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Pediatric Blood & Cancer Aug 2024
Topics: Humans; Brentuximab Vedotin; Hodgkin Disease; Nivolumab; Child; Antineoplastic Combined Chemotherapy Protocols; Male; Female; Antineoplastic Agents, Immunological; Adolescent; Immunotherapy; Doxorubicin; Vinblastine
PubMed: 38840433
DOI: 10.1002/pbc.31091 -
Supportive Care in Cancer : Official... Jun 2024Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of cooling remains unclear. Our aim was to determine whether increasing the duration of scalp cooling improves hair preservation.
METHODS
Patients with HER2-negative, non-metastatic, breast cancer received scalp cooling during adjuvant chemotherapy: three cycles of epirubicin/cyclophosphamide (EC) followed by three cycles of paclitaxel. The patients were randomly assigned to two groups. Group A (n=18) wore a Paxman cooling cap during each infusion and for 30 min post-infusion while Group B (n=19) wore the cap from 30 min before to 2 h after each infusion. All patients were asked to complete a questionnaire recording hair loss/regrowth, adverse events, and quality of life. Success of treatment was defined as <50% hair loss.
RESULTS
The success rates after each of the three cycles did not differ significantly between the two groups (EC: Group A: 40%, Group B: 44%; paclitaxel: Group A: 50%, Group B: 36%; p>0.05). Hair regrowth was significantly higher in Group B at the 8-week follow-up, but not at the 6-month follow-up. Head discomfort affected more patients in Group B than in Group A during the first session (94% vs. 62%, respectively; p=0.039).
CONCLUSION
Long duration scalp cooling during chemotherapy might increase patients' discomfort and does not appear to improve hair preservation.
Topics: Humans; Alopecia; Female; Breast Neoplasms; Pilot Projects; Middle Aged; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Paclitaxel; Adult; Scalp; Epirubicin; Quality of Life; Hypothermia, Induced; Time Factors; Aged; Surveys and Questionnaires
PubMed: 38839667
DOI: 10.1007/s00520-024-08579-z -
International Journal of Nanomedicine 2024The purpose of this study is to address the need for efficient drug delivery with high drug encapsulation efficiency and sustained drug release. We aim to create...
PURPOSE
The purpose of this study is to address the need for efficient drug delivery with high drug encapsulation efficiency and sustained drug release. We aim to create nanoparticle-loaded microgels for potential applications in treatment development.
METHODS
We adopted the process of ionic gelation to generate microgels from sodium alginate and carboxymethyl cellulose. These microgels were loaded with doxorubicin-conjugated amine-functionalized zinc ferrite nanoparticles (AZnFe-NPs). The systems were characterized using various techniques. Toxicity was evaluated in MCF-7 cells. In vitro release studies were conducted at different pH levels at 37 C, with the drug release kinetics being analyzed using various models.
RESULTS
The drug encapsulation efficiency of the created carriers was as high as 70%. The nanoparticle-loaded microgels exhibited pH-responsive behavior and sustained drug release. Drug release from them was mediated via a non-Fickian type of diffusion.
CONCLUSION
Given their high drug encapsulation efficiency, sustained drug release and pH-responsiveness, our nanoparticle-loaded microgels show promise as smart carriers for future treatment applications. Further development and research can significantly benefit the field of drug delivery and treatment development.
Topics: Doxorubicin; Humans; Delayed-Action Preparations; Drug Liberation; MCF-7 Cells; Ferric Compounds; Hydrogen-Ion Concentration; Microgels; Drug Carriers; Alginates; Amines; Carboxymethylcellulose Sodium; Nanoparticles; Zinc; Zinc Compounds; Cell Survival
PubMed: 38836007
DOI: 10.2147/IJN.S448594 -
AAPS PharmSciTech Jun 2024DOX liposomes have better therapeutic effects and lower toxic side effects. The targeting ability of liposomes is one of the key factors affecting the therapeutic effect...
DOX liposomes have better therapeutic effects and lower toxic side effects. The targeting ability of liposomes is one of the key factors affecting the therapeutic effect of DOX liposomes. This study developed two types of targeted liposomes. Sialic acid (SA)-modified liposomes were designed to target the highly expressed Siglec-1 receptor on tumor-associated macrophages surface. Phosphatidylserine (PS)-modified liposomes were designed to promote phagocytosis by monocyte-derived macrophages through PS apoptotic signaling. In order to assess and compare the therapeutic potential of different targeted pathways in the context of anti-tumor treatment, we compared four phosphatidylserine membrane materials (DOPS, DSPS, DPPS and DMPS) and found that liposomes prepared using DOPS as material could significantly improve the uptake ability of RAW264.7 cells for DOX liposomes. On this basis, normal DOX liposomes (CL-DOX) and SA-modified DOX liposomes (SAL-DOX), PS-modified DOX liposomes (PS-CL-DOX), SA and PS co-modified DOX liposomes (PS-SAL-DOX) were prepared. The anti-tumor cells function of each liposome on S180 and RAW264.7 in vitro was investigated, and it was found that SA on the surface of liposomes can increase the inhibitory effect. In vivo efficacy results exhibited that SAL-DOX and PS-CL-DOX were superior to other groups in terms of ability to inhibit tumor growth and tumor inhibition index, among which SAL-DOX had the best anti-tumor effect. Moreover, SAL-DOX group mice had high expression of IFN-γ as well as IL-12 factors, which could significantly inhibit mice tumor growth, improve the immune microenvironment of the tumor site, and have excellent targeted delivery potential.
