Angiogenesis in Renal Cell Carcinoma: Molecular Biology, Clinical Manifestations, and Case-Based Insights | Chapter 7 | Newer Frontiers in Urology, Volume II

 

Angiogenesis is the defining biological feature of clear-cell renal cell carcinoma (ccRCC). Loss of Von Hippel–Lindau (VHL) function stabilises hypoxia-inducible factors (HIFs), upregulating vascular endothelial growth factor (VEGF) and allied mediators that produce a hypervascular, leaky, and fragile tumour vasculature. This chapter offers a concise, clinically oriented review of renal cell carcinoma (RCC) angiogenesis centred on an exceptional case: a right-sided ccRCC with intratumoral arteriovenous (AV) shunting and venous collaterals that communicated with the second part of the duodenum, presenting as severe upper gastrointestinal (GI) bleeding. We translate the mechanism into management, emphasising rapid stabilisation, diagnostic angiography, endovascular embolisation, and definitive surgery; then situate contemporary systemic therapy [VEGF/VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs), immuno-oncology–TKI (IO–TKI) combinations, and HIF-2α inhibition] within decision frameworks that clinicians can apply. An expanded discussion links vessel biology to imaging signatures, resistance, perioperative strategies, and follow-up care. This case serves as a central framework for demonstrating how timely, multidisciplinary coordination can prevent catastrophic haemorrhage and ensure durable oncological control.

 

 

Author(s) Details

Rajan Ravichandran
Department of Urology & Renal Transplantation, Sri Ramachandra Institute of Higher Education & Research, Chennai, India.

 

Roshan Reddy
Department of Urology & Renal Transplantation, Sri Ramachandra Institute of Higher Education & Research, Chennai, India.

 

Vivek Meyyappan
Department of Urology & Renal Transplantation, Sri Ramachandra Institute of Higher Education & Research, Chennai, India.

 

Velmurugan Palaniyandi
Department of Urology & Renal Transplantation, Sri Ramachandra Institute of Higher Education & Research, Chennai, India.

 

Hariharasudhan Sekar
Department of Urology & Renal Transplantation, Sri Ramachandra Institute of Higher Education & Research, Chennai, India.

 

Sriram Krishnamoorthy
Department of Urology & Renal Transplantation, Sri Ramachandra Institute of Higher Education & Research, Chennai, India.

 

Please see the book here :- https://doi.org/10.9734/bpi/mono/978-93-47485-68-8/CH7

Investigating the Anti Angiogenic Activity of Carica papaya Leaf Extract | Chapter 8 | Research Perspectives of Microbiology and Biotechnology Vol. 4

 

Cancer is a major cause of death worldwide and angiogenesis is critical in cancer progression. The development of new blood vessels and the nutrition of tumor cells are heavily dependent on angiogenesis. Angiogenesis is the formation of new blood vessels from existing vasculature. In normal physiology, angiogenesis has a role in embryogenesis, the female reproductive cycle, and wound healing and bone formation [1]. There are several “on” and “off” switches that regulate the process. Decreasing or inhibiting angiogenesis can be therapeutic in cancer and other diseases. Thus, angiogenesis is an important process that occurs both during health and disease. This study was conducted to investigate the anti-angiogenic activity of Carica papaya leaf. Fresh green papaya leaves, were randomly collected from Yadav Nursery, Geeta Colony, East Delhi. The anti-angiogenic activity of papaya leaf was evaluated using the docking behaviour of known bioactive compounds of a leaf as ligands with angiogenic receptors VEGFR1 and VEGFR2 along with their putative binding sites using Swiss Dock Web server (In silico) and further based on docking results leaf aqueous extract was used for implantation in the chorioallantoic membrane (CAM) egg yolk angiogenesis model (in vivo). Docking studies and binding free energy calculations revealed that among known bioactive compounds of leaf Ascorbic acid, quercetin, riboflavin and lycopene have maximum free energy as compared to other investigated ligands. Similarly, CAM assay also showed the inhibitory effect of the Carica papaya leaf with respect to their reduction in length, size and junctions of blood capillaries compared to untreated egg yolk. The results showed that Ascorbic Acid, Quercetin, Riboflavin and, Lycopene (leaf compounds) can attenuate angiogenesis in pathological conditions and can be potent in drug discovery as well as medical science. Further studies need to be conducted to determine anti-angiogenic pathways followed by leaf extract or juice. It can be concluded that administration of Carica papaya leaf juice is safe and does induce anti angiogenic process during disease condition like Cancer.

 

 

Author(s) Details

Nidhi Tayal

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Sector-125, Noida - 201 313, India.

