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Frontiers in Pharmacology 2023Despite the low incidence of soft tissue sarcomas (STSs), hundreds of thousands of new STS cases are diagnosed annually worldwide, and approximately half of them... (Review)
Review
Despite the low incidence of soft tissue sarcomas (STSs), hundreds of thousands of new STS cases are diagnosed annually worldwide, and approximately half of them eventually progress to advanced stages. Currently, chemotherapy is the first-line treatment for advanced STSs. There are difficulties in selecting appropriate drugs for multiline chemotherapy, or for combination treatment of different STS histological subtypes. In this study, we first comprehensively reviewed the efficacy of various chemotherapeutic drugs in the treatment of STSs, and then described the current status of sensitive drugs for different STS subtypes. anthracyclines are the most important systemic treatment for advanced STSs. Ifosfamide, trabectedin, gemcitabine, taxanes, dacarbazine, and eribulin exhibit certain activities in STSs. Vinca alkaloid agents (vindesine, vinblastine, vinorelbine, vincristine) have important therapeutic effects in specific STS subtypes, such as rhabdomyosarcoma and Ewing sarcoma family tumors, whereas their activity in other subtypes is weak. Other chemotherapeutic drugs (methotrexate, cisplatin, etoposide, pemetrexed) have weak efficacy in STSs and are rarely used. It is necessary to select specific second- or above-line chemotherapeutic drugs depending on the histological subtype. This review aims to provide a reference for the selection of chemotherapeutic drugs for multi-line therapy for patients with advanced STSs who have an increasingly long survival.
PubMed: 37637411
DOI: 10.3389/fphar.2023.1199292 -
3 Biotech Jun 2023Vinca alkaloids including vincristine, vinblastine, vindesine, and vinflunine are chemotherapeutic compounds commonly used to treat various cancers. Vinca alkaloids are... (Review)
Review
Vinca alkaloids including vincristine, vinblastine, vindesine, and vinflunine are chemotherapeutic compounds commonly used to treat various cancers. Vinca alkaloids are one of the first microtubule-targeting agents to be produced and certified for the treatment of hematological and lymphatic neoplasms. Microtubule targeting agents like vincristine and vinblastine work by disrupting microtubule dynamics, causing mitotic arrest and cell death. The key issues facing vinca alkaloids applications include establishing an environment-friendly production technique based on microorganisms, as well as increasing bioavailability without causing harm to patient's health. The low yield of these vinca alkaloids from the plant and the difficulty of meeting their huge colossal demand around the globe prompted researchers to create a variety of approaches. Endophytes could thus be selected to produce beneficial secondary metabolites required for the biosynthesis of vinca alkaloids. This review covers the significant aspects of these vital drugs, from their discovery to the present day, in a concise manner. In addition, we emphasize the major hurdles that must be overcome in the coming years to improve vinca alkaloid's effectiveness.
PubMed: 37251731
DOI: 10.1007/s13205-023-03636-6 -
Cancers Jun 2023The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined...
Effect and Tolerance of N5 and N6 Chemotherapy Cycles in Combination with Dinutuximab Beta in Relapsed High-Risk Neuroblastoma Patients Who Failed at Least One Second-Line Therapy.
The anti-disialoganglioside (GD2) monoclonal antibody dinutuximab beta is approved for the maintenance treatment of high-risk neuroblastoma. Dinutuximab beta combined with different chemotherapy regimens is being investigated in various clinical settings. We conducted a retrospective clinical chart review of 25 patients with relapsed/refractory neuroblastoma who had failed ≥1 second-line therapy and received compassionate use treatment with dinutuximab beta long-term infusion combined with the induction chemotherapy regimens N5 (cisplatin, etoposide, vindesine) and N6 (vincristine, dacarbazine, ifosfamide, doxorubicin) recommended by the German Pediatric Oncology and Hematology Group [GPOH] guidelines. The treatment did not result in any unexpected severe toxicities or in any major treatment delays. Grade 3/4 pain was reported by 4/25 patients in cycle 1, decreasing to 0/9 patients in cycles 3 and 4. The median follow-up was 0.6 years. The best response in this group was 48% (12/25 patients), which included three patients with minor responses. At 1 year, the estimated event-free survival was 27% (95% confidence interval [CI] 8-47) and overall survival was 44% (95% CI 24-65). Combining long-term infusion of dinutuximab beta with N5 and N6 chemotherapy demonstrated an acceptable safety profile and encouraging objective response rates in heavily pretreated patients with high-risk neuroblastoma, warranting further evaluation in clinical trials.
