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Arquivos Brasileiros de Cardiologia 2024The introduction of anthracyclines in the treatment of children and adolescents with cancer has promoted a significant increase in survival, but also in morbidity and...
BACKGROUND
The introduction of anthracyclines in the treatment of children and adolescents with cancer has promoted a significant increase in survival, but also in morbidity and mortality rates due to cardiovascular (CV) complications.
OBJECTIVES
To determine the cardiovascular profile of pediatric patients treated with anthracyclines at a cancer center in Brazil and the incidence of CV complications.
METHODS
The following data were collected from the medical records of patients of both sexes, aged younger than 19 years - frequency and form of clinical presentation of general CV complications (G1) and CV complications related to ventricular dysfunction (G2) - and correlated with risk factors, age range and vital status, cardiovascular and cardioprotective medications. A p<0.05 was considered statistically significant.
RESULTS
A total of 326 patients were included, 214 (65.6%) were younger than 10 years and 192 (58.9%) of male sex. G1 complications occurred in 141 (43.3%) patients, and the most frequent was systemic arterial hypertension; G2 complications occurred in 84 patients (25.8%). Cumulative dose (CD) of anthracyclines > 250mg/m2 was used in 26.7% of patients and the association of G2 complications with this CD was not statistically significant (p=0.305; OR=1.330 and [95% CI = 0.770- 2.296]). The most used cardiac medications were diuretics (34.7% of patients).
CONCLUSIONS
In accordance with literature, the study showed a high incidence of CV complications in the treatment of children and adolescents with cancer, with general CV complications as the most prevalent.
Topics: Humans; Male; Female; Child; Anthracyclines; Brazil; Adolescent; Child, Preschool; Incidence; Cardiovascular Diseases; Risk Factors; Infant; Neoplasms; Retrospective Studies; Antibiotics, Antineoplastic; Cardiotoxicity; Sex Distribution; Young Adult
PubMed: 38922271
DOI: 10.36660/abc.20210352 -
Marine Drugs May 2024Experiments conducted on triple-negative breast cancer have shown that fucoidan from (FLt) exhibits cytotoxic and antitumor properties. However, further research is...
Experiments conducted on triple-negative breast cancer have shown that fucoidan from (FLt) exhibits cytotoxic and antitumor properties. However, further research is necessary to gain a complete understanding of its bioactivity and level of cytotoxicity. The cytotoxic effect of FLt was determined by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was analyzed using annexin V and caspase 3/7 staining kit and DNA fragmentation. In addition, transcriptional expression of antiapoptotic (Bcl-2 and XIAP) and proapoptotic (caspase 8, caspase 9, and AIF) genes were analyzed in TNBC 4T1 cells. After 72 h of culture, the IC for FLt was 561 μg/mL, while doxorubicin (Dox) had an IC of 0.04 μg/mL. In addition, assays for FLt + Dox were performed. Annexin V and caspase 3/7 revealed that FLt induces early and late-stage apoptosis. DNA fragmentation results support necrotic death of 4T1 cells. Similarly, transcripts that prevent cell death were decreased, while transcripts that promote cell death were increased. This study showed that FLt induces apoptosis by both caspase-dependent and caspase-independent mechanisms. These findings suggest that FLt may have potential applications in breast cancer treatment. Further research will provide more information to elucidate the mechanism of action of FLt.
Topics: Apoptosis; Cell Line, Tumor; Polysaccharides; Animals; Female; Caspases; Mice; Antineoplastic Agents; Doxorubicin; Humans; Adenocarcinoma; DNA Fragmentation; Breast Neoplasms; Triple Negative Breast Neoplasms; Kelp
PubMed: 38921562
DOI: 10.3390/md22060251 -
Journal of Nanobiotechnology Jun 2024Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still...
Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.