Priyansh Srivastava

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Sector-125, Noida - 201 313, India.

Nidhi Srivastava

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Sector-125, Noida - 201 313, India.

 

Please see the link:- https://doi.org/10.9734/bpi/rpmab/v4/353

Investigating the Anti Angiogenic Activity of Carica papaya Leaf Extract | Chapter 8 | Research Perspectives of Microbiology and Biotechnology Vol. 4

 

Cancer is a major cause of death worldwide and angiogenesis is critical in cancer progression. The development of new blood vessels and the nutrition of tumor cells are heavily dependent on angiogenesis. Angiogenesis is the formation of new blood vessels from existing vasculature. In normal physiology, angiogenesis has a role in embryogenesis, the female reproductive cycle, and wound healing and bone formation [1]. There are several “on” and “off” switches that regulate the process. Decreasing or inhibiting angiogenesis can be therapeutic in cancer and other diseases. Thus, angiogenesis is an important process that occurs both during health and disease. This study was conducted to investigate the anti-angiogenic activity of Carica papaya leaf. Fresh green papaya leaves, were randomly collected from Yadav Nursery, Geeta Colony, East Delhi. The anti-angiogenic activity of papaya leaf was evaluated using the docking behaviour of known bioactive compounds of a leaf as ligands with angiogenic receptors VEGFR1 and VEGFR2 along with their putative binding sites using Swiss Dock Web server (In silico) and further based on docking results leaf aqueous extract was used for implantation in the chorioallantoic membrane (CAM) egg yolk angiogenesis model (in vivo). Docking studies and binding free energy calculations revealed that among known bioactive compounds of leaf Ascorbic acid, quercetin, riboflavin and lycopene have maximum free energy as compared to other investigated ligands. Similarly, CAM assay also showed the inhibitory effect of the Carica papaya leaf with respect to their reduction in length, size and junctions of blood capillaries compared to untreated egg yolk. The results showed that Ascorbic Acid, Quercetin, Riboflavin and, Lycopene (leaf compounds) can attenuate angiogenesis in pathological conditions and can be potent in drug discovery as well as medical science. Further studies need to be conducted to determine anti-angiogenic pathways followed by leaf extract or juice. It can be concluded that administration of Carica papaya leaf juice is safe and does induce anti angiogenic process during disease condition like Cancer.

 

 

Author(s) Details

Nidhi Tayal

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Sector-125, Noida - 201 313, India.

Priyansh Srivastava

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Sector-125, Noida - 201 313, India.

Nidhi Srivastava

Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Sector-125, Noida - 201 313, India.

 

Please see the link:- https://doi.org/10.9734/bpi/rpmab/v4/353

In-vivo Anti-Angiogenic Activity of 2-Methoxyestradiol in Sarcoma 180 Tumour Cell Line | Chapter 5 | Medicine and Medical Research: New Perspectives Vol. 4

 

Cancer is a complex genetic disease. Since the last few decades, the incidence of cancer has increased in different parts of the world, and now the situation is very alarming. Cancer or tumour cells are disorganized, mitotically uncontrolled, and autonomous race of cell populations, which consistently violate the basic rules of cell division. Most primary tumours arising in humans are benign. Benign tumours are harmless in a sheath of fibrous tissue, with a few exceptions. It cannot spread through other tissues. Some tumour cells may cause clinical problems and harm that migrate to distant body sites, forming secondary tumours. This process is known as metastasis, which is dependent on angiogenesis. The process of angiogenesis, the formation of new blood vessels from preexisting ones, is a fascinating and critical aspect of tumour growth and metastasis. This intricate process, which involves a complex interplay of factors, is a crucial area of research in the fight against cancer. Most cancer treatments aim to target metastasis. Presently, surgery, radiation therapy, chemotherapy, combination chemotherapy, immunotherapy, hormone replacement therapy and anti-angiogenic therapy are standard methods of cancer treatment.

 

Low-dose chemotherapy combined with an anti-angiogenic drug therapy presents a promising approach to cancer treatment. The combination treatment of low-dose Cyclophosphamide – a cost-effective chemotherapeutic drug, with 2- Methoxyestradiol – a novel anti-angiogenic component, significantly enhances therapeutic efficacy. This is evidenced by the increased frequency of non-viable cell population, apoptosis, and survivability rate of the tumour-bearing host. 2-Methoxyestradiol (2-ME), an endogenous oestrogen metabolite, has been identified as a significant player in cancer therapy. Its ability to induce antiproliferative and apoptotic activities against proliferating cells and growing tumours, coupled with its dual nature of stimulating and inhibiting tumour angiogenesis and growth, underscores its importance in the field.

