Antiangiogenic Properties Research Articles

Effect of 2-methoxyestradiol on mammary tumor initiation and progression.

The anti-cancer agent 2-methoxyestradiol (2-ME) has been shown to have anti-proliferative and anti-angiogenic properties. Previously, the effect of 2-ME on early- and late-stage breast cancer (BC) was investigated in vivo using a transgenic mouse model (FVB/N-Tg(MMTV-PyVT)) of spontaneous mammary carcinoma. Anti-tumor effects were observed in late-stage BC with no effect on early-stage BC. Given the contrasting results obtained from the different BC stages, we have now investigated the effect of 2-ME when administered before the appearance of palpable tumors. Each mouse received 100 mg/kg 2-ME on day 30 after birth, twice per week for 28 days, while control mice received vehicle only. Animals were terminated on day 59. Lung and mammary tissue were obtained for immunohistochemical analysis of CD163 and CD3 expression, and histological examination was performed to analyze tumor necrosis. Additionally, blood samples were collected to measure plasma cytokine levels. 2-ME increased tumor mass when compared to the untreated animals (p = .0139). The pro-tumorigenic activity of 2-ME was accompanied by lower CD3+ T-cell numbers in the tumor microenvironment (TME) and high levels of the pro-inflammatory cytokine interleukin (IL)-1β. Conversely, 2-ME-treatment resulted in fewer CD163+ cells detectable in the TME, increased levels of tumor necrosis, increased IL-10 plasma levels, and low IL-6 and IL-27 plasma levels. Taken together, these findings suggest that 2-ME promotes early-stage BC development.

Repurposing the anti-angiogenic activity of homoeopathic medicines by employing Chick embryo model- An In-Ovo Study

Background: Homoeopathic medicines have the potential in treatment of patients suffering from cancers, Diabetic Retinopathy, and hemorrhagic disorders wherein anti- angiogenesis plays a vital role. Homoeopathic medicines have been used to treat haemorrhagic disorders. For example, Hamamelis is used in haemorrhages, varicose veins and in venous congestion. Thalaspi bursa is used in flabby condition of uterus, haemorrhagic conditions of uterine fibroid. This been said, their mechanism of action remains unknown. Therefore, this study was intended to establish angiogenic/anti-angiogenic effect of the selected homoeopathic medicines employing chick embryo model.
 Objective:
 
 To study the anti-angiogenic properties of selected homoeopathic medicines employing YSM assay in the chick embryo model.
 To test the toxicity of selected homoeopathic medicines through Chick embryo model.
 
 Materials and Method: Yolk Sac Membrane is widely utilized as an in vivo system to study angiogenesis and anti-angiogenesis. The images for all YSMs were captured and were analyzed for angiogenic/anti-angiogenic effect.
 Results: Significant anti-angiogenic effects were observed in 10% concentrations of Hamamelis200cH, Thalaspi bursa 200cH and Thalaspi bursa 1M. Reduction of vessel density and total vessel network length, total branching points, total nets and total segment symbolizes that these medicines have anti-angiogenic potential and so they help in treating menstrual disorders, which is followed with cramps and discharge of clots.
 Conclusion: The mechanism of action of selected homoeopathic medicines as anti- angiogenic agent is proved which can be used to combat various diseases like haemorrhages, varicose veins, in venous congestion and problems related to haemorrhagic disorders. This will further help to study the action of these Homoeopathic medicines as potential line of treatment in patients suffering from cancers, Diabetic Retinopathy, hemorrhagic disorders wherein anti- angiogenesis plays a vital role.

Preliminary study on vascular-targeted polyphenol nanoparticles in photodynamic therapy of port-wine stains

SignificanceA combination of polyphenol with near infrared photodynamic therapy (PDT) and vascular-targeting nanoparticles holds significant promise as a potential treatment for port-wine stains (PWS). The anti-angiogenic properties of the polyphenol, along with the targeted approach of the nanoparticles and the ability of PDT to selectively damage tissue, make this treatment approach particularly compelling. ApproachUsing EOMA cells for invitro experiment to examine the anti-angiogenesis effects of PDT using ELC, which is self-assembly Epigallocatechin-3-gallate (EGCG) nanoparticles loading with Ce6 photosensitizer. ResultsIn comparison to free Ce6, ELC resulted in increased intracellular uptake of Ce6, leading to improved cytotoxicity when used with laser while maintaining good biocompatibility. Furthermore, ELC enhanced the generation of reactive oxygen species (ROS) within cells. However, ELC did not demonstrate any advantages in inducing apoptosis. ConclusionsPDT using ELC is a promising method for PWS.

