Anti-angiogenesis Potential of Phytochemicals for the Therapeutic Management of Tumors

2020 ◽  
Vol 26 (2) ◽  
pp. 265-278 ◽  
Author(s):  
Samman Munir ◽  
Asad A. Shah ◽  
Muhammad Shahid ◽  
Muhammad S. Ahmed ◽  
Aqsa Shahid ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Angiogenesis Inhibitors ◽  
Metastatic Potential ◽  
Biologically Active ◽  
Angiogenic Potential ◽  
Recent Developments ◽  
Pharmaceutical Industries ◽  
Pathological Stages

The role of angiogeneses during the growth and progression of tumors is well documented. Likewise, a balance is generally maintained between the cellular proliferation and the apoptosis, therefore, the tumors can persist for years in a dormant phase. During the past few years, many hypotheses have been proposed relating to the importance of tumor angiogenesis for the development and spread of tumors and preventive or therapeutic capacity of angiogenesis inhibitors as a potential target for controlling the growth of cancerous tissue. The antiangiogenic based therapeutic approaches are considered as the most promising method for the control of tumors, as this therapeutic approach is less likely to attain the drug resistance. Further, the tumor vasculature is an important prognostic marker that can independently predict the pathological stages as well as the metastatic potential of tumors. Various biologically active phytochemicals have been extracted from the dietary sources and the plants that have engaged the scientist and pharmaceutical industries around the globe. The antioxidant, antiinflammatory, anti-proliferative and anti-angiogenic potential of these bioactive phytochemicals is evident from the in vitro studies using cell lines and investigations involving the animal models..The present review is focused on the promising role of anti-angiogenesis-based therapies for the management of tumors and the recent developments relating to the interplay of phytochemicals and angiogenesis for the suppression of tumor cells.

Vitamin D as potential therapeutic anticancer agent

2018 ◽  
pp. 1-3
Keyword(s):  
Vitamin D ◽  
Anticancer Activity ◽  
Anticancer Agent ◽  
Antitumor Agents ◽  
Metastatic Potential ◽  
Anticancer Properties ◽  
Chemotherapy Agents

The role of vitamin D is implicated in carcinogenesis through numerous biological processes like induction of apoptosis, modulation of immune system inhibition of inflammation and cell proliferation and promotion of cell differentiation. Its use as additional adjuvant drug with cancer treatment may be novel combination for improved outcome of different cancers. Numerous preclinical, epidemiological and clinical studies support the role of vitamin D as an anticancer agent. Anticancer properties of vitamin D have been studied widely (both in vivo and in vitro) among various cancers and found to have promising results. There are considerable data that indicate synergistic potential of calcitriol and antitumor agents. Possible mechanisms for modulatory anticancer activity of vitamin D include its antiproliferative, prodifferentiating, and anti-angiogenic and apoptic properties. Calcitriol reduces invasiveness and metastatic potential of many cancer cells by inhibiting angiogenesis and regulating expression of the key molecules involved in invasion and metastasis. Anticancer activity of vitamin D is synergistic or additive with the antineoplastic actions of several drugs including cytotoxic chemotherapy agents like paclitaxel, docetaxel, platinum base compounds and mitoxantrone. Benefits of addition of vitamin D should be weighed against the risk of its toxicity.

scholarly journals Extracellular Vesicles: Novel Opportunities to Understand and Detect Neoplastic Diseases

2021 ◽  
pp. 030098582199932
Author(s):  
Laura Bongiovanni ◽  
Anneloes Andriessen ◽  
Marca H. M. Wauben ◽  
Esther N. M. Nolte-’t Hoen ◽  
Alain de Bruin
Keyword(s):  
Extracellular Vesicles ◽  
Biologically Active ◽  
Liquid Biopsies ◽  
Donor Cells ◽  
Recent Developments ◽  
Veterinary Pathology ◽  
Cell Components ◽  
Potential Applications ◽  
Intercellular Communications

