scholarly journals Effects of decreased Rac activity and malignant state on oral squamous cell carcinoma

2019 ◽  
Author(s):  
Hani Al-Shareef ◽  
Yudai Matsuoka ◽  
Mikihiko Kogo ◽  
Hirokazu Nakahara

AbstractRac proteins, members of the Rho family of small GTP-binding proteins, have been implicated in transducing a number of signals for various biological mechanisms, including cell cytoskeleton organization, transcription, proliferation, migration, and cancer cell motility. Among human cancers, Rac proteins are highly activated by either overexpression of the genes, up-regulation of the protein, or by mutations that allow the protein to elude normal regulatory signaling pathways. Rac proteins are involved in controlling cell survival and apoptosis. The effects of Rac inhibition by the Rac-specific small molecule inhibitor NSC23766 or by transfection of dominant negative Rac (Rac-DN) were examined on three human-derived oral squamous cell carcinoma cell lines that exhibit different malignancy grades, OSC-20 (grade 3), OSC-19 (grade 4C), and HOC313 (grade 4D). Upon suppression of Rac, OSC-19 and HOC313 cells showed significant decreases in Rac activity and resulted in condensation of the nuclei and up- regulation of c-Jun N-terminal kinase (JNK), leading to caspase-dependent apoptosis. In contrast, OSC-20 cells showed only a slight decrease in Rac activity, which resulted in slight activation of JNK and no change in the nuclei. Fibroblasts treated with NSC23766 also showed only a slight decrease in Rac activity with no change in the nuclei or JNK activity. Our results indicated that apoptosis elicited by the inhibition of Rac depended on the extent of decreased Rac activity and the malignant state of the squamous cell carcinoma. In addition, activation of JNK strongly correlated with apoptosis. Rac inhibition may represent a novel therapeutic approach for cancer treatment.

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0212323
Author(s):  
Yudai Matsuoka ◽  
Hani Al-Shareef ◽  
Mikihiko Kogo ◽  
Hirokazu Nakahara

Rac proteins, members of the Rho family of small GTP-binding proteins, have been implicated in transducing a number of signals for various biological mechanisms, including cell cytoskeleton organization, transcription, proliferation, migration, and cancer cell motility. Among human cancers, Rac proteins are highly activated by either overexpression of the genes, up-regulation of the protein, or by mutations that allow the protein to elude normal regulatory signaling pathways. Rac proteins are involved in controlling cell survival and apoptosis. The effects of Rac inhibition by the Rac-specific small molecule inhibitor NSC23766 or by transfection of dominant negative Rac (Rac-DN) were examined on three human-derived oral squamous cell carcinoma cell lines that exhibit different malignancy grades, OSC-20 (grade 3), OSC-19 (grade 4C), and HOC313 (grade 4D). Upon suppression of Rac, OSC-19 and HOC313 cells showed significant decreases in Rac activity and resulted in condensation of the nuclei and up-regulation of c-Jun N-terminal kinase (JNK), leading to caspase-dependent apoptosis. In contrast, OSC-20 cells showed only a slight decrease in Rac activity, which resulted in slight activation of JNK and no change in the nuclei. Fibroblasts treated with NSC23766 also showed only a slight decrease in Rac activity with no change in the nuclei or JNK activity. Our results indicated that apoptosis elicited by the inhibition of Rac depended on the extent of decreased Rac activity and the malignant state of the squamous cell carcinoma. In addition, activation of JNK strongly correlated with apoptosis. Rac inhibition may represent a novel therapeutic approach for cancer treatment.


2019 ◽  
Vol 40 (1) ◽  
pp. 37-49 ◽  
Author(s):  
Seitaro NAKAZAWA ◽  
Ken-ichiro SAKATA ◽  
Shanshan LIANG ◽  
Kazuhito YOSHIKAWA ◽  
Hisashi IIZASA ◽  
...  

