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Frontiers in Public Health 2024Progressive glioblastoma (GBM) is a malignancy with extremely poor prognosis. Chemotherapy is one of the approved systemic treatment modalities. The aim of this study is...
BACKGROUND
Progressive glioblastoma (GBM) is a malignancy with extremely poor prognosis. Chemotherapy is one of the approved systemic treatment modalities. The aim of this study is to assess the cost-effectiveness of using bevacizumab (BEV) in combination with lomustine (LOM) regimen for the treatment of progressive glioblastoma in China.
METHODS
The estimation results are derived from a multicenter randomized phase III trial, which demonstrated improved survival in GBM patients receiving BEV+LOM combination therapy. To calculate the incremental cost-effectiveness ratio (ICER) from the perspective of Chinese society, a Markov model was established. Univariate deterministic analysis and probabilistic sensitivity analysis were employed to address the uncertainties within the model.
RESULTS
Compared to LOM monotherapy, the total treatment cost for BEV+LOM combination therapy increased from $2,646.70 to $23,650.98. The health-adjusted life years (QALYs) for BEV+LOM combination therapy increased from 0.26 QALYs to 0.51 QALYs, representing an increment of 0.25 QALYs. The incremental cost-effectiveness ratio (ICER) was $84,071.12. The cost-effectiveness curve indicates that within the willingness-to-pay (WTP) range of $35,906 per QALY, BEV+LOM combination therapy is not a cost-effective treatment option for unresectable malignant pleural mesothelioma patients.
CONCLUSIONS
Taken as a whole, the findings of this study suggest that, from the perspective of payers in China, BEV+LOM combination therapy as a first-line treatment for GBM is not a cost-effective option. However, considering the survival advantages this regimen may offer for this rare disease, it may still be one of the clinical treatment options for this patient population.
Topics: Bevacizumab; Glioblastoma; Humans; Cost-Benefit Analysis; Lomustine; Markov Chains; China; Antineoplastic Combined Chemotherapy Protocols; Quality-Adjusted Life Years; Brain Neoplasms; Cost-Effectiveness Analysis
PubMed: 38883194
DOI: 10.3389/fpubh.2024.1410355 -
Frontiers in Pharmacology 2024Celastrol (Cel) is a widely used main component of Chinese herbal medicine with strong anti-inflammatory, antiviral and antitumor activities. In the present study, we...
Celastrol (Cel) is a widely used main component of Chinese herbal medicine with strong anti-inflammatory, antiviral and antitumor activities. In the present study, we aimed to elucidate the cellular molecular protective mechanism of Cel against diabetes-induced inflammation and endothelial dysfunction. Type 2 diabetes (T2DM) was induced by db/db mice, and osmotic pumps containing Cel (100 μg/kg/day) were implanted intraperitoneally and were calibrated to release the drug for 28 days. In addition, human umbilical vein endothelial cells (HUVECs) were cultured in normal or high glucose and palmitic acid-containing (HG + PA) media in the presence or absence of Cel for 48 h. Cel significantly ameliorated the hyperglycemia-induced abnormalities in nuclear factor (erythroid-derived 2)-like protein 2 (Nrf2) pathway activity and alleviated HG + PA-induced oxidative damage. However, the protective effect of Cel was almost completely abolished in HUVECs transfected with short hairpin (sh)RNA targeting Nrf2, but not by nonsense shRNA. Furthermore, HG + PA reduced the phosphorylation of AMP-activated protein kinase (AMPK), the autophagic degradation of p62/Kelch-like ECH-associated protein 1 (Keap1), and the nuclear localization of Nrf2. However, these catabolic pathways were inhibited by Cel treatment in HUVECs. In addition, compound C (AMPK inhibitors) and reduced Cel-induced Nrf2 activation and angiogenesis in db/db mice. Taking these findings together, the endothelial protective effect of Cel in the presence of HG + PA may be at least in part attributed to its effects to reduce reactive oxygen species (ROS) and inflammation through p62/Keap1-mediated Nrf2 activation.
