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The British Journal of Ophthalmology Feb 2011Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of uveitic complications such as cystoid macular oedema (CMO), choroidal... (Review)
Review
Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of uveitic complications such as cystoid macular oedema (CMO), choroidal neovasularisation (CNV) and retinal neovascularisation (RNV). The use of intravitreal anti-VEGF therapies, namely bevacizumab and ranibizumab, has recently been described in the treatment of these complications. Evidence describing the use of intravitreal anti-VEGF therapy for these complications consists of case reports and case series, most of which are retrospective and have limitations in design and analysis. As such, the current level of evidence supporting the use of intravitreal anti-VEGF therapy for these complications of uveitis would be rated as very low. Furthermore, blockage of VEGF has not been shown to have an anti-inflammatory effect. Thus, treatment of the underlying inflammatory disease should play a central role in the management of uveitic CMO, CNV and RNV. A two-pronged treatment regimen that focuses on achieving disease quiescence through the use of corticosteroids and/or immunosuppressive agents, while treating complications that arise despite adequate disease quiescence with intravitreal anti-VEGF agents, may be useful. However, further data from prospective controlled trials are needed before the therapeutic role of anti-VEGF therapy in the uveitis treatment regimen can be fully determined.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Humans; Macular Edema; Ranibizumab; Uveitis; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 20494915
DOI: 10.1136/bjo.2009.177279 -
Current Oncology Reports Sep 2020Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways could potentiate improved outcomes in patients with... (Meta-Analysis)
Meta-Analysis
PURPOSE OF REVIEW
Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways could potentiate improved outcomes in patients with metastatic EGFR-mutated non-small cell lung cancer (NSCLC). The purpose of this systematic review and meta-analysis was to compare the efficacy of an EGFR tyrosine kinase inhibitor (TKI) plus a VEGF inhibitor with EGFR TKI alone for the treatment of EGFR-mutated NSCLC.
RECENT FINDINGS
We systematically searched for randomized controlled trials (RCT) that involved patients with EGFR-mutated metastatic NSCLC treated with combination therapy versus EGFR TKI alone. In a pooled analysis of 5 studies, treatment with the combination therapy was associated with statistically significant improvements in progression-free survival (hazard ratio [HR] 0.63, 95% CI [0.54, 0.75]) when compared with control. However, pooled data from 4 studies revealed no statistically significant differences between the 2 groups for overall survival (HR 1.00, 95% CI [0.68, 1.52]) and the objective response rate (relative risk [RR] 1.05, 95% CI [0.97, 1.14]). In patients with metastatic EGFR-mutated NSCLC, treatment with EGFR TKI plus VEGF inhibition provided significant improvements in progression-free survival, but not in overall survival or objective response rate, when compared with treatment with EGFR TKI alone.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Humans; Lung Neoplasms; Protein Kinase Inhibitors; Randomized Controlled Trials as Topic; Vascular Endothelial Growth Factor A
PubMed: 32945977
DOI: 10.1007/s11912-020-00981-0 -
Gene Jun 2023The dried tuber of Pinellia ternata (Thunb.) Breit, Pinelliae Rhizoma (PR, also named 'Banxia' in Chinese), is widely used in traditional medicine. This review aims to...
The dried tuber of Pinellia ternata (Thunb.) Breit, Pinelliae Rhizoma (PR, also named 'Banxia' in Chinese), is widely used in traditional medicine. This review aims to provide detail summary of active ingredients, pharmacological effects, toxic ingredients, detoxification strategies, and omic researches, etc. Pharmacological ingredients from PR are mainly classified into six categories: alkaloids, amino acids, polysaccharides, phenylpropanoids, essential oils, and glucocerebrosides. Diversity of chemical composition determines the broad-spectrum efficacy and gives a foundation for the comprehensive utilization of P. ternata germplasm resources. The pharmacological compounds are involved in inhibition of cancer cells by targeting various pathways, including activation of immune system, inhibition of proliferation and cycle, induction of apoptosis, and inhibition of angiogenesis. The pharmacological components of PR act on nervous system by targeting neurotransmitters, activating immune system, decreasing apoptosis, and increasing redox system. Lectins, one major class of the toxic ingredients extracted from raw PR, possess significant toxic effects on human cells. Inflammatory factors, cytochrome P450 proteins (CYP) family enzymes, mammalian target of rapamycin (mTOR) signaling factors, transforming growth factor-β (TGF-β) signaling factors, and nervous system, are considered to be the target sites of lectins. Recently, omic analysis is widely applied in Pinellia genus studies. Plastome genome-based molecular markers are deeply used for identifying and resolving phylogeny of Pinellia genus plants. Various omic works revealed and functional identified a series of environmental stress responsive factors and active component biosynthesis-related genes. Our review summarizes the recent progress in active and toxic ingredient evaluation, pharmacological effects, detoxification strategies, and functional gene identification and accelerates efficient utilization of this traditional herb.