Flavonoids with Anti-Angiogenesis Function in Cancer.

The formation of new blood vessels, known as angiogenesis, significantly impacts the development of multiple types of cancer. Consequently, researchers have focused on targeting this process to prevent and treat numerous disorders. However, most existing anti-angiogenic treatments rely on synthetic compounds and humanized monoclonal antibodies, often expensive or toxic, restricting patient access to these therapies. Hence, the pursuit of discovering new, affordable, less toxic, and efficient anti-angiogenic compounds is imperative. Numerous studies propose that natural plant-derived products exhibit these sought-after characteristics. The objective of this review is to delve into the anti-angiogenic properties exhibited by naturally derived flavonoids from plants, along with their underlying molecular mechanisms of action. Additionally, we summarize the structure, classification, and the relationship between flavonoids with their signaling pathways in plants as anti-angiogenic agents, including main HIF-1α/VEGF/VEGFR2/PI3K/AKT, Wnt/β-catenin, JNK1/STAT3, and MAPK/AP-1 pathways. Nonetheless, further research and innovative approaches are required to enhance their bioavailability for clinical application.

Investigation of the anticancer, antimigration and antiangiogenesis effects of an oxadiazole derivative in two- and three-dimensional cultured Ishikawa and Huvec cells; in vitro and in silico studies

Introduction: There are various methods used in cases of metastatic endometrial cancer. However, the prognosis is generally poor. Therefore, new anticancer agents are expected to exhibit the potential to prevent metastasis, as well as their effects on the viability of cancer cells. In in vitro conditions, the Ishikawa cell line represents endometrial adenocarcinoma and the Huvec cell line represents human umbilical vein endothelial cells. Oxadiazole derivatives may be promising new agents for endometrial cancer treatments by exhibiting anticancer and antiangiogenic properties. Objective: The aim of this study was to examine the anticancer, antimigration and antiangiogenic effects of 5-[(4-Phenylpiperazine-1-yl)methyl]-1,3,4-oxadiazol-2-thiol (FP-Oxa) on co-cultured Ishikawa and Huvec cells. Materials and Methods: In silico molecular docking, ADME and toxicity analyzes were performed for FP-Oxa. The effect on the viability of two- and three-dimensional mono- and co-culture models created with HUVEC and Ishikawa cells was evaluated by MTT analysis and IC50 values were calculated. The effect on the migration of two-dimensional cultured cells was determined by wound healing assay. Changes in VEGF expression in three-dimensional co-culture models were evaluated by immunofluorescence staining. Results: As a result of in silico analyses, it was determined that FP-Oxa was within the oral bioavailability limits, exhibited class 4 toxicity, and had inhibition potential by binding to VEGR2. While FP-Oxa clearly inhibited migration in two-dimensionally cultured Ishikawa cells, it did not show the same level of success in Huvec and co-cultured cells. It was effective in reducing VEGF expression in three-dimensional co-cultures. Conclusion: FP-Oxa may have various therapeutic effects on endometrial adenocarcinoma cells. It will be important to conduct biological activity studies in three-dimensional models that mimic the tumor structure created with different types of cancer cells.

