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Oxidative Medicine and Cellular... 2022Recent studies have demonstrated that homeobox A1 (HOXA1) is upregulated in lung cancer due to RNA modifications (N-methyladenosine), but the specific function of HOXA1...
OBJECTIVE
Recent studies have demonstrated that homeobox A1 (HOXA1) is upregulated in lung cancer due to RNA modifications (N-methyladenosine), but the specific function of HOXA1 in lung adenocarcinoma (LUAD) remains indistinct. Herein, we investigated the role of HOXA1 in LUAD biology.
METHODS
This study presented pancancer analysis of associations of HOXA1 with prognosis, TMB, and immune checkpoints. The expression of HOXA1 was detected in LUAD and normal tissues with immunohistochemistry and western blot. Through least absolute shrinkage and selection operator (LASSO) analysis, HOXA1-derived gene model was conducted in LUAD. Correlations of HOXA1 with immune cell infiltrations, immune checkpoints, HLAs, and chemotherapeutic sensitivity were evaluated. Colony formation, proliferation, and migration of LUAD cells with si-HOXA1 transfection were investigated, and the effects of HOXA1 on T cell exhaustion were assessed .
RESULTS
HOXA1 expression was a risk factor of overall survival, disease-specific survival, and progression-free interval of LUAD. HOXA1 exhibited prominent associations with immune cell infiltration, immune checkpoints, and HLAs. HOXA1-derived gene signature reliably and independently predicted LUAD outcomes. Also, high-risk cases presented increased sensitivity to cisplatin, paclitaxel, docetaxel, vinorelbine, and etoposide. HOXA1 knockdown exhibited an inhibitory effect on proliferation and migration abilities of LUAD cells. Silencing HOXA1 weakened the expression of antioxidative stress markers Nrf2/HO-1 and T cell exhaustion marker CD155 in LUAD cells. Moreover, LUAD cells with HOXA1 knockdown enhanced the CD8+ T cell response.
CONCLUSION
Our data support the oncogenic function and prognostic significance of HOXA1 that facilitates immune escape and alleviates oxidative stress of LUAD.
Topics: Adenocarcinoma of Lung; Cell Proliferation; Genes, Homeobox; Homeodomain Proteins; Humans; Lung Neoplasms; Oxidative Stress; Transcription Factors
PubMed: 35633885
DOI: 10.1155/2022/4102666 -
Fertility and Sterility Sep 2023
Topics: Pregnancy; Female; Humans; Vinorelbine; Pregnancy, Ectopic; Vinblastine; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Lung Neoplasms
PubMed: 37385396
DOI: 10.1016/j.fertnstert.2023.06.027 -
The Lancet. Oncology Dec 2022Shortages and unequal access to anticancer medicines for children and adolescents are a reality in Europe. The aim of the European Society for Paediatric Oncology...
BACKGROUND
Shortages and unequal access to anticancer medicines for children and adolescents are a reality in Europe. The aim of the European Society for Paediatric Oncology (SIOPE) Essential Anticancer Medicines Project was to provide a list of anticancer medicines that are considered essential in the treatment of paediatric cancers to help ensure their continuous access to all children and adolescents with cancer across Europe.
METHODS
This pan-European project, done between Jan 20, 2020, and Feb 18, 2022, was designed to be a systematic collection and review of treatment protocols and strategies that are used to treat childhood cancer in Europe. We formed 16 working groups on the basis of paediatric cancer types, and which were based on the existing SIOPE Clinical Trial Groups. Workings groups consisted of representatives from the SIOPE Clinical Trial Groups, Young SIOPE members, and senior paediatric oncology experts. Each group collected existing treatment protocols that are used to treat the respective cancer types in Europe. Medicines from the standard group of each protocol were extracted. For medicines not on the WHO Essential Medicines List for children (EMLc) 2017, working groups did a literature search to determine whether the medicines should be defined as essential, promising, or neither essential nor promising. Each group provided an individual summary, and all medicines that were considered essential by at least one group were combined in a joint list.
FINDINGS
The working groups identified 73 treatment protocols used in Europe and defined 66 medicines as essential. For several newer medicines, such as kinase inhibitors or tisagenlecleucel, the supporting evidence was insufficient to consider them essential, so these medicines were defined as promising. 25 medicines were considered promising by at least one working group. 22 (33%) of the 66 essential and none of the promising medicines were included in the WHO EMLc 2017. The WHO EMLc 2021 included two new medicines (everolimus and vinorelbine) following applications we made as a result of this project.
