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Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692 -
Frontiers in Oncology 2022Chemokines are a class of pro-inflammatory cytokines that can recruit and activate chemotactic cells. C-X-C motif chemokine ligand 5 (CXCL5) is a member of the chemokine...
Chemokines are a class of pro-inflammatory cytokines that can recruit and activate chemotactic cells. C-X-C motif chemokine ligand 5 (CXCL5) is a member of the chemokine family binding CXCR2 (C-X-C Motif Chemokine Receptor 2), a G-protein coupled receptor. Accumulated evidence has shown that dysregulated CXCL5 participates in tumor metastasis and angiogenesis in human malignant tumors. In this review, we summarized the advances in research on CXCL5, including its dysregulation in different tumors and the mechanism associated with tumor behavior (formation of the immunosuppressive microenvironment, promotion of tumor angiogenesis, and metastasis). We also summarized and discussed the perspective about the potential application of CXCL5 in tumor therapy targeting the tumor inflammatory microenvironment.
PubMed: 35978824
DOI: 10.3389/fonc.2022.944494 -
Biomolecules Sep 2022Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made... (Review)
Review
Prostate cancer is one of the leading causes of death for men worldwide. The development of resistance, toxicity, and side effects of conventional therapies have made prostate cancer treatment become more intensive and aggressive. Many phytochemicals isolated from plants have shown to be tumor cytotoxic. In vitro laboratory studies have revealed that natural compounds can affect cancer cell proliferation by modulating many crucial cellular signaling pathways frequently dysregulated in prostate cancer. A multitude of natural compounds have been found to induce cell cycle arrest, promote apoptosis, inhibit cancer cell growth, and suppress angiogenesis. In addition, combinatorial use of natural compounds with hormone and/or chemotherapeutic drugs seems to be a promising strategy to enhance the therapeutic effect in a less toxic manner, as suggested by pre-clinical studies. In this context, we systematically reviewed the currently available literature of naturally occurring compounds isolated from vegetables, fruits, teas, and herbs, with their relevant mechanisms of action in prostate cancer. As there is increasing data on how phytochemicals interfere with diverse molecular pathways in prostate cancer, this review discusses and emphasizes the implicated molecular pathways of cell proliferation, cell cycle control, apoptosis, and autophagy as important processes that control tumor angiogenesis, invasion, and metastasis. In conclusion, the elucidation of the natural compounds' chemical structure-based anti-cancer mechanisms will facilitate drug development and the optimization of drug combinations. Phytochemicals, as anti-cancer agents in the treatment of prostate cancer, can have significant health benefits for humans.
Topics: Antineoplastic Agents; Apoptosis; Hormones; Humans; Male; Neovascularization, Pathologic; Phytochemicals; Prostatic Neoplasms
PubMed: 36139145
DOI: 10.3390/biom12091306 -
Diagnostics (Basel, Switzerland) Dec 2022Breast cancer is one of the most common malignancies among women around the world. The basal or triple-negative subtype (TNBC) is a heterogeneous group of tumors,... (Review)
Review
Breast cancer is one of the most common malignancies among women around the world. The basal or triple-negative subtype (TNBC) is a heterogeneous group of tumors, characterized by its aggressive and metastatic nature, with low survival and worse prognosis. Research on genetic biomarkers, such as microRNAs (miRs) in TNBC, demonstrate their relevance in the prognosis of the disease. Therefore, the objective of this research was to verify the role of miRs in the prognosis of TNBC. A search was carried out in the PubMed (MEDLINE), Web of Science, and Scopus databases, with articles in the English language from 2010 to 2022. Only articles that analyzed the role of miRNAs in the prognosis of TNBC and that met the criteria of the MOOSE method were included. For the preparation and planning of this systematic review, a PRISMA checklist and the MOOSE method were used. The Newcastle-Ottawa Scale was used to analyze the quality of the included studies. The excluded criteria considered were: (1) studies that presented duplication in the databases; (2) reviews of the literature, clinical case reports, meta-analyses, conference abstracts, letters to the editor, theses, dissertations, and book chapters; (3) studies that stratified only women diagnosed with other subtypes of breast cancer subtypes; (4) experiments without a control or comparison group. After the bibliographic survey of the 2.274 articles found, 43 articles met the inclusion criteria, totaling 5421 patients with TNBC analyzed for this review. Six miRs (miR-155, miR-21, miR-27a/b/, miR-374a/b, miR-30a/c/e, and miR-301a) were included in the meta-analysis. A low expression of miR-155 was associated with reduced overall survival (OS) (HR: 0.68, 95% CI: 0.58-0.81). A high expression of miR-21 was a predictor of OS reduction (HR: 2.56; 95% CI: 1.49-4.40). In addition, high levels of miR-27a/b and miR-301a/b were associated with lower OS, while the decreased expression levels of miR-30 and miR-374a/b were associated with worse relapse-free survival (RFS) and shorter disease-free survival (DFS), respectively. The present study revealed that miRs play essential roles in the development of metastases, in addition to acting as suppressors of the disease, thus improving the prognosis of TNBC. However, the clinical application of these findings has not yet been investigated.
