scholarly journals Fibronectin in Cancer: Friend or Foe

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 27 ◽  
Author(s):  
Tsung-Cheng Lin ◽  
Cheng-Han Yang ◽  
Li-Hsin Cheng ◽  
Wen-Tsan Chang ◽  
Yuh-Rong Lin ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Poor Prognosis ◽  
Therapeutic Strategies ◽  
Malignant Progression ◽  
Metastatic Progression ◽  
Future Perspectives ◽  
Tumor Microenvironments ◽  
Tumor Transformation

The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies.

scholarly journals Tumor-associated macrophages: potential therapeutic strategies and future prospects in cancer

2021 ◽  
Vol 9 (1) ◽  
pp. e001341
Author(s):  
Chunxiao Li ◽  
Xiaofei Xu ◽  
Shuhua Wei ◽  
Ping Jiang ◽  
Lixiang Xue ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Cancer Cells ◽  
Poor Prognosis ◽  
Tumor Immunotherapy ◽  
Therapeutic Strategies ◽  
Preclinical Studies ◽  
Future Prospects ◽  
Tumor Associated Macrophages

Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.

scholarly journals Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 663
Author(s):  
Yu Yuan ◽  
Abdalla Adam ◽  
Chen Zhao ◽  
Honglei Chen
Keyword(s):  
Immune Evasion ◽  
Immune Checkpoint ◽  
Poor Prognosis ◽  
Target Therapy ◽  
Acquired Resistance ◽  
Immune Checkpoint Blockade ◽  
Therapeutic Strategies ◽  
Present Evidence ◽  
Immunosuppressive Factor

Release of immunoreactive negative regulatory factors such as immune checkpoint limits antitumor responses. PD-L1 as a significant immunosuppressive factor has been involved in resistance to therapies such as chemotherapy and target therapy in various cancers. Via interacting with PD-1, PD-L1 can regulate other factors or lead to immune evasion of cancer cells. Besides, immune checkpoint blockade targeting PD-1/PD-L1 has promising therapeutic efficacy in the different tumors, but a significant percentage of patients cannot benefit from this therapy due to primary and acquired resistance during treatment. In this review, we described the utility of PD-L1 expression levels for predicting poor prognosis in some tumors and present evidence for a role of PD-L1 in resistance to therapies through PD-1/PD-L1 pathway and other correlating signaling pathways. Afterwards, we elaborate the key mechanisms underlying resistance to PD-1/PD-L1 blockade in cancer immunotherapy. Furthermore, promising combination of therapeutic strategies for patients resistant to PD-1/PD-L1 blockade therapy or other therapies associated with PD-L1 expression was also summarized.

scholarly journals Role of Immunotherapy in Pulmonary Angiosarcoma: A Case Report

2021 ◽  
pp. 797-801
Author(s):  
Quang Tien Nguyen ◽  
Anh Tuan Pham ◽  
Thuy Thi Nguyen ◽  
Tam Thi Thanh Nguyen ◽  
Ky Van Le
Keyword(s):  
Case Report ◽  
Poor Prognosis ◽  
Checkpoint Inhibitor ◽  
Therapeutic Strategies ◽  
Clinical Entity ◽  
Rare Clinical Entity ◽  
Excellent Response ◽  
First Case

Pulmonary angiosarcoma is a rare clinical entity with a poor prognosis and no established therapeutic strategies. We present the first case to our knowledge of metastatic pulmonary angiosarcoma, treated with checkpoint inhibitor immunotherapy, and have an excellent response. Until now, patient has been treated with immunotherapy for 1 year, and his disease is stable and well-tolerated.

scholarly journals HOXB4 promotes the malignant progression of ovarian cancer via DHDDS

2019 ◽  
Author(s):  
Na Li ◽  
Jiao Xiong ◽  
Zhengyu Li
Keyword(s):  
Ovarian Cancer ◽  
Poor Prognosis ◽  
Malignant Progression ◽  
Stem Cell Markers ◽  
Tumor Proliferation ◽  
The Poor ◽  
Proliferation And Metastasis ◽  
Proliferation And Invasion ◽  
Tumor Proliferation And Metastasis

