ABSTRACT

Ginsenoside Rg_3, an active component of traditional Chinese medicine(TCM), was used as the substitute for cholesterol as the membrane material to prepare the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin and paclitaxel. The effect of the prepared drug-loading liposomes on triple-negative breast cancer in vitro was evaluated. Liposomes were prepared with the thin film hydration method, and the preparation process was optimized by single factor experiments. The physicochemical properties(e.g., particle size, Zeta potential, and stability) of the liposomes were characterized. The release behaviors of drugs in different media(pH 5.0 and pH 7.4) were evaluated. The antitumor activities of the liposomes were determined by CCK-8 on MDA-MB-231 and 4T1 cells. The cell scratch test was carried out to evaluate the effect of the liposomes on the migration of MDA-MB-231 and 4T1 cells. Further, the targeting ability of liposomes and the mechanism of lysosome escape were investigated. Finally, H9c2 cells were used to evaluate the potential cardiotoxicity of the preparation. The liposomes prepared were spheroid, with uniform particle size distribution, the ave-rage particle size of(107.81±0.01) nm, and the Zeta potential of(2.78±0.66) mV. The encapsulation efficiency of dihydroartemisinin and paclitaxel was 57.76%±1.38% and 99.66%±0.07%, respectively, and the total drug loading was 4.46%±0.71%. The accumulated release of dihydroartemisinin and paclitaxel from the liposomes at pH 5.0 was better than that at pH 7.4, and the liposomes could be stored at low temperature for seven days with good stability. Twenty-four hours after administration, the inhibition rates of the ginsenoside Rg_3-based liposomes loaded with dihydroartemisinin(70 μmol·L~(-1)) and paclitaxel on MDA-MB-231 and 4T1 cells were higher than those of the positive control(adriamycin) and free drugs(P<0.01).<0.05).<0.05),

PMID:37474984 | DOI:10.19540/j.cnki.cjcmm.20230410.301

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PubMed articles on: Cardio-Oncology

Cisplatin-based combination therapy for cancer

J Cancer Res Ther. 2023 Jul-Sep;19(3):530-536. doi: 10.4103/jcrt.jcrt_792_22.

ABSTRACT

Cisplatin, that is, cis-diamminedichloroplatinum is a coordinate compound that is mainly preferred as prior treatment against several solid tumors and malignancies like ovaries, head and neck, testicular, and lung cancers because of its anticancer activity. Cisplatin binds at the N7 position of purine and forms adducts, leading to altered activity of DNA that triggers apoptosis. DNA damage is followed by several signaling pathways like induced oxidative stress, upregulated p53, mitogen-activated protein kinase (MAPK), and Jun N-terminal kinases (JNK) or Akt pathways along with induced apoptosis. Additionally, cisplatin treatment comes with few disadvantages such as toxic effects, that is, hepatotoxicity, cardiotoxicity, neurotoxicity, etc., and drug resistance. Furthermore, to overcome cisplatin resistance and toxicological effects, combination drug therapy has been considered. The aim of the review is to focus on the molecular mechanism of action of cisplatin and combination drug therapy to reduce the side effects in cancer therapy.

PMID:37470570 | DOI:10.4103/jcrt.jcrt_792_22

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PubMed articles on: Cardio-Oncology

Mediators of Black-White inequities in cardiovascular mortality among survivors of 18 cancers in the USA

Int J Epidemiol. 2023 Jul 20:dyad097. doi: 10.1093/ije/dyad097. Online ahead of print.

ABSTRACT

BACKGROUND: This study aims to quantify Black-White inequities in cardiovascular disease (CVD) mortality among US survivors of 18 adult-onset cancers and the extent to which these inequities are explained by differences in socio-economic and clinical factors.

METHODS: Survivors of cancers diagnosed at ages 20-64 years during 2007-16 were identified from 17 Surveillance, Epidemiology and End Results registries. Associations between race and CVD mortality were examined using proportional hazards models. Mediation analyses were performed to quantify the contributions of potential mediators, including socio-economic [health insurance, neighbourhood socio-economic status (nSES), rurality] and clinical (stage, surgery, chemotherapy, radiotherapy) factors.

