scholarly journals Advances in Drugs Targeting Lymphangiogenesis for Preventing Tumor Progression and Metastasis

2022 ◽  
Vol 11 ◽  
Author(s):  
Chuqi Wang ◽  
Ming Chu
Keyword(s):  
Cancer Cells ◽  
Lymphatic Metastasis ◽  
Tumor Invasion ◽  
Molecular Mechanisms ◽  
Lymphatic Vessels ◽  
The Body ◽  
Regional Lymph Nodes ◽  
Cancer Management ◽  
The Past ◽  
Tight Correlation

Metastasis of cancer cells from the primary tumor to other organs and tissues in the body is the leading cause of death in patients with malignancies. One of the principal ways cancer cells travel is through lymphatic vessels, and tumor invasion into the regional lymph nodes is a hallmark of early metastasis; thus, the formation of especially peritumoral lymphatic vessels is essential for tumor transportation that gives rise to further progression. In the past few decades, tumor-induced lymphangiogenesis has been testified to its tight correlation with lymphatic metastasis and poor clinical outcomes in multiple types of human malignancies, which warrants novel potential therapeutic targets for cancer treatment. As the understanding of underlying molecular mechanisms has grown tremendously over the years, an inexorable march of anti-lymphangiogenic therapy also aroused terrific interest. As a result, a great number of drugs have entered clinical trials, and some of them exhibited predominant contributions in cancer management. Herein, this review provides an updated summary of the current advances in therapies preventing lymphatic metastasis and discusses the validity of different applications.

Potential Therapeutic Targets of Curcumin, Most Abundant Active Compound of Turmeric Spice: Role in the Management of Various Types of Cancer

2020 ◽  
Vol 15 ◽  
Author(s):  
Saleh A. Almatroodi ◽  
Mansoor Ali Syed ◽  
Arshad Husain Rahmani
Keyword(s):  
Clinical Trials ◽  
Cancer Cells ◽  
Active Compound ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Cell Signalling ◽  
Chemopreventive Agents ◽  
Signalling Molecules ◽  
Cancer Management ◽  
Induced Apoptosis

Background:: Curcumin, an active compound of turmeric spice is one of the most-studies natural compounds and have been widely recognized as chemopreventive agents. Several molecular mechanisms have been proven, curcumin and its analogs play a role in cancer prevention through modulating various cell signaling pathways as well as inhibition of carcinogenesis process. Objective:: To study the potential role of curcumin in the management of various types of cancer through modulating cell signalling molecules based on available literature and recent patents. Methods:: A wide-ranging literature survey was performed based on Scopus, PubMed, PubMed central and Google scholar for the implication of curcumin in cancer management along with special emphasis on human clinical trials. Moreover, patents were searched through www.google.com/patents, www.freepatentsonline.com and www.freshpatents.com. Result:: Recent studies based on cancer cells have proven that curcumin have potential effects against cancer cells, prevent the growth of cancer and act as cancer therapeutic agents. Besides, curcumin exerted anticancer effects through inducing apoptosis, activating tumor suppressor genes, cell cycle arrest, inhibiting tumor angiogenesis, initiation, promotion and progression stages of tumor. It was established that co-treatment of curcumin and anti-cancer drugs could induce apoptosis and also play a significant role in the suppression of the invasion and metastasis of cancer cells. Conclusion:: Accumulating evidences suggest that curcumin has potentiality to inhibit cancer growth, induced apoptosis and modulate various cell signalling pathways molecules. Well-designed clinical trials of curcumin based on human subjects are still needed to establish the bioavailability, mechanism of action, efficacy and safe dose in the management of various cancers.

