scholarly journals Functional properties of ion channels and transporters in tumour vascularization

2014 ◽  
Vol 369 (1638) ◽  
pp. 20130103 ◽  
Author(s):  
Alessandra Fiorio Pla ◽  
Luca Munaron
Keyword(s):  
Ion Channels ◽  
Endothelial Cell Proliferation ◽  
Cancer Therapies ◽  
Tumour Angiogenesis ◽  
Anti Cancer ◽  
Solid Tumour Growth ◽  
Tumour Vascularization

Vascularization is crucial for solid tumour growth and invasion, providing metabolic support and sustaining metastatic dissemination. It is now accepted that ion channels and transporters play a significant role in driving the cancer growth at all stages. They may represent novel therapeutic, diagnostic and prognostic targets for anti-cancer therapies. On the other hand, although the expression and role of ion channels and transporters in the vascular endothelium is well recognized and subject of recent reviews, only recently has their involvement in tumour vascularization been recognized. Here, we review the current literature on ion channels and transporters directly involved in the angiogenic process. Particular interest will be focused on tumour angiogenesis in vivo as well as in the different steps that drive this process in vitro , such as endothelial cell proliferation, migration, adhesion and tubulogenesis. Moreover, we compare the ‘transportome’ system of tumour vascular network with the physiological one.

scholarly journals Vitamin C, From Supplement to Treatment: A Re-Emerging Adjunct for Cancer Immunotherapy?

2021 ◽  
Vol 12 ◽  
Author(s):  
Léonce Kouakanou ◽  
Christian Peters ◽  
Christine E. Brown ◽  
Dieter Kabelitz ◽  
Leo D. Wang
Keyword(s):  
Vitamin C ◽  
Cancer Therapies ◽  
Delay Tumor Growth ◽  
Anti Cancer ◽  
Challenges And Opportunities ◽  
High Doses ◽  
Direct Killing

Vitamin C (VitC), in addition to its role as a general antioxidant, has long been considered to possess direct anti-cancer activity at high doses. VitC acts through oxidant and epigenetic mechanisms, which at high doses can exert direct killing of tumor cells in vitro and delay tumor growth in vivo. Recently, it has also been shown that pharmacologic-dose VitC can contribute to control of tumors by modulating the immune system, and studies have been done interrogating the role of physiologic-dose VitC on novel adoptive cellular therapies (ACTs). In this review, we discuss the effects of VitC on anti-tumor immune cells, as well as the mechanisms underlying those effects. We address important unanswered questions concerning both VitC and ACTs, and outline challenges and opportunities facing the use of VitC in the clinical setting as an adjunct to immune-based anti-cancer therapies.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

scholarly journals The Role of Herbal Bioactive Components in Mitochondria Function and Cancer Therapy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Fangfang Tao ◽  
Yanrong Zhang ◽  
Zhiqian Zhang
Keyword(s):  
Cancer Therapy ◽  
Cancer Cell ◽  
Apoptotic Cell ◽  
Redox Status ◽  
Cancer Therapies ◽  
Bioactive Components ◽  
Atp Production

Mitochondria are highly dynamic double-membrane organelles which play a well-recognized role in ATP production, calcium homeostasis, oxidation-reduction (redox) status, apoptotic cell death, and inflammation. Dysfunction of mitochondria has long been observed in a number of human diseases, including cancer. Targeting mitochondria metabolism in tumors as a cancer therapeutic strategy has attracted much attention for researchers in recent years due to the essential role of mitochondria in cancer cell growth, apoptosis, and progression. On the other hand, a series of studies have indicated that traditional medicinal herbs, including traditional Chinese medicines (TCM), exert their potential anticancer effects as an effective adjunct treatment for alleviating the systemic side effects of conventional cancer therapies, for reducing the risk of recurrence and cancer mortality and for improving the quality of patients’ life. An amazing feature of these structurally diverse bioactive components is that majority of them target mitochondria to provoke cancer cell-specific death program. The aim of this review is to summarize the in vitro and in vivo studies about the role of these herbs, especially their bioactive compounds in the modulation of the disturbed mitochondrial function for cancer therapy.

