scholarly journals Analysis of the anticancer effect of endostatin on oral squamous cell carcinoma based on results of experimental studies

Author(s):  
Г.М. Тугузбаева ◽  
В.Н. Павлов ◽  
Д.А. Еникеев

При плоскоклеточном раке полости рта основной причиной летальных исходов является метастазирование в регионарные лимфатические узлы. Злокачественный рост и формирование метастазов напрямую зависят от степени кровоснабжения первичного очага новообразования. Известно, что по мере прогрессирования опухолевый процесс сопровождается нарушением сбалансированной в норме системы регуляции ангиогенеза с превалированием уровня ангиогенных стимуляторов над ингибиторами. В связи с этим, использование антиангиогенных средств является патофизиологически обоснованным методом борьбы со злокачественным ростом. В обзоре обсуждаются данные доклинических исследований участия эндостатина, природного ингибитора ангиогенеза, в процессах подавления прогрессии и метастазирования плоскоклеточного рака челюстно-лицевой области. Проанализированы патогенетические механизмы ингибирования эндостатином опухолевого роста в экспериментальных моделях рака полости рта. Эндостатин можно рассматривать в качестве потенциального противоопухолевого средства для лечения данной нозологии. The main reason for cancer-associated mortality in patients with oral squamous cell carcinoma is metastatic spread to regional lymph nodes. It is known that the processes of malignant growth and metastasis are highly dependent on blood supply to the primary cancerous focus. The development of malignancy is accompanied by failure of the normally well-balanced system of angiogenesis regulation with prevalence of proangiogenic factors over inhibitors. Therefore, the use of angiogenic inhibitors is a pathophysiologically justified method aimed at suppression of cancer progression. This review presents reports of experimental studies on the role of endostatin, a natural inhibitor of angiogenesis, in processes of tumour shrinkage in squamous cell carcinoma of the maxillofacial region. The authors analysed pathogenic mechanisms of the anticancer effects exhibited by endostatin in preclinical models of oral malignancy. Endostatin can be regarded as a potential antitumor agent for the treatment of oral squamous cell carcinoma.

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling Mao ◽  
Xiaoweng Wu ◽  
Zhengpeng Gong ◽  
Ming Yu ◽  
Zhi Huang

Abstract Background/objective Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC). Methods The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively. Results A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells. Conclusion This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.


Life ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 336
Author(s):  
Lovorka Batelja-Vuletic ◽  
Cedna Tomasovic-Loncaric ◽  
Marcello Ceppi ◽  
Marco Bruzzone ◽  
Aleksandra Fucic ◽  
...  

Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral malignancy with low survival as it is very often diagnosed at an advanced stage, which is why the accurate profiling of the tumor is essential. The aim of this study was to, for the first time, compare in OSCC the frequency of AR, VEGF, MMP9, HiF1beta and Ki67 between the non-metastatic and metastatic disease. Materials and Methods: In the study, 96 non-metastatic and 91 metastatic OSCC patients were analysed for AR, VEGF, MMP9, HiF1beta and Ki67 levels by immunohistochemistry. Results: All of the tested biomarkers significantly differed between non-metastatic and metastatic disease. A significant association was found between >/=20% AR positive epithelium cells in cytoplasm, Ki67 and VEGF in cancer stroma. Ki67, HiF1beta, VEGF and MMP9 were significantly associated with TNM stages. Conclusion: Our results show for the first time an interplay between AR, VEGF, MMP9, HiF1beta and Ki67 in OSCC which may contribute to better diagnostics and therapy selection.


2021 ◽  
Vol 22 (20) ◽  
pp. 11108
Author(s):  
Sarah Adriana Scuderi ◽  
Giovanna Casili ◽  
Rossella Basilotta ◽  
Marika Lanza ◽  
Alessia Filippone ◽  
...  

Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.


