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Experimental and Therapeutic Medicine Mar 2022Peripherally inserted central catheters (PICCs) are used for the administration of chemotherapy drugs, including vinorelbine. The present study aimed to construct a...
Peripherally inserted central catheters (PICCs) are used for the administration of chemotherapy drugs, including vinorelbine. The present study aimed to construct a rabbit model with vinorelbine administration via PICC, and to dynamically monitor the formation of phlebitis and thrombosis. PICC was inserted into 48 rabbits following specific clinical procedures. The rabbits were randomly divided (n=6 per group) into the following eight groups: i) Control (PICC in place for 1 day); ii) 2nd day of PICC placement (received the first cycle of vinorelbine administration); iii) 3rd day of PICC placement; iv) 7th day of PICC placement; v) 14th day of PICC placement; vi) 21st day of PICC placement; vii) 23rd day of PICC placement (received the second cycle of vinorelbine administration); and viii) 24th day of PICC placement. Hematoxylin and eosin staining was performed on catheter, ear vein and anterior vena specimens. Prothrombin time was measured using an automatic coagulation analyzer, followed by routine blood tests. Serum levels of inflammation- and thrombosis-related factors, including C-reactive protein, D-dimer, interleukin-2, interleukin-6, P-selectin and E-selectin, were measured using ELISAs. X-ray examination confirmed that the rabbit model with vinorelbine administration via PICC was successfully constructed. On the 1st and 23rd day of PICC placement, thrombosis was observed in the catheter. Furthermore, on the 1st day of PICC placement, thrombosis was clearly observed in the ear vein and anterior vena samples. After vinorelbine administration, phlebitis occurred in the ear vein and anterior vena cava samples. With increasing time after vinorelbine administration via PICC, thrombosis and phlebitis were notably ameliorated. Moreover, on the day of vinorelbine administration, prothrombin time was significantly decreased and the serum levels of inflammation- and thrombosis-related factors were significantly increased compared with previous days. Collectively, the present study observed the formation and specific evolution of phlebitis and venous thrombosis after vinorelbine administration, providing a reference for the early prediction, timely prevention and treatment of PICC-related chemotherapy complications.
PubMed: 35126715
DOI: 10.3892/etm.2022.11135 -
Cells Dec 2021Mitochondria move along the microtubule network and produce bioenergy in the cell. However, there is no report of a relationship between bioenergetic activity of...
Mitochondria move along the microtubule network and produce bioenergy in the cell. However, there is no report of a relationship between bioenergetic activity of mitochondria and microtubule stability in mammalian cells. This study aimed to investigate this relationship. We treated HEK293 cells with microtubule stabilizers (Taxol and Epothilone D) or a microtubule disturber (vinorelbine), and performed live-cell imaging to determine whether mitochondrial morphology and bioenergetic activity depend on the microtubule status. Treatment with microtubule stabilizers enhanced the staining intensity of microtubules, significantly increased ATP production and the spare respiratory capacity, dramatically increased mitochondrial fusion, and promoted dynamic movement of mitochondria. By contrast, bioenergetic activity of mitochondria was significantly decreased in cells treated with the microtubule disturber. Our data suggest that microtubule stability promotes mitochondrial functional activity. In conclusion, a microtubule stabilizer can possibly recover mitochondrial functional activity in cells with unstable microtubules.
Topics: Adenosine Triphosphate; Cell Proliferation; Cell Respiration; Cell Shape; Cell Survival; Gene Expression Regulation; HEK293 Cells; Humans; Membrane Potential, Mitochondrial; Microtubules; Mitochondria; Oxygen Consumption; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 34944107
DOI: 10.3390/cells10123600 -
The Medical Letter on Drugs and... Nov 2022
Topics: Humans; Female; Breast Neoplasms; Antibodies, Monoclonal; Receptor, ErbB-2
PubMed: 36397195
DOI: No ID Found -
Frontiers in Oncology 2023Lung adenocarcinoma (LUAD) kills millions of people every year. Recently, FDA and researchers proved the significance of high tumor mutational burden (TMB) in treating...
A tumor mutational burden-derived immune computational framework selects sensitive immunotherapy/chemotherapy for lung adenocarcinoma populations with different prognoses.
BACKGROUND
Lung adenocarcinoma (LUAD) kills millions of people every year. Recently, FDA and researchers proved the significance of high tumor mutational burden (TMB) in treating solid tumors. But no scholar has constructed a TMB-derived computing framework to select sensitive immunotherapy/chemotherapy for the LUAD population with different prognoses.