PubMed: 37444475
DOI: 10.3390/cancers15133364 -
Blood Advances Oct 2021Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains...
Primary mediastinal B-cell lymphoma (PMBL) is a rare type of aggressive lymphoma typically affecting young female patients. The first-line standard of care remains debated. We performed a large multicenter retrospective study in 25 centers in France and Belgium to describe PMBL patient outcomes after first-line treatment in real-life settings. A total of 313 patients were enrolled and received rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone) (n = 180) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) delivered every 14 days (R-CHOP14, n = 76) or 21 days (R-CHOP21, n = 57) and consolidation strategies in modalities that varied according to time and institution, mainly guided by positron emission tomography. Consolidation autologous stem cell transplantation was performed for 46 (25.6%), 24 (31.6%), and 1 (1.8%) patient in the R-ACVBP, R-CHOP14, and R-CHOP21 groups, respectively (P < .001); only 17 (5.4%) patients received mediastinal radiotherapy. The end-of-treatment complete metabolic response rates were 86.3%, 86.8%, and 76.6% (P = .23) in the R-ACVBP, R-CHOP14, and R-CHOP21 groups. The median follow-up was 44 months, and the R-ACVBP, R-CHOP14, and R-CHOP21 three-year progression-free survival probabilities were 89.4% (95% confidence interval [CI], 84.8-94.2), 89.4% (95% CI, 82.7-96.6), and 74.7% (95% CI, 64-87.1) (P = .018). A baseline total metabolic tumor volume (TMTV) ≥360 cm3 was associated with a lower progression-free survival (hazard ratio, 2.18; 95% CI, 1.05-4.53). Excess febrile neutropenia (24.4% vs 5.3% vs 5.3%; P < .001) and mucositis (22.8% vs 3.9% vs 1.8%; P < .001) were observed with R-ACVBP compared with the R-CHOP regimens. Patients with PMBL treated with dose-dense immunochemotherapy without radiotherapy have excellent outcomes. R-ACVBP acute toxicity was higher than that of R-CHOP14. Our data confirmed the prognostic importance of baseline TMTV.
Topics: Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Female; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, Large B-Cell, Diffuse; Retrospective Studies; Transplantation, Autologous; Treatment Outcome
PubMed: 34461634
DOI: 10.1182/bloodadvances.2021004778 -
Clinical Lymphoma, Myeloma & Leukemia Oct 2020Despite its low frequency in all variants of diffuse large B-cell lymphoma (DLBCL), CD5 DLBCL has gradually gained the attention it deserves, the result of its poorer... (Review)
Review
Despite its low frequency in all variants of diffuse large B-cell lymphoma (DLBCL), CD5 DLBCL has gradually gained the attention it deserves, the result of its poorer outcomes compared to DLBCL without the CD5 signature. CD5 DLBCL is classified as activated B-cell-like (ABC)/non-germinal-center B-cell-like (GCB) DLBCL with elusive genetic features, and patients are frequently characterized as being older and female, and as having Eastern Cooperative Oncology Group performance status > 1, high International Prognostic Index score, tendency to develop B symptoms, and advanced-stage disease with high central nervous system relapse and bone marrow involvement rate. The mechanism underlying the poor prognosis in CD5 DLBCL has not been fully explored, and we summarize the reported potential mechanisms, including CD5-mediated B-cell receptor (BCR)-dependent and -independent pathways. The former involves the inhibition of BCR signaling, and the latter involves the BCR-independent overexpression of interleukin 10, Bcl-2 (antiapoptotic B-cell leukemia/lymphoma 2), cyclin D2, and CXCR4 (C-X-C motif chemokine receptor 4). The efficacy of traditional regimen R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is currently not satisfied in CD5 DLBCL. Therapies of larger doses, such as R-DA-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab), R-ACVBP (rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone), R-DA-EPOCH plus central nervous system prophylaxis, can improve the overall survival in CD5 DLBCL patients, while allogeneic hematopoietic stem-cell transplantation still remains controversial as a salvage treatment. In addition, some novel drugs, such as lenalidomide, CXCR4 antagonists, Bruton tyrosine kinase inhibitors, Bcl-2 inhibitors, and immunotherapy, have been reported to have encouraging results and may improve the outcomes of these patients. In the present review, we comprehensively summarize the biology, mechanism, and treatment of CD5 DLBCL.