 

Therefore, the biology of cancer cells is different than normal cells, and cancer biology research involves the realization of the biology of cancer to develop more avenues to diagnose, prevent, and treat cancer. This study provides an overview of some aspects of cancer biology.

 

Author (s) Details

Srabantika Mallick
Department of Medical Laboratory Technology, DPMI Paramedical College, Medinipur, West Bengal, India.

 

Samarendra Nath Banerjee
Department of Zoology, Rammohan College, Kolkata 700009, West Bengal, India.

Please see the book here:- https://doi.org/10.9734/bpi/mmrnp/v4/1828

 

Centella asiatica in Oncology: An Ancient Herb with Modern Anticancer Promise | Chapter 9 | Pharmaceutical Science: New Insights and Developments Vol. 5

Centella asiatica (L.) Urban, also known as Gotu Kola, has been traditionally used in Asian medicine for wound healing, neurological disorders, and skin conditions. In recent years, emerging scientific evidence has illuminated its remarkable anticancer properties. This chapter provides a critical review of the phytochemical constituents of Centella asiatica, their underlying mechanisms of action in various cancer types, in vitro and in vivo experimental findings, and the challenges associated with clinical translation. Emphasis is placed on the herb’s molecular targets and potential synergism with conventional chemotherapeutic agents (James & Dubery, 2009).

 

Author (s) Details

 

Sharmeen Shaikh
Siddhi’s Institute of Pharmacy, Thane 421401, India.

 

Pratiksha Salunkhe
Siddhi’s Institute of Pharmacy, Thane 421401, India.

 

Harshada Jadhav
Siddhi’s Institute of Pharmacy, Thane 421401, India.

 

Shoheb Shaikh
RSM’s NN Sattha College of Pharmacy, Ahilyanagar 414001, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/psnid/v5/5282

Exploring the Role of Adrenomedullin in Overcoming Resistance to Anti-VEGF Therapy in Oncology | Chapter 6 | Achievements and Challenges of Medicine and Medical Science Vol. 3

This study reviews the physiological and pathological processes mediated by AM, analyzing the advantages that the employment of anti-AM therapy may offer in oncology. The development, maintenance and metastasis of solid tumors are highly dependent on the formation of blood and lymphatic vessels from pre-existing ones through a series of processes that are respectively known as angiogenesis and lymphangiogenesis. Both are mediated by specific growth-stimulating molecules, such as the vascular endothelial growth factor (VEGF) and adrenomedullin (AM), secreted by diverse cell types that involve not only the cancerogenic ones, but also those constituting the tumor stroma (i.e., macrophages, pericytes, fibroblasts, and endothelial cells). In this sense, anti-angiogenic therapy represents a clinically-validated strategy in oncology. Current therapeutic approaches are mainly based on VEGF-targeting agents, which, unfortunately, are usually limited by toxicity and/or tumor-acquired resistance. AM is a ubiquitous peptide hormone mainly secreted in the endothelium with an important involvement in blood vessel development and cardiovascular homeostasis. In this review, we will introduce the state-of-the-art in terms of AM physiology, while putting a special focus on its pro-tumorigenic role, and discuss its potential as a therapeutic target in oncology. A large amount of research has evidenced AM overexpression in a vast majority of solid tumors and a correlation between AM levels and disease stage, progression and/or vascular density has been observed. In general, AM expression is upregulated by hypoxia, and the excessive production of this peptide is associated with poorer prognosis in cancer patients. Moreover, recent reports indicate that AM could be a master regulator upstream of the VEGF pathway and even induce HIF-1a expression, therefore attracting much interest as a therapeutic strategy. The analysis presented here indicates that the involvement of AM in the pathogenesis of cancer arises from: 1) direct promotion of cell proliferation and survival; 2) increased vascularization and the subsequent supply of nutrients and oxygen to the tumor; 3) and/or alteration of the cell phenotype into a more aggressive one. Furthermore, we have performed deep scrutiny of the pathophysiological prominence of each of the AM receptors (AM1 and AM2) in different cancers, highlighting their differential locations and functions, as well as regulatory mechanisms. From the therapeutic point of view, we summarize here an exhaustive series of preclinical studies showing a reduction of tumor angiogenesis, metastasis and growth following treatment with AM-neutralizing antibodies, AM receptor antagonists, or AM receptor interference. The study stated that current clinical trials with adrecizumab will be more than interesting in addressing the feasibility of this strategy in oncology. Nevertheless, the blockade of AM receptors might represent a more suitable alternative. Moreover, the recent FDA approval of the CGRP receptor-targeting erenumab/Aimovig® antibody encourages the application of the anti-AM receptors strategy in oncology. Anti-AM therapy is a promising strategy to be explored in oncology, not only as an anti-angiogenic alternative in the context of acquired resistance to VEGF treatment but also as a potential anti-metastatic approach.

