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Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
Advances in Clinical and Experimental... May 2024Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and... (Review)
Review
Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.
Topics: Humans; Vascular Calcification; Atherosclerosis; Animals; Wnt Signaling Pathway; Adaptor Proteins, Signal Transducing; Genetic Markers
PubMed: 37676098
DOI: 10.17219/acem/169567 -
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 -
International Journal of Molecular... May 2024Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets... (Review)
Review
Breast cancer, the most invasive cancer in women globally, necessitates novel treatments due to prevailing limitations of therapeutics. Search of news anticancer targets is more necessary than ever to tackle this pathology. Heat-Shock Protein 90 (HSP90), a chaperone protein, is implicated in breast cancer pathogenesis, rendering it an appealing target. Looking for alternative approach such as Plant-based compounds and natural HSP90 inhibitors offer promising prospects for innovative therapeutic strategies. This study aims to identify plant-based compounds with anticancer effects on breast cancer models and elucidate their mechanism of action in inhibiting the HSP90 protein. A systematic review was conducted and completed in January 2024 and included in vitro, in vivo, and in silico studies that investigated the effectiveness of plant-based HSP90 inhibitors tested on breast cancer models. Eleven studies were included in the review. Six plants and 24 compounds from six different classes were identified and proved to be effective against HSP90 in breast cancer models. The studied plant extracts showed a dose- and time-dependent decrease in cell viability. Variable IC50 values showed antiproliferative effects, with the plant demonstrating the lowest value. Withanolides was the most studied class. Fennel, , and extracts were shown to inhibit tumor growth and angiogenesis and modulate HSP90 expression as well as its cochaperone interactions in breast cancer mouse models. The identified plant extracts and compounds were proven effective against HSP90 in breast cancer models, and this inhibition showed promising effects on breast cancer biology. Collectively, these results urge the need of further studies to better understand the mechanism of action of HSP90 inhibitors using comparable methods for preclinical observations.
Topics: Animals; Female; Humans; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; HSP90 Heat-Shock Proteins; Plant Extracts; Neoplasms, Experimental
PubMed: 38791506
DOI: 10.3390/ijms25105468 -
Cancers Jan 2024Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be... (Review)
Review
Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be effective in cancer prevention and treatment. Among bioactive flavonoids found in fruits and vegetables, kaempferol (KMP) is known for its anti-inflammatory, antioxidant, and anticancer properties. This systematic review aims to highlight the potential therapeutic effects of KMP on different types of solid malignant tumors. This review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Science Direct, Scopus, and Google Scholar. After the application of study criteria, 64 studies were included. In vitro experiments demonstrated that KMP exerts antitumor effects by controlling tumor cell cycle progression, proliferation, apoptosis, migration, and invasion, as well as by inhibiting angiogenesis. KMP was also able to inhibit important markers that regulate epithelial-mesenchymal transition and enhanced the sensitivity of cancer cells to traditional drugs used in chemotherapy, including cisplatin and 5-fluorouracil. This flavonoid is a promising therapeutic compound and its combination with current anticancer agents, including targeted drugs, may potentially produce more effective and predictable results.
PubMed: 38339336
DOI: 10.3390/cancers16030585 -
Journal of Nanobiotechnology Apr 2024Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on... (Review)
Review
Rare earth nanomaterials (RE NMs), which are based on rare earth elements, have emerged as remarkable biomaterials for use in bone regeneration. The effects of RE NMs on osteogenesis, such as promoting the osteogenic differentiation of mesenchymal stem cells, have been investigated. However, the contributions of the properties of RE NMs to bone regeneration and their interactions with various cell types during osteogenesis have not been reviewed. Here, we review the crucial roles of the physicochemical and biological properties of RE NMs and focus on their osteogenic mechanisms. RE NMs directly promote the proliferation, adhesion, migration, and osteogenic differentiation of mesenchymal stem cells. They also increase collagen secretion and mineralization to accelerate osteogenesis. Furthermore, RE NMs inhibit osteoclast formation and regulate the immune environment by modulating macrophages and promote angiogenesis by inducing hypoxia in endothelial cells. These effects create a microenvironment that is conducive to bone formation. This review will help researchers overcome current limitations to take full advantage of the osteogenic benefits of RE NMs and will suggest a potential approach for further osteogenesis research.