METHODS
The datasets were collected from TCGA, GTEx, and GEO. We constructed the TMB-derived immune lncRNA prognostic index (TILPI) computing framework based on TMB-related genes identified by weighted gene co-expression network analysis (WGCNA), oncogenes, and immune-related genes. Furthermore, we mapped the immune landscape based on eight algorithms. We explored the immunotherapy sensitivity of different prognostic populations based on immunotherapy response, tumor immune dysfunction and exclusion (TIDE), and tumor inflammation signature (TIS) model. Furthermore, the molecular docking models were constructed for sensitive drugs identified by the pRRophetic package, oncopredict package, and connectivity map (CMap).
RESULTS
The TILPI computing framework was based on the expression of TMB-derived immune lncRNA signature (TILncSig), which consisted of AC091057.1, AC112721.1, AC114763.1, AC129492.1, LINC00592, and TARID. TILPI divided all LUAD patients into two populations with different prognoses. The random grouping verification, survival analysis, 3D PCA, and ROC curve (AUC=0.74) firmly proved the reliability of TILPI. TILPI was associated with clinical characteristics, including smoking and pathological stage. Furthermore, we estimated three types of immune cells threatening the survival of patients based on multiple algorithms. They were macrophage M0, T cell CD4 Th2, and T cell CD4 memory activated. Nevertheless, five immune cells, including B cell, endothelial cell, eosinophil, mast cell, and T cell CD4 memory resting, prolonged the survival. In addition, the immunotherapy response and TIDE model proved the sensitivity of the low-TILPI population to immunotherapy. We also identified seven intersected drugs for the LUAD population with poor prognosis, which included docetaxel, gemcitabine, paclitaxel, palbociclib, pyrimethamine, thapsigargin, and vinorelbine. Their molecular docking models and best binding energy were also constructed and calculated.
CONCLUSIONS
We divided all LUAD patients into two populations with different prognoses. The good prognosis population was sensitive to immunotherapy, while the people with poor prognosis benefitted from 7 drugs.
PubMed: 37456238
DOI: 10.3389/fonc.2023.1104137 -
Journal of Healthcare Engineering 2022We aimed to explore the epidemiological characteristics and changes of lung cancer and the clinical medication in England from 2001 to 2019. We searched related research...
We aimed to explore the epidemiological characteristics and changes of lung cancer and the clinical medication in England from 2001 to 2019. We searched related research using search engine systems such as MEDLINE, PubMed, and PsychINFO. Lung cancer is a serious disease and the prognosis is usually very poor. The overall mortality rate of lung cancer decreased year by year in England from 2001 to 2019, but men, the elderly, and people exposed to polluted air are still more likely to be infected with lung cancer or die as a result, the prevalence and mortality rate of lung cancer in the north of England is significantly higher than that in the south, and the gap is increasing year by year. Lung cancer has changeable risk factors such as quitting smoking and improving air quality, which can effectively reduce the related risk. Paclitaxel, docetaxel, gemcitabine, and vinorelbine are the main drugs for the treatment of lung cancer in England and the treatment of these drugs is beneficial to the survival and quality of life of patients. Men and the elderly are at high risk of lung cancer, which means that lung cancer has obvious gender inequality and age inequality. At the same time, based on the statistical data of lung cancer risk in different regions, it can be concluded that lung cancer also has strong geographical and economic inequality. Changing risk factors and using drugs can effectively reduce the risk of lung cancer and provide effective treatment.
Topics: Aged; Epidemiologic Studies; Humans; Lung Neoplasms; Male; Quality of Life; Smoking; Vinorelbine
PubMed: 35368924
DOI: 10.1155/2022/3577312 -
Journal of Oncology 2022To assess the application value of serum thymidine kinase 1 (TK1) and PC cell-derived growth factor (PCDGF), cytokeratin 19 fragment 21-1 (CYFRA21-1), neuron-specific...
OBJECTIVE
To assess the application value of serum thymidine kinase 1 (TK1) and PC cell-derived growth factor (PCDGF), cytokeratin 19 fragment 21-1 (CYFRA21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) plus enhanced CT scan in the diagnosis of nonsmall cell lung cancer (NSCLC) and chemotherapy monitoring.
METHODS
Between April 2019 and April 2021, 30 patients with NSCLC assessed for eligibility treated in our institution were included in the experimental group, and 30 healthy individuals screened out from physical examinations were recruited in the control group. The chemotherapy regimens included gemcitabine plus cisplatin, pemetrexed disodium plus cisplatin, and vinorelbine plus cisplatin. The application value of serum TK1, PCDGF, CYFRA21-1, NSE, CEA, and enhanced CT scan in the diagnosis and chemotherapy monitoring of NSCLC was analyzed.