Abstract Background: Homeobox B4 (HOXB4) is associated with the poor prognosis of various cancer types. However, how HOXB4 promotes ovarian cancer (OV) progression remains to be determined. Methods：The Cancer Genome Atlas (TCGA) database indicated that high level of HOXB4 in OV was correlated with poor prognosis. The biological functions of HOXB4 were confirmed through a colony formation, migration, and invasion assay. The effect of HOXB4 on the expression of EMT and cancer stem cell markers was detected. The transcriptional target of HOXB4 was DHDDS, which was detected by a ChIP assay. A xenograft tumor model was performed in nude mice to detect the role of HOXB4 in tumor proliferation and metastasis. Results：Results showed that the expression of HOXB4 was higher in OV tissues than in normal tissues and correlated with the poor prognosis of OV. HOXB4 knockdown suppressed the proliferation and invasion ability of OV cells in vitro. Conversely, these effects were enhanced by the up-regulation of HOXB4 in OV cells. The binding of two DNA motifs through HOXB4 regulated DHDDS expression and contributed to the malignant progression of OV. The role of HOXB4 in promoting tumor proliferation and metastasis was verified in mice. Further investigation revealed that HOXB4 triggered Snail and Zeb1 expression. Conclusion: Overall, HOXB4 overexpression was remarkably correlated with the poor prognosis of OV. HOXB4 up-regulated DHDDS, which co-contributed to the enhancer proliferation and invasion of OV cells, thus accelerating the malignant progression of OV.

scholarly journals Tumor-Associated Microglia and Macrophages in the Glioblastoma Microenvironment and their Implications for Therapy

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4255
Author(s):  
Rikke Sick Andersen ◽  
Atul Anand ◽  
Dylan Scott Lykke Harwood ◽  
Bjarne Winther Kristensen
Keyword(s):  
Poor Prognosis ◽  
Therapeutic Strategy ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Therapeutic Strategies ◽  
The Poor ◽  
Temozolomide Chemotherapy

Glioblastoma is the most frequent and malignant primary brain tumor. Standard of care includes surgery followed by radiation and temozolomide chemotherapy. Despite treatment, patients have a poor prognosis with a median survival of less than 15 months. The poor prognosis is associated with an increased abundance of tumor-associated microglia and macrophages (TAMs), which are known to play a role in creating a pro-tumorigenic environment and aiding tumor progression. Most treatment strategies are directed against glioblastoma cells; however, accumulating evidence suggests targeting of TAMs as a promising therapeutic strategy. While TAMs are typically dichotomously classified as M1 and M2 phenotypes, recent studies utilizing single cell technologies have identified expression pattern differences, which is beginning to give a deeper understanding of the heterogeneous subpopulations of TAMs in glioblastomas. In this review, we evaluate the role of TAMs in the glioblastoma microenvironment and discuss how their interactions with cancer cells have an extensive impact on glioblastoma progression and treatment resistance. Finally, we summarize the effects and challenges of therapeutic strategies, which specifically aim to target TAMs.

scholarly journals Infantile Brain Tumors: A Review of Literature and Future Perspectives

Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 670
Author(s):  
Valeria Simone ◽  
Daniela Rizzo ◽  
Alessandro Cocciolo ◽  
Anna Maria Caroleo ◽  
Andrea Carai ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Therapeutic Strategies ◽  
Clinical Applications ◽  
Review Of Literature ◽  
Future Perspectives ◽  
Older Children ◽  
Nervous System Tumors ◽  
Molecular Landscape ◽  
Specific Symptoms

Brain tumors in infants including those diagnosed in fetal age, newborns and under a year old represent less than 10% of pediatric nervous system tumors and present differently when compared with older children in terms of clinical traits, location and histology. The most frequent clinical finding is a macrocephaly but non-specific symptoms can also be associated. The prognosis is usually poor and depends on several factors. Surgery continues to be the main option in terms of therapeutic strategies whereas the role of chemotherapy is not yet well defined and radiotherapy is exceptionally undertaken. In view of this situation, a molecular characterization could assist in providing therapeutic options for these tumors. This review highlights the recent advances in the diagnosis and treatment of brain tumors in infants with a particular focus on the molecular landscape and future clinical applications.

scholarly journals TMIC-03. UPREGULATION OF THE NLRC4 INFLAMMASOME CONTRIBUTES TO POOR PROGNOSIS IN GLIOMA PATIENTS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi247-vi247
Author(s):  
Jaejoon Lim ◽  
Youngjoon Park ◽  
Minjun Kim ◽  
Juwon Ahn ◽  
KyuBum Kwack ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Tumor Development ◽  
The Cancer Genome Atlas ◽  
Immune Functions ◽  
Potential Therapeutic Target ◽  
Clinical Prognosis ◽  
Tumor Microenvironments ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Inflammation in tumor microenvironments is implicated in the pathogenesis of tumor development. In particular, inflammasomes, which modulate innate immune functions, are linked to tumor growth and anticancer responses. However, the role of the NLRC4 inflammasome in gliomas remains unclear. Here, we investigated whether the upregulation of the NLRC4 inflammasome is associated with the clinical prognosis of gliomas. We analyzed the protein expression and localization of NLRC4 in glioma tissues from 11 patients by immunohistochemistry. We examined the interaction between the expression of NLRC4 and clinical prognosis via a Kaplan-Meier survival analysis. The level of NLRC4 protein was increased in brain tissues, specifically, in astrocytes, from glioma patients. NLRC4 expression was associated with a poor prognosis in glioma patients, and the upregulation of NLRC4 in astrocytomas was associated with poor survival. Furthermore, hierarchical clustering of data from the Cancer Genome Atlas dataset showed that NLRC4 was highly expressed in gliomas relative to that in a normal healthy group. Our results suggest that the upregulation of the NLRC4 inflammasome contributes to a poor prognosis for gliomas and presents a potential therapeutic target and diagnostic marker.