Abstract 7298: A nutraceutical supplement derived from olive oil byproducts exhibits potential cancer preventive properties in preclinical studies and increases vitamin D levels

Abstract Introduction: Extra virgin olive oil is a basic component of the Mediterranean diet; it contains several molecules with antioxidant, anti-inflammatory, anti-angiogenic and pro-apoptotic properties against a variety of cancers and influencing cellular metabolism too. Olive mill waste water (OMWW), a liquid residue produced in vast amounts during olive oil extraction, represents an environmental issue but on the other side it is a rich source of phytochemicals with potential health benefits. Particularly, OMWWs are rich in different phenolic compounds, that show promise in preventing the development of several disease disorders, including cancer. We have assessed the anti-angiogenic and anti-tumor properties exerted by a nutraceutical from purified OMWW extract, in in vitro and in vivo models, and evaluated its effect in a human pilot study upon informed consent. Experimental procedures: OMWWs ability to affect cell proliferation and survival on different cancer cell lines was assessed by MTT. OMWWs interference with human umbilical endothelial vein cells (HUVECs) tube formation, migration and invasive capacities was studied by endothelial cell morphogenesis and migration assays. The inhibition of angiogenesis and tumor cell growth was investigated by the matrigel assay and tumour xenograft. To evaluate contribution of potential metabolomic biomarkers, SANIST (surface-activated chemical ionization-electrospray-NIST technology) mass spectrometric data-based platform has been employed on sera from a pilot study (Aiello et al, in preparation). Results: OMWW extract shown a potent inhibitory effect inhibiting cells proliferation of both cancer cell lines and HUVECs.OMWW inhibited several molecular targets expression, including IL8, Angiogenin, mTOR, VEGF, CXCR4, CXCL12 and CXCL8, in tumor cells and in TNF-α-stimulated HUVEC. We nalyzed sera from volunteers, after nutraceutical intervention with Oliphenoliaand we assessed several biological parameters. Endogenous vitamin D was significantly increased, as well as albumin, direct bilirubin, and calcium. We also observed glycemia and potassium decrease after Oliphenolia assumption. A previously unknow form of Vitamin D was also detected by mass spectrometry. Conclusions: OMWW extract has shown a stronger anti-angiogenic and anti-tumor properties, with potential chemo-preventive potentials. Results of human pilot study shows Oliphenolia as a promising and interesting natural dietary supplement, rich in polyphenol compounds, that can exert anti-inflammatory and antioxidant activities. Acknowledgements: This study was supported by a donation from the Fattoria La Vialla di Gianni, Antonio e Bandino Lo Franco - SAS (Arezzo, Italy). We are grateful to Professor Anna Aiello, and Professor Calogero Caruso, Palermo University for the pilot study. Citation Format: Adriana Albini, Luana Calabrone, Francesca Albini, Paola Corradino, Simone Cristoni, Douglas M. Noonan. A nutraceutical supplement derived from olive oil byproducts exhibits potential cancer preventive properties in preclinical studies and increases vitamin D levels [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7298.

Abstract 5400: CD160 regulates angiogenesis in activated human endothelial cells

Abstract Angiogenesis, the process of forming new blood vessels from pre-existing ones, plays a pivotal role in various physiological and pathological conditions. CD160, a cell surface receptor known for its modulatory function in the immune response, has recently garnered attention as a surface marker for activated endothelial cells. In this study, we investigate the anti-angiogenic effects of a novel anti-CD160 antibody. Using the tube formation assay, we evaluated the novel anti-CD160 antibody's ability to inhibit neovascularization potential in activated Human umbilical vein endothelial cells (HUVEC) in vitro. Our results revealed a significant reduction in total tube length, the number of branches, and closed networks, indicating the antibody's efficacy in impeding neovascularization. In addition, we explored the molecular mechanisms underlying CD160's anti-angiogenic properties, showing its ability to selectively decrease fibroblast growth factor-2-induced angiogenesis. Furthermore, we assessed the safety profile of our new anti-CD160 antibody by examining its impact on endothelial cell apoptosis. Encouragingly, our findings demonstrated no induction of apoptosis, suggesting the antibody's selective targeting of angiogenic processes without compromising endothelial cell viability, thus supporting CD160's vascular normalization properties. In conclusion, our research provides compelling evidence for the anti-angiogenic effects of the CD160 antibody, as evidenced by its inhibition of tube formation without inducing apoptosis in activated endothelial cells. These findings hold promising therapeutic implications for targeting angiogenesis in various pathological conditions, warranting further exploration for potential clinical applications. Keywords: CD160, Angiogenesis, Endothelial cells. HUVECs. Citation Format: Abdel-ilah AZIZ. CD160 regulates angiogenesis in activated human endothelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5400.

