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Journal of Clinical Oncology : Official... May 2024Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting mutation and/or BRCAness phenotype. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With -Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial.
PURPOSE
Literature evidence suggests that trabectedin monotherapy is effective in patients with recurrent ovarian cancer (OC) presenting mutation and/or BRCAness phenotype.
METHODS
A prospective, open-label, randomized phase III MITO-23 trial evaluated the activity and safety of trabectedin 1.3 mg/m given once every 3 weeks (arm A) in mutation carriers or patients with BRCAness phenotype (ie, patients who responded to ≥two previous platinum-based treatments) with recurrent OC, primary peritoneal carcinoma, or fallopian tube cancer in comparison with physician's choice chemotherapy in the control arm (arm B; pegylated liposomal doxorubicin, topotecan, gemcitabine, once-weekly paclitaxel, or carboplatin). The primary end point was overall survival (OS) evaluated in the intention-to-treat population.
RESULTS
Overall, 244 patients from 21 MITO centers were randomly assigned (arm A = 122/arm B = 122). More than 70% of patients received ≥three previous chemotherapy lines and 35.7% had received a poly (ADP-ribose) polymerase inhibitor (PARPi) before enrollment. Median OS was not significantly different between the arms: arm A: 15.8 versus arm B: 17.9 months ( = .304). Median progression-free survival was 4.9 months in arm A versus 4.4 months in arm B ( = .897). Among 208 patients evaluable for efficacy, the objective response rate was 17.1% in arm A and 21.4% in arm B, with comparable median duration of response (5.62 5.66 months, respectively). No superior effect was observed for trabectedin in the prespecified subgroup analyses according to mutational status, chemotherapy type, and pretreatment with a PARPi and/or platinum-free interval. Trabectedin showed a higher frequency of grade ≥3 adverse events (AEs), serious AEs, and serious adverse drug reactions compared with control chemotherapy.
CONCLUSION
Trabectedin did not improve median OS and showed a worse safety profile in comparison with physician's choice control chemotherapy.
Topics: Humans; Female; Trabectedin; Middle Aged; Ovarian Neoplasms; Aged; Adult; Mutation; Neoplasm Recurrence, Local; Phenotype; Prospective Studies; BRCA2 Protein; BRCA1 Protein; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Progression-Free Survival
PubMed: 38315944
DOI: 10.1200/JCO.23.01225 -
ACS Omega Sep 2023Nanoparticles have been suggested as drug-delivery systems for chemotherapeutic drugs to allow for controlled drug release profiles and selectivity to target cancer...
Nanoparticles have been suggested as drug-delivery systems for chemotherapeutic drugs to allow for controlled drug release profiles and selectivity to target cancer cells. In addition, nanoparticles can be used for the in situ generation and amplification of reactive oxygen species (ROS), which have been shown to be a promising strategy for cancer treatment. Thus, a targeted nanoscale drug-delivery platform could be used to synergistically improve cancer treatment by the action of chemotherapeutic drugs and ROS generation. Herein, we propose a promising chemotherapy strategy where the drug-loaded nanoparticles generate high doses of ROS together with the loaded ROS-generating chemotherapeutic drugs, which can damage the mitochondria and activate cell death, potentiating the therapeutic outcome in cancer therapy. In the present study, we have developed a dual-targeted drug-delivery nanoassembly consisting of a mesoporous silica core loaded with the chemotherapeutic, ROS-generating drug, paclitaxel (Px), and coated with a liposome layer for controlled drug release. Two different lung cancer-targeting ligands, folic acid and peptide GE11, were used to target the overexpressed nonsmall lung cancer receptors to create the final nanoassembly (MSN@Px) L-GF. Upon endocytosis by the cancer cells, the liposome layer was degraded by the intracellular lipases, and the drug was rapidly released at a rate of 65% within the first 20 h. In vitro studies confirmed that this nanoassembly was 8-fold more effective in cancer therapy compared to the free drug Px.
PubMed: 37779923
DOI: 10.1021/acsomega.3c02901 -
Carbohydrate Polymers Jul 2024To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL)....
