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Medicine Feb 2024Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory...
Therapeutic efficacy of high-dose chemotherapy with autologous stem-cell transplantation in 44 relapsed or refractory germ-cell tumor patients: A retrospective cohort study.
Despite having a higher mortality risk than conventional chemotherapeutics, high-dose chemotherapy (HDCT) has the potential to be curative in relapsed/refractory germ-cell tumors. Therefore, selecting the best patient group for this treatment is critical. This study aimed to determine the factors that affect survival in our relapsed/refractory GCT cohort who received HDCT and autologous stem-cell transplantation. Between September 2010 and 2020, we included in the study 44 relapsed/refractory male patients with GCT treated with HDCT plus autologous stem-cell transplantation. The patients' demographic features, clinical characteristics, and treatment outcomes were evaluated. Statistical analyses were performed to identify risk factors associated with survival. The median age of all cohorts was 28 years. Thirty-six patients had nonseminomatous tumors, and 8 patients had seminomatous tumors. The most common primary tumor sites were the gonads (75%), followed by the mediastinum (15.9%) and the retroperitoneum (9.1%). After HDCT, 11 patients had a complete response, 12 patients had a partial response, and 17 patients had a progressive disease, respectively. About 23 patients (52.3%) experienced at least 1 treatment-related grade 3 to 4 nonhematological toxicity. About 4 patients (10%) died due to HDCT-related toxicity. The total group's median progression-free survival (PFS) was 7 months, and the median overall survival (OS) was 14.9 months. Primary tumor site (hazard ratio [HR]: 1.84; P = .028), type of HDCT regimen (HR: 0.35; P = .010), and best response to HDCT (HR: 11.0; P < .0001) were independent prognostic risk factors for PFS. The only independent prognostic risk factor associated with OS was the best response to HDCT (HR: 6.62; P = .001). The results of the study promise the best response to HDCT as a primary measure for predicting survival in relapsed/refractory GCT. In contrast, primary mediastinal GCT is not a good candidate for HDCT. Furthermore, a carboplatin-etoposide regimen in combination with cyclophosphamide and paclitaxel may improve PFS.
Topics: Humans; Male; Adult; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Neoplasms, Germ Cell and Embryonal; Paclitaxel; Transplantation, Autologous; Etoposide; Salvage Therapy
PubMed: 38394499
DOI: 10.1097/MD.0000000000037213 -
Pharmaceutical Biology Dec 2024Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.
CONTEXT
Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.
OBJECTIVE
This study synthesizes PPT derivatives to assess their anticancer activities.
MATERIALS AND METHODS
Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound on A549 cell growth were evaluated through molecular docking, assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and tests in female BALB/c nude mice treated with (2 and 4 mg/kg). (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group.
RESULTS
Among the 16 PPT derivatives tested for cytotoxicity, exhibited potent effects against A549 cells (IC: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. -induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins.
DISCUSSION AND CONCLUSIONS
This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with call for extended research and clinical validation, leading to novel and more effective cancer therapies.
Topics: Mice; Animals; Humans; Female; Podophyllotoxin; Tubulin; Molecular Docking Simulation; Mice, Nude; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Drug Screening Assays, Antitumor; Antineoplastic Agents; Cell Proliferation; Cell Line, Tumor; Apoptosis; Tubulin Modulators
PubMed: 38393642
DOI: 10.1080/13880209.2024.2318350 -
Cytotherapy May 2024The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve...
Prognostic differences between carmustine, etoposide, cytarabine and melphalan (BEAM) and carmustine, etoposide, cytarabine, melphalan and fludarabine (BEAMF) regimens before autologous stem cell transplantation plus chimeric antigen receptor T therapy in patients with refractory/relapsed B-cell...
BACKGROUND AIMS
The combination therapy of autologous hematopoietic stem cell transplantation (ASCT) and chimeric antigen receptor T-cell (CART) therapy has been employed to improve outcomes for relapsed or refractory (R/R) B-cell non-Hodgkin-lymphoma (B-NHL). The widely used conditioning regimen before ASCT plus CART therapy reported in the literature was carmustine, etoposide, cytarabine and melphalan (BEAM). However, whether adding fludarabine to the BEAM regimen (BEAMF) can improve the survival of patients with R/R B-NHL remains unknown.