PubMed: 36611419
DOI: 10.3390/diagnostics13010127 -
Systematic Reviews May 2020Vascular endothelial growth factor (VEGF) is one of the angiogenesis regulators, which plays an important role in tumor angiogenesis and tumor progression. Current... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vascular endothelial growth factor (VEGF) is one of the angiogenesis regulators, which plays an important role in tumor angiogenesis and tumor progression. Current studies have found that VEGF plays an important role in hematologic diseases including acute myeloid leukemia (AML). However, the circulating levels of VEGF in AML were still controversial among published studies.
METHODS
Three databases including PubMed, EMBASE, and Cochrane Library databases were searched up to February 2020. All articles included in the meta-analysis met our inclusion and exclusion criteria. Studies will be screened and data extracted by two independent investigators. The Newcastle-Ottawa Scale (NOS) and the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool were applied to evaluate the quality of the included studies. A random-effects model was applied to pool the standardized mean difference (SMD). Heterogeneity test was performed by the Q statistic and quantified using I. All statistical analysis was conducted in Stata 12.0 software.
RESULTS
Fourteen case-control studies were finally included in this systematic review and meta-analysis. Heterogeneity was high in our included studies (I = 91.1%, P < 0.001). Sensitivity analysis showed no significant change when any one study was excluded using random-effect methods (P > 0.05). Egger's linear regression test showed that no publication bias existed (P > 0.05). Patients with AML, mainly those newly diagnosed and untreated, have higher VEGF levels (SMD = 0.85, 95% CI 0.28-1.42). Moreover, AML patients in n ≥ 40 group, plasma group, Asia and Africa group, and age ≥ 45 group had higher circulating VEGF levels (all P < 0.05).
CONCLUSIONS
Compared to healthy controls, our meta-analysis shows a significantly higher level of circulating VEGF in AML patients, and it is associated with sample size, sample type, region, and age.
Topics: Africa; Asia; Humans; Leukemia, Myeloid, Acute; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 32375879
DOI: 10.1186/s13643-020-01368-9 -
Cancer Cell International 2020Nestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer. Although the prognostic and clinicopathological impact of...
BACKGROUND
Nestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer. Although the prognostic and clinicopathological impact of nestin expression on breast cancer patients has been assessed in several independent studies, their results remained conflicting. Therefore, we performed this meta-analysis to elucidate the prognostic and clinicopathological association of nestin expression with breast cancer.
METHODS
A comprehensive literature search was performed in the electronic databases PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wangfang Data. The statistical analysis was conducted using Stata 15.0 and Review Manager 5.3.
RESULTS
A total of 15 studies with 6066 breast cancer patients were included in this meta-analysis. Pooled results indicated that positive expression of nestin was significantly associated with reduced breast cancer-specific survival (BCSS, univariate analysis, HR = 2.11, 95% CI [1.79, 2.49], P < 0.00001; multivariate analysis, HR = 1.30, 95% CI [1.06, 1.60], P = 0.01), worse overall survival (OS, univariate analysis, HR = 1.88, 95% CI [1.31, 2.71], P = 0.0007; multivariate analysis, HR = 1.89, 95% CI [1.34, 2.67], P = 0.0003) and poorer recurrence-free survival (univariate analysis, HR = 2.60, 95% CI [1.52, 4.46], P = 0.0005), but not with distant metastasis-free survival in univariate analysis (P > 0.05). In addition, increased nestin expression was correlated with younger age, higher tumor grade, larger tumor size, positive blood vessel invasion and high vascular proliferation index, but not with lymph node metastasis or lymph vessel invasion. Nestin was preferentially expressed in invasive ductal carcinoma, triple-negative breast cancer and basal-like subtypes. Nestin expression was inversely associated with the expression of ER and PR, but not with HER-2. Conversely, nestin expression was positively correlated with the expression of basal-like markers CK5, P-cadherin and EGFR. Moreover, nestin expression was strongly associated with the presence of five basal-like profiles (BLP1-5).
