The Expression of Glutaminases and their Association with Clinicopathological Parameters in the Head and Neck Cancers

2021 ◽  
Vol 22 ◽  
Author(s):  
Haneen A . Basheer ◽  
Lina Elsalem ◽  
Anwar Salem ◽  
Artysha Tailor ◽  
Keith Hunter ◽  
...  

Background: The increased glutamine metabolism is a characteristic feature of cancer cells. The interconversion between glutamine and glutamate is catalyzed by two glutaminase isoforms, GLS1 and GLS2, which appear to have different roles in different types of cancer. We investigated for the first time the protein expression of GLS1 and GLS2, and their correlation with advanced clinicopathological parameters in head and neck cancers. Method: Consecutive slides from a tissue microarray comprised of 80 samples ranging from normal to metastatic, were stained immunohistochemically for GLS1, GLS2, HIF-1α or CD147. Following analysis by two expert pathologists we carried out statistical analysis of the scores. Results: GLS1 and GLS2 are upregulated at protein level in head and neck tumours compared to normal tissues and this increased expression correlated positively (GLS1) and negatively (GLS2) with tumor grade, indicating a shift of expression between GLS enzyme isoforms based on tumor differentiation. Increased expression of GLS1 was associated with high CD147 expression; and elevated GLS2 expression was associated with both high CD147 and high HIF-1α expressions. The correlation of the GLS1 and GLS2 with HIF-1α or CD147 was strongly associated with more advanced clinicopathological parameters. Conclusion: The increased expression of GLS1 and GLS2 may be explored as a new treatment for head and neck cancers.

2020 ◽  
Vol 27 (3) ◽  
pp. 393-398
Author(s):  
Nooshin Mohammadzadeh ◽  
Fatemeh Mosaffa ◽  
Ehsan Khadivi ◽  
Rosa Jahangiri ◽  
Khadijeh Jamialahmadi

Background: DNA methyltransferase (DNMT) enzymes, encoded by DNMT1, DNMT3A andDNMT3B genes, play a major role in the development of cancers through aberrant promotermethylation. Due to little information about the biological and clinical significance of expressionchanges of these genes in Laryngeal Squamous Cell carcinoma (LSCC), the current study wasdesigned to evaluate the contribution of DNMTs expression as potential diagnostic biomarkersin progression of LSCC. Methods: DNMT1, DNMT3A and DNMT3B expressions in tumoral and normal tissues fromthirty-three LSCC patients were evaluated by relative comparative real-time PCR, prior toany therapeutic intervention. Relationship between genes expression and clinicopathologicalfeatures were also analyzed. Results: The mRNA expression levels of all three DNMTs (DNMT1, DNMT3A and DNMT3B)were significantly elevated in LSCC tumor specimens compared to that of non-tumor tissues(P<0.0001, P=0.011 and P<0.0001, respectively). The expression of DNMT1 and DNMT3Bwas strongly associated with histopathological tumor grade. Moreover, the mRNA expressionlevels of DNMT3A were significantly correlated with laryngopharyngeal reflux. No significantrelationships existed with other clinicopathological parameters. Conclusion: Data showed that the expression levels of DNMT1, DNMT3A and DNMT3Bmarkedly increased in LSCC tissues. DNMT1 and DNMT3B were mainly overexpressed in highgrade LSCC tumors, therefore, they may have a role in LSCC progression. It seems that thesegenes may serve as diagnostic biomarkers in development of LSCC.


Author(s):  
Kevin J. Harrington

AbstractDespite significant technical improvements in the management of patients with locoregionally-advanced head and neck cancers, too many patients fail to achieve durable remissions that ultimately translate into cures. Loco-regional recurrence and/or metastatic relapse after intensive local therapies remain the scourge of those who suffer from this disease, and the surgeons and physicians who treat them. Regrettably, until now, we have failed to develop effective adjuvant therapies that can be delivered after the completion of definitive loco-regional treatment in order to reduce the risk of disease relapse. In this chapter, approaches based on cytotoxic chemotherapy, targeted therapies directed against c-erbB/HER receptors and immune checkpoint inhibition will be discussed. Neither cytotoxic chemotherapy nor anti-HER-family targeted therapies have proven to be successful as adjuvant therapies for locoregionally-advanced head and neck cancers, but there is significant hope that anti-PD1/anti-PD-L1-targeted antibody therapies may deliver progress in this area for the first time.


2017 ◽  
Vol 16 (4) ◽  
pp. 56-61
Author(s):  
N.S. Grachev ◽  
◽  
I.N. Vorozhtsov ◽  
N.V. Babaskina ◽  
E.Yu. Iaremenko ◽  
...  

2016 ◽  
Vol 67 (2) ◽  
pp. 128-128
Author(s):  
Y. Miyagawa ◽  
T. Yamashita ◽  
S. Tanaka ◽  
Y. Tanaka ◽  
M. Tomifuji ◽  
...  

Nanomedicine ◽  
2020 ◽  
Vol 15 (29) ◽  
pp. 2837-2850
Author(s):  
Myxuan Huynh ◽  
Ivan Kempson ◽  
Eva Bezak ◽  
Wendy Phillips

Background: The use of gold nanoparticles (AuNPs) as radiosensitizers may offer a new approach in the treatment of head and neck cancers; minimizing treatment-associated toxicities and improving patient outcomes. AuNPs promote localized dose deposition; permitting improved local control and/or dose reduction. Aim: This work aimed to address the theoretical optimization of radiation doses, fractionation and nanoparticle injection schedules to maximize therapeutic benefits. Materials & methods: Probabilistic nanoparticle sensitization factors were incorporated into the individual cell-based HYP-RT computer model of tumor growth and radiotherapy. Results: Total dose outcomes across all radiation therapy treatment regimens were found to be significantly reduced with the presence of AuNPs, with bi-weekly injections showing the most decrease. Conclusion: Outcomes suggest the need for regular AuNP administration to permit effective radiosensitization.


Sign in / Sign up

Export Citation Format

Share Document