Copper(II) Complexes with 2,2':6',2″-Terpyridine Derivatives Displaying Dimeric Dichloro-μ-Bridged Crystal Structure: Biological Activities from 2D and 3D Tumor Spheroids to In Vivo Models.

Eight 2,2':6',2″-terpyridines, substituted at the 4'-position with aromatic groups featuring variations in π-conjugation, ring size, heteroatoms, and methoxy groups, were employed to enhance the antiproliferative potential of [Cu2Cl2(R-terpy)2](PF6)2. Assessing the cytotoxicity in A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), and HCT116DoxR (colorectal carcinoma resistant to doxorubicin) and normal primary fibroblasts revealed that Cu(II) complexes with 4-quinolinyl, 4-methoxy-1-naphthyl, 2-furanyl, and 2-pyridynyl substituents showed superior therapeutic potential in HCT116DoxR cells with significantly reduced cytotoxicity in normal fibroblasts (42-129× lower). Besides their cytotoxicity, the Cu(II) complexes are able to increase intracellular ROS and interfere with cell cycle progression, leading to cell death by apoptosis and autophagy. Importantly, they demonstrated antimetastatic and antiangiogenic properties without in vivo toxicity. In accordance with their nuclear accumulation, the Cu(II) complexes are able to cleave pDNA and interact with bovine serum albumin, which is a good indication of their ability for internalization and transport toward tumor cells.

Abstract 521: Anticancer mechanisms of epigallocatechin gallate revealed via cellular and molecular profiling

Abstract Introduction: Epigallocatechin gallate (EGCG) is a polyphenol present in green tea that is known for its anti-oxidant, anti-inflammatory, anti-angiogenic, pro-apoptotic, and anti-cancer properties. However, EGCG has not been systematically evaluated on a large panel of cancer cell lines. We hypothesized that EGCG exhibits varying effects on specific cancer cell genetic backgrounds and types. This study aimed to provide a comprehensive analysis of EGCG on both cell viability and gene expression profiles. Methods: 750 cancer cell lines were cultured and seeded in 1536-well plates for cell viability studies (by the CTD2 Center at the Broad Institute). After 24 h, cells were treated with 16 two-fold serial dilutions of EGCG. After 72 h, cell viability was assayed using CellTiter-Glo. For gene expression profiling (with the Broad Institute and NIH), 8 cell lines were treated with 10 µM EGCG for 6 and 24 h, and transcriptomes were assessed using Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays. The CMap large-scale transcriptome dataset was used for comparisons. Results: EGCG had the highest potency in the non-Hodgkins B-cell lymphoma cell line DoHH2 (IC50=0.42 µM), the myeloid leukemia cell line Ku812 (IC50=3.76 µM), and the multiple myeloma cell line KMS-28BM (IC50=4.57 µM). Tissue-of-origin analysis showed that EGCG was most potent against lymphoid cancers, and least potent against prostate cancers. Bioinformatics-based analyses found that EGCG-treated cells resembled cells overexpressing CHEK2, DDP4, CBLC, ZNF350, and TRAF6, and cells underexpressing TRIM16. EGCG-induced gene expression resembled lapatinib and sulfasalazine treatment. Conclusions: This study provides a comprehensive examination of the differential impact of EGCG treatment on cancer cells. Subsequent research on the timing and duration of the changes, along with pathway enrichment analyses, will potentially guide the translational potential of EGCG and its chemical analogs in personalized cancer treatment approaches. Citation Format: Aria Panchal, Jacqueline H. Law, Clement Lo, Kenneth W. Yip. Anticancer mechanisms of epigallocatechin gallate revealed via cellular and molecular profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 521.