Topics: Humans; Drugs, Chinese Herbal; Pinellia; Multiomics; Alkaloids; Lectins
PubMed: 37044184
DOI: 10.1016/j.gene.2023.147426 -
International Journal of Molecular... Jun 2022Most ovarian cancer cases are diagnosed at an advanced stage (III or IV), in which a primary debulking surgery combined with adjuvant systemic chemotherapy is the... (Review)
Review
Most ovarian cancer cases are diagnosed at an advanced stage (III or IV), in which a primary debulking surgery combined with adjuvant systemic chemotherapy is the standard management. Since targeted therapy is less toxic to human cells than systemic chemotherapy, it has drawn much attention and become more popular. Angiogenesis is a critical process during the proliferation of ovarian cancer cells. Currently, many studies have put emphases on anti-angiogenetic medication, such as bevacizumab, the first and most investigated angiogenesis inhibitor that can exert anti-neoplastic effects. Bevacizumab is a recombinant humanized monoclonal antibody that has been approved for first-line maintenance treatment of advanced ovarian cancer. This review is a summary of current literature about the molecular mechanisms of actions, safety, and effects of bevacizumab for use in advanced epithelial ovarian cancer. Some common side effects of bevacizumab will be also discussed. As an inhibitor of angiogenesis, bevacizumab binds to circulating vascular endothelial growth factor (VEGF) and thereby inhibits the binding of VEGF to its receptors on the surface of endothelial cells. Neutralization of VEGF prevents neovascularization and leads to apoptosis of tumor endothelial cells and a decrease in interstitial fluid pressure within the tumors, which allows greater capacity for chemotherapeutic drugs to reach specific targeted sites. Grossly, bevacizumab has demonstrated some significant therapeutic benefits in many randomized trials in combination with the standard chemotherapy for advanced epithelial ovarian cancer. Based on the available evidence, a higher dosage and a longer duration of bevacizumab appear to achieve better therapeutic effects and progression-free survival. On the other hand, patients with more severe diseases or at a higher risk of progression seem to benefit more from bevacizumab use. However, many unknown aspects of bevacizumab, including detailed mechanisms of actions, effectiveness, and safety for the treatment of ovarian cancer, warrant further investigation.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Ovarian Epithelial; Endothelial Cells; Female; Humans; Neovascularization, Pathologic; Ovarian Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 35805914
DOI: 10.3390/ijms23136911 -
Clinical Sarcoma Research 2020Osteosarcoma is a very aggressive primary bone tumour, affecting mainly young populations. Most cases diagnosed have distant macro- and micro-metastases at the time of... (Review)
Review
BACKGROUND
Osteosarcoma is a very aggressive primary bone tumour, affecting mainly young populations. Most cases diagnosed have distant macro- and micro-metastases at the time of diagnosis. Surgical resection with neoadjuvant and adjuvant therapies improves the overall and disease-free survival of patients. Doxycycline, a synthetic tetracycline, has been found to act either as an antibiotic drug or as a chemotherapeutic agent. Its anti-neoplastic role has been found to be significant, in vitro and in vivo laboratory trials, in various types of cancer, such as prostate, intestinal, central neural system cancers and osteosarcoma. Inhibition of metalloproteinases (MMPs) in different stages of tumour expansion is the most well-understood mechanism. MMPs are secreted molecules from various normal cells, such as fibroblasts, leucocytes and vascular smooth muscles, as well as from cells with high proliferative potential, such as tumour cells. In osteosarcoma, MMPs have been found to be overexpressed. MMPs help osteosarcoma cells survive, grow and produce metastases in distant sites, mainly in the lungs. Doxycycline blocks extracellular matrix and basic membrane degradation by suppressing MMP function. As a consequence, osteosarcoma cells lose their ability to invade and metastasize. Additionally, doxycycline eliminates the secretion of vascular endothelial growth factor (VEGF) and deprives the supply of circulating nutrients by its anti-angiogenesis action. The aim of this review is to evaluate doxycycline's action against osteosarcoma cells as an MMP-inhibitor and interpret its usage as a chemotherapeutic agent.
METHODS
We checked PubMed and Google Scholar for recently published data, on the tumour-supportive role of MMPs and VEGF in osteosarcoma cells. We further studied published experimental trials on the role of doxycycline as a tumour-suppressive agent via MMPs and VEGF inhibition.
RESULTS
MMPs and VEGF have been found to play a fundamental role in osteosarcoma cells survival and high aggressiveness by in vitro, in vivo and clinical trials. Nevertheless, doxycycline has proved its tumour-suppressive effect by in vivo experimental trials in various cancers but not yet in osteosarcoma.
