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Metabolism: Clinical and Experimental Sep 2022Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents,... (Review)
Review
Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents, but in fact, the specific modulation is not completely elucidated. Thus, this systematic review aims to provide an integrative perspective of the molecular mechanisms underlying the toxicity of anticancer agents on heart muscle while using a high-throughput technology, mass spectrometry (MS)-based proteomics. A literature search using PubMed database led to the selection of 27 studies, of which 13 reported results exclusively on animal models, 13 on cardiomyocyte-derived cell lines and only one included both animal and a cardiomyocyte line. The reported anticancer agents were the proteasome inhibitor carfilzomib, the anthracyclines daunorubicin, doxorubicin, epirubicin and idarubicin, the antimicrotubule agent docetaxel, the alkylating agent melphalan, the anthracenedione mitoxantrone, the tyrosine kinase inhibitors (TKIs) erlotinib, lapatinib, sorafenib and sunitinib, and the monoclonal antibody trastuzumab. Regarding the MS-based proteomic approaches, electrophoretic separation using two-dimensional (2D) gels coupled with tandem MS (MS/MS) and liquid chromatography-MS/MS (LC-MS/MS) were the most common. Overall, the studies highlighted 1826 differentially expressed proteins across 116 biological processes. Most of them were grouped in larger processes and critically analyzed in the present review. The selection of studies using proteomics on heart muscle allowed to obtain information about the anticancer therapy-induced modulation of numerous proteins in this tissue and to establish connections that have been disregarded in other studies. This systematic review provides interesting points for a comprehensive understanding of the cellular cardiotoxicity mechanisms of different anticancer drugs.
Topics: Animals; Antineoplastic Agents; Cardiotoxicity; Chromatography, Liquid; Proteomics; Tandem Mass Spectrometry
PubMed: 35809654
DOI: 10.1016/j.metabol.2022.155250 -
Frontiers in Oncology 2022Interstitial pneumonitis (IP), a potentially fatal complication of non-Hodgkin Lymphoma (NHL) patients received CHOP (cyclophosphamide and doxorubicin and vincristine...
OBJECTIVES
Interstitial pneumonitis (IP), a potentially fatal complication of non-Hodgkin Lymphoma (NHL) patients received CHOP (cyclophosphamide and doxorubicin and vincristine and prednisone)-like chemotherapy, negatively affected patients' clinical outcome and quality of life. We aimed to explore patient-related, disease-related and drug-related risk factors associated with IP and gain a better understanding of the incidence in NHL patients.
METHODS
Databases, including PubMed, Ovid, China National Knowledge Internet (CNKI), and Wanfang Database from inception to January 20, 2022, were searched to identify studies evaluating the risk factors and incidence of IP. The included studies were assessed by Newcastle-Ottawa Quality Scale and above 7 points was considered high quality. The statistical analysis of risk factors was assessed by RevMan software (version 5.3) and incidence of IP was calculated by R software (version 4.1.2). Fixed-or random-effects models were applied to estimated the relative risks (RRs) and 95% confidence interval (Cl).
RESULTS
A total of 12 studies comprised of 3423 NHL patients were included in the analysis. Among the 3 available patient-related risk factors, 6 disease-related risk factors and 3 drug-related risk factors, it was found that only drug-related risk factors were significantly associated with IP development: pegylated liposomes doxorubicin (PLD) replacement (RR = 3.25, 95% CI = 1.69-6.27, 64%), rituximab (RTX) addition (RR = 4.24, 95% CI = 2.58-6.96, 0) and granulocyte colony stimulating factor (G-CSF) administration (RR = 5.80, 95% CI = 3.05-11.05, 0). The pooled incidence of CHOP, R-CHOP, and R-CDOP regimen was 1.0% (95% CI 0.00-0.01, = 8%), 7.0% (95% CI 0.05-0.09, = 64%) and 22.0% (95% CI 0.13-0.32, = 87%) respectively.
CONCLUSION
PLD replacement, RTX addition and G-CSF administration were significant risk factors of IP for NHL patients received the CHOP-like chemotherapy. Clinicians should focus on these patients to detect and treat the IP development timely, which might bring benefit in patients' survival.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42022309884.
