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Scientific Reports Jun 2024Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis...
Cuproptosis is a newly defined form of programmed cell death that relies on mitochondria respiration. Long noncoding RNAs (lncRNAs) play crucial roles in tumorigenesis and metastasis. However, whether cuproptosis-related lncRNAs are involved in the pathogenesis of diffuse large B cell lymphoma (DLBCL) remains unclear. This study aimed to identify the prognostic signatures of cuproptosis-related lncRNAs in DLBCL and investigate their potential molecular functions. RNA-Seq data and clinical information for DLBCL were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Cuproptosis-related lncRNAs were screened out through Pearson correlation analysis. Utilizing univariate Cox, least absolute shrinkage and selection operator (Lasso) and multivariate Cox regression analysis, we identified seven cuproptosis-related lncRNAs and developed a risk prediction model to evaluate its prognostic value across multiple groups. GO and KEGG functional analyses, single-sample GSEA (ssGSEA), and the ESTIMATE algorithm were used to analyze the mechanisms and immune status between the different risk groups. Additionally, drug sensitivity analysis identified drugs with potential efficacy in DLBCL. Finally, the protein-protein interaction (PPI) network were constructed based on the weighted gene co-expression network analysis (WGCNA). We identified a set of seven cuproptosis-related lncRNAs including LINC00294, RNF139-AS1, LINC00654, WWC2-AS2, LINC00661, LINC01165 and LINC01398, based on which we constructed a risk model for DLBCL. The high-risk group was associated with shorter survival time than the low-risk group, and the signature-based risk score demonstrated superior prognostic ability for DLBCL patients compared to traditional clinical features. By analyzing the immune landscapes between two groups, we found that immunosuppressive cell types were significantly increased in high-risk DLBCL group. Moreover, functional enrichment analysis highlighted the association of differentially expressed genes with metabolic, inflammatory and immune-related pathways in DLBCL patients. We also found that the high-risk group showed more sensitivity to vinorelbine and pyrimethamine. A cuproptosis-related lncRNA signature was established to predict the prognosis and provide insights into potential therapeutic strategies for DLBCL patients.
Topics: Lymphoma, Large B-Cell, Diffuse; Humans; RNA, Long Noncoding; Prognosis; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Protein Interaction Maps; Male; Female; Gene Expression Profiling; Gene Regulatory Networks; Middle Aged
PubMed: 38839842
DOI: 10.1038/s41598-024-63433-w -
Cancer Drug Resistance (Alhambra,... 2024Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of...
Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between gene expression and NSCLC patients' survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Pentoxifylline slightly decreased the expression levels of CHI3L1, β-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.
PubMed: 38835347
DOI: 10.20517/cdr.2024.04 -
Scientific Reports May 2024The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with...
The effect of high-dose pyridoxine (PN) on activity of 5-fluorouracil (FUra) and folinic acid (FA)-containing regimens was studied in 50 patients including 14 with digestive tract, and 36 with breast carcinomas (BC) in advanced stages with poor prognostic characteristics. Patients with colorectal, and pancreas adenocarcinoma received oxaliplatin, irinotecan, FUra, FA (Folfirinox), and patients with squamous cell carcinoma of the esophagus had paclitaxel, carboplatin, FUra, FA (TCbF). Patients with BC received AVCF (doxorubicin, vinorelbine, cyclophosphamide, FUra, FA) followed by TCbF or TCbF only, and patients who overexpressed HER2 received TCbF plus trastuzumab and pertuzumab. PN (1000-3000 mg/day iv) preceded each administration of FUra and FA. 47 patients (94%) responded, including 16 (32%) with CR. Median tumor reduction was 93%. Median event-free survival (EFS) was 37.7 months. The 25 patients with tumor shrinkage ≥ 91% had EFS of 52% from 42 months onwards. Unexpected toxicity did not occur. PN enhances potency of chemotherapy regimens comprising FUra and FA.
Topics: Humans; Fluorouracil; Leucovorin; Pyridoxine; Female; Middle Aged; Aged; Male; Antineoplastic Combined Chemotherapy Protocols; Adult; Breast Neoplasms; Neoplasm Staging; Treatment Outcome
PubMed: 38802419
DOI: 10.1038/s41598-024-62860-z -
Cancers May 2024Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free...