Author(s):  
Nabanita Barma ◽  
Gopinath Barui ◽  
Anadi Roy Chowdhury

Introduction: Stathmin, one of the most important intracellular phosphoprotein that plays the vital role in the regulation of cell cycle and cell proliferation. It acts by disassembly of Microtubules (MT) that helps in the formation of mitotic spindle. It is overexpressed in various human cancers. Aim: To investigate the expression status of stathmin and its relation with clinicopathologic significance in Oral Squamous Cell Carcinoma (OSCC) and its association with age, sex, tobacco chewing, histomorphological features and pathological staging. Materials and Methods: A descriptive and observational study in cross-sectional design was conducted in a tertiary care centre of Kolkata, West Bengal, India, from January 2020 to March 2020 in the Department of Pathology of RG Kar Medical College and Hospital in collaboration with Department of Oto-Rhino-Laryngology of the same institute. Stathmin expression was assessed by immunohistochemistry (IHC) in 28 OSCC cases. The association between stathmin expression and clinicopathological parameters like age, sex, tobacco chewing, tumour site, histomorphological type, Tumor Nodes Metastases (TNM) stage and Worst Pattern Of Invasion (WPOI) were evaluated on the basis of Chi-square test and Fisher’s-exact test (software Statistical Package for the Social Sciences (SPSS) V 25.0). Results: Stathmin was overexpressed in 18 cases out of 28 cases of OSCC. In this study a positive association was observed between stathmin expression and age group, history of tobacco chewing, advanced T stage, advanced pTNM staging and WPOI of OSCC. Conclusion: The study suggests that overexpression of stathmin could contribute to cancer progression. There is a higher likelihood that stathmin may be used as a potential biomarker as well as therapeutic target for OSCC.


2019 ◽  
Vol 20 (22) ◽  
pp. 5779 ◽  
Author(s):  
Kiyofumi Takabatake ◽  
Tsuyoshi Shimo ◽  
Jun Murakami ◽  
Chang Anqi ◽  
Hotaka Kawai ◽  
...  

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of SHH expression appear to correlate with cancer progression. However, the role of SHH in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is still unclear. No studies have compared the expression of SHH in different subtypes of OSCC and focused on the relationship between the tumor parenchyma and stroma. In this study, we analyzed SHH and expression of its receptor, Patched-1 (PTCH), in the TME of different subtypes of OSCC. Fifteen endophytic-type cases (ED type) and 15 exophytic-type cases (EX type) of OSCC were used. H&E staining, immunohistochemistry (IHC), double IHC, and double-fluorescent IHC were performed on these samples. ED-type parenchyma more strongly expressed both SHH and PTCH than EX-type parenchyma. In OSCC stroma, CD31-positive cancer blood vessels, CD68- and CD11b-positive macrophages, and α-smooth muscle actin-positive cancer-associated fibroblasts partially expressed PTCH. On the other hand, in EX-type stroma, almost no double-positive cells were observed. These results suggest that autocrine effects of SHH induce cancer invasion, and paracrine effects of SHH govern parenchyma-stromal interactions of OSCC. The role of the SHH pathway is to promote growth and invasion.


MicroRNA ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Soheila Manifar ◽  
Maryam Koopaie ◽  
Shahab Shokouhi Lahiji

Background: Squamous Cell Carcinoma (SCC) includes more than 90% of malignancies of the oral cavity. Early diagnosis could effectively improve patients' quality of life and treatment outcomes of oral cancers. MicroRNAs as non-encoding genes have great potential to initiate or suppress cancer progression. Recent studies have shown that disruption of micro-RNA regulation is a common occurrence in cancers. Objective: This study set out to evaluate the expression of microRNA-15a (miR-15a) and microRNA-16-1 (miR-16-1) in the saliva of Oral Squamous Cell Carcinoma (OSCC) patients in comparison with a healthy control group. Methods: This case-control study was performed on fifteen patients with OSCC and fifteen healthy volunteers as the control group. A 5 ml of non-stimulating whole saliva was collected by spitting method from patients and controls and stored at -70oC. The expression of miR-15a and miR-16-1 was investigated using quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR). Results: MiR-15a and miR-16-1 were downregulated in OSCC patients compared with the control group (p<0.001). The sensitivity of miR-15a and miR-16-1 in differentiating OSCC patients from healthy individuals was 93.3% and 86.67%, respectively, and their specificity was 86.67% and 92.33%, respectively. The diagnostic accuracy of miR-15a was 90%, and miR-16-1 was 93.3%. Conclusion: The present study showed a decrease in the relative expression of miR-15a and miR-16-1 in OSCC patients compared with healthy individuals. It is probable to introduce salivary values of miR-15a and miR-16-1 as a non-invasive tool for early detection of OSCC. Decreased expression of miR-15a and miR-16-1 in OSCC indicates the possible effective role of these genes in OSCC etiopathogenesis.