METHODS
In total, 39 and 19 patients with R/R B-NHL were enrolled to compare clinical outcomes in the BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy, respectively.
RESULTS
The objective response (OR) rates at 3 months to BEAM and BEAMF regimens before ASCT plus CD19/22 CART therapy were 71.8% and 94.7%, respectively (P = 0.093). The BEAMF regimen showed a trend towards a superior duration of response compared with the BEAM regimen (P = 0.09). After a median follow-up of 28 months (range: 0.93-51.9 months), the BEAMF regimen demonstrated superior 2-year progression-free survival (PFS) (89.5% versus 63.9%; P = 0.048) and 2-year overall survival (OS) (100% vs 77.3%; P = 0.035) compared with the BEAM regimen. In the multivariable Cox regression analysis, OR at month 3 (responders) was remarkably correlated with better OS (hazard ratio: 0.112, P = 0.005) compared with OR (non-responders).
CONCLUSIONS
For patients with R/R B-NHL, the BEAMF regimen before ASCT plus CD19/22 CART therapy was correlated with superior PFS and OS than the BEAM regimen, and the BEAMF regimen is a promising alternative conditioning regimen for ASCT plus CAR-T therapy.
Topics: Humans; Male; Carmustine; Melphalan; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Middle Aged; Adult; Transplantation, Autologous; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Vidarabine; Prognosis; Aged; Lymphoma, B-Cell; Podophyllotoxin; Immunotherapy, Adoptive; Young Adult; Combined Modality Therapy; Transplantation Conditioning; Receptors, Chimeric Antigen
PubMed: 38385909
DOI: 10.1016/j.jcyt.2024.01.012 -
Scientific Reports Feb 2024Circulating endothelial cells (CEC) are arising as biomarkers for vascular diseases. However, whether they can be utilized as markers of endothelial cell (EC) senescence...
Circulating endothelial cells (CEC) are arising as biomarkers for vascular diseases. However, whether they can be utilized as markers of endothelial cell (EC) senescence in vivo remains unknown. Here, we present a protocol to isolate circulating endothelial cells for a characterization of their senescent signature. Further, we characterize different models of EC senescence induction in vitro and show similar patterns of senescence being upregulated in CECs of aged patients as compared to young volunteers. Replication-(ageing), etoposide-(DNA damage) and angiotensin II-(ROS) induced senescence models showed the expected cell morphology and proliferation-reduction effects. Expression of senescence-associated secretory phenotype markers was specifically upregulated in replication-induced EC senescence. All models showed reduced telomere lengths and induction of the INK4a/ARF locus. Additional p14ARF-p21 pathway activation was observed in replication- and etoposide-induced EC senescence. Next, we established a combined magnetic activated- and fluorescence activated cell sorting (MACS-FACS) based protocol for CEC isolation. Interestingly, CECs isolated from aged volunteers showed similar senescence marker patterns as replication- and etoposide-induced senescence models. Here, we provide first proof of senescence in human blood derived circulating endothelial cells. These results hint towards an exciting future of using CECs as mirror cells for in vivo endothelial cell senescence, of particular interest in the context of endothelial dysfunction and cardiovascular diseases.
Topics: Humans; Aged; Endothelial Cells; Etoposide; Cellular Senescence; Aging; Vascular Diseases
PubMed: 38383692
DOI: 10.1038/s41598-024-54455-5 -
The Journal of Dermatological Treatment Dec 2024
Topics: Humans; Sarcoma, Ewing; Etoposide; Ifosfamide; Neoadjuvant Therapy; Psoriasis; Thalidomide
PubMed: 38378173
DOI: 10.1080/09546634.2024.2319303 -
The Oncologist May 2024MAURIS is an Italian multicenter, open-label, phase IIIb ongoing trial, aiming at evaluating the safety and effectiveness of atezolizumab + carboplatin/etoposide in...
BACKGROUND
MAURIS is an Italian multicenter, open-label, phase IIIb ongoing trial, aiming at evaluating the safety and effectiveness of atezolizumab + carboplatin/etoposide in patients with newly diagnosed, extensive-stage small-cell lung cancer (ES-SCLC). The primary objective is the safety evaluation.
