Combination chemotherapy by means of two or more drugs is prone to suppressing or discouraging the inception of multidrug resistance, exploiting the fact that diverse drugs act in different points of ...the cellular cycle of amplifying tumor cells. For example, the combination of gemcitabine (GMC) with quercetin (QCT) showed a synergistic effect in inhibiting the migration of pancreatic cancer cells. Consequently, herein GMC and QCT have been loaded within biodegradable nanoparticles (NPs) based on poly(lactic‐co‐glycolic acid), externally decorated with hyaluronic acid (HA; viz., PPHA NPs), which plays a major role in drug targeting to tumors due to its ability to specifically interact with CD44 receptor, that is overexpressed in many tumors. The produced HA‐decorated NPs loaded with GMC and QCT showed an improved cytotoxicity and cellular uptake toward two cell lines of pancreatic ductal adenocarcinoma, namely Mia‐PaCa‐2 and PANC‐1, compared with both the bare drugs and the drugs loaded in NPs which do not expose HA on the surface. HA‐decorated NPs were also able to improve the anti‐inflammatory properties of QCT, therefore leading to a decrease of interleukin cellular levels in both cell lines, preliminarily stimulated with lipopolysaccharides. This result is of special interest also considering the crucial role of interleukins in progression, metastatic processes, and drug resistance of human pancreas cancer cells.
Gemcitabine (GMC) and quercetin (QCT) have been loaded within biodegradable nanoparticles (NPs) based on poly(lactic‐co‐glycolic acid), externally decorated with hyaluronic acid (HA). The produced HA‐decorated NPs loaded with GMC and QCT showed an improved cytotoxicity and cellular uptake toward both Mia‐PaCa‐2 and PANC‐1, compared with both the bare drugs and the drugs loaded in NPs which do not expose HA on the surface. HA‐decorated NPs were also able to improve the anti‐inflammatory properties of QCT, therefore leading to a decrease of interleukin cellular levels in both cell lines, preliminarily stimulated with lipopolysaccharides.
Resveratrol in Cancer Patients: From Bench to Bedside Berretta, Massimiliano; Bignucolo, Alessia; Di Francia, Raffaele ...
International journal of molecular sciences,
04/2020, Letnik:
21, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Resveratrol (3,5,4'-trihydroxystilbene) is a natural phytoalexin that accumulates in several vegetables and fruits like nuts, grapes, apples, red fruits, black olives, capers, red rice as well as red ...wines. Being both an extremely reactive molecule and capable to interact with cytoplasmic and nuclear proteins in human cells, resveratrol has been studied over the years as complementary and alternative medicine (CAM) for the therapy of cancer, metabolic and cardiovascular diseases like myocardial ischemia, myocarditis, cardiac hypertrophy and heart failure. This review will describe the main biological targets, cardiovascular outcomes, physico-chemical and pharmacokinetic properties of resveratrol in preclinical and clinical models implementing its potential use in cancer patients.
Among the most important traditional medicinal fungi,
has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to ...investigate the anti-inflammatory, anticancer and anti-metastatic activities of
extracts in melanoma and triple-negative breast cancer cells.
extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with
extract at different concentrations. Our study demonstrates, for the first time, how
extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly,
extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of
extract for the therapeutic management of melanoma and human triple-negative breast cancer.
Colorectal cancer(CRC) represents one of the most commonly diagnosed cancers worldwide.It is the second leading cause of cancer death in Western Countries.In the last decade the survival of patients ...with metastatic CRC has improved dramatically.Due to the advent of new drugs(irinotecan and oxaliplatin) and target therapies(i.e.,bevacizumab,cetuximab and panitumab),the median overall survival has risen from about 12 mo in the mid nineties to 30 mo recently.Many questions needing of right collocations and more clearness still exist regarding the prognostic factors and the predictive factors of response to therapy.Despite advances in dosing and scheduling of chemotherapy in both adjuvant and advanced settings,and a greater emphasis on early detection,the outlook still remains poor for most patients.Molecular analyses have shown that the natural history of all CRCs is not the same.Individual patients with same stage tumours may have different long term prognosis and response to therapy.In addition,some prognostic variables are likely to be more important than others.Here we review the role of prognostic factors and predictive factors according to the recently published English literature.
Glioblastoma multiforme (GBM) is the most aggressive brain tumor. Current therapeutic strategies are based on the use of Temozolomide (TMZ) and antihuman epidermal growth factor receptor (EGFR) ...drugs, such as Afatinib. However, clinically relevant drug‐resistance events are still present and closely related to a proinflammatory cancer brain microenvironment. The primary aim of this study is the association of Boswellic acid (BA), a molecule derived from Boswellia Serrata, with TMZ and Afatinibin different human GBM cells. We performed cell viability studies evaluating its antioxidant and anti‐inflammatory effects analyzing p65/NF‐κB and Leukotriene B4 expression and production of interleukins and growth factors (IL‐8, IL‐6, vascular endothelial growth factor, CXCL‐12, and MMP‐9). Considering the cardiotoxicity of TMZ and anti‐EGFR drugs, we evaluated the putative cardioprotective effects of BA in adult cardiomyocytes. BA significantly increased the anticancer activities of TMZ and Afatinib. These effects are related to its anti‐inflammatory and antioxidant effects, based on the inhibition of growth factors and proinflammatory interleukins. Notably, BA exerts also cardioprotective effects in combination to both drugs. This study provides evidences of anti‐inflammatory, cardioprotective, and chemo sensitizing effects of BA in glioblastoma cells giving a rationale for new translational studies based on the use of this natural molecule during conventional therapies.
Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because of its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert ...cardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address this issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin and fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from doxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer. H9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or in combination with doxorubicin. Cell viability was evaluated with a modified MTT method. The levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone (4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL-1β and IL-10, tumor necrosis factor-alpha (TNF-α), and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic size of nanoemulsions was around 100 nm. Cell viability enhancement was 35⁻40% higher in cardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with doxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a reduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL-1β, TNF-α and nitric oxide by around 35⁻40% and increased IL-10 production by 25⁻27% versus cells not treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had the best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals described herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress. These results set the stage for studies in preclinical models.
Introduction. Ozone therapy is an effective medical treatment for different diseases like mucositis, psoriasis, acute pain, neurovascular diseases, and cancer. The aim of this study is based on the ...association of different ozone concentration with 5-fluorouracil and cisplatin in human colon cancer cell (HT29 cell line) in order to investigate possible anticancer synergistic effects. Methods. HT29 cells were incubated with ozone at different concentration ranging from 10 up to 50 μg/ml at different incubation time alone or in combination with cisplatin and 5-fluorouracil. Cell viability was performed by using a modified MTT method. Anti-inflammatory studies were conducted incubating HT29 with or without 20, 30, or 50 μg/ml of ozone before exposure to lipopolysaccharides. Results. Ozone alone has a time and concentration dependent cytotoxicity against HT29 cells (IC50 at 24 h: 30 μg/ml). Association of ozone with drugs increases cytotoxicity by 15–20%. Preincubation of ozone at 50 μg/ml decreases IL-8, IL-6, and IL-1β production by 50, 56, and 70%, respectively, compared to untreated cells. Conclusion. These results indicated that ozone could be useful in colon cancer management in combination with 5-fluorouracil and cisplatin with significant inhibition of cytokines having a central role in colon cancer cell survival and chemoresistance.
Cetuximab is a monoclonal antibody to the EGFR that induces antibody-dependent cell cytotoxicity (ADCC) through Fcγ receptors on immune cells. Although SNPs in genes encoding Fcγ receptors are ...functionally relevant to cetuximab-mediated ADCC in colorectal cancer, a direct correlation between in vitro ADCC and clinical response to cetuximab is not defined. We therefore enrolled 96 consecutive metastatic colorectal cancer (mCRC) patients at diagnosis in a study that assessed FcγR status and cetuximab-mediated ADCC. Patients carrying the FcγRIIa H alleles 131H/Hand 131H/R had significantly higher ADCC compared with patients with the 131R/R alleles (P= 0.013). Patients carrying FcγRIIIa genotypes with the V alleles 158V/V and 158V/F displayed higher ADCC compared with patients carrying the 158F/F genotype (P= 0.001). Progression-free survival of patients with an FcγRIIIa 158V allele was significantly longer compared with patients carrying 158F/F (P= 0.05), whereas no significant difference was observed for overall survival. Twenty-eight of 50 mCRC patients with wild-type KRAS received cetuximab. The average ADCC-mediated killing was 30% of assay targets for patients who experienced cetuximab complete or partial response, 21% in patients with stable disease and 9% in patients with progressive disease. To characterize basal natural killer (NK) activity, cytotoxicity was evaluated in 39 of 96 mCRC patients. Patients who responded to first-line treatment had higher NK-cell cytotoxicity. Thus, although limited to this cohort of patients, in vitro cetuximab-mediated ADCC correlated with FcγR polymorphisms and predicted cetuximab responsiveness.
To assess the safety and efficacy of oxaliplatin (OXA) plus dual inhibition of thymidilate synthase during preoperative pelvic radiotherapy (RT) in patients with poor prognosis for rectal carcinoma.
...Sixty-three patients with the following characteristics, a clinical (c) stage T4, cN1-2, or cT3N0 of ≤5 cm from the anal verge and/or with a circumferential resection margin (CRM) of ≤5 mm (by magnetic resonance imaging), received three biweekly courses of chemotherapy with OXA, 100 mg/m2; raltitrexed (RTX), 2.5 mg/m2 on day 1, and 5-fluorouracil (5-FU), 900 mg/m2 (31 patients) or 800 mg/m2 (32 patients); levo-folinic acid (LFA), 250 mg/m2 on day 2, during pelvic RT (45 Gy). Pathologic response was defined as complete pathological response (ypCR), major (tumor regression grade(TRG) 2 to 3, with ypCRM-ve and ypN-ve) or minor or no response (TRG4 to -5, or ypCRM+ve, or ypN+ve). Adjuvant 5-FU/LFA regimen was given in cases of cT4, ypN+ve, or ypCRM+ve.
Overall, neutropenia (40%) and diarrhea (13%) were the most common grade≥3 toxicities, and tolerability was better with a 5-FU dose reduction. No significant difference in pathologic response was seen according 5-FU dosage: overall, a ypCR was obtained in 24 (39%) patients, and a major response in 20 (32%) patients. The 5-year probability of freedom from recurrence was 80% (95% confidence interval, 68%-92%); it was 56% for the minor/no response group, while it was around 90% for both the ypCR and the major response group.
OXA, RTX, and 5-FU/LFA administered during pelvic RT produced promising early and long-term results in rectal carcinoma patients with poor prognosis. The postoperative treatment strategy applied in our study supports the risk-adapted approach in postoperative management.
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