Abstract 5756: Silver graphene quantum dots as drug delivery platforms for anti-cancer application

Abstract Prostate cancer (PCa) stands as the most frequently diagnosed cancer and the third leading cause of cancer-related deaths among men in the United States (2019). Various cancer treatments, including Rehabilitation therapy, Immunotherapy, Hormone therapy, Stem Cell Therapy, and Chemotherapy, are available. However, chemotherapy has notable limitations due to its tendency to harm healthy cells, resulting in side effects such as nausea, vomiting, alopecia, diarrhea, anemia, bleeding, and sterility. In response to these challenges, we developed nanoparticle (NP) drug delivery platforms for cancer treatment. These platforms utilize silver graphene quantum dots nanocomposites (AgGQD), known for their ability to enhance drug therapies. Silver nanoparticles (AgNPs) exhibit toxicity towards both normal and cancer cells by impacting mitochondrial function, reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) release, cell cycle dysregulation, induction of apoptotic genes like Bax, micronucleus formation, chromosome aberration, and DNA damage. Additionally, AgNPs demonstrate antiangiogenic and antiproliferative properties by inhibiting PI3K phosphorylation of Akt, disrupting the signaling pathway, ultimately halting angiogenesis, depriving cells of oxygen, and causing tumor cell death. To mitigate the toxicity of AgNPs in healthy cells and enhance their performance as drug delivery platforms, graphene quantum dots (GQDs) were introduced in this study. Moreover, GQDs may contribute to improving the solubility of drugs with low water solubility. The NPs were synthesized using graphene quantum dots as reducing agents. The study involved identifying the IC50 value, conducting validation tests on AgGQD and AgGQD doped, and comparing their toxicity on cells. Confocal microscopy was employed to identify the intracellular location of the drug. Citation Format: Rafael A. Villanueva, Tori Cole, Nataniel Medina, Dr. Gerardo Morell, Brad Weiner. Silver graphene quantum dots as drug delivery platforms for anti-cancer application [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5756.

Abstract 6657: Oncolytic Vaccinia Virus Carrying OPCML Tumor Suppressor is active in Epithelial Ovarian Cancer

Abstract Objective: Epithelial Ovarian cancer (EOC) has the highest mortality rate among gynecologic malignancies, necessitating novel therapeutic approaches. Viral oncolytic immunotherapy with recombinant oncolytic vaccinia virus (OVV) offers promise for advanced-stage cancer treatment. OPCML is a GPI-anchored 3 Ig-domain tumor suppressor inactivated by somatic methylation in 87% of EOC. OVV with OPCML (OVV-OPCML) gene insertion may have potential as a therapeutic agent. This study explores the oncolytic, signaling-inhibitory, anti-angiogenic and synergistic immunotherapeutic properties of OVV-OPCML in EOC treatment, evaluating its therapeutic potential. Methods: To create OVV-OPCML, the virulent vaccinia virus Copenhagen strain F3L site was modified with OPCML cDNA, confirmed by qPCR and western blot. Oncolytic potential was assessed through in vitro and in vivo EOC cell infection with OVV-OPCML. Real-time cell analysis (RTCA) assessed cell proliferation. Xenograft tumor models in nude mice were used to evaluate in vivo oncolytic activity, while OVV-OPCML combined with anti-PD-1 treatment was tested using a syngeneic orthotopic EOC mouse model (ID8) in C57BL/6 immunocompetent mice. Serum IFN-γ and TNF-α were quantified via ELISA. Receptor Tyrosine Kinases, angiogenesis and phosphorylation together with immune markers were examined by western blotting and by multiplex immunohistochemistry (mIHC) analysis of tumor sections. Results: OVV-OPCML selectively infected OC cells, leading to viral replication and tumor cell death, while sparing normal ovarian cells in-vitro. OPCML protein expression increased post-infection. OVV-OPCML reduced ERBB2, EGFR, and FGFR1 expression in SKVO3 OV cells. Intratumoral or intraperitoneal (IP) OVV-OPCML administration in human ovarian cancer nude mouse models reduced tumor growth and improved survival. IP in-vivo OVV-OPCML in combination with anti-PD-1 treatment in vivo, in the IP ID8 syngeneic model demonstrated synergy with survival improvement. H&E staining showed tumor cell damage without significant harm to normal tissues. Protein expression of ERBB2, EGFR, FGFR1, and their phosphorylated forms decreased. CD31, VEGFR2, p-VEGFR2 (Tyr1175), and p-VEGFR2 (Tyr1214) downregulation suggested tumor angiogenesis disruption. OVV-OPCML treatment elevated serum TNF-α and INF-γ levels and increased CD8+ T cells and PD-L1 expression in OVV-OPCML treated syngeneic tumors. Conclusions: OPCML gene enhances OVV selectivity against OC cells through direct oncolysis and OPCML protein production, inhibiting specific RTKs, suppressing angiogenesis, and activating antitumor immune responses synergistically with anti-PD-1. OVV-OPCML therapy shows promise as a targeted strategy for ovarian cancer treatment. Citation Format: Yong Tang, Yingzhao Liu, Mingjing Deng, Fei Huang, Jiahu Wang, Paul Blake, Hani Gabra, Qi Wang. Oncolytic Vaccinia Virus Carrying OPCML Tumor Suppressor is active in Epithelial Ovarian Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6657.