Topics: CD5 Antigens; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male
PubMed: 32694049
DOI: 10.1016/j.clml.2020.05.003 -
Journal of Healthcare Engineering 2022To explore the relationship between vitamins levels and disease-related indicators in children with acute leukemia (AL).
OBJECTIVE
To explore the relationship between vitamins levels and disease-related indicators in children with acute leukemia (AL).
METHODS
A total of 107 hospitalized children with AL were enrolled in this study and assigned to one group in each of the following categories: infected group ( = 52) and noninfected group ( = 55); treatment remission group ( = 56) and nonremission group ( = 51); high-risk (HR) group ( = 44), intermediate risk (IR) group ( = 53), and slight risk (SR) group ( = 8); cyclophosphamide + cytosine arabinoside+6-mercaptopurine + pegaspargase group (CAML, = 15); methotrexate group (MTX, = 9); and vindesine + daunomycin + L-asparaginasum + prednisone (VALP, = 38). Hematological and serological parameters, hepatic and renal function, and changes in vitamins A, B1, B2, B6, B9, B12, C, D, and E serum content in children with AL were analyzed to investigate their relationship with AL disease-related factors.
RESULTS
The vitamin D level was significantly higher in the noninfected group than in the infected group ( < 0.05). Compared with the nonremission group, the level of vitamin B1 in the treatment remission group was significantly higher, while the levels of vitamin B6 and B12 were notably lower ( < 0.05). The levels of vitamins B6 and B12 were notably different among the treatment groups. Multivariate analysis showed that hemoglobin (Hb) and C-reactive protein (CRP) were predisposing factors of AL in children. The disease type (acute lymphoblastic leukemia/acute myelogenous leukemia) was the factor affecting remission in AL children. Abnormal kidney function and the occurrence of icterus were the influencing factors for the risk degree in AL children. Platelet (PLT) count, activated partial thromboplastin time (APTT), neutrophils (N), and immunophenotype were shown to affect the choice of therapeutic regimens.
CONCLUSION
There are notable vitamins imbalances in children with AL. The imbalances influence disease-related factors and therefore provide some references for the prognosis and treatment of AL.
Topics: Causality; Child; Humans; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Vitamins
PubMed: 35463661
DOI: 10.1155/2022/5330563 -
Cancer Cell International Jun 2022Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and... (Review)
Review
Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and drug therapy, along with others, which not only put a tremendous economic effect on patients but also develop drug resistance in patients with time. A significant number of cancer cases can be prevented/treated by implementing evidence-based preventive strategies. Plant-based drugs have evolved as promising preventive chemo options both in developing and developed nations. The secondary plant metabolites such as alkaloids have proven efficacy and acceptability for cancer treatment. Apropos, this review deals with a spectrum of promising alkaloids such as colchicine, vinblastine, vincristine, vindesine, vinorelbine, and vincamine within different domains of comprehensive information on these molecules such as their medical applications (contemporary/traditional), mechanism of antitumor action, and potential scale-up biotechnological studies on an in-vitro scale. The comprehensive information provided in the review will be a valuable resource to develop an effective, affordable, and cost effective cancer management program using these alkaloids.