Kallistatin Inhibits Endothelial Cell Proliferation, Migration and Adhesion in Vitro and Angiogenesis in the Ischemic Hindlimb of Rats

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 706-707
Author(s):  
Robert Q Miao ◽  
Jun Agata ◽  
Lee Chao ◽  
Julie Chao
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cell ◽  
Gene Delivery ◽  
Fluorescent Protein ◽  
Regional Blood Flow ◽  
Endothelial Cell Proliferation ◽  
Hek 293

P76 Kallistatin is a serine proteinase inhibitor (serpin) which has multifunctions including regulation of tissue kallikrein activity, blood pressure, inflammation and neointima hyperplasia. In this study, we investigated the potential role of kallistatin in vascular biology by studying its effects on the proliferation, migration and adhesion of cultured primary human endothelial cells in vitro, and angiogenesis in the ischemic hindlimb of rats. Purified kallistatin significantly inhibits cultured endothelial cell proliferation, migration and adhesion induced by VEGF or bFGF. To further investigate the role of kallistatin in vascular growth in vivo, we prepared adenovirus carrying the human kallistatin gene under the control of the cytomegalovirus promoter/enhancer (Ad.CMV-cHKBP). Expression of recombinant human kallistatin in HEK 293 cells transfected with Ad.CMV-cHKBP was identified by a specific ELISA. The effect of adenovirus-mediated kallistatin gene delivery on angiogenesis was evaluated in a rat model of hindlimb ischemia. Adenovirus carrying the human kallistatin or green fluorescent protein (GFP) gene were injected locally into the ischemic adductor at the time of surgery. Histological and morphometric analysis at 14 days post injection showed that adenovirus-mediated kallistatin gene delivery significantly reduced capillary density in the ischemic muscle as compared to that of control rats injected with GFP. The anti-angiogenic effect of kallistatin was associated with reduced regional blood flow in the ischemic hindlimb measured by microsphere assays. Expression of human kallistatin was identified in the injected muscle and immunoreactive human kallistatin levels were measured in the muscle and in the circulation of rats following kallistatin gene delivery. These results demonstrate a novel role of kallistatin in the inhibition of angiogenesis and in vascular remodeling.

scholarly journals Importance of T, NK, CAR T and CAR NK Cell Metabolic Fitness for Effective Anti-Cancer Therapy: A Continuous Learning Process Allowing the Optimization of T, NK and CAR-Based Anti-Cancer Therapies

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 183
Author(s):  
Adrien Krug ◽  
Adriana Martinez-Turtos ◽  
Els Verhoeyen
Keyword(s):  
Nk Cells ◽  
Nk Cell ◽  
Building Blocks ◽  
Cancer Therapies ◽  
Cell Therapies ◽  
Anti Cancer ◽  
Car T ◽  
Metabolic Fitness

Chimeric antigen receptor (CAR) T and CAR NK cell therapies opened new avenues for cancer treatment. Although original successes of CAR T and CAR NK cells for the treatment of hematological malignancies were extraordinary, several obstacles have since been revealed, in particular their use for the treatment of solid cancers. The tumor microenvironment (TME) is competing for nutrients with T and NK cells and their CAR-expressing counterparts, paralyzing their metabolic effective and active states. Consequently, this can lead to alterations in their anti-tumoral capacity and persistence in vivo. High glucose uptake and the depletion of key amino acids by the TME can deprive T and NK cells of energy and building blocks, which turns them into a state of anergy, where they are unable to exert cytotoxic activity against cancer cells. This is especially true in the context of an immune-suppressive TME. In order to re-invigorate the T, NK, CAR T and CAR NK cell-mediated antitumor response, the field is now attempting to understand how metabolic pathways might change T and NK responses and functions, as well as those from their CAR-expressing partners. This revealed ways to metabolically rewire these cells by using metabolic enhancers or optimizing pre-infusion in vitro cultures of these cells. Importantly, next-generation CAR T and CAR NK products might include in the future the necessary metabolic requirements by improving their design, manufacturing process and other parameters. This will allow the overcoming of current limitations due to their interaction with the suppressive TME. In a clinical setting, this might improve their anti-cancer effector activity in synergy with immunotherapies. In this review, we discuss how the tumor cells and TME interfere with T and NK cell metabolic requirements. This may potentially lead to therapeutic approaches that enhance the metabolic fitness of CAR T and CAR NK cells, with the objective to improve their anti-cancer capacity.

