scholarly journals CD276 is an important player in macrophage recruitment into the tumor and an upstream regulator for PAI-1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sibel Durlanik ◽  
Katrin Fundel-Clemens ◽  
Coralie Viollet ◽  
Heinrich J. Huber ◽  
Martin Lenter ◽  
...  
Keyword(s):  
Clinical Prognosis ◽  
Rigorous Evaluation ◽  
Macrophage Recruitment ◽  
Upstream Regulator ◽  
Lack Of Information ◽  
Important Player ◽  
Inhibitory Signaling ◽  
Support Tumor Growth ◽  
Poor Clinical Prognosis ◽  
Pai 1

AbstractMore than 70% of colorectal, prostate, ovarian, pancreatic and breast cancer specimens show expression of CD276 (B7–H3), a potential immune checkpoint family member. Several studies have shown that high CD276 expression in cancer cells correlates with a poor clinical prognosis. This has been associated with the presence of lower tumor infiltrating leukocytes. Among those, tumor-associated macrophages can comprise up to 50% of the tumor mass and are thought to support tumor growth through various mechanisms. However, a lack of information on CD276 function and interaction partner(s) impedes rigorous evaluation of CD276 as a therapeutic target in oncology. Therefore, we aimed to understand the relevance of CD276 in tumor-macrophage interaction by employing a 3D spheroid coculture system with human cells. Our data show a role for tumor-expressed CD276 on the macrophage recruitment into the tumor spheroid, and also in regulation of the extracellular matrix modulator PAI-1. Furthermore, our experiments focusing on macrophage-expressed CD276 suggest that the antibody-dependent CD276 engagement triggers predominantly inhibitory signaling networks in human macrophages.

scholarly journals SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jing Li ◽  
Ruiqin Wu ◽  
Mingo M. H. Yung ◽  
Jing Sun ◽  
Zhuqing Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Resistance ◽  
Kinase Activity ◽  
Regulatory Mechanism ◽  
Platinum Resistance ◽  
Platinum Drug ◽  
Clinical Prognosis ◽  
Platinum Resistant ◽  
Poor Clinical Prognosis ◽  
Stat Pathway

AbstractThe JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation is associated with a poor clinical prognosis and drug resistance. The mechanism regulating JAK2 activity is complex. Although translocation of JAK2 between nucleus and cytoplasm is an important regulatory mechanism, how JAK2 translocation is regulated and what is the physiological function of this translocation remain largely unknown. Here, we found that protease SENP1 directly interacts with and deSUMOylates JAK2, and the deSUMOylation of JAK2 leads to its accumulation at cytoplasm, where JAK2 is activated. Significantly, this novel SENP1/JAK2 axis is activated in platinum-resistant ovarian cancer in a manner dependent on a transcription factor RUNX2 and activated RUNX2/SENP1/JAK2 is critical for platinum-resistance in ovarian cancer. To explore the application of anti-SENP1/JAK2 for treatment of platinum-resistant ovarian cancer, we found SENP1 deficiency or treatment by SENP1 inhibitor Momordin Ic significantly overcomes platinum-resistance of ovarian cancer. Thus, this study not only identifies a novel mechanism regulating JAK2 activity, but also provides with a potential approach to treat platinum-resistant ovarian cancer by targeting SENP1/JAK2 pathway.

scholarly journals Suppression of tumor-associated neutrophils by lorlatinib attenuates pancreatic cancer growth and improves treatment with immune checkpoint blockade

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sebastian R. Nielsen ◽  
Jan E. Strøbech ◽  
Edward R. Horton ◽  
Rene Jackstadt ◽  
Anu Laitala ◽  
...  
Keyword(s):  
Cd8 T Cells ◽  
Immune Cell ◽  
Immune Checkpoint Blockade ◽  
Ductal Adenocarcinoma ◽  
Cancer Growth ◽  
Cancer Therapies ◽  
Cell Type ◽  
Clinical Prognosis ◽  
Tumor Associated Neutrophils ◽  
Poor Clinical Prognosis

AbstractPancreatic ductal adenocarcinoma (PDAC) patients have a 5-year survival rate of only 8% largely due to late diagnosis and insufficient therapeutic options. Neutrophils are among the most abundant immune cell type within the PDAC tumor microenvironment (TME), and are associated with a poor clinical prognosis. However, despite recent advances in understanding neutrophil biology in cancer, therapies targeting tumor-associated neutrophils are lacking. Here, we demonstrate, using pre-clinical mouse models of PDAC, that lorlatinib attenuates PDAC progression by suppressing neutrophil development and mobilization, and by modulating tumor-promoting neutrophil functions within the TME. When combined, lorlatinib also improves the response to anti-PD-1 blockade resulting in more activated CD8 + T cells in PDAC tumors. In summary, this study identifies an effect of lorlatinib in modulating tumor-associated neutrophils, and demonstrates the potential of lorlatinib to treat PDAC.