INTERPRETATION
Medicines that were defined as essential within this project should be available for the treatment of childhood and adolescent cancer continuously and across Europe. This list can be used to support and guide stakeholders and policy makers in negotiations on a national and European level regarding shortages, accessibility, and affordability of these medicines.
FUNDING
None.
Topics: Adolescent; Child; Humans; Neoplasms; Medical Oncology; Europe; Drugs, Essential; Antineoplastic Agents
PubMed: 36332647
DOI: 10.1016/S1470-2045(22)00623-4 -
Pharmacological Research Mar 2020The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is... (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of aidi injection combination with vinorelbine and cisplatin for advanced non-small-cell lung carcinoma: A systematic review and meta-analysis of 54 randomized controlled trials.
The Aidi injection contains multiple active ingredients, including astragaloside (Re, Rb1, and Rg1), ginsenoside, cantharidin, elentheroside E, and syringin, and it is administered with vinorelbine and cisplatin (NP) to treat non-small-cell lung carcinoma (NSCLC). In this study, we performed a systematic review and meta-analysis to determine the clinical efficacy and safety of the Aidi injection with NP, and the optimal threshold and treatment regimen to produce the desired responses. We collected all studies regarding the Aidi injection with NP for NSCLC from Chinese and English databases (up to April 2019). Risk of methodological bias was evaluated for each study. Data for analysis were extracted using a standard data extraction form. Evidence quality was assessed following the Grading of Recommendations Assessment, Development and Evaluation approach. We included 54 trials containing 4,053 patients for analysis. Combining the Aidi injection with NP significantly increased the objective response rate (odds ratio [OR], 1.32; confidence interval [CI], 1.23, 1.42), disease control rate (OR, 1.14; CI, 1.11, 1.18), and quality of life (OR, 1.80; CI, 1.61, 1.98), with decreased risks of myelosuppression, neutropenia, thrombocytopenia, anemia, gastrointestinal reaction, and liver dysfunction. For patients with a Karnofsky Performance Status score of ≥60, the Aidi injection (50 mL/day, two weeks/cycle, with two to three cycles) treatment with vinorelbine (25 mg/m) and cisplatin (30-35 mg/m or 40-50 mg/m) might be the optimal regimen for producing the desired tumor response and achieving a good safety level. Most results were robust, and their quality was moderate. The results suggest that administration of the Aidi injection and concomitant NP is beneficial to NSCLC, and provide evidence for the optimal threshold and treatment regimen that may improve tumor response with a good safety level.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drugs, Chinese Herbal; Humans; Injections; Lung Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Vinorelbine
PubMed: 31935454
DOI: 10.1016/j.phrs.2020.104637 -
Translational Andrology and Urology Dec 2022The 5-year overall survival rate in metastatic prostate adenocarcinoma (PRAD) is extremely low. Genomic studies of PRAD have improved our understanding of disease...
BACKGROUND
The 5-year overall survival rate in metastatic prostate adenocarcinoma (PRAD) is extremely low. Genomic studies of PRAD have improved our understanding of disease biology. However, the role of immune checkpoint genes (ICGs) in PRAD remains unclear.
METHODS
Univariate and multivariate analyses were used to analyze genes associated with metastasis-free survival (MFS) in The Cancer Genome Atlas (TCGA)-PRAD dataset. The expressions of and were detected via immunohistochemical assay and real-time fluorescence quantitative PCR (RT-PCR) assay in our in-house cohort. The expression of long non-coding RNAs (lncRNAs) , , and were detected via RT-PCR assay in our in-house cohort. Stepwise regression, Cox regression, and nomogram analyses were used to evaluate the prognostic role of these genes in both the TCGA dataset and in-house cohort. The "pRRophetic" R package was used to evaluate drug sensitivity in the TCGA cohort according to the gene mRNA expression level.
RESULTS
In our study, univariate and multivariate analyses revealed that the mRNA expressions of two ICGs, and , were independent factors affecting MFS in PRAD patients. A prognostic 2-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. The expressions of , , and were correlated with and . A prognostic lncRNA-ICG model predicted the MFS of PRAD patients with medium-to-high accuracy in the TCGA dataset and in-house cohort. In addition, correlation analyses between the sensitivity of doxorubicin, erlotinib, gemcitabine, or vinorelbine and , , , , and were conducted.