PubMed: 35720002
DOI: 10.3389/fonc.2022.880144 -
Frontiers in Oncology 2022Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm and is characterized as the most common subtype of non-Hodgkin lymphoma (NHL). Despite 60-70% of all...
BACKGROUND
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous neoplasm and is characterized as the most common subtype of non-Hodgkin lymphoma (NHL). Despite 60-70% of all patients being cured with R-CHOP therapeutic regimen (Cyclophosphamide, doxorubicin, vincristine, and prednisone, combined with rituximab), remaining patients display aggressive disease. Therefore, there is an urgent need to develop novel diagnostic, prognostic, and predictive biomarkers. Recently, exosomal miRNAs have been approved as novel biomarkers in DLBCL due to their potential involvement in lymphomagenesis.
MATERIAL AND METHODS
We conducted an investigation on the potential role of exosomal miRNAs as diagnostic, prognostic, and predictive biomarkers in DLBCL in the PubMed, Scopus, and Web of Science search engines. We searched by using a combination of keywords, such as diffuse large B-cell lymphoma, DLBCL, miRNA, microRNA, miR, exosome, exosomes, exosomal, extracellular vesicles, EVs, and secretome. Then, search results were narrowed based on specific inclusion and exclusion criteria.
RESULTS
Twelve articles were eligible for our systematic reviews. Among them, nine discussed diagnostic biomarkers, three considered prognostic significance, four evaluated therapeutic efficacy, two studies were conducted , and three assessed molecular pathways associated with these exosomal miRNAs in DLBCL.
DISCUSSION
According to our systematic review, exosomal miRNAs are not only useful for diagnosis and prognosis in DLBCL but are also promising therapeutic tools and predictors of response to therapy. Although promising results so far, more research is required to develop innovative biomarkers.
PubMed: 35719983
DOI: 10.3389/fonc.2022.904637 -
Journal of Oncology 2022This study aimed to review the potential chemoprotective effects of curcumin against the doxorubicin-induced cardiotoxicity. (Review)
Review
OBJECTIVE
This study aimed to review the potential chemoprotective effects of curcumin against the doxorubicin-induced cardiotoxicity.
METHODS
According to the PRISMA guideline, a comprehensive systematic search was performed in different electronic databases (Web of Science, PubMed, and Scopus) up to July 2021. One hundred and sixty-four studies were screened in accordance with a predefined set of inclusion and exclusion criteria. Eighteen eligible articles were finally included in the current systematic review.
RESULTS
According to the in vitro and in vivo findings, it was found that doxorubicin administration leads to decreased cell survival, increased mortality, decreased bodyweight, heart weight, and heart to the bodyweight ratio compared to the control groups. However, curcumin cotreatment demonstrated an opposite pattern in comparison with the doxorubicin-treated groups alone. Other findings showed that doxorubicin significantly induces biochemical changes in the cardiac cells/tissue. Furthermore, the histological changes on the cardiac tissue were observed following doxorubicin treatment. Nevertheless, for most of the cases, these biochemical and histological changes mediated by doxorubicin were reversed near to control groups following curcumin coadministration.
CONCLUSION
It can be mentioned that coadministration of curcumin alleviates the doxorubicin-induced cardiotoxicity. Curcumin exerts these cardioprotective effects through different mechanisms of antioxidant, antiapoptosis, and anti-inflammatory. Since the finding presented in this systematic review are based on in vitro and in vivo studies, suggesting the use of curcumin in cancer patients as a cardioprotector agent against cardiotoxicity mediated by doxorubicin requires further clinical studies.
PubMed: 35237323
DOI: 10.1155/2022/7277562 -
Translational Cancer Research May 2021With the advent of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) treatment has become considered the appropriate...
BACKGROUND
With the advent of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) treatment has become considered the appropriate chemotherapy treatment for aggressive or advanced-stage indolent B-cell non-Hodgkins lymphoma (NHL). In recent years, RCHOP-14 seems to have achieved better outcomes in patients with aggressive or advanced-stage indolent B-cell NHL than RCHOP-21.