Abstract 3007: AZGP1 inhibits angiogenesis in prostate cancer

Abstract AZGP1 is involved in various biological processes, including lipid metabolism, regulation of cell proliferation, migration and invasion, and immune response. The loss of AZGP1 is associated with worse clinical outcomes, and AZGP1 has been indicated as a potential biomarker for prostate cancer. However, the underlying mechanisms of AZGP1 function in prostate cancer are unknown. This study reports AZGP1's pivotal involvement in angiogenesis within the prostate cancer tumor environment. Neither knockout nor overexpression of AZGP1 affects in vitro prostate cancer cell proliferation, migration, or invasion. Morphologically, AZGP1-deficient mouse prostates appear normal, but exhibit increased fibroblast growth in periglandular stroma after 6 months. The overexpression of AZGP1 does not impact the growth of PC3 and DU145 tumors; instead, these tumors significantly reduced microvessel density, suggesting AZGP1 exhibits anti-angiogenic properties. Proteomic profiling shows distinct profile of angiogenesis-related proteins between PC3-AZGP1-OV and PC3 control cells, featuring proteins like PDCD6 and MMP9. This study provides insights into the anti-angiogenic attributes of AZGP1 in prostate cancer, underscoring its potential as a therapeutic target for prostate cancer. Citation Format: Ru Wen, G Edward Wen, Zhengyuan Qiu, Eric E Peterson, Fernando Jose Garcia Marques, Abel Bermudez, Jonathan R Pollack, Hongjuan Zhao, Sharon Pitteri, James Brooks. AZGP1 inhibits angiogenesis in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3007.

Hydrogels of Alginate Derivative‐Encased Nanodots Featuring Carbon‐Coated Manganese Ferrite Cores with Gold Shells to Offer Antiangiogenesis with Multimodal Imaging‐Based Theranostics

AbstractThe investigation seeks to develop gold‐shelled carbon‐coated manganese ferrite nanodots enclosed within oxidized alginate polymeric hydrogels (MNF@C‐Au@OSA) to improve encapsulation efficiency, biocompatibility, and multimodal imaging capabilities. These engineered particles, MNF@C‐Au@OSA, are crafted through a hydrothermal synthesis, succeeded by the application of gold nanoparticle shelling and subsequent encapsulation within hydrogels derived from synthesized alginate derivatives, enhancing their overall appeal. Diverse characterization methodologies are employed in order to validate the multiple steps of the synthesis process. The resulting engineered nanoparticles exhibit dual‐mode (T1 and T2) magnetic resonance imaging (MRI) contrast capabilities and compatibility with computed tomography (CT) and fluorescence‐based imaging. To illustrate minimal toxicity, A375 cell lines are utilized for in vitro testing, whereas zebrafish embryos are employed for in vivo assessments. A Chorioallantoic Membrane Model (CAM) is used to establish the antiangiogenic characteristics of MNF@C‐Au@OSA, which is confirmed by histopathological observations. Taking these studies together, one can conclude that the engineered MNF@C‐Au@OSA possesses multimodal imaging capabilities and has demonstrated antiangiogenic properties, thereby establishing them as potential theranostic agents.

TGF-β Signaling Pathways in the Development of Diabetic Retinopathy.

