scholarly journals Histone demethylase KDM4D inhibition suppresses renal cancer progression and angiogenesis through JAG1 signaling

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hao Yan ◽  
Liangsong Zhu ◽  
Jin Zhang ◽  
Zongming Lin
Keyword(s):  
Cancer Progression ◽  
Clear Cell ◽  
Tissue Microarrays ◽  
Histone Demethylase ◽  
Cell Renal Cell Carcinoma ◽  
Fuhrman Grade ◽  
Immunohistochemistry Analysis ◽  
Underlying Mechanisms ◽  
High Expression Level

AbstractKidney cancer, especially clear cell renal cell carcinoma (ccRCC), is one of the representative genitourinary tumors. Investigation of underlying mechanisms of ccRCC development is crucial for patient management. Histone demethylase KDM4D has been reported to be responsible for development of a variety of cancers. However, the role of KDM4D in ccRCC progression is poorly understood. In our study, we performed immunohistochemistry analysis of tissue microarrays first, and results showed that high expression level of KDM4D is connected with advanced Fuhrman grade (p = 0.0118) and lower overall survival (p = 0.0020). Then, we revealed that KDM4D can prompt ccRCC development by interacting with genes related to vessel morphogenesis. Finally, we disclosed that KDM4D directly interacts with JAG1 promoter and advances tumor angiogenesis by upregulating VEGFR-3 and antagonizing notch signaling. The results of our study indicate that KDM4D would be a potential prognostic marker and therapeutic target for ccRCC patients.

DDX39B Predicts Poor Survival and Associated with Clinical Benefit of Anti-PD-L1 Therapy in ccRCC

2021 ◽  
Vol 21 ◽  
Author(s):  
Jinhuan Wei ◽  
Jun Lu ◽  
Yun Cao ◽  
Gaosheng Yao ◽  
Yong Huang ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Clear Cell ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Therapy Response ◽  
Poor Survival ◽  
Cell Renal Cell Carcinoma ◽  
Fuhrman Grade

Background: Immune checkpoint inhibitors (ICI) have been shown to improve overall survival (OS) in clear cell renal cell carcinoma (ccRCC) patients. However, less than half of the ccRCC patients have objective response to ICI. Objective: We aim to assess the role of DDX39B in predicting ccRCC patients' OS and ICI therapy response. Methods: DDX39B was detected by immunohistochemistry in a tissue microarray of 305 ccRCC patients. DDX39B and its relationship with the prognosis of ccRCC were also evaluated in TCGA set and a RECA-EU set. The expression of DDX39B and patients survival was also analysed in two datasets of ccRCC patients treated with ICI. Results: Overexpression of DDX39B predicted poor OS of ccRCC patients in SYSU set, TCGA set, and a RECA-EU set. DDX39B expression was significantly positive with the expression of PD-L1 and other immunomodulators., DDX39B negatively correlated with cytotoxic T-lymphocyte and HDAC10 exon 3 inclusion in ccRCC. DDX39B knockdown decreased the expression of PD-L1 and increased the expression of HDAC10 exon 3 in renal cancer ACHN cells. Patients of ccRCC with lower levels of HDAC10 exon 3 inclusion have higher TNM stage, higher Fuhrman grade and poor OS. There was a tendency that patients with DDX39B high expression had longer OS and PFS than patients with DDX39B low expression in ccRCC patients treated with ICI. Conclusion: DDX39B gene is highly expressed in ccRCC and is closely related to patients’ OS. DDX39B might increase PD-L1 expression via the enhancement of HDAC10 exon 3 skipping, thereby promoting the ICI therapy response.

scholarly journals Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jazmine Arévalo ◽  
David Lorente ◽  
Enrique Trilla ◽  
María Teresa Salcedo ◽  
Juan Morote ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Independent Manner ◽  
Fuhrman Grade ◽  
Transcription 3 ◽  
Aggressive Subtype

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

scholarly journals Pancreatic ductal adenocarcinoma concomitant with pancreatic metastases of clear-cell renal cell carcinoma: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Lena Haeberle ◽  
Melanie Busch ◽  
Julian Kirchner ◽  
Georg Fluegen ◽  
Gerald Antoch ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Ductal Adenocarcinoma ◽  
Special Role ◽  
Cell Renal Cell Carcinoma ◽  
Pancreatic Metastases