RESULTS
Before treatment, the eligible patients had significantly higher serum levels of TK1, PCDGF, CYFRA21-1, NSE, and CEA than those of the healthy individuals included ( < 0.05). Clinical efficacy was categorized into good and poor, and the good efficacy included complete response and partial response, with the poor efficacy including stable disease and progressive disease. Patients with good clinical efficacy had lower levels of serum TK1, PCDGF, CYFRA21-1, NSE, and CEA than those with poor efficacy ( < 0.05). Joint detection showed a larger area under the curve (AUC) (0.900; 95%CI, 0.812-0.988), a higher sensitivity, and a superior detection outcome to the stand-alone detection ( < 0.05). Diagnostic results were similar between joint detection and pathological examination ( > 0.05).
CONCLUSION
The application of serum TK1, PCDGF, CYFRA21-1, NSE, and CEA assay plus enhanced CT scan shows high sensitivity and diagnostic accuracy in the diagnosis and chemotherapy monitoring of nonsmall cell lung cancer and thus provides a diagnostic reference basis.
PubMed: 35368891
DOI: 10.1155/2022/8800787 -
Biomolecules & Biomedicine Jan 2024Clinical application of chemotherapy in lung cancer is constrained by side effects, notably cardiotoxicity, the mechanisms of which remain elusive. This study assessed...
Clinical application of chemotherapy in lung cancer is constrained by side effects, notably cardiotoxicity, the mechanisms of which remain elusive. This study assessed the potential of specific miRNAs as biomarkers for chemotherapy-induced cardiotoxicity in lung cancer. We employed two lung adenocarcinoma cell lines (Calu6 and H1792) and ventricular normal human cardiac fibroblasts (NHCF-V) in single and co-culture experiments. Functional tests were conducted using 100 µM carboplatin and 1µM vinorelbine doses. The effects of carboplatin and vinorelbine, both individually and in combination, were evaluated at cellular and molecular levels 48h post-therapy for both mono- and co-cultures. miR-205-5p, miR-21-5p, and miR-30a-5p, modulated by anticancer treatments and influencing cardiotoxicity, were analyzed. Vinorelbine and carboplatin treatment promoted apoptosis and autophagy in lung cancer cells and cardiac fibroblasts more than in controls. Western blot analyses revealed BCL2 and p53 protein upregulation. Using qRT-PCR, we investigated the expression dynamics of miR-21-5p, miR-30c-5p, and miR-205-5p in co-cultured cardiomyocytes and lung cancer cells, revealing altered miRNA patterns from vinorelbine and carboplatin treatment. Our findings underscore the intricate relationship between chemotherapy, miRNA regulation, and cardiotoxicity, highlighting the importance of cardiac health in lung cancer treatment decisions.
Topics: Humans; Cardiotoxicity; Coculture Techniques; Vinorelbine; Carboplatin; Gene Expression Regulation, Neoplastic; Carcinoma, Non-Small-Cell Lung; MicroRNAs; Lung Neoplasms; Antineoplastic Agents
PubMed: 37622179
DOI: 10.17305/bb.2023.9272 -
Lung Cancer (Amsterdam, Netherlands) Mar 2021Little progress has been achieved in non-small cell lung cancer (NSCLC) patients with unresectable stage III disease and new drug schemes are warranted.
Phase II clinical trial with metronomic oral vinorelbine and tri-weekly cisplatin as induction therapy, subsequently concomitant with radiotherapy (RT) in patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC). Analysis of survival and value of ctDNA for patient selection.
BACKGROUND
Little progress has been achieved in non-small cell lung cancer (NSCLC) patients with unresectable stage III disease and new drug schemes are warranted.
MATERIAL AND METHODS
In this open-label, single-arm, phase II trial 65 treatment-naïve stage III NSCLC deemed surgically unresectable by a multidisciplinary team were treated with 2 cycles of induction cisplatin at 80 mg/m every 21 days plus metronomic oral vinorelbine at 50 mg/day every Monday, Wednesday and Friday. During the concomitant treatment with thoracic radiotherapy cisplatin was administered in the same manner but oral vinorelbine was reduced to 30 mg/day. The objective was to administer a total radiotherapy dose of 66 Gy in 33 daily fractions of 2 Gy. The primary endpoint was progression-free survival (PFS). Correlation between circulating tumor DNA (ctDNA) levels and survival was also evaluated.