CONCLUSIONS
This meta-analysis revealed the prognostic value and clinicopathological significance of nestin expression in breast cancer. Nestin is an independent prognostic factor for worse BCSS and OS of breast cancer patients. Nestin is also a valuable biomarker for unfavorable clinicopathological features and tumor angiogenesis of breast cancer. Therefore, nestin is a promising therapeutic target for malignant breast cancer, especially for TNBC and basal-like phenotype.
PubMed: 32467665
DOI: 10.1186/s12935-020-01252-5 -
Chinese Journal of Integrative Medicine Mar 2023Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of... (Review)
Review
Cancers have high morbidity and mortality rates worldwide. Current anticancer therapies have demonstrated specific signaling pathways as a target in the involvement of carcinogenesis. Autophagy is a quality control system for proteins and plays a fundamental role in cancer carcinogenesis, exerting an anticarcinogenic role in normal cells and can inhibit the transformation of malignant cells. Therefore, drugs aimed at autophagy can function as antitumor agents. Flavonoids are a class of polyphenolic secondary metabolites commonly found in plants and, consequently, consumed in diets. In this review, the systematic search strategy was used, which included the search for descriptors "flavonoids" AND "mTOR pathway" AND "cancer" AND "autophagy", in the electronic databases of PubMed, Cochrane Library, Web of Science and Scopus, from January 2011 to January 2021. The current literature demonstrates that flavonoids have anticarcinogenic properties, including inhibition of cell proliferation, induction of apoptosis, autophagy, necrosis, cell cycle arrest, senescence, impaired cell migration, invasion, tumor angiogenesis and reduced resistance to multiple drugs in tumor cells. We demonstrate the available evidence on the roles of flavonoids and autophagy in cancer progression and inhibition. (Registration No. CRD42021243071 at PROSPERO).
Topics: Humans; Flavonoids; Neoplasms; Antineoplastic Agents; Signal Transduction; Apoptosis; Cell Proliferation; Carcinogenesis; Cell Line, Tumor
PubMed: 35809179
DOI: 10.1007/s11655-022-3674-9 -
Medicine Jun 2022Earlier studies have shown that the superb microvascular imaging (SMI) can detect tumor angiogenesis to distinguish thyroid nodules, but there is no systematic review.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Earlier studies have shown that the superb microvascular imaging (SMI) can detect tumor angiogenesis to distinguish thyroid nodules, but there is no systematic review. This meta-analysis aimed to identify the accuracy of ultrasound SMI for the diagnosis of thyroid nodules.
METHODS
We searched PubMed, Cochrane Library, and CBM databases. A meta-analysis was conducted using STATA version 14.0 and Meta-Disc version 1.4 software. We calculated the summary statistics for sensitivity, specificity, positive and negative likelihood ratio (LR+/LR-), diagnostic odds ratio, and the synthetic receiver operating characteristic curve. Data will be pooled by either a fixed-effects model or a random-effects model according to the results of heterogeneity identification.
RESULTS
11 studies that met the inclusion criteria were included in this meta-analysis. The quality assessment of the study of diagnostic accuracy studies scores of all included studies were ≥22. A total of 1003 thyroid malignant nodules and 957 thyroid benign nodules were assessed. The main outcome included: the pooled sensitivity was 0.81 (95% confidence intervals (CI) = 0.79-0.84), and the pooled specificity was 0.86 (95% CI = 0.84-0.88); the pooled LR+ was 5.79 (95% CI = 4.44-7.54), and the pooled negative LR- was 0.23 (95% CI = 0.20-0.26); the pooled diagnostic odds ratio of SMI in the diagnosis of thyroid nodules was 26.84 (95% CI = 19.13-37.60). The area under the synthetic receiver operating characteristic curve was 0.89 (95% CI = 0.86-0.91). We found no evidence for publication bias (t = 0.72, P = .49).
CONCLUSION
Our meta-analysis indicates that SMI may have high diagnostic accuracy in distinguishing benign and malignant thyroid nodules.
SYSTEMATIC REVIEW REGISTRATION
INPLASY202080084.
