspektywy I Kierunki Przyszłych Badań Naukowychunclassified

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

Zamorano¹,

Lancellotti²,

Muñoz³

et al. 2016

Kardiol Pol

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“…Raltitrexed is another chemotherapeutic agent and a folate antimetabolite, which specifically inhibits TS activity. It has been approved for patients with advanced colorectal cancer in Europe and China (10,17,18) and unlike 5-FU it rarely induces fluoropyrimidine-associated cardiotoxicity (19,20). For cancer patients with f luoropyrimidine-induced cardiotoxicity or a history of cardiac disease, raltitrexed may be a suitable alternative to 5-FU (18).…”

mentioning

confidence: 99%

Raltitrexed induces mitochondrial-mediated apoptosis in SGC7901 human gastric cancer cells

Xue

Chen

Qin

et al. 2014

Molecular Medicine Reports

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Abstract. Raltitrexed is a specific inhibitor of thymidylate synthase (TS), which has been considered as a potential chemotherapeutic agent for the treatment of advanced gastric cancer. In the present study, the apoptosis mechanisms of raltitrexed in SGC7901 human gastric cancer cells were investigated. The cytotoxic activity of raltitrexed on SGC7901 cells was determined by cell counting kit-8 (CCK-8) assay. The CCK-8 assay indicated that raltitrexed inhibits SGC7901 cell growth in a dose-and time-dependent manner. The morphological changes were observed by fluorescent microscopy, and characteristic morphological changes, including nuclear shrinkage and apoptotic bodies, were observed following Hoechst 33258 staining. The effects on apoptosis, cell cycle, mitochondrial transmembrane potential and reactive oxygen species (ROS) were measured by flow cytometry. The analysis revealed that raltitrexed exerted a growth inhibitory effect by inducing time-dependent apoptosis and cell-cycle arrest at the G 0 /G 1 phase. In addition, a compromised mitochondrial membrane potential and overproduction of ROS demonstrated the involvement of the mitochondrial signaling pathway. Raltitrexed-induced caspase-3-dependent apoptosis was identified using a caspase-3 activity assay and pretreatment with the caspase-3 inhibitor, Ac-DEVD-CHO (sequence, Ac-Asp-Glu-Val-Asp-CHO). The activity of caspase-3 was analyzed with a spectrometer. The protein expression levels of Bax, Bcl-2, cytochrome c, cleaved caspase-3 and TS were examined by western blot and the mRNA expression level of TS was detected by quantitative polymerase chain reaction. The analysis revealed that the protein levels of Bax, cytochrome c and cleaved caspase-3 were significantly increased by raltitrexed, while Bcl-2 expression levels were reduced. Furthermore, raltitrexed increased the expression of the TS protein and mRNA in a time-dependent manner. These results indicate that raltitrexed induces the apoptosis of SGC7901 cells through the caspase-3-dependent mitochondrial signaling pathway and upregulates the expression of the TS protein and mRNA.

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“…It should be remembered that additional ECG abnormalities and arrhythmias may be observed [12]. Our study presents new findings that QT prolongation is possible, and changes in E'sept as well as in S'IVS and S'lat may occur.…”

Section: Discussionmentioning

confidence: 52%

Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study

et al. 2017

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A b s t r a c tBackground: Colorectal cancer (CRC) is the second most common cancer in women and the third in men in Poland. The role of chemotherapy (CTX) depends on the stage of CRC: adjuvant CTX is a standard treatment in stage III and should also be considered in stage II with risk factors. Aim:The aim of the paper was to assess the cardiovascular consequences of CTX in CRC enrolled to the ONCOECHO multicentre study (2012)(2013)(2014). To identify potential cardiotoxicity, we focused on myocardial function, heart rhythm and conduction disorders, and adverse cardiovascular events.Methods: Twenty-five CRC patients (12 women, mean age 61.3 years), all receiving six-month adjuvant CTX were included. Thirteen patients received 5-fluorouracil (5FU)-based CTX, and 12 patients received a capecitabine-based scheme. Subjects were assessed at baseline and followed-up three, six, and 12 months after the onset of treatment. In this analysis we focused on conduction abnormalities, systolic and diastolic function of the left ventricle (LV), and cardiovascular events. Results:In 12-month follow-up a decrease of selected tissue Doppler parameters (e.g. S'IVS, S'lat, and E'sept) was observed, and it was significant. LV structural parameters and ejection fraction (EF) remained unaffected. Changes in myocardial performance were not influenced by CTX regimen or treatment with beta-blockers or angiotensin-converting enzyme inhibitors. CTX did not affect LV structural parameters, EF, or conduction system, nor was it associated with cardiovascular events during the 12-month follow-up.Conclusions: CTX in CRC patients does not affect LV structural parameters and EF. It may, however, trigger subtle changes in myocardial performance detectable by tissue Doppler echocardiography after 12 months. Moreover, it causes a transient increase of QT, which resolves after CTX cessation.

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Fluoropyrimidine-associated cardiotoxicity: revisited

Cited by 231 publications

References 79 publications

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines

Raltitrexed induces mitochondrial-mediated apoptosis in SGC7901 human gastric cancer cells

Tissue Doppler echocardiography detects subclinical left ventricular dysfunction in patients undergoing chemotherapy for colon cancer: insights from ONCOECHO multicentre study

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