scholarly journals Targeting Mitochondrial Ion Channels to Fight Cancer

2018 ◽  
Vol 19 (7) ◽  
pp. 2060 ◽  
Author(s):  
Magdalena Bachmann ◽  
Roberto Costa ◽  
Roberta Peruzzo ◽  
Elena Prosdocimi ◽  
Vanessa Checchetto ◽  
...  
Keyword(s):  
Ion Channels ◽  
Tumor Development ◽  
Cancer Development ◽  
Cancer Growth ◽  
Altered Expression ◽  
New Frontier ◽  
Near Future

In recent years, several experimental evidences have underlined a new role of ion channels in cancer development and progression. In particular, mitochondrial ion channels are arising as new oncological targets, since it has been proved that most of them show an altered expression during tumor development and the pharmacological targeting of some of them have been demonstrated to be able to modulate cancer growth and progression, both in vitro as well as in vivo in pre-clinical mouse models. In this scenario, pharmacology of mitochondrial ion channels would be in the near future a new frontier for the treatment of tumors. In this review, we discuss the new advances in the field, by focusing our attention on the improvements in new drug developments to target mitochondrial ion channels.

scholarly journals THE BIOLOGICAL ACTIVITY OF EUROPEAN MISTLETOE (Viscum album) EXTRACTS AND THEIR PHARMACEUTICAL IMPACT

1970 ◽  
Vol 63 ◽  
Author(s):  
Simona Ioana Vicaş ◽  
Carmen Socaciu
Keyword(s):  
Biological Activity ◽  
Mechanism Of Action ◽  
Viscum Album ◽  
Cancer Therapies ◽  
Main Principle ◽  
Mistletoe Extracts ◽  
Comparison Of The Results

Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. The mistletoe lectins and viscotoxins have been identified as the main principle of mistletoe extracts that participating in biological activity of V. album. These compounds were isolated and studied in vitro and in vivo for their biological activity and mechanism of action. A comparison of the results to those using whole extracts indicated that lectins and viscotoxins are not the only bioactive compounds present in the mistletoe. In this paper, we review the recent studies regarding with cytotoxic activity on tumor cells of mistletoe extracts, as well as, the role of this semiparasitic plant in diabetics and hypertension illness.

scholarly journals Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ye Xiong ◽  
Jianrong Huang
Keyword(s):  
Liver Diseases ◽  
Molecular Mechanisms ◽  
Disease Treatment ◽  
Clinical Safety ◽  
Safety And Efficacy ◽  
Anti Cancer ◽  
Induction Of Apoptosis

AbstractArtemisinin and its derivatives belong to a family of drugs approved for the treatment of malaria with known clinical safety and efficacy. In addition to its anti-malarial effect, artemisinin displays anti-viral, anti-inflammatory, and anti-cancer effects in vivo and in vitro. Recently, much attention has been paid to the therapeutic role of artemisinin in liver diseases. Several studies suggest that artemisinin and its derivatives can protect the liver through different mechanisms, such as those pertaining to inflammation, proliferation, invasion, metastasis, and induction of apoptosis and autophagy. In this review, we provide a comprehensive discussion of the underlying molecular mechanisms and signaling pathways of artemisinin and its derivatives in treating liver diseases. Further pharmacological research will aid in determining whether artemisinin and its derivatives may serve as promising medicines for the treatment of liver diseases in the future.

scholarly journals LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical

2019 ◽  
Vol 20 (24) ◽  
pp. 6239
Author(s):  
Yu-Jiao Liu ◽  
Xiao-Yang Fan ◽  
An-Dong Wang ◽  
Yin-Zheng Xia ◽  
Wen-Rong Fu ◽  
...  
Keyword(s):  
Cancer Therapies ◽  
Therapeutic Value ◽  
Metabolic Remodeling ◽  
Anti Cancer ◽  
Tumor Progress ◽  
Caspase Family ◽  
Dependent Cell ◽  
Ros Burst

Based on the potential therapeutic value in targeting metabolism for the treatment of cancer, an organic arsenical PDT-BIPA was fabricated, which exerted selective anti-cancer activity in vitro and in vivo via targeting lactate dehydrogenase A (LDHA) to remodel the metabolic pathway. In details, the precursor PDT-BIPA directly inhibited the function of LDHA and converted the glycolysis to oxidative phosphorylation causing ROS burst and mitochondrial dysfunction. PDT-BIPA also altered several gene expression, such as HIF-1α and C-myc, to support the metabolic remodeling. All these changes lead to caspase family-dependent cell apoptosis in vivo and in vitro without obvious side effect. Our results provided this organic arsenical precursor as a promising anticancer candidate and suggested metabolism as a target for cancer therapies.

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