RESULTS: Among 904 995 survivors, 10 701 CVD deaths occurred (median follow-up, 43 months). Black survivors were more likely than White survivors to die from CVD for all 18 cancers with hazard ratios ranging from 1.30 (95% CI = 1.15-1.47) for lung cancer to 4.04 for brain cancer (95% CI = 2.79-5.83). The total percentage mediations (indirect effects) ranged from 24.8% for brain (95% CI=-5.2-59.6%) to 99.8% for lung (95% CI = 61.0-167%) cancers. Neighbourhood SES was identified as the strongest mediator for 14 cancers with percentage mediations varying from 25.0% for kidney cancer (95% CI = 14.1-36.3%) to 63.5% for lung cancer (95% CI = 36.5-108.7%). Insurance ranked second for 12 cancers with percentage mediations ranging from 12.3% for leukaemia (95% CI = 0.7-46.7%) to 31.3% for thyroid cancer (95% CI = 10.4-82.7%).

CONCLUSIONS: Insurance and nSES explained substantial proportions of the excess CVD mortality among Black survivors. Mitigating the effects of unequal access to care and differing opportunities for healthy living among neighbourhoods could substantially reduce racial inequities in CVD mortality among cancer survivors.

PMID:37471575 | DOI:10.1093/ije/dyad097

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PubMed articles on: Cardio-Oncology

Ferroptosis-induced Cardiotoxicity and Antitumor Drugs

Curr Med Chem. 2023 Jul 19. doi: 10.2174/0929867331666230719124453. Online ahead of print.

ABSTRACT

The induction of regulated cell death ferroptosis in tumors is emerging as an intriguing strategy for cancer treatment. Numerous antitumor drugs (e.g., doxorubicin, etoposide, tyrosine kinase inhibitors, trastuzumab, arsenic trioxide, 5-fluorouracil) induce ferroptosis. Although this mechanism of action is interesting for fighting tumors, the clinical use of drugs that induce ferroptosis is hampered by cardiotoxicity. Besides in cancer cells, ferroptosis induced by chemotherapeutics can occur in cardiomyocytes, and this feature represents an important drawback of antitumor therapy. This inconvenience has been tackled by developing less or no cardiotoxic antitumor drugs or by discovering cardioprotective agents (e.g., berberine, propofol, fisetin, salidroside, melatonin, epigallocatechin-3gallate, resveratrol) to use in combination with conventional chemotherapeutics. This review briefly summarizes the molecular mechanisms of Fer and describes the Fer-dependent mechanisms responsible for cardiac toxicity developed by cancer-suffering patients following the administration of some chemotherapeutics. Additionally, the pharmacological strategies very recently proposed for potentially preventing this inconvenience are considered.

PMID:37469161 | DOI:10.2174/0929867331666230719124453

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PubMed articles on: Cardio-Oncology

Unresectable stage III non-small cell lung cancer: could durvalumab be safe and effective in real-life clinical scenarios? Results of a single-center experience

Front Oncol. 2023 Jul 4;13:1208204. doi: 10.3389/fonc.2023.1208204. eCollection 2023.

ABSTRACT

INTRODUCTION: The standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by consolidation durvalumab as shown in the PACIFIC trial. The purpose of this study is to evaluate clinical outcomes and toxicities regarding the use of durvalumab in a real clinical scenario.

METHODS: A single-center retrospective study was conducted on patients with a diagnosis of unresectable stage III NSCLC who underwent radical CRT followed or not by durvalumab. Tumor response after CRT, pattern of relapse, overall survival (OS) and progression-free survival (PFS), and toxicity profile were investigated.

RESULTS: Eighty-five patients met the inclusion criteria. The median age was 67 years (range 45-82 years). Fifty-two patients (61.2%) started sequential therapy with durvalumab. The main reason for excluding patients from the durvalumab treatment was the expression of PD-L1 < 1%. Only two patients presented a grade 4 or 5 pneumonitis. A median follow-up (FU) of 20 months has been reached. Forty-five patients (52.9%) had disease progression, and 21 (24.7%) had a distant progression. The addition of maintenance immunotherapy confirmed a clinical benefit in terms of OS and PFS. Two-year OS and PFS were respectively 69.4% and 54.4% in the durvalumab group and 47.9% and 24.2% in the no-durvalumab group (p = 0.015, p = 0.007).

CONCLUSION: In this real-world study, patients treated with CRT plus durvalumab showed clinical outcomes and toxicities similar to the PACIFIC results. Maintenance immunotherapy after CRT has been shown to be safe and has increased the survival of patients in clinical practice.

PMID:37469420 | PMC:PMC10352832 | DOI:10.3389/fonc.2023.1208204

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PubMed articles on: Cardio-Oncology

Nuclear translocation of mitochondrial dehydrogenases as an adaptive cardioprotective mechanism

Nat Commun. 2023 Jul 19;14(1):4360. doi: 10.1038/s41467-023-40084-5.