PubMed: 38881873
DOI: 10.3389/fphar.2024.1360177 -
Scientific Reports Jun 2024We assessed the short-term effects of switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) on ocular blood flow in patients with...
We assessed the short-term effects of switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) on ocular blood flow in patients with treatment-resistant diabetic macular edema (DME). The medical records of 15 patients with DME who had received IVA injection ≥ 3 months before were retrospectively reviewed. The best-corrected visual acuity, central macular thickness (CMT) on optical coherence tomography, and mean blur rate (MBR) of all disc areas on laser speckle flowgraphy were measured before, 1 week after, and 4 weeks after IVA and IVF, respectively. The changes in visual acuity showed no significant difference after switching from IVA to IVF (P = 0.732). The mean CMT decreased significantly during the follow-up period (both P < 0.001). MBR showed no significant difference during the follow-up period (P = 0.26). However, it decreased significantly 4 weeks after IVF (P = 0.01) compared with the baseline value, but not 4 weeks after IVA (P = 0.074). A significant association was observed between decreased MBR and decreased CMT in patients who received IVF (correlation coefficient: 0.501, P = 0.005) but not in those who received IVA (P = 0.735). Thus, IVF maintained ocular blood flow reduction, although no significant differences in visual acuity and CMT changes were observed compared to IVA.
Topics: Humans; Macular Edema; Male; Female; Intravitreal Injections; Recombinant Fusion Proteins; Receptors, Vascular Endothelial Growth Factor; Middle Aged; Diabetic Retinopathy; Aged; Retrospective Studies; Visual Acuity; Tomography, Optical Coherence; Angiogenesis Inhibitors; Regional Blood Flow; Eye
PubMed: 38877041
DOI: 10.1038/s41598-024-63435-8 -
PloS One 2024Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far,...
BACKGROUND
Anti-vascular endothelial growth factor (VEGF) monoclonal antibodies (mAbs) are widely used for tumor treatment, including metastatic colorectal cancer (mCRC). So far, there are no biomarkers that reliably predict resistance to anti-VEGF mAbs like bevacizumab. A biomarker-guided strategy for early and accurate assessment of resistance could avoid the use of non-effective treatment and improve patient outcomes. We hypothesized that repeated analysis of multiple cytokines and angiogenic growth factors (CAFs) before and during treatment using machine learning could provide an accurate and earlier, i.e., 100 days before conventional radiologic staging, prediction of resistance to first-line mCRC treatment with FOLFOX plus bevacizumab.
PATIENTS AND METHODS
15 German and Austrian centers prospectively recruited 50 mCRC patients receiving FOLFOX plus bevacizumab as first-line treatment. Plasma samples were collected every two weeks until radiologic progression (RECIST 1.1) as determined by CT scans performed every 2 months. 102 pre-selected CAFs were centrally analyzed using a cytokine multiplex assay (Luminex, Myriad RBM).
RESULTS
Using random forests, we developed a predictive machine learning model that discriminated between the situations of "no progress within 100 days before radiological progress" and "progress within 100 days before radiological progress". We could further identify a combination of ten out of the 102 CAF markers, which fulfilled this task with 78.2% accuracy, 71.8% sensitivity, and 82.5% specificity.
CONCLUSIONS
We identified a CAF marker combination that indicates treatment resistance to FOLFOX plus bevacizumab in patients with mCRC within 100 days prior to radiologic progress.
Topics: Humans; Colorectal Neoplasms; Bevacizumab; Leucovorin; Antineoplastic Combined Chemotherapy Protocols; Female; Organoplatinum Compounds; Male; Fluorouracil; Middle Aged; Aged; Drug Resistance, Neoplasm; Prospective Studies; Adult; Neoplasm Metastasis; Biomarkers, Tumor
PubMed: 38875244
DOI: 10.1371/journal.pone.0304324 -
Immunity, Inflammation and Disease Jun 2024The heterogeneity of tumor endothelial cells (TECs) hinders the efficacy of antiangiogenic therapies (AATs). Only a small percentage of angiogenic TECs are considered...
