scholarly journals Reduced expression of ΔΝp63α in cervical squamous cell carcinoma

2011 ◽  
Vol 34 (3) ◽  
pp. 184 ◽  
Author(s):  
Ying Zhou ◽  
Qianqian Xu ◽  
Bin Ling ◽  
Weihua Xiao ◽  
Peishu Liu

Purpose: As a member of the p53 family, p63 is considered to be an important differentiation regulation transcriptional factor, but the roles of p63 in many epithelial tumourigenesis and metastasis processes are still not clear. This study was designed to investigate the expression of p63 and its isoform in normal tissues and squamous cell cancer tissues of uterine cervix, and its significance in cancer cell differentiation. Methods: The expression of p63 was assessed in cervical tissue and cell lines by immunohistochemistry, RT-PCR and Western Blotting. The relationships between p63 protein, various clinico-pathological features, and the differentiation marker involucrin were analyzed. Results: ΔΝp63α is the predominant isoform expressed in cervical epithelial tissues, and it is decreased in moderately or poorly differentiated cervical squamous carcinoma, as well as in the HeLa, SiHa and C33A cervical cancer cell lines. The expression level of ΔΝp63α was positively correlated with that of involucrin in cervical squamous cancer tissue, and the expression of ΔΝp63α is decreased with the degree of tumour invasion. Conclusion: The decrease of ΔΝp63α in cervical squamous cell cancer appears to be associated with the tumour progression, and ΔΝp63α may be a sensitive marker for cervical squamous cancer differentiation.

Oncotarget ◽  
2017 ◽  
Vol 8 (49) ◽  
pp. 86369-86383 ◽  
Author(s):  
Nene N. Kalu ◽  
Tuhina Mazumdar ◽  
Shaohua Peng ◽  
Li Shen ◽  
Vaishnavi Sambandam ◽  
...  

1997 ◽  
Vol 117 (sup529) ◽  
pp. 241-244 ◽  
Author(s):  
H. A. Jääskelä-Saari ◽  
K. J. A. Kairemo ◽  
H. A. Ramsay ◽  
R. Grénman

2016 ◽  
Vol 9 (2) ◽  
pp. 373-378 ◽  
Author(s):  
K.S. Schwab ◽  
A. Heine ◽  
T. Weimann ◽  
G. Kristiansen ◽  
P. Brossart

Management of patients with metastatic squamous cell skin cancer, refractory to initial therapy with standard chemotherapy and radiation protocols, remains difficult with poor overall prognosis and limited therapeutic options. Recently, promising response rates with nivolumab, a programmed death receptor-1-blocking antibody, in squamous cancer of the head and neck have been demonstrated. Considering the similar histological patterns of squamous cell cancer of the skin and squamous cell cancer of the head and neck, we assumed that nivolumab could also be effective in our patients with refractory metastatic squamous cell cancer of the skin. So far, there have been no clinical data on the therapeutic efficacy of nivolumab in squamous cell skin cancer. We here present a case of a patient with metastatic squamous cell skin cancer refractory to previous therapies, who showed a good response to nivolumab over a period of 5 months, but developed a serious hemolytic crisis under nivolumab treatment after eight applications.


2021 ◽  
Vol 11 ◽  
Author(s):  
Bashir Lawal ◽  
Ching-Yu Lee ◽  
Ntlotlang Mokgautsi ◽  
Maryam Rachmawati Sumitra ◽  
Harshita Khedkar ◽  
...  

BackgroundThe application of computational and multi-omics approaches has aided our understanding of carcinogenesis and the development of therapeutic strategies. NSC765598 is a novel small molecule derivative of salicylanilide. This study aims to investigate the ligand-protein interactions of NSC765598 with its potential targets and to evaluate its anticancer activities in vitro.MethodsWe used multi-computational tools and clinical databases, respectively, to identify the potential drug target for NSC765598 and analyze the genetic profile and prognostic relevance of the targets in multiple cancers. We evaluated the in vitro anticancer activities against the National Cancer Institute 60 (NCI60) human tumor cell lines and used molecular docking to study the ligand-protein interactions. Finally, we used the DTP-COMPARE algorithm to compare the NSC765598 anticancer fingerprints with NCI standard agents.ResultsWe identified mammalian target of rapamycin (mTOR)/epidermal growth factor receptor (EGFR)/inducible nitric oxide synthase (iNOS)/mitogen-activated protein 2 kinase 1 (MAP2K1)/fibroblast growth factor receptor (FGFR)/transforming growth factor-β1 (TGFB1) as potential targets for NSC765598. The targets were enriched in cancer-associated pathways, were overexpressed and were of prognostic relevance in multiple cancers. Among the identified targets, genetic alterations occurred most frequently in EGFR (7%), particularly in glioblastoma, esophageal squamous cell cancer, head and neck squamous cell cancer, and non–small-cell lung cancer, and were associated with poor prognoses and survival of patients, while other targets were less frequently altered. NSC765598 displayed selective antiproliferative and cytotoxic preferences for NSCLC (50% growth inhibition (GI50) = 1.12–3.95 µM; total growth inhibition (TGI) = 3.72–16.60 μM), leukemia (GI50 = 1.20–3.10 µM; TGI = 3.90–12.70 μM), melanoma (GI50 = 1.45–3.59 µM), and renal cancer (GI50 = 1.38–3.40 µM; TGI = 4.84–13.70 μM) cell lines, while panels of colon, breast, ovarian, prostate, and central nervous system (CNS) cancer cell lines were less sensitive to NSC765598. Interestingly, NSC765598 docked well into the binding cavity of the targets by conventional H-bonds, van der Waal forces, and a variety of π-interactions, with higher preferences for EGFR (ΔG = −11.0 kcal/mol), NOS2 (ΔG = −11.0 kcal/mol), and mTOR (ΔG = −8.8 kcal/mol). NSC765598 shares similar anti-cancer fingerprints with NCI standard agents displayed acceptable physicochemical values and met the criteria of drug-likeness.ConclusionNSC765598 displayed significant anticancer and potential multi-target properties, thus serve as a novel candidate worthy of further preclinical studies.


Sign in / Sign up

Export Citation Format

Share Document