Chemokines—What Is Their Role in Colorectal Cancer?

Colorectal cancer (CRC) is one of the leading causes of cancer-related death. It is the second most frequently diagnosed malignancy in Europe and third worldwide. Colorectal malignancies diagnosed at an early stage offer a promising survival rate. However, advanced tumors often present distant metastases even after the complete resection of a primary tumor. Therefore, novel biomarkers of CRC are sorely needed in the diagnosis and prognosis of this common malignancy. A family of chemokines are composed of small, secreted proteins. They are best known for their ability to stimulate the migration of several cell types. Some investigations have indicated that chemokines are involved in cancer development, including CRC. This article presents current knowledge regarding chemokines and their specific receptors in CRC progression. Moreover, the prime aim of this review is to summarize the potential role of these proteins as biomarkers in the diagnosis and prognosis of CRC.

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Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110151957 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4605-4610 ◽

Cited By ~ 7

Author(s):

Atena Soleimani ◽

Farzad Rahmani ◽

Gordon A. Ferns ◽

Mikhail Ryzhikov ◽

Amir Avan ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Suppressor ◽

Current Knowledge ◽

Akt Signaling ◽

Tumor Tissues ◽

Radio Therapy ◽

Signaling Axis ◽

Cancer Tumor ◽

Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

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The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management

International Journal of Molecular Sciences ◽

10.3390/ijms21103494 ◽

2020 ◽

Vol 21 (10) ◽

pp. 3494

Author(s):

Aldona Kasprzak ◽

Agnieszka Adamek

Keyword(s):

Colorectal Cancer ◽

Nervous System ◽

Liver Metastasis ◽

Current Knowledge ◽

Distant Metastases ◽

Colorectal Cancer Liver Metastases ◽

Functional Changes ◽

Metastasis Development ◽

Research Challenge

Colorectal cancer (CRC), classified as the third most prevalent cancer worldwide, remains to be a clinical and research challenge. It is estimated that ~50% of CRC patients die from distant metastases, with treatment of this complication still posing significant difficulties. While liver metastasis (LM) cascade is known in the literature, its mechanisms are still unclear and remain studied in different research models. A connection is suggested between nervous system dysfunctions and a range of Neurotransmitters (Nts) (including Neuropeptides, NPs), Neurotrophins (Ntt) and their receptors (Rs) in CRC liver metastasis development. Studies on the role of NP/NP-Rs in the progression and metastasis of CRC, show the complexity of brain–tumor interactions, caused by their different forms of release to the extracellular environment (endocrine, autocrine, paracrine and neurocrine). Many stages of LM are connected to the activity of pro-inflammatory, e.g., Corticotropin-releasing Hormone Receptor 1 (CRHR1), Neuropeptide Y (NPY) and Neurotensin (NT), anti-inflammatory, e.g., Calcitonin Gene-related Peptide (CGRP), CRHR2 and Vasoactive Intestinal Polypeptide (VIP) or dual role neuropeptides, e.g., Substance P (SP). The regulation of the local immunological profile (e.g., CRH/CRHRs), dysfunctions of enteroprotective role of NPs on epithelial cells (e.g., NT/NT-R), as well as structural-functional changes in enteric nervous system innervation of the tumor are also important. More research is needed to understand the exact mechanisms of communication between the neurons and tumor cells. The knowledge on the mechanisms regulating tumor growth and different stages of metastasis, as well as effects of the action of a numerous group of Nts/NPs/Ntt as growth factors, have implications for future therapeutic strategies. To obtain the best treatment outcomes, it is important to use signaling pathways common for many NPs, as well to develop a range of broad-spectrum antagonists. This review aims to summarize the current knowledge on the importance of neuroactive molecules in the promotion of the invasion-metastasis cascade in CRC, as well as the improvements of clinical management of CRC liver metastasis.