 

Author (s) Details

Ramiro Va´zquez
Preclinical Department, Early Drug Development Group (E2DG), Boulogne-Billancourt, France and Center for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.

 

Maria E. Riveiro
Preclinical Department, Early Drug Development Group (E2DG), Boulogne-Billancourt, France.

 

Caroline Berenguer-Daize
Aix Marseille University, CNRS, INP, Institute of NeuroPhysiopathology, Marseille, France.

 

Anthony O’Kane
Discovery and Scientific Affairs Department, Fusion Antibodies plc., Belfast, United Kingdom.

 

Julie Gormley
Discovery and Scientific Affairs Department, Fusion Antibodies plc., Belfast, United Kingdom.

 

Olivier Touzelet
Discovery and Scientific Affairs Department, Fusion Antibodies plc., Belfast, United Kingdom.

 

Keyvan Rezai
Department of Radio-Pharmacology, Institute Curie-René Huguenin Hospital, Saint-Cloud, France.

 

Mohamed Bekradda
Preclinical Department, Early Drug Development Group (E2DG), Boulogne-Billancourt, France.

 

L’Houcine Ouafik
Aix Marseille University, CNRS, INP, Institute of NeuroPhysiopathology, Marseille, France and APHM, CHU Nord, Service de Transfert d’Oncologie Biologique, Marseille, France.

 

Please see the book here:- https://doi.org/10.9734/bpi/acmms/v3/2837

Evaluating the Role of the Tyrosine Phosphatase SHP-2 in Mediating Adrenomedullin Proangiogenic Activity in Solid Tumors | Chapter 2 | Achievements and Challenges of Medicine and Medical Science Vol. 4

Adrenomedullin (AM) is widely expressed in a variety of tumor types and was shown to be mitogenic for many human cancer cell lines in vitro whereas several in vivo studies have also highlighted its strong contribution to neoplastic angiogenesis. VE-cadherin is an essential adhesion molecule in endothelial adherens junctions, and the integrity of these complexes is thought to be regulated by VE-cadherin tyrosine phosphorylation. It was previously shown that AM blockade correlates with elevated levels of phosphorylated VE-cadherin (pVE-cadherinY731) in endothelial cells, associated with impaired barrier function and a persistent increase in vascular endothelial cell permeability. However, the mechanism underlying this effect is unknown. To reveal these mechanisms, techniques such as endothelial cell culture, Western blot analysis, immunoprecipitation, RNA interference, SHP-2 inhibitors, permeability assay, Matrigel plug assay in vitro and in vivo, and in vivo tumor xenograft growth were used in this study. For statistical analysis, non-parametric analysis Kruskal-Wallis followed by Bonferroni test was performed using XLSTAT Software throughout the whole manuscript. In this article, it is demonstrated that the AM-mediated dephosphorylation of pVE-cadherin^Y731 takes place through activation of the tyrosine phosphatase SHP-2, as judged by the rise of its active fraction phosphorylated at tyrosine 542 (pSHP-2^Y542) in HUVECs and glioblastoma-derived-endothelial cells. Both pre-incubation of HUVECs with SHP-2 inhibitors NSC-87877 and SHP099 and SHP-2 silencing hindered AM-induced dephosphorylation of pVE-cadherin^Y731 in a dose dependent-manner, showing the role of SHP-2 in the regulation of endothelial cell contacts. Furthermore, SHP-2 inhibition impaired AM-induced HUVECs differentiation into cord-like structures in vitro and impeded AM-induced neovascularization in in vivo Matrigel plugs bioassays. Subcutaneously transplanted U87-glioma tumor xenograft mice treated with AM- receptors-blocking antibodies showed a decrease in pSHP-2^Y542 associated with VE-cadherin in nascent tumor vasculature when compared to control IgG-treated xenografts.

Our findings show that AM acts on VE-cadherin dynamics through pSHP-2^Y542 to finally modulate cell-cell junctions in the angiogenesis process, thereby promoting a stable and functional tumor vasculature. This data, together with the reported observation that SHP-2 negative mutant ECs failed to organize themselves into a highly vascularized network in the yolk sac of mouse embryos (23), support the role of SHP-2 as an important player in the signaling transduced by AM to regulate pro-angiogenic and vascular stabilizing activities in endothelial cells.

 

Author (s) Details

 

Romain Sigaud
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France.

 

Nadège Dussault
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France.

 

Caroline Berenguer-Daize
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France.

