scholarly journals Landscape Profiling Analysis of DPP4 in Malignancies: Therapeutic Implication for Tumor Patients With Coronavirus Disease 2019

2021 ◽  
Vol 11 ◽  
Author(s):  
Lingling Shu ◽  
Yang Liu ◽  
Jinyuan Li ◽  
Xiaoping Wu ◽  
Yang Li ◽  
...  

Severe coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by pneumonia, lymphopenia, and cytokine storms. Patients with underlying conditions, and especially cancer patients with impaired immunity, are particularly vulnerable to SARS-CoV-2 infection and complications. Although angiotensin converting enzyme II (ACE2) has been identified as a cellular binding receptor for SARS-CoV-2, immunopathological changes in severe cancer patients support the investigation of additional potential receptors such as dipeptidyl peptidase 4 (DPP4), a key immunoregulator. However, a comprehensive profiling analysis of DPP4 in malignancies remains obscure. In this study, using different datasets, we demonstrated the expression of DPP4 in healthy tissues and pan-cancers, showing the risk of different cancer types towards SARS-CoV-2 infection according to DPP4 expression levels. DPP4 expression was positively correlated with infiltrating levels of various immune cells and showed strong correlations with diverse immune marker sets in pan-cancer patients analyzed by Tumor Immune Estimation Resource (TIMER). These findings suggest that increased DPP4 expression in specific cancer patients might account for the high susceptibility to SARS-CoV-2 infection and the induction of cytokine storms. Due to the critical role of DPP4 in immunometabolism, our results indicate that pharmacological inhibition of DPP4 might provide beneficial therapeutic effects for SARS-CoV-2 treatment together with other strategies in specific tumor patients.

2019 ◽  
Vol 20 (5) ◽  
pp. 1237 ◽  
Author(s):  
Bhawna Sharma ◽  
Kalyan Nannuru ◽  
Sugandha Saxena ◽  
Michelle Varney ◽  
Rakesh Singh

Most breast cancer patients die due to bone metastasis. Although metastasis accounts for 5% of the breast cancer cases, it is responsible for most of the deaths. Sometimes even before the detection of a primary tumor, most of the patients have bone and lymph node metastasis. Moreover, at the time of death, breast cancer patients have the bulk of the tumor burden in their bones. Therapy options are available for the treatment of primary tumors, but there are minimal options for treating breast cancer patients who have bone metastasis. C-X-C motif chemokine receptor type 2 (CXCR2) receptor-mediated signaling has been shown to play a critical role during bone-related inflammations and its ligands C-X-C motif chemokine ligand 6 (CXCL6) and 8 (CXCL8) aid in the resorption of bone during bone metastasis. In this study, we tested the hypothesis that CXCR2 contributes to mammary tumor-induced osteolysis and bone metastasis. In the present study, we examined the role of both tumor cell-derived and host-derived CXCR2 in influencing mammary tumor cell bone metastasis. For understanding the role of tumor cell-derived CXCR2, we utilized Cl66 CXCR2 knockdown (Cl66-shCXCR2) and Cl66-Control cells (Cl66-Control) and observed a significant decrease in tumor growth and tumor-induced osteolysis in Cl66-shCXCR2 cells in comparison with the Cl66-Control cells. Next, for understanding the role of host-derived CXCR2, we utilized mice with genomic knockdown of CXCR2 (Cxcr2−/−) and injected Cl66-Luciferase (Cl66-Luc) or 4T1-Luciferase (4T1-Luc) cells. We observed decreased bone destruction and metastasis in the bone of Cxcr2−/− mice. Our data suggest the importance of both tumor cell- and host-derived CXCR2 signaling in the bone metastasis of breast cancer cells.


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 752 ◽  
Author(s):  
Rawat ◽  
Kadian ◽  
Gupta ◽  
Kumar ◽  
Chain ◽  
...  

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.


Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 245
Author(s):  
Ruggiero Gorgoglione ◽  
Valeria Impedovo ◽  
Christopher L. Riley ◽  
Deborah Fratantonio ◽  
Stefano Tiziani ◽  
...  