RESULTS
Fifty-five (78.5 %) patients completed treatment. Overall response rate, by RECIST criteria, was 66.2 %. Four (6.2 %) patients had complete response, 39 (60.0 %) partial response and 12 (18.5 %) stable disease. Seven patients (10.8 %) had progressive disease during the induction period. Median follow-up was 29.1 months (m), median PFS was 11.5 m (95 %CI: 9.6-15.4). PFS at 12 m in the intention-to-treat (ITT) population was 47.8 % (95 %CI: 35.1-59.4 %) and median OS was 35.6 m (95 %CI: 24.4-46.8). Grade ≥3 treatment-related adverse events occurred in 14 (21.5 %) patients during induction and in 13 (24.5 %) patients during concomitant treatment with esophagitis occurring in 3% and pneumonitis in 1.5 % of the patients. Patients with undetectable ctDNA after 3 m follow-up had median PFS and OS of 18.1 m (95 %CI: 8.8-NR) and not reached (NR) (95 %CI: 11.3-NR), respectively, compared with 8.0 m (95 %CI: 2.7-NR) and 24.7 m (95 %CI: 5.7-NR) for patients who remained ctDNA positive at that time point.
CONCLUSIONS
Metronomic oral vinorelbine and cisplatin obtains similar efficacy results with significantly lower toxicity than the same chemotherapy at standard doses. ctDNA can identify populations with particularly good prognosis.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Circulating Tumor DNA; Cisplatin; Humans; Induction Chemotherapy; Lung Neoplasms; Neoplasm Staging; Patient Selection; Survival Analysis; Treatment Outcome; Vinblastine; Vinorelbine
PubMed: 33453470
DOI: 10.1016/j.lungcan.2021.01.005 -
Blood Advances Apr 2022Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are...
Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML), as outcomes remain poor. Therapeutic options are limited in this heavily pretreated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline-based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate, defined as complete remission or complete remission with partial recovery of platelet count, was 71.4% (95% confidence interval [CI], 41.9-91.6) for those patients in first relapse (n = 14) and 47.4% (95% CI, 24.4-71.1) for patients in second or greater relapse or with refractory disease. Responses were seen across multiple high-risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year overall survival for patients in first relapse was 46.2% (95% CI, 19.1-73.3) and 50.0% (95% CI, 26.9-73.1) for patients who responded to TVTC. For pediatric and young adult patients with relapsed/refractory AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Child; Clofarabine; Humans; Leukemia, Myeloid, Acute; Recurrence; Thiotepa; Topotecan; Vinorelbine; Young Adult
PubMed: 35008101
DOI: 10.1182/bloodadvances.2021005753 -
Cancers Sep 2022Eribulin, a natural product-based microtubule targeting agent with cytotoxic and noncytotoxic mechanisms, is FDA approved for certain patients with advanced breast...
Eribulin, a natural product-based microtubule targeting agent with cytotoxic and noncytotoxic mechanisms, is FDA approved for certain patients with advanced breast cancer and liposarcoma. To investigate the feasibility of developing drug-specific predictive biomarkers, we quantified antiproliferative activities of eribulin versus paclitaxel and vinorelbine against 100 human cancer cell lines from the Cancer Cell Line Encyclopedia, and correlated results with publicly available databases to identify genes and pathways associated with eribulin response, either uniquely or shared with paclitaxel or vinorelbine. Mean expression ratios of 11,985 genes between the most and least sensitive cell line quartiles were sorted by -values and drug overlaps, yielding 52, 29 and 80 genes uniquely associated with eribulin, paclitaxel and vinorelbine, respectively. Further restriction to minimum 2-fold ratios followed by reintroducing data from the middle two quartiles identified 9 and 13 drug-specific unique fingerprint genes for eribulin and vinorelbine, respectively; surprisingly, no gene met all criteria for paclitaxel. Interactome and Reactome pathway analyses showed that unique fingerprint genes of both drugs were primarily associated with cellular signaling, not microtubule-related pathways, although considerable differences existed in individual pathways identified. Finally, four-gene (, , , ) and five-gene (, , , , ) multivariate regression models for eribulin and vinorelbine showed high statistical correlation with drug-specific responses across the 100 cell lines and accurately calculated predicted mean IC50s for the most and least sensitive cell line quartiles as surrogates for responders and nonresponders, respectively. Collectively, these results provide a foundation for developing drug-specific predictive biomarkers for eribulin and vinorelbine.
PubMed: 36139690
DOI: 10.3390/cancers14184532