METHODS
To verify the befitting chemotherapy regimens for patients with B-cell NHL, we searched the electronic databases for relevant English-language literature published in January 2020. The primary outcomes were complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Six eligible Phase II and III randomized controlled clinical trials (RCTs) and two high-quality observational comparative studies (OCSs) were extracted, with 5,565 patients with B-cell NHL involved in the evaluation.
RESULTS
The analysis demonstrated no significant difference in RCHOP-14 and RCHOP-21 CR rates [odds ratio (OR) =0.98, 95% CI: 0.77-1.24, P=0.85]. Compared with RCHOP-21, the merged hazard ratio (HR) after treatment with RCHOP-14 for PFS and OS was 0.94 (95% CI: 0.84-1.06, P=0.32) and 0.91 (95% CI: 0.83-1.01, P=0.08), respectively. A subgroup analysis based on the international prognostic index (IPI) score showed that both chemotherapy regimens were applicable in B-cell NHL patients with different prognoses. The frequency of toxic side-effects was similar between schemes.
CONCLUSIONS
The data presented suggest that the efficacy and safety of both regimens are comparable and that RCHOP-14 remains a viable plan in patients with B-cell NHL who prefer a shorter therapy course.
PubMed: 35116526
DOI: 10.21037/tcr-20-3123 -
Annals of Translational Medicine Dec 2021This study sought to evaluate the differences between trabectedin and doxorubicin in the treatment of soft-tissue sarcoma (STS).
BACKGROUND
This study sought to evaluate the differences between trabectedin and doxorubicin in the treatment of soft-tissue sarcoma (STS).
METHODS
Multiple databases, including PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure, were searched to retrieve relevant articles. Ultimately, the full text of 10 studies involving the use of trabectedin and doxorubicin in STS were reviewed. Review Manager 5.2 was used to evaluate the heterogeneity of the results of the selected articles. Forest plot, bias, and sensitivity analyses were carried out on the included articles.
RESULTS
Ten papers that met the criteria were included in this analysis. STS patients receiving trabectedin had longer progression-free survival than those receiving doxorubicin [overall mean difference (MD) =1.36, 95% confidence interval (CI): 1.04, 1.68, I=6%, fixed-effects model]. The experimental group also had a longer overall survival period than the control group (MD =3.92, 95% CI: 0.23, 7.60, P=0.04 and I=83%, random-effects model), and the experimental group had a better disease control rate than the control group (relative risk =1.2, P=0.03 and I=45%, fixed-effects model). From the publication bias analysis and sensitivity analysis, we can guarantee the results are robust and unbiased.
DISCUSSION
Our research showed that STS patients who received trabectedin had better clinical effects and a longer survival time than those who received doxorubicin.
PubMed: 35071458
DOI: 10.21037/atm-21-6033 -
Cancers Dec 2021Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse... (Review)
Review
Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.
Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche "Mario Negri", conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.
PubMed: 35008222
DOI: 10.3390/cancers14010061 -
Frontiers in Oncology 2021Stress granule (SG) formation is a well-known cellular mechanism for minimizing stress-related damage and increasing cell survival. In addition to playing a critical... (Review)
Review
Stress granule (SG) formation is a well-known cellular mechanism for minimizing stress-related damage and increasing cell survival. In addition to playing a critical role in the stress response, SGs have emerged as critical mediators in human health. It seems logical that SGs play a key role in cancer cell formation, development, and metastasis. Recent studies have shown that many SG components contribute to the anti-cancer medications' responses through tumor-associated signaling pathways and other mechanisms. SG proteins are known for their involvement in the translation process, control of mRNA stability, and capacity to function in both the cytoplasm and nucleus. The current systematic review aimed to include all research on the impact of SGs on the mechanism of action of anti-cancer medications and was conducted using a six-stage methodological framework and the PRISMA guideline. Prior to October 2021, a systematic search of seven databases for eligible articles was performed. Following the review of the publications, the collected data were subjected to quantitative and qualitative analysis. Notably, Bortezomib, Sorafenib, Oxaliplatin, 5-fluorouracil, Cisplatin, and Doxorubicin accounted for the majority of the medications examined in the studies. Overall, this systematic scoping review attempts to demonstrate and give a complete overview of the function of SGs in the mechanism of action of anti-cancer medications by evaluating all research.