The Role of Vitamin D and the Vitamin D Receptor in Bone Oncology

2018 ◽  
Vol 27 (03) ◽  
pp. 129-134 ◽  
Author(s):  
B. M. Holzapfel ◽  
F. Jakob ◽  
A. A. Kurth ◽  
G. Maier ◽  
K. Horas
Keyword(s):  
Vitamin D ◽  
Cancer Cells ◽  
Vitamin D Deficiency ◽  
Vitamin D Receptor ◽  
Molecular Mechanisms ◽  
Full Range ◽  
Cancer Cell Growth ◽  
The Past ◽  
Global Health Problem

SummaryVitamin D deficiency is a global health problem of enormous and increasing dimensions. In the past decades, numerous studies have centered on the role of vitamin D in the pathogenesis and course of many diseases including several types of cancer. Indeed, vitamin D has been widely acknowledged to be involved in the regulation of cell proliferation, differentiation and apoptosis in numerous cancer cells. While the full range of molecular mechanisms involveld in cancer cell growth and progression remains to be elucidated, recent research has deepened our understanding of the processes that may be affected by vitamin D or vitamin D deficiency.In this review, we consider the properties of bone that enable cancer cells to grow and thrive within the skeleton, and the role of vitamin D and the vitamin D receptor in the process of primary and secondary cancer growth in bone.

scholarly journals Emerging Roles for VEGF-D in Human Disease

Biomolecules ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 1 ◽  
Author(s):  
Steven Stacker ◽  
Marc Achen
Keyword(s):  
Blood Vessels ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Agent ◽  
Lymphatic Vessels ◽  
The Body ◽  
Vascular Endothelial ◽  
Animal Disease Models ◽  
Endothelial Growth Factor ◽  
Insight Into

Blood vessels and lymphatic vessels are located in many tissues and organs throughout the body, and play important roles in a wide variety of prevalent diseases in humans. Vascular endothelial growth factor-D (VEGF-D) is a secreted protein that can promote the remodeling of blood vessels and lymphatics in development and disease. Recent fundamental and translational studies have provided insight into the molecular mechanisms by which VEGF-D exerts its effects in human disease. Hence this protein is now of interest as a therapeutic and/or diagnostic target, or as a potential therapeutic agent, in a diversity of indications in cardiovascular medicine, cancer and the devastating pulmonary condition lymphangioleiomyomatosis. This has led to clinical trial programs to assess the effect of targeting VEGF-D signaling pathways, or delivering VEGF-D, in angina, cancer and ocular indications. This review summarizes our understanding of VEGF-D signaling in human disease, which is largely based on animal disease models and clinicopathological studies, and provides information about the outcomes of recent clinical trials testing agonists or antagonists of VEGF-D signaling.

scholarly journals Tumor Lymphangiogenesis as a Potential Therapeutic Target

2012 ◽  
Vol 2012 ◽  
pp. 1-23 ◽  
Author(s):  
Tam Duong ◽  
Peter Koopman ◽  
Mathias Francois
Keyword(s):  
Lymph Node ◽  
Cancer Cells ◽  
Primary Tumor ◽  
Molecular Mechanisms ◽  
Patient Survival ◽  
Regional Lymph Node ◽  
Lymphatic Vessels ◽  
Potential Therapeutic Target ◽  
Tumor Lymphangiogenesis

Metastasis the spread of cancer cells to distant organs, is the main cause of death for cancer patients. Metastasis is often mediated by lymphatic vessels that invade the primary tumor, and an early sign of metastasis is the presence of cancer cells in the regional lymph node (the first lymph node colonized by metastasizing cancer cells from a primary tumor). Understanding the interplay between tumorigenesis and lymphangiogenesis (the formation of lymphatic vessels associated with tumor growth) will provide us with new insights into mechanisms that modulate metastatic spread. In the long term, these insights will help to define new molecular targets that could be used to block lymphatic vessel-mediated metastasis and increase patient survival. Here, we review the molecular mechanisms of embryonic lymphangiogenesis and those that are recapitulated in tumor lymphangiogenesis, with a view to identifying potential targets for therapies designed to suppress tumor lymphangiogenesis and hence metastasis.

scholarly journals Lymphatic system and adipose tissue: Crosstalk in health and disease

