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Annals of Palliative Medicine Dec 2021Dose-limiting neurotoxicity is the major side effect caused by oxaliplatin treatment. Optimization of oxaliplatin-containing chemotherapeutic regimens may potentially...
BACKGROUND
Dose-limiting neurotoxicity is the major side effect caused by oxaliplatin treatment. Optimization of oxaliplatin-containing chemotherapeutic regimens may potentially benefit advanced gastric cancer (AGC) patients. We tried to reduce the dose of oxaliplatin and add a drug to compensate for the efficacy. This cohort study evaluated the efficacy and side effects of low-dose oxaliplatin combined with pegylated liposomal doxorubicin and S-1 (D-SOX) as first-line treatment for AGC.
METHODS
64 AGC patients treated in our hospital between January 2015 and December 2018 were included in this study. Among them, 29 cases received standard S-1 and oxaliplatin (SOX) regimen, and 35 cases received D-SOX. Progression-free survival (PFS), overall survival (OS), response rate (RR), and safety were analyzed.
DISCUSSION
The median PFS was 7.0 months [95% confidence interval (CI): 5.77 to 8.23 months] in the SOX group and 9.3 months (95% CI: 8.145 to 10.45 months) in the D-SOX group (P=0.021). The median OS was 12.5 months (95% CI: 7.00 to 17.97 months) in the SOX group and 18.7 months (95% CI: 14.485 to 22.9 months) in the D-SOX group (P=0.027). The incidence of treatment-related grade III-IV adverse events (AEs) was less than 10%. The RRs to these 2 regimens were similar (P=0.609). The incidence of neurotoxicity was significantly reduced in the D-SOX group (62.8% vs. 82.7%).
CONCLUSIONS
Low-dose oxaliplatin combined with S-1 and pegylated liposomal doxorubicin (PLD) regimen improved OS and PFS, while exhibiting better toxicity profile as compared with standard SOX regimen for AGC.
Topics: Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Doxorubicin; Humans; Oxaliplatin; Polyethylene Glycols; Stomach Neoplasms
PubMed: 35016420
DOI: 10.21037/apm-21-3584 -
International Journal of Biological... Dec 2023Despite many efforts, breast cancer remains one of the deadliest cancers and its treatment faces challenges related to cancer drug side effects and metastasis. Combining...
Despite many efforts, breast cancer remains one of the deadliest cancers and its treatment faces challenges related to cancer drug side effects and metastasis. Combining 3D printing and nanocarriers has created new opportunities in cancer treatment. In this work, 3D-printed gelatin-alginate nanocomposites containing doxorubicin-loaded niosomes (Nio-DOX@GT-AL) were recruited as an advanced potential pH-sensitive drug delivery system. Morphology, degradation, drug release, flow cytometry, cell cytotoxicity, cell migration, caspase activity, and gene expression of nanocomposites and controls (Nio-DOX and Free-DOX) were evaluated. Results show that the obtained niosome has a spherical shape and size of 60-80 nm. Sustained drug release and biodegradability were presented by Nio-DOX@GT-AL and Nio-DOX. Cytotoxicity analysis revealed that the engineered Nio-DOX@GT-AL scaffold had 90 % cytotoxicity against breast cancer cells (MCF-7), whereas exhibited <5 % cytotoxicity against the non-tumor breast cell line (MCF-10A), which was significantly more than the antitumor effect of the control samples. Scratch-assay as an indicator cell migration demonstrated a reduction of almost 60 % of the covered surface. Gene expression could provide an explanation for the antitumor effect of engineered nanocarriers, which significantly reduced metastasis-promoting genes (Bcl2, MMP-2, and MMP-9), and significantly enhanced the expression and activity of genes that promote apoptosis (CASP-3, CASP-8, and CASP-9). Also, considerable inhibition of metastasis-associated genes (Bax and p53) was observed. Moreover, flow-cytometry data demonstrated that Nio-DOX@GT-AL decreased necrosis and enhanced apoptosis drastically. The findings of this research can confirm that employing 3D-printing and niosomal formulation can be an effective strategy in designing novel nanocarriers for efficient drug delivery applications.