CONCLUSIONS
Our results provide new targets for predicting tumor metastasis in PRAD and treating patients with metastatic PRAD.
PubMed: 36632155
DOI: 10.21037/tau-22-711 -
Pediatric Hematology and Oncology May 2021
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Humans; Infusions, Intra-Arterial; Male; Meningeal Neoplasms; Positron-Emission Tomography; Rhabdomyosarcoma; Sirolimus; Vinorelbine
PubMed: 33439069
DOI: 10.1080/08880018.2020.1871138 -
Frontiers in Oncology 2021Suppressive tumor microenvironment is closely related to the progression and poor prognosis of lung adenocarcinoma (LUAD). Novel individual and universal immune-related...
BACKGROUND
Suppressive tumor microenvironment is closely related to the progression and poor prognosis of lung adenocarcinoma (LUAD). Novel individual and universal immune-related biomarkers to predict the prognosis and immune landscape of LUAD patients are urgently needed. Two-gene pairing patterns could integrate and utilize various gene expression data.
METHODS
The RNA-seq and relevant clinicopathological data of the LUAD project from the TCGA and well-known immune-related genes list from the ImmPort database were obtained. Co-expression analysis followed by an analysis of variance was performed to identify differentially expressed immune-related lncRNA (irlncRNA) (DEirlncRNA) between tumor and normal tissues. Two arbitrary DEirlncRNAs (DEirlncRNAs pair) in a tumor sample underwent pairwise comparison to generate a score (0 or 1). Next, Univariate analysis, Lasso regression and Multivariate analysis were used to screen survival-related DEirlncRNAs pairs and construct a prognostic model. The Acak information standard (AIC) values of the receiver operating characteristic (ROC) curve for 3 years are calculated to determine the cut-off point for high- or low-risk score. Finally, we evaluated the relationship between the risk score and overall survival, clinicopathological features, immune landscape, and chemotherapy efficacy.
RESULTS
Data of 54 normal and 497 tumor samples of LUAD were enrolled. After a strict screening process, 15 survival-independent-related DEirlncRNA pairs were integrated to construct a prognostic model. The AUC value of the 3-year ROC curve was 0.828. Kaplan-Meier analysis showed that patients with low risk lived longer than patients with high risk (p <0.001). Univariate and Multivariate Cox analysis suggested that the risk score was an independent factor of survival. The risk score was negatively associated with most tumor-infiltrating immune cells, immune score, and microenvironment scores. The low-risk group was correlated with increased expression of ICOS. The high-risk group had a connection with lower half inhibitory centration (IC50) of most chemotherapy drugs (e.g., etoposide, paclitaxel, vinorelbine, gemcitabine, and docetaxel) and targeted medicine-erlotinib, but with higher IC50 of methotrexate.
CONCLUSION
The established irlncRNA pairs-based model is a promising prognostic signature for LUAD patients. Furthermore, the prognostic signature has great potential in the evaluation of tumor immune landscape and guiding individualized treatment regimens.
PubMed: 35083132
DOI: 10.3389/fonc.2021.673567 -
Cancer Research Feb 2021Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic diseases, albeit only in a fraction of patients. The clinical success of cyclophosphamide...
Checkpoint inhibitors (CI) instigate anticancer immunity in many neoplastic diseases, albeit only in a fraction of patients. The clinical success of cyclophosphamide (C)-based haploidentical stem-cell transplants indicates that this drug may re-orchestrate the immune system. Using models of triple-negative breast cancer (TNBC) with different intratumoral immune contexture, we demonstrate that a combinatorial therapy of intermittent C, CI, and vinorelbine activates antigen-presenting cells (APC), and abrogates local and metastatic tumor growth by a T-cell-related effect. Single-cell transcriptome analysis of >50,000 intratumoral immune cells after therapy treatment showed a gene signature suggestive of a change resulting from exposure to a mitogen, ligand, or antigen for which it is specific, as well as APC-to-T-cell adhesion. This transcriptional program also increased intratumoral Tcf1 stem-like CD8 T cells and altered the balance between terminally and progenitor-exhausted T cells favoring the latter. Overall, our data support the clinical investigation of this therapy in TNBC. SIGNIFICANCE: A combinatorial therapy in mouse models of breast cancer increases checkpoint inhibition by activating antigen-presenting cells, enhancing intratumoral Tcf1 stem-like CD8 T cells, and increasing progenitor exhausted CD8 T cells.