MATERIALS AND METHODS
Patients received atezolizumab + carboplatin/etoposide Q3W for 4-6 cycles in the induction phase, followed by atezolizumab maintenance Q3W. We presented the interim analysis on safety (referring to the induction phase) and clinical effectiveness, in all patients (N = 154) and in subgroups that received ≤3 (N = 23), 4 (N = 43), and 5-6 cycles (N = 89) of induction.
RESULTS
At a median follow-up of 10.5 months, 139 patients (90.3%) discontinued treatment. Serious adverse events occurred in 29.9% of patients overall, and the rate was lower in patients with 5-6 cycles (19.1%) than in those with 4 (34.9%) or ≤3 (63.6%) cycles. Immune-mediated adverse events were reported in 14.9%, 15.7%, 11.6%, and 18.2% of patients, overall and by subgroup, respectively. The median overall survival and progression-free survival were 10.7 and 5.5 months, respectively. Overall, 111 patients (71.6%) had a tumor response.
CONCLUSIONS
Interim results provide further evidences about safety and efficacy profile of atezolizumab + carboplatin/etoposide treatment in a ES-SCLC patient population closer to that observed in clinical practice.
CLINICAL TRIAL REGISTRATION
Eudract No. 2019-001146-17, NCT04028050.
Topics: Humans; Carboplatin; Etoposide; Male; Female; Small Cell Lung Carcinoma; Lung Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal, Humanized; Middle Aged; Aged; Adult; Aged, 80 and over
PubMed: 38377176
DOI: 10.1093/oncolo/oyad342 -
Food Science & Nutrition Feb 2024Pinobanksin, as one of the flavonoids, has powerful biological activities but has been under-recognized. In this study, we optimized the extraction method of phragmites...
Pinobanksin, as one of the flavonoids, has powerful biological activities but has been under-recognized. In this study, we optimized the extraction method of phragmites from peony seed shells by using organic solvent extraction. The yield of PSMS was 10.54 ± 0.13% under the conditions of ethanol volume fraction 70%, extraction temperature 70°C, material-liquid ratio 1:25 g/mL, and extraction time 60 min; the optimized PSMS could be effectively separated in S-8 macroporous resin coupled with C18. The relative content of PSMS was increased from 0.42% in PSMS to 92.53% after C18 purification; the antioxidant activity test revealed that pinobanksin could exert antioxidant ability by binding catalase (CAT) enzyme. Second, it was found that pinobanksin could effectively inhibit the proliferation of SH-SY5Y cells, mainly by binding to BCL2-associated X (BAX), B-cell lymphoma-2 (BCL-2), and cyclin-dependent Kinase 4/6 (CDK4/6) to produce more hydrogen bonds to inhibit their activities. This study confirms the medicinal potential of pinobanksin and provides the basis for the proper understanding of pinobanksin and the development of related products.
PubMed: 38370064
DOI: 10.1002/fsn3.3786 -
Drug Delivery and Translational Research Aug 2024Neuroblastoma is a pediatric tumor that originates during embryonic development and progresses into aggressive tumors, primarily affecting children under two years old....
Neuroblastoma is a pediatric tumor that originates during embryonic development and progresses into aggressive tumors, primarily affecting children under two years old. Many patients are diagnosed as high-risk and undergo chemotherapy, often leading to short- and long-term toxicities. Nanomedicine offers a promising solution to enhance drug efficacy and improve physical properties. In this study, lipid-based nanomedicines were developed with an average size of 140 nm, achieving a high encapsulation efficiency of over 90% for the anticancer drug etoposide. Then, cytotoxicity and apoptosis-inducing effects of these etoposide nanomedicines were assessed in vitro using human cell lines, both cancerous and non-cancerous. The results demonstrated that etoposide nanomedicines exhibited high toxicity and selectively induced apoptosis only in cancerous cells.Next, the biosafety of these nanomedicines in C. elegans, a model organism, was evaluated by measuring survival, body size, and the effect on dividing cells. The findings showed that the nanomedicines had a safer profile than the free etoposide in this model. Notably, nanomedicines exerted etoposide's antiproliferative effect only in highly proliferative germline cells. Therefore, the developed nanomedicines hold promise as safe drug delivery systems for etoposide, potentially leading to an improved therapeutic index for neuroblastoma treatment.