Aspartate has a central role in cancer cell metabolism. Aspartate cytosolic availability is crucial for protein and nucleotide biosynthesis as well as for redox homeostasis. Since tumor cells display poor aspartate uptake from the external environment, most of the cellular pool of aspartate derives from mitochondrial catabolism of glutamine. At least four transporters are involved in this metabolic pathway: the glutamine (SLC1A5_var), the aspartate/glutamate (AGC), the aspartate/phosphate (uncoupling protein 2, UCP2), and the glutamate (GC) carriers, the last three belonging to the mitochondrial carrier family (MCF). The loss of one of these transporters causes a paucity of cytosolic aspartate and an arrest of cell proliferation in many different cancer types. The aim of this review is to clarify why different cancers have varying dependencies on metabolite transporters to support cytosolic glutamine-derived aspartate availability. Dissecting the precise metabolic routes that glutamine undergoes in specific tumor types is of upmost importance as it promises to unveil the best metabolic target for therapeutic intervention.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9304
Author(s):  
Mariati Abdul Rahman ◽  
Didi Erwandi Mohamad Haron ◽  
Robert J. Hollows ◽  
Zuleen Delina Fasya Abdul Ghani ◽  
Mustafa Ali Mohd ◽  
...  

Head and neck squamous cell carcinoma (HNSCC) represents a significant world health problem, with approximately 600,000 new cases being diagnosed annually. The prognosis for patients with HNSCC is poor and, therefore, the identification of biomarkers for screening, diagnosis and prognostication would be clinically beneficial. A limited number of studies have used lipidomics to profile lipid species in the plasma of cancer patients. However, the profile and levels of lysophosphatidic acid (LPA) species have not been examined in HNSCC. In this study, a targeted lipidomics approach using liquid chromatography triple quadrupole mass spectrometry (LCMS/MS) was used to analyse the concentration of LPA (16:0 LPA, 18:0 LPA, 18:1 LPA, 18:2 LPA and 20:4 LPA) in the plasma of patients with oral squamous cell carcinoma (OSCC) and nasopharyngeal carcinoma (NPC), together with healthy controls. The levels of three LPA species (18:1 LPA, 18:2 LPA and 20:4 LPA) were significantly lower in the plasma of OSCC patients, whilst the concentrations of all five LPA species tested were significantly lower in plasma from NPC patients. Furthermore, the order of abundance of LPA species in plasma was different between the control and cancer groups, with 16:0 LPA, 18:0 LPA levels being more abundant in OSCC and NPC patients. Medium to strong correlations were observed using all pairs of LPA species and a clear separation of the normal and tumour groups was observed using PCA analysis. In summary, the results of this study showed that the levels of several LPA species in the plasma of patients with OSCC and NPC were lower than those from healthy individuals. Understanding these variations may provide novel insights into the role of LPA in these cancers.


2017 ◽  
Vol 3 (s1) ◽  
pp. 47 ◽  
Author(s):  
Lefteris C Zacharia ◽  
Vasiliki Gkretsi

Primary tumors are seldom the cause of death for cancer patients as most patients die from metastatic disease. Thus, deciphering metastatic mechanisms and key molecules involved is of utmost importance for the improved survival of cancer patients. Metastasis is a complex process in which cancer cells dissociate from the original tumor and spread to distant sites of the body. During the metastatic process, cancer cells lose contact both with the extracellular matrix (ECM) and the neighboring cells within the primary tumor, thus invading though surrounding tissues. Therefore, ECM, and ECM-related adhesion proteins play a critical role in the metastatic process. Ras suppressor-1 (RSU-1) was first identified as a suppressor of Ras-dependent oncogenic transformation and is localized to cell-ECM adhesions where it is known to interact with the pro-survival adhesion protein PINCH-1. Although the connection to cancer is obvious, little is known regarding its expression in various cancer types. This opinion piece is focusing on recent literature regarding the expression of RSU-1 in various cancer types and the possible molecular mechanism of its action, pointing towards questions that need still to be addressed in this research field.


2021 ◽  
Vol 12 ◽  
Author(s):  
Haozhe Yu ◽  
Qicong Wang ◽  
Wenyu Wu ◽  
Weizhen Zeng ◽  
Yun Feng

Melatonin plays a critical role in the pathophysiological process including circadian rhythm, apoptosis, and oxidative stress. It can be synthesized in ocular tissues, and its receptors are also found in the eye, triggering more investigations concentrated on the role of melatonin in the eye. In the past decades, the protective and therapeutic potentials of melatonin for ocular diseases have been widely revealed in animal models. Herein, we construct a knowledge map of melatonin in treating ocular diseases through bibliometric analysis and review its current understanding and clinical evidence. The overall field could be divided into twelve topics through keywords co-occurrence analysis, in which the glaucoma, myopia, and retinal diseases were of greatest research interests according to the keywords burst detection. The existing clinical trials of melatonin in ocular diseases mainly focused on the glaucoma, and more research should be promoted, especially for various diseases and drug administration. We also discuss its bioavailability and further research topics including developing melatonin sensors for personalized medication, acting as stem cell therapy assistant drug, and consuming food-derived melatonin for facilitating its clinical transformation.


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