 

Christine Vellutini
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France.

 

Zohra Benyahia
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France.

 

Mylène Cayol
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France.

 

Fabrice Parat
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France.

 

Kamel Mabrouk
Aix Marseille University, CNRS, Institut de Chimie Radicalaire (ICR), Unité Mixte de Recherche (UMR) 7273 Chimie Radicalaire Organique et Polymères de Spécialité (CROPS), Marseille, France.

 

Ramiro Va zquez
Preclinical Department, Early Drug Development Group (E2DG), Boulogne-Billancourt, France and Center for Genomic Science of Istituto Italiano di Tecnologia, Center for Genomic Science, European School of Molecular Medicine (IIT@SEMM), Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.

 

Maria E. Riveiro
Preclinical Department, Early Drug Development Group (E2DG), Boulogne-Billancourt, France.

 

Philippe Metellus
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France and Centre Hospitalier Clairval, De´ partement de Neurochirurgie, Marseille, France.

 

L’Houcine Ouafik
Aix Marseille University, Centre National de la Recherche Scientifique (CNRS), Institut de Neurophysiopathologie (INP), Inst Neurophysiopathol, Marseille, France and Assistance Publique Hôpitaux de Marseille (APHM), Centre Hospitalo Universitaire (CHU) Nord, Service d’OncoBiologie, Marseille, France.

 

Please see the book here:- https://doi.org/10.9734/bpi/acmms/v4/2836  

Pivotal Roles of APN/AdipoRs Signaling in Maintaining Ocular Homeostasis and Protecting against Eye Ailments | Chapter 10 | Advancement and New Understanding in Medical Science Vol. 10

 This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Explaining the complex interactions between ocular diseases and the flexible fat-associated adipokine adiponectin (APN) has garnered a lot of attention in recent years. Discovering the complex connection between aging eye problems and adipocytokine and its receptors (AdipoRs) has become an exciting area of medical research. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN’s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues Targeting common aging eye diseases with treatment approaches could be made possible by the role that APN/AdipoRs play in mediating these effects. Furthermore, the interaction between APN signaling pathways and age-related macular degeneration (AMD) is unraveled in this review. The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of choroidal neovascularization (CNV), whereas the control peptide did not exert any inhibitory effect on CNV. The elucidation of these relationships fosters a deeper understanding of adipose tissue’s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging. The remarkable connection between fat, in the form of adiponectin, and t654r4dexzsight opens exciting avenues for advancing eye health and improving patient outcomes.

Author(s) Details:

Mayank Choubey,
Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA.

Munichandra B. Tirumalasetty,
Department of Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA.

Nalini S. Bora,
Department of Ophthalmology, Jones Eye Institute, Pat & Willard Walker Eye Research Center, 4301 West Markham, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Puran S. Bora,
Department of Ophthalmology, Jones Eye Institute, Pat & Willard Walker Eye Research Center, 4301 West Markham, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.

Please see the link here: https://stm.bookpi.org/ANUMS-V10/article/view/13958

An In-silico Study of Pathological Angiogenesis; Design of Anticancer Agent Inhibiting KLK – 12 | Chapter 3 | Novel Aspects on Chemistry and Biochemistry Vol. 9

A critical route for cancer metastases is pathological angiogenesis. A functional role in angiogenesis has been reported for the serine protease protein Kallikrein-12 (KLK-12). Cysteine-rich angiogenic inducer 61 (CYR61) protein is hydrolyzed by the KLK-12 protein, which also regulates the bioavailability of growth factors that induce angiogenesis. The chapter discusses the homology modeling of the KLK-12 protein, identify essential residues to be putatively linked to the natural substrate. Protein-Protein docking is done to characterize Trp35, Gln36, Gly38, Trp82 and His107 residues of the active site. Using Auto Dock Vina software, virtual screening studies were carried out to identify the substituted carboxamide scaffolds as a pharmacophore binding at the active site. Based on binding energy, ADME, and visual inspection, an isochromene carboxamide moiety is identified as antiangiogenic and cancer antagonists. The isochromene carboxamide scaffold has a stronger interaction behave as potent antiangiogenic ligand against KLK-12 in cancer.

Author(s) Details:

Jyothi Bandi,
Department of Chemistry, University College of Science, Osmania University, Hyderabad - 500007, Telangana State, India.

Navaneetha Nambigari,
Department of Chemistry, University College of Science, Osmania University, Hyderabad - 500007, Telangana State, India and Department of Chemistry, University College of Science, Saifabad, Osmania University, Hyderabad - 500004, Telangana State, India.