CONCLUSION
Doxycycline remains a promising chemotherapeutic agent against osteosarcoma via MMP inhibition, showing the need for further in vivo and clinical trials to be carried out in the future.
PubMed: 32377334
DOI: 10.1186/s13569-020-00128-6 -
Evidence-based Complementary and... 2020Colorectal cancer represents a heavy burden for health systems worldwide, being the third most common cancer worldwide. Despite the breakthroughs in medicine, current... (Review)
Review
OBJECTIVE
Colorectal cancer represents a heavy burden for health systems worldwide, being the third most common cancer worldwide. Despite the breakthroughs in medicine, current chemotherapeutic options continue to have important side effects and may not be effective in preventing disease progression. Cannabinoids might be substances with possible therapeutic potential for cancer because they can attenuate the side effects of chemotherapy and have antiproliferative and antimetastatic effects. We aim to determine, through a systematic review of experimental studies performed on animal CRC models, if cannabinoids can reduce the formation of preneoplastic lesions (aberrant crypt foci), number, and volume of neoplastic lesions.
MATERIALS AND METHODS
A systematic, qualitative review of the literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Embase, and Scopus databases were searched. We use the following Medical Subject Headings (MESH) terms in PubMed: "colorectal neoplasms," "colonic neoplasms," "colorectal cancer," "polyps," "rimonabant," "cannabidiol," "cannabinoids," "azoxymethane," "xenograft," and "mice." Only studies that met the eligibility criteria were included.
RESULTS
Eight experimental studies were included in the analysis after the full-text evaluation. Seven studies were azoxymethane (AOM) colorectal cancer models, and four studies were xenograft models. Cannabidiol botanical substance (CBD BS) and rimonabant achieved high aberrant crypt foci (ACF) reduction (86% and 75.4%, respectively). Cannabigerol, O-1602, and URB-602 demonstrated a high capacity for tumor volume reduction. Induction of apoptosis, interaction with cell survival, growth pathways, and angiogenesis inhibition were the mechanisms extracted from the studies that explain cannabinoids' actions on CRC.
CONCLUSIONS
Cannabinoids have incredible potential as antineoplastic agents as experimental models demonstrate that they can reduce tumor volume and ACF formation. It is crucial to conduct more experimental studies to understand the pharmacology of cannabinoids in CRC better.
PubMed: 32765628
DOI: 10.1155/2020/2371527 -
International Journal of Molecular... Nov 2023This systematic review aims to evaluate the influence of environmental enrichment (EE) on oncological factors in experimental studies involving various types of cancer... (Review)
Review
This systematic review aims to evaluate the influence of environmental enrichment (EE) on oncological factors in experimental studies involving various types of cancer models. A comprehensive search was conducted in three databases: PubMed (161 articles), Embase (335 articles), and Scopus (274 articles). Eligibility criteria were applied based on the PICOS strategy to minimize bias. Two independent researchers performed the searches, with a third participant resolving any discrepancies. The selected articles were analyzed, and data regarding sample characteristics and EE protocols were extracted. The outcomes focused solely on cancer and tumor-related parameters, including cancer type, description of the cancer model, angiogenesis, tumor occurrence, volume, weight, mice with tumors, and tumor inhibition rate. A total of 770 articles were identified across the three databases, with 12 studies meeting the inclusion criteria for this systematic review. The findings demonstrated that different EE protocols were effective in significantly reducing various aspects of tumor growth and development, such as angiogenesis, volume, weight, and the number of mice with tumors. Furthermore, EE enhanced the rate of tumor inhibition in mouse cancer models. This systematic review qualitatively demonstrates the impacts of EE protocols on multiple parameters associated with tumor growth and development, including angiogenesis, occurrence, volume, weight, and tumor incidence. Moreover, EE demonstrated the potential to increase the rate of tumor inhibition. These findings underscore the importance of EE as a valuable tool in the management of cancer.
Topics: Humans; Mice; Animals; Disease Models, Animal; Neoplasms; Medical Oncology
PubMed: 38003706
DOI: 10.3390/ijms242216516 -
Evidence-based Complementary and... 2021and its main ingredient nobiletin (NOB) have received widespread attention in recent years due to their antitumor effects. The antitumor effect of is related to the... (Review)
Review
and its main ingredient nobiletin (NOB) have received widespread attention in recent years due to their antitumor effects. The antitumor effect of is related to the traditional use, mainly in its Chinese medicinal properties of soothing the liver and promoting qi, resolving phlegm, and dispelling stagnation. Some studies have proved that and NOB are more effective for triple-negative breast cancer (TNBC), which is related to the syndrome of stagnation of liver qi. From the perspective of modern biomedical research, NOB has anticancer effects. Its potential molecular mechanisms include inhibition of the cell cycle, induction of apoptosis, and inhibition of angiogenesis, invasion, and migration. and NOB can also reduce the side effects of chemotherapy drugs and reverse multidrug resistance (MDR). However, more research studies are needed to clarify the underlying mechanisms. The modern evidence of and NOB in breast cancer treatment has a strong connection with the traditional concepts and laws of applying in Chinese medicine (CM). As a low-toxic anticancer drug candidate, NOB and its structural changes, , and compound prescriptions will attract scientists to use advanced technologies such as genomics, proteomics, and metabolomics to study its potential anticancer effects and mechanisms. On the contrary, there are relatively few studies on the anticancer effects of and NOB . The clinical application of and NOB as new cancer treatment drugs requires verification and further anticancer mechanism research. This review aims to provide reference for the treatment of breast cancer by Chinese medicine.