2021 ◽  
Vol 18 (3) ◽  
pp. 336-344
Author(s):  
V. V. Klimontov ◽  
D. M. Bulumbaeva
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Lymphatic System ◽  
Lymphatic Vessels ◽  
Inflammatory Cells ◽  
The Body ◽  
Push Button ◽  
Secondary Lymphedema

The lymphatic system (LS) is one of the main integrative systems of the body, providing protective and transport functions. In recent years, interactions between LS and adipose tissue (AT) have been of particular interest. Lymphatic vessels play an important role in metabolic and regulatory functions of AT, acting as a collector of lipolysis products and adipokines. In its turn, hormones and adipocytokines that produced in adipocytes (including leptin, adiponectin, IL-6, TNF-α, etc.) affect the function of lymphatic endothelial cells and control the growth of lymphatic vessels. Cooperation between LS and AT becomes pathogenetically and clinically important in lymphedema and obesity. It is known that both primary and secondary lymphedema are characterized by increased fat accumulation which is associated with the severity of lymphostasis and inflammation. Similarly, in obesity, the drainage function of LS is impaired, which is accompanied by perilymphatic mononuclear infiltration in the AT. The development of these changes is facilitated by endocrine dysfunction of adipocytes and impaired production of adipocytokines. The increase in the production of inflammatory mediators and the disruption of the traffic of inflammatory cells causes a further deterioration in the outflow of interstitial fluid and exacerbates the inflammation of the AT, thereby forming a vicious circle. The role of lymphangiogenesis in AT remodeling in obesity needs further research. Another promising area of research is the study of the role of intestinal LS in the development of obesity and related disorders. It has been shown that the transport of chylomicrons from the intestine depends on the expression of a number of molecular mediators (VEGF-C, DLL-4, neuropilin-1, VEGFR-1, CD36/FAT, etc.)in the endotheliocytes of the intestinal lymphatic vessels, as well as the functioning of «push-button» and “zippering” junctions between endothelial cells. New approach to the treatment of obesity based on blockade of lymphatic chylomicrontransport has been experimentally substantiated. Further identification of the molecular mechanisms and signaling pathways that determine the remodeling of AT in lymphedema and obesity are likely to provide new approaches to the treatment of these diseases.

scholarly journals The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis

2020 ◽  
Vol 21 (9) ◽  
pp. 3304
Author(s):  
James W.W. Winslow ◽  
Kirsten H. Limesand ◽  
Ningning Zhao
Keyword(s):  
Antioxidant Defense ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Immune Cell ◽  
The Body ◽  
Metal Transporters ◽  
Cellular Processes ◽  
The Past ◽  
Genes Encoding ◽  
Essential Nutrient

As an essential nutrient, manganese is required for the regulation of numerous cellular processes, including cell growth, neuronal health, immune cell function, and antioxidant defense. However, excess manganese in the body is toxic and produces symptoms of neurological and behavioral defects, clinically known as manganism. Therefore, manganese balance needs to be tightly controlled. In the past eight years, mutations of genes encoding metal transporters ZIP8 (SLC39A8), ZIP14 (SLC39A14), and ZnT10 (SLC30A10) have been identified to cause dysregulated manganese homeostasis in humans, highlighting the critical roles of these genes in manganese metabolism. This review focuses on the most recent advances in the understanding of physiological functions of these three identified manganese transporters and summarizes the molecular mechanisms underlying how the loss of functions in these genes leads to impaired manganese homeostasis and human diseases.

Nutraceutical and Functional Foods in Cancer Management and Therapy

2022 ◽  
pp. 1144-1182
Author(s):  
Sakshi Bajaj ◽  
Satish Manchanda
Keyword(s):  
Natural Products ◽  
Cancer Cells ◽  
Functional Foods ◽  
The Body ◽  
Food Industries ◽  
Cancer Management ◽  
Consumer Demands

Cancer is an insidious disease affecting mankind in every country. The progression of cancer cells from one part of the body to another (metastasis) is one of the biggest problems in curing cancer. The present study brings new hope of future therapies to fight cancer. Designing an appropriate food to maintain proper health has become a necessity worldwide. Due to this, the food industries in many countries are modifying their products as a response to consumer demands. In recent years, many of the natural products are gaining popularity as nutraceuticals.