Abstract Background Metastatic spread to the pancreas is a rare event. Renal cell carcinoma represents one possible site of origin of pancreatic metastases. Renal cell carcinoma often metastasizes late and exclusively to the pancreas, suggesting a special role of renal cell carcinoma among primaries metastasizing to the pancreas. Even rarer, renal cell carcinoma may occur simultaneously with pancreatic ductal adenocarcinoma. Case presentation We present the case of a 78-year-old male Caucasian patient with a history of clear-cell renal cell carcinoma treated with oncological left nephrectomy 20 years before. The patient was diagnosed with pancreatic ductal adenocarcinoma by fine-needle aspiration cytology. At our institution, he received neoadjuvant therapy with folic acid, fluorouracil, irinotecan, oxaliplatin for borderline-resectable pancreatic ductal adenocarcinoma, and subsequently underwent total pancreatectomy. Upon resection, pancreatic ductal adenocarcinoma as well as two metachronous metastases of clear-cell renal cell carcinoma occurring simultaneously and cospatially with pancreatic ductal adenocarcinoma were diagnosed in the pancreatic body. Conclusions Renal cell carcinoma metastases of the pancreas are rare and often occur decades after the initial diagnosis of renal cell carcinoma. The combination of renal cell carcinoma metastases and pancreatic ductal adenocarcinoma is even rarer. However, the possibility should be considered by clinicians, radiologists, and pathologists. The special role of renal cell carcinoma as a site of origin of pancreatic metastasis should be further elucidated.

CD151 expression can predict cancer progression in clear cell renal cell carcinoma

2011 ◽  
Vol 58 (2) ◽  
pp. 191-197 ◽  
Author(s):  
Seong H Yoo ◽  
Kyoungbun Lee ◽  
Ji Y Chae ◽  
Kyung C Moon
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically

2016 ◽  
Vol 35 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Antoni Vilaseca ◽  
Daniel P. Nguyen ◽  
Emily A. Vertosick ◽  
Renato B. Corradi ◽  
Mireia Musquera ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Fuhrman Grade ◽  
Obstructive Sleep

scholarly journals The Oncogenic Role of COL23A1 in Clear Cell Renal Cell Carcinoma

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Fujiang Xu ◽  
Kun Chang ◽  
Jian Ma ◽  
Yuanyuan Qu ◽  
Huyang Xie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Hypoxia-inducible factor (HIF): fuel for cancer progression

2021 ◽  
Vol 14 ◽  
Author(s):  
Saurabh Satija ◽  
Harpreet Kaur ◽  
Murtaza M. Tambuwala ◽  
Prabal Sharma ◽  
Manish Vyas ◽  
...  
Keyword(s):  
Biological Sciences ◽  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Oxygen Deficiency ◽  
Hypoxia Inducible Factor ◽  
Transcription Factor Activation ◽  
Underlying Mechanisms ◽  
Adaptive Reactions

Hypoxia is an integral part of tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mchanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.

scholarly journals An Evidence for a Novel Antiviral Mechanism of Teleost Fish: Serum-Derived Exosomes Inhibit Virus Replication Through Incorporating Mx1 Protein

2021 ◽  
Author(s):  
Changjun Guo ◽  
Jian He ◽  
Zhi-Min Li ◽  
Yuanyuan Wang ◽  
Chen nan nan ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Teleost Fish ◽  
Protein Composition ◽  
Underlying Mechanism ◽  
Antiviral Effect ◽  
Mandarin Fish ◽  
Underlying Mechanisms ◽  
Antiviral Mechanism ◽  
Fish Serum

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system–related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate antiviral effect for the exosomes of teleost fish. Exosomes were isolated from mandarin fish serum by ultracentrifugation could internalize into Mandarin fish fry (MFF-1) cells and inhibited Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigated the underlying mechanisms of exosomes in inhibiting ISKNV infection. The protein composition of serum-derived exosomes was by analysis mass spectrometry and found that myxovirus resistance 1 (Mx1) was incorporated in the exosomes. Furthermore, the scMx1 protein was proved transferred to the recipient cells though the exosomes. Our results found that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication and suggested an underlying mechanism of the serum-derived exosomes antivirus is that serum-derived exosomes incorporation of the Mx1 protein into exosomes and delivery into recipient cells. This study provided an evidence for the important antiviral role of exosomes in the immune system of teleost fish.

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