Topics: Humans; Female; Liposomes; Gelatin; Alginates; Doxorubicin; Drug Delivery Systems; Breast Neoplasms; Hydrogen-Ion Concentration; MCF-7 Cells; Drug Carriers; Nanoparticles; Drug Liberation
PubMed: 37689301
DOI: 10.1016/j.ijbiomac.2023.126808 -
International Journal of Molecular... Aug 2022To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into...
To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS-GPLGVRGDG-DOX&DOX micelles, where TPGS is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS-GPLGVRG-DOX&DOX micelles and TPGS-DOX&DOX micelles. During in vivo studies, TPGS-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.
Topics: Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Delivery Systems; Micelles; Peptides; Polyethylene Glycols; Polymers
PubMed: 36077102
DOI: 10.3390/ijms23179698 -
Journal of Nanobiotechnology Jun 2022Acute myeloid leukemia (AML) showed limited clinical therapeutic efficiency with chemotherapy for its multi-distributed lesions and hard-to-kill leukemia cells deep in...
BACKGROUND
Acute myeloid leukemia (AML) showed limited clinical therapeutic efficiency with chemotherapy for its multi-distributed lesions and hard-to-kill leukemia cells deep in the bone marrow.
RESULTS
Here, a biomimetic nanosystem (DR@PLip) based on platelet membrane (PM) coating and doxorubicin (DOX)/ginsenoside (Rg3) co-loading was developed to potentiate the local-to-systemic chemoimmunotherapy for AML. The PM was designed for long-term circulation and better leukemia cells targeting. The participation of Rg3 was proved to enhance the tumor sensitivity to DOX, thus initiating the anti-tumor immune activation and effectively combating the leukemia cells hiding in the bone marrow.
CONCLUSIONS
In conclusion, the strategy that combining immediate chemotherapy with long-term immunotherapy achieved improved therapeutic efficiency and prolonged survival, which provided a new perspective for the clinical treatment of AML.
Topics: Biomimetics; Doxorubicin; Ginsenosides; Humans; Immunotherapy; Leukemia, Myeloid, Acute
PubMed: 35701846
DOI: 10.1186/s12951-022-01491-w -
Circulation Jul 2013
Topics: Animals; Cardiotonic Agents; Chemical Engineering; Doxorubicin; Female; Humans; Male; Myocytes, Cardiac; Neuregulin-1
PubMed: 23757311
DOI: 10.1161/CIRCULATIONAHA.113.003688 -
BMC Veterinary Research Jan 2019Cancer is a significant health threat in cats. Chemoresistance is prevalent in solid tumors. The ionophore salinomycin has anti-cancer properties and may work...
BACKGROUND
Cancer is a significant health threat in cats. Chemoresistance is prevalent in solid tumors. The ionophore salinomycin has anti-cancer properties and may work synergistically with chemotherapeutics. The purpose of our study was to determine if salinomycin could decrease cancer cell viability when combined with doxorubicin in feline sarcoma and carcinoma cells.