Topics: Bleomycin; Animals; Mice; Rabbits; Hemangioma; Hyaluronic Acid; Needles; Delayed-Action Preparations; Drug Delivery Systems; Polyesters; Humans; Microspheres; Antibiotics, Antineoplastic; Drug Liberation
PubMed: 38918811
DOI: 10.1186/s12951-024-02557-7 -
Asian Pacific Journal of Cancer... Jun 2024Cytochrome P450 (CYP) are phase I metabolizing enzymes involved in detoxification of chemotherapeutic agents. Among the CYP gene family, including CYP1A1, CYP1B1, CYP2C,...
BACKGROUND
Cytochrome P450 (CYP) are phase I metabolizing enzymes involved in detoxification of chemotherapeutic agents. Among the CYP gene family, including CYP1A1, CYP1B1, CYP2C, CYP2D, CYP2E and CYP17, their significance in cancer susceptibility is well established. However, there remains limited understanding regarding the polymorphisms of CYP2C19*2 and CYP17 and their potential correlation with chemotherapy-induced toxicity reactions in breast cancer (BC) patients. In this study we intended to identify the association of CYP2C19*2 and CYP17 gene polymorphisms on drug response as well as toxicity reactions in BC patients undergoing adriamycin/paclitaxel based chemotherapy within Indian population.
METHODS
Two hundred BC patients receiving adriamycin and paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms of CYP2C19*2 (681G>A) and CYP17 (34T>C) isoforms of cytochrome p 450 gene was studied by PCR and RFLP analysis.
RESULTS
The univariate logistic regression analysis revealed significant associations between CYP2C19*2 (681 G>A) polymorphisms with hematological toxicities i.e., anemia (OR=9.77, 95% CI: 2.84-33.52; p=0.0003), neutropenia (OR=5.72, 95% CI: 1.75-18.68; p=0.003), febrile neutropenia (OR=4.29, 95% CI: 1.32-13.87; p=0.014) and thrombocytopenia (OR=5.86, 95% CI: 1.15-29.72); p=0.032) in BC patients. Additionally BC patients treated with adriamycin exhibited significant association between CYP2C19*2 polymorphism with chemotherapy induced nausea and vomiting (CINV) (OR=99.73, 95% CI: 5.70-174.64); p=0.001), fatigue (OR=83.29, 95% CI: 4.77-145.69); p=0.002), bodyache (OR=4.44, 95% CI: 1.24-15.91); p=0.021) and peripheral neuropathy (OR=12.00, 95% CI: 1.80-79.89); p=0.010. Furthermore, the regression analysis indicated an association between CYP17 with body ache (OR=2.77, 95% CI: 1.21-6.34; p=0.015) and peripheral neuropathy (OR=3.90, 95% CI: 1.59-9.53; p=0.002) in BC patients treated with paclitaxel chemotherapy.
CONCLUSION
The findings obtained from this study illustrated significant association of CYP2C9*2 (681G>A) polymorphism with adreamicin based chemotherapy induced toxicities and CYP17 (34T>C) polymorphism with paclitaxel induced bodyache and peripheral neuropathy in BC patients.
Topics: Humans; Female; Breast Neoplasms; Paclitaxel; Doxorubicin; Cytochrome P-450 CYP2C19; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Polymorphism, Single Nucleotide; Adult; Steroid 17-alpha-Hydroxylase; Prognosis; Follow-Up Studies; Aged
PubMed: 38918659
DOI: 10.31557/APJCP.2024.25.6.1977 -
Oncoimmunology 2024Regulatory T cells (Tregs) play a crucial role in mediating immunosuppression in the tumor microenvironment. Furthermore, Tregs contribute to the lack of efficacy and...