With a size range from 30 to 1000 nm, extracellular vesicles (EVs) are one of the smallest cell components able to transport biologically active molecules. They mediate intercellular communications and play a fundamental role in the maintenance of tissue homeostasis and pathogenesis in several types of diseases. In particular, EVs actively contribute to cancer initiation and progression, and there is emerging understanding of their role in creation of the metastatic niche. This fact underlies the recent exponential growth in EV research, which has improved our understanding of their specific roles in disease and their potential applications in diagnosis and therapy. EVs and their biomolecular cargo reflect the state of the diseased donor cells, and can be detected in body fluids and exploited as biomarkers in cancer and other diseases. Relatively few studies have been published on EVs in the veterinary field. This review provides an overview of the features and biology of EVs as well as recent developments in EV research including techniques for isolation and analysis, and will address the way in which the EVs released by diseased tissues can be studied and exploited in the field of veterinary pathology. Uniquely, this review emphasizes the important contribution that pathologists can make to the field of EV research: pathologists can help EV scientists in studying and confirming the role of EVs and their molecular cargo in diseased tissues and as biomarkers in liquid biopsies.

scholarly journals The Extracellular Small Leucine-Rich Proteoglycan Biglycan Is a Key Player in Gastric Cancer Aggressiveness

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1330
Author(s):  
Filipe Pinto ◽  
Liliana Santos-Ferreira ◽  
Marta T. Pinto ◽  
Catarina Gomes ◽  
Celso A. Reis
Keyword(s):  
Clinical Value ◽  
Knock Out ◽  
Angiogenic Potential ◽  
In Vivo Experiments ◽  
Cancer Aggressiveness ◽  
Advanced Stages ◽  
Oncogenic Gene

Biglycan (BGN gene), an extracellular proteoglycan, has been described to be associated with cancer aggressiveness. The purpose of this study was to clarify the clinical value of biglycan as a biomarker in multiple independent GC cohorts and determine the in vitro and in vivo role of biglycan in GC malignant features. We found that BGN is commonly over-expressed in all analyzed cohorts, being associated with disease relapse and poor prognosis in patients with advanced stages of disease. In vitro and in vivo experiments demonstrated that biglycan knock-out GC cells display major phenotypic changes with a lower cell survival, migration, and angiogenic potential when compared with biglycan expressing cells. Biglycan KO GC cells present increased levels of PARP1 and caspase-3 cleavage and a decreased expression of mesenchymal markers. Importantly, biglycan deficient GC cells that were supplemented with exogenous biglycan were able to restore biological features, such as survival, clonogenic and migratory capacities. Our in vitro and in vivo findings were validated in human GC samples, where BGN expression was associated with several oncogenic gene signatures that were associated with apoptosis, cell migration, invasion, and angiogenesis. This study provided new insights on biglycan role in GC that should be taken in consideration as a key cellular regulator with major impact in tumor progression and patients’ clinical outcome.

scholarly journals The State of the Art and Prospects for Osteoimmunomodulatory Biomaterials

Materials ◽  
2021 ◽  
Vol 14 (6) ◽  
pp. 1357
Author(s):  
Andreea-Mariana Negrescu ◽  
Anisoara Cimpean
Keyword(s):  
Foreign Bodies ◽  
Structural Characteristics ◽  
Critical Role ◽  
Fibrous Tissue ◽  
Bioactive Molecules ◽  
New Bone Formation ◽  
Recent Developments

The critical role of the immune system in host defense against foreign bodies and pathogens has been long recognized. With the introduction of a new field of research called osteoimmunology, the crosstalk between the immune and bone-forming cells has been studied more thoroughly, leading to the conclusion that the two systems are intimately connected through various cytokines, signaling molecules, transcription factors and receptors. The host immune reaction triggered by biomaterial implantation determines the in vivo fate of the implant, either in new bone formation or in fibrous tissue encapsulation. The traditional biomaterial design consisted in fabricating inert biomaterials capable of stimulating osteogenesis; however, inconsistencies between the in vitro and in vivo results were reported. This led to a shift in the development of biomaterials towards implants with osteoimmunomodulatory properties. By endowing the orthopedic biomaterials with favorable osteoimmunomodulatory properties, a desired immune response can be triggered in order to obtain a proper bone regeneration process. In this context, various approaches, such as the modification of chemical/structural characteristics or the incorporation of bioactive molecules, have been employed in order to modulate the crosstalk with the immune cells. The current review provides an overview of recent developments in such applied strategies.

scholarly journals HNRNPA2B1 promotes multiple myeloma progression by increasing AKT3 expression via m6A-dependent stabilization of ILF3 mRNA

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fengjie Jiang ◽  
Xiaozhu Tang ◽  
Chao Tang ◽  
Zhen Hua ◽  
Mengying Ke ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Proliferation ◽  
Cellular Proliferation ◽  
Aberrant Expression ◽  
The Stability ◽  
Induced Apoptosis ◽  
Proliferation In Vitro