FOXM1 is required for small cell lung cancer tumorigenesis and associated with poor clinical prognosis

Oncogene ◽  
2021 ◽  
Author(s):  
Sheng-Kai Liang ◽  
Chia-Chan Hsu ◽  
Hsiang-Lin Song ◽  
Yu-Chi Huang ◽  
Chun-Wei Kuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Clinical Prognosis ◽  
Poor Clinical Prognosis

scholarly journals 356 Polypoid melanoma is associated with aggressive histopathological characteristics and poor clinical prognosis

2021 ◽  
Vol 141 (5) ◽  
pp. S62
Author(s):  
E. Pedersen ◽  
P. Harms ◽  
L. Zhao ◽  
A. Andea ◽  
M. Chan ◽  
...  
Keyword(s):  
Clinical Prognosis ◽  
Poor Clinical Prognosis

Downregulated SASH1 expression indicates poor clinical prognosis in gastric cancer

2018 ◽  
Vol 74 ◽  
pp. 83-91 ◽  
Author(s):  
Nan Zhou ◽  
Can Liu ◽  
Xudong Wang ◽  
Qinsheng Mao ◽  
Qin Jin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Prognosis ◽  
Poor Clinical Prognosis

scholarly journals Advances in Diagnostic Imaging of Hepatopulmonary Syndrome

2022 ◽  
Vol 8 ◽  
Author(s):  
Bi-Wei Luo ◽  
Zhi-Yong Du
Keyword(s):  
Liver Disease ◽  
Pulmonary Complication ◽  
Hepatopulmonary Syndrome ◽  
Pulmonary Angiography ◽  
Pulmonary Perfusion ◽  
Clinical Prognosis ◽  
Vascular Dilatation ◽  
Progressive Liver Disease ◽  
Poor Clinical Prognosis ◽  
Timely Treatment

Hepatopulmonary syndrome (HPS) is a serious pulmonary complication of progressive liver disease that leads to a poor clinical prognosis. Patients with HPS may develop acute respiratory failure, which requires intensive care and therapy. At present, the only effective treatment is liver transplantation; therefore, early diagnosis and timely treatment are of considerable significance. The three main features of HPS are liver disease, oxygenation disorder, and intrapulmonary vascular dilatation (IPVD). Diagnosing HPS is challenging due to the difficulty in detecting the presence or absence of IPVD. As such, imaging examination is very important for detecting IPVD. This paper reviews the imaging methods for diagnosing HPS such as ultrasound, dynamic pulmonary perfusion imaging, pulmonary angiography, and computed tomography.

scholarly journals CDDO-ME Activates NRF2 to Inhibit The Pro-Invasion Ability of TAMs

2020 ◽  
Author(s):  
Ying Li ◽  
Yaxu Jia ◽  
Yurong Xu
Keyword(s):  
Breast Cancer ◽  
Tumor Invasion ◽  
Tumor Model ◽  
Breast Cancer Patients ◽  
Clinical Prognosis ◽  
T Cell Infiltration ◽  
Promote Tumor Growth ◽  
Nrf2 Activation ◽  
Tumor Immune Microenvironment ◽  
Poor Clinical Prognosis

Abstract Background: Tumor-associated macrophages can account for more than 50% of the cells in the tumor immune microenvironment of breast cancer patients. A high TAM density is related to a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy since TAMs promote tumor growth, development and metastasis. Results: We found that CDDO-ME significantly inhibited the tumor invasion-promoting ability of TAMs in the coculture system and further showed that CDDO-ME functioned by reducing ROS production in TAMs. The orthotopic 4T1 cell inoculation model and spontaneous MMTV-PyMT tumor model were used to evaluate the antitumor effect of CDDO-ME. The results showed that CDDO-ME significantly inhibited tumor metastasis and increased T cell infiltration into the tumor microenvironment. Mechanistically, NRF2 activation was necessary for CDDO-ME to exert its function. Conclusions: Overall, CDDO-ME can play a role in breast cancer as an anticancer drug targeting TAMs.

scholarly journals Endogenous BTG2 expression stimulates migration of bladder cancer cells and correlates with poor clinical prognosis for bladder cancer patients

2013 ◽  
Vol 108 (4) ◽  
pp. 973-982 ◽  
Author(s):  
N Wagener ◽  
J Bulkescher ◽  
S Macher-Goeppinger ◽  
I Karapanagiotou-Schenkel ◽  
G Hatiboglu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Clinical Prognosis ◽  
Bladder Cancer Cells ◽  
Poor Clinical Prognosis

scholarly journals Canine mammary cancer

2020 ◽  
Vol 51 (4) ◽  
pp. 425-439
Author(s):  
Alejandro Clavijo-Maldonado ◽  
Enio Ferreira ◽  
Carlos Vargas-Hernández ◽  
Fredy A. Rivera-Páez
Keyword(s):  
Mammary Cancer ◽  
Cellular Proliferation ◽  
Mammary Tissue ◽  
Clinical Approach ◽  
Comparative Oncology ◽  
Clinical Prognosis ◽  
Canine Mammary Cancer ◽  
Clinical Relationship ◽  
Her 2 ◽  
Poor Clinical Prognosis

Canine mammary cancer (CMC) is one of the most common neoplasms in intact females in comparison to other species. Several risk factors have been identified, including breed, genetic predisposition, age, reproductive history, hormonal influence, diet, and body condition, in addition to previous lesions to the mammary gland, such as mammary atypical hyperplasia. An understanding of the genetic markers for the disease and a clinical approach are important for establishing a specific therapy that can allow adequate patient survivorship. Overexpression of the HER-2 gene in canines and humans is associated with a poor clinical prognosis, mainly short survivorship, although the clinical relationship is not clear. The incidence of HER-2 in female dogs can range from 29.7% to 38%. However, overexpression of HER-2 is not necessarily associated with malignancy processes of the mammary tissue, although it participates in cellular proliferation. Finally, canines remain one of the most important models for comparative oncology with humans due to the great similarity in the spontaneous presentation and development of cancer, and in the high homology in the amino acid sequence.

Sign in / Sign up

Export Citation Format

Share Document