scholarly journals Targeting Mononuclear Phagocyte Receptors in Cancer Immunotherapy: New Perspectives of the Triggering Receptor Expressed on Myeloid Cells (TREM-1)

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1337
Author(s):  
Federica Raggi ◽  
Maria Bosco
Keyword(s):  
Tumor Progression ◽  
Cancer Immunotherapy ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Therapeutic Strategies ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Receptor Expression ◽  
Tumor Phenotype

Inflammatory cells are major players in the onset of cancer. The degree of inflammation and type of inflammatory cells in the tumor microenvironment (TME) are responsible for tilting the balance between tumor progression and regression. Cancer-related inflammation has also been shown to influence the efficacy of conventional therapy. Mononuclear phagocytes (MPs) represent a major component of the inflammatory circuit that promotes tumor progression. Despite their potential to activate immunosurveillance and exert anti-tumor responses, MPs are subverted by the tumor to support its growth, immune evasion, and spread. MP responses in the TME are dictated by a network of stimuli integrated through the cross-talk between activatory and inhibitory receptors. Alterations in receptor expression/signaling can create excessive inflammation and, when chronic, promote tumorigenesis. Research advances have led to the development of new therapeutic strategies aimed at receptor targeting to induce a tumor-infiltrating MP switch from a cancer-supportive toward an anti-tumor phenotype, demonstrating efficacy in different human cancers. This review provides an overview of the role of MP receptors in inflammation-mediated carcinogenesis and discusses the most recent updates regarding their targeting for immunotherapeutic purposes. We focus in particular on the TREM-1 receptor, a major amplifier of MP inflammatory responses, highlighting its relevance in the development and progression of several types of inflammation-associated malignancies and the promises of its inhibition for cancer immunotherapy.

scholarly journals Role of Interleukin-17 in Acute Pancreatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Guanqun Li ◽  
Hongze Chen ◽  
Liwei Liu ◽  
Peng Xiao ◽  
Yu Xie ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Poor Prognosis ◽  
Acinar Cells ◽  
Therapeutic Strategies ◽  
Pancreatic Tissue ◽  
Vital Role ◽  
Interleukin 17 ◽  
Systemic Manifestations ◽  
Pathogenic Process

Acute pancreatitis (AP) is a leading cause of death and is commonly accompanied by systemic manifestations that are generally associated with a poor prognosis. Many cytokines contribute to pancreatic tissue damage and cause systemic injury. Interleukin-17 (IL-17) is a cytokine that may play a vital role in AP. Specifically, IL-17 has important effects on the immune response and causes interactions between different inflammatory mediators in the AP-related microenvironment. In this literature review, we will discuss the existing academic understanding of IL-17 and the impacts of IL-17 in different cells (especially in acinar cells and immune system cells) in AP pathogenesis. The clinical significance and potential mechanisms of IL-17 on AP deterioration are emphasized. The evidence suggests that inhibiting the IL-17 cytokine family could alleviate the pathogenic process of AP, and we highlight therapeutic strategies that directly or indirectly target IL-17 cytokines in acute pancreatitis.

scholarly journals The emerging role of WWP1 in cancer development and progression

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaoli Hu ◽  
Jiangtao Yu ◽  
Zixia Lin ◽  
Renqian Feng ◽  
Zhi-wei Wang ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Patients ◽  
Clinical Features ◽  
Therapeutic Strategies ◽  
Review Article ◽  
Cancer Development ◽  
Ubiquitin Protein Ligase ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

AbstractEmerging evidence demonstrates that WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) participates into carcinogenesis and tumor progression. In this review article, we will describe the association between dysregulated WWP1 expression and clinical features of cancer patients. Moreover, we summarize the both oncogenic and tumor suppressive functions of WWP1 in a variety of human cancers. Furthermore, we briefly describe the downstream substrates of WWP1 and its upstream factors to regulate the expression of WWP1. Notably, targeting WWP1 by its inhibitors or natural compounds is potentially useful for treating human malignancies. Finally, we provide the perspectives regarding WWP1 in cancer development and therapies. We hope this review can stimulate the research to improve our understanding of WWP1-mediated tumorigenesis and accelerate the discovery of novel therapeutic strategies via targeting WWP1 expression in cancers.

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