Please see the link here: https://stm.bookpi.org/NACB-V9/article/view/13028

Perinatal Tissues to Study In vitro Mechanisms of Inflammation and Angiogenesis: Novel Insight on Diabetic Non-Healing Wound | Chapter 4 | Research Highlights in Disease and Health Research Vol. 3

 Impaired wound restorative is individual of the main diabetes mellitus complications befriended to various disadvantageous visage such as system which controls organization of a supporting-instigative and pro-oxidative atmosphere in addition to weakened peripheral ancestry flow and angiogenesis. Unfortunately, persuasive medicines are now lacking. Recently, with perinatal products, Amniotic Membrane (AM) has explained encouraging results in wound administration.Therefore, in this place the potential effect of AM on endothelial containers unique from the umbilical rope tone of gestational diabetes impressed women (GD-HUVEC), have happened examined. Indeed, GD-HUVEC have proved a pro-instigative phenotype and lower ship establishment on Matrigel distinguished to control HUVEC (C-HUVEC), thus exhibiting a valuable model for learning the antagonistic-inflammatory act of AM and neovascularization of incessant non-restorative wounds. The antagonistic-inflammatory features of AM have existed determined in Tumor Necrosis Factor- α (TNF- α) pre-stimulated containers utilizing a monocyte-endothelium cling assay and evaluating vascular cling fragments verbalization and sheet exposure, in addition to Nuclear Factor kappa-light-chain-enhancer of stimulated B containers (NF-kB) expression and basic fluctuation and Nitric Oxide (NO) bioavailability. Moreover, hose establishment ability was intentional in AM-acted C- and GD-HUVEC.The verdicts indicated that AM considerably diminished TNF- α aroused monocyte-endothelium interaction and sheath uncovering of the Vascular container and Intracellular stickiness molecules (VCAM-1 and ICAM-1, individually) in two together C- and GD-HUVEC. Strikingly, AM situation significantly upgraded hose-like construction interconnections in GD-HUVEC.Overall, these results display that, in our in vitro container model, AM attenuates TNF- α -raised swelling and improves angiogenesis, perhaps through the timbre of NO bioavailability, that plays a key role in the vascular equilibrium balance. This study desires that AM incessant wound curative improvement grant permission develop endothelial correct management, so interpreting allure dispassionate benefit on diabetic foot ulcers.

Author(s) Details:

Caterina Pipino,
Center for Advanced Studies and Technology-CAST (ex CeSI-MeT), Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio Chieti-Pescara, StemTeCh group, Chieti, Italy.

Ilaria Cappellacci,
Center for Advanced Studies and Technology-CAST (ex CeSI-MeT), Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio Chieti-Pescara, StemTeCh group, Chieti, Italy.

Javier Stelling-Ferez,
Regeneration, Molecular Oncology and TGFß, IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120, El Palmar Murcia, Spain and Department of Nutrition and Food Technology, UCAM, 30107, Guadalupe, Murcia, Spain.

Angel Bernabe-Garcia,
Regeneration, Molecular Oncology and TGFß, IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120, El Palmar Murcia, Spain.

Domitilla Mandatori,
Center for Advanced Studies and Technology-CAST (ex CeSI-MeT), Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio Chieti-Pescara, StemTeCh group, Chieti, Italy.

Nadia Di Pietrantonio,
Center for Advanced Studies and Technology-CAST (ex CeSI-MeT), Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio Chieti-Pescara, StemTeCh group, Chieti, Italy.            

Carlos Navalon,
Regeneration, Molecular Oncology and TGFß, IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120, El Palmar Murcia, Spain.

Francisco Jose Nicolas,
Regeneration, Molecular Oncology and TGFß, IMIB-Arrixaca, Hospital Clínico Universitario Virgen de la Arrixaca, 30120, El Palmar Murcia, Spain.

Assunta Pandolfi,
Center for Advanced Studies and Technology-CAST (ex CeSI-MeT), Department of Medical, Oral and Biotechnological Sciences, University G. d'Annunzio Chieti-Pescara, StemTeCh group, Chieti, Italy.