RESULTS
We established two new feline injection-site sarcoma cell lines, B4 and C10, and confirmed their tumorigenic potential in athymic nude mice. B4 was more resistant to doxorubicin than C10. Dose-dependent effects were not observed until 92 μM in B4 cells (p = 0.0006) vs. 9.2 μM (p = 0.0004) in C10 cells. Dose-dependent effects of salinomycin were observed at 15 μM in B4 cells (p = 0.025) and at 10 μM in C10 cells (p = 0.020). Doxorubicin plus 5 μM salinomycin decreased viability of B4 cells compared to either agent alone, but only at supra-pharmacological doxorubicin concentrations. However, doxorubicin plus 5 μM salinomycin decreased viability of C10 cells compared to either agent alone at doxorubicin concentrations that can be achieved in vivo (1.84 and 4.6 μM, p < 0.004). In SCCF1 cells, dose-dependent effects of doxorubicin and salinomycin were observed at 9.2 (p = 0.036) and 2.5 (p = 0.0049) μM, respectively. When doxorubicin was combined with either 1, 2.5, or 5 μM of salinomycin in SCCF1 cells, dose-dependent effects of doxorubicin were observed at 9.2 (p = 0.0021), 4.6 (p = 0.0042), and 1.84 (p = 0.0021) μM, respectively. Combination index calculations for doxorubicin plus 2.5 and 5 μM salinomycin in SCCF1 cells were 0.4 and 0.6, respectively.
CONCLUSIONS
We have developed two new feline sarcoma cell lines that can be used to study chemoresistance. We observed that salinomycin may potentiate (C10 cells) or work synergistically (SCCF1 cells) with doxorubicin in certain feline cancer cells. Further research is indicated to understand the mechanism of action of salinomycin in feline cancer cells as well as potential tolerability and toxicity in normal feline tissues.
Topics: Animals; Antineoplastic Agents; Carcinoma; Cats; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Resistance, Neoplasm; Drug Synergism; In Vitro Techniques; Mice; Pyrans; Sarcoma
PubMed: 30678671
DOI: 10.1186/s12917-019-1780-5 -
Molecules (Basel, Switzerland) Jul 2020Recently, nanogels have been identified as innovative formulations for enlarging the application of hydrogels (HGs) in the area of drug delivery or in diagnostic...
Recently, nanogels have been identified as innovative formulations for enlarging the application of hydrogels (HGs) in the area of drug delivery or in diagnostic imaging. Nanogels are HGs-based aggregates with sizes in the range of nanometers and formulated in order to obtain injectable preparations. Regardless of the advantages offered by peptides in a hydrogel preparation, until now, only a few examples of peptide-based nanogels (PBNs) have been developed. Here, we describe the preparation of stable PBNs based on Fmoc-Phe-Phe-OH using three different methods, namely water/oil emulsion (W/O), top-down, and nanogelling in water. The effect of the hydrophilic-lipophilic balance (HLB) in the formulation was also evaluated in terms of size and stability. The resulting nanogels were found to encapsulate the anticancer drug doxorubicin, chosen as the model drug, with a drug loading comparable with those of the liposomes.
Topics: Doxorubicin; Drug Carriers; Drug Liberation; Emulsions; Hydrophobic and Hydrophilic Interactions; Molecular Structure; Nanogels; Peptides; Theranostic Nanomedicine
PubMed: 32751321
DOI: 10.3390/molecules25153455 -
International Journal of Hyperthermia :... 2015To establish optimum conditions for anti-tumour therapy, we evaluated the efficacy of doxorubicin using liposomal doxorubicin and local hyperthermia to improve the...
PURPOSE
To establish optimum conditions for anti-tumour therapy, we evaluated the efficacy of doxorubicin using liposomal doxorubicin and local hyperthermia to improve the anti-tumour efficacy over liposomal doxorubicin alone in rabbit VX2 tumours.
MATERIALS AND METHODS
A VX2 tumour model was established in New Zealand white rabbits, which were randomly divided into five groups: 1) control, 2) free doxorubicin hydrochloride (Dox), 3) liposomal doxorubicin hydrochloride (L-Dox), 4) L-Dox plus 41 °C thermotherapy (L-Dox + 41 °C TT); and 5) L-Dox plus 43 °C thermotherapy (L-Dox + 43 °C TT). To achieve complete tumour remission, multiple high-dose administrations (5 mg/kg, once per week for a total of 3 weeks) were given. An ultrasound hyperthermia instrument was used to induce local hyperthermia and the systemic toxicity of Dox was evaluated by changes in weight, blood count and serum lactic dehydrogenase. The anti-tumour effect of Dox was evaluated by observing the gross tumour volume, weight and rabbit survival.