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Serum CXCL8 and Its Specific Receptor (CXCR2) in Gastric Cancer

Cancers ◽

10.3390/cancers13205186 ◽

2021 ◽

Vol 13 (20) ◽

pp. 5186

Author(s):

Elżbieta Pawluczuk ◽

Marta Łukaszewicz-Zając ◽

Mariusz Gryko ◽

Agnieszka Kulczyńska-Przybik ◽

Barbara Mroczko

Keyword(s):

Gastric Cancer ◽

Significant Risk ◽

Significant Risk Factor ◽

Enzyme Linked Immunosorbent Assay ◽

Promising Candidate ◽

Diagnosis And Prognosis ◽

Established Tumor ◽

Novel Biomarkers ◽

Specific Receptors

Gastric cancer (GC) is the second leading cause of cancer-related deaths worldwide. This malignancy is usually diagnosed at an advanced stage. Therefore, novel biomarkers useful in the early detection of GC are sorely needed. Some authors suggest the role of chemokines and their specific receptors in GC pathogenesis. The aim of the study was to investigate whether serum CXCL8 and its receptor (CXCR2) might be considered as potential candidates for biomarkers in the diagnosis and prognosis of GC. The study included 98 subjects: 64 GC patients and 34 healthy volunteers. CXCL8 and CXCR2 concentrations were assessed by the enzyme-linked immunosorbent assay (ELISA) method. Serum CXCL8 and CXCR2 concentrations were significantly higher in GC patients than in healthy controls, similar to the well-established tumor marker (CA19-9) and marker of inflammation (CRP). Diagnostic sensitivity of CXCL8 was the highest among all proteins tested and increased for the combined assessment with CA19-9. The area under the ROC curve for CXCL8 was higher than those for CXCR2 and classical tumor markers. Serum CXCL8 levels were indicated as a significant risk factor of GC occurrence. Our findings suggest that serum CXCL8 is a promising candidate for a biomarker in GC diagnosis and might be used as a significant predictor of GC risk.

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Granulocytes and Cells of Granulocyte Origin—The Relevant Players in Colorectal Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22073801 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3801

Author(s):

Izabela Siemińska ◽

Ewa Poljańska ◽

Jarek Baran

Keyword(s):

Colorectal Cancer ◽

Dietary Habits ◽

Current Knowledge ◽

Survival Rates ◽

Suppressor Cells ◽

Substantial Impact ◽

Different Types ◽

Methods Of Treatment ◽

Common Malignancy

Colorectal cancer (CRC) is one of the most common malignancy and cause of cancer death worldwide, and it still remains a therapeutic challenge for western medicine. There is strong evidence that, in addition to genetic predispositions, environmental factors have also a substantial impact in CRC development. The risk of CRC is attributed, among others to dietary habits, alcohol consumption, whereas physical activity, food containing dietary fiber, dairy products, and calcium supplements have a protective effect. Despite progress in the available therapies, surgery remains a basic treatment option for CRC. Implementation of additional methods of treatment such as chemo- and/or targeted immunotherapy, improved survival rates, however, the results are still far from satisfactory. One of the reasons may be the lack of deeper understanding of the interactions between the tumor and different types of cells, including tumor infiltrating granulocytes. While the role of neutrophils is quite well explored in many cancers, role of eosinophils and basophils is often underestimated. As part of this review, we focused on the function of different granulocyte subsets in CRC, emphasizing the beneficial role of eosinophils and basophils, as well as dichotomic mode of neutrophils action. In addition, we addressed the current knowledge on cells of granulocyte origin, specifically granulocytic myeloid derived suppressor cells (Gr-MDSCs) and their role in development and progression of CRC.

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Role of inflammation in the development of colorectal cancer

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200909092908 ◽

2020 ◽

Vol 20 ◽

Author(s):

Sridhar Muthusami ◽

R. Ileng Kumaran ◽

Kokelavani Nampalli Babu ◽

Sneha Krishnamoorthy ◽

Akash Guruswamy ◽

...

Keyword(s):

Colorectal Cancer ◽

Chronic Inflammation ◽

Interleukin 1 ◽

Cell Types ◽

Model Systems ◽

Cytokine Gene Expression ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

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Circulating Biomarkers of Colorectal Cancer (CRC)—Their Utility in Diagnosis and Prognosis

Journal of Clinical Medicine ◽

10.3390/jcm10112391 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2391

Author(s):

Marta Łukaszewicz-Zając ◽

Barbara Mroczko

Keyword(s):