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Yetao Wang ◽  
Suying Qian ◽  
Kesang Li

Targeted immune checkpoint-based immunotherapy has achieved remarkable success in the treatment of malignant tumors. Immune checkpoint inhibitor-programmed cell death protein 1 (PD-1) antibody opens a new era of immunotherapy for platinum-refractory recurrent/metastatic oral squamous cell carcinoma (OSCC). The overall survival of patients treated with immunological checkpoint inhibitors was significantly prolonged, and the overall incidence of grade 3-4 drug-related adverse events (AEs) occurred was lower. This article briefly describes the development of PD-1 inhibitors in the treatment of OSCC. The purpose of this review is to briefly highlight the clinical development of PD-1 inhibitors in OSCC therapy to date.


2016 ◽  
Vol 36 (4) ◽  
pp. 1989-1996 ◽  
Author(s):  
Limei Wang ◽  
Xiuyin Wu ◽  
Ping Huang ◽  
Zhijun Lv ◽  
Yuping Qi ◽  
...  

2012 ◽  
Vol 13 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Maryam Amirchaghmaghi ◽  
Nooshin Mohtasham ◽  
Pegah Mosannen Mozaffari

ABSTRACT Aim To compare cyclooxygenase 2 expression (COX2-E) between normal, oral leukoplakia lesions and different grades of oral squamous cell carcinoma (SCC). Materials and methods Around 90 paraffin embedded blocks consisting of 45 SCC, 15 leukoplakia and 17 controls were selected for immunohistochemistry (IHC) for detection of COX2- E. COX2-E was divided in four grades, as A (0-10%), B (11-40%), C (41-70%) and D (> 70%) cellularity. Results Mean age of the patients was 55.17 ± 18.41 (M:57.92 ± 16.87, F:52.19 ± 19.74). A significant difference was found in COX2 expression between SCC total and, basal and spinous layers of leukoplakia (p < 0.05). COX2-E in spinous layer of normal tissue was significantly lower than SCC (p = 0.000). COX2-E was significantly different in SCC grade 3 and leukoplakia (p = 0.001) and normal tissue (p = 0.000). COX2-E was significantly higher in SCC grade 3 compared to leukoplakia (basal layer) (p = 0.000). Conclusion We showed a significant higher COX2-E in SCC lesions compared to leukoplakias and normal controls. In our study COX2-E was not significantly different in SCC grades 1, 2 and 3 (p > 0.05). How to cite this article Amirchaghmaghi M, Mohtasham N, Mozaffari PM. Comparison of COX2 Expression between Oral Squamous Cell Carcinoma, Leukoplakia and Normal Mucosa. J Contemp Dent Pract 2012;13(2):205-209.


2013 ◽  
Vol 1 (2) ◽  
pp. 02-06
Author(s):  
SM Anwar Sadat ◽  
Sufia Nasrin Rita ◽  
Shoma Banik ◽  
Md Nazmul Hasan Khandker ◽  
Md Mahfuz Hossain ◽  
...  

A cross sectional study of 29 cases of oral squamous cell carcinoma with or without  cervical lymph node metastasis was done among Bangladeshi patients from January 2006 to December 2007. Majority of the study subjects (34.5%) belonged to the age group of 40-49 years. 58.6% of the study subjects were male, while remaining 41.4% of them were female. 51.7% of the lesions were located in the alveolar ridge where the other common sites were buccal mucosa (27.6%) and retro molar area (13.8%). Half of the study subjects (51.7%) were habituated to betel quid chewing followed by 37.9% and 10.3% were habituated to smoking and betel quid-smoking respectively. Grade I lesions was most prevalent (75.9%) in the study subjects.  Majority of cases presented with Stage IV lesions (55.2%). The sensitivity, specificity, positive predictive value, negative predictive value & accuracy of clinical palpation method for determining metastatic cervical lymph nodes were 93.33%, 64.29%, 73.68%, 90% and 79.3% respectively. Careful and repeated clinical palpation plays important role in evaluation of cervical lymph nodes though several modern techniques may help additionally in the management of oral cancer.DOI: http://dx.doi.org/10.3329/updcj.v1i2.13978 Update Dent. Coll. j. 2011: 1(2): 02-06


2011 ◽  
Vol 3 (6) ◽  
pp. 419-422
Author(s):  
Dr. Shool Rohit S Dr. Shool Rohit S ◽  
◽  
Dr. Anand P Zingade ◽  
Dr. Manish Kumar

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