scholarly journals Tools and Drugs for Purine-Binding Targets—Important Players in Inflammation and Cancer

Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 33
Author(s):  
Christa E. Müller
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Escape ◽  
Gold Rush ◽  
Innate Immune ◽  
Receptor Subtypes ◽  
Cancer Cell Proliferation ◽  
A2b Receptor ◽  
Cancer Tissues ◽  
Adenosine A2a

Despite decades of research, only few drugs have been approved that interact with purine receptors. Recently, new hypes and hopes have been created in the field, mainly due to the gold rush fever in immuno-oncology. Adenosine is one of the strongest immunosuppressant agents of the innate immune system. Cancer cells and tissues can release large amounts of ATP, which is immediately hydrolyzed by ectonucleotidases. These ecto-enzymes, including ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, CD203a), ectonucleoside diphospho­hydrolase 1 (NTPDase1, CD39), and ecto-5′-nucleotidase (CD73), are upregulated on many cancer cells, leading to the production of adenosine. The cloud of adenosine formed around cancer tissues contributes to immune escape by interacting with adenosine A2A and A2B receptor subtypes (A2AAR, A2BAR) on immune cells. In addition, activation of A2BARs by adenosine enhances cancer cell proliferation, metastasis, and angiogenesis. Blockade of A2A and A2B adenosine receptors and/or inhibition of adenosine formation by blocking ectonucleotidases are being pursued as novel principles that activate the immune system to defeat cancer. Recent progress in the development of adenosine receptor antagonists and ectonucleotidase inhibitors will be presented and discussed.

scholarly journals The Role of the Innate Immune System in Cancer Dormancy and Relapse

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5621
Author(s):  
Noah M. Chernosky ◽  
Ilaria Tamagno
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Immune Cells ◽  
Innate Immune System ◽  
Immune Escape ◽  
Disease Process ◽  
Innate Immune ◽  
Cancer Dormancy

Metastatic spread and recurrence are intimately linked to therapy failure, which remains an overarching clinical challenge for patients with cancer. Cancer cells often disseminate early in the disease process and can remain dormant for years or decades before re-emerging as metastatic disease, often after successful treatment. The interactions of dormant cancer cells and their metastatic niche, comprised of various stromal and immune cells, can determine the length of time that cancer cells remain dormant, as well as when they reactivate. New studies are defining how innate immune cells in the primary tumor may be corrupted to help facilitate many aspects of dissemination and re-emergence from a dormant state. Although the scientific literature has partially shed light on the drivers of immune escape in cancer, the specific mechanisms regulating metastasis and dormancy in the context of anti-tumor immunity are still mostly unknown. This review follows the journey of metastatic cells from dissemination to dormancy and the onset of metastatic outgrowth and recurrent tumor development, with emphasis on the role of the innate immune system. To this end, further research identifying how immune cells interact with cancer cells at each step of cancer progression will pave the way for new therapies that target the reactivation of dormant cancer cells into recurrent, metastatic cancers.

scholarly journals Why Target Innate Immune Cells in Cancers?

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 690
Author(s):  
Mary Poupot
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells

The immune system is a smart way to fight cancer, with its precise targeting of cancer cells sparing healthy cells [...]

ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

2021 ◽  
pp. 096032712198942
Author(s):  
Xiaoxue Zhang ◽  
Xianxin Xie ◽  
Kuiran Gao ◽  
Xiaoming Wu ◽  
Yanwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

scholarly journals PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengbin Chai ◽  
Li Wang ◽  
Yabing Zheng ◽  
Na Liang ◽  
Xiwei Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Expression Pattern ◽  
Colony Formation ◽  
Regulatory Mechanism ◽  
Cancer Cell Proliferation ◽  
Colon Cancer Cells ◽  
Cancer Tissues

Abstract Background CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research. Methods Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo. Results CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells. Conclusions PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.

scholarly journals ERK is a Pivotal Player of Chemo-Immune-Resistance in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 2505 ◽  
Author(s):  
Iris C. Salaroglio ◽  
Eleonora Mungo ◽  
Elena Gazzano ◽  
Joanna Kopecka ◽  
Chiara Riganti
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Immune Escape ◽  
Erk Signaling ◽  
Host Immune System ◽  
Immune Resistance ◽  
Survival Pathways ◽  
Extracellular Signal ◽  
Pros And Cons ◽  
And Migration

The extracellular signal-related kinases (ERKs) act as pleiotropic molecules in tumors, where they activate pro-survival pathways leading to cell proliferation and migration, as well as modulate apoptosis, differentiation, and senescence. Given its central role as sensor of extracellular signals, ERK transduction system is widely exploited by cancer cells subjected to environmental stresses, such as chemotherapy and anti-tumor activity of the host immune system. Aggressive tumors have a tremendous ability to adapt and survive in stressing and unfavorable conditions. The simultaneous resistance to chemotherapy and immune system responses is common, and ERK signaling plays a key role in both types of resistance. In this review, we dissect the main ERK-dependent mechanisms and feedback circuitries that simultaneously determine chemoresistance and immune-resistance/immune-escape in cancer cells. We discuss the pros and cons of targeting ERK signaling to induce chemo-immune-sensitization in refractory tumors.

miR-101 Inhibits Proliferation and Promotes Apoptosis of Gastric Cancer Cells Through Inhibition of Angiopoietin-Like Protein 2

2019 ◽  
Vol 9 (9) ◽  
pp. 1298-1303
Author(s):  
Jiping Xie ◽  
Qin Zhou
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Gastric Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Gastric Cancer Cells ◽  
Qrt Pcr ◽  
Gastric Cancer Cell Proliferation ◽  
Cancer Tissues ◽  
Relationship Of