AbstractN6-methyladenosine (m6A) modification is the most prevalent modification in eukaryotic RNAs while accumulating studies suggest that m6A aberrant expression plays an important role in cancer. HNRNPA2B1 is a m6A reader which binds to nascent RNA and thus affects a perplexing array of RNA metabolism exquisitely. Despite unveiled facets that HNRNPA2B1 is deregulated in several tumors and facilitates tumor growth, a clear role of HNRNPA2B1 in multiple myeloma (MM) remains elusive. Herein, we analyzed the function and the regulatory mechanism of HNRNPA2B1 in MM. We found that HNRNPA2B1 was elevated in MM patients and negatively correlated with favorable prognosis. The depletion of HNRNPA2B1 in MM cells inhibited cell proliferation and induced apoptosis. On the contrary, the overexpression of HNRNPA2B1 promoted cell proliferation in vitro and in vivo. Mechanistic studies revealed that HNRNPA2B1 recognized the m6A sites of ILF3 and enhanced the stability of ILF3 mRNA transcripts, while AKT3 downregulation by siRNA abrogated the cellular proliferation induced by HNRNPA2B1 overexpression. Additionally, the expression of HNRNPA2B1, ILF3 and AKT3 was positively associated with each other in MM tissues tested by immunohistochemistry. In summary, our study highlights that HNRNPA2B1 potentially acts as a therapeutic target of MM through regulating AKT3 expression mediated by ILF3-dependent pattern.

scholarly journals Cell-Penetrating Peptide and siRNA-Mediated Therapeutic Effects on Endometriosis and Cancer In Vitro Models

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1618
Author(s):  
Kristina Kiisholts ◽  
Kaido Kurrikoff ◽  
Piret Arukuusk ◽  
Ly Porosk ◽  
Maire Peters ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cellular Proliferation ◽  
Expression Patterns ◽  
In Vitro Models ◽  
Cell Penetrating Peptides ◽  
Biologically Active ◽  
Therapeutic Effects ◽  
Cell Penetrating ◽  
Proliferation And Invasion

Gene therapy is a powerful tool for the development of new treatment strategies for various conditions, by aiming to transport biologically active nucleic acids into diseased cells. To achieve that goal, we used highly potential delivery vectors, cell-penetrating peptides (CPPs), as oligonucleotide carriers for the development of a therapeutic approach for endometriosis and cancer. Despite marked differences, both of these conditions still exhibit similarities, like excessive, uncoordinated, and autonomous cellular proliferation and invasion, accompanied by overlapping gene expression patterns. Thus, in the current study, we investigated the therapeutic effects of CPP and siRNA nanoparticles using in vitro models of benign endometriosis and malignant glioblastoma. We demonstrated that CPPs PepFect6 and NickFect70 are highly effective in transfecting cell lines, primary cell cultures, and three-dimensional spheroids. CPP nanoparticles are capable of inducing siRNA-specific knockdown of therapeutic genes, ribonucleotide reductase subunit M2 (RRM2), and vascular endothelial growth factor (VEGF), which results in the reduction of in vitro cellular proliferation, invasion, and migration. In addition, we proved that it is possible to achieve synergistic suppression of endometriosis cellular proliferation and invasion by combining gene therapy and hormonal treatment approaches by co-administering CPP/siRNA nanoparticles together with the endometriosis-drug danazol. We suggest a novel target, RRM2, for endometriosis therapy and as a proof-of-concept, we propose a CPP-mediated gene therapy approach for endometriosis and cancer.

Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Subham Das ◽  
Saleem Akbar ◽  
Bahar Ahmed ◽  
Rikeshwar Prasad Dewangan ◽  
Mohammad Kashif Iqubal ◽  
...  
Keyword(s):  
Biological Activities ◽  
Neuroprotective Agents ◽  
Wide Range ◽  
Recent Developments ◽  
Ic50 Values ◽  
Structural Activity Relationship ◽  
Pharmaceutical Industries ◽  
Neurological Conditions ◽  
Nitrogen Containing Compounds

: As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact on chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is to discover novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in μM), recent patents, and a brief history as neuroprotective agents.