Daratumumab is being increasingly integrated into first-line multiple myeloma (MM) induction regimens, leading to improved response depth and longer progression-free survival. Autologous stem cell transplantation (ASCT) is commonly performed as a consolidation strategy following first-line induction in fit MM patients. We investigated a cohort of 155 MM patients who received ASCT after first-line induction with or without daratumumab (RVd, = 110; D-RVd, = 45), analyzing differences in stem cell mobilization, apheresis, and engraftment. In the D-RVd group, fewer patients successfully completed mobilization at the planned apheresis date (44% vs. 71%, = 0.0029), and more patients required the use of rescue plerixafor (38% vs. 28%, = 0.3052). The median count of peripheral CD34+ cells at apheresis was lower (41.37 vs. 52.19 × 10/L, = 0.0233), and the total number of collected CD34+ cells was inferior (8.27 vs. 10.22 × 10/kg BW, = 0.0139). The time to recovery of neutrophils and platelets was prolonged (12 vs. 11 days, = 0.0164; and 16 vs. 14 days, = 0.0002, respectively), and a higher frequency of erythrocyte transfusions (74% vs. 51%, = 0.0103) and a higher number of platelet concentrates/patients were required (4 vs. 2; = 0.001). The use of daratumumab during MM induction might negatively impact stem cell mobilization and engraftment in the context of ASCT.
PubMed: 38791933
DOI: 10.3390/cancers16101854 -
Medicine May 2024The aim of this study was to evaluate the efficacy and safety of recombinant human endostatin in combination with vinorelbine + cisplatin (NPE) for the treatment of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this study was to evaluate the efficacy and safety of recombinant human endostatin in combination with vinorelbine + cisplatin (NPE) for the treatment of advanced non-small cell lung cancer (NSCLC).
METHODS
Randomized controlled trials (RCTs) of NPE for advanced NSCLC in PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched using a computerized search of the database from the time of creation to May 2023. Two investigators independently extracted literature information and assessed the quality of the included literature. Meta-analysis was performed using RevMan 5.4.0 software.
RESULTS
A total of 24 RCTs with 2114 patients with advanced NSCLC were finally included. The results of meta-analysis showed that the total effective rate in the group received NPE regimen was significantly higher than those in the group without NPE regimen (RR = 1.70, 95% CI: 1.48-1.95, P < .00001). Meanwhile, the clinical benefit rate in the group received NPE regimen was also significantly higher than those in the group without NPE regimen (RR = 1.22, 95% CI: 1.15-1.29, P < .00001). However, there was no significant difference in the incidence of adverse event rate between the 2 groups (RR = 0.98, 95% CI: 0.76-1.27, P = .88).
CONCLUSIONS
Compared with NP (vinorelbine + cisplatin) regimens for patients with advanced NSCLC, NPE regimens improve the total effective rate and clinical benefit rate of treatment, but there can be no significant difference in adverse effects. Prospective randomized trials are needed to further validate the safety and efficacy of this treatment modality.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Endostatins; Lung Neoplasms; Cisplatin; Antineoplastic Combined Chemotherapy Protocols; Vinorelbine; Recombinant Proteins; Randomized Controlled Trials as Topic
PubMed: 38788043
DOI: 10.1097/MD.0000000000038027 -
Translational Breast Cancer Research :... 2024The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific...
BACKGROUND
The current study shows that the incidence rate of triple-negative breast cancer accounts for 10-17% of invasive ductal carcinoma of the breast. There is no specific treatment target, the age of onset is relatively small, and the recurrence rate is relatively fast. The prognosis of breast cancer in different subtypes is the most unsatisfactory, with a 5-year survival rate of less than 15%. We report a typical case of metastatic advanced triple-negative breast cancer who responded well to apatinib mesylate after chemotherapy failure and achieved significant progression-free survival, which is relatively rare in triple-negative breast cancer with limited treatment means.
CASE DESCRIPTION
A 55-year-old female was surgically diagnosed as triple-negative breast cancer on April 17, 2015. After surgery, she had lung metastasis after standard adjuvant chemotherapy and radiotherapy. After receiving the NX regimen (vinorelbine, capecitabine) for 8 cycles, she progressed. Because the patient refused later, she was adjusted to apatinib mesylate, and serious adverse reactions occurred during the treatment process. By adjusting the drug dose, and low-dose apatinib treatment, the lung lesions were close to complete response (CR), reaching a progression-free survival period of 45 months.