To alleviate skull defects and enhance the biological activity of taxifolin, this study utilized the thin-film dispersion method to prepare paclitaxel liposomes (TL). Thiolated chitosan (CSSH)-modified TL (CTL) was synthesized through charge interactions. Injectable hydrogels (BLG) were then prepared as hydrogel scaffolds loaded with TAX (TG), TL (TLG), and CTL (CTLG) using a Schiff base reaction involving oxidized dextran and carboxymethyl chitosan. The study investigated the bone reparative properties of CTLG through molecular docking, western blot techniques, and transcriptome analysis. The particle sizes of CTL were measured at 248.90 ± 14.03 nm, respectively, with zeta potentials of +36.68 ± 5.43 mV, respectively. CTLG showed excellent antioxidant capacity in vitro. It also has a good inhibitory effect on Escherichia coli and Staphylococcus aureus, with inhibition rates of 93.88 ± 1.59 % and 88.56 ± 2.83 % respectively. The results of 5-ethynyl-2 '-deoxyuridine staining, alkaline phosphatase staining and alizarin red staining showed that CTLG also had the potential to promote the proliferation and differentiation of mouse embryonic osteoblasts (MC3T3-E1). The study revealed that CTLG enhances the expression of osteogenic proteins by regulating the Wnt signaling pathway, shedding light on the potential application of TAX and bone regeneration mechanisms.
Topics: Animals; Chitosan; Quercetin; Liposomes; Wnt Signaling Pathway; Osteoblasts; Hydrogels; Cell Proliferation; Mice; Skull; Rats; Bone Regeneration; Rats, Sprague-Dawley; Osteogenesis; Staphylococcus aureus; Sulfhydryl Compounds; Anti-Bacterial Agents; Cell Differentiation; Escherichia coli; Male; Molecular Docking Simulation
PubMed: 38670750
DOI: 10.1016/j.carbpol.2024.122115 -
Therapeutic Advances in Medical Oncology 2024The approval of novel therapeutic agents remains widely reliant on evidence derived from large phase III randomized controlled trials. Liposomal irinotecan (ONIVYDE)... (Review)
Review
The approval of novel therapeutic agents remains widely reliant on evidence derived from large phase III randomized controlled trials. Liposomal irinotecan (ONIVYDE) stands out as the only drug that has demonstrated improved survival both as a first-line therapy in combination with oxaliplatin and 5-fluorouracil/leucovorin (5FU/LV) (NALIRIFOX) compared to the standard gemcitabine plus nab-paclitaxel in the NAPOLI3 trial, and as a second-line treatment in combination with 5FU/LV compared to the standard 5FU/LV in the NAPOLI1 trial. However, just as the white bear of the Dostoevsky's paradox, the judgment of these results is invariably distracted by the intrusive thought of how different they might be if compared to similar regimens containing standard-free irinotecan as FOLFIRINOX or FOLFIRI, respectively. Here, we present and thoroughly discuss the evidence encompassing the pharmacologic, preclinical, and clinical development of liposomal irinotecan that can dispel any intrusive thoughts and foster a rational and well-considered judgment of this agent and its potential integration into the therapeutic strategies for pancreatic ductal adenocarcinoma.
PubMed: 38584763
DOI: 10.1177/17588359241234487 -
Journal of Medical Case Reports Oct 2023An estimated 119,300 new cases of cervical cancer occur annually in China, accounting for 372,00 deaths. Cutaneous metastasis from cervical cancer is a rare event, with... (Review)
Review
BACKGROUND
An estimated 119,300 new cases of cervical cancer occur annually in China, accounting for 372,00 deaths. Cutaneous metastasis from cervical cancer is a rare event, with an incidence of 0.1-1.3% and typically a preterminal occurrence. Scalp metastasis from cervical cancer is exceptionally anecdotal, with only a dozen examples well documented.
CASE PRESENTATION
The patient is a 33-year-old Chinese woman who was diagnosed with International Federation of Gynecology and Obstetrics stage IVB cervical cancer in November 2021. From December 2021 to April 2022, the patient was enrolled in the clinical trial of sintilimab combined with chemotherapy and radiotherapy for treatment of stage IV cervical cancer and underwent six cycles of immunotherapy and chemotherapy (sintilimab plus paclitaxel liposome and cisplatin). Treatment was well tolerated and led to a partial response. The masses adjacent to the spine and iliac bone was largely reduced. Thus, radiotherapy of the metastatic residues was carried out and followed by radiotherapy to the primary tumor at the cervix uteri. However, by the time of the radiotherapy completion in October 2022, the patient noticed painless nodules at the left scapular region and the right hypochondrium. The following month, more nodules occurred on the scalp and trunk, including the left axilla, anterior abdomen, and left back, along with a lesion invading the sternum that caused acute bone pain. The cutaneous masses were white, discrete with a rubbery consistency, and fixed to the skin. Several nodules increased in size and eventually ulcerated. Fine‑needle aspiration cytology of the left back swellings revealed metastatic squamous cell carcinoma, P16 positive. No visceral or brain metastasis was observed at this point.