Topics: Etoposide; Caenorhabditis elegans; Animals; Humans; Apoptosis; Cell Line, Tumor; Nanomedicine; Lipids; Nanoparticles; Antineoplastic Agents, Phytogenic; Cell Survival; Cell Proliferation; Particle Size
PubMed: 38363484
DOI: 10.1007/s13346-023-01466-w -
Cancer Medicine Jan 2024High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of...
BACKGROUND
High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) remains an effective treatment for non-Hodgkin lymphoma (NHL). The limited availability of carmustine has prompted the exploration of novel alternative conditioning regimens. This study aimed to compare the efficacy and safety profile of GBM/GBC (gemcitabine, busulfan, and melphalan or cyclophosphamide) conditioning compared with the standard BEAM/BEAC regimens (carmustine, etoposide, cytarabine, and melphalan or cyclophosphamide) for ASCT in patients with NHL.
METHODS
A retrospective analysis was conducted on 231 NHL patients, who underwent ASCT from October 2010 to October 2021 at the Institute of Hematology & Blood Disease Hospital, including both first-line and salvage settings. This resulted in the inclusion of 112 patients in the GBM/GBC arm and 92 in the BEAM/BEAC arm. Propensity score matching was employed to validate the results.
RESULTS
Disease subtype distribution was similar between the GBM/GBC and BEAM/BEAC groups, with diffuse large B-cell lymphoma being the most common (58.9% vs. 58.7%), followed by PTCL (17.0% vs. 18.5%) and MCL (14.3% vs. 14.1%). At 3 months post-ASCT, complete response (CR) rates were comparable (GBM/GBC 93.5% vs. BEAM/BEAC 91.1%; p = 0.607). The 4-year progression-free survival (78.4% vs. 82.3%; p = 0.455) and 4-year overall survival (88.1% vs. 87.7%; p = 0.575) were also similar. Both groups exhibited low non-relapse mortality at 4 years (GBM/GBC 1.8% vs. BEAM/BEAC 3.5%; p = 0.790) with no transplant-related mortalities reported. The GBM/GBC cohort demonstrated a higher incidence of grade 3/4 oral mucositis and hepatic toxicity, whereas the BEAM/BEAC group had more frequent cases of bacteremia or sepsis (13 cases vs. 5 in GBM/GBC).
CONCLUSIONS
The GBM/GBC regimen is effective and well-tolerated, offering outcomes that are highly comparable to those in NHL patients conditioned with BEAM/BEAC, as demonstrated in a prognostically matched cohort.
Topics: Humans; Carmustine; Gemcitabine; Hematopoietic Stem Cell Transplantation; Melphalan; Retrospective Studies; Transplantation, Autologous; Lymphoma, Non-Hodgkin; Cyclophosphamide; Etoposide; Cytarabine; Antineoplastic Combined Chemotherapy Protocols; Transplantation Conditioning
PubMed: 38348996
DOI: 10.1002/cam4.6965 -
Frontiers in Immunology 2024Tracheal small cell carcinoma (SCC) is a rare malignancy, for which the optimal treatment strategy has yet to be determined. Currently, treatment largely aligns with the... (Review)
Review
Tracheal small cell carcinoma (SCC) is a rare malignancy, for which the optimal treatment strategy has yet to be determined. Currently, treatment largely aligns with the therapeutic guidelines established for small cell lung cancer, although numerous unresolved issues remain. This paper details a case study of a patient with Stage IIIB primary tracheal SCC, who was treated with an immune-combined etoposide-platinum(EP) regimen. This treatment offers valuable insights into innovative approaches for managing such malignancies. Furthermore, the study includes a comprehensive literature review to better contextualize the findings. The patient, admitted on May 2, 2023, had been experiencing persistent symptoms of airway discomfort for 15 days. A bronchoscopy performed on May 4 revealed tracheal SCC, classified as T4N2M0, IIIB. Following the CAPSTONE-1 study's methodology, the patient underwent six cycles of PD-L1(adebrelimab) combined with EP therapy, leading to significant relief of symptoms and the eventual disappearance of the tracheal mass.
Topics: Humans; Carcinoma, Small Cell; Antineoplastic Combined Chemotherapy Protocols; Etoposide; Small Cell Lung Carcinoma; Lung Neoplasms
PubMed: 38348051
DOI: 10.3389/fimmu.2024.1356268