CONCLUSIONS
Low-dose apatinib may be a promising anti-tumor drug for triple-negative breast cancer patients, which needs more samples to verify. This case may provide a reference for the treatment selection of triple-negative metastatic breast cancer in the future.
PubMed: 38751676
DOI: 10.21037/tbcr-23-24 -
Translational Breast Cancer Research :... 2023We report a case of metastatic human epidermal growth factor receptor-2 (HER2) positive breast cancer who achieved encouraging clinical benefits across multiple...
BACKGROUND
We report a case of metastatic human epidermal growth factor receptor-2 (HER2) positive breast cancer who achieved encouraging clinical benefits across multiple pyrotinib-based anti-HER2 therapies.
CASE DESCRIPTION
A 33-year-old woman was diagnosed with hormone receptor (HR) positive, HER2-positive breast cancer in June 2018, and did not receive adjuvant radiotherapy, chemotherapy, or anti-HER2 targeted therapy post-breast conserving surgery. By May 2020, she developed recurrence of the left breast mass with metastases in liver, bone and lymph nodes. She then received pyrotinib plus trastuzumab and nab-paclitaxel as first-line therapy. Both the left breast mass and liver metastases showed noticeable improvement, with the disease evaluated as partial response (PR). Despite this promising result, the patient developed brain metastases after first-line treatment. A combination regimen of pyrotinib retention plus inetetamab and vinorelbine were administered as second-line anti-HER2 therapy, and the brain metastases visibly shrunk, leading to PR, with the extracranial lesions remaining stable. Ultimately, due to brain lesions progression, the treatment was transitioned to trastuzumab deruxtecan. We applied next generation sequencing (NGS) to illustrate the efficacy of anti-HER2 therapy and minimal residual disease (MRD) to detect the disease status.
CONCLUSIONS
Pyrotinib is a promising antineoplastic agent for HER2-positive advanced breast cancer patients. Under the guidance of precision medicine, it is encouraged to utilize novel diagnostic and therapeutic methods to manage advanced breast cancer patients.
PubMed: 38751473
DOI: 10.21037/tbcr-23-26 -
Revista de Investigacion Clinica;... 2024Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic...
Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic targets to improve patient outcomes. Objectives: Our goal was to develop a novel multi-gene prognostic model linked to neutrophils for predicting lung squamous cell carcinoma prognosis. Methods: We utilized messenger RNA expression profiles and relevant clinical data of lung squamous cell carcinoma patients from the Cancer Genome Atlas database. Through K-means clustering, least absolute shrinkage and selection operator regression, and univariate/multivariate Cox regression analyses, we identified 12 neutrophil-related genes strongly related to patient survival and constructed a prognostic model. We verified the stability of the model in the Cancer Genome Atlas database and gene expression omnibus validation set, demonstrating the robust predictive performance of the model. Results: Immunoinfiltration analysis revealed remarkably elevated levels of infiltration for natural killer cells resting and monocytes in the high-risk group compared to the low-risk group, while macrophages had considerably lower infiltration in the high risk group. Most immune checkpoint genes, including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4, exhibited high expression levels in the high risk group. Tumor immune dysfunction and exclusion scores and immunophenoscore results suggested a potential inclination toward immunotherapy in the "RIC" version V2 revised high risk group. Moreover, prediction results from the CellMiner database revealed great correlations between drug sensitivity (e.g., Vinorelbine and PKI-587) and prognostic genes. Conclusion: Overall, our study established a reliable prognostic risk model that possessed significant value in predicting the overall survival of lung squamous cell carcinoma patients and may guide personalized treatment strategies. (Rev Invest Clin. 2024;76(2):116-31).
Topics: Humans; Lung Neoplasms; Neutrophils; Prognosis; Carcinoma, Squamous Cell; Male; Female; Biomarkers, Tumor; Middle Aged; Aged; Gene Expression Regulation, Neoplastic; RNA, Messenger
PubMed: 38740381
DOI: 10.24875/RIC.23000262 -
Cancer Medicine Apr 2024Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic...