BACKGROUND
The heterogeneity of tumor endothelial cells (TECs) hinders the efficacy of antiangiogenic therapies (AATs). Only a small percentage of angiogenic TECs are considered effective targets for AATs. Immunomodulatory ECs (IMECs), as a newly focused functional subgroup of endothelial cells (ECs), are being evaluated for their ability to regulate tumor immune balance and influence existing AATs.
METHODS
Based on single-cell transcriptome data from colorectal cancer in a publicly available database, we conducted a wide array of bioinformatic approaches to study EC subsets that meet the IMECs definition. Our investigation encompassed the gene expression signatures of these subsets, cellular composition differences, cell-cell interactions.
RESULTS
Two subsets that meet the IMECs definition were found in tumors and para-cancerous tissues. Combined with the results of gene ontological analysis and interaction with CD4 T cells, we found that IMECs can present MHC-II antigens to mature CD4 T cells. There were differences in the level of interaction between IMECs and different types of mature CD4 T cell subsets. In addition, IMEC subsets had different expression levels of angiogenesis related genes. The angiogenesis score of IMECs decreased after patients received immunotherapy. IMEC subsets do not depend on a single proangiogenic receptor and are involved in regulating angiogenesis, which may reduce the efficacy of AATs. The adverse effects of specific IMEC subsets on AATs were validated in the RNA-seq dataset of the bevacizumab treatment group.
CONCLUSION
Our study suggests the potential MHC-II antigen presentation capacity of IMECs and the enhanced angiogenesis characteristics within tumors. The function of IMECs in the vascular network may have a potentially adverse effect on AATs. Controlling the functional properties of IMECs may be a new angle for tumor therapy.
Topics: Humans; Colorectal Neoplasms; Endothelial Cells; Single-Cell Analysis; Transcriptome; Antigen Presentation; Neovascularization, Pathologic; Drug Resistance, Neoplasm; Gene Expression Profiling; Angiogenesis Inhibitors; Immunomodulation; CD4-Positive T-Lymphocytes
PubMed: 38874280
DOI: 10.1002/iid3.1311 -
Oncology Letters Aug 2024Skin metastasis from ovarian cancer is rare, and its prognosis is poor. Effective therapeutic strategies are currently lacking, but the combination of various treatment...
Skin metastasis from ovarian cancer is rare, and its prognosis is poor. Effective therapeutic strategies are currently lacking, but the combination of various treatment methods shrink the tumor and relieve symptoms. The present study reports a rare case of advanced ovarian cancer with skin metastases and intestinal wall thickening, along with a BRCA1 DNA repair associated (BRCA1) mutation. After standard first-line treatment and non-standard second-line treatment, the patient developed skin metastases. The patient's skin itching, pain and lesions were completely relieved after administering bevacizumab in combination with paclitaxel and carboplatin. After 4 months, skin metastases recurred along with anal distension during maintenance treatment with oral poly(ADP ribose) polymerase (PARP) inhibitors. The patient was treated again with bevacizumab combined with docetaxel, and the anal distension was significantly relieved. Angiogenesis therapy combined with chemotherapy is effective, but that the disease-free survival time is short, and PARP inhibitor maintenance effect is limited even in cases with a BRCA1 gene mutation.
PubMed: 38872856
DOI: 10.3892/ol.2024.14481 -
Cancer Medicine Jun 2024Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have...
Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.
BACKGROUND
Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2.
METHODS
In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed.
RESULTS
Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths.