Inhibition of Cytokine Receptor gp130 Signaling in Breast Cancer Cells Markedly Suppresses Secretion of Tissue Factor-Expressing Tumor Microparticles.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1935-1935
Author(s):  
Diego A. de Idiaquez ◽  
Dannielle E. Branam ◽  
Larry Lamb ◽  
Dongquan Chen ◽  
Lihong Teng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Flow Cytometry ◽  
Cancer Cells ◽  
Tissue Factor ◽  
Tumor Invasion ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Extracellular Proteins ◽  
Dominant Negative

Abstract gp130 is the common signaling receptor subunit for the IL-6 family of cytokines. We have previously shown that expression of a dominant negative (DN) gp130 inhibitory protein in MDA-MB-231 breast cancer cells decreased tumor invasion and angiogenesis in an orthotopic animal model (Cancer Research64:6924, 2004). In order to better understand the molecular mechanisms of this decreased malignancy, we determined global MDA-MB-231 gene expression in the presence of DN gp130. RNA was obtained from multiple independent single cell clones of MDA-MB-231 cells expressing either DN gp130 (n=5) or vector-only (n=5). Each clone was studied using Affymetrix U133A chips containing >22,000 genes. We identified 237 genes that were up- or down-regulated in the presence of DN gp130 at least 2-fold with p<0.05. Genes of interest were further studied by real-time PCR, western blot, and flow cytometry. We focused on extracellular proteins involved in proteolytic pathways. Six coagulation regulatory proteins were found to be differentially regulated by DN gp130: tissue factor (decreased), PAI-1 (decreased), alpha-2 antiplasmin (decreased), TFPI (increased), thrombomodulin (increased), and MMP-14 (increased). Thus, inhibition of gp130 signaling results in an anticoagulant phenotype in these cells. Tissue factor regulation was further studied. Cell surface tissue factor protein was down-regulated 10-fold in MDA-MB-231 DN gp130 cells compared to MDA-MB-231 control cells. Tumor microparticles (MP) were isolated from conditioned media by differential centrifugation. MDA-MB-231 MP contained uPA and MMP-9, as previously reported for MP from other tumors. Tissue factor was strongly expressed in control MP and nearly absent in MP from DN gp130 cells. Flow cytometry of tumor MP was used to quantitate tissue factor-expressing MP. There was a 50-fold decrease in double-labeled annexin V positive/tissue factor positive MP obtained from DN gp130 cells compared to control cells. In addition, the absolute number of tumor MP was decreased by 50% in the presence of DN gp130. In order to determine the mechanism of this regulation of breast cancer MP by gp130, the above list of 237 differentially expressed genes was re-examined. Proteins known to be enriched in MP- CD55, CD59, and three members of the tetraspanin family (including CD9) were significantly decreased in the presence of DN gp130. The expression of three proteins that are involved in the cellular production of MP were also significantly affected by DN gp130: Ca2+-dependent activator of protein for secretion 2, Rab11 interacting protein, and syntaxin 3. Our data supports a hypothesis in which signaling via IL-6 family cytokines induces a procoagulant gene expression program in breast cancer cells. As part of this program, the production of tumor MP are increased via gene regulation of cellular proteins that control MP processing. Additionally, the procoagulant properties of the tumor MP are increased due to an increase in tissue factor content. It has been reported that both activation of coagulation and production of tumor MP are involved in solid tumor invasion and metastasis. Inflammatory signaling by IL-6 family members in the tumor milieu could be important in this process. This hypothesis has clinical significance since potential pharmacologic approaches to specific gp130 inhibition are available.

scholarly journals Mechanisms of Lysophosphatidic Acid-Mediated Lymphangiogenesis in Prostate Cancer