Regulatory T cells (Tregs) play a crucial role in mediating immunosuppression in the tumor microenvironment. Furthermore, Tregs contribute to the lack of efficacy and hyperprogressive disease upon Programmed cell death protein 1 (PD-1) blockade immunotherapy. Thus, Tregs are considered a promising therapeutic target, especially when combined with PD-1 blockade. However, systemic depletion of Tregs causes severe autoimmune adverse events, which poses a serious challenge to Treg-directed therapy. Here, we developed a novel treatment to locally and predominantly damage Tregs by near-infrared duocarmycin photorelease (NIR-DPR). In this technology, we prepared anti-CD25 F(ab') conjugates, which site-specifically uncage duocarmycin in CD25-expressing cells upon exposure to NIR light. , CD25-targeted NIR-DPR significantly increased apoptosis of CD25-expressing HT2-A5E cells. When tumors were irradiated with NIR light , intratumoral CD25 Treg populations decreased and Ki-67 and Interleukin-10 expression was suppressed, indicating impaired functioning of intratumoral CD25 Tregs. CD25-targeted NIR-DPR suppressed tumor growth and improved survival in syngeneic murine tumor models. Of note, CD25-targeted NIR-DPR synergistically enhanced the efficacy of PD-1 blockade, especially in tumors with higher CD8/Treg PD-1 ratios. Furthermore, the combination therapy induced significant anti-cancer immunity including maturation of dendritic cells, extensive intratumoral infiltration of cytotoxic CD8 T cells, and increased differentiation into CD8 memory T cells. Altogether, CD25-targeted NIR-DPR locally and predominantly targets Tregs in the tumor microenvironment and synergistically improves the efficacy of PD-1 blockade, suggesting that this combination therapy can be a rational anti-cancer combination immunotherapy.
Topics: Animals; T-Lymphocytes, Regulatory; Mice; Programmed Cell Death 1 Receptor; Tumor Microenvironment; Duocarmycins; Immunoconjugates; Humans; Cell Line, Tumor; Female; Interleukin-2 Receptor alpha Subunit; Immune Checkpoint Inhibitors; Disease Models, Animal; Mice, Inbred C57BL; Apoptosis; Infrared Rays
PubMed: 38915782
DOI: 10.1080/2162402X.2024.2370544 -
PloS One 2024Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua...
BACKGROUND
Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification.
METHODS
The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments.
RESULTS
A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1β, STAT3, MMP-9, and TGF-β1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-β1/Smad2/3.
CONCLUSIONS
QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-β1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.
Topics: Pulmonary Fibrosis; Drugs, Chinese Herbal; Animals; Rats; Male; Network Pharmacology; Protein Interaction Maps; Bleomycin; Transforming Growth Factor beta1; Rats, Sprague-Dawley; Signal Transduction; Humans; COVID-19; Epithelial-Mesenchymal Transition; Medicine, Chinese Traditional; COVID-19 Drug Treatment
PubMed: 38913698
DOI: 10.1371/journal.pone.0305903 -
International Journal of Nanomedicine 2024The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative...
INTRODUCTION
The design of delivery tools that efficiently transport drugs into cells remains a major challenge in drug development for most pathological conditions. Triple-negative breast cancer (TNBC) is a very aggressive subtype of breast cancer with poor prognosis and limited effective therapeutic options.
PURPOSE
In TNBC treatment, chemotherapy remains the milestone, and doxorubicin (Dox) represents the first-line systemic treatment; however, its non-selective distribution causes a cascade of side effects. To address these problems, we developed a delivery platform based on the self-assembly of amphiphilic peptides carrying several moieties on their surfaces, aimed at targeting, enhancing penetration, and therapy.
METHODS
Through a single-step self-assembly process, we used amphiphilic peptides to obtain nanofibers decorated on their surfaces with the selected moieties. The surface of the nanofiber was decorated with a cell-penetrating peptide (gH625), an EGFR-targeting peptide (P22), and Dox bound to the cleavage sequence selectively recognized and cleaved by MMP-9 to obtain on-demand drug release. Detailed physicochemical and cellular analyses were performed.