Please see the link here: https://stm.bookpi.org/RHDHR-V3/article/view/9782

Changes in HER-2 and Matrix Metalloproteinase-2 Expression in Bone Marrow Micrometastasis and Stromal Cells in Men with Prostate Cancer as a Result of Androgen Blockade| Chapter 9 | Perspective of Recent Advances in Medical Research Vol. 1

 We interpret an immunocytochemical analysis of the impact of androgen inhibition on HER-2 and cast metalloproteinase-2 (MMP-2) expression in cartilage marrow micrometastases and the surrounding stromal containers in prostate cancer patients. Men accompanying prostate cancer who endured bone essence biopsy procedures had touch prepare taken during androgen abolition, before and after radical prostatectomy.Patients were defined as HER-2 helpful or negative, MMP-2 negative or an MMP-2 pattern described as border or main and stromal MMP-2 defined as positive or negative. The verbalization of the biomarkers was compared before and after beginning treatment, as well as all the while androgen blockade, concerning serum PSA at the time of sample and time of androgen blockade.There were 191 males contained, 35 before surgery and 43 after; skilled were no appreciable alternatives in HER-2 expression between groups, and neither MMP-2 main nor stromal expression was present. MMP-2 expression in two together micrometastasis and stroma was found to be really related to HER-2 verbalization. MMP-2 expression at the micrometastasis barrier was not connected with HER-2 expression and happen in the absence of androgen blockade.Androgen need lowers serum PSA by destroying HER-2 negative prostate cancer cells. Early pick of HER-2 positive cancer containers, on the other hand, leads to androgen independence and embellished expression of MMP-2 venture in the micrometastasis. Increased MMP-2 activity in micrometastasis boosts MMP-2 expression in encircling stromal cells, which concede possibility promote angiogenesis and tumour growth, developing in macrometastatic androgen independent disease.

Author(s) Details:

N. P. Murray,
Hospital de Carabineros of Chile, Simon Bolivar 2200 Nunoa, 7770199 Santiago, Chile and Circulating Tumor Cell Unit, Faculty of Medicine, University Finis Terrae Santiago, Chile.

E. Reyes,
Hospital de Carabineros of Chile, Simon Bolivar 2200 Nunoa, 7770199 Santiago, Chile and Universidad Diego Portales, Manuel Rodriguez Sur 415, 8370179 Santiago, Chile.

L. Badinez,
Foundation of Arturo Lopez Perez, Rancagua 878, Providencia, 7500921 Santiago, Chile.

N. Orellana,
Hospital de Carabineros of Chile, Simon Bolivar 2200 Nunoa, 7770199 Santiago, Chile.

C. Fuentealba,
Hospital de Carabineros of Chile, Simon Bolivar 2200 Nunoa, 7770199 Santiago, Chile.

R. Olivares,
Hospital de Carabineros of Chile, Simon Bolivar 2200 Nunoa, 7770199 Santiago, Chile.

J. Porcell,
Hospital de Carabineros of Chile, Simon Bolivar 2200 Nunoa, 7770199 Santiago, Chile.

R. Duenas,
Hospital de Carabineros of Chile, Simon Bolivar 2200 Nunoa, 7770199 Santiago, Chile.

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Consise Synthesis and Potential Anti-angiogenic activity of N-1 Substituted Indolylchalcone Hybrids on Chorioallantoic Membrane (CAM) Assay: A Recent Study | Chapter 9 | Technological Innovation in Pharmaceutical Research Vol. 5

 Synthesis of N-1 Substituted Indolylchalcone Hybrids and anti-angiogenic activity evaluation using the Chorioallantoic Membrane (CAM) Assay. According to the findings, N-1 substituted Indolylchalcone hybrids of 2-acetyl benzimidazole could be promising angiogenesis inhibitor analogs for managing uncontrolled neovascularization that occurs during malignant tumor development. The Claisen-Schmidt procedure, which involves condensation of N-1 substituted indole-3-carboxaldehyde and N1 substituted 2-acetylbenzimidazole, was utilized to make 30 Indolylchalcone hybrids. In alkylation and arylation, phase transfer catalysts, green catalysts such as anhydrous potassium carbonate (K2CO3), and PEG-400 are utilized. The antiangiogenic activity of all produced indolylchalcone hybrids was assessed using the in-vivo chorioallantoic membrane (CAM) assay method.

Conclusion: The synthesized Indolylchalcones, as indicated in the graph, have excellent anti-angiogenic properties that are dose dependent. Methyl >Ethyl>Cl-benzyl> Benzyl>Isobutyl>Isobutyl>Isobutyl>Isobutyl>Isobutyl>Isobutyl>Isobutyl>Isobutyl>Isobutyl>Is Analogs of 2-acetyl benzimidazole could be developed into powerful angiogenesis inhibitors in the future.

Author (s) Details

Dr. Anjali Mahesh Wanegaonkar
Bharati Vidyapeeth College of Pharmacy, Sector-8, CBD Belapur - Navi Mumbai- 400614, India.

Dr. Milind Jagannathji Bhitre
Department Pharmaceutical Chemistry C. U. Shah College of Pharmacy, S. N. D. T. Women’s University, Sir Vithaldas Vidyavihar, Juhu Road, Santacruz (West) Mumbai- 400 049, India.