Topics: Animals; Antigen-Presenting Cells; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; CD8-Positive T-Lymphocytes; Cell Adhesion; Cyclophosphamide; Female; Hepatocyte Nuclear Factor 1-alpha; Immune Checkpoint Inhibitors; Immunity, Cellular; Mice; Mice, Inbred BALB C; Programmed Cell Death 1 Receptor; Transcriptome; Triple Negative Breast Neoplasms; Vinorelbine
PubMed: 33268528
DOI: 10.1158/0008-5472.CAN-20-1818 -
Journal of Clinical Oncology : Official... Nov 2022Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Outcome for patients with metastatic rhabdomyosarcoma (RMS) is poor. This study presents the results of the MTS 2008 study with a pooled analysis including patients from the concurrent BERNIE study.
PATIENTS AND METHODS
In MTS 2008, patients with metastatic RMS received four cycles of ifosfamide, vincristine, and actinomycin D (IVA) plus doxorubicin, five cycles of IVA, and 12 cycles of maintenance chemotherapy (low-dose cyclophosphamide and vinorelbine). The BERNIE study randomly assigned patients to the addition or not of bevacizumab to the same chemotherapy. Local therapy (surgery/radiotherapy) was given to the primary tumor and all metastatic sites when feasible.
RESULTS
MTS 2008 included 270 patients (median age, 9.6 years; range, 0.07-20.8 years). With a median follow-up of 50.3 months, 3-year event-free survival (EFS) and overall survival (OS) were 34.9% (95% CI, 29.1 to 40.8) and 47.9% (95% CI, 41.6 to 53.9), respectively. In pooled analyses on 372 patients with a median follow-up of 55.2 months, 3-year EFS and OS were 35.5% (95% CI, 30.4 to 40.6) and 49.3% (95% CI, 43.9 to 54.5), respectively. Patients with ≤ 2 Oberlin risk factors (ORFs) had better outcome than those with ≥ 3 ORFs: 3-year EFS was 46.1% versus 12.5% ( < .0001) and 3-year OS 60.0% versus 26.0% ( < .0001). Induction chemotherapy and maintenance appeared tolerable; however, about two third of patients needed dose adjustments during maintenance.
CONCLUSION
Outcome remains poor for patients with metastatic RMS and multiple ORFs. Because of the design of the studies, it was not possible to determine whether the intensive induction regimen and/or the addition of maintenance treatment resulted in apparent improvement of outcome compared with historical cohorts. Further studies, with novel treatment approaches are urgently needed, to improve outcome for the group of patients with adverse prognostic factors.
Topics: Child; Humans; Disease-Free Survival; Antineoplastic Combined Chemotherapy Protocols; Rhabdomyosarcoma; Sarcoma; Ifosfamide; Vincristine; Cyclophosphamide; Dactinomycin; Doxorubicin; Neoplasms, Second Primary
PubMed: 35709412
DOI: 10.1200/JCO.21.02981 -
The Oncologist Dec 2020Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and...
INTRODUCTION
Desmoid tumors (DT) are rare collagen-forming tumors that can exhibit locally aggressive patterns of behavior. The aim of this study was to evaluate the efficacy and safety of treatment of DT with single-agent oral vinorelbine.
MATERIALS AND METHODS
A retrospective review of patients treated with vinorelbine 90 mg orally on days 1, 8, and 15 of a 28-day cycle from January 2004 to July 2019 was performed. Response was assessed using RECIST version 1.1. Descriptive statistics were employed.
RESULTS
A total of 29 patients were included. Response rate was 20.7% (6/29), and clinical benefit rate (response by RECIST 1.1 and/or clinical symptom improvement) was 65.5% (19/29). No patient experienced grade 3 or above toxicity. Common toxicities were grade 1-2 nausea (14/26, 48.3%), fatigue (9/26, 31.0%), and diarrhea (4/26, 13.8%).
CONCLUSION
Single-agent oral vinorelbine is an effective, safe, and well-tolerated treatment for DT. It represents a new oral alternative for management of DT.
Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Fibromatosis, Aggressive; Humans; Retrospective Studies; Treatment Outcome; Vinblastine; Vinorelbine
PubMed: 32918789
DOI: 10.1002/ONCO.13516