RESULTS
The obtained nanofiber (NF-Dox) had a length of 250 nm and a diameter of 10 nm, and it was stable under dilution, ionic strength, and different pH environments. The biological results showed that the presence of gH625 favored the complete internalization of NF-Dox after 1h in MDA-MB 231 cells, mainly through a translocation mechanism. Interestingly, we observed the absence of toxicity of the carrier (NF) on both healthy cells such as HaCaT and TNBC cancer lines, while a similar antiproliferative effect was observed on TNBC cells after the treatment with the free-Dox at 50 µM and NF-Dox carrying 7.5 µM of Dox.
DISCUSSION
We envision that this platform is extremely versatile and can be used to efficiently carry and deliver diverse moieties. The knowledge acquired from this study will provide important guidelines for applications in basic research and biomedicine.
Topics: Doxorubicin; Triple Negative Breast Neoplasms; Humans; Nanofibers; Cell Line, Tumor; Female; Drug Delivery Systems; Cell-Penetrating Peptides; Drug Liberation; Cell Survival; Peptides; Antibiotics, Antineoplastic; ErbB Receptors; Matrix Metalloproteinase 9; Drug Carriers
PubMed: 38911501
DOI: 10.2147/IJN.S453958 -
Biology Direct Jun 2024Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have...
BACKGROUND
Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML.
METHODS
In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML.
RESULTS
We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells.
CONCLUSIONS
Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.
Topics: Leukemia, Myeloid, Acute; Humans; HMGA2 Protein; MicroRNAs; Drug Resistance, Neoplasm; Doxorubicin; RNA, Long Noncoding; Mice; Animals; Cell Line, Tumor; HL-60 Cells; Gene Silencing; Apoptosis; Cell Proliferation; Female
PubMed: 38910243
DOI: 10.1186/s13062-024-00490-1 -
Journal of Nanobiotechnology Jun 2024Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our...
Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.
Topics: Animals; Autophagy; Mice; Exosomes; MicroRNAs; Cold Temperature; Osteogenesis; Mice, Inbred C57BL; Mesenchymal Stem Cells; Osteoporosis; Cell Differentiation; Bone and Bones; Female; Bone Density; Sirolimus
PubMed: 38910236
DOI: 10.1186/s12951-024-02640-z -
Medical Oncology (Northwood, London,... Jun 2024The purpose of the present study was in vitro determination of the combined effects of doxorubucin and 5-fluorouracil by 2D and 3D culture conditions on breast cancer...
The purpose of the present study was in vitro determination of the combined effects of doxorubucin and 5-fluorouracil by 2D and 3D culture conditions on breast cancer using MCF-7 cell line and CSCs isolated from these cells. In the first stage of this study, CSC isolation and their characterization were performed. In the next experimental period, the antiproliferative effects of 5-Fu and Dox on the MCF-7 and CSCs were demonstrated on 2D. To evaluate the synergistic/antagonistic effects of these chemotherapeutics, the CI was calculated. Additionally, 3D tumor spheroids were used as another model. In the last step, qRT-PCR analysis was performed to examine apoptosis-related gene expressions. In this study, it was clearly seen that CSCs obtained from the breast cancer cell line express stemness factors. In addition, the antiproliferative effects of 5-Fu and Dox on breast cancer and associated CSCs were very clear. Their synergistic effects were determined by CI values. Moreover, it was seen that combined theraphy changed the expression levels of genes related to apoptosis. Additionally, it was molecularly demonstrated that 3D tumoroids were more resistant than the others. In conclusion, the polychemotherapeutic approach was much more effective than the monotherapy. The fact that this effect was seen not only in breast cancer cells, but also in breast cancer stem cells. In addition, it was very promising that the results obtained were similar in both two-dimensional and three-dimensional tumoroids.
Topics: Humans; Fluorouracil; Neoplastic Stem Cells; Doxorubicin; Breast Neoplasms; Female; MCF-7 Cells; Spheroids, Cellular; Apoptosis; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Drug Synergism
PubMed: 38910198
DOI: 10.1007/s12032-024-02423-4