CONCLUSIONS
Cervical cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. So far, there is no clear guideline regarding skin metastases treatment. Such skin lesions warrant a thorough radiologic and pathologic workup to form a comprehensive management plan.
Topics: Female; Humans; Adult; Uterine Cervical Neoplasms; Scalp; Skin Neoplasms; Carcinoma, Squamous Cell; Cisplatin
PubMed: 37853494
DOI: 10.1186/s13256-023-04171-x -
International Journal of Biological... Jul 2023Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main...
3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation.
Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60-80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.
Topics: Female; Humans; Paclitaxel; Liposomes; Gelatin; Alginates; MCF-7 Cells; Breast Neoplasms; Printing, Three-Dimensional; Cell Line, Tumor
PubMed: 37156313
DOI: 10.1016/j.ijbiomac.2023.124697 -
Evidence-based Complementary and... 2023[This retracts the article DOI: 10.1155/2022/5651793.].
[This retracts the article DOI: 10.1155/2022/5651793.].
PubMed: 37501833
DOI: 10.1155/2023/9816837 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Jul 2023Ginsenoside 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, 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). Compared with free drugs, liposomes inhibited the migration of MDA-MB-231 and 4T1 cells(P<0.05). Liposomes demonstrated active targeting and lysosome escape. In particular, liposomes showed lower toxicity to H9c2 cells than free drugs(P<0.05), which indicated that the preparation had the potential to reduce cardiotoxicity. The findings prove that ginsenoside Rg_3 characterized by the combination of drug and excipient is an ideal substitute for lipids in liposomes and promoted the development of innovative TCM drugs for treating cancer.
Topics: Humans; Paclitaxel; Liposomes; Ginsenosides; Triple Negative Breast Neoplasms; Cardiotoxicity; Cell Line, Tumor
PubMed: 37474984
DOI: 10.19540/j.cnki.cjcmm.20230410.301 -
ACS Applied Bio Materials May 2024There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted...
There is a growing appeal for engineering drug delivery systems for controlled and local drug delivery. Conjugation of antibodies on the nanocarriers for targeted chemotherapeutic drugs has always been one of the main techniques. This work aims to develop a polycaprolactone/chitosan electrospun mat incorporated with paclitaxel/FeO-loaded niosomes (SPNs) decorated with trastuzumab (TbNs) for cancer therapy. SPNs and TbNs were analyzed by DLS, zeta potential, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy. Fabricated mats with distinct concentrations of TbNs were classified into four groups (G0 (0), G1 (1), G2 (2.5), and G3 (5%)) and were studied physicochemically, mechanically, and biologically. Paclitaxel release was also studied for 7 days under an alternative magnetic field (AMF). The optimized mat was nominated for an in vivo study to evaluate its tumor growth inhibition. Based on the results, the TbNs had a spherical core and shell morphology with a smooth surface. The zeta potential and the mean size of TbNs were equal to -14.7 mV and 221 nm. TbNs did not affect the morphology and quality of nanofibers, but in general, the presence of TbNs increased the elastic modulus, water uptake, and degradation. Regarding the release study, AMF showed a significant increase in accelerating paclitaxel release from mats, and most releases belonged to the mat with 5% of TbNs. Results from the in vivo study showed the effective and synergistic effects of AMF on drug release and significant tumor growth inhibition. To summarize, the proposed nanocarrier under AMF can be a good candidate for cancer therapy.
Topics: Paclitaxel; Trastuzumab; Breast Neoplasms; Female; Animals; Humans; Particle Size; Materials Testing; Mice; Liposomes; Polyethylene Glycols; Biocompatible Materials; Drug Screening Assays, Antitumor; Cell Proliferation; Drug Carriers; Antineoplastic Agents; Mice, Inbred BALB C; Drug Delivery Systems; Cell Survival
PubMed: 38602218
DOI: 10.1021/acsabm.4c00027 -
ACS Applied Bio Materials May 2024We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the...
We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and mouse veins after intravenous administration. The trackable liposome delivery provides and photothermal heat (∼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.
Topics: Liposomes; Animals; Infrared Rays; Mice; Skin Neoplasms; Precision Medicine; Paclitaxel; Materials Testing; Biocompatible Materials; Particle Size; Humans; Drug Delivery Systems; Drug Screening Assays, Antitumor
PubMed: 38709861
DOI: 10.1021/acsabm.4c00203