Diabetic retinopathy (DR), a prevalent complication of diabetes mellitus affecting a significant portion of the global population, has long been viewed primarily as a microvascular disorder. However, emerging evidence suggests that it should be redefined as a neurovascular disease with multifaceted pathogenesis rooted in oxidative stress and advanced glycation end products. The transforming growth factor-β (TGF-β) signaling family has emerged as a major contributor to DR pathogenesis due to its pivotal role in retinal vascular homeostasis, endothelial cell barrier function, and pericyte differentiation. However, the precise roles of TGF-β signaling in DR remain incompletely understood, with conflicting reports on its impact in different stages of the disease. Additionally, the BMP subfamily within the TGF-β superfamily introduces further complexity, with BMPs exhibiting both pro- and anti-angiogenic properties. Furthermore, TGF-β signaling extends beyond the vascular realm, encompassing immune regulation, neuronal survival, and maintenance. The intricate interactions between TGF-β and reactive oxygen species (ROS), non-coding RNAs, and inflammatory mediators have been implicated in the pathogenesis of DR. This review delves into the complex web of signaling pathways orchestrated by the TGF-β superfamily and their involvement in DR. A comprehensive understanding of these pathways may hold the key to developing targeted therapies to halt or mitigate the progression of DR and its devastating consequences.

PHA-665752's Antigrowth and Proapoptotic Effects on HSC-3 Human Oral Cancer Cells.

c-Met is a tyrosine-kinase receptor, and its aberrant activation plays critical roles in tumorigenesis, invasion, and metastatic spread in many human tumors. PHA-665752 (PHA) is an inhibitor of c-Met and has antitumor effects on many hematological malignancies and solid cancers. However, the activation and expression of c-Met and its role and the antitumor effect of PHA on human oral squamous cell carcinoma (OSCC) cells remain unclear. Here, we investigated the activation and expression of c-Met and the effects of PHA on the growth of a highly tumorigenic HSC-3 human OSCC cell line with high c-Met phosphorylation and expression. Of note, c-Met was highly expressed and phosphorylated on Y1234/1235 in HSC-3 cells, and PHA treatment significantly suppressed the growth and induced apoptosis of these cells. Moreover, PHA that inhibited the phosphorylation (activation) of c-Met further caused the reduced phosphorylation and expression levels of Src, protein kinase B (PKB), mammalian target of rapamycin (mTtor), and myeloid cell leukemia-1 (Mcl-1) in HSC-3 cells. In addition, the antiangiogenic property of PHA in HSC-3 cells was shown, as evidenced by the drug's suppressive effect on the expression of hypoxia-inducible factor-1α (HIF-1α), a critical tumor angiogenic transcription factor. Importantly, genetic ablation of c-Met caused the reduced growth of HSC-3 cells and decreased Src phosphorylation and HIF-1α expression. Together, these results demonstrate that c-Met is highly activated in HSC-3 human oral cancer cells, and PHA exhibits strong antigrowth, proapoptotic, and antiangiogenic effects on these cells, which are mediated through regulation of the phosphorylation and expression of multiple targets, including c-Met, Src, PKB, mTOR, Mcl-1, and HIF-1α.

Chitosan surface modification modulates the mucoadhesive, permeation and anti-angiogenic properties of gellan gum/bevacizumab nanoparticles

Bevacizumab (BVZ) was the first monoclonal antibody approved by the FDA and has shown an essential advance in the antitumor therapy of colorectal cancer (CRC), however, the systemic action of BVZ administered intravenously can trigger several adverse effects. The working hypothesis of the study was to promote the modulation of the mucoadhesion properties and permeability of the BVZ through the formation of nanoparticles (NPs) with gellan gum (GG) with subsequent surface modification with chitosan (CS). NPs comprising BVZ and GG were synthesized through polyelectrolyte complexation, yielding spherical nanosized particles with an average diameter of 264.0 ± 2.75 nm and 314.0 ± 0.01 nm, polydispersity index of 0.182 ± 0.01 e 0.288 ± 0.01, and encapsulation efficiency of 29.36 ± 0.67 e 60.35 ± 0.27 mV, for NPs without (NP_BVZ) and with surface modification (NP_BVZ + CS). The results showed a good ability of nanoparticles with surface modification to modulate the NPs biological properties.