CONCLUSIONS
Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Endostatins; Immunotherapy; Indoles; Lung Neoplasms; Neoplasm Staging; Quality of Life; Quinolines; Retrospective Studies
PubMed: 38872402
DOI: 10.1002/cam4.7349 -
Scientific Reports Jun 2024We identified characteristics of patients with subretinal fluid (SRF) in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and determined their...
We identified characteristics of patients with subretinal fluid (SRF) in macular edema (ME) secondary to branch retinal vein occlusion (BRVO) and determined their clinical outcomes after anti-vascular endothelial growth factor (VEGF) treatment. Fifty-seven eyes of BRVO patients with ME were divided into two groups according to the presence or absence of SRF at diagnosis. We compared the aqueous profiles, ocular and systemic characteristics at baseline, and the clinical outcomes. The SRF group had significantly greater central subfield thickness (CST) values and poorer best-corrected visual acuity (BCVA) at baseline compared to the non-SRF group. The former group had significantly higher aqueous levels of interleukin-8, VEGF, and placental growth factor. CST reduction and BCVA improvement during treatment were significantly greater in the SRF group than in the non-SRF group. Consequently, CST values were significantly lower in the SRF group than in the non-SRF group at 12 months, when BCVA did not differ significantly between the two groups. The SRF group required more frequent anti-VEGF treatment over 12 months and exhibited a higher rate of macular atrophy. Based on the aqueous profiles and the number of treatments required, the presence of SRF in BRVO patients appears to be associated with higher disease activity.
Topics: Humans; Retinal Vein Occlusion; Macular Edema; Male; Female; Aged; Subretinal Fluid; Middle Aged; Visual Acuity; Vascular Endothelial Growth Factor A; Tomography, Optical Coherence; Angiogenesis Inhibitors; Aged, 80 and over
PubMed: 38871805
DOI: 10.1038/s41598-024-64047-y -
The Journal of International Medical... Jun 2024This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged... (Review)
Review
Brentuximab vedotin therapy followed by autologous peripheral stem cell transplantation as a viable treatment option for an older adult with transformed lymphoma: a case report and literature review.
This report presents a case involving a woman aged >65 years who had been diagnosed with marginal zone lymphoma 3 years prior. The patient was hospitalized with enlarged inguinal lymph nodes, and pathological examination revealed that the lymphoma had transformed into diffuse large B-cell lymphoma. After two cycles of brentuximab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (BV-R-CHP) chemotherapy, the patient achieved complete remission. This treatment was followed by autologous hematopoietic stem cell transplantation and lenalidomide maintenance therapy. At the last follow-up, the patient had been in continuous remission for 24 months. This case study suggests that the utilization of BV and R-CHP in conjunction can result in rapid remission, and it can be followed by autologous hematopoietic stem cell transplantation and maintenance therapy with lenalidomide. This treatment approach exhibits potential as a viable option for older individuals with transformed lymphoma.
Topics: Humans; Female; Brentuximab Vedotin; Aged; Transplantation, Autologous; Antineoplastic Combined Chemotherapy Protocols; Lymphoma, Large B-Cell, Diffuse; Doxorubicin; Peripheral Blood Stem Cell Transplantation; Rituximab; Prednisone; Cyclophosphamide; Lenalidomide; Lymphoma, B-Cell, Marginal Zone; Combined Modality Therapy
PubMed: 38869106
DOI: 10.1177/03000605241258597 -
Journal of Translational Medicine Jun 2024Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated...
BACKGROUND
Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis.
METHODS
Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007.
RESULTS
tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-β1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007.
CONCLUSIONS
Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy.
Topics: Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Humans; RNA, Transfer; Mice, Inbred C57BL; Cell Proliferation; Choroidal Neovascularization; Male; Eye Diseases; Diabetes Mellitus, Experimental; Neovascularization, Pathologic; Diabetic Retinopathy; Mice; Human Umbilical Vein Endothelial Cells
PubMed: 38867291
DOI: 10.1186/s12967-024-05338-w