PubMed: 35004322
DOI: 10.3389/fonc.2021.797549 -
Blood Cancer Journal Jan 2022Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We... (Meta-Analysis)
Meta-Analysis
Front-line treatment for follicular lymphoma has evolved with the introduction of maintenance therapy, bendamustine (Benda), obinutuzumab (G), and lenalidomide (Len). We conducted a random-effects Bayesian network meta-analysis (NMA) of phase 3 randomized controlled trials (RCTs) to identify the regimens with superior efficacy. Progression-free survival (PFS) was compared between 11 modern regimens with different immunochemotherapy and maintenance strategies. G-Benda-G resulted in with the best PFS, with an HR of 0.41 compared to R-Benda, a surface under the cumulative ranking curve (SUCRA) of 0.97, a probability of being the best treatment (PbBT) of 72%, and a posterior ranking distribution (PoRa) of 1 (95% BCI 1-3). This was followed by R-Benda-R4 (HR = 0.49, PbBT = 25%, PoRa = 2) and R-Benda-R (HR = 0.60, PbBT = 3%, PoRa = 3). R-CHOP-R (HR = 0.96) and R-Len-R (HR = 0.97) had similar efficacy to R-Benda. Bendamustine was a better chemotherapy backbone than CHOP either with maintenance (R-Benda-R vs R-CHOP-R, HR = 0.62; G-Benda-G vs G-CHOP-G, HR = 0.55) or without maintenance therapy (R-Benda vs R-CHOP, HR = 0.68). Rituximab maintenance improved PFS following R-CHOP (R-CHOP-R vs R-CHOP, HR = 0.65) or R-Benda (R-Benda-R vs R-Benda, HR = 0.60; R-Benda-R4 vs R-Benda, HR = 0.49). In the absence of multi-arm RCTs that include all common regimens, this NMA provides an important and useful guide to inform treatment decisions.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Cyclophosphamide; Doxorubicin; Humans; Immunotherapy; Lymphoma, Follicular; Maintenance Chemotherapy; Prednisone; Progression-Free Survival; Randomized Controlled Trials as Topic; Rituximab; Treatment Outcome; Vincristine
PubMed: 34987165
DOI: 10.1038/s41408-021-00598-x -
Frontiers in Oncology 2021Neoadjuvant chemotherapy has been accepted as an effective curative treatment for muscle-invasive bladder cancer patients and has resulted in better survival outcomes...
Curative Effect and Survival Assessment Comparing Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin and Cisplatin as Neoadjuvant Therapy for Bladder Cancer: A Systematic Review and Meta-Analysis.
BACKGROUND
Neoadjuvant chemotherapy has been accepted as an effective curative treatment for muscle-invasive bladder cancer patients and has resulted in better survival outcomes than radical cystectomy or a cisplatin-based regimen. In the present study, we aimed to compare the two most commonly used cisplatin-based neoadjuvant chemotherapies, gemcitabine plus cisplatin and methotrexate plus vinblastine plus doxorubicin plus cisplatin, by summarizing and analyzing clinical data and outcomes of published research.
METHODS
We searched for qualified studies that compared these two types of neoadjuvant chemotherapy, including 4 randomized controlled trials and 14 retrospective studies. Data and information on pathological responses and long-term survival studies were extracted and analyzed separately.
RESULTS
A total of 18 studies with 3116 patients were selected from 1188 studies, which contained data on pathological complete response, pathological partial response, and overall survival. In contrast to the results of previous studies, there was no significant difference in pathological complete response (odds ratio, 0.97; 95% confidence interval, 0.81-1.15), pathological partial response (odds ratio, 0.85; 95% confidence interval, 0.72-1.14), and overall survival (hazard ratio, 0.99; 95% confidence interval, 0.83-1.17) between GC and MVAC in this meta-analysis.
CONCLUSION
No significant differences were observed between GC and MVAC in the muscle-invasive bladder cancer treatment due to the similar curative effect and parallel long survival outcomes due to the similar curative effect and parallel long survival outcomes. The priority selection of GC or MVAC in the clinic should be guided by further investigation, and the clinical standard strategy still counts on the results of more randomized controlled trials in the future.
PubMed: 34900663
DOI: 10.3389/fonc.2021.678896