Therapeutic applications of melatonin in disorders related to the gastrointestinal tract and control of appetite.

Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now understood, the gastrointestinal tract (GIT) and other areas of the body are sites of melatonin production. According to recent studies, the GIT and adjacent organs depend critically on a massive amount of melatonin. Not unexpectedly, melatonin's many biological properties, such as its antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-metastasis, and antiangiogenic properties, have drawn the attention of researchers more and more. Because melatonin is an antioxidant, it produces a lot of secretions in the GIT's mucus and saliva, which shields cells from damage and promotes the development of certain GIT-related disorders. Melatonin's ability to alter cellular behavior in the GIT and other associated organs, such as the liver and pancreas, is another way that it functions. This behavior alters the secretory and metabolic activities of these cells. In this review, we attempted to shed fresh light on the many roles that melatonin plays in the various regions of the gastrointestinal tract by focusing on its activities for the first time.

Pharmacological potential of Fridericia Chica: traditional knowledge and chemical composition

The Fridericia chica is a shrub widely distributed throughout the Brazilian territory. In traditional knowledge, it is used for various pathologies. It is a plant of interest in phytotherapy as it is part of the National List of Medicinal Plants of Interest to the Brazilian Unified Health System – RENISUS. Among the scientific studies conducted, the potential antioxidant, analgesic, anti-inflammatory, immunomodulatory, healing, gastroprotective, antibacterial, antifungal, antiprotozoal, antiviral, antitumor, antiangiogenic, photoprotective, diuretic, and hepatoprotective properties have been demonstrated. Furthermore, the assays report the low toxicity of the extracts. Therefore, Fridericia chica is a plant with pharmacological potential for the development of new medications. This article contributes to the dissemination of the species' pharmacological potential and the imminent observation of traditional knowledge.

Hyaluronan: Sources, Structure, Features and Applications.

Hyaluronan (HA) is a non-sulfated glycosaminoglycan that is present in a variety of body tissues and organs. Hyaluronan has a wide range of biological activities that are frequently influenced by molar mass; however, they also depend greatly on the source, purity, and kind of impurities in hyaluronan. High-molar-mass HA has anti-inflammatory, immunosuppressive, and antiangiogenic properties, while low-molar-mass HA has opposite properties. A number of chemical modifications have been performed to enhance the stability of HA and its applications in medical practice. Hyaluronan is widely applied in medicine, such as viscosupplementation, ophthalmology, otolaryngology, wound healing, cosmetics, and drug delivery. In this review, we summarized several medical applications of polymers based on the hyaluronan backbone.

Phytochemicals Showing Antiangiogenic Effect in Pre-clinical Models and their Potential as an Alternative to Existing Therapeutics.

Angiogenesis, the formation of new blood vessels from a pre-existing vascular network, is an important hallmark of several pathological conditions, such as tumor growth and metastasis, proliferative retinopathies, including proliferative diabetic retinopathy and retinopathy of prematurity, age-related macular degeneration, rheumatoid arthritis, psoriasis, and endometriosis. Putting a halt to pathology-driven angiogenesis is considered an important therapeutic strategy to slow down or reduce the severity of pathological disorders. Considering the attrition rate of synthetic antiangiogenic compounds from the lab to reaching the market due to severe side effects, several compounds of natural origin are being explored for their antiangiogenic properties. Employing pre-clinical models for the evaluation of novel antiangiogenic compounds is a promising strategy for rapid screening of antiangiogenic compounds. These studies use a spectrum of angiogenic model systems that include HUVEC two-dimensional culture, nude mice, chick chorioallantoic membrane, transgenic zebrafish, and dorsal aorta from rats and chicks, depending upon available resources. The present article emphasizes the antiangiogenic activity of the phytochemicals shown to exhibit antiangiogenic behavior in these well-defined existing angiogenic models and highlights key molecular targets. Different models help to get a quick understanding of the efficacy and therapeutics mechanism of emerging lead molecules. The inherent variability in assays and corresponding different phytochemicals tested in each study prevent their immediate utilization in clinical studies. This review will discuss phytochemicals discovered using suitable preclinical antiangiogenic models, along with a special mention of leads that have entered clinical evaluation.