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 413 ◽  
Author(s):  
Pei-Yi Wu ◽  
Yueh-Chien Lin ◽  
Yuan-Li Huang ◽  
Wei-Min Chen ◽  
Chien-Chin Chen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lysophosphatidic Acid ◽  
Molecular Mechanisms ◽  
Lymphatic Vessels ◽  
Treatment Modalities ◽  
Regional Lymph Nodes ◽  
Castration Resistant ◽  
Tumor Lymphangiogenesis ◽  
Factor C ◽  
Endothelial Growth Factor

Prostate cancer (PCa) is the most common noncutaneous cancer in men worldwide. One of its major treatments is androgen deprivation therapy, but PCa frequently relapses as aggressive castration resistant local tumors and distal metastases. Hence, the development of novel agents or treatment modalities for advanced PCa is crucial. Many tumors, including PCa, first metastasize to regional lymph nodes via lymphatic vessels. Recent findings demonstrate that the bioactive lipid lysophosphatidic acid (LPA) promotes PCa progression by regulating vascular endothelial growth factor-C (VEGF-C), a critical mediator of tumor lymphangiogenesis and lymphatic metastasis. Many of the underlying molecular mechanisms of the LPA–VEGF-C axis have been described, revealing potential biomarkers and therapeutic targets that may aid in the diagnosis and treatment of advanced PCa. Herein, we review the literature that illustrates a functional role for LPA signaling in PCa progression. These discoveries may be especially applicable to anti-lymphangiogenic strategies for the prevention and therapy of metastatic PCa.

scholarly journals Cannabis sativa L. and Nonpsychoactive Cannabinoids: Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Federica Pellati ◽  
Vittoria Borgonetti ◽  
Virginia Brighenti ◽  
Marco Biagi ◽  
Stefania Benvenuti ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Fibre Type ◽  
Molecular Mechanisms ◽  
Cannabis Sativa ◽  
The Body ◽  
Alternative Pathways ◽  
Receptor Complexes ◽  
Cancer Models ◽  
Loss Of Appetite

In the last decades, a lot of attention has been paid to the compounds present in medicinal Cannabis sativa L., such as Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), and their effects on inflammation and cancer-related pain. The National Cancer Institute (NCI) currently recognizes medicinal C. sativa as an effective treatment for providing relief in a number of symptoms associated with cancer, including pain, loss of appetite, nausea and vomiting, and anxiety. Several studies have described CBD as a multitarget molecule, acting as an adaptogen, and as a modulator, in different ways, depending on the type and location of disequilibrium both in the brain and in the body, mainly interacting with specific receptor proteins CB1 and CB2. CBD is present in both medicinal and fibre-type C. sativa plants, but, unlike Δ9-THC, it is completely nonpsychoactive. Fibre-type C. sativa (hemp) differs from medicinal C. sativa, since it contains only few levels of Δ9-THC and high levels of CBD and related nonpsychoactive compounds. In recent years, a number of preclinical researches have been focused on the role of CBD as an anticancer molecule, suggesting CBD (and CBD-like molecules present in the hemp extract) as a possible candidate for future clinical trials. CBD has been found to possess antioxidant activity in many studies, thus suggesting a possible role in the prevention of both neurodegenerative and cardiovascular diseases. In animal models, CBD has been shown to inhibit the progression of several cancer types. Moreover, it has been found that coadministration of CBD and Δ9-THC, followed by radiation therapy, causes an increase of autophagy and apoptosis in cancer cells. In addition, CBD is able to inhibit cell proliferation and to increase apoptosis in different types of cancer models. These activities seem to involve also alternative pathways, such as the interactions with TRPV and GRP55 receptor complexes. Moreover, the finding that the acidic precursor of CBD (cannabidiolic acid, CBDA) is able to inhibit the migration of breast cancer cells and to downregulate the proto-oncogene c-fos and the cyclooxygenase-2 (COX-2) highlights the possibility that CBDA might act on a common pathway of inflammation and cancer mechanisms, which might be responsible for its anticancer activity. In the light of all these findings, in this review we explore the effects and the molecular mechanisms of CBD on inflammation and cancer processes, highlighting also the role of minor cannabinoids and noncannabinoids constituents of Δ9-THC deprived hemp.

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