ANGPTL2 abnormal expression is associated with various tumors. miR-101 abnormalities are associated with gastric cancer. There is a targeted relationship of miR-101 with ANGPTL2. This study intends to assess miR-101’s role gastric cancer cells. The gastric cancer tissues and adjacent tissues were collected to detect miR-101 and ANGPTL2 by qRT-PCR. Gastric cancer SGC7901 cells were divided into miR-NC group and miR-101 mimic group followed by analysis of ANGPTL2 expression by qRT-PCR and western blot, apoptosis by flow cytometry, and cell proliferation by EdU staining. Gastric cancer tissues had significantly decreased miR-101 and increased ANGPTL2 mRNA expression than adjacent tissues. The survival of patients with lower miR-101 level was significantly lower than higher miR-101 patients. There was a relationship between miR-101 and ANGPTL2. miR-101 mimic transfection significantly reduced ANGPTL2 expression, reduced cell proliferation and increased cell apoptosis. Abnormal miR-101 and ANGPTL2 expression is found in gastric cancer. miR-101 inhibits ANGPTL2 expression and gastric cancer cell proliferation and induces apoptosis.

scholarly journals Convergent Evolution by Cancer and Viruses in Evading the NKG2D Immune Response

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3827
Author(s):  
Richard Baugh ◽  
Hena Khalique ◽  
Leonard W. Seymour
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cancer Cells ◽  
Innate Immune System ◽  
Cell Transformation ◽  
Innate Immune ◽  
Immune Mediated ◽  
Pathogenic Viruses ◽  
Group 2 ◽  
Immune Defences

The natural killer group 2 member D (NKG2D) receptor and its family of NKG2D ligands (NKG2DLs) are key components in the innate immune system, triggering NK, γδ and CD8+ T cell-mediated immune responses. While surface NKG2DL are rarely found on healthy cells, expression is significantly increased in response to various types of cellular stress, viral infection, and tumour cell transformation. In order to evade immune-mediated cytotoxicity, both pathogenic viruses and cancer cells have evolved various mechanisms of subverting immune defences and preventing NKG2DL expression. Comparisons of the mechanisms employed following virus infection or malignant transformation reveal a pattern of converging evolution at many of the key regulatory steps involved in NKG2DL expression and subsequent immune responses. Exploring ways to target these shared steps in virus- and cancer-mediated immune evasion may provide new mechanistic insights and therapeutic opportunities, for example, using oncolytic virotherapy to re-engage the innate immune system towards cancer cells.

scholarly journals COVID-19 immunologic and toxicological implication: Innate immune sensor and immune escape

2021 ◽  
Vol 5 (1) ◽  
pp. 001-017
Author(s):  
M Luisetto ◽  
Ilman Ahnaf ◽  
Khan Farhan Ahmad ◽  
Edbey Khaled ◽  
Hamid Gamal Abdul ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Escape ◽  
Severe Disease ◽  
Point Of View ◽  
Innate Immune ◽  
Severe Condition ◽  
New Variant ◽  
Rapid Emergence ◽  
New Strategies ◽  
Viral Respiratory

Related COVID-19 and new Variant and treatment like vaccine it is relevant to deeply verify the immunologic implication and in a special way regarding the innate immune sensor system and the evasion of the immune system. This can be crucial to search for new strategies to fight this severe disease under a Toxicology-antidotes point of view. The rapid emergence of a new variant is under study by researchers because some of these show different responses to antibodies as reported in literature (vaccine efficacy?). In this article after a review part it is submitted a collection of hypothesis of solution to contrast COVID-19. Spread and mortality and project hypothesis. A new toxicological approach also in a viral respiratory disease can be a novelty to adequately fight this severe condition and this focusing not only towards specific immunity but also a specific measures. A toxicological approach in drug- vaccine like products designing makes it possible to get the clinical outcomes needed.

scholarly journals CD47 suppresses phagocytosis by repositioning SIRPA and preventing integrin activation

2019 ◽  
Author(s):  
Meghan A. Morrissey ◽  
Ronald D. Vale
Keyword(s):  
Immune System ◽  
Cancer Cells ◽  
Innate Immune System ◽  
Chemical Activation ◽  
Innate Immune ◽  
Integrin Activation ◽  
Signaling Axis ◽  
Potential Applications ◽  
Inhibitory Signaling ◽  
New Strategies

SummaryMacrophages must engulf dead cells, debris, and pathogens, while selecting against healthy cells to prevent autoimmunity. Healthy cells express CD47 on their surface, which activates the SIRPA receptor on macrophages to suppress engulfment. Cancer cells overexpress CD47 to evade clearance by the innate immune system, making the CD47-SIRPA signaling axis an appealing therapeutic target. However, the mechanism by which CD47-SIRPA inhibits engulfment remains poorly understood. Here, we dissect SIRPA signaling using a reconstituted target with varying concentrations of activating and inhibitor ligands. We find that SIRPA is excluded from the phagocytic synapse between the macrophage and its target unless CD47 is present. Artificially directing SIRPA to the kinase-rich synapse in the absence of CD47 activates SIRPA and suppresses engulfment, indicating that the localization of the receptor is critical for inhibitory signaling. CD47-SIRPA inhibits integrin activation in the macrophage, reducing macrophage-target contact and suppressing phagocytosis. Chemical activation of integrins can override this effect and drive engulfment of CD47-positive targets, including cancer cells. These results suggest new strategies for overcoming CD47-SIRPA inhibition of phagocytosis with potential applications in cancer immunotherapy.

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