Topics: Osteogenesis; Endothelial Cells; Bone Regeneration; Osteoclasts; Nanostructures; Cell Differentiation
PubMed: 38627717
DOI: 10.1186/s12951-024-02442-3 -
Nutrients May 2024Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate,... (Review)
Review
Liver cancer ranks third globally among causes of cancer-related deaths, posing a significant public health challenge. However, current treatments are inadequate, prompting a growing demand for novel, safe, and effective therapies. Natural products (NPs) have emerged as promising candidates in drug development due to their diverse biological activities, low toxicity, and minimal side effects. This paper begins by reviewing existing treatment methods and drugs for liver cancer. It then summarizes the therapeutic effects of NPs sourced from various origins on liver cancer. Finally, we analyze the potential mechanisms of NPs in treating liver cancer, including inhibition of angiogenesis, migration, and invasion; regulation of the cell cycle; induction of apoptosis, autophagy, pyroptosis, and ferroptosis; influence on tumor metabolism; immune regulation; regulation of intestinal function; and regulation of key signaling pathways. This systematic review aims to provide a comprehensive overview of NPs research in liver cancer treatment, offering a foundation for further development and application in pharmaceuticals and functional foods.
Topics: Humans; Biological Products; Liver Neoplasms; Apoptosis; Signal Transduction; Antineoplastic Agents; Animals; Antineoplastic Agents, Phytogenic; Autophagy
PubMed: 38892575
DOI: 10.3390/nu16111642 -
Journal of Orthopaedic Surgery and... Apr 2024Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood... (Review)
Review
Hormonal necrosis of the femoral head is caused by long-term use of glucocorticoids and other causes of abnormal bone metabolism, lipid metabolism imbalance and blood microcirculation disorders in the femoral head, resulting in bone trabecular fracture, bone tissue necrosis collapse, and hip dysfunction. It is the most common type of non-traumatic necrosis of the femoral head, and its pathogenesis is complex, while impaired blood circulation is considered to be the key to its occurrence. There are a large number of microvessels in the femoral head, among which H-type vessels play a decisive role in the "angiogenesis and osteogenesis coupling", and thus have an important impact on the occurrence and development of femoral head necrosis. Glucocorticoids can cause blood flow injury of the femoral head mainly through coagulation dysfunction, endothelial dysfunction and impaired angiogenesis. Glucocorticoids may inhibit the formation of H-type vessels by reducing the expression of HIF-1α, PDGF-BB, VGEF and other factors, thus causing damage to the "angiogenesis-osteogenesis coupling" and reducing the ability of necrosis reconstruction and repair of the femoral head. Leads to the occurrence of hormonal femoral head necrosis. Therefore, this paper reviewed the progress in the study of the mechanism of hormone-induced femoral head necrosis based on microvascular blood flow at home and abroad, hoping to provide new ideas for the study of the mechanism of femoral head necrosis and provide references for clinical treatment of femoral head necrosis.
Topics: Humans; Femur Head Necrosis; Microvessels; Glucocorticoids; Femur Head; Microcirculation; Neovascularization, Pathologic
PubMed: 38671500
DOI: 10.1186/s13018-024-04748-2 -
Archivio Italiano Di Urologia,... Oct 2023Renal cell carcinoma (RCC) is regarded as one of the most common malignant tumors. Various concomitant medications in RCC patients undergoing surgery are investigated to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Renal cell carcinoma (RCC) is regarded as one of the most common malignant tumors. Various concomitant medications in RCC patients undergoing surgery are investigated to explore the potential for improving survival and preventing disease recurrence, including statin. It has been observed that these drugs induce apoptosis, thereby inhibiting tumor growth and angiogenesis. We aimed to perform a systematic review and meta-analysis to enhance the level of evidence for statin in RCC.
METHODS
A systematic literature search was conducted in several online databases, including PubMed, Scopus, and Sciencedirect, using terms relevant to the use of statins in RCC patients undergoing nephrectomy for publications published up to July 2023, according to a registered review procedure (CRD42023452318). The Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the included study. Review Manager 5.4 was used for all analyses.
RESULTS
Seven articles was eligible for our study. The analysis revealed that patients receiving statin had a better overall survival compared to patients who does not receive statin (HR 0.71, 95% CI 0.51-0.97, p = 0.03, I2 = 76%). However, there was insignificant difference in terms of CSS, DFS, and PFS between RCC patients receiving statin and without statin.
CONCLUSIONS
Statin has substantial benefits for improving OS. Even though the outcomes for CSS, DFS, and PFS were insignificant, the potential role of statins as a supplementary therapy in surgically treated RCC still requires further investigation.
Topics: Humans; Carcinoma, Renal Cell; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Neoplasms; Neoplasm Recurrence, Local; Nephrectomy
PubMed: 37791546
DOI: 10.4081/aiua.2023.11672 -
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