Topics: Diagnosis, Differential; Humans; Odds Ratio; ROC Curve; Sensitivity and Specificity; Thyroid Nodule; Ultrasonography
PubMed: 35713460
DOI: 10.1097/MD.0000000000029505 -
Biomedicine & Pharmacotherapy =... Oct 2020Cancer is a major cause of death in the world. Chemotherapy can extend the life of cancer patients to some extent, but the quality of life is reduced. Therefore, the...
Cancer is a major cause of death in the world. Chemotherapy can extend the life of cancer patients to some extent, but the quality of life is reduced. Therefore, the quest for more efficient and less toxic medication strategies is still at the forefront of current research. Hedyotis diffusa Willd (HDW), a Chinese herb medicine, has received great attention in the past two decades and has been well documented in clinics for antitumor activity in a variety of human cancers. This review discussed a total of 58 different kinds of active antitumor components isolated from HDW, including iridoids, flavonoids, flavonol glycosides, anthraquinones, phenolic acids, and their derivatives, sterols, and volatile oils. Their antitumor activities include inhibition of tumor cell proliferation, induction of tumor cell apoptosis and tumor angiogenesis, regulation of the host immune response, anti-inflammatory and antioxidant, and protective autophagy. Besides, we provide up-to-date and systematic evidence for HDW antitumor activities and the possible underlying molecular mechanisms and reference for further development of novel drugs and dosage formulation in control of human cancers.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Drugs, Chinese Herbal; Hedyotis; Humans; Plant Extracts
PubMed: 34321173
DOI: 10.1016/j.biopha.2020.110735 -
Frontiers in Pharmacology 2024Platinum-based dual-drug first-line chemotherapy is commonly employed in the treatment of patients with advanced non-small cell lung cancer (NSCLC), although its...
The efficacy of bevacizumab combined with platinum-containing chemotherapy in the treatment of advanced non-small cell lung cancer in China: a systematic review and meta-analysis of randomized clinical trials.
Platinum-based dual-drug first-line chemotherapy is commonly employed in the treatment of patients with advanced non-small cell lung cancer (NSCLC), although its clinical efficacy is limited. Bevacizumab can antagonize vascular endothelial cell growth factor (VEGF), which inhibit tumor angiogenesis and prevent tumor invasion and development. However, a comprehensive meta-analysis evaluating the effectiveness and safety of combining bevacizumab with platinum-based chemotherapy in advanced NSCLC patients is lacking. Randomized controlled trials (RCTs) investigating the combination therapy of bevacizumab and platinum-based chemotherapy for treating advanced NSCLC were searched across six databases. Data on objective response rate (ORR), disease control rate (DCR), 1-year survival rate, 2-year survival rate, 3-year survival rate, VEGF levels, and side effects were synthesized. Relative risk degree (RR) along with 95% confidence interval (CI) was used as statistical analysis measures for binary outcomes while continuous variables were analyzed using mean difference (MD) along with 95% CI. Heterogeneity was evaluated by Chi-squared and I tests. If there was heterogeneity, subgroup analysis was performed. Sensitivity analysis of the main outcome measures and assessment of publication bias were also performed. According to our screening criteria, a total of Forty-nine RCTs were included, involving data from 4268 patients. The results of this analysis showed that compared with platinum-containing chemotherapy alone, bevacizumab combined with platinum-containing chemotherapy significantly improved ORR (RR [95% CI], 1.53 [1.44, 1.63], < 0.00001), DCR (RR [95% CI], 1.24 [1.19, 1.29], < 0.0001), 1-year survival rate (RR [95% CI], 1.34 [1.15, 1.57], = 0.0003), 2-year survival rate (RR [95% CI], 2.16 [1.35, 3.43], = 0.001), 3-year survival rate (RR [95% CI], 2.00 [1.21, 3.30], = 0.007). In addition, bevacizumab with platinum-containing chemotherapy observably decreased the VEGF levels (RR [95% CI], -67.35 [-91.46, -43.25], < 0.00001). Combination therapy involving bevacizumab demonstrated improved antitumor effects compared to chemotherapy alone in terms of ORR, DCR, 1-year survival rate, 2-year survival rate, 3-year survival rate, and VEGF levels without an increased incidence of adverse reactions. These analyses' results can provide clinicians guidance when selecting appropriate treatments for patients diagnosed with advanced non-small cell lung cancer.
PubMed: 38318133
DOI: 10.3389/fphar.2024.1293039