PubMed: 34257674
DOI: 10.1155/2021/2847466 -
Expert Opinion on Pharmacotherapy Feb 2008Pegaptanib sodium, the first aptamer therapeutic approved for use and the first antiangiogenic agent used to treat ocular neovascular disease, acts by inhibiting the 165... (Review)
Review
BACKGROUND
Pegaptanib sodium, the first aptamer therapeutic approved for use and the first antiangiogenic agent used to treat ocular neovascular disease, acts by inhibiting the 165 isoform of vascular endothelial growth factor believed primarily responsible for pathologic ocular neovascularization and vascular permeability.
OBJECTIVE
To briefly present the pharmacology, clinical efficacy and safety, and role of pegaptanib in treating ocular neovascular diseases.
METHODS
A systematic literature review and synopsis.
RESULTS/CONCLUSION
After more than 10 years in development, clinical trials have shown pegaptanib efficacy in treating choroidal neovascularization of age-related macular degeneration. Its excellent ocular and systemic safety profiles have been confirmed in up to 3 years of experience. Early phase, well-controlled studies also suggest therapeutic benefit in diabetic retinopathy and retinal vein occlusion.
Topics: Aged; Angiogenesis Inhibitors; Aptamers, Nucleotide; Choroidal Neovascularization; Humans; Macular Degeneration; Protein Isoforms; Vascular Endothelial Growth Factor A
PubMed: 18220500
DOI: 10.1517/14656566.9.3.499 -
Journal of Vascular Research 2022Of the 200 million patients worldwide affected by peripheral arterial disease (PAD), 4% will inevitably require major limb amputation. Previous systematic reviews... (Review)
Review
BACKGROUND
Of the 200 million patients worldwide affected by peripheral arterial disease (PAD), 4% will inevitably require major limb amputation. Previous systematic reviews presented a conflicting body of evidence in terms of vascular endothelial growth factor (VEGF) family member effects upon PAD natural progression. Despite that, modulation of intrinsic angiogenesis mechanisms targeting the VEGF family members still confers an attractive therapeutic target. The aim of the present study was to evaluate current evidence of VEGF modulation in the context of PAD.
METHODS
This is a systematic literature review conducted according to the PRISMA guidelines and registered under PROSPERO database [CRD42021285988]. Independent literature search was performed up to April 1, 2022, on six databases. A total of 22 eligible studies were identified [N: 3, interventional patient studies; N: 19, animal studies]. Animal studies were appraised by the SYRCLE risk of bias tool, while human participant studies were assessed by the Newcastle Ottawa scale. Overall, quality of evidence was deemed fair for both animal and human studies. Main study outcomes were percentage change of injured vessel lumen stenosis and neointimal area formation upon VEGF modulation (inhibition or activation) in comparison with control group.
FINDINGS
Nineteen animal models and three human participant studies were included in the systematic review and assessed separately. Positive modulation of VEGF-A in animal models resulted in a median decrease of 65.58% [95% CI 45.2; 71.87] in lumen stenosis [14 studies]. Furthermore, positive modulation of VEGF-A was found to reduce neointimal area proliferation by a median decrease of 63.41% [95% CI 41.6; 79.59] [14 studies]. Median end of study duration was 28 days [range: 14-84 days]. Data were insufficient to assess these outcomes with respect to VEGF-B or VEGF-C modulation. The limited number of available human studies presented inadequate outcome assessment despite their overall fair NOS grading.
INTERPRETATION
VEGF-A-positive modulation decreases lumen stenosis and neointimal hyperplasia in PAD simulation animal models. Previously identified variability among outcomes was found to strongly stem from the variability of experimental designs. Clinical applicability and safety profile of VEGF-A in the context of PAD remain to be defined by a robust and uniformly designed body of further animal model-based experiments.
Topics: Animals; Humans; Vascular Endothelial Growth Factor A; Constriction, Pathologic; Peripheral Arterial Disease
PubMed: 36380643
DOI: 10.1159/000527079