scholarly journals Correlation among 16 biological factors [p53, p21waf1, MIB-1 (Ki-67), p16INK4A, cyclin D1, E-cadherin, Bcl-2, TNF-α, NF-κB, TGF-β, MMP-7, COX-2, EGFR, HER2/neu, ER, and HIF-1α] and clinical outcomes following curative chemoradiation therapy in 10 patients with esophageal squamous cell carcinoma

2013 ◽  
Vol 5 (3) ◽  
pp. 903-910 ◽  
Author(s):  
SHINO SHIBATA-KOBAYASHI ◽  
HIDEOMI YAMASHITA ◽  
KAE OKUMA ◽  
KENSHIRO SHIRAISHI ◽  
HIROSHI IGAKI ◽  
...  
2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17522-e17522
Author(s):  
Elizabeth Mathew Iype ◽  
Lakshmi S ◽  
Rajan Balakrishnan

e17522 Background: Laryngeal Squamous cell carcinoma is widely prevalent in India and is the fourth leading cancer in males. The possibility that specific tumour characteristics (demonstrable by immunohistochemistry) may aid the clinician in choosing optimal treatments for a specific tumour, holds great promise. Objectives of the present study were to study the expression of select molecular markers p53, Bcl-2 (Apoptotic markers), EGFR, Ki67, Cyclin D1 (Proliferation markers) and Cox-2 (Inflammatory marker) in LSCC so as to form a hypothesis that a particular group of markers will be useful in determining the prognosis of LSCC. Methods: We studied 72 cases of laryngeal squamous cell carcinoma in an attempt to determine relationship between their clinicopathological characteristics and treatment outcome with the six molecular markers. Samples from patients who underwent laryngectomy from Jan 2006 to Dec 2010 were taken and analyzed prospectively and followed up till Dec 2015 or till death. . Immunoreactivity in tissue sections was evaluated as negative when no positive cells were observed within the tumor, weak (1+) , moderate (2+) , and strong or intense (3+) . Data were analyzed using SPSS software package. Chi squared test or exact test were used to test the associations. Logistic regression analysis was used to estimate the odds ratios and 95% confidence intervals. The disease free survival time of each patient was calculated by taking the difference between the date of surgery and the recurrence date/ death date/ the last follow up date whichever is applicable. Results: Proliferation markers EGFR, Cyclin D1 and Ki 67, individually and collectively were predictive of extracapsular spread and perineural spread of tumour. Node negative patients having intense expression of Cyclin D1 or Ki 67 has bad prognosis.. The significant expression of Cox-2 was highly predictive of Node positivity. In older patients and in T4 stage the presence of P53 / Bcl-2 resulted in worse overall survival. Markers of aggressiveness were identified as p53, Bcl-2 Cox-2. Markers of invasiveness were EGFR, Cyclin D1 and Ki 67. Markers predicting survival were p53, BCl-2, Cyclin D1 and Ki 67. Conclusions: If Proliferation markers are detected preoperatively in biopsy specimens, has important implications in planning aggressive management Cyclin D1 or Ki 67 in Node negative patients indicate need for a neck dissection or irradiation. Cox-2 assessment will be useful in predicting the occult nodal metastasis for prophylactic treatment


2021 ◽  
Vol 22 (4) ◽  
pp. 1716
Author(s):  
Anita Hryniewicz-Jankowska ◽  
Jaroslaw Wierzbicki ◽  
Renata Tabola ◽  
Kamilla Stach ◽  
Khalid Sossey-Alaoui ◽  
...  

Inhibition of the protein neddylation process by the small-molecule inhibitor MLN4924 has been recently indicated as a promising direction for cancer treatment. However, the knowledge of all biological consequences of MLN4924 for cancer cells is still incomplete. Here, we report that MLN4924 inhibits tumor necrosis factor-alpha (TNF-α)-induced matrix metalloproteinase 9 (MMP9)-driven cell migration. Using real-time polymerase chain reaction (PCR) and gelatin zymography, we found that MLN4924 inhibited expression and activity of MMP9 at the messenger RNA (mRNA) and protein levels in both resting cells and cells stimulated with TNF-α, and this inhibition was closely related to impaired cell migration. We also revealed that MLN4924, similar to TNF-α, induced phosphorylation of inhibitor of nuclear factor kappa B-alpha (IκB-α). However, contrary to TNF-α, MLN4924 did not induce IκB-α degradation in treated cells. In coimmunoprecipitation experiments, nuclear IκB-α which formed complexes with nuclear factor kappa B p65 subunit (NFκB/p65) was found to be highly phosphorylated at Ser32 in the cells treated with MLN4924, but not in the cells treated with TNF-α alone. Moreover, in the presence of MLN4924, nuclear NFκB/p65 complexes were found to be enriched in c-Jun and cyclin dependent kinase inhibitor 1 A (CDKN1A/p21) proteins. In these cells, NFκB/p65 was unable to bind to the MMP9 gene promoter, which was confirmed by the chromatin immunoprecipitation (ChIP) assay. Taken together, our findings identified MLN4924 as a suppressor of TNF-α-induced MMP9-driven cell migration in esophageal squamous cell carcinoma (ESCC), likely acting by affecting the nuclear ubiquitin–proteasome system that governs NFκB/p65 complex formation and its DNA binding activity in regard to the MMP9 promoter, suggesting that inhibition of neddylation might be a new therapeutic strategy to prevent invasion/metastasis in ESCC patients.


Oral Oncology ◽  
2002 ◽  
Vol 38 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Juan Carlos de Vicente ◽  
Agustı́n Herrero-Zapatero ◽  
Manuel Florentino Fresno ◽  
Juan Sebastián López-Arranz

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