BACKGROUND
Apatinib is an oral small-molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptor-2. Oral vinorelbine is a semisynthetic chemotherapeutic agent of vinorelbine alkaloids. Apatinib and oral vinorelbine have been proved to be effective in the treatment of metastatic breast cancer (mBC). At present, several small sample clinical trials have explored the efficacy of apatinib combined with oral vinorelbine in the treatment of mBC.
METHODS
This retrospective study included 100 human epidermal growth factor receptor-2 (HER2)-negative mBC patients who received low-dose apatinib (250 mg orally per day) plus oral vinorelbine until disease progression or intolerance during February 2017 and March 2023. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), and safety were analyzed by SPSS 26.0 software and GraphPad Prism 8 software. Cox proportional hazards regression model for univariate and multivariate was used to identify factors significantly related to PFS and OS.
RESULTS
The median follow-up time for this study was 38.1 months. Among 100 patients with HER2-negative mBC, 66 were hormone receptor (HR)-positive/HER2-negative and 34 were triple-negative breast cancer (TNBC). The median PFS and OS were 6.0 months (95% CI, 5.2-6.8 months) and 23.0 months (95% CI, 19.9-26.1 months). There were no statistical differences in PFS (p = 0.239) and OS (p = 0.762) between the HR-positive /HER2-negative and TNBC subgroups. The ORR, CBR, and DCR were 21.0%, 58.0%, and 78.0%, respectively. Ninety-five patients (95.0%) experienced varying grades of adverse events (AEs) and 38.0% of patients for Grades 3-4. The most common Grades 3-4 AEs that we observed were neutropenia (30.0%) and leukopenia (25.0%).
CONCLUSION
Low-dose apatinib combined with oral vinorelbine demonstrates potential efficacy and well tolerated for pretreated HER2-negative mBC.
Topics: Humans; Female; Pyridines; Vinorelbine; Middle Aged; Receptor, ErbB-2; Antineoplastic Combined Chemotherapy Protocols; Adult; Retrospective Studies; Aged; Breast Neoplasms; Administration, Oral; Progression-Free Survival
PubMed: 38659376
DOI: 10.1002/cam4.7181 -
BMC Cancer Apr 2024This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11) on therapeutic efficacy and prognosis in patients with... (Meta-Analysis)
Meta-Analysis
Effect of the STK11 mutation on therapeutic efficacy and prognosis in patients with non-small cell lung cancer: a comprehensive study based on meta-analyses and bioinformatics analyses.
BACKGROUND
This study aimed to systematically analyze the effect of a serine/threonine kinase (STK11) mutation (STK11) on therapeutic efficacy and prognosis in patients with non-small cell lung cancer (NSCLC).
METHODS
Candidate articles were identified through a search of relevant literature published on or before April 1, 2023, in PubMed, Embase, Cochrane Library, CNKI and Wanfang databases. The extracted and analyzed data included the hazard ratios (HRs) of PFS and OS, the objective response rate (ORR) of immune checkpoint inhibitors (ICIs), and the positive rates of PD-L1 expression. The HR of PFS and OS and the merged ratios were calculated using a meta-analysis. The correlation between STK11 and clinical characteristics was further analyzed in NSCLC datasets from public databases.
RESULTS
Fourteen retrospective studies including 4317 patients with NSCLC of whom 605 had STK11 were included. The meta-analysis revealed that the ORR of ICIs in patients with STK11 was 10.1% (95%CI 0.9-25.2), and the positive rate of PD-L1 expression was 41.1% (95%CI 25.3-57.0). STK11 was associated with poor PFS (HR = 1.49, 95%CI 1.28-1.74) and poor OS (HR = 1.44, 95%CI 1.24-1.67). In the bioinformatics analysis, PFS and OS in patients with STK11 alterations were worse than those in patients without alterations (p < 0.001, p = 0.002). Nutlin-3a, 5-fluorouracil, and vinorelbine may have better sensitivity in patients with STK11 than in those with STK11.
CONCLUSIONS
Patients with STK11-mutant NSCLC had low PD-L1 expression and ORR to ICIs, and their PFS and OS were worse than patients with STK11 after comprehensive treatment. In the future, more reasonable systematic treatments should be explored for this subgroup of patients with STK11-mutant NSCLC.
Topics: Humans; AMP-Activated Protein Kinase Kinases; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutation; Prognosis; Protein Serine-Threonine Kinases; Retrospective Studies
PubMed: 38632512
DOI: 10.1186/s12885-024-12130-y