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Critical Overview: Ocular Angiogenesis | Chapter 9 | Current Topics in Medicine and Medical Research Vol.3

 Angiogenesis is the formation of new blood vessels from preexisting vasculature, being mediated and

regulated by a complex composed of growth factors, cytokines, cell signaling molecules and
extracellular matrix components. The most important pro-angiogenesis regulator molecules are
vascular endothelial factor (VEGF), fibroblasts growth factors (FGFs), hypoxia-inducible factor 1 (HIF-
1), platelet-derived growth factor (PDGF) and angiopoietins (Ang). Ocular angiogenesis can occur in
retina, choroid, and cornea of the eye, leading to severe visual impairment, being related to a broad
spectrum of disorders such as wet age-related macular degeneration (AMD), diabetic retinopathy
(DR), retinopathy of prematurity (ROP), neovascular glaucoma (NVG) and corneal neovascularization
(CNV). Monotherapy or laser-adjunctive inhibition of VEGF, as the humanized monoclonal anti-VEGF
antibody (Bevacizumab, Ranibizumab) and the “VEGF-trap” molecules (Aflibercept) have become the
gold standard therapy for these ocular angiogenic diseases. The current frontier of anti-angiogenic
ocular treatment lies in reducing the treatment burden of frequent injections needed and increase the
efficacy and the visual outcomes. New drugs are being developed with the goal of extending
treatment intervals and increased efficiency such as: Brolucizumab, Faricimab, Abicipar pegol and
Combercept. As a different approach to extend treatment burden, there is the Port Delivery System
that may address the irregular dosing of current treatment and launch us into an era of continuous
angiogenic suppression. This chapter Ocular Angiogenesis provide an emerging view of the clinical
features of pathological angiogenesis in the eye, the molecular mechanisms including growth factors
and other molecules involved in the pathological vessel growth, and the progress made in the
development of new treatments.

Author(s) Details

B. Z. Fetter
Department of Biochemistry, Molecular Biology Division, Federal University of São Paulo, Brazil.

B. O. Augusto
Department of Biochemistry, Molecular Biology Division, Federal University of São Paulo, Brazil.

A. T. Grupenmacher
Department of Ophthalmology and Visual Sciences, Federal University of São Paulo, Brazil.

C. V. Regatieri
Department of Biochemistry, Molecular Biology Division, Federal University of São Paulo, Brazil and Department of Ophthalmology and Visual Sciences, Federal University of São Paulo, Brazil.

J. L. Dreyfuss
Department of Biochemistry, Molecular Biology Division, Federal University of São Paulo, Brazil.

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Assessment of Microvessel Density and Angiogenesis in Endometrial Carcinomas | Chapter 7 | Research Trends and Challenges in Medical Science Vol.3 Assessment

Objective: To evaluate the role of angiogenesis in tumor growth by the assessment of microvessel density and to quantify angiogenesis as an important variable in endometrial cancers.  Materials and Methods: 103 cases of endometrial malignancies (epithelial tumors-76 cases, stromal tumors-07 cases and metastatic tumors-20 cases) were analysed for histological types, grades and features like depth of invasion and vascular invasion. Microvessel counts were performed by examining the microvessels thoroughly in terms of count, morphology and density after staining the tissues by hematoxylin & eosin stain, reticulin and immunostain CD34. Results: On H&E stain - Microvessel density (MVD) in endometrial malignancy ranged from 3.0 - 13.5 and mean MVD was 8.78. On Reticulin stain - MVD ranged from 3.5 - 15.2 and mean MVD was 9.76.  CD34 sections showed very small microvessels or even single endothelial cells with the highest total counts and the MVD ranged from 6.5-16.8 with Mean MVD of 11.7. The counts increased with the grade of the tumor in the absence of necrosis or haemorrhage. MVD counts also increased with the stage, being 8.12 in Stage I disease, 8.65 in Stage II and 10.8 in stage III disease. Atypical hyperplasia was found to be associated with epithelial tumors in 8 cases, making it a significant finding. Conclusions: Role of angiogenesis assumes greater significance with increasing severity of lesions, higher grade and stage of the tumor and seems to have an important diagnostic and prognostic significance. 

Author(s) Details

 Dr. Kafil Akhtar
Department of Pathology, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh,  U. P. -202002, India.  

Dr. Sumbul Warsi
Department of Pathology, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh,   U. P. -202002, India.

Dr. Rana Khalid Sherwani
Department of Pathology, Jawaharlal Nehru Medical College, Faculty of Medicine, Aligarh Muslim University, Aligarh,   U. P. -202002, India.

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