2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Jannan Ghapanchi ◽  
Zahra Ranjbar ◽  
Mohammad Javad Mokhtari ◽  
Fatemeh Koohpeima ◽  
Maryam Derakhshan ◽  
...  

Lack of protein-coding capacity is a main characteristic of long noncoding RNAs (lncRNAs) which, as molecular biomarkers, have found a novel pharmacological application in cancer and are reported to be important regulators of gene expression. H19 is reportedly involved in cancer progression and tumorigenesis. One of the most common types of head and neck cancers is oral squamous cell carcinoma (OSCC). The main objective of the present study was to evaluate the correlation of OSCC susceptibility with H19 gene in an Iranian population. This research was performed on 400 subjects of both sexes referred to the Namazi Hospital affiliated with the Shiraz University of Medical Sciences (SUMS). Individuals aged 15-88 years were divided into two groups: pathologically diagnosed patients with new-onset OSCC and healthy controls. After written and informed consent was obtained from the individuals, genomic DNA was extracted. The tetra-primer ARMS-PCR technique was performed for DNA genotyping by the use of specific primer pairs. The susceptibility of OSCC and H19 gene polymorphism sites was further analyzed (rs217727 and rs2107425). The allele and genotype frequencies of H19 rs2107425 polymorphism were similar between OSCC cases and controls. The H19 rs217727T allele frequency was significantly higher in OSCC cases (P=0.002), and the polymorphism of H19 rs217727 was associated with OSCC susceptibility in the codominant (OR=6.04, 95%CI=1.70−21.42, P=0.001 for TT genotype), dominant (OR=1.62, 95%CI=1.08−2.43, P=0.01), and recessive (OR=5.32, 95%CI=1.51−18.69, P=0.003) models. This study showed that rs217727 and OSCC susceptibility were statistically correlated in the Iranian population.


2021 ◽  
Vol 15 (10) ◽  
pp. 2666-2669
Author(s):  
Fiza Shafiq ◽  
Abbas Saleem Khan ◽  
Sajjad Ahmad ◽  
Malik Arshman Khan ◽  
Sikandar Javed , Bajwa ◽  
...  

Background: Oral cancer represents a significant component of the global cancer burden. It develops as a result of multiple risk factors. The main histological form of oral cancer is oral squamous cell carcinoma (OSCC). The disintegration of the extracellular matrix (ECM) is one of the key hallmarks of cancer progression, which stimulates the invasion of tumoral cells into the neighbouring tissue. Matrix metalloproteinases-9 (MMP-9) can degrade different elements of the ECM and basement membrane. Methods: A total of 35 histologically diagnosed cases of OSCC (n=25) and healthy individuals (n=10) as control were included. Immunohistochemical staining was performed on all cases. The results were analysed using SPSS version 20. Results: Increased expression of MMP-9 was observed in OSCC cases (n=23/25; 92%) as compared to healthy individuals. Statistically, a significant relation was observed while comparing the grade of staining intensity and MMP-9 expression among OSCC cases (p=0.001). Conclusion: The present study is planned to assess the immunohistochemical expression of MMP-9 in diagnosed cases of OSCC and healthy individuals. Increased expression of MMP-9 was observed in OSCC as compared to healthy individuals. Evaluation of MMP-9 could be of clinical importance in OSCC and can be used as a diagnostic predictive marker of OSCC. Keywords: Oral squamous cell carcinoma; Matrix Metalloproteinase -9; Immunohistochemistry


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