RESULTS
The white blood cell count following administration of Dox or L-Dox was lower than for control animals and those treated with L-Dox + 41 °C TT. There was no difference between the groups with regard to the red blood cell count. Compared with the control and Dox groups, tumour proliferation was significantly inhibited following administration of L-Dox, L-Dox + 41 °C TT and L-Dox + 43 °C TT, as evidenced by the difference in tumour volume, weight and survival time. Differences in tumour proliferation were also found between the L-Dox and thermotherapy groups.
CONCLUSION
Local hyperthermia combined with L-Dox can significantly improve anti-tumour efficacy and reduce systemic toxicity.
Topics: Animals; Antibiotics, Antineoplastic; Combined Modality Therapy; Doxorubicin; Hyperthermia, Induced; Neoplasms; Polyethylene Glycols; Rabbits; Treatment Outcome; Tumor Burden
PubMed: 26726929
DOI: 10.3109/02656736.2015.1078502 -
ACS Applied Materials & Interfaces Apr 2023Despite the enormous advancements in nanomedicine research, a limited number of nanoformulations are available on the market, and few have been translated to clinics. An...
Despite the enormous advancements in nanomedicine research, a limited number of nanoformulations are available on the market, and few have been translated to clinics. An easily scalable, sustainable, and cost-effective manufacturing strategy and long-term stability for storage are crucial for successful translation. Here, we report a system and method to instantly formulate NF achieved with a nanoscale polyelectrolyte coacervate-like system, consisting of anionic pseudopeptide poly(l-lysine isophthalamide) derivatives, polyethylenimine, and doxorubicin (Dox) via simple "mix-and-go" addition of precursor solutions in seconds. The coacervate-like nanosystem shows enhanced intracellular delivery of Dox to patient-derived multidrug-resistant (MDR) cells in 3D tumor spheroids. The results demonstrate the feasibility of an instant drug formulation using a coacervate-like nanosystem. We envisage that this technique can be widely utilized in the nanomedicine field to bypass the special requirement of large-scale production and elongated shelf life of nanomaterials.
Topics: Humans; Feasibility Studies; Doxorubicin; Neoplasms; Nanostructures; Drug Carriers; Nanoparticles; Cell Line, Tumor; Drug Delivery Systems
PubMed: 36976817
DOI: 10.1021/acsami.2c21586 -
Nature Communications Mar 2024Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC...
Myeloid derived suppressor cells (MDSCs) are key regulators of immune responses and correlate with poor outcomes in hematologic malignancies. Here, we identify that MDSC mitochondrial fitness controls the efficacy of doxorubicin chemotherapy in a preclinical lymphoma model. Mechanistically, we show that triggering STAT3 signaling via β2-adrenergic receptor (β2-AR) activation leads to improved MDSC function through metabolic reprograming, marked by sustained mitochondrial respiration and higher ATP generation which reduces AMPK signaling, altering energy metabolism. Furthermore, induced STAT3 signaling in MDSCs enhances glutamine consumption via the TCA cycle. Metabolized glutamine generates itaconate which downregulates mitochondrial reactive oxygen species via regulation of Nrf2 and the oxidative stress response, enhancing MDSC survival. Using β2-AR blockade, we target the STAT3 pathway and ATP and itaconate metabolism, disrupting ATP generation by the electron transport chain and decreasing itaconate generation causing diminished MDSC mitochondrial fitness. This disruption increases the response to doxorubicin and could be tested clinically.
Topics: Humans; Myeloid-Derived Suppressor Cells; Glutamine; Hematologic Neoplasms; Adenosine Triphosphate; Doxorubicin; Succinates
PubMed: 38555305
DOI: 10.1038/s41467-024-47096-9