Colorectal Cancer ◽

Inflammatory Mediators ◽

Colorectal Adenomas ◽

Global Burden ◽

Circulating Biomarkers ◽

Specific Nature ◽

Diagnosis And Prognosis ◽

Specific Proteins ◽

Novel Biomarkers ◽

Number Of Publications

The global burden of colorectal cancer (CRC) is expected to increase, with 2.2 million new cases and 1.1 million annual deaths by 2030. Therefore, the establishment of novel biomarkers useful in the early diagnosis of CRC is of utmost importance. A number of publications have documented the significance of the overexpression of several specific proteins, such as inflammatory mediators, in CRC progression. However, little is known about the potential utility of these proteins as circulating blood tumor biomarkers of CRC. Therefore, in the present review we report the results of our previous original studies as well as the findings of other authors who investigated whether inflammatory mediators might be used as novel biomarkers in the diagnosis and prognosis of CRC. Our study revealed that among all of the tested proteins, serum M-CSF, CXCL-8, IL-6 and TIMP-1 have the greatest value in the diagnosis and progression of CRC. Serum TIMP-1 is useful in differentiating between CRC and colorectal adenomas, whereas M-CSF and CRP are independent prognostic factors for the survival of patients with CRC. This review confirms the promising significance of these proteins as circulating biomarkers for CRC. However, due to their non-specific nature, further validation of their sensitivity and specificity is required.

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Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽

10.3390/immuno1020006 ◽

2021 ◽

Vol 1 (2) ◽

pp. 78-90

Author(s):

Johannes Burtscher ◽

Grégoire P. Millet

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Current Knowledge ◽

Cell Types ◽

Brain Cell ◽

Special Focus ◽

Molecular Alterations ◽

Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

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Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis

Open Life Sciences ◽

10.1515/biol-2021-0053 ◽

2021 ◽

Vol 16 (1) ◽

pp. 523-536

Author(s):

Minghao Li ◽

Jianbin Zhuang ◽

Di Kang ◽

Yuzhuo Chen ◽

Weiliang Song

Keyword(s):

Colorectal Cancer ◽

Cancer Biology ◽

Spindle Pole ◽

Circular Rnas ◽

Cell Progression ◽

Crc Management ◽

Common Malignancy

Abstract Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis in vitro and weakened tumor growth in vivo. circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression in vitro via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

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Crucial Role of Extracellular Vesicles in Bronchial Asthma

International Journal of Molecular Sciences ◽

10.3390/ijms20102589 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2589 ◽

Cited By ~ 7

Author(s):

Tatsuya Nagano ◽

Masahiro Katsurada ◽

Ryota Dokuni ◽

Daisuke Hazama ◽

Tatsunori Kiriu ◽

...

Keyword(s):

Bronchial Asthma ◽

Extracellular Vesicles ◽

Bronchoalveolar Lavage Fluid ◽

Cell Types ◽

Lavage Fluid ◽

Generation Process ◽

Intracellular Proteins ◽

Novel Biomarkers ◽

Microarray Analyses

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.

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Role of colonoscopy in colorectal cancer

Revista do Hospital das Clínicas ◽

10.1590/s0041-87812001000100005 ◽

2001 ◽

Vol 56 (1) ◽

pp. 25-35 ◽

Cited By ~ 2

Author(s):

Sergio Eduardo Alonso Araujo ◽

Paulo Roberto Arruda Alves ◽

Angelita Habr-Gama

Keyword(s):

Colorectal Cancer ◽

Cost Effective ◽

Risk Groups ◽

Premalignant Lesions ◽

Average Risk ◽

Colonoscopic Polypectomy ◽

Histologic Diagnosis ◽

Improvement In Survival ◽

Common Malignancy

Colorectal cancer (CRC) represents the third most common malignancy throughout the world. Little or no improvement in survival has been effectively achieved in the last 50 years. Extensive epidemiological and genetic data are able to identify more precisely definite risk-groups so screening and early diagnosis can be more frequently accomplished. CRC is best detected by colonoscopy, which allows sampling for histologic diagnosis. Colonoscopy is the gold standard for detection of small and premalignant lesions, although it is not cost-effective for screening average-risk population. Colonoscopic polypectomy and mucosal resection constitute curative treatment for selective cases of invasive CRC. Similarly, alternative trans-colonoscopic treatment can be offered for adequate palliation, thus avoiding surgery.

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