Abstract 115: Nuclear CaMKII is a Histone H3 Kinase that Remodels Chromatin During Cardiac Hypertrophy

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Salma Mahmoud ◽  
Muhammad Kunhi ◽  
Gillian H Little ◽  
Yan Bai ◽  
Woojin An ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Cardiac Muscle ◽  
Chromatin Remodeling ◽  
Cellular Proliferation ◽  
Recombinant Adenovirus ◽  
Phosphorylation Site ◽  
Histone H3 ◽  
Functional Link

Background and Purpose: Calcium/calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous serine/threonine kinase implicated in pathological events such as cardiac hypertrophy. In this study we investigated the role of a specific nuclear isoform of CaMKII in chromatin remodeling and in transcriptional regulation in cardiac muscle. Methods: Comprehensive experimental approaches performed in primary cardiomyocyte cultures were used including chromatin immunoprecipitation assays (ChIP), q-PCR, chromatin remodeling assays, in vitro phosphorylation/transcription assays, production of recombinant adenovirus, siRNA technology, fluorescence microscopy and mass spectrometry. Results: We found that CaMKIIδB targets specific components of chromatin during cardiac hypertrophy and binds to nucleosomes through its association domain in a cooperative model. CaMKIIδB also increased chromatin relaxation, and this action was dependent on its kinase activity. The observation that CaMKIIδB interacts with chromatin suggested to us that histones maybe novel substrates of the kinase in cardiac muscle. To test this hypothesis, we performed in vitro kinase assays and found that histone H3 is a bona fide CaMKIIδB substrate and Ser-10 appears to be a predominant phosphorylation site. Increased histone H3 Ser-10 phosphorylation was observed following hypertrophic stimulation and was not associated with cellular proliferation, whereas depletion of CaMKIIδB significantly reduced histone H3 Ser-10 phosphorylation in primary cardiomyocytes. Interestingly, we found that H3 S10 phosphorylation and recruitment of CaMKIIδB occur at promoters of fetal cardiac genes. To establish the functional link between H3 phosphorylation by CaMKIIδB, chromatin remodeling and transcription activation, we developed an in vitro transcription system and using it we found that CaMKIIδB increased chromatin accessibility and mediated transcription of the Mef2 transcription factor. Conclusion: Taken together, these findings highlight a new role of CaMKIIδB as relevant histone H3 kinase and link for the first time epigenetic changes by CaMKII to cardiac hypertrophy.

RAS and Leukemia: From Basic Mechanisms to Gene-Directed Therapy

1999 ◽  
Vol 17 (3) ◽  
pp. 1071-1071 ◽  
Author(s):  
Darrin M. Beaupre ◽  
Razelle Kurzrock
Keyword(s):  
Signaling Pathways ◽  
Posttranslational Modification ◽  
Antitumor Agents ◽  
Biologically Active ◽  
Ras Signaling ◽  
Farnesyl Transferase ◽  
Therapeutic Implications ◽  
Farnesyl Transferase Inhibitors

PURPOSE AND DESIGN: The purpose of this review is to provide an overview of the literature linking Ras signaling pathways and leukemia and to discuss the biologic and potential therapeutic implications of these observations. A search of MEDLINE from 1966 to October 1998 was performed. RESULTS: A wealth of data has been published on the role of Ras pathways in cancer. To be biologically active, Ras must move from the cytoplasm to the plasma membrane. Importantly, a posttranslational modification—addition of a farnesyl group to the Ras C-terminal cysteine—is a requisite for membrane localization of Ras. Farnesylation of Ras is catalyzed by an enzyme that is designated farnesyltranferase. Recently, several compounds have been developed that can inhibit farnesylation. Preclinical studies indicate that these molecules can suppress transformation and tumor growth in vitro and in animal models, with little toxicity to normal cells. CONCLUSION: An increasing body of data suggests that disruption of Ras signaling pathways, either directly through mutations or indirectly through other genetic aberrations, is important in the pathogenesis of a wide variety of cancers. Molecules such as farnesyl transferase inhibitors that interfere with the function of Ras may be exploitable in leukemia (as well as in solid tumors) as novel antitumor agents.

scholarly journals Downstream Neighbor of SON (DONSON) Expression Is Enhanced in Phenotypically Aggressive Prostate Cancers

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3439 ◽  
Author(s):  
Niklas Klümper ◽  
Marthe von Danwitz ◽  
Johannes Stein ◽  
Doris Schmidt ◽  
Anja Schmidt ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Locally Advanced ◽  
Metastatic Potential ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Cancer Genome Atlas ◽  
Prostate Cancers ◽  
Migration Capacity

Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods: DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.

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