Topics: Liposomes; Animals; Mice; N-Acetylneuraminic Acid; RAW 264.7 Cells; Phosphatidylserines; Doxorubicin; Tumor-Associated Macrophages; Cell Line, Tumor; Antineoplastic Agents; Phagocytosis; Drug Delivery Systems; Apoptosis
PubMed: 38834759
DOI: 10.1208/s12249-024-02837-3 -
Molecular Cancer Jun 2024The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in...
The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxifying anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S. In this study, we examined different clinically relevant anthracycline drugs for a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. The different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical studies, as it potently kills cancer cells, lacks cardiotoxicity, and can be safely administered even after the maximum cumulative dose of either doxorubicin or idarubicin has been reached. Retrospective analysis of aclarubicin used as second-line treatment for relapsed/refractory AML patients showed survival effects similar to its use in first line, leading to a notable 23% increase in 5-year overall survival compared to other intensive chemotherapies. Considering individual anthracyclines as distinct entities unveils new treatment options, such as the identification of aclarubicin, which significantly improves the survival outcomes of AML patients while mitigating the treatment-limiting side-effects. Building upon these findings, an international multicenter Phase III prospective study is prepared, to integrate aclarubicin into the treatment of relapsed/refractory AML patients.
Topics: Animals; Female; Humans; Male; Aclarubicin; Anthracyclines; Antineoplastic Agents; Leukemia, Myeloid, Acute; Treatment Outcome
PubMed: 38831402
DOI: 10.1186/s12943-024-02034-7 -
Life Sciences Aug 2024Malnutrition is a common problem in developing countries, and the impact of severe malnutrition on optimal treatment outcomes of chemotherapy in pediatric cancer...
BACKGROUND
Malnutrition is a common problem in developing countries, and the impact of severe malnutrition on optimal treatment outcomes of chemotherapy in pediatric cancer patients is well documented. However, despite being a more prevalent and distinct entity, moderate malnutrition is until now unexplored for its effects on treatment outcomes.
AIMS
In this study we aimed to investigate the molecular basis of altered pharmacokinetics and cardiotoxicity of doxorubicin observed in early-life chronic moderate protein deficiency malnutrition.
MATERIALS AND METHODS
We developed an animal model of early-life moderate protein-deficiency malnutrition and validated it using clinical samples. This model was used to study pharmacokinetic and toxicity changes and was further utilized to study the molecular changes in liver and heart to get mechanistic insights.
KEY FINDINGS
Here we show that moderate protein-deficiency malnutrition in weanling rats causes changes in drug disposition in the liver by modification of hepatic ABCC3 and MRP2 transporters through the TNFα signalling axis. Furthermore, malnourished rats in repeat-dose doxorubicin toxicity study showed higher toxicity and mortality. A higher accumulation of doxorubicin in the heart was observed which was associated with alterations in cardiac metabolic pathways and increased cardiotoxicity.
SIGNIFICANCE
Our findings indicate that moderate malnutrition causes increased susceptibility towards toxic side effects of chemotherapy. These results may necessitate further investigations and new guidelines on the dosing of chemotherapy in moderately malnourished pediatric cancer patients.
Topics: Animals; Doxorubicin; Rats; Cardiotoxicity; Male; Weaning; Liver; Protein-Energy Malnutrition; Humans; Antibiotics, Antineoplastic; Female; Disease Models, Animal; Rats, Wistar
PubMed: 38830506
DOI: 10.1016/j.lfs.2024.122765 -
Molecular Biology Reports Jun 2024Cancer and multidrug resistance are regarded as concerns related to poor health outcomes. It was found that the monolayer of 2D cancer cell cultures lacks many important...
BACKGROUND
Cancer and multidrug resistance are regarded as concerns related to poor health outcomes. It was found that the monolayer of 2D cancer cell cultures lacks many important features compared to Multicellular Tumor Spheroids (MCTS) or 3D cell cultures which instead have the ability to mimic more closely the in vivo tumor microenvironment. This study aimed to produce 3D cell cultures from different cancer cell lines and to examine the cytotoxic activity of anticancer medications on both 2D and 3D systems, as well as to detect alterations in the expression of certain genes levels.
METHOD
3D cell culture was produced using 3D microtissue molds. The cytotoxic activities of colchicine, cisplatin, doxorubicin, and paclitaxel were tested on 2D and 3D cell culture systems obtained from different cell lines (A549, H1299, MCF-7, and DU-145). IC50 values were determined by MTT assay. In addition, gene expression levels of PIK3CA, AKT1, and PTEN were evaluated by qPCR.