PubMed: 35655306
DOI: 10.1186/s12935-022-02624-9 -
International Journal of Molecular... Mar 2023Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and...
Cardiovascular complications combined with COVID-19 (SARS-CoV-2) lead to a poor prognosis in patients. The common pathogenesis of ischemic cardiomyopathy (ICM) and COVID-19 is still unclear. Here, we explored potential molecular mechanisms and biomarkers for ICM and COVID-19. Common differentially expressed genes (DEGs) of ICM (GSE5406) and COVID-19 (GSE164805) were identified using GEO2R. We performed enrichment and protein-protein interaction analyses and screened key genes. To confirm the diagnostic performance for these hub genes, we used external datasets (GSE116250 and GSE211979) and plotted ROC curves. Transcription factor and microRNA regulatory networks were constructed for the validated hub genes. Finally, drug prediction and molecular docking validation were performed using cMAP. We identified 81 common DEGs, many of which were enriched in terms of their relation to angiogenesis. Three DEGs were identified as key hub genes (, , and ) in the protein-protein interaction analysis. These hub genes had high diagnostic performance in the four datasets (AUC > 0.7). Mir-16-5p and KLF9 transcription factor co-regulated these hub genes. The drugs vindesine and ON-01910 showed good binding performance to the hub genes. We identified , , and as markers for the co-pathogenesis of ICM and COVID-19, and showed that co-pathogenesis of ICM and COVID-19 may be related to angiogenesis. Vindesine and ON-01910 were predicted as potential therapeutic agents. Our findings will contribute to a deeper understanding of the comorbidity of ICM with COVID-19.
Topics: Humans; Systems Biology; Molecular Docking Simulation; Vindesine; COVID-19; SARS-CoV-2; Computational Biology; Myocardial Ischemia; Comorbidity; MicroRNAs; Biomarkers; Transcription Factors; Cardiomyopathies; Gene Expression Profiling
PubMed: 37047484
DOI: 10.3390/ijms24076511 -
Frontiers in Oncology 2021Although pegylated liposomal doxorubicin (PLD) has been approved in combination with bortezomib for relapsed/refractory multiple myeloma (MM), the antitumor efficacy and...
Pegylated Liposomal Doxorubicin in Vindesine-Based and Bortezomib-Based Regimens for Patients With Newly Diagnosed Multiple Myeloma: A Retrospective Study of Efficacy and Safety.
PURPOSE
Although pegylated liposomal doxorubicin (PLD) has been approved in combination with bortezomib for relapsed/refractory multiple myeloma (MM), the antitumor efficacy and tolerability of PLD in different regimens for patients with newly diagnosed MM (NDMM) have not been fully defined.
METHODS
A total of 249 NDMM patients diagnosed between January 2008 and October 2019 were included in this retrospective study. Among them, 112 patients received vindesine-based chemotherapy (35 vDD and 77 vAD) and 137 received bortezomib-based chemotherapy (58 VDD and 79 VD).
RESULTS
In bortezomib-containing regimens, the complete response rate (48.3 30.4%, p = 0.033) and very good partial response or better rate (74.1 . 57.0%, p = 0.038) of VDD were significantly higher than those of VD subgroup. While no superior survival was found between VDD and VD subgroup. In vindesine-containing regimens, no statistical significance was identified between vDD and vAD in terms of response rate and survival. The occurrence rates of all cardiac AEs were similar between VDD and VD.
CONCLUSIONS
The vDD regimen was similar with vAD in the aspect of response rate, survival, and toxicity in NDMM patients. The addition of PLD to VD brought deeper response without increased toxicity, while no superior survival was found.
PubMed: 33842312
DOI: 10.3389/fonc.2021.597453