For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
4
views
33
references
 Top references
cited by
0
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      213
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      High Immunoexpression of COX-2 as a Metastatic Risk Factor in ccRCC without PD-L1 Involvement

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Clear cell renal cell carcinoma (ccRCC) is the most lethal type of malignancy of the urinary tract system as it is resistant to chemotherapy and radiation and has a survival rate of less than 5% in cases of metastasis. Inflammation plays an essential role in the metastasis of ccRCC. Cyclooxygenase-2 (COX-2) is an inflammatory protein that affects the processes of carcinogenesis, invasion, migration, metastasis, and angiogenesis. COX-2 can modulate programmed death ligand-1 (PD-L1) expression and play a role in immune evasion, meaning that tumor cells are able to escape the body’s immune response and more easily metastasize.

          Purpose

          This study aims to determine the role of COX-2 and PD-L1 in the occurrence of ccRCC metastases.

          Materials and Methods

          This study is an observational analytical study, which employed a cross-sectional approach to examine the paraffin block samples of 40 ccRCC cases from Dr. Hasan Sadikin Hospital Bandung, Indonesia, between 2014 and 2021. Immunoexpression was measured using immunohistochemical staining for COX-2 in tumor cells and for PD-L1 in immune cells. PD-L1 calculation was measured using Qupath 0.2.3. digital software. Metastatic data were obtained using radiological imaging and pathological examinations. Meanwhile, the data were analyzed using the chi-square test for COX-2 and Fischer’s exact test for PD-L1.

          Results

          The research results revealed a significant association between COX-2 and the occurrence of metastases in ccRCC (p=0.001) with a prevalence odds ratio of 10.28. Positive PD-L1 immunoexpression of the immune cells (≥1%) was found in 14% (3/21) of the metastatic group and 5% (1/19) of the non-metastatic group (p=0.607). There was no association between COX-2 and PD-L1 immunoexpression (p=0.278).

          Conclusion

          This study shows that metastases in ccRCC patients are ten times as likely to be associated with high COX-2 immunoexpression than low COX-2 immunoexpression. COX-2 plays a role in the process of ccRCC metastasis without PD-L1 involvement.

          Related collections

          Most cited references33

          • Record: found
          • Abstract: found
          • Article: not found

          Cyclooxygenase-2 in cancer: A review

          Nasser Hashemi Goradel, Masoud Najafi, Eniseh Salehi … (2019)
          Cyclooxygenase-2 (COX-2) is frequently expressed in many types of cancers exerting a pleiotropic and multifaceted role in genesis or promotion of carcinogenesis and cancer cell resistance to chemo- and radiotherapy. COX-2 is released by cancer-associated fibroblasts (CAFs), macrophage type 2 (M2) cells, and cancer cells to the tumor microenvironment (TME). COX-2 induces cancer stem cell (CSC)-like activity, and promotes apoptotic resistance, proliferation, angiogenesis, inflammation, invasion, and metastasis of cancer cells. COX-2 mediated hypoxia within the TME along with its positive interactions with YAP1 and antiapoptotic mediators are all in favor of cancer cell resistance to chemotherapeutic drugs. COX-2 exerts most of the functions through its metabolite prostaglandin E2. In some and limited situations, COX-2 may act as an antitumor enzyme. Multiple signals are contributed to the functions of COX-2 on cancer cells or its regulation. Members of mitogen-activated protein kinase (MAPK) family, epidermal growth factor receptor (EGFR), and nuclear factor-κβ are main upstream modulators for COX-2 in cancer cells. COX-2 also has interactions with a number of hormones within the body. Inhibition of COX-2 provides a high possibility to exert therapeutic outcomes in cancer. Administration of COX-2 inhibitors in a preoperative setting could reduce the risk of metastasis in cancer patients. COX-2 inhibition also sensitizes cancer cells to treatments like radio- and chemotherapy. Chemotherapeutic agents adversely induce COX-2 activity. Therefore, choosing an appropriate chemotherapy drugs along with adjustment of the type and does for COX-2 inhibitors based on the type of cancer would be an effective adjuvant strategy for targeting cancer.
          Article 0 comments Cited 203 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Resistance to Systemic Therapies in Clear Cell Renal Cell Carcinoma: Mechanisms and Management Strategies

            Peter Makhov, Shreyas Joshi, Pooja Ghatalia … (2018)
            Renal cell carcinoma (RCC) is the most common form of kidney cancer. It is categorized into various subtypes, with clear cell RCC (ccRCC) representing about 85% of all RCC tumors. The lack of sensitivity to chemotherapy and radiation therapy prompted research efforts into novel treatment options. The development of targeted therapeutics, including multi-targeted tyrosine kinase inhibitors (TKIs) and mTOR inhibitors, has been a major breakthrough in ccRCC therapy. More recently, other therapeutic strategies, including immune checkpoint inhibitors, have emerged as effective treatment options against advanced ccRCC. Furthermore, recent advances in disease biology, tumor microenvironment, and mechanisms of resistance formed the basis for attempts to combine targeted therapies with newer generation immunotherapies to take advantage of possible synergy. This review focuses on the current status of basic, translational, and clinical studies on mechanisms of resistance to systemic therapies in ccRCC.
            Article 0 comments Cited 192 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Host expression of PD-L1 determines efficacy of PD-L1 pathway blockade–mediated tumor regression

              Heng Lin, Shuang Wei, Elaine Hurt … (2018)
              Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice. In contrast, neither knockout nor overexpression of PD-L1 in tumor cells had an effect on PD-L1 blockade efficacy. Human and murine studies showed high levels of functional PD-L1 expression in dendritic cells and macrophages in the tumor microenvironments and draining lymph nodes. Additionally, expression of PD-L1 on dendritic cells and macrophages in ovarian cancer and melanoma patients correlated with the efficacy of treatment with either anti-PD-1 alone or in combination with anti-CTLA-4. Thus, PD-L1-expressing dendritic cells and macrophages may mechanistically shape and therapeutically predict clinical efficacy of PD-L1/PD-1 blockade.
              Article 0 comments Cited 188 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Res Rep Urol
                Journal ID (iso-abbrev): Res Rep Urol
                Journal ID (publisher-id): rru
                Journal ID (pmc): rru
                Title: Research and Reports in Urology
                Publisher: Dove
                ISSN (Electronic): 2253-2447
                Publication date (Electronic): 24 August 2021
                Publication date Collection: 2021
                Volume: 13
                Pages: 623-630
                Affiliations
                [1 ]Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin Hospital , Bandung, Indonesia
                Author notes
                Correspondence: Lestari Putri Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital , Jl. Pasteur No. 38, Bandung, 40161, IndonesiaTel +6282217755916Fax +62222031447 Email lestariputri_dr@yahoo.com
                Article
                Publisher ID: 324510
                DOI: 10.2147/RRU.S324510
                PMC ID: 8403071
                SO-VID: 0cd39c6c-2f95-4cd8-a8b8-f0f49728a940
                Copyright © © 2021 Suryanti et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 15 June 2021
                Date accepted : 09 August 2021
                Page count
                Figures: 2, Tables: 10, References: 36, Pages: 8
                Categories
                Subject: Original Research

                Keywords: clear cell renal cell carcinoma,cyclooxygenase-2,metastasis,programmed death ligand-1
                Data availability:
                Keywords: clear cell renal cell carcinoma, cyclooxygenase-2, metastasis, programmed death ligand-1

                Comments

                Comment on this article