RESULTS
Similar cytotoxic activities were observed on both 3D and 2D cell cultures, however, higher concentrations of anticancer medications were needed for the 3D system. For instance, paclitaxel showed an IC50 of 6.234 µM and of 13.87 µM on 2D and 3D H1299 cell cultures, respectively. Gene expression of PIK3CA in H1299 cells also showed a higher fold change in 3D cell culture compared to 2D system upon treatment with doxorubicin.
CONCLUSION
When compared to 2D cell cultures, the behavior of cells in the 3D system showed to be more resistant to anticancer treatments. Due to their shape, growth pattern, hypoxic core features, interaction between cells, biomarkers synthesis, and resistance to treatment penetration, the MCTS have the advantage of better simulating the in vivo tumor conditions. As a result, it is reasonable to conclude that 3D cell cultures may be a more promising model than the traditional 2D system, offering a better understanding of the in vivo molecular changes in response to different potential treatments and multidrug resistance development.
Topics: Humans; Antineoplastic Agents; Cell Line, Tumor; Spheroids, Cellular; Cell Culture Techniques; Doxorubicin; Paclitaxel; Cisplatin; Tumor Microenvironment; Neoplasms; Drug Resistance, Neoplasm; Cell Culture Techniques, Three Dimensional; MCF-7 Cells; Gene Expression Regulation, Neoplastic; Cell Survival
PubMed: 38829450
DOI: 10.1007/s11033-024-09669-1 -
Chemical Communications (Cambridge,... Jun 2024We developed prodrug nanoparticles that release drugs through intracellular dissolution and a cancer-specific hydrogen peroxide response. To reveal the unclear mechanism...
We developed prodrug nanoparticles that release drugs through intracellular dissolution and a cancer-specific hydrogen peroxide response. To reveal the unclear mechanism regarding drug release from nanoparticles by reacting with hydrogen peroxide in cancer cells, this study demonstrates the evaluation of drug release kinetics under conditions simulated in cancer cells.
Topics: Hydrogen Peroxide; Humans; Prodrugs; Drug Liberation; Nanoparticles; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Solubility; Drug Carriers; Doxorubicin
PubMed: 38829169
DOI: 10.1039/d4cc02252a -
International Journal of Nanomedicine 2024The tumor microenvironment (TME) has attracted considerable attention as a potential therapeutic target for cancer. High levels of reactive oxygen species (ROS) in the...
INTRODUCTION
The tumor microenvironment (TME) has attracted considerable attention as a potential therapeutic target for cancer. High levels of reactive oxygen species (ROS) in the TME may act as a stimulus for drug release. In this study, we have developed ROS-responsive hyaluronic acid-bilirubin nanoparticles (HABN) loaded with doxorubicin (DOX@HABN) for the specific delivery and release of DOX in tumor tissue. The hyaluronic acid shell of the nanoparticles acts as an active targeting ligand that can specifically bind to CD44-overexpressing tumors. The bilirubin core has intrinsic anti-cancer activity and ROS-responsive solubility change properties.
METHODS & RESULTS
DOX@HABN showed the HA shell-mediated targeting ability, ROS-responsive disruption leading to ROS-mediated drug release, and synergistic anti-cancer activity against ROS-overproducing CD44-overexpressing HeLa cells. Additionally, intravenously administered HABN-Cy5.5 showed remarkable tumor-targeting ability in HeLa tumor-bearing mice with limited distribution in major organs. Finally, intravenous injection of DOX@HABN into HeLa tumor-bearing mice showed synergistic anti-tumor efficacy without noticeable side effects.
CONCLUSION
These findings suggest that DOX@HABN has significant potential as a cancer-targeting and TME ROS-responsive nanomedicine for targeted cancer treatment.
Topics: Hyaluronic Acid; Tumor Microenvironment; Animals; Reactive Oxygen Species; Humans; Doxorubicin; Nanoparticles; Mice; HeLa Cells; Nanomedicine; Hyaluronan Receptors; Bilirubin; Drug Liberation; Mice, Inbred BALB C; Mice, Nude; Xenograft Model Antitumor Assays; Drug Carriers; Antineoplastic Agents; Neoplasms
PubMed: 38828202
DOI: 10.2147/IJN.S460468 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2024
Topics: Humans; Lymphoma, Mantle-Cell; Male; Female; Bone Marrow; Prognosis; SOXC Transcription Factors; Retrospective Studies; Cyclin D1; PAX5 Transcription Factor; Biopsy; CD79 Antigens; Antigens, CD20; CD5 Antigens; Antineoplastic Combined Chemotherapy Protocols; Immunophenotyping; Cyclophosphamide; Vincristine; Prednisone; Aged; Middle Aged; Adult; Doxorubicin
PubMed: 38825910
DOI: 10.3760/cma.j.cn112151-20230926-00217